Tricyclononene carboxamide derivatives as novel anti-HIV-1 agents

被引：19

作者：

Dong, Ming-xin ^{[1
]}

Zhang, Jian ^{[3
]}

Peng, Xu-qing ^{[1
]}

Lu, Hong ^{[2
]}

Yun, Liu-hong ^{[4
]}

Jiang, Shibo ^{[2
]}

Dai, Qiu-yun ^{[1
]}

机构：

[1] Beijing Inst Biotechnol, Beijing 100071, Peoples R China

[2] New York Blood Ctr, Lindsley F Kimball Res Inst, New York, NY 10065 USA

[3] Shanghai Jiao Tong Univ, Key Lab Cell Differentiat & Apoptosis, Dept Pathophysiol, Chinese Minist Educ,Sch Med, Shanghai 200025, Peoples R China

[4] Bejing Inst Toxicol & Pharmacol, Beijing 100850, Peoples R China

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2010年 / 45卷 / 09期

关键词：

HIV-1; Inhibitor; Synthesis; Tricyclononene carboxamide derivatives; anti-HIV-1; activity; QSAR; NONPEPTIDE CCR5 ANTAGONIST; HIV FUSION INHIBITORS; GP41 CORE STRUCTURE; SMALL-MOLECULE; POTENT; IDENTIFICATION; DESIGN; COMFA;

D O I：

10.1016/j.ejmech.2010.05.070

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

By modifying the chemical structure of anti-orthopoxvirus compound ST-246, we designed and synthesized a series of tricyclononene carboxamide derivatives and tested their anti-HIV-1 activity and cytotoxicity. We found that benzoimidazol-containing compound 7g was highly effective in inhibiting HIV-1 R5 infection with an IC50 value of 0.41 mu M and a selectivity index of 292, but it exhibited no significant inhibitory activity on HIV-1 reverse transcriptase, integrase and protease. CoMFA was used to analyze structure-activity relationships with good predictive power (r(2) = 0.921; q(2) = 0.582). Moreover, the CoMFA model showed that the length of the molecule, the amide, and the amine moieties all played crucial roles in anti-HIV activity. These results suggest that 7g may serve as a lead for the development of novel anti-HIV-1 therapies. (C) 2010 Elsevier Masson SAS. All rights reserved.

引用

页码：4096 / 4103

页数：8

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