Synthesis and biological evaluation of CHX-DAPYs as HIV-1 non-nucleoside reverse transcriptase inhibitors.
Synthesis and biological evaluation of CHX-DAPYs as HIV-1 non-nucleoside reverse transcriptase inhibitors.
复制标题
DOI：
10.1016/j.bmc.2014.03.020
复制
发表时间：
2014-06
影响因子：
3.5
通讯作者：
Zihong Yan;Hai-Qiu Wu;Wen‐xue Chen;Yan Wu;H. Piao;Qiu-Qin He;Fener Chen;E. De Clercq;C. Pannec
中科院分区：
文献类型：
--
作者：
Zihong Yan;Hai-Qiu Wu;Wen‐xue Chen;Yan Wu;H. Piao;Qiu-Qin He;Fener Chen;E. De Clercq;C. Pannec
合成了一系列新的二芳基嘧啶类化合物(DAPY)，其特征是在第一翼和中心嘧啶环之间的亚甲基连接物上有一个卤素原子，并在MT-4细胞培养中评价了它们的抗HIV活性。最有希望的两个化合物7f和7g对野生型HIV-1表现出良好的活性，其低纳米分子EC50值分别为0.005和0.009μM，与所有参比药物齐多夫定、拉米夫定、奈韦拉平、依法韦林、地拉韦啶和依特拉韦林的效力相当或更强。特别是，7G对双突变体103N+10181C也表现出很强的活性，EC50值为8.2.μM。对这一新系列CHX-DAPY的初步构效关系和分子对接分析进行了研究。
A series of new diarylpyrimidines (DAPYs) characterized by a halogen atom on the methylene linker between wing I and the central pyrimidine ring was synthesized and evaluated for their anti-HIV activity in MT-4 cell cultures. The two most promising compounds7fand7gshowed excellent activity against wild-type HIV-1 with low nanomolar EC50values of 0.005 and 0.009 μM, respectively, which were comparable to or more potent than all the reference drugs zidovudine (AZT), lamivudine (3TC), nevirapine (NEV), efavirenz (EFV), delaviridine (DLV) and etravirine (ETV). In particular,7galso displayed strong activity against the double mutant strain 103N + 181C with an EC50value of 8.2 μM. The preliminary structure–activity relationship (SAR) and molecular docking analysis of this new series of CHX-DAPYs were also investigated.