methyl 2-amino-4-piperidinoethoxy-5-methoxybenzoate | 1352738-41-0

• 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: methyl 2-amino-4-piperidinoethoxy-5-methoxybenzoate
• 英文别名: 2-amino-5-methoxy-4-(2-(piperidin-1-yl)ethoxy)benzoic acid methyl ester；Methyl 2-amino-5-methoxy-4-(2-piperidin-1-ylethoxy)benzoate
• CAS: 1352738-41-0
• 化学式: C₁₆H₂₄N₂O₄
• 分子量: 308.378
• InChiKey: GKURDGUKRXKWBT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  74
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 2-amino-4-piperidinoethoxy-5-methoxybenzoate 在 四丁基溴化铵 、 甲酸铵 、 sodium hydroxide 、 三氯氧磷 作用下， 以 丁酮 为溶剂， 反应 31.0h， 生成 N-(3-bromophenyl)-N'-{4-[(6-methoxy-7-piperidinoethoxyquinazolin-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
• 作为产物：
  描述：

  methyl 3-methoxy-4-piperidinoethoxybenzoate 在 氢气 、 硝酸 、 四氯化锡 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 22.0h， 生成 methyl 2-amino-4-piperidinoethoxy-5-methoxybenzoate
  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

• 4-取代苯胺喹唑啉类衍生物及其制备方法和 用途
  申请人：中国药科大学

  公开号：CN105884699B

  公开（公告）日：2019-05-07

  本发明公开了一类新型4‑取代苯胺喹唑啉类衍生物或其药学上可接受的盐、多晶型物、溶剂合物或立体异构体，及其制备方法和应用。本发明中的4‑取代苯胺喹唑啉类化合物在生物学测试中，对EGFR和VEGFR‑2具有良好的抑制活性，并在体外抗人肿瘤细胞增殖活性试验中显示出明显的效果。