4''-(3'-(2,4-diamino-1,3,5-triazaspiro[5.5]undeca-2,4-dien-1-yloxy)propyloxy)benzonitrile hydrochloride | 1208149-69-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 4''-(3'-(2,4-diamino-1,3,5-triazaspiro[5.5]undeca-2,4-dien-1-yloxy)propyloxy)benzonitrile hydrochloride
• 英文别名: 4-[3-[(2,4-Diamino-1,3,5-triazaspiro[5.5]undeca-1,3-dien-5-yl)oxy]propoxy]benzonitrile;hydrochloride
• CAS: 1208149-69-2
• 化学式: C₁₈H₂₄N₆O₂*ClH
• 分子量: 392.888
• InChiKey: FBBPYNSXQFIENS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.29
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  122
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2,4-diamino-1,3,5-triazaspiro[5.5]undeca-2,4-dien-1-ol hydrochloride 、 1-溴-3-(4-氰基苯氧基)丙烷 在 sodium hydroxide 、 盐酸 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 水 为溶剂， 反应 0.5h， 以53.4%的产率得到4''-(3'-(2,4-diamino-1,3,5-triazaspiro[5.5]undeca-2,4-dien-1-yloxy)propyloxy)benzonitrile hydrochloride
  参考文献：
  名称：

  Antifolate and antiproliferative activity of 6,8,10-triazaspiro[4.5]deca-6,8-dienes and 1,3,5-triazaspiro[5.5]undeca-1,3-dienes

  摘要：

  Two series of triazaspiroalkanedienes, bearing a substituted phenoxy propyloxy side chain, were identified as potent mammalian DHFR inhibitors. One series has a 6,5-spiro bicyclic ring system and the other series has a 6,6-spiro bicyclic system. Both series were synthesized and tested for in vitro mammalian DHFR inhibitory activity and antiproliferative activity against A549 human lung-cancer cells. Compound 3c showed the highest antiproliferative activity against A549 cells with an IC50 value of 27.1 nM. Rescue experiment confirmed its antifolate antiproliferative mechanism. The excellent antifolate and antiproliferative activity of selected analogues presented in this study warrants further investigation as potential leads in the anticancer drug discovery. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.11.065

文献信息

• Antifolate and antiproliferative activity of 6,8,10-triazaspiro[4.5]deca-6,8-dienes and 1,3,5-triazaspiro[5.5]undeca-1,3-dienes
  作者：Xiang Ma、Wai-Keung Chui

  DOI：10.1016/j.bmc.2009.11.065

  日期：2010.1

  Two series of triazaspiroalkanedienes, bearing a substituted phenoxy propyloxy side chain, were identified as potent mammalian DHFR inhibitors. One series has a 6,5-spiro bicyclic ring system and the other series has a 6,6-spiro bicyclic system. Both series were synthesized and tested for in vitro mammalian DHFR inhibitory activity and antiproliferative activity against A549 human lung-cancer cells. Compound 3c showed the highest antiproliferative activity against A549 cells with an IC50 value of 27.1 nM. Rescue experiment confirmed its antifolate antiproliferative mechanism. The excellent antifolate and antiproliferative activity of selected analogues presented in this study warrants further investigation as potential leads in the anticancer drug discovery. (C) 2009 Elsevier Ltd. All rights reserved.