Studies on the structure-activity relationship of 1,3,3,4-tetra-substituted pyrrolidine embodied CCR5 receptor antagonists. Part 1: Tuning the N-substituents

被引：5

作者：

Ben, Li ^{[2
]}

Jones, Eric Dale ^{[3
]}

Zhou, Enkun ^{[1
]}

Li, Chen ^{[4
]}

Baylis, Dean Cameron ^{[3
]}

Yu, Shanghai ^{[5
]}

Wang, Miao ^{[5
]}

He, Xing ^{[1
]}

Coates, Jonathan Alan Victor ^{[3
]}

Rhodes, David Ian ^{[3
]}

Pei, Gang ^{[2
]}

Deadman, John Joseph ^{[3
]}

Xie, Xin ^{[1
]}

Ma, Dawei ^{[5
]}

机构：

[1] Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, State Key Lab Drug Res, Shanghai 201203, Peoples R China

[2] Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China

[3] Avexa Ltd, Richmond, Vic 3121, Australia

[4] Shanghai Targetdrug Co Ltd, Shanghai 20023, Peoples R China

[5] Chinese Acad Sci, Shanghai Inst Organ Chem, State Key Lab Bioorgan & Nat Prod Chem, Shanghai 200032, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 14期

基金：

中国国家自然科学基金;

关键词：

CCR5; antagonists; Anti-HIV; SMALL-MOLECULE; HIV-1; INHIBITORS; POTENT; DISCOVERY; INFECTION; ENTRY;

D O I：

10.1016/j.bmcl.2010.05.102

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel series of CCR5 antagonists has been identified, utilizing the lead, nifeviroc, which were further modified based on bioisosteric principles. Lead optimization was pursued by balancing potential toxicity and potency. Potent analogues with low toxic properties were successfully developed by formation of urea and amide bonds at the nitrogen at position 4- of the pyrrolidine ring. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：4012 / 4014

页数：3

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