Strategies in the design of prodrugs of anti-HIV agents

• Published in: Current topics in medicinal chemistry Vol. 3; no. 13; p. 1467
• Main Authors: Calogeropoulou, Theodora, Detsi, Anastasia, Lekkas, Eleni, Koufaki, Maria
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 01-01-2003
• Subjects: Anti-HIV Agents - chemical synthesis; Anti-HIV Agents - chemistry; Anti-HIV Agents - pharmacology; Drug Design; Drug Resistance, Viral; Humans; Prodrugs - chemical synthesis; Prodrugs - chemistry; Prodrugs - pharmacology; Reverse Transcriptase Inhibitors - chemical synthesis; Reverse Transcriptase Inhibitors - chemistry; Reverse Transcriptase Inhibitors - pharmacology; Structure-Activity Relationship
• ISSN: 1568-0266
• DOI: 10.2174/1568026033451763

Control of AIDS requires development of special therapeutic strategies in order to reduce the level of monocyte/macrophage HIV infection, to prevent spread of HIV within the monocyte/macrophage reservoir, to maintain a therapeutically effective drug concentration in sanctuaries such as the brain and to overcome the problem of cellular resistance mechanisms. A popular approach towards this end has been the development of prodrugs of anti-HIV drugs. This review covers the different strategies devised for the design of prodrugs of anti-HIV agents with emphasis on the recent findings in this field of research. Thus, prodrugs of nucleoside reverse transcriptase inhibitors (NRTIs) including, 5'-O carboxylic ester derivatives, 5'-O- monophosphate analogues, macromolecular derivatives, prodrugs of purine nucleosides, prodrugs of acyclic nucleosides, homo and hetero dinucleotides, prodrugs of non-classical nucleoside analogues, boranophosphate triesters of NRTIs, and prodrugs of protease inhibitors including acyl-substituted prodrugs, prodrugs with increased water solubility, monophosphate prodrugs, and conjugates of HIV protease inhibitors with a reverse transcriptase inhibitor through spontaneously cleavable linkers, constitute the subject of this review.