1: J Med Chem 1998 Mar 26;41(7):1138-45
Published erratum appears in J Med Chem 1998 Jul 30;41(16):3102
Synthesis and anticonvulsant activity of 2(3H)-benzoxazolone and 2(3H)-benzothiazolone
derivatives.
Ucar H, Van derpoorten K, Cacciaguerra S, Spampinato S, Stables JP, Depovere
P, Isa M, Masereel B, Delarge J, Poupaert JH
Laboratory of Medicinal Chemistry, School of Pharmacy, University of Louvain,
Bruxelles, Belgium. ucar@cmfa.ucl.ac.be
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.
PMID: 9544213, UI: 98205854