Substituted oxindole derivatives as protein tyrosine and as protein serine/threonine kinase inhibitors and compositions and methods of treating chemotherapy and radiation therapy side effects

摘要

Compounds of formula (I): wherein X is N, CH, CCF₃, or C(C_1-12 aliphatic); R⁴ is sulfonic acid, C_1-12 aliphatic-sulfonyl, sulfonyl-C_1-12 aliphatic, C_1-12 aliphatic-sulfonyl-C_1-6 aliphatic, C_1-6 aliphatic-amino, R⁷-sulfonyl, R⁷ sulfonyl-C_1-12 aliphatic, R⁷-aminosulfonyl, R⁷-aminosulfonyl-C_1-12 aliphatic, R⁷-sulfonylamino, R⁷-sulfonylamino-C_1-12 aliphatic, aminosulfonylamino, di-C_1-12 aliphatic amino, di-C_1-12 aliphatic aminocarbonyl, di-C_1-12 aliphatic aminosulfonyl, di-C_1-12 aliphatic amino, di-C_1-12 aliphatic aminocarbonyl, di-C_1-12 aliphatic aminosulfonyl-C_1-12 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 cancer chemotherapy or radiotherapy.