Combinatorial Diversification of Indinavir: In Vivo Mixture Dosing of an HIV Protease Inhibitor Library

Abstract An efficient combination solution-phase/solid-phase route enabling the diversification of the P 1 ′, P 2 ′, and P 3 subsites of indinavir has been established. The synthetic sequence can facilitate the rapid generation of HIV protease inhibitors possessing more favorable pharmacokinetic properties as well as enhanced potencies. Multiple compound dosing in vivo may also accelerate the identification of potential drug candidates.