Development of Potent Serotonin-3(5-HT_3) Receptor Antagonists. I. Structure-Activity Relationships of 2-Alkoxy-4-amino-5-chlorobenzamide Derivatives

• 原田 博史

  Exploratory Research Laboratories, Dainippon Pharmaceutical Co. Ltd.

• 森江 俊哉

  Exploratory Research Laboratories, Dainippon Pharmaceutical Co. Ltd.

• 広川 美視

  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.

抄録

A new series of 2-alkoxy-4-amino-5-chlorobenzamide derivatives bearing five- to seven-membered heteroalicyclic rings in the amine moiety was synthesized and evaluated for serotonin-3 (5-HT_3) receptor antagonistic activity by assaying the ability to antagonize the von Bezold-Jarisch reflex in rats. The five- to seven-membered heteroalicycles comprise pyrrolidine, morpholine, 1,4-thiazine, piperidine, piperazine, 1,4-oxazepine, 1,4-thiazepine, azepine, and 1,4-diazepine rings. Among them, some benzamide derivatives having a 1,4-diazepine ring showed a potent 5-HT_3 receptor antagonistic activity. In particular, 4-amino-5-chloro-N-(1,4-dimethylhexahydro-1H-1,4-diazepin-6-yl)-2-ethoxybenzamide (96) and the 1-benzyl-4-methylhexahydro-1H-1,4-diazepine analogue 103 showed potent 5-HT_3 receptor antagonistic activity without 5-HT_4 receptor binding affinity.

収録刊行物

• Chemical & pharmaceutical bulletin

  Chemical & pharmaceutical bulletin 43 (8), 1364-1378, 1995-08-15

  公益社団法人日本薬学会

キーワード

• serotonin-3 receptor antagonjst
• von Bezold-Jarisch reflex
• 1H-1, 4-diazepine
• mosapride
• serotonin-4 receptor agonist

詳細情報

• CRID: 1570572702394008320
• NII論文ID: 110003631667
• NII書誌ID: AA00602100
• ISSN: 00092363
• 本文言語コード: en
• データソース種別:
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