Synthesis and evaluation of [2-(4-quinolyloxy)phenyl]methanone derivatives: novel selective inhibitors of transforming growth factor-beta kinase.
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.
Shimizu
Toshiyuki
T
KIRIN Pharma Co Ltd, Shibuya, Tokyo, Japan. tshimizu@kirin.co.jp
Kimura
Kaname
K
Sakai
Teruyuki
T
Kawakami
Kazuki
K
Miyazaki
Tetsuko
T
Nakouji
Masayoshi
M
Ogawa
Akira
A
Ohuchi
Hitomi
H
Shimizu
Kiyoshi
K
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
D011804:Quinolines; D051899:Smad2 Protein; D051900:Smad3 Protein; D016212:Transforming Growth Factor beta; D008156:Luciferases; D030201:Activin Receptors, Type I