Synthesis and Evaluation of Nove1 2-Oxo-1,2-dihydro-3-quinolinecarboxamide Derivatives as Potent Selective Serotonin 5-HT4 Receptor Agonists

• SUZUKI Masaji

  Research Center Taisho Pharmaceutical Co., Ltd.

• OHUCHI Yutaka

  Research Center Taisho Pharmaceutical Co., Ltd.

• ASANUMA Hajime

  Research Center Taisho Pharmaceutical Co., Ltd.

• KANEKO Toshie

  Research Center Taisho Pharmaceutical Co., Ltd.

• YOKOMORI Sadakazu

  Research Center Taisho Pharmaceutical Co., Ltd.

• ITO Chika

  Research Center Taisho Pharmaceutical Co., Ltd.

• ISOBE Yoshihiko

  Research Center Taisho Pharmaceutical Co., Ltd.

• MURAMATSU Makoto

  Research Center Taisho Pharmaceutical Co., Ltd.

書誌事項

タイトル別名

• Synthesis and Evaluation of Novel 2-Oxo-1,2-dihydro-3-quinolinecarboxamide Derivatives as Potent and Selective Serotonin 5-HT4 Receptor Agonists.

抄録

A series of 8'-substituted N-(endo-8-azabicyclo[3.2.1]oct-3-yl)-1-isopropyl-2-oxo-1, 2-dihydro-3-quinolinecarboxamides were synthesized. The 5-HT₄ receptor agonistic activity was evaluated using the isolated guinea pig ileum preparation. Of the compounds synthesized, N-(endo-8-(3-hydroxypropyl)-8-azabicyclo[3.2.1]oct-3-yl)-1-isopropyl-2-oxo-1, 2-dihydro-3-quinolinecarboxamide (15a, TS-951) exhibited the most potent serotonin 5-HT₄ receptor agonistic activity. This compound had a high affinity for the serotonin 5-HT₄ receptor althought it had no affinities for other broad spectrum receptors. Furthermore, it remarkably enhanced gastrointestinal motility in conscious fed dogs without unfavorable effects that non-selective serotonin 5-HT₄ receptor agonist has. TS-951 may be useful in improving gastrointestinal dysfunction.

収録刊行物

• ＣＨＥＭＩＣＡＬ　＆　ＰＨＡＲＭＡＣＥＵＴＩＣＡＬ　ＢＵＬＬＥＴＩＮ

  ＣＨＥＭＩＣＡＬ　＆　ＰＨＡＲＭＡＣＥＵＴＩＣＡＬ　ＢＵＬＬＥＴＩＮ 49 (1), 29-39, 2001

  公益社団法人 日本薬学会

キーワード

• quinolinecarboxamide
• TS-951
• serotonin 5-HT<SUB>4</SUB> receptor agonist
• structure-activity relationship

詳細情報

• CRID: 1390001204162452864
• NII論文ID: 110003615748
• NII書誌ID: AA00602100
• DOI: 10.1248/cpb.49.29
• COI: 1:CAS:528:DC%2BD3MXkvVamsQ%3D%3D
• ISSN: 13475223
• ISSN: 00092363
• NDL書誌ID: 5622373
• PubMed: 11201221
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I5622373
• Web Site: http://www.jstage.jst.go.jp/article/cpb/49/1/49_1_29/_pdf
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可