2-cyano-4-((1-(2-hydroxyethyl)piperidin-4-yl)methoxy)-N-methyl-6-(spiro[3.5]nonan-7-ylmethylamino)pyrimidine-5-carboxamide | 1082374-02-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 2-cyano-4-((1-(2-hydroxyethyl)piperidin-4-yl)methoxy)-N-methyl-6-(spiro[3.5]nonan-7-ylmethylamino)pyrimidine-5-carboxamide
• 英文别名: 2-cyano-4-[[1-(2-hydroxyethyl)piperidin-4-yl]methoxy]-N-methyl-6-(spiro[3.5]nonan-7-ylmethylamino)pyrimidine-5-carboxamide
• CAS: 1082374-02-4
• 化学式: C₂₅H₃₈N₆O₃
• 分子量: 470.615
• InChiKey: PUFJEFSFBMWBSG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  34
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  123
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-cyano-N-methyl-4-(piperidin-4-ylmethoxy)-6-(spiro[3.5]nonan-7-ylmethylamino)pyrimidine-5-carboxamide 、 2-溴乙醇 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以49%的产率得到2-cyano-4-((1-(2-hydroxyethyl)piperidin-4-yl)methoxy)-N-methyl-6-(spiro[3.5]nonan-7-ylmethylamino)pyrimidine-5-carboxamide
  参考文献：
  名称：

  Overcoming hERG issues for brain-penetrating cathepsin S inhibitors: 2-Cyanopyrimidines. Part 2

  摘要：

  We describe here orally active and brain-penetrant cathepsin S selective inhibitors, which are virtually devoid of hERG K(+) channel affinity, yet exhibit nanomolar potency against cathepsin S and over 100-fold selectivity to cathepsin L. The new non-peptidic inhibitors are based on a 2-cyanopyrimidine scaffold bearing a spiro[3.5] non-6-yl-methyl amine at the 4-position. The brain-penetrating cathepsin S inhibitors demonstrate potential clinical utility for the treatment of multiple sclerosis and neuropathic pain. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.08.067