2&apos;,6,7-取代 2-苯基-4-■■酮-3-羧酸衍生物之合成及細胞致毒活性; Synthesis and Cytotoxicity of 2&apos;,6,7-Substituted 2-Phenyl-4-quinolone-3-carboxylic acid Derivatives

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Title:	2',6,7-取代 2-苯基-4-■■酮-3-羧酸衍生物之合成及細胞致毒活性;Synthesis and Cytotoxicity of 2',6,7-Substituted 2-Phenyl-4-quinolone-3-carboxylic acid Derivatives
Authors:	方亞齡;Fang Ya-Ling
Contributors:	中國醫藥學院藥物化學研究所
Keywords:	細胞致毒活性;抗有絲分裂;抗癌活性;cytotoxicity;antimitotic;anticancer
Date:	1992
Issue Date:	2009-12-23
Abstract:	過去已合成出一系列3',6-substituted 2-phenyl-4-quinolone-3-carboxylic acids並評估其細胞致毒活性，結果顯示部分化合物具有明顯的活性，由於此項初步結果，因而從事2',6,7-substituted 2-phenyl-4-quinolone-3-carboxylic acids之合成。首先substituted anilines 1-5和substituted benzoyl chlorides 6-10反應得到相對應的benzamides 11-24；接著將化合物11-24與PCl5進行氯化反應形成carboximidoyl chlorides，爾後再與sodium diethylmalonate反應而生成相對應的中間體；此相對應的中間體直接加熱環化即可獲得ethyl substituted 2-phenyl-4-quinolone-3-carboxylates 31-42；最後水解化合物31-42而得到標的化合物carboxylic acids 45-56。檢視標的化合物45-56及其中間體的藥理活性，包括：細胞致毒活性、嗜中性白血球過氧化物形成之抑制活性、嗜中性白血球脫顆粒反應之抑制活性、肥胖細胞脫顆粒反應之抑制活性、TNF-α形成之抑制活性及一氧化氮形成之抑制活性，結果顯示部分化合物具有明顯的活性。其中，29, 30, 43, 44及56具有明顯的細胞致毒活性、32, 36及40具有明顯抑制嗜中性白血球過氧化物形成之活性、43及44具有優越的TNF-α形成之抑制活性。; In a previous paper, a series of 3',6-substituted 2-phenyl-4-quinolone-3-carboxylic acids were synthesized, and their cytotoxicity was evaluated. Some of 3',6-substituted 2-phenyl-4-quinolone-3-carboxylic acids showed significant activity. Encouraged by the initial result, 2',6,7-substituted 2-phenyl-4-quinolone-3-carboxylic acids were synthesized. Reaction of substituted anilines 1-5 with substituted benzoyl chlorides 6-10 yielded the corresponding benzamides 11-24. Chlorination of compounds 11-24 with PCl5 afforded the carboximidoyl chlorides that treated with sodium diethylmalonate to give their corresponding intermediates. These intermediates were thermally cyclized into their corresponding ethyl substituted 2-phenyl-4-quinolone-3-carboxylates 31-42 that were hydrolyzed into the target compounds, carboxylic acids 45-56. The target compounds 45-56 and their intermediates were examined for their cytotoxicity, inhibitory effect on neutrophil superoxide formation, neutrophil degranulation, mast cell degranulation, TNF-α formation and nitrile accumulation. Some of these compounds showed significant activities. Among them, 29, 30, 43, 44 and 56 exhibited significant cytotoxicity, 32, 36 and 40 exhibited significant inhibitory effect on neutrophil superoxide formation and 43, 44 exhibited potent inhibitory effect on TNF-α formation.
Appears in Collections:	[Graduate Institute of Pharmaceutical Chemistry] Theses & dissertations

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