β-Naphthoflavone analogs as potent and soluble aryl hydrocarbon receptor agonists: Improvement of solubility by disruption of molecular planarity

Yuji Fujita, Mitsuhiro Yonehara, Masashi Tetsuhashi, Tomomi Noguchi-Yachide, Yuichi Hashimoto, Minoru Ishikawa

研究成果: Article査読

33 被引用数 (Scopus)

抄録

The physiological role of aryl hydrocarbon receptor (AhR) is not yet fully understood, and investigation is hampered by the limited solubility of reported AhR ligands in aqueous media. To achieve improved solubility, we focused on our previous finding that planarity-disruption of molecules leads to less efficient crystal packing and greater aqueous solubility. Here, we describe chemical modification of an AhR agonist, β-naphthoflavone, focusing on planarity-disruption. As expected, introduction of substituents at the ortho-positions of the phenyl group resulted in greater solubility. Among the compounds prepared, the fluoro analog showed more potent AhR agonistic activity and greater solubility than did β-naphthoflavone. Our results indicate that this strategy to improve aqueous solubility, that is, introduction of substituent(s) that disrupt planarity, may be generally applicable to bicyclic molecules.

本文言語English
ページ(範囲)1194-1203
ページ数10
ジャーナルBioorganic and Medicinal Chemistry
18
3
DOI
出版ステータスPublished - 2010 2 1
外部発表はい

ASJC Scopus subject areas

  • 生化学
  • 分子医療
  • 分子生物学
  • 薬科学
  • 創薬
  • 臨床生化学
  • 有機化学

フィンガープリント

「β-Naphthoflavone analogs as potent and soluble aryl hydrocarbon receptor agonists: Improvement of solubility by disruption of molecular planarity」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル