- Synthesis and structure-activity relationship for new series of 4-phenoxyquinoline derivatives as specific inhibitors of platelet-derived growth factor receptor tyrosine kinase
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We discovered a new series of 4-phenoxyquinoline derivatives as potent and selective inhibitors of the platelet-derived growth factor receptor (PDGFr) tyrosine kinase. We researched the highly potent and selective inhibitors on the basis of both PDGFr and epidermal growth factor receptor (EGFr) inhibitory activity. First, we found a compound, Ki6783 (1), which inhibited PDGFr autophosphorylation at 0.13 μM, but it did not inhibit EGFr autophosphorylation at 100 μM. After extensive explorations, we found the two desired compounds, Ki6896 (2) and Ki6945 (3), which are substituted by benzoyl and benzamide at the 4-position of the phenoxy group on 4-phenoxyquinoline, respectively. These inhibitory activities were 0.31 and 0.050 μM, respectively, but neither of them inhibited EGFr autophosphorylation at 100 μM. We further investigated the profile of both compounds toward various tyrosine and serine/threonine kinases. The three compounds specifically inhibited PDGFr rather than the other kinases.
- Kubo, Kazuo,Ohyama, Shin-Ichi,Shimizu, Toshiyuki,Takami, Atsuya,Murooka, Hideko,Nishitoba, Tsuyoshi,Kato, Shinichiro,Yagi, Mikio,Kobayashi, Yoshiko,Iinuma, Noriko,Isoe, Toshiyuki,Nakamura, Kazuhide,Iijima, Hiroshi,Osawa, Tatsushi,Izawa, Toshio
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p. 5117 - 5133
(2007/10/03)
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- Synthesis and structure-activity relationships of benzophenone hydrazone derivatives with insecticidal activity
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A broad range of benzophenone hydrazone derivatives was prepared and tested against selected chewing insect pests, allowing the analysis of structure-activity relationships. Good activity was found only when the aromatic rings were substituted at the 4-positions with an halogen atom and a triflate or perhaloalkoxy group. In contrast, a number of substituents on the hydrazone part led to active compounds, the best results being achieved with acyl-type substituents. The excellent laboratory and greenhouse activity of the best representatives was confirmed in semi-field trials against Spodoptera littoralis. ° 2001 Society of Chemical Industry.
- Boeger, Manfred,Duerr, Dieter,Gsell, Laurenz,Hall, Roger G.,Karrer, Friedrich,Kristiansen, Odd,Maienfisch, Peter,Pascual, Alfons,Rindlisbacher, Alfred
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p. 191 - 202
(2007/10/03)
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- Quinoline and quinazoline derivatives inhibiting platelet-derived growth factor receptor autophosphorylation and pharmaceutical compositions containing the same
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The present invention relates to novel quinoline derivatives and quinazoline derivatives represented by the following formula (I): STR1 [wherein R 1 and R 2 are each independently H or C 1 -C 4 -alkyl, or R 1 and R 2 together form C 1 -C 3 -alkylene, X is O, S or CH 2, W is CH or N, and Q is a substituted aryl group or substituted heteroaryl group] and their pharmaceutically acceptable salts, having platelet-derived growth factor receptor autophosphorylation inhibitory activity, to pharmaceutical compositions containing these compounds, and to methods for the treatment of diseases associated with abnormal cell growth such as tumors.
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