5-bromo-N-(3-methoxyphenyl)-N-methylthiophene-2-carboxamide | 1396244-11-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-bromo-N-(3-methoxyphenyl)-N-methylthiophene-2-carboxamide
• CAS: 1396244-11-3
• 化学式: C₁₃H₁₂BrNO₂S
• mdl: MFCD15494831
• 分子量: 326.214
• InChiKey: DIIPNVKGDKJSNL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.153
• 拓扑面积：
  57.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-bromo-N-(3-methoxyphenyl)-N-methylthiophene-2-carboxamide 在 四(三苯基膦)钯 、 boron trifluoride dimethyl sulfide 、 sodium carbonate 作用下， 以 乙二醇二甲醚 、 二氯甲烷 、 水 为溶剂， 反应 12.0h， 生成 5-(4-cyanophenyl)-N-(3-hydroxyphenyl)-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 、 N-甲基-3-甲氧基苯胺 在 三乙胺 作用下， 反应 3.0h， 以98%的产率得到5-bromo-N-(3-methoxyphenyl)-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-溴噻吩-2-羰酰氯 、 N-甲基-3-甲氧基苯胺 、 三乙胺 在 5-bromo-N-(3-methoxyphenyl)-N-methylthiophene-2-carboxamide 、 ethyl acetate n-hexane 作用下， 以afforded the desired compound as colorless solid (320 mg, 98%)的产率得到5-bromo-N-(3-methoxyphenyl)-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

文献信息

• [EN] BIARYL DERIVATIVES AS SELECTIVE 17BETA-HYDROXYSTEROID DEHYDROGENASE TYPE 2 INHIBITORS<br/>[FR] DÉRIVÉS BIARYLE EN TANT QU'INHIBITEURS SÉLECTIFS DE LA 17BÊTA-HYDROXYSTÉROÏDE DÉSHYDROGÉNASE DE TYPE 2
  申请人：UNIV SAARLAND

  公开号：WO2012117097A1

  公开（公告）日：2012-09-07

  The invention relates to selective, non-steroidal 17beta-hydroxysteroid dehydrogenase type 2 (17beta-HSD2) inhibitors of formula (I), their production and use, notably for the treatment and prophylaxis of sex steroid deficient diseases like osteoporosis in men and women.

  本发明涉及选择性的，非类固醇17β-羟基类固醇脱氢酶2型（17β-HSD2）抑制剂的公式（I），它们的生产和用途，特别是用于治疗和预防性激素缺乏病，如男女骨质疏松症。
• Structural Optimization of 2,5-Thiophene Amides as Highly Potent and Selective 17β-Hydroxysteroid Dehydrogenase Type 2 Inhibitors for the Treatment of Osteoporosis
  作者：Sandrine Marchais-Oberwinkler、Kuiying Xu、Marie Wetzel、Enrico Perspicace、Matthias Negri、Arne Meyer、Alex Odermatt、Gabriele Möller、Jerzy Adamski、Rolf W. Hartmann

  DOI：10.1021/jm3014053

  日期：2013.1.10

  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.
• BIARYL DERIVATIVES AS SELECTIVE 17BETA-HYDROXYSTEROID DEHYDROGENASE TYPE 2 INHIBITORS
  申请人：Hartmann Rolf

  公开号：US20140057953A1

  公开（公告）日：2014-02-27

  The invention relates to selective, non-steroidal 17beta-hydroxysteroid dehydrogenase type 2 (l7beta-HSD2) inhibitors of formula (I), their production and use, notably for the treatment and prophylaxis of sex steroid deficient diseases like osteoporosis in men and women.

  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。