Quinolic acid derivatives

Details Quinolic acid derivatives Quinolic acid derivatives

1997-07-03

1998-07-21

Morris, Patricia L.

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

C07D21542

Patent

active

057837007

ABSTRACT:
Coupled to the N-methyl-D-aspartate (NMDA) receptor complex is a strychnine-insensitive binding site for glycine. Pharmacological antagonism of glycine at this site may produce anticonvulsant activity. Twelve 4-urea-5,7-dichlorokynurenic acid derivatives were synthesized and subsequently screened in mice for anticonvulsant activity using MES, Met, and TTE tests, and a rotorod test was used to determine neurotoxicity. Seven of the derivatives had anticonvulsant activity in TTE testing at 100 mg/kg. One derivative had an ED.sub.50 value of 134 mg/kg in TTE testing. Two derivatives had MES activity. Only one derivative was neurotoxic in the rotorod test. Compounds were screened at a 10 uM concentration for activity in displacing 5,7-dichlorokynurenic acid from synaptosomal membrane fragments. Nine of the twelve compounds synthesized and tested have demonstrated anticonvulsant activity. Thus, compounds of the present invention should be usable for the treatment of epilepsy, neurodegenerative diseases, and other syndromes involving inhibition or excessive stimulation of the NMDA receptor complex.

REFERENCES:
patent: 4788188 (1988-11-01), Vernieres et al.
patent: 5017576 (1991-05-01), Dubroeucq et al.
patent: 5026700 (1991-06-01), Harrison et al.
patent: 5208707 (1991-07-01), Nichols et al.
patent: 5250541 (1993-10-01), Moroni et al.
patent: 5252584 (1993-10-01), Carling et al.
patent: 5270309 (1993-12-01), Leeson
patent: 5344922 (1994-09-01), Nichols et al.
patent: 5348962 (1994-09-01), Kulagowski et al.
patent: 5493027 (1996-02-01), Nichols et al.
Leeson et al., 4-Amido-2-carboxytetrahydroquinolines. Structure-Activity Relationships for Antagonism at the Glycide Site of the NMDA Receptor, J. Med. Chem., 35:1954-1968 (1992).
Carling et al., 2-Carboxytetrahydroquinolines. Conformational and Stereochemical Requirements for Antagonism of the Glycine Site on the NMDA Receptor, J. Med. Chem., 35:1954-1968 (1992).
Leeson et al., Kynurenic Acid Derivatives. Structure-Activity Relationships for Excitatory Amino Acid Antagonism and Identification of Potent and Selective Antagonists, J. Med. Chem., 34:1243-1252 (1991).

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