In search of a novel anti-HIV drug:: Multidisciplinary coordination in the discovery of 4-[[4-[[4-[(1E)-2-cyanoethenyl]-2,6dimethylphenyl] amino]-2-pyrimidinyl]amino]-benzonitrile (R278474, rilpivirine)
In search of a novel anti-HIV drug:: Multidisciplinary coordination in the discovery of 4-[[4-[[4-[(1E)-2-cyanoethenyl]-2,6dimethylphenyl] amino]-2-pyrimidinyl]amino]-benzonitrile (R278474, rilpivirine)
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DOI：
10.1021/jm040840e
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发表时间：
2005-03-24
影响因子：
7.3
通讯作者：
Stoffels, P
中科院分区：
文献类型：
--
作者：
Janssen, PAJ;Lewi, PJ;Stoffels, P
理想情况下，一种抗艾滋病毒药物应该：(1)对野生型和突变型艾滋病毒具有高度活性，而不允许突破；(2)口服生物利用度高，消除半衰期长，低剂量每日口服一次；（三）不良影响极小；(4)易于合成和配制。R278474是一种新的二酰基嘧啶（DAPY）非核苷逆转录酶抑制剂（NNRTI），似乎符合这些标准，适合用于HIV-1感染的高依从性口服治疗。R278474的发现是药物化学家、病毒学家、晶体学家、分子建模师、毒理学家、分析化学家、药剂师和其他许多人共同努力的结果。
Ideally, an anti-HIV drug should (1) be highly active against wild-type and mutant HIV without allowing breakthrough; (2) have high oral bioavailability and long elimination half-life, allowing once-daily oral treatment at low doses; (3) have minimal adverse effects; and (4) be easy to synthesize and formulate. R278474, a new diarylpyrimidine (DAPY) non-nucleoside reverse transcriptase inhibitor (NNRTI), appears to meet these criteria and to be suitable for high compliance oral treatment of HIV-1 infection. The discovery of R278474 was the result of a coordinated multidisciplinary effort involving medicinal chemists, virologists, crystallographers, molecular modelers, toxicologists, analytical chemists, pharmacists, and many others.