N-(3-bromophenyl)-N'-(2-methyl-4-hydroxyphenyl)urea | 1609458-51-6

• 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: N-(3-bromophenyl)-N'-(2-methyl-4-hydroxyphenyl)urea
• 英文别名: 1-(3-Bromophenyl)-3-(4-hydroxy-2-methylphenyl)urea；1-(3-bromophenyl)-3-(4-hydroxy-2-methylphenyl)urea
• CAS: 1609458-51-6
• 化学式: C₁₄H₁₃BrN₂O₂
• 分子量: 321.173
• InChiKey: QKKHTVSTSFZICQ-UHFFFAOYSA-N

物化性质

• 熔点：
  204-206 °C
• 沸点：
  366.2±42.0 °C(predicted)
• 密度：
  1.599±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  61.4
• 氢给体数：
  3
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-chloro-6-methoxy-7-(2-(pyrrolidin-1-yl)ethoxy)quinazoline 、 N-(3-bromophenyl)-N'-(2-methyl-4-hydroxyphenyl)urea 在 四丁基溴化铵 、 sodium hydroxide 作用下， 以 丁酮 为溶剂， 反应 1.0h， 以25%的产率得到N-(3-bromophenyl)-N'-{3-methyl-4-[(6-methoxy-7-pyrrolidinoethoxyquinazolin-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
• 作为产物：
  描述：

  4-氨基-3-甲基苯酚 、 3-溴苯基异氰酸酯 在 吡啶 作用下， 反应 1.0h， 以89%的产率得到N-(3-bromophenyl)-N'-(2-methyl-4-hydroxyphenyl)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

文献信息

• Synthesis and biological evaluation of di-aryl urea derivatives as c-Kit inhibitors
  作者：Séverine Ravez、Stéphane Arsenlis、Amélie Barczyk、Anthony Dupont、Raphaël Frédérick、Stéphanie Hesse、Gilbert Kirsch、Patrick Depreux、Laurence Goossens

  DOI：10.1016/j.bmc.2015.10.035

  日期：2015.11

  Inhibition of receptor tyrosine kinases (RTKs) continued to be a successful approach for the treatment of many types of human cancers and many potent small molecules kinase inhibitors have been discovered the last decade. In the present study, we describe the synthesis of thienopyrimidine derivatives and their pharmacological evaluation against nine kinases (EGFR, PDGFR-ss, c-Kit, c-Met, Src, Raf, VEGFR-1, -2 and -3). Most of the synthesized compounds showed from moderate to potent activities against c-Kit with IC50 values in the nanomolar range. Among them, 4-anilino(urea) thienopyrimidine analogs showed selectivity and potent c-Kit inhibition with IC50 values less than 6 nM. Docking simulation was performed for the most promising compound 9 into the c-Kit active site to determine the potential binding mode. This study reveal that the 4-anilino(urea) thienopyrimidine is an interesting scaffold to design novel potent and selective c-Kit inhibitors which may make promising candidates for cancers where c-Kit receptors are overexpressed. (C) 2015 Elsevier Ltd. All rights reserved.
• 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.