Cardiovascular diseases

1-PHENYLPYRROLIDIN-2-ONE DERIVATIVES AS PERK INHIBITORS (Fri, 24 Mar 2017)
The invention is directed to substituted pyrrolidinone and imidazolidinone derivatives. Specifically, the invention is directed to compounds according to Formula I: (I) wherein R1, R2, R3, R4, R5, R6, R7, X and Y are as defined herein. The compounds of the invention are inhibitors of PERK and can be useful in the treatment of cancer, pre-cancerous syndromes and diseases/injuries associated with activated unfolded protein response pathways, such as Alzheimer's disease, neuropathic pain, spinal cord injury, traumatic brain injury, ischemic stroke, stroke, Parkinson's disease, diabetes, metabolic syndrome, metabolic disorders, Huntington's disease, Creutzfeldt- Jakob Disease, fatal familial insomnia, Gerstmann-Sträussler-Scheinker syndrome, and related prion diseases, amyotrophic lateral sclerosis, progressive supranuclear palsy, myocardial infarction, cardiovascular disease, inflammation, organ fibrosis, chronic and acute diseases of the liver, fatty liver disease, liver steatosis, liver fibrosis, chronic and acute diseases of the lung, lung fibrosis, chronic and acute diseases of the kidney, kidney fibrosis, chronic traumatic encephalopathy (CTE), neurodegeneration, dementias, frontotemporal dementias, tauopathies, Pick's disease, Neimann-Pick's disease, amyloidosis, cognitive impairment, atherosclerosis, ocular diseases, arrhythmias, in organ transplantation and in the transportation of organs for transplantation. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting PERK activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
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TRIAZOLONE COMPOUNDS AS PERK INHIBITORS (Fri, 24 Mar 2017)
The invention is directed to substituted triazolidinone derivatives. Specifically, the invention is directed to compounds according to Formula I: (I) wherein R1, R2, R3, R4, R5, X, Y, Y1, and Z are as defined herein. The compounds of the invention are inhibitors of PERK and can be useful in the treatment of cancer, pre-cancerous syndromes, as Alzheimer's disease, neuropathic pain, spinal cord injury, traumatic brain injury, ischemic stroke, stroke, Parkinson disease, diabetes, metabolic syndrome, metabolic disorders, Huntington's disease, Creutzfeldt-Jakob Disease, fatal familial insomnia, Gerstmann-Sträussler-Scheinker syndrome, and related prion diseases, amyotrophic lateral sclerosis, progressive supranuclear palsy, myocardial infarction, cardiovascular disease, inflammation, organ fibrosis, chronic and acute diseases of the liver, fatty liver disease, liver steatosis, liver fibrosis, chronic and acute diseases of the lung, lung fibrosis, chronic and acute diseases of the kidney, kidney fibrosis, chronic traumatic encephalopathy (CTE), neurodegeneration, dementias, frontotemporal dementias, tauopathies, Pick's disease, Neimann-Pick's disease, amyloidosis, cognitive impairment, atherosclerosis, ocular diseases, arrhythmias, in organ transplantation and in the transportation of organs for transplantation. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting PERK activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
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IMIDAZOLIDINONE DERIVATIVES AS INHIBITORS OF PERK (Fri, 24 Mar 2017)
The invention is directed to substituted imidazolidinone derivatives. Specifically, the invention is directed to compounds according to Formula I (I) wherein R1, R2, R3, R4, R5, R6, R7, X, Y1, Y2 and Z are defined herein. The compounds of the invention are inhibitors of PERK and can be useful in the treatment of cancer, pre-cancerous syndromes, as Alzheimer's disease, neuropathic pain, spinal cord injury, traumatic brain injury, ischemic stroke, stroke, Parkinson disease, diabetes, metabolic syndrome, metabolic disorders, Huntington's disease, Creutzfeldt-Jakob Disease, fatal familial insomnia, Gerstmann-Sträussler-Scheinker syndrome, and related prion diseases, amyotrophic lateral sclerosis, progressive supranuclear palsy, myocardial infarction, cardiovascular disease, inflammation, organ fibrosis, chronic and acute diseases of the liver, fatty liver disease, liver steatosis, liver fibrosis, chronic and acute diseases of the lung, lung fibrosis, chronic and acute diseases of the kidney, kidney fibrosis, chronic traumatic encephalopathy (CTE), neurodegeneration, dementias, frontotemporal dementias, tauopathies, Pick's disease, Neimann-Pick's disease, amyloidosis, cognitive impairment, atherosclerosis, ocular diseases, arrhythmias, in organ transplantation and in the transportation of organs for transplantation. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting PERK activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
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CYCLOALKYL-HYDROXYL COMPOUNDS AND COMPOSITIONS FOR CHOLESTEROL MANAGEMENT AND RELATED USES (Fri, 17 Mar 2017)
<p id="p-0001" num="0000">The present invention relates to novel cycloalkyl-hydroxyl compounds, compositions comprising hydroxyl compounds, and methods useful for treating and preventing a variety of diseases and conditions such as, but not limited to aging, Alzheimer's Disease, cancer, cardiovascular disease, diabetic nephropathy, diabetic retinopathy, a disorder of glucose metabolism, dyslipidemia, dyslipoproteinemia, hypertension, impotence, inflammation, insulin resistance, lipid elimination in bile, obesity, oxysterol elimination in bile, pancreatitis, Parkinson's disease, a peroxisome proliferator activated receptor-associated disorder, phospholipid elimination in bile, renal disease, septicemia, Syndrome X, thrombotic disorder. Compounds and methods of the invention can also be used to modulate C reactive protein or enhance bile production in a patient. In certain embodiments, the compounds, compositions, and methods of the invention are useful in combination therapy with other therapeutics, such as hypocholesterolemic and hypoglycemic agents.</p>
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BETA- AND GAMMA-AMINO-ISOQUINOLINE AMIDE COMPOUNDS AND SUBSTITUTED BENZAMIDE COMPOUNDS (Fri, 17 Mar 2017)
<p id="p-0001" num="0000">Disclosed are beta and gamma-amino isoquinoline amide compounds and substituted benzamide compounds. In particular, the invention provides compounds that affect the function of kinases in a cell and that are useful as therapeutic agents or with therapeutic agents. The compounds of the invention are useful in the treatment of a variety of diseases and conditions including eye diseases such as glaucoma, cardiovascular diseases, and diseases characterized by abnormal growth, such as cancers. The invention further provides compositions containing the beta or gamma-amino isoquinoline amide compounds or substituted benzamide compounds.</p>
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HETEROCYCLYL-BUTANAMIDE DERIVATIVES (Fri, 17 Mar 2017)
<p id="p-0001" num="0000">Compounds of the formula I</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="21.59mm" wi="61.55mm" file="US20170073347A1-20170316-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">in which W, X and Y have the meanings indicated in Claim <b>1,</b> are inhibitors of Tankyrase, and can be employed, inter alia, for the treatment of diseases such as cancer, cardiovascular diseases, central nervous system injury and different forms of inflammation.</p>
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CYANO THIENOTRIAZOLODIAZEPINES AND USES THEREOF (Fri, 17 Mar 2017)
The present invention provides compounds and pharmaceutically compositions thereof. The compounds and compositions are binders of bromodomains and/or bromodomain-containing proteins (e.g., bromo and extra terminal (BET) proteins). Also provided are methods, uses, and kits using the compounds and pharmaceutical compositions for inhibiting the activity (e.g., increased activity) of bromodomains and/or bromodomain-containing proteins and for treating and/or preventing in a subject diseases associated with bromodomains or bromodomain-containing proteins (e.g., proliferative diseases, cardiovascular diseases, viral infections, fibrotic diseases, metabolic diseases, endocrine diseases, and radiation poisoning). The compounds, pharmaceutical compositions, and kits are also useful for male contraception.
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AGENTS FOR USE IN THE TREATMENT OF CARDIOVASCULAR AND INFLAMMATORY DISEASES STRUCTURALLY BASED ON 4(1 H)-QUINOLONE (Fri, 10 Mar 2017)
<p id="p-0001" num="0000">The present invention provides a compound of formula I, a tautomer thereof, or a pharmaceutically acceptable salt or N-oxide thereof for use in the treatment or prevention of cardiovascular disease or of an inflammatory disease or condition:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.86mm" wi="53.17mm" file="US20170066722A1-20170309-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">wherein:</li> <li id="ul0002-0002" num="0000">V is N or CR<sub>3</sub>;</li> <li id="ul0002-0003" num="0000">X is N or CR<sub>4</sub>;</li> <li id="ul0002-0004" num="0000">Y is N or CR<sub>5</sub>;</li> <li id="ul0002-0005" num="0000">Z is N or CR<sub>6</sub>;</li> <li id="ul0002-0006" num="0000">B is —(C═O)R<sub>1</sub>, a 5- to 10-membered heteroaryl group, or a group</li> <li id="ul0002-0007" num="0000">-L′″-NRR′, wherein R and R′ are the same or different and each represents a hydrogen atom, a C<sub>1</sub>-C<sub>6 </sub>alkyl group or a C<sub>1</sub>-C<sub>6 </sub>haloalkyl group;</li> <li id="ul0002-0008" num="0000">R<sub>1 </sub>is a 5- to 10-membered heterocyclyl group, or —OR′, wherein R′ is a hydrogen atom, a C<sub>1</sub>-C<sub>6 </sub>alkyl group or a C<sub>1</sub>-C<sub>6 </sub>haloalkyl group, or R<sub>1 </sub>is a proteinogenic α amino acid, which is linked to the carbonyl moiety in the compound of formula (I) via the α amino group, which amino acid is optionally esterified at the α carboxylic acid group with a C<sub>1</sub>-C<sub>6 </sub>alkyl group or a C<sub>6</sub>-C<sub>10 </sub>aryl group, or R<sub>1 </sub>is —NR″R′″, —NR<sup>IV</sup>-L′″-CONR″R′″, or —NR<sup>IV</sup>-L′″-COOR, wherein R, R″, R′″ and R<sup>IV </sup>are the same or different and each represents a hydrogen atom, a C<sub>1</sub>-C<sub>6 </sub>alkyl group or a C<sub>1</sub>-C<sub>6 </sub>haloalkyl group;</li> <li id="ul0002-0009" num="0000">either (a) W is N and R<sub>9 </sub>and R<sub>2 </sub>together form a bond, or (b) W is CR<sub>8</sub>, R<sub>8 </sub>and R<sub>9 </sub>together form a bond and R<sub>2 </sub>is a hydrogen atom, or a C<sub>1</sub>-C<sub>6 </sub>alkyl, C<sub>1</sub>-C<sub>6 </sub>haloalkyl, C<sub>6</sub>-C<sub>10 </sub>aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocyclyl, -L′-A<sub>2</sub>, C<sub>3</sub>-C<sub>10 </sub>cycloalkyl, or —COOR′ group, wherein R′ is a hydrogen atom or C<sub>1</sub>-C<sub>6 </sub>alkyl group, or, when Z is a moiety CR<sub>6</sub>, R<sub>2 </sub>may form, together with R<sub>6 </sub>and the carbon and nitrogen atoms which connect R<sub>2 </sub>and R<sub>6 </sub>in the formula (I), a 5- to 6-membered heterocyclic ring;</li> <li id="ul0002-0010" num="0000">R<sub>3 </sub>is a hydrogen atom, a halogen atom, or a hydroxy, C<sub>1</sub>-C<sub>6 </sub>alkyl, C<sub>1</sub>-C<sub>6 </sub>alkoxy, C<sub>1</sub>-C<sub>6 </sub>haloalkyl, C<sub>1</sub>-C<sub>6 </sub>haloalkoxy, nitro, or —NR′R″ group, wherein R′ and R″ are the same or different and each represent a hydrogen atom or C<sub>1</sub>-C<sub>6 </sub>alkyl group;</li> <li id="ul0002-0011" num="0000">R<sub>4 </sub>and R<sub>5 </sub>are the same or different and each represent a hydrogen atom, a halogen atom, or a hydroxyl, C<sub>1</sub>-C<sub>8 </sub>alkyl, C<sub>1</sub>-C<sub>8 </sub>haloalkyl, C<sub>1</sub>-C<sub>6 </sub>alkoxy, C<sub>1</sub>-C<sub>6 </sub>haloalkoxy, nitro, —NR′R″, —CO<sub>2</sub>R′″, C<sub>6</sub>-C<sub>10 </sub>aryl, 5- to 10-membered heteroaryl, 5 to 10-membered heterocyclyl, or —CO—(C<sub>1</sub>-C<sub>6 </sub>alkyl) group, wherein R′, R″ and R′″ are the same or different and each represent a hydrogen atom or C<sub>1</sub>-C<sub>6 </sub>alkyl group, or R<sub>4 </sub>and R<sub>5 </sub>and the carbon atoms bonded to R<sub>4 </sub>and R<sub>5 </sub>together form a 5- to 6-membered heterocyclic ring;</li> <li id="ul0002-0012" num="0000">R<sub>6 </sub>is a hydrogen atom, a halogen atom, or a C<sub>1</sub>-C<sub>6 </sub>alkyl, C<sub>1</sub>-C<sub>6 </sub>haloalkyl, C<sub>1</sub>-C<sub>6 </sub>alkoxy, C<sub>1</sub>-C<sub>6 </sub>haloalkoxy or —CO<sub>2</sub>R′ group, wherein R′ is hydrogen or C<sub>1</sub>-C<sub>6 </sub>alkyl, or, when W is a moiety CR<sub>8</sub>, R<sub>6 </sub>may form, together with R<sub>2 </sub>and the carbon and nitrogen atoms which connect R<sub>6 </sub>and R<sub>2 </sub>in the formula (I), a 5- to 6-membered heterocyclic ring;</li> <li id="ul0002-0013" num="0000">R<sub>7 </sub>is a hydrogen atom, a halogen atom, or a C<sub>1</sub>-C<sub>6 </sub>alkyl, or C<sub>1</sub>-C<sub>6 </sub>haloalkyl group,</li> <li id="ul0002-0014" num="0000">A<sub>2 </sub>represents a C<sub>6</sub>-C<sub>10 </sub>aryl or 5- to 10-membered heteroaryl group;</li> <li id="ul0002-0015" num="0000">L′, and L′″ are the same or different and each represent a C<sub>1</sub>-C<sub>6 </sub>alkylene, C<sub>2</sub>-C<sub>6 </sub>alkenylene, or C<sub>2</sub>-C<sub>6 </sub>alkynylene group;</li> <li id="ul0002-0016" num="0000">said aryl, heteroaryl, cycloalkyl and heterocyclyl groups being unsubstituted or substituted with one or more substituents selected from halogen, hydroxy, C<sub>1</sub>-C<sub>4 </sub>alkyl, C<sub>1</sub>-C<sub>4 </sub>hydroxyalkyl, C<sub>1</sub>-C<sub>4 </sub>alkoxy, C<sub>1</sub>-C<sub>4 </sub>haloalkyl, C<sub>1</sub>-C<sub>4 </sub>haloalkoxy, —SOR, —SO<sub>2</sub>R, —NR′R″, —NR′(C═O)R″, —COOR, nitro and cyano substituents, wherein R, R′ and R″ are the same or different and each represents a hydrogen atom or C<sub>1</sub>-C<sub>4 </sub>alkyl group.</li> </ul> </li> </ul> </p>
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ENANTIOMERS OF THE N-(2-AMINO-5-FLUORO-2-METHYLPENTYL)-8-[(2,6-DIFLUOROBENZYL)OXY]-2-METHYLIMIDAZO[1,2-A]PYRIDINE-3-CARBOXAMIDE, AS WELL AS OF THE DI- AND TRIFLUORO DERIVATIVES FOR THE TREATMENT OF CARDIOVASCULAR DISEASES (Fri, 03 Mar 2017)
<p id="p-0001" num="0000">The present application relates to novel 6-hydrogen-substituted imidazo[1,2-a]pyridine-3-carboxamides, to processes for preparation thereof, to the use thereof, alone or in combinations, for treatment and/or prophylaxis of diseases, and to the use thereof for production of medicaments for treatment and/or prophylaxis of diseases, especially for treatment and/or prophylaxis of cardiovascular disorders.</p>
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DEUTERATED COMPOUNDS AND USES THEREOF (Fri, 03 Mar 2017)
The present invention provides for the treatment, prevention, and/or reduction of a risk of a disease, disorder, or condition in which aldehyde toxicity is implicated in the pathogenesis, including ocular disorders, skin disorders, conditions associated with injurious effects from blister agents, and autoimmune, inflammatory, neurological and cardiovascular diseases by the use of a primary amine to scavenge toxic aldehydes, such as MDA and HNE.
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ALDEHYDE CONJUGATES AND USES THEREOF (Fri, 03 Mar 2017)
The present invention provides compounds and methods of use thereof for the treatment, prevention, and/or reduction of a risk of a disease, disorder, or condition in which aldehyde toxicity is implicated in the pathogenesis, including ocular disorders, skin disorders, conditions associated with injurious effects from blister agents, and autoimmune, inflammatory, neurological and cardiovascular diseases by the use of a primary amine to scavenge toxic aldehydes, such as MDA and HNE.
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IMIDAZO[1,2-A]PYRIDINES AS STIMULATORS OF SOLUBLE GUANYLATE CYCLASE FOR TREATING CARDIOVASCULAR DISEASES (Fri, 24 Feb 2017)
<p id="p-0001" num="0000">The present application relates to novel heterocyclyl- and heteroaryl-substituted imidazo[1,2-a]pyridines, to processes for preparation thereof, to the use thereof, alone or in combinations, for the treatment and/or prophylaxis of diseases, and to the use thereof for production of medicaments for the treatment and/or prophylaxis of diseases, especially for the treatment and/or prophylaxis of cardiovascular disorders.</p>
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IMIDAZO[1,2-A]PYRIDINES AS SOLUBLE GUANYLATE CYCLASE STIMULATORS FOR THE TREATMENT OF CARDIOVASCULAR DISEASES (Fri, 24 Feb 2017)
<p id="p-0001" num="0000">The present application relates to novel substituted imidazo[1,2-a]pyridine-3-carboxamides, to processes for preparation thereof, to the use thereof, alone or in combinations, for treatment and/or prophylaxis of diseases, and to the use thereof for production of medicaments for treatment and/or prophylaxis of diseases, especially for treatment and/or prophylaxis of cardiovascular disorders.</p>
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MELDRUM'S ACID, BARBITURIC ACID AND PYRAZOLONE DERIVATIVES SUBSTITUTED WITH HYDROXYLAMINE AS HNO DONORS (Fri, 24 Feb 2017)
<p id="p-0001" num="0000">The disclosed subject matter provides certain N-substituted hydroxylamine derivative compounds, pharmaceutical compositions and kits comprising such compounds, and methods of using such compounds or pharmaceutical compositions. In particular, the disclosed subject matter provides methods of using such compounds or pharmaceutical compositions for treating, preventing, or delaying the onset and/or development of a disease or condition. In some embodiments, the disease or condition is selected from cardiovascular diseases, ischemia, reperfusion injury, cancerous disease, pulmonary hypertension and conditions responsive to nitroxyl therapy.</p>
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Inhibitors of the renal outer medullary potassium channel (Wed, 22 Feb 2017)
<p id="p-0001" num="0000">The present invention provides compounds of Formula I</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="24.81mm" wi="57.32mm" file="US09573961-20170221-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and conditions associated with excessive salt and water retention. </p>
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BENZOIC ACID COMPOUNDS FOR REDUCING URIC ACID (Fri, 17 Feb 2017)
<p id="p-0001" num="0000">Uric acid in mammalian subjects is reduced and excretion of uric acid is increased by administering a compound of Formula I. The uric acid-lowering effects of the compounds of this invention are used to treat or prevent a variety of conditions including gout, hyperuricemia, elevated levels of uric acid that do not meet the levels customarily justifying a diagnosis of hyperuricemia, renal dysfunction, kidney stones, cardiovascular disease, risk for developing cardiovascular disease, tumor-lysis syndrome, cognitive impairment, early-onset essential hypertension, and <i>Plasmodium falciparum</i>-induced inflammation.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="19.22mm" wi="69.85mm" file="US20170042844A1-20170216-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">In Formula I, t is 0 or 1; q is 0 or 1; and r is 0, 1 or 2. R<sup>7 </sup>is hydrogen or alkyl having from 1 to 3 carbon atoms. R<sup>6 </sup>is hydrogen, hydroxy, halo, alkyl having from 1 to 3 carbon atoms, alkoxy having from 1 to 3 carbon atoms, nitro, thio, alkylthio, or cyano. X is C(O) or NH(R<sup>8</sup>) wherein R<sup>8 </sup>is hydrogen or alkyl having from 1 to 3 carbon atoms; provided that when X is C(O), r is 0 and t is 0. A is phenyl, unsubstituted or substituted by 1 or 2 groups selected from halo, hydroxy, methyl, ethyl, perfluoromethyl, methoxy, ethoxy, perfluoromethoxy, nitro, and amino; or a 5 or 6 membered heteroaromatic ring having 1 or 2 ring heteroatoms selected from N, S and O and the heteroaromatic ring is covalently bound to the remainder of the compound of Formula I by a ring carbon; or cycloalkyl having from 3 to 6 ring carbon atoms wherein the cycloalkyl is unsubstituted or one or two ring carbons are independently monosubstituted by methyl or ethyl.</p>
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INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL (Fri, 10 Feb 2017)
<p id="p-0001" num="0000">The present invention provides compounds of Formula (I) and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="36.58mm" wi="69.85mm" file="US20170037037A1-20170209-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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PHARMACEUTICAL COMPOSITION AND THERAPEUTIC COMBINATION COMPRISING A CHOLESTERYL ESTER TRANSFER PROTEIN INHIBITOR AND AN ATP CITRATE LYASE INHIBITOR – AMPK ACTIVATOR (Fri, 10 Feb 2017)
The present invention relates to a pharmaceutical composition and a therapeutic combination comprising a novel cholesteryl ester transfer protein (CETP) inhibitor and an adenosine triphosphate citrate lyase inhibitor/adenosine monophosphate-activated protein kinase activator, which may be used in the treatment of subjects suffering from or having an increased risk for cardiovascular diseases, in particular hyperlipidemia or mixed dyslipidemia.
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PHARMACEUTICAL COMPOSITION AND THERAPEUTIC COMBINATION COMPRISING A CHOLESTERYL ESTER TRANSFER PROTEIN INHIBITOR AND A CHOLESTEROL ABSORPTION INHIBITOR (Fri, 10 Feb 2017)
The present invention relates to a pharmaceutical composition and a therapeutic combination comprising a novel cholesteryl ester transfer protein (CETP) inhibitor and a cholesterol absorption inhibitor, which may be used in the treatment of subjects suffering from or having an increased risk for cardiovascular diseases, in particular hyperlipidemia or mixed dyslipidemia.
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1,3,4-OXADIAZOLE DERIVATIVE COMPOUNDS AS HISTONE DEACETYLASE 6 INHIBITOR, AND THE PHARMACEUTICAL COMPOSITION COMPRISING THE SAME (Fri, 10 Feb 2017)
The present invention relates to novel compounds having histone deacetylase 6 (HDAC6) in-hibitory activity, stereoisomers thereof or pharmaceutically acceptable salts thereof, the use thereof for the preparation of therapeutic medicaments, pharmaceutical compositions containing the same, a method for treating diseases using the composition, and methods for preparing the novel compounds. The novel compounds, stereoisomers thereof or pharmaceutically acceptable salts thereof according to the present invention have histone deacetylase (HDAC) inhibitory activity and are effective for the prevention or treatment of HDAC6-mediated diseases, including infectious diseases; neoplasms; endocrine, nutritional and metabolic diseases; mental and be-havioral disorders; neurological diseases; diseases of the eye and adnexa; cardiovascular diseases; respiratory diseases; digestive diseases; diseases of the skin and subcutaneous tissue; diseases of the musculoskeletal system and connective tissue; or congenital malformations, de¬ formations and chromosomal abnormalities.
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NOVEL MACROCYCLIC COMPOUNDS (Fri, 03 Feb 2017)
<p id="p-0001" num="0000">The present invention relates to novel macrocyclic compounds of general formula (I) as described and defined herein, and methods for their preparation, their use for the treatment and/or prophylaxis of disorders, in particular of hyper-proliferative disorders and/or virally induced infectious diseases and/or of cardiovascular diseases. The invention further relates to intermediate compounds useful in the preparation of said compounds of general formula (I).</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="60.11mm" wi="56.56mm" file="US20170029439A1-20170202-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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1,3,4-OXADIAZOLE SULFAMIDE DERIVATIVE COMPOUNDS AS HISTONE DEACETYLASE 6 INHIBITOR, AND THE PHARMACEUTICAL COMPOSITION COMPRISING THE SAME (Fri, 03 Feb 2017)
The present invention relates to novel compounds having histone deacetylase 6 (HDAC6) inhibitory activity, stereoisomers thereof or pharmaceutically acceptable salts thereof, the use thereof for the preparation of therapeutic medicaments, pharmaceutical compositions containing the same, a method for treating diseases using the composition, and methods for preparing the novel compounds. The novel compounds, stereoisomers thereof or pharmaceutically acceptable salts thereof according to the present invention have histone deacetylase (HDAC) inhibitory activity and are effective for the prevention or treatment of HDAC6-mediated diseases, including infectious diseases; neoplasms; endocrine, nutritional and metabolic diseases; mental and behavioral disorders; neurological diseases; diseases of the eye and adnexa; cardiovascular diseases; respiratory diseases; digestive diseases; diseases of the skin and subcutaneous tissue; diseases of the musculoskeletal system and connective tissue; or congenital malformations, deformations and chromosomal abnormalities.
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METABOLICALLY ROBUST ANALOGS OF CYP-EICOSANOIDS FOR THE TREATMENT OF CARDIAC DISEASE (Fri, 27 Jan 2017)
The present invention relates to compounds according to general formula (I) which are metabolically robust analogues of bioactive lipid mediators derived from omega-3 polyunsaturated fatty acids (n-3 PUFAs).The present invention further relates to compositions containing one or more of these compounds and to the use of these compounds or compositions for the treatment or prevention of cardiovascular diseases.
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COMPOSITIONS AND METHODS FOR REDUCING CHRONIC LOW-LEVEL INFLAMMATION (Fri, 20 Jan 2017)
<p id="p-0001" num="0000">The invention relates to compositions and methods for reducing chronic low-level inflammation associated with chronic conditions. Specifically, the invention relates to compositions of hydrophobic derivatives of aspirin and/or hydrophobic derivatives of sesamol in combination with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and their methods for reducing chronic low-level inflammation associated with chronic conditions including obesity, metabolic syndrome, diabetes, cardiovascular disease, cancer, auto-immune disorders, ocular and neurological disorders in a mammal.</p>
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DISUBSTITUTED 5-FLUORO PYRIMIDINE DERIVATIVES CONTAINING A SULFONDIIMINE GROUP (Fri, 20 Jan 2017)
<p id="p-0001" num="0000">The present invention relates to 5-fluoro pyrimidine derivatives containing a sulfondiimine group of general formula (I) as described and defined herein, and methods for their preparation, their use for the treatment and/or prophylaxis of disorders, in particular of hyper-proliferative disorders and/or virally induced infectious diseases and/or of cardiovascular diseases. The invention further relates to intermediate compounds useful in the preparation of said compounds of general formula (I).</p>
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RNA-CODED ANTIBODY (Thu, 19 Jan 2017)
The present application describes an antibody-coding, non-modified or modified RNA and the use thereof for expression of this antibody, for the preparation of a pharmaceutical composition, in particular a passive vaccine, for treatment of tumours and cancer diseases, cardiovascular diseases, infectious diseases, auto-immune diseases, virus diseases and monogenetic diseases, e.g. also in gene therapy. The present invention furthermore describes an in vitro transcription method, in vitro methods for expression of this antibody using the RNA according to the invention and an in vivo method.
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USES OF DIAZEPANE DERIVATIVES (Fri, 13 Jan 2017)
<p id="p-0001" num="0000">The present invention provides compounds of Formula (II) (e.g., compounds of Formula (I)), and pharmaceutically compositions thereof. Compounds of Formula (II) are believed to be binders of bromodomains and/or bromodomain-containing proteins (e.g., bromo and extra terminal (BET) proteins). Also provided are methods, uses, and kits using the compounds and pharmaceutical compositions for inhibiting the activity (e.g., increased activity) of bromodomains and/or bromodomain-containing proteins and for treating and/or preventing in a subject diseases associated with bromodomains or bromodomain-containing proteins (e.g., proliferative diseases, cardiovascular diseases, viral infections, fibrotic diseases, metabolic diseases, endocrine diseases, and radiation poisoning). The compounds, pharmaceutical compositions, and kits are also useful for male contraception.</p>
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RNA-CODED ANTIBODY (Thu, 12 Jan 2017)
The present application describes an antibody-coding, non-modified or modified RNA and the use thereof for expression of this antibody, for the preparation of a pharmaceutical composition, in particular a passive vaccine, for treatment of tumours and cancer diseases, cardiovascular diseases, infectious diseases, auto-immune diseases, virus diseases and monogenetic diseases, e.g. also in gene therapy. The present invention furthermore describes an in vitro transcription method, in vitro methods for expression of this antibody using the RNA according to the invention and an in vivo method.
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5-FLUORO-N-(PYRIDIN-2-YL)PYRIDIN-2-AMINE DERIVATIVES CONTAINING A SULFONE GROUP (Fri, 06 Jan 2017)
<p id="p-0001" num="0000">The present invention relates to 5-fluoro-N-(pyridin-2-yl)pyridin-2-amine derivatives containing a sulfone group of general formula (I) as described and defined herein, and methods for their preparation, their use for the treatment and/or prophylaxis of disorders, in particular of hyper-proliferative disorders and/or virally induced infectious diseases and/or of cardiovascular diseases. The invention further relates to intermediate compounds useful in the preparation of said compounds of general formula (I).</p>
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AMINOTRIAZOLE- AND AMINOTETRAZOLE-BASED KDM1A INHIBITORS AS EPIGENETIC MODULATORS (Fri, 06 Jan 2017)
<p id="p-0001" num="0000">In some aspects, the present invention provides compounds of the formula (IV), wherein the variables are as defined herein, which may be used as inhibitors of histone demethylase or spermine oxidase. Also provided herein are pharmaceutical compositions of the compounds and methods using the compounds in the treatment of diseases such as cancer and cardiovascular disease.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="79.25mm" wi="73.32mm" file="US20170001968A1-20170105-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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INHIBITORS OF MITOCHONDRIAL PYRUVATE DEHYDROGENASE KINASE ISOFORMS 1-4 AND USES THEREOF (Fri, 06 Jan 2017)
<p id="p-0001" num="0000">The present disclosure relates to the identification of PDK inhibitors and their use in the treatment of diseases such as diabetes, cardiovascular disease and cancer. The invention relates to the development of robust PDK inhibitors that can be used to improve glucose metabolism and correct metabolic dysfunction in vivo. Based on the unique structural features present in the ATP-binding pocket of PDK2, a single functional-group change was made in a known Hsp90 inhibitor that binds to the corresponding pocket of the latter protein from the GHKL family. This approach efficiently converted the Hsp90 inhibitor to a highly specific inhibitor for all PDK isoforms. These final PDK inhibitors of this series robustly augments PDC activity with reduced phosphorylation in tissues.</p>
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IMIDAZOPYRAZINONE DERIVATIVES (Fri, 06 Jan 2017)
<p id="p-0001" num="0000">Compounds of the formula I</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="30.06mm" wi="58.84mm" file="US20170002010A1-20170105-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">in which R<sup>1 </sup>and R<sup>2 </sup>have the meanings indicated in Claim <b>1,</b> are inhibitors of Tankyrase, and can be employed, inter alia, for the treatment of diseases such as cancer, cardiovascular diseases, central nervous system injury and different forms of inflammation.</p>
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PCSK9 QUANTIFICATION BY IMMUNODETECTION (Fri, 30 Dec 2016)
<p id="p-0001" num="0000">The present disclosure relates to, among other things, systems for detecting the level of specific lipoprotein-bound level of PCSK9, and optionally free PCSK9, lipoprotein or portions thereof and/or PCSK9 unbound lipoproteins present in a biological sample. The present invention also relates to methods of assessing the level of specific lipoprotein-bound level of PCSK9, and optionally free PCSK9, Apo B and/or PCSK9 unbound lipoproteins present in a biological sample, determining whether a subject is at increased risk for cardiovascular disease and monitoring the risk for developing cardiovascular disease.</p>
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NOVEL 5-HT2 ANTAGONISTS (Fri, 30 Dec 2016)
The present invention relates to 1-amidino-3-aryl-2-pyrazoline derivatives of the general formula I The invention specifically relates to such derivatives which exhibit antagonizing activity towards serotonin 5-HT2B receptors. The present invention also relates to use of said compounds as a medicament and for the treatment of fibrosis, cardiovascular diseases, pain, IBD, and other inflammatory diseases, as well as pharmaceutical compositions comprising one or more of said compounds and methods of treatment.
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NOVEL 5-HT2 ANTAGONISTS (Thu, 29 Dec 2016)
The present invention relates to 1-amidino-3-aryl-2-pyrazoline derivatives of the general formula I The invention specifically relates to such derivatives which exhibit antagonizing activity towards serotonin 5-HT 2B receptors. The present invention also relates to use of said compounds as a medicament and for the treatment of fibrosis, cardiovascular diseases, pain, IBD, and other inflammatory diseases, as well as pharmaceutical compositions comprising one or more of said compounds and methods of treatment.
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INHIBITORS OF C-JUN-N-TERMINAL KINASE (JNK) (Fri, 23 Dec 2016)
<p id="p-0001" num="0000">The present invention provides novel compounds according to Formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="35.98mm" wi="70.36mm" file="US20160368910A1-20161222-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">where Ring A, Ring B, X, L<sub>1</sub>, L<sub>2</sub>, R<sup>A</sup>, R<sup>C</sup>, R<sup>D</sup>, R<sup>E</sup>, m, n, and p are as defined herein. Compounds of the present invention are contemplated useful for the prevention and treatment of a variety of human diseases associated with kinase activity, for example, proliferative diseases, neurodegenerative diseases, metabolic disorders, inflammatory diseases, and cardiovascular diseases.</p>
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FUSED HETEROCYCLIC COMPOUNDS AS ION CHANNEL MODULATORS (Fri, 16 Dec 2016)
<p id="p-0001" num="0000">The present disclosure relates to compounds that are sodium channel inhibitors and to their use in the treatment of various disease states, including cardiovascular diseases and diabetes. In particular embodiments, the structure of the compounds is given by Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="16.51mm" wi="55.54mm" file="US20160362421A1-20161215-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein Q, R<sup>1</sup>, X<sup>1</sup>, X<sup>2</sup>, Y and R<sup>2 </sup>are as described herein, to methods for the preparation and use of the compounds and to pharmaceutical compositions containing the same.</p>
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Replacement Therapy for Natriuretic Peptide Deficiencies (Fri, 09 Dec 2016)
<p id="p-0001" num="0000">Use and methods of use of natriuretic peptide mimetics which bind to and activate natriuretic peptide receptor A in patients with a defect, condition, syndrome, disease or mutation resulting in a functional active ANP<sub>99-126 </sub>deficiency, for treatment or prophylaxis of cardiovascular disease, including but not limited to hypertension, acute coronary syndrome, cardiomyopathy, cardiac remodeling, left-ventricular hypertrophy, congestive heart failure, heart failure, high blood pressure and coronary artery disease, including use of mimetics with a plurality of amino acid residues and at least one amino acid surrogate of formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="18.88mm" wi="69.85mm" file="US20160354443A1-20161208-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">where R, R′, Q, Y, W, Z, J, x and n are as defined in the specification.</p>
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FUSED BENZOXAZEPINONES AS ION CHANNEL MODULATORS (Thu, 08 Dec 2016)
The present disclosure relates to compounds that are sodium channel inhibitors and to their use in the treatment of various disease states, including cardiovascular diseases and diabetes.
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TRIMETHYLAMINE COMPOUNDS AS RISK PREDICTORS OF CARDIOVASCULAR DISEASE (Fri, 02 Dec 2016)
<p id="p-0001" num="0000">Methods of characterizing a test subject's risk of having or developing cardiovascular disease are provided. The methods include using an analytic device to determine levels of choline-related trimethylamine-containing compounds such as trimethylamine N-oxide, choline, or betaine in a biological sample obtained from the subject and comparing the levels of the choline-related trimethylamine-containing compound in the subject's biological sample to a control value. The test subject's risk of having cardiovascular disease is then characterized as higher if the levels of the choline-related trimethylamine-containing compound are higher than the control value. Also provided are methods of identifying a subject at risk of experiencing a complication of atherosclerotic cardiovascular disease, and methods of evaluating the efficacy of a cardiovascular therapeutic agent in a subject with cardiovascular disease using levels of choline-related trimethylamine-containing compounds.</p>
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FUSED BENZOXAZEPINONES AS ION CHANNEL MODULATORS (Thu, 01 Dec 2016)
The present disclosure relates to compounds that are sodium channel inhibitors and to their use in the treatment of various disease states, including cardiovascular diseases and diabetes.
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NOVEL DGAT2 INHIBITORS (Fri, 25 Nov 2016)
The present invention provides compounds of the Formula below: [Formula should be inserted here] Where A, X, R, and R2-R3 are as described herein; methods of treating patients for hypertriglyceridemia and cardiovascular disease including dyslipidemia and atherosclerosis, and processes for preparing the compounds.
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DIAMINOPYRIMIDINE BENZENESULFONE DERIVATIVES AND USES THEREOF (Fri, 18 Nov 2016)
<p id="p-0001" num="0000">The present invention provides compounds of Formula (II) (e.g., compounds of Formula (I)), and pharmaceutically compositions thereof. Compounds of Formula (II) are believed to be binders of bromodomains and/or bromodomain-containing proteins (e.g., bromo and extra terminal (BET) proteins). Also provided are methods, uses, and kits using the compounds and pharmaceutical compositions for inhibiting the activity (e.g., increased activity) of bromodomains and/or bromodomain-containing proteins and for treating and/or preventing in a subject diseases associated with bromodomains or bromodomain-containing proteins (e.g., proliferative diseases, cardiovascular diseases, viral infections, fibrotic diseases, metabolic diseases, endocrine diseases, and radiation poisoning). The compounds, pharmaceutical compositions, and kits are also useful for male contraception.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="69.93mm" wi="76.20mm" file="US20160332993A1-20161117-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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USE OF CD24 FOR LOWERING LOW-DENSITY LIPOPROTEIN CHOLESTEROL LEVELS (Fri, 11 Nov 2016)
The present invention relates to the use of a CD24 protein for lowering low-density lipoprotein cholesterol levels, treating and preventing atherosclerosis, and for reducing risk of cardiovascular disease.
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PYRAZOLE DERIVATIVES USEFUL AS 5-LIPOXYGENASE ACTIVATING PROTEIN (FLAP) INHIBITORS (Fri, 11 Nov 2016)
The present application relates to novel compounds of formula (I) to their utility in treating and/or preventing clinical conditions including cardiovascular diseases (CVD), to methods for their therapeutic use, to pharmaceutical compositions containing them and to processes for preparing such compounds.
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Anti-aP2 Antibodies and Antigen Binding Agents to Treat Metabolic Disorders (Fri, 04 Nov 2016)
<p id="p-0001" num="0000">This invention is in the area of improved anti-aP2 antibodies and antigen binding agents, and compositions thereof, which target the lipid chaperone aP2/FABP4 (referred to as “aP2”) for use in treating disorders such as diabetes, obesity, cardiovascular disease, fatty liver disease, and/or cancer, among others. In one aspect, improved treatments for aP2 mediated disorders are disclosed in which serum aP2 is targeted and the biological activity of aP2 is neutralized or modulated using low-binding affinity aP2 monoclonal antibodies, providing lower fasting blood glucose levels, improved systemic glucose metabolism, increased systemic insulin sensitivity, reduced fat mass, reduced liver steatosis, reduced cardiovascular disease and/or a reduced risk of developing cardiovascular disease.</p>
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PHTHALAZINE DERIVATIVES (Fri, 04 Nov 2016)
<p id="p-0001" num="0000">Compounds of the formula I</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="24.21mm" wi="60.54mm" file="US20160318876A1-20161103-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">in which R<sup>1</sup>, X and n have the meanings indicated in Claim <b>1</b>, are inhibitors of Tankyrase, and can be employed, inter alia, for the treatment of diseases such as cancer, cardiovascular diseases, central nervous system injury and different forms of inflammation.</p>
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FUSED HETEROCYCLIC COMPOUNDS AS ION CHANNEL MODULATORS (Fri, 04 Nov 2016)
<p id="p-0001" num="0000">The present disclosure relates to compounds that are sodium channel inhibitors and to their use in the treatment of various disease states, including cardiovascular diseases and diabetes. In particular embodiments, the structure of the compounds is given by Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="28.79mm" wi="58.67mm" file="US20160317504A1-20161103-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein X, Y, Z, R<sup>2</sup>, R<sup>3</sup>, R<sup>4</sup>, p and q are as described herein, to methods for the preparation and use of the compounds and to pharmaceutical compositions containing the same.</p>
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ANTI-AP2 ANTIBODIES AND ANTIGEN BINDING AGENTS TO TREAT METABOLIC DISORDERS (Fri, 04 Nov 2016)
This invention is in the area of improved anti-aP2 antibodies and antigen binding agents, and compositions thereof, which target the lipid chaperone aP2/FABP4 (referred to as "aP2") for use in treating disorders such as diabetes, obesity, cardiovascular disease, fatty liver disease, and/or cancer, among others. In one aspect, improved treatments for aP2 mediated disorders are disclosed in which serum aP2 is targeted and the biological activity of aP2 is neutralized or modulated using low-binding affinity aP2 monoclonal antibodies, providing lower fasting blood glucose levels, improved systemic glucose metabolism, increased systemic insulin sensitivity, reduced fat mass, reduced liver steatosis, reduced cardiovascular disease and/or a reduced risk of developing cardiovascular disease.
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FUSED BENZOXAZEPINONES AS ION CHANNEL MODULATORS (Thu, 03 Nov 2016)
The present disclosure relates to compounds that are sodium channel inhibitors and to their use in the treatment of various disease states, including cardiovascular diseases and diabetes.
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NOVEL DIHYDROPYRIDOISOQUINOLINONES AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF INFLAMMATORY DISORDERS (Fri, 28 Oct 2016)
A compound according to Formula (I): wherein R1, LA, CyA, RA, R2, R3, and R4 are as described herein. The present invention relates to novel compounds according to Formula I that antagonize GPR84, a G-protein-coupled receptor that is involved in inflammatory conditions, and methods for the production of these novel compounds, pharmaceutical compositions comprising these compounds, and methods for the prevention and/or treatment of inflammatory conditions, pain, neuroinflammatory conditions, neurodegenerative conditions, infectious diseases, autoimmune diseases, endocrine and/or metabolic diseases, cardiovascular diseases, leukemia, and/or diseases involving impairment of immune cell functions by administering a compound of the invention.
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COMPOUNDS AND THEIR USE AS BACE1 INHIBITORS (Fri, 28 Oct 2016)
The present invention relates to compounds of Formula (I) or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein X, Y, Z, Q, W, m, u, ring (A), R2, R3, R4, R5 and R6, are as defined in the specification and claims. The present invention provides a pharmaceutical composition containing the compounds of Formula (I) and a therapeutic method of treating and/or preventing Downs syndrome, β-amyloid angiopathy, disorders associated with cognitive impairment, Alzheimer's disease, memory loss, attention deficit symptoms associated with Alzheimer's disease, neurodegenerative diseases, pre-senile dementia, senile dementia and dementia associated with Parkinson's disease, Alzheimer's disease and/or Down syndrome, age-related macular degeneration (AMD), glaucoma, olfactory function impairment, traumatic brain injury, progressive muscle diseases, Type II diabetes mellitus and cardiovascular diseases (stroke).
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FUSED BENZOXAZEPINONES AS ION CHANNEL MODULATORS (Thu, 27 Oct 2016)
The present disclosure relates to compounds that are sodium channel inhibitors and to their use in the treatment of various disease states, including cardiovascular diseases and diabetes.
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FUSED BENZOXAZEPINONES AS ION CHANNEL MODULATORS (Thu, 27 Oct 2016)
The present disclosure relates to compounds that are sodium channel inhibitors and to their use in the treatment of various disease states, including cardiovascular diseases and diabetes.
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COMPOSITIONS AND METHODS TO ASSESS THE CAPACITY OF HDL TO SUPPORT REVERSE CHOLESTEROL TRANSPORT (Fri, 21 Oct 2016)
<p id="p-0001" num="0000">The invention provides compositions and methods for assessing the capacity of high density lipoprotein (HDL) to support reverse cholesterol transport in blood by measuring exchange if HDL-specific spin-labeled lipoprotein probes and electron paramagnetic spectroscopy. The invention also provides methods to identify individuals at risk for cardiovascular disease, to monitor the treatment of cardiovascular disease and in the development of therapies to treat cardiovascular disease. The invention also provides methods to identify individuals at risk for Alzheimer's disease, to monitor the treatment of Alzheimer's disease and in the development of therapies to treat Alzheimer's disease.</p>
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3-SPIROCYCLIC-6-HYDROXAMIC ACID TETRALINS AS HDAC INHIBITORS (Fri, 21 Oct 2016)
<p id="p-0001" num="0000">The present invention is directed to inhibitors of histone deacetylases (HDACs) such as HDAC6 and HDAC11, and their use in the treatment of diseases such as cell proliferative diseases (e.g., cancer), neurological (e.g., neurodegenerative disease or neurodevelopmental disease), inflammatory or autoimmune disease, infection, metabolic disease, hematologic disease, or cardiovascular disease.</p>
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3-SPIRO-7-HYDROXAMIC ACID TETRALINS AS HDAC INHIBITORS (Fri, 21 Oct 2016)
<p id="p-0001" num="0000">The present invention is directed to inhibitors of histone deacetylases (HDACs) such as HDAC6, and their use in the treatment of diseases such as cell proliferative diseases (e.g., cancer), neurological (e.g., neurodegenerative disease or neurodevelopmental disease), inflammatory or autoimmune disease, infection, metabolic disease, hematologic disease, or cardiovascular disease.</p>
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SUBSTITUTED AZA-BICYCLIC IMIDAZOLE DERIVATIVES USEFUL AS TRPM8 RECEPTOR MODULATORS (Fri, 21 Oct 2016)
<p id="p-0001" num="0000">The present invention is directed to substituted aza-bicyclic imidazole derivatives, pharmaceutical compositions containing them and their use in the treatment of disorders and conditions modulated by TRP M8, including for example, inflammatory pain, inflammatory hyperalgesia, inflammatory hypersensitivity condition, neuropathic pain, neuropathic cold allodynia, inflammatory somatic hyperalgesia, inflammatory visceral hyperalgesia, cardiovascular disease aggravated by cold and pulmonary disease aggravated by cold.</p>
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INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIM CHANNEL (Fri, 21 Oct 2016)
<p id="p-0001" num="0000">The present invention provides compounds of Formula (I) (Formula (I)) including pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="31.83mm" wi="68.92mm" file="US20160304515A1-20161020-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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IMIDAZOLONE DERIVATIVES, PHARMACEUTICAL COMPOSITIONS AND USES THEREOF (Fri, 21 Oct 2016)
<p id="p-0001" num="0000">This application relates to imidazolone compounds, pharmaceutically acceptable salts, solvents, polymorphs or prodrugs thereof, and further relates to pharmaceutical combinations comprising the foregoing substances and uses for preventing and treating protein kinase related diseases such as cancer, metabolic diseases, and cardiovascular diseases.</p>
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3-SPIRO-7-HYDROXAMIC ACID TETRALINS AS HDAC INHIBITORS (Fri, 21 Oct 2016)
The present invention is directed to compounds of Formulae I and II which are inhibitors of histone deacetylases (HDACs) such as HDAC6, and their use in the treatment of diseases such as cell proliferative diseases (e.g., cancer), neurological (e.g., neurodegenerative disease or neurodevelopmental disease), inflammatory or autoimmune disease, infection, metabolic disease, hematologic disease, or cardiovascular disease.
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3-SPIROCYCLIC-6-HYDROXAMIC ACID TETRALINS AS HDAC INHIBITORS (Fri, 21 Oct 2016)
The present invention is directed to inhibitors of histone deacetylases (HDACs) such as HDAC6 and HDAC11, and their use in the treatment of diseases such as cell proliferative diseases (e.g., cancer), neurological (e.g., neurodegenerative disease or neurodevelopmental disease), inflammatory or autoimmune disease, infection, metabolic disease, hematologic disease, or cardiovascular disease.
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COMPOSITIONS AND METHODS FOR MODULATING HYDROXYLATION OF ACC2 BY PHD3 (Fri, 14 Oct 2016)
Compositions and methods useful for treating a number of human disorders including, but not limited to, cancer, cardiovascular disease, obesity, and metabolic disorders are provided. For example, the disclosure features compositions and methods for modulating the hydroxylation of ACC2 by PHD3 in vitro or in vivo. Also provided are methods for monitoring and/or detecting the expression of PHD3 and/or levels of ACC2 hydroxylation, which are useful for, inter alia, determining whether a cancer cell is sensitive to glycolytic pathway inhibitors or inhibitors of fatty acid metabolism.
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USE OF PCSK9 AND LDL-R ACTIVITY FOR TREATING CARDIOVASCULAR RISK (Fri, 07 Oct 2016)
<p id="p-0001" num="0000">The present disclosure provides methods of assessing cardiovascular risk in a subject and/or of treating a subject having or at risk of developing a cardiovascular disease or disorder. In some embodiments, the method comprises determining an activity level of PCSK9 and/or a level of PCSK9 in a sample obtained from the subject, and initiating or modifying a treatment regimen.</p>
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Compositions and methods for adipocyte modulation (Wed, 05 Oct 2016)
<p id="p-0001" num="0000">Modified stilbenoids and formulations thereof are provided. The modified stilbenoids can include one or more amino or amino-alkyl substituents. The formulation can be for the treatment or prevention of obesity and the modified stilbenoid present in an effective amount to alleviate or prevent the onset of one or more symptoms of obesity. Methods of making the modified stilbenoids and formulations thereof are provided. Methods are provided for treating a subject with a modified stilbenoid in an effective amount to alleviate or prevent one or more symptoms associated with diabetes, cardiovascular disease, high blood pressure, deep vein thrombosis, osteoarthritis, obstructive sleep apnea, cancer, and non-alcoholic fatty liver disease. The administration of the modified stilbenoids can result in decreased levels of PKCδII, PKCδVIII, substantially unaltered expression of PKCδI; a decreased number of adipocytes; increased weight and/or fat loss; or a combination thereof.</p>
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METHODS FOR CALIBRATED ION MOBILITY ANALYSIS AND USES THEREOF (Fri, 30 Sep 2016)
<p id="p-0001" num="0000">The present invention relates to improved ion mobility analysis (IMA) methods that can accurately quantify particle concentration in a sample solution. Specifically, reference particles of known solution-phase concentration are used for calibration. In addition, by exploiting spectral deconvolution techniques, the concentrations of subpopulations within the particles can also be accurately quantified. The improved IMA methods permit, for the first time, the quantification of absolute concentrations of HDL particles and subpopulations thereof in a biological sample. The correlations of HDL particle concentrations and conditions such as LCAT deficiency and cardiovascular diseases have been established. Accordingly, the present invention also provide methods to determine whether a subject is at risk to develop or is suffering from these conditions by using HDL particle concentration as a clinical metric.</p>
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SUPERCHARGED PROTEINS FOR CELL PENETRATION (Fri, 30 Sep 2016)
<p id="p-0001" num="0000">Compositions, preparations, systems, and related methods for delivering a supercharged protein, or a complex of a supercharged protein and an agent (e.g., nucleic acids, peptides, proteins, small molecules) to cells are provided. Such systems and methods include the use of supercharged proteins. For example, superpositively charged proteins may be associated with nucleic acids (which typically have a net negative charge) via electrostatic interactions. In some embodiments, such systems and methods involve altering the primary sequence of a protein in order to “supercharge” the protein (e.g., to generate a superpositively-charged protein). In some embodiments, complexes comprising supercharged proteins and one or more agents to be delivered are useful as therapeutic agents. In some embodiments, complexes and/or pharmaceutical compositions thereof are administered to a subject in need thereof. The inventive complexes or pharmaceutical compositions thereof may be used to treat proliferative diseases, infectious diseases, cardiovascular diseases, inborn errors in metabolism, genetic diseases, etc.</p>
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PIPERAZINE DERIVATIVES AS FASN INHIBITORS (Fri, 30 Sep 2016)
<p id="p-0001" num="0000">Compounds of the formula I</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.26mm" wi="69.85mm" file="US20160280655A1-20160929-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">in which R, X<sup>1</sup>, X<sup>2</sup>, X<sup>3</sup>, X<sup>4</sup>, R<sup>1</sup>, R<sup>2 </sup>and q have the meanings indicated in Claim <b>1,</b> are inhibitors of fatty acid synthase, and can be employed, inter alia, for the treatment of diseases such as cancer, cardiovascular diseases, central nervous system injury and different forms of inflammation.</p>
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TRIMETHYLAMINE COMPOUNDS AS RISK PREDICTORS OF CARDIOVASCULAR DISEASE (Thu, 22 Sep 2016)
Methods of characterizing a test subject's risk of having or developing cardiovascular disease are provided. The methods include using an analytic device to determine levels of choline-related trimethylamine-containing compounds such as trimethylamine N-oxide, choline, or betaine in a biological sample obtained from the subject and comparing the levels of the choline-related trimethylamine-containing compound in the subject's biological sample to a control value. The test subject's risk of having cardiovascular disease is then characterized as higher if the levels of the choline-related trimethylamine-containing compound are higher than the control value. Also provided are methods of identifying a subject at risk of experiencing a complication of atherosclerotic cardiovascular disease, and methods of evaluating the efficacy of a cardiovascular therapeutic agent in a subject with cardiovascular disease using levels of choline-related trimethylamine-containing compounds.
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AMINO, AMIDO AND HETEROCYCLIC COMPOUNDS AS MODULATORS OF RAGE ACTIVITY AND USES THEREOF (Fri, 16 Sep 2016)
<p id="p-0001" num="0000">Amino, amido, and heterocyclic compounds are disclosed. The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, diabetes complications, inflammation, and neurodegeneration, obesity, cancer, ischemia/reperfusion injury, cardiovascular disease and other diseases related to RAGE activity.</p>
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CONJUGATE COMPRISING FOLIC ACID AND INDOLE-3-CARBINOL FOR MEDICAL USE (Fri, 16 Sep 2016)
<p id="p-0001" num="0000">Conjugates of indole-3-carbinol are described for medical use and, particularly, for the prevention and treatment of neoplastic, inflammatory, cardiovascular diseases and other diseases, and of the metabolic syndrome.</p>
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3-AMINOCYCLOPENTANE CARBOXAMIDE DERIVATIVES (Fri, 16 Sep 2016)
<p id="p-0001" num="0000">Compounds of the formula I</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="24.38mm" wi="64.18mm" file="US20160264517A1-20160915-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000">in which R<sup>1</sup>, R<sup>4</sup>, R, X<sup>1</sup>, X<sup>2</sup>, X<sup>3</sup>, X<sup>4</sup>, q and W have the meanings indicated in Claim <b>1, </b></li> <li id="ul0001-0002" num="0000">are inhibitors of fatty acid synthase, and can be employed, inter alia, for the treatment of diseases such as cancer, cardiovascular diseases, central nervous system injury and different forms of inflammation.</li> </ul> </p>
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Branched 3-phenylpropionic acid derivatives and their use (Fri, 16 Sep 2016)
<p id="p-0001" num="0000">The present application relates to novel 3-phenylpropionic acid derivatives which carry a branched or cyclic alkyl substituent in the 3-position, to processes for their preparation, to their use for the treatment and/or prevention of diseases and to their use for preparing medicaments for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of cardiovascular diseases.</p>
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PYRROLO PYRIMIDINE DERIVATIVE (Thu, 15 Sep 2016)
The compound represented by general formula (I) has strong Axl inhibition activity by means of a pyridone ring structure being introduced into a pyrrolo pyrimidine skeleton, and so the result can serve as a treatment agent for Axl-related diseases, for example cancers such as acute myeloid leukemia, melanoma, breast cancer, pancreatic cancer, and glial tumors, renal disease, immune system disorders, and cardiovascular disease.
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Inhibitors of the Renal Outer Medullary Potassium Channel (Fri, 09 Sep 2016)
<p id="p-0001" num="0000">The present invention provides compounds of Formula I</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="33.95mm" wi="69.00mm" file="US20160257670A1-20160908-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.</p>
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FLUORESCENT IN-SITU DETECTION OF LIPID PARTICLE APOLIPOPROTEINS WITHIN PRIMARY ELECTROPHORETIC MATRIX (Fri, 02 Sep 2016)
<p id="p-0001" num="0000">The present invention relates to, among other things, a gel electrophoresis system for detecting the level of specific Apolipoproteins and/or lipoprotein particles present in intact lipid particles in a biological sample. The system includes a gel substrate to receive a biological sample, at least two lipoprotein-binding complexes. Each complex includes an antibody that binds a lipoprotein particle or a portion thereof, which is bound to a signal producing molecule capable of producing or causing production of a detectable signal. The system also includes a device for detecting the detectable signal. The present invention also relates to methods of assessing the level of specific Apolipoproteins and/or lipoprotein particles present in a biological sample, determining whether a subject is at increased risk for cardiovascular disease, and monitoring the risk for developing cardiovascular disease.</p>
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RHO KINASE INHIBITORS (Fri, 26 Aug 2016)
<p id="p-0001" num="0000">Disclosed are novel substituted 2H-isoquinolin-1-one and 3H-quinazolin-4-one derivatives useful as inhibitors of Rho kinase and for treating a variety of diseases and disorders that are mediated or sustained through the activity of Rho kinase, including cardiovascular diseases, pharmaceutical compositions comprising such compounds, methods for using such compounds and processes for making such compounds.</p>
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Anti-Inflammatory Compounds and Use Thereof (Fri, 26 Aug 2016)
<p id="p-0001" num="0000">Compounds of the general formula</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="10.33mm" wi="56.05mm" file="US20160243137A1-20160825-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">are disclosed with activity towards treating diseases related to inflammation, such as cancer, neurodegenerative and cardiovascular diseases. Pharmaceutical compositions and methods of use are also disclosed.</p>
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NOVEL FUNCTIONALIZED 5-(PHENOXYMETHYL)-1,3-DIOXANE ANALOGS EXHIBITING CYTOCHROME P450 INHIBITION AND THEIR METHOD OF USE (Fri, 26 Aug 2016)
<p id="p-0001" num="0000">Pharmaceutical compositions described in this document comprise 5-(phenoxymethyl)-1,3-dioxane analogs having a disease-modifying action in the treatment of diseases associated with the production of cortisol that include metabolic syndrome, obesity, headache, depression, hypertension, diabetes mellitus, Cushing's Syndrome, pseudo-Cushing syndrome, cognitive impairment, dementia, heart failure, renal failure, psoriasis, glaucoma, cardiovascular disease, cancer, stroke, incidentalomas, or any diseases involving the overproduction of cortisol.</p>
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NOVEL COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF INFLAMMATORY DISORDERS (Fri, 26 Aug 2016)
<p id="p-0001" num="0000">The present invention discloses compounds according to Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="49.28mm" wi="69.85mm" file="US20160244443A1-20160825-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">Wherein R<sup>1a</sup>, R<sup>1b</sup>, R<sup>2</sup>, R<sup>4</sup>, R<sup>5</sup>, R<sup>6a</sup>, R<sup>6b</sup>, R<sup>7</sup>, R<sup>8</sup>, W, X, Cy, and the subscript a are as defined herein. The present invention relates to compounds inhibiting autotaxin (NPP2 or ENPP2), methods for their production, pharmaceutical compositions comprising the same, and methods of treatment using the same, for the prophylaxis and/or treatment of diseases involving fibrotic diseases, proliferative diseases, inflammatory diseases, autoimmune diseases, respiratory diseases, cardiovascular diseases, neurodegenerative diseases, dermatological disorders, and/or abnormal angiogenesis associated diseases by administering the compound of the invention.</p>
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4-(ORTHO)-FLUOROPHENYL-5-FLUOROPYRIMIDIN-2-YL AMINES CONTAINING A SULFONE GROUP (Thu, 25 Aug 2016)
The present invention relates to 4-(ortho)-fluorophenyl-5-fluoropyrimidin-2-yl amine derivatives of general formula (I) as described and defined herein, and methods for their preparation, their use for the treatment and/or prophylaxis of disorders, in particular of hyper-proliferative disorders and/or virally induced infectious diseases and/or of cardiovascular diseases. The invention further relates to intermediate compounds useful in the preparation of said compounds of general formula (I).
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Pyridopyrimidine derivatives and use thereof (Wed, 24 Aug 2016)
<p id="p-0001" num="0000">The invention provides novel substituted pyridopyrimidines represented by Formula I or a pharmaceutically acceptable salt, solvate, polymorph, ester, tautomer or prodrug thereof, and a composition comprising these compounds. The compounds provided can be used as inhibitors of the phosphoinositide 3′ OH kinase family (PI3K) for the treatment of inflammatory diseases, cancer, cardiovascular diseases, allergy, asthma and autoimmune disorders.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="26.75mm" wi="68.16mm" file="US09422298-20160823-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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INHIBITORS OF RENAL OUTER MEDULLARY POTASSIUM CHANNEL (Fri, 19 Aug 2016)
Disclosed are compounds of Formula I and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.
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AZA-HETEROARYL COMPOUNDS AS PI3K-GAMMA INHIBITORS (Fri, 19 Aug 2016)
The present invention provides aza-heteroaryl derivatives of Formula I: and pharmaceutically acceptable salts thereof, wherein X, Y, Z, A, W, R4, R5, and R6 are defined herein, that inhibit the activity of phosphoinositide 3-kinases-gamma (PI3Kϒ) and are useful in the treatment of diseases related to the activity of PI3Kϒ including, for example, autoimmune diseases, cancer, cardiovascular diseases, and neurodegenerative diseases.
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INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL (Fri, 19 Aug 2016)
The present invention provides compounds of Formula (I); and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.
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OMEGA-3 FATTY ACID PRODRUG COMPOUNDS AND USES THEREOF (Fri, 19 Aug 2016)
Provided herein are prodrug compounds, their preparation and their uses, such as treating liver diseases or non-liver diseases via intervening in the molecular pathways in the liver. Novel prodrug compounds of eicosapentaenoic and docosahexaenoic acids, their preparation and their uses are described. Some embodiments are related to novel prodrug compounds that are absorbed in the intestine and taken up via the hepatic portal vein to the liver. Some embodiments are directed to the use of the prodrugs to change eicosapentaenoic and docosahexaenoic acids absorption routes. Another aspect includes the use of prodrugs to treat diseases that benefit from enhanced eicosapentaenoic and docosahexaenoic acids distribution to the liver and like tissues and cells, including but not limited to fatty liver, and metabolic and cardiovascular diseases where the liver is involved in the production and/or the homeostasis control of the biochemical end products, e.g. glucose, cholesterol, fatty acids, triglycerides, lipoproteins, and apolipoproteins.
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Aza-heteroaryl compounds as PI3K-gamma inhibitors (Fri, 12 Aug 2016)
<p id="p-0001" num="0000">The present invention provides aza-heteroaryl derivatives of Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.77mm" wi="58.76mm" file="US09586949-20170307-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> and pharmaceutically acceptable salts thereof, wherein X, Y, Z, A, W, R<sup>4</sup>, R<sup>5</sup>, and R<sup>6 </sup>are defined herein, that inhibit the activity of phosphoinositide 3-kinases-gamma (PI3Kγ) and are useful in the treatment of diseases related to the activity of PI3Kγ including, for example, autoimmune diseases, cancer, cardiovascular diseases, and neurodegenerative diseases. </p>
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ISOTHIAZOLOPYRIMIDINONES, PYRAZOLOPYRIMIDINONES, AND PYRROLOPYRIMIDINONES AS UBIQUITIN-SPECIFIC PROTEASE 7 INHIBITORS (Fri, 12 Aug 2016)
The disclosure relates to inhibitors of USP7 inhibitors useful in the treatment of cancers, neurodegenerative diseases, immunological disorders, inflammatory disorders, cardiovascular diseases, ischemic diseases, viral infections and diseases, and bacterial infections and diseases, having the Formula (I): where R1, R2, R3, R4, R5, R5', X1, X2, X3, n, and m are described herein.
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QUINAZOLINONES AND AZAQUINAZOLINONES AS UBIQUITIN-SPECIFIC PROTEASE 7 INHIBITORS (Fri, 12 Aug 2016)
The present disclosure relates to inhibitors of USP7 inhibitors useful in the treatment of cancers, neurodegenerative diseases, immunological disorders, inflammatory disorders, cardiovascular diseases, ischemic diseases, viral infections and diseases, and bacterial infections and diseases, having the Formula: (I) where R1, R2, R3, R4, R4, X1, Y1, Y2, Y3, Y4, n, and m are described herein.
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COMPOUNDS FOR THE PREVENTION AND TREATMENT OF VASCULAR DISEASE (Fri, 12 Aug 2016)
A composition for treating or preventing disease, especially vascular disease, including a composition chosen from FORMULAS I-VIII, ligands thereof, analogs thereof, a pharmaceutically acceptable salt thereof, a solvate thereof, an ester thereof, tautomer thereof, or combinations thereof. A combination drug formulation for treating and preventing cardiovascular disease, including the compositions of FORMULA I, FORMULA III, and FORMULA VI. A method of treating or preventing disease, by administering a pharmaceutically effective amount of at least one of the compositions of FORMULAS I-VIII, a ligand thereof, an analog thereof, a pharmaceutically acceptable salt thereof, a solvate thereof, an ester thereof, a tautomer thereof, or combinations thereof to a subject. Methods of treating or preventing vascular disease, arthritis, metastatic cancer, and diabetes.
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Substituted aza-bicyclic imidazole derivatives useful as TRPM8 receptor modulators (Wed, 10 Aug 2016)
<p id="p-0001" num="0000">The present invention is directed to substituted aza-bicyclic imidazole derivatives, pharmaceutical compositions containing them and their use in the treatment of disorders and conditions modulated by TRP M8, including for example, inflammatory pain, inflammatory hyperalgesia, inflammatory hypersensitivity condition, neuropathic pain, neuropathic cold allodynia, inflammatory somatic hyperalgesia, inflammatory visceral hyperalgesia, cardiovascular disease aggravated by cold and pulmonary disease aggravated by cold.</p>
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Processes for Preparing Medicaments for the Treatment of Cardiovascular Diseases and Intermediates for Use Therein (Fri, 05 Aug 2016)
<p id="p-0001" num="0000">The present invention provides a compound of formula N wherein: X is CH<sub>2</sub>, oxygen or sulphur; R<sub>1</sub>, R<sub>2 </sub>and R<sub>3 </sub>are the same or different and signify hydrogens, halogens, alkyl, alkyloxy, hydroxy, nitro, alkylcarbonylamino, alkylamino or dialkylamino group, wherein N is in the form of the individual R- and S-enantiomer or a mixture of the (R)- and (S)-enantiomer. The present invention also provides a compound of formula MA. The present invention also provides processes for preparing the above compounds, and processes involving their use. The compounds are particularly useful as intermediates in the synthesis of peripherally-selective inhibitors of dopamine-β-hydroxylase.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="59.77mm" wi="56.90mm" file="US20160221981A1-20160804-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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NOVEL CYTOCHROME P450 INHIBITORS AND THEIR METHOD OF USE (Fri, 05 Aug 2016)
<p id="p-0001" num="0000">Embodiments of the present invention relate to novel cytochrome P450 inhibitors and pharmaceutical compositions thereof having a disease-modifying action in the treatment of diseases associated with the production of cortisol that include metabolic syndrome, obesity, headache, depression, hypertension, diabetes mellitus, Cushing's Syndrome, pseudo-Cushing syndrome, cognitive impairment, dementia, heart failure, renal failure, psoriasis, glaucoma, cardiovascular disease, cancer, stroke or incidentalomas.</p>
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INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL (Fri, 05 Aug 2016)
The present invention provides compounds of Formula (I): and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.
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Fused heterocyclic compounds as ion channel modulators (Wed, 03 Aug 2016)
<p id="p-0001" num="0000">The present disclosure relates to compounds that are sodium channel inhibitors and to their use in the treatment of various disease states, including cardiovascular diseases and diabetes. In particular embodiments, the structure of the compounds is given by Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="16.51mm" wi="55.37mm" file="US09403782-20160802-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein Q, R<sup>1</sup>, X<sup>1</sup>, X<sup>2</sup>, Y and R<sup>2 </sup>are as described herein, to methods for the preparation and use of the compounds and to pharmaceutical compositions containing the same. </p>
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NOVEL COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF INFLAMMATORY DISORDERS (Fri, 29 Jul 2016)
<p id="p-0001" num="0000">The present invention discloses compounds according to Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="49.36mm" wi="69.85mm" file="US20160214986A1-20160728-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">Wherein R<sup>1a</sup>, R<sup>1b</sup>, R<sup>2</sup>, R<sup>4</sup>, R<sup>5</sup>, R<sup>6</sup>, R<sup>7</sup>, R<sup>8</sup>, W, X, Y, Z, Cy, and the subscript a are as defined herein. The present invention relates to compounds inhibiting autotaxin (NPP2 or ENPP2), methods for their production, pharmaceutical compositions comprising the same, and methods of treatment using the same, for the prophylaxis and/or treatment of diseases involving fibrotic diseases, proliferative diseases, inflammatory diseases, autoimmune diseases, respiratory diseases, cardiovascular diseases, neurodegenerative diseases, dermatological disorders, and/or abnormal angiogenesis associated diseases by administering the compound of the invention.</p>
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Preparation and Uses of Obeticholic Acid (Fri, 29 Jul 2016)
<p id="p-0001" num="0000">The present invention relates to obeticholic acid:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="36.24mm" wi="60.28mm" file="US20160215014A1-20160728-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or a pharmaceutically acceptable salt, solvate or amino acid conjugate thereof. Obeticholic acid is useful for the treatment or prevention of a FXR mediated disease or condition, cardiovascular disease or cholestatic liver disease, and for reducing HDL cholesterol, for lowering triglycerides in a mammal, or for inhibition of fibrosis. The present invention also relates to processes for the synthesis of obeticholic acid.</p>
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EBI2 MODULATORS (Fri, 29 Jul 2016)
<p id="p-0001" num="0000">Provided herein are small molecule Epstein-Barr virus-induced G-protein coupled receptor 2 (EBI2) modulator compounds, compositions comprising the compounds, and methods of using the compounds and compositions comprising the compounds. EBI2 is a therapeutic target for the treatment of a variety of diseases or conditions. In some embodiments, EBI2 is a therapeutic target for the treatment of diseases or conditions such as, but not limited to, autoimmune diseases or conditions, cancer, and cardiovascular disease.</p>
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SYNTHETIC APELIN FATTY ACID CONJUGATES WITH IMPROVED HALF-LIFE (Fri, 29 Jul 2016)
<p id="p-0001" num="0000">The invention provides a conjugate, or a pharmaceutically acceptable salt thereof, comprising a synthetic polypeptide of Formula I:</p> <p id="p-0002" num="0000"> <br/> <?in-line-formulae description="In-line Formulae" end="lead"?>Q-R-P-R-L-C*-H-K-G-P-(Nle)-C*-F  (I)<?in-line-formulae description="In-line Formulae" end="tail"?> </p> <p id="p-0003" num="0000">or a amide or ester thereof; and a fatty acid selected from:</p> <p id="p-0004" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="129.71mm" wi="39.71mm" file="US20160213743A1-20160728-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0005" num="0000">wherein said fatty acid is covalently linked to the N-terminus of the peptide via one of its carboxylic acid functionality, optionally via a polyethylene glycol linker; and wherein the two cysteine amino acids labeled with “*” form a disulfide bond between the thiol functionalities of their side chain. The conjugates are agonist of the APJ receptor. The invention also relates to a method for manufacturing the conjugates of the invention, and its therapeutic uses such as treatment or prevention of acute decompensated heart failure (ADHF), chronic heart failure, pulmonary hypertension, atrial fibrillation, Brugada syndrome, ventricular tachycardia, atherosclerosis, hypertension, restenosis, ischemic cardiovascular diseases, cardiomyopathy, cardiac fibrosis, arrhythmia, water retention, diabetes (including gestational diabetes), obesity, peripheral arterial disease, cerebrovascular accidents, transient ischemic attacks, traumatic brain injuries, amyotrophic lateral sclerosis, burn injuries (including sunburn) and preeclampsia. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.</p>
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MODULATORS OF FARNESOID X RECEPTOR AND METHODS FOR THE USE THEREOF (Fri, 29 Jul 2016)
Compounds, compositions and methods are provided for treating the FXR-mediated disease or process in a mammal, comprising administering to the mammal a therapeutically effective amount of a compound claimed, wherein the FXR-mediated disease or condition linked to chronic liver diseases such as nonalcoholic fatty liver disease and nonalcoholic steatohepatitis; gastrointestinal diseases; cardiovascular diseases; metabolic diseases such as diabetes and obesity; inflammation, or cancer etc..
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SYNTHETIC APELIN FATTY ACID CONJUGATES WITH IMPROVED HALF-LIFE (Fri, 29 Jul 2016)
The invention provides a conjugate, or a pharmaceutically acceptable salt thereof, comprising a synthetic polypeptide of Formula I: Q-R-P-R-L-C*-H-K-G-P-(Nle)-C*-F (I) or a amide or ester thereof; and a fatty acid selected from: wherein said fatty acid is covalently linked to the N-terminus of the peptide via one of its carboxylic acid functionality, optionally via a polyethylene glycol linker; and wherein the two cysteine amino acids labeled with "*" form a disulfide bond between the thiol functionalities of their side chain. The conjugates are agonist of the APJ receptor. The invention also relates to a method for manufacturing the conjugates of the invention, and its therapeutic uses such as treatment or prevention of acute decompensated heart failure (ADHF), chronic heart failure, pulmonary hypertension, atrial fibrillation, Brugada syndrome, ventricular tachycardia, atherosclerosis, hypertension, restenosis, ischemic cardiovascular diseases, cardiomyopathy, cardiac fibrosis, arrhythmia, water retention, diabetes (including gestational diabetes), obesity, peripheral arterial disease, cerebrovascular accidents, transient ischemic attacks, traumatic brain injuries, amyotrophic lateral sclerosis, burn injuries (including sunburn) and preeclampsia. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.
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Inhibitors of the Renal Outer Medullary Potassium Channel (Fri, 22 Jul 2016)
<p id="p-0001" num="0000">The present invention provides compounds of Formula I</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="28.87mm" wi="59.01mm" file="US20160207922A1-20160721-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.</p>
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PREDICTING CORONARY ARTERY DISEASE AND RISK OF CARDIOVASCULAR EVENTS (Fri, 08 Jul 2016)
<p id="p-0001" num="0000">Methods of assessing the risk of cardiovascular disease in a subject by detecting the level of at least one metabolite in a sample from the subject are disclosed herein. The level of the metabolite is indicative of the risk of cardiovascular disease in the subject. The metabolites may be acylcarnitines, amino acids, ketones, free fatty acids or hydroxybutyrate. The cardiovascular disease may be risk of a cardiovascular event, presence of coronary artery disease or risk of development of coronary artery disease.</p>
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COMPOSITIONS AND METHODS FOR MODULATING ANGIOPOIETIN-LIKE 3 EXPRESSION (Fri, 08 Jul 2016)
<p id="p-0001" num="0000">Provided herein are methods, compounds, and compositions for reducing expression of an ANGPTL3 mRNA and protein in an animal. Also provided herein are methods, compounds, and compositions for reducing lipids and/or glucose in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate any one or more of cardiovascular disease and/or metabolic disease, or a symptom thereof, in an individual in need thereof.</p>
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PYRROLOTRIAZINONE AND IMIDASOTRIAZINONE DERIVATIVES AS OBIQUITIN-SPECIFIC PROTEASE 7 CUSP? ) INHIBITORS FOR THE TREATMENT OF CANCER AND OTHER USP7 MEDIATED DISEASES (Fri, 08 Jul 2016)
The invention relates to pyrrolo[2,1-f][1,2,4]triazin-4(3H)-one and imidazo[5,1-f][1,2,4]triazin-4(3H)-one derivatives as inhibitors of the ubiquitin-specific protease 7 (USP7) useful in the treatment of cancers, neurodegenerative diseases, immunological disorders, inflammatory disorders, cardiovascular diseases, ischemic diseases, viral infections and diseases, and bacterial infections and diseases, having the Formula (I) where Rl, R2, R3, R4, Rs, Rs', R6, Xl, X2, m, and n are described herein.
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PYRROLO AND PYRAZOLOPYRIMIDINES AS UBIQUITIN-SPECIFIC PROTEASE 7 INHIBITORS (Fri, 08 Jul 2016)
The invention relates to inhibitors of USP7 inhibitors useful in the treatment of cancers, neurodegenerative diseases, immunological disorders, inflammatory disorders, cardiovascular diseases, ischemic diseases, viral infections and diseases, and bacterial infections and diseases, having the Formula: (I) where m, n, X1, X2, R1-R5, R5' and R6 are described herein.
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OXOQUINAZOLINYL-BUTANAMIDE DERIVATIVES (Fri, 01 Jul 2016)
<p id="p-0001" num="0000">Compounds of the formula I</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="33.19mm" wi="71.37mm" file="US20160184310A1-20160630-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">in which R<sup>1</sup>-R<sup>3 </sup>and Z have the meanings indicated in Claim <b>1</b>, are inhibitors of Tankyrase, and can be employed, inter alia, for the treatment of diseases such as cancer, cardiovascular diseases, central nervous system injury and different forms of inflammation.</p>
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PIPERIDINE UREA DERIVATIVES (Fri, 01 Jul 2016)
<p id="p-0001" num="0000">Compounds of the formula I</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="19.81mm" wi="57.07mm" file="US20160184285A1-20160630-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">in which R<sup>1</sup>-R<sup>3 </sup>have the meanings indicated in Claim <b>1, </b> <br/> are inhibitors of Tankyrase, and can be employed, inter alia, for the treatment of diseases such as cancer, cardiovascular diseases, central nervous system injury and different forms of inflammation. </p>
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TRADITIONAL CHINESE MEDICINE COMPOSITION (Fri, 01 Jul 2016)
<p id="p-0001" num="0000">A traditional Chinese medicine composition and preparation thereof for treating cardiovascular diseases is provided. The traditional Chinese medicine composition consists of: by weight percentage, phenolic acid derivatives 30%˜80%, tanshinones 2%˜10% and saponins 15%˜60%.</p>
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PYRROLOTRIAZINONES AND IMIDAZOTRIAZINONES AS UBIQUITIN-SPECIFIC PROTEASE 7 INHIBITORS (Fri, 01 Jul 2016)
<p id="p-0001" num="0000">The invention relates to inhibitors of USP7 inhibitors useful in the treatment of cancers, neurodegenerative diseases, immunological disorders, inflammatory disorders, cardiovascular diseases, ischemic diseases, viral infections and diseases, and bacterial infections and diseases, having the Formula:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.26mm" wi="64.69mm" file="US20160185786A1-20160630-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">where R<sub>1</sub>, R<sub>2</sub>, R<sub>3</sub>, R<sub>4</sub>, R<sub>5</sub>, R<sub>5′</sub>, R<sub>6</sub>, X<sub>1</sub>, X<sub>2</sub>, m, and n are described herein.</p>
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PYRROLO AND PYRAZOLOPYRIMIDINES AS UBIQUITIN-SPECIFIC PROTEASE 7 INHIBITORS (Fri, 01 Jul 2016)
<p id="p-0001" num="0000">The invention relates to inhibitors of USP7 inhibitors useful in the treatment of cancers, neurodegenerative diseases, immunological disorders, inflammatory disorders, cardiovascular diseases, ischemic diseases, viral infections and diseases, and bacterial infections and diseases, having the Formula:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.26mm" wi="64.60mm" file="US20160185785A1-20160630-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">where m, n, X<sub>1</sub>, X<sub>2</sub>, R<sub>1</sub>-R<sub>5</sub>, R<sub>5′</sub> and R<sub>6 </sub>are described herein.</p>
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RNA-CODED ANTIBODY (Fri, 01 Jul 2016)
<p id="p-0001" num="0000">The present application describes an antibody-coding, non-modified or modified RNA and the use thereof for expression of this antibody, for the preparation of a pharmaceutical composition, in particular a passive vaccine, for treatment of tumours and cancer diseases, cardiovascular diseases, infectious diseases, autoimmune diseases, virus diseases and monogenetic diseases, e.g. also in gene therapy. The present invention furthermore describes an in vitro transcription method, in vitro methods for expression of this antibody using the RNA according to the invention and an in vivo method.</p>
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VITAMIN D3 DERIVATIVES AND PHARMACEUTICAL USE THEREOF (Fri, 01 Jul 2016)
The present invention relates to vitamin D3 derivatives of the following formula, wherein each symbol has the same meaning as defined herein, and pharmaceutical or medical use thereof for treating metabolic disease, liver disease, obesity, diabetes, cardiovascular disease, or cancer in a patient in need thereof.
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MAGNETIC SEPARATION OF LIPOPROTEINS USING DEXTRAN SULFATE (Fri, 24 Jun 2016)
<p id="p-0001" num="0000">The invention provides apparatus and methods of preparation of lipoproteins from a biological sample, including HDL, LDL, Lp(a), IDL, and VLDL, for diagnostic purposes utilizing differential charged-particle mobility analysis methods. Further provided are methods for analyzing the size distribution of lipoproteins by differential charged-particle mobility, which lipoproteins are prepared by methods of the invention. Further provided are methods for assessing lipid-related health risk, cardiovascular condition, risk of cardiovascular disease, and responsiveness to a therapeutic intervention, which methods utilize lipoprotein size distributions determined by methods of the invention.</p>
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1,3-DISUBSTITUTED CYCLOPENTANE DERIVATIVES (Fri, 24 Jun 2016)
<p id="p-0001" num="0000">Compounds of the formula I</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="33.36mm" wi="69.85mm" file="US20160176824A1-20160623-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">in which R, Y, R<sup>1</sup>, X<sup>1</sup>, X<sup>2</sup>, X<sup>3 </sup>and q have the meanings indicated in claim <b>1</b>, are inhibitors of fatty acid synthase, and can be employed, inter alia, for the treatment of diseases such as cancer, cardiovascular diseases, central nervous system injury and different forms of inflammation.</p>
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Preparation and Uses of Obeticholic Acid (Fri, 24 Jun 2016)
<p id="p-0001" num="0000">The present invention relates to obeticholic acid:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="36.83mm" wi="59.10mm" file="US20160176913A1-20160623-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or a pharmaceutically acceptable salt, solvate or amino acid conjugate thereof. Obeticholic acid is useful for the treatment or prevention of a FXR mediated disease or condition, cardiovascular disease or cholestatic liver disease, and for reducing HDL cholesterol, for lowering triglycerides in a mammal, or for inhibition of fibrosis. The present invention also relates to processes for the synthesis of obeticholic acid.</p>
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SPIROCYCLIC EBI2 MODULATORS (Fri, 24 Jun 2016)
<p id="p-0001" num="0000">Provided herein are small molecule Epstein-Barr virus-induced G-protein coupled receptor 2 (EBI2) modulator compounds, compositions comprising the compounds, and methods of using the compounds and compositions comprising the compounds. In some embodiments, EBI2 is a therapeutic target for the treatment of diseases or conditions such as, but not limited to, autoimmune diseases or conditions, cancer, and cardiovascular disease.</p>
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TRADITIONAL CHINESE MEDICINE COMPOSITION, AND PREPARATION AND APPLICATION THEREOF (Fri, 24 Jun 2016)
<p id="p-0001" num="0000">A traditional Chinese medicine composition for treating cardiovascular disease, and a preparation thereof, particularly a micro drop pill preparation thereof, and a method for preparing the preparation; the method for preparing the micro drop pill preparation can be used to prepare drop pills, coated drop pills, and drop pill capsules with a high drug loading capacity.</p>
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MODULATORS OF HEPATIC LIPOPROTEIN METABOLISM (Fri, 24 Jun 2016)
The invention relates to compounds for modulating hepatic cholesterol metabolism. The invention includes methods of making and using the compounds. These compounds or pharmaceutically acceptable salts thereof are useful for treating, preventing, and/or alleviating a cholesterol related disorder, a cardiovascular disease and/or liver disease in a human or animal.
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RNA-CODED ANTIBODY (Fri, 17 Jun 2016)
<p id="p-0001" num="0000">The present application describes an antibody-coding, non-modified or modified RNA and the use thereof for expression of this antibody, for the preparation of a pharmaceutical composition, in particular a passive vaccine, for treatment of tumours and cancer diseases, cardiovascular diseases, infectious diseases, autoimmune diseases, virus diseases and monogenetic diseases, e.g. also in gene therapy. The present invention furthermore describes an in vitro transcription method, in vitro methods for expression of this antibody using the RNA according to the invention and an in vivo method.</p>
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RNA-CODED ANTIBODY (Fri, 17 Jun 2016)
<p id="p-0001" num="0000">The present application describes an antibody-coding, non-modified or modified RNA and the use thereof for expression of this antibody, for the preparation of a pharmaceutical composition, in particular a passive vaccine, for treatment of tumours and cancer diseases, cardiovascular diseases, infectious diseases, autoimmune diseases, virus diseases and monogenetic diseases, e.g. also in gene therapy. The present invention furthermore describes an in vitro transcription method, in vitro methods for expression of this antibody using the RNA according to the invention and an in vivo method.</p>
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RNA-CODED ANTIBODY (Fri, 17 Jun 2016)
<p id="p-0001" num="0000">The present application describes an antibody-coding, non-modified or modified RNA and the use thereof for expression of this antibody, for the preparation of a pharmaceutical composition, in particular a passive vaccine, for treatment of tumours and cancer diseases, cardiovascular diseases, infectious diseases, autoimmune diseases, virus diseases and monogenetic diseases, e.g. also in gene therapy. The present invention furthermore describes an in vitro transcription method, in vitro methods for expression of this antibody using the RNA according to the invention and an in vivo method.</p>
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BIOCONJUGATES OF SYNTHETIC APELIN POLYPEPTIDES (Fri, 17 Jun 2016)
<p id="p-0001" num="0000">The invention provides a bioconjugates comprising a synthetic polypeptide of Formula I′ (SEQ ID NO: 1):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="7.96mm" wi="69.85mm" file="US20160166634A1-20160616-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">or an amide, an ester or a salt thereof, wherein X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12 and X13 are defined herein and a half-life extending moiety wherein the peptide and the half-life extending moiety are covalently linked or fuse, optionally via a linker. The polypeptides are agonist of the APJ receptor. The invention also relates to a method for manufacturing the bioconjugates of the invention, and its therapeutic uses such as treatment or prevention of acute decompensated heart failure (ADHF), chronic heart failure, pulmonary hypertension, atrial fibrillation, Brugada syndrome, ventricular tachycardia, atherosclerosis, hypertension, restenosis, ischemic cardiovascular diseases, cardiomyopathy, cardiac fibrosis, arrhythmia, water retention, diabetes (including gestational diabetes), obesity, peripheral arterial disease, cerebrovascular accidents, transient ischemic attacks, traumatic brain injuries, amyotrophic lateral sclerosis, burn injuries (including sunburn) and preeclampsia. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.</li> </ul> </li> </ul> </p>
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RNA-CODED ANTIBODY (Fri, 17 Jun 2016)
<p id="p-0001" num="0000">The present application describes an antibody-coding, non-modified or modified RNA and the use thereof for expression of this antibody, for the preparation of a pharmaceutical composition, in particular a passive vaccine, for treatment of tumours and cancer diseases, cardiovascular diseases, infectious diseases, autoimmune diseases, virus diseases and monogenetic diseases, e.g. also in gene therapy. The present invention furthermore describes an in vitro transcription method, in vitro methods for expression of this antibody using the RNA according to the invention and an in vivo method.</p>
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MK2 INHIBITORS (Fri, 10 Jun 2016)
<p id="p-0001" num="0000">The present invention relates to compounds of general Formula I</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="38.52mm" wi="65.62mm" file="US20160159800A1-20160609-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or a pharmaceutically acceptable salt thereof. The compounds can be used in the treatment of immune, autoimmune, inflammatory diseases, cardiovascular diseases, infectious diseases, bone resorption disorders, neurodegenerative diseases or proliferative diseases.</p>
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ENGINEERED POLYPEPTIDES HAVING ENHANCED DURATION OF ACTION (Thu, 09 Jun 2016)
Compounds are provided having inter alia good duration of action, high potency and/or convenient dosing regimens including oral administration. The compounds are engineered polypeptides which incorporate an albumin binding domain in combination with one or more biologically active polypeptides. Also provided are pharmaceutical compositions and methods of treatment for diseases and disorders including obesity and overweight, diabetes, dyslipidemia, hyperlipidemia, Alzheimer's disease, fatty liver disease, short bowel syndrome, Parkinson's disease, cardiovascular disease, and other and disorders of the central nervous system.
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Thyroid hormone analogs (Wed, 08 Jun 2016)
<p id="p-0001" num="0000">Provided herein are compounds of the formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.77mm" wi="60.45mm" file="USRE046024-20160607-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of diseases such as obesity, hyperlipidemia, hypercholesterolemia and diabetes and other related disorders and diseases, and may be useful for other diseases such as NASH, atherosclerosis, cardiovascular diseases, hypothyroidism, thyroid cancer and other disorders and diseases related thereto. </p>
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RNA-CODED ANTIBODY (Fri, 03 Jun 2016)
<p id="p-0001" num="0000">The present application describes an antibody-coding, non-modified or modified RNA and the use thereof for expression of this antibody, for the preparation of a pharmaceutical composition, in particular a passive vaccine, for treatment of tumours and cancer diseases, cardiovascular diseases, infectious diseases, autoimmune diseases, virus diseases and monogenetic diseases, e.g. also in gene therapy. The present invention furthermore describes an in vitro transcription method, in vitro methods for expression of this antibody using the RNA according to the invention and an in vivo method.</p>
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OXAZOLIDINONE DERIVATIVES AS PPAR LIGANDS (Fri, 03 Jun 2016)
<p id="p-0001" num="0000">The present invention relates to a family of differently substituted oxazolidinones and to the pharmaceutically acceptable salts, esters, prodrugs, tautomers, solvates and hydrates thereof, which show affinity for the alpha and gamma subtypes of the peroxisome proliferator-activated receptors (PPAR) and which, therefore, modulate the actions regulated by said receptors, such as inducing satiety, controlling ingestion and modulating metabolic effects, and thus are useful for the administration thereof as a pharmacological tool and as drugs for the treatment and/or prevention of metabolic diseases and cardiovascular diseases.</p>
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RNA-CODED ANTIBODY (Fri, 03 Jun 2016)
<p id="p-0001" num="0000">The present application describes an antibody-coding, non-modified or modified RNA and the use thereof for expression of this antibody, for the preparation of a pharmaceutical composition, in particular a passive vaccine, for treatment of tumours and cancer diseases, cardiovascular diseases, infectious diseases, autoimmune diseases, virus diseases and monogenetic diseases, e.g. also in gene therapy. The present invention furthermore describes an in vitro transcription method, in vitro methods for expression of this antibody using the RNA according to the invention and an in vivo method.</p>
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SULFOXIMINE SUBSTITUTED 5-FLUORO-N-(PYRIDIN-2-YL)PYRIDIN-2-AMINE DERIVATIVES AND THEIR USE AS CDK9 KINASE INHIBITORS (Fri, 27 May 2016)
<p id="p-0001" num="0000">The present invention relates to 5-fluoro-N-(pyridin-2-yl)pyridin-2-amine derivatives containing a sulfoximine group of general formula (I) as described and defined herein, and methods for their preparation, their use for the treatment and/or prophylaxis of disorders, in particular of hyper-proliferative disorders and/or virally induced infectious diseases and/or of cardiovascular diseases. The invention further relates to intermediate compounds useful in the preparation of said compounds of general formula (I).</p>
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TRADITIONAL CHINESE MEDICINE COMPOSITION, AND PREPARATION AND APPLICATION THEREOF (Fri, 27 May 2016)
<p id="p-0001" num="0000">A traditional Chinese medicine composition for treating cardiovascular disease, and a preparation thereof, particularly a micro drop pill preparation thereof, and a method for preparing the preparation; the method for preparing the micro drop pill preparation can be used to prepare drop pills, coated drop pills, and drop pill capsules with a high drug loading capacity.</p>
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RNA-CODED ANTIBODY (Fri, 27 May 2016)
<p id="p-0001" num="0000">The present application describes an antibody-coding, non-modified or modified RNA and the use thereof for expression of this antibody, for the preparation of a pharmaceutical composition, in particular a passive vaccine, for treatment of tumours and cancer diseases, cardiovascular diseases, infectious diseases, autoimmune diseases, virus diseases and monogenetic diseases, e.g. also in gene therapy. The present invention furthermore describes an in vitro transcription method, in vitro methods for expression of this antibody using the RNA according to the invention and an in vivo method.</p>
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SUBSTITUTED BRIDGED UREA ANALOGS AS SIRTUIN MODULATORS (Fri, 27 May 2016)
The present invention relates to novel substituted bridged urea analog compounds of Formula (I) or pharmaceutically acceptable salts thereof, corresponding pharmaceutical compositions, processes for making and use of such compounds, alone or in combination with other therapeutic agents, as Sirtuin Modulators useful for increasing lifespan of a cell, and for use in treating and/or preventing a wide variety of diseases and disorders, which include, but are not limited to, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity.
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SUBSTITUTED BRIDGED UREA ANALOGS AS SIRTUIN MODULATORS (Fri, 27 May 2016)
The present invention relates to novel substituted bridged urea analog compounds of Formula (I) or pharmaceutically acceptable salts thereof, corresponding pharmaceutical compositions, processes for making and use of such compounds, alone or in combination with other therapeutic agents, as Sirtuin Modulators useful for increasing lifespan of a cell, and in treating and/or preventing a wide variety of diseases and disorders, which include, but are not limited to, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity.
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SUBSTITUTED BRIDGED UREA ANALOGS AS SIRTUIN MODULATORS (Fri, 27 May 2016)
The present invention relates to novel substituted bridged urea analog compounds of Formula (I) or pharmaceutically acceptable salts thereof, corresponding pharmaceutical compositions, processes for making and use of such compounds, alone or in combination with other therapeutic agents, as Sirtuin Modulators useful for increasing lifespan of a cell, and in treating and/or preventing a wide variety of diseases and disorders, which include, but are not limited to, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. (I)
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SUBSTITUTED BRIDGED UREA ANALOGS AS SIRTUIN MODULATORS (Fri, 27 May 2016)
The present invention relates to novel substituted bridged urea analog compounds of Formula (I) or pharmaceutically acceptable salts thereof, corresponding pharmaceutical compositions, processes for making and use of such compounds, alone or in combination with other therapeutic agents, as Sirtuin Modulators useful for increasing lifespan of a cell, and in treating and/or preventing a wide variety of diseases and disorders, which include, but are not limited to, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity.
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MONOCARBOXYLATE TRANSPORT MODULATORS AND USES THEREOF (Fri, 27 May 2016)
The invention generally relates to the field of monocarboxylate transport modulators, e.g., monocarboxylate transport inhibitors, and more particularly to new substituted-quinolone compounds, the synthesis and use of these compounds and their pharmaceutical compositions, e.g., in treating, modulating, forestalling and/or reducing physiological conditions associated with monocarboxylate transport activity such as in treating cancer and other neoplastic disorders, inflammatory diseases, disorders of abnormal tissue growth and fibrosis including cardiomyopathy, obesity, diabetes, cardiovascular diseases, tissue and organ transplant rejection, and malaria.
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CARDIOVASCULAR DISEASE RISK ASSESSMENT (Fri, 27 May 2016)
The invention provides improved methods for analyzing cardiovascular disease risk. According to the invention, an algorithm that considers LDL and HDL subfractions, along with Lp(a) provides significant improvement in predicting CVD versus standard assays that include standard risk factors. Methods of the invention comprise measuring LDL and HDL subfractions in addition to Lp(a) without reference to standard risk factor measurements, such as CRP, total cholesterol, body mass index, weight, triglycerides, and the like. It is unexpected that an algorithm focusing only on LDL and HDL subfractions and Lp(a) would be more informative as to CVD risk than measurements that are much more comprehensive in terms of the markers that are reviewed. In particular, the sdLDL-C subfraction of LDL and the ApoA- 1 in large alpha- 1 HDL are most informative in conjunction with Lp(a).
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SUBSTITUTED BRIDGED UREA ANALOGS AS SIRTUIN MODULATORS (Fri, 27 May 2016)
The present invention relates to novel substituted bridged urea compounds, corresponding related analogs, pharmaceutical compositions and methods of use thereof. Sirtuin-modulating compounds of the present invention may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders, which include, but are not limited to, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. The present invention also related to compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.
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Use of 4-[ethyl(dimethyl)ammonio]butanoate in the treatment of cardiovascular disease (Fri, 20 May 2016)
<p id="p-0001" num="0000">New compound 4-[ethyl(dimethyl)ammonio]butanoate, method of preparation thereof and use in the treatment of cardiovascular disease.</p>
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TRADITIONAL CHINESE MEDICINE COMPOSITION, AND PREPARATION AND APPLICATION THEREOF (Thu, 19 May 2016)
A traditional Chinese medicine composition for treating cardiovascular disease, and a preparation thereof, particularly a micro drop pill preparation thereof, and a method for preparing the preparation; the method for preparing the micro drop pill preparation can be used to prepare drop pills, coated drop pills, and drop pill capsules with a high drug loading capacity.
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OXAZOLIDINONE DERIVATIVES AS PPAR LIGANDS (Thu, 19 May 2016)
The present invention relates to a family of differently substituted oxazolidinones and to the pharmaceutically acceptable salts, esters, prodrugs, tautomers, solvates and hydrates thereof, which show affinity for the alpha and gamma subtypes of the peroxisome proliferator-activated receptors (PPAR) and which, therefore, modulate the actions regulated by said receptors, such as inducing satiety, controlling ingestion and modulating metabolic effects, and thus are useful for the administration thereof as a pharmacological tool and as drugs for the treatment and/or prevention of metabolic diseases and cardiovascular diseases.
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TRADITIONAL CHINESE MEDICINE COMPOSITION, AND PREPARATION AND APPLICATION THEREOF (Thu, 19 May 2016)
A traditional Chinese medicine composition for treating cardiovascular disease, and a preparation thereof, particularly a micro drop pill preparation thereof, and a method for preparing the preparation; the method for preparing the micro drop pill preparation can be used to prepare drop pills, coated drop pills, and drop pill capsules with a high drug loading capacity.
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COMPOSITIONS AND METHODS FOR TREATMENT OF CARDIOVASCULAR DISEASE (Fri, 13 May 2016)
<p id="p-0001" num="0000">Provided herein are compositions for the treatment and/or prevention of cardiovascular disease (CVD), and methods of application and use thereof. In particular, the present invention provides treatment and/or prevention of cardiovascular disease with 3,3-dimethyl-1-butanol (DMB) and related compounds, and pharmaceutical formulations thereof.</p> <p id="p-0002" num="0000">In other embodiments, the present invention provides methods of administering a gut flora targeting antibiotic to a subject prior to a procedure that is associated with a risk of causing thrombosis, heart-attack, and/or platelet hyper-responsiveness.</p>
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Apoptosis signal-regulating kinase inhibitors (Fri, 13 May 2016)
<p id="p-0001" num="0000">The present invention relates to compounds of Formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.01mm" wi="66.80mm" file="US09586932-20170307-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein X<sup>1</sup>, X<sup>2</sup>, X<sup>3</sup>, X<sup>4</sup>, X<sup>5</sup>, X<sup>6</sup>, X<sup>7</sup>, X<sup>8</sup>, R<sup>1</sup>, R<sup>2</sup>, R<sup>3 </sup>are as defined above. The compounds have apoptosis signal-regulating kinase (“ASK1”) inhibitory activity, and are thus useful in the treatment of ASK1-mediated conditions, including autoimmune disorders, inflammatory diseases, cardiovascular diseases and neurodegenerative diseases. The invention also relates to pharmaceutical compositions comprising one or more of the compounds of Formula (I), and to methods of preparing the compounds of Formula (I). </p>
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INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL (Sat, 07 May 2016)
The present invention provides compounds of Formula I, and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.
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NUCLEOSIDE KINASE INHIBITORS (Sat, 07 May 2016)
The present invention relates to method of inhibiting protein kinase activity which comprises contacting a protein kinase with a compound of formula (I), or the N-oxide, pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or stereoisomer thereof, wherein the dash bond, X, R1, R2, R3, R4, R5, R6, R7, R8, and R9 are as defined in the claims. The invention further relates to the compounds of formula (I) per se, as well as to their use as a medicament, and for use or in a method of treatment of a disease mediated by a protein kinase selected from cancer, metabolic diseases, rheumatoid arthritis, psoriasis, inflammatory bowel disease, cardiovascular diseases, Vogt-Koyanagi-Harada syndrome (non-infectious blindness), and Alzheimer. The invention also provides a method for preparing the compounds of formula (I).
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INHIBITORS OF RENAL OUTER MEDULLARY POTASSIUM CHANNEL (Sat, 07 May 2016)
Compounds of Formula (I) and the pharmaceutically acceptable salts thereof are provided as inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.
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INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL (Sat, 07 May 2016)
The present invention provides compounds of Formula I and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.
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INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL (Sat, 07 May 2016)
The present invention provides compounds of Formula I and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.
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INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL (Sat, 07 May 2016)
The present invention provides compounds of Formula I and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.
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INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL (Sat, 07 May 2016)
The present invention provides compounds of Formula I : (I) and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.
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INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL (Sat, 07 May 2016)
The present invention provides compounds of Formula I and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.
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PHTHALAZINE DERIVATIVES (Thu, 05 May 2016)
Compounds of the formula (I), in which R<sp>1</sp>, X and n have the meanings indicated in Claim 1, are inhibitors of Tankyrase, and can be employed, inter alia, for the treatment of diseases such as cancer, cardiovascular diseases, central nervous system injury and different forms of inflammation.
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N-substituted hydroxylamine derivatives with carbon-based leaving groups (Fri, 29 Apr 2016)
<p id="p-0001" num="0000">The disclosed subject matter provides certain N-substituted hydroxylamine derivative compounds, pharmaceutical compositions and kits comprising such compounds, and methods of using such compounds or pharmaceutical compositions. In particular, the disclosed subject matter provides methods of using such compounds or pharmaceutical compositions for treating, preventing, or delaying the onset and/or development of a disease or condition. In some embodiments, the disease or condition is selected from cardiovascular diseases, ischemia, reperfusion injury, cancerous disease, pulmonary hypertension and conditions responsive to nitroxyl therapy.</p>
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LIPOPROTEIN PARTICLE NUMBER FROM MEASUREMENTS OF LIPOPROTEIN PARTICLE PHOSPHOLIPID CONCENTRATION IN LIPOPROTEIN PARTICLE MEMBRANE BILAYER (Fri, 29 Apr 2016)
This application describes a method for measuring the molar concentrations of lipoprotein particles and lipoprotein subclass particles in bodily fluid by Multipixel Capillary Isotachophoresis Laser Induced Fluorescence (MPCE-ITP-LIF) and compositional analysis of spherical lipoprotein particles. The ability to measure several kinds of lipoproteins and particles in one unified system provides a useful diagnostic tool for predicting the risk of developing metabolic diseases such as cardiovascular disease and cardiodiabetes.
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NOVEL COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF INFLAMMATORY DISORDERS (Thu, 28 Apr 2016)
The present invention discloses compounds according to Formula I: Wherein R <sp>1a</sp>, R <sp>1b</sp>, R <sp>2</sp>, R <sp>4</sp>, R<sp>5</sp>, R <sp>6</sp>, R <sp>7</sp>, R <sp>8</sp>, W, X, Y, Z, Cy, and the subscript a are as defined herein. The present invention relates to compounds inhibiting autotaxin (NPP2 or ENPP2), methods for their production, pharmaceutical compositions comprising the same, and methods of treatment using the same, for the prophylaxis and/or treatment of diseases involving fibrotic diseases,proliferative diseases, inflammatory diseases, autoimmune diseases, respiratory diseases, cardiovascular diseases, neurodegenerative diseases, dermatological disorders, and/or abnormal angiogenesis associated diseases by administering the compound of the invention.
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COMPOUNDS FOR THE PREVENTION AND TREATMENT OF CARDIOVASCULAR DISEASES (Fri, 22 Apr 2016)
<p id="p-0001" num="0000">The present disclosure relates to compounds, which are useful for regulating the expression of apolipoprotein A-I (ApoA-I), and their use for treatment and prevention of cardiovascular disease and related disease states, including cholesterol- or lipid-related disorders, such as, for example, atherosclerosis.</p>
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CYCLIC POLYPEPTIDES FOR THE TREATMENT OF HEART FAILURE (Fri, 22 Apr 2016)
<p id="p-0001" num="0000">The invention provides a cyclic polypeptide of Formula I (SEQ ID NO: 1):</p> <p id="p-0002" num="0000"> <br/> <?in-line-formulae description="In-line Formulae" end="lead"?>X1-R-X3-X4-L-S-X7-X8-X9-X10-X11-X12-X13  I<?in-line-formulae description="In-line Formulae" end="tail"?> </p> <p id="p-0003" num="0000">or an amide, an ester or a salt thereof, or a bioconjugate thereof, wherein X1, X3, X4, X7, X8, X9, X10, X11, X12 and X13 are defined herein. The polypeptides are agonist of the APJ receptor. The invention also relates to a method for manufacturing the polypeptides of the invention or bioconjugates thereof, and their therapeutic uses such as treatment or prevention of acute decompensated heart failure (ADHF), chronic heart failure, pulmonary hypertension, atrial fibrillation, Brugada syndrome, ventricular tachycardia, atherosclerosis, hypertension, restenosis, ischemic cardiovascular diseases, cardiomyopathy, cardiac fibrosis, arrhythmia, water retention, diabetes (including gestational diabetes), obesity, peripheral arterial disease, cerebrovascular accidents, transient ischemic attacks, traumatic brain injuries, amyotrophic lateral sclerosis, burn injuries (including sunburn) and preeclampsia. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.</p>
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Preparation and Uses of Obeticholic Acid (Fri, 22 Apr 2016)
<p id="p-0001" num="0000">The present invention relates to obeticholic acid:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="36.83mm" wi="59.18mm" file="US20160108082A1-20160421-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or a pharmaceutically acceptable salt, solvate or amino acid conjugate thereof. Obeticholic acid is useful for the treatment or prevention of a FXR mediated disease or condition, cardiovascular disease or cholestatic liver disease, and for reducing HDL cholesterol, for lowering triglycerides in a mammal, or for inhibition of fibrosis. The present invention also relates to processes for the synthesis of obeticholic acid.</p>
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LIPOPROTEIN PARTICLE NUMBER FROM MEASUREMENTS OF LIPOPROTEIN PARTICLE PHOSPHOLIPID CONCENTRATION IN LIPOPROTEIN PARTICLE MEMBRANE BILAYER (Fri, 22 Apr 2016)
<p id="p-0001" num="0000">This application describes a method for measuring the molar concentrations of lipoprotein particles and lipoprotein subclass particles in bodily fluid by Multipixel Capillary Isotachophoresis Laser Induced Fluorescence (MPCE-ITP-LIF) and compositional analysis of spherical lipoprotein particles. The ability to measure several kinds of lipoproteins and particles in one unified system provides a useful diagnostic tool for predicting the risk of developing metabolic diseases such as cardiovascular disease and cardiodiabetes.</p>
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INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL (Fri, 22 Apr 2016)
The present invention provides compounds of Formula (I) and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.
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FLUORINATED BENZOFURANYL-PYRIMIDINE DERIVATIVES CONTAINING A SULFONE GROUP (Fri, 22 Apr 2016)
The present invention relates to fluorinated benzofuranyl-pyrimidine derivatives containing a sulfone group of general formula (I) as described and defined herein, and methods for their preparation, their use for the treatment and/or prophylaxis of disorders, in particular of hyper-proliferative disorders and/or virally induced infectious diseases and/or of cardiovascular diseases. The invention further relates to intermediate compounds useful in the preparation of said compounds of general formula (I). R2 represents the group (a).
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FLUORINATED BENZOFURANYL-PYRIMIDINE DERIVATIVES CONTAINING A SULFOXIMINE GROUP (Fri, 22 Apr 2016)
The present invention relates to fluorinated benzofuranyl-pyrimidine derivatives containing a sulfoximine group of general formula (I) as described and defined herein, and methods for their preparation, their use for the treatment and/or prophylaxis of disorders, in particular of hyper- proliferative disorders and/or virally induced infectious diseases and/or of cardiovascular diseases. The invention further relates to intermediate compounds useful in the preparation of said compounds of general formula (I).
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Amino, Amido and heterocyclic compounds as modulators of RAGE activity and uses thereof (Fri, 15 Apr 2016)
<p id="p-0001" num="0000">Amino, amido, and heterocyclic compounds are disclosed. The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, diabetes complications, inflammation, and neurodegeneration, obesity, cancer, ischemia/reperfusion injury, cardiovascular disease and other diseases related to RAGE activity.</p>
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SUBSTITUTED AMIDE COMPOUNDS (Fri, 15 Apr 2016)
The present invention is directed at substituted amide compounds of formula (I), pharmaceutical compositions containing such compounds and the use of such compounds to reduce plasma lipid levels, such as LDL-cholesterol and triglycerides and accordingly to treat diseases which are exacerbated by high levels of LDL-cholesterol and triglycerides, such as atherosclerosis and cardiovascular diseases, in mammals, including humans.(Formula I)
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FUSED HETEROCYCLIC COMPOUNDS AS ION CHANNEL MODULATORS (Fri, 08 Apr 2016)
<p id="p-0001" num="0000">The present disclosure relates to compounds that are sodium channel inhibitors and to their use in the treatment of various disease states, including cardiovascular diseases and diabetes. In particular embodiments, the structure of the compounds is given by Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="25.82mm" wi="69.93mm" file="US20160096846A1-20160407-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein Z<sup>1</sup>, Z<sup>2</sup>, Z<sup>3</sup>, Z<sup>4</sup>, X, Y, R<sup>2</sup>, R<sup>3 </sup>and R<sup>4 </sup>are as described herein, to methods for the preparation and use of the compounds and to pharmaceutical compositions containing the same.</p>
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TREATING AND PREVENTING DISEASE WITH TMA AND TMAO LOWERING AGENTS (Fri, 01 Apr 2016)
<p id="p-0001" num="0000">Provided herein are compositions, systems, and methods for treating a disease, such as kidney and/or cardiovascular disease, with an agent that reduces the production of trimethylamine (TMA) or trimethylamine-n-oxide (TMAO) in a subject. In certain embodiments, the agent is: i) 3,3-dimethyl-1-butanol (DMB) or a DMB derivative or related compound, ii) acetylsalicylic acid or derivative thereof (e.g., with an enteric coating for delivery to the colon and/or cecum); iii) a flavin monooxygenase 3 (FMO3) inhibitor; iv) a gut TMA lyase inhibitor; v) an antibiotic or antimicrobial; vi) a probiotic or prebiotic; vii) an antiplatelet agent; or viii) a TMA and/or TMAO sequestering agent.</p>
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COMPOSITIONS AND METHODS FOR THE TREATMENT OF CARDIOVASCULAR DISEASES AND DIABETES (Fri, 01 Apr 2016)
The compositions and compounds of formula I which includes a salt of ranolazine or its polymorphs, enantiomers, stereoisomers, solvates, and hydrates thereof. These salts may be formulated as pharmaceutical compositions. The pharmaceutical compositions may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment of angina, angina pectoris, diabetes, hyperglycemia, elevated glucose levels, deep venous thrombosis, prevention of secondary venous thromboembolism and complications of atrial fibrillation such as stroke and additional risk factor for stroke.
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SUBSTITUTED BRIDGED UREA ANALOGS AS SIRTUIN MODULATORS (Fri, 25 Mar 2016)
<p id="p-0001" num="0000">Provided herein are novel substituted bridged urea and related analogs and methods of use thereof. The sirtuin-modulating compounds may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders including, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. Also provided are compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.</p>
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Preparation and Uses of Obeticholic Acid (Fri, 18 Mar 2016)
<p id="p-0001" num="0000">The present invention relates to obeticholic acid:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="36.75mm" wi="60.45mm" file="US20160074419A1-20160317-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or a pharmaceutically acceptable salt, solvate or amino acid conjugate thereof. Obeticholic acid is useful for the treatment or prevention of a FXR mediated disease or condition, cardiovascular disease or cholestatic liver disease, and for reducing HDL cholesterol, for lowering triglycerides in a mammal, or for inhibition of fibrosis. The present invention also relates to processes for the synthesis of obeticholic acid.</p>
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Fused Heterocyclic Compounds as Selective BMP Inhibitors (Fri, 11 Mar 2016)
<p id="p-0001" num="0000">The present invention provides small molecule inhibitors of BMP signaling. These compounds may be used to modulate cell growth, differentiation, proliferation, and apoptosis, and thus may be useful for treating diseases or conditions associated with BMP signaling, including inflammation, cardiovascular disease, hematological disease, cancer, and bone disorders, as well as for modulating cellular differentiation and/or proliferation.</p>
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MODULATION OF APOLIPOPROTEIN CIII (APOCIII) EXPRESSION (Fri, 04 Mar 2016)
<p id="p-0001" num="0000">Provided herein are methods, compounds, and compositions for reducing expression of ApoCIII mRNA and protein in an animal. Also provided herein are methods, compounds, and compositions for increasing HDL levels and/or improving the ratio of TG to HDL and reducing plasma lipids and plasma glucose in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate any one or more of cardiovascular disease or metabolic disorder, or a symptom thereof.</p>
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CYCLODEXTRIN-BASED POLYMERS FOR THERAPEUTIC DELIVERY (Fri, 04 Mar 2016)
<p id="p-0001" num="0000">Provided are methods relating to the use of CDP-therapeutic agent conjugates for the treatment of a disease or disorder, e.g., autoimmune disease, inflammatory disease, central nervous system disorder, cardiovascular disease, or metabolic disorder. Also provided are CDP-therapeutic agent conjugates, particles comprising CDP-therapeutic agent conjugates, and compositions comprising CDP-therapeutic agent conjugates.</p>
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SUBSTITUTED AMIDE COMPOUNDS (Fri, 04 Mar 2016)
<p id="p-0001" num="0000">The present invention is directed at substituted amide compounds, pharmaceutical compositions containing such compounds and the use of such compounds to reduce plasma lipid levels, such as LDL-cholesterol and triglycerides and accordingly to treat diseases which are exacerbated by high levels of LDL-cholesterol and triglycerides, such as atherosclerosis and cardiovascular diseases, in mammals, including humans.</p>
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SOLUBLE EPOXIDE HYDROLASE INHIBITORS AND USES THEREOF (Fri, 04 Mar 2016)
The present invention features compounds having soluble epoxide hydrolase inhibitory activity. The compounds of the invention, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing various medical conditions, such as cardiovascular diseases, respiratory diseases, inflammation, and diabetes.
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Thiazolidinediones of omega-3 polyunsaturated acids as new insulin sensitizers for treating type2 diabetes (Fri, 26 Feb 2016)
<p id="p-0001" num="0000">The present invention relates to thiazolidinedione derivatives of omega-3 fatty acids as insulin sensitizers, and their use in treating Type2 diabetes, obesity, hypertriglyceridemia, cardiovascular diseases, metabolic diseases, inflammation, renal anemia, and/or Alzheimer's disease: and for modulating activity of peroxisome proliferator-activated receptors (PPARs).</p>
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Plant based formulation for the prevention and management of metabolic syndrome and cardiovascular disease mortality risk (Fri, 26 Feb 2016)
<p id="p-0001" num="0000">The invention relates to a plant based formulation for the prevention and management of Metabolic Syndrome and Cardiovascular disease mortality risk comprising an effective amount of a hydro-alcoholic extract of <i>Salacia parviflora, Tribulus terrestris </i>and <i>Dioscorea glabra. </i></p>
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DIPHENYL ETHER COMPOUNDS FOR THE TREATMENT OF LUNG DISORDERS (Thu, 25 Feb 2016)
Described herein are compounds of formula (I), their derivatives, analogs, tautomeric forms, stereoisomers, polymorphs, hydrates, solvates, pharmaceutically acceptable salts and compositions, metabolites and prodrugs thereof, for use in treating liver diseases such as non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), and other fibrotic diseases of the liver; diabetic complications such as macro (ischemic heart disease, cerebrovascular disease and peripheral vascular disease) and micro (cataract, retinopathy nephropathy neuropathy, maculopathy and glaucoma) vascular complication; and cardiovascular diseases such as atherosclerosis, restenosis, hypertension, vasospasm, and cardiac hypertrophy; and lung disorders and lung fibrosis.
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N-ACYLOXYSULFONAMIDE AND N-HYDROXY-N-ACYLSULFONAMIDE DERIVATIVES (Fri, 19 Feb 2016)
<p id="p-0001" num="0000">The invention provides certain N-acyloxysulfonamide and N-hydroxy-N-acylsulfonamide derivative compounds, pharmaceutical compositions and kits comprising such compounds, and methods of using such compounds or pharmaceutical compositions. In particular, the invention provides methods of using such compounds or pharmaceutical compositions for treating, preventing, or delaying the onset and/or develop of a disease or condition. In some embodiments, the disease or condition is selected from cardiovascular diseases, ischemia, reperfusion injury, cancerous disease, pulmonary hypertension and conditions responsive to nitroxyl therapy.</p>
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BMP INHIBITORS AND METHODS OF USE THEREOF (Fri, 19 Feb 2016)
<p id="p-0001" num="0000">The present invention provides small molecule inhibitors of BMP signaling. These compounds may be used to modulate cell growth, differentiation, proliferation, and apoptosis, and thus may be useful for treating diseases or conditions associated with BMP signaling, including inflammation, cardiovascular disease, hematological disease, cancer, and bone disorders, as well as for modulating cellular differentiation and/or proliferation. These compounds may also be used to reduce circulating levels of ApoB-100 or LDL and treat or prevent acquired or congenital hypercholesterolemia or hyperlipoproteinemia; diseases, disorders, or syndromes associated with defects in lipid absorption or metabolism; or diseases, disorders, or syndromes caused by hyperlipidemia.</p>
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NOVEL CYCLOSPORIN DERIVATIVES AND USES THEREOF (Fri, 12 Feb 2016)
<p id="p-0001" num="0000">The present invention relates to a compound of the Formula (I)): or pharmaceutically acceptable salt thereof, wherein the symbols are as defined in the specification; a pharmaceutical composition comprising the same, a method for treating or preventing viral infections, inflammation, dry eye, central nervous disorders, cardiovascular diseases, cancer, obesity, diabetes, muscular dystrophy, and hair loss.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="103.89mm" wi="76.20mm" file="US20160039879A1-20160211-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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HALOARYL SUBSTITUTED AMINOPURINES, COMPOSITIONS THEREOF,AND METHODS OF TREATMENT THEREWITH (Fri, 12 Feb 2016)
<p id="p-0001" num="0000">Provided herein are Aminopurine Compounds having the following structure:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="21.34mm" wi="57.40mm" file="US20160039822A1-20160211-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">wherein R<sup>1</sup>, R<sup>2 </sup>and R<sup>3 </sup>are as defined herein, compositions comprising an effective amount of an Aminopurine Compound and methods for treating or preventing cancer, a cardiovascular disease, a renal disease, an autoimmune condition, an inflammatory condition, macular degeneration, ischemia-reperfusion injury, pain and related syndromes, disease-related wasting, an asbestos-related condition, pulmonary hypertension or a condition treatable or preventable by inhibition of the JNK pathway comprising administering an effective amount of an Aminopurine Compound to a patient in need thereof.</li> </ul> </li> </ul> </p>
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SUBSTITUTED HYDROXAMIC ACIDS AND USES THEREOF (Fri, 12 Feb 2016)
<p id="p-0001" num="0000">This invention provides compounds of formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.77mm" wi="56.47mm" file="US20160039789A1-20160211-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">wherein R<sup>1a</sup>, R<sup>1b</sup>, R<sup>a</sup>, R<sup>2a</sup>, R<sup>2b</sup>, R<sup>1</sup>, and X have values as described in the specification, useful as inhibitors of HDAC6. The invention also provides pharmaceutical compositions comprising the compounds of the invention and methods of using the compositions in the treatment of proliferative, inflammatory, infectious, neurological or cardiovascular diseases or disorders.</li> </ul> </li> </ul> </p>
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PYRAZOLE DERIVATIVE (Fri, 12 Feb 2016)
<p id="p-0001" num="0000">Provided are a compound expressed by formula (I) or a pharmacologically permissible salt thereof, as well as a drug or drug composition that contains this compound as an active ingredient, having a xanthine oxidase inhibiting effect that is very useful for treating or preventing diseases that are contributed to by xanthine oxidase, such as gout, hyperuricemia, tumor lysis syndrome, urinary tract stones, hypertension, dyslipidemia, diabetes, cardiovascular disease such as heart failure and arterial sclerosis, renal disease such as diabetic near opacity and the like, respiratory disease such as chronic obstructive pulmonary disease and the like, autoimmune diseases such as inflammatory bowel disease, and the like. [In the formula, A, X, Y, Z, R, and R<sup>1 </sup>have the meaning set forth in claim <b>1</b>].</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="32.51mm" wi="69.85mm" file="US20160039784A1-20160211-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Organic compounds (Fri, 12 Feb 2016)
<p id="p-0001" num="0000">The invention relates to novel inhibitors of phosphodiesterase 1 (PDE1), useful for the treatment of diseases or disorders characterized by disruption of or damage to certain cGMP/PKG mediated pathways (e.g., in cardiac tissue). The invention further relates to pharmaceutical composition comprising the same and methods of treatment of cardiovascular disease and related disorders, e.g., congestive heart disease, atherosclerosis, myocardial infarction, and stroke.</p>
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ORGANIC COMPOUNDS (Fri, 12 Feb 2016)
The invention relates to novel inhibitors of phosphodiesterase 1 (PDE1), useful for the treatment of diseases or disorders characterized by disruption of or damage to certain cGMP/PKG mediated pathways (e.g., in cardiac tissue). The invention further relates to pharmaceutical composition comprising the same and methods of treatment of cardiovascular disease and related disorders, e.g., congestive heart disease, atherosclerosis, myocardial infarction, and stroke.
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ORGANIC COMPOUNDS (Fri, 12 Feb 2016)
The invention relates to novel inhibitors of phosphodiesterase 1 (PDE1), useful for the treatment of diseases or disorders characterized by disruption of or damage to certain cGMP/PKG mediated pathways (e.g., in cardiac tissue). The invention further relates to pharmaceutical composition comprising the same and methods of treatment of cardiovascular disease and related disorders, e.g., congestive heart disease, atherosclerosis, myocardial infarction, and stroke.
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PIPERAZINE DERIVATIVES AS LIVER X RECEPTOR MODULATORS (Fri, 12 Feb 2016)
Provided are novel compounds of Formula (I): pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are liver X receptor modulators, and which are useful in the treatment of diseases and disorders associated with the liver X receptor. Also provided are the compounds of Formula (I) and pharmaceutical compositions thereof for treating atherosclerosis, cardiovascular disease, Alzheimer's disease, dermatitis, dyslipidemia, cancer and other diseases or disorders.
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ORGANIC COMPOUNDS (Fri, 12 Feb 2016)
The invention relates to novel inhibitors of phosphodiesterase 1 (PDE1), useful for the treatment of diseases or disorders characterized by disruption of or damage to certain cGMP/PKG mediated pathways (e.g., in cardiac tissue). The invention further relates to pharmaceutical composition comprising the same and methods of treatment of cardiovascular disease and related disorders, e.g., congestive heart disease, atherosclerosis, myocardial infarction, and stroke.
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DIHYDROPTERIDINONE DERIVATIVES AND USES THEREOF (Fri, 12 Feb 2016)
The present disclosure provides compounds of Formula (I), and pharmaceutically compositions thereof. Compounds of Formula (I) have been found to bind bromodomains and/or bromodomain-containing proteins (e.g., bromo and extra terminal (BET) proteins). Also provided are methods, uses, and kits of the compounds and pharmaceutical compositions for inhibiting the activity (e.g., increased activity) of bromodomains and/or bromodomain-containing proteins and for treating and/or preventing in a subject diseases associated with bromodomains or bromodomain-containing proteins (e.g., proliferative diseases, cardiovascular diseases, viral infections, fibrotic diseases, neurological diseases, metabolic diseases, endocrine diseases, and radiation poisoning). The compounds, pharmaceutical compositions, and kits are also useful for male contraception.
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NOVEL FATTY ACIDS AND THEIR USE IN CONJUGATION TO BIOMOLECULES (Fri, 05 Feb 2016)
<p id="p-0001" num="0000">The invention provides a conjugate comprising a biomolecule linked to a fatty acid via a linker wherein the fatty acid has the following Formulae A1, A2 or A3:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="66.38mm" wi="54.02mm" file="US20160030585A1-20160204-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">wherein R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4</sup>, Ak, n, m and p are defined herein. The invention also relates to a method for manufacturing the conjugate of the invention such as GDF15 conjugate, and its therapeutic uses such as treatment or prevention of metabolic disorders or diseases, type 2 diabetes mellitus, obesity, pancreatitis, dyslipidemia, alcoholic and nonalcoholic fatty liver disease/steatohepatitis and other progressive liver diseases, insulin resistance, hyperinsulinemia, glucose intolerance, hyperglycemia, metabolic syndrome, hypertension, cardiovascular disease, atherosclerosis, peripheral arterial disease, stroke, heart failure, coronary heart disease, diabetic complications (including but not limited to chronic kidney disease), neuropathy, gastroparesis and other metabolic disorders. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.</li> </ul> </li> </ul> </p>
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Substituted hydroxamic acids and uses thereof (Fri, 05 Feb 2016)
<p id="p-0001" num="0000">This invention provides compounds of formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="23.88mm" wi="60.71mm" file="US09321731-20160426-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein R<sup>1</sup>, R<sup>2</sup>, G, m, n, p and q have values as described in the specification, useful as inhibitors of HDAC6. The invention also provides pharmaceutical compositions comprising the compounds of the invention and methods of using the compositions in the treatment of proliferative, inflammatory, infectious, neurological or cardiovascular diseases or disorders.</p>
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Estrogen receptor ligands and methods of use thereof (Fri, 05 Feb 2016)
<p id="p-0001" num="0000">The present invention relates to a novel class of nuclear receptor binding agents (NRBAs). The NRBA compounds are applicable for use in the prevention and/or treatment of a variety of diseases and conditions including, inter alia, prevention and treatment of hormone-related diseases, cancers, inflammation, osteoporosis, peripheral vascular disease, reducing circulating lipid levels, and cardiovascular disease.</p>
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PYRAZOLE DERIVATIVE (Thu, 04 Feb 2016)
Provided are a compound expressed by formula (I) or a pharmacologically permissible salt thereof, as well as a drug or drug composition that contains this compound as an active ingredient, having a xanthine oxidase inhibiting effect that is very useful for treating or preventing diseases that are contributed to by xanthine oxidase, such as gout, hyperuricemia, tumor lysis syndrome, urinary tract stones, hypertension, dyslipidemia, diabetes, cardiovascular disease such as heart failure and arterial sclerosis, renal disease such as diabetic near opacity and the like, respiratory disease such as chronic obstructive pulmonary disease and the like, autoimmune diseases such as inflammatory bowel disease, and the like. [In the formula, A, X, Y, Z, R, and R 1 have the meaning set forth in claim 1.]
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ANTI-MACROPHAGE MANNOSE RECEPTOR SINGLE VARIABLE DOMAINS FOR USE IN CARDIOVASCULAR DISEASES (Fri, 29 Jan 2016)
<p id="p-0001" num="0000">The disclosure relates to the field of cardiovascular diseases. In particular, immunoglobulin single variable domains directed against macrophage mannose receptor (MMR) are provided that can be used in the diagnosis, prognosis and/or monitoring of cardiovascular diseases or as therapeutics. Also, the anti-macrophage mannose receptor (MMR) immunoglobulin single variable domains of the disclosure are useful at different stages of cardiovascular diseases, including post-infarction cardiovascular events. Further, the anti-macrophage mannose receptor (MMR) immunoglobulin single variable domains of the disclosure are particularly useful for the in vivo targeting and/or imaging of vulnerable atherosclerotic plaques.</p>
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INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL (Fri, 29 Jan 2016)
<p id="p-0001" num="0000">The present invention provides compounds of Formula I</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="31.58mm" wi="71.63mm" file="US20160024091A1-20160128-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.</p>
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P2X7 MODULATORS (Fri, 29 Jan 2016)
<p id="p-0001" num="0000">The present invention is directed to a compound of Formula (I) or (Ia) The invention also relates to pharmaceutical compositions comprising compounds of Formula (I) or (Ia) and methods comprising administering of compounds of Formula (I) or (Ia) for treating rheumatoid arthritis, osteoarthritis, psoriasis, septic shock, allergic dermatitis, asthma, allergic asthma, mild to severe asthma, steroid resistant asthma, idiopathic pulmonary fibrosis, allergic rhinitis, chronic obstructive pulmonary disease; airway hyper-responsiveness, diseases of the nervous and neuro-immune system, acute and chronic pain states of neuropathic pain, inflammatory pain, spontaneous pain, opioid induced pain, diabetic neuropathy, postherpetic neuralgia, low back pain, chemotherapy-induced neuropathic pain, fibromyalgia, diseases involved with and without neuroinflammation of the central nervous system, mood disorders, major depression, major depressive disorder, treatment resistant depression, bipolar disorder, anxious depression, anxiety, cognition, sleep disorders, multiple sclerosis, epileptic seizures, Parkinson's disease, schizophrenia, Alzheimer's disease, Huntington's disease, autism, spinal cord injury and cerebral ischemia/traumatic brain injury, stress-related disorders, diseases of the cardiovascular, metabolic, gastrointestinal and urogenital systems such as diabetes, diabetes mellitus, thrombosis, irritable bowel syndrome, irritable bowel disease, Crohn's disease, ischemic heart disease, ischaemia, hypertension, cardiovascular disease, myocardial infarction, and lower urinary tract dysfunction such as incontinence, lower urinary tract syndrome, Polycystic Kidney Disease, Glomerulonephritis, skeletal disorders, osteoporosis, osteopetrosis, and glaucoma, interstitial cystitis, cough, ureteric obstruction, sepsis, Amyotrophic Lateral Sclerosis, Chaga's Disease, <i>chlamydia</i>, neuroblastoma, Tuberculosis, and migraine.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="30.48mm" wi="65.02mm" file="US20160024082A1-20160128-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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P2X7 MODULATORS (Fri, 22 Jan 2016)
<p id="p-0001" num="0000">The present invention is directed to a compound of Formula (I) Formula (I) The invention also relates to pharmaceutical compositions comprising compounds of Formula (I) and methods comprising administering to a subject at least one compound selected from compounds of Formula (I) for treating diseases mediated by P2X7 receptor activity, such as rheumatoid arthritis, osteoarthritis, psoriasis, septic shock, allergic dermatitis, asthma, allergic asthma, mild to severe asthma, steroid resistant asthma, idiopathic pulmonary fibrosis, allergic rhinitis, chronic obstructive pulmonary disease; airway hyper-responsiveness, diseases of the nervous and neuro-immune system, acute and chronic pain states of neuropathic pain, inflammatory pain, spontaneous pain, opioid induced pain, diabetic neuropathy, postherpetic neuralgia, low back pain, chemotherapy-induced neuropathic pain, fibromyalgia, diseases involved with and without neuroinflammation of the central nervous system, mood disorders, major depression, major depressive disorder, treatment resistant depression, bipolar disorder, anxious depression, anxiety, cognition, sleep disorders, multiple sclerosis, epileptic seizures, Parkinson's disease, schizophrenia, Alzheimer's disease, Huntington's disease, autism, spinal cord injury and cerebral ischemia/traumatic brain injury, stress-related disorders, diseases of the cardiovascular, metabolic, gastrointestinal and urogenital systems such as diabetes, diabetes mellitus, thrombosis, irritable bowel syndrome, irritable bowel disease, Crohn's disease, ischemic heart disease, ischaemia, hypertension, cardiovascular disease, myocardial infarction, and lower urinary tract dysfunction such as incontinence, lower urinary tract syndrome, Polycystic Kidney Disease, Glomerulonephritis, skeletal disorders, osteoporosis, osteopetrosis, and glaucoma, interstitial cystitis, cough, ureteric obstruction, sepsis, Amyotrophic Lateral Sclerosis, Chaga's Disease, <i>chlamydia</i>, neuroblastoma, Tuberculosis, and migraine.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="25.40mm" wi="62.40mm" file="US20160016962A1-20160121-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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NON-HIGH DENSITY LIPOPROTEIN DERIVED CVD MARKERS (Fri, 22 Jan 2016)
<p id="p-0001" num="0000">The present invention inter alia relates to methods and uses involving the determination of lipid/lipid concentration ratios in order to diagnose, predict, prevent and/or treat atherosclerosis or cardiovascular disease (CVD) and its complications including, e.g., acute myocardial infarction. The methods include analyzing lipid concentrations and resulting lipid/lipid concentration ratios of a non-high density lipoprotein samples from patients and comparing them to a control.</p>
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Methods, Compounds, and Compositions for the Treatment of Angiotensin-Related Diseases (Fri, 22 Jan 2016)
<p id="p-0001" num="0000">Disclosed are small molecule non-peptidic compounds, as well as methods and compositions for the treatment of angiotensin-related diseases and disorders, including cardiovascular diseases, metabolic diseases, gastrointestinal diseases, renal diseases, inflammatory/autoimmune diseases, neurological diseases, bone marrow diseases and cancer.</p>
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INHIBITORS OF RENAL OUTER MEDULLARY POTASSIUM CHANNEL (Fri, 22 Jan 2016)
Compounds of Formula I and the pharmaceutically acceptable salts thereof are provided as inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.
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COMPOSITIONS AND METHODS FOR INHIBITING BMP (Fri, 22 Jan 2016)
The present invention provides small-molecule inhibitors of BMP signaling and compositions and methods for inhibiting BMP signaling. These compounds and compositions may be used to modulate cell growth, differentiation, proliferation, and apoptosis, and thus may be useful for treating diseases or conditions associated with BMP signaling, including inflammation, cardiovascular disease, hematological disease, cancer, and bone disorders, as well as for modulating cellular differentiation and/or proliferation. These compounds and compositions may also be used to reduce circulating levels of ApoB-100 or LDL and treat or prevent acquired or congenital hypercholesterolemia or hyperlipoproteinemia; diseases, disorders, or syndromes associated with defects in lipid absorption or metabolism; or diseases, disorders, or syndromes caused by hyperlipidemia.
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ORGANIC COMPOSITIONS TO TREAT APOC3-RELATED DISEASES (Fri, 22 Jan 2016)
The present disclosure relates to compositions and methods for treating APOC3-related diseases such as: hypertriglyceridemia (e.g., Type V Hypertriglyceridemia), abnormal lipid metabolism, abnormal cholesterol metabolism, atherosclerosis, hyperlipidemia, diabetes, including Type 2 diabetes, obesity, cardiovascular disease, and coronary artery disease, among other disorders relating to abnormal metabolism or otherwise, using a therapeutically effective amount of a RNAi agent to APOC3.
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INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL (Fri, 22 Jan 2016)
The present invention provides compounds of Formula I and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.
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INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL (Fri, 22 Jan 2016)
The present invention provides compounds of Formula (I) and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.
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XANTHOHUMOL-BASED COMPOUNDS AND COMPOSITIONS THEREOF, AND METHODS OF MAKING AND USING THE SAME (Fri, 15 Jan 2016)
<p id="p-0001" num="0000">Disclosed herein are compounds capable of ameliorating, treating, and preventing metabolic syndrome, or risk factors associated with metabolic syndrome, such as obesity, diabetes, and/or cardiovascular disease. In some embodiments, the compounds can function as mild mitochondrial uncouplers and thereby reduce markers of metabolic syndrome by improving insulin sensitivity and glucose metabolism. Methods of making the compounds also are disclosed herein, along with compositions and formulations suitable for administration to a subject. In some embodiments, the compounds (or compositions thereof) can be formulated and administered as dietary supplements.</p>
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OXAZEPINES AS ION CHANNEL MODULATORS (Thu, 14 Jan 2016)
The present disclosure relates to compounds that are sodium channel inhibitors and to their use in the treatment of various disease states, including cardiovascular diseases and diabetes. In particular embodiments, the structure of the compounds is given by Formula I: wherein Y, Z, n, R1 and R3 are as described herein, to methods for the preparation and use of the compounds and to pharmaceutical compositions containing the same.
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INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL (Fri, 08 Jan 2016)
<p id="p-0001" num="0000">The present invention provides compounds of Formula I</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="22.10mm" wi="59.52mm" file="US20160002259A1-20160107-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure, kidney disease, edema, and conditions associated with excessive salt and water retention.</p>
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SUBSTITUTED N-(1H-INDAZOL-4-YL)IMIDAZO[1,2-a]PYRIDINE-3-CARBOXAMIDE COMPOUNDS AS TYPE III RECEPTOR TYROSINE KINASE INHIBITORS (Fri, 08 Jan 2016)
<p id="p-0001" num="0000">Compounds useful in the treatment of fibrosis, bone-related diseases, cancer, autoimmune disorders, inflammatory diseases, cardiovascular diseases, pain and burns in a mammal.</p>
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VACCINES AND MONOCLONAL ANTIBODIES TARGETING TRUNCATED VARIANTS OF OSTEOPONTIN AND USES THEREOF (Fri, 08 Jan 2016)
The present invention provides monoclonal antibodies specific for one or more truncated variants of human osteopontin and vaccines comprising at least one isolated osteopontin peptide, as well methods for manufacturing said antibodies and vaccines. Furthermore, a diagnostic method making use of said antibodies is provided. Said antibodies and vaccines are used in therapy, especially in treatment and/or prevention of Type-2 diabetes and cardiovascular disease.
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COMBINATION OF NITROPRUSSIDE AND A SULFIDE SALT AS AN HNO-RELEASING THERAPEUTIC FOR THE TREATMENT OR PREVENTION OF CARDIOVASCULAR DISEASES (Fri, 01 Jan 2016)
<p id="p-0001" num="0000">The present invention relates to the combination of a nitroprusside salt or a solvate thereof with a sulfide salt or a solvate thereof for use in the treatment or prevention of a cardiovascular disease/disorder, such as heart failure, heart attack or hypertension.</p>
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NOVEL USES (Fri, 01 Jan 2016)
<p id="p-0001" num="0000">The invention relates to the administration of inhibitors of phosphodiesterase 1 (PDE1) for the treatment of diseases or disorders characterized by disruption of or damage to various cGMP/PKG mediated pathways. In one embodiment the invention relates to inhibitors of phosphodiesterase 1 (PDE1) for treatment of cardiovascular disease and related disorders, e.g., congestive heart disease, atherosclerosis, myocardial infarction, and stroke.</p>
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ANTI-PCSK9 COMPOUNDS AND METHODS FOR THE TREATMENT AND/OR PREVENTION OF CARDIOVASCULAR DISEASES (Fri, 01 Jan 2016)
<p id="p-0001" num="0000">Disclosed are compounds that modulate the physiological action of the proprotein convertase subtilisin kexin type 9 (PCSK9), and methods of using these modulators to reduce LDL-cholesterol levels and/or for the treatment and/or prevention of cardiovascular disease (CVD), including treatment of hypercholesterolemia.</p>
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Azole benzene derivative (Fri, 01 Jan 2016)
<p id="p-0001" num="0000">The present invention provides: a compound represented by formula (I) or a pharmaceutically acceptable salt thereof, which has an excellent inhibitory activity on xanthine oxidase and is useful as a therapeutic agent or a prophylactic agent for diseases associated with xanthine oxidase, such as gout, hyperuricemia, tumor lysis syndrome, urinary tract stone, hypertension, dyslipidemia, diabetes, cardiovascular diseases including arteriosclerosis and heart failure, renal diseases including diabetic nephropathy, respiratory diseases including chronic obstructive pulmonary disease, inflammatory bowel disease or autoimmune diseases; and a medicine or a pharmaceutical composition comprising the compound or the salt as an active ingredient.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="34.37mm" wi="69.85mm" file="US09388174-20160712-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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NOVEL DIHYDROPYRIDOISOQUINOLINONES AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF INFLAMMATORY DISORDERS (Thu, 31 Dec 2015)
A compound according to Formula I: wherein R1, LA, GA, R2a, R2b, R3, R4, R5, and R6 are as described herein. The present invention relates to novel compounds according to Formula I that antagonize GPR84, a G-protein-coupled receptor that is involved in inflammatory conditions, and methods for the production of these novel compounds, pharmaceutical compositions comprising these compounds, and methods for the prevention and/or treatment of inflammatory conditions (for example inflammatory bowel diseases (IBD), rheumatoid arthritis, vasculitis), lung diseases (e.g., chronic obstructive pulmonary disease (COPD) and lung interstitial diseases (e.g., idiopathic pulmonary fibrosis (IPF))), neuroinflammatory conditions, infectious diseases, autoimmune diseases, endocrine and/or metabolic diseases, diseases involving impairment of immune cell functions, pain, neurodegenerative conditions, cardiovascular diseases, and/or leukemia by administering a compound of the invention.
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FATTY ACIDS AND THEIR USE IN CONJUGATION TO BIOMOLECULES (Thu, 31 Dec 2015)
The invention provides a conjugate comprising a biomolecule linked to a fatty acid via a linker wherein the fatty acid has the following Formulae A1, A2 or A3: wherein R1, R2, R3, R4, Ak, n, m and p are defined herein. The invention also relates to a method for manufacturing the conjugate of the invention such as GDF15 conjugate, and its therapeutic uses such as treatment or prevention of metabolic disorders or diseases, type 2 diabetes mellitus, obesity, pancreatitis, dyslipidemia, alcoholic and nonalcoholic fatty liver disease/steatohepatitis and other progressive liver diseases, insulin resistance, hyperinsulinemia, glucose intolerance, hyperglycemia, metabolic syndrome, hypertension, cardiovascular disease, atherosclerosis, peripheral arterial disease, stroke, heart failure, coronary heart disease, diabetic complications (including but not limited to chronic kidney disease), neuropathy, gastroparesis and other metabolic disorders. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.
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PHARMACEUTICAL COMPOSITIONS COMPRISING NITROXYL DONORS (Fri, 25 Dec 2015)
<p id="p-0001" num="0000">The present disclosure provides nitroxyl donating pharmaceutical compositions comprising N-substituted hydroxylamine derivatives. The compositions are highly efficacious in treating cardiovascular diseases (e.g., heart failure), have a suitable toxicological profile, and are sufficiently stable for intravenous or oral administration.</p>
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NOVEL COMPOUND HAVING SKIN-WHITENING, ANTI-OXIDIZING AND PPAR ACTIVITIES AND MEDICAL USE THEREOF (Fri, 25 Dec 2015)
<p id="p-0001" num="0000">Provided are a novel compound having skin-whitening, anti-oxidizing and PPAR activities and a medical use thereof, and the compound has skin-whitening activities for the suppression of tyrosinase, and accordingly, is useful for use in skin-whitening pharmaceutical composition or cosmetic products; has anti-oxidant activities, and accordingly, is useful for the prevention and treatment of skin-aging; and has PPAR activities, and in particular, PPARα and PPARγ activities, and accordingly, is useful for use in pharmaceutical compositions or health foods which are effective for the prevention and treatment of obesity, metabolic disease, or cardiovascular disease.</p>
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AGENTS FOR USE IN THE TREATMENT OF CARDIOVASCULAR AND INFLAMMATORY DISEASES STRUCTURALLY BASED ON 4(1 H)-QUINOLONE (Fri, 18 Dec 2015)
The present invention provides a compound of formula I, a tautomer thereof, or a pharmaceutically acceptable salt or N-oxide thereof for use in the treatment or prevention of a cardiovascular disease or of an inflammatory disease or condition:
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NEW INDANYLOXYDIHYDROBENZOFURANYLACETIC ACIDS (Thu, 17 Dec 2015)
The present invention relates to compounds of general formula I, (I) wherein the group R<sp>1</sp> is defined as in claim 1, which have valuable pharmacological properties, in particular bind to the G-protein coupled receptor 40 (GPR40, also known as free fatty acid receptor FFAR 1) and modulate its activity. The compounds are suitable for the treatment and prevention of diseases which can be influenced by this receptor; metabolic diseases, such as diabetes, more specifically type 2 diabetes mellitus, and conditions associated with the disease, including insulin resistance, obesity, cardiovascular disease and dyslipidemia.
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USE OF LYMPHOCYTE ACTIVATION GENE 3 (LAG-3) EXPRESSION PROFILING AS A BIOMARKER FOR ASSESSING INFLAMMASOMES, CHRONIC INFLAMMATORY DISEASES AND DYSFUNCTIONAL HDL (Fri, 11 Dec 2015)
<p id="p-0001" num="0000">A method for determining whether a subject has or is predisposed to abnormal expression of inflammasomes and/or to dysfunctional HDL suitable for use in diagnosing atherosclerosis, chronic inflammatory disease, Incident Cardiovascular Disease (ICD) and other pathologies characterized by an inflammatory response. Specifically, a protein assay that measures LAG-3 can be used as a diagnostic predictor of pathologies such as infection, inflammation, chronic inflammatory disease, and coronary artery disease. The diagnostic is combined with the therapeutic use of a remediating drug for treatment.</p>
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AZOLE BENZENE DERIVATIVE (Thu, 10 Dec 2015)
The present invention provides: a compound represented by formula (I) or a pharmaceutically acceptable salt thereof, which has an excellent inhibitory activity on xanthine oxidase and is useful as a therapeutic agent or a prophylactic agent for diseases associated with xanthine oxidase, such as gout, hyperuricemia, tumor lysis syndrome, urinary tract stone, hypertension, dyslipidemia, diabetes, cardiovascular diseases including arteriosclerosis and heart failure, renal diseases including diabetic nephropathy, respiratory diseases including chronic obstructive pulmonary disease, inflammatory bowel disease or autoimmune diseases; and a medicine or a pharmaceutical composition comprising the compound or the salt as an active ingredient.
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USE OF sCD14 OR ITS FRAGMENTS OR DERIVATIVES FOR RISK STRATIFICATION, DIAGNOSIS AND PROGNOSIS (Fri, 04 Dec 2015)
<p id="p-0001" num="0000">The present invention relates to a method for diagnosis of a cardiovascular disease or condition or atherosclerosis and for a method for evaluating the risk of a subject of developing the same. Methods are further provided for evaluating a subject's risk of mortality, for evaluating whether a subject will benefit from a certain treatment or whether a subject needs to be hospitalized or whether a subject may be discharged. The present invention provides sCD14 or a fragment or derivative thereof (including in particular sCD14-ST) as a novel marker for cardiovascular risk in general, more specifically as a marker for cardiovascular disease or condition, or atherosclerosis.</p>
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Omefibrates for Treating Dyslipidemia and Cardiovascular Disease (Fri, 04 Dec 2015)
<p id="p-0001" num="0000">The present invention relates to the fibric acid derivatives of omega-3 fatty acids and their use in treating Type2 diabetes, obesity, hypertriglyceridemia, cardiovascular diseases, metabolic syndrome, cancer, Alzheimer's disease; and their use for modulating activity of peroxisome proliferator-activated receptors (PPARs).</p>
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Cycloalkyl-hydroxyl compounds and compositions for cholesterol management and related uses (Fri, 04 Dec 2015)
<p id="p-0001" num="0000">The present invention relates to novel cycloalkyl-hydroxyl compounds, compositions comprising hydroxyl compounds, and methods useful for treating and preventing a variety of diseases and conditions such as, but not limited to aging, Alzheimer's Disease, cancer, cardiovascular disease, diabetic nephropathy, diabetic retinopathy, a disorder of glucose metabolism, dyslipidemia, dyslipoproteinemia, hypertension, impotence, inflammation, insulin resistance, lipid elimination in bile, obesity, oxysterol elimination in bile, pancreatitis, Parkinson's disease, a peroxisome proliferator activated receptor-associated disorder, phospholipid elimination in bile, renal disease, septicemia, Syndrome X, thrombotic disorder. Compounds and methods of the invention can also be used to modulate C reactive protein or enhance bile production in a patient. In certain embodiments, the compounds, compositions, and methods of the invention are useful in combination therapy with other therapeutics, such as hypocholesterolemic and hypoglycemic agents.</p>
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TGR5 AGONIST COMPLEXES FOR TREATING DIABETES AND CANCER (Fri, 04 Dec 2015)
Provided herein are complexes of metformin or metformin analogues and a TGR5 ligand that are useful in treating diseases including diabetes, cardiovascular disease, and cancer.
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3-CARBOXY-N-ETHYL-N,N-DIMETHYLPROPAN-1-AMINIUM SALTS FOR USE IN THE TREATMENT OF CARDIOVASCULAR DISEASE (Tue, 01 Dec 2015)

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CRYSTAL FORM OF COMPOUND USED AS MINERALOCORTICOID RECEPTOR ANTAGONIST AND PREPARATION METHOD THEREFOR (Fri, 27 Nov 2015)
<p id="p-0001" num="0000">The present invention belongs to the technical field of medicines, and relates to a crystal form of a compound used as a mineralocorticoid receptor antagonist and a preparation method therefor, and in particular, to a method for preparing a compound 2-chloro-4-[(3S,3aR)-3-cyclopentyl-7-(4-hydroxypiperidin-1-carbonyl)-3,3a,4,5-tetrahydro-2H-pyrazolo[3,4-f]quinolin-2-yl]benzonitrile of formula (1); a crystal form thereof, a preparation method for the crystal form, and the use of the crystal form in the preparation of drugs for the treatment and/or prevention of renal injury or cardiovascular diseases.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="41.23mm" wi="69.85mm" file="US20150336950A1-20151126-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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PPAR MODULATORS (Fri, 27 Nov 2015)
The present application relates to amorfrutin analogs and uses as PPAR modulators for the treatment of metabolic syndrome, obesity, hyperlipidemia, elevated fasting blood glucose, elevated blood pressure, low HDL cholesterol, type 2 diabetes, cardiovascular disease, a neurodegenerative disease, malaria or irritable bowel syndrome.
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REPLACEMENT THERAPY FOR NATRIURETIC PEPTIDE DEFICIENCIES (Fri, 20 Nov 2015)
Use and methods of use of natriuretic peptide mimetics which bind to and activate natriuretic peptide receptor A in patients with a defect, condition, syndrome, disease or mutation resulting in a functional active ΑΝΡ99-126 deficiency, for treatment or prophylaxis of cardiovascular disease, including but not limited to hypertension, acute coronary syndrome, cardiomyopathy, cardiac remodeling, left-ventricular hypertrophy, congestive heart failure, heart failure, high blood pressure and coronary artery disease, including use of mimetics with a plurality of amino acid residues and at least one amino acid surrogate of formula (I) where R, R', Q, Y, W, Z, J, x and n are as defined in the specification.
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COMPOSITIONS AND METHODS FOR THE TREATMENT OF ATHEROSCLEROTIC CARDIOVASCULAR DISEASES WITH PDE4 MODULATORS (Fri, 20 Nov 2015)
Provided herein are methods of treating, preventing or managing atherosclerosis by administering a PDE4 modulator. Pharmaceutical compositions, dosage forms, and kits suitable for use in methods are also provided.
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Statins of omega-3 polyunsaturated acids for treating hypercholesterolemia (Fri, 13 Nov 2015)
<p id="p-0001" num="0000">The present invention relates to novel statin derivatives of omega-3 fatty acids, and their use in treating hypercholesterolemia, obesity, hypertriglyceridemia, cardiovascular diseases, and metabolic diseases, and Alzheimer's disease.</p>
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HETEROCYCLYL-BUTANAMIDE DERIVATIVES (Fri, 13 Nov 2015)
Compounds of the formula I, in which W, X and Y have the meanings indicated in Claim 1, are inhibitors of Tankyrase, and can be employed, inter alia, for the treatment of diseases such as cancer, cardiovascular diseases, central nervous system injury and different forms of inflammation.
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Compositions and methods for modulating angiopoietin-like 3 expression (Fri, 06 Nov 2015)
<p id="p-0001" num="0000">Provided herein are methods, compounds, and compositions for reducing expression of an ANGPTL3 mRNA and protein in an animal. Also provided herein are methods, compounds, and compositions for reducing lipids and/or glucose in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate any one or more of cardiovascular disease and/or metabolic disease, or a symptom thereof, in an individual in need thereof.</p>
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COMPOSITIONS AND METHODS FOR MODULATING ANGIOPOIETIN-LIKE 3 EXPRESSION (Fri, 06 Nov 2015)
Provided herein are methods, compounds, and compositions for reducing expression of an ANGPTL3 mRNA and protein in an animal. Also provided herein are methods, compounds, and compositions for reducing lipids and/or glucose in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate any one or more of cardiovascular disease and/or metabolic disease, or a symptom thereof, in an individual in need thereof.
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Apolipoprotein A-I Mimics (Thu, 05 Nov 2015)
Provided are peptides, compositions thereof, and methods for treating or preventing dyslipidemia, a cardiovascular disease, endothelial dysfunction, a macrovascular disorder, or a microvascular disorder.
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USE OF SCD14 OR ITS FRAGMENTS OR DERIVATIVES FOR RISK STRATISFACTION, DIAGNOSIS AND PROGNOSIS (Thu, 05 Nov 2015)
The present invention relates to a method for diagnosis of a cardiovascular disease or condition or atherosclerosis and for a method for evaluating the risk of a subject of developing the same. Methods are further provided for evaluating a subject's risk of mortality, for evaluating whether a subject will benefit from a certain treatment or whether a subject needs to be hospitalized or whether a subject may be discharged. The present invention provides sCD14 or a fragment or derivative thereof (including in particular sCD14-ST) as a novel marker for cardiovascular risk in general, more specifically as a marker for cardiovascular disease or condition, or atherosclerosis.
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CRYSTAL FORM OF COMPOUND USED AS MINERALOCORTICOID RECEPTOR ANTAGONIST AND PREPARATION METHOD THEREFOR (Thu, 29 Oct 2015)
The present invention belongs to the technical field of medicines, and relates to a crystal form of a compound used as a mineralocorticoid receptor antagonist and a preparation method therefor, and in particular, to a method for preparing a compound 2-chloro-4-[(3S,3aR)-3-cyclopentyl-7-(4-hydroxypiperidin-1-carbonyl)-3,3a,4,5-tetrahydro-2H -pyrazolo[3,4-f]quinolin-2-yl]benzonitrile of formula (1); a crystal form thereof, a preparation method for the crystal form, and the use of the crystal form in the preparation of drugs for the treatment and/or prevention of renal injury or cardiovascular diseases.
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SUBSTITUTED PYRIDINE-2-CARBOXAMIDE COMPOUNDS AS APOPTOSIS SIGNAL-REGULATING KINASE INHIBITORS (Thu, 29 Oct 2015)
The present invention relates to compounds of Formula (I) wherein variables are as defined above. The compounds have apoptosis signal-regulating kinase ("ASKl") inhibitory activity, and are thus useful in the treatment of ASKl -mediated conditions, including autoimmune disorders, inflammatory diseases, cardiovascular diseases, diabetes, diabetic nephropathy, cardio-renal diseases, including kidney disease, fibrotic diseases, respiratory diseases, COPD, idiopathic pulmonary fibrosis, acute lung injury, acute and chronic liver diseases, and neurodegenerative diseases.
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RHO KINASE INHIBITORS (Fri, 23 Oct 2015)
<p id="p-0001" num="0000">Disclosed are novel substituted 2H-isoquinolin-1-one and 3H-quinazolin-4-one derivatives useful as inhibitors of Rho kinase and for treating a variety of diseases and disorders that are mediated or sustained through the activity of Rho kinase, including cardiovascular diseases, pharmaceutical compositions comprising such compounds, methods for using such compounds and processes for making such compounds.</p>
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Inhibitors of the Renal Outer Medullary Potassium Channel (Fri, 23 Oct 2015)
<p id="p-0001" num="0000">The present invention provides compounds of Formula I</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="17.70mm" wi="69.77mm" file="US20150299198A1-20151022-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and conditions associated with excessive salt and water retention.</p>
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Beta- and gamma-amino-isoquinoline amide compounds and substituted benzamide compounds (Fri, 23 Oct 2015)
<p id="p-0001" num="0000">Disclosed are beta and gamma-amino isoquinoline amide compounds and substituted benzamide compounds. In particular, the invention provides compounds that affect the function of kinases in a cell and that are useful as therapeutic agents or with therapeutic agents. The compounds of the invention are useful in the treatment of a variety of diseases and conditions including eye diseases such as glaucoma, cardiovascular diseases, and diseases characterized by abnormal growth, such as cancers. The invention further provides compositions containing the beta or gamma-amino isoquinoline amide compounds or substituted benzamide compounds.</p>
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Apoptosis signal-regulating kinase inhibitors (Thu, 22 Oct 2015)
The present invention relates to compounds of Formula (I): where in X1, X2, X3, X4, X5, X6, X7, X8, R1, R2, R3 are as defined above. The compounds have apoptosis signal-regulating kinase ("ASK1") inhibitory activity, and are thus useful in the treatment of ASK1-mediated conditions, including autoimmune disorders, inflammatory diseases, cardiovascular diseases and neurodegenerative diseases. The invention also relates to pharmaceutical compositions comprising one or more of the compounds of Formula (I), and to methods of preparing the compounds of Formula (I).
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N-(PYRIDIN-2-YL)PYRIMIDIN-4-AMINE DERIVATIVES CONTAINING A SULFOXIMINE GROUP (Fri, 16 Oct 2015)
<p id="p-0001" num="0000">The present invention relates to disubstituted N-(pyridin-2-yl)pyrimidin-4-amine derivatives containing a sulfoximine group of general formula (I) as described and defined herein, and methods for their preparation, their use for the treatment and/or prophylaxis of disorders, in particular of hyper-proliferative disorders and/or virally induced infectious diseases and/or of cardiovascular diseases. The invention further relates to intermediate compounds useful in the preparation of said compounds of general formula (I).</p>
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5-FLUORO-N-(PYRIDIN-2-YL)PYRIDIN-2-AMINE DERIVATIVES CONTAINING A SULFOXIMINE GROUP (Fri, 16 Oct 2015)
<p id="p-0001" num="0000">The present invention relates to 5-fluoro-N-(pyridin-2-yl)pyridin-2-amine derivatives containing a sulfoximine group of general formula (I) as described and defined herein, and methods for their preparation, their use for the treatment and/or prophylaxis of disorders, in particular of hyper-proliferative disorders and/or virally induced infectious diseases and/or of cardiovascular diseases. The invention further relates to intermediate compounds useful in the preparation of said compounds of general formula (I).</p>
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4-(ortho)-fluorophenyl-5-fluoropyrimidin-2-yl amines containing a sulfoximine group (Fri, 16 Oct 2015)
<p id="p-0001" num="0000">The present invention relates to 4-(ortho)-fluorophenyl-5-fluoropyrimidin-2-yl amine derivatives containing a sulfoximine group of general formula (I) as described and defined herein, and methods for their preparation, their use for the treatment and/or prophylaxis of disorders, in particular of hyper-proliferative disorders and/or virally induced infectious diseases and/or of cardiovascular diseases. The invention further relates to intermediate compounds useful in the preparation of said compounds of general formula (I).</p>
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NOVEL PRODRUGS AND COMBINATIONS FOR TREATMENT OF HYPERTENSION AND CARDIOVASCULAR DISEASES (Fri, 16 Oct 2015)
The invention relates a pharmaceutical composition comprising (i) prodrugs of NEP inhibitors, (ii) mutual prodrugs of angiotensin receptor antagonist and a NEP inhibitor, (iii) a combination of an angiotensin receptor antagonist prodrug and a NEP inhibitor and (iv) a combination of angiotensin receptor antagonist including prodrug, a NEP inhibitor prodrug and a diuretic drug (v) a combination of angiotensin receptor antagonist, a NEP inhibitor prodrug and a calcium channel blocker. The angiotensin receptor antagonist is selected from the group selected from the group consisting of allisartan, elisartan, candesartan, eprosartan, irbesartan, losartan, saprisartan, tasosartan, telmisartan and valsartan. The invention also includes a method for treating hypertension, heart failure such as (acute and chronic) congestive heart failure, left ventricular dysfunction and hypertrophic cardiomyopathy, diabetic cardiac myopathy, supraventricular and ventricular arrhythmias, atrial fibrillation, atrial flutter, detrimental vascular remodeling, myocardial infarction and its sequelae, atherosclerosis, angina (whether unstable or stable), renal insufficiency (diabetic and non-diabetic), heart failure, angina pectoris, diabetes, secondary aldosteronism, primary and secondary pulmonary hypertension, renal failure conditions, such as diabetic nephropathy, glomerulonephritis, scleroderma, glomerular sclerosis, proteinuria of primary renal disease, and also renal vascular hypertension, diabetic retinopathy, the management of other vascular disorders, such as migraine, peripheral vascular disease, Raynaud's disease, luminal hyperplasia, cognitive dysfunction (such as Alzheimer's), glaucoma and stroke.
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NOVEL MACROCYCLIC COMPOUNDS (Fri, 16 Oct 2015)
The present invention relates to novel macrocyclic compounds of general formula (I) as described and defined herein, and methods for their preparation, their use for the treatment and/or prophylaxis of disorders, in particular of hyper-proliferative disorders and/or virally induced infectious diseases and/or of cardiovascular diseases. The invention further relates to intermediate compounds useful in the preparation of said compounds of general formula (I).
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5-FLUORO-N-(PYRIDIN-2-YL)PYRIDIN-2-AMINE DERIVATIVES CONTAINING A SULFOXIMINE GROUP (Thu, 15 Oct 2015)
The present invention relates to 5-fluoro-<i>N</i>-(pyridin-2-yl)pyridin-2-amine derivatives containing a sulfoximine group of general formula (I) as described and defined herein, and methods for their preparation, their use for the treatment and/or prophylaxis of disorders, in particular of hyper-proliferative disorders and/or virally induced infectious diseases and/or of cardiovascular diseases. The invention further relates to intermediate compounds useful in the preparation of said compounds of general formula (I).
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COMPOSITION FOR PREVENTING OR TREATING HEART DISEASE (Fri, 09 Oct 2015)
<p id="p-0001" num="0000">The present invention relates to a composition for preventing or treating heart disease, and more particularly, to a composition for preventing or treating heart disease, comprising (+)-syringaresinol. Specifically, (+)-syringaresinol as an active ingredient may exhibit excellent effect of preventing or improving heart disease by promoting SIRT1 expression and suppressing death of cardiomyocytes induced by reactive oxygen species. Accordingly, the composition according to the present disclosure may be used to prevent, improve or treat heart diseases including cardiovascular diseases.</p>
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Human LCAT Antigen Binding Proteins and Their Use in Therapy (Fri, 09 Oct 2015)
<p id="p-0001" num="0000">Antigen binding proteins that activate LCAT are provided. Nucleic acids encoding the antigen binding proteins and vectors and cells containing such nucleic acids are also provided. The antigen binding proteins have value in therapeutic methods in which it is useful to modulate HDL particle size, increase plasma levels of HDL-C, and increase reverse cholesterol transport. Accordingly, the antigen binding proteins have utility in the treatment and prevention of atherosclerosis, various cardiovascular diseases and cholesterol-related disorders, inflammatory conditions, thrombosis-related conditions, metabolic syndrome, diabetes and insulin-resistance. The LCAT antigen binding proteins are also useful in treating the consequences, symptoms, and/or pathology associated with either genetic or acquired LCAT deficiency, including chronic kidney disease (CKD).</p>
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DISUBSTITUTED 5-FLUORO PYRIMIDINE DERIVATIVES CONTAINING A SULFONDIIMINE GROUP (Fri, 09 Oct 2015)
The present invention relates to 5-fluoro pyrimidine derivatives containing a sulfondiimine group of general formula (I) as described and defined herein, and methods for their preparation, their use for the treatment and/or prophylaxis of disorders, in particular of hyper-proliferative disorders and/or virally induced infectious diseases and/or of cardiovascular diseases. The invention further relates to intermediate compounds useful in the preparation of said compounds of general formula (I).
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IMIDAZOPYRIDINE COMPOUNDS (Thu, 08 Oct 2015)
[Problem] A pharmaceutical composition for treating or preventing various cardiovascular diseases, which have sGC activities based on improvement of cGMP signals, is provided. [Means for Solution] It was found that imidazo[1,2-a]pyridine compounds having a carbamoyl group at the 3-position and a particular cyclic group at the 8-position via a methyleneoxy group, or a salt thereof have sGC activation, and are useful as active ingredients of pharmaceutical compositions for treating or preventing various sGC-related cardiovascular diseases, in particular, peripheral arterial diseases, intermittent claudication, critical limb ischemia, hypertension, and pulmonary hypertension, thereby completing the present invention.
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INHIBITORS OF PROTEIN KINASES (Fri, 02 Oct 2015)
<p id="p-0001" num="0000">Compounds of general Formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="22.94mm" wi="69.85mm" file="US20150272947A1-20151001-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>a</sup>, A, B and x are as defined herein are inhibitors of protein kinases in particular members of the cyclin-dependent kinase family and/or the glycogen synthase kinase 3 family and are useful in preventing and/or treating any type of pain, inflammatory disorders, cancer, immunological diseases, proliferative diseases, infectious diseases, cardiovascular diseases, metabolic disorders, renal diseases, neurologic and neuropsychiatric diseases and neurodegenerative diseases.</p>
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4-CARBOXAMIDO-ISOINDOLINONE DERIVATIVES AS SELECTIVE PARP-1 INHIBITORS (Fri, 02 Oct 2015)
<p id="p-0001" num="0000">There are provided substituted 4-carboxamido-isoindolinone derivatives which selectively inhibit the activity of poly (ADP-ribose) polymerase PARP-1 with respect to poly (ADP-ribose) polymerase PARP-2. The compounds of this invention are therefore useful in treating diseases such as cancer, cardiovascular diseases, central nervous system injury and different forms of inflammation. The present invention also provides methods for preparing these compounds, pharmaceutical compositions comprising these compounds, and methods of treating diseases utilizing pharmaceutical compositions comprising these compounds.</p>
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5-FLUORO-N-(PYRIDIN-2-YL)PYRIDIN-2-AMINE DERIVATIVES CONTAINING A SULFONE GROUP (Fri, 02 Oct 2015)
<p id="p-0001" num="0000">The present invention relates to 5-fluoro-N-(pyridin-2-yl)pyridin-2-amine derivatives containing a sulfone group of general formula (I) as described and defined herein, and methods for their preparation, their use for the treatment and/or prophylaxis of disorders, in particular of hyper-proliferative disorders and/or virally induced infectious diseases and/or of cardiovascular diseases. The invention further relates to intermediate compounds useful in the preparation of said compounds of general formula (I).</p>
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N-(PYRIDIN-2-YL)PYRIMIDIN-4-AMINE DERIVATIVES CONTAINING A SULFONE GROUP (Fri, 02 Oct 2015)
<p id="p-0001" num="0000">The present invention relates to N-(pyridin-2-yl)pyrimidin-4-amine derivatives containing a sulfone group of general formula (I) as described and defined herein, and methods for their preparation, their use for the treatment and/or prophylaxis of disorders, in particular of hyper-proliferative disorders and/or virally induced infectious diseases and/or of cardiovascular diseases. The invention further relates to intermediate compounds useful in the preparation of said compounds of general formula (I).</p>
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Bioreducible Poly (Beta-Amino Ester)s For siRNA Delivery (Fri, 02 Oct 2015)
<p id="p-0001" num="0000">Degradable polymers were synthesized that self-assemble with nucleic acids, proteins, hydrophobic drugs, and other small molecules to form particles that are effective for delivery into a cell, tissue and/or organism either in vitro or in vivo. The presently disclosed polymers demonstrate differential cell-type specificity, an ability to promote endosomal escape to protect the cargos from degradation and enhance delivery to the cytoplasm, and/or bioreducibility, which enables triggered intracellular drug release to be tuned to promote optimal delivery to the target cell type. The presently disclosed materials may be used to treat a wide variety of conditions or diseases, such as cancer, cardiovascular diseases, infectious diseases, and ophthalmic diseases.</p>
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1H-Indole-3-Carboxamide Derivatives And Use Thereof As P2Y12 Antagonists (Fri, 02 Oct 2015)
<p id="p-0001" num="0000">The invention relates to compounds corresponding to formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="43.35mm" wi="42.67mm" file="US20150274703A1-20151001-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">and to the use thereof as P2Y 12 receptor antagonists for the treatment of cardiovascular diseases.</p>
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COMPOSITIONS AND METHODS FOR INHIBITING BMP (Fri, 02 Oct 2015)
The present invention provides small molecule inhibitors of BMP signaling and compositions and methods for inhibiting BMP signaling. These compounds and compositions may be used to modulate cell growth, di.fferentia.tion, proliferation, and apoptosis, and thus may be useful tor treating diseases or conditions associated with BMP signaling, including inflammation, cardiovascular disease, hematological disease, cancer, and bone disorders, as well as for modulating cellular differentiation and/or proliferation. These compounds and compositions may also be used to reduce circulating levels of ApoB- 100 or LDL and treat or prevent acquired or congenital, hypercholesterolemia or hyperlipoproteinemia; diseases, disorders, or syndromes associated with defects in lipid absorption or metabolism; or diseases, disorders, or syndromes caused by hyperlipidemia.
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FUMARATE-CO-RELEASING MOLECULE HYBRIDS, THEIR USE IN THE TREATMENT OF INFLAMMATORY OR CARDIOVASCULAR DISEASES AND THEIR PROCESS OF PREPARATION (Fri, 25 Sep 2015)
The present invention relates to hybrid fumarate-CO-releasing molecules capable of increasing heme oxygenase-1 (HO-1) activity and HO-1 protein expression and simultaneously releasing CO, their synthesis and their use in therapeutic applications, in particular their use in the treatment of inflammatory or cardiovascular diseases.
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3-AMINOCYCLOPENTANE CARBOXAMIDE DERIVATIVES (Thu, 24 Sep 2015)
Compounds of the formula (I) in which R<sp>1</sp>, R<sp>4</sp>, R, X<sp>1</sp>, X<sp>2</sp>, X<sp>3</sp>, X<sp>4</sp>, q and W have the meanings indicated in Claim 1, are inhibitors of fatty acid synthase, and can be employed, inter alia, for the treatment of diseases such as cancer, cardiovascular diseases, central nervous system injury and different forms of inflammation.
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N-(PYRIDIN-2-YL)PYRIMIDIN-4-AMINE DERIVATIVES CONTAINING A SULFOXIMINE GROUP (Thu, 24 Sep 2015)
The present invention relates to disubstituted N-(pyridin-2-yl)pyrimidin-4-amine derivatives containing a sulfoximine group of general formula (I) as described and defined herein, and methods for their preparation, their use for the treatment and/ or prophylaxis of disorders, in particular of hyper- proliferative disorders and/or virally induced infectious diseases and/or of cardiovascular diseases. The invention further relates to intermediate compounds useful in the preparation of said compounds of general formula (I).
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4-(ORTHO)-FLUOROPHENYL-5-FLUOROPYRIMIDIN-2-YL AMINES CONTAINING A SULFOXIMINE GROUP (Thu, 24 Sep 2015)
The present invention relates to 4-(ortho)-fluorophenyl-5-fluoropyrimidin-2-yl amine derivatives containing a sulfoximine group of general formula (I) as described and defined herein, and methods for their preparation, their use for the treatment and/or prophylaxis of disorders, in particular of hyper-proliferative disorders and/or virally induced infectious diseases and/or of cardiovascular diseases. The invention further relates to intermediate compounds useful in the preparation of said compounds of general formula (I).
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4-(ORTHO)-FLUOROPHENYL-5-FLUOROPYRIMIDIN-2-YL AMINES CONTAINING A SULFONE GROUP (Fri, 18 Sep 2015)
<p id="p-0001" num="0000">The present invention relates to 4-(ortho)-fluorophenyl-5-fluoropyrimidin-2-yl amine derivatives of general formula (I) as described and defined herein, and methods for their preparation, their use for the treatment and/or prophylaxis of disorders, in particular of hyper-proliferative disorders and/or virally induced infectious diseases and/or of cardiovascular diseases. The invention further relates to intermediate compounds useful in the preparation of said compounds of general formula (I).</p>
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LIPOPROTEIN ANALYSIS BY DIFFERENTIAL CHARGED-PARTICLE MOBILITY (Fri, 18 Sep 2015)
<p id="p-0001" num="0000">The invention provides methods of preparation of lipoproteins from a biological sample, including HDL, LDL, Lp(a), IDL, and VLDL, for diagnostic purposes utilizing differential charged particle mobility analysis methods. Further provided are methods for analyzing the size distribution of lipoproteins by differential charged particle mobility, which lipoproteins are prepared by methods of the invention. Further provided are methods for assessing lipid-related health risk, cardiovascular condition, risk of cardiovascular disease, and responsiveness to a therapeutic intervention, which methods utilize lipoprotein size distributions determined by methods of the invention.</p>
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SYSTEM AND METHOD FOR ASSESSING QUANITITES OR SIZES OF LIPOPROTEIN PARTICLES FROM LIPOPROTEIN PARTICLE COMPOSITIONS (Fri, 18 Sep 2015)
<p id="p-0001" num="0000">This invention relates to methods for assessing quantities of spherical or substantially spherical lipoprotein particles or portions thereof present in a biological sample based on the measurement of free cholesterol and/or phospholipid content in the lipoprotein particles. The invention also relates to the use of the assessed quantities of the lipoprotein particles or portions thereof to determine whether a subject is at increased risk for cardiovascular diseases and cardiodiabetes.</p>
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TREATMENT OF MALE ANDROGEN DEFICIENCY SYMPTOMS OR DISEASES WITH SEX STEROID PRECURSOR COMBINED WITH SERM (Fri, 18 Sep 2015)
Novel methods for prevention, reduction or elimination of the incidence of male androgen deficiency symptoms or diseases including male hypogonadism-associated symptoms and diseases associated with low serum testosterone and/or low DHEA or low total androgens in susceptible warm-blooded animals including humans involving administration of an amount of a sex steroid precursor, particularly dehydroepiandrosterone (DHEA) and a selective estrogen receptor modulator (SERM) (particularly acolbifene), an antiestrogen or a prodrug of the two. The symptoms or diseases are loss of libido, erectile dysfunction, tiredness, loss of energy, depression, bone loss, muscle loss, muscle weakness, fat accumulation, memory loss, cognition loss, Alzheimer's disease, dementia, loss of body hair, fertility problems, insomnia, gynecomastia, anemia, hot flushes, sweats, decreased sense of well-being, obesity, osteoporosis, hypercholesterolemia, hyperlipidemia, atherosclerosis, hypertension, insulin resistance, cardiovascular disease and type 2 diabetes. Pharmaceutical compositions for delivery of active ingredient(s) and kit(s) useful to the invention are also disclosed.
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CHEMICAL COMPOUNDS ACTING AS PERK INHIBITORS (Fri, 18 Sep 2015)
The invention is directed to substituted pyrrolidinone derivatives. Specifically, the invention is directed to compounds according to Formula X: wherein R41, R42, R43, R44, R45, R46, and R47 are defined herein. The compounds of the invention are inhibitors of PERK and can be useful in the treatment of cancer and diseases associated with activated unfolded protein response pathways, such as Alzheimer's disease, stroke, diabetes, Parkinson disease, Huntington's disease, Creutzfeldt- Jakob Disease, and related prion diseases, amyotrophic lateral sclerosis, myocardial infarction, neurodegeneration, cardiovascular disease, atherosclerosis, ocular diseases, and arrhythmias, more specifically cancers of the breast, colon, pancreas and lung. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting PERK activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
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5-FLUORO-N-(PYRIDIN-2-YL)PYRIDIN-2-AMINE DERIVATIVES CONTAINING A SULFONE GROUP (Fri, 18 Sep 2015)
The present invention relates to 5-fluoro-N-(pyridin-2-yl)pyridin-2-amine derivatives containing a sulfone group of general formula (I) as described and defined herein, and methods for their preparation, their use for the treatment and/or prophylaxis of disorders, in particular of hyper-proliferative disorders and/or virally induced infectious diseases and/or of cardiovascular diseases. The invention further relates to intermediate compounds useful in the preparation of said compounds of general formula (I).
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COMPOSITIONS AND METHODS FOR REDUCING CHRONIC LOW-LEVEL INFLAMMATION (Fri, 18 Sep 2015)
The invention relates to compositions and methods for reducing chronic low-level inflammation associated with chronic conditions. Specifically, the invention relates to compositions of hydrophobic derivatives of aspirin and/or hydrophobic derivatives of sesamol in combination with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and their methods for reducing chronic low-level inflammation associated with chronic conditions including obesity, metabolic syndrome, diabetes, cardiovascular disease, cancer, auto-immune disorders, ocular and neurological disorders in a mammal.
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Hydropyrrolopyrrole derivatives for use as fatty acid synthase inhibitors (Fri, 11 Sep 2015)
<p id="p-0001" num="0000">Compounds of the formula I</p> <p id="h-0001" num="0000">in which R<sup>1</sup>, R<sup>2</sup>, R, X<sup>1</sup>, X<sup>2</sup>, X<sup>3</sup>, X<sup>4</sup>, n1, n2, n3 and n4 have the meanings indicated in claim <b>1, </b></p> <p id="h-0002" num="0000">are inhibitors of Tankyrase, and can be employed, inter alia, for the treatment of diseases such as cancer, cardiovascular diseases, central nervous system injury and different forms of inflammation.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="23.20mm" wi="49.19mm" file="US09416133-20160816-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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APOPTOSIS SIGNAL-REGULATING KINASE INHIBITORS (Fri, 04 Sep 2015)
<p id="p-0001" num="0000">The present invention relates to compounds of Formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="33.27mm" wi="69.93mm" file="US20150246910A1-20150903-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">Wherein variables are as defined above. The compounds have apoptosis signal-regulating kinase (“ASK1”) inhibitory activity, and are thus useful in the treatment of ASK1-mediated conditions, including autoimmune disorders, inflammatory diseases, cardiovascular diseases, diabetes, diabetic nephropathy, cardio-renal diseases, including kidney disease, fibrotic diseases, respiratory diseases, COPD, idiopathic pulmonary fibrosis, acute lung injury, acute and chronic liver diseases, and neurodegenerative diseases.</p>
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KLF5 MODULATORS (Fri, 04 Sep 2015)
<p id="p-0001" num="0000">The invention provides potent inhibitors of small molecule inhibitors of Krüppel-like factor 5 (KLF5) expression. Compounds of the invention are small molecule inhibitors of KLF5 expression which can be effective delay or prevent colon cancer onset, halt growth of existing tumors, and/or decrease reoccurrence. The compounds can be effective vs. many tumor types whose progression is in part mediated by KLF5, including colorectal cancers. Lowering KLF5 levels with an inhibitor of this invention may also impact other disease states, including diabetes, obesity, lipid homeostasis, cardiovascular disease, and arthritis.</p>
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Benzimidazole derivatives as PI3 kinase inhibitors (Fri, 04 Sep 2015)
<p id="p-0001" num="0000">This invention relates to the use of benzimidazole derivatives for the modulation, notably the inhibition of the activity or function of the phosphoinositide 3′ OH kinase family (hereinafter PI3 kinases), suitably, PI3Kα, PI3Kδ, PI3Kβ, and/or PI3Kγ. Suitably, the present invention relates to the use of benzimidazoles in the treatment of one or more disease states selected from: autoimmune disorders, inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, allergy, asthma, pancreatitis, multiorgan failure, kidney diseases, platelet aggregation, cancer, sperm motility, transplantation rejection, graft rejection and lung injuries. More suitably, the present invention relates to PI3Kβ selective benzimidazoles compounds for treating cancer.</p>
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Cyclic nitro compounds, pharmaceutical compositions thereof and uses thereof (Fri, 04 Sep 2015)
<p id="p-0001" num="0000">The present invention provides cyclic nitro compound, pharmaceutical compositions of cyclic nitro compounds and methods of using cyclic nitro compounds and/or pharmaceutical compositions thereof to treat or prevent diseases or disorders characterized by abnormal cell proliferation, such as cancer, inflammation, cardiovascular disease and autoimmune disease.</p>
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FUSED HETEROCYCLIC COMPOUNDS AS ION CHANNEL MODULATORS (Fri, 28 Aug 2015)
<p id="p-0001" num="0000">The present disclosure relates to compounds that are sodium channel inhibitors and to their use in the treatment of various disease states, including cardiovascular diseases and diabetes. In particular embodiments, the structure of the compounds is given by Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="17.36mm" wi="55.46mm" file="US20150239904A1-20150827-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein Y, Z, n, R<sup>1 </sup>and R<sup>3 </sup>are as described herein, to methods for the preparation and use of the compounds and to pharmaceutical compositions containing the same.</p>
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Quinazolinone derivatives as PARP inhibitors (Fri, 28 Aug 2015)
<p id="p-0001" num="0000">Compounds of the formula I</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="28.96mm" wi="63.25mm" file="US09388142-20160712-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> in which R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, X<sup>1</sup>, X<sup>2 </sup>and Y have the meanings indicated in Claim <b>1</b>, are inhibitors of Tankyrase, and can be employed, inter alia, for the treatment of diseases such as cancer, cardiovascular diseases, central nervous system injury and different forms of inflammation. </p>
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Condensation product of theanine derivative and carboxylic acid coumarin derivative, its intermediate, preparation method and use thereof (Fri, 28 Aug 2015)
<p id="p-0001" num="0000">The present invention relates to a compound as represented by formula (I), which is a condensation product of a theanine derivative and a carboxylic acid coumarin derivative, compounds as represented by formula (II) and formula (III), both of which are intermediates of the condensation product, a method for preparing these compounds, a pharmaceutical composition comprising the compounds, and a use thereof in preparing a medicament for prevention and treatment of tumors, inflammation, cardiovascular diseases, immune deficiency diseases and the like.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="47.58mm" wi="69.85mm" file="US09518038-20161213-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> Wherein, </p> <p id="p-0003" num="0000"> <tables id="TABLE-US-00001" num="00001"> <table frame="none" colsep="0" rowsep="0"> <tgroup align="left" colsep="0" rowsep="0" cols="5"> <colspec colname="offset" colwidth="14pt" align="left"/> <colspec colname="1" colwidth="42pt" align="left"/> <colspec colname="2" colwidth="63pt" align="left"/> <colspec colname="3" colwidth="56pt" align="left"/> <colspec colname="4" colwidth="42pt" align="left"/> <thead> <row> <entry/> <entry namest="offset" nameend="4" align="center" rowsep="1"/> </row> </thead> <tbody valign="top"> <row> <entry/> <entry>(Ia)</entry> <entry>R═CH<sub>3</sub></entry> <entry>R<sub>1</sub>═H</entry> <entry>R<sub>2</sub>═H</entry> </row> <row> <entry/> <entry>(Ib)</entry> <entry>R═CH<sub>2</sub>CH<sub>3</sub></entry> <entry>R<sub>1</sub>═H</entry> <entry>R<sub>2</sub>═H</entry> </row> <row> <entry/> <entry>(Ic)</entry> <entry>R═CH<sub>2</sub>CH<sub>3</sub></entry> <entry>R<sub>1</sub>═Cl</entry> <entry>R<sub>2</sub>═H</entry> </row> <row> <entry/> <entry>(Id)</entry> <entry>R═CH<sub>2</sub>CH<sub>3</sub></entry> <entry>R<sub>1</sub>═Br</entry> <entry>R<sub>2</sub>═H</entry> </row> <row> <entry/> <entry>(Ie)</entry> <entry>R═CH<sub>2</sub>CH<sub>3</sub></entry> <entry>R<sub>1</sub>═F</entry> <entry>R<sub>2</sub>═H</entry> </row> <row> <entry/> <entry>(If)</entry> <entry>R═CH<sub>2</sub>CH<sub>3</sub></entry> <entry>R<sub>1</sub>═NO<sub>2</sub></entry> <entry>R<sub>2</sub>═H</entry> </row> <row> <entry/> <entry>(Ig)</entry> <entry>R═CH<sub>2</sub>CH<sub>3</sub></entry> <entry>R<sub>1</sub>═Cl</entry> <entry>R<sub>2</sub>═Cl</entry> </row> <row> <entry/> <entry>(Ih)</entry> <entry>R═CH<sub>2</sub>CH<sub>3</sub></entry> <entry>R<sub>1</sub>═Br</entry> <entry>R<sub>2</sub>═Br</entry> </row> <row> <entry/> <entry>(Ii)</entry> <entry>R═CH<sub>2</sub>CH<sub>3</sub></entry> <entry>R<sub>1</sub>═NH<sub>2</sub></entry> <entry>R<sub>2</sub>═H</entry> </row> <row> <entry/> <entry namest="offset" nameend="4" align="center" rowsep="1"/> </row> </tbody> </tgroup> </table> </tables> </p> <p id="p-0004" num="0000"><chemistry id="CHEM-US-00002" num="00002"> <img id="EMI-C00002" he="19.39mm" wi="69.85mm" file="US09518038-20161213-C00002.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> Wherein, </p> <p id="p-0005" num="0000"> <tables id="TABLE-US-00002" num="00002"> <table frame="none" colsep="0" rowsep="0"> <tgroup align="left" colsep="0" rowsep="0" cols="3"> <colspec colname="offset" colwidth="49pt" align="left"/> <colspec colname="1" colwidth="77pt" align="left"/> <colspec colname="2" colwidth="91pt" align="left"/> <thead> <row> <entry/> <entry namest="offset" nameend="2" align="center" rowsep="1"/> </row> </thead> <tbody valign="top"> <row> <entry/> <entry>(IIa)</entry> <entry>R═CH<sub>3</sub></entry> </row> <row> <entry/> <entry>(IIb)</entry> <entry>R═CH<sub>2</sub>CH<sub>3</sub></entry> </row> <row> <entry/> <entry namest="offset" nameend="2" align="center" rowsep="1"/> </row> </tbody> </tgroup> </table> </tables> </p> <p id="p-0006" num="0000"><chemistry id="CHEM-US-00003" num="00003"> <img id="EMI-C00003" he="27.86mm" wi="69.85mm" file="US09518038-20161213-C00003.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> Wherein, </p> <p id="p-0007" num="0000"> <tables id="TABLE-US-00003" num="00003"> <table frame="none" colsep="0" rowsep="0"> <tgroup align="left" colsep="0" rowsep="0" cols="4"> <colspec colname="offset" colwidth="28pt" align="left"/> <colspec colname="1" colwidth="56pt" align="left"/> <colspec colname="2" colwidth="70pt" align="left"/> <colspec colname="3" colwidth="63pt" align="left"/> <thead> <row> <entry/> <entry namest="offset" nameend="3" align="center" rowsep="1"/> </row> </thead> <tbody valign="top"> <row> <entry/> <entry>(IIIc)</entry> <entry>R<sub>1</sub>═Cl</entry> <entry>R<sub>2</sub>═H</entry> </row> <row> <entry/> <entry>(IIId)</entry> <entry>R<sub>1</sub>═Br</entry> <entry>R<sub>2</sub>═H</entry> </row> <row> <entry/> <entry>(IIIe)</entry> <entry>R<sub>1</sub>═F</entry> <entry>R<sub>2</sub>═H</entry> </row> <row> <entry/> <entry>(IIIf)</entry> <entry>R<sub>1</sub>═NO<sub>2</sub></entry> <entry>R<sub>2</sub>═H</entry> </row> <row> <entry/> <entry>(IIIg)</entry> <entry>R<sub>1</sub>═Cl</entry> <entry>R<sub>2</sub>═Cl</entry> </row> <row> <entry/> <entry>(IIIh)</entry> <entry>R<sub>1</sub>═Br</entry> <entry>R<sub>2</sub>═Br</entry> </row> <row> <entry/> <entry namest="offset" nameend="3" align="center" rowsep="1"/> </row> </tbody> </tgroup> </table> </tables> </p>
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N-(PYRIDIN-2-YL)PYRIMIDIN-4-AMINE DERIVATIVES CONTAINING A SULFONE GROUP (Thu, 27 Aug 2015)
The present invention relates to N-(pyridin-2-yl)pyrimidin-4-amine derivatives containing a sulfone group of general formula (I) as described and defined herein, and methods for their preparation, their use for the treatment and/or prophylaxis of disorders, in particular of hyper-proliferative disorders and/or virally induced infectious diseases and/or of cardiovascular diseases. The invention further relates to intermediate compounds useful in the preparation of said compounds of general formula (I).
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5-FLUORO-N-(PYRIDIN-2-YL)PYRIDIN-2-AMINE DERIVATIVES CONTAINING A SULFONE GROUP (Thu, 27 Aug 2015)
The present invention relates to 5-fluoro-N-(pyridin-2-yl)pyridin-2-amine derivatives containing a sulfone group of general formula (I) as described and defined herein, and methods for their preparation, their use for the treatment and/or prophylaxis of disorders, in particular of hyper-proliferative disorders and/or virally induced infectious diseases and/or of cardiovascular diseases. The invention further relates to intermediate compounds useful in the preparation of said compounds of general formula (I).
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Imidazopyridine compounds (Fri, 21 Aug 2015)
<p id="p-0001" num="0000">[Problem]</p> <p id="p-0002" num="0000">A pharmaceutical composition for treating or preventing various cardiovascular diseases, which have sGC activities based on improvement of cGMP signals, is provided.</p> <p id="p-0003" num="0000">[Means for Solution]</p> <p id="p-0004" num="0000">It was found that imidazo[1,2-a]pyridine compounds having a carbamoyl group at the 3-position and a particular cyclic group at the 8-position via a methyleneoxy group, or a salt thereof have sGC activation, and are useful as active ingredients of pharmaceutical compositions for treating or preventing various sGC-related cardiovascular diseases, in particular, peripheral arterial diseases, intermittent claudication, critical limb ischemia, hypertension, and pulmonary hypertension, thereby completing the present invention.</p>
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KETOHEXOKINASE (KHK) IRNA COMPOSITIONS AND METHODS OF USE THEREOF (Fri, 21 Aug 2015)
The present invention relates to RNAi agents, e.g., double- stranded RNAi agents, targeting the ketohexokinase (KHK) gene, and methods of using such RNAi agents to inhibit expression of KHK and methods of treating subjects having a KHK-associated disorder, e.g., liver disease (e.g., fatty liver, steatohepatitis), dyslipidemia (e.g., hyperlipidemia, high LDL cholesterol, low HDL cholesterol, hypertriglyceridemia, postprandial hypertriglyceridemia), disorders of glycemic control (e.g., insulin resistance, diabetes), cardiovascular disease (e.g., hypertension, endothelial cell dysfunction), kidney disease (e.g., acute kidney disorder, tubular dysfunction, proinflammatory changes to the proximal tubules), metabolic syndrome, adipocyte dysfunction, visceral adipose deposition, obesity, hyperuricemia, gout, eating disorders, and excessive sugar craving.
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Diazeniumdiolate heterocyclic derivatives (Wed, 19 Aug 2015)
<p id="p-0001" num="0000">A compound having the structure: useful for treating hypertension, Pulmonary Arterial Hypertension (PAH), congestive heart failure, conditions resulting from excessive water retention, cardiovascular disease, diabetes, oxidative stress, endothelial dysfunction, cirrhosis, pre-eclampsia, osteoporosis or nephropathy.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="19.47mm" wi="57.32mm" file="US09108920-20150818-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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COMBINATIONS WITH A BACKBONE-CYCLIZED PEPTIDE (Fri, 14 Aug 2015)
<p id="p-0001" num="0000">A novel combination comprising a β-hairpin peptidomimetic of the formula cyclo(-Thr-Trp-Ile-Dab-Orn-<sup>D</sup>Dab-Dab-Trp-Dab-Dab-Ala-Ser-<sup>D</sup>Pro-Pro) (I), and a further compound with antibiotic activity, that enable therapeutic control of specific bacterial infections in human or animals at doses of the individual compounds lower than either of the compounds administered alone. The combination can be used as a medicament to treat e.g. skin or soft tissue infections; eye, ear, blood stream, or intra-abdominal infections; infections related to respiratory diseases, to bone diseases, to cardiovascular diseases, to genitourinal diseases, or to gastrointestinal diseases.</p>
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COMPOSITIONS AND METHODS COMPRISING C16:1n7-PALMITOLEATE (Fri, 14 Aug 2015)
<p id="p-0001" num="0000">One embodiment described herein is related to methods and compositions, such as nutraceutical formulations and dietary supplements, comprising C16:1n7-palmitoleate or derivatives thereof. The methods and compositions comprising C16:1n7-palmitoleate, or derivatives thereof, safely and effectively prevent or mitigate manifestations of cardiovascular disease, including coronary artery disease and the accumulation of cholesterol or lipid deposits in the blood vessels of a subject.</p>
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COMPOSITIONS AND METHODS TO INHIBIT EZH2 FOR THE TREATMENT OF CARDIOVASCULAR DISEASES (Fri, 14 Aug 2015)
The present invention relates to compositions and methods for treatment and/or prevention of a cardiovascular disease. In one embodiment, the invention provides compositions and methods for decreasing one or more of the level, production, and activity of EZH2.
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AMINOTRIAZOLE- AND AMINOTETRAZOLE-BASED KDM1A INHIBITORS AS EPIGENETIC MODULATORS (Fri, 14 Aug 2015)
In some aspects, the present invention provides compounds of the formula (IV), wherein the variables are as defined herein, which may be used as inhibitors of histone demethylase or spermine oxidase. Also provided herein are pharmaceutical compositions of the compounds and methods using the compounds in the treatment of diseases such as cancer and cardiovascular disease.
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N-arylaminomethylene benzothiophenones for treatment of cardiovascular disease (Wed, 12 Aug 2015)
<p id="p-0001" num="0000">The invention relates to N-arylaminomethylenebenzothiophenones of General Formula (I) for use as a drug for the treatment of cardiovascular diseases:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="16.17mm" wi="34.46mm" file="US09102667-20150811-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein E is S, O, or CH<sub>2</sub>, D is CH or NH, and Ar is a phenyl or naphtyl moiety substituted by an electron-withdrawing group, an unsubstituted heteroaryl residue, or a heteroaryl residue substituted by alkyl or an electron-withdrawing group. </p>
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COMBINATIONS WITH A BACKBONE-CYCLIZED PEPTIDE (Fri, 07 Aug 2015)
<p id="p-0001" num="0000">A novel combination comprising a β-hairpin peptidomimetic of the formula cyclo(-Thr-Trp-Ile-Dab-Orn-<sup>D</sup>Dab-Dab-Trp-Dab-Dab-Ala-Ser-<sup>D</sup>Pro-Pro) (I), and a compound of the glycylcycline class, especially tigecycline, that enable therapeutic control of specific bacterial infections in human or animals at doses of the individual compounds lower than either of the compounds administered alone. The combination can be used as a medicament to treat e.g. skin or soft tissue infections; eye, ear, blood stream, or intra-abdominal infections; infections related to respiratory diseases, to bone diseases, to cardiovascular diseases, to genitourinal diseases, or to gastrointestinal diseases.</p>
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DIHYDROPTERIDINONE DERIVATIVES AND USES THEREOF (Fri, 07 Aug 2015)
The present invention provides compounds of Formula (I), and pharmaceutically compositions thereof. Compounds of Formula (I) are binders of bromodomains and/or bromodomain-containing proteins (e.g., bromo and extra terminal (BET) proteins). Also provided are methods, uses, and kits using the compounds and pharmaceutical compositions for inhibiting the activity (e.g., increased activity) of bromodomains and/or bromodomain- containing proteins and for treating and/or preventing in a subject diseases associated with bromodomains or bromodomain-containing proteins (e.g., proliferative diseases, cardiovascular diseases, viral infections, fibrotic diseases, metabolic diseases, endocrine diseases, and radiation poisoning). The compounds, pharmaceutical compositions, and kits are also useful for male contraception.
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DIAMINOPYRIMIDINE BENZENESULFONE DERIVATIVES AND USES THEREOF (Fri, 07 Aug 2015)
The present invention provides compounds of Formula (II) (e.g., compounds of Formula (I)), and pharmaceutically compositions thereof. Compounds of Formula (II) are believed to be binders of bromodomains and/or bromodomain-containing proteins (e.g., bromo and extra terminal (BET) proteins). Also provided are methods, uses, and kits using the compounds and pharmaceutical compositions for inhibiting the activity (e.g., increased activity) of bromodomains and/or bromodomain-containing proteins and for treating and/or preventing in a subject diseases associated with bromodomains or bromodomain-containing proteins (e.g., proliferative diseases, cardiovascular diseases, viral infections, fibrotic diseases, metabolic diseases, endocrine diseases, and radiation poisoning). The compounds, pharmaceutical compositions, and kits are also useful for male contraception.
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DIAZEPANE DERIVATIVES AND USES THEREOF (Fri, 07 Aug 2015)
The present invention provides compounds of any one of Formulae (I), (II-C) (e.g., Formula (II)), and (III), and pharmaceutically compositions thereof. Compounds of any one of Formulae (I), (II-C), and (III) are believed to be binders of bromodomains and/or bromodomain-containing proteins (e.g., bromo and extra terminal (BET) proteins). Also provided are methods, uses, and kits using the compounds and pharmaceutical compositions for inhibiting the activity (e.g., increased activity) of bromodomains and/or bromodomain- containing proteins and for treating and/or preventing in a subject diseases associated with bromodomains or bromodomain-containing proteins (e.g., proliferative diseases, cardiovascular diseases, viral infections, fibrotic diseases, metabolic diseases, endocrine diseases, and radiation poisoning). The compounds, pharmaceutical compositions, and kits are also useful for male contraception.
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USES OF DIAZEPANE DERIVATIVES (Fri, 07 Aug 2015)
The present invention provides compounds of Formula (II) (e.g., compounds of Formula (I)), and pharmaceutically compositions thereof. Compounds of Formula (II) are believed to be binders of bromodomains and/or bromodomain-containing proteins (e.g., bromo and extra terminal (BET) proteins). Also provided are methods, uses, and kits using the compounds and pharmaceutical compositions for inhibiting the activity (e.g., increased activity) of bromodomains and/or bromodomain-containing proteins and for treating and/or preventing in a subject diseases associated with bromodomains or bromodomain-containing proteins (e.g., proliferative diseases, cardiovascular diseases, viral infections, fibrotic diseases, metabolic diseases, endocrine diseases, and radiation poisoning). The compounds, pharmaceutical compositions, and kits are also useful for male contraception.
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CONDENSATION PRODUCT OF THEANINE DERIVATIVE AND CARBOXYLIC ACID COUMARIN DERIVATIVE, INTERMEDIATE OF THE CONDENSATION PRODUCT, METHOD FOR PREPARING SAME, AND USE THEREOF (Thu, 06 Aug 2015)
The present invention relates to a compound as represented by formula (I), which is a condensation product of a theanine derivative and a carboxylic acid coumarin derivative, compounds as represented by formula (II) and formula (III), both of which are intermediates of the condensation product, a method for preparing these compounds, a pharmaceutical composition comprising the compounds, and a use thereof in preparing a medicament for prevention and treatment of tumors, inflammation, cardiovascular diseases, immune deficiency diseases and the like. Wherein, Wherein, Wherein.
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(AZA-)isoquinolinone derivatives (Fri, 31 Jul 2015)
<p id="p-0001" num="0000">Compounds of the formula I</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="24.72mm" wi="63.84mm" file="US09376433-20160628-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> in which R<sup>1</sup>, X, Y and n have the meanings indicated in claim <b>1,</b> are inhibitors of Tankyrase, and can be employed, inter alia, for the treatment of diseases such as cancer, cardiovascular diseases, central nervous system injury and different forms of inflammation. </p>
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BENZOIMIDAZOLE-CARBOXYLIC ACID AMIDE DERIVATIVES FOR TREATING METABOLIC OR CARDIOVASCULAR DISEASES (Thu, 30 Jul 2015)
The present invention relates to benzoimidazole-carboxylic acid amide compounds of the formula I, in which R', R", R"', R<sp>1</sp>, R<sp>2</sp>, R<sp>3</sp>, R<sp>4</sp>, R<sp>5</sp>, R<sp>6</sp> and Z are defined as indicated below. The compounds of the formula I are APJ receptor modulators, and are useful for the treatment of diseases associated with increased blood pressure for example. The invention furthermore relates to the use of compounds of the formula I, in particular as active ingredients in pharmaceuticals, and pharmaceutical compositions comprising them.
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Diagnostic method of cardiovascular disease (Fri, 17 Jul 2015)
<p id="p-0001" num="0000">Biological metabolites LysoPC (18:0), LysoPC (20:3), fatty acid (16:1), fatty acid (18:0), fatty acid (18:1), fatty acid (18:2) and fatty acid (22:6) according to the present disclosure allow for simple and accurate diagnosis of a cardiovascular disease since their level in the blood of a subject increases or decreases if the subject has a cardiovascular disease such as myocardial infarction or angina. In addition, whereas the existing biomarkers can diagnose only whether myocardial infarction occurs or not, the biological metabolites according to the present disclosure can diagnose not only myocardial infarction but also unstable angina occurring prior to the onset of myocardial infarction stage by stage.</p>
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