(S)-tert-butyl (1-(1-(3-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl)propan-2-yl)carbamate | 1244640-38-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: (S)-tert-butyl (1-(1-(3-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl)propan-2-yl)carbamate
• 英文别名: tert-butyl N-[(2S)-1-[1-(3-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl]propan-2-yl]carbamate
• CAS: 1244640-38-7
• 化学式: C₂₁H₃₁FN₄O₃
• 分子量: 406.501
• InChiKey: YBXKUVXSCSDDLK-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  73.9
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (S)-tert-butyl (1-(1-(3-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl)propan-2-yl)carbamate 在 盐酸 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 N,N-dimethyl-d₆-formamide 为溶剂， 反应 16.0h， 生成 3,4-difluoro-N-[(2S)-1-[1-(3-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl]propan-2-yl]benzamide
  参考文献：
  名称：

  Development of Dual PLD1/2 and PLD2 Selective Inhibitors from a Common 1,3,8-Triazaspiro[4.5]decane Core: Discovery of ML298 and ML299 That Decrease Invasive Migration in U87-MG Glioblastoma Cells

  摘要：

  An iterative parallel synthesis effort identified a PLD2 selective inhibitor, ML298 (PLD1 IC50 > 20 000 nM, PLD2 IC50 = 355 nM) and a dual PLD1/2 inhibitor, ML299 (PLD1 IC50 = 6 nM, PLD2 IC50 = 20 nM). SAR studies revealed that a small structural change (incorporation of a methyl group) increased PLD1 activity within this classically PLD2-preferring core and that the effect was enantiospecific. Both probes decreased invasive migration in U87-MG glioblastoma cells.

  DOI：

  10.1021/jm301782e
• 作为产物：
  描述：

  N-苄基哌啶酮 在 palladium on activated charcoal 、 氢气 、 溶剂黄146 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 87.75h， 生成 (S)-tert-butyl (1-(1-(3-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl)propan-2-yl)carbamate
  参考文献：
  名称：

  Development of Dual PLD1/2 and PLD2 Selective Inhibitors from a Common 1,3,8-Triazaspiro[4.5]decane Core: Discovery of ML298 and ML299 That Decrease Invasive Migration in U87-MG Glioblastoma Cells

  摘要：

  An iterative parallel synthesis effort identified a PLD2 selective inhibitor, ML298 (PLD1 IC50 > 20 000 nM, PLD2 IC50 = 355 nM) and a dual PLD1/2 inhibitor, ML299 (PLD1 IC50 = 6 nM, PLD2 IC50 = 20 nM). SAR studies revealed that a small structural change (incorporation of a methyl group) increased PLD1 activity within this classically PLD2-preferring core and that the effect was enantiospecific. Both probes decreased invasive migration in U87-MG glioblastoma cells.

  DOI：

  10.1021/jm301782e

文献信息

• Design, Synthesis, and Biological Evaluation of Halogenated <i>N</i>-(2-(4-Oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)ethyl)benzamides: Discovery of an Isoform-Selective Small Molecule Phospholipase D2 Inhibitor
  作者：Robert R. Lavieri、Sarah A. Scott、Paige E. Selvy、Kwangho Kim、Satyawan Jadhav、Ryan D. Morrison、J. Scott Daniels、H. Alex Brown、Craig W. Lindsley

  DOI：10.1021/jm100814g

  日期：2010.9.23

  Phospholipase D (PLD) catalyzes the conversion of phosphatidylcholine to the lipid second messenger phosphatidic acid. Two mammalian isoforms of PLD have been identified, PLD I and PLD2, which share 53% sequence identity and are subject to different regulatory mechanisms. Inhibition of PLD enzymatic activity leads to increased cancer cell apoptosis, decreased cancer cell invasion, and decreased metastasis of cancer cells; therefore, the development of isoform-specific, PLD inhibitors is a novel approach for the treatment of cancer. Previously, we developed potent dual PLD1/PLD2, PLD1-specific (> 1700-fold selective), and moderately PLD2-preferring (> 10-fold preferring) inhibitors. Here, we describe a matrix library strategy that afforded the most potent (PLD2 IC(50) = 20 nM) and selective (75-fold selective versus PLD1) PLD2 inhibitor to date. N-(2-(1-(3-fluorophenyl)-4-oxo-1.3.8-triazaspiro[4.5]decan-8-yl)ethyl)-2-naphthamide (22a), with an acceptable DMPK profile. Thus, these new isoform-selective PLD inhibitors will enable researchers to dissect the signaling roles and therapeutic potential of individual PLD isoforms to an unprecedented degree.
• Development of Dual PLD1/2 and PLD2 Selective Inhibitors from a Common 1,3,8-Triazaspiro[4.5]decane Core: Discovery of ML298 and ML299 That Decrease Invasive Migration in U87-MG Glioblastoma Cells
  作者：Matthew C. O’Reilly、Sarah A. Scott、Kyle A. Brown、Thomas H. Oguin、Paul G. Thomas、J. Scott Daniels、Ryan Morrison、H. Alex Brown、Craig W. Lindsley

  DOI：10.1021/jm301782e

  日期：2013.3.28

  An iterative parallel synthesis effort identified a PLD2 selective inhibitor, ML298 (PLD1 IC50 > 20 000 nM, PLD2 IC50 = 355 nM) and a dual PLD1/2 inhibitor, ML299 (PLD1 IC50 = 6 nM, PLD2 IC50 = 20 nM). SAR studies revealed that a small structural change (incorporation of a methyl group) increased PLD1 activity within this classically PLD2-preferring core and that the effect was enantiospecific. Both probes decreased invasive migration in U87-MG glioblastoma cells.