N-((S)-3-{4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-1,2,4-oxadiazol-3-yl]-2-ethyl-6-methyl-phenoxy}-2-hydroxy-propyl)-2-hydroxy-acetamide | 1262414-10-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-((S)-3-{4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-1,2,4-oxadiazol-3-yl]-2-ethyl-6-methyl-phenoxy}-2-hydroxy-propyl)-2-hydroxy-acetamide
• 英文别名: N-((S)-3-{4-[5-(2-cyclopentyl-6-methoxypyridin-4-yl)[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methylphenoxy}-2-hydroxypropyl)-2-hydroxyacetamide；N-((S)-3-{4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenoxy}-2-hydroxy-propyl)-2-hydroxy-acetamide；N-[(2S)-3-[4-[5-(2-cyclopentyl-6-methoxypyridin-4-yl)-1,2,4-oxadiazol-3-yl]-2-ethyl-6-methylphenoxy]-2-hydroxypropyl]-2-hydroxyacetamide
• CAS: 1262414-10-7
• 化学式: C₂₇H₃₄N₄O₆
• 分子量: 510.59
• InChiKey: NNMWYVILJDPOIT-NRFANRHFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  37
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  140
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  2-氯-6-甲氧基异烟酸甲酯 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 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 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 22.67h， 生成 N-((S)-3-{4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-1,2,4-oxadiazol-3-yl]-2-ethyl-6-methyl-phenoxy}-2-hydroxy-propyl)-2-hydroxy-acetamide
  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

文献信息

• [EN] NEW PROCESS FOR THE PREPARATION OF 2-CYCLOPENTYL-6-METHOXY-ISONICOTINIC ACID<br/>[FR] NOUVEAU PROCÉDÉ DE PRÉPARATION D'ACIDE 2-CYCLOPENTYL-6-MÉTHOXY-ISONICOTINIQUE
  申请人：ACTELION PHARMACEUTICALS LTD

  公开号：WO2013175397A1

  公开（公告）日：2013-11-28

  The present invention relates to new processes for the preparation of 2-cyclopentyl-6-methoxy-isonicotinic acid, which is a useful intermediate for the synthesis of pyridine-4-yl derivatives as immunomodulating agent. Moreover, the present invention also relates to new intermediates used in those processes.

  本发明涉及一种制备2-环戊基-6-甲氧基吡啶-4-基甲酸的新工艺，该化合物是合成吡啶-4-基衍生物作为免疫调节剂的有用中间体。此外，本发明还涉及用于这些工艺的新中间体。
• [EN] PYRIDIN-4-YL DERIVATIVES<br/>[FR] DÉRIVÉS PYRIDIN-4-YLIQUES
  申请人：ACTELION PHARMACEUTICALS LTD

  公开号：WO2011007324A1

  公开（公告）日：2011-01-20

  The invention relates to pyridine derivatives of Formula (I), wherein A, R1, R2, R3, and R4 are as described in the description, their preparation and their use as pharmaceutically active compounds. Said compounds particularly act as immunomodulating agents.

  该发明涉及式（I）的吡啶衍生物，其中A、R1、R2、R3和R4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。这些化合物特别作为免疫调节剂。
• PYRIDIN-4-YL DERIVATIVES
  申请人：Bolli Martin

  公开号：US20120108638A1

  公开（公告）日：2012-05-03

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

  该发明涉及式（I）的吡啶衍生物，其中A、R1、R2、R3和R4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。这些化合物特别作为免疫调节剂。
• NEW PROCESS FOR THE PREPARATION OF 2-CYCLOPENTYL-6-METHOXY-ISONICOTINIC ACID
  申请人：ACTELION PHARMACEUTICALS LTD

  公开号：US20150133669A1

  公开（公告）日：2015-05-14

  The present invention relates to new processes for the preparation of 2-cyclopentyl-6-methoxy-isonicotinic acid, which is a useful intermediate for the synthesis of pyridine-4-yl derivatives as immunomodulating agent. Moreover, the present invention also relates to new intermediates used in those processes.

  本发明涉及制备2-环戊基-6-甲氧基异烟酸的新工艺，该化合物是合成吡啶-4-基衍生物免疫调节剂的有用中间体。此外，本发明还涉及在这些工艺中使用的新中间体。
• PYRIDIN-4-YL DERIVATIVES AS S1P1/EDG1 AGONISTS
  申请人：Actelion Pharmaceuticals Ltd.

  公开号：EP2454255B1

  公开（公告）日：2013-11-06