3-amino-5-(1-methyl-1-phenylethyl)-2-phenyl-2H-pyrazole | 1026706-34-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-amino-5-(1-methyl-1-phenylethyl)-2-phenyl-2H-pyrazole
• 英文别名: 2-Phenyl-5-(2-phenylpropan-2-yl)pyrazol-3-amine
• CAS: 1026706-34-2
• 化学式: C₁₈H₁₉N₃
• 分子量: 277.369
• InChiKey: DALWMBUNMZTAJO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  43.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  异氰酸苯酯 、 3-amino-5-(1-methyl-1-phenylethyl)-2-phenyl-2H-pyrazole 以 四氢呋喃 为溶剂， 生成 1-[5-(1-Methyl-1-phenyl-ethyl)-2-phenyl-2H-pyrazol-3-yl]-3-phenyl-urea
  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：

  2-苯基丙酸乙酯 在 sodium hydride 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 7.0h， 生成 3-amino-5-(1-methyl-1-phenylethyl)-2-phenyl-2H-pyrazole
  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