Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Diketoacid Inhibitors of HIV-1 Integrase: From L-708,906 to Raltegravir and Beyond

Author(s): K. D. Beare, M. J. Coster and P. J. Rutledge

Volume 19 , Issue 8 , 2012

Page: [1177 - 1192] Pages: 16

DOI: 10.2174/092986712799320565

Price: $65

Abstract

HIV-1 integrase is one of the three viral enzymes essential to HIV replication. Consequently the development of therapeutics targeting this enzyme has been a major focus of antiretroviral research over the past two decades. Several classes of integrase inhibitors have been identified; of these the diketoacids (DKAs) show greatest promise: raltegravir (Merck & Co) has been approved by the US Food and Drug Administration (FDA) for HIV-1 therapy, while elvitegravir (Gilead Sciences/ Japan Tobacco) has reached phase III clinical trials. This review considers the development of DKA-based inhibitors from early screening studies through to the release of raltegravir. SAR data collated from numerous studies are compared and analysed, shedding light on the geometric and electronic requirements for effective binding to HIV-1 integrase. This information will in turn aid the rational design of future generations of integrase inhibitors.

Keywords: AIDS, antiretroviral drugs, diketoacid, DKA, elvitegravir, HIV, HIV-1 integrase, integramycin, integrase inhibitors, raltegravir, SAR


Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy