DPPA | 289038-87-5

• 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: DPPA
• 英文别名: 3-(Chloromethyl)benzoyl azide
• CAS: 289038-87-5
• 化学式: C₈H₆ClN₃O
• 分子量: 195.608
• InChiKey: YNEJAZJBKUMNRA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  31.4
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  DPPA 在 potassium carbonate 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 Methyl 4-[[3-(prop-2-ynylcarbamoylamino)phenyl]methoxy]benzoate
  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 0.5h， 生成 DPPA
  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 benzothiepines having activity as inhibitors of ileal bile acid transport and taurocholate uptake
  申请人：G.D. Searle & Co.

  公开号：US20020013476A1

  公开（公告）日：2002-01-31

  Provided are novel benzothiepines, derivatives, and analogs thereof; pharmaceutical compositions containing them; and methods of using these compounds and compositions in medicine, particularly in the prophylaxis and treatment of hyperlipidemic conditions such as those associated with atherosclerosis or hypercholesterolemia, in mammals.

  提供了新型苯并噻吩类化合物及其衍生物和类似物；含有它们的药物组合物；以及在医学中使用这些化合物和组合物的方法，特别是在哺乳动物中预防和治疗高脂血症状，如与动脉粥样硬化或高胆固醇血症相关的情况。
• Novel benzothiepines having activity as inhibitors of lleal bile acid transport and taurocholate uptake
  申请人：G.D. Searle & Co.

  公开号：US20040014803A1

  公开（公告）日：2004-01-22

  Provided are novel benzothiepines, derivatives, and analogs thereof; pharmaceutical compositions containing them; and methods of using these compounds and compositions in medicine, particularly in the prophylaxis and treatment of hyperlipidemic conditions such as those associated with atherosclerosis or hypercholesterolemia, in mammals.

  提供了新型苯硫杂吲哚类化合物及其衍生物和类似物；含有它们的药物组合物；以及在医学中使用这些化合物和组合物的方法，特别是在哺乳动物中预防和治疗高脂血症状，如与动脉粥样硬化或高胆固醇血症相关的情况。
• Novel mono- and di-fluorinated benzothiepine compouds as inhibitors of apical sodium co-dependent bile acid transport (ASBT) and taurocholate uptake
  申请人：G.D. SEARLE, LLC

  公开号：US20040067872A1

  公开（公告）日：2004-04-08

  Mono-fluorinated and di-fluorinated benzothiepine apical sodium co-dependent bile acid transport (ASBT) inhibitors are disclosed together with methods of making the same, methods of using the same to treat hyperlipidemic conditions as well as pharmaceutical compositions containing the same compounds.

  本发明公开了单氟和二氟苯并噻吩顶部钠依赖性胆酸转运体（ASBT）抑制剂，以及制备这些抑制剂的方法，使用这些抑制剂治疗高脂血症的方法，以及含有这些化合物的药物组合物。
• Novel mono- and di-fluorinated beozothiepine copmunds as inhibitors of apical sodium co-dependent bile acid transport (ASBT) and taurocholate uptake
  申请人：G.D. SEARLE, LLC

  公开号：US20040176438A1

  公开（公告）日：2004-09-09

  Mono-fluorinated and di-fluorinated benzothiepine apical sodium co-dependent bile acid transport (ASBT) inhibitors are disclosed together with methods of making the same, methods of using the same to treat hyperlipidemic conditions as well as pharmaceutical compositions containing the same compounds.

  本文披露了单氟和双氟苯并噻吩顶部钠依赖性胆汁酸转运体（ASBT）抑制剂的方法，以及制备这些抑制剂的方法，使用这些抑制剂治疗高脂血症状况的方法，以及含有这些化合物的制药组合物。
• Preparation of benzothiepines having activity as inhibitors of ileal bile acid transport and taurocholate uptake
  申请人：G.D. Searle & Co.

  公开号：EP1466911A2

  公开（公告）日：2004-10-13

  Methods are provided for preparing benzothiepines, derivatives, and analogs thereof, which have activity as inhibitors of ileal bile acid transport and taurocholate uptake.

  本研究提供了制备苯并噻吩类、其衍生物和类似物的方法，它们具有作为回肠胆汁酸转运和牛磺胆酸盐摄取抑制剂的活性。