N-(3-bromo-phenyl)-N'-{3-methyl-4-[(6-methoxy-7-piperidinopropoxyquinazolin-4-yl)oxy]phenyl}urea hydrochloride | 1609458-68-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-(3-bromo-phenyl)-N'-{3-methyl-4-[(6-methoxy-7-piperidinopropoxyquinazolin-4-yl)oxy]phenyl}urea hydrochloride
• 英文别名: 1-(3-Bromophenyl)-3-[4-[6-methoxy-7-(3-piperidin-1-ylpropoxy)quinazolin-4-yl]oxy-2-methylphenyl]urea;hydrochloride；1-(3-bromophenyl)-3-[4-[6-methoxy-7-(3-piperidin-1-ylpropoxy)quinazolin-4-yl]oxy-2-methylphenyl]urea;hydrochloride
• CAS: 1609458-68-5
• 化学式: C₃₁H₃₄BrN₅O₄*ClH
• 分子量: 657.007
• InChiKey: AMMOQTODJHUPTQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.82
• 重原子数：
  42
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  97.8
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3-溴苯基异氰酸酯 在 吡啶 、 四丁基溴化铵 、 sodium hydroxide 作用下， 以 丁酮 为溶剂， 反应 2.0h， 生成 N-(3-bromo-phenyl)-N'-{3-methyl-4-[(6-methoxy-7-piperidinopropoxyquinazolin-4-yl)oxy]phenyl}urea hydrochloride
  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

文献信息

• Inhibition of tumor cell growth and angiogenesis by 7-Aminoalkoxy-4-aryloxy-quinazoline ureas, a novel series of multi-tyrosine kinase inhibitors
  作者：Séverine Ravez、Amélie Barczyk、Perrine Six、Aurélie Cagnon、Antonio Garofalo、Laurence Goossens、Patrick Depreux

  DOI：10.1016/j.ejmech.2014.04.007

  日期：2014.5

  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.