1-oxo-1-[5-(2-pyridyl)oxazol-2-yl]-7-(4-(trifluoromethyl)phenyl)hept-6-yne | 945413-56-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-oxo-1-[5-(2-pyridyl)oxazol-2-yl]-7-(4-(trifluoromethyl)phenyl)hept-6-yne
• 英文别名: 1-(5-pyridin-2-yl-1,3-oxazol-2-yl)-7-[4-(trifluoromethyl)phenyl]hept-6-yn-1-one
• CAS: 945413-56-9
• 化学式: C₂₂H₁₇F₃N₂O₂
• 分子量: 398.384
• InChiKey: FRVVFKPSVCWWTK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  56
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-oxo-1-[5-(2-pyridyl)oxazol-2-yl]-7-(4-(trifluoromethyl)phenyl)hept-6-yne 在 palladium on activated charcoal 氢气 作用下， 以 乙酸乙酯 为溶剂， 以93%的产率得到1-oxo-1-[5-(2-pyridyl)oxazol-2-yl]-7-(4-(trifluoromethyl)phenyl)heptane
  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：

  6-庚炔酸 在 bis-triphenylphosphine-palladium(II) chloride 、 silver carbonate 正丁基锂 、 草酰氯 、 四丁基氯化铵 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 22.03h， 生成 1-oxo-1-[5-(2-pyridyl)oxazol-2-yl]-7-(4-(trifluoromethyl)phenyl)hept-6-yne
  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
• 作为试剂：
  描述：

  1-oxo-1-[5-(2-pyridyl)oxazol-2-yl]-7-(trimethylsilyl)hept-6-yne 、 4-碘三氟甲苯 在 1-oxo-1-[5-(2-pyridyl)oxazol-2-yl]-7-(4-(trifluoromethyl)phenyl)hept-6-yne 、 SiO2 作用下， 以PTLC (SiO2, 50% EtOAc-hexanes) afforded 4z (28 mg, 0.070 mmol, 60%) as a yellow solid的产率得到
  参考文献：
  名称：

  TRICYCLIC INHIBITORS OF FATTY ACID AMIDE HYDROLASE

  摘要：

  本发明揭示了一系列取代的噁唑化合物，其中在2位具有α-酮基侧链，在5位具有芳香、杂芳或杂环取代基。这些化合物表现出脂肪酸酰胺水解酶的抑制作用，并且对于治疗涉及该酶的恶性状况是有用的。

  公开号：

  US20100216750A1

文献信息

• US8124778B2
  申请人：——

  公开号：US8124778B2

  公开（公告）日：2012-02-28
• [EN] TRICYCLIC INHIBITORS OF FATTY ACID AMIDE HYDROLASE<br/>[FR] INHIBITEURS TRICYCLIQUES DE L'HYDROLASE AMIDE DES ACIDES GRAS FAAH
  申请人：BOGER DALE L

  公开号：WO2008150492A1

  公开（公告）日：2008-12-11

  [EN] A series of substituted oxazole compounds having an alpha keto side chain at the 2 position and an aromatic, heteroaromatic or heterocycle substituent at the 5 position are disclosed. These compounds exhibit inhibition of fatty acid amid hydrolase and are useful for treatment of malconditions involving that enzyme.
  [FR] La présente invention concerne une série de composés d'oxazole substitués comprenant une chaîne latérale alpha céto en position 2 et un substituant aromatique, hétéroaromatique ou hétérocyclique en position 5. Ces composés présentent une inhibition de l'enzyme FAAH et sont utiles pour le traitement de troubles impliquant cette enzyme.
• 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.
• TRICYCLIC INHIBITORS OF FATTY ACID AMIDE HYDROLASE
  申请人：Boger Dale L.

  公开号：US20100216750A1

  公开（公告）日：2010-08-26

  A series of substituted oxazole compounds having an alpha keto side chain at the 2 position and an aromatic, heteroaromatic or heterocycle substituent at the 5 position are disclosed. These compounds exhibit inhibition of fatty acid amid hydrolase and arc useful for treatment of malconditions involving that enzyme.

  本发明揭示了一系列取代的噁唑化合物，其中在2位具有α-酮基侧链，在5位具有芳香、杂芳或杂环取代基。这些化合物表现出脂肪酸酰胺水解酶的抑制作用，并且对于治疗涉及该酶的恶性状况是有用的。