Discovery and SAR development of thienopyridones: a class of small molecule AMPK activators.
AMP-activated protein kinase (AMPK) is well established as a sensor and regulator of intracellular and whole-body energy metabolism. A high-throughput screen was performed in order to identify chemotypes that are bound by AMPK. A novel thienopyridone compound (1) was identified and subsequently optimized. The structure-activity relationships that emerged from this effort are described.
Zhao
Gang
G
Metabolic Disease Research, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064, USA. zhaoxing2@yahoo.com
Iyengar
Rajesh R
RR
Judd
Andrew S
AS
Cool
Barbara
B
Chiou
William
W
Kifle
Lemma
L
Frevert
Ernst
E
Sham
Hing
H
Kym
Philip R
PR
D055372:AMP-Activated Protein Kinases; D001681:Biological Assay; D004734:Energy Metabolism / Q000187:drug effects* / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects* / Q000502:physiology; D020536:Enzyme Activators / Q000737:chemistry / Q000494:pharmacology*; D009097:Multienzyme Complexes / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D020536:Enzyme Activators; D009097:Multienzyme Complexes; D011725:Pyridines; C446540:thienopyridine; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases