title: C-8 Modifications of 3-alkyl-1,8-dibenzylxanthines as inhibitors of human cytosolic phosphoenolpyruvate carboxykinase.
abstract: New modifications on the C-8 4-aminobenzyl unit of the previously reported 3-alkyl-1,8-dibenzylxanthine inhibitors of cPEPCK are presented. The most active compound reported here is the 5-chloro-1,3-dimethyl-1H-pyrazole-4-sulfonic acid amide derivative 2 with an IC(50) of 0.29+/-0.08 microM. An X-ray analysis of a heteroaromatic sulfonamide is presented showing a new pi-pi interaction.
authors.affiliation: Department of Discovery Chemistry, Roche Research Center, Hoffmann-La Roche Inc., Nutley, NJ 07110, USA.
authors.forename: Sherrie L
authors.initials: SL
authors.lastname: Pietranico
authors.forename: Louise H
authors.initials: LH
authors.lastname: Foley
authors.forename: Nicholas
authors.initials: N
authors.lastname: Huby
authors.forename: Weiya
authors.initials: W
authors.lastname: Yun
authors.forename: Pete
authors.initials: P
authors.lastname: Dunten
authors.forename: John
authors.initials: J
authors.lastname: Vermeulen
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: Katherine
authors.initials: K
authors.lastname: Toth
authors.forename: Gwendolyn
authors.initials: G
authors.lastname: Ramsey
authors.forename: Mary-Lou
authors.initials: ML
authors.lastname: Gubler
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Wertheimer
mesh_terms: D003600:Cytosol / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000037:antagonists & inhibitors*; D014970:Xanthines / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D014970:Xanthines; D010729:Phosphoenolpyruvate Carboxykinase (GTP)