Substituted amide derivatives and methods of use

Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Inhibitors of p38

The present invention relates to inhibitors of p38, a mammalian protein kinase involved cell proliferation, cell death and response to extracellular stimuli. The invention also relates to methods for producing these inhibitors. The invention also provides pharmaceutical compositions comprising the inhibitors of the invention and methods of utilizing those compositions in the treatment and prevention of various disorders.

Substituted heterocycles and methods of use

Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Substituted heterocycles and methods of use

Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Heterocyclic inhibitors of P38

Nitrogen-containing heterocyclyl ketones and methods of use

Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Compounds and methods of use

Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Nitrogen-Containing heterocyclyl ketones and methods of use

Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Fused heterocyclic derivatives and methods of use

Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Bis-aryl kinase inhibitors and method

Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Crystallized P38 complexes

This invention provides certain crystallized, protein kinase-ligand complexes, in particular P38-ligand complexes, and their structure coordinates. The structure coordinates are based on the structure of a phosphorylated P38γ complex which has now been solved and which reveals new structural information useful for understanding the activated states of other, related kinase proteins as described herein. The key structural features of the proteins, particularly the shape of the substrate binding site, are useful in methods for designing or identifying selective inhibitors of the protein kinases, particularly P38γ and in solving the structures of other proteins with similar features. The structure coordinates may be encoded in a data storage medium for use with a computer for graphical three-dimensional representation of the structure and for computer-aided molecular design of new inhibitors.

Inhibitors of p38

The present invention relates to inhibitors of p38, a mammalian protein kinase involved cell proliferation, cell death and response to extracellular stimuli. The invention also relates to methods for producing these inhibitors. The invention also provides pharmaceutical compositions comprising the inhibitors of the invention and methods of utilizing those compositions in the treatment and prevention of various disorders.

SUBSTITUTED AMIDE DERIVATIVES AND METHODS OF USE

Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Fused heterocyclic derivatives and methods of use

Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Substituted heterocycles and methods of use

Selected compounds are effective for prophylaxis and treatment of diseases, such as c-met mediated diseases and/or HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Bis-aryl kinase inhibitors and method

Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

INHIBITORS OF p38

The present invention relates to inhibitors of p38, a mammalian protein kinase involved cell proliferation, cell death and response to extracellular stimuli. The invention also relates to methods for producing these inhibitors. The invention also provides pharmaceutical compositions comprising the inhibitors of the invention and methods of utilizing those compositions in the treatment and prevention of various disorders.

Fused heterocyclic derivatives and methods of use

Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

FUSED HETEROCYCLIC DERIVATIVES AND METHODS OF USE

Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

FUSED HETEROCYCLIC DERIVATIVES AND METHODS OF USE

Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes. 2. A compound of wherein Ris phenyl claim 1 , naphthyl claim 1 , benzodioxolyl claim 1 , benzooxazolyl claim 1 , benzoisoxazolyl claim 1 , pyridinyl claim 1 , pyrimidinyl claim 1 , pyrazinyl claim 1 , pyrimidinyl claim 1 , pyrazidinyl claim 1 , isoquinolinyl claim 1 , quinolinyl claim 1 , quinazolinyl claim 1 , quinazolinonyl claim 1 , quinoxalinyl claim 1 , naphthyridinyl claim 1 , benzotriazinyl claim 1 , triazolopyridinyl claim 1 , triazolopyrimidinyl claim 1 , triazolopyridazinyl claim 1 , imidazopyridinyl claim 1 , imidazopyrimidinyl claim 1 , imidazopyridazinyl claim 1 , pyrrolopyridinyl claim 1 , pyrrolopyrimidinyl claim 1 , pyrrolopyridazinyl claim 1 , pyrazolopyridinyl claim 1 , pyrazolopyrimidinyl claim 1 , pyrazolopyridazinyl claim 1 , cinnolinyl claim 1 , thienopyridinyl claim 1 , thienopyrimidinyl claim 1 , thienopyridazinyl claim 1 , furopyridinyl claim 1 , furopyrimidinyl claim 1 , furopyrazidinyl claim 1 , benzofuranyl claim 1 , benzoimidazolyl claim 1 , indolyl claim 1 , benzoisoxazolyl claim 1 , benzothiazolyl claim 1 , or benzoisothiazolyl any of which may be optionally independently substituted with one or more Rgroups as allowed by valance.3. A compound of wherein Ris H claim 2 , halo claim 2 , cyano claim 2 , alkynyl claim 2 , —C(═O)NRR claim 2 , —N(R)C(═O)R claim 2 , —N(R)C(═O)OR claim 2 , phenyl claim 2 , naphthyl claim 2 , pyrrolyl claim 2 , imidazolyl claim 2 , pyrazolyl claim 2 , triazolyl claim 2 , tetrazolyl claim 2 , furanyl claim 2 , thienyl claim 2 , ...

Protein kinase modulators and method of use

The present invention relates to chemical compounds having a general formula I wherein A, B, D, E, G, H1-5 and R1-4 are defined herein, and synthetic intermediates, which are capable of modulating various protein kinase receptor enzymes and, thereby, influencing various disease states and conditions related to the activities of these kinases. For example, the compounds are capable of modulating kinase enzymes thereby influencing the process of angiogenesis and treating angiogenesis-related diseases and other poliferative disorders, including cancer and inflammation. The invention also includes pharmaceutical compositions, including the compounds, and methods of treating disease states related to the activity of protein kinases.

Substituted pyridines and pyrimidines and their use in treatment of cancer

Selected pyridine and pyrimidine compounds of Formula I are effective for prophylaxis and treatment of diseases, such as c-met mediated diseases and/or HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

FUSED HETEROCYCLIC DERIVATIVES AND METHODS OF USE

Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes. 2. A compound of wherein Ris phenyl claim 1 , naphthyl claim 1 , benzodioxolyl claim 1 , benzooxazolyl claim 1 , benzoisoxazolyl claim 1 , pyridinyl claim 1 , pyrimidinyl claim 1 , pyrazinyl claim 1 , pyrimidinyl claim 1 , pyrazidinyl claim 1 , isoquinolinyl claim 1 , quinolinyl claim 1 , quinazolinyl claim 1 , quinazolinonyl claim 1 , quinoxalinyl claim 1 , naphthyridinyl claim 1 , benzotriazinyl claim 1 , triazolopyridinyl claim 1 , triazolopyrimidinyl claim 1 , triazolopyridazinyl claim 1 , imidazopyridinyl claim 1 , imidazopyrimidinyl claim 1 , imidazopyridazinyl claim 1 , pyrrolopyridinyl claim 1 , pyrrolopyrimidinyl claim 1 , pyrrolopyridazinyl claim 1 , pyrazolopyridinyl claim 1 , pyrazolopyrimidinyl claim 1 , pyrazolopyridazinyl claim 1 , cinnolinyl claim 1 , thienopyridinyl claim 1 , thienopyrimidinyl claim 1 , thienopyridazinyl claim 1 , furopyridinyl claim 1 , furopyrimidinyl claim 1 , furopyrazidinyl claim 1 , benzofuranyl claim 1 , benzoimidazolyl claim 1 , indolyl claim 1 , benzoisoxazolyl claim 1 , benzothiazolyl claim 1 , or benzoisothiazolyl any of which may be optionally independently substituted with one or more Rgroups as allowed by valance.3. A compound of wherein Ris H claim 2 , halo claim 2 , cyano claim 2 , alkynyl claim 2 , —C(═O)NRR claim 2 , —N(R)C(═O)R claim 2 , —N(R)C(═O)OR claim 2 , phenyl claim 2 , naphthyl claim 2 , pyrrolyl claim 2 , imidazolyl claim 2 , pyrazolyl claim 2 , triazolyl claim 2 , tetrazolyl claim 2 , furanyl claim 2 , thienyl claim 2 , ...

Aryl nitrogen-containing bicyclic compounds and methods of use

The present invention comprises a new class of compounds useful for the prophylaxis and treatment of protein kinase mediated diseases, including inflammation, cancer and related conditions. The compounds have a general Formula I wherein A1, A2, A3, B, R1, R2, R3 and R4 are defined herein. Accordingly, the invention also comprises pharmaceutical compositions comprising the compounds of the invention, methods for the prophylaxis and treatment of kinase mediated diseases using the compounds and compositions of the invention, and intermediates and processes useful for the preparation of compounds of the invention.

Protein kinase modulators and method of use

The present invention relates to chemical compounds having a general formula I wherein A, B, D, E, G, H1-5 and R1-4 are defined herein, and synthetic intermediates, which are capable of modulating various protein kinase receptor enzymes and, thereby, influencing various disease states and conditions related to the activities of these kinases. For example, the compounds are capable of modulating kinase enzymes thereby influencing the process of angiogenesis and treating angiogenesis-related diseases and other proliferative disorders, including cancer and inflammation. The invention also includes pharmaceutical compositions, including the compounds, and methods of treating disease states related to the activity of protein kinases.

Substituted heterocycles and methods of use

Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

HETEROCYCLES AS PROTEIN KINASE INHIBITORS

Selected fused imidazole or triazole derivatives are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Fused heterocyclic derivatives and methods of use

Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Heterocycles as protein kinase inhibitors

Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds of Formula I, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Protein kinase modulators and method of use

The present invention relates to chemical compounds having a general formula I wherein A, B, D, E, G, H1-5 and R1-4 are defined herein, and synthetic intermediates, which are capable of modulating various protein kinase receptor enzymes and, thereby, influencing various disease states and conditions related to the activities of these kinases. For example, the compounds are capable of modulating kinase enzymes thereby influencing the process of angiogenesis and treating angiogenesis-related diseases and other poliferative disorders, including cancer and inflammation. The invention also includes pharmaceutical compositions, including the compounds, and methods of treating disease states related to the activity of protein kinases.

Crystallized P38 complexes

This invention provides certain crystallized, protein kinase-ligand complexes, in particular P38-ligand complexes, and their structure coordinates. The structure coordinates are based on the structure of a phosphorylated P38gamma complex which has now been solved and which reveals new structural information useful for understanding the activated states of other, related kinase proteins as described herein. The key structural features of the proteins, particularly the shape of the substrate binding site, are useful in methods for designing or identifying selective inhibitors of the protein kinases, particularly P38gamma and in solving the structures of other proteins with similar features. The structure coordinates may be encoded in a data storage medium for use with a computer for graphical three-dimensional representation of the structure and for computer-aided molecular design of new inhibitors.

Fused heterocyclic derivatives and methods of use

Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Inhibitors of P38

The present invention relates to inhibitors of p38, a mammalian protein kinase involved cell proliferation, cell death and response to extracellular stimuli. The invention also relates to methods for producing these inhibitors. The invention also provides pharmaceutical compositions comprising the inhibitors of the invention and methods of utilizing those compositions in the treatment and prevention of various disorders. ...

Substituted heterocycles and methods of use

Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

USE OF CBP/EP300 BROMODOMAIN INHIBITORS FOR CANCER IMMUNOTHERAPY

The present invention relates to use of CBP/EP300 bromodomain inhibitors for the treatment of cancer. 1. A method for treating or delaying progression of cancer in an individual comprising administering an effective amount of a CBP/EP300 bromodomain inhibitor to the individual.2. A method of enhancing immune function in an individual having cancer comprising administering an effective amount of a CBP/EP300 bromodomain inhibitor to the individual.3. The method of claim 1 , wherein CD8 T cells in the individual have enhanced priming claim 1 , activation claim 1 , proliferation and/or cytolytic activity relative to prior to the administration of the CBP/EP300 bromodomain inhibitor.4. The method of claim 3 , wherein the number of CD8 T cells is elevated relative to prior to administration of the CBP/EP300 bromodomain inhibitor.5. The method of claim 3 , wherein the CD8 T cell is an antigen-specific CD8 T cell.6. The method of claim 1 , wherein the cancer has elevated levels of T-cell infiltration.7. The method of claim 1 , wherein the cancer is associated with increased intratumoral Treg cell density.8. The method of claim 1 , wherein the cancer is selected from acoustic neuroma claim 1 , acute leukemia claim 1 , acute lymphocytic leukemia claim 1 , acute myelocytic leukemia claim 1 , acute t-cell leukemia claim 1 , basal cell carcinoma claim 1 , bile duct carcinoma claim 1 , bladder cancer claim 1 , brain cancer claim 1 , breast cancer claim 1 , bronchogenic carcinoma claim 1 , cervical cancer claim 1 , chondrosarcoma claim 1 , chordoma claim 1 , choriocarcinoma claim 1 , chronic leukemia claim 1 , chronic lymphocytic leukemia claim 1 , chronic myelocytic leukemia claim 1 , chronic myelogenous leukemia claim 1 , colon cancer claim 1 , colorectal cancer claim 1 , craniopharyngioma claim 1 , cystadenocarcinoma claim 1 , diffuse large B-cell lymphoma claim 1 , dysproliferative changes claim 1 , embryonal carcinoma claim 1 , endometrial cancer claim 1 , endotheliosarcoma ...

Substituted amide derivatives and methods of use

Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Compounds and methods of use

Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Fused heterocyclic derivatives and methods of use

Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Compounds and methods of use

Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Inhibitors of p38

The present invention relates to inhibitors of p38, a mammalian protein kinase involved cell proliferation, cell death and response to extracellular stimuli. The invention also relates to methods for producing these inhibitors. The invention also provides pharmaceutical compositions comprising the inhibitors of the invention and methods of utilizing those compositions in the treatment and prevention of various disorders.

Compounds and methods of use

Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

METHOD OF TREATING CANCER WITH SUBSTITUTED AMIDE DERIVATIVES

Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes. 3. The method of wherein Ris independently selected at each occurrence from H claim 1 , cyano claim 1 , aminocarbonyl claim 1 , C-alkylaminocarbonyl claim 1 , C-alkyl claim 1 , C-alkoxy claim 1 , C-alkylamino-C-alkoxy claim 1 , 5-6 membered heterocyclyl-C-alkoxy claim 1 , C-cycloalkyl-C-alkoxy claim 1 , 5-6 membered heterocyclyl-C-(hydroxyalkoxy) claim 1 , C-cycloalkyl-C-(hydroxyalkoxy) claim 1 , C-alkoxy-C-alkoxy claim 1 , phenyloxy-Calkoxy claim 1 , 5-6 membered heterocyclyloxy-C-alkoxy claim 1 , cycloalkyloxy-C-alkoxy claim 1 , 5-6 membered heterocyclyloxy claim 1 , and C-cycloalkyloxy; and pharmaceutically acceptable salts thereof.4. The method of wherein Ris independently selected from H claim 1 , methyl claim 1 , cyano claim 1 , heterocyclic claim 1 , heteroaryl claim 1 , aminocarbonyl claim 1 , methylaminocarbonyl claim 1 , methoxy claim 1 , dimethylaminopropoxy claim 1 , 3-(morpholin-4-yl)propoxy claim 1 , 3-(pyrrolidin-1-yl)propoxy claim 1 , 2-hydroxy-3-(morpholin-4-yl)propoxy claim 1 , 3-(1 claim 1 ,2 claim 1 ,4-triazol-1-yl)propoxy claim 1 , 3-(4-methylpiperazin-1-yl)propoxy claim 1 , 3-(piperidin-4-yl)propoxy claim 1 , dimethylaminoethoxy and diethylaminoethoxy; and pharmaceutically acceptable salts thereof.5. The method of wherein R is selected from 6 claim 1 ,7-dimethoxy-4-quinolinyl claim 1 , 7-methoxy-4 quinolinyl claim 1 , 6-methoxy-7-(dimethylaminopropoxy)-4-quinolinyl claim 1 , 6-methoxy-7-(3-(morpholin-4-yl)propoxy)-4-quinolinyl claim 1 , 6-methoxy-7-(3-(pyrrolidin- ...

Inhibitors of p38

The present invention relates to inhibitors of p38, a mammalian protein kinase involved cell proliferation, cell death and response to extracellular stimuli. The invention also relates to methods for producing these inhibitors. The invention also provides pharmaceutical compositions comprising the inhibitors of the invention and methods of utilizing those compositions in the treatment and prevention of various disorders.

Method of treating cancer with substituted amide derivatives

Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Inhibitors of p38

The present invention relates to inhibitors of p38, a mammalian protein kinase involved in cell proliferation, cell death and response to extracellular stimuli. The invention also relates to methods for producing these inhibitors. The invention also provides pharmaceutical compositions comprising the inhibitors of the invention and methods of utilizing those compositions in the treatment and prevention of various disorders.

FUSION PROTEINS AND METHODS FOR IDENTIFYING BROMODOMAIN INHIBITING COMPOUNDS

The present invention relates to fusion proteins comprising at least one chromatin binding module and at least one reporter module, wherein a plurality of fusion proteins are capable of forming foci, and associated methods for identifying bromodomain inhibiting compounds. 1. A fusion protein comprising at least one chromatin binding module and at least one reporter module , wherein a plurality of fusion proteins are capable of forming foci.2. The fusion protein of claim 1 , wherein the fusion protein comprises a first chromatin binding polypeptide comprising at least one chromatin binding module claim 1 , wherein at least one of the chromatin binding modules of the first chromatin binding polypeptide have been deleted claim 1 , substituted and/or replaced with at least one chromatin binding module of a second chromatin binding polypeptide.32. The fusion protein of any one of - claims 1 , wherein the fusion protein comprises a first chromatin binding polypeptide comprising at least one chromatin binding module claims 1 , wherein at least one of the chromatin binding modules of the first chromatin binding polypeptide have been replaced with at least one bromodomain module of a second chromatin binding polypeptide.43. The fusion protein of any one of - claims 1 , wherein the at least one reporter module comprises at least one fluorescent reporter module.5. The fusion protein of claim 4 , wherein the at least one reporter module comprises EGFP claim 4 , TurboGFP claim 4 , dsRed2 claim 4 , dsRed-Express2 or ZsGreen.65. The fusion protein of any one of - claims 1 , wherein the fusion protein comprises a nuclear localization signal (NLS).7. The fusion protein of claim 6 , wherein the NLS is the SV40 Large T-antigen NLS or the NLS of nucleoplasmin.87. The fusion protein of any one of - claims 1 , wherein the at least one chromatin binding module is located 5′ of the reporter module.97. The fusion protein of any one of - claims 1 , wherein the at least one chromatin binding ...

FUSION PROTEINS AND METHODS FOR IDENTIFYING BROMODOMAIN INHIBITING COMPOUNDS

The present invention relates methods for identifying bromodomain inhibiting compounds. 1. A method for determining whether a test compound is a bromodomain inhibiting compound comprising (a) contacting a cell that comprises a fusion protein , wherein a plurality of fusion proteins are capable of forming foci , with the test compound and (b) determining whether the test compound causes an increase in formation of fusion protein foci , wherein an increase in formation of foci indicates that the test compound is a bromodomain inhibiting compound , wherein each fusion protein comprises at least one bromodomain and a reporter module.2. The method of claim 1 , wherein the cell is a CHO-K1 claim 1 , COS-7 claim 1 , HEK293 claim 1 , HEK293T claim 1 , HEK293FT claim 1 , HeLa claim 1 , MDCK or U2OS cell.3. The method of claim 2 , wherein the cell is a COS-7 claim 2 , HeLa or U2OS cell.4. The method of claim 1 , wherein each fusion protein comprises at least one bromodomain and a reporter module that is a fluorescent protein that is capable of multimerizing.5. The method of claim 1 , wherein the reporter module is EGFP claim 1 , TurboGFP dsRed2 claim 1 , dsRed-Express2 or ZsGreen.6. The method of claim 1 , wherein the fusion protein comprises a nuclear localization signal (NLS).7. The method of claim 6 , wherein the NLS is the SV40 Large T-antigen NLS or the NLS of nucleoplasmin.8. The method of claim 1 , wherein the bromodomain comprises at least one bromodomain of any one of BRG1 claim 1 , PCAF/KAT2B claim 1 , BAZ2B claim 1 , BRD1 claim 1 , BRD8 claim 1 , BRFP1 claim 1 , BRFP3 claim 1 , BRG1 claim 1 , CBP/CREBBP claim 1 , PCAF/KAT2B claim 1 , TRIM24 and/or ZMYND8.9. The method of claim 1 , wherein the bromodomain comprises at least one bromodomain of any one of BRD2 claim 1 , BRD3 claim 1 , BRD4 claim 1 , BRD9 claim 1 , BRDT claim 1 , and/or BRG1.10. The method of claim 1 , wherein the bromodomain comprises at least one bromodomain of any one of BRG1 claim 1 , BRPF1 claim 1 ...

PYRAZOLO COMPOUNDS AND USES THEREOF

Provided are compounds useful as inhibitors of one or more histone demethylases, such as KDM5. The invention also provides pharmaceutically acceptable compositions comprising compounds of the present invention and methods of using the present composition in the treatment of various disorders. 3. The compound according to claim 2 , wherein Ris hydrogen.4. The compound according to claim 1 , wherein Ris hydrogen.5. The compound according to claim 1 , wherein Ris Calkyl.6. The compound according to claim 5 , wherein Ris methyl.7. The compound according to claim 1 , wherein Ris optionally substituted Caliphatic.8. The compound according to claim 7 , wherein Ris methyl claim 7 , ethyl claim 7 , propyl claim 7 , cyclopropyl claim 7 , isopropyl claim 7 , isobutyl claim 7 , propargyl claim 7 , or allyl.9. The compound according to claim 7 , wherein the Caliphatic group is substituted with —OCH.10. The compound according to claim 1 , wherein Ris optionally substituted Caliphatic.11. The compound according to claim 10 , wherein Ris methyl.12. The compound according to claim 10 , wherein the Caliphatic group is substituted with —OH or —OCalkyl.13. The compound according to claim 12 , wherein Ris —CHOH claim 12 , —CHCHOH claim 12 , —CHCHCHOH claim 12 , —CHOCHCH claim 12 , —CHOCH claim 12 , —CHCHCHOCH claim 12 , —CH(OH)CH claim 12 , or —CHCHOCH.14. The compound according to claim 10 , wherein the Caliphatic group is substituted with —NHCalkyl or —NH(Calkyl).15. The compound according to claim 14 , wherein Ris —CHNHCH.16. The compound according to claim 10 , wherein Ris optionally substituted benzyl.19. The compound according to claim 10 , wherein Ris —CF.20. The compound according to claim 1 , wherein Ris —COR or —C(O)N(R′).21. The compound according to claim 20 , wherein Ris —COEt claim 20 , —COBn claim 20 , —CONHCH claim 20 , or —CONHCHCH.22. The compound according to claim 1 , wherein Ris a 5-6 membered monocyclic heteroaryl ring having 1-3 heteroatoms independently selected ...

THERAPEUTIC COMPOUNDS AND USES THEREOF

The present invention relates to compounds formula (I): 2. The method of wherein the treatment further comprises the administration of a cytotoxic agent or radiation.3. The method of wherein the cytotoxic agent is a chemotherapeutic agent.4. The method of wherein the proliferative disorder is lung cancer claim 1 , melanoma claim 1 , colorectal cancer claim 1 , pancreatic cancer claim 1 , or breast cancer.5. The method of wherein Ris H claim 1 , Calkyl claim 1 , Calkenyl claim 1 , Calkynyl claim 1 , carbocyclyl claim 1 , heterocyclyl claim 1 , halo claim 1 , —OR claim 1 , —SR claim 1 , —N(R) claim 1 , —CN claim 1 , —NO claim 1 , —C(O)R claim 1 , —COR claim 1 , —C(O)N(R) claim 1 , —C(O)SR claim 1 , —C(O)C(O)R claim 1 , —C(O)CHC(O)R claim 1 , —C(S)N(R) claim 1 , —C(S)OR claim 1 , —S(O)R claim 1 , —SOR claim 1 , —SON(R) claim 1 , —N(R)C(O)R claim 1 , —N(R)C(O)N(R) claim 1 , —N(R)SOR claim 1 , —N(R)N(R) claim 1 , —N(R)N(R) claim 1 , —N(R)C(═N(R))N(R) claim 1 , —C═NOR claim 1 , —C(═N(R))N(R) claim 1 , —OC(O)R claim 1 , or —OC(O)N(R) claim 1 , wherein each Calkyl claim 1 , Calkenyl claim 1 , Calkynyl claim 1 , carbocyclyl claim 1 , and heterocyclyl of Rand Ris independently optionally substituted with one or more groups R.6. The method of wherein claim 1 , Ris H claim 1 , Calkyl claim 1 , carbocyclyl claim 1 , halo claim 1 , —CN claim 1 , wherein any Calkyl or carbocyclyl is optionally substituted with one or more groups independently selected from carbocyclyl claim 1 , halo claim 1 , —CN claim 1 , and —O—R.7. The method of wherein Ris H claim 1 , methyl claim 1 , ethyl claim 1 , isopropyl claim 1 , cyclopropyl claim 1 , methoxy claim 1 , fluoro claim 1 , chloro claim 1 , or cyano; or wherein Rand Rtaken together with the atoms to which they are attached form a 5 membered carbocyclyl.8. The method of wherein Ris H claim 1 , Calkyl claim 1 , Calkenyl claim 1 , Calkynyl claim 1 , carbocyclyl claim 1 , heterocyclyl claim 1 , halo claim 1 , —OR claim 1 , —SR claim 1 , —N(R) ...

PYRAZOLO COMPOUNDS AND USES THEREOF

The present invention relates to compounds useful as inhibitors of one or more histone demethylses. The invention also provides pharmaceutically acceptable compositions comprising compounds of the present invention and methods of using said compositions in the treatment of various disorders. 3. The compound according to claim 2 , wherein Ris hydrogen.4. The compound according to claim 1 , wherein Ris hydrogen.5. The compound according to claim 1 , wherein Ris optionally substituted Caliphatic.6. The compound according to claim 5 , wherein Ris methyl claim 5 , ethyl claim 5 , propyl claim 5 , cyclopropyl claim 5 , isopropyl claim 5 , isobutyl claim 5 , propargyl claim 5 , or allyl.7. The compound according to claim 1 , wherein Ris optionally substituted Caliphatic.8. The compound according to claim 7 , wherein the Caliphatic group is substituted with —OH or —OCalkyl.9. The compound according to claim 7 , wherein the Caliphatic group is substituted with —NHCalkyl or —NH(Calkyl).10. The compound according to claim 7 , wherein Ris optionally substituted benzyl.12. The compound according to claim 7 , wherein Ris —CF.13. The compound according to claim 1 , wherein Ris —COR or —C(O)N(R′).14. The compound according to claim 1 , wherein Ris a 5-6 membered monocyclic heteroaryl ring having 1-3 heteroatoms independently selected from nitrogen claim 1 , oxygen claim 1 , or sulfur.15. The compound according to claim 1 , wherein neither of Rand Ris hydrogen.22. The method of claim 20 , wherein the 2-oxoglutarate dependent enzyme is a JARID family enzyme. This application claims priority from U.S. Provisional Application No. 61/778,759, filed 13 Mar. 2013. The entire content of this provisional application is hereby incorporated herein by reference.The present invention relates to compounds useful as inhibitors of histone demethylases.Packaging the 3 billion nucleotides of the human genome into the nucleus of a cell requires tremendous compaction. To accomplish this feat, DNA in ...

THERAPEUTIC COMPOUNDS AND USES THEREOF

The present invention relates to compounds of formula (I): 2. (canceled)3. The compound of wherein Ris Calkyl or Calkenyl claim 1 , wherein each Calkyl and claim 1 , Calkenyl is optionally substituted with one or more groups R.4. (canceled)5. The compound of wherein Ris Calkyl or Calkenyl claim 1 , wherein each Calkyl and Calkenyl is optionally substituted with one or more groups independently selected from carbocyclyl claim 1 , —F claim 1 , —Cl claim 1 , —O—R claim 1 , —O—C(O)—R claim 1 , —C(O)—R claim 1 , and —C(O)—O—R.6. The compound of wherein Ris Calkyl or Calkenyl claim 1 , wherein each Calkyl and Calkenyl is optionally substituted with one or more groups independently selected from Ccycloalkyl.7. The compound of wherein Ris methyl claim 1 , butyl claim 1 , 2-propenyl claim 1 , 2-buten-1-yl claim 1 , 3-buten-1-yl or 2-cyclopropylethyl.8. (canceled)9. The compound of wherein Ris H or Calkyl wherein each Calkyl is optionally substituted with one or more groups R.1013-. (canceled)14. The compound of wherein Ris hydrogen claim 1 , Calkyl claim 1 , or Ccycloalkyl claim 1 , wherein each Calkyl and Ccycloalkyl is optionally substituted with one or more substituent groups independently selected from —O—R.15. The compound of wherein Ris hydrogen claim 1 , methyl claim 1 , ethyl claim 1 , cyclopropyl claim 1 , cyclobutyl claim 1 , or 2-methoxyethyl.1618-. (canceled)19. The compound of wherein Ris Calkyl that is optionally substituted with one or more substituent groups independently selected from oxo claim 1 , Calkyl claim 1 , Calkenyl claim 1 , Calkynyl claim 1 , carbocyclyl claim 1 , heterocyclyl claim 1 , —F claim 1 , —Cl claim 1 , —Br claim 1 , —I claim 1 , —NO claim 1 , —N(R) claim 1 , —CN claim 1 , —C(O)—N(R) claim 1 , —S(O)—N(R) claim 1 , —S(O)—N(R) claim 1 , —O—R claim 1 , —S—R claim 1 , —O—C(O)—R claim 1 , —O—C(O)—O—R claim 1 , —C(O)—R claim 1 , —C(O)—O—R claim 1 , —S(O)—R claim 1 , —S(O)—R claim 1 , —O—C(O)—N(R) claim 1 , —N(R)—C(O)—OR claim 1 , —N(R)—C(O)—N(R ...

THERAPEUTIC COMPOUNDS AND USES THEREOF

The present invention relates to compounds of formula (I): 2. The compound of wherein Ris methyl that is substituted with one or more groups R.3. The compound of wherein Ris ethyl that is substituted with one or more groups R.47-. (canceled)8. The compound of wherein Ris butyl claim 1 , 2-cyclopropylethyl claim 1 , cyclopentylmethyl claim 1 , 2-penten-1-yl claim 1 , cyclohexylmethyl claim 1 , cyclobutylmethyl claim 1 , 2-cyclohexylethyl claim 1 , pentyl claim 1 , 2-methylpropyl claim 1 , 2-buten-1-yl claim 1 , butyl claim 1 , 2-furylmethyl claim 1 , 3-methylbut-1-yl claim 1 , 2-propenyl claim 1 , 3-methyl-2-buten-1-yl claim 1 , 3-buten-1-yl claim 1 , 2-methoxyethyl claim 1 , 3-methoxypropyl claim 1 , or 4-methoxybenzyl.910-. (canceled)11. The compound of wherein Ris methyl.1213-. (canceled)14. The compound of wherein Q is C-Ccycloalkyl that is optionally substituted with one or more groups R.15. The compound of wherein Q is aryl that is optionally substituted with one or more groups R.16. The compound of wherein Q is phenyl that is optionally substituted with one or more groups R.17. The compound of wherein Q is C-Cheterocycloalkyl that is optionally substituted with one or more groups R.18. The compound of wherein Q is heteroaryl that is optionally substituted with one or more groups R.2024-. (canceled)25. The compound of claim 1 , wherein each Ris independently selected from oxo claim 1 , Calkyl claim 1 , heterocyclyl claim 1 , —F claim 1 , —Cl claim 1 , —CN claim 1 , —C(O)—N(R) claim 1 , —O—R claim 1 , and —N(R)—S(O)—R claim 1 , wherein any Calkyl or heterocyclyl is optionally substituted with one or more groups independently selected from —O—Rand Calkyl that is optionally substituted with one or more groups independently selected from oxo and halo.2627-. (canceled)30. A composition comprising a compound of formula (I) as described in or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable adjuvant claim 1 , carrier claim 1 , or ...

Therapeutic compounds and uses thereof

The present invention relates to compounds of formula (I): and to salts thereof, wherein R 1 , R 2 , and Q have any of the values defined in the specification, and compositions and uses thereof. The compounds are useful as inhibitors of bromodomains. Also included are pharmaceutical compositions comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, and methods of using such compounds and salts in the treatment of various bromodomain-mediated disorders.

Pyrazolo compounds and uses thereof

Provided are compounds useful as inhibitors of one or more histone demethylses, such as KDM5. The invention also provides pharmaceutically acceptable compositions comprising compounds of the present invention and methods of using the present composition in the treatment of various disorders.

Inhibitors of p38

THE PRESENT INVENTION RELATES TO INHIBITORS OF P38, A MAMMALIAN PROTEIN KINASE INVOLVED CELL PROLIFERATION, CELL DEATH AND RESPONSE TO EXTRACELLULAR STIMULI. THE INVENTION ALSO RELATES TO METHODS FOR PRODUCING THESE INHIBITORS. THE INVENTION ALSO PROVIDES PHARMACEUTICAL COMPOSITIONS COMPRISING THE INHIBITORS OF THE INVENTION AND METHODS OF UTILIZING THOSE COMPOSITIONS IN THE TREATMENT AND PREVENTION OF VARIOUS DISORDERS.

Protein kinase modulators and method of use

The present invention relates to chemical compounds having a general formula (I) wherein A, B, D, E, G, H1-5 and R1-4 are defined herein, and synthetic intermediates, which are capable of modulating various protein kinase receptor enzymes and, thereby, influencing various disease states and conditions related to the activities of these kinases. For example, the compounds are capable of modulating kinase enzymes thereby influencing the process of angiogenesis and treating angiogenesis-related diseases and other poliferative disorders, including cancer and inflammation. The invention also includes pharmaceutical compositions, including the compounds, and methods of treating disease states related to the activity of protein kinases.

Fused heterocyclic derivatives useful as inhibitors of the hepatocyte growth factor receptor

Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Use of CBP/EP300 bromodomain inhibitors for cancer immunotherapy

The present invention relates to use of CBP/EP300 bromodomain inhibitors for the treatment of cancer.

Antiproliferative compounds

The present invention relates to compounds formula (I) and to salts thereof, wherein R1-R4 and A have any of the values defined in the specification, and compositions and uses thereof. The compounds are useful as inhibitors of histone demethylases, such as KDM5. Also included are pharmaceutically acceptable compositions comprising the compounds of the present invention and methods of using said compositions in the treatment of various disorders.

Substituted heterocycles and methods of use

Selected compounds of Formula (I) are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases such as cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes. R - X - W - A - Y - R Formula (I) wherein R is X is O, S, NR2 or CR3R4 W is an substituted or unsubstituted aryl or substituted or unsubstituted 5- or 6- membered heteroaryl.

Heterocyclic inhibitor of p38

【課題】強力な、ｐ３８の活性化と関係した様々な状態の処置に有用なｐ３８（ｐ３８−特異的インヒビターを含む）を開発すること。 【解決手段】本発明は、細胞増殖、細胞死、および細胞外刺激に対する応答に関与する哺乳動物のタンパク質キナーゼであるｐ３８のインヒビターに関する。本発明はまた、これらのインヒビターの産生方法に関する。本発明はまた、本発明のインヒビターを含有する薬学的組成物、ならびに様々な障害の処置および予防において、これらの組成物を利用する方法を提供する。 【選択図】なし

Heterocyclic inhibitors of p38

The present invention relates to inhibitors of p38, a mammalian protein kinase involved in cell proliferation, cell death and response to extracellular stimuli. The invention also relates to methods for producing these inhibitors. The invention also provides pharmaceutical compositions comprising the inhibitors of the invention and methods of utilizing those compositions in the treatment and prevention of various disorders.

Substituted amide derivatives as protein kinase inhibitors

Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Heterocyclic inhibitors of p38

The present invention relates to inhibitors of p38, a mammalian proteine kinase involved in cell proliferation, cell death and response to extracellular stimuli. The invention also relates to methods for producing these inhibitors. The invention also provides pharmaceutical compositions comprising the inhibitors of the invention and methods of using these compositions in the treatment and prevention of various disorders.

Compounds and methods of use

Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutically compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Pyrazolo compounds and uses thereof

Use of cbp/ep300 bromodomain inhibitors for cancer immunotherapy

The present invention relates to use of CBP/EP300 bromodomain inhibitors for the treatment of cancer.

Heterocyclic compounds for use in the treatment of cancer and the inhibition of angiogenesis

Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutically compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Protein kinase modulators and method of use

The present invention relates to chemical compounds having a general formula (I) wherein A, B, D, E, G, H1-5 and R1-4 are defined herein, and synthetic intermediates, which are capable of modulating various protein kinase receptor enzymes and, thereby, influencing various disease states and conditions related to the activities of these kinases. For example, the compounds are capable of modulating kinase enzymes thereby influencing the process of angiogenesis and treating angiogenesis-related diseases and other poliferative disorders, including cancer and inflammation. The invention also includes pharmaceutical compositions, including the compounds, and methods of treating disease states related to the activity of protein kinases.

Nitrogenated heterocyclic derivatives as protein kinase modulators and use for the treatment of angiogenesis and cancer

The present invention relates to chemical compounds having a general formula (I) wherein A, B, D, E, G, H1-5 and R1-4 are defined herein, and synthetic intermediates, which are capable of modulating various protein kinase receptor enzymes and, thereby, influencing various disease states and conditions related to the activities of these kinases. For example, the compounds are capable of modulating kinase enzymes thereby influencing the process of angiogenesis and treating angiogenesis-related diseases and other poliferative disorders, including cancer and inflammation. The invention also includes pharmaceutical compositions, including the compounds, and methods of treating disease states related to the activity of protein kinases.

Nitrogen-containing heterocyclyl ketones and their use as c-met inhibitors

Selected compounds defined by Formula I, II, III, IV or V are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases.

Substituted amide derivatives as protein kinase inhibitors

Therapeutic compounds and uses thereof

The present invention relates to compounds of formula (I): and to salts thereof, wherein R 1 , R 2 , and Q have any of the values defined in the specification, and compositions and uses thereof. The compounds are useful as inhibitors of bromodomains. Also included are pharmaceutical compositions comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, and methods of using such compounds and salts in the treatment of various bromodomain-mediated disorders.

Antiproliferative compounds

Substituted amide derivatives as protein kinase inhibitors

Use of cbp/ep300 bromodomain inhibitors for cancer immunotherapy

The present invention relates to use of CBP/EP300 bromodomain inhibitors for the treatment of cancer.

Quinolines and quinazoline analogs and their use as medicaments for treating cancer

Selected compounds of Formula (I) are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases such as cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes. R - X - W - A - Y - R Formula (I) wherein R is X is O, S, NR2 or CR3R4 W is an substituted or unsubstituted aryl or substituted or unsubstituted 5- or 6- membered heteroaryl.

use of cbp / ep300 bromodomain inhibitors for cancer immunotherapy

a presente invenção refere-se ao uso de inibidores de bromodomínio cbp/ep300 para o tratamento de câncer. The present invention relates to the use of cbp / ep300 bromodomain inhibitors for the treatment of cancer.

Pyrazolo compounds and uses thereof

【課題】ヒストン脱メチル化酵素の阻害剤として有用な化合物を提供すること。【解決手段】ＫＤＭ５等の、１つ以上のヒストン脱メチル化酵素の阻害剤として有用な化合物が提供される。本発明はまた、本発明の化合物を含む薬学的に許容される組成物、及び様々な障害の治療において本組成物を使用する方法を提供する。本発明の化合物及びその薬学的に許容される組成物は、例えば十文字ドメイン含有タンパク質等の２−オキソグルタル酸依存性酵素、タンパク質のＨ３Ｋ４（ヒストン３Ｋ４）脱メチル化酵素ファミリーのメンバー、及び／またはヒストン脱メチル化酵素のＪＡＲＩＤサブファミリーのメンバーを含む、ヒストン脱メチル化酵素の阻害剤として有効であることが発見されている。【選択図】なし

Fused heterocyclic derivatives and methods of use as c-Met inhibitors

Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

SUBSTITUTED PYRROLOPYRIDINES USED AS BROMODOMA INHIBITORS

Fused heterocyclic derivatives and methods of use

Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Heterocycles as protein kinase inhibitors

Selected fused imidazole or triazole derivatives are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Compounds and methods of use

Fusion proteins and methods for identifying bromodomain inhibiting compounds

Substituted amide derivatives as protein kinase inhibitors

Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Substituted Amide Derivatives as Protein Kinase Suspensions

Επιλεγμένες ενώσεις είναι αποτελεσματικές για την πρόληψη και τη θεραπεία ασθενειών, όπως ασθενειών που προκαλούνται μέσω HGF. Η εφεύρεση περιλαμβάνει νέες ενώσεις, ανάλογες ενώσεις, προφάρμακα και φαρμακευτικώς αποδεκτά άλατα αυτών, φαρμακευτικές συνθέσεις και μεθόδους για την πρόληψη και τη θεραπεία ασθενειών κι άλλων παθήσεων ή καταστάσεων που ενέχουν καρκίνο κλπ. Η παρούσα εφεύρεση επίσης σχετίζεται με μεθόδους παρασκευής τέτοιων ενώσεων όπως επίσης και με ενδιάμεσες ενώσεις χρήσιμες σε τέτοιες μεθόδους. Selected compounds are effective for the prevention and treatment of diseases, such as HGF-induced diseases. The invention includes novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for the prevention and treatment of diseases and other diseases or conditions involving cancer etc. The present invention also relates to methods of preparing such compounds as well. with intermediates useful in such methods.

FUSIONED HETEROCICLIC DERIVATIVES AND METHODS OF USE

Los compuestos seleccionados resultan eficaces para la profilaxis y el tratamiento de enfermedades, tales como las enfermedades mediadas por el factor HGF. La invencion incluye novedos compuestos, analogos, profarmacos y sus sales farmaceuticamente aceptables, composiciones farmaceuticas y metodos destinados a la profilaxis y el tratamiento de enfermedades y demas dolencias o estados que se relacionan con el cancer y otroas patalogias similares.

Aryl nitrogen-containing bicyclic compounds and methods of use

The present invention comprises a new class of compounds useful for the prophylaxis and treatment of protein kinase mediated diseases, including inflammation, cancer and related conditions. The compounds have a general Formula I, wherein A1, A2, A3, B, R1, R2, R3 and R4 are defined herein. Accordingly, the invention also comprises pharmaceutical compositions comprising the compounds of the invention, methods for the prophylaxis and treatment of kinase mediated diseases using the compounds and compositions of the invention, and intermediates and processes useful for the preparation of compounds of the invention.

Aryl nitrogen-containing bicyclic compounds and their use as kinase inhibitors.

La presente invencion comprende una nueva clase de compuestos utiles para la profilaxis y tratamiento de enfermedades mediadas por proteina ciansa, incluyendo inflamacion, cancer y condiciones relacionadas. Los compuestos tienen la Formula I general, en donde Al, A2, A3, B, R1, R2, R3 y R4 se definen en la presente. En consecuencia, la invencion tambien comprende composiciones farmaceuticas que comprenden los compuestos de la invencion, metodos para la profilaxis y tratamiento de enfermedades mediadas por cinasa usando los compuestos y composiciones de la invencion, e intermediarios y procesos utiles para la preparacion de compuestos de la invencion.

Aryl nitrogen-containing bicyclic compounds and methods of use

The present invention comprises a new class of compounds useful for the prophylaxis and treatment of protein kinase mediated diseases, including inflammation, cancer and related conditions. The compounds have a general Formula I, wherein A1, A2, A3, B, R1, R2, R3 and R4 are defined herein. Accordingly, the invention also comprises pharmaceutical compositions comprising the compounds of the invention, methods for the prophylaxis and treatment of kinase mediated diseases using the compounds and compositions of the invention, and intermediates and processes useful for the preparation of compounds of the invention.

Substituted heterocycles and methods of use

Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Substituted heterocycles and methods of use

Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Heterocyclic p38 inhibitors and pharmaceutical compositions containing them

Heterocyclic compounds containing nitrogen of the general formula Ia, whose general symbols are defined in patent claims. These compounds are p38 inhibitors, that is mammalian protein kinase involved in cell proliferation, cell death and response to extracellular stimuli. Further, there are described pharmaceutical compositions comprising these compounds and use of these compounds in preparation of medicaments for treatment and prevention of various diseases.

Fused heterocyclic derivatives and methods of use as c-met inhibitors

Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Heterocyclen als proteinkinaseinhibitoren

Heterosiklik P38 inhibitörleri

Heterocyclische inhibitoren von p38

Substituted heterocycles and methods of use

Penghambat-penghambat heterosiklik p38

Pyrazolo[1,5-A]pyrimidin-7(4H)-onehistone demethylase inhibitors

The present invention relates to compounds formula (I): and to salts thereof, wherein R 1 -R 4 and A have any of the values defined in the specification, and compositions and uses thereof. The compounds are useful as inhibitors of histone demethylases, such as KDM5. Also included are pharmaceutically acceptable compositions comprising the compounds of the present invention and methods of using said compositions in the treatment of various disorders.