tert-butyl 4-(((2-cyano-5-(methylcarbamoyl)-6-((spiro[4.5]decan-8-ylmethyl)amino)pyrimidin-4-yl)oxy)methyl)piperidine-1-carboxylate | 1181310-87-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: tert-butyl 4-(((2-cyano-5-(methylcarbamoyl)-6-((spiro[4.5]decan-8-ylmethyl)amino)pyrimidin-4-yl)oxy)methyl)piperidine-1-carboxylate
• CAS: 1181310-87-1
• 化学式: C₂₉H₄₄N₆O₄
• 分子量: 540.706
• InChiKey: FNVPMSQNNXMIRP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  39.0
• 可旋转键数：
  7.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  129.47
• 氢给体数：
  2.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(((2-cyano-5-(methylcarbamoyl)-6-((spiro[4.5]decan-8-ylmethyl)amino)pyrimidin-4-yl)oxy)methyl)piperidine-1-carboxylate 在 盐酸 、 乙酸乙酯 作用下， 反应 0.5h， 以100%的产率得到2-cyano-N-methyl-4-(piperidin-4-ylmethoxy)-6-((spiro[4.5]decan-8-ylmethyl)amino)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
• 作为产物：
  描述：

  {Spiro[4.5]decan-8-yl}methanamine 、 tert-butyl 4-(((6-chloro-2-cyano-5-(methylcarbamoyl)pyrimidin-4-yl)oxy)methyl)piperidine-1-carboxylate 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 生成 tert-butyl 4-(((2-cyano-5-(methylcarbamoyl)-6-((spiro[4.5]decan-8-ylmethyl)amino)pyrimidin-4-yl)oxy)methyl)piperidine-1-carboxylate
  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