Structure-activity relationships of diamine inhibitors of cytochrome P450 (CYP) 3A as novel pharmacoenhancers. Part II: P2/P3 region and discovery of cobicistat (GS-9350)

A series of novel 1,4-diamine-based CYP3A inhibitors were designed and evaluated. A potent and selective inhibitor of CYP3A, cobicistat (35, GS-9350) was discovered as a novel pharmacoenhancer.