Abstract: The present disclosure relates to novel compounds, pharmaceutical compositions containing such compounds, and their use in prevention and treatment of cancer and related diseases and conditions.

Abstract: The present disclosure provides compounds represented by Formula I-A: A1-L1-B1 I-A and the pharmaceutically acceptable salts, hydrates, and solvates thereof, wherein A1, B1, and L1 are as defined as set forth in the specification. The present disclosure also provides compounds of Formula I-A for use to treat a condition or disorder responsive to degradation of MDM2 protein such as cancer.

Abstract: Compounds of formula (1a) and pharmaceutically acceptable salts, solvates, and hydrates thereof and related methods of modulatin perforin activity on a cell: wherein Ring A is selected from a 6-10 membered aryl, 5-6 membered cycloalkyi, 5-6 membered heteroaryl or 5-6 membered heterocyclyl, wherein the heteroaryl and heterocyclyl rings comprise at least one heteroatom selected from N, O or S; and wherein the aryl, cycloalkyi, heteroaryl or heterocyclyl rings are optionally substituted with 1 to 3 substituents selected from halo, nitro, —C1-Cealkyl, —C1-Ceaminoalkyl, —C1-C6hydroxyalkyl, -haloC1-C6alkyl, —C1-C6alkoxyl, -haloC1—C<aIkoxyl, heteroaryl, aryl, hydroxyl, —C(0)Ci-C6alkyl, —OC(0)Ci-C6alkyl, —CH2OC(O)CrC6alkyl, —C(O)OC1, —C6alkyI, —NHC(O)C1, —C6alkyl, —NHS(O)2C1-C6alkyl, —S(O)2C1-C6alkyl, —S(O)2NH2, and —C(O)NJJ; Ring B is a 6-10 membered arylene or a 5-6 membered heteroarylene comprising at least one heteroatom selected from N, 0 or S; and wherein the aryl or heteroaryl is optionally, substituted wit

Abstract: The present invention relates to compounds of formula (I): in which Y, Y, R, R 2, R 3 and R 4 are defined in the Summary of the Invention; capable of inhibiting the tyrosine kinase enzymatic activity of the Abelson protein (ABL1), the Abelson-related protein (ABL2) and related chimeric proteins, in particular BCR-ABL1. The invention further provides a process for the preparation of compounds of the invention, pharmaceutical preparations comprising such compounds and methods of using such compounds in the treatment of cancers.

Abstract: The present invention provides for compounds of formula (I) wherein A, Y, J, R1, R2, and R3 have any of the values defined therefor in the specification, and pharmaceutically acceptable salts thereof,that are useful as agents in the treatment of diseases and conditions, including inflammatory diseases, diabetes, obesity, cancer, and AIDS. Also provided are pharmaceutical compositions comprising one or more compounds of formula (I).

Abstract: The present invention relates to bicyclic himbacine derivatives of the formula or a pharmaceutically acceptable salt thereof, wherein: X is —O—, —N(R), —C(R8)(R9) or —C(O)—; and Y is —O—, —N(R), —C(R8)(R9) or —C(O)— and the remaining variables are described herein. The compounds of the invention are effective inhibitors of the PAR-1 receptor. The inventive compounds may be used for the treatment or prophylaxis of disease states such as ACS, secondary prevention of myocardial infarction or stroke, or PAD.

Abstract: The present application relates to the use of one or more compounds of Formula (I) or pharmaceutically acceptable solvates or prodrugs thereof, for treating cancer or for treating or preventing a viral infection.

Abstract: Compounds of the present invention and pharmaceutically acceptable compositions thereof, are useful as modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator (“CFTR”). The present invention also relates to methods of treating ABC transporter mediated diseases using compounds of the present invention.

Abstract: The present invention is directed to compounds of formula I and pharmaceutically acceptable salts, esters, and prodrugs thereof which are inhibitors of Syk kinase. The present invention is also directed to intermediates used in making such compounds, the preparation of such a compound, pharmaceutical compositions containing such a compound, methods of inhibition Syk kinase activity, methods of inhibition the platelet aggregation, and methods to prevent or treat a number of conditions mediated at least in part by Syk kinase activity, such as Non Hodgkin's Lymphoma.

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: 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 present invention relates to compounds of Formula (I), methods for preparing these compounds, compositions, intermediates and derivatives thereof and for treating glucokinase mediated disorders. More particularly, the compounds of the present invention are glucokinase modulators useful for treating disorders including, but not limited to, type II diabetes.

Abstract: The present invention relates to novel vanilloid receptor ligands, to a process for the production thereof, to pharmaceutical preparations containing these compounds and to the use of these compounds for the production of pharmaceutical preparations.

Abstract: Disclosed are compounds, compositions and methods for treating various diseases, syndromes, conditions and disorders, including pain. Such compounds are represented by Formula (I) as follows: wherein Q and Z are defined herein.

Abstract: The present invention relates generally to affinity ligands and chemical affinity ligand-matrix conjugates for use as chromatographic adsorbents and methods which utilize the adsorbents in the purification of proteins by affinity chromatography. The affinity ligand-matrix conjugates of the present invention comprise ligands of general formula (I): wherein m represents an integer from 0-2, n represents an integer from 0-6, p represents an integer from 0-4, R1 represents H or C1-3 alkyl, R2 is an optional substituent, and X is the position at which the ligand is immobilized, optionally via a linker.

Abstract: The present invention relates to heterocyclic compounds in all their stereoisomeric and tautomeric forms; and their pharmaceutically acceptable salts, pharmaceutically acceptable solvates and pharmaceutically acceptable polymorphs. The invention also relates to processes for the manufacture of the heterocyclic compounds and to pharmaceutical compositions containing them. The compounds and their pharmaceutical compositions are useful in the prevention and treatment of diseases or disorders mediated by diacylglycerol acyltransferase (DGAT), particularly DGAT1. The present invention further provides a method of treatment of such diseases or disorders by administering a therapeutically effective amount of the compounds or their pharmaceutical compositions, to a mammal in need thereof.

Abstract: Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein Q is a bond or —N(R5)—; T is a bond, —O—, —C(O)—; S, —N(R5)—, or —C(R6?R7?); U is a bond or —C(R6)(R7)— Y is C or N; Z is C or N; ring A, including variables Y and Z, is a three to nine membered cycloalkyl, cycloalkenyl, heterocyclyl, heterocyclenyl, aryl, and heteroaryl ring having 0 to 4, preferably 0 to 2, heteroatoms independently selected from the group consisting of O, S, N and —N(R)—, wherein ring A is unsubstituted or substituted with 1 to 5 independently selected R1 moieties and/or oxo when ring A is cycloalkyl, cycloalkenyl, heterocyclyl or heterocyclenyl; and R, R1, R2, R3, R4, R5, R6, R6, R7 and R7? are as defined in the specification; pharmaceutical compositions comprising the compounds of formula I and the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases.

Abstract: The present invention relates to small molecule potentiators of metabotropic receptors, in particular of the mGlu2 receptor. The present invention also relates to the use of these compounds for the prevention or treatment of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which metabotropic glutamate receptors are involved. The present invention thus provides compounds of formula I and variables defined herein.

Abstract: The present invention relates to compounds useful as inhibitors of PI3K, particularly of PI3K?. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders.

Abstract: Novel conjugates and immunogens derived from lenalidomide and antibodies generated by these immunogens are useful in immunoassays for the quantification and monitoring of thalidomide and lenalidomide in biological fluids.

Abstract: Compounds of the present invention and pharmaceutically acceptable compositions thereof, are useful as modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator (“CFTR”). The present invention also relates to methods of treating ABC transporter mediated diseases using compounds of the present invention.

Abstract: The invention relates to aryl-substituted polycyclic amines of formula I, especially bicyclic amines, and to the physiologically tolerated salts and physiologically functional derivatives thereof; where the symbols and radicals are explained in the description, as well as to pharmaceutical compositions containing them and to methods of treatment using them.

Abstract: The present invention relates to ?-hydroxy and amino-substituted carboxylic acids, which act as matrix metalloproteinase inhibitors, particularly diastereomerically pure ?-hydroxy carboxylic acids, corresponding processes for their synthesis, and pharmaceutical compositions containing the compounds of the present invention. Compounds of the present invention are useful in the treatment of various inflammatory, autoimmune, and allergic diseases, such as methods of treating asthma, rheumatoid arthritis, COPD, rhinitis, osteoarthritis, psoriatic arthritis, psoriasis, pulmonary fibrosis, wound healing disorders, pulmonary inflammation, acute respiratory distress syndrome, perodontitis, multiple sclerosis, gingivitis, atherosclerosis, neointimal proliferation, which leads to restenosis and ischemic heart failure, stroke, renal diseases, tumor metastasis, and other inflammatory disorders characterized by the over-expression and over-activation of a matrix metalloproteinase.

Abstract: The present invention relates to ?-hydroxy and amino-substituted carboxylic acids, which act as matrix metalloproteinase inhibitors, particularly diastereomerically pure ?-hydroxy carboxylic acids, corresponding processes for their synthesis, and pharmaceutical compositions containing the compounds of the present invention. Compounds of the present invention are useful in the treatment of various inflammatory, autoimmune, and allergic diseases, such as methods of treating asthma, rheumatoid arthritis, COPD, rhinitis, osteoarthritis, psoriatic arthritis, psoriasis, pulmonary fibrosis, wound healing disorders, pulmonary inflammation, acute respiratory distress syndrome, perodontitis, multiple sclerosis, gingivitis, atherosclerosis, neointimal proliferation, which leads to restenosis and ischemic heart failure, stroke, renal diseases, tumor metastasis, and other inflammatory disorders characterized by the over-expression and over-activation of a matrix metalloproteinase.

Abstract: The present invention provides for compounds of formula (I) wherein A, Y, J, R1, R2, and R3 have any of the values defined therefor in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of diseases and conditions, including inflammatory diseases, diabetes, obesity, cancer, and AIDS. Also provided are pharmaceutical compositions comprising one or more compounds of formula I.

Abstract: The invention relates to enantiomerically pure 3-(phthalimido)piperidines and processes for preparing enantiomerically pure 3-(phthalimido)piperidines.

Abstract: The present invention relates to compound of formula (I): or pharmaceutically acceptable salts thereof, wherein R1-R7, A and HET are as defined herein. The invention also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.

Abstract: The invention provides novel compounds having the general formula (I) wherein R1, R2, R3, R4, R5, R6, A1, A2, A3, A4, A5 and n are as described herein, compositions including the compounds and methods of using the compounds. The compounds are useful, for example, as aldosterone synthase (CYP11B2 or CYP11B1) inhibitors for the treatment or prophylaxis of chronic kidney disease, congestive heart failure, hypertension, primary aldosteronism and Cushing syndrome.

Abstract: The present invention relates to the crystal structure of the serine protease kallikrein 7 and to the use of this crystal structure in drug discovery. The present invention also relates to compounds binding specifically to this active site of kallikrein 7.

Abstract: The present application provides compounds, including all stereoisomers, solvates, prodrugs and pharmaceutically acceptable forms thereof according to Formula I wherein R1, R4, R5, R3, R3a, W, D, R2a, R2b and R2c are defined herein. Additionally, the present application provides pharmaceutical compositions containing at least one compound according to Formula I and optionally at least one additional therapeutic agent. Finally, the present application provides methods for treating a patient suffering from an MCHR-1 modulated disease or disorder such as, for example, obesity, diabetes, depression, anxiety or intestinal inflammation, by administration of a therapeutically effective dose of a compound according to Formula I.

Abstract: The present invention relates to new kinase inhibitors, more specifically ROCK inhibitors, compositions, in particular pharmaceuticals, comprising such inhibitors, and to uses of such inhibitors in the treatment and prophylaxis of disease. In particular, the present invention relates to new ROCK inhibitors, compositions, in particular pharmaceuticals, comprising such inhibitors, and to uses of such inhibitors in the treatment and prophylaxis of disease. In addition, the invention relates to methods of treatment and use of said compounds in the manufacture of a medicament for the application to a number of therapeutic indications including sexual dysfunction, inflammatory diseases, ophthalmic diseases and Respiratory diseases.

Abstract: Glucagon receptor antagonist compounds are disclosed. The compounds are useful for treating type 2 diabetes and related conditions. Pharmaceutical compositions and methods of treatment are also included.

Abstract: The present invention relates to heterocyclic compounds in all their stereoisomeric and tautomeric forms; and their pharmaceutically acceptable salts, pharmaceutically acceptable solvates and pharmaceutically acceptable polymorphs. The invention also relates to processes for the manufacture of the heterocyclic compounds and to pharmaceutical compositions containing them. The said compounds and their pharmaceutical compositions are useful in the prevention and treatment of diseases or disorders mediated by diacylglycerol acyltransferase (DGAT), particularly DGAT1. The present invention further provides a method of treatment of such diseases or disorders by administering a therapeutically effective amount of said compounds or their pharmaceutical compositions, to a mammal in need thereof.

Abstract: The present invention relates to the crystal structure of the serine protease kallikrein 7 and to the use of this crystal structure in drug discovery. The present invention also relates to compounds binding specifically to this active site of kallikrein 7.

Abstract: The present invention relates to compounds and related technetium and rhenium complexes thereof which are suitable for imaging or therapeutic treatment of tissues, organs, or tumors. In another embodiment, the invention relates to methods of imaging tissues, organs, or tumors using radiolabeled metal complexes, particularly tissues, organs, or tumors which express certain receptors to which the compounds or complexes of the invention have an affinity. The present invention also relates to methods of treating cancer, particularly those cancer lines which express certain receptors to which the compounds or complexes of the invention have an affinity. In yet another embodiment, the present invention provides methods of imaging and/or inhibiting receptors or neuroreceptors using compounds or complexes of the invention which have an affinity for the receptor or neuroreceptor to be imaged and/or inhibited.

Abstract: Substituted 6-amino-nicotinamides, pharmaceutical compositions containing these compounds and also use of these compounds in the treatment and/or prophylaxis of pain and further diseases and/or disorders.

Abstract: The present invention relates generally to affinity ligands and chemical affinity ligand-matrix conjugates for use as chromatographic adsorbents and methods which utilise the adsorbents in the purification of proteins by affinity chromatography. The affinity ligand-matrix conjugates of the present invention comprise ligands of general formula (I): wherein m represents an integer from 0-2, n represents an integer from 0-6, p represents an integer from 0-4, R1 represents H or C1-3 alkyl, R2 is an optional substituent, and X is the position at which the ligand is immobilized, optionally via a linker.

Abstract: The present invention relates to compounds that are suitable for treatment of disease states and influence cellular vesicular systems, especially the formation and/or function of lipid droplets, said compound having the general formula I (I) wherein X are each independently hydrogen, halogen, —C1-20-alkyl, —C2-20-alkenyl, —C2-20-alkinyl, —C5-6-cykloalkyl, aryl, aralkyl, adamantyl, heterocyclic, hydroxyl, hydroxyalkyl, Or —N—(R1, R2) group; n is 0, 1, 2, 3, or 4; R1 and R2 may each be independently hydrogen, straight or branching alkyl, cyclo-alkyl, aryl, aralkyl, heterocyclic group, wherein each is un-substituted or halogen substituted; or R1 and R2 together with the nitrogen in between them form a 5 or 6 member ring; A is a single bond, —O—, —S—, —CH2-, or —NH—; Y is O or S; Z is O or S; R? and R? are each independently methyl, ethyl, isopropyl, isobuthyl, sec-butyl or terc-butyl; with the restriction that: X(n) cannot all be fluorine, and A be a single bond, and Y, as well as Z be O, and R?, as well as R? b

Abstract: The compounds shown by their structural formulas in the specification have analgesic and or immunostimulant activity in mammals.

Abstract: The invention is concerned with novel carbocyclyl fused cyclic amines of formula (I) wherein A, X1 to X3, Y1 to Y3, Z, R1, R2, m and n are as defined in the description and in the claims, as well as physiologically acceptable salts thereof. These compounds inhibit the coagulation factor Xa and can be used as medicaments.

Abstract: Disclosed are compounds which inhibit the activity of NAMPT, compositions containing the compounds and methods of treating diseases during which NAMPT is expressed. Disclosed are compounds which inhibit the activity of ROCK, compositions containing the compounds and methods of treating diseases during which ROCK is expressed.

Abstract: Heterocyclic-substituted tricyclics of the formula or a pharmaceutically acceptable salt or solvate of said compound, isomer or racemic mixture wherein represents an optional double bond, the dotted line is optionally a bond or no bond, resulting in a double bond or a single bond, as permitted by the valency requirement and wherein E, A, G M, Het, B, X, R3, R10, R11, R32 and R33 are herein defined and the remaining substituents are as defined in the specification, are disclosed, as well as pharmaceutical compositions containing them and a method of treating diseases associated with thrombosis, atherosclerosis, restenosis, hypertension, angina pectoris, arrhythmia, heart failure, and cancer by administering said compounds. Combination therapy with other cardiovascular agents is also claimed.

Abstract: Compounds of formula I: wherein R1, R2, R3, R4, R5, R6, R7, R8, R9 and n are as defined in the description, processes for the preparing the compounds, new intermediates employed in the preparation, pharmaceutical compositions containing the compounds, and uses of the compounds in therapy.

Abstract: Compounds useful for the treatment of spinal muscular atrophy or other uses, as well as methods of using such compounds to increase SMN expression, increase EAAT2 expression, or increase the expression of a nucleic acid that encodes a translational stop codon introduced by mutation or frameshift.

Abstract: Compounds having the structure of formula I are described. The compounds can inhibit hepatitis C virus (HCV) replication, and in particular can inhibit the function of the HCV NS5A protein.

Abstract: The present invention relates to an amide compound or a pharmaceutically acceptable salt thereof, a preparation method thereof, and a pharmaceutical composition comprising the same. The inventive amide compound facilitates bone formation and inhibits bone loss, and is therefore useful for preventing and treating bone disorders such as osteoporosis, osteodystrophy, bone fracture, periodontal disease, Paget's disease, bone metastasis, and rheumatoid arthritis.

Abstract: The invention relates to non-crystalline lenalidomide in the form of a storage-stable intermediate, i.e. preferably amorphous lenalidomide together with a surface stabiliser in the form of a stable intermediate or a storage-stable intermediate, containing lenalidomide and matrix material, wherein the lenalidomide is present in the form of a solid solution (i.e. molecularly disperse). The invention further relates to methods of producing stable amorphous or molecularly disperse lenalidomide and pharmaceutical formulations containing stable amorphous or molecularly disperse lenalidomide. In a second aspect, the invention advantageously relates to dry-processing methods for lenalidomide, especially amorphous and disperse lenalidomide.

Abstract: The present invention relates to a compound of formula (I): or a pharmaceutically acceptable salt or solvate thereof, wherein: Ring A is (4-12)-membered heterocyclyl; Ring B is a fused benzene ring selected from the group consisting of: Ring A, ring B, ring C, R1, R1a, R2, R3, R4, L2, n, t, w, and z are as defined in the specification. The invention also relates to pharmaceutical compositions comprising the compounds of formula (I) and methods of treating a condition that is mediated by the modulation of glucokinase, the method comprising administering to a mammal an effective amount of a compound of formula (I).

Abstract: The present invention relates to compounds useful as inhibitors of PI3K, particularly of PI3K?. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders.

Abstract: Compounds of Formula (I) or (II) useful for the treatment of spinal muscular atrophy or other uses, as well as methods of using such compounds to increase SMN expression, increase EAAT2 expression, or increase the expression of a nucleic acid that encodes a translational stop codon introduced by mutation or frameshift.