C-8 Modifications of 3-alkyl-1,8-dibenzylxanthines as inhibitors of human cytosolic phosphoenolpyruvate carboxykinase.
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.
Pietranico
Sherrie L
SL
Department of Discovery Chemistry, Roche Research Center, Hoffmann-La Roche Inc., Nutley, NJ 07110, USA.
Foley
Louise H
LH
Huby
Nicholas
N
Yun
Weiya
W
Dunten
Pete
P
Vermeulen
John
J
Wang
Ping
P
Toth
Katherine
K
Ramsey
Gwendolyn
G
Gubler
Mary-Lou
ML
Wertheimer
Stanley J
SJ
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*
D004791:Enzyme Inhibitors; D014970:Xanthines; D010729:Phosphoenolpyruvate Carboxykinase (GTP)