1-({[3,4-dichlorophenyl]amino}carbonyl)cyclopropanecarboxylic acid

• 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-({[3,4-dichlorophenyl]amino}carbonyl)cyclopropanecarboxylic acid
• 英文别名: 1-({3,4-dichloroanilino}carbonyl)cyclopropanecarboxylic acid；1-[(3,4-Dichlorophenyl)carbamoyl]cyclopropane-1-carboxylic acid
• 化学式: C₁₁H₉Cl₂NO₃
• 分子量: 274.103
• InChiKey: FVUHWLSXSVPNFL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  66.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(4-氨基苯基)-1H-吲唑-3-胺 、 1-({[3,4-dichlorophenyl]amino}carbonyl)cyclopropanecarboxylic acid 在 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 8.5h， 生成 N-[4-(3-amino-1H-indazol-4-yl)phenyl]-N-(3,4-dichlorophenyl)cyclopropane-1,1-dicarboxamide
  参考文献：
  名称：

  Discovery of novel anti-angiogenesis agents. Part 6: Multi-targeted RTK inhibitors

  摘要：

  Angiogenesis is modulated by a multitude of pro-angiogenic factors including VEGFR-2, Tie-2, and EphB4. Moreover, their crosstalk also had been well elaborated. We have identified several diarylureabased VEGFR-2 inhibitors as potential anti-angiogenesis agents. As a continuation to our previous research, two series of diaryl malonamide and diaryl thiourea derivatives have been developed as multiplex VEGFR-2/Tie-2/EphB4 inhibitors. Interestingly, the biological evaluation indicated that several compounds bearing trifluoromethyl or trifluoromethoxyl exhibited promising multiplex inhibition against angiogenesis-related VEGFR-2, Tie-2, and EphB4. The representative compound (18a) displayed both potent multi-targeted RTK inhibition and considerable antiproliferative activities against human umbilical vein endothelial cells (EA.hy926). These results will contribute to the discovery of novel mutitargeted anti-angiogenesis agents. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.12.059
• 作为产物：
  描述：

  1,1-环丙基二羧酸 、 3,4-二氯苯胺 在 氯化亚砜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 4.5h， 以40%的产率得到1-({[3,4-dichlorophenyl]amino}carbonyl)cyclopropanecarboxylic acid
  参考文献：
  名称：

  一种具有抗肿瘤活性的环丙二酰胺类化合物 及其制备方法和应用

  摘要：

  本发明提供了一种具有抗肿瘤活性的环丙二酰胺类化合物及其制备方法和应用，该化合物的结构式为其中R1为卤素基团，R2为卤素基团或或者R1、R2共同形成该化合物对VEGFR‑2激酶有很好的抑制活性，能够通过抑制VEGFR‑2激酶的活性，阻断其诱导的信号通路，抑制肿瘤细胞的增生和迁移，从而可应用于抗肿瘤药物的制备。且该化合物的制备方法具有原料易得，反应条件温和，反应过程操作简单，所用试剂便宜的优点。

  公开号：

  CN105924403B

文献信息

• 一种具有抗肿瘤活性的环丙二酰胺化合物及其制备方法和应用
  申请人：西安交通大学

  公开号：CN105906568A

  公开（公告）日：2016-08-31

  本发明提供了一种具有抗肿瘤活性的环丙二酰胺化合物及其制备方法和应用，该化合物的结构式为其中R1、R2为卤素基团，或者R1、R2共同形成该化合物对VEGFR‑2激酶有很好的抑制活性，能够通过抑制VEGFR‑2激酶的活性，阻断其诱导的信号通路，抑制肿瘤细胞的增生和迁移，从而可应用于抗肿瘤药物的制备。且该化合物的制备方法具有原料易得，反应条件温和，反应过程操作简单，所用试剂便宜的优点。
• 一种具有抗肿瘤活性的环丙二酰胺类化合物 及其制备方法和应用
  申请人：西安交通大学

  公开号：CN105924403B

  公开（公告）日：2018-07-17

  本发明提供了一种具有抗肿瘤活性的环丙二酰胺类化合物及其制备方法和应用，该化合物的结构式为其中R1为卤素基团，R2为卤素基团或或者R1、R2共同形成该化合物对VEGFR‑2激酶有很好的抑制活性，能够通过抑制VEGFR‑2激酶的活性，阻断其诱导的信号通路，抑制肿瘤细胞的增生和迁移，从而可应用于抗肿瘤药物的制备。且该化合物的制备方法具有原料易得，反应条件温和，反应过程操作简单，所用试剂便宜的优点。
• Discovery of novel anti-angiogenesis agents. Part 7: Multitarget inhibitors of VEGFR-2, TIE-2 and EphB4
  作者：Chuansheng Li、Yuanyuan Shan、Ying Sun、Ru Si、Liyuan Liang、Xiaoyan Pan、Binghe Wang、Jie Zhang

  DOI：10.1016/j.ejmech.2017.10.030

  日期：2017.12

  Herein, we embarked on a structural optimization campaign aiming at the discovery of second generation anti-angiogenesis agents with our previously reported BPS-7 as lead compound. A library of 27 compounds has been afforded based on the highly conserved ATP-binding pocket of VEGFR-2, Tie-2, and EphB4. Several title compounds exhibited simultaneous inhibitory effects against three angiogenic RTKs. These compounds with a 'triplet' inhibition profile have been identified as novel anti-angiogenic and anticancer agents. The representative VDAU11 displayed prominent anti-angiogenic and anticancer potency and could be considered as a candidate for further optimization. These results indicate that N(pyridin-2-yl)acrylamide could serve as a novel hinge-binding group of triple inhibitors. (C) 2017 Elsevier Masson SAS. All rights reserved.
• Discovery of novel anti-angiogenesis agents. Part 6: Multi-targeted RTK inhibitors
  作者：Lin Zhang、Yuanyuan Shan、Chuansheng Li、Ying Sun、Ping Su、Jinfeng Wang、Lisha Li、Xiaoyan Pan、Jie Zhang

  DOI：10.1016/j.ejmech.2016.12.059

  日期：2017.2

  Angiogenesis is modulated by a multitude of pro-angiogenic factors including VEGFR-2, Tie-2, and EphB4. Moreover, their crosstalk also had been well elaborated. We have identified several diarylureabased VEGFR-2 inhibitors as potential anti-angiogenesis agents. As a continuation to our previous research, two series of diaryl malonamide and diaryl thiourea derivatives have been developed as multiplex VEGFR-2/Tie-2/EphB4 inhibitors. Interestingly, the biological evaluation indicated that several compounds bearing trifluoromethyl or trifluoromethoxyl exhibited promising multiplex inhibition against angiogenesis-related VEGFR-2, Tie-2, and EphB4. The representative compound (18a) displayed both potent multi-targeted RTK inhibition and considerable antiproliferative activities against human umbilical vein endothelial cells (EA.hy926). These results will contribute to the discovery of novel mutitargeted anti-angiogenesis agents. (C) 2017 Elsevier Masson SAS. All rights reserved.