title: Design & synthesis of N'-[substituted] pyridine-4-carbohydrazides as potential anticonvulsant agents.
abstract: A series of N'-[substituted] pyridine-4-carbohydrazides were designed and synthesized keeping in view the structural requirement of pharmacophore and evaluated for anticonvulsant activity and neurotoxicity. The anticonvulsant activity of the titled compounds was established after intraperitoneal administration in three seizure models, which include MES, scMET and 6 Hz model. The most active compound of the series was N'-[4-(4-fluorophenoxy)benzylidene]pyridine-4-carbohydrazide PCH 6, which showed a MES ED50 value of 128.3 mg/kg and 6 Hz ED50 value of 53.3 mg/kg in mice. The median toxic dose (TD50) was 343.6 mg/kg, providing compound PCH 6 with a protection index of 2.67 in the MES test and 6.44 in 6 Hz test. A computational study was also carried out, including calculation of pharmacophore pattern, prediction of pharmacokinetic properties and docking studies.
authors.affiliation: School of Pharmaceutical Sciences, Shobhit University, Meerut 250110, India. tripathilaxmi@rediffmail.com
authors.forename: Laxmi
authors.initials: L
authors.lastname: Tripathi
authors.forename: Ranjit
authors.initials: R
authors.lastname: Singh
authors.forename: James P
authors.initials: JP
authors.lastname: Stables
mesh_terms: D000465:Algorithms; D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004597:Electroshock / Q000009:adverse effects; D006834:Hydrazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D015394:Molecular Structure; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D010433:Pentylenetetrazole; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*; D013237:Stereoisomerism
chemical_list: D000927:Anticonvulsants; D006834:Hydrazines; D011725:Pyridines; C019289:carbohydrazide; D010433:Pentylenetetrazole