HIV-1 PROTEASE INHIBITORS BASED ON HYDROXYETHYLENE DIPEPTIDE ISOSTERES - AN INVESTIGATION INTO THE ROLE OF THE P1' SIDE-CHAIN ON STRUCTURE ACTIVITY

被引：40

作者：

YOUNG, SD

PAYNE, LS

THOMPSON, WJ

GAFFIN, N

LYLE, TA

BRITCHER, SF

GRAHAM, SL

SCHULTZ, TH

DEANA, AA

DARKE, PL

ZUGAY, J

SCHLEIF, WA

QUINTERO, JC

EMINI, EA

ANDERSON, PS

HUFF, JR

机构：

[1] MERCK SHARP & DOHME LTD,DEPT MOLEC BIOL,W POINT,PA 19486

[2] MERCK SHARP & DOHME LTD,DEPT VIRUS & CELL BIOL,W POINT,PA 19486

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1992年 / 35卷 / 10期

关键词：

D O I：

10.1021/jm00088a004

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A systematic investigation was undertaken to determine the role of the P1' sidechain in a series of hydroxyethylene isostere based inhibitors of HIV-1 protease. Substitution and homologation of the benzyl P1' side chain of the Phe-Phe isostere based pseudo peptides 1 (L-682,679) and 2 (L-685,434) with various heteroalkyl groups leads to a series of extremely potent inhibitors of the enzyme. Several examples of the most potent inhibitors were very effective in an ex vivo cell based viral spread assay using human H9 T-lymphocytes and the IIIb isolate of HIV-1. Compound 19 is 120 times more potent than 1 and 16 times more potent than 2 in inhibiting the spread of infection in this assay.

引用

页码：1702 / 1709

页数：8

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