Synthesis and in vivo anticonvulsant activity of 2-methyl-2-3-(5- piperazin-1-yl-1,3,4]oxadiazol-2-yl)-phenyl]-propionitrile derivatives

Harish, K. P. and Mohana, K. N. and Mallesha, L. and Veeresh, B. (2014) Synthesis and in vivo anticonvulsant activity of 2-methyl-2-3-(5- piperazin-1-yl-1,3,4]oxadiazol-2-yl)-phenyl]-propionitrile derivatives. Archiv der Pharmazie, 347 (4). pp. 256-267. ISSN 0365-6233

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Abstract

A series of new 2-methyl-2-3-(5-piperazin-1-yl-1,3,4]oxadiazol-2-yl)- phenyl]-propionitrile derivatives 8a-o, 9a-c, 10a-d, and 11a-d were synthesized to meet the structural requirements essential for anticonvulsant property. The structures of all the synthesized compounds were confirmed by means of 1 H NMR, 13 C NMR, and mass spectral studies. The purity of the novel compounds was confirmed by elemental analyses. All the compounds were screened for their anticonvulsant activity against maximal electroshock (MES) seizure method and their neurotoxic effects were determined by rotorod test. Compounds 8d, 8e, and 8f were found to be the most potent of this series. The same compounds showed no neurotoxicity at the maximum dose administered (100 mg/kg). The efforts were also made to establish the structure-activity relationships among the synthesized compounds. The pharmacophore model was used to validate the anticonvulsant activity of the synthesized molecules.

Item Type:	Article
Uncontrolled Keywords:	3, animal experiment, animal model, carbon nuclear magnetic resonance, drug synthesis, in vivo study, mass spectrometry, nonhuman, proton nuclear magnetic resonance, structure activity relation, unclassified drug, animal, Animals, chemistry, Structure-Activity Relationship, synthesis, dose response, Dose-Response Relationship, Drug, male, Male, rat, Rats, Wistar, Wistar rat, priority journal, Mass Spectrometry, article, validation study, nuclear magnetic resonance spectroscopy, phenytoin, Animal, disease model, Disease Models, neuroprotection, drug megadose, anticonvulsant activity, neurotoxicity, 1 (2, Nitriles, nitrile, Magnetic Resonance Spectroscopy, anticonvulsive agent, electroshock seizure, Anticonvulsants, electric shock, Seizures, 2 3 5 (4 4 (tert butyl)phenyl)sulfonyl]piperazine 1 yl] 1, 2 3 5 4 (3, 2 3 5 4 (4 bromobenzoyl)piperazine 1 yl] 1, 2 3 5 4 (4 bromobenzyl)piperazine 1 yl 1, 2 3 5 4 (biphenyl 4 sulfonyl) piperazin 1 yl 1, 2 3 5 4 (3, 2 3 5 4 (4 bromo 3 methylphenyl)sulfonylpiperazine 1 yl 1, 2 3 5 4 (4 bromophenyl)sulfonylpiperazine 1 yl 1, 2 3 5 4 (4 iodophenyl)sulfonylpiperazine 1 yl 1, 2 methyl 2 3 5 (4 tosylpiperazine 1 yl) 1, 2 methyl 2 3 5 4 (2 nitrophenyl)piperazine 1 yl] 1, 2 methyl 2 3 5 4 (4 phenoxy benzenesulfonyl)piperazin 1 yl 1, 2 methyl 2 3 5 4 (4 phenoxybenzoyl)piperazine 1 yl] 1, 2 methyl 2 3 5 4 (4 phenoxybenzyl)piperazine 1 yl 1, 2 methyl 2 3 5 4 (4 phenoxyphenyl)piperazine 1 yl 1, 2 methyl 2 3 5 4 (methylsulfonyl)piperazin 1 yl 1, 2 methyl 2 3 5 4 (naphthalene 2 yl sulfonyl)piperazine 1 yl 1, 2 methyl 2 3 5 4 (2 nitrophenyl)sulfonyl]piperazine 1yl] 1, 2 methyl 2 3 5 4 3 (trifluoromethyl)phenylsulfonyl piperazine 1 yl 1, 2 methyl 2 3 5 4 2 nitro 4 (triflouromethyl)benzoyl] piperazine 1 yl] 1, 2 methyl 2 3 5 4 2 nitro 4 (trifluoromethyl)benzyl] piperazine 1 yl] 1, 2 methyl 2 3 5 4 2 nitro 4 (trifluoromethyl)phenyl]piperazine 1 yl] 1, 2 methyl 23 5 4 2 nitro 4 (trifluoromethyl)phenyl] sulfonyl]piperazine 1 yl] 1, 4 4 5 3 (2 cyanopropan 2 yl)phenyl] 1, 4 oxadiazol 2 yl]phenyl]propanenitrile, 4 oxadiazole 2 yl]phenyl] 2 methyl propanenitrile, 4 oxadiazole 2 yl]phenyl] 2 methylpropanenitrile, 4 oxadiazole 2 yl]phenyl] propanenitrile, 4 oxadiazole 2 yl]phenyl]propanenitrile, 4 oxadiazole 2 yl]piperazine 1 yl]sulfonyl]benzonitrile, 4]oxadiazol 2 yl] phenyl] 2 methyl propionitrile, 4]oxadiazol 2 yl] phenyl] propionitrile, 4]oxadiazol 2 yl] piperazine, 5 dichloro thiophene 3 sulfonyl) 4 5 (4 methoxyphenyl) 1, 5 dimethylisoxazol 4 yl)methyl]piperazine 1 yl] 1, 5 dimethylisoxazole 4 carbonyl)piperazine 1 yl] 1, 5 dimethylisoxazole 4 yl)sulfonyl] piperazine 1 yl] 1, Electroshock, maximal electroshock seizure, propionitrile
Subjects:	C Chemical Science > Chemistry
Divisions:	Department of > Chemistry
Depositing User:	Arshiya Kousar Library Assistant
Date Deposited:	20 Jun 2019 10:22
Last Modified:	21 Jun 2019 07:55
URI:	http://eprints.uni-mysore.ac.in/id/eprint/3513

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