Cardiovascular diseases

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.
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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.
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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.
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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.
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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.
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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.
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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.
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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).
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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.
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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.
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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.
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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="30.90mm" wi="69.85mm" file="US20170283416A1-20171005-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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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.
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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>
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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>
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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="30.82mm" wi="65.02mm" file="US20170275283A1-20170928-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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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>
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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.
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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.
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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.
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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>
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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>
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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.
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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.
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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="US20170232016A1-20170817-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">and pharmaceutically acceptable salts thereof, wherein X, Y, Z, A, W, R<sup>4</sup>, R<sup>5</sup>, and R<sup>6 </sup>are defined herein, that inhibit the activity of phosphoinositide 3-kinases-gamma (PI3Kγ) and are useful in the treatment of diseases related to the activity of PI3Kγ including, for example, autoimmune diseases, cancer, cardiovascular diseases, and neurodegenerative diseases.</p>
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ORGANIC COMPOUNDS (Fri, 18 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>
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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>
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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.
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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>
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FLUORINATED BENZOFURANYL-PYRIMIDINE DERIVATIVES CONTAINING A SUFLONE 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 hyperproliferative 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="US20170226092A1-20170810-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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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>
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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>
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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="US20170217938A1-20170803-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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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>
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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>
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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>
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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.
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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>
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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.
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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.
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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.
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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.
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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
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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.
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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.
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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.
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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.
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FUMARATE-CO-RELEASING MOLECULE HYBRIDS, THEIR USE IN THE TREATMENT OF INFLAMMATORY OR CARDIOVASCULAR DISEASES AND THEIR PROCESS OF PREPARATION (Fri, 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="US20170174716A1-20170622-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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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="33.19mm" wi="73.58mm" file="US20170173031A1-20170622-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">Wherein variables are as defined above. The compounds have apoptosis signal-regulating kinase (“ASK1”) inhibitory activity, and are thus useful in the treatment of ASK1-mediated conditions, including autoimmune disorders, inflammatory diseases, cardiovascular diseases, diabetes, diabetic nephropathy, cardio-renal diseases, including kidney disease, fibrotic diseases, respiratory diseases, COPD, idiopathic pulmonary fibrosis, acute lung injury, acute and chronic liver diseases, and neurodegenerative diseases.</p>
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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.
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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>
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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.
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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>
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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>
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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.
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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>
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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>
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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>
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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>
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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.
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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.
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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.
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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>
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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.
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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.
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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.
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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.
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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.
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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).
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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).
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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.
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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.
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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="US20170088527A1-20170330-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein X, Y, Z, R<sup>2</sup>, R<sup>3</sup>, R<sup>4</sup>, p and q are as described herein, to methods for the preparation and use of the compounds and to pharmaceutical compositions containing the same.</p>
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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>
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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>
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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>
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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.
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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).
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1-PHENYLPYRROLIDIN-2-ONE DERIVATIVES AS PERK INHIBITORS (Fri, 24 Mar 2017)
The invention is directed to substituted pyrrolidinone and imidazolidinone derivatives. Specifically, the invention is directed to compounds according to Formula I: (I) wherein R1, R2, R3, R4, R5, R6, R7, X and Y are as defined herein. The compounds of the invention are inhibitors of PERK and can be useful in the treatment of cancer, pre-cancerous syndromes and diseases/injuries associated with activated unfolded protein response pathways, such as Alzheimer's disease, neuropathic pain, spinal cord injury, traumatic brain injury, ischemic stroke, stroke, Parkinson's disease, diabetes, metabolic syndrome, metabolic disorders, Huntington's disease, Creutzfeldt- Jakob Disease, fatal familial insomnia, Gerstmann-Sträussler-Scheinker syndrome, and related prion diseases, amyotrophic lateral sclerosis, progressive supranuclear palsy, myocardial infarction, cardiovascular disease, inflammation, organ fibrosis, chronic and acute diseases of the liver, fatty liver disease, liver steatosis, liver fibrosis, chronic and acute diseases of the lung, lung fibrosis, chronic and acute diseases of the kidney, kidney fibrosis, chronic traumatic encephalopathy (CTE), neurodegeneration, dementias, frontotemporal dementias, tauopathies, Pick's disease, Neimann-Pick's disease, amyloidosis, cognitive impairment, atherosclerosis, ocular diseases, arrhythmias, in organ transplantation and in the transportation of organs for transplantation. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting PERK activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
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TRIAZOLONE COMPOUNDS AS PERK INHIBITORS (Fri, 24 Mar 2017)
The invention is directed to substituted triazolidinone derivatives. Specifically, the invention is directed to compounds according to Formula I: (I) wherein R1, R2, R3, R4, R5, X, Y, Y1, and Z are as defined herein. The compounds of the invention are inhibitors of PERK and can be useful in the treatment of cancer, pre-cancerous syndromes, as Alzheimer's disease, neuropathic pain, spinal cord injury, traumatic brain injury, ischemic stroke, stroke, Parkinson disease, diabetes, metabolic syndrome, metabolic disorders, Huntington's disease, Creutzfeldt-Jakob Disease, fatal familial insomnia, Gerstmann-Sträussler-Scheinker syndrome, and related prion diseases, amyotrophic lateral sclerosis, progressive supranuclear palsy, myocardial infarction, cardiovascular disease, inflammation, organ fibrosis, chronic and acute diseases of the liver, fatty liver disease, liver steatosis, liver fibrosis, chronic and acute diseases of the lung, lung fibrosis, chronic and acute diseases of the kidney, kidney fibrosis, chronic traumatic encephalopathy (CTE), neurodegeneration, dementias, frontotemporal dementias, tauopathies, Pick's disease, Neimann-Pick's disease, amyloidosis, cognitive impairment, atherosclerosis, ocular diseases, arrhythmias, in organ transplantation and in the transportation of organs for transplantation. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting PERK activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
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IMIDAZOLIDINONE DERIVATIVES AS INHIBITORS OF PERK (Fri, 24 Mar 2017)
The invention is directed to substituted imidazolidinone derivatives. Specifically, the invention is directed to compounds according to Formula I (I) wherein R1, R2, R3, R4, R5, R6, R7, X, Y1, Y2 and Z are defined herein. The compounds of the invention are inhibitors of PERK and can be useful in the treatment of cancer, pre-cancerous syndromes, as Alzheimer's disease, neuropathic pain, spinal cord injury, traumatic brain injury, ischemic stroke, stroke, Parkinson disease, diabetes, metabolic syndrome, metabolic disorders, Huntington's disease, Creutzfeldt-Jakob Disease, fatal familial insomnia, Gerstmann-Sträussler-Scheinker syndrome, and related prion diseases, amyotrophic lateral sclerosis, progressive supranuclear palsy, myocardial infarction, cardiovascular disease, inflammation, organ fibrosis, chronic and acute diseases of the liver, fatty liver disease, liver steatosis, liver fibrosis, chronic and acute diseases of the lung, lung fibrosis, chronic and acute diseases of the kidney, kidney fibrosis, chronic traumatic encephalopathy (CTE), neurodegeneration, dementias, frontotemporal dementias, tauopathies, Pick's disease, Neimann-Pick's disease, amyloidosis, cognitive impairment, atherosclerosis, ocular diseases, arrhythmias, in organ transplantation and in the transportation of organs for transplantation. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting PERK activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
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CYCLOALKYL-HYDROXYL COMPOUNDS AND COMPOSITIONS FOR CHOLESTEROL MANAGEMENT AND RELATED USES (Fri, 17 Mar 2017)
<p id="p-0001" num="0000">The present invention relates to novel cycloalkyl-hydroxyl compounds, compositions comprising hydroxyl compounds, and methods useful for treating and preventing a variety of diseases and conditions such as, but not limited to aging, Alzheimer's Disease, cancer, cardiovascular disease, diabetic nephropathy, diabetic retinopathy, a disorder of glucose metabolism, dyslipidemia, dyslipoproteinemia, hypertension, impotence, inflammation, insulin resistance, lipid elimination in bile, obesity, oxysterol elimination in bile, pancreatitis, Parkinson's disease, a peroxisome proliferator activated receptor-associated disorder, phospholipid elimination in bile, renal disease, septicemia, Syndrome X, thrombotic disorder. Compounds and methods of the invention can also be used to modulate C reactive protein or enhance bile production in a patient. In certain embodiments, the compounds, compositions, and methods of the invention are useful in combination therapy with other therapeutics, such as hypocholesterolemic and hypoglycemic agents.</p>
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BETA- AND GAMMA-AMINO-ISOQUINOLINE AMIDE COMPOUNDS AND SUBSTITUTED BENZAMIDE COMPOUNDS (Fri, 17 Mar 2017)
<p id="p-0001" num="0000">Disclosed are beta and gamma-amino isoquinoline amide compounds and substituted benzamide compounds. In particular, the invention provides compounds that affect the function of kinases in a cell and that are useful as therapeutic agents or with therapeutic agents. The compounds of the invention are useful in the treatment of a variety of diseases and conditions including eye diseases such as glaucoma, cardiovascular diseases, and diseases characterized by abnormal growth, such as cancers. The invention further provides compositions containing the beta or gamma-amino isoquinoline amide compounds or substituted benzamide compounds.</p>
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Heterocyclyl-butanamide derivatives (Fri, 17 Mar 2017)
<p id="p-0001" num="0000">Compounds of the formula I</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="21.59mm" wi="61.55mm" file="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>
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CYANO THIENOTRIAZOLODIAZEPINES AND USES THEREOF (Fri, 17 Mar 2017)
The present invention provides compounds and pharmaceutically compositions thereof. The compounds and compositions are binders of bromodomains and/or bromodomain-containing proteins (e.g., bromo and extra terminal (BET) proteins). Also provided are methods, uses, and kits using the compounds and pharmaceutical compositions for inhibiting the activity (e.g., increased activity) of bromodomains and/or bromodomain-containing proteins and for treating and/or preventing in a subject diseases associated with bromodomains or bromodomain-containing proteins (e.g., proliferative diseases, cardiovascular diseases, viral infections, fibrotic diseases, metabolic diseases, endocrine diseases, and radiation poisoning). The compounds, pharmaceutical compositions, and kits are also useful for male contraception.
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AGENTS FOR USE IN THE TREATMENT OF CARDIOVASCULAR AND INFLAMMATORY DISEASES STRUCTURALLY BASED ON 4(1 H)-QUINOLONE (Fri, 10 Mar 2017)
<p id="p-0001" num="0000">The present invention provides a compound of formula I, a tautomer thereof, or a pharmaceutically acceptable salt or N-oxide thereof for use in the treatment or prevention of cardiovascular disease or of an inflammatory disease or condition:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.86mm" wi="53.17mm" file="US20170066722A1-20170309-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">wherein:</li> <li id="ul0002-0002" num="0000">V is N or CR<sub>3</sub>;</li> <li id="ul0002-0003" num="0000">X is N or CR<sub>4</sub>;</li> <li id="ul0002-0004" num="0000">Y is N or CR<sub>5</sub>;</li> <li id="ul0002-0005" num="0000">Z is N or CR<sub>6</sub>;</li> <li id="ul0002-0006" num="0000">B is —(C═O)R<sub>1</sub>, a 5- to 10-membered heteroaryl group, or a group</li> <li id="ul0002-0007" num="0000">-L′″-NRR′, wherein R and R′ are the same or different and each represents a hydrogen atom, a C<sub>1</sub>-C<sub>6 </sub>alkyl group or a C<sub>1</sub>-C<sub>6 </sub>haloalkyl group;</li> <li id="ul0002-0008" num="0000">R<sub>1 </sub>is a 5- to 10-membered heterocyclyl group, or —OR′, wherein R′ is a hydrogen atom, a C<sub>1</sub>-C<sub>6 </sub>alkyl group or a C<sub>1</sub>-C<sub>6 </sub>haloalkyl group, or R<sub>1 </sub>is a proteinogenic α amino acid, which is linked to the carbonyl moiety in the compound of formula (I) via the α amino group, which amino acid is optionally esterified at the α carboxylic acid group with a C<sub>1</sub>-C<sub>6 </sub>alkyl group or a C<sub>6</sub>-C<sub>10 </sub>aryl group, or R<sub>1 </sub>is —NR″R′″, —NR<sup>IV</sup>-L′″-CONR″R′″, or —NR<sup>IV</sup>-L′″-COOR, wherein R, R″, R′″ and R<sup>IV </sup>are the same or different and each represents a hydrogen atom, a C<sub>1</sub>-C<sub>6 </sub>alkyl group or a C<sub>1</sub>-C<sub>6 </sub>haloalkyl group;</li> <li id="ul0002-0009" num="0000">either (a) W is N and R<sub>9 </sub>and R<sub>2 </sub>together form a bond, or (b) W is CR<sub>8</sub>, R<sub>8 </sub>and R<sub>9 </sub>together form a bond and R<sub>2 </sub>is a hydrogen atom, or a C<sub>1</sub>-C<sub>6 </sub>alkyl, C<sub>1</sub>-C<sub>6 </sub>haloalkyl, C<sub>6</sub>-C<sub>10 </sub>aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocyclyl, -L′-A<sub>2</sub>, C<sub>3</sub>-C<sub>10 </sub>cycloalkyl, or —COOR′ group, wherein R′ is a hydrogen atom or C<sub>1</sub>-C<sub>6 </sub>alkyl group, or, when Z is a moiety CR<sub>6</sub>, R<sub>2 </sub>may form, together with R<sub>6 </sub>and the carbon and nitrogen atoms which connect R<sub>2 </sub>and R<sub>6 </sub>in the formula (I), a 5- to 6-membered heterocyclic ring;</li> <li id="ul0002-0010" num="0000">R<sub>3 </sub>is a hydrogen atom, a halogen atom, or a hydroxy, C<sub>1</sub>-C<sub>6 </sub>alkyl, C<sub>1</sub>-C<sub>6 </sub>alkoxy, C<sub>1</sub>-C<sub>6 </sub>haloalkyl, C<sub>1</sub>-C<sub>6 </sub>haloalkoxy, nitro, or —NR′R″ group, wherein R′ and R″ are the same or different and each represent a hydrogen atom or C<sub>1</sub>-C<sub>6 </sub>alkyl group;</li> <li id="ul0002-0011" num="0000">R<sub>4 </sub>and R<sub>5 </sub>are the same or different and each represent a hydrogen atom, a halogen atom, or a hydroxyl, C<sub>1</sub>-C<sub>8 </sub>alkyl, C<sub>1</sub>-C<sub>8 </sub>haloalkyl, C<sub>1</sub>-C<sub>6 </sub>alkoxy, C<sub>1</sub>-C<sub>6 </sub>haloalkoxy, nitro, —NR′R″, —CO<sub>2</sub>R′″, C<sub>6</sub>-C<sub>10 </sub>aryl, 5- to 10-membered heteroaryl, 5 to 10-membered heterocyclyl, or —CO—(C<sub>1</sub>-C<sub>6 </sub>alkyl) group, wherein R′, R″ and R′″ are the same or different and each represent a hydrogen atom or C<sub>1</sub>-C<sub>6 </sub>alkyl group, or R<sub>4 </sub>and R<sub>5 </sub>and the carbon atoms bonded to R<sub>4 </sub>and R<sub>5 </sub>together form a 5- to 6-membered heterocyclic ring;</li> <li id="ul0002-0012" num="0000">R<sub>6 </sub>is a hydrogen atom, a halogen atom, or a C<sub>1</sub>-C<sub>6 </sub>alkyl, C<sub>1</sub>-C<sub>6 </sub>haloalkyl, C<sub>1</sub>-C<sub>6 </sub>alkoxy, C<sub>1</sub>-C<sub>6 </sub>haloalkoxy or —CO<sub>2</sub>R′ group, wherein R′ is hydrogen or C<sub>1</sub>-C<sub>6 </sub>alkyl, or, when W is a moiety CR<sub>8</sub>, R<sub>6 </sub>may form, together with R<sub>2 </sub>and the carbon and nitrogen atoms which connect R<sub>6 </sub>and R<sub>2 </sub>in the formula (I), a 5- to 6-membered heterocyclic ring;</li> <li id="ul0002-0013" num="0000">R<sub>7 </sub>is a hydrogen atom, a halogen atom, or a C<sub>1</sub>-C<sub>6 </sub>alkyl, or C<sub>1</sub>-C<sub>6 </sub>haloalkyl group,</li> <li id="ul0002-0014" num="0000">A<sub>2 </sub>represents a C<sub>6</sub>-C<sub>10 </sub>aryl or 5- to 10-membered heteroaryl group;</li> <li id="ul0002-0015" num="0000">L′, and L′″ are the same or different and each represent a C<sub>1</sub>-C<sub>6 </sub>alkylene, C<sub>2</sub>-C<sub>6 </sub>alkenylene, or C<sub>2</sub>-C<sub>6 </sub>alkynylene group;</li> <li id="ul0002-0016" num="0000">said aryl, heteroaryl, cycloalkyl and heterocyclyl groups being unsubstituted or substituted with one or more substituents selected from halogen, hydroxy, C<sub>1</sub>-C<sub>4 </sub>alkyl, C<sub>1</sub>-C<sub>4 </sub>hydroxyalkyl, C<sub>1</sub>-C<sub>4 </sub>alkoxy, C<sub>1</sub>-C<sub>4 </sub>haloalkyl, C<sub>1</sub>-C<sub>4 </sub>haloalkoxy, —SOR, —SO<sub>2</sub>R, —NR′R″, —NR′(C═O)R″, —COOR, nitro and cyano substituents, wherein R, R′ and R″ are the same or different and each represents a hydrogen atom or C<sub>1</sub>-C<sub>4 </sub>alkyl group.</li> </ul> </li> </ul> </p>
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ENANTIOMERS OF THE N-(2-AMINO-5-FLUORO-2-METHYLPENTYL)-8-[(2,6-DIFLUOROBENZYL)OXY]-2-METHYLIMIDAZO[1,2-A]PYRIDINE-3-CARBOXAMIDE, AS WELL AS OF THE DI- AND TRIFLUORO DERIVATIVES FOR THE TREATMENT OF CARDIOVASCULAR DISEASES (Fri, 03 Mar 2017)
<p id="p-0001" num="0000">The present application relates to novel 6-hydrogen-substituted imidazo[1,2-a]pyridine-3-carboxamides, to processes for preparation thereof, to the use thereof, alone or in combinations, for treatment and/or prophylaxis of diseases, and to the use thereof for production of medicaments for treatment and/or prophylaxis of diseases, especially for treatment and/or prophylaxis of cardiovascular disorders.</p>
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DEUTERATED COMPOUNDS AND USES THEREOF (Fri, 03 Mar 2017)
The present invention provides for the treatment, prevention, and/or reduction of a risk of a disease, disorder, or condition in which aldehyde toxicity is implicated in the pathogenesis, including ocular disorders, skin disorders, conditions associated with injurious effects from blister agents, and autoimmune, inflammatory, neurological and cardiovascular diseases by the use of a primary amine to scavenge toxic aldehydes, such as MDA and HNE.
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ALDEHYDE CONJUGATES AND USES THEREOF (Fri, 03 Mar 2017)
The present invention provides compounds and methods of use thereof for the treatment, prevention, and/or reduction of a risk of a disease, disorder, or condition in which aldehyde toxicity is implicated in the pathogenesis, including ocular disorders, skin disorders, conditions associated with injurious effects from blister agents, and autoimmune, inflammatory, neurological and cardiovascular diseases by the use of a primary amine to scavenge toxic aldehydes, such as MDA and HNE.
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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.
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IMIDAZO[1,2-A]PYRIDINES AS STIMULATORS OF SOLUBLE GUANYLATE CYCLASE FOR TREATING CARDIOVASCULAR DISEASES (Fri, 24 Feb 2017)
<p id="p-0001" num="0000">The present application relates to novel heterocyclyl- and heteroaryl-substituted imidazo[1,2-a]pyridines, to processes for preparation thereof, to the use thereof, alone or in combinations, for the treatment and/or prophylaxis of diseases, and to the use thereof for production of medicaments for the treatment and/or prophylaxis of diseases, especially for the treatment and/or prophylaxis of cardiovascular disorders.</p>
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IMIDAZO[1,2-A]PYRIDINES AS SOLUBLE GUANYLATE CYCLASE STIMULATORS FOR THE TREATMENT OF CARDIOVASCULAR DISEASES (Fri, 24 Feb 2017)
<p id="p-0001" num="0000">The present application relates to novel substituted imidazo[1,2-a]pyridine-3-carboxamides, to processes for preparation thereof, to the use thereof, alone or in combinations, for treatment and/or prophylaxis of diseases, and to the use thereof for production of medicaments for treatment and/or prophylaxis of diseases, especially for treatment and/or prophylaxis of cardiovascular disorders.</p>
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MELDRUM'S ACID, BARBITURIC ACID AND PYRAZOLONE DERIVATIVES SUBSTITUTED WITH HYDROXYLAMINE AS HNO DONORS (Fri, 24 Feb 2017)
<p id="p-0001" num="0000">The disclosed subject matter provides certain N-substituted hydroxylamine derivative compounds, pharmaceutical compositions and kits comprising such compounds, and methods of using such compounds or pharmaceutical compositions. In particular, the disclosed subject matter provides methods of using such compounds or pharmaceutical compositions for treating, preventing, or delaying the onset and/or development of a disease or condition. In some embodiments, the disease or condition is selected from cardiovascular diseases, ischemia, reperfusion injury, cancerous disease, pulmonary hypertension and conditions responsive to nitroxyl therapy.</p>
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Inhibitors of the renal outer medullary potassium channel (Wed, 22 Feb 2017)
<p id="p-0001" num="0000">The present invention provides compounds of Formula I</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="24.81mm" wi="57.32mm" file="US09573961-20170221-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and conditions associated with excessive salt and water retention. </p>
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BENZOIC ACID COMPOUNDS FOR REDUCING URIC ACID (Fri, 17 Feb 2017)
<p id="p-0001" num="0000">Uric acid in mammalian subjects is reduced and excretion of uric acid is increased by administering a compound of Formula I. The uric acid-lowering effects of the compounds of this invention are used to treat or prevent a variety of conditions including gout, hyperuricemia, elevated levels of uric acid that do not meet the levels customarily justifying a diagnosis of hyperuricemia, renal dysfunction, kidney stones, cardiovascular disease, risk for developing cardiovascular disease, tumor-lysis syndrome, cognitive impairment, early-onset essential hypertension, and <i>Plasmodium falciparum</i>-induced inflammation.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="19.22mm" wi="69.85mm" file="US20170042844A1-20170216-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">In Formula I, t is 0 or 1; q is 0 or 1; and r is 0, 1 or 2. R<sup>7 </sup>is hydrogen or alkyl having from 1 to 3 carbon atoms. R<sup>6 </sup>is hydrogen, hydroxy, halo, alkyl having from 1 to 3 carbon atoms, alkoxy having from 1 to 3 carbon atoms, nitro, thio, alkylthio, or cyano. X is C(O) or NH(R<sup>8</sup>) wherein R<sup>8 </sup>is hydrogen or alkyl having from 1 to 3 carbon atoms; provided that when X is C(O), r is 0 and t is 0. A is phenyl, unsubstituted or substituted by 1 or 2 groups selected from halo, hydroxy, methyl, ethyl, perfluoromethyl, methoxy, ethoxy, perfluoromethoxy, nitro, and amino; or a 5 or 6 membered heteroaromatic ring having 1 or 2 ring heteroatoms selected from N, S and O and the heteroaromatic ring is covalently bound to the remainder of the compound of Formula I by a ring carbon; or cycloalkyl having from 3 to 6 ring carbon atoms wherein the cycloalkyl is unsubstituted or one or two ring carbons are independently monosubstituted by methyl or ethyl.</p>
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Inhibitors of the renal outer medullary potassium channel (Fri, 10 Feb 2017)
<p id="p-0001" num="0000">The present invention provides compounds of Formula (I) and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="36.58mm" wi="69.85mm" file="US09718808-20170801-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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1,3,4-OXADIAZOLE DERIVATIVE COMPOUNDS AS HISTONE DEACETYLASE 6 INHIBITOR, AND THE PHARMACEUTICAL COMPOSITION COMPRISING THE SAME (Fri, 10 Feb 2017)
The present invention relates to novel compounds having histone deacetylase 6 (HDAC6) in-hibitory activity, stereoisomers thereof or pharmaceutically acceptable salts thereof, the use thereof for the preparation of therapeutic medicaments, pharmaceutical compositions containing the same, a method for treating diseases using the composition, and methods for preparing the novel compounds. The novel compounds, stereoisomers thereof or pharmaceutically acceptable salts thereof according to the present invention have histone deacetylase (HDAC) inhibitory activity and are effective for the prevention or treatment of HDAC6-mediated diseases, including infectious diseases; neoplasms; endocrine, nutritional and metabolic diseases; mental and be-havioral disorders; neurological diseases; diseases of the eye and adnexa; cardiovascular diseases; respiratory diseases; digestive diseases; diseases of the skin and subcutaneous tissue; diseases of the musculoskeletal system and connective tissue; or congenital malformations, de¬ formations and chromosomal abnormalities.
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PHARMACEUTICAL COMPOSITION AND THERAPEUTIC COMBINATION COMPRISING A CHOLESTERYL ESTER TRANSFER PROTEIN INHIBITOR AND A CHOLESTEROL ABSORPTION INHIBITOR (Fri, 10 Feb 2017)
The present invention relates to a pharmaceutical composition and a therapeutic combination comprising a novel cholesteryl ester transfer protein (CETP) inhibitor and a cholesterol absorption inhibitor, which may be used in the treatment of subjects suffering from or having an increased risk for cardiovascular diseases, in particular hyperlipidemia or mixed dyslipidemia.
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PHARMACEUTICAL COMPOSITION AND THERAPEUTIC COMBINATION COMPRISING A CHOLESTERYL ESTER TRANSFER PROTEIN INHIBITOR AND AN ATP CITRATE LYASE INHIBITOR – AMPK ACTIVATOR (Fri, 10 Feb 2017)
The present invention relates to a pharmaceutical composition and a therapeutic combination comprising a novel cholesteryl ester transfer protein (CETP) inhibitor and an adenosine triphosphate citrate lyase inhibitor/adenosine monophosphate-activated protein kinase activator, which may be used in the treatment of subjects suffering from or having an increased risk for cardiovascular diseases, in particular hyperlipidemia or mixed dyslipidemia.
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NOVEL MACROCYCLIC COMPOUNDS (Fri, 03 Feb 2017)
<p id="p-0001" num="0000">The present invention relates to novel macrocyclic compounds of general formula (I) as described and defined herein, and methods for their preparation, their use for the treatment and/or prophylaxis of disorders, in particular of hyper-proliferative disorders and/or virally induced infectious diseases and/or of cardiovascular diseases. The invention further relates to intermediate compounds useful in the preparation of said compounds of general formula (I).</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="60.11mm" wi="56.56mm" file="US20170029439A1-20170202-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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1,3,4-OXADIAZOLE SULFAMIDE DERIVATIVE COMPOUNDS AS HISTONE DEACETYLASE 6 INHIBITOR, AND THE PHARMACEUTICAL COMPOSITION COMPRISING THE SAME (Fri, 03 Feb 2017)
The present invention relates to novel compounds having histone deacetylase 6 (HDAC6) inhibitory activity, stereoisomers thereof or pharmaceutically acceptable salts thereof, the use thereof for the preparation of therapeutic medicaments, pharmaceutical compositions containing the same, a method for treating diseases using the composition, and methods for preparing the novel compounds. The novel compounds, stereoisomers thereof or pharmaceutically acceptable salts thereof according to the present invention have histone deacetylase (HDAC) inhibitory activity and are effective for the prevention or treatment of HDAC6-mediated diseases, including infectious diseases; neoplasms; endocrine, nutritional and metabolic diseases; mental and behavioral disorders; neurological diseases; diseases of the eye and adnexa; cardiovascular diseases; respiratory diseases; digestive diseases; diseases of the skin and subcutaneous tissue; diseases of the musculoskeletal system and connective tissue; or congenital malformations, deformations and chromosomal abnormalities.
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METABOLICALLY ROBUST ANALOGS OF CYP-EICOSANOIDS FOR THE TREATMENT OF CARDIAC DISEASE (Fri, 27 Jan 2017)
The present invention relates to compounds according to general formula (I) which are metabolically robust analogues of bioactive lipid mediators derived from omega-3 polyunsaturated fatty acids (n-3 PUFAs).The present invention further relates to compositions containing one or more of these compounds and to the use of these compounds or compositions for the treatment or prevention of cardiovascular diseases.
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COMPOSITIONS AND METHODS FOR REDUCING CHRONIC LOW-LEVEL INFLAMMATION (Fri, 20 Jan 2017)
<p id="p-0001" num="0000">The invention relates to compositions and methods for reducing chronic low-level inflammation associated with chronic conditions. Specifically, the invention relates to compositions of hydrophobic derivatives of aspirin and/or hydrophobic derivatives of sesamol in combination with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and their methods for reducing chronic low-level inflammation associated with chronic conditions including obesity, metabolic syndrome, diabetes, cardiovascular disease, cancer, auto-immune disorders, ocular and neurological disorders in a mammal.</p>
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Disubstituted 5-fluoro pyrimidine derivatives containing a sulfondiimine group (Fri, 20 Jan 2017)
<p id="p-0001" num="0000">The present invention relates to 5-fluoro pyrimidine derivatives containing a sulfondiimine group of general formula (I) as described and defined herein, and methods for their preparation, their use for the treatment and/or prophylaxis of disorders, in particular of hyper-proliferative disorders and/or virally induced infectious diseases and/or of cardiovascular diseases. The invention further relates to intermediate compounds useful in the preparation of said compounds of general formula (I).</p>
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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.
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RNA-CODED ANTIBODY (Thu, 19 Jan 2017)
The present application describes an antibody-coding, non-modified or modified RNA and the use thereof for expression of this antibody, for the preparation of a pharmaceutical composition, in particular a passive vaccine, for treatment of tumours and cancer diseases, cardiovascular diseases, infectious diseases, auto-immune diseases, virus diseases and monogenetic diseases, e.g. also in gene therapy. The present invention furthermore describes an in vitro transcription method, in vitro methods for expression of this antibody using the RNA according to the invention and an in vivo method.
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USES OF DIAZEPANE DERIVATIVES (Fri, 13 Jan 2017)
<p id="p-0001" num="0000">The present invention provides compounds of Formula (II) (e.g., compounds of Formula (I)), and pharmaceutically compositions thereof. Compounds of Formula (II) are believed to be binders of bromodomains and/or bromodomain-containing proteins (e.g., bromo and extra terminal (BET) proteins). Also provided are methods, uses, and kits using the compounds and pharmaceutical compositions for inhibiting the activity (e.g., increased activity) of bromodomains and/or bromodomain-containing proteins and for treating and/or preventing in a subject diseases associated with bromodomains or bromodomain-containing proteins (e.g., proliferative diseases, cardiovascular diseases, viral infections, fibrotic diseases, metabolic diseases, endocrine diseases, and radiation poisoning). The compounds, pharmaceutical compositions, and kits are also useful for male contraception.</p>
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RNA-CODED ANTIBODY (Thu, 12 Jan 2017)
The present application describes an antibody-coding, non-modified or modified RNA and the use thereof for expression of this antibody, for the preparation of a pharmaceutical composition, in particular a passive vaccine, for treatment of tumours and cancer diseases, cardiovascular diseases, infectious diseases, auto-immune diseases, virus diseases and monogenetic diseases, e.g. also in gene therapy. The present invention furthermore describes an in vitro transcription method, in vitro methods for expression of this antibody using the RNA according to the invention and an in vivo method.
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5-FLUORO-N-(PYRIDIN-2-YL)PYRIDIN-2-AMINE DERIVATIVES CONTAINING A SULFONE GROUP (Fri, 06 Jan 2017)
<p id="p-0001" num="0000">The present invention relates to 5-fluoro-N-(pyridin-2-yl)pyridin-2-amine derivatives containing a sulfone group of general formula (I) as described and defined herein, and methods for their preparation, their use for the treatment and/or prophylaxis of disorders, in particular of hyper-proliferative disorders and/or virally induced infectious diseases and/or of cardiovascular diseases. The invention further relates to intermediate compounds useful in the preparation of said compounds of general formula (I).</p>
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INHIBITORS OF MITOCHONDRIAL PYRUVATE DEHYDROGENASE KINASE ISOFORMS 1-4 AND USES THEREOF (Fri, 06 Jan 2017)
<p id="p-0001" num="0000">The present disclosure relates to the identification of PDK inhibitors and their use in the treatment of diseases such as diabetes, cardiovascular disease and cancer. The invention relates to the development of robust PDK inhibitors that can be used to improve glucose metabolism and correct metabolic dysfunction in vivo. Based on the unique structural features present in the ATP-binding pocket of PDK2, a single functional-group change was made in a known Hsp90 inhibitor that binds to the corresponding pocket of the latter protein from the GHKL family. This approach efficiently converted the Hsp90 inhibitor to a highly specific inhibitor for all PDK isoforms. These final PDK inhibitors of this series robustly augments PDC activity with reduced phosphorylation in tissues.</p>
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AMINOTRIAZOLE- AND AMINOTETRAZOLE-BASED KDM1A INHIBITORS AS EPIGENETIC MODULATORS (Fri, 06 Jan 2017)
<p id="p-0001" num="0000">In some aspects, the present invention provides compounds of the formula (IV), wherein the variables are as defined herein, which may be used as inhibitors of histone demethylase or spermine oxidase. Also provided herein are pharmaceutical compositions of the compounds and methods using the compounds in the treatment of diseases such as cancer and cardiovascular disease.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="79.25mm" wi="73.32mm" file="US20170001968A1-20170105-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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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>
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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.
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PCSK9 QUANTIFICATION BY IMMUNODETECTION (Fri, 30 Dec 2016)
<p id="p-0001" num="0000">The present disclosure relates to, among other things, systems for detecting the level of specific lipoprotein-bound level of PCSK9, and optionally free PCSK9, lipoprotein or portions thereof and/or PCSK9 unbound lipoproteins present in a biological sample. The present invention also relates to methods of assessing the level of specific lipoprotein-bound level of PCSK9, and optionally free PCSK9, Apo B and/or PCSK9 unbound lipoproteins present in a biological sample, determining whether a subject is at increased risk for cardiovascular disease and monitoring the risk for developing cardiovascular disease.</p>
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NOVEL 5-HT2 ANTAGONISTS (Fri, 30 Dec 2016)
The present invention relates to 1-amidino-3-aryl-2-pyrazoline derivatives of the general formula I The invention specifically relates to such derivatives which exhibit antagonizing activity towards serotonin 5-HT2B receptors. The present invention also relates to use of said compounds as a medicament and for the treatment of fibrosis, cardiovascular diseases, pain, IBD, and other inflammatory diseases, as well as pharmaceutical compositions comprising one or more of said compounds and methods of treatment.
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NOVEL 5-HT2 ANTAGONISTS (Thu, 29 Dec 2016)
The present invention relates to 1-amidino-3-aryl-2-pyrazoline derivatives of the general formula I The invention specifically relates to such derivatives which exhibit antagonizing activity towards serotonin 5-HT 2B receptors. The present invention also relates to use of said compounds as a medicament and for the treatment of fibrosis, cardiovascular diseases, pain, IBD, and other inflammatory diseases, as well as pharmaceutical compositions comprising one or more of said compounds and methods of treatment.
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INHIBITORS OF C-JUN-N-TERMINAL KINASE (JNK) (Fri, 23 Dec 2016)
<p id="p-0001" num="0000">The present invention provides novel compounds according to Formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="35.98mm" wi="70.36mm" file="US20160368910A1-20161222-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">where Ring A, Ring B, X, L<sub>1</sub>, L<sub>2</sub>, R<sup>A</sup>, R<sup>C</sup>, R<sup>D</sup>, R<sup>E</sup>, m, n, and p are as defined herein. Compounds of the present invention are contemplated useful for the prevention and treatment of a variety of human diseases associated with kinase activity, for example, proliferative diseases, neurodegenerative diseases, metabolic disorders, inflammatory diseases, and cardiovascular diseases.</p>
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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.
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Fused heterocyclic compounds as ion channel modulators (Fri, 16 Dec 2016)
<p id="p-0001" num="0000">The present disclosure relates to compounds that are sodium channel inhibitors and to their use in the treatment of various disease states, including cardiovascular diseases and diabetes. In particular embodiments, the structure of the compounds is given by Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="16.51mm" wi="55.54mm" file="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>
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Replacement Therapy for Natriuretic Peptide Deficiencies (Fri, 09 Dec 2016)
<p id="p-0001" num="0000">Use and methods of use of natriuretic peptide mimetics which bind to and activate natriuretic peptide receptor A in patients with a defect, condition, syndrome, disease or mutation resulting in a functional active ANP<sub>99-126 </sub>deficiency, for treatment or prophylaxis of cardiovascular disease, including but not limited to hypertension, acute coronary syndrome, cardiomyopathy, cardiac remodeling, left-ventricular hypertrophy, congestive heart failure, heart failure, high blood pressure and coronary artery disease, including use of mimetics with a plurality of amino acid residues and at least one amino acid surrogate of formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="18.88mm" wi="69.85mm" file="US20160354443A1-20161208-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">where R, R′, Q, Y, W, Z, J, x and n are as defined in the specification.</p>
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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.
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FUSED BENZOXAZEPINONES AS ION CHANNEL MODULATORS (Thu, 08 Dec 2016)
The present disclosure relates to compounds that are sodium channel inhibitors and to their use in the treatment of various disease states, including cardiovascular diseases and diabetes.
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TRIMETHYLAMINE COMPOUNDS AS RISK PREDICTORS OF CARDIOVASCULAR DISEASE (Fri, 02 Dec 2016)
<p id="p-0001" num="0000">Methods of characterizing a test subject's risk of having or developing cardiovascular disease are provided. The methods include using an analytic device to determine levels of choline-related trimethylamine-containing compounds such as trimethylamine N-oxide, choline, or betaine in a biological sample obtained from the subject and comparing the levels of the choline-related trimethylamine-containing compound in the subject's biological sample to a control value. The test subject's risk of having cardiovascular disease is then characterized as higher if the levels of the choline-related trimethylamine-containing compound are higher than the control value. Also provided are methods of identifying a subject at risk of experiencing a complication of atherosclerotic cardiovascular disease, and methods of evaluating the efficacy of a cardiovascular therapeutic agent in a subject with cardiovascular disease using levels of choline-related trimethylamine-containing compounds.</p>
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FUSED BENZOXAZEPINONES AS ION CHANNEL MODULATORS (Thu, 01 Dec 2016)
The present disclosure relates to compounds that are sodium channel inhibitors and to their use in the treatment of various disease states, including cardiovascular diseases and diabetes.
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NOVEL DGAT2 INHIBITORS (Fri, 25 Nov 2016)
The present invention provides compounds of the Formula below: [Formula should be inserted here] Where A, X, R, and R2-R3 are as described herein; methods of treating patients for hypertriglyceridemia and cardiovascular disease including dyslipidemia and atherosclerosis, and processes for preparing the compounds.
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DIAMINOPYRIMIDINE BENZENESULFONE DERIVATIVES AND USES THEREOF (Fri, 18 Nov 2016)
<p id="p-0001" num="0000">The present invention provides compounds of Formula (II) (e.g., compounds of Formula (I)), and pharmaceutically compositions thereof. Compounds of Formula (II) are believed to be binders of bromodomains and/or bromodomain-containing proteins (e.g., bromo and extra terminal (BET) proteins). Also provided are methods, uses, and kits using the compounds and pharmaceutical compositions for inhibiting the activity (e.g., increased activity) of bromodomains and/or bromodomain-containing proteins and for treating and/or preventing in a subject diseases associated with bromodomains or bromodomain-containing proteins (e.g., proliferative diseases, cardiovascular diseases, viral infections, fibrotic diseases, metabolic diseases, endocrine diseases, and radiation poisoning). The compounds, pharmaceutical compositions, and kits are also useful for male contraception.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="69.93mm" wi="76.20mm" file="US20160332993A1-20161117-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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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.
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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.
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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.
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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>
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PYRAZOLE DERIVATIVES USEFUL AS 5-LIPOXYGENASE ACTIVATING PROTEIN (FLAP) INHIBITORS (Fri, 11 Nov 2016)
The present application relates to novel compounds of formula (I) to their utility in treating and/or preventing clinical conditions including cardiovascular diseases (CVD), to methods for their therapeutic use, to pharmaceutical compositions containing them and to processes for preparing such compounds.
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USE OF CD24 FOR LOWERING LOW-DENSITY LIPOPROTEIN CHOLESTEROL LEVELS (Fri, 11 Nov 2016)
The present invention relates to the use of a CD24 protein for lowering low-density lipoprotein cholesterol levels, treating and preventing atherosclerosis, and for reducing risk of cardiovascular disease.
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Use of CD24 for lowering low-density lipoprotein cholesterol levels (Fri, 11 Nov 2016)
The present invention relates to the use of a CD24 protein for lowering low-density lipoprotein cholesterol levels, treating and preventing atherosclerosis, and for reducing risk of cardiovascular disease.
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FUSED HETEROCYCLIC COMPOUNDS AS ION CHANNEL MODULATORS (Fri, 04 Nov 2016)
<p id="p-0001" num="0000">The present disclosure relates to compounds that are sodium channel inhibitors and to their use in the treatment of various disease states, including cardiovascular diseases and diabetes. In particular embodiments, the structure of the compounds is given by Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="28.79mm" wi="58.67mm" file="US20160317504A1-20161103-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein X, Y, Z, R<sup>2</sup>, R<sup>3</sup>, R<sup>4</sup>, p and q are as described herein, to methods for the preparation and use of the compounds and to pharmaceutical compositions containing the same.</p>
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Anti-aP2 Antibodies and Antigen Binding Agents to Treat Metabolic Disorders (Fri, 04 Nov 2016)
<p id="p-0001" num="0000">This invention is in the area of improved anti-aP2 antibodies and antigen binding agents, and compositions thereof, which target the lipid chaperone aP2/FABP4 (referred to as “aP2”) for use in treating disorders such as diabetes, obesity, cardiovascular disease, fatty liver disease, and/or cancer, among others. In one aspect, improved treatments for aP2 mediated disorders are disclosed in which serum aP2 is targeted and the biological activity of aP2 is neutralized or modulated using low-binding affinity aP2 monoclonal antibodies, providing lower fasting blood glucose levels, improved systemic glucose metabolism, increased systemic insulin sensitivity, reduced fat mass, reduced liver steatosis, reduced cardiovascular disease and/or a reduced risk of developing cardiovascular disease.</p>
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Phthalazine derivatives (Fri, 04 Nov 2016)
<p id="p-0001" num="0000">Compounds of the formula I</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="24.21mm" wi="60.54mm" file="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>
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ANTI-AP2 ANTIBODIES AND ANTIGEN BINDING AGENTS TO TREAT METABOLIC DISORDERS (Fri, 04 Nov 2016)
This invention is in the area of improved anti-aP2 antibodies and antigen binding agents, and compositions thereof, which target the lipid chaperone aP2/FABP4 (referred to as "aP2") for use in treating disorders such as diabetes, obesity, cardiovascular disease, fatty liver disease, and/or cancer, among others. In one aspect, improved treatments for aP2 mediated disorders are disclosed in which serum aP2 is targeted and the biological activity of aP2 is neutralized or modulated using low-binding affinity aP2 monoclonal antibodies, providing lower fasting blood glucose levels, improved systemic glucose metabolism, increased systemic insulin sensitivity, reduced fat mass, reduced liver steatosis, reduced cardiovascular disease and/or a reduced risk of developing cardiovascular disease.
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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.
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Anti-aP2 antibodies and antigen binding agents to treat metabolic disorders (Fri, 04 Nov 2016)
This invention is in the area of improved anti-aP2 antibodies and antigen binding agents, and compositions thereof, which target the lipid chaperone aP2/FABP4 (referred to as "aP2") for use in treating disorders such as diabetes, obesity, cardiovascular disease, fatty liver disease, and/or cancer, among others. In one aspect, improved treatments for aP2 mediated disorders are disclosed in which serum aP2 is targeted and the biological activity of aP2 is neutralized or modulated using low-binding affinity aP2 monoclonal antibodies, providing lower fasting blood glucose levels, improved systemic glucose metabolism, increased systemic insulin sensitivity, reduced fat mass, reduced liver steatosis, reduced cardiovascular disease and/or a reduced risk of developing cardiovascular disease.
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FUSED BENZOXAZEPINONES AS ION CHANNEL MODULATORS (Thu, 03 Nov 2016)
The present disclosure relates to compounds that are sodium channel inhibitors and to their use in the treatment of various disease states, including cardiovascular diseases and diabetes.
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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.
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NOVEL DIHYDROPYRIDOISOQUINOLINONES AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF INFLAMMATORY DISORDERS (Fri, 28 Oct 2016)
A compound according to Formula (I): wherein R1, LA, CyA, RA, R2, R3, and R4 are as described herein. The present invention relates to novel compounds according to Formula I that antagonize GPR84, a G-protein-coupled receptor that is involved in inflammatory conditions, and methods for the production of these novel compounds, pharmaceutical compositions comprising these compounds, and methods for the prevention and/or treatment of inflammatory conditions, pain, neuroinflammatory conditions, neurodegenerative conditions, infectious diseases, autoimmune diseases, endocrine and/or metabolic diseases, cardiovascular diseases, leukemia, and/or diseases involving impairment of immune cell functions by administering a compound of the invention.
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COMPOUNDS AND THEIR USE AS BACE1 INHIBITORS (Fri, 28 Oct 2016)
The present invention relates to compounds of Formula (I) or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein X, Y, Z, Q, W, m, u, ring (A), R2, R3, R4, R5 and R6, are as defined in the specification and claims. The present invention provides a pharmaceutical composition containing the compounds of Formula (I) and a therapeutic method of treating and/or preventing Downs syndrome, β-amyloid angiopathy, disorders associated with cognitive impairment, Alzheimer's disease, memory loss, attention deficit symptoms associated with Alzheimer's disease, neurodegenerative diseases, pre-senile dementia, senile dementia and dementia associated with Parkinson's disease, Alzheimer's disease and/or Down syndrome, age-related macular degeneration (AMD), glaucoma, olfactory function impairment, traumatic brain injury, progressive muscle diseases, Type II diabetes mellitus and cardiovascular diseases (stroke).
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FUSED BENZOXAZEPINONES AS ION CHANNEL MODULATORS (Thu, 27 Oct 2016)
The present disclosure relates to compounds that are sodium channel inhibitors and to their use in the treatment of various disease states, including cardiovascular diseases and diabetes.
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FUSED BENZOXAZEPINONES AS ION CHANNEL MODULATORS (Thu, 27 Oct 2016)
The present disclosure relates to compounds that are sodium channel inhibitors and to their use in the treatment of various disease states, including cardiovascular diseases and diabetes.
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IMIDAZOLONE DERIVATIVES, PHARMACEUTICAL COMPOSITIONS AND USES THEREOF (Fri, 21 Oct 2016)
<p id="p-0001" num="0000">This application relates to imidazolone compounds, pharmaceutically acceptable salts, solvents, polymorphs or prodrugs thereof, and further relates to pharmaceutical combinations comprising the foregoing substances and uses for preventing and treating protein kinase related diseases such as cancer, metabolic diseases, and cardiovascular diseases.</p>
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COMPOSITIONS AND METHODS TO ASSESS THE CAPACITY OF HDL TO SUPPORT REVERSE CHOLESTEROL TRANSPORT (Fri, 21 Oct 2016)
<p id="p-0001" num="0000">The invention provides compositions and methods for assessing the capacity of high density lipoprotein (HDL) to support reverse cholesterol transport in blood by measuring exchange if HDL-specific spin-labeled lipoprotein probes and electron paramagnetic spectroscopy. The invention also provides methods to identify individuals at risk for cardiovascular disease, to monitor the treatment of cardiovascular disease and in the development of therapies to treat cardiovascular disease. The invention also provides methods to identify individuals at risk for Alzheimer's disease, to monitor the treatment of Alzheimer's disease and in the development of therapies to treat Alzheimer's disease.</p>
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INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIM CHANNEL (Fri, 21 Oct 2016)
<p id="p-0001" num="0000">The present invention provides compounds of Formula (I) (Formula (I)) including pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="31.83mm" wi="68.92mm" file="US20160304515A1-20161020-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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3-spirocyclic-6-hydroxamic acid tetralins as HDAC inhibitors (Fri, 21 Oct 2016)
<p id="p-0001" num="0000">The present invention is directed to inhibitors of histone deacetylases (HDACs) such as HDAC6 and HDAC11, and their use in the treatment of diseases such as cell proliferative diseases (e.g., cancer), neurological (e.g., neurodegenerative disease or neurodevelopmental disease), inflammatory or autoimmune disease, infection, metabolic disease, hematologic disease, or cardiovascular disease.</p>
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3-spiro-7-hydroxamic acid tetralins as HDAC inhibitors (Fri, 21 Oct 2016)
<p id="p-0001" num="0000">The present invention is directed to inhibitors of histone deacetylases (HDACs) such as HDAC6, and their use in the treatment of diseases such as cell proliferative diseases (e.g., cancer), neurological (e.g., neurodegenerative disease or neurodevelopmental disease), inflammatory or autoimmune disease, infection, metabolic disease, hematologic disease, or cardiovascular disease.</p>
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Substituted aza-bicyclic imidazole derivatives useful TRPM8 receptor modulators (Fri, 21 Oct 2016)
<p id="p-0001" num="0000">The present invention is directed to substituted aza-bicyclic imidazole derivatives, pharmaceutical compositions containing them and their use in the treatment of disorders and conditions modulated by TRP M8, including for example, inflammatory pain, inflammatory hyperalgesia, inflammatory hypersensitivity condition, neuropathic pain, neuropathic cold allodynia, inflammatory somatic hyperalgesia, inflammatory visceral hyperalgesia, cardiovascular disease aggravated by cold and pulmonary disease aggravated by cold.</p>
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3-SPIROCYCLIC-6-HYDROXAMIC ACID TETRALINS AS HDAC INHIBITORS (Fri, 21 Oct 2016)
The present invention is directed to inhibitors of histone deacetylases (HDACs) such as HDAC6 and HDAC11, and their use in the treatment of diseases such as cell proliferative diseases (e.g., cancer), neurological (e.g., neurodegenerative disease or neurodevelopmental disease), inflammatory or autoimmune disease, infection, metabolic disease, hematologic disease, or cardiovascular disease.
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3-SPIRO-7-HYDROXAMIC ACID TETRALINS AS HDAC INHIBITORS (Fri, 21 Oct 2016)
The present invention is directed to compounds of Formulae I and II which are inhibitors of histone deacetylases (HDACs) such as HDAC6, and their use in the treatment of diseases such as cell proliferative diseases (e.g., cancer), neurological (e.g., neurodegenerative disease or neurodevelopmental disease), inflammatory or autoimmune disease, infection, metabolic disease, hematologic disease, or cardiovascular disease.
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Compositions and methods for modulating angiopoietin-like 3 expression (Fri, 21 Oct 2016)
Provided herein are methods, compounds, and compositions for reducing expression of an ANGPTL3 mRNA and protein in an animal. Also provided herein are methods, compounds, and compositions for reducing lipids and/or glucose in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate any one or more of cardiovascular disease and/or metabolic disease, or a symptom thereof, in an individual in need thereof.
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COMPOSITIONS AND METHODS FOR MODULATING HYDROXYLATION OF ACC2 BY PHD3 (Fri, 14 Oct 2016)
Compositions and methods useful for treating a number of human disorders including, but not limited to, cancer, cardiovascular disease, obesity, and metabolic disorders are provided. For example, the disclosure features compositions and methods for modulating the hydroxylation of ACC2 by PHD3 in vitro or in vivo. Also provided are methods for monitoring and/or detecting the expression of PHD3 and/or levels of ACC2 hydroxylation, which are useful for, inter alia, determining whether a cancer cell is sensitive to glycolytic pathway inhibitors or inhibitors of fatty acid metabolism.
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Novel macrocyclic compounds (Fri, 14 Oct 2016)
The present invention relates to novel macrocyclic compounds of general formula (I) as described and defined herein, and methods for their preparation, their use for the treatment and/or prophylaxis of disorders, in particular of hyper-proliferative disorders and/or virally induced infectious diseases and/or of cardiovascular diseases. The invention further relates to intermediate compounds useful in the preparation of said compounds of general formula (I).
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USE OF PCSK9 AND LDL-R ACTIVITY FOR TREATING CARDIOVASCULAR RISK (Fri, 07 Oct 2016)
<p id="p-0001" num="0000">The present disclosure provides methods of assessing cardiovascular risk in a subject and/or of treating a subject having or at risk of developing a cardiovascular disease or disorder. In some embodiments, the method comprises determining an activity level of PCSK9 and/or a level of PCSK9 in a sample obtained from the subject, and initiating or modifying a treatment regimen.</p>
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Compositions and methods for adipocyte modulation (Wed, 05 Oct 2016)
<p id="p-0001" num="0000">Modified stilbenoids and formulations thereof are provided. The modified stilbenoids can include one or more amino or amino-alkyl substituents. The formulation can be for the treatment or prevention of obesity and the modified stilbenoid present in an effective amount to alleviate or prevent the onset of one or more symptoms of obesity. Methods of making the modified stilbenoids and formulations thereof are provided. Methods are provided for treating a subject with a modified stilbenoid in an effective amount to alleviate or prevent one or more symptoms associated with diabetes, cardiovascular disease, high blood pressure, deep vein thrombosis, osteoarthritis, obstructive sleep apnea, cancer, and non-alcoholic fatty liver disease. The administration of the modified stilbenoids can result in decreased levels of PKCδII, PKCδVIII, substantially unaltered expression of PKCδI; a decreased number of adipocytes; increased weight and/or fat loss; or a combination thereof.</p>
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METHODS FOR CALIBRATED ION MOBILITY ANALYSIS AND USES THEREOF (Fri, 30 Sep 2016)
<p id="p-0001" num="0000">The present invention relates to improved ion mobility analysis (IMA) methods that can accurately quantify particle concentration in a sample solution. Specifically, reference particles of known solution-phase concentration are used for calibration. In addition, by exploiting spectral deconvolution techniques, the concentrations of subpopulations within the particles can also be accurately quantified. The improved IMA methods permit, for the first time, the quantification of absolute concentrations of HDL particles and subpopulations thereof in a biological sample. The correlations of HDL particle concentrations and conditions such as LCAT deficiency and cardiovascular diseases have been established. Accordingly, the present invention also provide methods to determine whether a subject is at risk to develop or is suffering from these conditions by using HDL particle concentration as a clinical metric.</p>
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SUPERCHARGED PROTEINS FOR CELL PENETRATION (Fri, 30 Sep 2016)
<p id="p-0001" num="0000">Compositions, preparations, systems, and related methods for delivering a supercharged protein, or a complex of a supercharged protein and an agent (e.g., nucleic acids, peptides, proteins, small molecules) to cells are provided. Such systems and methods include the use of supercharged proteins. For example, superpositively charged proteins may be associated with nucleic acids (which typically have a net negative charge) via electrostatic interactions. In some embodiments, such systems and methods involve altering the primary sequence of a protein in order to “supercharge” the protein (e.g., to generate a superpositively-charged protein). In some embodiments, complexes comprising supercharged proteins and one or more agents to be delivered are useful as therapeutic agents. In some embodiments, complexes and/or pharmaceutical compositions thereof are administered to a subject in need thereof. The inventive complexes or pharmaceutical compositions thereof may be used to treat proliferative diseases, infectious diseases, cardiovascular diseases, inborn errors in metabolism, genetic diseases, etc.</p>
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Piperazine derivatives as FASN inhibitors (Fri, 30 Sep 2016)
<p id="p-0001" num="0000">Compounds of the formula I</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.26mm" wi="69.85mm" file="US09809552-20171107-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> in which R, X<sup>1</sup>, X<sup>2</sup>, X<sup>3</sup>, X<sup>4</sup>, R<sup>1</sup>, R<sup>2 </sup>and q have the meanings indicated in Claim <b>1, </b> <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>
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Fumarate-CO-releasing molecule hybrids, their use in the treatment of inflammatory or cardiovascular diseases and their process of preparation (Fri, 30 Sep 2016)
The present invention relates to hybrid fumarate-CO-releasing molecules capable of increasing heme oxygenase-1 (HO-1) activity and HO-1 protein expression and simultaneously releasing CO, their synthesis and their use in therapeutic applications, in particular their use in the treatment of inflammatory or cardiovascular diseases.
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KETONE DERIVATIVES OF IMIDAZOLES, PHARMACEUTICAL COMBINATIONS AND USES THEREOF (Thu, 29 Sep 2016)
This application relates to ketone compounds of imidazoles, 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.
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TRIMETHYLAMINE COMPOUNDS AS RISK PREDICTORS OF CARDIOVASCULAR DISEASE (Thu, 22 Sep 2016)
Methods of characterizing a test subject's risk of having or developing cardiovascular disease are provided. The methods include using an analytic device to determine levels of choline-related trimethylamine-containing compounds such as trimethylamine N-oxide, choline, or betaine in a biological sample obtained from the subject and comparing the levels of the choline-related trimethylamine-containing compound in the subject's biological sample to a control value. The test subject's risk of having cardiovascular disease is then characterized as higher if the levels of the choline-related trimethylamine-containing compound are higher than the control value. Also provided are methods of identifying a subject at risk of experiencing a complication of atherosclerotic cardiovascular disease, and methods of evaluating the efficacy of a cardiovascular therapeutic agent in a subject with cardiovascular disease using levels of choline-related trimethylamine-containing compounds.
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Branched 3-phenylpropionic acid derivatives and their use (Fri, 16 Sep 2016)
<p id="p-0001" num="0000">The present application relates to novel 3-phenylpropionic acid derivatives which carry a branched or cyclic alkyl substituent in the 3-position, to processes for their preparation, to their use for the treatment and/or prevention of diseases and to their use for preparing medicaments for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of cardiovascular diseases.</p>
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AMINO, AMIDO AND HETEROCYCLIC COMPOUNDS AS MODULATORS OF RAGE ACTIVITY AND USES THEREOF (Fri, 16 Sep 2016)
<p id="p-0001" num="0000">Amino, amido, and heterocyclic compounds are disclosed. The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, diabetes complications, inflammation, and neurodegeneration, obesity, cancer, ischemia/reperfusion injury, cardiovascular disease and other diseases related to RAGE activity.</p>
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CONJUGATE COMPRISING FOLIC ACID AND INDOLE-3-CARBINOL FOR MEDICAL USE (Fri, 16 Sep 2016)
<p id="p-0001" num="0000">Conjugates of indole-3-carbinol are described for medical use and, particularly, for the prevention and treatment of neoplastic, inflammatory, cardiovascular diseases and other diseases, and of the metabolic syndrome.</p>
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3-aminocyclopentane carboxamide derivatives (Fri, 16 Sep 2016)
<p id="p-0001" num="0000">Compounds of the formula I</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="24.38mm" wi="64.18mm" file="US09732032-20170815-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000">in which R<sup>1</sup>, R<sup>4</sup>, R, X<sup>1</sup>, X<sup>2</sup>, X<sup>3</sup>, X<sup>4</sup>, q and W have the meanings indicated in Claim <b>1</b>, are inhibitors of fatty acid synthase, and can be employed, inter alia, for the treatment of diseases such as cancer, cardiovascular diseases, central nervous system injury and different forms of inflammation.</li> </ul> </p>
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PYRROLO PYRIMIDINE DERIVATIVE (Thu, 15 Sep 2016)
The compound represented by general formula (I) has strong Axl inhibition activity by means of a pyridone ring structure being introduced into a pyrrolo pyrimidine skeleton, and so the result can serve as a treatment agent for Axl-related diseases, for example cancers such as acute myeloid leukemia, melanoma, breast cancer, pancreatic cancer, and glial tumors, renal disease, immune system disorders, and cardiovascular disease.
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Inhibitors of the Renal Outer Medullary Potassium Channel (Fri, 09 Sep 2016)
<p id="p-0001" num="0000">The present invention provides compounds of Formula I</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="33.95mm" wi="69.00mm" file="US20160257670A1-20160908-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.</p>
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FLUORESCENT IN-SITU DETECTION OF LIPID PARTICLE APOLIPOPROTEINS WITHIN PRIMARY ELECTROPHORETIC MATRIX (Fri, 02 Sep 2016)
<p id="p-0001" num="0000">The present invention relates to, among other things, a gel electrophoresis system for detecting the level of specific Apolipoproteins and/or lipoprotein particles present in intact lipid particles in a biological sample. The system includes a gel substrate to receive a biological sample, at least two lipoprotein-binding complexes. Each complex includes an antibody that binds a lipoprotein particle or a portion thereof, which is bound to a signal producing molecule capable of producing or causing production of a detectable signal. The system also includes a device for detecting the detectable signal. The present invention also relates to methods of assessing the level of specific Apolipoproteins and/or lipoprotein particles present in a biological sample, determining whether a subject is at increased risk for cardiovascular disease, and monitoring the risk for developing cardiovascular disease.</p>
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RHO KINASE INHIBITORS (Fri, 26 Aug 2016)
<p id="p-0001" num="0000">Disclosed are novel substituted 2H-isoquinolin-1-one and 3H-quinazolin-4-one derivatives useful as inhibitors of Rho kinase and for treating a variety of diseases and disorders that are mediated or sustained through the activity of Rho kinase, including cardiovascular diseases, pharmaceutical compositions comprising such compounds, methods for using such compounds and processes for making such compounds.</p>
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Anti-Inflammatory Compounds and Use Thereof (Fri, 26 Aug 2016)
<p id="p-0001" num="0000">Compounds of the general formula</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="10.33mm" wi="56.05mm" file="US20160243137A1-20160825-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">are disclosed with activity towards treating diseases related to inflammation, such as cancer, neurodegenerative and cardiovascular diseases. Pharmaceutical compositions and methods of use are also disclosed.</p>
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NOVEL FUNCTIONALIZED 5-(PHENOXYMETHYL)-1,3-DIOXANE ANALOGS EXHIBITING CYTOCHROME P450 INHIBITION AND THEIR METHOD OF USE (Fri, 26 Aug 2016)
<p id="p-0001" num="0000">Pharmaceutical compositions described in this document comprise 5-(phenoxymethyl)-1,3-dioxane analogs having a disease-modifying action in the treatment of diseases associated with the production of cortisol that include metabolic syndrome, obesity, headache, depression, hypertension, diabetes mellitus, Cushing's Syndrome, pseudo-Cushing syndrome, cognitive impairment, dementia, heart failure, renal failure, psoriasis, glaucoma, cardiovascular disease, cancer, stroke, incidentalomas, or any diseases involving the overproduction of cortisol.</p>
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NOVEL COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF INFLAMMATORY DISORDERS (Fri, 26 Aug 2016)
<p id="p-0001" num="0000">The present invention discloses compounds according to Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="49.28mm" wi="69.85mm" file="US20160244443A1-20160825-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">Wherein R<sup>1a</sup>, R<sup>1b</sup>, R<sup>2</sup>, R<sup>4</sup>, R<sup>5</sup>, R<sup>6a</sup>, R<sup>6b</sup>, R<sup>7</sup>, R<sup>8</sup>, W, X, Cy, and the subscript a are as defined herein. The present invention relates to compounds inhibiting autotaxin (NPP2 or ENPP2), methods for their production, pharmaceutical compositions comprising the same, and methods of treatment using the same, for the prophylaxis and/or treatment of diseases involving fibrotic diseases, proliferative diseases, inflammatory diseases, autoimmune diseases, respiratory diseases, cardiovascular diseases, neurodegenerative diseases, dermatological disorders, and/or abnormal angiogenesis associated diseases by administering the compound of the invention.</p>
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Ketohexokinase (KHK) iRNA compositions and methods of use thereof (Fri, 26 Aug 2016)
The present invention relates to RNAi agents, e.g., double- stranded RNAi agents, targeting the ketohexokinase (KHK) gene, and methods of using such RNAi agents to inhibit expression of KHK and methods of treating subjects having a KHK-associated disorder, e.g., liver disease (e.g., fatty liver, steatohepatitis), dyslipidemia (e.g., hyperlipidemia, high LDL cholesterol, low HDL cholesterol, hypertriglyceridemia, postprandial hypertriglyceridemia), disorders of glycemic control (e.g., insulin resistance, diabetes), cardiovascular disease (e.g., hypertension, endothelial cell dysfunction), kidney disease (e.g., acute kidney disorder, tubular dysfunction, proinflammatory changes to the proximal tubules), metabolic syndrome, adipocyte dysfunction, visceral adipose deposition, obesity, hyperuricemia, gout, eating disorders, and excessive sugar craving.
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4-(ORTHO)-FLUOROPHENYL-5-FLUOROPYRIMIDIN-2-YL AMINES CONTAINING A SULFONE GROUP (Thu, 25 Aug 2016)
The present invention relates to 4-(ortho)-fluorophenyl-5-fluoropyrimidin-2-yl amine derivatives of general formula (I) as described and defined herein, and methods for their preparation, their use for the treatment and/or prophylaxis of disorders, in particular of hyper-proliferative disorders and/or virally induced infectious diseases and/or of cardiovascular diseases. The invention further relates to intermediate compounds useful in the preparation of said compounds of general formula (I).
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Pyridopyrimidine derivatives and use thereof (Wed, 24 Aug 2016)
<p id="p-0001" num="0000">The invention provides novel substituted pyridopyrimidines represented by Formula I or a pharmaceutically acceptable salt, solvate, polymorph, ester, tautomer or prodrug thereof, and a composition comprising these compounds. The compounds provided can be used as inhibitors of the phosphoinositide 3′ OH kinase family (PI3K) for the treatment of inflammatory diseases, cancer, cardiovascular diseases, allergy, asthma and autoimmune disorders.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="26.75mm" wi="68.16mm" file="US09422298-20160823-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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OMEGA-3 FATTY ACID PRODRUG COMPOUNDS AND USES THEREOF (Fri, 19 Aug 2016)
Provided herein are prodrug compounds, their preparation and their uses, such as treating liver diseases or non-liver diseases via intervening in the molecular pathways in the liver. Novel prodrug compounds of eicosapentaenoic and docosahexaenoic acids, their preparation and their uses are described. Some embodiments are related to novel prodrug compounds that are absorbed in the intestine and taken up via the hepatic portal vein to the liver. Some embodiments are directed to the use of the prodrugs to change eicosapentaenoic and docosahexaenoic acids absorption routes. Another aspect includes the use of prodrugs to treat diseases that benefit from enhanced eicosapentaenoic and docosahexaenoic acids distribution to the liver and like tissues and cells, including but not limited to fatty liver, and metabolic and cardiovascular diseases where the liver is involved in the production and/or the homeostasis control of the biochemical end products, e.g. glucose, cholesterol, fatty acids, triglycerides, lipoproteins, and apolipoproteins.
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INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL (Fri, 19 Aug 2016)
The present invention provides compounds of Formula (I); and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.
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AZA-HETEROARYL COMPOUNDS AS PI3K-GAMMA INHIBITORS (Fri, 19 Aug 2016)
The present invention provides aza-heteroaryl derivatives of Formula I: and pharmaceutically acceptable salts thereof, wherein X, Y, Z, A, W, R4, R5, and R6 are defined herein, that inhibit the activity of phosphoinositide 3-kinases-gamma (PI3Kϒ) and are useful in the treatment of diseases related to the activity of PI3Kϒ including, for example, autoimmune diseases, cancer, cardiovascular diseases, and neurodegenerative diseases.
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INHIBITORS OF RENAL OUTER MEDULLARY POTASSIUM CHANNEL (Fri, 19 Aug 2016)
Disclosed are compounds of Formula I and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.
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Aza-heteroaryl compounds as PI3K-gamma inhibitors (Fri, 12 Aug 2016)
<p id="p-0001" num="0000">The present invention provides aza-heteroaryl derivatives of Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.77mm" wi="58.76mm" file="US09586949-20170307-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> and pharmaceutically acceptable salts thereof, wherein X, Y, Z, A, W, R<sup>4</sup>, R<sup>5</sup>, and R<sup>6 </sup>are defined herein, that inhibit the activity of phosphoinositide 3-kinases-gamma (PI3Kγ) and are useful in the treatment of diseases related to the activity of PI3Kγ including, for example, autoimmune diseases, cancer, cardiovascular diseases, and neurodegenerative diseases. </p>
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COMPOUNDS FOR THE PREVENTION AND TREATMENT OF VASCULAR DISEASE (Fri, 12 Aug 2016)
A composition for treating or preventing disease, especially vascular disease, including a composition chosen from FORMULAS I-VIII, ligands thereof, analogs thereof, a pharmaceutically acceptable salt thereof, a solvate thereof, an ester thereof, tautomer thereof, or combinations thereof. A combination drug formulation for treating and preventing cardiovascular disease, including the compositions of FORMULA I, FORMULA III, and FORMULA VI. A method of treating or preventing disease, by administering a pharmaceutically effective amount of at least one of the compositions of FORMULAS I-VIII, a ligand thereof, an analog thereof, a pharmaceutically acceptable salt thereof, a solvate thereof, an ester thereof, a tautomer thereof, or combinations thereof to a subject. Methods of treating or preventing vascular disease, arthritis, metastatic cancer, and diabetes.
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QUINAZOLINONES AND AZAQUINAZOLINONES AS UBIQUITIN-SPECIFIC PROTEASE 7 INHIBITORS (Fri, 12 Aug 2016)
The present disclosure relates to inhibitors of USP7 inhibitors useful in the treatment of cancers, neurodegenerative diseases, immunological disorders, inflammatory disorders, cardiovascular diseases, ischemic diseases, viral infections and diseases, and bacterial infections and diseases, having the Formula: (I) where R1, R2, R3, R4, R4, X1, Y1, Y2, Y3, Y4, n, and m are described herein.
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ISOTHIAZOLOPYRIMIDINONES, PYRAZOLOPYRIMIDINONES, AND PYRROLOPYRIMIDINONES AS UBIQUITIN-SPECIFIC PROTEASE 7 INHIBITORS (Fri, 12 Aug 2016)
The disclosure relates to inhibitors of USP7 inhibitors useful in the treatment of cancers, neurodegenerative diseases, immunological disorders, inflammatory disorders, cardiovascular diseases, ischemic diseases, viral infections and diseases, and bacterial infections and diseases, having the Formula (I): where R1, R2, R3, R4, R5, R5', X1, X2, X3, n, and m are described herein.
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Substituted aza-bicyclic imidazole derivatives useful as TRPM8 receptor modulators (Wed, 10 Aug 2016)
<p id="p-0001" num="0000">The present invention is directed to substituted aza-bicyclic imidazole derivatives, pharmaceutical compositions containing them and their use in the treatment of disorders and conditions modulated by TRP M8, including for example, inflammatory pain, inflammatory hyperalgesia, inflammatory hypersensitivity condition, neuropathic pain, neuropathic cold allodynia, inflammatory somatic hyperalgesia, inflammatory visceral hyperalgesia, cardiovascular disease aggravated by cold and pulmonary disease aggravated by cold.</p>
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Processes for Preparing Medicaments for the Treatment of Cardiovascular Diseases and Intermediates for Use Therein (Fri, 05 Aug 2016)
<p id="p-0001" num="0000">The present invention provides a compound of formula N wherein: X is CH<sub>2</sub>, oxygen or sulphur; R<sub>1</sub>, R<sub>2 </sub>and R<sub>3 </sub>are the same or different and signify hydrogens, halogens, alkyl, alkyloxy, hydroxy, nitro, alkylcarbonylamino, alkylamino or dialkylamino group, wherein N is in the form of the individual R- and S-enantiomer or a mixture of the (R)- and (S)-enantiomer. The present invention also provides a compound of formula MA. The present invention also provides processes for preparing the above compounds, and processes involving their use. The compounds are particularly useful as intermediates in the synthesis of peripherally-selective inhibitors of dopamine-β-hydroxylase.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="59.77mm" wi="56.90mm" file="US20160221981A1-20160804-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Cytochrome P450 inhibitors and their method of use (Fri, 05 Aug 2016)
<p id="p-0001" num="0000">Embodiments of the present invention relate to novel cytochrome P450 inhibitors and pharmaceutical compositions thereof having a disease-modifying action in the treatment of diseases associated with the production of cortisol that include metabolic syndrome, obesity, headache, depression, hypertension, diabetes mellitus, Cushing's Syndrome, pseudo-Cushing syndrome, cognitive impairment, dementia, heart failure, renal failure, psoriasis, glaucoma, cardiovascular disease, cancer, stroke or incidentalomas.</p>
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INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL (Fri, 05 Aug 2016)
The present invention provides compounds of Formula (I): and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.
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N-ACYLOXYSULFONAMIDE AND N-HYDROXY-N-ACYLSULFONAMIDE DERIVATIVES (Fri, 05 Aug 2016)
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.
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Agonistic human LCAT antigen binding proteins and their use in therapy (Fri, 05 Aug 2016)
Antigen binding proteins that activate LCAT are provided. Nucleic acids encoding the antigen binding proteins and vectors and cells containing such nucleic acids are also provided. The antigen binding proteins have value in therapeutic methods in which it is useful to modulate HDL particle size, increase plasma levels of HDL-C, and increase reverse cholesterol transport. Accordingly, the antigen binding proteins have utility in the treatment and prevention of atherosclerosis, various cardiovascular diseases and cholesterol-related disorders, inflammatory conditions, thrombosis-related conditions, metabolic syndrome, diabetes and insulin-resistance. The LCAT antigen binding proteins are also useful in treating the consequences, symptoms, and/or pathology associated with either genetic or acquired LCAT deficiency, including chronic kidney disease (CKD).
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Derivatives of 5-benzylisoquinoline for the treatment of cardiovascular diseases (Fri, 05 Aug 2016)
The invention relates to novel isoquinoline derivatives of formula (I), to the synthesis thereof, and to the use of same in the prevention and/or treatment of pathologies resulting from the activation of the RhoA/ROCK pathway and the phosphorylation of the light chain of myosin. X represents a group -C(=0)-, -CH(OH)- or -CH<sb>2</sb>-, and the other substituents represent various groups such as those defined in claim 1.
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Fused heterocyclic compounds as ion channel modulators (Wed, 03 Aug 2016)
<p id="p-0001" num="0000">The present disclosure relates to compounds that are sodium channel inhibitors and to their use in the treatment of various disease states, including cardiovascular diseases and diabetes. In particular embodiments, the structure of the compounds is given by Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="16.51mm" wi="55.37mm" file="US09403782-20160802-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein Q, R<sup>1</sup>, X<sup>1</sup>, X<sup>2</sup>, Y and R<sup>2 </sup>are as described herein, to methods for the preparation and use of the compounds and to pharmaceutical compositions containing the same. </p>
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SYNTHETIC APELIN FATTY ACID CONJUGATES WITH IMPROVED HALF-LIFE (Fri, 29 Jul 2016)
<p id="p-0001" num="0000">The invention provides a conjugate, or a pharmaceutically acceptable salt thereof, comprising a synthetic polypeptide of Formula I:</p> <p id="p-0002" num="0000"> <br/> <?in-line-formulae description="In-line Formulae" end="lead"?>Q-R-P-R-L-C*-H-K-G-P-(Nle)-C*-F  (I)<?in-line-formulae description="In-line Formulae" end="tail"?> </p> <p id="p-0003" num="0000">or a amide or ester thereof; and a fatty acid selected from:</p> <p id="p-0004" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="129.71mm" wi="39.71mm" file="US20160213743A1-20160728-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0005" num="0000">wherein said fatty acid is covalently linked to the N-terminus of the peptide via one of its carboxylic acid functionality, optionally via a polyethylene glycol linker; and wherein the two cysteine amino acids labeled with “*” form a disulfide bond between the thiol functionalities of their side chain. The conjugates are agonist of the APJ receptor. The invention also relates to a method for manufacturing the conjugates of the invention, and its therapeutic uses such as treatment or prevention of acute decompensated heart failure (ADHF), chronic heart failure, pulmonary hypertension, atrial fibrillation, Brugada syndrome, ventricular tachycardia, atherosclerosis, hypertension, restenosis, ischemic cardiovascular diseases, cardiomyopathy, cardiac fibrosis, arrhythmia, water retention, diabetes (including gestational diabetes), obesity, peripheral arterial disease, cerebrovascular accidents, transient ischemic attacks, traumatic brain injuries, amyotrophic lateral sclerosis, burn injuries (including sunburn) and preeclampsia. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.</p>
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Preparation and Uses of Obeticholic Acid (Fri, 29 Jul 2016)
<p id="p-0001" num="0000">The present invention relates to obeticholic acid:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="36.24mm" wi="60.28mm" file="US20160215014A1-20160728-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or a pharmaceutically acceptable salt, solvate or amino acid conjugate thereof. Obeticholic acid is useful for the treatment or prevention of a FXR mediated disease or condition, cardiovascular disease or cholestatic liver disease, and for reducing HDL cholesterol, for lowering triglycerides in a mammal, or for inhibition of fibrosis. The present invention also relates to processes for the synthesis of obeticholic acid.</p>
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EBI2 modulators (Fri, 29 Jul 2016)
<p id="p-0001" num="0000">Provided herein are small molecule Epstein-Barr virus-induced G-protein coupled receptor 2 (EBI2) modulator compounds, compositions comprising the compounds, and methods of using the compounds and compositions comprising the compounds. EBI2 is a therapeutic target for the treatment of a variety of diseases or conditions. In some embodiments, EBI2 is a therapeutic target for the treatment of diseases or conditions such as, but not limited to, autoimmune diseases or conditions, cancer, and cardiovascular disease.</p>
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Compounds and pharmaceutical compositions thereof for the treatment of inflammatory disorders (Fri, 29 Jul 2016)
<p id="p-0001" num="0000">The present invention discloses compounds according to Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="49.36mm" wi="69.85mm" file="US09796719-20171024-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> Wherein R<sup>1a</sup>, R<sup>1b</sup>, R<sup>2</sup>, R<sup>4</sup>, R<sup>5</sup>, R<sup>6</sup>, R<sup>7</sup>, R<sup>8</sup>, W, X, Y, Z, Cy, and the subscript a are as defined herein. The present invention relates to compounds inhibiting autotaxin (NPP2 or ENPP2), methods for their production, pharmaceutical compositions comprising the same, and methods of treatment using the same, for the prophylaxis and/or treatment of diseases involving fibrotic diseases, proliferative diseases, inflammatory diseases, autoimmune diseases, respiratory diseases, cardiovascular diseases, neurodegenerative diseases, dermatological disorders, and/or abnormal angiogenesis associated diseases by administering the compound of the invention. </p>
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MODULATORS OF FARNESOID X RECEPTOR AND METHODS FOR THE USE THEREOF (Fri, 29 Jul 2016)
Compounds, compositions and methods are provided for treating the FXR-mediated disease or process in a mammal, comprising administering to the mammal a therapeutically effective amount of a compound claimed, wherein the FXR-mediated disease or condition linked to chronic liver diseases such as nonalcoholic fatty liver disease and nonalcoholic steatohepatitis; gastrointestinal diseases; cardiovascular diseases; metabolic diseases such as diabetes and obesity; inflammation, or cancer etc..
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SYNTHETIC APELIN FATTY ACID CONJUGATES WITH IMPROVED HALF-LIFE (Fri, 29 Jul 2016)
The invention provides a conjugate, or a pharmaceutically acceptable salt thereof, comprising a synthetic polypeptide of Formula I: Q-R-P-R-L-C*-H-K-G-P-(Nle)-C*-F (I) or a amide or ester thereof; and a fatty acid selected from: wherein said fatty acid is covalently linked to the N-terminus of the peptide via one of its carboxylic acid functionality, optionally via a polyethylene glycol linker; and wherein the two cysteine amino acids labeled with "*" form a disulfide bond between the thiol functionalities of their side chain. The conjugates are agonist of the APJ receptor. The invention also relates to a method for manufacturing the conjugates of the invention, and its therapeutic uses such as treatment or prevention of acute decompensated heart failure (ADHF), chronic heart failure, pulmonary hypertension, atrial fibrillation, Brugada syndrome, ventricular tachycardia, atherosclerosis, hypertension, restenosis, ischemic cardiovascular diseases, cardiomyopathy, cardiac fibrosis, arrhythmia, water retention, diabetes (including gestational diabetes), obesity, peripheral arterial disease, cerebrovascular accidents, transient ischemic attacks, traumatic brain injuries, amyotrophic lateral sclerosis, burn injuries (including sunburn) and preeclampsia. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.
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Synthetic apelin fatty acid conjugates with improved half-life (Fri, 29 Jul 2016)
The invention provides a conjugate, or a pharmaceutically acceptable salt thereof, comprising a synthetic polypeptide of Formula I: Q-R-P-R-L-C*-H-K-G-P-(Nle)-C*-F (I) or a amide or ester thereof; and a fatty acid selected from: wherein said fatty acid is covalently linked to the N-terminus of the peptide via one of its carboxylic acid functionality, optionally via a polyethylene glycol linker; and wherein the two cysteine amino acids labeled with "*" form a disulfide bond between the thiol functionalities of their side chain. The conjugates are agonist of the APJ receptor. The invention also relates to a method for manufacturing the conjugates of the invention, and its therapeutic uses such as treatment or prevention of acute decompensated heart failure (ADHF), chronic heart failure, pulmonary hypertension, atrial fibrillation, Brugada syndrome, ventricular tachycardia, atherosclerosis, hypertension, restenosis, ischemic cardiovascular diseases, cardiomyopathy, cardiac fibrosis, arrhythmia, water retention, diabetes (including gestational diabetes), obesity, peripheral arterial disease, cerebrovascular accidents, transient ischemic attacks, traumatic brain injuries, amyotrophic lateral sclerosis, burn injuries (including sunburn) and preeclampsia. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.
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Inhibitors of the renal outer medullary potassium channel (Fri, 22 Jul 2016)
<p id="p-0001" num="0000">The present invention provides compounds of Formula I</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="28.87mm" wi="59.01mm" file="US09751881-20170905-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 chronic kidney disease and conditions associated with excessive salt and water retention. </p>
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PREDICTING CORONARY ARTERY DISEASE AND RISK OF CARDIOVASCULAR EVENTS (Fri, 08 Jul 2016)
<p id="p-0001" num="0000">Methods of assessing the risk of cardiovascular disease in a subject by detecting the level of at least one metabolite in a sample from the subject are disclosed herein. The level of the metabolite is indicative of the risk of cardiovascular disease in the subject. The metabolites may be acylcarnitines, amino acids, ketones, free fatty acids or hydroxybutyrate. The cardiovascular disease may be risk of a cardiovascular event, presence of coronary artery disease or risk of development of coronary artery disease.</p>
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COMPOSITIONS AND METHODS FOR MODULATING ANGIOPOIETIN-LIKE 3 EXPRESSION (Fri, 08 Jul 2016)
<p id="p-0001" num="0000">Provided herein are methods, compounds, and compositions for reducing expression of an ANGPTL3 mRNA and protein in an animal. Also provided herein are methods, compounds, and compositions for reducing lipids and/or glucose in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate any one or more of cardiovascular disease and/or metabolic disease, or a symptom thereof, in an individual in need thereof.</p>
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PYRROLOTRIAZINONE AND IMIDASOTRIAZINONE DERIVATIVES AS OBIQUITIN-SPECIFIC PROTEASE 7 CUSP? ) INHIBITORS FOR THE TREATMENT OF CANCER AND OTHER USP7 MEDIATED DISEASES (Fri, 08 Jul 2016)
The invention relates to pyrrolo[2,1-f][1,2,4]triazin-4(3H)-one and imidazo[5,1-f][1,2,4]triazin-4(3H)-one derivatives as inhibitors of the ubiquitin-specific protease 7 (USP7) useful in the treatment of cancers, neurodegenerative diseases, immunological disorders, inflammatory disorders, cardiovascular diseases, ischemic diseases, viral infections and diseases, and bacterial infections and diseases, having the Formula (I) where Rl, R2, R3, R4, Rs, Rs', R6, Xl, X2, m, and n are described herein.
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PYRROLO AND PYRAZOLOPYRIMIDINES AS UBIQUITIN-SPECIFIC PROTEASE 7 INHIBITORS (Fri, 08 Jul 2016)
The invention relates to inhibitors of USP7 inhibitors useful in the treatment of cancers, neurodegenerative diseases, immunological disorders, inflammatory disorders, cardiovascular diseases, ischemic diseases, viral infections and diseases, and bacterial infections and diseases, having the Formula: (I) where m, n, X1, X2, R1-R5, R5' and R6 are described herein.
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RNA-CODED ANTIBODY (Fri, 01 Jul 2016)
<p id="p-0001" num="0000">The present application describes an antibody-coding, non-modified or modified RNA and the use thereof for expression of this antibody, for the preparation of a pharmaceutical composition, in particular a passive vaccine, for treatment of tumours and cancer diseases, cardiovascular diseases, infectious diseases, autoimmune diseases, virus diseases and monogenetic diseases, e.g. also in gene therapy. The present invention furthermore describes an in vitro transcription method, in vitro methods for expression of this antibody using the RNA according to the invention and an in vivo method.</p>
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TRADITIONAL CHINESE MEDICINE COMPOSITION (Fri, 01 Jul 2016)
<p id="p-0001" num="0000">A traditional Chinese medicine composition and preparation thereof for treating cardiovascular diseases is provided. The traditional Chinese medicine composition consists of: by weight percentage, phenolic acid derivatives 30%˜80%, tanshinones 2%˜10% and saponins 15%˜60%.</p>
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PYRROLO AND PYRAZOLOPYRIMIDINES AS UBIQUITIN-SPECIFIC PROTEASE 7 INHIBITORS (Fri, 01 Jul 2016)
<p id="p-0001" num="0000">The invention relates to inhibitors of USP7 inhibitors useful in the treatment of cancers, neurodegenerative diseases, immunological disorders, inflammatory disorders, cardiovascular diseases, ischemic diseases, viral infections and diseases, and bacterial infections and diseases, having the Formula:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.26mm" wi="64.60mm" file="US20160185785A1-20160630-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">where m, n, X<sub>1</sub>, X<sub>2</sub>, R<sub>1</sub>-R<sub>5</sub>, R<sub>5′</sub> and R<sub>6 </sub>are described herein.</p>
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OXOQUINAZOLINYL-BUTANAMIDE DERIVATIVES (Fri, 01 Jul 2016)
<p id="p-0001" num="0000">Compounds of the formula I</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="33.19mm" wi="71.37mm" file="US20160184310A1-20160630-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">in which R<sup>1</sup>-R<sup>3 </sup>and Z have the meanings indicated in Claim <b>1</b>, are inhibitors of Tankyrase, and can be employed, inter alia, for the treatment of diseases such as cancer, cardiovascular diseases, central nervous system injury and different forms of inflammation.</p>
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PYRROLOTRIAZINONES AND IMIDAZOTRIAZINONES AS UBIQUITIN-SPECIFIC PROTEASE 7 INHIBITORS (Fri, 01 Jul 2016)
<p id="p-0001" num="0000">The invention relates to inhibitors of USP7 inhibitors useful in the treatment of cancers, neurodegenerative diseases, immunological disorders, inflammatory disorders, cardiovascular diseases, ischemic diseases, viral infections and diseases, and bacterial infections and diseases, having the Formula:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.26mm" wi="64.69mm" file="US20160185786A1-20160630-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">where R<sub>1</sub>, R<sub>2</sub>, R<sub>3</sub>, R<sub>4</sub>, R<sub>5</sub>, R<sub>5′</sub>, R<sub>6</sub>, X<sub>1</sub>, X<sub>2</sub>, m, and n are described herein.</p>
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Piperidine urea derivatives (Fri, 01 Jul 2016)
<p id="p-0001" num="0000">Compounds of the formula I</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="19.81mm" wi="57.07mm" file="US09770446-20170926-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> in which R<sup>1</sup>-R<sup>3 </sup>have the meanings indicated in Claim <b>1, </b> <br/> are inhibitors of Tankyrase, and can be employed, inter alia, for the treatment of diseases such as cancer, cardiovascular diseases, central nervous system injury and different forms of inflammation. </p>
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VITAMIN D3 DERIVATIVES AND PHARMACEUTICAL USE THEREOF (Fri, 01 Jul 2016)
The present invention relates to vitamin D3 derivatives of the following formula, wherein each symbol has the same meaning as defined herein, and pharmaceutical or medical use thereof for treating metabolic disease, liver disease, obesity, diabetes, cardiovascular disease, or cancer in a patient in need thereof.
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SPIROCYCLIC EBI2 MODULATORS (Fri, 24 Jun 2016)
<p id="p-0001" num="0000">Provided herein are small molecule Epstein-Barr virus-induced G-protein coupled receptor 2 (EBI2) modulator compounds, compositions comprising the compounds, and methods of using the compounds and compositions comprising the compounds. In some embodiments, EBI2 is a therapeutic target for the treatment of diseases or conditions such as, but not limited to, autoimmune diseases or conditions, cancer, and cardiovascular disease.</p>
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MAGNETIC SEPARATION OF LIPOPROTEINS USING DEXTRAN SULFATE (Fri, 24 Jun 2016)
<p id="p-0001" num="0000">The invention provides apparatus and methods of preparation of lipoproteins from a biological sample, including HDL, LDL, Lp(a), IDL, and VLDL, for diagnostic purposes utilizing differential charged-particle mobility analysis methods. Further provided are methods for analyzing the size distribution of lipoproteins by differential charged-particle mobility, which lipoproteins are prepared by methods of the invention. Further provided are methods for assessing lipid-related health risk, cardiovascular condition, risk of cardiovascular disease, and responsiveness to a therapeutic intervention, which methods utilize lipoprotein size distributions determined by methods of the invention.</p>
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1,3-Disubstituted cyclopentane derivatives (Fri, 24 Jun 2016)
<p id="p-0001" num="0000">Compounds of the formula I</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="33.36mm" wi="69.85mm" file="US09718785-20170801-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> in which R, Y, R<sup>1</sup>, X<sup>1</sup>, X<sup>2</sup>, X<sup>3 </sup>and q have the meanings indicated in claim <b>1</b>, are inhibitors of fatty acid synthase, and can be employed, inter alia, for the treatment of diseases such as cancer, cardiovascular diseases, central nervous system injury and different forms of inflammation. </p>
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Preparation and uses of obeticholic acid (Fri, 24 Jun 2016)
<p id="p-0001" num="0000">The present invention relates to obeticholic acid:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="36.83mm" wi="59.10mm" file="US09732116-20170815-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> or a pharmaceutically acceptable salt, solvate or amino acid conjugate thereof. Obeticholic acid is useful for the treatment or prevention of a FXR mediated disease or condition, cardiovascular disease or cholestatic liver disease, and for reducing HDL cholesterol, for lowering triglycerides in a mammal, or for inhibition of fibrosis. The present invention also relates to processes for the synthesis of obeticholic acid. </p>
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TRADITIONAL CHINESE MEDICINE COMPOSITION, AND PREPARATION AND APPLICATION THEREOF (Fri, 24 Jun 2016)
<p id="p-0001" num="0000">A traditional Chinese medicine composition for treating cardiovascular disease, and a preparation thereof, particularly a micro drop pill preparation thereof, and a method for preparing the preparation; the method for preparing the micro drop pill preparation can be used to prepare drop pills, coated drop pills, and drop pill capsules with a high drug loading capacity.</p>
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MODULATORS OF HEPATIC LIPOPROTEIN METABOLISM (Fri, 24 Jun 2016)
The invention relates to compounds for modulating hepatic cholesterol metabolism. The invention includes methods of making and using the compounds. These compounds or pharmaceutically acceptable salts thereof are useful for treating, preventing, and/or alleviating a cholesterol related disorder, a cardiovascular disease and/or liver disease in a human or animal.
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RNA-CODED ANTIBODY (Fri, 17 Jun 2016)
<p id="p-0001" num="0000">The present application describes an antibody-coding, non-modified or modified RNA and the use thereof for expression of this antibody, for the preparation of a pharmaceutical composition, in particular a passive vaccine, for treatment of tumours and cancer diseases, cardiovascular diseases, infectious diseases, autoimmune diseases, virus diseases and monogenetic diseases, e.g. also in gene therapy. The present invention furthermore describes an in vitro transcription method, in vitro methods for expression of this antibody using the RNA according to the invention and an in vivo method.</p>
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BIOCONJUGATES OF SYNTHETIC APELIN POLYPEPTIDES (Fri, 17 Jun 2016)
<p id="p-0001" num="0000">The invention provides a bioconjugates comprising a synthetic polypeptide of Formula I′ (SEQ ID NO: 1):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="7.96mm" wi="69.85mm" file="US20160166634A1-20160616-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">or an amide, an ester or a salt thereof, wherein X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12 and X13 are defined herein and a half-life extending moiety wherein the peptide and the half-life extending moiety are covalently linked or fuse, optionally via a linker. The polypeptides are agonist of the APJ receptor. The invention also relates to a method for manufacturing the bioconjugates of the invention, and its therapeutic uses such as treatment or prevention of acute decompensated heart failure (ADHF), chronic heart failure, pulmonary hypertension, atrial fibrillation, Brugada syndrome, ventricular tachycardia, atherosclerosis, hypertension, restenosis, ischemic cardiovascular diseases, cardiomyopathy, cardiac fibrosis, arrhythmia, water retention, diabetes (including gestational diabetes), obesity, peripheral arterial disease, cerebrovascular accidents, transient ischemic attacks, traumatic brain injuries, amyotrophic lateral sclerosis, burn injuries (including sunburn) and preeclampsia. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.</li> </ul> </li> </ul> </p>
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RNA-CODED ANTIBODY (Fri, 17 Jun 2016)
<p id="p-0001" num="0000">The present application describes an antibody-coding, non-modified or modified RNA and the use thereof for expression of this antibody, for the preparation of a pharmaceutical composition, in particular a passive vaccine, for treatment of tumours and cancer diseases, cardiovascular diseases, infectious diseases, autoimmune diseases, virus diseases and monogenetic diseases, e.g. also in gene therapy. The present invention furthermore describes an in vitro transcription method, in vitro methods for expression of this antibody using the RNA according to the invention and an in vivo method.</p>
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RNA-CODED ANTIBODY (Fri, 17 Jun 2016)
<p id="p-0001" num="0000">The present application describes an antibody-coding, non-modified or modified RNA and the use thereof for expression of this antibody, for the preparation of a pharmaceutical composition, in particular a passive vaccine, for treatment of tumours and cancer diseases, cardiovascular diseases, infectious diseases, autoimmune diseases, virus diseases and monogenetic diseases, e.g. also in gene therapy. The present invention furthermore describes an in vitro transcription method, in vitro methods for expression of this antibody using the RNA according to the invention and an in vivo method.</p>
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RNA-CODED ANTIBODY (Fri, 17 Jun 2016)
<p id="p-0001" num="0000">The present application describes an antibody-coding, non-modified or modified RNA and the use thereof for expression of this antibody, for the preparation of a pharmaceutical composition, in particular a passive vaccine, for treatment of tumours and cancer diseases, cardiovascular diseases, infectious diseases, autoimmune diseases, virus diseases and monogenetic diseases, e.g. also in gene therapy. The present invention furthermore describes an in vitro transcription method, in vitro methods for expression of this antibody using the RNA according to the invention and an in vivo method.</p>
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Fused heterocyclic compounds as ion channel modulators (Fri, 17 Jun 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.
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Fused heterocyclic compounds as ion channel modulators (Fri, 17 Jun 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.
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MK2 INHIBITORS (Fri, 10 Jun 2016)
<p id="p-0001" num="0000">The present invention relates to compounds of general Formula I</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="38.52mm" wi="65.62mm" file="US20160159800A1-20160609-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or a pharmaceutically acceptable salt thereof. The compounds can be used in the treatment of immune, autoimmune, inflammatory diseases, cardiovascular diseases, infectious diseases, bone resorption disorders, neurodegenerative diseases or proliferative diseases.</p>
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Aminopyrimidines useful as kinase inhibitors (Fri, 10 Jun 2016)
Compounds and pharmaceutically acceptable compositions thereof that are useful as inhibitors of protein kinases. These compounds are represented by formula I: or a pharmaceutically acceptable salt thereof, wherein R', RX, R , Q, and Ht are as defined herein. These compounds and pharmaceutically acceptable compositions thereof are useful for inhibiting kinases in vitro, in vivo, and ex vivo. Such uses include treating or preventing a variety of diseases, disorders or conditions, including, but not limited to, autoimmune diseases, inflammatory diseases, bone diseases, metabolic diseases, neurological and neurodegenerative diseases, cancer, cardiovascular diseases, allergies and asthma, Alzheimer's disease, and hormone-related diseases. Other uses include the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors.
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ENGINEERED POLYPEPTIDES HAVING ENHANCED DURATION OF ACTION (Thu, 09 Jun 2016)
Compounds are provided having inter alia good duration of action, high potency and/or convenient dosing regimens including oral administration. The compounds are engineered polypeptides which incorporate an albumin binding domain in combination with one or more biologically active polypeptides. Also provided are pharmaceutical compositions and methods of treatment for diseases and disorders including obesity and overweight, diabetes, dyslipidemia, hyperlipidemia, Alzheimer's disease, fatty liver disease, short bowel syndrome, Parkinson's disease, cardiovascular disease, and other and disorders of the central nervous system.
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OXOQUINAZOLINYL-BUTANAMIDE DERIVATIVES (Thu, 09 Jun 2016)
Compounds of the formula I in which R<sp>1</sp>-R<sp>3</sp> and Z have the meanings indicated in Claim 1, are inhibitors of Tankyrase, and can be employed, inter alia, for the treatment of diseases such as cancer, cardiovascular diseases, central nervous system injury and different forms of inflammation.
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1,3-DISUBSTITUTED CYCLOPENTANE DERIVATIVES (Thu, 09 Jun 2016)
Compounds of the formula (I) in which R, Y, R<sp>1</sp>, X<sp>1</sp>, X<sp>2</sp>, X<sp>3</sp> and q have the meanings indicated in Claim 1, are inhibitors of fatty acid synthase, and can be employed, inter alia, for the treatment of diseases such as cancer, cardiovascular diseases, central nervous system injury and different forms of inflammation.
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Thyroid hormone analogs (Wed, 08 Jun 2016)
<p id="p-0001" num="0000">Provided herein are compounds of the formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.77mm" wi="60.45mm" file="USRE046024-20160607-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of diseases such as obesity, hyperlipidemia, hypercholesterolemia and diabetes and other related disorders and diseases, and may be useful for other diseases such as NASH, atherosclerosis, cardiovascular diseases, hypothyroidism, thyroid cancer and other disorders and diseases related thereto. </p>
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OXAZOLIDINONE DERIVATIVES AS PPAR LIGANDS (Fri, 03 Jun 2016)
<p id="p-0001" num="0000">The present invention relates to a family of differently substituted oxazolidinones and to the pharmaceutically acceptable salts, esters, prodrugs, tautomers, solvates and hydrates thereof, which show affinity for the alpha and gamma subtypes of the peroxisome proliferator-activated receptors (PPAR) and which, therefore, modulate the actions regulated by said receptors, such as inducing satiety, controlling ingestion and modulating metabolic effects, and thus are useful for the administration thereof as a pharmacological tool and as drugs for the treatment and/or prevention of metabolic diseases and cardiovascular diseases.</p>
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RNA-CODED ANTIBODY (Fri, 03 Jun 2016)
<p id="p-0001" num="0000">The present application describes an antibody-coding, non-modified or modified RNA and the use thereof for expression of this antibody, for the preparation of a pharmaceutical composition, in particular a passive vaccine, for treatment of tumours and cancer diseases, cardiovascular diseases, infectious diseases, autoimmune diseases, virus diseases and monogenetic diseases, e.g. also in gene therapy. The present invention furthermore describes an in vitro transcription method, in vitro methods for expression of this antibody using the RNA according to the invention and an in vivo method.</p>
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RNA-CODED ANTIBODY (Fri, 03 Jun 2016)
<p id="p-0001" num="0000">The present application describes an antibody-coding, non-modified or modified RNA and the use thereof for expression of this antibody, for the preparation of a pharmaceutical composition, in particular a passive vaccine, for treatment of tumours and cancer diseases, cardiovascular diseases, infectious diseases, autoimmune diseases, virus diseases and monogenetic diseases, e.g. also in gene therapy. The present invention furthermore describes an in vitro transcription method, in vitro methods for expression of this antibody using the RNA according to the invention and an in vivo method.</p>
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Ketone derivatives of imidazoles, pharmaceutical combinations and uses thereof (Fri, 03 Jun 2016)
This application relates to ketone compounds of imidazoles, pharmaceutically acceptable salts, solvates, 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.
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RNA-CODED ANTIBODY (Fri, 27 May 2016)
<p id="p-0001" num="0000">The present application describes an antibody-coding, non-modified or modified RNA and the use thereof for expression of this antibody, for the preparation of a pharmaceutical composition, in particular a passive vaccine, for treatment of tumours and cancer diseases, cardiovascular diseases, infectious diseases, autoimmune diseases, virus diseases and monogenetic diseases, e.g. also in gene therapy. The present invention furthermore describes an in vitro transcription method, in vitro methods for expression of this antibody using the RNA according to the invention and an in vivo method.</p>
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TRADITIONAL CHINESE MEDICINE COMPOSITION, AND PREPARATION AND APPLICATION THEREOF (Fri, 27 May 2016)
<p id="p-0001" num="0000">A traditional Chinese medicine composition for treating cardiovascular disease, and a preparation thereof, particularly a micro drop pill preparation thereof, and a method for preparing the preparation; the method for preparing the micro drop pill preparation can be used to prepare drop pills, coated drop pills, and drop pill capsules with a high drug loading capacity.</p>
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Sulfoximine substituted 5-fluoro-N-(pyridin-2-yl)pyridin-2-amine derivatives and their use as CDK9 kinase inhibitors (Fri, 27 May 2016)
<p id="p-0001" num="0000">The present invention relates to 5-fluoro-N-(pyridin-2-yl)pyridin-2-amine derivatives containing a sulfoximine group of general formula (I) as described and defined herein, and methods for their preparation, their use for the treatment and/or prophylaxis of disorders, in particular of hyper-proliferative disorders and/or virally induced infectious diseases and/or of cardiovascular diseases. The invention further relates to intermediate compounds useful in the preparation of said compounds of general formula (I).</p>
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SUBSTITUTED BRIDGED UREA ANALOGS AS SIRTUIN MODULATORS (Fri, 27 May 2016)
The present invention relates to novel substituted bridged urea analog compounds of Formula (I) or pharmaceutically acceptable salts thereof, corresponding pharmaceutical compositions, processes for making and use of such compounds, alone or in combination with other therapeutic agents, as Sirtuin Modulators useful for increasing lifespan of a cell, and for use in treating and/or preventing a wide variety of diseases and disorders, which include, but are not limited to, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity.
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SUBSTITUTED BRIDGED UREA ANALOGS AS SIRTUIN MODULATORS (Fri, 27 May 2016)
The present invention relates to novel substituted bridged urea analog compounds of Formula (I) or pharmaceutically acceptable salts thereof, corresponding pharmaceutical compositions, processes for making and use of such compounds, alone or in combination with other therapeutic agents, as Sirtuin Modulators useful for increasing lifespan of a cell, and in treating and/or preventing a wide variety of diseases and disorders, which include, but are not limited to, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity.
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SUBSTITUTED BRIDGED UREA ANALOGS AS SIRTUIN MODULATORS (Fri, 27 May 2016)
The present invention relates to novel substituted bridged urea analog compounds of Formula (I) or pharmaceutically acceptable salts thereof, corresponding pharmaceutical compositions, processes for making and use of such compounds, alone or in combination with other therapeutic agents, as Sirtuin Modulators useful for increasing lifespan of a cell, and in treating and/or preventing a wide variety of diseases and disorders, which include, but are not limited to, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. (I)
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SUBSTITUTED BRIDGED UREA ANALOGS AS SIRTUIN MODULATORS (Fri, 27 May 2016)
The present invention relates to novel substituted bridged urea analog compounds of Formula (I) or pharmaceutically acceptable salts thereof, corresponding pharmaceutical compositions, processes for making and use of such compounds, alone or in combination with other therapeutic agents, as Sirtuin Modulators useful for increasing lifespan of a cell, and in treating and/or preventing a wide variety of diseases and disorders, which include, but are not limited to, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity.
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MONOCARBOXYLATE TRANSPORT MODULATORS AND USES THEREOF (Fri, 27 May 2016)
The invention generally relates to the field of monocarboxylate transport modulators, e.g., monocarboxylate transport inhibitors, and more particularly to new substituted-quinolone compounds, the synthesis and use of these compounds and their pharmaceutical compositions, e.g., in treating, modulating, forestalling and/or reducing physiological conditions associated with monocarboxylate transport activity such as in treating cancer and other neoplastic disorders, inflammatory diseases, disorders of abnormal tissue growth and fibrosis including cardiomyopathy, obesity, diabetes, cardiovascular diseases, tissue and organ transplant rejection, and malaria.
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CARDIOVASCULAR DISEASE RISK ASSESSMENT (Fri, 27 May 2016)
The invention provides improved methods for analyzing cardiovascular disease risk. According to the invention, an algorithm that considers LDL and HDL subfractions, along with Lp(a) provides significant improvement in predicting CVD versus standard assays that include standard risk factors. Methods of the invention comprise measuring LDL and HDL subfractions in addition to Lp(a) without reference to standard risk factor measurements, such as CRP, total cholesterol, body mass index, weight, triglycerides, and the like. It is unexpected that an algorithm focusing only on LDL and HDL subfractions and Lp(a) would be more informative as to CVD risk than measurements that are much more comprehensive in terms of the markers that are reviewed. In particular, the sdLDL-C subfraction of LDL and the ApoA- 1 in large alpha- 1 HDL are most informative in conjunction with Lp(a).
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SUBSTITUTED BRIDGED UREA ANALOGS AS SIRTUIN MODULATORS (Fri, 27 May 2016)
The present invention relates to novel substituted bridged urea compounds, corresponding related analogs, pharmaceutical compositions and methods of use thereof. Sirtuin-modulating compounds of the present invention may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders, which include, but are not limited to, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. The present invention also related to compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.
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Use of 4-[ethyl(dimethyl)ammonio]butanoate in the treatment of cardiovascular disease (Fri, 20 May 2016)
<p id="p-0001" num="0000">New compound 4-[ethyl(dimethyl)ammonio]butanoate, method of preparation thereof and use in the treatment of cardiovascular disease.</p>
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Cardiovascular disease risk assessment (Fri, 20 May 2016)
<p id="p-0001" num="0000">The invention provides methods for analyzing cardiovascular disease risk. Methods of the invention provide a probability of an individual developing cardiovascular disease based on parameters including blood levels of sdLDL-C, ApoA-I in α-1 HDL, and Lp(a) along with information about the patient's age and history of blood pressure treatment, smoking, and diabetes. Methods of the invention do not rely on standard risk factor measurements, such as CRP, total cholesterol, body mass index, weight, triglycerides, and the like.</p>
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OXAZOLIDINONE DERIVATIVES AS PPAR LIGANDS (Thu, 19 May 2016)
The present invention relates to a family of differently substituted oxazolidinones and to the pharmaceutically acceptable salts, esters, prodrugs, tautomers, solvates and hydrates thereof, which show affinity for the alpha and gamma subtypes of the peroxisome proliferator-activated receptors (PPAR) and which, therefore, modulate the actions regulated by said receptors, such as inducing satiety, controlling ingestion and modulating metabolic effects, and thus are useful for the administration thereof as a pharmacological tool and as drugs for the treatment and/or prevention of metabolic diseases and cardiovascular diseases.
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TRADITIONAL CHINESE MEDICINE COMPOSITION, AND PREPARATION AND APPLICATION THEREOF (Thu, 19 May 2016)
A traditional Chinese medicine composition for treating cardiovascular disease, and a preparation thereof, particularly a micro drop pill preparation thereof, and a method for preparing the preparation; the method for preparing the micro drop pill preparation can be used to prepare drop pills, coated drop pills, and drop pill capsules with a high drug loading capacity.
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TRADITIONAL CHINESE MEDICINE COMPOSITION, AND PREPARATION AND APPLICATION THEREOF (Thu, 19 May 2016)
A traditional Chinese medicine composition for treating cardiovascular disease, and a preparation thereof, particularly a micro drop pill preparation thereof, and a method for preparing the preparation; the method for preparing the micro drop pill preparation can be used to prepare drop pills, coated drop pills, and drop pill capsules with a high drug loading capacity.
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COMPOSITIONS AND METHODS FOR TREATMENT OF CARDIOVASCULAR DISEASE (Fri, 13 May 2016)
<p id="p-0001" num="0000">Provided herein are compositions for the treatment and/or prevention of cardiovascular disease (CVD), and methods of application and use thereof. In particular, the present invention provides treatment and/or prevention of cardiovascular disease with 3,3-dimethyl-1-butanol (DMB) and related compounds, and pharmaceutical formulations thereof.</p> <p id="p-0002" num="0000">In other embodiments, the present invention provides methods of administering a gut flora targeting antibiotic to a subject prior to a procedure that is associated with a risk of causing thrombosis, heart-attack, and/or platelet hyper-responsiveness.</p>
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Apoptosis signal-regulating kinase inhibitors (Fri, 13 May 2016)
<p id="p-0001" num="0000">The present invention relates to compounds of Formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.01mm" wi="66.80mm" file="US09586932-20170307-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein X<sup>1</sup>, X<sup>2</sup>, X<sup>3</sup>, X<sup>4</sup>, X<sup>5</sup>, X<sup>6</sup>, X<sup>7</sup>, X<sup>8</sup>, R<sup>1</sup>, R<sup>2</sup>, R<sup>3 </sup>are as defined above. The compounds have apoptosis signal-regulating kinase (“ASK1”) inhibitory activity, and are thus useful in the treatment of ASK1-mediated conditions, including autoimmune disorders, inflammatory diseases, cardiovascular diseases and neurodegenerative diseases. The invention also relates to pharmaceutical compositions comprising one or more of the compounds of Formula (I), and to methods of preparing the compounds of Formula (I). </p>
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1,3-DIAMINOCYCLOPENTANE CARBOXAMIDE DERIVATIVES (Fri, 13 May 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="24.55mm" wi="66.12mm" file="US20160130214A1-20160512-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">in which R<sup>1</sup>, R<sup>4</sup>, R<sup>6</sup>, R, X<sup>1</sup>, X<sup>2</sup>, X<sup>3</sup>, X<sup>4</sup>, q and W have the meanings indicated in claim <b>1, </b> <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>
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Fused heterocyclic compounds as sodium channel modulators (Fri, 13 May 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 Q, R , X , X2, Y and R2 are as described herein, to methods for the preparation and use of the compounds and to pharmaceutical compositions containing the same.
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SULFOXIMINE SUBSTITUTED 5-FLUORO-N-(PYRIDIN-2-YL)PYRIDIN-2-AMINE DERIVATIVES AND THEIR USE AS CDK9 KINASE INHIBITORS (Thu, 12 May 2016)
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).
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INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL (Sat, 07 May 2016)
The present invention provides compounds of Formula I and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.
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INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL (Sat, 07 May 2016)
The present invention provides compounds of Formula I and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.
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INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL (Sat, 07 May 2016)
The present invention provides compounds of Formula I : (I) and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.
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INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL (Sat, 07 May 2016)
The present invention provides compounds of Formula I and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.
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INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL (Sat, 07 May 2016)
The present invention provides compounds of Formula I and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.
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INHIBITORS OF RENAL OUTER MEDULLARY POTASSIUM CHANNEL (Sat, 07 May 2016)
Compounds of Formula (I) and the pharmaceutically acceptable salts thereof are provided as inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.
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INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL (Sat, 07 May 2016)
The present invention provides compounds of Formula I, and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.
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NUCLEOSIDE KINASE INHIBITORS (Sat, 07 May 2016)
The present invention relates to method of inhibiting protein kinase activity which comprises contacting a protein kinase with a compound of formula (I), or the N-oxide, pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or stereoisomer thereof, wherein the dash bond, X, R1, R2, R3, R4, R5, R6, R7, R8, and R9 are as defined in the claims. The invention further relates to the compounds of formula (I) per se, as well as to their use as a medicament, and for use or in a method of treatment of a disease mediated by a protein kinase selected from cancer, metabolic diseases, rheumatoid arthritis, psoriasis, inflammatory bowel disease, cardiovascular diseases, Vogt-Koyanagi-Harada syndrome (non-infectious blindness), and Alzheimer. The invention also provides a method for preparing the compounds of formula (I).
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PHTHALAZINE DERIVATIVES (Thu, 05 May 2016)
Compounds of the formula (I), in which R<sp>1</sp>, X and n have the meanings indicated in Claim 1, are inhibitors of Tankyrase, and can be employed, inter alia, for the treatment of diseases such as cancer, cardiovascular diseases, central nervous system injury and different forms of inflammation.
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N-substituted hydroxylamine derivatives with carbon-based leaving groups (Fri, 29 Apr 2016)
<p id="p-0001" num="0000">The disclosed subject matter provides certain N-substituted hydroxylamine derivative compounds, pharmaceutical compositions and kits comprising such compounds, and methods of using such compounds or pharmaceutical compositions. In particular, the disclosed subject matter provides methods of using such compounds or pharmaceutical compositions for treating, preventing, or delaying the onset and/or development of a disease or condition. In some embodiments, the disease or condition is selected from cardiovascular diseases, ischemia, reperfusion injury, cancerous disease, pulmonary hypertension and conditions responsive to nitroxyl therapy.</p>
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LIPOPROTEIN PARTICLE NUMBER FROM MEASUREMENTS OF LIPOPROTEIN PARTICLE PHOSPHOLIPID CONCENTRATION IN LIPOPROTEIN PARTICLE MEMBRANE BILAYER (Fri, 29 Apr 2016)
This application describes a method for measuring the molar concentrations of lipoprotein particles and lipoprotein subclass particles in bodily fluid by Multipixel Capillary Isotachophoresis Laser Induced Fluorescence (MPCE-ITP-LIF) and compositional analysis of spherical lipoprotein particles. The ability to measure several kinds of lipoproteins and particles in one unified system provides a useful diagnostic tool for predicting the risk of developing metabolic diseases such as cardiovascular disease and cardiodiabetes.
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NOVEL COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF INFLAMMATORY DISORDERS (Thu, 28 Apr 2016)
The present invention discloses compounds according to Formula I: Wherein R <sp>1a</sp>, R <sp>1b</sp>, R <sp>2</sp>, R <sp>4</sp>, R<sp>5</sp>, R <sp>6</sp>, R <sp>7</sp>, R <sp>8</sp>, W, X, Y, Z, Cy, and the subscript a are as defined herein. The present invention relates to compounds inhibiting autotaxin (NPP2 or ENPP2), methods for their production, pharmaceutical compositions comprising the same, and methods of treatment using the same, for the prophylaxis and/or treatment of diseases involving fibrotic diseases,proliferative diseases, inflammatory diseases, autoimmune diseases, respiratory diseases, cardiovascular diseases, neurodegenerative diseases, dermatological disorders, and/or abnormal angiogenesis associated diseases by administering the compound of the invention.
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1,3-DIAMINOCYCLOPENTANE CARBOXAMIDE DERIVATIVES (Thu, 28 Apr 2016)
Compounds of the formula I in which R<sp>1</sp>, R<sp>4</sp>, R<sp>6</sp>, R, X<sp>1</sp>, X<sp>2</sp>, X<sp>3</sp>, X<sp>4</sp>, q and W have the meanings indicated in Claim 1, are inhibitors of fatty acid synthase, and can be employed, inter alia, for the treatment of diseases such as cancer, cardiovascular diseases, central nervous system injury and different forms of inflammation.
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Preparation and Uses of Obeticholic Acid (Fri, 22 Apr 2016)
<p id="p-0001" num="0000">The present invention relates to obeticholic acid:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="36.83mm" wi="59.18mm" file="US20160108082A1-20160421-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or a pharmaceutically acceptable salt, solvate or amino acid conjugate thereof. Obeticholic acid is useful for the treatment or prevention of a FXR mediated disease or condition, cardiovascular disease or cholestatic liver disease, and for reducing HDL cholesterol, for lowering triglycerides in a mammal, or for inhibition of fibrosis. The present invention also relates to processes for the synthesis of obeticholic acid.</p>
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LIPOPROTEIN PARTICLE NUMBER FROM MEASUREMENTS OF LIPOPROTEIN PARTICLE PHOSPHOLIPID CONCENTRATION IN LIPOPROTEIN PARTICLE MEMBRANE BILAYER (Fri, 22 Apr 2016)
<p id="p-0001" num="0000">This application describes a method for measuring the molar concentrations of lipoprotein particles and lipoprotein subclass particles in bodily fluid by Multipixel Capillary Isotachophoresis Laser Induced Fluorescence (MPCE-ITP-LIF) and compositional analysis of spherical lipoprotein particles. The ability to measure several kinds of lipoproteins and particles in one unified system provides a useful diagnostic tool for predicting the risk of developing metabolic diseases such as cardiovascular disease and cardiodiabetes.</p>
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COMPOUNDS FOR THE PREVENTION AND TREATMENT OF CARDIOVASCULAR DISEASES (Fri, 22 Apr 2016)
<p id="p-0001" num="0000">The present disclosure relates to compounds, which are useful for regulating the expression of apolipoprotein A-I (ApoA-I), and their use for treatment and prevention of cardiovascular disease and related disease states, including cholesterol- or lipid-related disorders, such as, for example, atherosclerosis.</p>
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Cyclic polypeptides for the treatment of heart failure (Fri, 22 Apr 2016)
<p id="p-0001" num="0000">The invention provides a cyclic polypeptide of Formula I (SEQ ID NO: 1): <br/> <?in-line-formulae description="In-line Formulae" end="lead"?>X1-R-X3-X4-L-S-X7-X8-X9-X10-X11-X12-X13  I<?in-line-formulae description="In-line Formulae" end="tail"?> </p> <p id="p-0002" num="0000">or an amide, an ester or a salt thereof, or a bioconjugate thereof, wherein X1, X3, X4, X7, X8, X9, X10, X11, X12 and X13 are defined herein. The polypeptides are agonist of the APJ receptor. The invention also relates to a method for manufacturing the polypeptides of the invention or bioconjugates thereof, and their therapeutic uses such as treatment or prevention of acute decompensated heart failure (ADHF), chronic heart failure, pulmonary hypertension, atrial fibrillation, Brugada syndrome, ventricular tachycardia, atherosclerosis, hypertension, restenosis, ischemic cardiovascular diseases, cardiomyopathy, cardiac fibrosis, arrhythmia, water retention, diabetes (including gestational diabetes), obesity, peripheral arterial disease, cerebrovascular accidents, transient ischemic attacks, traumatic brain injuries, amyotrophic lateral sclerosis, burn injuries (including sunburn) and preeclampsia. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.</p>
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INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL (Fri, 22 Apr 2016)
The present invention provides compounds of Formula (I) and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.
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FLUORINATED BENZOFURANYL-PYRIMIDINE DERIVATIVES CONTAINING A SULFONE GROUP (Fri, 22 Apr 2016)
The present invention relates to fluorinated benzofuranyl-pyrimidine derivatives containing a sulfone group of general formula (I) as described and defined herein, and methods for their preparation, their use for the treatment and/or prophylaxis of disorders, in particular of hyper-proliferative disorders and/or virally induced infectious diseases and/or of cardiovascular diseases. The invention further relates to intermediate compounds useful in the preparation of said compounds of general formula (I). R2 represents the group (a).
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FLUORINATED BENZOFURANYL-PYRIMIDINE DERIVATIVES CONTAINING A SULFOXIMINE GROUP (Fri, 22 Apr 2016)
The present invention relates to fluorinated benzofuranyl-pyrimidine derivatives containing a sulfoximine group of general formula (I) as described and defined herein, and methods for their preparation, their use for the treatment and/or prophylaxis of disorders, in particular of hyper- proliferative disorders and/or virally induced infectious diseases and/or of cardiovascular diseases. The invention further relates to intermediate compounds useful in the preparation of said compounds of general formula (I).
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Amino, Amido and heterocyclic compounds as modulators of RAGE activity and uses thereof (Fri, 15 Apr 2016)
<p id="p-0001" num="0000">Amino, amido, and heterocyclic compounds are disclosed. The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, diabetes complications, inflammation, and neurodegeneration, obesity, cancer, ischemia/reperfusion injury, cardiovascular disease and other diseases related to RAGE activity.</p>
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SUBSTITUTED AMIDE COMPOUNDS (Fri, 15 Apr 2016)
The present invention is directed at substituted amide compounds of formula (I), pharmaceutical compositions containing such compounds and the use of such compounds to reduce plasma lipid levels, such as LDL-cholesterol and triglycerides and accordingly to treat diseases which are exacerbated by high levels of LDL-cholesterol and triglycerides, such as atherosclerosis and cardiovascular diseases, in mammals, including humans.(Formula I)
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Substituted phenylalanine derivatives (Fri, 15 Apr 2016)
The invention relates to substituted phenylalanine derivatives and to methods for the production thereof, in addition to the use of said derivatives for producing drugs for the treatment and/or prophylaxis of diseases, in particular cardiovascular diseases and/or perioperative heavy blood loss.
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Fused heterocyclic compounds as ion channel modulators (Fri, 08 Apr 2016)
<p id="p-0001" num="0000">The present disclosure relates to compounds that are sodium channel inhibitors and to their use in the treatment of various disease states, including cardiovascular diseases and diabetes. In particular embodiments, the structure of the compounds is given by Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="25.82mm" wi="69.93mm" file="US09598435-20170321-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>
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Treating and preventing disease with TMA and TMAO lowering agents (Fri, 01 Apr 2016)
<p id="p-0001" num="0000">Provided herein are compositions, systems, and methods for treating a disease, such as kidney and/or cardiovascular disease, with an agent that reduces the production of trimethylamine (TMA) or trimethylamine-n-oxide (TMAO) in a subject. In certain embodiments, the agent is: i) 3,3-dimethyl-1-butanol (DMB) or a DMB derivative or related compound, ii) acetylsalicylic acid or derivative thereof (e.g., with an enteric coating for delivery to the colon and/or cecum); iii) a flavin monooxygenase 3 (FMO3) inhibitor; iv) a gut TMA lyase inhibitor; v) an antibiotic or antimicrobial; vi) a probiotic or prebiotic; vii) an antiplatelet agent; or viii) a TMA and/or TMAO sequestering agent.</p>
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COMPOSITIONS AND METHODS FOR THE TREATMENT OF CARDIOVASCULAR DISEASES AND DIABETES (Fri, 01 Apr 2016)
The compositions and compounds of formula I which includes a salt of ranolazine or its polymorphs, enantiomers, stereoisomers, solvates, and hydrates thereof. These salts may be formulated as pharmaceutical compositions. The pharmaceutical compositions may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment of angina, angina pectoris, diabetes, hyperglycemia, elevated glucose levels, deep venous thrombosis, prevention of secondary venous thromboembolism and complications of atrial fibrillation such as stroke and additional risk factor for stroke.
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3-substituted cyclopentylamine derivatives (Fri, 01 Apr 2016)
Compounds of formula (I) in which R, W, R<sp>1</sp>, R<sp>4</sp>, X<sp>1</sp>, X<sp>2</sp>, X<sp>3</sp>, X<sp>4</sp> and q have the meanings indicated in Claim 1, are inhibitors of fatty acid synthase, and can be employed, inter alia, for the treatment of diseases such as cancer, cardiovascular diseases, central nervous system injury and different forms of inflammation.
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Substituted bridged urea analogs as sirtuin modulators (Fri, 25 Mar 2016)
<p id="p-0001" num="0000">Provided herein are novel substituted bridged urea and related analogs and methods of use thereof. The sirtuin-modulating compounds may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders including, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. Also provided are compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="44.03mm" wi="61.55mm" file="US09765075-20170919-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Processes for preparing medicaments for the treatment of cardiovascular diseases and intermediates for use therein (Fri, 25 Mar 2016)
The present invention provides a compound of formula N wherein: X is CH<sb>2</sb>, oxygen or sulphur; R<sb>1</sb>, R<sb>2</sb> and R<sb>3</sb> are the same or different and signify hydrogens, halogens, alkyl, alkyloxy, hydroxy, nitro, alkylcarbonylamino, alkylamino or dialkylamino group, wherein N is in the form of the individual R- and S-enantiomer or a mixture of the (R)- and (S)-enantiomer. The present invention also provides a compound of formula MA. The present invention also provides processes for preparing the above compounds, and processes involving their use. The compounds are particularly useful as intermediates in the synthesis of peripherally-selective inhibitors of dopamine-ß-hydroxylase.
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Preparation and Uses of Obeticholic Acid (Fri, 18 Mar 2016)
<p id="p-0001" num="0000">The present invention relates to obeticholic acid:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="36.75mm" wi="60.45mm" file="US20160074419A1-20160317-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or a pharmaceutically acceptable salt, solvate or amino acid conjugate thereof. Obeticholic acid is useful for the treatment or prevention of a FXR mediated disease or condition, cardiovascular disease or cholestatic liver disease, and for reducing HDL cholesterol, for lowering triglycerides in a mammal, or for inhibition of fibrosis. The present invention also relates to processes for the synthesis of obeticholic acid.</p>
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Piperidine urea derivatives (Fri, 18 Mar 2016)
Compounds of the formula I in which R<sp>1</sp>-R<sp>3</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.
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Fused heterocyclic compounds as selective BMP inhibitors (Fri, 11 Mar 2016)
<p id="p-0001" num="0000">The present invention provides small molecule inhibitors of BMP signaling. These compounds may be used to modulate cell growth, differentiation, proliferation, and apoptosis, and thus may be useful for treating diseases or conditions associated with BMP signaling, including inflammation, cardiovascular disease, hematological disease, cancer, and bone disorders, as well as for modulating cellular differentiation and/or proliferation.</p>
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Oxoquinazolinyl-butanamide derivatives (Fri, 11 Mar 2016)
Compounds of the formula I in which R<sp>1</sp>-R<sp>3</sp> and Z have the meanings indicated in Claim 1, are inhibitors of Tankyrase, and can be employed, inter alia, for the treatment of diseases such as cancer, cardiovascular diseases, central nervous system injury and different forms of inflammation.
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1,3-disubstituted cyclopentane derivatives (Fri, 11 Mar 2016)
Compounds of the formula (I) in which R, Y, R<sp>1</sp>, X<sp>1</sp>, X<sp>2</sp>, X<sp>3</sp> and q have the meanings indicated in Claim 1, are inhibitors of fatty acid synthase, and can be employed, inter alia, for the treatment of diseases such as cancer, cardiovascular diseases, central nervous system injury and different forms of inflammation.
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CYCLODEXTRIN-BASED POLYMERS FOR THERAPEUTIC DELIVERY (Fri, 04 Mar 2016)
<p id="p-0001" num="0000">Provided are methods relating to the use of CDP-therapeutic agent conjugates for the treatment of a disease or disorder, e.g., autoimmune disease, inflammatory disease, central nervous system disorder, cardiovascular disease, or metabolic disorder. Also provided are CDP-therapeutic agent conjugates, particles comprising CDP-therapeutic agent conjugates, and compositions comprising CDP-therapeutic agent conjugates.</p>
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SUBSTITUTED AMIDE COMPOUNDS (Fri, 04 Mar 2016)
<p id="p-0001" num="0000">The present invention is directed at substituted amide compounds, pharmaceutical compositions containing such compounds and the use of such compounds to reduce plasma lipid levels, such as LDL-cholesterol and triglycerides and accordingly to treat diseases which are exacerbated by high levels of LDL-cholesterol and triglycerides, such as atherosclerosis and cardiovascular diseases, in mammals, including humans.</p>
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MODULATION OF APOLIPOPROTEIN CIII (APOCIII) EXPRESSION (Fri, 04 Mar 2016)
<p id="p-0001" num="0000">Provided herein are methods, compounds, and compositions for reducing expression of ApoCIII mRNA and protein in an animal. Also provided herein are methods, compounds, and compositions for increasing HDL levels and/or improving the ratio of TG to HDL and reducing plasma lipids and plasma glucose in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate any one or more of cardiovascular disease or metabolic disorder, or a symptom thereof.</p>
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SOLUBLE EPOXIDE HYDROLASE INHIBITORS AND USES THEREOF (Fri, 04 Mar 2016)
The present invention features compounds having soluble epoxide hydrolase inhibitory activity. The compounds of the invention, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing various medical conditions, such as cardiovascular diseases, respiratory diseases, inflammation, and diabetes.
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Thiazolidinediones of omega-3 polyunsaturated acids as new insulin sensitizers for treating type2 diabetes (Fri, 26 Feb 2016)
<p id="p-0001" num="0000">The present invention relates to thiazolidinedione derivatives of omega-3 fatty acids as insulin sensitizers, and their use in treating Type2 diabetes, obesity, hypertriglyceridemia, cardiovascular diseases, metabolic diseases, inflammation, renal anemia, and/or Alzheimer's disease: and for modulating activity of peroxisome proliferator-activated receptors (PPARs).</p>
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Plant based formulation for the prevention and management of metabolic syndrome and cardiovascular disease mortality risk (Fri, 26 Feb 2016)
<p id="p-0001" num="0000">The invention relates to a plant based formulation for the prevention and management of Metabolic Syndrome and Cardiovascular disease mortality risk comprising an effective amount of a hydro-alcoholic extract of <i>Salacia parviflora, Tribulus terrestris </i>and <i>Dioscorea glabra. </i></p>
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Preparation, Uses And Solid Forms Of Obeticholic Acid (Fri, 26 Feb 2016)
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.
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DIPHENYL ETHER COMPOUNDS FOR THE TREATMENT OF LUNG DISORDERS (Thu, 25 Feb 2016)
Described herein are compounds of formula (I), their derivatives, analogs, tautomeric forms, stereoisomers, polymorphs, hydrates, solvates, pharmaceutically acceptable salts and compositions, metabolites and prodrugs thereof, for use in treating liver diseases such as non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), and other fibrotic diseases of the liver; diabetic complications such as macro (ischemic heart disease, cerebrovascular disease and peripheral vascular disease) and micro (cataract, retinopathy nephropathy neuropathy, maculopathy and glaucoma) vascular complication; and cardiovascular diseases such as atherosclerosis, restenosis, hypertension, vasospasm, and cardiac hypertrophy; and lung disorders and lung fibrosis.
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N-ACYLOXYSULFONAMIDE AND N-HYDROXY-N-ACYLSULFONAMIDE DERIVATIVES (Fri, 19 Feb 2016)
<p id="p-0001" num="0000">The invention provides certain N-acyloxysulfonamide and N-hydroxy-N-acylsulfonamide derivative compounds, pharmaceutical compositions and kits comprising such compounds, and methods of using such compounds or pharmaceutical compositions. In particular, the invention provides methods of using such compounds or pharmaceutical compositions for treating, preventing, or delaying the onset and/or develop of a disease or condition. In some embodiments, the disease or condition is selected from cardiovascular diseases, ischemia, reperfusion injury, cancerous disease, pulmonary hypertension and conditions responsive to nitroxyl therapy.</p>
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BMP inhibitors and methods of use thereof (Fri, 19 Feb 2016)
<p id="p-0001" num="0000">The present invention provides small molecule inhibitors of BMP signaling. These compounds may be used to modulate cell growth, differentiation, proliferation, and apoptosis, and thus may be useful for treating diseases or conditions associated with BMP signaling, including inflammation, cardiovascular disease, hematological disease, cancer, and bone disorders, as well as for modulating cellular differentiation and/or proliferation. These compounds may also be used to reduce circulating levels of ApoB-100 or LDL and treat or prevent acquired or congenital hypercholesterolemia or hyperlipoproteinemia; diseases, disorders, or syndromes associated with defects in lipid absorption or metabolism; or diseases, disorders, or syndromes caused by hyperlipidemia.</p>
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