5-(3-fluorophenyl)-N-(3-methoxyphenethyl)-N-methylthiophene-2-carboxamide | 1396240-49-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: 5-(3-fluorophenyl)-N-(3-methoxyphenethyl)-N-methylthiophene-2-carboxamide
• 英文别名: 5-(3-fluorophenyl)-N-[2-(3-methoxyphenyl)ethyl]-N-methylthiophene-2-carboxamide
• CAS: 1396240-49-5
• 化学式: C₂₁H₂₀FNO₂S
• 分子量: 369.46
• InChiKey: DYIJGEVBSOUHJX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  57.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-(3-fluorophenyl)-N-(3-methoxyphenethyl)-N-methylthiophene-2-carboxamide 在 boron trifluoride dimethyl sulfide 作用下， 以 二氯甲烷 为溶剂， 反应 14.0h， 以78%的产率得到5-(3-fluorophenyl)-N-(3-hydroxyphenethyl)-N-methylthiophene-2-carboxamide
  参考文献：
  名称：

  Structural Optimization of 2,5-Thiophene Amides as Highly Potent and Selective 17β-Hydroxysteroid Dehydrogenase Type 2 Inhibitors for the Treatment of Osteoporosis

  摘要：

  Inhibition of 17 beta-HSD2 is an attractive mechanism for the treatment of osteoporosis. We report here the optimization of human 17 beta-HSD2 inhibitors in the 2,5-thiophene amide class by varying the size of the linker (n equals 0 and 2) between the amide moiety and the phenyl group. While none of the phenethylamides (n = 2) were active, most of the anilides (n = 0) turned out to moderately or strongly inhibit 17 beta-HSD2. The four most active compounds showed an ICso of around 60 nM and a very good selectivity toward 17 beta-HSD1, 17 beta-HSD4, 17 beta-HSD5, 11 beta-HSD1, 11 beta-HSD2 and the estrogen receptors alpha and beta. The investigated compounds inhibited monkey 17 beta-HSD2 moderately, and one of them showed good inhibitory activity on mouse 17 beta-HSD2. SAR studies allowed a first characterization of the human 17 beta-HSD2 active site, which is predicted to be considerably larger than that of 17 beta-HSD1.

  DOI：

  10.1021/jm3014053
• 作为产物：
  描述：

  5-溴噻吩-2-羰酰氯 在 四(三苯基膦)钯 、 sodium carbonate 、 三乙胺 作用下， 以 乙二醇二甲醚 、 水 为溶剂， 反应 9.0h， 生成 5-(3-fluorophenyl)-N-(3-methoxyphenethyl)-N-methylthiophene-2-carboxamide
  参考文献：
  名称：

  Structural Optimization of 2,5-Thiophene Amides as Highly Potent and Selective 17β-Hydroxysteroid Dehydrogenase Type 2 Inhibitors for the Treatment of Osteoporosis

  摘要：

  Inhibition of 17 beta-HSD2 is an attractive mechanism for the treatment of osteoporosis. We report here the optimization of human 17 beta-HSD2 inhibitors in the 2,5-thiophene amide class by varying the size of the linker (n equals 0 and 2) between the amide moiety and the phenyl group. While none of the phenethylamides (n = 2) were active, most of the anilides (n = 0) turned out to moderately or strongly inhibit 17 beta-HSD2. The four most active compounds showed an ICso of around 60 nM and a very good selectivity toward 17 beta-HSD1, 17 beta-HSD4, 17 beta-HSD5, 11 beta-HSD1, 11 beta-HSD2 and the estrogen receptors alpha and beta. The investigated compounds inhibited monkey 17 beta-HSD2 moderately, and one of them showed good inhibitory activity on mouse 17 beta-HSD2. SAR studies allowed a first characterization of the human 17 beta-HSD2 active site, which is predicted to be considerably larger than that of 17 beta-HSD1.

  DOI：

  10.1021/jm3014053
• 作为试剂：
  描述：

  5-bromo-N-(3-methoxyphenethyl)-N-methylthiophene-2-carboxamide 、 3-氟苯基硼酸 在 四(三苯基膦)钯 5-(3-fluorophenyl)-N-(3-methoxyphenethyl)-N-methylthiophene-2-carboxamide 、 ethyl acetate n-hexane 作用下， 反应 6.0h， 以afforded the desired compound as colorless solid (60 mg, 81%)的产率得到5-(3-fluorophenyl)-N-(3-methoxyphenethyl)-N-methylthiophene-2-carboxamide
  参考文献：
  名称：

  BIARYL DERIVATIVES AS SELECTIVE 17BETA-HYDROXYSTEROID DEHYDROGENASE TYPE 2 INHIBITORS

  摘要：

  该发明涉及公式(I)的选择性、非甾体17β-羟基类固醇脱氢酶2（17β-HSD2）抑制剂的生产和用途，特别是用于治疗和预防男性和女性骨质疏松等性激素缺乏病。

  公开号：

  US20140057953A1