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 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.
Hill
Ronald A
RA
Division of Basic Pharmaceutical Sciences, College of Pharmacy, The University of Louisiana at Monroe, Monroe, LA 71209, USA. rhill@ulm.edu
Rudra
Sonali
S
Peng
Bo
B
Roane
David S
DS
Bounds
Jeffrey K
JK
Zhang
Yang
Y
Adloo
Ahmad
A
Lu
Tiansheng
T
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
D006878:Hydroxides; D013453:Sulfonylurea Compounds; D014316:Tritium; C031356:hydroxide ion; D005905:Glyburide