Synthesis and Evaluation of Novel Carbocyclic Oxetanocin A (COA-Cl) Derivatives as Potential Tube Formation Agents

• Sakakibara Norikazu

  Faculty of Pharmaceutical Sciences at Kagawa Campus, Tokushima Bunri University

• Igarashi Junsuke

  Department of Cardiovascular Physiology, Faculty of Medicine, Kagawa University

• Takata Maki

  Department of Pharmaco-Bio-Informatics, Faculty of Medicine, Kagawa University

• Demizu Yosuke

  Division of Organic Chemistry, National Institute of Health Sciences

• Misawa Takashi

  Division of Organic Chemistry, National Institute of Health Sciences

• Kurihara Masaaki

  Division of Organic Chemistry, National Institute of Health Sciences

• Konishi Ryoji

  Department of Pharmaco-Bio-Informatics, Faculty of Medicine, Kagawa University

• Kato Yoshihisa

  Faculty of Pharmaceutical Sciences at Kagawa Campus, Tokushima Bunri University

• Maruyama Tokumi

  Faculty of Pharmaceutical Sciences at Kagawa Campus, Tokushima Bunri University

• Tsukamoto Ikuko

  Department of Pharmaco-Bio-Informatics, Faculty of Medicine, Kagawa University

抄録

Six novel carbocyclic oxetanocin A analogs (2-chloro-C.OXT-A; COA-Cl) with various hydroxymethylated or spiro-conjugated cyclobutane rings at the N⁹-position of the 2-chloropurine moiety were synthesized and evaluated using human umbilical vein endothelial cells. All prepared compounds (2a–f) showed good to moderate activity with angiogenic potency. Among these compounds, 100 µM cis–trans-2′,3′-bis(hydroxymethyl)cyclobutyl derivative (2b), trans-3′-hydroxymethylcyclobutyl analog (2d), and 3′,3′-bis(hydroxymethyl)cyclobutyl derivative (2e) had greater angiogenic activity, with relative tube areas of 3.43±0.44, 3.32±0.53, and 3.59±0.83 (mean±standard deviation (S.D.)), respectively, which was comparable to COA-Cl (3.91±0.78). These data may be important for further development of this class of compounds as potential tube formation agents.

収録刊行物

• ＣＨＥＭＩＣＡＬ　＆　ＰＨＡＲＭＡＣＥＵＴＩＣＡＬ　ＢＵＬＬＥＴＩＮ

  ＣＨＥＭＩＣＡＬ　＆　ＰＨＡＲＭＡＣＥＵＴＩＣＡＬ　ＢＵＬＬＥＴＩＮ 63 (9), 701-709, 2015

  公益社団法人 日本薬学会

キーワード

• 2-chloro-carbocyclic oxetanocin A
• 2-chloro-C.OXT-A
• nucleoside derivative
• angiogenic activity

詳細情報

• CRID: 1390001204177214848
• NII論文ID: 130005096030
• NII書誌ID: AA00602100
• DOI: 10.1248/cpb.c15-00386
• ISSN: 13475223
• ISSN: 00092363
• NDL書誌ID: 026700022
• PubMed: 26329863
• Web Site: http://id.ndl.go.jp/bib/026700022
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I026700022
• Web Site: https://www.jstage.jst.go.jp/article/cpb/63/9/63_c15-00386/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2016154413
• 本文言語コード: en
• データソース種別:
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  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
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