Synthesis and in vitro calcium antagonist activity of 4-aryl-7,7-dimethyl/1,7,7-trimethyl-1,2,3,4,5,6,7,8-octahydroquinazoline-2,5-dione derivatives.

In this study, a series of 4-aryl-7,7-dimethyl and 1,7,7-trimethyl-1,2,3,4,5,6,7,8-octahydroquinazoline-2,5-diones (1-25) were synthesized by condensing urea or N-methylurea with 5,5-dimethyl-1,3-cyclohexanedione and appropriate aromatic aldehydes according to the Biginelli reaction. The structures of the compounds were confirmed by spectral data and elementary analysis. The calcium antagonist activity of the compounds was tested in vitro on isolated rat ileum and lamb carotid artery. Compounds 16 and 19 were the most active derivatives on isolated rat ileum compared with the standard nicardipine. On isolated aortic strips of lamb the calcium antagonist activity of compound 16 (maximum relaxant effect: 38.83+/-5.84%) was found as high as that of nicardipine (maximum relaxant effect: 35.50+/-4.16%) used as a reference drug.