Aminopyridine carboxamides as c-Jun N-terminal kinase inhibitors: targeting the gatekeeper residue and beyond.
The structure-activity relationships of 5,6-positions of aminopyridine carboxamide-based c-Jun N-terminal Kinase (JNK) inhibitors were explored to expand interaction with the kinase specificity and ribose-binding pockets. The syntheses of analogues and the impact of structural modification on in vitro potency and cellular activity are described.
Liu
Gang
G
Metabolic Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064-6101, USA. gang.liu@abbott.com
Zhao
Hongyu
H
Liu
Bo
B
Xin
Zhili
Z
Liu
Mei
M
Kosogof
Christi
C
Szczepankiewicz
Bruce G
BG
Wang
Sanyi
S
Clampit
Jill E
JE
Gum
Rebecca J
RJ
Haasch
Deanna L
DL
Trevillyan
James M
JM
Sham
Hing L
HL
D000577:Amides / Q000737:chemistry / Q000494:pharmacology*; D000631:Aminopyridines / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D011485:Protein Binding; D012266:Ribose / Q000378:metabolism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D000577:Amides; D000631:Aminopyridines; D004791:Enzyme Inhibitors; D012266:Ribose; D048031:JNK Mitogen-Activated Protein Kinases