Synthesis and structure--activity relationships of fused imidazopyridines: a new series of benzodiazepine receptor ligands.

Article Details

Citation

Takada S, Sasatani T, Chomei N, Adachi M, Fujishita T, Eigyo M, Murata S, Kawasaki K, Matsushita A

Synthesis and structure--activity relationships of fused imidazopyridines: a new series of benzodiazepine receptor ligands.

J Med Chem. 1996 Jul 5;39(14):2844-51. doi: 10.1021/jm9600609.

PubMed ID
8709114 [ View in PubMed
]
Abstract

2-Arylimidazo[4,5-c]quinolines and analogous fused imidazopyridines were synthesized and evaluated as benzodiazepine receptor ligands. Affinity to the receptors was greatly affected by the bulkiness of the aryl group at the 2-position, compared to the pyrazoloquinolines such as CGS-9896. Derivatives with an isoxazole moiety at the 2-position showed high binding affinity and in vivo activity. In the imidazo[4,5-c]quinoline series, substitution at the 6-position decreased or abolished activity. Most derivatives with an unsubstituted isoxazolyl group showed antagonist or inverse agonist activity except for the 7-halo analogues, which exhibited agonist activity. On the other hand, 5-methylisoxazol-3-yl or 3-methylisoxazol-5-yl derivatives generally exhibited agonist activity. A similar substitution effect on the isoxazole moiety was observed in the imidazopyridines fused with a nonaromatic ring. From the detailed pharmacological evaluation, S-8510, 2-(3-isoxazolyl)-3,6,7,9-tetrahydroimidazo[4,5-d]pyrano++ +[4,3-b]pyridine monophosphate, possessing weak inverse agonist activity was selected as a therapeutic candidate for the treatment of some symptoms of senile dementia.

DrugBank Data that Cites this Article

Drugs