Premium
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
Author(s) -
Huang Boshi,
Kang Dongwei,
Tian Ye,
Daelemans Dirk,
De Clercq Erik,
Pannecouque Christophe,
Zhan Peng,
Liu Xinyong
Publication year - 2021
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.13760
Subject(s) - etravirine , cytotoxicity , chemistry , pyrimidine , stereochemistry , potency , reverse transcriptase , human immunodeficiency virus (hiv) , docking (animal) , structure–activity relationship , lead compound , combinatorial chemistry , in vitro , biochemistry , rna , biology , virology , medicine , nursing , gene
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.