Benzoxazole benzenesulfonamides as allosteric inhibitors of fructose-1,6-bisphosphatase.
A series of novel benzoxazole benzenesulfonamides was synthesized as inhibitors of fructose-1,6-bisphosphatase (FBPase-1). Extensive SAR studies led to a potent inhibitor, 53, with an IC(50) of 0.57microM. Compound 17 exhibited excellent bioavailability and a good pharmacokinetic profile in rats.
Lai
Chunqiu
C
Metabolic Disease Research, GPRD, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064, USA. Chunqiu.lai@abbott.com
Gum
Rebecca J
RJ
Daly
Melissa
M
Fry
Elizabeth H
EH
Hutchins
Charles
C
Abad-Zapatero
Celerino
C
von Geldern
Thomas W
TW
D000494:Allosteric Regulation; D000818:Animals; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D006597:Fructose-Bisphosphatase / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D051381:Rats; D013449:Sulfonamides / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D013449:Sulfonamides; D006597:Fructose-Bisphosphatase