title: The discovery of potent and selective 4-aminothienopyridines as B-Raf kinase inhibitors.
abstract: A series of novel, potent 4-aminothienopyridine B-Raf kinase inhibitors was designed and synthesized using knowledge-based design. Compounds 5f, and 6k exhibited not only excellent potency in both enzyme assay (IC(50)=5.1, 16.6 nM) and cellular assay (IC(50)=0.2, 0.2 μM), but also had an outstanding selectivity profile against other kinases.
authors.affiliation: GlaxoSmithKline Research & Development, Research Triangle Park, NC 27709, USA. jun.x.tang@gsk.com
authors.forename: Jun
authors.initials: J
authors.lastname: Tang
authors.forename: Karen E
authors.initials: KE
authors.lastname: Lackey
authors.forename: Scott H
authors.initials: SH
authors.lastname: Dickerson
mesh_terms: D000631:Aminopyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D010671:Phenylurea Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D058924:Thienopyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000631:Aminopyridines; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D058924:Thienopyridines; D048493:Proto-Oncogene Proteins B-raf