Potent cyclic urea HIV protease inhibitors with benzofused heterocycles as P2/P2′ groups

✍ Scribed by James D. Rodgers; Barry L. Johnson; Haisheng Wang; Roger A. Greenberg; Susan Erickson-Viitanen; Ronald M. Klabe; Beverly C. Cordova; Marlene M. Rayner; Gilbert N. Lam; Chong-Hwan Chang

• Publisher: Elsevier Science
• Year: 1996
• Tongue: English
• Weight: 274 KB
• Volume: 6
• Category: Article
• ISSN: 0960-894X
• DOI: 10.1016/s0960-894x(96)00531-8

✦ Synopsis

A series of benzofused heterocycles was examined to replace the metabolically unstable benzyl alcohol P2/P2' groups of DMP 323 (1). Extremely potent inhibitors of HIV protease (Ki < 0.01 nM) and excellent antiviral activity (ICgo = 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.