3-(2,5-dichlorophenyl)-1H-pyrazol-4-amine | 1250205-38-9

• 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-(2,5-dichlorophenyl)-1H-pyrazol-4-amine
• 英文别名: 5-(2,5-dichlorophenyl)-1H-pyrazol-4-amine
• CAS: 1250205-38-9
• 化学式: C₉H₇Cl₂N₃
• 分子量: 228.081
• InChiKey: PABSPKVVVAABOO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  54.7
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-(2,5-dichlorophenyl)-1H-pyrazol-4-amine 、 吡唑并[1,5-a]嘧啶-3-羧酸 在 4-二甲氨基吡啶 、 caesium carbonate 、 N,N-二异丙基乙胺 、 ((3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl)oxy)tri(pyrrolidin-1-yl)phosphonium hexafluorophosphate(V) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 17.5h， 生成 N-[3-(2,5-dichlorophenyl)-1-methyl-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
• 作为产物：
  描述：

  di-tert-butyl 1-(dimethylamino)-3-(2,5-dichlorophenyl)-3-oxoprop-1-en-2-yliminodicarbonate 在 肼 、 盐酸 作用下， 以 乙醇 、 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 4.5h， 生成 3-(2,5-dichlorophenyl)-1H-pyrazol-4-amine
  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

文献信息

• PYRAZOLOPYRIMIDINE JAK INHIBITOR COMPOUNDS AND METHODS
  申请人：Genentech, Inc.

  公开号：US20140107099A1

  公开（公告）日：2014-04-17

  The invention provides JAK kinase inhibitors of Formula Ia, enantiomers, diasteriomers or pharmaceutically acceptable salts thereof, wherein R 1 , R 2 , R 7 and Z are defined herein, a pharmaceutical composition that includes a compound of Formula Ia and a pharmaceutically acceptable carrier, adjuvant or vehicle, and methods of treating or lessening the severity of a disease or condition responsive to the inhibition of a JAK kinase activity in a patient.

  本发明提供了JAK激酶抑制剂Ia的公式，其对映体、对映异构体或其药学上可接受的盐，其中R1，R2，R7和Z在此定义，以及包括公式Ia化合物和药学上可接受的载体、佐剂或载体的制药组合物，以及用于治疗或减轻患者对JAK激酶活性抑制敏感的疾病或病情严重程度的方法。
• US8637526B2
  申请人：——

  公开号：US8637526B2

  公开（公告）日：2014-01-28