3-[(E)-1-(3-methoxy-7-methyl-1,2-benzoxazol-5-yl)-4-(5-methyl-1,3,4-oxadiazol-2-yl)but-1-enyl]benzonitrile | 1013421-34-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并异恶唑
• 英文名称: 3-[(E)-1-(3-methoxy-7-methyl-1,2-benzoxazol-5-yl)-4-(5-methyl-1,3,4-oxadiazol-2-yl)but-1-enyl]benzonitrile
• CAS: 1013421-34-5
• 化学式: C₂₃H₂₀N₄O₃
• 分子量: 400.437
• InChiKey: AHSUAILGPAEYMM-UFWORHAWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  98
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  5-碘-3-甲氧基-7-甲基-1,2-苯并恶唑 、 3-[4-(5-methyl-1,3,4-oxadiazol-2-yl)-1-tributylstannylbut-1-enyl]benzonitrile 在 四(三苯基膦)钯 copper(l) iodide 、 cesium fluoride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以99%的产率得到3-[(E)-1-(3-methoxy-7-methyl-1,2-benzoxazol-5-yl)-4-(5-methyl-1,3,4-oxadiazol-2-yl)but-1-enyl]benzonitrile
  参考文献：
  名称：

  Inhibition of tubulin polymerization by select alkenyldiarylmethanes

  摘要：

  During studies on the alkenyldiarylmethane (ADAM) class of non-nucleoside reverse transcriptase inhibitors (NNRTIs), analogues were discovered that exhibit low micromolar and submicromolar cytotoxicities. Since the ADAMs are structurally related to the tubulin polymerization inhibitor CC-5079, a set of 14 ADAMs were tested for inhibition of tubulin polymerization in an attempt to identify the biological target responsible for their cytotoxicity. The results indicate that, overall, the ADAMs are poor inhibitors of tubulin polymerization. However, the two most cytotoxic compounds, 15 and 16, are in fact active as inhibitors of tubulin assembly with IC50 values of 3.7 +/- 0.3 and 2.8 +/- 0.2 mu M, respectively, and they both inhibit the binding of colchicine to tubulin. Both compounds were investigated for anticancer activity in the National Cancer Institute's panel of 60 human cancer cell lines, and both compounds consistently displayed submicromolar cytotoxicities with mean-graph midpoint (MGM) values of 0.31 +/- 0.08 and 0.47 +/- 0.09 mu M, respectively. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.11.114

文献信息

• Inhibition of tubulin polymerization by select alkenyldiarylmethanes
  作者：Matthew D. Cullen、Taradas Sarkar、Ernest Hamel、Tracy L. Hartman、Karen M. Watson、Robert W. Buckheit、Christophe Pannecouque、Erik De Clercq、Mark Cushman

  DOI：10.1016/j.bmcl.2007.11.114

  日期：2008.1

  During studies on the alkenyldiarylmethane (ADAM) class of non-nucleoside reverse transcriptase inhibitors (NNRTIs), analogues were discovered that exhibit low micromolar and submicromolar cytotoxicities. Since the ADAMs are structurally related to the tubulin polymerization inhibitor CC-5079, a set of 14 ADAMs were tested for inhibition of tubulin polymerization in an attempt to identify the biological target responsible for their cytotoxicity. The results indicate that, overall, the ADAMs are poor inhibitors of tubulin polymerization. However, the two most cytotoxic compounds, 15 and 16, are in fact active as inhibitors of tubulin assembly with IC50 values of 3.7 +/- 0.3 and 2.8 +/- 0.2 mu M, respectively, and they both inhibit the binding of colchicine to tubulin. Both compounds were investigated for anticancer activity in the National Cancer Institute's panel of 60 human cancer cell lines, and both compounds consistently displayed submicromolar cytotoxicities with mean-graph midpoint (MGM) values of 0.31 +/- 0.08 and 0.47 +/- 0.09 mu M, respectively. (c) 2007 Elsevier Ltd. All rights reserved.