title: Regioselective synthesis of novel 4,5-diaryl functionalized 3,4-dihydropyrimidine-2(1H)-thiones via a non-Biginelli-type approach and evaluation of their in vitro anticancer activity.
abstract: An easy and novel approach to synthesize 4,5-diaryl functionalized 3,4-dihydropyrimidine-2(1H)-thiones via addition of aryllithiums to 5-aryl substituted pyrimidine-2(1H)-thiones, which could be regarded as a method complementary to the most widely used Biginelli-type synthesis, is described. In the reaction of aryllithiums with N-(Me)Bn substituted pyrimidine-2(1H)-thiones a high degree of regioselectivity of addition, leading to 4-aryl adducts, was achieved. Selected compounds tested for their in vitro anticancer activity against four human cancer cell lines showed the greatest activity against breast cancer (MCF7). 1-Benzyl-4-(3-hydroxyphenyl)-5-phenyl substituted 3,4-dihydropyrimidine-2(1H)-thione (10g) exhibiting 10-fold more potent activity than the best known monastrol (MON) stands as a promising candidate for further scaffold and asymmetric synthesis.
authors.affiliation: Institute of Chemistry and Environmental Protection, West Pomeranian University of Technology, Szczecin, Al. Piastów 42, Szczecin, 71-065 Poland. sosnicki@zut.edu.pl.
authors.forename: Jacek G
authors.initials: JG
authors.lastname: Sośnicki
authors.forename: Łukasz
authors.initials: Ł
authors.lastname: Struk
authors.forename: Mateusz
authors.initials: M
authors.lastname: Kurzawski
authors.forename: Magdalena
authors.initials: M
authors.lastname: Perużyńska
authors.forename: Gabriela
authors.initials: G
authors.lastname: Maciejewska
authors.forename: Marek
authors.initials: M
authors.lastname: Droździk
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D066244:Proton Magnetic Resonance Spectroscopy; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013871:Thiones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D011743:Pyrimidines; D013871:Thiones; C400223:monastrol