ethyl 5-amino-1-(2-oxo-2-phenylethyl)-1Hpyrazole-4-carboxylate | 851772-84-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: ethyl 5-amino-1-(2-oxo-2-phenylethyl)-1Hpyrazole-4-carboxylate
• 英文别名: Ethyl 5-amino-1-phenacylpyrazole-4-carboxylate
• CAS: 851772-84-4
• 化学式: C₁₄H₁₅N₃O₃
• 分子量: 273.291
• InChiKey: DPRMHDFOEIALIE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  87.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-氟苯基异氰酸酯 、 ethyl 5-amino-1-(2-oxo-2-phenylethyl)-1Hpyrazole-4-carboxylate 以 甲苯 为溶剂， 反应 12.0h， 以32%的产率得到ethyl 5-[(3-(2-fluorophenyl)ureido)]-1-(2-oxo-2-phenylethyl)-1H-pyrazole-4-carboxylate
  参考文献：
  名称：

  Design, synthesis and biological evaluation of new pyrazolyl-ureas and imidazopyrazolecarboxamides able to interfere with MAPK and PI3K upstream signaling involved in the angiogenesis

  摘要：

  Taking into account the structure activity relationship information given by our previous studies, we designed and synthesized a small library of pyrazolylureas and imidazopyrazolecarboxamides fluorinated on urea moiety and differently decorated on pyrazole nucleus. All compounds were preliminary screened by Western blotting technique to evaluate their activity on MAPK and PI3K pathways by monitoring ERK1/2, p38MAPK and Akt phosphorylation, and also screened with a wound healing assay to assess their capacity in inhibiting endothelial cell migration, using human umbilical vein endothelial cells stimulated with VEGF. Pyrazoles and imidazopyrazoles did not show the same activity profile. SAR consideration showed that specific substituents and their position in pyrazole nucleus, as well as the type of substituent on the phenylurea moiety play a pivotal role in determining increase or decrease of kinases phosphorylation. On the other hand the loss of flexibility in imidazopyrazole derivatives is responsible for activity potentiation. Screening of the compound library for inhibition of endothelial cell migration, a function required for angiogenesis, showed significant activity for compound 3. This compound might interfere with cell migration by modulating the activity of different upstream target kinases. Therefore, compound 3 represents a potential inhibitor of angiogenesis. Furthermore, it may be used as a tool to identify unknown mediators of endothelial migration and thereby unveiling new therapeutic targets for controlling pathological angiogenesis in diseases such as cancers. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.03.066
• 作为产物：
  描述：

  2-hydrazino-1-phenylethanol 在 三氧化硫吡啶 、 三乙胺 作用下， 以 二甲基亚砜 、 甲苯 为溶剂， 反应 8.5h， 生成 ethyl 5-amino-1-(2-oxo-2-phenylethyl)-1Hpyrazole-4-carboxylate
  参考文献：
  名称：

  Design, synthesis and biological evaluation of new pyrazolyl-ureas and imidazopyrazolecarboxamides able to interfere with MAPK and PI3K upstream signaling involved in the angiogenesis

  摘要：

  Taking into account the structure activity relationship information given by our previous studies, we designed and synthesized a small library of pyrazolylureas and imidazopyrazolecarboxamides fluorinated on urea moiety and differently decorated on pyrazole nucleus. All compounds were preliminary screened by Western blotting technique to evaluate their activity on MAPK and PI3K pathways by monitoring ERK1/2, p38MAPK and Akt phosphorylation, and also screened with a wound healing assay to assess their capacity in inhibiting endothelial cell migration, using human umbilical vein endothelial cells stimulated with VEGF. Pyrazoles and imidazopyrazoles did not show the same activity profile. SAR consideration showed that specific substituents and their position in pyrazole nucleus, as well as the type of substituent on the phenylurea moiety play a pivotal role in determining increase or decrease of kinases phosphorylation. On the other hand the loss of flexibility in imidazopyrazole derivatives is responsible for activity potentiation. Screening of the compound library for inhibition of endothelial cell migration, a function required for angiogenesis, showed significant activity for compound 3. This compound might interfere with cell migration by modulating the activity of different upstream target kinases. Therefore, compound 3 represents a potential inhibitor of angiogenesis. Furthermore, it may be used as a tool to identify unknown mediators of endothelial migration and thereby unveiling new therapeutic targets for controlling pathological angiogenesis in diseases such as cancers. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.03.066

文献信息

• [EN] PHENYL-ANILINE SUBSTITUTED BICYCLIC COMPOUNDS USEFUL AS KINASE INHIBITORS<br/>[FR] COMPOSES BICYCLIQUES A SUBSTITUTION PHENYL-ANILINE UTILISES COMME INHIBITEUR DE LA KINASE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2005042537A1

  公开（公告）日：2005-05-12

  Compounds having the formula (I), and pharmaceutically acceptable salts, prodrugs, and solvates thereof, are useful as kinase inhibitors, wherein R, R1 , R2, R5, R6a, R6b, J, K, X and Z are as described in the specification.

  具有化学式（I）的化合物，以及其药学上可接受的盐、前药和溶剂化合物，可用作激酶抑制剂，其中R、R1、R2、R5、R6a、R6b、J、K、X和Z如规范中所述。
• PHENYL-ANILINE SUBSTITUTED BICYCLIC COMPOUNDS USEFUL AS KINASE INHIBITORS
  申请人：Das Jagabandhu

  公开号：US20080167304A1

  公开（公告）日：2008-07-10

  Compounds having the formula (I), and pharmaceutically acceptable salts, prodrugs, and solvates thereof, are useful as kinase inhibitors, wherein R, R 1 , R 2 , R 5 , R 6a , R 6b , J, K, X and Z are as described in the specification.
• US7419978B2
  申请人：——

  公开号：US7419978B2

  公开（公告）日：2008-09-02
• US7642257B2
  申请人：——

  公开号：US7642257B2

  公开（公告）日：2010-01-05
• Design, synthesis and biological evaluation of new pyrazolyl-ureas and imidazopyrazolecarboxamides able to interfere with MAPK and PI3K upstream signaling involved in the angiogenesis
  作者：Elda Meta、Chiara Brullo、Adama Sidibe、Beat A. Imhof、Olga Bruno

  DOI：10.1016/j.ejmech.2017.03.066

  日期：2017.6

  Taking into account the structure activity relationship information given by our previous studies, we designed and synthesized a small library of pyrazolylureas and imidazopyrazolecarboxamides fluorinated on urea moiety and differently decorated on pyrazole nucleus. All compounds were preliminary screened by Western blotting technique to evaluate their activity on MAPK and PI3K pathways by monitoring ERK1/2, p38MAPK and Akt phosphorylation, and also screened with a wound healing assay to assess their capacity in inhibiting endothelial cell migration, using human umbilical vein endothelial cells stimulated with VEGF. Pyrazoles and imidazopyrazoles did not show the same activity profile. SAR consideration showed that specific substituents and their position in pyrazole nucleus, as well as the type of substituent on the phenylurea moiety play a pivotal role in determining increase or decrease of kinases phosphorylation. On the other hand the loss of flexibility in imidazopyrazole derivatives is responsible for activity potentiation. Screening of the compound library for inhibition of endothelial cell migration, a function required for angiogenesis, showed significant activity for compound 3. This compound might interfere with cell migration by modulating the activity of different upstream target kinases. Therefore, compound 3 represents a potential inhibitor of angiogenesis. Furthermore, it may be used as a tool to identify unknown mediators of endothelial migration and thereby unveiling new therapeutic targets for controlling pathological angiogenesis in diseases such as cancers. (C) 2017 Elsevier Masson SAS. All rights reserved.