5-氟-2-吲哚基脱氯卤培米特 | 939055-18-2

• 物质功能分类: 生物化工 - 生化试剂 - 激动剂抑制剂
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 中文名称: 5-氟-2-吲哚基脱氯卤培米特
• 中文别名: 化合物FIPI
• 英文名称: 5-fluoro-2-indolyl des-chlorohalopemide
• 英文别名: 5-fluoro-2-indolyl deschlorohalopemide；FIPI；5-fluoro-N-[2-[4-(2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]ethyl]-1H-indole-2-carboxamide
• CAS: 939055-18-2
• 化学式: C₂₃H₂₄FN₅O₂
• 分子量: 421.474
• InChiKey: LHABRXRGDLASIH-UHFFFAOYSA-N

物化性质

• 密度：
  1.349±0.06 g/cm3(Predicted)
• 溶解度：
  DMSO：14.67 mg/mL（34.81 mM；需要超声波和加热）

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  80.5
• 氢给体数：
  3
• 氢受体数：
  4

制备方法与用途

生物活性

FIPI（5-氟-2-吲哚基去氯卤培米特）是卤培米特的衍生物，是一种有效且选择性的磷脂酶 D 抑制剂。其对 PLD1 和 PLD2 的 IC50 值分别为 25 nM 和 20 nM。

Target	Value
PLD2	20 nM (细胞外分析)
PLD1	25 nM (细胞外分析)

体外研究

尽管 FIPI 的清除率大于 2 L/h/kg，其半衰期超过 5 小时，最大血药浓度是 PLD2 半数有效浓度的 10 倍以上，且生物利用度为 18%。FIPI 以剂量依赖的方式抑制 PLD1 和 PLD2，约在 25 nM 时观察到 50% 的活性损失。FIPI 并非不可逆自杀性抑制剂，但也不易完全逆转。IPI 不改变 PLD 的亚细胞定位、PIP2 的可接近性、肌动蛋白应力纤维或上游信号事件。FIPI 可恢复由 PLD2 抑制的膜褶皱和细胞伸展，并以剂量依赖的方式减弱氯化汞诱导的 PLD 活化及 MAECs 中激动剂和氧化剂诱导的 PLD 活化。

反应信息

• 作为产物：
  描述：

  4-（2-酮酸-1-苯并咪唑）哌啶 在 N-甲基吗啉 、 盐酸 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 18.0h， 生成 5-氟-2-吲哚基脱氯卤培米特
  参考文献：
  名称：

  Optimization of Halopemide for Phospholipase D2 inhibition

  摘要：

  Halopemide, which was identified by HTS to inhibit phospholipase D2 (PLD2), provided the basis for an exploratory effort to identify potent inhibitors of PLD2 for use as inflammatory mediators. Parallel synthesis and purification were utilized to rapidly identify orally available amide analogs derived from indole 2-carboxylic acids with superior potency versus PLD2. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.01.059

文献信息

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

  公开号：EP2931277A1

  公开（公告）日：2015-10-21
• METHODS AND COMPOSITIONS OF TREATING HIV INFECTION
  申请人：Vanderbilt University

  公开号：EP2931040A1

  公开（公告）日：2015-10-21
• MODULATION OF PHOSPHOLIPASE D FOR THE TREATMENT OF NEURODEGENERATIVE DISORDERS
  申请人：DiPaolo Gilbert

  公开号：US20120178719A1

  公开（公告）日：2012-07-12

  The present invention relates to methods of treating neurodegenerative diseases comprising administering, to a subject in need of such treatment, one or more agent that inhibits or reduces the action, including the catalytic activity, of an enzyme of the phospholipase D family, such as phospholipase D1 and/or phospholipase D2. The present invention also relates to cell-based assays which may be used to identify agents that inhibit or reduce the activity of enzymes of the phospholipase D family and that may be used in the treatment of neurodegenerative diseases.
• Modulation of Phospholipase D for the Treatment of the Acute and Chronic Effects of Ethanol
  申请人：DiPaolo Gilbert

  公开号：US20120302604A1

  公开（公告）日：2012-11-29

  The present invention relates to methods of decreasing the negative effects of alcohol on behavior as well as inhibiting the toxic effects of alcohol, comprising administering, to a subject, an effective amount of an inhibitor of phospholipase D.
• 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).