1-(3-(chloromethyl)phenyl)-3-(prop-2-yn-1-yl)urea | 1373331-84-0

• 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: 1-(3-(chloromethyl)phenyl)-3-(prop-2-yn-1-yl)urea
• 英文别名: 1-((3-chloromethyl)phenyl)-3-(2-propynyl)urea；1-[3-(Chloromethyl)phenyl]-3-prop-2-ynylurea
• CAS: 1373331-84-0
• 化学式: C₁₁H₁₁ClN₂O
• 分子量: 222.674
• InChiKey: FVJONZRWJFEMKI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  41.1
• 氢给体数：
  2
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1-(3-(chloromethyl)phenyl)-3-(prop-2-yn-1-yl)urea 、 4-甲基苄胺 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以25.53%的产率得到1-(3-((4-methylbenzylamino)methyl)phenyl)-3-(prop-2-yn-1-yl)urea
  参考文献：
  名称：

  Synthesis and evaluation of 1-(substituted)-3-prop-2-ynylureas as antiangiogenic agents

  摘要：

  Novel urea derivatives of alkynes have been designed, synthesized, and evaluated as potential cancer therapeutics leads. The most active 1-((3-chloromethyl)phenyl)-3-prop-2-ynylurea (1) exhibited cytotoxic effect against HELA and MCF-7 cell lines with IC50 values of 1.55 mu M and 1.48 mu M, respectively. Further investigation on tube formation assay in human vein umbilical cells (HUVEC) demonstrated that 1 and methyl 4-(3-(3-ethynylureido)benzyloxy) benzoate (6) possess antiangiogenic activity, with minimum effective dose of 25 nM (for 1) and 6.25 mu M (for 6). The ED50 of 1 and 6 were found to be 0.26 mu M and 17.52 mu M, respectively. The results from in vitro tyrosine kinase assay indicated the EGFR inhibition of 1 over other kinases (VEGFR2, FGFR1 and PDGFR beta). The cytotoxicity of 1 against EGFR over-expressing cell line A431 (IC50 36 nM) was comparable to that of erlotinib. The binding mode of 1 from docking simulation in the EGFR active site revealed that the urea motif formed hydrogen bonding with Lys745, Thr854 and Asp855 in hydrophobic pocket of EGFR. Compound 1 is considered as a potential lead for further optimization. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.02.029
• 作为产物：
  描述：

  3-(氯甲基)苯甲酸 在 叠氮磷酸二苯酯 、 三乙胺 作用下， 以 1,4-二氧六环 为溶剂， 反应 3.5h， 生成 1-(3-(chloromethyl)phenyl)-3-(prop-2-yn-1-yl)urea
  参考文献：
  名称：

  Synthesis and evaluation of 1-(substituted)-3-prop-2-ynylureas as antiangiogenic agents

  摘要：

  Novel urea derivatives of alkynes have been designed, synthesized, and evaluated as potential cancer therapeutics leads. The most active 1-((3-chloromethyl)phenyl)-3-prop-2-ynylurea (1) exhibited cytotoxic effect against HELA and MCF-7 cell lines with IC50 values of 1.55 mu M and 1.48 mu M, respectively. Further investigation on tube formation assay in human vein umbilical cells (HUVEC) demonstrated that 1 and methyl 4-(3-(3-ethynylureido)benzyloxy) benzoate (6) possess antiangiogenic activity, with minimum effective dose of 25 nM (for 1) and 6.25 mu M (for 6). The ED50 of 1 and 6 were found to be 0.26 mu M and 17.52 mu M, respectively. The results from in vitro tyrosine kinase assay indicated the EGFR inhibition of 1 over other kinases (VEGFR2, FGFR1 and PDGFR beta). The cytotoxicity of 1 against EGFR over-expressing cell line A431 (IC50 36 nM) was comparable to that of erlotinib. The binding mode of 1 from docking simulation in the EGFR active site revealed that the urea motif formed hydrogen bonding with Lys745, Thr854 and Asp855 in hydrophobic pocket of EGFR. Compound 1 is considered as a potential lead for further optimization. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.02.029

文献信息

• Novel VEGFR-2 kinase inhibitors identified by the back-to-front approach
  作者：Kingkan Sanphanya、Suvara K. Wattanapitayakul、Suwadee Phowichit、Valery V. Fokin、Opa Vajragupta

  DOI：10.1016/j.bmcl.2013.03.042

  日期：2013.5

  We report a novel VEGFR-2 inhibitor, developed by the back-to-front approach. Docking experiments indicated that the 3-chloromethylphenylurea motif of the lead compound occupied the back pocket of VEGFR-2 kinase. An attempt was made to enhance the binding affinity of 1 by expanding the structure to access the front pocket using a triazole linker. A library of 1,4-(disubstituted)-1H-1,2,3-triazoles were screened in silico, and one compound (VH02) was identified with an IC50 against VEGFR-2 of 0.56 mu M. VH02 showed antiangiogenic effects, inhibiting tube formation in HUVEC cells (EA.hy926) at 0.3 mu M, 13 times lower than its cytotoxic dose. These enzymatic and cellular activities suggest that VH02 has potential as a lead for further optimization. (C) 2013 Elsevier Ltd. All rights reserved.
• Synthesis and evaluation of 1-(substituted)-3-prop-2-ynylureas as antiangiogenic agents
  作者：Kingkan Sanphanya、Suvara K. Wattanapitayakul、Orawin Prangsaengtong、Michiko Jo、Keiichi Koizumi、Naotoshi Shibahara、Aroonsri Priprem、Valery V. Fokin、Opa Vajragupta

  DOI：10.1016/j.bmcl.2012.02.029

  日期：2012.4

  Novel urea derivatives of alkynes have been designed, synthesized, and evaluated as potential cancer therapeutics leads. The most active 1-((3-chloromethyl)phenyl)-3-prop-2-ynylurea (1) exhibited cytotoxic effect against HELA and MCF-7 cell lines with IC50 values of 1.55 mu M and 1.48 mu M, respectively. Further investigation on tube formation assay in human vein umbilical cells (HUVEC) demonstrated that 1 and methyl 4-(3-(3-ethynylureido)benzyloxy) benzoate (6) possess antiangiogenic activity, with minimum effective dose of 25 nM (for 1) and 6.25 mu M (for 6). The ED50 of 1 and 6 were found to be 0.26 mu M and 17.52 mu M, respectively. The results from in vitro tyrosine kinase assay indicated the EGFR inhibition of 1 over other kinases (VEGFR2, FGFR1 and PDGFR beta). The cytotoxicity of 1 against EGFR over-expressing cell line A431 (IC50 36 nM) was comparable to that of erlotinib. The binding mode of 1 from docking simulation in the EGFR active site revealed that the urea motif formed hydrogen bonding with Lys745, Thr854 and Asp855 in hydrophobic pocket of EGFR. Compound 1 is considered as a potential lead for further optimization. (C) 2012 Elsevier Ltd. All rights reserved.