Hybrid diarylbenzopyrimidine non-nucleoside reverse transcriptase inhibitors as promising new leads for improved anti-HIV-1 chemotherapy

作者：Zeng Zhao Sen; He Qiu Qin; Liang Yong Hong; Feng Xiao Qing; Chen Fen Er^*; De Clercq Erik; Balzarini Jan; Pannecouque Christophe

来源：Bioorganic & Medicinal Chemistry, 2010, 18(14): 5039-5047.

DOI：10.1016/j.bmc.2010.05.081

• HIV-1
• Reverse transcriptase
• NNRTIs
• DABPs
• Molecular hybridization
• SAR

Molecular hybridization of the known anti-HIV-1 template DPC083 and etravirine based on docking model overlay has been generated a novel series of diarylbenzopyrimidine analogues (DABPs) (5a-z). These new hybrids were assessed for their activity against HIV in MT-4 cell cultures. Most of these compounds showed good activity against wild-type HIV-1 and mutant viruses. In particular, compound 5r showed the most potent activity against wild-type HIV-1 with an EC(50) value of 1.8 nM, and with a selectivity index up to 111,954. It also proved more active against mutant L100I, K103N, Y188L, and K103N + Y181C RT HIV-1 strains than efavirenz.

• 出版日期2010-7-15
• 单位河北医科大学; 复旦大学