N-[2-[1-(3-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4,5]dec-8-yl]ethyl]-2-naphthalenecarboxamide | 1244639-78-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: N-[2-[1-(3-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4,5]dec-8-yl]ethyl]-2-naphthalenecarboxamide
• 英文别名: VU-0364739；N-{2-[1-(3-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl]ethyl}naphthalene-2-carboxamide；N-[2-[1-(3-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl]ethyl]naphthalene-2-carboxamide
• CAS: 1244639-78-8
• 化学式: C₂₆H₂₇FN₄O₂
• 分子量: 446.524
• InChiKey: MSTXJJGAXXJCBY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  33
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  64.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  8-(2-aminoethyl)-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83%的产率得到N-[2-[1-(3-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4,5]dec-8-yl]ethyl]-2-naphthalenecarboxamide
  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

• ANTIVIRAL THERAPIES WITH PHOSPHOLIPASE D INHIBITORS
  申请人：Vanderbilt University

  公开号：EP2760447A1

  公开（公告）日：2014-08-06
• 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.
• COMBINATION THERAPY FOR THE TREATMENT OF CANCER USING AN ANTI-C-MET ANTIBODY
  申请人：SAMSUNG ELECTRONICS CO., LTD.

  公开号：US20150010575A1

  公开（公告）日：2015-01-08

  A target substance used for combination treatment with an anti-c-Met antibody, a pharmaceutical composition for combination administration for preventing and/or treating cancer including an anti-c-Met antibody and an inhibitor against the target substance as active ingredients, a method for preventing and/or treating cancer including co-administering an anti-c-Met antibody and an inhibitor against the target substance, and a method for screening a drug for preventing and/or treating cancer using the target substance.
• 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.