2-((6-butoxy-4-chloroquinazolin-7-yl)oxy)-N,N-diethylethan-1-amine | 1352785-95-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 2-((6-butoxy-4-chloroquinazolin-7-yl)oxy)-N,N-diethylethan-1-amine
• CAS: 1352785-95-5
• 化学式: C₁₈H₂₆ClN₃O₂
• 分子量: 351.876
• InChiKey: KDCUXZNXVOEXMG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.18
• 重原子数：
  24.0
• 可旋转键数：
  10.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  47.48
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  N-(3-bromophenyl)-N'-(2-methyl-4-hydroxyphenyl)urea 、 2-((6-butoxy-4-chloroquinazolin-7-yl)oxy)-N,N-diethylethan-1-amine 在 四丁基溴化铵 、 sodium hydroxide 作用下， 以 丁酮 为溶剂， 反应 1.0h， 以52%的产率得到N-(3-bromo-phenyl)-N'-{3-methyl-4-[(6-butoxy-7-[2-(diethylaminoe)thoxy]quinazolin-4-yl)oxy]phenyl}urea
  参考文献：
  名称：

  Inhibition of tumor cell growth and angiogenesis by 7-Aminoalkoxy-4-aryloxy-quinazoline ureas, a novel series of multi-tyrosine kinase inhibitors

  摘要：

  Several regulatory and signaling molecules governing angiogenesis are targets of interest for the development of drugs in the cancer, including growth factors such as Vascular Endothelial Growth Factor (VEGF) and Platelet-Derived Growth Factor (PDGF). A series of 4-aryloxy-6,7-dimethoxyquinazolines, previously synthesized in our laboratory, has shown a nanomolar inhibition of kinase enzymatic activity of VEGFR, PDGFR and c-Kit. We have therefore studied the impact of the variation in the 7-position substitution of the quinazoline core. Substitution by aminoalkoxy chains led to new highly potent ATP-competitive inhibitors of VEGFR, PDGFR and c-Kit enzyme with IC50 values in the nanomolar range and this substitution has increased greatly antiproliferative activity on cancer cell lines (PC3, MCF7, HT29) and HUVEC (human umbilical vein endothelial cells). One of the most promising compounds (36) was assessed for its ability to limit the induction of web like network of capillary tubes by the human umbilical vascular endothelial cells (HUVEC) and for its ability to inhibit invasion. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.04.007