Exploitation of the 3-quinolinecarbonitrile template for SRC tyrosine kinase inhibitors.
In 2000, Wyeth reported that the 3-quinolinecarbonitrile ring system was a template for EGFR inhibitors. It soon became apparent that the group at C-4 of this core was responsible for kinase selectivity. A 4-(2,4-dichloro-5-methoxyanilino) substituent provided potent inhibitors of Src, a non-receptor tyrosine kinase that plays a key role in cell signaling. One compound from this series, SKI-606, bosutinib, is currently in clinical trials for the treatment of cancer.
Boschelli
Diane H
DH
Chemical and Screening Sciences, Wyeth Research, 401 N. Middletown Road, Pearl River, NY 10956, USA. Bosched@wyeth.com
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D011804:Quinolines / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D019061:src-Family Kinases / Q000037:antagonists & inhibitors*
D000970:Antineoplastic Agents; D011804:Quinolines; D019061:src-Family Kinases