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Bioorg Med Chem Lett. 2010 Mar 1;20(5):1585-8. doi: 10.1016/j.bmcl.2010.01.086. Epub 2010 Jan 21.
A series of N1-heterocyclic pyrimidinediones were extensively evaluated as HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs). Inhibitor 1 is active against NNRTI-resistant viruses including RT mutant K103N. The co-crystal structure of inhibitor 1 with HIV-1 RT revealed that H-bonds are formed with K101 and K103. Efforts to improve the suboptimal pharmacokinetic profile of 1 resulted in the discovery of compound 13, which represents the lead compound in this series with improved pharmacokinetics and similar potency as inhibitor 1.
一系列 N1-杂环嘧啶二酮类化合物被广泛评估为 HIV-1 非核苷逆转录酶抑制剂（NNRTIs）。抑制剂 1 对包括 RT 突变 K103N 在内的 NNRTI 耐药病毒具有活性。抑制剂 1 与 HIV-1 RT 的共晶结构表明，它与 K101 和 K103 形成氢键。为了改善 1 的不理想药代动力学特性而进行的努力导致了化合物 13 的发现，它是该系列中具有改善的药代动力学特性和与抑制剂 1 相似的效力的先导化合物。
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