| 1620568-12-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• CAS: 1620568-12-8
• 化学式: C₂₅H₂₉N₃O₆
• 分子量: 467.522
• InChiKey: BZJJNNXDYBVXKO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.98
• 重原子数：
  34.0
• 可旋转键数：
  7.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  114.04
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  在 4-二甲氨基吡啶 、 palladium 10% on activated carbon 、 氢气 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 18.0h， 生成 benzyl (2-(1-((4-(((tert-butoxycarbonyl)amino)methyl)phenyl)carbamoyl)-4-oxoazetidin-2-yl)acetyl)glycinate
  参考文献：
  名称：

  Targeting integrins αvβ3 and α5β1 with new β-lactam derivatives

  摘要：

  The αvβ3 and α5β1 integrins are widely expressed in different cancer types and recognize the tripeptide Arg-Gly-Asp (RGD) motif present in several extracellular matrix proteins. We report here the design, synthesis and biological activity of some new β-lactam derivatives specifically designed to target integrins. The new molecules contain the azetidinone as the only cyclic framework armed with carboxylic acid and amine terminals spaced from 9 to 14 atoms to switch on recognition by integrins. All tested molecules showed a concentration-dependent enhancement in fibronectin-mediated adhesion of K562 and SK-MEL-24 cells; in particular 1, expressed a higher affinity towards α5β1 integrin (EC50 of 12 nM) and 2 was more selective for integrin αvβ3 (EC50 of 11 nM).

  DOI：

  10.1016/j.ejmech.2014.06.041
• 作为产物：
  描述：

  4-(N-BOC-氨甲基)苯胺 在 sodium hexamethyldisilazane 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 0.75h， 生成
  参考文献：
  名称：

  Targeting integrins αvβ3 and α5β1 with new β-lactam derivatives

  摘要：

  The αvβ3 and α5β1 integrins are widely expressed in different cancer types and recognize the tripeptide Arg-Gly-Asp (RGD) motif present in several extracellular matrix proteins. We report here the design, synthesis and biological activity of some new β-lactam derivatives specifically designed to target integrins. The new molecules contain the azetidinone as the only cyclic framework armed with carboxylic acid and amine terminals spaced from 9 to 14 atoms to switch on recognition by integrins. All tested molecules showed a concentration-dependent enhancement in fibronectin-mediated adhesion of K562 and SK-MEL-24 cells; in particular 1, expressed a higher affinity towards α5β1 integrin (EC50 of 12 nM) and 2 was more selective for integrin αvβ3 (EC50 of 11 nM).

  DOI：

  10.1016/j.ejmech.2014.06.041

文献信息

• New β-Lactam Derivatives Modulate Cell Adhesion and Signaling Mediated by RGD-Binding and Leukocyte Integrins
  作者：Monica Baiula、Paola Galletti、Giulia Martelli、Roberto Soldati、Laura Belvisi、Monica Civera、Samantha Deianira Dattoli、Santi Mario Spampinato、Daria Giacomini

  DOI：10.1021/acs.jmedchem.6b00576

  日期：2016.11.10

  and leukocyte integrins is reported. The compound library was evaluated by investigating the effects on integrin-mediated cell adhesion and cell signaling in cell lines expressing αvβ3, αvβ5, αvβ6, α5β1, αIIbβ3, α4β1, and αLβ2 integrins. SAR analysis of the new series of azetidinones enabled the recognition of structural elements associated with integrin selectivity. We obtained selective and potent agonists

  报道了设计和合成靶向RGD结合和白细胞整联蛋白的一系列新的β-内酰胺衍生物。所述化合物库通过研究对整合素介导的细胞粘附和细胞系中的细胞信号传导表达α的影响评价v β 3，α v β 5，α v β 6，α 5 β 1，α IIB β 3，α 4 β 1，以及α大号β 2整联蛋白。新的氮杂环丁酮系列的SAR分析使人们认识到与整联蛋白选择性有关的结构元素。我们获得选择性和可诱导的细胞粘附和促进细胞有效激动剂信令α介导的v β 3，α v β 5，α 5 β 1，或α 4 β 1整合素，和拮抗剂的整α v β 3和α 5 β 1，以及α 4 β 1和α大号β 2，防止了由各自的内源性激动剂引起的作用。