title: Synthesis and in vivo anticonvulsant activity of 2-methyl-2-[3-(5-piperazin-1-yl-[1,3,4]oxadiazol-2-yl)-phenyl]-propionitrile derivatives.
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.
authors.affiliation: Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore, Karnataka, India.
authors.forename: Kikkeri P
authors.initials: KP
authors.lastname: Harish
authors.forename: Kikkeri N
authors.initials: KN
authors.lastname: Mohana
authors.forename: Lingappa
authors.initials: L
authors.lastname: Mallesha
authors.forename: Bantal
authors.initials: B
authors.lastname: Veeresh
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D009570:Nitriles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000188:drug therapy*; D013329:Structure-Activity Relationship
chemical_list: D000927:Anticonvulsants; D009570:Nitriles; C005557:propionitrile
keywords: 1,3,4-Oxadiazole; Anticonvulsant; MES; Rotorod test; Sulfonyl chloride