DESIGN AND SYNTHESIS OF NONPEPTIDE PEPTIDOMIMETIC INHIBITORS OF RENIN

被引：28

作者：

SMITH, AB ^{[1
]}

AKAISHI, R ^{[1
]}

JONES, DR ^{[1
]}

KEENAN, TP ^{[1
]}

GUZMAN, MC ^{[1
]}

HOLCOMB, RC ^{[1
]}

SPRENGELER, PA ^{[1
]}

WOOD, JL ^{[1
]}

HIRSCHMANN, R ^{[1
]}

HOLLOWAY, MK ^{[1
]}

机构：

[1] MERCK SHARP & DOHME LTD,RES LABS,DEPT MOLEC SYST,W POINT,PA 19486

来源：

BIOPOLYMERS | 1995年 / 37卷 / 01期

关键词：

D O I：

10.1002/bip.360370106

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The desire to replace the amide backbone of renin inhibitors with a new scaffold led us to explore vinylogous amides (enaminones). An initial attempt proved unsuccessful, a result explained after the fact via docking experiments. Based on this lesson, we designed a different vinylogous amide scaffold which incorporated one or more pyrrolinone rings into the backbone. Three of the four compounds gave IC(50)s in the 0.6 to 18 mu M range. These compounds did not inhibit HIV-1 protease. Taken together, the results reported herein provide insights into the role of hydrogen bonding and steric interactions for binding to renin. (C) 1994 John Wiley & Sons, Inc.

引用

页码：29 / 53

页数：25

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