Structural Optimization of Ghrelin Receptor Inverse Agonists to Improve Lipophilicity and Avoid Mechanism-Based CYP3A4 Inactivation

• Takahashi Bitoku

  Asubio Pharma Co., Ltd.

• Funami Hideaki

  Asubio Pharma Co., Ltd.

• Shibata Makoto

  Asubio Pharma Co., Ltd.

• Maruoka Hiroshi

  Asubio Pharma Co., Ltd.

• Koyama Makoto

  Asubio Pharma Co., Ltd.

• Kanki Satomi

  Asubio Pharma Co., Ltd.

• Muto Tsuyoshi

  Asubio Pharma Co., Ltd.

抄録

Structural optimization of 2-aminonicotinamide derivatives as ghrelin receptor inverse agonists is reported. So as to avoid mechanism-based inactivation (MBI) of CYP3A4, 1,3-benzodioxol ring of the lead compound was modified. Improvement of the main activity and lipophilicity was achieved simultaneously, leading to compound 18a, which showed high lipophilic ligand efficiency (LLE) and low MBI activity.

収録刊行物

• ＣＨＥＭＩＣＡＬ　＆　ＰＨＡＲＭＡＣＥＵＴＩＣＡＬ　ＢＵＬＬＥＴＩＮ

  ＣＨＥＭＩＣＡＬ　＆　ＰＨＡＲＭＡＣＥＵＴＩＣＡＬ　ＢＵＬＬＥＴＩＮ 63 (10), 825-832, 2015

  公益社団法人 日本薬学会

キーワード

• ghrelinR
• inverse agonist
• obesity
• mechanism-based inactivation
• ligand-lipophilicity efficiency

詳細情報

• CRID: 1390001204178833792
• NII論文ID: 130005100927
• NII書誌ID: AA00602100
• DOI: 10.1248/cpb.c15-00285
• ISSN: 13475223
• ISSN: 00092363
• NDL書誌ID: 026764369
• PubMed: 26423040
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I026764369
• Web Site: https://www.jstage.jst.go.jp/article/cpb/63/10/63_c15-00285/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2016154748
• 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