POTENT CYCLIC UREA HIV PROTEASE INHIBITORS WITH BENZOFUSED HETEROCYCLES AS P2 P2' GROUPS/

Authors
RODGERS JD JOHNSON BL WANG HS GREENBERG RA ERICKSONVIITANEN S KLABE RM CORDOVA BC RAYNER MM LAM GN CHANG CH
Citation
Jd. Rodgers et al., POTENT CYCLIC UREA HIV PROTEASE INHIBITORS WITH BENZOFUSED HETEROCYCLES AS P2 P2' GROUPS/, Bioorganic & medicinal chemistry letters, 6(24), 1996, pp. 2919-2924
Citations number
18
Categorie Soggetti
Chemistry Inorganic & Nuclear","Chemistry Medicinal
Journal title
Bioorganic & medicinal chemistry letters → ACNP
ISSN journal
0960894X
Volume
6
Issue
24
Year of publication
1996
Pages
2919 - 2924
Database
ISI
SICI code
0960-894X(1996)6:24<2919:PCUHPI>2.0.ZU;2-V
Abstract
A series of benzofused heterocycles was examined to replace the metabo lically unstable benzyl alcohol P2/P2' groups of DMP 323 (1). Extremel y potent inhibitors of HIV protease (Ki < 0.01 nM) and excellent antiv iral activity (IC90 = 8 nM) were found. An X-ray crystal structure of benzimidazolone 5a bound to HIV protease showed H-bonds to Asp30 and a bridging water molecule to Gly48. Copyright (C) 1996 The DuPont Merck Pharmaceutical Company. Published by Elsevier Science Ltd