Design Synthesis and Characterization of Novel 3,4- Dihydropyrimidinones as Agents for Metabolic Disorders

Abstract

Metabolic syndrome is a combination of medical disorders that, in concert, increase the risk of developing cardiovascular disease and diabetes. In 1893, the synthesis of functionalized 3, 4-dihydropyrimidin-2(1H)-ones (DHPMs) via three-component condensation reaction of an aromatic aldehyde, urea and ethyl acetoacetate was reported for the first time by P. Biginelli. In the past decades, such Biginelli-type dihydropyrimidones have received a considerable amount of attention due to the interesting pharmacological properties associated with this heterocyclic scaffold. In this study novel approach towards Biginelli reaction is with the use of catalysts focusing a cheap, efficient, mild and fast reaction with higher yields. The reaction is optimized with different reaction conditions like temperature, reaction time, catalyst to substrate ratio, and solvents. A series of novel benzyl 4-(6-methylquinolin-3-yl)-6- methyl-2-oxo-1, 2, 3, 4-tetrahydropyrimidine-5-carboxylate derivatives have been synthesized by optimized Biginelli reaction as agonist of target for metabolic disorders. Dihydropyrimidinones are well known compounds as calcium channel modulators, a1a adrenoceptor-selective antagonists and compounds that target the mitotic machinery. Here, the work is carried out for DHPMs selectively target receptor agonistic activity as anti diabetic along with its other biological profile. The synthesized compounds are characterized by TLC, melting point, and % yield. Structural elucidation is done by IR, 1HNMR, MASS Spectroscopy. HPLC analysis governs the purity of compounds. In silico studies, cytotoxicity and anti diabetic activity will be carried out in due course.