PYRIDYL- AND PYRIMIDINYL-SUBSTITUTED PYRROLE-, THIOPHENE- AND FURANE-DERIVATIVES AS KINASE INHIBITORS

摘要

Disclosed are 5-(2-amino-pyrimidin-4-yl)-1H-pyrrole-3-carboxylic acid amide derivatives as represented by the general formula (I), wherein: wherein G is nitrogen atom; W is NR1; R1 and R3? independently represent hydrogen or an optionally substituted group selected from alkyl, cycloalkyl, alkenyl, alkynyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heterocyclyloxy-alkyl and alkoxycarbonyl group; R2 is hydrogen or halogen atom, or an optionally substituted group selected from aryl, cycloalkyl and heterocyclyl group; R4 is hydrogen or halogen atom, or an optionally substituted alkyl or alkenyl group; R5 is hydrogen or halogen atom; R6 is hydrogen atom or the amino group NHR7; R7 is hydrogen, an optionally substituted group selected from alkyl, aryl, cycloalkyl and heterocyclyl or -CO-R1; or a pharmaceutically acceptable salt thereof. Representative compounds include 5-(2-amino-pyrimidin-4-yl)-2-phenyl-1H-pyrrole-3-carboxylic acid amide, 5-(2-amino -pyrimidin-4-y1)-2-thiophen-3-yl-1H-pyrrole-3-carboxylic acid amide, 5-(2-amino -pyrimidin-4-yl)-2-(5-methyl-thiophen-2-yl)-1H-pyrrole-3-carboxylic acid amide and 5-(2-amino-5-chloro-pyrimidin-4-yl)-2-(2-fluoro-phenyl)-1H-pyrrole-3-carboxylic acid amide. Further disclosed is a pharmaceutical composition which comprises a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof, as defined above, at least one pharmaceutically acceptable excipient, carrier and/or diluent and optionally one or more chemotherapeutic agents for treating cell proliferative disorders caused by and/or associated with an altered protein kinase activity or associated with an altered Cdc7 kinase, and particularly for the treatment of cancer, benign prostate hyperplasia, familial adenomatosis, polyposis, neuro-fibromatosis, psoriasis, vascular smooth cell proliferation associated with atherosclerosis, pulmonary fibrosis, arthritis glomerulonephritis and post-surgical stenosis and restenosis.