| 2615912-31-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• CAS: 2615912-31-5
• 化学式: C₃₄H₄₈BN₃O₅
• 分子量: 589.583
• InChiKey: FIBTYUUEHSIOAQ-LXFBAYGMSA-N

物化性质

• 沸点：
  758.1±60.0 °C (Predicted,Press: 760 Torr)
• 密度：
  1.16±0.1 g/cm³ (Predicted,Temp: 20 °C; Press: 760 Torr)
• pKa：
  10.80±0.40 (Predicted,Most Basic Temp: 25 °C)

计算性质

• 辛醇/水分配系数(LogP)：
  5.04
• 重原子数：
  43.0
• 可旋转键数：
  8.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  89.99
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  在 copper dichloride 、 三氟乙酸 作用下， 以 甲醇 、 水 、 二氯甲烷 为溶剂， 反应 21.33h， 以46 mg的产率得到(S)-3-(3-chlorophenyl)-4-oxo-4-((R)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)pyrrolidin-1-yl)butanoic acid
  参考文献：
  名称：

  Discovery of the first potent and selective αvβ5 integrin inhibitor based on an amide-containing core

  摘要：

  Integrins α_vβ₅ and α_vβ₃ are closely related, proangiogenic members of the wider RGD-binding integrin family. Due to their high sequence homology, the development of α_vβ₅-selective compounds has remained elusive to synthetic and medicinal chemists. Herein, we describe a survey of SAR around a series of amide-containing 3-aryl-succinamic acid-based RGD mimetics. This resulted in the discovery of α,α,α-trifluorotolyl 12 which exhibits 800 × selectivity for α_vβ₅versus α_vβ₃ with a pyrrolidine amide linker that confers selectivity for α_vβ₅ by positioning a key aryl ring in the SDL of α_vβ₅ with good complementarity; binding in this mode is disfavoured in α_vβ₃ due to clashes with key residues in the β₃-subunit. Compound 12 exhibits selective inhibition by a cell adhesion assay, high passive permeability and solubility which enables potential use of this inhibitor as an α_vβ₅-selective in vitro tool compound.

  DOI：

  10.1016/j.ejmech.2020.112719
• 作为产物：
  描述：

  3-溴苯乙酸 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 双氧水 、 potassium acetate 、 sodium hexamethyldisilazane 、 三甲基乙酰氯 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 lithium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 4.25h， 生成
  参考文献：
  名称：

  Discovery of the first potent and selective αvβ5 integrin inhibitor based on an amide-containing core

  摘要：

  Integrins α_vβ₅ and α_vβ₃ are closely related, proangiogenic members of the wider RGD-binding integrin family. Due to their high sequence homology, the development of α_vβ₅-selective compounds has remained elusive to synthetic and medicinal chemists. Herein, we describe a survey of SAR around a series of amide-containing 3-aryl-succinamic acid-based RGD mimetics. This resulted in the discovery of α,α,α-trifluorotolyl 12 which exhibits 800 × selectivity for α_vβ₅versus α_vβ₃ with a pyrrolidine amide linker that confers selectivity for α_vβ₅ by positioning a key aryl ring in the SDL of α_vβ₅ with good complementarity; binding in this mode is disfavoured in α_vβ₃ due to clashes with key residues in the β₃-subunit. Compound 12 exhibits selective inhibition by a cell adhesion assay, high passive permeability and solubility which enables potential use of this inhibitor as an α_vβ₅-selective in vitro tool compound.

  DOI：

  10.1016/j.ejmech.2020.112719