Ethyl 5-amino-1-butylpyrazole-4-carboxylate | 159709-53-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: Ethyl 5-amino-1-butylpyrazole-4-carboxylate
• CAS: 159709-53-2
• 化学式: C₁₀H₁₇N₃O₂
• 分子量: 211.264
• InChiKey: GFSDVTIKONKZNN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  15
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  70.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Ethyl 5-amino-1-butylpyrazole-4-carboxylate 在 trans-N,N'-dimethyl-1,2-cyclohexyldiamine 、 bis-triphenylphosphine-palladium(II) chloride 、 potassium phosphate 、 copper(l) iodide 作用下， 以 1,4-二氧六环 、 水 、 甲苯 为溶剂， 反应 91.5h， 生成 5-[acetyl-(2'-cyano-biphenyl-4-yl)-amino]-1-butyl-1H-pyrazole-4-carboxylic acid ethyl ester
  参考文献：
  名称：

  Application of Ullmann and Ullmann–Finkelstein reactions for the synthesis of N-aryl-N-(1H-pyrazol-3-yl) acetamide or N-(1-aryl-1H-pyrazol-3-yl) acetamide derivatives and pharmacological evaluation

  摘要：

  Ullmann-type reactions are becoming a major tool in medicinal chemistry. In this article, we describe the use of these Copper-catalyzed reactions with various precursors, acyl-heteroarylamines or pyrazoles of interest for pharmacomodulation. To the medicinal chemist they offer new, usually untapped disconnection approaches to compounds of interest. They thus open the way to new original analogues of bioactive compounds possibly not patented, from common building-blocks. They also allow C to N bioisosteric replacements, which sometimes are synthetically challenging. We report for the first time the critical effect of acetylamino substituents on the regioselective arylation of unsymmetrical pyrazoles that are useful for medicinal chemists. Finally, we have applied this strategy to the design of novel AT, receptor antagonists. Though this family has been extensively investigated in the past 30 years, N-arylation and C to N replacement made possible by Ullmann chemistry, can produce original antagonists. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.05.056
• 作为产物：
  描述：

  草酸丁肼 、 ethyl (ethoxymethylene)cyanoacetate 在 三乙胺 作用下， 以 乙醇 为溶剂， 反应 6.0h， 生成 Ethyl 5-amino-1-butylpyrazole-4-carboxylate
  参考文献：
  名称：

  Application of Ullmann and Ullmann–Finkelstein reactions for the synthesis of N-aryl-N-(1H-pyrazol-3-yl) acetamide or N-(1-aryl-1H-pyrazol-3-yl) acetamide derivatives and pharmacological evaluation

  摘要：

  Ullmann-type reactions are becoming a major tool in medicinal chemistry. In this article, we describe the use of these Copper-catalyzed reactions with various precursors, acyl-heteroarylamines or pyrazoles of interest for pharmacomodulation. To the medicinal chemist they offer new, usually untapped disconnection approaches to compounds of interest. They thus open the way to new original analogues of bioactive compounds possibly not patented, from common building-blocks. They also allow C to N bioisosteric replacements, which sometimes are synthetically challenging. We report for the first time the critical effect of acetylamino substituents on the regioselective arylation of unsymmetrical pyrazoles that are useful for medicinal chemists. Finally, we have applied this strategy to the design of novel AT, receptor antagonists. Though this family has been extensively investigated in the past 30 years, N-arylation and C to N replacement made possible by Ullmann chemistry, can produce original antagonists. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.05.056

文献信息

• 5-Amino-pyrazoles as potent and selective p38α inhibitors
  作者：Jagabandhu Das、Robert V. Moquin、Alaric J. Dyckman、Tianle Li、Sidney Pitt、Rosemary Zhang、Ding Ren Shen、Kim W. McIntyre、Kathleen Gillooly、Arthur M. Doweyko、John A. Newitt、John S. Sack、Hongjian Zhang、Susan E. Kiefer、Kevin Kish、Murray McKinnon、Joel C. Barrish、John H. Dodd、Gary L. Schieven、Katerina Leftheris

  DOI：10.1016/j.bmcl.2010.10.034

  日期：2010.12

  The synthesis and structure-activity relationships (SAR) of p38 alpha MAP kinase inhibitors based on a 5-amino-pyrazole scaffold are described. These studies led to the identification of compound 2j as a potent and selective inhibitor of p38 alpha MAP kinase with excellent cellular potency toward the inhibition of TNF alpha production. Compound 2j was highly efficacious in vivo in inhibiting TNF alpha production in an acute murine model of TNF alpha production. X-ray co-crystallography of a 5-amino-pyrazole analog 2f bound to unphosphorylated p38 alpha is also disclosed. (C) 2010 Elsevier Ltd. All rights reserved.