1-(3-fluorophenyl)-1,3,8-triazaspiro<4.5>decan-4-one | 97861-33-1

• 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-fluorophenyl)-1,3,8-triazaspiro<4.5>decan-4-one
• 英文别名: 1-(3-fluorophenyl)-1,3,8-triazaspiro[4.5]decan-4-one
• CAS: 97861-33-1
• 化学式: C₁₃H₁₆FN₃O
• 分子量: 249.288
• InChiKey: OHLLOJKEFUJQEL-UHFFFAOYSA-N

物化性质

• 沸点：
  493.7±45.0 °C(Predicted)
• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  18
• 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：
  4

反应信息

• 作为反应物：
  描述：

  1-(3-fluorophenyl)-1,3,8-triazaspiro<4.5>decan-4-one 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 40.5h， 生成 4-fluoro-N-[(2R)-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 、 水 为溶剂， 反应 63.25h， 生成 1-(3-fluorophenyl)-1,3,8-triazaspiro<4.5>decan-4-one
  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

• Examination of a series of 8-[3-[bis(4-fluorophenyl)amino]propyl]-1-aryl-1,3,8-triazaspiro[4.5]decan-4-ones as potential antipsychotic agents
  作者：Lawrence D. Wise、Ian C. Pattison、Donald E. Butler、Horace A. DeWald、Edward P. Lewis、Sandra J. Lobbestael、Haile Tecle、Linda L. Coughenour、David A. Downs、B. P. H. Poschel

  DOI：10.1021/jm00150a011

  日期：1985.12

  8-[3-[Bis(4-fluorophenyl)amino]propyl]-1-phenyl-1,3,8- triazaspiro[4.5]decan-4-one (3) and related compounds have been shown to have antipsychotic profiles in biochemical and behavioral pharmacological test models. The dose of 3 necessary to produce catalepsy in rats is much greater than that required for activity in behavioral tests predictive of antipsychotic efficacy, for example the suppression of high base line medial forebrain bundle self-stimulation in rats. This suggests that 3 would have a reduced propensity for neurological side effects. The effects of substitution on the 1-phenyl moiety and on the N-3 nitrogen atom of the triazaspirodecanone portion of 3 were examined. Results from this study suggest that behavioral activity is sensitive to substituents on the 1-phenyl moiety while substituents on the N-3 nitrogen are more generally tolerated. In both rats and squirrel monkeys compound 3 was found to have a similar separation between doses inhibiting Sidman avoidance activity and those causing catalepsy. However, in an extrapyramidal side effect (EPS) test model using haloperidol-sensitized cebus monkeys, 3 elicited signs of EPS at doses approximating those previously determined to be efficacious.
• 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.
• WISE, L. D.;PATTISON, I. C.;BUTLER, D. E.;DEWALD, H. A.;LEWIS, E. P.;LOBB+, J. MED. CHEM., 1985, 28, N 12, 1811-1817
  作者：WISE, L. D.、PATTISON, I. C.、BUTLER, D. E.、DEWALD, H. A.、LEWIS, E. P.、LOBB+

  DOI：——

  日期：——
• 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.