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Optimization of the Antiviral Potency and Lipophilicity of Halogenated 2,6-Diarylpyridinamines as a Novel Class of HIV-1 NNRTIS 期刊论文

编号：

05a9193c-bd74-450e-8abb-081531a0314f
作者：

Wu, ZhiYuan^[1];Liu, Na^[1];Qin, Bingjie^[1];Huang, Li^[2];Yu, Fei^[3];Qian, Keduo^[4];MorrisNatschke, Susan L.^[4];Jiang, Shibo(姜世勃)^[3,5,6]Chen, Chin Ho^[2];Lee, KuoHsiung^[4,7];Xie, Lan^[1];
语种：

English
期刊：

CHEMMEDCHEM ISSN：1860-7179 2014 年 9 卷 7 期 (1546 - 1555) ; JUL
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关键词：

anti-HIV activity antiviral agents diarylpyridinamines drug-like properties lipophilicity
摘要：

Nineteen new halogenated diarylpyridinamine (DAPA) analogues modified at the phenoxy C-ring were synthesized and evaluated for anti-HIV activity and certain drug-like properties. Ten compounds showed high anti-HIV activity (EC50<10 nm). In particular, (E)-6-(2 ''-bromo-4 ''-cyanovinyl-6 ''-methoxy) phenoxy-N-2-(4'-cyanophenyl) pyridin-2,3-diamine (8c) displayed low-nanomolar antiviral potency (3-7 nm) against wild-type and drug-resistant viral strains bearing the E138K or K101E mutations, which are associated with resistance to rilvipirine (1b). Compound 8c exhibited much lower resistance fold changes (RFC: 1.1-2.1) than 1b (RFC: 11.8-13.0). Compound 8c also exhibited better metabolic stability (in vitro half-life) than 1b in human liver microsomes, possessed low lipophilicity (clogD: 3.29; measured logP: 3.31), and had desirable lipophilic efficiency indices (LE>0.3, LLE>5, LELP<10). With balanced potency and drug-like properties, 8c merits further development as an anti-HIV drug candidate.
推荐引用方式
GB/T 7714：

Wu Zhi-Yuan,Liu Na,Qin Bingjie, et al. Optimization of the Antiviral Potency and Lipophilicity of Halogenated 2,6-Diarylpyridinamines as a Novel Class of HIV-1 NNRTIS [J].CHEMMEDCHEM,2014,9(7):1546-1555.
APA：

Wu Zhi-Yuan,Liu Na,Qin Bingjie,Huang Li,&Xie Lan.(2014).Optimization of the Antiviral Potency and Lipophilicity of Halogenated 2,6-Diarylpyridinamines as a Novel Class of HIV-1 NNRTIS .CHEMMEDCHEM,9(7):1546-1555.
MLA：

Wu Zhi-Yuan, et al. "Optimization of the Antiviral Potency and Lipophilicity of Halogenated 2,6-Diarylpyridinamines as a Novel Class of HIV-1 NNRTIS" .CHEMMEDCHEM 9,7(2014):1546-1555.

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