(S)-N-(1-(1-(3-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl)propan-2-yl)-2-naphthamide | 1244640-42-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (S)-N-(1-(1-(3-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl)propan-2-yl)-2-naphthamide
• 英文别名: N-[(2S)-1-[1-(3-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl]propan-2-yl]naphthalene-2-carboxamide
• CAS: 1244640-42-3
• 化学式: C₂₇H₂₉FN₄O₂
• 分子量: 460.551
• InChiKey: MNKBFXBSNSUUTP-IBGZPJMESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  64.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-N-(1-(1-(3-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl)propan-2-yl)-2-naphthamide 、 三氟乙酸 以 水 、 乙腈 为溶剂， 反应 0.08h， 以19.3 mg的产率得到(S)-N-(1-(1-(3-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl)propan-2-yl)-2-naphthamide 2,2,2-trifluoroacetate
  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：

  (S)-8-(2-aminopropyl)-1-(3-fluorophenyl)-1,3,8-triazaspiro[4.5]decan-4-one dihydrochloride 、 2-萘甲酰氯 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以9%的产率得到(S)-N-(1-(1-(3-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl)propan-2-yl)-2-naphthamide
  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

文献信息

• 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.
• 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.
• METHODS AND COMPOSITIONS COMPRISING AKT INHIBITORS AND/OR PHOSPHOLIPASE D INHIBITORS
  申请人：Vanderbilt University

  公开号：US20170319611A1

  公开（公告）日：2017-11-09

  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.
• US9453017B2
  申请人：——

  公开号：US9453017B2

  公开（公告）日：2016-09-27