4-Aryl-5-oxo-1,2,3,4,5,6,7,8 -octahydroquinazoline-2-thione derivatives: Synthesis, enantiomeric separation and in vitro screening as calcium antagonists

SARAÇ S., Yarim M., Ertan M., Erol K., Aktan Y.

Bollettino Chimico Farmaceutico, vol.136, no.11, pp.657-664, 1997 (Scopus) identifier identifier

  • Publication Type: Article / Article
  • Volume: 136 Issue: 11
  • Publication Date: 1997
  • Journal Name: Bollettino Chimico Farmaceutico
  • Journal Indexes: Scopus
  • Page Numbers: pp.657-664
  • Keywords: Anellated tetrahydropyrimidine-2-thiones, pharmacology, synthesis, Calcium antagonists, Octahydroquinazoline-2-thiones, pharmacology, synthesis
  • Istanbul Medipol University Affiliated: No


Fourteen new 4-aryl-oxo-1,2,3,4,5,6,7,8-octahydroquinazoline-2-thione derivatives were synthesized and screened in vitro for their calcium antagonistic activities. The compounds were prepared by reacting 1,3-cyclo- hexanedione with appropriate aromatic aldehydes and thiurea under modified Biginelli reaction conditions. The structures of the compounds were proved by IR, 1H-NMR, mass spectroscopy and elemental analysis. The compounds synthesized exerted calcium antagonistic action on smooth musculature by inhibiting BaCL-induced contractions of isolated rat ileum. It was found that compound 121 having 3-methoxyphenyl group at the 4(th) position was the most potent compound in this sirie (pEC50: 4.00 ± 0.20). Rasemic compound 121 was resolved into its enantiomers by high performance liquid chromatography (HPLC) using a commercially available cellulose tris(p-methylbenzuate) chiral stationary phase, known as Chiralcel OJ. The enantiomeric ratio was validated and peak identification for each enantiomer was established according to their optical rotation sign.