4-bromo-9-chloro-N-cyclohexyl-5H-pyrido[4,3-b]indol-1-amine | 1338377-59-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• 英文名称: 4-bromo-9-chloro-N-cyclohexyl-5H-pyrido[4,3-b]indol-1-amine
• CAS: 1338377-59-5
• 化学式: C₁₇H₁₇BrClN₃
• 分子量: 378.699
• InChiKey: TXDVHLXUOBHODO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.88
• 重原子数：
  22.0
• 可旋转键数：
  2.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  40.71
• 氢给体数：
  2.0
• 氢受体数：
  2.0

反应信息

• 作为产物：
  描述：

  3-氯苯肼盐酸盐 在 sodium hydroxide 作用下， 以 二苯醚 、 水 为溶剂， 反应 4.0h， 生成 4-bromo-7-chloro-N-cyclohexyl-5H-pyrido[4,3-b]indol-1-amine 、 4-bromo-9-chloro-N-cyclohexyl-5H-pyrido[4,3-b]indol-1-amine
  参考文献：
  名称：

  Discovery of 1-Amino-5H-pyrido[4,3-b]indol-4-carboxamide Inhibitors of Janus Kinase 2 (JAK2) for the Treatment of Myeloproliferative Disorders

  摘要：

  The JAK-STAT pathway mediates signaling by cytokines, which control survival, proliferation, and differentiation of a variety of cells. In recent years, a single point mutation (V617F) in the tyrosine kinase JAK2 was found to be present with a high incidence in myeloproliferative disorders (MPDs). This mutation led to hyperactivation of JAK.2, cytokine-independent signaling, and subsequent activation of downstream signaling networks. The genetic, biological, and physiological evidence suggests that JAK2 inhibitors could be effective in treating MPDs. De novo design efforts of new scaffolds identified 1-amino-5H-pyrido [4,3-b]indol-4-carboxamides as a new viable lead series. Subsequent optimization of cell potency, metabolic stability, and off-target activities of the leads led to the discovery of 7-(2-aminopyrimidin-5-yl)-1-{[(1R)-1-cyclopropyl-2,2,2-trifluoroethyl]amino}-5H-pyrido[4,3-b]indole-4-carboxamide (65). Compound 65 is a potent, orally active inhibitor of JAK2 with excellent selectivity, PK profile, and in vivo efficacy in animal models.

  DOI：

  10.1021/jm200909u