There is still an urgent need to develop nonnucleoside reverse transcriptase (RT) inhibitors (NNRTI) with a high-genetic barrier to resistance that facilitate patient adherence and allow durable suppression of HIV-1 replication. In this study, we describe the synthesis of a novel series of N-aminoimidazole (NAIM) analogs. Each of the NAIM analogs display potent activity against wild-type recombinant purified HIV-1 RT as well as RTs containing the K103N or Y181C resistance mutations. The analogs, however, do not exhibit significant antiviral activity in cell culture and were, in general, cytotoxic. Nevertheless, these data suggest that the NAIM backbone may provide a suitable scaffold from which inhibitors active against NNRTI-resistant HIV-1 could be developed.

中文翻译：

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一系列新型氨基咪唑类似物的合成和抗 HIV-1 活性

仍然迫切需要开发具有高遗传耐药屏障的非核苷逆转录酶 (RT) 抑制剂 (NNRTI)，以促进患者依从性并持久抑制 HIV-1 复制。在这项研究中，我们描述了一系列新型 N-氨基咪唑 (NAIM) 类似物的合成。每个 NAIM 类似物都显示出针对野生型重组纯化 HIV-1 RT 以及含有 K103N 或 Y181C 抗性突变的 RT 的有效活性。然而，类似物在细胞培养物中不表现出显着的抗病毒活性，并且通常具有细胞毒性。尽管如此，这些数据表明 NAIM 骨架可以提供合适的支架，从中可以开发出对 NNRTI 抗性 HIV-1 有活性的抑制剂。