Chiral resolution and molecular modeling investigation of rac-2-cyclopentylthio-6[1-(2,6-difluorophenyl)ethyl]-3,4-dihydro-5-methylpyrimidin-4(3H)-one (MC-1047), a potent anti-HIV-1 reverse transcriptase agent of the DABO class

Authors
Quaglia, MG Mai, A Sbardella, G Artico, M Ragno, R Massa, S Del Piano, D Setzu, G Doratiotto, S Cotichini, V
Citation
Mg. Quaglia et al., Chiral resolution and molecular modeling investigation of rac-2-cyclopentylthio-6[1-(2,6-difluorophenyl)ethyl]-3,4-dihydro-5-methylpyrimidin-4(3H)-one (MC-1047), a potent anti-HIV-1 reverse transcriptase agent of the DABO class, CHIRALITY, 13(2), 2000, pp. 75-80
Citations number
19
Categorie Soggetti
Chemistry & Analysis
Journal title
CHIRALITY
ISSN journal
08990042 → ACNP
Volume
13
Issue
2
Year of publication
2000
Pages
75 - 80
Database
ISI
SICI code
0899-0042(2000)13:2<75:CRAMMI>2.0.ZU;2-C
Abstract
rac-2-Cyclopentylthio-6-[1-(2,6-difluorophenyl)ethyl]-3,4-dihydromethylpyri midin-4 (3H)-one (MC-1047) is a potent inhibitor of HIV-1 multiplication in acutely infected cells. MC-1047 racemate has been resolved by chiral HPLC using, as chiral stationary phase (CSP), a commercially available (RR)-Whel k-01 column. The optical purity and the circular dichroism (CD) of the two resolved enantiomers were determined and their biological activities tested in in vitro assays. Molecular modeling inspection of the binding of (R) an d (S) enantiomers to the non-nucleoside binding site (NNBS) of reverse tran scriptase (RT) using the defined model of F-2-S-DABO/RT complex indicates t he (R) enantiomer as the more active isomer. Chirality 13:75-80, 2001. (C) 2001 Wiley-Liss. Inc.