4-fluoro-N-[2-[1-(3-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl]ethyl]benzamide | 1244639-82-4

• 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: 4-fluoro-N-[2-[1-(3-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl]ethyl]benzamide
• CAS: 1244639-82-4
• 化学式: C₂₂H₂₄F₂N₄O₂
• 分子量: 414.455
• InChiKey: AUTVGUGBVJTDOF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  64.7
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  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-二甲基甲酰胺 为溶剂， 反应 36.5h， 生成 4-fluoro-N-[2-[1-(3-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl]ethyl]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

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.
• METHODS AND COMPOSITIONS OF TREATING HIV INFECTION
  申请人：Vanderbilt University

  公开号：US20140163055A1

  公开（公告）日：2014-06-12

  Disclosed are methods of treating HIV infections comprising, in one aspect, administering compounds that are phospholipase D inhibitors. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
• METHODS AND COMPOSITIONS COMPRISING AKT INHIBITORS AND/OR PHOSPHOLIPASE D INHIBITORS
  申请人：Vanderbilt University

  公开号：US20140378524A1

  公开（公告）日：2014-12-25

  Disclosed are methods of treating viral infections or disorders of uncontrolled proliferation comprising, in one aspect, administering compounds that are phospholipase D inhibitors and/or Akt therapeutic agents. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
• ANTIVIRAL THERAPIES WITH PHOSPHOLIPASE D INHIBITORS
  申请人：Lindsley Craig W.

  公开号：US20150025041A1

  公开（公告）日：2015-01-22

  Disclosed are methods of treating viral infections comprising, in one aspect, administering compounds that are phospholipase D inhibitors. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention. In accordance with the purpose(s) of the invention, as embodied and broadly described herein, the invention, in one aspect, relates to antiviral therapies. For example, compounds having Phospholipase D activity (e.g., isoform selective Phospholipase D inhibitors) can be useful in antiviral therapies (e.g., influenza treatments).
• Methods and Compositions for Treating HIV Infection
  申请人：Vanderbilt University

  公开号：US20160296506A1

  公开（公告）日：2016-10-13

  Disclosed are methods of treating HIV infections comprising, in one aspect, administering compounds that are phospholipase D inhibitors. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.