Synthesis, anticonvulsant and anti-inflammatory studies of new 1,4-dihydropyridin-4-yl-phenoxyacetohydrazones
No Thumbnail Available
Date
2013
Journal Title
Journal ISSN
Volume Title
Publisher
Elsevier Masson SAS infos@masson.fr 62 rue Camille Desmoulins Issy les Moulineaux Cedex 92442
Abstract
The present work involves design and synthesis of new substituted 1,4-dihydropyridin-4-yl-phenoxyacetohydrazones (4a-s, 5a-h), starting from 4-hydroxybenzaldehyde. The final compounds were screened for their in vivo anticonvulsant activity by MES, scPTZ and 6 Hz methods, while their anti-inflammatory screening was performed by Carrageenan induced Paw Edema method. The results indicated that compounds carrying electron donating groups are anticonvulsant active, while most of the tested compounds exhibited significant anti-inflammatory activity. Compounds 4k, l, 4p-s, and 5c showed rapid anti-inflammatory activity within 30 min and appeared as lead compounds. Further, Neurotoxicity study revealed that all the tested compounds are non-toxic up to 300 mg/kg doses. Selected compounds were also subjected to analgesic screening following Tail immersion method and they exhibited good activity. © 2013 Elsevier Masson SAS. All rights reserved.
Description
Keywords
1,4 dihydropyridin 4 yl phenoxyacetohydrazone derivative, anticonvulsive agent, antiinflammatory agent, carrageenan, diethyl 4 [(n' (1h indol 3 yl)methylene) 2 phenoxyacetohydrazide] 2,6 dimethyl 1,4 dihydropyridine 3,5 dicarboxylate, diethyl 4 [n' ((5 methylthiophen 2 yl)methylene) 2 phenoxyacetohydrazide] 2,6 dimethyl 1,4 dihydropyridine 3,5 dicarboxylate, diethyl 4 [n' (1 (1h indol 3 yl)ethylidene) 2 phenoxyacetohydrazide] 2,6 dimethyl 1,4 dihydropyridine 3,5 dicarboxylate, diethyl 4 [n' (1 (4 bromophenyl)ethylidene) 2 phenoxyacetohydrazide] 2,6 dimethyl 1,4 dihydropyridine 3,5 dicarboxylate, diethyl 4 [n' (1 (4 fluorophenyl)ethylidene) 2 phenoxyacetohydrazide] 2,6 dimethyl 1,4 dihydropyridine 3,5 dicarboxylate, diethyl 4 [n' (1 (4 nitrophenyl)ethylidene) 2 phenoxyacetohydrazide] 2,6 dimethyl 1,4 dihydropyridine 3,5 dicarboxylate, diethyl 4 [n' (1 (thiophen 2 yl)ethylidene) 2 phenoxyacetohydrazide] 2,6 dimethyl 1,4 dihydropyridine 3,5 dicarboxylate, diethyl 4 [n' (1 phenylethylidene) 2 phenoxyacetohydrazide] 2,6 dimethyl 1,4 pyridine 3,5 dicarboxylate, diethyl 4 [n' (2 hydroxy phenyl) 2 phenoxyacetohydrazide] 2,6 dimethyl 1,4 dihydropyridine 3,5 dicarboxylate, diethyl 4 [n' (2,4 dihydroxy benzylidine) 2 phenoxyacetohydrazide] 2,6 dimethyl 1,4 dihydropyridine 3,5 dicarboxylate, diethyl 4 [n' (3,4 dimethoxy benzylidine) 2 phenoxyacetohydrazide] 2,6 dimethyl 1,4 dihydropyridine 3,5 dicarboxylate, diethyl 4 [n' (3,4,5 trimethoxybenzylidene) 2 phenoxyacetohydrazide] 2,6 dimethyl 1,4 dihydropyridine 3,5 dicarboxylate, diethyl 4 [n' (4 bromo 2 hydroxybenzylidene) 2 phenoxyacetohydrazide] 2,6 dimethyl 1,4 dihydropyridine 3,5 dicarboxylate, diethyl 4 [n' (4 bromo benzylidine) 2 phenoxyacetohydrazide] 2,6 dimethyl 1,4 dihydropyridine 3,5 dicarboxylate, diethyl 4 [n' (4 chloro benzylidine) 2 phenoxyacetohydrazide] 2,6 dimethyl 1,4 dihydropyridine 3,5 dicarboxylate, diethyl 4 [n' (4 dimethylamino benzylidine) 2 phenoxyacetohydrazide] 2,6 dimethyl 1,4 dihydropyridine 3,5 dicarboxylate, diethyl 4 [n' (4 hydroxy 3 ethoxy benzylidine) 2 phenoxyacetohydrazide] 2,6 dimethyl 1,4 dihydropyridine 3,5 dicarboxylate, diethyl 4 [n' (4 hydroxy 3 methoxy benzylidine] 2 phenoxyacetohydrazide 2,6 dimethyl 1,4 dihydropyridine 3,5 dicarboxylate, diethyl 4 [n' (4 hydroxy benzylidine) 2 phenoxyacetohydrazide] 2,6 dimethyl 1,4 dihydropyridine 3,5 dicarboxylate, diethyl 4 [n' (4 methyl benzylidine) 2 phenoxyacetohydrazide] 2,6 dimethyl 1,4 dihydropyridine 3,5 dicarboxylate, diethyl 4 [n' (4 nitro benzylidine) 2 phenoxyacetohydrazide] 2,6 dimethyl 1,4 dihydropyridine 3,5 dicarboxylate, diethyl 4 [n' (pyridin 4 yl methylene) 2 phenoxyacetohydrazide] 2,6 dimethyl 1,4 dihydropyridine 3,5 dicarboxylate, diethyl 4 [n' (thiophen 2 yl methylene) 2 phenoxyacetohydrazide] 2,6 dimethyl 1,4 dihydropyridine 3,5 dicarboxylate, diethyl [n' 4 ((1 hydroxynaphthalen 2 yl)methylene) 2 phenoxyacetohydrazide] 2,6 dimethyl 1,4 dihydropyridine 3,5 dicarboxylate, hydrazone derivative, unclassified drug, unindexed drug, anticonvulsant activity, antiinflammatory activity, article, controlled study, drug design, drug synthesis, female, immersion, in vivo study, male, mouse, neurotoxicity, nonhuman, paw edema, rat, Analgesic, Anti-inflammatory, Anticonvulsant, Dihydropyridine, Hydrazone, Neurotoxicity, Animals, Anti-Inflammatory Agents, Non-Steroidal, Anticonvulsants, Carrageenan, Disease Models, Animal, Dose-Response Relationship, Drug, Edema, Electroshock, Female, Hydrazones, Male, Mice, Molecular Structure, Pyridines, Rats, Rats, Wistar, Seizures
Citation
European Journal of Medicinal Chemistry, 2013, 70, , pp. 341-349