Synthesis and biological evaluation of imidazole thioacetanilides as novel non-nucleoside HIV-1 reverse transcriptase inhibitors

Peng Zhan; Xinyong Liu; Junjie Zhu; Zengjun Fang; Zhenyu Li; Christophe Pannecouque; Erik De Clercq

doi:10.1016/j.bmc.2009.07.028

Synthesis and biological evaluation of imidazole thioacetanilides as novel non-nucleoside HIV-1 reverse transcriptase inhibitors

Bioorg Med Chem. 2009 Aug 15;17(16):5775-81. doi: 10.1016/j.bmc.2009.07.028. Epub 2009 Jul 18.

Authors

Peng Zhan¹, Xinyong Liu, Junjie Zhu, Zengjun Fang, Zhenyu Li, Christophe Pannecouque, Erik De Clercq

Affiliation

¹ Institute of Medicinal Chemistry, Shandong University, Jinan, PR China.

PMID: 19643613
DOI: 10.1016/j.bmc.2009.07.028

Abstract

A series of 2-(1-aryl-1H-imidazol-2-ylthio)acetamide [imidazole thioacetanilide (ITA)] derivatives were synthesized and evaluated as potent inhibitors of human immunodeficiency virus type-1 (HIV-1). Among them, the most potent HIV-1 inhibitors were 4a5 (EC(50)=0.18microM), and 4a2 (EC(50)=0.20microM), which were more effective than the lead compound L1 (EC(50)=2.053microM) and the reference drugs nevirapine and delavirdine. The preliminary structure-activity relationship (SAR) of the newly synthesized congeners is discussed.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetanilides / chemical synthesis*
Acetanilides / chemistry
Acetanilides / pharmacology
Anti-HIV Agents / chemical synthesis*
Anti-HIV Agents / chemistry
Anti-HIV Agents / pharmacology
Binding Sites
Computer Simulation
HIV Reverse Transcriptase / antagonists & inhibitors*
HIV Reverse Transcriptase / metabolism
Humans
Imidazoles / chemical synthesis
Imidazoles / chemistry*
Imidazoles / pharmacology
Structure-Activity Relationship

Substances

Acetanilides
Anti-HIV Agents
Imidazoles
reverse transcriptase, Human immunodeficiency virus 1
HIV Reverse Transcriptase
thioacetanilide