Bioorganic & Medicinal Chemistry Letters ( IF 2.5 ) Pub Date : 2018-03-05 , DOI: 10.1016/j.bmcl.2018.03.012 Boshi Huang , Xinhao Liu , Ye Tian , Dongwei Kang , Zhongxia Zhou , Dirk Daelemans , Erik De Clercq , Christophe Pannecouque , Peng Zhan , Xinyong Liu
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:
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。