N-(5-tert-butyl-2-phenylpyrazol-3-yl)formamide | 443912-85-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-(5-tert-butyl-2-phenylpyrazol-3-yl)formamide
• CAS: 443912-85-4
• 化学式: C₁₄H₁₇N₃O
• 分子量: 243.308
• InChiKey: SXKOCAJOOBJYPP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  46.9
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-(5-tert-butyl-2-phenylpyrazol-3-yl)formamide 在 dimethyl sulfide borane 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 49.5h， 生成 1-(5-Tert-butyl-2-phenylpyrazol-3-yl)-3-(4-chlorophenyl)-1-methylurea
  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：

  新戊酰基乙腈 以 甲苯 为溶剂， 反应 4.0h， 生成 N-(5-tert-butyl-2-phenylpyrazol-3-yl)formamide
  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

文献信息

• UREA COMPOUND, PREPARATION METHOD THEREFOR AND MEDICAL USE THEREOF
  申请人：Ancureall Pharmaceutical (Shanghai) Co., Ltd.

  公开号：EP3424924A1

  公开（公告）日：2019-01-09

  Provided are a urea compound represented by general formula (I), a pharmaceutically acceptable salt thereof, a preparation method therefor, and use thereof as an FLT3 tyrosine protein kinase inhibitor, particularly in the prevention and/or treating of cancer.

  本发明提供了通式（I）代表的脲化合物、其药学上可接受的盐、其制备方法，以及其作为FLT3酪氨酸蛋白激酶抑制剂的用途，特别是在预防和/或治疗癌症中的用途。