title: Orally active aminopyridines as inhibitors of tetrameric fructose-1,6-bisphosphatase.
abstract: A novel sulfonylureido pyridine series exemplified by compound 19 yielded potent inhibitors of FBPase showing significant glucose reduction and modest glycogen lowering in the acute db/db mouse model for Type-2 diabetes. Our inhibitors occupy the allosteric binding site and also extend into the dyad interface region of tetrameric FBPase.
authors.affiliation: F. Hoffmann-La Roche Ltd, Discovery Research Basel, CH-4070 Basel, Switzerland.
authors.forename: Paul
authors.initials: P
authors.lastname: Hebeisen
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Haap
authors.forename: Bernd
authors.initials: B
authors.lastname: Kuhn
authors.forename: Peter
authors.initials: P
authors.lastname: Mohr
authors.forename: Hans Peter
authors.initials: HP
authors.lastname: Wessel
authors.forename: Ulrich
authors.initials: U
authors.lastname: Zutter
authors.forename: Stephan
authors.initials: S
authors.lastname: Kirchner
authors.forename: Armin
authors.initials: A
authors.lastname: Ruf
authors.forename: Jörg
authors.initials: J
authors.lastname: Benz
authors.forename: Catherine
authors.initials: C
authors.lastname: Joseph
authors.forename: Rubén
authors.initials: R
authors.lastname: Alvarez-Sánchez
authors.forename: Marcel
authors.initials: M
authors.lastname: Gubler
authors.forename: Brigitte
authors.initials: B
authors.lastname: Schott
authors.forename: Agnes
authors.initials: A
authors.lastname: Benardeau
authors.forename: Effie
authors.initials: E
authors.lastname: Tozzo
authors.forename: Eric
authors.initials: E
authors.lastname: Kitas
mesh_terms: D000284:Administration, Oral; D000495:Allosteric Site; D000631:Aminopyridines / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D018360:Crystallography, X-Ray; D003924:Diabetes Mellitus, Type 2; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006597:Fructose-Bisphosphatase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D008099:Liver / Q000201:enzymology; D051379:Mice; D015394:Molecular Structure
chemical_list: D000631:Aminopyridines; D004791:Enzyme Inhibitors; D006597:Fructose-Bisphosphatase