Abstract: Small molecule disruptors of Beclin-1/Bc1-2 protein-protein interactions induce autophagy and hence are useful for treating a variety of indications where stimulation of autophagy is therapeutically useful, including cancer, infection immunity, neurodegeneration, longevity.

Abstract: Small molecule disruptors of Beclin-1/Bcl-2 protein-protein interactions induce autophagy and hence are useful for treating a variety of indications where stimulation of autophagy is therapeutically useful, including cancer, infection immunity, neurodegeneration, longevity.

Abstract: Disclosed herein is an efficient, environment friendly and commercially viable process for preparation of chloromethylated compound of formula I in substantially pure form and high yield, from the compound of formula II. The process includes contacting the compound of formula II with a chloromethylating agent generated in-situ by reaction of a formaldehyde precursor and hydrogen chloride, in a suitable solvent/contacting medium and in the presence of a catalytic amount of a short chain/low molecular weight carboxylic acid of formula III. I II III wherein, R1, R2, R3 and R4 are as defined in the description.

Abstract: The present invention relates to new tri(hetero)aryl pyrazoles, methods for their preparation, their use for treating and/or preventing diseases as well as their use in the preparation of drugs for treating and/or preventing diseases, in particular retroviral diseases in humans and/or animals.

Abstract: The present invention provides a compound of formula I: a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

Abstract: The present invention embodiments relate to compound of Formula I or pharmaceutically acceptable enantiomers, salts or solvates thereof. The invention further relates in certain embodiments to the use of the compounds of Formula I as TDO2 inhibitors. The invention also relates in certain embodiments to the use of the compounds of Formula I for the treatment and/or prevention of cancer, neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease and Huntington's disease, chronic viral infections such as HCV and HIV, depression, and obesity. The invention also relates in certain embodiments to a process for manufacturing compounds of Formula I.

Abstract: In one aspect, the invention relates to substituted 1-benzylindolin-2-one analog compounds, derivatives thereof, and related compounds, which are useful as positive allosteric modulators of the muscarinic acetylcholine receptor M1 (mAChR M1); synthesis methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Abstract: In one aspect, the invention relates to substituted 4-(1H-pyrazol-4-yl)benzyl analogs compounds, derivatives thereof, and related compounds, which are useful as positive allosteric modulators of the muscarinic acetylcholine receptor M1 (mAChR M1); synthesis methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Abstract: The invention relates to ROR modulators; compositions comprising an effective amount of a ROR modulator; and methods for treating or preventing diseases associated with ROR.

Abstract: Disclosed are novel calcium release-activated calcium (CRAC) channel inhibitors, methods for preparing them, pharmaceutical compositions containing them, and methods of treatment using them. The present disclosure also relates to methods for treating non-small cell lung cancer (NSCLC) with CRAC inhibitors, and to methods for identifying therapeutics for treating and of diagnosing cancer.

Abstract: Provided herein are compounds of the formula (I): 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 degenerative diseases and disorders.

Abstract: The present invention relates to compounds of the formula I, wherein A, D, E, G, R10, R11, R30, R40, R50 and R60 have the meanings indicated in the claims, which are valuable pharmaceutical active compounds. They are inhibitors of the protease cathepsin A, and are useful for the treatment of diseases such as atherosclerosis, heart failure, renal diseases, liver diseases or inflammatory diseases, for example. The invention furthermore relates to processes for the preparation of the compounds of the formula I, their use and pharmaceutical compositions comprising them.

Abstract: Provided herein are novel compounds, pharmaceutical compositions for use, inter alia, in methods of reducing Wnt-mediated effects and treating cancer.

Abstract: Invented are novel heterocyclic carboxamide compounds, the use of such compounds as inhibitors of protein kinase B activity and in the treatment of cancer and arthritis.

Abstract: The present invention relates to the identification of compounds and pharmaceutical compositions thereof for treating subjects with amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. The invention also provides methods of preparing the provided compounds.

Abstract: Provided herein are 3,5-diaminopyrazoles, for example, compounds of Formula IA, that are useful for modulating regulated-in-COPD kinase activity, and pharmaceutical compositions thereof. Also provided herein are methods of their use for treating, preventing, or ameliorating one or more symptoms of a RC kinase-mediated disorder, disease, or condition.

Abstract: Compounds are provided that act as potent antagonists of the CCR(9) receptor. Animal testing demonstrates that these compounds are useful for treating inflammation, a hallmark disease for CCR(9). The compounds are generally aryl sulfonamide derivatives and are useful in pharmaceutical compositions, methods for the treatment of CCR(9)-mediated diseases, and as controls in assays for the identification of CCR(9) antagonists.

Abstract: The present invention relates to a 6-pyrazolylamido-3-substituted azabicyclo[3.1.0]hexane derivatives useful as calcium channel blockers, pharmaceutically acceptable salts thereof and medical use of the calcium channel inhibiting effect of the compounds for treatment of diseases.

Abstract: The present invention provides isoindolinone and pyrrolopyridinone derivatives, as well as their compositions and methods of use, that inhibit the activity of the serine/threonine kinase, Akt, and are useful in the treatment of diseases related to the activity of Akt including, for example, cancer and other diseases.

Abstract: A compound of formula (I) useful for the treatment or prevention of hepatitis C viral infection, (Formula (I)) wherein: X1 and X2 are each independently CRB or N; RB is H, (C1-6)alkyl, (C1-6)haloalkyl, halo.

Abstract: The present invention relates to a 6-pyrazolylamido-3-substituted azabicyclo[3.1.0]hexane derivatives useful as calcium channel blockers, pharmaceutically acceptable salts thereof and medical use of the calcium channel inhibiting effect of the compounds for treatment of diseases.

Abstract: This invention concerns compounds of the general formula (1): and derivatives thereof, which are antagonists of 5-HT6 receptors, wherein the symbols have the meanings given in the description.

Abstract: Some embodiments include compositions and methods of using or identifying compounds that modulate the activity of the granulocyte colony-stimulating factor receptor (GCFR). Some embodiments include use of compounds to treat certain disorders, such as hematopoietic or neurological disorders.

Abstract: Novel dihydropyrazole derivatives of formula (I) wherein L, R, R3, R4, R5, R6, R7, X1, X2, X3, X4, Y, m and n have the meaning according to the claims, are positive allosteric modulators of the FSH receptor, and can be employed, inter alia, for the treatment of fertility disorders.

Abstract: The present invention relates to N-substituted aminobenzocycloheptene, aminotetraline, aminoindane and phenalkylamine derivatives of the formula (I), (II), (III) or (IV) or a physiologically tolerated salt thereof. The invention relates to pharmaceutical compositions comprising such N-substituted amino-benzocycloheptene, aminotetraline, aminoindane and phenalkylamine derivatives, and the use of such N-substituted aminobenzocycloheptene, aminotetraline, aminoindane and phenalkylamine derivatives for therapeutic purposes. The N-substituted aminobenzocycloheptene, aminotetraline, aminoindane and phenalkylamine derivatives are GlyT1 inhibitors.

Abstract: In one aspect, the invention relates to substituted 2-(4-heterocyclylbenzyl)isoindolin-1-one analogs compounds, derivatives thereof, and related compounds, which are useful as positive allosteric modulators of the muscarinic acetylcholine receptor M1 (mAChR M1); synthesis methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Abstract: Provided herein are compounds of the formula (I): 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 degenerative diseases and disorders.

Abstract: Disclosed is a compound represented by formula (1) or a pharmacologically acceptable salt thereof. (In the formula, R1 is optionally substituted heteroaryl etc.; R2 is hydrogen etc.; R3 and R4 are each independently hydrogen etc., R5 is the following group: (wherein Y is optionally substituted five membered heteroaryl etc., R9a is optionally substituted aryl etc., R9b and R9c are each dependently hydrogen etc., and m is the integral 0 etc.) etc.; R6 is hydrogen etc.; and R7 is hydrogen etc.

Abstract: This invention relates to 2-Aza-bicyclo[2.2.1]heptane-3-carboxylic acid (cyano-methyl)-amides of formula 1 and their use as inhibitors of Cathepsin C, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of diseases connected with dipeptidyl peptidase I activity, e.g. respiratory diseases.

Abstract: This invention relates to 2-Aza-bicyclo[2.2.1]heptane-3-carboxylic acid(benzyl-cyano-methyl)-amides of formula 1 and their use as inhibitors of Cathepsin C, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of diseases connected with dipeptidyl peptidase I activity, e.g. respiratory diseases.

Abstract: The present invention provides compounds having formula (I): and pharmaceutically acceptable derivatives thereof, wherein R1, R2 and B are as described generally and in classes and subclasses herein, and additionally provides pharmaceutical compositions thereof, and methods for the use thereof for the treatment of any of a number of conditions or diseases in which HGF/SF or the activities thereof, or agonists or antagonists thereof have a therapeutically useful role.

Abstract: The instant invention provides compounds of formula I which are JAK inhibitors, and as such are useful for the treatment of JAK-mediated diseases such as rheumatoid arthritis, asthma, COPD and cancer.

Abstract: Described herein are compounds of Formula (I), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5-mediated disorders are also described.

Abstract: The invention provides new pyridopyrazine compounds according to formula (I) which are highly selective as Ras-Raf-Mek-Erk signal transduction pathway inhibitors and in particular are highly selective Erk inhibitors.

Abstract: Novel dihydropyrazole derivatives of formula (I) wherein L, R, R3, R4, R5, R6, R7, X1, X2, X3, X4, Y, m and n have the meaning according to the claims, are positive allosteric modulators of the FSH receptor, and can be employed, inter alia, for the treatment of fertility disorders.

Abstract: Compounds corresponding to the general formula (I) wherein R2 represents a group C1-10-alkyl, C3-10-cycloalkyl, C3-7-cycloalkyl-C1-6-alkyl, C1-6-alkyl-C3-7-cycloalkyl, C3-7-cycloalkyl-C3-7-cycloalkyl, C1-6-alkylthio-C-1-10-alkyl, C1-6-alkoxy-C1-10-alkyl, hydroxy-C1-10-alkyl, hydroxy-C1-6-alkyl-C3-7-cycloalkyl-C1-6-alkyl, hydroxy-C3-10-cycloalkyl, C1-10-fluoroalkyl or C3-10-fluorocycloalkyl; an optionally substituted heterocyclic group; a group C1-10-alkyl substituted with an optionally substituted heterocyclic group; X6 represents a group chosen from hydrogen, fluorine, chlorine and bromine atoms or a group C1-6-alkyl, C3-7-cycloalkyl, C3-7-cycloalkyl-C1-6-alkyl, C1-6-fluoroalkyl or cyano; and R7 represents an aryl group such as phenyl or naphthyl, optionally substituted with one or more substituents, in the form of the base or of an acid-addition salt, and the therapeutic use thereof.

Abstract: In one aspect, the invention relates to substituted 4-(1H-pyrazol-4-yl)benzyl analogs compounds, derivatives thereof, and related compounds, which are useful as positive allosteric modulators of the muscarinic acetylcholine receptor M1 (mAChR M1); synthesis methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Abstract: Provided herein are compounds that inhibit or partially inhibit the activity of leucine rich repeat kinases. Also provided herein are methods of treatment of CNS disorders comprising administration of inhibitors of leucine rich repeat kinases.

Abstract: The invention provides a compound of Formula (Ie), pharmaceutically acceptable salts, or stereoisomers thereof wherein the variables are defined herein. The compounds of the invention are useful for treating immunological and oncological conditions.

Abstract: Disclosed are compounds and compositions of the formula I as described herein which are inhibitors of MMP-13. Also disclosed are methods of using and making compounds of the formula I.

Abstract: Compounds, methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds, and methods of using such compounds to treat, prevent or diagnose diseases, disorders, or conditions associated with one or more of the lysophosphatidic acid receptors are provided.

Abstract: In one aspect, the invention relates to substituted 1-benzylindolin-2-one analog compounds, derivatives thereof, and related compounds, which are useful as positive allosteric modulators of the muscarinic acetylcholine receptor M1 (mAChR M1); synthesis methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Abstract: Pyrazole compounds of formula (Ia) or (Ib) and pharmaceutically acceptable salts thereof, wherein Ra, Rb, Rc, Rd, Y1, Y2, Y3, Y4, Y5, Z, R1, R2, n and R3 have one of the meanings as indicated in the specification and claims, to their use as medicaments, to pharmaceutical formulations containing the compounds and to pharmaceutical formulations containing the compounds in combination with one or more active substances.

Abstract: The present invention relates to compounds of Formula (I), wherein X1, X2, X3, X4, R1, R2, R3, and Q are as defined herein, useful as N-type calcium channel blockers.

Abstract: The present invention is directed to compounds of formula I and 1a: which are tropomyosin-related kinase (Trk) family protein kinase inhibitors, and hence are useful in the treatment of pain, inflammation, cancer, restenosis, atherosclerosis, psoriasis, thrombosis, a disease, disorder, injury, or malfunction relating to dysmyelination or demyelination or a disease or disorder associated with abnormal activities of nerve growth factor (NGF) receptor TrkA.

Abstract: The present invention relates N-5-membered, fused, heteroaryl-methylene-N-cycloalkyl-carboxamide derivatives, their thiocarboxamide or N-substituted carboximidamide analogues, all of formula (I) wherein A represents a carbo-linked 5-membered heterocyclyl group; T represents O, S, N—Rc, N—ORd, N—NRcRd or N—CN; Z1 to Z3; W1 to W5; Y1 to Y3 and p represent various substituents; their process of preparation; their use as fungicide active agents, particularly in the form of fungicide compositions and methods for the control of phytopathogenic fungi, notably of plants, using these compounds or compositions.

Abstract: The present invention relates to pyrazole compounds of formula (I) and pharmaceutically acceptable salts thereof having CRTH2 antagonistic activity, wherein L, Y1, Y2, Y3, Y4, Y5, Z, R1, R2, R3 and n have one of the meanings as indicated in the specification and claims, to their use as medicaments, to pharmaceutical compositions containing said compounds and to pharmaceutical compositions containing said compounds in combination with one or more active substances.

Abstract: Imidazopyrazines of Formula I and pharmaceutically acceptable salts and mixtures thereof, are provided herein. Pharmaceutical compositions comprising at least one chemical entity and one or more pharmaceutically acceptable vehicle are also provided. Methods of treating patients suffering from certain diseases and disorders responsive to the inhibition of Syk activity, which comprises administering to such patients an amount of at least one chemical entity effective to reduce signs or symptoms of the disease or disorder are disclosed. These diseases include cancer (e.g., B-cell lymphoma and leukemia), autoimmune diseases, inflammatory diseases, acute inflammatory reactions, and allergic disorders. Methods of treatment include administering at least one chemical entity as a single active agent or administering at least one chemical entity in combination with one or more other therapeutic agents. Also provided are methods for determining the presence or absence of Syk kinase in a sample.

Abstract: This invention relates generally to stimulating neurogenesis (e.g., post-natal neurogenesis, e.g., post-natal hippocampal neurogenesis) and protection from neuron cell death.

Abstract: Provided is a novel therapeutic means for Alzheimer's disease. In particular, provided is a compound represented by the following general formula (I): [wherein Ar1 represents 2-methoxy-4-(2-pyridylmethoxy)phenyl etc. and Ar2 represents a 1H-indol-6-yl group etc.] or a salt thereof.