Synthesis and Evaluation of some Novel Condensed 2-Chloromethyl-4-Chloro/4-Hydroxypyrimidines for Antihyperlipidemic Activity

Abstract:

Researchers have established a link between atherosclerosis and elevated blood cholesterol levels. Lipid lowering is one of the major approaches in prevention of cardiovascular diseases and stroke. In spite of extensive research and development of numerous drugs, antihyperlipidemic therapy is still deprived of the efficacy, safety and thorough knowledge of the exact mechanisms for the real cause of hyperlipidemia. Condensed 2-substituted pyrimidines have emerged out as a class of bioactive compounds exhibiting good antihyperlipidemic properties. In this study, twelve condensed 2-chloromethyl-4-hydroxy/4-chloropyrimidines (I-XII) were synthesized under microwave irradiation and evaluated for antihyperlipidemic activity on Spargue dawley rats fed with high fat diet. Ezetimibe was used as a standard drug. All the compounds showed a dose dependent activity profile (decreased serum triglyceride and cholesterol and increased serum HDL levels) at the dose levels of 25, 50 and 100 mg/kg, comparable to the standard drug. The compounds VI, VII, VIII and XII of the series affected the lipid profile of the test animals, more significantly and comparable to the standard drug.

Key words: Atherosclerosis, Condensed pyrimidines, Antihyperlipaemic, Ezetimibe, Cholesterol absorption inhibitors.