Please use this identifier to cite or link to this item: http://hdl.handle.net/20.500.12779/5035
Title: Parallel Solution-Phase and Microwave-Assisted Synthesis of New S-DABO Derivatives Endowed with Subnanomolar Anti-HIV-1 Activity
Authors: Manetti, Fabrizio 
J. A., Este
I., CLOTET CODINA
M., ARMAND UGON
G., Maga
E., Crespan
R., Cancio
Mugnaini, Claudia 
C., Bernardini
A., Togninelli
C., Carmi
M., Alongi
Petricci, Elena 
S., Massa
Corelli, Federico 
Botta, Maurizio 
Issue Date: 2005
Project: None 
Journal: JOURNAL OF MEDICINAL CHEMISTRY
Abstract: 
A simple and efficient methodology for the parallel solution-phase synthesis has been set up to obtain a series of thiouracils, in turn selectively S-benzylated under microwave irradiation to give new S-DABOs. Biological screening led to the identification of compounds with nanomolar activity toward both the highly purified recombinant human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) enzyme (wild-type and mutants) and wild-type (wt) and mutant HIV-1 strains. In particular, 20 was found to be the most potent S-DABO reported so far (ID50 = 26 nM toward the isolated wt enzyme) with subnanomolar activity toward both the wt and the pluriresistant virus (IRLL98) HIV-1 strain (EC50 < 0.14 nM and EC50 = 0.22 nM, respectively). Molecular modeling calculations were also performed to investigate the binding mode of such compounds onto the non-nucleoside reverse transcriptase inhibitor binding site and to rationalize the relationships between their chemical structure and activity values toward wt RT.
Description: 
36239
URI: http://hdl.handle.net/20.500.12779/5035
ISSN: 0022-2623
DOI: 10.1021/jm050744t
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