title: Design and synthesis of 6-anilinoindazoles as selective inhibitors of c-Jun N-terminal kinase-3.
abstract: The structure-based design and synthesis of a new series of c-Jun N-terminal kinase-3 inhibitors with selectivity against JNK1 and p38alpha is reported. The novel series of substituted 6-anilinoindazoles were designed based on a combination of hits from high throughput screening and X-ray crystal structure information of the compounds crystallized into the JNK3 ATP binding active site.
authors.affiliation: Department of Medicinal Chemistry, AstraZeneca R&D Södertälje, S-15185 Södertälje, Sweden. britt-marie.swahn@astrazeneca.com
authors.forename: Britt-Marie
authors.initials: BM
authors.lastname: Swahn
authors.forename: Fernando
authors.initials: F
authors.lastname: Huerta
authors.forename: Elisabet
authors.initials: E
authors.lastname: Kallin
authors.forename: Jonas
authors.initials: J
authors.lastname: Malmström
authors.forename: Tatjana
authors.initials: T
authors.lastname: Weigelt
authors.forename: Jenny
authors.initials: J
authors.lastname: Viklund
authors.forename: Patrick
authors.initials: P
authors.lastname: Womack
authors.forename: Yafeng
authors.initials: Y
authors.lastname: Xue
authors.forename: Liselotte
authors.initials: L
authors.lastname: Ohberg
mesh_terms: D001665:Binding Sites; D018360:Crystallography, X-Ray; D015195:Drug Design; D007191:Indazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D048057:Mitogen-Activated Protein Kinase 10 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D048308:Mitogen-Activated Protein Kinase 14 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048055:Mitogen-Activated Protein Kinase 8 / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017434:Protein Structure, Tertiary; D012680:Sensitivity and Specificity; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D007191:Indazoles; D047428:Protein Kinase Inhibitors; D048057:Mitogen-Activated Protein Kinase 10; D048308:Mitogen-Activated Protein Kinase 14; D048055:Mitogen-Activated Protein Kinase 8