methyl {(2R,4S)-1-[(1R)-4,4-dimethyl-1-(3,3,3-trifluoropropyl)pentyl]-3,3-difluoro-2-[4-(trifluoromethyl)phenyl]piperidin-4-yl}acetate | 1011481-24-5

• 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: methyl {(2R,4S)-1-[(1R)-4,4-dimethyl-1-(3,3,3-trifluoropropyl)pentyl]-3,3-difluoro-2-[4-(trifluoromethyl)phenyl]piperidin-4-yl}acetate
• 英文别名: methyl 2-[(2R,4S)-3,3-difluoro-1-[(4R)-1,1,1-trifluoro-7,7-dimethyloctan-4-yl]-2-[4-(trifluoromethyl)phenyl]piperidin-4-yl]acetate
• CAS: 1011481-24-5
• 化学式: C₂₅H₃₃F₈NO₂
• 分子量: 531.53
• InChiKey: FBYQOYPEYDYWKM-QKNQBKEWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.9
• 重原子数：
  36
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  methyl {(2R,4S)-1-[(1R)-4,4-dimethyl-1-(3,3,3-trifluoropropyl)pentyl]-3,3-difluoro-2-[4-(trifluoromethyl)phenyl]piperidin-4-yl}acetate 在 水 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 {(2R,4S)-1-[(1R)-4,4-dimethyl-1-(3,3,3-trifluoropropyl)pentyl]-3,3-difluoro-2-[4-(trifluoromethyl)phenyl]piperidin-4-yl}acetic acid
  参考文献：
  名称：

  Fluorinated piperidine acetic acids as γ-secretase modulators

  摘要：

  We report herein a novel series of difluoropiperidine acetic acids as modulators of gamma-secretase. Synthesis of 2-aryl-3,3-difluoropiperidine analogs was facilitated by a unique and selective beta-difluorination with Selectfluor (R). Compounds 1f and 2c were selected for in vivo assessment and demonstrated selective lowering of A beta 42 in a genetically engineered mouse model of APP processing. Moreover, in a 7-day safety study, rats treated orally with compound 1f (250 mg/kg per day, AUC(0-24) = 2100 mu M h) did not exhibit Notch-related effects. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.11.034
• 作为产物：
  描述：

  在 硼烷四氢呋喃络合物 作用下， 以 四氢呋喃 为溶剂， 生成 methyl {(2R,4S)-1-[(1R)-4,4-dimethyl-1-(3,3,3-trifluoropropyl)pentyl]-3,3-difluoro-2-[4-(trifluoromethyl)phenyl]piperidin-4-yl}acetate
  参考文献：
  名称：

  Fluorinated piperidine acetic acids as γ-secretase modulators

  摘要：

  We report herein a novel series of difluoropiperidine acetic acids as modulators of gamma-secretase. Synthesis of 2-aryl-3,3-difluoropiperidine analogs was facilitated by a unique and selective beta-difluorination with Selectfluor (R). Compounds 1f and 2c were selected for in vivo assessment and demonstrated selective lowering of A beta 42 in a genetically engineered mouse model of APP processing. Moreover, in a 7-day safety study, rats treated orally with compound 1f (250 mg/kg per day, AUC(0-24) = 2100 mu M h) did not exhibit Notch-related effects. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.11.034

文献信息

• DIFLUORINATED PIPERIDINES FOR TREATMENT OF ALZHEIMER'S DISEASE AND RELATED CONDITIONS
  申请人：Stanton Matthew G.

  公开号：US20100010041A1

  公开（公告）日：2010-01-14

  Compounds of formula (I). Selectively inhibit production of Aβ(1-42) and hence find use in treatment of diseases associated with deposition of β-amyloid in the brain.

  公式为(I)的化合物，能够选择性地抑制Aβ(1-42)的产生，因此可用于治疗与β-淀粉样蛋白在大脑中沉积相关的疾病。
• WO2008/30391
  申请人：——

  公开号：——

  公开（公告）日：——