Benzoxazole benzenesulfonamides as allosteric inhibitors of fructose-1,6-bisphosphatase

Chunqiu Lai; Rebecca J Gum; Melissa Daly; Elizabeth H Fry; Charles Hutchins; Celerino Abad-Zapatero; Thomas W von Geldern

doi:10.1016/j.bmcl.2006.01.014

Benzoxazole benzenesulfonamides as allosteric inhibitors of fructose-1,6-bisphosphatase

Bioorg Med Chem Lett. 2006 Apr 1;16(7):1807-10. doi: 10.1016/j.bmcl.2006.01.014. Epub 2006 Jan 30.

Authors

Chunqiu Lai¹, Rebecca J Gum, Melissa Daly, Elizabeth H Fry, Charles Hutchins, Celerino Abad-Zapatero, Thomas W von Geldern

Affiliation

¹ Metabolic Disease Research, GPRD, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064, USA. Chunqiu.lai@abbott.com

PMID: 16446092
DOI: 10.1016/j.bmcl.2006.01.014

Abstract

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.

MeSH terms

Allosteric Regulation
Animals
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacokinetics
Enzyme Inhibitors / pharmacology*
Fructose-Bisphosphatase / antagonists & inhibitors*
Models, Molecular
Rats
Sulfonamides / chemistry
Sulfonamides / pharmacokinetics
Sulfonamides / pharmacology*

Substances

Enzyme Inhibitors
Sulfonamides
Fructose-Bisphosphatase