Hydroxyl-Substituted sulfonylureas as potent inhibitors of specific [ 3H]Glyburide binding to rat brain synaptosomes

We are seeking to discover potent CNS-active sulfonylureas with structural features that allow for the formation of several types of prodrugs. We report herein the syntheses of compounds comprising an initial series of hydroxyl-substituted analogues of the potent ATP-sensitive potassium channel bloc...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry 2003-05, Vol.11 (9), p.2099-2113
Main Authors: Hill, Ronald A., Rudra, Sonali, Peng, Bo, Roane, David S., Bounds, Jeffrey K., Zhang, Yang, Adloo, Ahmad, Lu, Tiansheng
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Brain - drug effects
Brain - metabolism
Dose-Response Relationship, Drug
General and cellular metabolism. Vitamins
Glyburide - antagonists & inhibitors
Glyburide - metabolism
Hydroxides - chemistry
Hydroxides - pharmacology
Medical sciences
Pharmacology. Drug treatments
Protein Binding - drug effects
Protein Binding - physiology
Rats
Sulfonylurea Compounds - chemistry
Sulfonylurea Compounds - pharmacology
Synaptosomes - drug effects
Synaptosomes - metabolism
Tritium - metabolism
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Summary:We are seeking to discover potent CNS-active sulfonylureas with structural features that allow for the formation of several types of prodrugs. We report herein the syntheses of compounds comprising an initial series of hydroxyl-substituted analogues of the potent ATP-sensitive potassium channel blockers glyburide (glibenclamide) and gliquidone. Somewhat unexpectedly, several of the compounds were found to be comparably potent to glyburide as inhibitors of specific [ 3H]glyburide binding in rat brain preparations. Graphic
ISSN:0968-0896
1464-3391
DOI:10.1016/S0968-0896(02)00606-5