title: Facile preparation of new 4-phenylamino-3-quinolinecarbonitrile Src kinase inhibitors via 7-fluoro intermediates: identification of potent 7-amino analogs.
abstract: A more efficient preparation of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-fluoro-6-methoxy-3-quinolinecarbonitrile (2), the penultimate intermediate in the synthesis of bosutinib (1a), was developed. New 7-alkoxy-4-phenylamino-3-quinolinecarbonitrile Src inhibitors were prepared from 5 and 9, the 6-ethoxy and 6-hydrogen analogs of 2. In addition, the fluoro group of 2 was readily displaced by primary and secondary amines to give 7-amino analogs. Two of these 7-amino analogs, 15 and 18, were potent Src inhibitors with in vivo activity.
authors: Chemical and Screening Sciences, Wyeth Research, 401 N. Middletown Road, Pearl River, NY 10965, USA. bosched@wyeth.com
authors: Diane H
authors: DH
authors: Boschelli
authors: Biqi
authors: B
authors: Wu
authors: Fei
authors: F
authors: Ye
authors: Haris
authors: H
authors: Durutlic
authors: Jennifer M
authors: JM
authors: Golas
authors: Judy
authors: J
authors: Lucas
authors: Frank
authors: F
authors: Boschelli
mesh_terms: D000588:Amines; D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D009570:Nitriles / Q000138:chemical synthesis* / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D019061:src-Family Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000588:Amines; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D011804:Quinolines; D019061:src-Family Kinases