2-fluoro-4-[5-(3-fluoro-5-hydroxyphenyl)thien-2-yl]phenol | 1193524-97-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 2-fluoro-4-[5-(3-fluoro-5-hydroxyphenyl)thien-2-yl]phenol
• 英文别名: 2-fluoro-4-[5-(3-fluoro-5-hydroxyphenyl)thiophen-2-yl]phenol
• CAS: 1193524-97-8
• 化学式: C₁₆H₁₀F₂O₂S
• 分子量: 304.317
• InChiKey: KYLWDDSTKITRCN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  68.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-(3-fluoro-4-methoxyphenyl)-5-(3-fluoro-5-methoxyphenyl)thiophene 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 以38%的产率得到2-fluoro-4-[5-(3-fluoro-5-hydroxyphenyl)thien-2-yl]phenol
  参考文献：
  名称：

  New Insights into the SAR and Binding Modes of Bis(hydroxyphenyl)thiophenes and -benzenes: Influence of Additional Substituents on 17β-Hydroxysteroid Dehydrogenase Type 1 (17β-HSD1) Inhibitory Activity and Selectivity

  摘要：

  17 beta-Hydroxystcroid dehydrogenase type 1 (17 beta-HSD1) is responsible for the catalytic reduction of weakly active E1 to highly potent E2. E2 stimulates the proliferation of hormone-dependent diseases via activation of the estrogen receptor alpha (ER alpha). Because of the overexpression of 17 beta-HSD1 in mammary tumors, this enzyme should be an attractive target for the treatment of estrogen-dependent pathologies. Recently, we have reported on a series of potent 17 beta-HSD1 inhibitors: bis(hydroxyphenyl) azoles, thiophenes, and benzenes. In this paper, different substituents are introduced into the core structure and the biological properties of the corresponding inhibitors are evaluated. Computational methods and analysis of different X-rays of 17 beta-HSD1 lead to identification of two different binding modes for these inhibitors. The fluorine compound 23 exhibits an IC50 of 8 nM and is the most potent nonsteroidal inhibitor described so far. It also shows a high selectivity (17 beta-HSD2, ER alpha) and excellent pharmacokinetic properties after peroral application to rats.

  DOI：

  10.1021/jm901195w

文献信息

• New Insights into the SAR and Binding Modes of Bis(hydroxyphenyl)thiophenes and -benzenes: Influence of Additional Substituents on 17β-Hydroxysteroid Dehydrogenase Type 1 (17β-HSD1) Inhibitory Activity and Selectivity
  作者：Emmanuel Bey、Sandrine Marchais-Oberwinkler、Matthias Negri、Patricia Kruchten、Alexander Oster、Tobias Klein、Alessandro Spadaro、Ruth Werth、Martin Frotscher、Barbara Birk、Rolf W. Hartmann

  DOI：10.1021/jm901195w

  日期：2009.11.12

  17 beta-Hydroxystcroid dehydrogenase type 1 (17 beta-HSD1) is responsible for the catalytic reduction of weakly active E1 to highly potent E2. E2 stimulates the proliferation of hormone-dependent diseases via activation of the estrogen receptor alpha (ER alpha). Because of the overexpression of 17 beta-HSD1 in mammary tumors, this enzyme should be an attractive target for the treatment of estrogen-dependent pathologies. Recently, we have reported on a series of potent 17 beta-HSD1 inhibitors: bis(hydroxyphenyl) azoles, thiophenes, and benzenes. In this paper, different substituents are introduced into the core structure and the biological properties of the corresponding inhibitors are evaluated. Computational methods and analysis of different X-rays of 17 beta-HSD1 lead to identification of two different binding modes for these inhibitors. The fluorine compound 23 exhibits an IC50 of 8 nM and is the most potent nonsteroidal inhibitor described so far. It also shows a high selectivity (17 beta-HSD2, ER alpha) and excellent pharmacokinetic properties after peroral application to rats.