Orally active anti-proliferation agents: novel diphenylamine derivatives as FGF-R2 autophosphorylation inhibitors |
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Authors: | Shimizu Toshiyuki Fujiwara Yasunari Osawa Tatsushi Sakai Teruyuki Kubo Kinya Kubo Kazuo Nishitoba Tsuyoshi Kimura Kaname Senga Terufumi Murooka Hideko Iwai Akemi Fukushima Kayoko Yoshino Tetsuya Miwa Atsushi |
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Affiliation: | Pharmaceutical Research Laboratories, Kirin Brewery Co., Ltd., 3 Miyahara, Takasaki, Gunma, 370-1295, Japan. tshimuzu@kirin.co.jp |
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Abstract: | (6,7-Disubstituted-quinolin-4-yloxy-phenyl)(4-substituted-phenyl)amine derivatives were synthesized and evaluated by a cellular autophosphorylation assay for FGF-R2 in the human scirrhous gastric carcinoma cell line, OCUM-2MD3. We also performed metabolic stability studies showing that substitutions at the 7-position of quinoline affect its biological stability. In this study, we achieved a remarkable improvement in the solubility and metabolic stability of the diphenylamine derivative. The most promising compound 15e showed a significant decrease in tumor volume when orally administered. |
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