title: Synthesis and SAR of 1,9-dihydro-9-hydroxypyrazolo[3,4-b]quinolin-4-ones as novel, selective c-Jun N-terminal kinase inhibitors.
abstract: 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.
authors.affiliation: Metabolic Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-6098, USA. mei.liu@abbott.com
authors.forename: Mei
authors.initials: M
authors.lastname: Liu
authors.forename: Zhili
authors.initials: Z
authors.lastname: Xin
authors.forename: Jill E
authors.initials: JE
authors.lastname: Clampit
authors.forename: Sanyi
authors.initials: S
authors.lastname: Wang
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Gum
authors.forename: Deanna L
authors.initials: DL
authors.lastname: Haasch
authors.forename: James M
authors.initials: JM
authors.lastname: Trevillyan
authors.forename: Cele
authors.initials: C
authors.lastname: Abad-Zapatero
authors.forename: Elizabeth H
authors.initials: EH
authors.lastname: Fry
authors.forename: Hing L
authors.initials: HL
authors.lastname: Sham
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
mesh_terms: 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
chemical_list: D004791:Enzyme Inhibitors; D015363:Quinolones; D048031:JNK Mitogen-Activated Protein Kinases