title: Synthesis and Anti-HIV-1 Evaluation of Some Novel MC-1220 Analogs as Non-Nucleoside Reverse Transcriptase Inhibitors.
abstract: Some novel MC-1220 analogs were synthesized by condensation of 4,6-dichloro-N-methylpyrimidin-2-amine derivatives (1a,b and 15) and/or 4-chloro-6-methoxy-N,N,5-trimethylpyrimidin-2-amine (2a) with the sodium salt of 2,6-difluorophenylacetonitrile followed by treatment with aqueous sodium hydroxide in methanol, alkylation, reduction, halogenation, and/or acidic hydrolysis. All synthesized compounds were evaluated for their activity against HIV-1. The most active compound in this study was compound 7, which showed activity against HIV-1 comparable to that of MC-1220. The only difference in structure between compound 7 and MC-1220 is a fluoro atom instead of a CH3 group.
authors.affiliation: Department of Physics, Chemistry and Pharmacy, Nucleic Acid Centre, University of Southern Denmark, Odense M, Denmark.|Faculty of Pharmacy and Pharmaceutical Industries, Department of Pharmaceutical Chemistry, Sinai University, Al-Arish, North Sinai, Egypt.
authors.forename: Yasser M
authors.initials: YM
authors.lastname: Loksha
authors.affiliation: Department of Physics, Chemistry and Pharmacy, Nucleic Acid Centre, University of Southern Denmark, Odense M, Denmark.
authors.forename: Erik B
authors.initials: EB
authors.lastname: Pedersen
authors.affiliation: Dipartimento di Scienze e Tecnologie Biomediche, Sezione di Microbiologia e Virologia Generale e Biotecnologie Microbiche, Universita di Cagliari, Monserrato, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Loddo
authors.affiliation: Dipartimento di Scienze e Tecnologie Biomediche, Sezione di Microbiologia e Virologia Generale e Biotecnologie Microbiche, Universita di Cagliari, Monserrato, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: La Colla
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002460:Cell Line; D002478:Cells, Cultured; D005464:Fluorobenzenes / Q000494:pharmacology*; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors*; D015497:HIV-1 / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D011744:Pyrimidinones / Q000494:pharmacology*; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: C506288:6-(1-(2,6-difluorophenyl)ethyl)-2-(dimethylamino)-5-methylpyrimidin-4(3H)-one; D019380:Anti-HIV Agents; D005464:Fluorobenzenes; D011744:Pyrimidinones; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase
keywords: 2,6-Difluorobenzyl cyanide; 4,6-Dichloro-N,N-dimethylpyrimidin-2-amine; HIV-1; MC-1220 analogs; Non-nucleoside reverse transcriptase inhibitor (NNRTI)