ALPHA-HYDROXYAMIDE DERIVED AMINODIOLS AS POTENT INHIBITORS OF HIV PROTEASE

被引：12

作者：

AHMAD, S ^{[1
]}

ASHFAQ, A ^{[1
]}

ALAM, M ^{[1
]}

BISACCHI, GS ^{[1
]}

CHEN, P ^{[1
]}

CHENG, PTW ^{[1
]}

GREYTOK, JA ^{[1
]}

HERMSMEIER, MA ^{[1
]}

LIN, PF ^{[1
]}

LIS, KA ^{[1
]}

MERCHANT, Z ^{[1
]}

MITT, T ^{[1
]}

SKOOG, M ^{[1
]}

SPERGEL, SH ^{[1
]}

TINO, JA ^{[1
]}

VITE, GD ^{[1
]}

COLONNO, RJ ^{[1
]}

ZAHLER, R ^{[1
]}

BARRISH, JC ^{[1
]}

机构：

[1] BRISTOL MYERS SQUIBB CO,PHARMACEUT RES INST,WALLINGFORD,CT 06492

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1995年 / 5卷 / 15期

关键词：

D O I：

10.1016/0960-894X(95)00293-3

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel series of HIV protease inhibitors has been prepared. Replacement of the P-2 carbamate of compound 1 [IC50 = 125 nM] with an alpha-hydroxy amide moiety results in a significant increase in anti-HIV protease activity [e. g., compound 25a; IC50 = 15 nM]. Furthermore, isomers with (R) absolute configuration at the P-2 site show greater inhibitory activity than the corresponding (S)-isomers. A proposed binding mode based on molecular modeling is used to rationalize the structure-activity relationships.

引用

页码：1729 / 1734

页数：6

共 21 条

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