A Novel Dual Antagonist of Thromboxane A2 and Leukotriene D4 Receptors: Synthesis and Structure-Activity Relationships of Chloroquinolylviny Derivatives

• Okamoto Yoshinori

  Chemistry Research Laboratories, Astellas Pharmaceutical Inc.

• Yokota Masaki

  Chemistry Research Laboratories, Astellas Pharmaceutical Inc.

• Kawazoe Soichiro

  Process Chemistry Laboratories, Astellas Pharmaceutical Inc.

• Kubota Hirokazu

  Chemistry Research Laboratories, Astellas Pharmaceutical Inc.

• Nagaoka Hitoshi

  Chemistry Research Laboratories, Astellas Pharmaceutical Inc.

• Arakida Yasuhito

  Planning & Administration Dept., Astellas Pharmaceutical Inc.

• Takeuchi Makoto

  Chemistry Research Laboratories, Astellas Pharmaceutical Inc.

書誌事項

タイトル別名

• A Novel Dual Antagonist of Thromboxane A2 and Leukotriene D4 Receptors: Synthesis and Structure-Activity Relationships of Chloroquinolylvinyl Derivatives
• Novel Dual Antagonist of Thromboxane A2 and Leukotriene D4 Receptors Synthesis and Structure Activity Relationships of Chloroquinolylviny Derivatives

抄録

To discover an orally active thromboxane A₂ (TXA₂) and leukotriene D₄ (LTD₄) dual antagonist, we designed and synthesized chloroquinolylvinyl derivatives based on the structures of the TXA₂ antagonist daltroban and the LTD₄ antagonist montelukast. Among these derivatives, 4-{[(2-(4-chlorophenylsulfonylamino)-1-{3-[(E)-2-(7-chloro-2-quinolyl)vinyl]phenyl}ethyl)thio]methyl}benzoic acid (18d) showed potent inhibitory activity against U46619-induced aggregation of guinea pig platelets and LTD₄-induced contraction in the guinea pig ileum, with IC₅₀ values of 340 nm and 0.40 nm, respectively. Oral administration of 18 d also inhibited both the LTD₄-induced acceleration of plasma leakage to skin in guinea pig and the U46619-induced increase in airway resistance in guinea pig with ED₅₀ values of 0.47 mg/kg and 3.3 mg/kg, respectively.

収録刊行物

• ＣＨＥＭＩＣＡＬ　＆　ＰＨＡＲＭＡＣＥＵＴＩＣＡＬ　ＢＵＬＬＥＴＩＮ

  ＣＨＥＭＩＣＡＬ　＆　ＰＨＡＲＭＡＣＥＵＴＩＣＡＬ　ＢＵＬＬＥＴＩＮ 54 (5), 603-610, 2006

  公益社団法人 日本薬学会

キーワード

• leukotriene D₄
• thromboxane A₂
• dual antagonist
• structure–activity relationship

詳細情報

• CRID: 1390282679144996864
• NII論文ID: 110004836339
• NII書誌ID: AA00602100
• DOI: 10.1248/cpb.54.603
• COI: 1:CAS:528:DC%2BD28Xmt1ehsrg%3D
• ISSN: 13475223
• ISSN: 00092363
• NDL書誌ID: 7892760
• PubMed: 16651753
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I7892760
• Web Site: http://www.jstage.jst.go.jp/article/cpb/54/5/54_5_603/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2007003983
• 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