Abstract: The present invention is related to oxindole derivatives, compositions containing the same, and methods of use and manufacture of the same. Such compounds generally are useful pharmacologically as agents in those disease states alleviated by the alteration of mitogen activated signaling pathways in general, and in particular in the inhibition or antagonism of protein kinases, which pathologically involve aberrant cellular proliferation. Such disease states include tumor growth, restenosis, atherosclerosis, pain and thrombosis. In particular, the present invention relates to a series of substituted oxindole compounds, which exhibit Trk family protein tyrosine kinase inhibition, and which are useful in cancer therapy and chronic pain indications.

Abstract: Substituted aza-oxindole derivatives useful as cyclin dependent kinase 11 inhibitors, for preventing/reducing the severity of epithelial cytotoxicity side-effects (e.g., alopecia, plantar-palmar syndrome, mucositis) induced by chemoptherapy and/or radiation therapy in a patient receiving such therapy.

Abstract: Compounds of formula (I): wherein X is N, CH, CCF3, or C(C1-12 aliphatic); R4 is sulfonic acid, C1-12 aliphatic-sulfonyl, sulfonyl-C1-12 aliphatic, C1-12 aliphatic-sulfonyl-C1-6 aliphatic, C1-6 aliphatic-amino, R7-sulfonyl, R7 sulfonyl-C1-12 aliphatic, R7-aminosulfonyl, R7aminosulfonyl-C1-12 aliphatic, R7-sulfonylamino, R7-sulfonylamino-C1-12 aliphatic, aminosulfonylamino, di-C1-12 aliphatic amino, di-C1-12 aliphatic aminocarbonyl, di-C1-12 aliphatic aminosulfonyl, di-C1-12 aliphatic amino, di-C1-12 aliphatic aminocarbonyl, di-C1-12 aliphatic aminosulfonyl-C1-12 aliphatic, (R8)1-3-Arylamino, (R8)1-3-Arylsulfonyl, (R8)1-3-Aryl-aminosulfonyl, (R8)1-3-Aryl-sulfonylamino, Het-amino, Het-sulfonyl, Het-aminosulfonyl, aminoiminoamino, or aminoiminoaminosulfonyl, R5 is hydrogen; and further wherein R4 and R5 are optionally joined to form a fused ring, pharmaceutical formulations comprising them and their use in therapy, especially in the treatment of diseases mediated by CDK2 activity, such as alopecia induced by can

Abstract: Compounds of formula (I): wherein X is N, CH, CCF3, or C(C1-12 aliphatic); R4 is sulfonic acid, C1-12 aliphatic-sulfonyl, sulfonyl-C1-12 aliphatic, C1-12 aliphatic-sulfonyl-C1-6 aliphatic, C1-6 aliphatic-amino, R7-sulfonyl, R7 sulfonyl-C1-12 aliphatic, R7-aminosulfonyl, R7-aminosulfonyl-C1-12 aliphatic, R7-sulfonylamino, R7-sulfonylamino-C1-12 aliphatic, aminosulfonylamino, di-C1-12 aliphatic amino, di-C1-12 aliphatic aminocarbonyl, di-C1-12 aliphatic aminosulfonyl, di-C1-12 aliphatic amino, di-C1-12 aliphatic aminocarbonyl, di-C1-12 aliphatic aminosulfonyl-C1-12 aliphatic, (R8)1-3-Arylamino, (R8)1-3-Arylsulfonyl, (R8)1-3-Aryl-aminosulfonyl, (R8)1-3-Aryl-sulfonylamino, Het-amino, Het-sulfonyl, Het-aminosulfonyl, aminoiminoamino, or aminoiminoaminosulfonyl, R5 is hydrogen; and further wherein R4 and R5 are optionally joined to form a fused ring, pharmaceutical formulations comprising them and their use in therapy, especially in the treatment of diseases mediated by CDK2 activity, such as alopecia induced by ca

Abstract: Compounds of formula (I): wherein X is N, CH, CCF3, or C(C1-12 aliphatic); R4 is sulfonic acid, C1-12 aliphatic-sulfonyl, sulfonyl-C1-12 aliphatic, C1-12 aliphatic-sulfonyl-C1-6 aliphatic, C1-6 aliphatic-amino, R7-sulfonyl, R7 sulfonyl-C1-12 aliphatic, R7-aminosulfonyl, R7-aminosulfonyl-C1-12 aliphatic, R7-sulfonylamino, R7-sulfonylamino-C1-12 aliphatic, aminosulfonylamino, di-C1-12 aliphatic amino, di-C1-12 aliphatic aminocarbonyl, di-Cl1-12 aliphatic aminosulfonyl, di-C1-12 aliphatic amino, di-C1-12 aliphatic aminocarbonyl, di-C1-12 aliphatic aminosulfonyl-C1-12 aliphatic, (R8)1-3-Arylamino, (R8)1-3-Arylsulfonyl, (R8)1-3-Aryl-aminosulfonyl, (R8)1-3-Aryl-sulfonylamino, Het-amino, Het-sulfonyl, Het-aminosulfonyl, aminoiminoamino, or aminoiminoaminosulfonyl, R5 is hydmogen; and further wherein R4 and R5 are optionally joined to form a fused ring, pharmaceutical formulations comprising them and their use in therapy, especially in the treatment of diseases mediated by CDK2 activity, such as alopecia induced by c

Abstract: Compounds of formula (I): wherein X is N, CH, CCF3, or C(C1-12 aliphatic); R4 is sulfonic acid, C1-12 aliphatic-sulfonyl, sulfonyl-C1-12 aliphatic, C1-12 aliphatic-sulfonyl-C1-6 aliphatic, C1-6 aliphatic-amino, R7-sulfonyl, R7 sulfonyl-C1-12 aliphatic, R7-aminosulfonyl, R7-aminosulfonyl-C1-12 aliphatic, R7-sulfonylamino, R7-sulfonylamino-C1-12 aliphatic, aminosulfonylamino, di-C1-12 aliphatic amino, di-C1-12 aliphatic aminocarbonyl, di-C1-12 aliphatic aminosulfonyl, di-C1-12 aliphatic amino, di-C1-12 aliphatic aminocarbonyl, di-C1-12 aliphatic aminosulfonyl-C1-12 aliphatic, (R8)1-3-Arylamino, (R8)1-3-Arylsulfonyl, (R8)1-3-Aryl-aminosulfonyl, (R8)1-3-Aryl-sulfonylamino, Het-amino, Het-sulfonyl, Het-aminosulfonyl, aminoiminoamino, or aminoiminoaminosulfonyl, R5 is hydrogen; and further wherein R4 and R5 are optionally joined to form a fused ring, pharmaceutical formulations comprising them and their use in therapy, especially in the treatment of diseases mediated by CDK2 activity, such as alopecia induced by ca

Abstract: The present invention relates generally to novel substituted oxindole compounds and compositions. Such compounds and compositions have utility as pharmacological agents in treating diseases or conditions alleviated by the inhibition or antagonism of protein kinase activated signalling pathways. In particular, the present invention relates to a series of substituted oxindole compounds, which exhibit protein tyrosine kinase and protein serine/threonine kinase inhibition, and which are useful in inhibiting tumor growth via inhibition of such kinases as well as protecting a patient undergoing chemotherapy from chemotherapy induced alopecia.

Abstract: Compounds of general formula (I) wherein: R1 is H or optionally joined with R2 to form a fused ring selected from the group consisting of five to ten membered aryl, heteroaryl or heterocyclyl rings, R2 and R3 are independently H, HET, aryl, C1-12 aliphatic, CN, NO2, halogen, R10, —OR10, —SR10, —S(O)R10, —SO2R10, —NR10R11, —NR11R12, —NR12COR11, —NR12CO2R11, —NR12CONR11R12, —NO12SO2R11, —NR12C(NR 12)NHR11, —COR11, —CO2R11, —CONR12R11, —SO2NR12R11, —OCONR12R11, C(NR12)NR12R11, R6 and R7 are independently halogen, CN, NO2, —CONR10R11, —SO2NR10R11, —NR10R11, or —OR11, where R10 and R11 are as defined below; R8 is OH, NHSO2R12 or NHCOCF3; and their use in therapy, especially in the treatment of disorders mediated by cRaf1 kinase.