DPPA | 117098-59-6

• 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: DPPA
• 英文别名: 3-chloromethyl-phenyl isocyanate；3-Chlormethyl-phenylisocyanat；3-(Chloromethyl)-phenylisocyanate；1-(chloromethyl)-3-isocyanatobenzene
• CAS: 117098-59-6
• 化学式: C₈H₆ClNO
• mdl: MFCD19233682
• 分子量: 167.595
• InChiKey: CAOAUHIGHKUBRZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.125
• 拓扑面积：
  29.4
• 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 1.0h， 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 2.5h， 生成 DPPA
  参考文献：
  名称：

  Novel VEGFR-2 kinase inhibitors identified by the back-to-front approach

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2013.03.042

文献信息

• Thiopyrimidine and isothiazolopyrimidine kinase inhibitors
  申请人：——

  公开号：US20040014756A1

  公开（公告）日：2004-01-22

  Compounds having the formula 1 are useful for inhibiting protein tyrosine kinases. The present invention also discloses methods of making the compounds, compositions containing the compounds, and methods of treatment using the compounds.

  具有以下化学式的化合物对抑制蛋白酪氨酸激酶具有用处。本发明还公开了制备这些化合物的方法、含有这些化合物的组合物，以及使用这些化合物进行治疗的方法。
• [EN] THIOPYRIMIDINE AND ISOTHIAZOLOPYRIMIDINE KINASE INHIBITORS<br/>[FR] INHIBITEURS DES THIOPYRIMIDINE ET ISOTHIAZOLOPYRIMIDINE KINASES
  申请人：ABBOTT LAB

  公开号：WO2003080625A1

  公开（公告）日：2003-10-02

  Compounds having the formula are useful for inhibiting protein tyrosine kinases. The present invention also discloses methods of making the compounds, compositions containing the compounds, and methods of treatment using the compounds.

  具有公式的化合物对于抑制蛋白酪氨酸激酶非常有用。本发明还公开了制备该化合物的方法，含有该化合物的组合物以及使用该化合物进行治疗的方法。
• Thiopyrimidine and isothiazolopyrimidine Kinase Inhibitors
  申请人：Michaelides R. Michael

  公开号：US20060276490A1

  公开（公告）日：2006-12-07

  Compounds having the formula are useful for inhibiting protein tyrosine kinases. The present invention also discloses methods of making the compounds, compositions containing the compounds, and methods of treatment using the compounds.

  具有公式的化合物对于抑制蛋白酪氨酸激酶是有用的。本发明还揭示了制备该化合物的方法，含有该化合物的组合物以及使用该化合物的治疗方法。
• Substituted 4-Amino-Pyrrolotriazine Derivatives Useful for Treating Hyper-Proliferative Disorders and Diseases Associated with Angiogenesis
  申请人：Dixon Julie

  公开号：US20100063038A1

  公开（公告）日：2010-03-11

  This invention relates to novel pyrrozolotriazine compounds, pharmaceutical compositions containing such compounds and and the use of those compounds or compositions for treating hyper-proliferative and/or angiogenesis disorders, as a sole agent or in combination with other active ingredients.

  本发明涉及新型吡唑三嗪化合物，包含这些化合物的制药组合物以及使用这些化合物或组合物治疗过度增殖和/或血管生成失调的方法，作为唯一活性成分或与其他活性成分联合使用。
• Hydroxylgruppen und Urethano-aryl-sulfonsäuregruppen enthaltende Verbindungen und Verfahren zu deren Herstellung; Verwendung dieser Verbindungen als Reaktionskomponente für Polyisocyanate
  申请人：BAYER AG

  公开号：EP0000724A1

  公开（公告）日：1979-02-21

  Verfahren zur Herstellung von mindestens eine Hydroxylgruppe und mindestens eine Urethano- aryl- sulfonsäuregruppe aufweisenden Verbindungen vom durchschnittlichen Molekulargewicht 300 bis 12000, dadurch gekennzeichnet, dass mindestens zwei Hydroxylgruppen aufweisende Verbindungen vom Molekulargewicht 62 bis 10000 bei 0-190°C mit aromatischen Isocyanatosulfonsäuren umgesetzt werden, wobei das Aequivalent- Verhältnis der Gesamtemenge an lsocyanatgruppen (einschliesslich der gegebenenfalls in dimerisierter Form vorhandenen Isocyanatgruppen) zu Sulfonsäuregruppen 0,5 bis 50 und das Aequivalent-Verhältnis aus der Summe der Hydroxyl- Gruppen der mindestens zwei Hydroxylgruppen aufweisenden Verbindungen zu NCO-Gruppen 1,5 bis 30 beträgt. Verwendung dieser Verbindungen als Reaktionskomponente für Polyisocyanate.

  一种制备具有至少一个羟基和至少一个脲基芳基磺酸基团且平均分子量为 300 至 12,000 的化合物的工艺，其特征在于至少两种具有羟基且分子量为 62 至 10,000 的化合物在 0-190°C 下与芳香族异氰酸基磺酸反应、其中异氰酸酯基团（包括以二聚体形式存在的异氰酸酯基团）的总量与磺酸基团的当量比为 0.5 至 50，含有至少两个羟基的化合物的羟基总和与 NCO 基团的当量比为 1.5 至 30。 将这些化合物用作多异氰酸酯的反应组分。