title: A multidisciplinary approach for the identification of novel HIV-1 non-nucleoside reverse transcriptase inhibitors: S-DABOCs and DAVPs.
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).
authors: Dipartimento Farmaco Chimico Tecnologico, University of Siena, Via Alcide de Gasperi 2, 53100 Siena, Italy.
authors: Marco
authors: M
authors: Radi
authors: Chiara
authors: C
authors: Falciani
authors: Lorenzo
authors: L
authors: Contemori
authors: Elena
authors: E
authors: Petricci
authors: Giovanni
authors: G
authors: Maga
authors: Alberta
authors: A
authors: Samuele
authors: Samantha
authors: S
authors: Zanoli
authors: Montserrat
authors: M
authors: Terrazas
authors: Marinunzia
authors: M
authors: Castria
authors: Andrea
authors: A
authors: Togninelli
authors: José A
authors: JA
authors: Esté
authors: Imma
authors: I
authors: Clotet-Codina
authors: Mercedes
authors: M
authors: Armand-Ugón
authors: Maurizio
authors: M
authors: Botta
mesh_terms: D015195:Drug Design; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D009154:Mutation; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D018894:Reverse Transcriptase Inhibitors; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase