(5-tert-butyl-2-phenyl-2H-pyrazol-3-yl)acetic acid | 443912-82-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (5-tert-butyl-2-phenyl-2H-pyrazol-3-yl)acetic acid
• 英文别名: 2-(3-tert-butyl-1-phenyl-1H-pyrazol-5-yl)acetic acid；2-(5-tert-butyl-2-phenylpyrazol-3-yl)acetic acid
• CAS: 443912-82-1
• 化学式: C₁₅H₁₈N₂O₂
• 分子量: 258.32
• InChiKey: LGFWUKKBQVHRIN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  55.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  对氯苯胺 、 (5-tert-butyl-2-phenyl-2H-pyrazol-3-yl)acetic acid 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 以0.093 g的产率得到2-(5-tert-Butyl-2-phenyl-2H-pyrazol-3-yl)-N-(4-chloro-phenyl)-acetamide
  参考文献：
  名称：

  Pyrazole Urea-Based Inhibitors of p38 MAP Kinase:  From Lead Compound to Clinical Candidate

  摘要：

  We report on a series of N-pyrazole, N'-aryl ureas and their mode of binding to p38 mitogen activated protein kinase. Importantly, a key binding domain that is distinct from the adenosine 5'-triphoshate (ATP) binding site is exposed when the conserved activation loop, consisting in part of Asp168-Phe169-Gly170, adopts a conformation permitting lipophilic and hydrogen bonding interactions between this class of inhibitors and the protein. We describe the correlation of the structure-activity relationships and crystallographic structures of these inhibitors with p38. In addition, we incorporated another binding pharmacophore that forms a hydrogen bond at the ATP binding site. This modification affords significant improvements in binding, cellular, and in vivo potencies resulting in the selection of 45 (BIRB 796) as a clinical candidate for the treatment of inflammatory diseases.

  DOI：

  10.1021/jm020057r
• 作为产物：
  描述：

  trifluoromethanesulfonic acid 5-tert-butyl-2-phenyl-2H-pyrazol-3-yl ester 在 9-borabicyclo[3.3.1]nonane dimer 、 四(三苯基膦)钯 、 jones reagent 、 lithium chloride 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 丙酮 为溶剂， 反应 6.0h， 生成 (5-tert-butyl-2-phenyl-2H-pyrazol-3-yl)acetic acid
  参考文献：
  名称：

  Pyrazole Urea-Based Inhibitors of p38 MAP Kinase:  From Lead Compound to Clinical Candidate

  摘要：

  We report on a series of N-pyrazole, N'-aryl ureas and their mode of binding to p38 mitogen activated protein kinase. Importantly, a key binding domain that is distinct from the adenosine 5'-triphoshate (ATP) binding site is exposed when the conserved activation loop, consisting in part of Asp168-Phe169-Gly170, adopts a conformation permitting lipophilic and hydrogen bonding interactions between this class of inhibitors and the protein. We describe the correlation of the structure-activity relationships and crystallographic structures of these inhibitors with p38. In addition, we incorporated another binding pharmacophore that forms a hydrogen bond at the ATP binding site. This modification affords significant improvements in binding, cellular, and in vivo potencies resulting in the selection of 45 (BIRB 796) as a clinical candidate for the treatment of inflammatory diseases.

  DOI：

  10.1021/jm020057r