2-[(1-methylethyl)oxy]-5-[3-(2,3,4,5-tetrahydro-1,4-benzoxazepin-8-yl)-1,2,4-oxadiazol-5-yl]benzonitrile hydrochloride | 1167415-84-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: 2-[(1-methylethyl)oxy]-5-[3-(2,3,4,5-tetrahydro-1,4-benzoxazepin-8-yl)-1,2,4-oxadiazol-5-yl]benzonitrile hydrochloride
• 英文别名: 2-(1-methylethyloxy)-5-(3-(2,3,4,5-tetrahydro-1,4-benzoxazepin-8-yl)-1,2,4-oxadiazol-5-yl)benzonitrile hydrochloride
• CAS: 1167415-84-0
• 化学式: C₂₁H₂₀N₄O₃*ClH
• 分子量: 412.876
• InChiKey: UFMDPYXEMMDQOC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.97
• 重原子数：
  29.0
• 可旋转键数：
  4.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  93.2
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为产物：
  描述：

  1,1-dimethylethyl 8-[(hydroxyamino)(imino)methyl]-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate 在 盐酸 、 1-羟基苯并三唑 、 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 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-[(1-methylethyl)oxy]-5-[3-(2,3,4,5-tetrahydro-1,4-benzoxazepin-8-yl)-1,2,4-oxadiazol-5-yl]benzonitrile hydrochloride
  参考文献：
  名称：

  Optimization of Sphingosine-1-phosphate-1 Receptor Agonists: Effects of Acidic, Basic, and Zwitterionic Chemotypes on Pharmacokinetic and Pharmacodynamic Profiles

  摘要：

  The efficacy of the recently approved drug fingolimod (FTY720) in multiple sclerosis patients results from the action of its phosphate metabolite on sphingosine-1-phosphate S1P(1) receptors, while a variety of side effects have been ascribed to its S1P(3) receptor activity. Although S1P and phospho-fingolimod share the same structural elements of a zwitterionic headgroup and lipophilic tail, a variety of chemotypes have been found to show S1P(1) receptor agonism. Here we describe a study of the tolerance of the S1P(1) and S1P(3) receptors toward bicyclic heterocycles of systematically varied shape and connectivity incorporating acidic, basic, or zwitterionic headgroups. We compare their physicochemical properties, their performance in in vitro and in vivo pharmacokinetic models, and their efficacy in peripheral lymphocyte lowering. The campaign resulted in the identification of several potent S1P(1) receptor agonists with good selectivity vs S1P(3) receptors, efficacy at <1 mg/kg oral doses, and developability properties suitable for progression into preclinical development.

  DOI：

  10.1021/jm5010336