(S)-1-amino-3-(4-(3-(2-(diethylamino)-6-methylpyridin-4-yl)-1,2,4-oxadiazol-5-yl)-2-ethyl-6-methylphenoxy)propan-2-ol | 1062671-14-0

• 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-(4-(3-(2-(diethylamino)-6-methylpyridin-4-yl)-1,2,4-oxadiazol-5-yl)-2-ethyl-6-methylphenoxy)propan-2-ol
• CAS: 1062671-14-0
• 化学式: C₂₄H₃₃N₅O₃
• 分子量: 439.558
• InChiKey: MFUDARFOPMVNMZ-FQEVSTJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.52
• 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：
  110.53
• 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-(4-(3-(2-(diethylamino)-6-methylpyridin-4-yl)-1,2,4-oxadiazol-5-yl)-2-ethyl-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 作用下， 以 二氯甲烷 为溶剂， 反应 1.17h， 以85 mg的产率得到(S)-N-(3-(4-(3-(2-(diethylamino)-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-5-yl)-2-ethyl-6-methylphenoxy)-2-hydroxypropyl)-2-hydroxyacetamide
  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
• 作为产物：
  描述：

  2-甲基-6-乙基苯胺 在 sodium chlorite 、 sodium dihydrogenphosphate dihydrate 、 乌洛托品 、 硫酸 、 氨 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 、 sodium hydroxide 、 sodium nitrite 作用下， 以 甲醇 、 二氯甲烷 、 水 、 二甲基亚砜 、 异丙醇 为溶剂， 反应 44.0h， 生成 (S)-1-amino-3-(4-(3-(2-(diethylamino)-6-methylpyridin-4-yl)-1,2,4-oxadiazol-5-yl)-2-ethyl-6-methylphenoxy)propan-2-ol
  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