cis-<2-(1,1'-biphenyl-4-yl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl>methyl methanesulfonate | 145782-17-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: cis-<2-(1,1'-biphenyl-4-yl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl>methyl methanesulfonate
• 英文别名: (+/-)-cis-[2-(1,1'-biphenyl-4-yl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methyl methanesulfonate；cis-[2-(1,1'-biphenyl-4-yl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methyl methanesulfonate；[(2R,4R)-2-(imidazol-1-ylmethyl)-2-(4-phenylphenyl)-1,3-dioxolan-4-yl]methyl methanesulfonate
• CAS: 145782-17-8；145782-18-9
• 化学式: C₂₁H₂₂N₂O₅S
• 分子量: 414.482
• InChiKey: ARCBCBCTOQJJRR-RTWAWAEBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  88
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  cis-<2-(1,1'-biphenyl-4-yl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl>methyl methanesulfonate 、 ethyl (4-mercaptophenyl)carbamate 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 2.0h， 以96%的产率得到(+/-)-cis-[4-[[2-(1,1'-biphenyl-4-yl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methylthio]phenyl]carbamic acid ethyl ester
  参考文献：
  名称：

  New Structural Analogues of Tubulozole Induce Apoptosis, [Ca2+]i Modifications and Cytoskeletal Disorganization in Glial (GL15) and Neuronal-like (PC12) Cell Lines

  摘要：

  The synthesis and the biological activity of (+/-)-cis- and (+/-)-trans-[4-[[2-(1,1'-biphenyl-4-yl)-2-(1H-imidazol-1-ylmethyl)-1, 3-dioxolan-4-yl]methylthio]phenyl]carbamic acid ethyl esters (2a and 2b) are discussed. They were designed as structural analogues of Tubulozole, a synthetic tubulin polymerisation inhibitor with antimitotic properties. Biological tests were carried out on PC12, a neuronal-like cell line derived from rat pheochromocytoma, and on GL15, a cell line derived from human glioblastoma. The exposure (from 5 to 20 h) of GL15 and PC12 cells to different concentrations (0.1-1000 microM; IC50 approximately 1 microM) of 2a or 2b resulted in a drastic decrease in the number of viable cells without an apparent effect on the cell distribution in the various phases of the cell cycle. Compound 2a or 2b (10 microM) induced cell death by activating apoptosis. This was correlated with the activation of an oscillating Ca(2+)-dependent mechanism which increased the intracellular calcium concentration ([Ca2+]i) via Ca(2+)-release from internal stores. Moreover, 2a (10 microM) also induced severe damage of cytoskeletal F-actin filaments after a 5 h incubation in GL15 cells. This was also observed but to a smaller extent, for 2b. Under the same experimental conditions, PC12 cells showed similar actin deregulation.

  DOI：

  10.1002/1521-4184(200011)333:11<373::aid-ardp373>3.0.co;2-6
• 作为产物：
  描述：

  cis/trans-<2-(1,1'-biphenyl-4-yl)-2-bromomethyl-1,3-dioxolan-4-yl>methanol 在 吡啶 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 N,N-二甲基乙酰胺 、 水 为溶剂， 反应 104.0h， 生成 cis-<2-(1,1'-biphenyl-4-yl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl>methyl methanesulfonate
  参考文献：
  名称：

  抗菌和抗真菌剂，XV：联苯苄唑和酮康唑结构类似物的合成和抗真菌活性

  摘要：

  顺式和反式 1-乙酰基-4-{4-[[2-(1,1'-联苯-4-基)-2-(1H-咪唑-1-基甲基)-的合成和抗真菌活性报道了 1,3-二氧戊环-4-基]-甲氧基]苯基}哌嗪 3 和 4。基于 1H- 和 13C-NMR 数据对非对映异构体的顺式/反式异构体对进行立体化学分配。在测试衍生物中，顺-和反-[2-(1,1'-联苯-4-基)-2-(1H-咪唑-1-基甲基)-1,3 -dioxolan-4-yl]甲醇 9 和 10。

  DOI：

  10.1002/ardp.19923251102

文献信息

• Antibacterial and Antifungal Agents, XV: Synthesis and Antifungal Activity of Structural Analogues of Bifonazole and Ketoconazole
  作者：Giorgio Stefancich、Marino Artico、Giorgio Ortar、Romano Silvestri、Giovanna Simonetti、Germana Apuzzo、Marco Artico

  DOI：10.1002/ardp.19923251102

  日期：——

  The synthesis and antifungal activities of the cis‐ and trans‐1‐acetyl‐4‐4‐[[2‐(1,1′‐biphenyl‐4‐yl)‐2‐(1H‐imidazol‐1‐ylmethyl)‐1,3‐dioxolan‐4‐yl]‐methoxy]phenyl}piperazines 3 and 4 are reported. Stereochemical assignments to diastereomeric pairs of cis/trans isomers were made on the basis of 1H‐ and 13C‐NMR data. Among test derivatives the best activity was shown by the benzoyl esters of the cis‐

  顺式和反式 1-乙酰基-4-4-[[2-(1,1'-联苯-4-基)-2-(1H-咪唑-1-基甲基)-的合成和抗真菌活性报道了 1,3-二氧戊环-4-基]-甲氧基]苯基}哌嗪 3 和 4。基于 1H- 和 13C-NMR 数据对非对映异构体的顺式/反式异构体对进行立体化学分配。在测试衍生物中，顺-和反-[2-(1,1'-联苯-4-基)-2-(1H-咪唑-1-基甲基)-1,3 -dioxolan-4-yl]甲醇 9 和 10。
• New Structural Analogues of Tubulozole Induce Apoptosis, [Ca2+]i Modifications and Cytoskeletal Disorganization in Glial (GL15) and Neuronal-like (PC12) Cell Lines
  作者：Sabrina Castellano、Maria Addolorata Mariggiò、Simone Guarnieri、Giorgio Stefancich、Tiziana Pietrangelo

  DOI：10.1002/1521-4184(200011)333:11<373::aid-ardp373>3.0.co;2-6

  日期：2000.11

  The synthesis and the biological activity of (+/-)-cis- and (+/-)-trans-[4-[[2-(1,1'-biphenyl-4-yl)-2-(1H-imidazol-1-ylmethyl)-1, 3-dioxolan-4-yl]methylthio]phenyl]carbamic acid ethyl esters (2a and 2b) are discussed. They were designed as structural analogues of Tubulozole, a synthetic tubulin polymerisation inhibitor with antimitotic properties. Biological tests were carried out on PC12, a neuronal-like cell line derived from rat pheochromocytoma, and on GL15, a cell line derived from human glioblastoma. The exposure (from 5 to 20 h) of GL15 and PC12 cells to different concentrations (0.1-1000 microM; IC50 approximately 1 microM) of 2a or 2b resulted in a drastic decrease in the number of viable cells without an apparent effect on the cell distribution in the various phases of the cell cycle. Compound 2a or 2b (10 microM) induced cell death by activating apoptosis. This was correlated with the activation of an oscillating Ca(2+)-dependent mechanism which increased the intracellular calcium concentration ([Ca2+]i) via Ca(2+)-release from internal stores. Moreover, 2a (10 microM) also induced severe damage of cytoskeletal F-actin filaments after a 5 h incubation in GL15 cells. This was also observed but to a smaller extent, for 2b. Under the same experimental conditions, PC12 cells showed similar actin deregulation.