Design, synthesis, and biological evaluation of novel trifluoromethyl indoles as potent HIV-1 NNRTIs with an improved drug resistance profile

被引：43

作者：

Jiang, Hai-Xia ^{[1
]}

Zhuang, Dao-Min ^{[2
]}

Huang, Ying ^{[1
]}

Cao, Xing-Xin ^{[1
]}

Yao, Jian-Hua ^{[1
]}

Li, Jing-Yun ^{[2
]}

Wang, Jian-Yong ^{[3
]}

Zhang, Chen ^{[1
]}

Jiang, Biao ^{[1
,3
]}

机构：

[1] Chinese Acad Sci, Shanghai Inst Organ Chem, CAS Key Lab Synthet Chem Nat Subst, Shanghai 200032, Peoples R China

[2] Beijing Inst Microbiol & Epidemiol, State Key Lab Pathogen & Biosecur, Dept AIDS Res, Beijing, Peoples R China

[3] Chinese Acad Sci, Shanghai Adv Res Inst, Shanghai 201210, Peoples R China

来源：

ORGANIC & BIOMOLECULAR CHEMISTRY | 2014年 / 12卷 / 21期

基金：

中国国家自然科学基金;

关键词：

NONNUCLEOSIDE REVERSE-TRANSCRIPTASE; ETRAVIRINE-CONTAINING REGIMEN; INHIBITORS; MUTATIONS; DISCOVERY; TOXICITY; FAILURE; ANALOGS; TMC125; AGENTS;

D O I：

10.1039/c3ob42186d

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

novel series of trifluoromethyl indole derivatives have been designed, synthesized and evaluated for anti-HIV-1 activities in MT-2 cells. The hydrophobic constant, acute toxicity, carcinogenicity and mutagenicity were predicted. Trifluoromethyl indoles 10i and 10k showed extremely promising activities against WT HIV-1 with IC50 values at the low nanomolar level, similar to efavirenz, better than nevirapine, and also possessed higher potency towards the drug-resistant mutant strain Y181C than nevirapine. Preliminary SAR and docking studies of detailed binding mode provided some insights for discovery of more potent NNRTIs.

引用

页码：3446 / 3458

页数：13

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