HIV-1 protease inhibitors containing an N-hydroxyamino acid core structure

Two series of peptidomimetics containing an N-hydroxyamino acid core struct ure were prepared by mixed solution solid-phase synthesis and tested for in hibitory activity against the human immunodeficirncy virus (HIV-1) protease (Pr) and the virus in cell culture. In general. N-hydroxy Gly containing p seudopeptides displayed modest HIV Pr inhibition (IC(50)greater than or equ al to 930 nM). In the N-hydroxy Phr derivatives. Fmoc-Phe-psi [CO-N(OH)]-Ph e-Pro-NHtBu was the best inhibitor of the series (IC50 = 144 nM) showing sa tisfactory inhibition or HIV replication in cell culture (ED50 = 98 nM) and remarkable stability against cell culture and plasma enzymes. (C) 2001 Els evier Science Ltd. All rights reserved.