Abstract: The present invention is related to oxindole derivatives of structure (I), 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 exhihit Trk family protein tyrosine kinase inhibition, and which are useful in cancer therapy and chronic pain indications.

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 formula (I) or salts thereof, wherein the dotted line represents a single or double bond, R1 is alkyl or amino optionally substituted by alkyl, alkanoyl or benzyl group; R2, R3, R4 and R5 are the same or different and each is selected from hydrogen, phenyl, halo, nitro, a group S(O)nR8 wherein n is the integer 0, 1 or 2 and R8 is halo or alkyl or a group NR9R10 wherein R9 and R10 are both hydrogen, a group NR11R12 wherein R11 and R12 are the same or different and each is hydrogen or alkyl, a group OR13 wherein R13 is hydrogen or C1-4 of alkyl optionally substituted by halo; a C1-4 aliphatic group optionally substituted by a group OR14 or NR14R15 wherein R14 and R15 are the same or different and each is hydrogen or alkyl; or two of R2 to R5 are linked together to form a benzo group, or one of R2 to R5 is a group X—Y—R16 wherein X is CH2, NR17, CO or S(O)m and Y is CH2, NR17, O or S(O)m, or X—Y is O, NR17, —CH═CH— or N═N—, are disclosed as pharmacologic

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.

Abstract: A family of compounds having the general structural formula where W is a reverse hydroxamic acid group, and R1, R2, R3, R4, R5 and R6 are as described in the specification, or a pharmaceutically acceptable salt, solvate, biohydrolyzable ester, biohydrolyzable amide, affinity reagent, or prodrug thereof. Also described are methods for their preparation, pharmaceutical compositions including such compounds and their use in medicine.

Abstract: Compounds of the formula (I) or salts thereof, ##STR1## wherein the dotted line represents a single or double bond, R.sup.1 is alkyl or amino optionally substituted by alkyl, alkanoyl or benzyl group: R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are the same or different and each is selected from hydrogen, phenyl, halo, nitro, a group S(O).sub.n R.sup.8 wherein n is the integer 0, 1 or 2 and R.sup.8 is halo or alkyl or a group NR.sup.9 R.sup.10 are both hydrogen, a group NR.sup.11 R.sup.12 wherein R.sup.11 and R.sup.12 are the same or different and each is hydrogen or alkyl, a group OR.sup.13 wherein R.sup.13 is hydrogen or C.sub.1-4 alkyl substituted by halo; a C.sub.1-4 aliphatic group optionally substituted by a group OR.sup.14 or NR.sup.14 R.sup.15 wherein R.sup.14 and R.sup.15 are the same or different and each is hydrogen or alkyl; ot two of R.sup.2 to R.sup.5 are linked together to form a benzp group, one of R.sup.2 to R.sup.3 is a group X--Y--R.sup.16 wherein X is CH.sub.2, NR.sup.17, CO, or S(O).sub.

Abstract: The present invention relates to benzoquinazoline thymidylate synthase inhibitors, processes for preparing them and pharmaceutical formulations containing them.

Abstract: The present invention relates to bezoquinazoline thymidylate synthase inhibitors, to pharmaceutical formulations containing them and to their use in medicine.