A Novel Series of Thromboxane A2 Synthetase Inhibitors with Free Radical Scavenging and Anti-peroxidative Activities.

• KAMIYA Shoji

  Research Laboratories, Kyoto Pharmaceutical Industries, Ltd.

• SHIRAHASE Hiroaki

  Research Laboratories, Kyoto Pharmaceutical Industries, Ltd.

• NAKAMURA Shohei

  Research Laboratories, Kyoto Pharmaceutical Industries, Ltd.

• KANDA Mamoru

  Research Laboratories, Kyoto Pharmaceutical Industries, Ltd.

• MATSUI Hiroshi

  Research Laboratories, Kyoto Pharmaceutical Industries, Ltd.

• YOSHIMI Akihisa

  Research Laboratories, Kyoto Pharmaceutical Industries, Ltd.

• KASAI Masayasu

  Research Laboratories, Kyoto Pharmaceutical Industries, Ltd.

• TAKAHASHI Kenji

  Research Laboratories, Kyoto Pharmaceutical Industries, Ltd.

• KURAHASHI Kazuyoshi

  Pharmacology Division, Radioisotope Research Center, Kyoto University

書誌事項

タイトル別名

• Novel Series of Thromboxane A2 Synthetase Inhibitors with Free Radical Scavenging and Anti peroxidative Activities

抄録

A novel series of indoline derivatives with imidazole and carboxyl moieties were synthesized and evaluated for their thromboxane A₂ (TXA₂) synthetase inhibiting, radical scavenging and anti-peroxidative activities. Among the compounds synthesized, 3-{5-substituted-3-[2-(imidazol-1-yl)ethyl]indolin-1-yl}propionic acids showed free radical scavenging activity and inhibitory effects on lipid-peroxidation of rat brain homogenate and on arachidonate-induced TXA₂-dependent aggregation of rabbit platelets. The anti-platelet and anti-peroxidative activities were related to the lipophilicity of the 5-substituent. The 5-hexyloxy derivative (13) showed about 35-fold higher inhibitory activity on TXA₂ synthesis than that of ozagrel and about 100-fold higher activity on lipid peroxidation than that of α-tocopherol. Compound 13 showed in vivo anti-thrombotic effect in mice and ex vivo anti-peroxidative activity in rats.

収録刊行物

• ＣＨＥＭＩＣＡＬ　＆　ＰＨＡＲＭＡＣＥＵＴＩＣＡＬ　ＢＵＬＬＥＴＩＮ

  ＣＨＥＭＩＣＡＬ　＆　ＰＨＡＲＭＡＣＥＵＴＩＣＡＬ　ＢＵＬＬＥＴＩＮ 49 (5), 563-571, 2001

  公益社団法人 日本薬学会

キーワード

• indoline derivative
• thromboxane A<SUB>2</SUB> synthetase inhibitor
• radical scavenger
• anti-peroxidation

詳細情報

• CRID: 1390282679141246592
• NII論文ID: 110003615942
• NII書誌ID: AA00602100
• DOI: 10.1248/cpb.49.563
• COI: 1:CAS:528:DC%2BD3MXjt1altb4%3D
• ISSN: 13475223
• ISSN: 00092363
• NDL書誌ID: 5763383
• PubMed: 11383607
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I5763383
• Web Site: http://www.jstage.jst.go.jp/article/cpb/49/5/49_5_563/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2001236763
• 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