Study on Zwitter-Ionization of Drugs. II. Synthesis and Pharmacological Activity of Some N-[3-(5H-Dibenzo[a, d]cyclohepten-5-ylidene)propyl]-N-methylamino- and N-[3-(6H-Dibenz[b, e]oxepin-11-ylidene)propyl]-N-methylamino-alkanoic Acid Derivatives and Rela
スポンサーリンク
概要
- 論文の詳細を見る
A series of N-[3-(5H-dibenzo[a, d]cyclohepten-5-ylidene)propyl]-N-methylamino- (6a) and N-[3-(6H-dibenz-[b, e]oxepin-11-ylidene)propyl]-N-methylamino-alkanoic acid derivatives (6b) and related compounds (6c-f) were synthesized and examined for pharmacological activities in vitro, i.e., inhibitory effect on monoamine [noradrenaline (NA) and 5-hydroxytryptamine (5-HT)] uptake, inhibitory effect on 5-HT-, histamine-, acetylcholine- and NA-induced contraction, and binding affinity for α_2-adrenoceptor and dopamine D_2-receptor. In vitro tests indicated that zwitter-ionization was capable of maintaining H_1-antihistaminic activity while greatly reducing other pharmacological activities. Further, 6a-f showed much stonger inhibitory effects on compound 48/80-induced lethality in rats than did the corresponding N, N-dimethylamines (2a-f). 3-[N-[3-(6H-Dibenz[b, e]oxepin-11-ylidene)propyl]-N-methylamino]-propionic acid (6b-2), selected as a candidate antiallergic agent of a new type, equally potent in rats and guinea-pigs, exhibited strong inhibitory effects on 48 h homologous passive cutaneous anaphylaxis (PCA) in rats (ED_<50>=0.019 mg/kg, p.o.) and on histamine-induced bronchoconstriction in anesthetized guinea-pigs (ED_<50>=0.0067 mg/kg, p.o.).
- 社団法人日本薬学会の論文
- 1993-11-15
著者
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加藤 日出男
北陸製薬株式会社
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大橋 徹生
北陸製薬株式会社
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伊藤 安夫
Research and Development Division, Hokuriku Seiyaku Co., Ltd.,
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澤西 啓之
the First Division of the Research Laboratory for Development of Medicine, Hokuriku University
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村松 広美
北陸大学薬学部附属創薬研究施設
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垣内 正人
北陸製薬株式会社研究開発本部
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村松 広美
The First Division of the Research Laboratory for Development of Medicine, Hokuriku University
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岩崎 信彦
Central Research Laboratories, Hokuriku Seiyaku Co., Ltd.,
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垣内 正人
Central Research Laboratories, Hokuriku Seiyaku Co., Ltd.,
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大橋 徹生
Central Research Laboratories, Hokuriku Seiyaku Co., Ltd.,
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加藤 日出男
Central Research Laboratories, Hokuriku Seiyaku Co., Ltd.,
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伊藤 安夫
Central Research Laboratories, Hokuriku Seiyaku Co., Ltd.,
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岩崎 信彦
Research And Development Division Hokuriku Seiyaku Co. Ltd.
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澤西 啓之
北陸大・薬
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澤西 啓之
The First Division Of The Research Laboratory For Development Of Medicine Hokuriku University
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伊藤 安夫
Research And Development Division Hokuriku Seiyaku Co. Ltd.
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加藤 日出男
北陸製薬株式会社中央研究所
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