4-(6,8-dioxaspiro[3.5]nonan-7-ylmethylamino)-2-cyano-N-methyl-6-((1-methylpiperidin-4-yl)methoxy)pyrimidine-5-carboxamide | 1082373-94-1

• 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: 4-(6,8-dioxaspiro[3.5]nonan-7-ylmethylamino)-2-cyano-N-methyl-6-((1-methylpiperidin-4-yl)methoxy)pyrimidine-5-carboxamide
• 英文别名: 2-cyano-4-(6,8-dioxaspiro[3.5]nonan-7-ylmethylamino)-N-methyl-6-[(1-methylpiperidin-4-yl)methoxy]pyrimidine-5-carboxamide
• CAS: 1082373-94-1
• 化学式: C₂₂H₃₂N₆O₄
• 分子量: 444.534
• InChiKey: OMKHPTMZDIWOCX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  122
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  聚合甲醛 、 4-(((6,8-dioxaspiro[3.5]nonan-7-yl)methyl)amino)-2-cyano-N-methyl-6-(piperidin-4-ylmethoxy)pyrimidine-5-carboxamide 在 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 反应 1.5h， 生成 4-(6,8-dioxaspiro[3.5]nonan-7-ylmethylamino)-2-cyano-N-methyl-6-((1-methylpiperidin-4-yl)methoxy)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

文献信息

• Overcoming hERG issues for brain-penetrating cathepsin S inhibitors: 2-Cyanopyrimidines. Part 2
  作者：Osamu Irie、Takatoshi Kosaka、Masashi Kishida、Junichi Sakaki、Keiichi Masuya、Kazuhide Konishi、Fumiaki Yokokawa、Takeru Ehara、Atsuko Iwasaki、Yuki Iwaki、Yuko Hitomi、Atsushi Toyao、Hiroki Gunji、Naoki Teno、Genji Iwasaki、Hajime Hirao、Takanori Kanazawa、Keiko Tanabe、Peter C. Hiestand、Marzia Malcangio、Alyson J. Fox、Stuart J. Bevan、Mohammed Yaqoob、Andrew J. Culshaw、Terance W. Hart、Allan Hallett

  DOI：10.1016/j.bmcl.2008.08.067

  日期：2008.10

  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.