Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, 250012 Jinan, Shandong, P.R.China.
Eur J Med Chem. 2011 Oct;46(10):5039-45. doi: 10.1016/j.ejmech.2011.08.011. Epub 2011 Aug 12.
The development of novel HIV-1 NNRTIs offers the possibility of generating novel structures with increased potency. Based on the bioisosteric principle, a novel series of 2-(2-(2,4-dichlorophenyl)-2H-1,2,4-triazol-3-ylthio)-N-arylacetamide derivatives were designed, synthesized using a simple and efficient synthetic route, structurally confirmed by spectral analysis, evaluated for their anti-HIV activity in MT-4 cells and their inhibitory effect on HIV-1 RT. The results showed that some of the new compounds displayed low micromolar potency for inhibiting HIV-1 replication and promising activities against several selected resistant strains that confer resistance to current NNRTIs. However, all newly synthesized derivatives were not active against HIV-2 replication.
新型 HIV-1 NNRTIs 的开发提供了产生具有更高效力的新型结构的可能性。基于生物等排原理，设计了一系列新型的 2-(2-(2,4-二氯苯基)-2H-1,2,4-三唑-3-基硫代)-N-芳基乙酰胺衍生物，采用简单高效的合成路线合成，通过光谱分析进行结构确证，并在 MT-4 细胞中评估其抗 HIV 活性及其对 HIV-1 RT 的抑制作用。结果表明，一些新化合物对抑制 HIV-1 复制具有低微摩尔效力，对几种对当前 NNRTIs 产生耐药性的选定耐药株具有有前景的活性。然而，所有新合成的衍生物均对 HIV-2 复制没有活性。
