Title: Exploitation of the 3-Quinolinecarbonitrile Template for Src Tyrosine Kinase Inhibitors
VOLUME: 8 ISSUE: 10
Author(s):Diane H. Boschelli
Affiliation:Chemical and Screening Sciences, Wyeth Research, 401 N. Middletown Road, Pearl River, NY 10965.
Keywords:3-Quinolinecarbonitrile, kinase, Src, cancer, Abl, CML, SKI-606, bosutinib
Abstract: 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.
