2-(4-甲氧基-3-甲基苯基)-5-(3-甲氧基苯基)噻吩 | 1193525-42-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 中文名称: 2-(4-甲氧基-3-甲基苯基)-5-(3-甲氧基苯基)噻吩
• 中文别名: 2-(4-甲氧基-3-甲基苯基)-5-(3-甲氧苯基)噻吩
• 英文名称: 2-(4-methoxy-3-methylphenyl)-5-(3-methoxyphenyl)thiophene
• CAS: 1193525-42-6
• 化学式: C₁₉H₁₈O₂S
• 分子量: 310.417
• InChiKey: JLZQUHZSYFHTOL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  46.7
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  2-(4-甲氧基-3-甲基苯基)-5-(3-甲氧基苯基)噻吩 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 以79%的产率得到4-[5-(3-羟基苯基)-2-噻吩基]-2-甲基苯酚
  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
• 作为产物：
  描述：

  2-溴-5-(3-甲氧基苯基)噻吩 、 4-甲氧基-3-甲基苯硼酸 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 水 、 甲苯 为溶剂， 反应 20.0h， 以54%的产率得到2-(4-甲氧基-3-甲基苯基)-5-(3-甲氧基苯基)噻吩
  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.