Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Patent
1993-01-22
1996-02-20
Rothman, Alan L.
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
546159, C07D21518, C07D21546
Patent
active
054930278
ABSTRACT:
Coupled to the N-methyl-D-aspartate (NMDA) receptor-channel complex is a strychnine-insensitive binding site for glycine. Pharmacological antagonism of glycine binding at this site can produce anticonvulsant activity. Derivatives of kynurenic acid, pyridine and 2-carboxy-indole were synthesized and evaluated as antagonists of glycine binding and for anticonvulsant effects. Compounds were tested in mice against seizures induced by electroshock and pentylenetetrazole, and in the rotorod assay for neurologic deficit. The derivatives were also assayed for binding at the NMDA-associated glycine site. The most potent anticonvulsant was ethyl 4-methylamino-5,7-dichloro-2-quinoline carboxylate. This compound provided protection against maximal electroshock (MES) induced seizures at a dose of 30 mg/kg. Other compounds were active at 100 mg/kg dose level, including 5-fluoro-2-indole carboxylic acid and the diethyl ester of 2,6-pyridine dicarboxylic acid.
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Nichols Alfred C.
Yielding K. Lemone
Board of Regents , The University of Texas System
M. Mach D. Margaret
Rothman Alan L.
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