title: Synthesis and evaluation of [2-(4-quinolyloxy)phenyl]methanone derivatives: novel selective inhibitors of transforming growth factor-beta kinase.
abstract: We synthesized and evaluated various [2-(4-quinolyloxy)phenyl]methanone derivatives. These compounds had novel chemical structures that were distinct from those of previously reported inhibitors. Biological data suggested that these compounds inhibited transforming growth factor-beta signaling by interacting with the ATP-binding pocket of the transforming growth factor-beta type I receptor kinase domain. Here, we report on the synthesis and structure-activity relationships of the compounds in this series.
authors.affiliation: KIRIN Pharma Co Ltd, Shibuya, Tokyo, Japan. tshimizu@kirin.co.jp
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Shimizu
authors.forename: Kaname
authors.initials: K
authors.lastname: Kimura
authors.forename: Teruyuki
authors.initials: T
authors.lastname: Sakai
authors.forename: Kazuki
authors.initials: K
authors.lastname: Kawakami
authors.forename: Tetsuko
authors.initials: T
authors.lastname: Miyazaki
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Nakouji
authors.forename: Akira
authors.initials: A
authors.lastname: Ogawa
authors.forename: Hitomi
authors.initials: H
authors.lastname: Ohuchi
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Shimizu
mesh_terms: D030201:Activin Receptors, Type I / Q000037:antagonists & inhibitors* / Q000378:metabolism; D045744:Cell Line, Tumor; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D010766:Phosphorylation; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D011804:Quinolines; D051899:Smad2 Protein; D051900:Smad3 Protein; D016212:Transforming Growth Factor beta; D008156:Luciferases; D030201:Activin Receptors, Type I