Among the FDA approved drugs for the treatment of AIDS, non-nucleoside reverse transcriptase inhibitors (NNRTIs) are essential components of first-line anti-HIV-1 therapy because of the less-severe adverse effects associated with NNRTIs administration in comparison to therapies based on other anti-HIV-1 agents. In this contest, 3,4-dihydro-2-alkoxy-6-benzyl-4-oxypyrimidines (DABOs) have been the object of many studies aimed at identifying novel analogues endowed with potent inhibitory activity towards HIV-1 wild type and especially drug-resistant mutants. Accordingly, based on the encouraging results obtained from the biological screening of our internal collection of S-DABO derivatives, we started with the systematic functionalization of the pyrimidine scaffold to identify the minimal required structural features for RT inhibition. Herein, we describe how the combination of synthetic, biological, and molecular modeling studies led to the identification of two novel subclasses of S-DABO analogues: S-DABO cytosine analogues (S-DABOCs) and 4-dimethyamino-6-vinylpyrimidines (DAVPs).

Radi, M., Falciani, C., Contemori, L., Petricci, E., G., M., A., S., et al. (2008). A Multidisciplinary Approach for the Identification ofNovel HIV-1 Non-Nucleoside Reverse TranscriptaseInhibitors: S-DABOCs and DAVPs. CHEMMEDCHEM, 3, 573-593 [10.1002/cmdc.200700198].

A Multidisciplinary Approach for the Identification ofNovel HIV-1 Non-Nucleoside Reverse TranscriptaseInhibitors: S-DABOCs and DAVPs

RADI, MARCO;FALCIANI, CHIARA;CONTEMORI, LORENZO;PETRICCI, ELENA;CASTRIA, MARINUNZIA;TOGNINELLI, ANDREA;BOTTA, MAURIZIO
2008

Abstract

Among the FDA approved drugs for the treatment of AIDS, non-nucleoside reverse transcriptase inhibitors (NNRTIs) are essential components of first-line anti-HIV-1 therapy because of the less-severe adverse effects associated with NNRTIs administration in comparison to therapies based on other anti-HIV-1 agents. In this contest, 3,4-dihydro-2-alkoxy-6-benzyl-4-oxypyrimidines (DABOs) have been the object of many studies aimed at identifying novel analogues endowed with potent inhibitory activity towards HIV-1 wild type and especially drug-resistant mutants. Accordingly, based on the encouraging results obtained from the biological screening of our internal collection of S-DABO derivatives, we started with the systematic functionalization of the pyrimidine scaffold to identify the minimal required structural features for RT inhibition. Herein, we describe how the combination of synthetic, biological, and molecular modeling studies led to the identification of two novel subclasses of S-DABO analogues: S-DABO cytosine analogues (S-DABOCs) and 4-dimethyamino-6-vinylpyrimidines (DAVPs).
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11365/21003
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