Adams J L, Boehm J C, Kassis S, Gorycki P D, Webb E F, Hall R, Sorenson M, Lee J C, Ayrton A, Griswold D E, Gallagher T F
SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406, USA.
Bioorg Med Chem Lett. 1998 Nov 17;8(22):3111-6. doi: 10.1016/s0960-894x(98)00549-6.
Pyrimidine analogs of the pyrimidinylimidazole 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.
