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Current Medicinal Chemistry


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

Current Developments in the Synthesis and Biological Activity of HIV-1 Double-Drug Inhibitors

Author(s): Clare I. Muhanji and Roger Hunter

Volume 14 , Issue 11 , 2007

Page: [1207 - 1220] Pages: 14

DOI: 10.2174/092986707780597952

Price: $65


A combination of different HIV inhibitors into a single molecular entity is a strategy that is growing in popularity in HIVchemotherapy research. The high levels of resistance elicited by both nucleoside and non-nucleoside reverse transcriptase inhibitors has prompted the design of double-drugs combining these two entities with the aim of addressing the emergence of resistance. The strategy involves combining two different inhibitors into a single chemical entity via a linker, with the aim of improving the physicochemical characteristics of the individual compounds. Linkers may be sub-divided into cleavable and non-cleavable. While the former result in regeneration of the parent drugs of the double-drug once in the cell cytoplasm, the latter type is designed to allow the double-drug to target two active sites in a simultaneous or bifunctional fashion, which are located in close proximity. The linkers have been attached at the C-5, C-5 or N-3 positions of the nucleoside, and in some of the substrates synthesized, a synergistic anti-HIV activity has been observed. This review focuses on the design and synthesis of anti-HIV double-drugs reported to date.

Keywords: Anti-HIV, Bifunctional drugs, Chemokine Receptor, Combination therapy, Double-drug, NRTI, NNRTI, Protease, Reverse Transcriptase

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