Paper Citing NAMD - Abstract
Mugnaini, Claudia; Alongi, Maddalena; Togninelli, Andrea; Gevariya, Harsukh; Brizzi, Antonella; Manetti, Fabrizio; Bernardini, Cesare; Angeli, Lucilla; Tafi, Andrea; Bellucci, Luca; Corelli, Federico; Massa, Silvio; Maga, Giovanni; Samuele, Alberta; Facchim, Marcella; Clotet-Codina, Imma; Armand-Ugon, Mercedes; Este, Jos A.; Botta, Maurizio
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
JOURNAL OF MEDICINAL CHEMISTRY, 50:6580-6595, DEC 27 2007
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.
