Non-Nucleoside HIV-1 Reverse Transcriptase (RT) Inhibitors: Past, Present, and Future Perspectives

• Published in: Current pharmaceutical design Vol. 8; no. 8; pp. 615 - 657
• Main Authors: Campiani, Giuseppe, Ramunno, Anna, Maga, Giovanni, Nacci, Vito, Fattorusso, Caterina, Catalanotti, Bruno, Morelli, Elena, Novellino, Ettore
• Format: Journal Article
• Language: English
• Published: United Arab Emirates Bentham Science Publishers Ltd 01.01.2002
• Subjects: Acquired Immunodeficiency Syndrome - drug therapy; Anti-HIV Agents - chemistry; Anti-HIV Agents - therapeutic use; Benzodiazepinones - chemistry; Benzodiazepinones - therapeutic use; Benzoxazines; Delavirdine - chemistry; Delavirdine - therapeutic use; Drug Design; Drug Evaluation, Preclinical - trends; Drug Resistance, Viral; Drug Therapy, Combination; HIV Reverse Transcriptase - antagonists & inhibitors; HIV-1 - drug effects; Human immunodeficiency virus 1; Humans; Molecular Structure; Nevirapine - chemistry; Nevirapine - therapeutic use; Non-nucleoside reverse transcriptase inhibitors; Nucleosides - chemistry; Nucleosides - therapeutic use; Oxazines - chemistry; Oxazines - therapeutic use; Reverse Transcriptase Inhibitors - chemistry; Reverse Transcriptase Inhibitors - therapeutic use; Spiro Compounds - chemistry; Spiro Compounds - therapeutic use; Thymidine - analogs & derivatives; Thymidine - chemistry; Thymidine - therapeutic use
• ISSN: 1381-6128; 1873-4286
• DOI: 10.2174/1381612024607207

Along with nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs) have gained a definitive and important place in the treatment of HIV-1 infections, and are in rapid development. These compounds can be grouped into two classes: the first generation NNRTIs, mainly discovered by random screening, and the second generation NNRTIs, developed as a result of comprehensive strategies involving molecular modelling, rationale-based drug synthesis, biological and pharmacokinetic evaluations. The recent boom of NNRTIs is mainly due to their antiviral potency, high specificity and low toxicity. The rapid emergence of drug-resistant HIV-1 strains induced by the first generation drugs is a disadvantage bypassed, in part, by the broad spectrum second generation NNRTIs. Starting from the first generation, this review will focus on the second generation NNRTIs dealing with the recent and most interesting published results, highlighting the guidelines for the development of a third generation of NNRTIs.