title: A novel family of diarylpyrimidines (DAPYs) featuring a diatomic linker: Design, synthesis and anti-HIV activities.
abstract: To improve the conformational flexibility and positional adaptability of the traditional diarylpyrimidines (DAPYs), a family of diarylpyrimidines featuring a C-N diatomic linker between the left wing benzene ring and the central pyrimidine was firstly designed, synthesized, and evaluated for in vitro anti-HIV activity. Most of target molecules showed excellent activities against wild-type (WT) HIV-1. Among them the most potent two compounds 12h and 12r displayed extremely potent WT HIV-1 inhibitory activities with an EC50 of 2.6 nM and 3.0 nM, respectively, while their selective index (CC50/EC50) values were both over 1000. Another compound 12b (EC50 14.9 nM) was also noteworthy due to its high SI of 18,614. Moreover, all of compounds were evaluated for their WT HIV-1 reverse transcriptase activities, which shown that the newly synthesized CH2NH-DAPYs bind to HIV-1 RT and belong to the genuine NNRTIs. However, the synthesized compounds lack the activities against HIV-1 double mutant (RES056) and HIV-2 (ROD). Thus it is an upcoming objective to improve the activities against HIV-1 double mutants.
authors.affiliation: Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Wuhan 430073, China. Electronic address: shuangxigu@163.com.
authors.forename: Shuang-Xi
authors.initials: SX
authors.lastname: Gu
authors.affiliation: Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Wuhan 430073, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Qiao
authors.affiliation: School of Chemistry & Environmental Engineering, Wuhan Institute of Technology, Wuhan 430073, China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Zhu
authors.affiliation: Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Wuhan 430073, China.
authors.forename: Qi-Chao
authors.initials: QC
authors.lastname: Shu
authors.affiliation: Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Wuhan 430073, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Wuhan 430073, China. Electronic address: xiulianju2008@aliyun.com.
authors.forename: Xiu-Lian
authors.initials: XL
authors.lastname: Ju
authors.affiliation: KU Leuven, Department of Microbiology and Immunology, Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, B-3000 Leuven, Belgium.
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
authors.affiliation: KU Leuven, Department of Microbiology and Immunology, Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, B-3000 Leuven, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.affiliation: KU Leuven, Department of Microbiology and Immunology, Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, B-3000 Leuven, Belgium.
authors.forename: Christophe
authors.initials: C
authors.lastname: Pannecouque
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D015498:HIV-2 / Q000187:drug effects* / Q000235:genetics; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D011743:Pyrimidines
keywords: Anti-HIV activities; Diarylpyrimidines; HIV-1 reverse transcriptase inhibitors