N-[(1R)-1-cyclobutyl-2,2,2-trifluoroethyl]-(S)-2-methylpropane-2-sulfinamide | 1338377-75-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 亚磺酸及其衍生物
• 英文名称: N-[(1R)-1-cyclobutyl-2,2,2-trifluoroethyl]-(S)-2-methylpropane-2-sulfinamide
• 英文别名: (S)-N-((R)-1-Cyclobutyl-2,2,2-trifluoroethyl)-2-methylpropane-2-sulfinamide；(S)-N-[(1R)-1-cyclobutyl-2,2,2-trifluoroethyl]-2-methylpropane-2-sulfinamide
• CAS: 1338377-75-5
• 化学式: C₁₀H₁₈F₃NOS
• 分子量: 257.32
• InChiKey: HAVMAKZERUEGDI-BCTVWOGZSA-N

物化性质

• 沸点：
  287.0±50.0 °C(Predicted)
• 密度：
  1.240±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  48.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-[(1R)-1-cyclobutyl-2,2,2-trifluoroethyl]-(S)-2-methylpropane-2-sulfinamide 在 盐酸 、 tris-(dibenzylideneacetone)dipalladium(0) 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 sodium t-butanolate 作用下， 以 1,4-二氧六环 、 甲醇 、 乙二醇二甲醚 为溶剂， 反应 16.5h， 生成 7-chloro-1-{[(1R)-1-cyclobutyl-2,2,2-trifluoroethyl]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
• 作为产物：
  描述：

  环丁基甲醛 在 四甲基氟化铵 、 4-甲基苯磺酸吡啶 、 magnesium sulfate 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 N-[(1R)-1-cyclobutyl-2,2,2-trifluoroethyl]-(S)-2-methylpropane-2-sulfinamide
  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