4-(5-nitrothiophen-3-yl)pyrimidine | 17808-16-1

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: 4-(5-nitrothiophen-3-yl)pyrimidine
• 英文别名: 4-(5-nitro-thiophen-3-yl)-pyrimidine；5-Nitro-3--thiophen
• CAS: 17808-16-1
• 化学式: C₈H₅N₃O₂S
• 分子量: 207.213
• InChiKey: CSLYVMYZUKEDAH-UHFFFAOYSA-N

物化性质

• 沸点：
  353.2±32.0 °C(Predicted)
• 密度：
  1.454±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  99.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(5-nitrothiophen-3-yl)pyrimidine 在 palladium 10% on activated carbon 、 氢气 、 三乙胺 、 1-(甲磺酰基)-1H-苯并三唑 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基乙酰胺 、 乙酸乙酯 为溶剂， 160.0 ℃ 、101.33 kPa 条件下， 反应 4.25h， 生成 2-(3-methoxyphenyl)-N-[4-(pyrimidin-4-yl)thiophen-2-yl]acetamide
  参考文献：
  名称：

  Design, Synthesis, and Structure–Activity Relationships of Pyridine-Based Rho Kinase (ROCK) Inhibitors

  摘要：

  The Rho kinases (ROCK1 and ROCK2) are highly homologous serine/threonine kinases that act on substrates associated with cellular motility, morphology, and contraction and are of therapeutic interest in diseases associated with cellular migration and contraction, such as hypertension, glaucoma, and erectile dysfunction. Beginning with compound 4, an inhibitor of ROCK1 identified through high-throughput screening, systematic exploration of SAR, and application of structure-based design, led to potent and selective ROCK inhibitors. Compound 37 represents significant improvements in inhibition potency, kinase selectivity, and CYP inhibition and possesses pharmacokinetics suitable for in vivo experimentation.

  DOI：

  10.1021/acs.jmedchem.5b00424
• 作为产物：
  描述：

  3-二甲基氨基-1-噻吩-3-丙烯酮 在 硫酸 、 potassium nitrate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 98.0h， 生成 4-(5-nitrothiophen-3-yl)pyrimidine
  参考文献：
  名称：

  Design, Synthesis, and Structure–Activity Relationships of Pyridine-Based Rho Kinase (ROCK) Inhibitors

  摘要：

  The Rho kinases (ROCK1 and ROCK2) are highly homologous serine/threonine kinases that act on substrates associated with cellular motility, morphology, and contraction and are of therapeutic interest in diseases associated with cellular migration and contraction, such as hypertension, glaucoma, and erectile dysfunction. Beginning with compound 4, an inhibitor of ROCK1 identified through high-throughput screening, systematic exploration of SAR, and application of structure-based design, led to potent and selective ROCK inhibitors. Compound 37 represents significant improvements in inhibition potency, kinase selectivity, and CYP inhibition and possesses pharmacokinetics suitable for in vivo experimentation.

  DOI：

  10.1021/acs.jmedchem.5b00424

文献信息

• [EN] COMPOSITIONS USEFUL AS INHIBITORS OF ROCK AND OTHER PROTEIN KINASES<br/>[FR] COMPOSITIONS UTILES EN TANT QU'INHIBITEURS DE ROCK ET D'AUTRES PROTEINES KINASES
  申请人：VERTEX PHARMA

  公开号：WO2004041813A1

  公开（公告）日：2004-05-21

  The present invention relates to substitute thiazole and thiophene derivatives useful as inhibitors of rock and other protein kinaeses. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders, including proliferative, cardiac and neurodegenerative diseases.

  本发明涉及替代噻唑和噻吩衍生物，可用作岩石和其他蛋白激酶的抑制剂。该发明还提供了包括所述化合物的药学上可接受的组合物，以及在治疗各种疾病、病况或紊乱，包括增殖性、心脏和神经退行性疾病中使用这些组合物的方法。
• Compositions useful as inhibitors of rock and other protein kinases
  申请人：——

  公开号：US20040122016A1

  公开（公告）日：2004-06-24

  The present invention relates to compounds useful as inhibitors of protein kinases. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders.

  本发明涉及用作蛋白激酶抑制剂的化合物。该发明还提供包含该化合物的药学上可接受的组合物，并提供使用该组合物治疗各种疾病、病症或障碍的方法。
• COMPOSITIONS USEFUL AS INHIBITORS OF ROCK AND OTHER PROTEIN KINASES
  申请人：VERTEX PHARMACEUTICALS INCORPORATED

  公开号：EP1558607A1

  公开（公告）日：2005-08-03