Structural modifications of CH(OH)-DAPYs as new HIV-1 non-nucleoside reverse transcriptase inhibitors.
Structural modifications of CH(OH)-DAPYs as new HIV-1 non-nucleoside reverse transcriptase inhibitors.
复制标题
DOI：
10.1016/j.bmc.2014.02.030
复制
发表时间：
2014-04
影响因子：
3.5
通讯作者：
Zihong Yan;Xia-Yun Huang;Hai-Qiu Wu;Wen‐xue Chen;Qiu-Qin He;Fener Chen;E. De Clercq;C. Pannecouque
中科院分区：
文献类型：
--
作者：
Zihong Yan;Xia-Yun Huang;Hai-Qiu Wu;Wen‐xue Chen;Qiu-Qin He;Fener Chen;E. De Clercq;C. Pannecouque
合成了一系列CR2(OH)-二芳基嘧啶衍生物（CR2(OH)-DAPYs），在I翼和中心嘧啶之间的CH（OH）连接上具有疏水性基团，并在MT-4细胞培养中评估了它们的抗hiv活性。除化合物3k外，其余化合物对野生型HIV-1均表现出抑制活性，ec50值范围为7.21±1.99 ~ 0.067±0.006 μM。其中，化合物3的抗hiv -1活性最强（EC50= 0.067±0.006 μM, SI > 592），比参比药物奈韦拉平（NVP）和德拉维定（DLV）的抗hiv -1活性高约2倍。此外，还研究了这些新衍生物与HIV-1 RT的结合模式和初步的SAR研究。
A series of CR2(OH)-diarylpyrimidine derivatives (CR2(OH)-DAPYs) featuring a hydrophobic group at CH(OH) linker between wing I and the central pyrimidine were synthesized and evaluated for their anti-HIV activity in MT-4 cell cultures. All the target compounds except for compound3kdisplayed inhibitory activity against HIV-1 wild-type with EC50values ranging from 7.21 ± 1.99 to 0.067 ± 0.006 μM. Among them, compound3dshowed the most potent anti-HIV-1 activity (EC50= 0.067 ± 0.006 μM, SI > 592), which was approximately 2-fold more potent than the reference drugs nevirapine (NVP) and delaviridine (DLV) in the same assay. In addition, the binding modes with HIV-1 RT and the preliminary SAR studies of these new derivatives were also investigated.