In the present work, we described the synthesis, antiviral profiles and metabolic stability in human plasma of compound 6, a potential carbonate prodrug of HIV-1 NNRTI drug candidate RDEA427. Compound 6 was found to inhibit the wild-type (WT) and K103N/Y181C double mutant HIV-1 strains at nano- and submicromolar concentrations, respectively. Moreover, it displayed potent HIV-1 reverse transcriptase inhibitory activity (IC₅₀ = 0.264 μM). Further stability test in human plasma showed that 6 could release its active form RDEA427 in a linearly time-independent manner, possibly acting as a potential prodrug.

中文翻译：

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首次发现具有抗HIV-1 K103N / Y181C双突变株亚微摩尔抑制活性的NNRTI候选药物RDEA427的潜在碳酸盐前药

在当前的工作中，我们描述了化合物6的合成，抗病毒谱和在人体血浆中的代谢稳定性，化合物6是HIV-1 NNRTI候选药物RDEA427的潜在碳酸盐前药。发现化合物6分别在纳摩尔和亚微摩尔浓度下抑制野生型（WT）和K103N / Y181C双重突变HIV-1菌株。此外，它显示出有效的HIV-1逆转录酶抑制活性（IC ₅₀  = 0.264μM）。在人体血浆中的进一步稳定性测试表明，6可以线性独立于时间的方式释放RDEA427的活性形式，可能是潜在的前药。