2-cyano-6-(2-(3-(4-phenoxymethylphenyl)propanoyl)oxazol-5-yl)pyridine | 1012329-62-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 2-cyano-6-(2-(3-(4-phenoxymethylphenyl)propanoyl)oxazol-5-yl)pyridine
• 英文别名: 2-Cyano-6-(2-(3-(4-(phenoxymethyl)phenyl)propanoyl)oxazol-5-yl)pyridine；6-[2-[3-[4-(phenoxymethyl)phenyl]propanoyl]-1,3-oxazol-5-yl]pyridine-2-carbonitrile
• CAS: 1012329-62-2
• 化学式: C₂₅H₁₉N₃O₃
• 分子量: 409.444
• InChiKey: ILNRAGIQTMVESE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  89
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-cyano-6-(2-(3-(4-phenoxymethylphenyl)propanoyl)oxazol-5-yl)pyridine 在 sodium azide 、 zinc dibromide 作用下， 以 水 、 异丙醇 为溶剂， 反应 24.0h， 以55%的产率得到3-(4-phenoxymethyl-phenyl)-1-{5-[6-(1H-tetrazol-5-yl)-pyridin-2-yl]-oxazol-2-yl}-propan-1-one
  参考文献：
  名称：

  Optimization of α-Ketooxazole Inhibitors of Fatty Acid Amide Hydrolase

  摘要：

  A series of alpha-ketooxazoles containing conformational constraints in the flexible C2 acyl side chain of 2 (OL-135) and representative oxazole C5 substituents were prepared and examined as inhibitors of fatty acid amide hydrolase (FAAH). Exceptionally potent and selective FAAH inhibitors emerged from the series (e.g., 6, K-i = 200 and 260 pM for rat and rhFAAH). With simple and small C5 oxazole substituents, each series bearing a biphenylethyl, phenoxyphenethyl, or (phenoxymethyl)phenethyl C2 side chain was found to follow a well-defined linear relationship between -log K-i and Hammett sigma(p) of a magnitude (rho = 2.7-3.0) that indicates that the substituent electronic effect dominates, confirming its fundamental importance to the series and further establishing its predictive value. Just as significantly, the nature of the C5 oxazole substituent substantially impacts the selectivity of the inhibitors whereas the effect of the C2 acyl chain was more subtle but still significant even in the small series examined. Combination of these independent features, which display generalized trends across a range of inhibitor series, simultaneously improves FAAH potency and selectivity and can provide exquisitely selective and potent FAAH inhibitors.

  DOI：

  10.1021/jm701210y
• 作为产物：
  描述：

  2-cyano-6-(2-(1-hydroxy-3-(4-(phenoxymethyl)phenyl)propyl)oxazol-5-yl)pyridine 在 戴斯-马丁氧化剂 作用下， 以 二氯甲烷 为溶剂， 反应 2.5h， 以74%的产率得到2-cyano-6-(2-(3-(4-phenoxymethylphenyl)propanoyl)oxazol-5-yl)pyridine
  参考文献：
  名称：

  Optimization of α-Ketooxazole Inhibitors of Fatty Acid Amide Hydrolase

  摘要：

  A series of alpha-ketooxazoles containing conformational constraints in the flexible C2 acyl side chain of 2 (OL-135) and representative oxazole C5 substituents were prepared and examined as inhibitors of fatty acid amide hydrolase (FAAH). Exceptionally potent and selective FAAH inhibitors emerged from the series (e.g., 6, K-i = 200 and 260 pM for rat and rhFAAH). With simple and small C5 oxazole substituents, each series bearing a biphenylethyl, phenoxyphenethyl, or (phenoxymethyl)phenethyl C2 side chain was found to follow a well-defined linear relationship between -log K-i and Hammett sigma(p) of a magnitude (rho = 2.7-3.0) that indicates that the substituent electronic effect dominates, confirming its fundamental importance to the series and further establishing its predictive value. Just as significantly, the nature of the C5 oxazole substituent substantially impacts the selectivity of the inhibitors whereas the effect of the C2 acyl chain was more subtle but still significant even in the small series examined. Combination of these independent features, which display generalized trends across a range of inhibitor series, simultaneously improves FAAH potency and selectivity and can provide exquisitely selective and potent FAAH inhibitors.

  DOI：

  10.1021/jm701210y

文献信息

• TETRACYCLIC INHIBITORS OF FATTY ACID AMIDE HYDROLASE
  申请人：Boger Dale L.

  公开号：US20100249078A1

  公开（公告）日：2010-09-30

  Certain tetracyclic compounds are described, which may be used in pharmaceutical compositions and methods for treating disease states, disorders, and conditions mediated by fatty acid amide hydrolase (FAAH) activity. Thus, the compounds may be administered to treat, e.g., anxiety, pain, inflammation, sleep disorders, eating disorders, or movement disorders (such as multiple sclerosis).

  本文描述了某些四环化合物，可用于制备药物组合物和方法，用于治疗由脂肪酸酰胺水解酶（FAAH）活性介导的疾病状态、障碍和病况。因此，这些化合物可以用于治疗焦虑、疼痛、炎症、睡眠障碍、进食障碍或运动障碍（例如多发性硬化）。
• Tetracyclic inhibitors of fatty acid amide hydrolase
  申请人：Boger Dale L.

  公开号：US08372823B2

  公开（公告）日：2013-02-12

  Certain tetracyclic compounds are described, which may be used in pharmaceutical compositions and methods for treating disease states, disorders, and conditions mediated by fatty acid amide hydrolase (FAAH) activity. Thus, the compounds may be administered to treat, e.g., anxiety, pain, inflammation, sleep disorders, eating disorders, or movement disorders (such as multiple sclerosis).

  本文描述了某些四环类化合物，可用于制备药物组合物和治疗由脂肪酸酰胺酶（FAAH）活性介导的疾病状态、疾病和病症的方法。因此，该化合物可用于治疗焦虑、疼痛、炎症、睡眠障碍、饮食障碍或运动障碍（如多发性硬化）等疾病。
• WO2008/147553
  申请人：——

  公开号：——

  公开（公告）日：——
• US8372823B2
  申请人：——

  公开号：US8372823B2

  公开（公告）日：2013-02-12
• [EN] TETRACYCLIC INHIBITORS OF FATTY ACID AMIDE HYDROLASE<br/>[FR] INHIBITEURS TÉTRACYCLIQUES D'HYDROLASE D'AMIDE D'ACIDE GRAS
  申请人：BOGER DALE L

  公开号：WO2008147553A1

  公开（公告）日：2008-12-04

  [EN] Certain tetracyclic compounds are described, which may be used in pharmaceutical compositions and methods for treating disease states, disorders, and conditions mediated by fatty acid amide hydrolase (FAAH) activity. Thus, the compounds may be administered to treat, e.g., anxiety, pain, inflammation, sleep disorders, eating disorders, or movement disorders (such as multiple sclerosis).
  [FR] L'invention concerne certains composés tétracycliques, qui peuvent être utilisés dans des compositions pharmaceutiques et des procédés pour traiter des états maladifs, des troubles et des affections véhiculés par une activité de l'hydrolase d'amide d'acide gras (FAAH). Ainsi, les composés peuvent être administrés pour traiter, par exemple, l'anxiété, la douleur, l'inflammation, les troubles du sommeil, les troubles de l'alimentation ou les troubles du mouvement (tels que la sclérose en plaques).