benzyl 4-(2,5-difluorophenyl)-4-hydroxypiperidine-1-carboxylate | 1375206-51-1

• 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: benzyl 4-(2,5-difluorophenyl)-4-hydroxypiperidine-1-carboxylate
• CAS: 1375206-51-1
• 化学式: C₁₉H₁₉F₂NO₃
• 分子量: 347.362
• InChiKey: RGTLRGUEKNWWOW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  benzyl 4-(2,5-difluorophenyl)-4-hydroxypiperidine-1-carboxylate 在 盐酸 、 三氟化硼 、 三乙胺 、 间氯过氧苯甲酸 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 生成
  参考文献：
  名称：

  Lead optimization of 4,4-biaryl piperidine amides as γ-secretase inhibitors

  摘要：

  Alzheimer's disease is a major unmet medical need with pathology characterized by extracellular pro-teinaceous plaques comprised primarily of beta-amyloid. gamma-Secretase is a critical enzyme in the cellular pathway responsible for the formation of a range of beta-amyloid peptides; one of which, A beta 42, is believed to be responsible for the neuropathological features of the disease. Herein, we report 4,4 disubstituted piperidine gamma-secretase inhibitors that were optimized for in vitro cellular potency and pharmacokinetic properties in vivo. Key agents were further characterized for their ability to lower cerebral A beta 42 production in an APP-YAC mouse model. This structural series generally suffered from sub-optimal pharmacokinetics but hypothesis driven lead optimization enabled the discovery of gamma-secretase inhibitors capable of lowering cerebral A beta 42 production in mice. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.03.038
• 作为产物：
  描述：

  1-Cbz-4-哌啶酮 、 2,5-二氟溴苯 在 异丙基氯化镁 作用下， 生成 benzyl 4-(2,5-difluorophenyl)-4-hydroxypiperidine-1-carboxylate
  参考文献：
  名称：

  Lead optimization of 4,4-biaryl piperidine amides as γ-secretase inhibitors

  摘要：

  Alzheimer's disease is a major unmet medical need with pathology characterized by extracellular pro-teinaceous plaques comprised primarily of beta-amyloid. gamma-Secretase is a critical enzyme in the cellular pathway responsible for the formation of a range of beta-amyloid peptides; one of which, A beta 42, is believed to be responsible for the neuropathological features of the disease. Herein, we report 4,4 disubstituted piperidine gamma-secretase inhibitors that were optimized for in vitro cellular potency and pharmacokinetic properties in vivo. Key agents were further characterized for their ability to lower cerebral A beta 42 production in an APP-YAC mouse model. This structural series generally suffered from sub-optimal pharmacokinetics but hypothesis driven lead optimization enabled the discovery of gamma-secretase inhibitors capable of lowering cerebral A beta 42 production in mice. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.03.038

文献信息

• Lead optimization of 4,4-biaryl piperidine amides as γ-secretase inhibitors
  作者：Joshua Close、Richard Heidebrecht、John Hendrix、Chaomin Li、Ben Munoz、Laura Surdi、Solomon Kattar、Paul Tempest、Paul Moses、Xiaoliu Geng、Bethany Hughes、Nadya Smotrov、Chris Moxham、Jennifer Chapnick、Ilona Kariv、George Nikov、Julie Elizabeth Burke、Sujal Deshmukh、Valentina Jeliazkova-Mecheva、John Kevin Leach、Damaris Diaz、Lin Xu、Ziping Yang、Gloria Kwei、Lily Moy、Sanjiv Shah、Flobert Tanga、Candia Kenefic、Dan Savage、Mark Shearman、Richard G. Ball、Michael J. McNevin、Amanda Markarewicz、Thomas Miller

  DOI：10.1016/j.bmcl.2012.03.038

  日期：2012.5

  Alzheimer's disease is a major unmet medical need with pathology characterized by extracellular pro-teinaceous plaques comprised primarily of beta-amyloid. gamma-Secretase is a critical enzyme in the cellular pathway responsible for the formation of a range of beta-amyloid peptides; one of which, A beta 42, is believed to be responsible for the neuropathological features of the disease. Herein, we report 4,4 disubstituted piperidine gamma-secretase inhibitors that were optimized for in vitro cellular potency and pharmacokinetic properties in vivo. Key agents were further characterized for their ability to lower cerebral A beta 42 production in an APP-YAC mouse model. This structural series generally suffered from sub-optimal pharmacokinetics but hypothesis driven lead optimization enabled the discovery of gamma-secretase inhibitors capable of lowering cerebral A beta 42 production in mice. (C) 2012 Elsevier Ltd. All rights reserved.