Design and synthesis of a new series of cyclopropylamino-linking diarylpyrimidines as HIV non-nucleoside reverse transcriptase inhibitors

• Published in: European journal of pharmaceutical sciences 2014-10, Vol.62, p.334-341
• Main Authors: Liu, Yang, Meng, Ge, Zheng, Aqun, Chen, Fener, Chen, Wenxue, Clercq, Erik De, Pannecouque, Christophe, Balzarini, Jan
• Format: Article
• Language: English
• Subjects: Anti-HIV activity; Anti-HIV Agents - chemical synthesis; Anti-HIV Agents - chemistry; Anti-HIV Agents - pharmacology; Cell Line, Tumor; Cyclopropylamine; Diarylpyrimidine; Drug Design; HIV-1 - drug effects; HIV-2 - drug effects; Humans; Non-nucleoside RT inhibitors; Pyrimidines - chemical synthesis; Pyrimidines - chemistry; Pyrimidines - pharmacology; Reverse Transcriptase Inhibitors - chemical synthesis; Reverse Transcriptase Inhibitors - chemistry; Reverse Transcriptase Inhibitors - pharmacology; SAR; Structure-Activity Relationship
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2014.06.003

[Display omitted] A new series of 29 diarylpyrimidine analogues featuring a cyclopropylamino group between the pyrimidine scaffold and the aryl wing have been synthesized. All of the new compounds have been characterized by spectra analysis. The target molecules were evaluated for their in vitro anti-HIV activity with FDA-approved drugs as references. Some of the compounds exhibited moderate to potent activities against wild-type HIV-1. The compound 4-((4-((cyclopropylamino)(2,5-difluorophenyl)methyl)pyrimidin-2-yl)amino)benzonitrile (1e) displayed potent anti-HIV-1 activity against WT HIV-1 with an IC50 of 0.099μM and a selectivity index of 2302. The preliminary structure–activity relationship (SAR) of this new series of compounds was also investigated.