非プロスタノイド骨格を有する新規プロスタサイクリン類縁体の創製と立体選択的合成研究

• 服部 浩二

  アステラス製薬(株) 化学研究所

書誌事項

タイトル別名

• Discovery of Novel Prostacyclin Mimetics with Highly Potent and Selective IP Receptor Agonists
• ヒプロスタノイド コッカク オ ユウスル シンキ プロスタサイクリン ルイエンタイ ノ ソウセイ ト リッタイ センタクテキ ゴウセイ ケンキュウ

抄録

Prostacyclin (PGI₂) is primarily secreted from vascular endothelium and plays an extremely important inhibitory role in platelet aggregation and as a vasodilator in maintaining homeostatic circulation. Despite fascinating pharmacological properties, the inherent instability and side effect of prostacyclin limit its therapeutic applicability. In this paper, we described that discovery of three classes of prostacyclin mimetics without PG skeleton, which are cycloalkene skeleton type (FR 181560, FR 181157), tetrahydronaphthalene skeleton type (FK 788), and amino acid type (FR 193264, FR 193262). Several designed prostacyclin mimetics exhibited potent PGI₂ agonistic activity with good selectivity for IP receptor and bioavailability. The specific compounds were prepared by asymmetric synthesis with high selectivity. Furthermore, we also described metabolism study using rat and human liver microsomes to lead new drug design (FR 223346, FR 232149).

収録刊行物

• 有機合成化学協会誌

  有機合成化学協会誌 64 (9), 923-933, 2006

  公益社団法人 有機合成化学協会

キーワード

• prostacyclin
• PGI<SUB>2</SUB>
• prostanoid
• IP receptor
• agonist
• asymmetric synthesis
• bioavailability
• FK 788
• metabolism

詳細情報

• CRID: 1390282680289601536
• NII論文ID: 10018052326
• NII書誌ID: AN0024521X
• DOI: 10.5059/yukigoseikyokaishi.64.923
• ISSN: 18836526
• ISSN: 00379980
• NDL書誌ID: 8091388
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I8091388
• 本文言語コード: ja
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可