Yan Zi-Hong, Wu Hai-Qiu, Chen Wen-Xue, Wu Yan, Piao Hu-Ri, He Qiu-Qin, Chen Fen-Er, De Clercq Erik, Pannecouque Christophe
Department of Chemistry, Fudan University, Shanghai 200433, People's Republic of China.
College of Pharmacy, Yanbian University, Yanji 133000, People's Republic of China.
Bioorg Med Chem. 2014 Jun 15;22(12):3220-6. doi: 10.1016/j.bmc.2014.03.020. Epub 2014 Mar 27.
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 compounds 7f and 7g showed excellent activity against wild-type HIV-1 with low nanomolar EC50 values 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, 7g also displayed strong activity against the double mutant strain 103N + 181C with an EC50 value of 8.2 μM. The preliminary structure-activity relationship (SAR) and molecular docking analysis of this new series of CHX-DAPYs were also investigated.
合成了一系列新型二芳基嘧啶（DAPYs），其特征在于在翼I与中心嘧啶环之间的亚甲基连接基上有一个卤原子，并在MT-4细胞培养物中评估了它们的抗HIV活性。两种最有前景的化合物7f和7g对野生型HIV-1表现出优异的活性，其低纳摩尔EC50值分别为0.005和0.009 μM，与所有参考药物齐多夫定（AZT）、拉米夫定（3TC）、奈韦拉平（NEV）、依非韦伦（EFV）、地拉韦啶（DLV）和依曲韦林（ETV）相当或更有效。特别是，7g对双突变株103N + 181C也表现出强活性，EC50值为8.2 μM。还研究了这一系列新型CHX-DAPYs的初步构效关系（SAR）和分子对接分析。
Zotero 插件