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Discovery of 6-benzyloxyquinolines as c-Met selective kinase inhibitors
Hiroki Nishii1, Takashi Chiba, Kenji Morikami
1Department of Chemistry Research 2, Chugai Pharmaceutical Co, Ltd, 200 Kajiwara, Kamakura, Kanagawa 247-8530, Japan.
Abstract:
A novel quinoline derivative that selectively inhibits c-Met kinase was identified. The molecular design is based on a result of the analysis of a PF-2341066 (1)/c-Met cocrystal structure (PDB code: 2wgj). The kinase selectivity of the derivatives is discussed from the view point of the sequence homology of the kinases, the key interactions found in X-ray cocrystal structures, and the structure-activity relationship (SAR) obtained in this work.
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