Microwave assisted synthesis and pharmacological evaluation of few derivatives of 1,4-dihydropyridines containing 1,3,4-oxadiazoles

Abstract

In the view of extensive literature survey which revealed the anticonvulsant profile of 1,4-dihydropyridines and 1,3,4-oxadiazoles, we have coupled these two moieties with the aim of achieving enhanced anticonvulsant effect. The synthesis of novel compounds comprised of four steps; firstly the Hantzsch dihydropyridines were prepared, then their esters were prepared and then their corresponding hydrazides were prepared from which the final compounds were synthesized. A greener approach is employed by using chloramine-T as an efficient and safer oxidative catalyst for the synthesis of oxadiazole, and the use of microwave technique for accelerating the chemical reactions. The structures of the newly synthesized compounds were confirmed on the basis of IR, 1H-NMR and Mass analyses. Acute toxicity study was done to determine LD50 of the newly synthesized compounds. Some of the synthesized compounds were evaluated for their anticonvulsant effect by PTZ induced convulsions method. Statistical testing was done by one way ANOVA followed by Dunnetts test. The compounds AN1242 and CA7212 showed highest percentage of protection against convulsions at the dose of 15 mg/kg among the evaluated compounds compared to control.