Synthesis and SAR of 1,9-dihydro-9-hydroxypyrazolo[3,4-b]quinolin-4-ones as novel, selective c-Jun N-terminal kinase inhibitors.
A novel class of 1,9-dihydro-9-hydroxypyrazolo[3,4-b]quinolin-4-ones as c-Jun-N-terminal kinase (JNK) inhibitors is described. These compounds were synthesized via the condensation of 2-nitrobenzaldehydes and hydroxypyrazoles. The structure-activity relationships (SAR) and kinase selectivity profile of the inhibitors are also discussed. Compound 16 was identified as a potent JNK inhibitor with good cellular potency.
Liu
Mei
M
Metabolic Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-6098, USA. mei.liu@abbott.com
Xin
Zhili
Z
Clampit
Jill E
JE
Wang
Sanyi
S
Gum
Rebecca J
RJ
Haasch
Deanna L
DL
Trevillyan
James M
JM
Abad-Zapatero
Cele
C
Fry
Elizabeth H
EH
Sham
Hing L
HL
Liu
Gang
G
D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D015363:Quinolones / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D015363:Quinolones; D048031:JNK Mitogen-Activated Protein Kinases