(S)-1-amino-3-(2-ethyl-4-(5-(6-isobutyl-4-methoxypyridin-2-yl)-1,2,4-oxadiazol-3-yl)-6-methylphenoxy)propan-2-ol | 1186606-63-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (S)-1-amino-3-(2-ethyl-4-(5-(6-isobutyl-4-methoxypyridin-2-yl)-1,2,4-oxadiazol-3-yl)-6-methylphenoxy)propan-2-ol
• CAS: 1186606-63-2
• 化学式: C₂₄H₃₂N₄O₄
• 分子量: 440.542
• InChiKey: SWOSMMLYHXSGIQ-IBGZPJMESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.57
• 重原子数：
  32.0
• 可旋转键数：
  10.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  116.52
• 氢给体数：
  2.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  羟基乙酸 、 (S)-1-amino-3-(2-ethyl-4-(5-(6-isobutyl-4-methoxypyridin-2-yl)-1,2,4-oxadiazol-3-yl)-6-methylphenoxy)propan-2-ol 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以71 mg的产率得到(S)-N-(3-(2-ethyl-4-(5-(6-isobutyl-4-methoxypyridin-2-yl)-1,2,4-oxadiazol-3-yl)-6-methylphenoxy)-2-hydroxypropyl)-2-hydroxyacetamide
  参考文献：
  名称：

  Novel S1P1 receptor agonists – Part 5: From amino-to alkoxy-pyridines

  摘要：

  In a previous communication we reported on the discovery of aminopyridine 1 as a potent, selective and orally active S1P(1) receptor agonist. More detailed studies revealed that this compound is phototoxic in vitro. As a result of efforts aiming at eliminating this undesired property, a series of alkoxy substituted pyridine derivatives was discovered. The photo irritancy factor (PIF) of these alkoxy pyridines was significantly lower than the one of aminopyridine 1 and most compounds were not phototoxic. Focused SAR studies showed, that 2-, 3-, and 4-pyridine derivatives delivered highly potent S1P(1) receptor agonists. While the 2-pyridines were clearly more selective against S1PR(3), the corresponding 3- or 4 pyridine analogues showed significantly longer oral half-lives and as a consequence longer pharmacological duration of action after oral administration. One of the best compounds, cyclopentoxy-pyridine 45b lacked phototoxicity, showed EC50 values of 0.7 and 140 nM on S1PR(1) and S1PR(3), respectively, and maximally reduced the blood lymphocyte count for at least 24 h after oral administration of 10 mg/kg to Wistar rats. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.03.020
• 作为产物：
  描述：

  在 氨 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 甲苯 为溶剂， 反应 44.0h， 生成 (S)-1-amino-3-(2-ethyl-4-(5-(6-isobutyl-4-methoxypyridin-2-yl)-1,2,4-oxadiazol-3-yl)-6-methylphenoxy)propan-2-ol
  参考文献：
  名称：

  Novel S1P1 receptor agonists – Part 5: From amino-to alkoxy-pyridines

  摘要：

  In a previous communication we reported on the discovery of aminopyridine 1 as a potent, selective and orally active S1P(1) receptor agonist. More detailed studies revealed that this compound is phototoxic in vitro. As a result of efforts aiming at eliminating this undesired property, a series of alkoxy substituted pyridine derivatives was discovered. The photo irritancy factor (PIF) of these alkoxy pyridines was significantly lower than the one of aminopyridine 1 and most compounds were not phototoxic. Focused SAR studies showed, that 2-, 3-, and 4-pyridine derivatives delivered highly potent S1P(1) receptor agonists. While the 2-pyridines were clearly more selective against S1PR(3), the corresponding 3- or 4 pyridine analogues showed significantly longer oral half-lives and as a consequence longer pharmacological duration of action after oral administration. One of the best compounds, cyclopentoxy-pyridine 45b lacked phototoxicity, showed EC50 values of 0.7 and 140 nM on S1PR(1) and S1PR(3), respectively, and maximally reduced the blood lymphocyte count for at least 24 h after oral administration of 10 mg/kg to Wistar rats. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.03.020