Pyrimidinylimidazole inhibitors of CSBP/P38 kinase demonstrating decreased inhibition of hepatic cytochrome P450 enzymes
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.
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.
p. 3111 - 3116
(2007/10/03)
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