Synthesis and Structure-Activity Relationship of 3-Substituted Benzamide, Benzo[b]furan-7-carboxamide, 2,3-Dihydrobenzo[b]furan-7-carboxamide, and Indole-5-carboxamide Derivatives as Selective Serotonin 5-HT_4 Receptor Agonists

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概要

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• The title compounds (6-9) were prepared and evaluated for serotonin 5-HT_4 agonistic activity in in vitro tests. Introducing a propyl or allyl group at the 3-position of benzamide caused only a slight enhancement of agonistic activity. Construction of the benzo[b]furan skeleton and 2,3-dihydrobenzo[b]furan skeleton caused a significant enhancement of the activity. 4-Amino-N-[2-(1-azabicyclo[3.3.0]octan-5-yl)ethyl]-5-chloro-2-methylbenzo[b]furan-7-carboxamide (7b) hemifumarate was as potent as cisapride. 4-Amino-N-[2-(1-azabicyclo[3.3.0]octan-5-yl)ethyl]-5-chloro-2,3-dihydro-2-methylbenzo[b]furan-7-carboxamide (8a) hemifumarate, 4-amino-N-[2-(1-azabicyclo-[3.3.0]octan-5-yl)ethyl]-5-chloro-2,3-dihydro-2-ethylbenzo[b]furan-7-carboxamide (8c) hemifumarate, and 4-amino-N-[2-(1-azabicyclo[3.3.0]octan-5-yl)ethyl]-5-chloro-2,3-dihydro-2,3-dimethylbenzo[b]furan-7-carboxamide (8d) hemifumarate were potent than cisapride. Furthermore, 8a hemifumarate was free from dopamine D_1,D_2,serotonin 5-HT_1,5-HT_2 and muscarine M_1,M_2 receptor binding activity in the in vitro tests. On the other hand, construction of the indole skeleton caused a remarkable decrease in activity.

• 公益社団法人日本薬学会の論文
• 1998-01-15

著者

• KATAOKA Tadashi

  Gifu Pharmaceutical University

• KAKIGAMI Takuji

  General Research Park, Sanwa Kagaku Kenkyusho Co., Ltd.,

• USUI Toshinao

  General Research Park, Sanwa Kagaku Kenkyusho Co., Ltd.,

• TSUKAMOTO Katsura

  General Research Park, Sanwa Kagaku Kenkyusho Co., Ltd.,

• Usui Toshinao

  Drug Discovery Research Department Sanwa Kagaku Kenkyusho Co. Ltd.

• Kakigami Takuji

  General Research Park Sanwa Kagaku Kenkyusho Co. Ltd.

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