2', 6'-Dimethylphenoxyacetyl: A New Achiral High Affinity P3-P2 Ligand for Peptidomimetic-Based HIV Protease Inhibitors

…, V Gorys, C Grand-Maître, D Lamarre…

Index: Beaulieu, Pierre L.; Anderson, Paul C.; Cameron, Dale R.; Croteau, Gilbert; Gorys, Vida; Grand-Maitre, Chantal; Lamarre, Daniel; Liard, Francine; Paris, William; Plamondon, Louis; Soucy, Francois; Thibeault, Diane; Wernic, Dominik; Yoakim, Christiane; Pav, Susan; Tong, Liang Journal of Medicinal Chemistry, 2000 , vol. 43, # 6 p. 1094 - 1108

Full Text: HTML

Citation Number: 35

Abstract

Starting from palinavir (1), our lead HIV protease inhibitor, we have discovered a new series of truncated analogues in which the P3-P2 quinaldic-valine portion of 1 was replaced by 2', 6'-dimethylphenoxyacetyl. With EC50's in the 1-2 nM range, some of these compounds are among the most potent inhibitors of HIV replication in vitro, reported to date. One of the most promising members in this series (compound 27, BILA 2185 BS) exhibited a favorable ...