8-(benzyloxy)-5-[(1R)-1-{[tert-butyl(dimethyl)silyl]oxy}-2-{[2-(4-{2-[4-({3-[(R)-cyclohexyl(hydroxy)phenylmethyl]-1H-1,2,4-triazol-1-yl}methyl)piperidin-1-yl]ethyl}phenyl)ethyl]amino}ethyl]quinolin-2(1H)-one | 1204122-69-9

• 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: 8-(benzyloxy)-5-[(1R)-1-{[tert-butyl(dimethyl)silyl]oxy}-2-{[2-(4-{2-[4-({3-[(R)-cyclohexyl(hydroxy)phenylmethyl]-1H-1,2,4-triazol-1-yl}methyl)piperidin-1-yl]ethyl}phenyl)ethyl]amino}ethyl]quinolin-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-phenylmethoxy-1H-quinolin-2-one
• CAS: 1204122-69-9
• 化学式: C₅₅H₇₂N₆O₄Si
• 分子量: 909.3
• InChiKey: QPQUIVHPWICHFW-ANHJSVPISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.36
• 重原子数：
  66
• 可旋转键数：
  20
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  114
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  8-(benzyloxy)-5-[(1R)-1-{[tert-butyl(dimethyl)silyl]oxy}-2-{[2-(4-{2-[4-({3-[(R)-cyclohexyl(hydroxy)phenylmethyl]-1H-1,2,4-triazol-1-yl}methyl)piperidin-1-yl]ethyl}phenyl)ethyl]amino}ethyl]quinolin-2(1H)-one 在 氟化铵 、 甲酸铵 、 palladium diacetate 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 26.0h， 生成 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 、 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 154.0h， 生成 8-(benzyloxy)-5-[(1R)-1-{[tert-butyl(dimethyl)silyl]oxy}-2-{[2-(4-{2-[4-({3-[(R)-cyclohexyl(hydroxy)phenylmethyl]-1H-1,2,4-triazol-1-yl}methyl)piperidin-1-yl]ethyl}phenyl)ethyl]amino}ethyl]quinolin-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

• Triazol Derivatives Useful For The Treatment of Diseases
  申请人：Jones Lyn Howard

  公开号：US20100010040A1

  公开（公告）日：2010-01-14

  The invention relates to compounds of formula (1) and to processes for the preparation of, intermediates used in the preparation of, compositions containing and the uses of, such derivatives. The compounds according to the present invention are useful in numerous diseases, disorders and conditions, in particular inflammatory, allergic and respiratory diseases, disorders and conditions.

  本发明涉及公式（1）的化合物，以及制备中间体，含有该衍生物的组合物和使用该衍生物的方法的过程。根据本发明的化合物在许多疾病，疾病和状况中有用，特别是在炎症，过敏和呼吸系统疾病，疾病和状况中有用。
• Triazol derivatives useful for the treatment of diseases
  申请人：Pfizer Inc.

  公开号：US08263623B2

  公开（公告）日：2012-09-11

  The invention relates to compounds of formula (1) and to processes for the preparation of, intermediates used in the preparation of, compositions containing and the uses of, such derivatives. The compounds according to the present invention are useful in numerous diseases, disorders and conditions, in particular inflammatory, allergic and respiratory diseases, disorders and conditions.

  本发明涉及式（1）的化合物，以及制备这些衍生物所使用的中间体、含有这些衍生物的组合物以及这些衍生物的用途。根据本发明的化合物在许多疾病、障碍和病况中具有有益的作用，尤其是在炎症、过敏和呼吸系统疾病、障碍和病况中。
• 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.