Synthesis and Pharmacological Evaluation of Pyrroloazepine Derivatives as Potent Antihypertensive Agents with Antiplatelet Aggregation Activity

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概要

• 論文の詳細を見る

• A series of 1-aminoalkyl-pyrrolo[2,3-c]azepin-8-one derivatives was synthesized and evaluated as α_1 adrenergic and serotonin 2 (5-HT_2) receptor antagonists, with the aim of finding a novel antihypertensive agent potently exhibiting both activities. Some compounds with a 4-[4-(4-fluorobenzoyl)piperidino]butyl group at the 1-position exhibited both activities, and varied significantly in terms of the substituents at the 4-position of the pyrroloazepine ring. Among the compounds obtained in this study, (E)-1-[4-[4-(4-fluorobenzoyl)piperidino]butyl]-4-hydroxyimino-7-methyl-1,4,5,6,7,8-hexahydropyrrolo[2,3-c]azepin-8-one (15a, SUN9221) displayed potent α_1-adrenergic antagonistic activity (pA_2=8.89±0.21) and 5-HT_2 antagonistic activity (pA_2=8.74±0.22) in isolated guinea pig arteries. This compound exhibited antihypertensive activity and a duration of action equivalent to orally administered prazosin or doxazosin, 3 mg/kg, in conscious spontaneously hypertensive rats, as well as potent antiplatelet aggregation activity.

• 公益社団法人日本薬学会の論文
• 1999-02-15

著者

• Inomata Norio

  Suntory Institute for Biomedical Research

• Mizuno A

  Suntory Institute For Biomedical Research

• Yoshida Maki

  Suntory Institute For Biomedical Research

• Inomata N

  Suntory Institute For Biomedical Research

• Inomata Norio

  Laboratory Of Experimental:molecular Pharmacology Suntory Institute For Biomedical Research

• Shibata M

  Fumakilla Ltd.

• Miyazaki Tomoko

  Suntory Institute For Biomedical Research Wakayamadai

• Mizuno Akira

  Suntory Institute For Biomedical Research

• KAMEI Tomoe

  Suntory Institute for Biomedical Research

• SHIBATA Makoto

  Suntory Institute for Biomedical Research

• TAKIGUCHI Chikako

  Suntory Institute for Biomedical Research

• Mizuno A

  Meiji Pharmaceutical Univ. Tokyo Jpn

• Kamei T

  Suntory Institute For Biomedical Research

• TATSUOKA TOSHIO

  Suntory Institute for Biomedical Research

• Tatsuoka T

  Suntory Institute For Biomedical Research

• MIYA Mikiko

  Suntory Institute for Biomedical Research

• Miyazaki Tomoko

  Suntory Institute For Biomedical Research

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