5-bromo-N-methyl-N-(3-methylphenyl)thiophene-2-carboxamide | 1252464-84-8

• 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-methyl-N-(3-methylphenyl)thiophene-2-carboxamide
• 英文别名: 5-bromo-N-methyl-N-m-tolylthiophene-2-carboxamide
• CAS: 1252464-84-8
• 化学式: C₁₃H₁₂BrNOS
• 分子量: 310.214
• InChiKey: KYYSKFKGGDEGJC-UHFFFAOYSA-N

物化性质

• 熔点：
  103-104 °C
• 沸点：
  428.1±45.0 °C(Predicted)
• 密度：
  1.485±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  48.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-bromo-N-methyl-N-(3-methylphenyl)thiophene-2-carboxamide 在 四(三苯基膦)钯 、 三氟二甲基硫醚络合物 、 caesium carbonate 作用下， 以 乙二醇二甲醚 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 0.33h， 生成 5-(4-hydroxy-3-methylphenyl)-N-methyl-N-(m-tolyl)thiophene-2-carboxamide
  参考文献：
  名称：

  Metabolic stability optimization and metabolite identification of 2,5-thiophene amide 17β-hydroxysteroid dehydrogenase type 2 inhibitors

  摘要：

  17 beta-HSD2 is a promising new target for the treatment of osteoporosis. In this paper, a rational strategy to overcome the metabolic liability in the 2,5-thiophene amide class of 17 beta-HSD2 inhibitors is described, and the biological activity of the new inhibitors. Applying different strategies, as lowering the cLogP or modifying the structures of the molecules, compounds 27, 31 and 35 with strongly improved metabolic stability were obtained. For understanding biotransformation in the 2,5-thiophene amide class the main metabolic pathways of three properly selected compounds were elucidated. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.09.061
• 作为产物：
  描述：

  5-溴-2-羧基噻吩 在 氯化亚砜 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 4.5h， 生成 5-bromo-N-methyl-N-(3-methylphenyl)thiophene-2-carboxamide
  参考文献：
  名称：

  Metabolic stability optimization and metabolite identification of 2,5-thiophene amide 17β-hydroxysteroid dehydrogenase type 2 inhibitors

  摘要：

  17 beta-HSD2 is a promising new target for the treatment of osteoporosis. In this paper, a rational strategy to overcome the metabolic liability in the 2,5-thiophene amide class of 17 beta-HSD2 inhibitors is described, and the biological activity of the new inhibitors. Applying different strategies, as lowering the cLogP or modifying the structures of the molecules, compounds 27, 31 and 35 with strongly improved metabolic stability were obtained. For understanding biotransformation in the 2,5-thiophene amide class the main metabolic pathways of three properly selected compounds were elucidated. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.09.061
• 作为试剂：
  描述：

  5-溴噻吩-2-羰酰氯 、 3-(甲氨基)甲苯 、 三乙胺 在 5-bromo-N-methyl-N-(3-methylphenyl)thiophene-2-carboxamide 、 FC(CH2Cl2) 作用下， 以yielded the desired compound as colourless solid (300 mg, 97%)的产率得到5-bromo-N-methyl-N-(3-methylphenyl)thiophene-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.
• Metabolic stability optimization and metabolite identification of 2,5-thiophene amide 17β-hydroxysteroid dehydrogenase type 2 inhibitors
  作者：Emanuele M. Gargano、Enrico Perspicace、Nina Hanke、Angelo Carotti、Sandrine Marchais-Oberwinkler、Rolf W. Hartmann

  DOI：10.1016/j.ejmech.2014.09.061

  日期：2014.11

  17 beta-HSD2 is a promising new target for the treatment of osteoporosis. In this paper, a rational strategy to overcome the metabolic liability in the 2,5-thiophene amide class of 17 beta-HSD2 inhibitors is described, and the biological activity of the new inhibitors. Applying different strategies, as lowering the cLogP or modifying the structures of the molecules, compounds 27, 31 and 35 with strongly improved metabolic stability were obtained. For understanding biotransformation in the 2,5-thiophene amide class the main metabolic pathways of three properly selected compounds were elucidated. (C) 2014 Elsevier Masson SAS. All rights reserved.
• 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。