(4-bromo-2-thienyl)(3-methoxyphenyl)methanone | 1255940-23-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (4-bromo-2-thienyl)(3-methoxyphenyl)methanone
• 英文别名: (4-Bromothiophen-2-yl)-(3-methoxyphenyl)methanone
• CAS: 1255940-23-8
• 化学式: C₁₂H₉BrO₂S
• 分子量: 297.172
• InChiKey: SCANUBAQOUQMQF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  54.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (4-bromo-2-thienyl)(3-methoxyphenyl)methanone 、 4-甲氧基-3-甲基苯硼酸 在 四(三苯基膦)钯 、 caesium carbonate 作用下， 以 乙二醇二甲醚 、 水 为溶剂， 反应 2.0h， 以71%的产率得到[4-(4-methoxy-3-methylphenyl)-2-thienyl](3-methoxyphenyl)methanone
  参考文献：
  名称：

  Bicyclic Substituted Hydroxyphenylmethanones as Novel Inhibitors of 17β-Hydroxysteroid Dehydrogenase Type 1 (17β-HSD1) for the Treatment of Estrogen-Dependent Diseases

  摘要：

  Estradiol (E2), the most important estrogen in humans, is involved in the initiation and progression of estrogen-dependent diseases such as breast cancer and endometriosis. Its local production in the target cell is regulated by 17 beta-hydroxysteroid dehydrogenase type 1 (17 beta-HSD1), which catalyzes E2-formation by reduction of the weak estrogen estrone (E1). Because the enzyme is expressed M the diseased tissues, inhibition of 17 beta-HSD1 is considered as a promising therapy for the treatment of estrogen-dependent diseases. For the development of novel inhibitors, a structure-and ligand-based design strategy was applied, resulting in bicyclic substituted hydroxyphenylmethanones. In vitro testing revealed high inhibitory potencies toward human placental 17 beta-HSD1. Compounds were further evaluated with regard to selectivity (17 beta-HSD2, estrogen receptors ER alpha and ER beta), intracellular activity (T47D cells), and metabolic stability. The most promising compounds, 14 and 15, showed IC50 values in the low nanomolar range in the cell-free and cellular assays (8-27 nM), more than 30-fold selectivity toward 17 beta-HSD2 and no affinity toward the ERs. The data obtained make these inhibitors interesting candidates for further preclinical evaluation.

  DOI：

  10.1021/jm101073q
• 作为产物：
  描述：

  (4-bromo-2-thienyl)(3-methoxyphenyl)methanol 在 2-iodoxybenzoic acid 作用下， 以 四氢呋喃 为溶剂， 反应 18.0h， 以79%的产率得到(4-bromo-2-thienyl)(3-methoxyphenyl)methanone
  参考文献：
  名称：

  [EN] SELECTIVE 17BETA-HYDROXYSTEROID DEHYDROGENASE TYPE 1 INHIBITORS
  [FR] INHIBITEURS SÉLECTIFS DE LA 17-BÊTA-HYDROXYSTÉROÏDE DÉSHYDROGÉNASE DE TYPE 1

  摘要：

  这项发明涉及选择性的、非类固醇17β-羟基类固醇脱氢酶1型（17β-HSD1）抑制剂的生产和使用，特别用于治疗和/或预防激素相关疾病。

  公开号：

  WO2012025638A1

文献信息

• [EN] SELECTIVE 17BETA-HYDROXYSTEROID DEHYDROGENASE TYPE 1 INHIBITORS<br/>[FR] INHIBITEURS SÉLECTIFS DE LA 17-BÊTA-HYDROXYSTÉROÏDE DÉSHYDROGÉNASE DE TYPE 1
  申请人：UNIV SAARLAND

  公开号：WO2012025638A1

  公开（公告）日：2012-03-01

  The invention relates to selective, non-steroidal 17beta-hydroxysteroid dehydrogenase type 1 (17β-HSD1) inhibitors their production and use, especially for the treatment and/or prophylaxis of hormone-related diseases.

  这项发明涉及选择性的、非类固醇17β-羟基类固醇脱氢酶1型（17β-HSD1）抑制剂的生产和使用，特别用于治疗和/或预防激素相关疾病。
• SELECTIVE 17BETA-HYDROXYSTEROID DEHYDROGENASE TYPE 1 INHIBITORS
  申请人：Universität des Saarlandes

  公开号：EP2609089A1

  公开（公告）日：2013-07-03
• Bicyclic Substituted Hydroxyphenylmethanones as Novel Inhibitors of 17β-Hydroxysteroid Dehydrogenase Type 1 (17β-HSD1) for the Treatment of Estrogen-Dependent Diseases
  作者：Alexander Oster、Stefan Hinsberger、Ruth Werth、Sandrine Marchais-Oberwinkler、Martin Frotscher、Rolf W. Hartmann

  DOI：10.1021/jm101073q

  日期：2010.11.25

  Estradiol (E2), the most important estrogen in humans, is involved in the initiation and progression of estrogen-dependent diseases such as breast cancer and endometriosis. Its local production in the target cell is regulated by 17 beta-hydroxysteroid dehydrogenase type 1 (17 beta-HSD1), which catalyzes E2-formation by reduction of the weak estrogen estrone (E1). Because the enzyme is expressed M the diseased tissues, inhibition of 17 beta-HSD1 is considered as a promising therapy for the treatment of estrogen-dependent diseases. For the development of novel inhibitors, a structure-and ligand-based design strategy was applied, resulting in bicyclic substituted hydroxyphenylmethanones. In vitro testing revealed high inhibitory potencies toward human placental 17 beta-HSD1. Compounds were further evaluated with regard to selectivity (17 beta-HSD2, estrogen receptors ER alpha and ER beta), intracellular activity (T47D cells), and metabolic stability. The most promising compounds, 14 and 15, showed IC50 values in the low nanomolar range in the cell-free and cellular assays (8-27 nM), more than 30-fold selectivity toward 17 beta-HSD2 and no affinity toward the ERs. The data obtained make these inhibitors interesting candidates for further preclinical evaluation.