5-chloro-N-(3-(3-chlorophenyl)-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide | 1403963-83-6

• 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-chloro-N-(3-(3-chlorophenyl)-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide
• 英文别名: 5-chloro-N-[5-(3-chlorophenyl)-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide
• CAS: 1403963-83-6
• 化学式: C₁₆H₁₀Cl₂N₆O
• 分子量: 373.201
• InChiKey: WGGAYCIVHMEJMD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  88
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-chloro-N-(3-(3-chlorophenyl)-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide 在 氨 作用下， 以 乙醇 为溶剂， 反应 1.83h， 以77%的产率得到5-amino-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid [3-(3-chloro-phenyl)-1H-pyrazol-4-yl]-amide
  参考文献：
  名称：

  Discovery of Potent and Selective Pyrazolopyrimidine Janus Kinase 2 Inhibitors

  摘要：

  The discovery of somatic Jak2 mutations in patients with chronic myeloproliferative neoplasms has led to significant interest in disc-ova-ring selective Jak2 inhibitors for use in treating these disorders. A high-throughput screening effort identified the pyrazolo[1,5-a]pyrimidine scaffold as a potent inhibit-or of Jak2. Optimization of lead compounds 7a-b and 8 in this chemical series for activity against Jak2, selectivity against other Jak family kinases, and good in vivo pharmacokinetic properties led to the discovery of 7j. In a SET2 xenograft model that is dependent on Jak2 for growth, 7j demonstrated a time-dependent knock-down of pSTAT5, a downstream target of Jak2.

  DOI：

  10.1021/jm3012239
• 作为产物：
  描述：

  3-iodopyrazolo[1,5-a]pyrimidin-5(4H)-one 在 水 、 palladium diacetate 、 三乙胺 、 N,N-二异丙基乙胺 、 lithium hydroxide 、 三氯氧磷 作用下， 以 二氯甲烷 为溶剂， 反应 10.17h， 生成 5-chloro-N-(3-(3-chlorophenyl)-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide
  参考文献：
  名称：

  Discovery of Potent and Selective Pyrazolopyrimidine Janus Kinase 2 Inhibitors

  摘要：

  The discovery of somatic Jak2 mutations in patients with chronic myeloproliferative neoplasms has led to significant interest in disc-ova-ring selective Jak2 inhibitors for use in treating these disorders. A high-throughput screening effort identified the pyrazolo[1,5-a]pyrimidine scaffold as a potent inhibit-or of Jak2. Optimization of lead compounds 7a-b and 8 in this chemical series for activity against Jak2, selectivity against other Jak family kinases, and good in vivo pharmacokinetic properties led to the discovery of 7j. In a SET2 xenograft model that is dependent on Jak2 for growth, 7j demonstrated a time-dependent knock-down of pSTAT5, a downstream target of Jak2.

  DOI：

  10.1021/jm3012239