title: Discovery of potent, highly selective, and orally bioavailable pyridine carboxamide c-Jun NH2-terminal kinase inhibitors.
abstract: C-Jun NH2 terminal kinases (JNKs) are important cell signaling enzymes. JNK1 plays a central role in linking obesity and insulin resistance. JNK2 and JNK3 may be involved in inflammatory and neurological disorders, respectively. Small-molecule JNK inhibitors could be valuable tools to study the therapeutic benefits of inhibiting these enzymes and as leads for potential drugs targeting JNKs. In this report, we disclose a series of potent and highly selective JNK inhibitors with good pharmacokinetic profiles.
authors.affiliation: Metabolic Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064-6098, USA. Hongyu.zhao@abbott.com
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhao
authors.forename: Michael D
authors.initials: MD
authors.lastname: Serby
authors.forename: Zhili
authors.initials: Z
authors.lastname: Xin
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Szczepankiewicz
authors.forename: Mei
authors.initials: M
authors.lastname: Liu
authors.forename: Christi
authors.initials: C
authors.lastname: Kosogof
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.forename: Lissa T J
authors.initials: LT
authors.lastname: Nelson
authors.forename: Eric F
authors.initials: EF
authors.lastname: Johnson
authors.forename: Sanyi
authors.initials: S
authors.lastname: Wang
authors.forename: Terry
authors.initials: T
authors.lastname: Pederson
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Gum
authors.forename: Jill E
authors.initials: JE
authors.lastname: Clampit
authors.forename: Deanna L
authors.initials: DL
authors.lastname: Haasch
authors.forename: Cele
authors.initials: C
authors.lastname: Abad-Zapatero
authors.forename: Elizabeth H
authors.initials: EH
authors.lastname: Fry
authors.forename: Cristina
authors.initials: C
authors.lastname: Rondinone
authors.forename: James M
authors.initials: JM
authors.lastname: Trevillyan
authors.forename: Hing L
authors.initials: HL
authors.lastname: Sham
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
mesh_terms: D000284:Administration, Oral; D000577:Amides / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D001682:Biological Availability; D018360:Crystallography, X-Ray; D006801:Humans; D066298:In Vitro Techniques; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D051379:Mice; D008861:Microsomes / Q000378:metabolism; D008958:Models, Molecular; D011725:Pyridines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D013816:Thermodynamics
chemical_list: D000577:Amides; D011725:Pyridines; D048031:JNK Mitogen-Activated Protein Kinases