Synthesis and pharmacokinetics of potent carbamate HIV-1 protease inhibitors containing novel high affinity hydroxyethylamine isosteres

Abstract Using the hydroxyethylamine isosteres 1 and 2 containing the novel cis -octahydrothienopyridine moiety, substantial enhancement of binding potencies for HIV-1 protease inhibitors which incorporate carbamate linked heterocyclic P 2 ligands has been realized. This increase in binding has led to a very potent antiviral compound (LY326188). The pharmacokinetics of selected derivatives are detailed in this report.