title: Synthesis and anticonvulsant activity of 2(3H)-benzoxazolone and 2(3H)-benzothiazolone derivatives.
abstract: A series of 2(3H)-benzoxazolone and 2(3H)-benzothiazolone derivatives were synthesized and evaluated for anticonvulsant activity. The compounds were assayed, intraperitoneally in mice and per os in rats, against seizures induced by maximal electroshock (MES) and pentylenetetrazole (scMet). Neurologic deficit was evaluated by the rotarod test. The compounds were prepared to determine the relationship between the 2(3H)-benzoxazolone and 2(3H)-benzothiazolone derivatives' structures and anticonvulsant activity. Several of these compounds showed significant anticonvulsant activity. Compounds 43 and 45 were the most active of the series against MES-induced seizures with ED50 values of 8.7 and 7.6 mg/kg, respectively. Compound 45 displayed good protection against MES-induced seizures and low toxicity in rats with an oral ED50 of 18.6 mg/kg and a protective index (PI = TD50/ED50) of < 26.9. In vitro receptor binding studies revealed that compounds 43 and 45 bind to sigma 1 receptors with nanomolar affinities.
authors.affiliation: Laboratory of Medicinal Chemistry, School of Pharmacy, University of Louvain, Bruxelles, Belgium. ucar@cmfa.ucl.ac.be
authors.forename: H
authors.initials: H
authors.lastname: Ucar
authors.forename: K
authors.initials: K
authors.lastname: Van derpoorten
authors.forename: S
authors.initials: S
authors.lastname: Cacciaguerra
authors.forename: S
authors.initials: S
authors.lastname: Spampinato
authors.forename: J P
authors.initials: JP
authors.lastname: Stables
authors.forename: P
authors.initials: P
authors.lastname: Depovere
authors.forename: M
authors.initials: M
authors.lastname: Isa
authors.forename: B
authors.initials: B
authors.lastname: Masereel
authors.forename: J
authors.initials: J
authors.lastname: Delarge
authors.forename: J H
authors.initials: JH
authors.lastname: Poupaert
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D004558:Electric Stimulation; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D010080:Oxazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D012640:Seizures / Q000188:drug therapy; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000927:Anticonvulsants; D010080:Oxazoles; D013844:Thiazoles