title: Hydroxyl-substituted sulfonylureas as potent inhibitors of specific [3H]glyburide binding to rat brain synaptosomes.
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.
authors.affiliation: Division of Basic Pharmaceutical Sciences, College of Pharmacy, The University of Louisiana at Monroe, Monroe, LA 71209, USA. rhill@ulm.edu
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Hill
authors.forename: Sonali
authors.initials: S
authors.lastname: Rudra
authors.forename: Bo
authors.initials: B
authors.lastname: Peng
authors.forename: David S
authors.initials: DS
authors.lastname: Roane
authors.forename: Jeffrey K
authors.initials: JK
authors.lastname: Bounds
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ahmad
authors.initials: A
authors.lastname: Adloo
authors.forename: Tiansheng
authors.initials: T
authors.lastname: Lu
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005905:Glyburide / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006878:Hydroxides / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D051381:Rats; D013453:Sulfonylurea Compounds / Q000737:chemistry / Q000494:pharmacology*; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism; D014316:Tritium / Q000378:metabolism
chemical_list: D006878:Hydroxides; D013453:Sulfonylurea Compounds; D014316:Tritium; C031356:hydroxide ion; D005905:Glyburide