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

Ronald A Hill; Sonali Rudra; Bo Peng; David S Roane; Jeffrey K Bounds; Yang Zhang; Ahmad Adloo; Tiansheng Lu

doi:10.1016/s0968-0896(02)00606-5

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

Bioorg Med Chem. 2003 May 1;11(9):2099-113. doi: 10.1016/s0968-0896(02)00606-5.

Authors

Ronald A Hill¹, Sonali Rudra, Bo Peng, David S Roane, Jeffrey K Bounds, Yang Zhang, Ahmad Adloo, Tiansheng Lu

Affiliation

¹ Division of Basic Pharmaceutical Sciences, College of Pharmacy, The University of Louisiana at Monroe, Monroe, LA 71209, USA. rhill@ulm.edu

PMID: 12670661
DOI: 10.1016/s0968-0896(02)00606-5

Abstract

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 [(3)H]glyburide binding in rat brain preparations.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain / drug effects*
Brain / metabolism
Dose-Response Relationship, Drug
Glyburide / antagonists & inhibitors*
Glyburide / metabolism
Hydroxides / chemistry
Hydroxides / pharmacology*
Protein Binding / drug effects
Protein Binding / physiology
Rats
Sulfonylurea Compounds / chemistry
Sulfonylurea Compounds / pharmacology*
Synaptosomes / drug effects*
Synaptosomes / metabolism
Tritium / metabolism

Substances

Hydroxides
Sulfonylurea Compounds
Tritium
hydroxide ion
Glyburide