5-Chloroindoloyl glycine amide inhibitors of glycogen phosphorylase: synthesis, in vitro, in vivo, and X-ray crystallographic characterization.
The synthesis, in vitro, and in vivo biological characterization of a series of achiral 5-chloroindoloyl glycine amide inhibitors of human liver glycogen phosphorylase A are described. Improved potency over previously reported compounds in cellular and in vivo assays was observed. The allosteric binding site of these compounds was shown by X-ray crystallography to be the same as that reported previously for 5-chloroindoloyl norstatine amides.
Wright
Stephen W
SW
Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA. stephen_w_wright@groton.pfizer.com
Rath
Virginia L
VL
Genereux
Paul E
PE
Hageman
David L
DL
Levy
Carolyn B
CB
McClure
Lester D
LD
McCoid
Scott C
SC
McPherson
R Kirk
RK
Schelhorn
Teresa M
TM
Wilder
Donald E
DE
Zavadoski
William J
WJ
Gibbs
E Michael
EM
Treadway
Judith L
JL
D000495:Allosteric Site; D000577:Amides / Q000138:chemical synthesis* / Q000494:pharmacology; D000614:Aminocaproates / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D005998:Glycine / Q000737:chemistry / Q000494:pharmacology; D024981:Glycogen Phosphorylase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008099:Liver / Q000201:enzymology / Q000378:metabolism
C501381:5-chloroindoloyl glycine amide; D000577:Amides; D000614:Aminocaproates; D004791:Enzyme Inhibitors; D007211:Indoles; C034495:3-amino-2-hydroxy-5-methylhexanoic acid; D024981:Glycogen Phosphorylase; D005998:Glycine