Novel thienopyrrole glycogen phosphorylase inhibitors: synthesis, in vitro SAR and crystallographic studies.
Two series of novel thienopyrrole inhibitors of recombinant human liver glycogen phosphorylase a (GPa) which are effective in reducing glucose output from rat hepatocytes are described. Representative compounds have been shown to bind at the dimer interface site of the rabbit muscle enzyme by X-ray crystallography.
Whittamore
Paul R O
PR
AstraZeneca, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK. paul.whittamore@astrazeneca.com
Addie
Matthew S
MS
Bennett
Stuart N L
SN
Birch
Alan M
AM
Butters
Michael
M
Godfrey
Linda
L
Kenny
Peter W
PW
Morley
Andrew D
AD
Murray
Paul M
PM
Oikonomakos
Nikos G
NG
Otterbein
Ludovic R
LR
Pannifer
Andrew D
AD
Parker
Jeremy S
JS
Readman
Kristy
K
Siedlecki
Pawel S
PS
Schofield
Paul
P
Stocker
Andy
A
Taylor
Melvyn J
MJ
Townsend
Linda A
LA
Whalley
David P
DP
Whitehouse
Jennifer
J
D000818:Animals; D018360:Crystallography, X-Ray; D024981:Glycogen Phosphorylase / Q000037:antagonists & inhibitors*; D006801:Humans; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D013329:Structure-Activity Relationship
D011758:Pyrroles; D024981:Glycogen Phosphorylase