title: Synthesis and anticonvulsant activities of novel 2-(cyclopentylmethylene)hydrazinyl-1,3-thiazoles in mouse models of seizures.
abstract: Synthesis, characterization and investigation of in vivo anticonvulsant activities of 13 novel cyclopentanecarbaldehyde-based 2,4-disubstituted 1,3-thiazoles are presented. Their structures were determined using (1)H and (13)C NMR, FAB(+)-MS, HRMS and elemental analyses. The results of anticonvulsant screening reveal that seven intraperitoneally administered compounds: 3a, 3b, 3d, 3e, 3f, 3k and 3m containing F-, Cl-, Br-, CF3-, CH3- and adamantyl substituents demonstrated significant anticonvulsant activity in the pentylenetetrazole model with median effective doses (ED50) ≤ 20 mg/kg, respectively, which was approximately seven-fold lower than that reported for the reference drug, ethosuximide. Noteworthy, none of these compounds impaired animals' motor skills in the rotarod test.
authors.affiliation: a Department of Chemical Technology and Pharmaceuticals , Faculty of Pharmacy, Collegium Medicum, Nicolaus Copernicus University , Bydgoszcz , Poland and.
authors.forename: Krzysztof Z
authors.initials: KZ
authors.lastname: Łączkowski
authors.affiliation: b Chair of Pharmacodynamics, Faculty of Pharmacy, Medical College, Jagiellonian University , Krakow , Poland.
authors.forename: Kinga
authors.initials: K
authors.lastname: Sałat
authors.affiliation: a Department of Chemical Technology and Pharmaceuticals , Faculty of Pharmacy, Collegium Medicum, Nicolaus Copernicus University , Bydgoszcz , Poland and.
authors.forename: Konrad
authors.initials: K
authors.lastname: Misiura
authors.affiliation: b Chair of Pharmacodynamics, Faculty of Pharmacy, Medical College, Jagiellonian University , Krakow , Poland.
authors.forename: Adrian
authors.initials: A
authors.lastname: Podkowa
authors.affiliation: b Chair of Pharmacodynamics, Faculty of Pharmacy, Medical College, Jagiellonian University , Krakow , Poland.
authors.forename: Natalia
authors.initials: N
authors.lastname: Malikowska
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000494:pharmacology*; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D004195:Disease Models, Animal; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D051379:Mice; D010862:Pilocarpine / Q000008:administration & dosage; D066244:Proton Magnetic Resonance Spectroscopy; D045442:Rotarod Performance Test; D012640:Seizures / Q000517:prevention & control*; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D000927:Anticonvulsants; D013844:Thiazoles; D010862:Pilocarpine
keywords: Anticonvulsant drugs; PTZ model; epilepsy; rotarod test; thiazoles