title: 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.
abstract: rac-2-Cyclopentylthio-6-[1-(2,6-difluorophenyl)ethyl]-3,4-dihydro-5-methylpyrimidin-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 (R,R)-Whelk-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) and (S) enantiomers to the non-nucleoside binding site (NNBS) of reverse transcriptase (RT) using the defined model of F(2)-S-DABO/RT complex indicates the (R) enantiomer as the more active isomer.
authors.affiliation: Istituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Studi Farmaceutici, Università degli Studi di Roma "La Sapienza," Roma, Italy. quaglia@uniroma1.it
authors.forename: M
authors.initials: M
authors.lastname: Quaglia
authors.forename: A
authors.initials: A
authors.lastname: Mai
authors.forename: G
authors.initials: G
authors.lastname: Sbardella
authors.forename: M
authors.initials: M
authors.lastname: Artico
authors.forename: R
authors.initials: R
authors.lastname: Ragno
authors.forename: S
authors.initials: S
authors.lastname: Massa
authors.forename: D
authors.initials: D
authors.lastname: del Piano
authors.forename: G
authors.initials: G
authors.lastname: Setzu
authors.forename: S
authors.initials: S
authors.lastname: Doratiotto
authors.forename: V
authors.initials: V
authors.lastname: Cotichini
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry* / Q000302:isolation & purification* / Q000494:pharmacology; D002460:Cell Line; D002942:Circular Dichroism; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D011744:Pyrimidinones / Q000737:chemistry* / Q000302:isolation & purification* / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry* / Q000302:isolation & purification* / Q000494:pharmacology
chemical_list: C425326:2-cyclopentylthio-6-(1-(2,6-difluorophenyl)ethyl)-3,4-dihydro-5-methylpyrimidin-4(3H)-one; D019380:Anti-HIV Agents; D011744:Pyrimidinones; D018894:Reverse Transcriptase Inhibitors