title: 2-(Alkyl/aryl)amino-6-benzylpyrimidin-4(3H)-ones as inhibitors of wild-type and mutant HIV-1: enantioselectivity studies.
abstract: The single enantiomers of two pyrimidine-based HIV-1 non-nucleoside reverse transcriptase inhibitors, 1 (MC1501) and 2 (MC2082), were tested in both cellular and enzyme assays. In general, the R forms were more potent than their S counterparts and racemates and (R)-2 was more efficient than (R)-1 and the reference compounds, with some exceptions. Interestingly, (R)-2 displayed a faster binding to K103N RT with respect to WT RT, while (R)-1 showed the opposite behavior.
authors.affiliation: Istituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Chimica e Tecnologie del Farmaco, Università degli Studi di Roma La Sapienza, P.le A. Moro 5, 00185 Rome, Italy.
authors.forename: Dante
authors.initials: D
authors.lastname: Rotili
authors.forename: Alberta
authors.initials: A
authors.lastname: Samuele
authors.forename: Domenico
authors.initials: D
authors.lastname: Tarantino
authors.forename: Rino
authors.initials: R
authors.lastname: Ragno
authors.forename: Ira
authors.initials: I
authors.lastname: Musmuca
authors.forename: Flavio
authors.initials: F
authors.lastname: Ballante
authors.forename: Giorgia
authors.initials: G
authors.lastname: Botta
authors.forename: Ludovica
authors.initials: L
authors.lastname: Morera
authors.forename: Marco
authors.initials: M
authors.lastname: Pierini
authors.forename: Roberto
authors.initials: R
authors.lastname: Cirilli
authors.forename: Maxim B
authors.initials: MB
authors.lastname: Nawrozkij
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Gonzalez
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
authors.forename: Marino
authors.initials: M
authors.lastname: Artico
authors.forename: José A
authors.initials: JA
authors.lastname: Esté
authors.forename: Giovanni
authors.initials: G
authors.lastname: Maga
authors.forename: Antonello
authors.initials: A
authors.lastname: Mai
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology; D001555:Benzene Derivatives / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D057075:Enzyme Assays; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D009154:Mutation; D011744:Pyrimidinones / Q000737:chemistry* / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D001555:Benzene Derivatives; D011744:Pyrimidinones; D054303:HIV Reverse Transcriptase