PYRIDO [2,3-D] PYRIMIDINES AND 4-AMINOPYRIMIDINES AS INHIBITORS OF CELLULAR PROLIFERATION

摘要

This invention provides pyridopyrimidines and 4-aminopyrimidines that are useful for treating cell proliferatives disorders, such as cancer and restenosis. We have now discovered a group of 7,8-dihydro-2-(amino and thio)pyrido[2,3-d]pyrimidines and 2,4-diaminopyrimidines that are potent inhibitors of cyclin-dependent kinases (cdks) and growth factor-mediated kinases. The compounds are readily synthesized and can be administered by a variety of routes, including orally, and have sufficient bioavailability. This invention provides compounds of Formula (I) and Formula (II) where W is NH, S, SO, or SO2, R<1> includes phenyl and substituted phenyl, R<2> includes alkyl and cycloalkyl, R<3> includes alkyl and hydrogen, R<8> and R<9> include hydrogen and alkyl, and Z is carboxy. This invention also provides pharmaceutical formulations comprising a compound of Formula (I or II) together with a pharmaceutically acceptable carrier, diluent, or excipient therefor.