Chemistry and Structure-activity Relationship of the Styrylquinoline-type HIV Integrase Inhibitors

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2010 Jul 27

PMID 20657464

Citations 12

Authors

Jean-Francois Mouscadet

Didier Desmaele

Affiliations

Soon will be listed here.

Abstract

In spite of significant progress in anti-HIV-1 therapy, current antiviral chemo-therapy still suffers from deleterious side effects and emerging drug resistance. Therefore, the development of novel antiviral drugs remains a crucial issue for the fight against AIDS. HIV-1 integrase is a key enzyme in the replication cycle of the retrovirus since it catalyzes the integration of the reverse transcribed viral DNA into the chromosomal DNA. Efforts to develop anti-integrase drugs started during the early nineties, culminating with the recent approval of Raltegravir. The discovery and the development of the styrylquinoline inhibitor class was an important step in the overall process. In this review we have described the key synthetic issues and the structure-activity relationship of this family of integrase inhibitors. Crystallographic and docking studies that shed light on their mechanism of action are also examined.

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