Discovery of N-(3-{4-[(3-Fluorobenzyl)oxy]phenoxy}propyl)-2-pyridin-4-ylacetamide as a Potent and Selective Reverse NCX Inhibitor

• Kuramochi Takahiro

  Drug Discovery Research, Astellas Pharma Inc.

• Kakefuda Akio

  Drug Discovery Research, Astellas Pharma Inc.

• Yamada Hiroyoshi

  Drug Discovery Research, Astellas Pharma Inc.

• Ogiyama Takashi

  Drug Discovery Research, Astellas Pharma Inc.

• Taguchi Taku

  QA & RA and Pharmacovigilance, Astellas Pharma Inc.

• Sakamoto Shuichi

  I Technology, Astellas Pharma Inc.

抄録

In the setting of heart failure and myocardial ischemia-reperfusion, the sodium–calcium exchanger (NCX) can lead to calcium overload, which is responsible for contractile dysfunction and arrhythmia. NCX is an attractive target for treatment in heart failure and myocardial ischemia-reperfusion. We have designed and synthesized a series of benzyloxyphenyl derivatives based on compound 3. These derivatives have been evaluated for their inhibitory activity against both the reverse and forward modes of NCX. We have discovered a novel potent and selective reverse NCX inhibitor (12) with an IC₅₀ value of 0.085 μM against reverse NCX.

収録刊行物

• ＣＨＥＭＩＣＡＬ　＆　ＰＨＡＲＭＡＣＥＵＴＩＣＡＬ　ＢＵＬＬＥＴＩＮ

  ＣＨＥＭＩＣＡＬ　＆　ＰＨＡＲＭＡＣＥＵＴＩＣＡＬ　ＢＵＬＬＥＴＩＮ 53 (8), 1043-1047, 2005

  公益社団法人 日本薬学会

キーワード

• sodium–calcium exchanger (NCX)
• anti-arrhythmics
• transporter

詳細情報

• CRID: 1390001204170828800
• NII論文ID: 10016656235
• NII書誌ID: AA00602100
• DOI: 10.1248/cpb.53.1043
• ISSN: 13475223
• ISSN: 00092363
• NDL書誌ID: 7373216
• PubMed: 16079546
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I7373216
• Web Site: http://www.jstage.jst.go.jp/article/cpb/53/8/53_8_1043/_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