3-硼-5-氯苯甲酰胺 | 957120-53-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 3-硼-5-氯苯甲酰胺
• 中文别名: (3-氨基甲酰-5-氯苯基)硼酸
• 英文名称: 3-carbamoyl-5-chlorophenylboronic acid
• 英文别名: (3-Carbamoyl-5-chlorophenyl)boronic acid
• CAS: 957120-53-5
• 化学式: C₇H₇BClNO₃
• mdl: MFCD09800858
• 分子量: 199.401
• InChiKey: YFWFJKMZBNMWMC-UHFFFAOYSA-N

物化性质

• 沸点：
  392.8±52.0 °C(Predicted)
• 密度：
  1.47±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.81
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  83.6
• 氢给体数：
  3
• 氢受体数：
  3

安全信息

• 海关编码：
  2931900090
• 危险性防范说明：
  P210,P261,P264,P271,P280,P302+P352,P304+P340,P305+P351+P338,P312,P332+P313,P337+P313,P362,P370+P378,P403+P233,P403+P235,P405,P501
• 危险性描述：
  H315,H319,H335

反应信息

• 作为反应物：
  描述：

  3-bromo-1-ethyl-1H-pyrrole-2,5-dione 、 3-硼-5-氯苯甲酰胺 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 cesium fluoride 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 2.0h， 以31%的产率得到3-chloro-5-(1-ethyl-2,5-dioxo-pyrrol-3-yl)benzamide
  参考文献：
  名称：

  Small Molecule Binding Sites on the Ras:SOS Complex Can Be Exploited for Inhibition of Ras Activation

  摘要：

  Constitutively active mutant KRas displays a reduced rate of GTP hydrolysis via both intrinsic and GTPase-activating protein-catalyzed mechanisms, resulting in the perpetual activation of Ras pathways. We describe a fragment screening campaign using X-ray crystallography that led to the discovery of three fragment binding sites on the Ras:SOS complex. The identification of tool compounds binding at each of these sites allowed exploration of two new approaches to Ras pathway inhibition by stabilizing or covalently modifying the Ras:SOS complex to prevent the reloading of Ras with GTP. Initially, we identified ligands that bound reversibly to the Ras:SOS complex in two distinct sites, but these compounds were not sufficiently potent inhibitors to validate our stabilization hypothesis. We conclude by demonstrating that covalent modification of Cys118 on Ras leads to a novel mechanism of inhibition of the SOS-mediated interaction between Ras and Raf and is effective at inhibiting the exchange of labeled GDP in both mutant (G12C and G12V) and wild type Ras.

  DOI：

  10.1021/jm501660t

文献信息

• Small Molecule Binding Sites on the Ras:SOS Complex Can Be Exploited for Inhibition of Ras Activation
  作者：Jon J. G. Winter、Malcolm Anderson、Kevin Blades、Claire Brassington、Alexander L. Breeze、Christine Chresta、Kevin Embrey、Gary Fairley、Paul Faulder、M. Raymond V. Finlay、Jason G. Kettle、Thorsten Nowak、Ross Overman、S. Joe Patel、Paula Perkins、Loredana Spadola、Jonathan Tart、Julie A. Tucker、Gail Wrigley

  DOI：10.1021/jm501660t

  日期：2015.3.12

  Constitutively active mutant KRas displays a reduced rate of GTP hydrolysis via both intrinsic and GTPase-activating protein-catalyzed mechanisms, resulting in the perpetual activation of Ras pathways. We describe a fragment screening campaign using X-ray crystallography that led to the discovery of three fragment binding sites on the Ras:SOS complex. The identification of tool compounds binding at each of these sites allowed exploration of two new approaches to Ras pathway inhibition by stabilizing or covalently modifying the Ras:SOS complex to prevent the reloading of Ras with GTP. Initially, we identified ligands that bound reversibly to the Ras:SOS complex in two distinct sites, but these compounds were not sufficiently potent inhibitors to validate our stabilization hypothesis. We conclude by demonstrating that covalent modification of Cys118 on Ras leads to a novel mechanism of inhibition of the SOS-mediated interaction between Ras and Raf and is effective at inhibiting the exchange of labeled GDP in both mutant (G12C and G12V) and wild type Ras.