5-[(1R)-1-{[tert-butyl(dimethyl)silyl]oxy}-2-{[2-(4-{2-[4-(3-[(R)-cyclohexyl(hydroxy)phenylmethyl]-1H-1,2,4-triazol-1-ylmethyl)piperidin-1-yl]ethyl}phenyl)ethyl]amino}ethyl]-8-hydroxyquinolin-2(1H)-one | 1204122-71-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 5-[(1R)-1-{[tert-butyl(dimethyl)silyl]oxy}-2-{[2-(4-{2-[4-(3-[(R)-cyclohexyl(hydroxy)phenylmethyl]-1H-1,2,4-triazol-1-ylmethyl)piperidin-1-yl]ethyl}phenyl)ethyl]amino}ethyl]-8-hydroxyquinolin-2(1H)-one
• 英文别名: 5-[(1R)-1-[tert-butyl(dimethyl)silyl]oxy-2-[2-[4-[2-[4-[[3-[(R)-cyclohexyl-hydroxy-phenylmethyl]-1,2,4-triazol-1-yl]methyl]piperidin-1-yl]ethyl]phenyl]ethylamino]ethyl]-8-hydroxy-1H-quinolin-2-one
• CAS: 1204122-71-3
• 化学式: C₄₈H₆₆N₆O₄Si
• 分子量: 819.175
• InChiKey: JLYOTVVGMUCKSA-AWXZYBQUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.49
• 重原子数：
  59
• 可旋转键数：
  17
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  125
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  5-[(1R)-1-{[tert-butyl(dimethyl)silyl]oxy}-2-{[2-(4-{2-[4-(3-[(R)-cyclohexyl(hydroxy)phenylmethyl]-1H-1,2,4-triazol-1-ylmethyl)piperidin-1-yl]ethyl}phenyl)ethyl]amino}ethyl]-8-hydroxyquinolin-2(1H)-one 在 氟化铵 作用下， 以 甲醇 为溶剂， 反应 24.0h， 以78%的产率得到PF-04810097
  参考文献：
  名称：

  Molecular hybridization yields triazole bronchodilators for the treatment of COPD

  摘要：

  A 1,2,4-triazole motif was employed as a bioisostere for the ester commonly used in muscarinic antagonists, and subsequent integrative conjugation to a beta(2) agonist quinolinone furnished a new class of bifunctional MABAs for the treatment of COPD. Medicinal chemistry optimization using the principles of 'inhalation by design' furnished a clinical candidate with desirable pharmacological, pharmacokinetic and biopharmaceutical properties. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.10.008
• 作为产物：
  描述：

  2-环己基-2-羟基苯乙酸 在 盐酸 、 D-酪氨酸甲酯 、 氨 、 甲酸铵 、 palladium diacetate 、 碳酸氢钠 、 caesium carbonate 、 一水合肼 、 溶剂黄146 、 N,N-二异丙基乙胺 、 N,N'-羰基二咪唑 作用下， 以 1,4-二氧六环 、 乙醇 、 水 、 丙酮 、 甲苯 、 乙腈 、 丁酮 为溶剂， 反应 156.0h， 生成 5-[(1R)-1-{[tert-butyl(dimethyl)silyl]oxy}-2-{[2-(4-{2-[4-(3-[(R)-cyclohexyl(hydroxy)phenylmethyl]-1H-1,2,4-triazol-1-ylmethyl)piperidin-1-yl]ethyl}phenyl)ethyl]amino}ethyl]-8-hydroxyquinolin-2(1H)-one
  参考文献：
  名称：

  Molecular hybridization yields triazole bronchodilators for the treatment of COPD

  摘要：

  A 1,2,4-triazole motif was employed as a bioisostere for the ester commonly used in muscarinic antagonists, and subsequent integrative conjugation to a beta(2) agonist quinolinone furnished a new class of bifunctional MABAs for the treatment of COPD. Medicinal chemistry optimization using the principles of 'inhalation by design' furnished a clinical candidate with desirable pharmacological, pharmacokinetic and biopharmaceutical properties. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.10.008

文献信息

• Molecular hybridization yields triazole bronchodilators for the treatment of COPD
  作者：Lyn H. Jones、Jane Burrows、Neil Feeder、Paul Glossop、Kim James、Rhys M. Jones、Amy S. Kenyon、Sheena Patel、Dannielle F. Roberts、Matthew D. Selby、Ross S. Strang、Emilio F. Stuart、Michael A. Trevethick、Jessica Watson、Karen N. Wright、Nick Clarke

  DOI：10.1016/j.bmcl.2015.10.008

  日期：2015.11

  A 1,2,4-triazole motif was employed as a bioisostere for the ester commonly used in muscarinic antagonists, and subsequent integrative conjugation to a beta(2) agonist quinolinone furnished a new class of bifunctional MABAs for the treatment of COPD. Medicinal chemistry optimization using the principles of 'inhalation by design' furnished a clinical candidate with desirable pharmacological, pharmacokinetic and biopharmaceutical properties. (C) 2015 Elsevier Ltd. All rights reserved.