3-[5-(4-acetyl-3-hydroxy-2-propyl-phenoxymethyl)-pyridin-2-yloxy]-benzonitrile

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-[5-(4-acetyl-3-hydroxy-2-propyl-phenoxymethyl)-pyridin-2-yloxy]-benzonitrile
• 英文别名: 3-[5-[(4-Acetyl-3-hydroxy-2-propylphenoxy)methyl]pyridin-2-yl]oxybenzonitrile
• 化学式: C₂₄H₂₂N₂O₄
• 分子量: 402.45
• InChiKey: QKFLVUSTRPXQRP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  92.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-[5-(4-acetyl-3-hydroxy-2-propyl-phenoxymethyl)-pyridin-2-yloxy]-benzonitrile 在 sodium azide 、 三乙胺盐酸盐 作用下， 以 甲苯 为溶剂， 生成 1-(2-hydroxy-3-propyl-4-{6-[3-(1H-tetrazol-5-yl)-phenoxy]-pyridin-3-ylmethoxy}-phenyl)-ethanone
  参考文献：
  名称：

  Discovery of dual positive allosteric modulators (PAMs) of the metabotropic glutamate 2 receptor and CysLT1 antagonists for treating migraine headache

  摘要：

  Pyridylmethylsulfonamide series were the first reported example of positive allosteric modulators (PAM) of the mGlu(2) receptor. The hydroxyacetophenone scaffold is a second series of mGlu(2) PAMs we have identified. This series of molecules are potent mGlu(2) potentiators and possess significant CysLT1 (cysteinyl leukotriene receptor 1) antagonist activity, showing in vivo efficacy in a dural plasma protein extravasation (PPE) model of migraine. In this paper, we describe the dual SAR, pharmacokinetics and preclinical in vivo efficacy data for a tetrazole containing hydroxyacetophenone scaffold. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.11.049
• 作为产物：
  描述：

  3-氯苯腈 在 potassium carbonate 、 caesium carbonate 作用下， 以 N,N-二甲基乙酰胺 、 丙酮 为溶剂， 生成 3-[5-(4-acetyl-3-hydroxy-2-propyl-phenoxymethyl)-pyridin-2-yloxy]-benzonitrile
  参考文献：
  名称：

  Discovery of dual positive allosteric modulators (PAMs) of the metabotropic glutamate 2 receptor and CysLT1 antagonists for treating migraine headache

  摘要：

  Pyridylmethylsulfonamide series were the first reported example of positive allosteric modulators (PAM) of the mGlu(2) receptor. The hydroxyacetophenone scaffold is a second series of mGlu(2) PAMs we have identified. This series of molecules are potent mGlu(2) potentiators and possess significant CysLT1 (cysteinyl leukotriene receptor 1) antagonist activity, showing in vivo efficacy in a dural plasma protein extravasation (PPE) model of migraine. In this paper, we describe the dual SAR, pharmacokinetics and preclinical in vivo efficacy data for a tetrazole containing hydroxyacetophenone scaffold. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.11.049

文献信息

• Potentiators Of Glutamate Receptors
  申请人：Aicher Daniel Thomas

  公开号：US20080096930A1

  公开（公告）日：2008-04-24

  The present invention provides compounds of formula (I); pharmaceutical compositions thereof, and methods of using the same, processes or preparing the same, and intermediates thereof.

  本发明提供了式（I）的化合物；其制药组合物和使用方法，制备方法或中间体。
• POTENTIATORS OF GLUTAMATE RECEPTORS
  申请人：ELI LILLY AND COMPANY

  公开号：EP1817300B1

  公开（公告）日：2010-03-17
• US7858646B2
  申请人：——

  公开号：US7858646B2

  公开（公告）日：2010-12-28
• Discovery of dual positive allosteric modulators (PAMs) of the metabotropic glutamate 2 receptor and CysLT1 antagonists for treating migraine headache
  作者：Maria-Jesus Blanco、Dana R. Benesh、James A. Knobelsdorf、Albert Khilevich、Guillermo S. Cortez、Fese Mokube、Thomas D. Aicher、Todd M. Groendyke、Fredrik P. Marmsater、Tony P. Tang、Kirk W. Johnson、Amy Clemens-Smith、Mark A. Muhlhauser、Steven Swanson、John Catlow、Renee Emkey、Michael P. Johnson、Jeffrey M. Schkeryantz

  DOI：10.1016/j.bmcl.2016.11.049

  日期：2017.1

  Pyridylmethylsulfonamide series were the first reported example of positive allosteric modulators (PAM) of the mGlu(2) receptor. The hydroxyacetophenone scaffold is a second series of mGlu(2) PAMs we have identified. This series of molecules are potent mGlu(2) potentiators and possess significant CysLT1 (cysteinyl leukotriene receptor 1) antagonist activity, showing in vivo efficacy in a dural plasma protein extravasation (PPE) model of migraine. In this paper, we describe the dual SAR, pharmacokinetics and preclinical in vivo efficacy data for a tetrazole containing hydroxyacetophenone scaffold. (C) 2016 Elsevier Ltd. All rights reserved.