title: 2,4-Dimethoxyphenylsemicarbazones with anticonvulsant activity against three animal models of seizures: synthesis and pharmacological evaluation.
abstract: Various 2,4-dimethoxyphenylsemicarbazones were synthesized starting from 2,4-dimethoxyaniline via a phenylcarbamate intermediate. The structures were confirmed by spectral and elemental analyses. The anticonvulsant activity of the synthesized compounds was established after intraperitoneal administration in three seizure models in mice which include maximal electroshock seizure, subcutaneous pentylenetetrazole, and subcutaneous strychnine-induced seizure screens. Nine compounds exhibited protection in all the three seizure models, and N1-(2,4-dimethoxyphenyl)-N4-(propan-2-one)semicarbazone (17) emerged as the most active compound with no neurotoxicity. These compounds were found to elevate gamma-aminobutyric acid (GABA) levels in the midbrain and medulla oblongata regions equipotent to clobazam.
authors.affiliation: Medicinal Chemistry Research Laboratory, Pharmacy group, Birla Institute of Technology and Science, Pilani 333031, India.
authors.forename: Rathinasabapathy
authors.initials: R
authors.lastname: Thirumurugan
authors.forename: Dharmarajan
authors.initials: D
authors.lastname: Sriram
authors.forename: Amrita
authors.initials: A
authors.lastname: Saxena
authors.forename: James
authors.initials: J
authors.lastname: Stables
authors.forename: Perumal
authors.initials: P
authors.lastname: Yogeeswari
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D015394:Molecular Structure; D010100:Oxygen / Q000737:chemistry*; D051381:Rats; D012640:Seizures / Q000378:metabolism / Q000517:prevention & control*; D012664:Semicarbazones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D000927:Anticonvulsants; D012664:Semicarbazones; D005680:gamma-Aminobutyric Acid; D010100:Oxygen