tert-butyl-2-{2,2-bis(3,5-dimethyl-1H-pyrazolyl)}-acetamidethylcarbamate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: tert-butyl-2-{2,2-bis(3,5-dimethyl-1H-pyrazolyl)}-acetamidethylcarbamate
• 英文别名: tert-butyl N-(2-(2,2-bis(3,5-dimethyl-1H-pyrazol-1-yl)acetamido)ethyl)carbamate；tert-butyl N-[2-[[2,2-bis(3,5-dimethylpyrazol-1-yl)acetyl]amino]ethyl]carbamate
• 化学式: C₁₉H₃₀N₆O₃
• 分子量: 390.486
• InChiKey: XEUMRBLOHNYIRX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  103
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  zinc perchlorate 、 tert-butyl-2-{2,2-bis(3,5-dimethyl-1H-pyrazolyl)}-acetamidethylcarbamate 以 甲醇 为溶剂， 反应 6.0h， 以74%的产率得到[(tert-butyl N-(2-(2,2-bis(3,5-dimethyl-1H-pyrazol-1-yl)acetamido)ethyl)carbamate)₂Zn](perchlorate)₂
  参考文献：
  名称：

  Effect of glucosamine conjugation to zinc(II) complexes of a bis-pyrazole ligand: Syntheses, characterization and anticancer activity

  摘要：

  The bis(3,5-dimethyl-1H- pyrazol-1yl)acetic acid (bdmpza) ligand was conjugated with tert-butyl-N-(2-aminoethyl) carbonate, methyl-2-amino-4-(methylthio)butanoate and 1,3,4,6-tetra-O-acetyl-beta-D-glucosamine hydrochloride via amide coupling method to form three ligands L1-L3 which were then reacted with Zn(II) salts to form four zinc complexes (1-4). The complexes were characterized by H-1 NMR, C-13 NMR, electrospray ionization mass spectrometry (ESI-MS), FT-IR, CHN analyses. Complexes 1, 2 and 4 were also characterized by single crystal X-ray diffraction. It was found that Zn(II) salts could selectively remove the acetyl group from anomeric position leaving everything else intact. The cytotoxicity studies of the ligand and the complexes showed that the conjugation to acetylated glucosamine enhances cytotoxic ability although the complexes become more hydrophilic. Cytotoxicity studies in human breast adenocarcinoma (MCF-7), human cervical cancer (HeLa WT) and human lung adenocarcinoma (A549) showed that the acetylated glucosamine conjugation to the bis-pyrazole ligated Zn(II) complex led to 2-4 fold increase in cytotoxicity (IC50 values ca. 57-80 mu M) against HeLa WT and MCF-7 cell lines. The Zn(II) complex bearing the acetylated glucosamine inhibits the cell cycle in the G2/M phase of MCF-7 cell line. ICP-MS data shows more accumulation of Zn(II) inside the cell upon use of complex 4 as compared to Zn(II) salts or the other presented complexes. Further studies suggest that the mitochondrial transmembrane potential changes in the presence of complex 4 and caspase-7 is activated by Zn(II) salts but the activation is much more by complex 4 and hence there is apoptosis and dose dependent chromatin condensation/nuclear fragmentation as observed by microscopy. (C) 2014 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.jinorgbio.2014.07.009
• 作为产物：
  描述：

  N-叔丁氧羰基-1,2-乙二胺 、 bis(3,5-dimethylpyrazol-1-yl)acetic acid 在 1,3-dicyclohexylpropa-1,2-diene 作用下， 以 二氯甲烷 、 叔丁醇 为溶剂， 反应 72.0h， 以73%的产率得到tert-butyl-2-{2,2-bis(3,5-dimethyl-1H-pyrazolyl)}-acetamidethylcarbamate
  参考文献：
  名称：

  蛋氨酸结合双吡唑基配体的 铜（ii）配合物促进DNA切割的双重途径†

  摘要：

  已经合成了三种基于双吡唑的配体的Cu II配合物，并通过X射线晶体学对其结构进行了表征。配体（L2）之一包含通过酰胺键与双吡唑羧酸酯共轭的蛋氨酸酯。1-3与CT DNA的复合物的结合常数约为10 4 M -1。晶体结构表明，轴向Cu-O键（约2.31（4）Å）相对不稳定，因此在抗坏血酸和氧的氧化还原循环中，一个或两个轴向Cu-O键可能会打开，从而促进铜氧反应并产生ROS。配合物1-3的化学核酸酶活性在黑暗中，显示在抗坏血酸（H 2 A）存在下100μM浓度的超螺旋DNA完全松弛。机理研究表明，络合物1和2过氧物种而显示的参与3个两者的单线态氧的节目和参与过氧在DNA裂解物种。否则在黑暗中单线态氧的形成是不利的，但是蛋氨酸作为L2中的侧链臂的存在可能会激活由金属生成的过氧物种生成单线态氧。DNA裂解研究的结果表明，蛋氨酸基铜（II）复合物可以促进DNA切割的双重途径。探测这些复合物对MCF-

  DOI：

  10.1039/c3dt51296g

文献信息

• Copper(ii) complex of methionine conjugated bis-pyrazole based ligand promotes dual pathway for DNA cleavage
  作者：Sudipta Bhattacharyya、Amrita Sarkar、Suman Kr Dey、Gregor P. Jose、Arindam Mukherjee、Tapas K. Sengupta

  DOI：10.1039/c3dt51296g

  日期：——

  suggests that the axial Cu–O bonds (ca. 2.31(4) Å) are relatively labile and hence during the redox cycle with ascorbic acid and oxygen one or both the axial Cu–O bonds might open to promote copper oxygen reaction and generate ROS. The chemical nuclease activity of complexes 1–3 in dark, show complete relaxation of supercoiled DNA at 100 μM concentration in presence of ascorbic acid (H2A). The mechanistic

  已经合成了三种基于双吡唑的配体的Cu II配合物，并通过X射线晶体学对其结构进行了表征。配体（L2）之一包含通过酰胺键与双吡唑羧酸酯共轭的蛋氨酸酯。1-3与CT DNA的复合物的结合常数约为10 4 M -1。晶体结构表明，轴向Cu-O键（约2.31（4）Å）相对不稳定，因此在抗坏血酸和氧的氧化还原循环中，一个或两个轴向Cu-O键可能会打开，从而促进铜氧反应并产生ROS。配合物1-3的化学核酸酶活性在黑暗中，显示在抗坏血酸（H 2 A）存在下100μM浓度的超螺旋DNA完全松弛。机理研究表明，络合物1和2过氧物种而显示的参与3个两者的单线态氧的节目和参与过氧在DNA裂解物种。否则在黑暗中单线态氧的形成是不利的，但是蛋氨酸作为L2中的侧链臂的存在可能会激活由金属生成的过氧物种生成单线态氧。DNA裂解研究的结果表明，蛋氨酸基铜（II）复合物可以促进DNA切割的双重途径。探测这些复合物对MCF-
• Effect of glucosamine conjugation to zinc(II) complexes of a bis-pyrazole ligand: Syntheses, characterization and anticancer activity
  作者：Sudipta Bhattacharyya、Amrita Sarkar、Suman Kr. Dey、Arindam Mukherjee

  DOI：10.1016/j.jinorgbio.2014.07.009

  日期：2014.11

  The bis(3,5-dimethyl-1H- pyrazol-1yl)acetic acid (bdmpza) ligand was conjugated with tert-butyl-N-(2-aminoethyl) carbonate, methyl-2-amino-4-(methylthio)butanoate and 1,3,4,6-tetra-O-acetyl-beta-D-glucosamine hydrochloride via amide coupling method to form three ligands L1-L3 which were then reacted with Zn(II) salts to form four zinc complexes (1-4). The complexes were characterized by H-1 NMR, C-13 NMR, electrospray ionization mass spectrometry (ESI-MS), FT-IR, CHN analyses. Complexes 1, 2 and 4 were also characterized by single crystal X-ray diffraction. It was found that Zn(II) salts could selectively remove the acetyl group from anomeric position leaving everything else intact. The cytotoxicity studies of the ligand and the complexes showed that the conjugation to acetylated glucosamine enhances cytotoxic ability although the complexes become more hydrophilic. Cytotoxicity studies in human breast adenocarcinoma (MCF-7), human cervical cancer (HeLa WT) and human lung adenocarcinoma (A549) showed that the acetylated glucosamine conjugation to the bis-pyrazole ligated Zn(II) complex led to 2-4 fold increase in cytotoxicity (IC50 values ca. 57-80 mu M) against HeLa WT and MCF-7 cell lines. The Zn(II) complex bearing the acetylated glucosamine inhibits the cell cycle in the G2/M phase of MCF-7 cell line. ICP-MS data shows more accumulation of Zn(II) inside the cell upon use of complex 4 as compared to Zn(II) salts or the other presented complexes. Further studies suggest that the mitochondrial transmembrane potential changes in the presence of complex 4 and caspase-7 is activated by Zn(II) salts but the activation is much more by complex 4 and hence there is apoptosis and dose dependent chromatin condensation/nuclear fragmentation as observed by microscopy. (C) 2014 Elsevier Inc. All rights reserved.