Please use this identifier to cite or link to this item: http://hdl.handle.net/20.500.12779/5293
Title: Dihydro-alkylthio-benzyl-oxopyrimidines as Inhibitors of Reverse Transcriptase: Synthesis and Rationalization of the Biological Data on Both Wild-Type Enzyme and Relevant Clinical Mutants
Authors: Mugnaini, Claudia 
Alongi, M
Togninelli, A
Gevariya, H
Brizzi, Antonella 
Manetti, Fabrizio 
Bernardini, C
Angeli, L
Tafi, Andrea 
Bellucci, L
Corelli, Federico 
Massa, Silvio
Maga, G
Samuele, A
Facchini, M
CLOTET CODINA, I
ARMAND UGON, M
ESTE J., A
Botta, Maurizio 
Issue Date: 2007
Project: None 
Journal: JOURNAL OF MEDICINAL CHEMISTRY
Abstract: 
A series of novel S-DABO analogues, characterized by different substitution patterns at positions 2, 5, and 6 of the heterocyclic ring, were synthesized in a straightforward fashion by means of parallel synthesis and evaluated as inhibitors of human immunodeficiency virus type-1 (HIV-1). Most of the compounds proved to be highly active on the wild-type enzyme both in enzymatic and cellular assays, with one of them emerging as the most active reverse transcriptase inhibitor reported so far (EC50wt = 25 pM). The general loss of potency displayed by the compounds toward clinically relevant mutant strains was deeply studied through a molecular modeling approach, leading to the evidence that the dynamic of the entrance in the non-nucleoside binding pocket could represent the basis of the inhibitory activity of the molecules.
Description: 
38260
URI: http://hdl.handle.net/20.500.12779/5293
ISSN: 0022-2623
DOI: 10.1021/jm0708230
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