1-benzyl-4-((3-fluorophenyl)amino)piperidine-4-carboxamide | 1244639-58-4

• 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: 1-benzyl-4-((3-fluorophenyl)amino)piperidine-4-carboxamide
• 英文别名: 1-Benzyl-4-(3-fluoroanilino)piperidine-4-carboxamide
• CAS: 1244639-58-4
• 化学式: C₁₉H₂₂FN₃O
• 分子量: 327.402
• InChiKey: FNMZSPCHPLHJHP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  58.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-benzyl-4-((3-fluorophenyl)amino)piperidine-4-carboxamide 在 氢氧化钾 、 溶剂黄146 作用下， 以 乙二醇 、 水 为溶剂， 反应 4.0h， 生成 1-Benzyl-4-(3-fluoroanilino)piperidine-4-carboxylic acid
  参考文献：
  名称：

  WO2006/44497

  摘要：

  公开号：
• 作为产物：
  描述：

  1-benzyl-4-(3-fluorophenylamino)piperidine-4-carbonitrile 在 硫酸 、 sodium hydroxide 作用下， 以 水 为溶剂， 反应 18.0h， 生成 1-benzyl-4-((3-fluorophenyl)amino)piperidine-4-carboxamide
  参考文献：
  名称：

  WO2006/44497

  摘要：

  公开号：

文献信息

• Triaza-spirodecanones as DDR1 inhibitors
  申请人：Hoffmann La-Roche Inc.

  公开号：US10239876B2

  公开（公告）日：2019-03-26

  The present invention relates to compounds of formula (I): or pharmaceutically acceptable salts thereof, wherein L and R1 to R5 are as described herein, as well as processes for their manufacture, pharmaceutical compositions comprising them, and their use as medicaments.

  本发明涉及式（I）化合物： 或其药学上可接受的盐，其中 L 和 R1 至 R5 如本文所述，以及它们的制造工艺、包含它们的药物组合物和它们作为药物的用途。
• 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.
• TRIAZA-SPIRODECANONES AS DDR1 INHIBITORS
  申请人：F. Hoffmann-La Roche AG

  公开号：EP3317279B1

  公开（公告）日：2021-01-27
• WO2006/44497
  申请人：——

  公开号：——

  公开（公告）日：——
• 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.