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.

Fourteen new 4-aryl-5-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 thiourea 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 BaCl2-induced contractions of isolated rat ileum. It was found that compound 12l having 3-methoxyphenyl group at the 4th position was the most potent compound in this series (pEC50: 4.00 +/- 0.20). Rasemic compound 12l was resolved into its enantiomers by high performance liquid chromatography (HPLC) using a commercially available cellulose tris(p-methylbenzoate) 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.