7-((2-[(cyclopropylcarbonyl)-amino]pyridin-4-yl)oxy)-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid | 942077-42-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 7-((2-[(cyclopropylcarbonyl)-amino]pyridin-4-yl)oxy)-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid
• 英文别名: 7-({2-[(cyclopropylcarbonyl)amino]pyridin-4-yl}oxy)-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid；7-[2-(cyclopropanecarbonylamino)pyridin-4-yl]oxy-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid
• CAS: 942077-42-1
• 化学式: C₂₀H₂₀N₂O₄
• 分子量: 352.39
• InChiKey: QPLPDUNAOYQIOS-UHFFFAOYSA-N

物化性质

• 沸点：
  631.4±55.0 °C(Predicted)
• 密度：
  1.383±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  88.5
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  7-((2-[(cyclopropylcarbonyl)-amino]pyridin-4-yl)oxy)-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid 在 盐酸 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.58h， 生成 N-[3-(aminomethyl)-5-(trifluoromethyl)phenyl]-7-((2-[(cyclopropylcarbonyl)amino]pyridin-4-yl)oxy)-1,2,3,4-tetrahydronaphthalene-2-carboxamide hydrochloride
  参考文献：
  名称：

  Design and Optimization of Potent and Orally Bioavailable Tetrahydronaphthalene Raf Inhibitors

  摘要：

  Inhibition of mutant B-Raf signaling, through either direct inhibition of the enzyme or inhibition of MEK, the direct substrate of Raf, has been demonstrated preclinically to inhibit tumor growth. Very recently, treatment of B-Raf mutant melanoma patients with a selective B-Raf inhibitor has resulted in promising preliminary evidence of antitumor activity. This article describes the design and optimization of tetrahydronaphthalene-derived compounds as potent inhibitors of the Raf pathway in vitro and in vivo. These compounds possess good pharmacokinetic properties in rodents and inhibit B-Raf mutant tumor growth in mouse xenograft models.

  DOI：

  10.1021/jm101479y
• 作为产物：
  描述：

  7-甲氧基-1-萘满酮 在 硫酸 、 palladium 10% on activated carbon 、 氢溴酸 、 氢气 、 sodium hydride 、 caesium carbonate 、 溶剂黄146 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 65.0~100.0 ℃ 、206.85 kPa 条件下， 反应 5.67h， 生成 7-((2-[(cyclopropylcarbonyl)-amino]pyridin-4-yl)oxy)-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid
  参考文献：
  名称：

  Design and Optimization of Potent and Orally Bioavailable Tetrahydronaphthalene Raf Inhibitors

  摘要：

  Inhibition of mutant B-Raf signaling, through either direct inhibition of the enzyme or inhibition of MEK, the direct substrate of Raf, has been demonstrated preclinically to inhibit tumor growth. Very recently, treatment of B-Raf mutant melanoma patients with a selective B-Raf inhibitor has resulted in promising preliminary evidence of antitumor activity. This article describes the design and optimization of tetrahydronaphthalene-derived compounds as potent inhibitors of the Raf pathway in vitro and in vivo. These compounds possess good pharmacokinetic properties in rodents and inhibit B-Raf mutant tumor growth in mouse xenograft models.

  DOI：

  10.1021/jm101479y

文献信息

• SUBSTITUTED HYDROXAMIC ACIDS AND USES THEREOF
  申请人：Calderwood Emily F.

  公开号：US20120015942A1

  公开（公告）日：2012-01-19

  This invention provides compounds of formula (I): wherein R 1a , R 1b , R 1c , R 2a , R 2b , R 2c , and R 2d have values as described in the specification, useful as inhibitors of HDAC6. The invention also provides pharmaceutical compositions comprising the compounds of the invention and methods of using the compositions in the treatment of proliferative, inflammatory, infectious, neurological or cardiovascular diseases or disorders.

  这项发明提供了式（I）的化合物： 其中R1a、R1b、R1c、R2a、R2b、R2c和R2d的取值如规范中所述，可用作HDAC6的抑制剂。该发明还提供了包括该发明化合物的药物组合物，以及在治疗增殖性、炎症性、感染性、神经系统或心血管疾病或紊乱中使用这些组合物的方法。
• Bicyclic compounds with kinase inhibitory activity
  申请人：Calderwood F. Emily

  公开号：US20070149533A1

  公开（公告）日：2007-06-28

  The present invention provides novel bicyclic compounds useful as inhibitors of protein kinases. The invention also provides pharmaceutical compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various diseases.

  本发明提供了一种新颖的双环化合物，可用作蛋白激酶抑制剂。本发明还提供了包括本发明化合物的制药组合物以及使用该组合物治疗各种疾病的方法。
• SUBSTITUTED HYDOXAMIC ACIDS AND USES THEREOF
  申请人：Calderwood Emily F.

  公开号：US20140243334A1

  公开（公告）日：2014-08-28

  This invention provides compounds of formula (I): wherein R 1a , R 1b , R 1c , R 2a , R 2b , R 2c , and R 2d have values as described in the specification, useful as inhibitors of HDAC6. The invention also provides pharmaceutical compositions comprising the compounds of the invention and methods of using the compositions in the treatment of proliferative, inflammatory, infectious, neurological or cardiovascular diseases or disorders.

  本发明提供了式(I)的化合物：其中R1a，R1b，R1c，R2a，R2b，R2c和R2d具有规范中描述的值，可用作HDAC6的抑制剂。该发明还提供了包含该发明化合物的药物组成物，并且提供了使用该组成物治疗增生性、炎症性、感染性、神经系统或心血管疾病或障碍的方法。
• WO2007/67444
  申请人：——

  公开号：——

  公开（公告）日：——
• US8110687B2
  申请人：——

  公开号：US8110687B2

  公开（公告）日：2012-02-07