Design, synthesis, and biological evaluation of piperidinyl‐substituted [1,2,4]triazolo[1,5‐a]pyrimidine derivatives as potential anti‐HIV‐1 agents with reduced cytotoxicity
Boshi Huang, Dongwei Kang, Ye Tian, Dirk Daelemans, Erik De Clercq, Christophe Pannecouque, Peng Zhan, Xinyong Liu
Abstract
Abstract Taking the previously reported compound BH‐7d as the lead, we designed and synthesized a series of piperidinyl‐substituted [1,2,4]triazolo[1,5‐a]pyrimidines, and their anti‐HIV activities as well as cytotoxicities were evaluated. Several compounds exhibited moderate anti‐HIV (IIIB) potency, among which 2b was the most active one (EC 50 = 4.29 μM). Structure–activity relationships derived from the antiretroviral results were analyzed. Additionally, most compounds demonstrated reduced cytotoxicity (CC 50 > 200 μM) compared with those of BH‐7d and etravirine. Molecular docking study further revealed the binding conformation of 2b in the binding pocket of HIV‐1 reverse transcriptase.