1,2,3-Thiadiazole thioacetanilides as a novel class of potent HIV-1 non-nucleoside reverse transcriptase inhibitors

Peng Zhan; Xinyong Liu; Yuan Cao; Yan Wang; Christophe Pannecouque; Erik De Clercq

doi:10.1016/j.bmcl.2008.09.055

1,2,3-Thiadiazole thioacetanilides as a novel class of potent HIV-1 non-nucleoside reverse transcriptase inhibitors

Bioorg Med Chem Lett. 2008 Oct 15;18(20):5368-71. doi: 10.1016/j.bmcl.2008.09.055. Epub 2008 Sep 18.

Authors

Peng Zhan¹, Xinyong Liu, Yuan Cao, Yan Wang, Christophe Pannecouque, Erik De Clercq

Affiliation

¹ Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, Jinan, Shandong 250012, PR China.

PMID: 18824350
DOI: 10.1016/j.bmcl.2008.09.055

Abstract

A novel series of 1,2,3-thiadiazole thioacetanilide (TTA) derivatives have been designed, synthesized and evaluated for its anti-HIV activities in MT-4 cells. Some derivatives proved to be highly effective in inhibiting HIV-1 replication at nanomolar concentrations. Among them, 2-[4-(2,4-dichlorophenyl)-1,2,3-thiadiazol-5-ylthio]-N-(2-nitrophenyl)acetamide 7d2 was identified as the most promising compound (EC(50)=0.059+/-0.02 microM, CC(50)>283.25 microM, SI>4883). The structure-activity relationship (SAR) of these novel structural congeners is discussed.

Publication types

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

MeSH terms

Anti-HIV Agents / chemical synthesis*
Anti-HIV Agents / pharmacology
Biological Assay
Cell Line
Chemistry, Pharmaceutical / methods*
Drug Design
Drug Evaluation, Preclinical
HIV Infections / drug therapy*
HIV Reverse Transcriptase / antagonists & inhibitors
HIV-1 / metabolism
Humans
Models, Chemical
Reverse Transcriptase Inhibitors / chemical synthesis*
Reverse Transcriptase Inhibitors / pharmacology
Structure-Activity Relationship
Thiadiazoles / chemical synthesis*
Thiadiazoles / pharmacology
Virus Replication

Substances

Anti-HIV Agents
Reverse Transcriptase Inhibitors
Thiadiazoles
HIV Reverse Transcriptase