RATIONAL DESIGN OF POTENT, BIOAVAILABLE, NONPEPTIDE CYCLIC UREAS AS HIV PROTEASE INHIBITORS

被引：870

作者：

LAM, PYS ^{[1
]}

JADHAV, PK ^{[1
]}

EYERMANN, CJ ^{[1
]}

HODGE, CN ^{[1
]}

RU, Y ^{[1
]}

BACHELER, LT ^{[1
]}

MEEK, JL ^{[1
]}

OTTO, MJ ^{[1
]}

RAYNER, MM ^{[1
]}

WONG, YN ^{[1
]}

CHANG, CH ^{[1
]}

WEBER, PC ^{[1
]}

JACKSON, DA ^{[1
]}

SHARPE, TR ^{[1
]}

ERICKSONVIITANEN, S ^{[1
]}

机构：

[1] DUPONT MERCK PHARMACEUT CO, DEPT CHEM & PHYS SCI, WILMINGTON, DE 19880 USA

来源：

SCIENCE | 1994年 / 263卷 / 5145期

关键词：

D O I：

10.1126/science.8278812

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Mechanistic information and structure-based design methods have been used to design a series of nonpeptide cyclic ureas that are potent inhibitors of human immunodeficiency virus (HIV) protease and HIV replication. A fundamental feature of these inhibitors is the cyclic urea carbonyl oxygen that mimics the hydrogen-bonding features of a key structural water molecule. The success of the design in both displacing and mimicking the structural water molecule was confirmed by x-ray crystallographic studies. Highly selective, preorganized inhibitors with relatively low molecular weight and high oral bioavailability were synthesized.

引用

页码：380 / 384

页数：5

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