Synthesis of 3,4-Dihydro-1H-Pyrimidine-5-Carbohydrazide Derivatives and Their Pharmacological Screening

Six new 3,4-Dihydro-1H-pyrimidine-5-carbohydrazide Derivatives (3a-f) have been synthesized in a three step reaction. In first step 5-(Ethoxycarbonyl)-6-methyl-4-substitutedaryl-3,4-dihydropyrimidin-2(1H)-ones obtained (1a-f) and in second step 4-Substitutedaryl-6-methyl-2-pyrimidinone-5-Carbohydrazides (2a-f). Third step involves synthesis of 4-Substitutedaryl-6-methyl-2-pyrimidinone-5-(N-p-tosyl) Carbohydrazides (3a-f). Their structures are confirmed by IR, ¹H-NMR, C¹³NMR and Mass. 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 c1-8 exerted comparative anti-hypertensive activity at 10 mg/kg dose level compared to nifedipine. Compounds 3c, 3e, 3f and 2b, 2c, 2f showed excellent results on evaluation by direct method. Test compounds 3c, 3e and 2f 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 3b, 3c and 3e showed low ulcerogenic activity.