2-cyclohexyl-6-methoxyisonicotinic acid | 1262413-90-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 2-cyclohexyl-6-methoxyisonicotinic acid
• 英文别名: 2-cyclohexyl-6-methoxy-isonicotinic acid；2-cyclohexyl-6-methoxypyridine-4-carboxylic acid
• CAS: 1262413-90-0
• 化学式: C₁₃H₁₇NO₃
• 分子量: 235.283
• InChiKey: DUYRFOATVWSZJZ-UHFFFAOYSA-N

物化性质

• 沸点：
  446.9±45.0 °C(Predicted)
• 密度：
  1.174±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  59.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-cyclohexyl-6-methoxyisonicotinic acid 在 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 、 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.67h， 生成 (S)-N-(3-(4-(5-(2-cyclohexyl-6-methoxypyridin-4-yl)-1,2,4-oxadiazol-3-yl)-2-ethyl-6-methylphenoxy)-2-hydroxypropyl)-2-hydroxyacetamide
  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
• 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 、 lithium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 水 为溶剂， 反应 2.0h， 生成 2-cyclohexyl-6-methoxyisonicotinic acid
  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] 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。
• Pyridin-4-yl derivatives
  申请人：Bolli Martin

  公开号：US08658675B2

  公开（公告）日：2014-02-25

  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.

  本发明涉及式(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物活性化合物的用途。这些化合物特别作为免疫调节剂。
• PYRIDIN-4-YL DERIVATIVES AS S1P1/EDG1 AGONISTS
  申请人：Actelion Pharmaceuticals Ltd.

  公开号：EP2454255B1

  公开（公告）日：2013-11-06
• US8658675B2
  申请人：——

  公开号：US8658675B2

  公开（公告）日：2014-02-25