Potent non-nucleoside inhibitors of the measles virus RNA-dependent RNA polymerase complex
Potent non-nucleoside inhibitors of the measles virus RNA-dependent RNA polymerase complex
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DOI：
10.1021/jm701239a
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发表时间：
2008-07-10
影响因子：
7.3
通讯作者：
Snyder, James P.
中科院分区：
文献类型：
--
作者：
Sun, Aiming;Yoon, Jeong-Joong;Snyder, James P.
麻疹病毒（MV）是已知的最具传染性的病原体之一。尽管存在疫苗，但每年约有35万人死于MV或相关并发症。抗麻疹化合物可以减少这些统计数据，并提供一种补充疫苗治疗的疗法。我们最近描述了针对MV感染的细胞的高通量筛选命中化合物1（16677），其具有通过抑制病毒的RNA依赖性RNA聚合酶复合物（RdRp）的作用在250 nM下消除病毒繁殖的能力。化合物1-甲基-3-（三氟甲基）-N-[4-磺酰基苯基]-1H-吡唑-5-甲酰胺，1在1，2-吡唑环上带有关键的CF 3部分。阐述的初步结构活性（SAR）的研究，目前的工作提出了合成和SAR的范围更广的低纳摩尔nonpeptidic MV抑制剂和推测的CF 3功能的作用。
Measles virus (MV) is one of the most infectious pathogens known. In spite of the existence of a vaccine, approximately 350000 deaths/year result from MV or associated complications. Antimeasles compounds Could conceivably diminish these statistics and provide a therapy that complements vaccine treatment. We recently described a high-throughput screening hit compound 1 (16677) against MV-infected cells with the capacity to eliminate viral reproduction at 250 nM by inhibiting the action of the virus's RNA-dependent RNA polymerase complex (RdRp). The compound, 1-methyl-3-(trifluoroi-nethyl)-N-[4-sulfonylphenyl]-1H-pyrazole-5-carboxamide, 1 carries a critical CF3 moiety on the 1,2-pyrazole ring. Elaborating on the preliminary structure-activity (SAR) study, the present work presents the synthesis and SAR of a much broader range of low nanomolar nonpeptidic MV inhibitors and speculates on the role of the CF3 functionality.