Cycloalkylpiperazines as HIV-1 protease inhibitors: enhanced oral absorption

Abstract

A series of HIV-1 protease inhibitors containing various acyclic or cyclic alkylpiperazine derivatives were prepared. They exhibit excellent potency in the enzyme inhibition assay and in a whole cell assay demonstrating the lowest CIC 95 IC 50 ratios observed in the hydroxyethylpiperazine class of inhibitors. Oral pharmacokinetic studies in dogs have been carried out on two compounds in this series and an excellent oral absorption profile was obtained for inhibitor 13, which possesses a cyclopropylpiperazine unit.