Synthesis and pharmacological investigation of 3-(substituted 1-phenylethanone)-4-(substituted phenyl)-1, 2, 3, 4-tetrahydropyrimidine-5-carboxylates

Fifteen new ethyl 6-methyl-2-methoxy-3-(substituted 1-phenylethanone)-4-(substituted phenyl)-1, 2, 3, 4-tetrahydropyrimidine-5-carboxylates ( 6a – o ) have been synthesized in a two step reaction. In first step ethyl acetoacetate, s -methylisourea and appropriate benzaldehydes reacted in a single step reaction to obtain ethyl 6-methyl-2-methoxy-4-(substituted phenyl)-1, 4-dihydropyrimidine-5-carboxylates ( 4a – e ). Second step involves synthesis of reaction between substituted phenacyl bromides and 1-4-dihydropyrimidine-5-carboxylates ( 6a – o ). Their structures are confirmed by IR, 1 H NMR, mass and elemental analyses. The compounds were tested for antihypertensive activity by non-invasive tail-cuff, and evaluated by carotid artery cannulation method for determining the diastolic blood pressure. Hypertension was induced by DOCA-salt. Anti-inflammatory activity was carried out by carrageenan induced rat-paw oedema method. Test compounds 6b , 6c , 6e , 6f , 6j , 6h , 6k , 6l , 6m , 6n and 6o exerted comparative antihypertensive activity at 10 mg/kg dose level compared to nifedipine. Compounds 6j , 6m and 6o showed excellent results on evaluation by direct method. Test compounds 6a – 6h , 6l , 6m , 6n and 6o exerted moderate to comparative anti-inflammatory activity at the 100 mg/kg dose level compared to indomethacin. Their further investigation for analgesic activity and acute ulcerogenesis was carried out, compounds 6m , 6f , 6k , 6o showed excellent to good analgesic activity and low ulcerogenic activity.