Abstract: The present invention relates to indoline-based compounds that inhibit Rho-associated protein kinase (ROCK) activity. In particular, the present invention relates to compounds, pharmaceutical compositions and methods of use, such as methods of inhibiting ROCK activity and methods for treating, for example cerebral cavernous malformation syndrome (CCM) and cardiovascular diseases using the compounds and pharmaceutical compositions of the present invention.

Abstract: The present disclosure relates generally to compositions and methods of treating neoplastic diseases or cancers, such as glioblastoma and non-Hodgkin's lymphomas, or other cancers in which the subject suffers from an advanced solid tumor, comprising a combination of, or administering a combination of, a bromodomain and extra-terminal protein (BET) inhibitor and at least one chemotherapeutic agent, which does not inhibit BET directly. The BET inhibitor/chemotherapeutic agent combination, or combination therapy, can yield synergistic effects, thereby increasing the effectiveness of the cancer treatment as compared with the administration of either the BET inhibitor or the chemotherapeutic agent alone.

Abstract: Disclosed is a compound as shown in formula (I), an optical isomer thereof or a pharmaceutically acceptable salt thereof, and the present invention relates to the use of same in the preparation of a drug for treating FXR-related diseases.

Abstract: The present invention relates to indoline-based compounds that inhibit Rho-associated protein kinase (ROCK) activity. In particular, the present invention relates to compounds, pharmaceutical compositions and methods of use, such as methods of inhibiting ROCK activity and methods for treating, for example cerebral cavernous malformation syndrome (CCM) and cardiovascular diseases using the compounds and pharmaceutical compositions of the present invention.

Abstract: Novel bromodomain and extraterminal domain (BET) inhibitors contanining substituted 2-pyridones and therapeutic methods of treating conditions and diseases using these novel BET inhibitors are provided.

Abstract: The present invention relates to substituted heterocyclic derivative compounds, compositions comprising said compounds, and the use of said compounds and compositions for epigenetic regulation by inhibition of bromodomain-mediated recognition of acetyl lysine regions of proteins, such as histones. Said compositions and methods are useful for the treatment of cancer and neoplastic disease.

Abstract: The invention describes phospho-amino pincer-type ligands, metal complexes thereof, and catalytic methods comprising such metal complexes for conversion of carbon dioxide to methanol, conversion of aldehydes into alcohols, conversion of aldehydes in the presence of a trifluoromethylation agent into trifluorinated secondary alcohols, cycloaddition of carbon dioxide to an epoxide to provide cyclic carbonates or preparation of an amide from the combination of an alcohol and an amine.

Abstract: Provided herein are compounds of formula I: wherein the variables are defined herein, processes of making them, and methods of treating cancer comprising administering such compounds.

Abstract: Described herein is the bromodomain inhibitor 4-[2-(cyclopropylmethoxy)-5-methylsulfonylphenyl]-2-methylisoquinolin-1-one, including crystalline forms, amorphous forms, solvates, and hydrates thereof, as well as pharmaceutical compositions that include this bromodomain inhibitor. In some embodiments, the pharmaceutical composition comprises 4-[2-(cyclopropylmethoxy)-5-methylsulfonylphenyl]-2-methylisoquinolin-1-one that has been processed by micronization or spray dried dispersion. In some embodiments, the pharmaceutical composition further comprises at least one polymer. In some embodiments, the pharmaceutical composition comprises a solid polymer matrix comprising 4-[2-(cyclopropylmethoxy)-5-methylsulfonylphenyl]-2-methylisoquinolin-1-one and at least one polymer. Pharmaceutical compositions comprising 4-[2-(cyclopropylmethoxy)-5-methylsulfonylphenyl]-2-methylisoquinolin-1-one are useful for the treatment of cancer or neoplastic disease.

Abstract: Disclosed herein are compounds of Formula (I), methods of synthesizing compounds of Formula (I), and methods of using compounds of Formula (I) as an analgesic.

Abstract: The present disclosure relates generally to compositions and methods of treating neoplastic diseases or cancers, such as glioblastoma and non-Hodgkin's lymphomas, or other cancers in which the subject suffers from an advanced solid tumor, comprising a combination of, or administering a combination of, a bromodomain and extra-terminal protein (BET) inhibitor and at least one chemotherapeutic agent, which does not inhibit BET directly. The BET inhibitor/chemotherapeutic agent combination, or combination therapy, can yield synergistic effects, thereby increasing the effectiveness of the cancer treatment as compared with the administration of either the BET inhibitor or the chemotherapeutic agent alone.

Abstract: The present disclosure relates to compound (I) wherein R1 and R2 independently represent a hydrogen atom, a (C1-C4)alkoxy group, a fluoro(C1-C4)alkoxy group, a hydroxyl group, a benzyloxy group, a di(C1-C4)alkylamino group, a pyridyl-vinyl group, a pyrimidinyl-vinyl group, a styryl group, or a —NHCOphenyl group; R3, R4 and R5 independently represent a hydrogen atom, a (C1-C4)alkyl group, a CONHR6 group, a —CONR7R8 group, a —SO2NHR6 group, or a heteroaryl group optionally substituted by a halogen atom, a —(CH2)nNR7R8 group or a hydroxy(C1-C4)alkyl group; R6 represents a hydrogen atom, a —(CHR9)m(CH2)nNR7R8 group or a (C1-C6)alkyl group optionally substituted by a hydroxyl group; or anyone of its pharmaceutically acceptable salt, for use in a method for preventing, inhibiting or treating a disease in a patient suffering thereof, said disease involving a deregulated p53. Some of said compounds are new and also form part of the disclosure.

Abstract: The present disclosure relates to substituted heterocyclic derivative therapeutic compounds, compositions comprising said compounds, and the use of said compounds and compositions for epigenetic regulation by inhibition of bromodomain-mediated recognition of acetyl lysine regions of proteins, such as histones. Said compositions and methods are useful for the treatment of diseases mediated by aberrant cell signalling, such as inflammatory disorders, cancer and neoplastic disease.

Abstract: The present disclosure relates generally to compositions and methods of treating neoplastic diseases or cancers, such as glioblastoma and non-Hodgkin's lymphomas, or other cancers in which the subject suffers from an advanced solid tumor, comprising a combination of, or administering a combination of, a bromodomain and extra-terminal protein (BET) inhibitor and at least one chemotherapeutic agent, which does not inhibit BET directly. The BET inhibitor/chemotherapeutic agent combination, or combination therapy, can yield synergistic effects, thereby increasing the effectiveness of the cancer treatment as compared with the administration of either the BET inhibitor or the chemotherapeutic agent alone.

Abstract: The present invention relates to substituted heterocyclic derivative compounds, compositions comprising said compounds, and the use of said compounds and compositions for epigenetic regulation by inhibition of bromodomain-mediated recognition of acetyl lysine regions of proteins, such as histones. Said compositions and methods are useful for the treatment of cancer and neoplastic disease.

Abstract: The present invention relates to novel compounds, pharmaceutical compositions containing such compounds and to their use in therapy.

Abstract: A method of reacting amine compounds with halons and perhalogenated compounds, resulting in the conversion of these ozone-depleting species into non-volatile salts and a variety of other amine derivatives is disclosed.

Abstract: The present invention provides methods of treating cognitive deficits associated with mental retardation. The methods comprise combining cognitive training protocols and a general administration of phosphodiesterase 4 inhibitors.

Abstract: The present disclosure relates to crystalline solid forms of [(4-hydroxy-1-methyl-7-phenoxy-isoquinoline-3-carbonyl)-amino]-acetic acid, the process of preparing the forms, and pharmaceutical compositions and methods of use thereof.

Abstract: The present invention relates to identification of a compound which inhibits the enzyme NMPRTase and glioma cancer cell growth and further used for glioma therapy. Pre-B-cell colony enhancing factor 1 gene (PBEF1) encodes nicotinamide phosphoribosyltransferase (NMPRTase), which catalyzes the rate limiting step in the salvage pathway of NAD metabolism in mammalian cells. PBEF1 transcript and protein levels have been shown to be elevated in glioblastoma and a chemical inhibitor of NMPRTase has been shown to specifically inhibit cancer cells. Here a structure based drug discovery approach has been reported with an aim to develop novel inhibitors for glioblastoma therapy. Present invention relates to virtual screening using docking of ligands from a large library of 13,000 compounds against NMPRTase as the macromolecular target resulting in short listing of 34 possible ligands, of which six were tested experimentally, using the NMPRTase enzyme inhibition assay and further with the glioma cell viability assays.

Abstract: Substituted isoquinolinone compounds and pharmaceutical compositions that modulate kinase activity, including PI3 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including PI3 kinase activity, are described herein.

Abstract: The present disclosure relates to crystalline solid forms of [(4-hydroxy-1-methyl-7-phenoxy-isoquinoline-3-carbonyl)-amino]-acetic acid, the process of preparing the forms, and pharmaceutical compositions and methods of use thereof.

Abstract: Compounds represented by the formulas wherein each symbol is as defined in the specification, and a prodrug thereof have a superior renin inhibitory activity, and are useful as agents for the prophylaxis or treatment of hypertension, various organ damages attributable to hypertension and the like.

Abstract: The present invention relates to phenalkylamine derivatives of the formula (I) or (II) or a physiologically tolerated salt thereof. The invention relates to pharmaceutical compositions comprising such phenalkylamine derivatives, and the use of such phenalkylamine derivatives for therapeutic purposes. The phenalkylamine derivatives are GlyT1 inhibitors.

Abstract: This invention relates to compounds of general formula (I) in which R1, R2, U, V, L, M, R5, m, X, Y and Z are as defined herein, and the pharmaceutically acceptable salts thereof, to pharmaceutical compositions comprising such compounds and salts, and to methods of using such compounds, salts and compositions for the treatment of abnormal cell growth, including cancer.

Abstract: Chemical compounds are provided which act on GPR17 receptors and are useful in the treatment or amelioration of chronic and/or acute neurodegenerative diseases, such as multiple sclerosis, inflammatory diseases, pathologies involving the immune system, cardiovascular diseases, and renal diseases.

Abstract: Compounds which directly inhibit IRE-1? activity in vitro, prodrugs, and pharmaceutically acceptable salts thereof. Such compounds and prodrugs are useful for treating diseases associated with the unfolded protein response or with regulated IRE1-dependent decay (RIDD) and can be used as single agents or in combination therapies.

Abstract: The present invention relates to substituted heterocyclic derivative compounds, compositions comprising said compounds, and the use of said compounds and compositions for epigenetic regulation by inhibition of bromodomain-mediated recognition of acetyl lysine regions of proteins, such as histones. Said compositions and methods are useful for the treatment of cancer and neoplastic disease.

Abstract: The invention provides bicyclic sulfone compounds, pharmaceutical compositions, methods of inhibiting RORy activity, reducing the amount of iL-17 in a subject, and treating immune disorders and inflammatory disorders using such bicyclic sulfone compounds. Another aspect of the invention provides a method of treating a subject suffering from a medical disorder. The method comprises administering to the subject a therapeutically effective amount of one or more bicyclic sulfone compounds described herein. In certain other embodiments, the disorder is rheumatoid arthritis.

Abstract: The present invention relates to substituted heterocyclic derivative compounds, compositions comprising said compounds, and the use of said compounds and compositions for epigenetic regulation by inhibition of bromodomain-mediated recognition of acetyl lysine regions of proteins, such as histones. Said compositions and methods are useful for the treatment of cancer and neoplastic disease.

Abstract: Chronic myelogenous leukemia (CML), and in particular imatinib resistant CML is treated using compositions and methods in which a Rad51-inhibitor and a kinase inhibitor are administered. Most preferably, the Rad51 inhibitor comprises an indolyl isoquinoline structure and the kinase inhibitor is a BCR-ABL inhibitor.

Abstract: Compounds and pharmaceutical compositions that modulate kinase activity, including PI3 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including PI3 kinase activity, are described herein.

Abstract: The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain 3-aryl-5-substituted-2H-isoquinolin-1-one compounds that, inter alia, inhibit PARP (e.g., PARP1, TNKS1, TNKS2, etc.) and/or Wnt signalling. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit PARP (e.g., PARP1, TNKS1, TNKS2, etc.); to inhibit Wnt signalling; to treat disorders that are ameliorated by the inhibition of PARP (e.g., PARP1, TNKS1, TNKS2, etc.); to treat disorders that are ameliorated by the inhibition of Wnt signalling; to treat proliferative conditions such as cancer, etc.

Abstract: This invention provides a compound of formula A The compound provided herein can affect the opening of, or otherwise modulate, voltage-gated potassium channels. The compound provided herein is useful for the treatment and prevention of diseases and disorders which are affected by activation or modulation of potassium ion channels. One such condition is seizure disorders.

Abstract: There are provided substituted isoquinolin-1(2H)-one derivatives which selectively inhibit the activity of poly (ADP-ribose) polymerase PARP-1 with respect to poly (ADP-ribose) polymerase PARP-2. The compounds of the present invention are therefore useful in treating diseases such as cancer, cardiovascular diseases, central nervous system injury and different forms of inflammation. The present invention also provides methods for preparing these compounds, pharmaceutical compositions comprising these compounds, and methods of treating diseases utilizing pharmaceutical compositions comprising these compounds. A screening method for the identification of compounds capable of binding several PARP proteins, as well the probes used in such method, are further objects of the invention.

Abstract: The present invention relates to compounds which are inhibitors of microsomal triglyceride transfer protein and/or apolipoprotein B (Apo B) secretion. These compounds can be useful for the prevention and treatment of various diseases, particularly atherosclerosis and its clinical sequelae, for lowering serum lipids, and related ailments. The invention further relates to pharmaceutical compositions comprising the compounds and to methods of treating diseases, such as hypertriglyceridemia, hyperchylomicronemia, atherosclerosis, obesity, and related conditions using the compounds. A method for decreasing apolipoprotein B (apo B) secretion is also provided.

Abstract: 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.

Abstract: This present invention discloses a heterocyclic substituted acardite derivate and application thereof, namely compounds in the general formula (1) or the general formula (2) or pharmaceutically acceptable salts thereof, wherein A is monosubstituted or polysubstituted quinoline, isoquinoline, quinazoline, pyrrole or pyrimidine, and the substituent is halogen, C1-5alkyl, C1-5haloalkyl, C1-5alkoxy, C1-5haloalkoxy, C1-5alkylamino, C1-5haloalkylamino, amino or nitryl; R1 is C1-5alkyl; R2 is one or more selected from hydrogen, halogen, alkyl, alkoxy, haloalkyl or haloalkoxy; and R3 is one or more selected from hydrogen, halogen, alkyl, alkoxy, haloalkyl or haloalkoxy. The compound of the present invention and the pharmaceutically acceptable salt thereof can be used for treating tumor or leukemia.

Abstract: The present disclosure relates to crystalline solid forms of [(4-hydroxy-1-methyl-7-phenoxy-isoquinoline-3-carbonyl)-amino]-acetic acid, the process of preparing the forms, and pharmaceutical compositions and methods of use thereof.

Abstract: The present invention relates to novel compounds of formula (I), and compositions capable of inhibiting PHD1 enzyme activity selectively over other isoforms, for example, PHD2 and/or PHD3 enzymes. The invention also relates to compounds of formula (I) for use in disorders such as muscle degeneration, colitis, IBD, and certain ischemias.

Abstract: The present invention provides compounds of Formula (I), or a pharmaceutically acceptable salt thereof, where R1, R2, R3, R4, R5, R6, A and n are as defined herein. A deuteriated derivative of the compound of Formula (I) is also provided.

Abstract: The present invention relates to cyanoisoquinoline compounds suitable for use in treating hypoxia inducible factor-mediated and/or erythropoietin-associated conditions.

Abstract: The present invention relates to the polymorphic forms of the compound of Formula (I), preparation thereof including the preparation of intermediates and pharmaceutical compositions, and use of a polymorph above in the treatment of a disease, a disorder or a condition, or in the manufacturing of a medicament for the treatment of a disease, a disorder or a condition.

Abstract: Compounds and pharmaceutical compositions that modulate kinase activity, including PI3 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including PI3 kinase activity, are described herein.

Abstract: The present disclosure is generally directed to antiviral compounds, and more specifically directed to combinations of compounds which can inhibit the function of the NS5A protein encoded by Hepatitis C virus (HCV), compositions comprising such combinations, and methods for inhibiting the function of the NS5A protein.

Abstract: The present invention provides compounds of Formula I, or pharmaceutically acceptable salts thereof, that are inhibitors of voltage-gated sodium channels, in particular Nav 1.7. The compounds are useful for the treatment of diseases treatable by inhibition of sodium channels such as pain disorders. Also provided are pharmaceutical compositions containing compounds of the present invention.

Abstract: The present invention provides a method for treatment of high cholesterol by reducing low density lipoprotein cholesterol (LDL-C) and/or very low density Opoproiein cholesterol (VLDL-C) in subjects In need thereof by administering a compound that inhibits HIF hydroxylase activity. The method is useful, for reducing LDL cholesterol levels and total cholesterol levels even In subjects already undergoing treatment with other cholesterol-lowering medications, for example statins, fibrates, nicotinic acids and bile acid-binding resins, and in patients having chronic kidney disease or end stage renal disease, inter alia.

Abstract: The invention provides a compound of formula (I): or a salt or prodrug thereof, wherein R1, R4-R8, R10, R2?-R6?, W, and A have any of the values described in the specification, as well as compositions comprising a compound of formula (I). The compounds are useful as antibacterial agents.

Abstract: The present invention is related to a compound of formula (I), wherein A is a nonaromatic heterocyclic ring, Ar is either absent or phenylene; ? is a radical of formula (II), R2 is a hydrophobic moiety; and G is a radical containing one or more moieties selected from the group consisting of NH, OH and a basic moiety. The compounds are inhibitors of integrins, especially antagonists of the fibronectin receptor alpha5beta1, useful as anti-angiogenic agents.

Abstract: The present invention relates to the use of an agent that inhibits the activity of an enzyme that mediates repair of a DNA strand break in the manufacture of a medicament for the treatment of diseases caused by a defect in a gene that mediates homologous recombination.