Aethylen-bis-iminosalicyliden-diphosphonsaeure-diaethylester | 36032-64-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: Aethylen-bis-iminosalicyliden-diphosphonsaeure-diaethylester
• 英文别名: diethyl(ethane-1,2-diylbis(azanediyl))bis((2-hydroxyphenyl)methylene)bis(hydrogen phosphonate)；Ethoxy-[[2-[[[ethoxy(hydroxy)phosphoryl]-(2-hydroxyphenyl)methyl]amino]ethylamino]-(2-hydroxyphenyl)methyl]phosphinic acid
• CAS: 36032-64-1
• 化学式: C₂₀H₃₀N₂O₈P₂
• 分子量: 488.414
• InChiKey: HHPLAOVYWUJMNN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.4
• 重原子数：
  32
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  158
• 氢给体数：
  6
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  Aethylen-bis-iminosalicyliden-diphosphonsaeure-diaethylester 在 盐酸 作用下， 生成 [乙烷-1,2-二基二[亚氨基[(2-羟基苯基)亚甲基]]]二膦酸
  参考文献：
  名称：

  Giron-Forest,D.; Thomas,G., Bulletin de la Societe Chimique de France, 1972, p. 296 - 301

  摘要：

  DOI：
• 作为产物：
  描述：

  二乙基亚磷酸氢酯 、 N,N'-双(亚水杨基)乙二胺 生成 Aethylen-bis-iminosalicyliden-diphosphonsaeure-diaethylester
  参考文献：
  名称：

  Giron-Forest,D.; Thomas,G., Bulletin de la Societe Chimique de France, 1972, p. 296 - 301

  摘要：

  DOI：

文献信息

• Potent inhibition of protein tyrosine phosphatases by quinquedentate binuclear copper complexes: synthesis, characterization and biological activities
  作者：Qingming Wang、Miaoli Zhu、Liping Lu、Caixia Yuan、Shu Xing、Xueqi Fu

  DOI：10.1039/c1dt11006c

  日期：——

  Three phosphono-containing multidentate ligands were employed to synthesize quinquedentate binuclear copper complexes, [Cu2L2] (1–3) (H2L1 = diethyl(propane-1,3-diylbis(azanediyl))bis((2-hydroxyphenyl)methylene)bis(hydrogen phosphonate), H2L2 = diethyl(ethane-1,2-diylbis(azanediyl))bis((2-hydroxyphenyl)methylene)bis(hydrogen phosphonate), H2L3 = diethyl(hexane-1,6-diylbis(azanediyl))bis((2-hydroxyphenyl)methylene)bis(hydrogen phosphonate)), which were characterized by elemental analysis, IR, X-ray diffraction analysis, electrospray ionization mass spectra. Complexes 1 and 2 crystallized in the triclinic system with space group P. The speciation of the Cu–H2L1 system in aqueous solution was investigated by potentiometric pH titrations. The three dicopper complexes exhibited potent and almost the same inhibitory effects against protein tyrosine phosphatase 1B (PTP1B) and T-cell protein tyrosine phosphatase (TCPTP) with IC50 of 0.16–0.24 μM, about 10-fold stronger inhibition than against Src homology phosphatase 1 (SHP-1), 30-fold than against Src homology phosphatase 2 (SHP-2) and more than 100-fold than against megakaryocyte protein-tyrosine phosphatase 2 (PTP-MEG2). Fluorescence titrations revealed complex 1 bond to the five PTPs with molar ratio of 1 : 1 and binding constants of 1.62 × 106, 3.09 × 106, 1.95 × 105, 2.24 × 105, 1.55 × 104 M−1 for PTP1B, TCPTP, SHP-1, SHP-2 and PTP-MEG2, respectively, consistent with the inhibitory abilities from IC50 and Ki values. Also, the three copper complexes could inhibit phosphatase activity of cell extracts from C6 rat glioma cells. The results suggested the structures of copper complexes influence selectivity over different PTPs.

  采用三种含磷多叉配体合成了五价双核铜配合物 [Cu2L2] (1-3)（H2L1 = 二乙基(丙烷-1,3-二基双(偶氮二基))双((2-羟基苯基)亚甲基)双(膦酸氢盐)、H2L2 = 二乙基(乙烷-1、H2L3=(己烷-1,6-二基双(偶氮二基))双((2-羟基苯基)亚甲基)双(膦酸氢盐)二乙基)，它们通过元素分析、红外光谱、X 射线衍射分析和电喷雾质谱进行了表征。通过电位 pH 滴定法研究了 Cu-H2L1 体系在水溶液中的形态。这三种二氯化铜复合物对蛋白酪氨酸磷酸酶 1B (PTP1B) 和 T 细胞蛋白酪氨酸磷酸酶 (TCPTP) 具有强效且几乎相同的抑制作用，IC50 为 0.16-0.24 μM，抑制作用比 Src 同源磷酸酶 1 (SHP-1) 强 10 倍，比 Src 同源磷酸酶 2 (SHP-2) 强 30 倍，比巨核细胞蛋白-酪氨酸磷酸酶 2 (PTP-MEG2) 强 100 倍以上。荧光滴定显示，复合物 1 与五种 PTP 的摩尔比为 1 ：1，与 PTP1B、TCPTP、SHP-1、SHP-2 和 PTP-MEG2 的结合常数分别为 1.62 × 106、3.09 × 106、1.95 × 105、2.24 × 105、1.55 × 104 M-1，与 IC50 和 Ki 值的抑制能力一致。此外，这三种铜复合物还能抑制 C6 大鼠胶质瘤细胞提取物的磷酸酶活性。结果表明，铜复合物的结构会影响对不同 PTPs 的选择性。
• Exploration of α-aminophosphonate N-derivatives as novel, potent and selective inhibitors of protein tyrosine phosphatases
  作者：Qingming Wang、Miaoli Zhu、Ruiting Zhu、Liping Lu、Caixia Yuan、Shu Xing、Xueqi Fu、Yuhua Mei、Qingwei Hang

  DOI：10.1016/j.ejmech.2012.01.038

  日期：2012.3

  Seventeen alpha-aminophosphonates are synthesized. Their compositions and structures are established by EA, UV, FT-IR, H-1 NMR, C-13 NMR, P-31 NMR and ESI-MS. Compounds 1-4 are confirmed by X-ray crystallography. PIP inhibition shows compounds 1-5, 12, 15 are moderate competitive inhibitors with some selectivity. The most potent inhibitor is compound 5 with the lowest IC50 value about 6.64 mu M against PTP1B, about 2-fold and 25-fold stronger than against TCPTP and PTP-MEG2 while it doesn't inhibit SHP-1 and SHP-2. The binding constant of 5 to PTP1B is 2.23 x 10(5) M-1 and binding ratio approximates 1:1. Cell viability and apoptosis assays indicate 5 is cell permeable with lower cytotoxicity. The results indicate alpha-aminophosphonates are possibly developed to effective and selective inhibitors of PTPs. (C) 2012 Elsevier Masson SAS. All rights reserved.