2-[3-(2-Fluorophenyl)-1,2,4-oxadiazol-5-yl]benzoic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-[3-(2-Fluorophenyl)-1,2,4-oxadiazol-5-yl]benzoic acid
• 化学式: C₁₅H₉FN₂O₃
• 分子量: 284.246
• InChiKey: JPYFHMXIDLYKLT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  76.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-[3-(2-Fluorophenyl)-1,2,4-oxadiazol-5-yl]benzoic acid 在 碳酸氢钠 作用下， 以 四氢呋喃 、 水 为溶剂， 生成
  参考文献：
  名称：

  1,2,4-Triazolsulfone: A novel isosteric replacement of acylsulfonamides in the context of Na V 1.7 inhibition

  摘要：

  Recently, the identification of several classes of aryl sulfonamides and acyl sulfonamides that potently inhibit Na(v)1.7 and demonstrate high levels of selectivity over other Na-v isoforms have been reported. The fully ionizable nature of these inhibitors has been shown to be an important part of the pharmacophore for the observed potency and isoform selectivity. The requirement of this functionality, however, has presented challenges associated with optimization toward inhibitors with drug-like properties and minimal off-target activity. In an effort to obviate these challenges, we set out to develop an orally bioavailable, selective Na(v)1.7 inhibitor, lacking these acidic functional groups. Herein, we report the discovery of a novel series of inhibitors wherein a triazolesulfone has been designed to serve as a bioisostere for the acyl sulfonamide. This work culminated in the delivery of a potent series of inhibitors which demonstrated good levels of selectivity over Na v 1.5 and favorable pharmacokinetics in rodents. (C) 2018 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2018.04.035