Current Topics in Medicinal Chemistry 2008-01-01

Exploitation of the 3-quinolinecarbonitrile template for SRC tyrosine kinase inhibitors.

Diane H Boschelli

Index: Curr. Top. Med. Chem 8(10) , 922-34, (2008)

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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.