title: 3,5-Disubstituted quinolines as novel c-Jun N-terminal kinase inhibitors.
abstract: The structure-based design and synthesis of a novel series of c-Jun N-terminal kinase (JNK) inhibitors with selectivity against p38 is reported. The unique structure of 3,5-disubstituted quinolines (2) was developed from the previously reported 4-(2,7-phenanthrolin-9-yl)phenol (1). The X-ray crystal structure of 16a in JNK3 reveals an unexpected binding mode for this new scaffold with protein.
authors.affiliation: Department of Medicinal Chemistry, Scripps Florida, 5353 Parkside Drive, RF-2, Jupiter, FL 33458, USA. rjiang@scripps.edu
authors.forename: Rong
authors.initials: R
authors.lastname: Jiang
authors.forename: Derek
authors.initials: D
authors.lastname: Duckett
authors.forename: Weiming
authors.initials: W
authors.lastname: Chen
authors.forename: Jeff
authors.initials: J
authors.lastname: Habel
authors.forename: Yuan Yuan
authors.initials: YY
authors.lastname: Ling
authors.forename: Philip
authors.initials: P
authors.lastname: LoGrasso
authors.forename: Theodore M
authors.initials: TM
authors.lastname: Kamenecka
mesh_terms: D018360:Crystallography, X-Ray; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D010618:Phenanthrolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D011804:Quinolines / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
chemical_list: D010618:Phenanthrolines; D011804:Quinolines; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases