7-chloro-1-{[(1S)-1-cyclopropylethyl]amino}-5H-pyrido[4,3-b]indole-4-carbonitrile | 1338377-52-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 7-chloro-1-{[(1S)-1-cyclopropylethyl]amino}-5H-pyrido[4,3-b]indole-4-carbonitrile
• 英文别名: 7-chloro-1-[[(1S)-1-cyclopropylethyl]amino]-5H-pyrido[4,3-b]indole-4-carbonitrile
• CAS: 1338377-52-8
• 化学式: C₁₇H₁₅ClN₄
• 分子量: 310.786
• InChiKey: YTAVEWBHCDLHIF-VIFPVBQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  64.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  7-chloro-1-{[(1S)-1-cyclopropylethyl]amino}-5H-pyrido[4,3-b]indole-4-carbonitrile 在 双氧水 、 potassium carbonate 作用下， 以 水 、 二甲基亚砜 为溶剂， 以84%的产率得到7-chloro-1-{[(1S)-1-cyclopropylethyl]amino}-5H-pyrido[4,3-b]indole-4-carboxamide
  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
• 作为产物：
  描述：

  间氯苯肼 在 N-溴代丁二酰亚胺(NBS) 、 四(三苯基膦)钯 、 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 1,4-二氧六环 、 二苯醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 94.25h， 生成 7-chloro-1-{[(1S)-1-cyclopropylethyl]amino}-5H-pyrido[4,3-b]indole-4-carbonitrile
  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

文献信息

• Discovery of 1-Amino-5<i>H</i>-pyrido[4,3-<i>b</i>]indol-4-carboxamide Inhibitors of Janus Kinase 2 (JAK2) for the Treatment of Myeloproliferative Disorders
  作者：Jongwon Lim、Brandon Taoka、Ryan D. Otte、Kerrie Spencer、Christopher J. Dinsmore、Michael D. Altman、Grace Chan、Craig Rosenstein、Sujata Sharma、Hua-Poo Su、Alexander A. Szewczak、Lin Xu、Hong Yin、Joan Zugay-Murphy、C. Gary Marshall、Jonathan R. Young

  DOI：10.1021/jm200909u

  日期：2011.10.27

  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.