Substituted alkylpyridines as P3′ ligands for the hydroxyethylpiperazine class of HIV-1 protease inhibitors: Improved pharmacokinetic profiles

Abstract As a systematic approach to develop HIV-1 protease inhibitors exhibiting desirable pharmacokinetic profiles, hydroxyethylpiperazine series of inhibitors containing various mono- or dialkyl-substituted pyridylmethyl groups have been examined. Very high enzyme inhibitory potency and antiviral activity in a whole cell assay were observed with these inhibitors and, when administered orally to dogs, selected compounds in this series exhibited prolonged half-lives compared to the non-substituted pyridylmethyl compound 1 .