设计、合成和评估二芳基嘧啶和二芳基苯胺作为有效的非核苷 HIV-1 逆转录酶抑制剂。
Design, synthesis, and evaluation of diarylpyridines and diarylanilines as potent non-nucleoside HIV-1 reverse transcriptase inhibitors.
机构信息
Beijing Institute of Pharmacology & Toxicology, 27 Tai-Ping Road, Beijing 100850, China.
出版信息
J Med Chem. 2010 Dec 9;53(23):8287-97. doi: 10.1021/jm100738d. Epub 2010 Nov 4.
Abstract
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.
摘要
基于我们之前鉴定的非核苷类逆转录酶抑制剂（NNRTIs）的结构和活性，我们设计并合成了两组衍生物，二芳基吡啶（A）和二芳基苯胺（B），并分别在 TZM-bl 和 MT-2 细胞中测试了它们对 HIV-1NL4-3 和 IIIB 感染的抗 HIV-1 活性。结果表明，大多数化合物表现出较强的抗 HIV-1 活性，EC50 值低至纳摩尔级，其中一些化合物，如 13m、14c 和 14e，具有亚纳摩尔级的 EC50 值，在相同的测定中比依曲韦林（TMC125，1）更有效。值得注意的是，这些化合物对多耐药株的感染也具有高度有效性，表明这些化合物具有很大的潜力，可进一步开发为一类新型的 NNRTIs，具有改善的抗病毒疗效和耐药性特征。
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