Cardiovascular diseases

COMPOUNDS AND THEIR USE AS BACE1 INHIBITORS (Fri, 20 Jul 2018)
<p id="p-0001" num="0000">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), R<sup>2</sup>, R<sup>3</sup>, R<sup>4</sup>, R<sup>5 </sup>and R<sup>6</sup>, 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).</p>
>> Read More

NITRIC OXIDE-RELEASING PRODRUG MOLECULE (Thu, 19 Jul 2018)
Provided are a type of compounds that can be used for treating cardiovascular diseases and compositions containing the compounds. The compounds and the compositions can improve lipid metabolism disorders by increasing high-density lipoprotein cholesterol in blood; in addition, the compounds and the compositions can also release nitric oxide, and reduce the onset risk of cardiovascular diseases by means of relaxing blood vessels, lowering blood pressure, inhibiting platelet adhesion and aggregation and maintaining vascular tension, and thus play an important role in preventing and treating the occurrence and development of cardiovascular diseases.
>> Read More

DETECTION OF TRANSIENT TROPONIN PEAKS FOR DIAGNOSIS OF SUBJECTS AT HIGH RISK OF CARDIOVASCULAR DISEASE (Fri, 13 Jul 2018)
The present invention provides a method to assess troponin peaks in a subject to estimate CHD risk, said method comprising a) fine-temporal serial testing in body fluid samples obtained from the subject the concentration of troponin; b) assessment of troponin peaks in a subject, wherein preferably an accumulative peak score is computed, and whereby peak height and peak frequency are indicative for the risk of CHD in the subject; c) the troponin peaks are assessed and corresponding CHD risk computed in an ongoing fashion; d) a clinical algorithm is used to determine an increased CHD risk in the subject. The present invention also provides a method to use above method to select a suitable therapy against CHD for the subject, to monitor treatment effectiveness and to guide treatment course in a subject. In an alternative, the assessment of troponin peaks will be performed in combination with the assessment of NT-proBNP peaks to estimate CHD risk.
>> Read More

DIMERS OF COVALENT NFKB INHIBITORS (Fri, 29 Jun 2018)
Provided herein are compounds and methods for modulating the NFĸB pathway. More particularly, provided are inhibitors of the NFĸB pathway and the uses of such inhibitors in regulating diseases and disorders, e.g., to treat cancer, autoimmune diseases, inflammatory diseases, diabetes, cardiovascular diseases, or neurological diseases.
>> Read More

PREPARATION OF THE NON-CRYSTALLINE FORM OF OBETICHOLIC ACID (Thu, 21 Jun 2018)
The present invention relates to obeticholic acid: 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.
>> Read More

Tricyclic Derivative Compound, Method for Preparing Same, and Pharmaceutical Composition Comprising Same (Fri, 15 Jun 2018)
<p id="p-0001" num="0000">The present invention relates to novel tricyclic derivative compounds, and more specifically to tricyclic derivative compounds, optical isomers thereof, racemates thereof, or pharmaceutically acceptable salts thereof, which have excellent activity against PARP-1, tankyrase-1 or tankyrase-2. The tricyclic derivative compounds, optical isomers thereof, racemates thereof or pharmaceutically acceptable salts thereof according to the present invention have inhibitory activity against PARP-1, tankyrase-1, or tankyrase-2, and thus can be effectively used for the prevention or treatment of neuropathic pain, neurodegenerative diseases, cardiovascular diseases, diabetic neuropathy, inflammatory diseases, osteoporosis, or cancer.</p>
>> Read More

NOVEL DGAT2 INHIBITORS (Fri, 15 Jun 2018)
<p id="p-0001" num="0000">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.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="35.64mm" wi="66.72mm" file="US20180162825A1-20180614-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

QUINAZOLINONES AND AZAQUINAZOLINONES AS UBIQUITIN-SPECIFIC PROTEASE 7 INHIBITORS (Fri, 15 Jun 2018)
<p id="p-0001" num="0000">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:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.26mm" wi="65.19mm" file="US20180162835A1-20180614-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>4′</sub>, X<sub>1</sub>, Y<sub>1</sub>, Y<sub>2</sub>, Y<sub>3</sub>, Y<sub>4</sub>, n, and m are described herein.</p>
>> Read More

SYNTHETIC TRITERPENOIDS AND METHODS OF USE IN THE TREATMENT OF DISEASE (Fri, 15 Jun 2018)
<p id="p-0001" num="0000">The present invention concerns methods for treating and preventing renal/kidney disease, insulin resistance/diabetes, fatty liver disease, and/or endothelial dysfunction/cardiovascular disease using synthetic triterpenoids, optionally in combination with a second treatment or prophylaxis.</p>
>> Read More

SULFONAMIDES AS INHIBITORS OF THE UPTAKE OF EXTRACELLULAR CITRATE (Fri, 15 Jun 2018)
Sulfonamides of formula (I), wherein A, R1, and R2 are as defined in the specification and the claims, can be used as medicaments for the treatment of metabolic and/or cardiovascular diseases.
>> Read More

COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS FOR MODULATING SGK ACTIVITY, AND METHODS THEREOF (Fri, 15 Jun 2018)
The invention provides novel chemical compounds useful for treating one or more of autoimmune diseases, cancer, cardiovascular diseases, inflammatory diseases and diabetes, or a related disease or disorder thereof, and pharmaceutical composition and methods of preparation and use thereof.
>> Read More

RNA-CODED BISPECIFIC ANTIBODY (Thu, 07 Jun 2018)
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.
>> Read More

1,3,4-OXADIAZOLE AMIDE DERIVATIVE COMPOUND AS HISTONE DEACETYLASE 6 INHIBITOR, AND PHARMACEUTICAL COMPOSITION CONTAINING SAME (Thu, 07 Jun 2018)
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 6 (HDAC6) 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.
>> Read More

LIPOPROTEIN ANALYSIS BY DIFFERENTIAL CHARGED-PARTICLE MOBILITY (Thu, 07 Jun 2018)
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.
>> Read More

CHOLIC ACID DERIVATIVE, AND PREPARATION METHOD AND MEDICAL USE THEREOF (Fri, 01 Jun 2018)
<p id="p-0001" num="0000">The present invention relates to a cholic acid derivative, and a preparation method and a medical use thereof. In particular, the present invention relates to a cholic acid derivative of formula (I), a stereoisomer, or a pharmaceutically acceptable salt thereof. The series of compounds can be used to treat FXR mediated diseases, including cardiovascular disease, atherosclerosis, arteriosclerosis, hypercholesterolemia, hyperlipidemia and chronic hepatitis diseases, chronic liver diseases, gastrointestinal diseases, nephrosis, heart vascular diseases, metabolic diseases, cancer (for example colorectal cancer) or neurological diseases, such as strokes and other diseases, with a wide range of medical applications, and are expected to develop into a new generation of FXR agonists.</p>
>> Read More

SUBSTITUTED BICYCLE HETEROCYCLIC DERIVATIVES USEFUL AS ROMK CHANNEL INHIBITORS (Fri, 25 May 2018)
Disclosed are compounds of Formula (I) or a salt thereof, wherein R1 is (II) or (III); each W is independently NR1b or O; Z is a bond or CHR1d; and R1, R2, Rd, R3, L1, L2, R1a, R1b, R1c, and n are define herein. Also disclosed are methods of using such compounds as inhibitors of ROMK, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating cardiovascular diseases.
>> Read More

PHARMACEUTICAL COMPOSITIONS COMPRISING NITROXYL DONORS (Fri, 25 May 2018)
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.
>> Read More

NITRITE SALTS OF 1, 1-DIMETHYLBIGUANIDE, PHARMACEUTICAL COMPOSITIONS, AND METHODS OF USE (Fri, 18 May 2018)
Provided herein are nitrite salts of 1,1-dimethylbiguanide; and isotopic variants thereof; and pharmaceutically acceptable hydrates and solvates thereof. Also provided herein are their pharmaceutical compositions and methods of use for treating, preventing, or ameliorating one or more symptoms of diseases associated with and/or caused by an abnormal blood glucose level. Further provided herein are methods of their use for treating, preventing, or ameliorating one or more symptoms of a cardiovascular disease.
>> Read More

METHYLGLYOXAL-SCAVENGING CYCLIC PEPTIDES AND THEIR USE FOR THE PREVENTION AND TREATMENT OF DISEASES ASSOCIATED WITH ELEVATED METHYLGLYOXAL LEVELS (Fri, 18 May 2018)
The present invention relates to cyclic peptide compounds which inhibit or antagonize the binding of methylglyoxal (MG) and/or other reactive carbonyl species (RCS) to an arginine-or lysine- containing protein. Preferred scavenger compounds are said cyclic peptides comprising a specific amino acid motif and a hydrophobic modification, and pharmaceutical compositions thereof. The present invention furthermore relates to the use of the cyclic peptides as scavenger or antagonists of methylglyoxal and/or related reactive carbonyl species (RCS). The present invention furthermore relates to the use of the cyclic peptides for the prevention and/or treatment of a disease caused by or associated with methylglyoxal (MG) and/or reactive carbonyl species (RCS), in particular caused by or associated with elevated MG levels, such as diabetes and its associated complications, cardiovascular diseases and obesity.
>> Read More

P2X7 MODULATORS (Thu, 17 May 2018)
The present invention is directed to a compound of Formula (I) or (la). The invention also relates to pharmaceutical compositions comprising compounds of Formula (I) or (la) and methods comprising administering of compounds of Formula (I) or (la) 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 neuroimmune 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, Glomemlonephritis, skeletal disorders, osteoporosis, osteopetrosis, and glaucoma, interstitial cystitis, cough, ureteric obstruction, sepsis, Amyotrophic Lateral Sclerosis, Chaga's Disease, chlamydia, neuroblastoma, Tuberculosis, and migraine.
>> Read More

NOVEL COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF INFLAMMATORY DISORDERS (Fri, 11 May 2018)
<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="50.46mm" wi="69.85mm" file="US20180127425A1-20180510-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>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.</li> </ul> </li> </ul> </p>
>> Read More

NITRITE SALTS OF 1,1-DIMETHYLBIGUANIDE, PHARMACEUTICAL COMPOSITIONS, AND METHODS OF USE (Fri, 11 May 2018)
<p id="p-0001" num="0000">Provided herein are nitrite salts of 1,1-dimethylbiguanide; and isotopic variants thereof; and pharmaceutically acceptable hydrates and solvates thereof. Also provided herein are their pharmaceutical compositions and methods of use for treating, preventing, or ameliorating one or more symptoms of diseases associated with and/or caused by an abnormal blood glucose level. Further provided herein are methods of their use for treating, preventing, or ameliorating one or more symptoms of a cardiovascular disease.</p>
>> Read More

MODULATORS OF FARNESOID X RECEPTOR AND METHODS FOR THE USE THEREOF (Fri, 04 May 2018)
<p id="p-0001" num="0000">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.</p>
>> Read More

3-AMINO ALKYLATED INDOLE DERIVATIVE, METHOD FOR THE PREPARATION THEREOF, AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME (Fri, 04 May 2018)
The present invention relates to a compound represented by Chemical Formula 1, or a pharmaceutically acceptable salt thereof. The compound according to the present invention can be usefully used for the prevention or treatment of cardiovascular diseases.
>> Read More

PHENYL PHTHALAZINE DERIVATIVE, METHOD FOR THE PREPARATION THEREOF, AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME (Fri, 04 May 2018)
The present invention relates to a compound represented by Chemical Formula 1, or a pharmaceutically acceptable salt thereof. The compound according to the present invention can be usefully used for the prevention or treatment of cardiovascular diseases.
>> Read More

HYPERPOLARIZED [3- 13C]ACETOACETATE AND METHODS OF USING THE SAME (Fri, 04 May 2018)
The present invention relates to hyperpolarized [3-13C]acetoacetate. Provided are [3-13C]acetoacetate and compositions comprising said [3-13C]acetoacetate. Further provided are methods of preparing and using hyperpolarized [3- 13C]acetoacetate in the determination of the spatial and temporal distribution and metabolism of [3-13C]acetoacetate and/or its metabolites in a cell or subject, preferably by magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and/or magnetic resonance spectroscopic imaging (MRSI), whereby conditions, diseases, or disorders associated with the metabolism of acetoacetate and/or other ketone bodies can be diagnosed. The conditions, diseases, or disorders to be diagnosed preferably are cancer, diabetes, cardiovascular diseases, or neurodegenerative diseases.
>> Read More

CARBOHYDRATE-FUNCTIONALIZED NANOPARTICLES AND USES THEREOF (Fri, 04 May 2018)
The present disclosure relates to carbohydrate-functionalized nanoparticles and methods of treating cardiovascular disease (for example, atherosclerosis).
>> Read More

USE OF CD24 FOR LOWERING LOW-DENSITY LIPOPROTEIN CHOLESTEROL LEVELS (Fri, 27 Apr 2018)
<p id="p-0001" num="0000">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.</p>
>> Read More

HYDROXYALKYL-SUBSTITUTED TRIAZOLE DERIVATIVES AND USES THEREOF (Fri, 27 Apr 2018)
The present invention relates to novel 3-(hydroxyalkyl)-1,2,4-triazole derivatives, to processes for the preparation of such compounds, to pharmaceutical compositions containing such compounds, and to the use of such compounds or compositions for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of renal and/or cardiovascular diseases.
>> Read More

TRICYCLIC DERIVATIVE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL COMPOSITION COMPRISING SAME (Thu, 26 Apr 2018)
The present invention relates to novel tricyclic derivative compounds, and more specifically to tricyclic derivative compounds, optical isomers thereof, racemates thereof, or pharmaceutically acceptable salts thereof, which have excellent activity against PARP-1, tankyrase-1 or tankyrase-2. The tricyclic derivative compounds, optical isomers thereof, racemates thereof or pharmaceutically acceptable salts thereof according to the present invention have inhibitory activity against PARP-1, tankyrase-1, or tankyrase-2, and thus can be effectively used for the prevention or treatment of neuropathic pain, neurodegenerative diseases, cardiovascular diseases, diabetic neuropathy, inflammatory diseases, osteoporosis, or cancer.
>> Read More

COMPOUNDS FOR THE PREVENTION AND TREATMENT OF CARDIOVASCULAR DISEASES (Fri, 20 Apr 2018)
<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>
>> Read More

NOVEL CYCLOSPORIN DERIVATIVES AND USES THEREOF (Fri, 20 Apr 2018)
<p id="p-0001" num="0000">The present invention relates to a compound of the Formula (I)):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="44.11mm" wi="75.69mm" file="US20180105558A1-20180419-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">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>
>> Read More

METHOD FOR DETERMINING RISKS ASSOCIATED WITH CARDIOVASCULAR DISEASES (Fri, 06 Apr 2018)
The present invention relates to a novel method for determining risk of cardiovascular diseases comprising detecting of MMP-8 and CRP in a sample, and comparing the detected amounts with respective predetermined values of MMP-8 and CRP, wherein the detection of elevated levels of MMP-8 and CRP is indicative of presence or risk of cardiovascular event or disease. The present invention relates also to the use of detection of MMP-8 and CRP for predicting a risk for getting a cardiovascular event, for monitoring the effect of therapy on cardiovascular event or on cardiovascular disease, or for detecting the presence of a subclinical cardiovascular disease. Also, a method for constructing a risk prediction model for a presence of CVD disease or a risk of CVD events is presented.
>> Read More

SUBSTITUTED N-(1H-INDAZOL-4-YL)IMIDAZO[1,2-a]PYRIDINE-3-CARBOXAMIDE COMPOUNDS AS TYPE III RECEPTOR TYROSINE KINASE INHIBITORS (Fri, 06 Apr 2018)
[007801 Compounds of Formula I: and pharmaceutically acceptable salts thereof in which R', R2, R, R4, R5 and R6 have the meanings given in the specification, are inhibitors of cFMS and are useful in the treatment of fibrosis, bone-related diseases, cancer, autoimmune disorders, inflammatory diseases, cardiovascular diseases, pain and burns in a mammal.
>> Read More

CYCLIC NITRO COMPOUNDS, PHARMACEUTICAL COMPOSITIONS THEREOF AND USES THEREOF (Fri, 30 Mar 2018)
<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>
>> Read More

SUBSTITUTED N-(lH-INDAZOL-4-YL)IMIDAZO[l,2-a]PYRIDINE-3-CARBOXAMIDE COMPOUNDS AS TYPE III RECEPTOR TYROSINE KINASE INHIBITORS (Fri, 30 Mar 2018)
<p id="p-0001" num="0000">Compounds of Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="42.42mm" wi="63.84mm" file="US20180086758A1-20180329-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">and pharmaceutically acceptable salts thereof in which R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4</sup>, R<sup>5 </sup>and R<sup>6 </sup>have the meanings given in the specification, are inhibitors of cFMS and are useful in the treatment of fibrosis, bone-related diseases, cancer, autoimmune disorders, inflammatory diseases, cardiovascular diseases, pain and burns in a mammal.</p>
>> Read More

SUBSTITUTED 1-METHYL-1,2,3,4-TETRAHYDROISOQUINOLINE MOLECULES AS PCSK9 ALLOSTERIC BINDERS (Fri, 30 Mar 2018)
The present invention relates to PCSK9 allosteric binding compounds of Formula I: (Formula (I)) and pharmaceutically acceptable salts thereof, wherein X1, X2, Y, R1, R2, RA, RB and n are as defined herein. The present invention also relates to compositions which comprise an allosteric binding compound of the invention or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. The invention further relates, inter alia, to methods for inducing PCSK9 protein degradation in a subject, and methods for treating atherosclerosis, hypercholesterolemia, coronary heart disease, metabolic syndrome, acute coronary syndrome, or related cardiovascular disease and cardiometabolic conditions, comprising administering to a subject an effective amount of a compound or a pharmaceutically acceptable salt of the invention. The invention also provides a means for the in vitro labeling, detection and/or quantification of PCSK9 in biological samples.
>> Read More

ANTI-PCSK9 COMPOUNDS AND METHODS FOR THE TREATMENT AND/OR PREVENTION OF CARDIOVASCULAR DISEASES (Fri, 23 Mar 2018)
<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>
>> Read More

USE OF 3-CARBOXY-N-ETHYL-N,N-DIMETHYLPROPAN-1-AMINIUM SALTS IN THE TREATMENT OF CARDIOVASCULAR DISEASE (Fri, 23 Mar 2018)
<p id="p-0001" num="0000">Salts of 3-carboxy-N-ethyl-N,N-dimethylpropan-1-aminium, method of preparation thereof and use in the treatment of cardiovascular disease.</p>
>> Read More

DI-SUBSTITUTED PYRAZOLE COMPOUNDS FOR THE TREATMENT OF DISEASES (Fri, 16 Mar 2018)
Provided herein are compounds, pharmaceutical compositions comprising the compounds, and methods of using the compounds and compositions in treating a condition, disease, or disorder associated with abnormal activation of the SREBP pathway, including metabolic disorders such as obesity, cancer, cardiovascular disease, and nonalcoholic fatty liver disease (NAFLD) wherein the compound is according to Formula (I).
>> Read More

USE OF RECOMBINANT LYMPHOCYTE ACTIVATION GENE-3 (Fri, 16 Mar 2018)
A method for classifying patients at risk for cardiovascular disease, other chronic inflammatory diseases, cardiovascular and/or non-cardiovascular morbidity and mortality based on a risk assessment for lymphocyte activation gene 3 (LAG3) protein deficiency, and for mediating the risk using recombinant lymphocyte activation gene-3 or LAG3 mimetic as a companion therapeutic alone or in combination with a statin and/or an anti-hyperlipidemic drug, The risk assessment is two-prong, beginning with a qualitative determination whether a subject has of is predisposed to abnormal expression of inflammasomes, heightened risk for inflammation and/or to dysfunctional HDL, followed, by a quantitative assay or genetic screen for a polymorphism that occurs in the coding sequence of the LAG3 gene. Given positive indication, recombinant LAG3 and/or LAG3 mimetic is used alone or in combination with the therapeutic use of a cholesterol mediating, drug for treatment.
>> Read More

TRICYCLIC ANALOGUES, PREPARATION METHOD AND USES THEREOF (Fri, 09 Mar 2018)
<p id="p-0001" num="0000">The present invention relates to a series of analogues of natural product Pyripyropene A represented by general formula I and a preparation method and use thereof. More particularly, the present invention relates to analogues of the natural product Pyripyropene A, a preparation method and use thereof as the acyl-CoA:cholesterol acyltransferase 2 (ACAT2) inhibitors for the treatment of cardiovascular diseases such as atherosclerosis and the like.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="34.97mm" wi="55.03mm" file="US20180064696A1-20180308-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

CHOLIC ACID DERIVATIVE, AND PREPARATION METHOD AND MEDICAL USE THEREOF (Thu, 08 Mar 2018)
The present invention relates to a cholic acid derivative, and a preparation method and a medical use thereof. In particular, the present invention relates to a cholic acid derivative with the structure of formula (I), a stereoisomer, or a pharmaceutically acceptable salt thereof. The series of compounds can be used to treat FXR mediated diseases, comprising cardiovascular disease, atherosclerosis, arteriosclerosis, hypercholesterolemia, hyperlipidemia and chronic hepatitis diseases, chronic liver diseases, gastrointestinal diseases, nephrosis, heart vascular diseases, metabolic diseases, cancer (for example colorectal cancer) or neurological signs, such as strokes and other diseases, with a wide range of medical applications, and are expected to develop into a new generation of FXR agonist.
>> Read More

ALDEHYDE TRAPPING COMPOUNDS AND USES THEREOF (Fri, 02 Mar 2018)
The present invention provides compounds and methods 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.
>> Read More

ALDEHYDE TRAPPING COMPOUNDS AND METHODS OF USE THEREOF (Fri, 02 Mar 2018)
The present invention provides compounds and methods 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.
>> Read More

Beta-amino-isoquinolinyl amide compounds (Fri, 23 Feb 2018)
<p id="p-0001" num="0000">Disclosed are alpha-aryl-beta-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 isoquinoline amide compounds.</p>
>> Read More

ALDEHYDE TRAPPING COMPOUNDS AND USES THEREOF (Fri, 23 Feb 2018)
<p id="p-0001" num="0000">The present invention provides compounds and methods 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.</p>
>> Read More

N-ACYLOXYSULFONAMIDE AND N-HYDROXY-N-ACYLSULFONAMIDE DERIVATIVES (Fri, 23 Feb 2018)
<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>
>> Read More

BETA-AMINO-ISOQUINOLINYL AMIDE COMPOUNDS (Fri, 23 Feb 2018)
Disclosed are alpha-axyl-beta-axmno 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 isoquinoline amide compounds.
>> Read More

COMPOUNDS USEFUL FOR ALTERING THE LEVELS OF BILE ACIDS FOR THE TREATMENT OF DIABETES AND CARDIOMETABOLIC DISEASE (Fri, 23 Feb 2018)
Described herein are compounds of Formula I or a pharmaceutically acceptable salt thereof. The compounds of Formula I act as Cyp8b1 inhibitors and can be useful in preventing, treating or acting as a remedial agent for diabetes and cardiovascular disease.
>> Read More

COMPOUNDS USEFUL FOR ALTERING THE LEVELS OF BILE ACIDS FOR THE TREATMENT OF DIABETES AND CARDIOMETABOLIC DISEASE (Fri, 23 Feb 2018)
Described herein are compounds of Formula (I) or a pharmaceutically acceptable salt thereof. The compounds of Formula I act as Cyp8b1 inhibitors and can be useful in preventing, treating or acting as a remedial agent for diabetes and cardiovascular disease.
>> Read More

Lactone intermediates of nicotinamide riboside and nicotinate riboside (Thu, 22 Feb 2018)
A compound of formula I or IA: wherein R1 is an optional substituent; n is 0-4; R2 and R3 are selected from hydrogen and a substituent, or R2 and R3 join together to form an optional substituted ring; X is an anion. The compounds of formula I or IA can be reduced or decyclised to form nicotinamide ribosides or nicotinate ribosides and thus offer a new route to these compounds (see claim 1 for a new route to a compound of formula V or VA from a compound of formula I or IA). In another aspect, the compound of formula I or IA find use in the treatment of aging, stress, cardiovascular disease, cell death, cancer, metabolic disorder, neuronal disease, blood coagulation disorder, weight control, inflammatory disease, flushing, viral infection, fungal infection, dietary deficiency of vitamin B3, pellagra, pellagra-like condition, vitamin B3 deficiency, or a mitochondrial disease or disorder.
>> Read More

SUBSTITUTED BRIDGED UREA ANALOGS AS SIRTUIN MODULATORS (Fri, 16 Feb 2018)
<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>
>> Read More

COMPOSITIONS AND METHODS FOR TREATING DISEASE (Fri, 16 Feb 2018)
Embodiments of the invention provide pharmaceutical compositions and methods for preventing and treating disease and promoting the health in subjects at risk of cardiovascular disease and/or kidney disease. Additional embodiments of the present invention provide compositions and methods useful for treating and preventing a cardiovascular disease or a kidney disease.
>> Read More

CARDIOVASCULAR DISEASE RISK ASSESSMENT (Fri, 09 Feb 2018)
<p id="p-0001" num="0000">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).</p>
>> Read More

Methods, Compounds, and Compositions for the Treatment of Angiotensin-Related Diseases (Fri, 02 Feb 2018)
<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. In particular, the invention provides compounds, methods and compositions for the treatment of metabolic diseases and disorders, such as diabetes mellitus, diabetes-related cardiovascular disorders, diabetes-related dermal ulcerations, diabetes related hypertension, and diabetes-related ophthalmic diseases.</p>
>> Read More

FUSED HETEROCYCLIC COMPOUNDS AS ION CHANNEL MODULATORS (Thu, 01 Feb 2018)
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 Q, R 1 , X 1 , X 2 , Y and R 2 are as described herein, to methods for the preparation and use of the compounds and to pharmaceutical compositions containing the same.
>> Read More

New uses and methods (Thu, 01 Feb 2018)
Extracts from Fraxinus angustifolia and their use in reversing obesity-related and/or metabolic syndrome-related gut microbiota dysbiosis and/or treating or preventing hepatic steatosis, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), leaky gut, intestinal hyperpermeability, gut microbiota dysbiosis-induced cardiovascular diseases, cardiometabolic diseases, low grade inflammation, atherosclerosis, obesity, insulin resistance, glucose intolerance, prediabetes and/or diabetes. The extract may be used in modulating or adjusting gut microbiota, reducing body fat and/or reducing blood glucose concentration. Levels of the bacterial groups Burkholderiales, Sutterellacae, Parasutterella, Betaproteobacteria, Enterorhabdus, Prevotellaceae, Flavonifractor, Clostridium IV, Butyricicoccus, Coriobacteriaceae, Lactobacillaceae and Rikenellaceae, may be increased. The extract may be obtained from Fraxinus angustifolia samara. The extract may contain secoiridoids including nuzhenide, GL3, oleoside methyl ester, excelside B, GL5 and salidroside.
>> Read More

3-SUBSTITUTED CYCLOPENTYLAMINE DERIVATIVES (Fri, 26 Jan 2018)
<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="24.13mm" wi="61.89mm" file="US20180022738A1-20180125-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">in which R, W, R<sup>1</sup>, R<sup>4</sup>, X<sup>1</sup>, X<sup>2</sup>, X<sup>3</sup>, X<sup>4 </sup>and q have the meanings indicated in Claim <b>1, </b> <br/> 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>
>> Read More

N-SUBSTITUTED 8-[(2,6-DIFLUOROBENZYL)OXY]-2,6-DIMETHYLIMIDAZO[1,2-A]PYRAZIN-3-CARBOXAMIDE DERIVATIVES AS STIMULATORS OF SOLUBLE GUANYLATE CYCLASE (SGC) FOR THE TREATMENT OF CARDIOVASCULAR DISEASES (Fri, 26 Jan 2018)
<p id="p-0001" num="0000">The present application relates to novel substituted imidazo[1,2-a]pyrazine carboxamides, to processes for their preparation, to their use, alone or in combinations, for the treatment and/or prophylaxis of diseases, and to their use for producing medicaments for the treatment and/or prophylaxis of diseases, in particular for the treatment and/or prophylaxis of cardiovascular disorders.</p>
>> Read More

ISOQUINOLINE DERIVATIVES AS PERK INHIBITORS (Fri, 26 Jan 2018)
The invention is directed to substituted isoquinoline derivatives and uses thereof. Specifically, the invention is directed to compounds according to Formula I and the use of compounds of Formula (I) in treating disease states: (I) wherein R1, R2, R3, R4, R5, R6, R7 and X 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 associated with activated unfolded protein response pathways, such as Alzheimer's disease, 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, ather osclerosis, 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.
>> Read More

CLASS OF TRICYCLIC ANALOGUE, PREPARATION METHOD AND USE THEREOF (Thu, 25 Jan 2018)
The present invention relates to a series of analogues having a structure of a natural product Pyripyropene A as represented by formula I, and preparation method and use thereof, and particularly relates to analogues of the natural product Pyripyropene A, preparation method and application thereof in treating cardiovascular diseases such as atherosclerosis, etc. as an inhibitor of an acyl-coenzyme A: cholesterol acyltransferase 2 (ACAT2).
>> Read More

INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL (Fri, 19 Jan 2018)
<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="21.08mm" wi="68.75mm" file="US20180016263A1-20180118-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

Compounds and pharmaceutical compositions thereof for the treatment of inflammatory disorders (Fri, 19 Jan 2018)
The present invention discloses compounds according to Formula I: Wherein R Ia, Ri, R2 , R4 R', R6a, R6', R7, R', 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. 1ia Rl Rib
>> Read More

NOVEL COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF INFLAMMATORY DISORDERS (Thu, 18 Jan 2018)
The present invention discloses compounds according to Formula I: Wherein R 1a , R 1b , R 2 , R 4 , R 5 , R 6a , R 6b , R 7 , R 8 , 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.
>> Read More

LIPOPROTEIN ANALYSIS BY DIFFERENTIAL CHARGED-PARTICLE MOBILITY (Fri, 12 Jan 2018)
<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>
>> Read More

HETEROCYCLIC COMPOUNDS AS PI3K-y INHIBITORS (Fri, 12 Jan 2018)
<p id="p-0001" num="0000">This application 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="42.76mm" wi="55.37mm" file="US20180009816A1-20180111-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or pharmaceutically acceptable salts or stereoisomers thereof, which are inhibitors of PI3K-γ which are useful for the treatment of disorders such as autoimmune diseases, cancer, cardiovascular diseases, and neurodegenerative diseases.</p>
>> Read More

INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL (Fri, 12 Jan 2018)
<p id="p-0001" num="0000">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.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="30.90mm" wi="64.09mm" file="US20180009807A1-20180111-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

Substituted pyrazolo[1,5-a]-pyridine-3-carboxamides and use thereof (Wed, 10 Jan 2018)
The invention relates to a new type of substituted pyrazolo[1,5-a]-pyridine-3-carboxamides, to a method for producing same, to the use thereof alone or in combinations for treating and/or preventing diseases and to the use thereof for producing medicaments for treating and/or preventing diseases, in particular for treating and/or preventing cardiovascular diseases.
>> Read More

N-substituted 8-[(2,6-difluorobenzyl)oxy]-2,6-dimethylimidazo[1,2-a]pyrazin-3-carboxamide derivatives as stimulators of soluble guanylate cylase (SGC) for the treatment of cardiovascular diseases (Wed, 10 Jan 2018)
The invention relates to n-substituted 8-[(2,6-difluorobenzyl)oxy]-2,6-dimethylimidazo[1,2-a]pyrazin-3-carboxamide derivatives as stimulators of soluble guanylate cyclase (sGC) for the treatment of cardiovascular diseases, such as for example heart insufficiency, angina pectoris, hypertension, pulmonary hypertension, ischaemia, vascular diseases, renal insufficiency, thromboembolic diseases, fibrotic diseases, arteriosclerosis, dementia diseases and erectile dysfunction.
>> Read More

PHARMACEUTICAL COMPOSITION AND THERAPEUTIC COMBINATION COMPRISING A CHOLESTERYL ESTER TRANSFER PROTEIN INHIBITOR AND HMG CoA REDUCTASE INHIBITORS (Fri, 05 Jan 2018)
<p id="p-0001" num="0000">The present invention relates to a pharmaceutical composition and a therapeutic combination comprising a novel cholesteryl ester transfer protein (CETP) inhibitor and a HMG CoA Reductase 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.</p>
>> Read More

NOVEL USES (Fri, 05 Jan 2018)
<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>
>> Read More

BICYCLIC IMIDAZOLE DERIVATIES USEFUL FOR THE TREATMENT OF RENAL DISEASE, CARDIOVASCULAR DISEASES AND FIBROTIC DISORDERS (Fri, 05 Jan 2018)
The present invention relates to compounds of formula I: and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, R5 and n are as defined herein. The invention also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.
>> Read More

CARBOXAMIDE-SUBSTITUTED PYRAZOLES AND TRI(HETERO)ARYL-PYRAZOLES FOR USE IN METHODS OF TREATING AND / OR PREVENTING CARDIOVASCULAR DISEASES AND / OR COMORBIDITIES THEREOF (Thu, 04 Jan 2018)
The present invention relates to carboxamide-substituted pyrazoles and tri(hetero)aryl pyrazoles, pharmaceutical formulations containing such compounds, a process for manufacture and the use of such compounds in methods of reducing the heart rate and accordingly for its use in methods of treating and/or preventing cardiovascular diseases and/or cardiovascular comorbidities, which are exacerbated by an increased heart rate of ‰¥ 90 beats/min. (bpm), such as cardiac arrhythmia, hypertensive heart disease, tachycardia, inappropriate sinus tachycardia, angina pectoris and stable angina pectoris, myocardial ischemia, coronary artery disease, heart failure, and stroke, as well as the cardiovascular comorbidities diabetes, metabolic syndrome, obesity, and chronic kidney disease in mammals, including humans.
>> Read More

Diagnostics and Therapeutics for Diseases Associated With G-Protein Coupled Receptor AdipoR2 (AdipoR2) (Fri, 29 Dec 2017)
<p id="p-0001" num="0000">The invention provides human AdipoR2 which is associated with the cardiovascular diseases, dermatological diseases, gastroenterological diseases, cancer, hematological diseases, respiratory diseases, inflammation, neurological diseases, urological diseases. The invention also provides assays for the identification of compounds useful in the treatment or prevention of cardiovascular diseases, dermatological diseases, gastroenterological diseases, cancer, hematological diseases, respiratory diseases, inflammation, neurological diseases, urological diseases. The invention also features compounds which bind to and/or activate or inhibit the activity of AdipoR2 as well as pharmaceutical compositions comprising such compounds.</p>
>> Read More

CYCLODEXTRIN-BASED POLYMERS FOR THERAPEUTIC DELIVERY (Fri, 29 Dec 2017)
<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>
>> Read More

COMPOSITIONS AND METHODS FOR TREATING CARDIOVASCULAR DISEASE (Fri, 29 Dec 2017)
The invention provides PCSK9 inhibitors, compositions comprising the PCSK9 inhibitors, and methods of identifying and using the PCSK9 inhibitors.
>> Read More

HETEROCYCLIC COMPOUNDS AS PI3K-γ INHIBITORS (Fri, 29 Dec 2017)
This application relates to compounds of Formula (I) or pharmaceutically acceptable salts or stereoisomers thereof, which are inhibitors of PI3K-γ which are useful for the treatment of disorders such as autoimmune diseases, cancer, cardiovascular diseases, and neurodegenerative diseases.
>> Read More

MECHANISTIC TARGET OF RAPAMYCIN SIGNALING PATHWAY INHIBITORS AND THERAPEUTIC APPLICATIONS THEREOF (Fri, 29 Dec 2017)
Selective mTOR inhibitors of formulas (I)-(III), processes for their preparation, pharmaceutical compositions containing them, and their use in the treatment of diseases and disorders, arising from abnormal cell growth, functions, or behaviors mediated by an mTOR kinase and/or one or more PI3K enzyme, are provided. Such diseases and disorder include cancer, immune disorders, cardiovascular disease, viral infection, inflammation, metabolism/endocrine function disorders and neurological disorders.
>> Read More

NOVEL COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF INFLAMMATORY DISORDERS (Fri, 22 Dec 2017)
<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="70.53mm" file="US20170362227A1-20171221-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.</p> <p id="p-0004" num="0000">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>
>> Read More

SUBSTITUTED BRIDGED UREA ANALOGS AS SIRTUIN MODULATORS (Fri, 22 Dec 2017)
<p id="p-0001" num="0000">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.</p>
>> Read More

2-SPIRO-5- AND 6-HYDROXAMIC ACID INDANES AS HDAC INHIBITORS (Fri, 22 Dec 2017)
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.
>> Read More

Novel 5-HT2 antagonists (Fri, 22 Dec 2017)
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<sb>2B</sb> 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.
>> Read More

SUBSTITUTED BRIDGED UREA ANALOGS AS SIRTUIN MODULATORS (Fri, 15 Dec 2017)
<p id="p-0001" num="0000">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.</p>
>> Read More

SUBSTITUTED BRIDGED UREA ANALOGS AS SIRTUIN MODULATORS (Fri, 15 Dec 2017)
<p id="p-0001" num="0000">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.</p>
>> Read More

MODULATORS OF SOCE, COMPOSITIONS, AND USES THEREOF (Fri, 15 Dec 2017)
Compounds of Formula (I) able to modulate Store Operated Calcium Entry (SOCE). The disclosure also relates to the use of compounds of formula (I) for treatment of pathological conditions in which SOCE modulation might be beneficial, such as neglecting disorders linked to loss-or gain-of-function STIM1/Orai1 mutations, allergic disorders, pain, inflammatory diseases, autoimmune diseases or disorders, cancer and other proliferative diseases, neurodegenerative disorders, myelodysplastic syndromes, haematological diseases, cardiovascular diseases, degenerative diseases of the musculoskeletal system, liver diseases and disorders, kidney diseases, type I diabetes, graft rejection, graft-versus-host disease, allogeneic or xenogeneic transplantation, thyroiditis and viral infections.
>> Read More

CHEMCICAL COMPOUNDS (Fri, 15 Dec 2017)
The invention is directed to substituted pyrrolidine derivatives. Specifically, the invention is directed to compounds according to Formula III: wherein A, B, L1, L2, L3, R1, R2, R3, R4, R5, R6, R9, R10, R30, Y1, Y2, z2, z4, z5, and z6 are as defined herein, and salts thereof. The compounds of the invention are inhibitors of the ATF4 pathway and can be useful in the treatment of cancer, pre-cancerous syndromes and diseases associated with activated unfolded protein response pathways, such as Alzheimer's disease, spinal cord injury, traumatic brain injury, ischemic stroke, stroke, diabetes, Parkinson disease, Huntington's disease, Creutzfeldt-Jakob Disease, and related prion diseases, progressive supranuclear palsy, amyotrophic lateral sclerosis, myocardial infarction, cardiovascular disease, inflammation, fibrosis, chronic and acute diseases of the liver, chronic and acute diseases of the lung, chronic and acute diseases of the kidney, chronic traumatic encephalopathy (CTE), neurodegeneration, dementia, 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 the ATF4 pathway and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
>> Read More

CHEMICAL COMPOUNDS AS ATF4 PATHWAY INHIBITORS (Fri, 15 Dec 2017)
The invention is directed to substituted piperidine derivatives. Specifically, the invention is directed to compounds according to Formula IIII: wherein A, B, X, Y, L1, L2, L3, R1, R2, R3, R4, R5, R6, R9, z2, z4, z5, and z6 are as defined herein, and salts thereof. The compounds of the invention are inhibitors of the ATF4 pathway and can be useful in the treatment of cancer, pre-cancerous syndromes and diseases associated with activated unfolded protein response pathways, such as Alzheimer's disease, spinal cord injury, traumatic brain injury, ischemic stroke, stroke, diabetes, Parkinson disease, Huntington's disease, Creutzfeldt-Jakob Disease, and related prion diseases, progressive supranuclear palsy, amyotrophic lateral sclerosis, myocardial infarction, cardiovascular disease, inflammation, fibrosis, chronic and acute diseases of the liver, chronic and acute diseases of the lung, chronic and acute diseases of the kidney, chronic traumatic encephalopathy (CTE), neurodegeneration, dementia, 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 the ATF4 pathway and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
>> Read More

COMPOSITIONS AND METHODS FOR LOWERING TRIGLYCERIDES WITHOUT RAISING LDL-C LEVELS (Fri, 15 Dec 2017)
Provided herein are methods of preventing and/or treating myocardial infarction and/or stroke in a subject by administering ethyl eicosapentaenoate (E-EPA). Preferably, the subject is previously identified as having dyslipidemia, is on stable statin therapy and has a fasting baseline triglyceride level of about 200 mg/dL to about 500 mg/dL and optionally has established cardiovascular disease or has a high risk of developing cardiovascular disease. Compositions may be formulated for daily administration to provide about 4 g of the ethyl eicosapentaenoate per day. Further provided are methods of lowering triglyceride levels in a subject on stable statin therapy having baseline fasting triglycerides of about 200 mg/dl to about 500 mg/dl, by administering polyunsaturated fatty acids, for example about Ig to about 4g of eicosapentaenoic acid (EPA) per day. Such therapy, when used daily for 12 weeks, lowers fasting triglycerides and decreases LDL-C, or does not increase LDL-C.
>> Read More

HYDROXYL COMPOUNDS AND COMPOSITIONS FOR CHOLESTEROL MANAGEMENT AND RELATED USES (Fri, 08 Dec 2017)
<p id="p-0001" num="0000">The present invention relates to novel 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, pancreatitius, Parkinson's disease, a peroxisome proliferator activated receptor-associated disorder, phospholipid elimination in bile, renal disease, septicemia, metabolic syndrome disorders (e.g., 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>
>> Read More

Pyrrolo and pyrazolopyrimidines as ubiquitin-specific protease 7 inhibitors (Wed, 29 Nov 2017)
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.
>> Read More

Synthetic apelin fatty acid conjugates with improved half-life (Wed, 29 Nov 2017)
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.
>> Read More

NOVEL CYCLOSPORIN DERIVATIVES AND USES THEREOF (Fri, 24 Nov 2017)
A compound of the Formula (I) is disclosed: (I) or pharmaceutically acceptable salt thereof, wherein the symbols are as defined in the specification. Also described are a pharmaceutical composition comprising the same and a method for treating or preventing viral infections, inflammation, dry eye, central nervous disorders, cardiovascular diseases, cancer, obesity, diabetes, muscular dystrophy, lung, and liver, and kindey diseases, and hair loss using the same.
>> Read More

TRPV4 ANTAGONIST (Fri, 24 Nov 2017)
The present invention relates to a novel compound useful as a TRPV4 antagonist, specifically the compound 1-(((5S,7R)-3-(5-cyclopropylpyrazin-2-yl)-7-hydroxy-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile, pharmaceutically acceptable salts thereof and pharmaceutical compositions containing the compound. The compound of the invention can be useful in the treatment of a disease state selected from: atherosclerosis, disorders related to vasogenic edema, postsurgical abdominal edema, ocular edema, cerebral edema, local and systemic edema, fluid retention, sepsis, hypertension, inflammation, bone related dysfunctions and congestive heart failure, pulmonary disorders, chronic obstructive pulmonary disorder, ventilator induced lung injury, high altitude induced pulmonary edema, acute respiratory distress syndrome, acute lung injury, pulmonary fibrosis, sinusitis/rhinitis, asthma, cough; including acute cough, sub-acute cough and chronic cough, pulmonary hypertension, overactive bladder, cystitis, pain, motor neuron disorders, genetic gain of function disorders, cardiovascular disease, renal dysfunction, stroke, glaucoma, retinopathy, endometriosis, pre-term labor, dermatitis, pruritus, pruritus in liver disease, diabetes, metabolic disorder, obesity, migraine, pancreatitis, tumor suppression, immunosuppression, osteoarthritis, crohn's disease, colitis, diarrhea, intestinal irregularity (hyperreactivity/hyporeactivity), fecal incontinence, irritable bowel syndrome (IBS), constipation, intestinal pain and cramping, celiac disease, lactose intolerance, and flatulence.
>> Read More

Amide-substituted pyridinyltriazole derivatives and uses thereof (Fri, 10 Nov 2017)
<p id="p-0001" num="0000">The present invention relates to novel 5-(carboxamide)-1-pyridinyl-1,2,4-triazole derivatives, to processes for the preparation of such compounds, to pharmaceutical compositions containing such compounds, and to the use of such compounds or compositions for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of renal and cardiovascular diseases.</p>
>> Read More

AMIDE-SUBSTITUTED PYRIDINYLTRIAZOLE DERIVATIVES AND USES THEREOF (Fri, 10 Nov 2017)
The present invention relates to novel 5-(carboxamide)-1-pyridinyl-1,2,4-triazole derivatives, to processes for the preparation of such compounds, to pharmaceutical compositions containing such compounds, and to the use of such compounds or compositions for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of renal and cardiovascular diseases.
>> Read More

HYDROXYALKYL-SUBSTITUTED HETEROARYLTRIAZOLE DERIVATIVES AND USES THEREOF (Fri, 10 Nov 2017)
The present invention relates to novel 5-(hydroxyalkyl)-1-heteroaryl-1,2,4-triazole derivatives, to processes for the preparation of such compounds, to pharmaceutical compositions containing such compounds, and to the use of such compounds or compositions for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of renal and cardiovascular diseases.
>> Read More

AMIDE-SUBSTITUTED PHENYLTRIAZOLE DERIVATIVES AND USES THEREOF (Fri, 10 Nov 2017)
The present invention relates to novel 5-(carboxamide)-1-phenyl-1,2,4-triazole derivatives, to processes for the preparation of such compounds, to pharmaceutical compositions containing such compounds, and to the use of such compounds or compositions for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of renal and cardiovascular diseases.
>> Read More

ADENINE DERIVATIVES AS PROTEIN KINASE INHIBITORS (Fri, 10 Nov 2017)
The present invention relates to a compound suitable for use as a kinase inhibitor according to general formula (I) [compound (C), herein after], or the N- oxide, pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or stereoisomer thereof, formula (I) wherein A, R1, R2, R3, R3', R4, R4', X, Y, Z, T are as defined in the claims. The invention further relates to an in vitro 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. 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, inflammatory disorders, cardiovascular diseases, viral induced diseases, circulatory diseases, fibro-proliferative diseases and pain sensitization disorders.
>> Read More

AMIDE-SUBSTITUTED ARYLTRIAZOLE DERIVATIVES AND USES THEREOF (Fri, 10 Nov 2017)
The present invention relates to novel 5-(carboxamide)-1-aryl-1,2,4-triazole derivatives, to processes for the preparation of such compounds, to pharmaceutical compositions containing such compounds, and to the use of such compounds or compositions for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of renal and cardiovascular diseases.
>> Read More

FLUOROALKYL-SUBSTITUTED ARYLTRIAZOLE DERIVATIVES AND USES THEREOF (Fri, 10 Nov 2017)
The present invention relates to novel 5-( fluoroalkyl)-1-aryl-1,2,4-triazole derivatives, to processes for the preparation of such compounds, to pharmaceutical compositions containing such compounds, and to the use of such compounds or compositions for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of renal and cardiovascular diseases.
>> Read More

USE OF RECOMBINANT LYMPHOCYTE ACTIVATION GENE-3 AS A COMPANION THERAPEUTIC FOR PATIENTS AT RISK FOR CARDIOVASCULAR DISEASE AND OTHER CHRONIC INFLAMMATORY DISEASES (Fri, 03 Nov 2017)
<p id="p-0001" num="0000">A method for classifying patients at risk for cardiovascular disease, other chronic inflammatory diseases, cardiovascular and/or non-cardiovascular morbidity and mortality based on a risk assessment for lymphocyte activation gene 3 (LAG3) protein deficiency, and for mediating the risk using recombinant lymphocyte activation gene-3 or LAG3 mimetic as a companion therapeutic alone or in combination with a statin and/or an anti-hyperlipidemic drug. The risk assessment is two-prong, beginning with a qualitative determination whether a subject has or is predisposed to abnormal expression of inflammasomes, heightened risk for inflammation and/or to dysfunctional HDL, followed by a quantitative assay or genetic screen for a polymorphism that occurs in the coding sequence of the LAG3 gene. Given positive indication, recombinant LAG3 and/or LAG3 mimetic is used alone or in combination with the therapeutic use of a cholesterol mediating drug for treatment.</p>
>> Read More

Fused Heterocyclic Compounds as Selective BMP Inhibitors (Fri, 03 Nov 2017)
<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>
>> Read More

DI-SUBSTITUTED PYRAZOLE COMPOUNDS FOR THE TREATMENT OF DISEASES (Fri, 03 Nov 2017)
Provided herein are compounds, pharmaceutical compositions comprising the compounds, and methods of using the compounds and compositions in treating a condition, disease, or disorder associated with abnormal activation of the SREBP pathway, including metabolic disorders such as obesity, cancer, cardiovascular disease, and nonalcoholic fatty liver disease (NAFLD) wherein the compound is according to Formula (I).
>> Read More

COVALENT BTK INHIBITORS AND USES THEREOF (Fri, 03 Nov 2017)
The present invention features compounds having BTK 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.
>> Read More

Compositions and Methods for Inhibiting BMP (Fri, 27 Oct 2017)
<p id="p-0001" num="0000">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.</p>
>> Read More

Measurement Of Serum Lipoproteins (Fri, 27 Oct 2017)
<p id="p-0001" num="0000">Although a more accurate estimate of a person's risk of cardiovascular disease can be made on the basis of the number of lipoprotein particles per unit volume in the person's blood, current methods all rely on measuring the mass of lipoprotein cholesterol per unit volume. It has been discovered that a rapid and accurate lipoprotein particle count can be obtained by photometry. A method and apparatus are provided for measuring the number of lipoprotein particles in a sample using photometry.</p>
>> Read More

SUBSTITUTED BICYCLIC HETEROCYCLIC COMPOUNDS (Fri, 27 Oct 2017)
Disclosed are compounds of Formula (I), or a salt thereof, wherein: X is CR4 or N; Y is CR4 or N, provided that Y is N only if X is N; R1 is Formulae (A) or (B); each W is independently NR1b or O; Z is a bond or CHR1d; and R1, R2, R3, R4, L1, R1a, R1b, R1c, and n are defined herein. Also disclosed are methods of using such compounds as inhibitors of ROMK, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating cardiovascular diseases.
>> Read More

QUINOLINE COMPOUNDS AS MODULATORS OF RAGE ACTIVITY AND USES THEREOF (Fri, 27 Oct 2017)
Quinoline compounds are disclosed that have a formula represented by the following: and wherein Cy, R1, R4a, R4b, and n are as described herein. 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.
>> Read More

Novel dihydropyridoisoquinolinones and pharmaceutical compositions thereof for the treatment of inflammatory disorders (Fri, 27 Oct 2017)
A compound according to Formula (I): wherein R<sp>1</sp>, L<sb>A</sb>, Cy<sb>A</sb>, R<sp>A</sp>, R<sp>2</sp>, R<sp>3</sp>, and R<sp>4</sp> 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.
>> Read More

USE OF MARKERS IN THE IDENTIFICATION OF CARDIOTOXIC AGENTS (Wed, 18 Oct 2017)
The invention provides methods for the diagnosis and prognosis of cardiovascular disease, and for monitoring of the treatment of cardiovascular disease, including heart failure and cardiomyopathy. The invention further provides methods for identifying an agent for treating cardiomyopathy or heart failure, for identifying a cardiotoxic agent, and for identifying a rescue agent to reduce or prevent drug-induced toxicity, by using one or more biomarkers selelcted from the group consisting of CCDC47, HMOX1, PTX3, PAI1, IL27, IGFBP7, Emmprin, CFL2, EDIL3, NUCB1, PE D18:0-20:3/D18:1-20:2/D16:0-22:3; PE D18:0-22:5/D18:1-22:4; PE D16:1-22:6; PE P18:1-18:1/P18:0-18:2/P16:0-20:2; LPC 20:3; and PC-LI-183-D18:22-22:6, or any of the other biomarkers provided herein. The invention further provides kits for practicing the methods of the invention.
>> Read More

Inhibitors of the renal outer medullary potassium channel (Fri, 06 Oct 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="30.82mm" wi="65.02mm" file="US09862720-20180109-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

DUAL ACE C-DOMAIN/NEP INHIBITORS (Fri, 06 Oct 2017)
A superior dual ACE/NEP inhibitor is a combination that selectively targets the ACE C-domain in addition to inhibiting NEP. Such a dual ACE C-domain/NEP inhibitor can be used in the treatment of diverse cardiovascular diseases, including hypertension and heart failure.
>> Read More

INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">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.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.94mm" wi="51.48mm" file="US20170275292A1-20170928-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL (Fri, 29 Sep 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="28.28mm" wi="69.85mm" file="US20170275298A1-20170928-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL (Fri, 29 Sep 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="22.61mm" wi="59.01mm" file="US20170275302A1-20170928-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

Inhibitors of the renal outer medullary potassium channel (Fri, 29 Sep 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>
>> Read More

METHODS OF TREATING OR REDUCING THE RISK OF CARDIOVASCULAR EVENTS AND RELATED DISEASES USING SGLT-2 INHIBITORS (Fri, 15 Sep 2017)
The present invention relates to the use of certain SGLT-2 inhibitors, such as ertugliflozin or a pharmaceutically acceptable salt or a co-crystal thereof, for treating, reducing the risk of and/or preventing heart failure, myocardial infarction, cardiovascular disease or cardiovascular death in animals without type 2 or type 1 diabetes mellitus, or in animals with pre-diabetes, or in animals with type 2 or type 1 diabetes mellitus or pre-diabetes.
>> Read More

20-HETE RECEPTOR (GPR75) ANTAGONISTS AND METHODS OF USE (Fri, 15 Sep 2017)
The present invention concerns compounds and their use to treat cardiovascular disease, renal disease, thrombic disease, stroke, metabolic syndrome, cell proliferation, and ischemic cardiovascular disorders. Compounds of the present invention display significant potency as antagonists of 20-hydroxyeicosatetraenoic acid (20-HETE), and function as anti-hypertensive, anti-inflammatory, or anti-growth agents.
>> Read More

NOVEL COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF FIBROSIS (Sat, 09 Sep 2017)
The present invention discloses compounds according to Formula I, wherein R1a, R1b, R2a, R2b, R3, R4, R5, R6a, X, Cy1, Cy2, and the subscript n and m are as defined herein. The present invention relates to antagonists compounds of sphingosine 1-phosphate (SIP) receptor, 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, inflammatory diseases, autoimmune diseases, metabolic diseases, cardiovascular diseases, and/or proliferative diseases by administering the compound of the invention.
>> Read More

TOXIC ALDEHYDE RELATED DISEASES AND TREATMENT (Fri, 25 Aug 2017)
<p id="p-0001" num="0000">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.</p>
>> Read More

SOLUBLE EPOXIDE HYDROLASE INHIBITORS AND USES THEREOF (Fri, 25 Aug 2017)
<p id="p-0001" num="0000">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.</p>
>> Read More

SUBSTITUTED BENZOAZEPINES AS TOLL-LIKE RECEPTOR MODULATORS (Thu, 24 Aug 2017)
Provided are benzazepine derivatives useful for modulation of signaling through the Toll-like receptors TLR7 and/or TLR8. The benzazepine derivatives have use in treating or preventing disease, including cancer, autoimmune disease, fibrotic disease, cardiovascular disease, infectious disease, inflammatory disorder, graft rejection, or graft-versus-host disease.
>> Read More

SUBSTITUTED BENZOAZEPINES AS TOLL-LIKE RECEPTOR MODULATORS (Thu, 24 Aug 2017)
Provided are compounds of formula (II) useful for modulation of signaling through the Toll-like receptors TLR7 and/or TLR8. The compounds have use in treating or preventing disease, including cancer, autoimmune disease, fibrotic disease, cardiovascular disease, infectious disease, inflammatory disorder, graft rejection, or graft-versus-host disease.
>> Read More

Pharmaceutical composition and therapeutic combination comprising a cholesteryl ester transfer protein inhibitor and HMG CoA reductase inhibitors (Sat, 19 Aug 2017)
The present invention relates to a pharmaceutical composition and a therapeutic combination comprising a novel cholesteryl ester transfer protein (CETP) inhibitor and a HMG CoA Reductase 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.
>> Read More

Amino-substituted annulated pyrimidines and use thereof (Sat, 19 Aug 2017)
The invention relates to novel amino-substituted annulated pyrimidines, to methods for the production thereof, to the use thereof on its own or combination for the treatment and/or prophylaxis of diseases and to the use thereof for producing medicaments for the treatment and/or prophylaxis of diseases, in particular for the treatment and/or prophylaxis of cardiovascular diseases.
>> Read More

Substituted quinoline-4-carboxamides and use thereof (Sat, 19 Aug 2017)
The present application relates to novel substituted quinoline-4-carboxamides, which act as stimulators of soluble guanylate cyclase, and to the use thereof, to methods for the production thereof, to the use thereof alone or in combinations to treat and/or prevent diseases, and to the use thereof to produce drugs for treating and/or preventing diseases, in particular for treating and/or preventing cardiovascular diseases.
>> Read More

Soluble epoxide hydrolase inhibitors and uses thereof (Sat, 19 Aug 2017)
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.
>> Read More

CYCLIC POLYPEPTIDES FOR THE TREATMENT OF HEART FAILURE (Fri, 18 Aug 2017)
<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"?> <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, 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.</li> </ul> </li> </ul> </p>
>> Read More

Organic compounds (Fri, 18 Aug 2017)
<p id="p-0001" num="0000">The invention relates to novel inhibitors of phosphodiesterase 1 (PDE1), according to Formula I, below,</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="33.19mm" wi="46.06mm" file="US10005789-20180626-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein R<sub>1</sub>, R<sub>2</sub>, R<sub>3 </sub>and R<sub>4 </sub>are as defined herein, 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>
>> Read More

Aza-heteroaryl compounds as PI3K-gamma inhibitors (Fri, 18 Aug 2017)
<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="58.50mm" file="US10022387-20180717-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>
>> Read More

NOVEL CLASS OF COMPOUNDS FOR THE TREATMENT OF CARDIOVASCULAR DISEASE (Fri, 18 Aug 2017)
The present invention relates to the field of medicine, specifically the field of treatment and prevention of cardiovascular diseases.
>> Read More

ORGANIC COMPOUNDS (Fri, 11 Aug 2017)
<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>
>> Read More

Preparation and Uses of Obeticholic Acid (Fri, 11 Aug 2017)
<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="US20170226149A1-20170810-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>
>> Read More

PIPERAZINE DERIVATIVES AS LIVER X RECEPTOR MODULATORS (Fri, 11 Aug 2017)
<p id="p-0001" num="0000">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.</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="US20170226067A1-20170810-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

Fluorinated benzofuranyl-pyrimidine derivatives containing a sulfone group (Fri, 11 Aug 2017)
<p id="p-0001" num="0000">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). R<sup>2 </sup>represents the group (a).</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="72.31mm" wi="65.11mm" file="US09902716-20180227-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

Organic compounds (Fri, 04 Aug 2017)
<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>
>> Read More

NOVEL 3-AMINO-PYRROLO[3,4-C]PYRAZOLE-5(1H, 4H,6H) CARBALDEHYDE DERIVATIVES (Fri, 04 Aug 2017)
<p id="p-0001" num="0000">The present invention relates to compounds and pharmaceutically acceptable salts of Formulas A and B:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="92.03mm" wi="69.93mm" file="US20170217991A1-20170803-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein A, B, R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4</sup>, R<sup>5</sup>, R<sup>6</sup>, R<sup>7</sup>, R<sup>8</sup>, R<sup>9 </sup>and R<sup>10 </sup>are as defined above. The invention further relates to pharmaceutical compositions comprising the compounds and pharmaceutically acceptable salts and to methods of treating diabetes mellitus and its complications, cancer, ischemia, inflammation, central nervous system disorders, cardiovascular disease, Alzheimer's disease and dermatological disase pression, virus diseases, inflammatory disorders, or diseases in which the liver is a target organ.</p>
>> Read More

4-aryl-N-phenyl-1,3,5-triazin-2-amines containing a sulfoximine group (Fri, 04 Aug 2017)
<p id="p-0001" num="0000">The present invention relates to 4-aryl-N-phenyl-1,3,5-triazin-2-amines containing a sulfoximine group of general formula (I) or (Ia) 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) or (Ia).</p>
>> Read More

Fluorinated benzofuranyl-pyrimidine derivatives containing a sulfoximine group (Fri, 04 Aug 2017)
<p id="p-0001" num="0000">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).</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="30.40mm" wi="67.14mm" file="US09884849-20180206-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

Fluorinated benzofuranyl-pyrimidine derivatives containing a sulfoximine group (Wed, 02 Aug 2017)
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).
>> Read More

IRAK4 INHIBITING AGENTS (Fri, 28 Jul 2017)
Provided are compounds of Formula I, or pharmaceutically acceptable salts thereof, and methods for their use and production. Formula (I) The compounds are IRAK-4 inhibitors useful for treating an inflammatory disease, an autoimmune disease, cancer, a cardiovascular disease, a disease of the central nervous system, a disease of the skin, an ophthalmic disease and condition, and a bone disease.
>> Read More

Ring-fused pyrimidines and triazines and use thereof for the treatment and/or prophylaxis of cardiovascular diseases (Wed, 26 Jul 2017)
The invention relates to novel ring-fused pyrimidines and triazines, to methods for the production thereof, use thereof on its own or combined for the treatment and/or prophylaxis of diseases and to the use thereof for producing medicaments for the treatment and/or prophylaxis of diseases, in particular for the treatment and/or prophylaxis of cardiovascular diseases.
>> Read More

5-fluoro-N-(pyridin-2-yl)pyridin-2-amine derivatives containing a sulfoximine group (Fri, 21 Jul 2017)
<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>
>> Read More

EGF(A) ANALOGUES WITH FATTY ACID SUBSTITUENTS (Fri, 21 Jul 2017)
The invention relates to compounds derived from the EGF(A) domain of LDL-R, in particular compounds comprising a peptide analogue of the wild-type EGF(A) (LDL-R(293- 332)) sequence and at least one substituent comprising at least one fatty acid group. The invention also relates to a pharmaceutical composition thereof and use a medicament. The novel EGF(A) compounds of the invention are useful as treatment e.g. in the field of cholesterol lowering, dyslipidaemia and cardiovascular disease.
>> Read More

FLAVONOIDE-TYPE COMPOUNDS BEARING AN O-RHAMNOSYL RESIDUE (Fri, 21 Jul 2017)
The present invention relates to compounds of formula (I) These compounds are useful in the treatment of many diseases such as a skin disease, an allergy, an autoimmune disease, a cardiovascular disease, a lung disease, asthma, a bacterial, viral or parasitic disease, metabolic syndrome, cancer, Alzheimer's disease or diabetes and are furthermore useful in the preparation of cosmetics and for use in food and animal feed.
>> Read More

Inhibitors of the renal outer medullary potassium channel (Fri, 14 Jul 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="31.16mm" wi="64.52mm" file="US09926317-20180327-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

APOPTOSIS SIGNAL-REGULATING KINASE INHIBITORS (Fri, 14 Jul 2017)
<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="24.98mm" wi="66.80mm" file="US20170196844A1-20170713-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">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>
>> Read More

TGR5 AGONIST COMPLEXES FOR TREATING DIABETES AND CANCER (Fri, 14 Jul 2017)
<p id="p-0001" num="0000">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.</p>
>> Read More

Compositions and Methods for Inhibiting BMP (Fri, 14 Jul 2017)
<p id="p-0001" num="0000">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.</p>
>> Read More

INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL (Fri, 14 Jul 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="31.58mm" wi="66.38mm" file="US20170197989A1-20170713-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

NOVEL COMPOUNDS WHICH ACTIVATE ESTROGEN RECEPTORS AND COMPOSITIONS AND METHODS OF USING THE SAME (Fri, 14 Jul 2017)
Provided are compounds of formulae provided herein. The compounds may include pathway-preferential estrogens (PaPEs) derivatives with tissue-selective activities. Also provided are pharmaceutical compositions comprising the compounds, as well as methods of treating a disease or condition including administering the compounds. The disease or condition may include postmenopausal symptoms, cardiovascular disease, stroke, vascular disease, bone disease, metabolic disease, arthritis, osteoporosis, obesity, vasomotor/hot flush, cognitive decline, cancer including breast cancer.
>> Read More

PYRIDINE AND PYRIDIMINE COMPOUNDS AS PI3K-GAMMA INHIBITORS (Fri, 14 Jul 2017)
The present disclosure provides compounds of Formula I, or pharmaceutically acceptable salts thereof, that modulate 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.
>> Read More

PYRIDINE AND PYRIDIMINE COMPOUNDS AS PI3K-GAMMA INHIBITORS (Fri, 07 Jul 2017)
<p id="p-0001" num="0000">The present disclosure provides compounds of Formula I, or pharmaceutically acceptable salts thereof, that modulate 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> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="40.22mm" wi="52.83mm" file="US20170190689A1-20170706-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

Compositions and Methods for Inhibiting BMP (Fri, 07 Jul 2017)
<p id="p-0001" num="0000">The present invention provides small molecules 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.</p>
>> Read More

Substituted bridged urea analogs as sirtuin modulators (Fri, 07 Jul 2017)
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. Figure 1. H-NMR Spectrum of Compound 1
>> Read More

Deuterated dipeptide boric acids or esters thereof, and synthetic methods and uses of the compounds (Wed, 05 Jul 2017)
Deuterated dipeptide boric acids or esters thereof, or crystal forms thereof, or pharmaceutically acceptable hydrates or solvates thereof are disclosed. The general structure of the compounds is shown as a formula (a) in the specification, wherein R1, R2, R3, R4, R5 and R6 are independently selected from hydrogen, deuterium or halogens, or C1-C4 alkyl one or a plurality of or all hydrogen atoms of which are deuterated; and at least one of the R1, the R2, the R3, the R4, the R5 and the R6 is deuterated or deuterium. The compounds can effectively inhibit proteasomes and effectively treat or prevent cancer, cardiovascular disease, inflammation, immune disease, nephropathy, vasculogenesis or prostate disease.
>> Read More

POLYMORPHIC CRYSTALLINE FORMS OF OBETICHOLIC ACID (Fri, 30 Jun 2017)
The present application relates to crystalline forms A, D, F, G and I of obeticholic acid. These crystalline forms are useful in the production of Obeticholic acid (in particular its purification), which is a drug 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.
>> Read More

4-AMINO-2-(1H-PYRAZOLO[3,4-B]PYRIDIN-3-YL)-6-OXO-6,7-DIHYDRO-5H-PYRROLO[2,3-D]PYRIMIDINE DERIVATIVES AND THE RESPECTIVE (1H-INDAZOL-3-YL) DERIVATIVES AS CGMP MODULATORS FOR TREATING CARDIOVASCULAR DISEASES (Fri, 30 Jun 2017)
The invention provides compounds of the Formula (I) or a pharmaceutically acceptable salts thereof, wherein X, Y, Z, R1, R2, R4, Ra, and the subscripts m, p, and q are as described herein. The compounds or their pharmaceutically acceptable salts can modulate the body's production of cyclic guanosine monophosphate ("cGMP"), and are generally suitable for the therapy and prophylaxis of diseases which are associated with a disturbed cGMP balance, such as cardiovascular disease, endothelial dysfunction, diastolic dysfunction, atherosclerosis, hypertension, heart failure, pulmonary hypertension (WHO groups I, II, III, IV), angina pectoris, thrombosis, restenosis, myocardial infarction, stroke, cardiac insufficiency, fibrosis, pulmonary hypertonia, erectile dysfunction, asthma, acute respiratory distress syndrome (ARDS), chronic kidney disease, cystic fibrosis, sickle cell anemia, scleroderma, Raynaud's Syndrome, diabetes, diabetic retinopathy, cirrhosis of the liver, chronic obstructive pulmonary disease (COPD), acute lung injury, pulmonary fibrosis or interstitial lung disease. The invention also provides pharmaceutical compositions which comprise compounds of Formula (I) or pharmaceutically acceptable salts thereof. The invention also relates to the compounds or their pharmaceutically acceptable salts for use in the therapy and prophylaxis of the abovementioned diseases and for preparing pharmaceuticals for this purpose.
>> Read More

4-amino-2-(1H-pyrazolo[3,4-b]pyridin-3-yl)-6-oxo-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine derivatives and the respective (1H-indazol-3-yl) derivatives as cGMP modulators for treating cardiovascular diseases (Fri, 30 Jun 2017)
The invention provides compounds of the Formula (I) or a pharmaceutically acceptable salts thereof, wherein X, Y, Z, R<sp>1</sp>, R<sp>2</sp>, R<sp>4</sp>, R<sp>a</sp>, and the subscripts m, p, and q are as described herein. The compounds or their pharmaceutically acceptable salts can modulate the body's production of cyclic guanosine monophosphate ("cGMP"), and are generally suitable for the therapy and prophylaxis of diseases which are associated with a disturbed cGMP balance, such as cardiovascular disease, endothelial dysfunction, diastolic dysfunction, atherosclerosis, hypertension, heart failure, pulmonary hypertension (WHO groups I, II, III, IV), angina pectoris, thrombosis, restenosis, myocardial infarction, stroke, cardiac insufficiency, fibrosis, pulmonary hypertonia, erectile dysfunction, asthma, acute respiratory distress syndrome (ARDS), chronic kidney disease, cystic fibrosis, sickle cell anemia, scleroderma, Raynaud's Syndrome, diabetes, diabetic retinopathy, cirrhosis of the liver, chronic obstructive pulmonary disease (COPD), acute lung injury, pulmonary fibrosis or interstitial lung disease. The invention also provides pharmaceutical compositions which comprise compounds of Formula (I) or pharmaceutically acceptable salts thereof. The invention also relates to the compounds or their pharmaceutically acceptable salts for use in the therapy and prophylaxis of the abovementioned diseases and for preparing pharmaceuticals for this purpose.
>> Read More

LOW ERUCTATION COMPOSITION AND METHODS FOR TREATING AND/OR PREVENTING CARDIOVASCULAR DISEASE IN A SUBJECT WITH FISH ALLERGY/HYPERSENSITIVITY (Fri, 30 Jun 2017)
In various embodiments, the present invention provides pharmaceutical compositions comprising fatty acids and methods for treating subjects using same.
>> Read More

Preparation, Uses and Solid Forms of Obeticholic Acid (Fri, 30 Jun 2017)
The present invention relates to obeticholic acid: 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.
>> Read More

Polymorphic crystalline forms of obeticholic acid (Fri, 30 Jun 2017)
The present application relates to crystalline forms A, D, F, G and I of obeticholic acid. These crystalline forms are useful in the production of Obeticholic acid (in particular its purification), which is a drug 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.
>> Read More

Apoptosis signal-regulating kinase inhibitors (Fri, 23 Jun 2017)
<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="30.56mm" wi="72.56mm" file="US09943521-20180417-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> 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>
>> Read More

Fumarate-CO-releasing molecule hybrids, their use in the treatment of inflammatory or cardiovascular diseases and their process of preparation (Fri, 23 Jun 2017)
<p id="p-0001" num="0000">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.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="42.42mm" wi="69.85mm" file="US09944669-20180417-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

1H-IMIDAZO[4,5-B]PYRIDINYL AND 2-OXO-2,3-DIHYDRO-1H-IMIDAZO[4,5-B]PYRIDINYL HETEROCYCLIC BET BROMODOMAIN INHIBITORS (Fri, 23 Jun 2017)
Substituted 1H-imidazo[4,5-b]pyridinyl and 2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridinyl heterocyclic compounds, which are useful as inhibitors of BET protein function by binding to bromodomains, compositions comprising said compounds, and their use in therapy are disclosed herein. These compounds are useful in the treatment of diseases and conditions, such as, cancer, autoimmune diseases, inflammation and cardiovascular diseases.
>> Read More

Danproone compound 15-site amide derivative, and preparation process and application thereof (Wed, 14 Jun 2017)
The invention belongs to the field of pharmacy, and relates to a danproone compound 15-site amide derivative, and a preparation process and application thereof. The preparation process comprises the following preparation steps: (1) preparation of a danproone intermediate; (2) preparation of a danproone-1,5-aminomethyl; (3) preparation of the danproone compound 15-site amide derivative. The derivative is applied to preparing a micro-capsule type sustained release solid dispersion body of a medicament for preventing and treating cardiovascular diseases. Through thin layer chromatography analysis and solubility property research, the polarities of the danproone compound 15-site amide derivative are enhanced compared with those of danproone compounds, and the bioavailability is improved. The preparation of an intermediate of the micro-capsule type sustained release solid dispersion body is beneficial to further preparation of various preparations, such as pills, tablets, capsules and powder injections, for clinical application; new possibility is provided for the development of a new medicament for preventing and treating the cardiovascular diseases and the utilization of radix salviae miltiorrhizae.
>> Read More

BENZIMIDAZOLE COMPOUNDS AND THEIR APPLICATION IN CARDIOVASCULAR DISEASES (Fri, 02 Jun 2017)
<p id="p-0001" num="0000">The present invention provides substituted benzimidazoles, pharmaceutical composition comprising the substituted benzimidazoles, and their use for preventing or treating a subject suffering from diseases or conditions associated with platelet activation aggregation and/or platelet activation.</p>
>> Read More

NOVEL AZOLE DERIVATIVES AS APELIN RECEPTOR AGONIST (Fri, 02 Jun 2017)
The present invention relates to a novel azole derivative as an apelin receptor agonist and a method for treating cardiovascular disease, diabetic disease, renal disease, hypertension, and arteriosclerosis, etc., using the same. The present invention provides a compound represented by formula (I) or a pharmacologically acceptable salt thereof wherein X1 represents -N= or -CH=, X2 represents -CH= or -N=, R1 and R2 each represent a C1 to C6 alkoxy group or the like, R3 represents a heteroaryl group (the heteroaryl group is optionally substituted by a methyl group or the like) or the like, and R4 represents a C1 to C6 alkylthio group or a C2 to C6 alkenyl group (the C1 to C6 alkylthio group and the C2 to C6 alkenyl group are each optionally substituted by one carboxy group or the like) or the like.
>> Read More

Dihydropteridinone derivatives and uses thereof (Fri, 26 May 2017)
<p id="p-0001" num="0000">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.</p>
>> Read More

MODULATORS OF THE RELAXIN RECEPTOR 1 (Fri, 26 May 2017)
<p id="p-0001" num="0000">Disclosed are modulators of the human relaxin receptor 1, for example, of formula (I), wherein A, R<sup>1</sup>, and R<sup>2 </sup>are as defined herein, that are useful in treating mammalian relaxin receptor 1 mediated facets of human health, e.g., cardiovascular disease. Also disclosed is a composition comprising a pharmaceutically suitable carrier and at least one compound of the disclosure, and a method for therapeutic intervention in a facet of mammalian health that is mediated by a human relaxin receptor 1.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="15.58mm" wi="50.04mm" file="US20170144984A1-20170525-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

BENZIMIDAZOLE DERIVATIVES AS PI3 KINASE INHIBITORS (Thu, 25 May 2017)
The invention relates to benzimidazole derivatives of formula (I) which modulate, notably inhibit the activity or function of the phosphoinositide 3'-OH kinase family (PI3 kinases), suitably PI3K±, PI3K´, PI3K² and/or PI3K³. The invention further relates to these benzimidazoles for use in the treatment of 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. Especially, the invention relates to PI3K² selective benzimidazoles for use in treating cancer.
>> Read More

VACCINES AND MONOCLONAL ANTIBODIES TARGETING TRUNCATED VARIANTS OF OSTEOPONTIN AND USES THEREOF (Fri, 19 May 2017)
<p id="p-0001" num="0000">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.</p>
>> Read More

ORGANIC COMPOSITIONS TO TREAT APOC3-RELATED DISEASES (Fri, 19 May 2017)
<p id="p-0001" num="0000">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.</p>
>> Read More

HETEROCYCLIC COMPOUNDS AS PI3K-y INHIBITORS (Fri, 12 May 2017)
<p id="p-0001" num="0000">This application 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="54.95mm" wi="58.59mm" file="US20170129899A1-20170511-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or pharmaceutically acceptable salts or stereoisomers thereof, which are inhibitors of PI3K-γ which are useful for the treatment of disorders such as autoimmune diseases, cancer, cardiovascular diseases, and neurodegenerative diseases.</p>
>> Read More

COMPOSITIONS AND METHODS FOR TREATING AND/OR PREVENTING CARDIOVASCULAR DISEASE (Fri, 12 May 2017)
<p id="p-0001" num="0000">In various embodiments, the present invention provides pharmaceutical compositions comprising fatty acids and methods for treating subjects using same.</p>
>> Read More

1,4-DICARBONYL-PIPERIDYL DERIVATIVES (Fri, 12 May 2017)
Compounds of the formula I in which Z, W, Q, R 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.
>> Read More

5-DEOXY-IRILIN B HAVING ANGIOTENSIN-I-CONVERTING ENZYME INHIBITION ACTIVITY DERIVED FROM SALICORNIA SPP. AND COMPOSITION CONTAINING THE SAME (Fri, 12 May 2017)
A compound having antihypertensive activity, especially 5-deoxy-irilin B having angiotensin-I-converting enzyme inhibition activity, derived from Salicornia SPP., a salty sauce containing the same, and a composition for the prevention and treatment of hypertension containing the same are provided. The Salicornia SPP.-derived salty sauce having superior sensory and functional properties can be produced through cutting or grinding and then hydrolyzing of Salicornia SPP. alone, thus increasing the amounts of polyphenols, which is effective in the treatment of hypertension, and glutamic acid, which is responsible for a savory taste; through purification, thus improving sensory properties such as removal of unpleasant tastes and odors and decoloration; and through concentration under reduced pressure, thus exhibiting both a savory taste and a salty taste, and can also be efficiently utilized as functional foods and medications for the prevention of hypertension and cardiovascular disease, and contains large amounts of organic nutrients and is thus nutritionally useful.
>> Read More

HETEROCYCLIC COMPOUNDS AS PI3K-GAMMA INHIBITORS (Fri, 12 May 2017)
This application relates to compounds of Formula (I): or pharmaceutically acceptable salts or stereoisomers thereof, which are inhibitors of PI3K-γ which are useful for the treatment of disorders such as autoimmune diseases, cancer, cardiovascular diseases, and neurodegenerative diseases.
>> Read More

1,4-dicarbonyl-piperidyl derivatives (Fri, 12 May 2017)
Compounds of the formula I in which Z, W, Q, R 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.
>> Read More

PPAR MODULATORS (Fri, 05 May 2017)
<p id="p-0001" num="0000">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.</p>
>> Read More

Benzimidazole derivatives as PI3 kinase inhibitors (Fri, 28 Apr 2017)
<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>
>> Read More

OXADIAZOLE AMINE DERIVATIVE COMPOUNDS AS HISTONE DEACETYLASE 6 INHIBITOR, AND THE PHARMACEUTICAL COMPOSITION COMPRISING THE SAME (Fri, 21 Apr 2017)
The present disclosure 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 disclosure 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.
>> Read More

CONFORMATIONALLY CONSTRAINED MACROCYCLIC COMPOUNDS AS PIN1 MODULATORS (Fri, 21 Apr 2017)
Conformationally constrained macrocyclic compounds of formula (I), including substituents E, G, and Q, as defined in the description and the claims, and salts thereof, have the property to modulate the activity of the peptidyl-prolyl cis/trans isomerases Pin1. Thus, these compounds and pharmaceutical compositions containing said compounds may be useful in the treatment and/or prevention of diseases or conditions in the area of proliferative disorders and diseases, such as e.g. cancer, inflammatory diseases, transplant rejection, viral infections, osteolytic bone diseases, cardiac diseases, cardiovascular diseases, respiratory diseases, acute neurological diseases, neurodegenerative diseases, immune disorders, and lymphoproliferative theileriosis.
>> Read More

CONFORMATIONALLY CONSTRAINED MACROCYCLIC COMPOUNDS (Fri, 21 Apr 2017)
Conformationally constrained macrocyclic compounds of formula (I), including substituents E with at least one ester moiety, G and Q, as defined in the description and the claims, and salts thereof, can be metabolized to compounds that have the property to modulate the activity of the peptidyl-prolyl cis/trans isomerase Pin1. In addition, they show antiproliferative activity on various cancer cell lines. Thus, these compounds and pharmaceutical compositions containing said compounds may be useful in the treatment and/or prevention of diseases or conditions in the area of proliferative disorders and diseases, such as e.g. cancer, inflammatory diseases, transplant rejection, viral infections, osteolytic bone diseases, cardiac diseases, cardiovascular diseases, respiratory diseases, acute neurological diseases, neurodegenerative diseases, immune disorders, and lymphoproliferative theileriosis.
>> Read More

CONFORMATIONALLY CONSTRAINED MACROCYCLIC COMPOUNDS (Fri, 21 Apr 2017)
Formula (I); Conformationally constrained macrocyclic compounds of formula (I), including substituents E with at least one ester moiety, G and Q, as defined in the description and the claims, and salts thereof, can be metabolized to compounds that have the property to modulate the activity of the peptidyl-prolyl cis/trans isomerase Pin1. In addition, they show antiproliferative activity on various cancer cell lines. Thus, these compounds and pharmaceutical compositions containing said compounds may be useful in the treatment and/or prevention of diseases or conditions in the area of proliferative disorders and diseases, such as e.g. cancer, inflammatory diseases, transplant rejection, viral infections, osteolytic bone diseases, cardiac diseases, cardiovascular diseases, respiratory diseases, acute neurological diseases, neurodegenerative diseases, immune disorders, and lymphoproliferative theileriosis.
>> Read More

CONFORMATIONALLY CONSTRAINED MACROCYCLIC COMPOUNDS AS PIN1 MODULATORS (Fri, 21 Apr 2017)
Conformationally constrained macrocyclic compounds of formula (I), including substituents E, G, and Q, as defined in the description and the claims, and salts thereof, have the property to modulate the activity of the peptidyl-prolyl cis/trans isomerases Pin1. Thus, these compounds and pharmaceutical compositions containing said compounds may be useful in the treatment and/or prevention of diseases or conditions in the area of proliferative disorders and diseases, such as e.g. cancer, inflammatory diseases, transplant rejection, viral infections, osteolytic bone diseases, cardiac diseases, cardiovascular diseases, respiratory diseases, acute neurological diseases, neurodegenerative diseases, immune disorders, and lymphoproliferative theileriosis.
>> Read More

Oxadiazole amine derivative compounds as histone deacetylase 6 inhibitor, and the pharmaceutical composition comprising the same (Fri, 21 Apr 2017)
The present disclosure 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 disclosure 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.
>> Read More

NOVEL MODIFIED MACROCYCLIC COMPOUNDS (Fri, 14 Apr 2017)
The present invention relates to novel modified 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).
>> Read More

ASGR INHIBITORS (Fri, 07 Apr 2017)
Antigen binding proteins that interact with ASGR, ASGR-1 and/or ASGR-2 are described as well as methods of making and using such antigen binding proteins. Methods of treating and preventing cardiovascular disease by administering a pharmaceutically effective amount of ASGR, ASGR-1 and/or ASGR-2 antigen binding proteins. Methods of treating and preventing cardiovascular disease by administering a pharmaceutically effective amount of interfering RNA compositions that reduce expression of ASGR, ASGR-1 and/or ASGR-2 are described.
>> Read More

NOVEL MACROCYCLIC SULFONDIIMINE COMPOUNDS (Fri, 07 Apr 2017)
The present invention relates to novel macrocyclic sulfondiimine 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).
>> Read More

ASGR inhibitors (Fri, 07 Apr 2017)
Antigen binding proteins that interact with ASGR, ASGR-1 and/or ASGR-2 are described as well as methods of making and using such antigen binding proteins. Methods of treating and preventing cardiovascular disease by administering a pharmaceutically effective amount of ASGR, ASGR-1 and/or ASGR-2 antigen binding proteins. Methods of treating and preventing cardiovascular disease by administering a pharmaceutically effective amount of interfering RNA compositions that reduce expression of ASGR, ASGR-1 and/or ASGR-2 are described.
>> Read More

SUBSTITUTED PYRIDINE-2-CARBOXAMIDE COMPOUNDS AS APOPTOSIS SIGNAL-REGULATING KINASE INHIBITORS (Thu, 06 Apr 2017)
The present invention relates to compounds of Formula (I): 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.
>> Read More

ASGR INHIBITORS (Fri, 31 Mar 2017)
<p id="p-0001" num="0000">Antigen binding proteins that interact with ASGR, ASGR-1 and/or ASGR-2 are described as well as methods of making and using such antigen binding proteins. Methods of treating and preventing cardiovascular disease by administering a pharmaceutically effective amount of ASGR, ASGR-1 and/or ASGR-2 antigen binding proteins. Methods of treating and preventing cardiovascular disease by administering a pharmaceutically effective amount of interfering RNA compositions that reduce expression of ASGR, ASGR-1 and/or ASGR-2 are described.</p>
>> Read More

COMPOSITIONS AND METHODS FOR THE TREATMENT OF ATHEROSCLEROTIC CARDIOVASCULAR DISEASES WITH PDE4 MODULATORS (Fri, 31 Mar 2017)
<p id="p-0001" num="0000">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.</p>
>> Read More

Replacement Therapy for Natriuretic Peptide Deficiencies (Fri, 31 Mar 2017)
<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="19.13mm" wi="69.85mm" file="US20170087205A1-20170330-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>
>> Read More

Fused heterocyclic compounds as ion channel modulators (Fri, 31 Mar 2017)
<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="27.60mm" wi="58.67mm" file="US09920018-20180320-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> 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>
>> Read More

HIGHLY EFFICIENT NRF2 ACTIVATORS-CO-RELEASING MOLECULE HYBRIDS, THEIR USE IN THE TREATMENT OF INFLAMMATORY OR CARDIOVASCULAR DISEASES AND THEIR PROCESS OF PREPARATION (Fri, 31 Mar 2017)
The present invention relates to highly efficient Nrf2 activators-CO-releasing molecules of formula (I) and (II) capable of increasing 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, wherein CORM represents a carbonyl metal complex chosen from among: Mn(CO)5, formula (III), (IV), (V), (VI), (VII), (VIII) and (IX).
>> Read More

HETEROCYCLIC HO-1 INDUCERS, THEIR USE IN THE TREATMENT OF INFLAMMATORY OR CARDIOVASCULAR DISEASES AND THEIR PROCESS OF PREPARATION (Fri, 31 Mar 2017)
The present invention relates to modified fumarate molecules capable of activating HO-1 protein expression, their synthesis and their use in therapeutic applications, in particular their use in the treatment of inflammatory and cardiovascular diseases.
>> Read More

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.
>> Read More

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.
>> Read More

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.
>> Read More

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 R<sp>1</sp>, R<sp>2</sp>, R<sp>3</sp>, R<sp>4</sp>, R<sp>5</sp>, R<sp>6</sp>, R<sp>7</sp>, 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.
>> Read More

Substituted benzoazepines as toll-like receptor modulators (Thu, 23 Mar 2017)
Provided are compositions and methods useful for modulation of signaling through the Toll-like receptors TLR7 and/or TLR8. The compositions and methods have use in treating or preventing disease, including cancer, autoimmune disease, fibrotic disease, cardiovascular disease, infectious disease, inflammatory disorder, graft rejection, or graft-versus-host disease.
>> Read More

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>
>> Read More

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="US09809598-20171107-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> 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>
>> Read More

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>
>> Read More

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.
>> Read More

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 (<i>e.g.</i>, bromo and extra terminal (BET) proteins). Also provided are methods, uses, and kits using the compounds and pharmaceutical compositions for inhibiting the activity (<i>e.g.</i>, 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 (<i>e.g.</i>, 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.
>> Read More

Difluromethyl-substituted oxazolidinone compounds and application thereof (Thu, 16 Mar 2017)
The invention relates to difluromethyl-substituted oxazolidinone compounds and application thereof, especially the application of the compounds as drugs for treatment and prevention of cardiovascular diseases. To be specific, the invention relates to the compounds shown in a general formula (I) or the enantiomers, diastereoisomers, hydrates, solvates or pharmaceutically acceptable salts of the compounds, wherein each variable is defined as in the specification. The invention further relates to the compounds shown in the general formula (I) or (Ia) or the application of the enantiomers, diastereoisomers, hydrates, solvates or pharmaceutically acceptable salts or pharmaceutical compositions of the compounds, especially the application in inhibiting CETP. Please the formula in the specification.
>> Read More

6-chlorine-substituted imidazo[1,2-a]pyridine carboxamides and the use thereof as soluble guanylate cyclase stimulators (Thu, 16 Mar 2017)
The present application relates to new 6-chlorine-substituted imidazo[1,2-a]pyridine-3-carboxamides, to a method for the production thereof, to the use thereof alone or in combinations for treating and/or preventing diseases and to the use thereof for producing medicaments for treating and/or preventing diseases, in particular for treating and/or preventing cardiovascular diseases.
>> Read More

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>
>> Read More

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>
>> Read More

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.
>> Read More

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.
>> Read More

Piperazine derivatives as liver X receptor modulators (Fri, 03 Mar 2017)
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.
>> Read More

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.
>> Read More

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.
>> Read More

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>
>> Read More

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>
>> Read More

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>
>> Read More

Substituted piperidinyl-tetrahydroquinolines and their use as [alpha]-2c adrenoreceptor antagonists (Thu, 23 Feb 2017)
The invention relates to novel substituted piperidinyl-tetrahydroquinolines of formula (I), methods for producing same, their use for treating and/or preventing diseases, and their use in the production of medications for treating and/or preventing diseases, particularly for treating and/or preventing diabetic microangiopathies, diabetic abscesses of the extremities, particularly promoting tissue repair in diabetic foot ulcers, diabetic heart failure, diabetic coronary microvascular heart diseases, peripheral vascular and cardiovascular diseases, thromboembolic diseases and ischaemia, peripheral circulatory disorders, Raynaud's phenomenon, CREST syndrome, microcirculatory disorders, intermittent claudication, and peripheral and autonomic neuropathies.
>> Read More

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>
>> Read More

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>
>> Read More

Fumarate-co-releasing molecule hybrids, their use in the treatment of inflammatory or cardiovascular diseases and their process of preparation (Thu, 16 Feb 2017)
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.
>> Read More

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="US09718808-20170801-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

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.
>> Read More

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.
>> Read More

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.
>> Read More

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.
>> Read More

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="US09963464-20180508-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

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.
>> Read More

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.
>> Read More

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.</p>
>> Read More

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.
>> Read More

Fused ring pyrimidine compound, intermediate, and preparation method, composition and use thereof (Fri, 27 Jan 2017)
Disclosed are a fused ring pyrimidine compound, and an intermediate, a preparation method, a composition and a use thereof. The fused ring pyrimidine compound is a compound as shown in formula I, a tautomer, an enantiomer, a diastereoisomer, a pharmaceutically acceptable salt, a metabolite, a metabolic precursor or a prodrug thereof, wherein the above-mentioned compound is used for the preparation of a medicine for preventing, remitting or treating one or more of immune system diseases, autoimmune diseases, cell proliferative diseases, allergic disorders and cardiovascular diseases, and the compound has a strong inhibitory effect on the Janus kinase, FGFR kinase, FLT3 kinase and Src family kinase.
>> Read More

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>
>> Read More

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>
>> Read More

MODULATION OF APOLIPOPROTEIN CIII (APOCIII) EXPRESSION (Fri, 20 Jan 2017)
Provided herein are methods, compounds, and compositions for reducing expression of ApoClil 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.
>> Read More

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.
>> Read More

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>
>> Read More

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.
>> Read More

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>
>> Read More

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>
>> Read More

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="US09718826-20170801-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> in which R<sup>1 </sup>and R<sup>2 </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>
>> Read More

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>
>> Read More

Vaccines and monoclonal antibodies targeting truncated variants of osteopontin and uses thereof (Fri, 06 Jan 2017)
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.
>> Read More

Mastic tetracyclic triterpenoid components with 11 beta-hydroxysteroid dehydrogenase 1 inhibitory activity, composition of mastic tetracyclic triterpenoid components and application (Thu, 05 Jan 2017)
The invention provides mastic tetracyclic triterpenoid components with 11 beta-hydroxysteroid dehydrogenase 1 inhibitory activity, a composition of the mastic tetracyclic triterpenoid components and application, and novel application of mastic tetracyclic triterpenoid components with structures of the general formulas I-IV as 11 beta-HDS inhibitors. As a class of 11 beta-HSD inhibitors in novel structure types, the mastic tetracyclic triterpenoid components have certain selective inhibition effects on 11 beta-HSD1 and are expected to be developed into medicine for regulating lipid metabolism and treating diabetes, obesity, cardiovascular diseases and the like.
>> Read More

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>
>> Read More

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.
>> Read More

Deuterated thienopiperidine derivatives, manufacturing method, and application thereof (Fri, 30 Dec 2016)
The present invention discloses deuterated thienopiperidine derivatives, a manufacturing method, and an application thereof. The deuterated thienopiperidine derivatives in the present invention are of the following formula (I). The present invention also comprises the application of the deuterated thienopiperidine derivatives as a drug for treating and preventing cardiovascular diseases.
>> Read More

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.
>> Read More

3-(PYRIMIDINE-2-YL)IMIDAZO[1,2-A]PYRIDINES (Thu, 29 Dec 2016)
The application relates to novel 3-(pyrimidine-2-yl) imidazo[1,2-a]pyridines of formula (I), methods for producing same, the use thereof alone or in combinations for treating and/or preventing diseases, and the use thereof for producing medicaments for treating and/or preventing diseases, in particular for treating and/or preventing cardiovascular diseases.
>> Read More

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>
>> Read More

Heterocyclyl-butanamide derivatives (Fri, 23 Dec 2016)
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.
>> Read More

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="US09682998-20170620-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>
>> Read More

Tricyclic derivative compound, method for preparing same, and pharmaceutical composition comprising same (Fri, 16 Dec 2016)
The present invention relates to a novel tricyclic derivative compound and, more specifically, to a tricyclic derivative compound having excellent inhibitory activity against PARP-1, tankyrase-1, or tankyrase-2, optical isomers thereof, a racemate thereof, or a pharmaceutically acceptable salt thereof. The tricyclic derivative compound, optical isomers thereof, racemate thereof, or pharmaceutically acceptable salt thereof according to the present invention can be usefully used for the prevention or treatment of neuropathic pain, neurodegenerative diseases, cardiovascular diseases, diabetic neuropathy, inflammatory diseases, osteoporosis, or cancer through inhibitory activity against PARP-1, tankyrase-1, or tankyrase-2.
>> Read More

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>
>> Read More

Fatty acids and their use in conjugation to biomolecules (Fri, 09 Dec 2016)
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 R<sp>1</sp>, R<sp>2</sp>, R<sp>3</sp>, R<sp>4</sp>, 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.
>> Read More

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.
>> Read More

Fused heterocyclic compounds as ion channel modulators (Fri, 02 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="25.82mm" wi="53.34mm" file="US09676760-20170613-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> 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>
>> Read More

Diazepane derivatives and uses thereof (Fri, 02 Dec 2016)
<p id="p-0001" num="0000">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.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="206.08mm" wi="75.52mm" file="US09695172-20170704-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

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>
>> Read More

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.
>> Read More

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.
>> Read More

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.</p>
>> Read More

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>
>> Read More

Inhibitors of the renal outer medullary potassium channel (Fri, 18 Nov 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.
>> Read More

Inhibitors of the renal outer medullary potassium channel (Fri, 18 Nov 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.
>> Read More

Six novel flavone saponin meroterpenoid compounds in clinopodium chinense (Thu, 17 Nov 2016)
The invention relates to application for patent protection for chemical structures of six flavone saponin meroterpenoid compounds with a novel structure and separated from clinopodium chinense, as well as an application of the six flavone saponin meroterpenoid compounds in preparation of drugs for treatment and/or prevention of cardiovascular diseases. Herb of clinopodium chinense is extracted with water or/and an alcohol solvent, and after the n-butyl alcohol extract is purified and enriched through macroporous resin, an 50-85% ethanol eluate is obtained. Six novel flavone saponin meroterpenoid components are obtained through separation of the 50-85% ethanol eluate through various separation techniques of column chromatography and the like. The chemical structures of the six flavone saponin meroterpenoid compounds with novel structures, which are obtained after separation, are identified through a modern spectrum technique (IR, UV, MS, 1D-NMR, 2D-NMR), and are separately named as clinoposide A(1), clinoposide B (2), clinoposide C (3), clinoposide D (4), clinoposide E (5), and clinoposide D (6). The six new compounds are structurally characterized by being flavone saponin meroterpenoid compounds with the novel structures.
>> Read More

FUSED HETEROCYCLIC COMPOUNDS AS ION CHANNEL MODULATORS (Thu, 17 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. In particular embodiments, the structure of the compounds is given by Formula I: wherein X, Y, Z, R<sp>2</sp>, R<sp>3</sp>, R<sp>4</sp>, p and q are as described herein, to methods for the preparation and use of the compounds and to pharmaceutical compositions containing the same.
>> Read More

Apolipoprotein A-I mimics (Fri, 11 Nov 2016)
<p id="p-0001" num="0000">Provided are peptides, compositions thereof, and methods for treating or preventing dyslipidemia, a cardiovascular disease, endothelial dysfunction, a macrovascular disorder, or a microvascular disorder.</p>
>> Read More

Thienomethylpiperazine derivatives as inhibitors of soluble epoxide hydrolase (Fri, 11 Nov 2016)
<p id="p-0001" num="0000">The present invention relates to compounds of the formula (I), wherein R1, R2, R3, R4 and X have the meanings indicated in the claims. The compounds of formula I are valuable pharmacologically active compounds. They are highly potent and selective soluble epoxide hydrolase inhibitors and are suitable, for example, for the therapy and prophylaxis of renal failure, diabetic nephropathy, type 2 diabetes mellitus, cardiovascular diseases, inflammatory diseases or could show beneficial effects in pain, dyslipidemia, atherosclerosis wound healing and stroke. The invention furthermore relates to processes for the preparation of compounds of the formula I, their use, in particular as active ingredients in pharmaceuticals, and pharmaceutical preparations comprising them.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="24.30mm" wi="66.38mm" file="US09776991-20171003-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

Inhibitors of the renal outer medullary potassium channel (Fri, 11 Nov 2016)
<p id="p-0001" num="0000">Novel spirocyclic compounds of formula I: and pharmaceutically acceptable salts thereof are disclosed 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. Pharmaceutical compositions and methods of treatment are also included.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="24.72mm" wi="60.79mm" file="US09839629-20171212-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

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.
>> Read More

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.
>> Read More

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.
>> Read More

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.
>> Read More

Substituted imidazo[1,2-a]pyridinecarboxamides and their use (Thu, 10 Nov 2016)
The invention relates to novel substituted imidazo[1,2-a]pyridino-3-carboxamides, to methods for their production, their use alone or in combination for the treatment and/or prophylaxis of diseases, and their use for producing medicaments for the treatment and/or prophylaxis of diseases, especially for the treatment and/or prophylaxis of cardiovascular diseases.
>> Read More

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>
>> Read More

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="US09751842-20170905-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> 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>
>> Read More

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>
>> Read More

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.
>> Read More

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.
>> Read More

Substituted pyridine-2-carboxamide compounds as apoptosis signal-regulating kinase inhibitors (Fri, 04 Nov 2016)
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 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.
>> Read More

IMIDAZOPYRAZINONE DERIVATIVES (Thu, 03 Nov 2016)
Compounds of the formula (I) in which R<sp>1</sp> and R<sp>2</sp> 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.
>> Read More

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.
>> Read More

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).
>> Read More

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.
>> Read More

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), R<sp>2</sp>, R<sp>3</sp>, R<sp>4</sp>, R<sp>5</sp> and R<sp>6</sp>, 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).
>> Read More

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.
>> Read More

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.
>> Read More

FUSED HETEROCYCLIC COMPOUNDS 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. In particular embodiments, the structure of the compounds is given by Formula (I); wherein n, R<sp>1</sp>, R<sp>2</sp>, R<sp>2'</sp>, R<sp>3</sp>, R<sp>4</sp>, R<sp>5</sp>, R<sp>6</sp> and R<sp>7</sp> are as described herein, and to methods for the preparation and use of the compounds and to pharmaceutical compositions containing the same.
>> Read More

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>
>> Read More

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>
>> Read More

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>
>> Read More

Substituted aza-bicyclic imidazole derivatives useful 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>
>> Read More

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>
>> Read More

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="US10000484-20180619-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

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.
>> Read More

Site Search