(S)-N,N-diethyl-4-(3-(3-ethyl-5-methyl-4-(oxiran-2-ylmethoxy)phenyl)-1,2,4-oxadiazol-5-yl)-6-methylpyridin-2-amine | 1062670-10-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (S)-N,N-diethyl-4-(3-(3-ethyl-5-methyl-4-(oxiran-2-ylmethoxy)phenyl)-1,2,4-oxadiazol-5-yl)-6-methylpyridin-2-amine
• 英文别名: diethyl-{4-[3-((S)-3-ethyl-5-methyl-4-oxiranylmethoxy-phenyl)-[1,2,4]oxadiazol-5-yl]-6-methyl-pyridin-2-yl}-amine；N,N-diethyl-4-[3-[3-ethyl-5-methyl-4-[[(2S)-oxiran-2-yl]methoxy]phenyl]-1,2,4-oxadiazol-5-yl]-6-methylpyridin-2-amine
• CAS: 1062670-10-3
• 化学式: C₂₄H₃₀N₄O₃
• 分子量: 422.527
• InChiKey: NAFWEMZKRXDSBO-FQEVSTJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  31
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  76.8
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (S)-N,N-diethyl-4-(3-(3-ethyl-5-methyl-4-(oxiran-2-ylmethoxy)phenyl)-1,2,4-oxadiazol-5-yl)-6-methylpyridin-2-amine 在 氨 作用下， 以 甲醇 为溶剂， 反应 18.0h， 生成 (S)-1-amino-3-(4-(5-(2-(diethylamino)-6-methylpyridin-4-yl)-1,2,4-oxadiazol-3-yl)-2-ethyl-6-methylphenoxy)propan-2-ol
  参考文献：
  名称：

  AMINO-PYRIDINE DERIVATIVES AS S1P1 /EDG1 RECEPTOR AGONISTS

  摘要：

  该发明涉及新型氨基吡啶衍生物，其制备以及它们作为药用活性化合物的用途。这些化合物特别作为免疫调节剂。

  公开号：

  US20100087417A1
• 作为产物：
  描述：

  3-ethyl-4-hydroxy-5-methylbenzaldehyde 在 吡啶 、 盐酸羟胺 、 四甲基氯化铵 、 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 、 氯甲酸三氯甲酯 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 乙腈 为溶剂， 反应 88.5h， 生成 (S)-N,N-diethyl-4-(3-(3-ethyl-5-methyl-4-(oxiran-2-ylmethoxy)phenyl)-1,2,4-oxadiazol-5-yl)-6-methylpyridin-2-amine
  参考文献：
  名称：

  Practical and Scalable Synthesis of S1P₁ Receptor Agonist ACT-209905

  摘要：

  A practical and scalable route for the fast delivery of 12 kg of S1P(1) agonist (ACT-209905) has been developed. ACT-209905 is composed of an amino pyridine group, an oxadiazole spacer, a 2-ethyl-5-methylphenol moiety and a chiral 1-amino-2-propanol side chain. The convergent synthesis consists of 16 steps with 9 isolated intermediates and is chromatography-free. Key building blocks are accessed from low-cost starting materials, such as acetone, diethyl oxalate, cyanoacetamide, and 2-ethyl-5-methyl aniline. A Negishi coupling that was troubled by the use of metal reagents and concomitant metal waste streams has been replaced by a less expensive Guareschi-Thorpe reaction to build up an amino isonicotinic acid. The chiral 1-amino-2-propanol moiety was secured by selective ring-opening of an epoxide with lithium hexamethyldisilazide as an ammonia surrogate, thus omitting the notorious double alkylated byproduct.

  DOI：

  10.1021/op200326s

文献信息

• Amino-pyridine derivatives as S1P1 /EDG1 receptor agonists
  申请人：Bolli Martin

  公开号：US08592460B2

  公开（公告）日：2013-11-26

  The invention relates to novel amino-pyridine derivatives, their preparation and their use as pharmaceutically active compounds. Said compounds particularly act as immunomodulating agents.

  本发明涉及新型氨基吡啶衍生物，其制备以及其用作药物活性化合物。这些化合物特别作为免疫调节剂。
• WO2008/114157
  申请人：——

  公开号：——

  公开（公告）日：——
• Novel S1P₁ Receptor Agonists − Part 3: From Thiophenes to Pyridines
  作者：Martin H. Bolli、Stefan Abele、Magdalena Birker、Roberto Bravo、Daniel Bur、Ruben de Kanter、Christopher Kohl、Julien Grimont、Patrick Hess、Cyrille Lescop、Boris Mathys、Claus Müller、Oliver Nayler、Markus Rey、Michael Scherz、Gunther Schmidt、Jürgen Seifert、Beat Steiner、Jörg Velker、Thomas Weller

  DOI：10.1021/jm4014696

  日期：2014.1.9

  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.
• AMINO- PYRIDINE DERIVATIVES AS S1P1 /EDG1 RECEPTOR AGONISTS
  申请人：Actelion Pharmaceuticals Ltd.

  公开号：EP2125797A1

  公开（公告）日：2009-12-02
• US8592460B2
  申请人：——

  公开号：US8592460B2

  公开（公告）日：2013-11-26