(4-((2-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)amino)phenyl)(morpholino)methanone | 1608120-33-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: (4-((2-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)amino)phenyl)(morpholino)methanone
• CAS: 1608120-33-7
• 化学式: C₂₁H₂₃ClN₆O₃
• 分子量: 442.905
• InChiKey: FEAHLVNEGQDRTN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.39
• 重原子数：
  31.0
• 可旋转键数：
  4.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  94.4
• 氢给体数：
  1.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  4-(叔丁基)-N-(2-甲基-3-(4,4,5,5-四甲基-1,3,2-二氧硼戊环-2-基)苯基) 、 (4-((2-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)amino)phenyl)(morpholino)methanone 在 potassium phosphate 、 四(三苯基膦)钯 作用下， 以 乙醇 、 水 、 甲苯 为溶剂， 以95%的产率得到
  参考文献：
  名称：

  Purine derivatives as potent Bruton’s tyrosine kinase (BTK) inhibitors for autoimmune diseases

  摘要：

  Investigation of various heterocyclic core isosteres of imidazopyrazines 1 & 2 yielded purine derivatives 3 & 8 as potent and selective BTK inhibitors. Subsequent SAR studies of the purine series led to the discovery of 20 as a leading compound. Compound 20 is very selective when screened against a panel of 400 kinases and is a potent inhibitor in cellular assays of human B cell function including B-Cell proliferation and CD86 cell surface expression and exhibited in vivo efficacy in a mouse PCA model. Its X-ray co-crystal structure with BTK shows that the high selectivity is gained from filling a BTK specific lipophilic pocket. However, physical and ADME properties leading to low oral exposure hindered further development. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.02.075
• 作为产物：
  描述：

  2,6-二氯嘌呤 在 potassium tert-butylate 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 生成 (4-((2-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)amino)phenyl)(morpholino)methanone
  参考文献：
  名称：

  Purine derivatives as potent Bruton’s tyrosine kinase (BTK) inhibitors for autoimmune diseases

  摘要：

  Investigation of various heterocyclic core isosteres of imidazopyrazines 1 & 2 yielded purine derivatives 3 & 8 as potent and selective BTK inhibitors. Subsequent SAR studies of the purine series led to the discovery of 20 as a leading compound. Compound 20 is very selective when screened against a panel of 400 kinases and is a potent inhibitor in cellular assays of human B cell function including B-Cell proliferation and CD86 cell surface expression and exhibited in vivo efficacy in a mouse PCA model. Its X-ray co-crystal structure with BTK shows that the high selectivity is gained from filling a BTK specific lipophilic pocket. However, physical and ADME properties leading to low oral exposure hindered further development. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.02.075