Design, Synthesis, and Evaluation of Diarylpyridines and Diarylanilines as Potent Non-nucleoside HIV-1 Reverse Transcriptase Inhibitors
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- 作者：Xingtao Tian ; Bingjie Qin ; Zhiyuan Wu ; Xiaofeng Wang ; Hong Lu ; Susan L. Morris-Natschke ; Chin Ho Chen ; Shibo Jiang ; Kuo-Hsiung Lee ; Lan Xie
- 刊名：Journal of Medicinal Chemistry
- 出版年：2010
- 出版时间：December 9, 2010
- 年：2010
- 卷：53
- 期：23
- 页码：8287-8297
- 全文大小：965K
- 年卷期：v.53,no.23(December 9, 2010)
- ISSN：1520-4804
文摘
On the basis of the structures and activities of our previously identified non-nucleoside reverse transcriptase inhibitors (NNRTIs), we designed and synthesized two sets of derivatives, diarylpyridines (A) and diarylanilines (B), and tested their anti-HIV-1 activity against infection by HIV-1 NL4-3 and IIIB in TZM-bl and MT-2 cells, respectively. The results showed that most compounds exhibited potent anti-HIV-1 activity with low nanomolar EC50 values, and some of them, such as 13m, 14c, and 14e, displayed high potency with subnanomolar EC50 values, which were more potent than etravirine (TMC125, 1) in the same assays. Notably, these compounds were also highly effective against infection by multi-RTI-resistant strains, suggesting a high potential to further develop these compounds as a novel class of NNRTIs with improved antiviral efficacy and resistance profile.