2-ethyl-4-[5-(2-ethyl-6-methyl-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenol | 1011261-54-3

• 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-ethyl-4-[5-(2-ethyl-6-methyl-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenol
• 英文别名: 2-ethyl-4-[5-(2-ethyl-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methylphenol；2-ethyl-4-[5-(2-ethyl-6-methylpyridin-4-yl)[1,2,4]oxadiazol-3-yl]-6-methylphenol；2-ethyl-4-[5-(2-ethyl-6-methylpyridin-4-yl)-1,2,4-oxadiazol-3-yl]-6-methylphenol
• CAS: 1011261-54-3
• 化学式: C₁₉H₂₁N₃O₂
• 分子量: 323.395
• InChiKey: VIFMDWRCBUVHLC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  72
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-ethyl-4-[5-(2-ethyl-6-methyl-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenol 在 氨 、 sodium hydroxide 作用下， 以 甲醇 、 水 、 异丙醇 为溶剂， 生成 (S)-1-amino-3-{2-ethyl-4-[5-(2-ethyl-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-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
• 作为产物：
  描述：

  ethyl 2-methyl-6-vinylisonicotinate 在 盐酸 、 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 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 为溶剂， 20.0~100.0 ℃ 、101.33 kPa 条件下， 反应 40.0h， 生成 2-ethyl-4-[5-(2-ethyl-6-methyl-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenol
  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

文献信息

• Pyridin-4-yl derivatives as immunomodulating agents
  申请人：Bolli Martin

  公开号：US20100063108A1

  公开（公告）日：2010-03-11

  The invention relates to pyridine derivatives of Formula (I) wherein A, R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are as described in the description, their preparation and their use as pharmaceutically active compounds. Said compounds particularly act as immunomodulating agents.

  该发明涉及公式（I）中的吡啶衍生物，其中A、R1、R2、R3、R4、R5和R6如描述中所述，它们的制备以及它们作为药用活性化合物的用途。所述化合物特别作为免疫调节剂。
• WO2008/29371
  申请人：——

  公开号：——

  公开（公告）日：——
• PYRIDIN-4-YL DERIVATIVES AS IMMUNOMODULATING AGENTS
  申请人：Actelion Pharmaceuticals Ltd.

  公开号：EP2069336A1

  公开（公告）日：2009-06-17
• US8580824B2
  申请人：——

  公开号：US8580824B2

  公开（公告）日：2013-11-12
• [EN] PYRIDIN-4-YL DERIVATIVES AS IMMUNOMODULATING AGENTS<br/>[FR] DÉRIVÉS DE PYRIDIN-4-YLE EN TANT QU'AGENTS IMMUNOMODULATEURS
  申请人：ACTELION PHARMACEUTICALS LTD

  公开号：WO2008029371A1

  公开（公告）日：2008-03-13

  [EN] The invention relates to pyridine derivatives of Formula (I) wherein A, R¹, R², R³, R⁴, R⁵, and R⁶ are as described in the description, their preparation and their use as pharmaceutically active compounds. Said compounds particularly act as immunomodulating agents.
  [FR] Dérivés de pyridin-4-yle de formule (I), dans laquelle A, R¹, R², R³, R⁴, R⁵, et R⁶ sont tels que spécifiés dans la description, ainsi que leur élaboration et leur utilisation comme composés pharmaceutiquement actifs. Ces composés agissent en particulier comme agents immunomodulateurs.