1-(3-(2-Cyano-6-(3-(trifluoromethyl)phenyl)pyrimidin-4-yl)propylamino)cyclopropanecarboxamide | 1257301-89-5

• 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: 1-(3-(2-Cyano-6-(3-(trifluoromethyl)phenyl)pyrimidin-4-yl)propylamino)cyclopropanecarboxamide
• 英文别名: 1-[3-[2-cyano-6-[3-(trifluoromethyl)phenyl]pyrimidin-4-yl]propylamino]cyclopropane-1-carboxamide
• CAS: 1257301-89-5
• 化学式: C₁₉H₁₈F₃N₅O
• 分子量: 389.38
• InChiKey: PJWDCICTRLASSV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  105
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  4-(3-oxo-propyl)-6-(3-trifluoromethyl-phenyl)-pyrimidine-2-carbonitrile 、 1-氨基-环丙烷羧酰胺(9ci) 在 三乙酰氧基硼氢化钠 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 生成 1-(3-(2-Cyano-6-(3-(trifluoromethyl)phenyl)pyrimidin-4-yl)propylamino)cyclopropanecarboxamide
  参考文献：
  名称：

  Optimisation of 2-cyano-pyrimidine inhibitors of cathepsin K: Improving selectivity over hERG

  摘要：

  Several structure-guided optimisation strategies were explored in order to improve the hERG selectivity profile of cathepsin K inhibitor 1, whilst maintaining its otherwise excellent in vitro and in vivo profile. Ultimately, attenuation of c log P and pK(a) properties proved a successful approach and led to the discovery of a potent analogue 23, which, in addition to the desired selectivity over hERG (>1000-fold), displayed a highly attractive overall profile. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.08.101

文献信息

• Optimisation of 2-cyano-pyrimidine inhibitors of cathepsin K: Improving selectivity over hERG
  作者：Zoran Rankovic、Jiaqiang Cai、Jennifer Kerr、Xavier Fradera、John Robinson、Ashvin Mistry、William Finlay、George McGarry、Fiona Andrews、Wilson Caulfield、Iain Cumming、Maureen Dempster、John Waller、Wullie Arbuckle、Mark Anderson、Iain Martin、Ann Mitchell、Clive Long、Mark Baugh、Paul Westwood、Emma Kinghorn、Phil Jones、Joost C.M. Uitdehaag、Mario van Zeeland、Dominique Potin、Laurent Saniere、Andre Fouquet、François Chevallier、Hortense Deronzier、Cecile Dorleans、Eric Nicolai

  DOI：10.1016/j.bmcl.2010.08.101

  日期：2010.11

  Several structure-guided optimisation strategies were explored in order to improve the hERG selectivity profile of cathepsin K inhibitor 1, whilst maintaining its otherwise excellent in vitro and in vivo profile. Ultimately, attenuation of c log P and pK(a) properties proved a successful approach and led to the discovery of a potent analogue 23, which, in addition to the desired selectivity over hERG (>1000-fold), displayed a highly attractive overall profile. (C) 2010 Elsevier Ltd. All rights reserved.