1-(3,4-difluorophenyl)-1,3,8-triazaspiro[4.5]decan-4-one | 1244639-69-7

• 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: 1-(3,4-difluorophenyl)-1,3,8-triazaspiro[4.5]decan-4-one
• CAS: 1244639-69-7
• 化学式: C₁₃H₁₅F₂N₃O
• 分子量: 267.278
• InChiKey: MCPCAAGIGZANKF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  44.4
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(3,4-difluorophenyl)-1,3,8-triazaspiro[4.5]decan-4-one 、 Boc-L-丙氨醛 在 macroporous triacetoxyborohydride 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 以36%的产率得到(S)-tert-butyl (1-(1-(3,4-difluorophenyl)-4-oxo-1,3,8-triazaspiro[4,5]decan-8-yl)propan-2-yl)carbamate
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Halogenated N-(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

  摘要：

  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.

  DOI：

  10.1021/jm100814g
• 作为产物：
  描述：

  8-Benzyl-1-(3,4-difluorophenyl)-1,3,8-triazaspiro[4.5]decan-4-one 在 10% palladium on carbon 、 氢气 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 生成 1-(3,4-difluorophenyl)-1,3,8-triazaspiro[4.5]decan-4-one
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Halogenated N-(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

  摘要：

  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.

  DOI：

  10.1021/jm100814g