7-(2-aminopyrimidin-5-yl)-1-[(dicyclopropylmethyl)amino]-5H-pyrido[4,3-b]indole-4-carboxamide | 1160756-26-2

• 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-(2-aminopyrimidin-5-yl)-1-[(dicyclopropylmethyl)amino]-5H-pyrido[4,3-b]indole-4-carboxamide
• 英文别名: Jak2-IA；7-(2-aminopyrimidin-5-yl)-1-(dicyclopropylmethylamino)-5H-pyrido[4,3-b]indole-4-carboxamide
• CAS: 1160756-26-2
• 化学式: C₂₃H₂₃N₇O
• 分子量: 413.482
• InChiKey: HBDARCLZIJMRIA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  136
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  7-(2-aminopyrimidin-5-yl)-1-[(dicyclopropylmethyl)amino]-5H-pyrido[4,3-b]indole-4-carboxamide 、 3-乙炔基吡啶 、 Dicaesio carbonate 在 双(三环己基膦)二氯化钯 氮气 、 乙酸乙酯 、 水 、 Brine 作用下， 以 二甲基亚砜 为溶剂， 反应 12.08h， 生成 1-[(2-Hydroxy-1,2-dimethylpropyl)amino]-7-(pyridin-3-ylethynyl)-5H-pyrido[4,3-b]indole-4-carboxamide
  参考文献：
  名称：

  Inhibitors of janus kinases

  摘要：

  本发明提供了抑制四种已知的哺乳动物JAK激酶（JAK1、JAK2、JAK3和TYK2）和PDK1的化合物。本发明还提供了包含这种抑制剂化合物的组合物和通过将该化合物用于需要治疗骨髓增生性疾病或癌症的患者来抑制JAK1、JAK2、JAK3、TYK2和PDK1活性的方法。

  公开号：

  US08431569B2
• 作为产物：
  描述：

  间氯苯肼 在 potassium phosphate 、 tris-(dibenzylideneacetone)dipalladium(0) 、 四(三苯基膦)钯 、 双氧水 、 potassium carbonate 、 N,N-二异丙基乙胺 、 三氯氧磷 、 三环己基膦 作用下， 以 1,4-二氧六环 、 二苯醚 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 196.25h， 生成 7-(2-aminopyrimidin-5-yl)-1-[(dicyclopropylmethyl)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

文献信息

• [EN] INHIBITORS OF JANUS KINASES<br/>[FR] INHIBITEURS DE JANUS KINASES
  申请人：MERCK & CO INC

  公开号：WO2009075830A1

  公开（公告）日：2009-06-18

  The instant invention provides for compounds that inhibit the four known mammalian JAK kinases (JAK1, JAK2, JAK3 and TYK2) and PDK1. The invention also provides for compositions comprising such inhibitory compounds and methods of inhibiting the activity of JAK1, JAK2, JAK3 TYK2 and PDK1 by administering the compound to a patient in need of treatment for myeloproliferative disorders or cancer.

  本发明提供了抑制四种已知哺乳动物JAK激酶（JAK1、JAK2、JAK3和TYK2）和PDK1的化合物。本发明还提供了包含这些抑制剂化合物的组合物以及通过向需要治疗骨髓增生性疾病或癌症的患者施用该化合物来抑制JAK1、JAK2、JAK3 TYK2和PDK1活性的方法。
• INHIBITORS OF JANUS KINASES
  申请人：Young Jonathan R.

  公开号：US20100267709A1

  公开（公告）日：2010-10-21

  The instant invention provides for compounds that inhibit the four known mammalian JAK kinases (JAK1, JAK2, JAK3 and TYK2) and PDK1. The invention also provides for compositions comprising such inhibitory compounds and methods of inhibiting the activity of JAK1, JAK2, JAK3 TYK2 and PDK1 by administering the compound to a patient in need of treatment for myeloproliferative disorders or cancer.

  本发明提供了抑制四种已知哺乳动物JAK激酶（JAK1、JAK2、JAK3和TYK2）和PDK1的化合物。本发明还提供了包含这种抑制剂化合物的组合物和通过将该化合物用于需要治疗骨髓增生性疾病或癌症的患者中，抑制JAK1、JAK2、JAK3、TYK2和PDK1活性的方法。
• 5H-pyrido[4,3-b]indoles as INHIBITORS OF JANUS KINASES
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP2231143B1

  公开（公告）日：2013-07-03
• JAK INHIBITION BLOCKS RNA INTERFERENCE ASSOCIATED TOXICITIES
  申请人：Tao Weikang

  公开号：US20120157500A1

  公开（公告）日：2012-06-21

  The instant invention provides a method for treating patients by administering a JAK inhibitor. The instant invention provides a method for treating patients by administering a JAK inhibitor wherein the JAK inhibitor is a JAK2 inhibitor. The instant invention provides a method for treating patients by administering a JAK inhibitor wherein the JAK inhibitor is selected from selected from Jak2-IA, AG490, Pyridone 6, WP1066, LS104, TG101209, TG101348, CP690,550, CP352,664, INCB18424, WHI-P154, CMP6, SB1518, XL019, CEP-701, INCB20, AUH-6-96 and AZ960.
• US8431569B2
  申请人：——

  公开号：US8431569B2

  公开（公告）日：2013-04-30