ethyl (E)-3-(4-(phenylthio)phenyl)acrylate | 945414-32-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: ethyl (E)-3-(4-(phenylthio)phenyl)acrylate
• 英文别名: Ethyl (E)-3-(4-(phenylthio)phenyl)acrylate；ethyl (E)-3-(4-phenylsulfanylphenyl)prop-2-enoate
• CAS: 945414-32-4
• 化学式: C₁₇H₁₆O₂S
• 分子量: 284.379
• InChiKey: DBWGGENZTYKVSM-JLHYYAGUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  51.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl (E)-3-(4-(phenylthio)phenyl)acrylate 在 bismuth(III) chloride 、 sodium hydroxide 、 sodium tetrahydroborate 、 草酰氯 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 为溶剂， 反应 20.0h， 生成
  参考文献：
  名称：

  Structure−Activity Relationships of α-Ketooxazole Inhibitors of Fatty Acid Amide Hydrolase

  摘要：

  A systematic study of the structure-activity relationships of 2b (OL-135), a potent inhibitor of fatty acid amide hydrolase (FAAH), is detailed targeting the C2 acyl side chain. A series of aryl replacements or substituents for the terminal phenyl group provided effective inhibitors (e.g., 5c, aryl = 1- napthyl, K-i = 2.6 nM), with 5hh (aryl = 3-ClPh, K-i = 900 pM) being 5-fold more potent than 2b. Conformationally restricted C2 side chains were examined, and many provided exceptionally potent inhibitors, of which 11j (ethylbiphenyl side chain) was established to be a 750 pM inhibitor. A systematic series of heteroatoms (O, NMe, S), electron-withdrawing groups (SO, SO2), and amides positioned within and hydroxyl substitutions on the linking side chain were investigated, which typically led to a loss in potency. The most tolerant positions provided effective inhibitors (12p, 6-position S, K-i = 3 nM, or 13d, 2-position OH, K-i = 8 nM) comparable in potency to 2b. Proteome-wide screening of selected inhibitors from the systematic series of > 100 candidates prepared revealed that they are selective for FAAH over all other mammalian serine proteases.

  DOI：

  10.1021/jm061414r
• 作为产物：
  描述：

  苯硫酚 在 正丁基锂 、 potassium carbonate 作用下， 以 四氢呋喃 、 正己烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.58h， 生成 ethyl (E)-3-(4-(phenylthio)phenyl)acrylate
  参考文献：
  名称：

  Structure−Activity Relationships of α-Ketooxazole Inhibitors of Fatty Acid Amide Hydrolase

  摘要：

  A systematic study of the structure-activity relationships of 2b (OL-135), a potent inhibitor of fatty acid amide hydrolase (FAAH), is detailed targeting the C2 acyl side chain. A series of aryl replacements or substituents for the terminal phenyl group provided effective inhibitors (e.g., 5c, aryl = 1- napthyl, K-i = 2.6 nM), with 5hh (aryl = 3-ClPh, K-i = 900 pM) being 5-fold more potent than 2b. Conformationally restricted C2 side chains were examined, and many provided exceptionally potent inhibitors, of which 11j (ethylbiphenyl side chain) was established to be a 750 pM inhibitor. A systematic series of heteroatoms (O, NMe, S), electron-withdrawing groups (SO, SO2), and amides positioned within and hydroxyl substitutions on the linking side chain were investigated, which typically led to a loss in potency. The most tolerant positions provided effective inhibitors (12p, 6-position S, K-i = 3 nM, or 13d, 2-position OH, K-i = 8 nM) comparable in potency to 2b. Proteome-wide screening of selected inhibitors from the systematic series of > 100 candidates prepared revealed that they are selective for FAAH over all other mammalian serine proteases.

  DOI：

  10.1021/jm061414r

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：——
• Structure−Activity Relationships of α-Ketooxazole Inhibitors of Fatty Acid Amide Hydrolase
  作者：Christophe Hardouin、Michael J. Kelso、F. Anthony Romero、Thomas J. Rayl、Donmienne Leung、Inkyu Hwang、Benjamin F. Cravatt、Dale L. Boger

  DOI：10.1021/jm061414r

  日期：2007.7.1

  A systematic study of the structure-activity relationships of 2b (OL-135), a potent inhibitor of fatty acid amide hydrolase (FAAH), is detailed targeting the C2 acyl side chain. A series of aryl replacements or substituents for the terminal phenyl group provided effective inhibitors (e.g., 5c, aryl = 1- napthyl, K-i = 2.6 nM), with 5hh (aryl = 3-ClPh, K-i = 900 pM) being 5-fold more potent than 2b. Conformationally restricted C2 side chains were examined, and many provided exceptionally potent inhibitors, of which 11j (ethylbiphenyl side chain) was established to be a 750 pM inhibitor. A systematic series of heteroatoms (O, NMe, S), electron-withdrawing groups (SO, SO2), and amides positioned within and hydroxyl substitutions on the linking side chain were investigated, which typically led to a loss in potency. The most tolerant positions provided effective inhibitors (12p, 6-position S, K-i = 3 nM, or 13d, 2-position OH, K-i = 8 nM) comparable in potency to 2b. Proteome-wide screening of selected inhibitors from the systematic series of > 100 candidates prepared revealed that they are selective for FAAH over all other mammalian serine proteases.