title: Discovery of aminopyridines substituted with benzoxazole as orally active c-Met kinase inhibitors.
abstract: We report the synthesis and biological evaluation of aminopyridines substituted with benzoxazole. The SAR of the aminopyridines was explored to improve the inhibitory activity against c-Met and to decrease hERG affinity. These studies led to the discovery of amide 24 which showed good c-Met inhibitory potency, low affinity to hERG and favorable pharmacokinetic properties in rats.
authors.affiliation: Bio-Organic Science Division, Korea Research Institute of Chemical Technology, PO Box 107, Daejeon 305-600, Republic of Korea.
authors.forename: Sung Yun
authors.initials: SY
authors.lastname: Cho
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Han
authors.forename: Jae Du
authors.initials: JD
authors.lastname: Ha
authors.forename: Jae Wook
authors.initials: JW
authors.lastname: Ryu
authors.forename: Chong Ock
authors.initials: CO
authors.lastname: Lee
authors.forename: Heejung
authors.initials: H
authors.lastname: Jung
authors.forename: Nam Sook
authors.initials: NS
authors.lastname: Kang
authors.forename: Hyoung Rae
authors.initials: HR
authors.lastname: Kim
authors.forename: Jong Sung
authors.initials: JS
authors.lastname: Koh
authors.forename: Jongkook
authors.initials: J
authors.lastname: Lee
mesh_terms: D000284:Administration, Oral; D000631:Aminopyridines / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D001583:Benzoxazoles / Q000737:chemistry*; D055808:Drug Discovery; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D000631:Aminopyridines; D001583:Benzoxazoles; D047428:Protein Kinase Inhibitors; C080835:RON protein; D020794:Receptor Protein-Tyrosine Kinases