Pyrimidinylimidazole inhibitors of CSBP/p38 kinase demonstrating decreased inhibition of hepatic cytochrome P450 enzymes

JL Adams, JC Boehm, S Kassis, PD Gorycki…

Index: Adams, Jerry L.; Boehm, Jeffrey C.; Kassis, Shouki; Gorycki, Peter D.; Webb, Edward F.; Hall, Ralph; Sorenson, Margaret; Lee, John C.; Ayrton, Andrew; Griswold, Don E.; Gallagher, Timothy F. Bioorganic and Medicinal Chemistry Letters, 1998 , vol. 8, # 22 p. 3111 - 3116

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Citation Number: 144

Abstract

Pyrimidine analogs of the pyridinylimidazole class of CSBP/p38 kinase inhibitors were prepared in an effort to reduce the potent inhibition of hepatic cytochrome P450 observed for the pyridinyl compounds. The substitution of pyrimidin-4-yl, 2-methoxypyrimidin-4-yl, or 2- methylaminopyrimidin-4-yl for pyridin-4-yl effectively dissociates CSBP/p38 kinase from P450 inhibition for this series and furthermore achieves an increase in oral activity.