Synthesis and Structure-Activity Relationships of 4-Amino-5-chloro-2-ethoxybenzamides with Six- and Seven-Membered Heteroalicycles as Potential Gastroprokinetic Agents

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概要

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• A new series of 4-amino-5-chloro-2-ethoxybenzamides 3b-f and 5-8 bearing six and seven-membered heteroalicycles was prepared and evaluated for gastroprokinetic activity. Compounds 3b-e, derived by replacement of the morpholine oxygen of 4-amino-N-[(4-benzyl-2-morpholinyl)methyl]-5-chloro-2-ethoxybenzamide (3a) with other atoms (sulfur, nitrogen and carbon), generally exhibited a potent gastric emptying activity. N-(4-Benzyl-3-morpholinyl)methylbenzamide (5a) and its analogues 5b-e had weaker activity. However, N-(4-benzyl-3-morpholinyl)ethylbenzamide 8 was as potent as 3a. Benzamides 6a-e, having seven-membered heteroalicycles, showed fairly potent activity.Molecular superimpositions of 5a, 6a and 8 upon 3a using computer graphics suggested that the direction of the N-benzyl group greatly influences the gastric emptying activity, whereas the location of the alicyclic nitrogen is less critical.

• 社団法人日本薬学会の論文
• 1995-07-15

著者

• 原田 博史

  Dainippon Pharmaceutical Co. Ltd.

• 原田 博史

  Exploratory Research Laboratories, Dainippon Pharmaceutical Co., Ltd.,

• 森江 俊哉

  Exploratory Research Laboratories, Dainippon Pharmaceutical Co., Ltd.,

• 吉田 直之

  Exploratory Research Laboratories, Dainippon Pharmaceutical Co., Ltd.,

• 賀登 志朗

  Exploratory Research Laboratories, Dainippon Pharmaceutical Co., Ltd.,

• 藤原 厳

  Exploratory Research Laboratories, Dainippon Pharmaceutical Co., Ltd.,

• 松本 純一

  Exploratory Research Laboratories, Dainippon Pharmaceutical Co., Ltd.,

• 森江 俊哉

  大日本製薬株式会社創薬研究所

• 松本 純一

  Exploratory Research Laboratories Dainippon Pharmaceutical Company Ltd.

• 吉田 直之

  大日本製薬(株)薬理研究所

• Kato Satoru

  Kanazawa Univ. Kanazawa Jpn

• 賀登 志朗

  大日本製薬株式会社創薬研究所

• Yoshida Naoko

  Institute For Medical And Dental Engineering Tokyo Medical And Dental University

• Kato S

  Discovery Research Laboratories I Dainippon Pharmaceutical Co. Ltd.

• Kato S

  Chemistry Research Laboratories Dainippon Pharmaceutical Co. Ltd.

• 吉田 直之

  大日本製薬株式会社創薬研究所第一薬理研究部

• Yoshida Naotoshi

  Medicinal Plant Garden Faculty Of Pharmaceutical Sciences Hokkaido University

• 吉田 直之

  大日本製薬株式会社創薬研究所

• 松本 純一

  Exploratory Research Laboratories Dainippon Pharmaceutical Co. Ltd.

• Harada H

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.

• 藤原 厳

  Exploratory Research Laboratories Dainippon Pharmaceutical Co. Ltd.

• Kato Satoru

  Department Of Molecular Neurobiology Graduate School Of Medicine University Of Kanazawa

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