(S)-3-(4-(5-(2-(diethylamino)-6-methylpyridin-4-yl)-[1,3,4]oxadiazol-2-yl)-2-ethyl-6-methylphenoxy)propane-1,2-diol | 1062671-27-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (S)-3-(4-(5-(2-(diethylamino)-6-methylpyridin-4-yl)-[1,3,4]oxadiazol-2-yl)-2-ethyl-6-methylphenoxy)propane-1,2-diol
• 英文别名: (2S)-3-[4-[5-[2-(diethylamino)-6-methylpyridin-4-yl]-1,3,4-oxadiazol-2-yl]-2-ethyl-6-methylphenoxy]propane-1,2-diol
• CAS: 1062671-27-5
• 化学式: C₂₄H₃₂N₄O₄
• 分子量: 440.542
• InChiKey: UPQLDVCMIQYNAU-FQEVSTJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  32
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  105
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  tert-butyl 2-chloro-6-(diethylamino)isonicotinate 在 盐酸 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 伯吉斯试剂 、 palladium 10% on activated carbon 、 氢气 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 20.0~110.0 ℃ 、100.0 kPa 条件下， 反应 61.25h， 生成 (S)-3-(4-(5-(2-(diethylamino)-6-methylpyridin-4-yl)-[1,3,4]oxadiazol-2-yl)-2-ethyl-6-methylphenoxy)propane-1,2-diol
  参考文献：
  名称：

  Novel S1P₁ Receptor Agonists − Part 3: From Thiophenes to Pyridines

  摘要：

  In preceding communications we summarized our medicinal chemistry efforts leading to the identification of potent, selective, and orally active S1P(1) agonists such as the thiophene derivative 1. As a continuation of these efforts, we replaced the thiophene in 1 by a 2-, 3-, or 4-pyridine and obtained less lipophilic, potent, and selective S1P(1) agonists (e.g., 2) efficiently reducing blood lymphocyte count in the rat. Structural features influencing the compounds' receptor affinity profile and pharmacokinetics are discussed. In addition, the ability to penetrate brain tissue has been studied for several compounds. As a typical example for these pyridine based S1P(1) agonists, compound 53 showed EC50 values of 0.6 and 352 nM for the S1P(1), and S1P(3) receptor, respectively, displayed favorable PK properties, and penetrated well into brain tissue. In the rat, compound 53 maximally reduced the blood lymphocyte count for at least 24 h after oral dosing of 3 mg/kg.

  DOI：

  10.1021/jm4014696