Hybrid chemistry. Part 4: Discovery of etravirine–VRX-480773 hybrids as potent HIV-1 non-nucleoside reverse transcriptase inhibitors. Issue 15 (1st August 2015)

• Record Type: Journal Article
• Authors: Wan, Zheng-Yong; Tao, Yuan; Wang, Ya-Feng; Mao, Tian-Qi; Yin, Hong; Chen, Fen-Er; Piao, Hu-Ri; De Clercq, Erik; Daelemans, Dirk; Pannecouque, Christophe
• Is Part Of: Bioorganic & medicinal chemistry. Volume 23:Issue 15(2015)
• Page Start: 4248
• Page End: 4255
• Publication Date: 2015-08-01
• Subjects: Antiviral agent -- Biological activity -- Etravirine -- Molecular hybridization -- VRX-480773; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2015.06.048
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: A novel series of etravirine–VRX-480773 hybrids were designed using structure-guided molecular hybridization strategy and fusing the pharmacophore templates of etravirine and VRX-480773. The anti-HIV-1 activity and cytotoxicity was evaluated in MT-4 cell cultures. The most active hybrid compound in this series, N -(2-chlorophenyl)-2-((4-(4-cyano-2, 6-dimethylphenoxy)pyrimidin-2-yl)thio)acetamide 3d (EC50 = 0.24, SI >1225), was more potent than delavirdine (EC50 = 0.66 μM, SI >67) in the anti-HIV-1 in vitro cellular assay. Studies of structure-activity relationships established a correlation between anti-HIV activity and the substitution pattern of the acetanilide group.