Design, synthesis and evaluation of dialkyl 4-(benzo[d][1,3]dioxol-6-yl)-1,4-dihydro-2,6-dimethyl-1-substituted pyridine-3,5-dicarboxylates as potential anticonvulsants and their molecular properties prediction

•A series of 4-aryl-1,4-dihydropyridines were synthesized by Hantzsch reaction.•All the compounds were evaluated for anticonvulsant and antioxidant activities.•Compounds 8a, 8f and 8k showed good anticonvulsant activity.•These compounds also obeyed the Lipinski's rule-of-five.•Selected compounds were also evaluated for antinociceptive activity.

The present study is on the development of dialkyl 4-(benzo[d][1,3]dioxol-6-yl)-1,4-dihydro-2,6-dimethyl-1-substituted pyridine-3,5-dicarboxylate derivatives as isosteric analogues of isradipine and nifedipine, by the replacement of benzofurazanyl and 2-nitrophenyl groups respectively with benzo[d][1,3]dioxo-6-yl group, as potential anticonvulsants. Fivfteen new derivatives (8a–8o) were synthesized and tested for anticonvulsant activity using maximal electroshock and subcutaneous pentylenetetrazole induced seizure methods. Compound 8f possessing free NH group in 1,4-dihydropyridine ring, diethyl ester functionality at the positions 3 and 5 showed significant anticonvulsant and antioxidant activities. This was also supported by molecular properties prediction data. Selected compounds were evaluated for antinociceptive activity in capsaicin induced nociception assay at 10 mg/kg body weight, but displayed no significant activity at the tested dose.

Graphical abstractA novel series of 4-aryl-1,4-dihydropyridines (8a–8o) is designed and synthesized, which displayed good anticonvulsant and antioxidant activities. Compound 8f exhibited good anticonvulsant activity comparable to diazepam and also passed the Lipinski's rule-of-five.Figure optionsDownload full-size imageDownload as PowerPoint slide