Abstract: Disclosed herein are heterocyclic compounds and compositions useful in the treatment of ITK mediated diseases, such as inflammation, having the structure of Formula (I): wherein R1, R2, and X are as defined in the detailed description. Methods of inhibition of ITK activity in a human or animal subject are also provided.

Abstract: Disclosed herein are arylpyridinone compounds and compositions useful in the treatment of ITK mediated diseases, such as inflammation, having the structure of Formula (I): wherein R1, R2, and X are as defined in the detailed description. Methods of inhibition of ITK activity in a human or animal subject are also provided.

Abstract: Disclosed herein are heterocyclic compounds and compositions useful in the treatment of ITK mediated diseases, such as inflammation, having the structure of Formula (I): wherein R1, R2, and X are as defined in the detailed description. Methods of inhibition of ITK activity in a human or animal subject are also provided.

Abstract: Disclosed herein are heterocyclic compounds and compositions useful in the treatment of ITK mediated diseases, such as inflammation, having the structure of Formula (I): wherein R1, R2, and X are as defined in the detailed description. Methods of inhibition of ITK activity in a human or animal subject are also provided.

Abstract: The present disclosure provides methyl/fluoro-pyridinyl-methoxy substituted pyridinone-pyridinyl compounds and fluoro-pyrimidinyl-methoxy substituted pyridinone-pyridinyl compounds useful in the treatment of p38 kinase mediated diseases, such as lymphoma and auto-inflammatory disease, including rheumatoid arthritis, having the structure of Formula (I): wherein R1, R2, R3, R4, R5 and X are as defined in the detailed description; pharmaceutical compositions comprising at least one of the compounds; and methods for treating p38 kinase mediated diseases using the compound.

Abstract: Disclosed herein are substituted pyrrolopyridine and pyrrolopyrazine compounds and compositions useful in the treatment of TAK mediated diseases, such as cancer, having the structure of Formula (I): wherein R1, R2, R3, and R4 are as defined in the detailed description. Methods of modulation of TAK activity in a human or animal subject are also provided, providing therapeutic benefit to subjects with disease conditions, especially cancer.

Abstract: Disclosed herein are heterocyclic compounds and compositions useful in the treatment of ITK mediated diseases, such as inflammation, having the structure of Formula (I): wherein R1, R2, and X are as defined in the detailed description. Methods of inhibition of ITK activity in a human or animal subject are also provided.

Abstract: The present disclosure provides methyl/difluorophenyl-methoxy substituted pyridinone-pyridinyl compounds, methyl-pyridinyl-methoxy substituted pyridinone-pyridinyl compounds, and methyl-pyrimidinyl-methoxy substituted pyridinone-pyridinyl compounds useful in the treatment of p38 kinase mediated diseases, such as lymphoma and auto-inflammatory disease, having the structure of Formula (I): wherein R1, R2, R3 and X are as defined in the detailed description; pharmaceutical compositions comprising at least one of the compounds; and methods for treating p38 kinase mediated diseases using the compound.

Abstract: The present disclosure provides methyl/fluoro-pyridinyl-methoxy substituted pyridinone-pyridinyl compounds and fluoro-pyrimidinyl-methoxy substituted pyridinone-pyridinyl compounds useful in the treatment of p38 kinase mediated diseases, such as lymphoma and auto-inflammatory disease, including rheumatoid arthritis, having the structure of Formula (I): wherein R1, R2, R3, R4, R5 and X are as defined in the detailed description; pharmaceutical compositions comprising at least one of the compounds; and methods for treating p38 kinase mediated diseases using the compound.

Abstract: The present disclosure provides methyl/fluoro-pyridinyl-methoxy substituted pyridinone-pyridinyl compounds and fluoro-pyrimidinyl-methoxy substituted pyridinone-pyridinyl compounds useful in the treatment of p38 kinase mediated diseases, such as lymphoma and auto-inflammatory disease, including rheumatoid arthritis, having the structure of Formula (I): wherein R1, R2, R3, R4, R5 and X are as defined in the detailed description; pharmaceutical compositions comprising at least one of the compounds; and methods for treating p38 kinase mediated diseases using the compound.

Abstract: Disclosed herein are substituted pyrrolopyridine and pyrrolopyrazine compounds and compositions useful in the treatment of TAK mediated diseases, such as cancer, having the structure of Formula (I): wherein R1, R2, R3, and R4 are as defined in the detailed description. Methods of modulation of TAK activity in a human or animal subject are also provided, providing therapeutic benefit to subjects with disease conditions, especially cancer.

Abstract: The present disclosure provides pyrimidinone-phenyl-pyrimidinyl compounds useful in the treatment of p38 kinase mediated diseases, such as lymphoma and inflammatory disease, having the structure of Formula (I): wherein R1, R2, R3, R4 and R5 are as defined in the detailed description; pharmaceutical compositions comprising at least one of the compounds; and methods for treating p38 kinase mediated diseases using the compound.

Abstract: The present disclosure provides methyl/fluoro-pyridinyl-methoxy substituted pyridinone-pyridinyl compounds and fluoro-pyrimidinyl-methoxy substituted pyridinone-pyridinyl compounds useful in the treatment of p38 kinase mediated diseases, such as lymphoma and auto-inflammatory disease, including rheumatoid arthritis, having the structure of Formula (I): wherein R1, R2, R3, R4, R5 and X are as defined in the detailed description; pharmaceutical compositions comprising at least one of the compounds; and methods for treating p38 kinase mediated diseases using the compound.

Abstract: The present disclosure provides pyridine urea compounds useful in the treatment of p38 kinase mediated diseases, such as lymphoma and auto-inflammatory disease, having the structure of Formula (I): wherein R1, R2, R3, R4, R5, V and W are as defined in the detailed description; pharmaceutical compositions comprising at least one of the compounds; and methods for treating p38 kinase mediated diseases using the compound.

Abstract: The present disclosure provides methyl/difluorophenyl-methoxy substituted pyridinone-pyridinyl compounds, methyl-pyridinyl-methoxy substituted pyridinone-pyridinyl compounds, and methyl-pyrimidinyl-methoxy substituted pyridinone-pyridinyl compounds useful in the treatment of p38 kinase mediated diseases, such as lymphoma and auto-inflammatory disease, having the structure of Formula (I): wherein R1, R2, R3 and X are as defined in the detailed description; pharmaceutical compositions comprising at least one of the compounds; and methods for treating p38 kinase mediated diseases using the compound.

Abstract: The present disclosure provides pyridine urea compounds useful in the treatment of p38 kinase mediated diseases, such as lymphoma and auto-inflammatory disease, having the structure of Formula (I): wherein R1, R2, R3, R4, R5, V and W are as defined in the detailed description; pharmaceutical compositions comprising at least one of the compounds; and methods for treating p38 kinase mediated diseases using the compound.

Abstract: This invention is directed generally to proteinase (also known as “protease”) inhibitors, and, more particularly, to piperidinyl- and piperazinyl-sulfonylmethyl hydroxamic acids that, inter alia, inhibit matrix metalloproteinase (also known as “matrix metalloprotease” or “MMP”) activity and/or aggrecanase activity. Such hydroxamic acids generally correspond in structure to the following formula: (wherein A1, A2, Y, E1, E2, E3, and Rx are as defined in this specification), and further include salts of such compounds. This invention also is directed to compositions of such hydroxamic acids, intermediates for the syntheses of such hydroxamic acids, methods for making such hydroxamic acids, and methods for treating conditions (particularly pathological conditions) associated with MMP activity and/or aggrecanase activity.

Abstract: This invention is directed to aromatic sulfone hydroxamic acids (including hydroxamates) and salts thereof that, inter alia, inhibit matrix metalloproteinase (also known as “matrix metalloprotease” or “MMP”) activity and/or aggrecanase activity. This invention also is directed to a prevention or treatment method that comprises administering such a compound or salt in an MMP-inhibiting and/or aggrecanase-inhibiting effective amount to an animal, particularly a mammal having (or disposed to having) a pathological condition associated with MMP and/or aggrecanase activity.

Abstract: A treatment process is disclosed that comprises administering an effective amount of an aromatic sulfone hydroxamic acid that exhibits excellent inhibitory activity of one or more matrix metalloprotease (MMP) enzymes, such as MMP-2, MMP-9, and MMP-13, while exhibiting substantially less inhibition at least of MMP-1 to a host having a condition associated with pathological matrix metalloprotease activity. The administered enzyme inhibitor corresponds in structure to formula (I), below, or a pharmaceutically acceptable salt thereof, wherein R1 and R2 are both hydrido or R1 and R2 together with the atoms to which they are bonded form a 5- to 8-membered ring containing one, two, or three heteroatoms in the ring that are oxygen, sulfur, or nitrogen. R3 in formula (I) is an optionally substituted aryl or optionally substituted heteroaryl radical.

Abstract: A treatment process is disclosed that comprises administering an effective amount of an aromatic sulfone hydroxamic acid that exhibits excellent inhibitory activity of one or more matrix metalloprotease (MMP) enzymes, such as MMP-2, MMP-9 and MMP-13, while exhibiting substantially less inhibition at least of MMP-1 to a host having a condition associated with pathological matrix metalloprotease activity. Also disclosed are metalloprotease inhibitor compounds having those selective activities, processes for manufacture of such compounds and pharmaceutical compositions using an inhibitor.