2-[1-(tert-butyldimethylsilyloxy)-7-phenylheptyl]oxazole-5-carboxylic acid methyl ester | 914482-91-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-[1-(tert-butyldimethylsilyloxy)-7-phenylheptyl]oxazole-5-carboxylic acid methyl ester
• 英文别名: methyl 2-(1-(tert-butyldimethylsilyloxy)-7-phenylheptyl)oxazole-5-carboxylate；Methyl 2-(1-(tert-butyldimethylsiloxy)-7-phenylheptyl)oxazole-5-carboxylate；methyl 2-[1-[tert-butyl(dimethyl)silyl]oxy-7-phenylheptyl]-1,3-oxazole-5-carboxylate
• CAS: 914482-91-0
• 化学式: C₂₄H₃₇NO₄Si
• 分子量: 431.648
• InChiKey: LSEABXXQPORODB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.72
• 重原子数：
  30
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  61.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-[1-(tert-butyldimethylsilyloxy)-7-phenylheptyl]oxazole-5-carboxylic acid methyl ester 在 lithium hydroxide 、 N-羟基-7-氮杂苯并三氮唑 、 四丁基氟化铵 、 戴斯-马丁氧化剂 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.17h， 生成
  参考文献：
  名称：

  Delineation of a Fundamental α-Ketoheterocycle Substituent Effect for Use in the Design of Enzyme Inhibitors

  摘要：

  The synthesis and examination of a systematic series of 5-substituted 2-keto oxazoles as inhibitors of fatty acid amide hydrolase (FAAH) defined a fundamental substituent effect that led to the discovery of inhibitors with Ki's as low as 400 pM. The intrinsic basis of the relationship (-log Ki vs sigmap), which relates Ki with the Hammett sigmap constant of the substituent, the magnitude of the effect (rho = 3.01), and its predictive value (R2 = 0.91) suggest a widespread applicability in studies beyond FAAH.

  DOI：

  10.1021/ja064522b
• 作为产物：
  描述：

  7-phenylheptanal 在 咪唑 、 甲醇 、 硼烷四氢呋喃络合物 、 叔丁基锂 作用下， 以 四氢呋喃 、 甲苯 、 Petroleum ether 、 正戊烷 为溶剂， 反应 3.5h， 生成 2-[1-(tert-butyldimethylsilyloxy)-7-phenylheptyl]oxazole-5-carboxylic acid methyl ester
  参考文献：
  名称：

  Delineation of a Fundamental α-Ketoheterocycle Substituent Effect for Use in the Design of Enzyme Inhibitors

  摘要：

  The synthesis and examination of a systematic series of 5-substituted 2-keto oxazoles as inhibitors of fatty acid amide hydrolase (FAAH) defined a fundamental substituent effect that led to the discovery of inhibitors with Ki's as low as 400 pM. The intrinsic basis of the relationship (-log Ki vs sigmap), which relates Ki with the Hammett sigmap constant of the substituent, the magnitude of the effect (rho = 3.01), and its predictive value (R2 = 0.91) suggest a widespread applicability in studies beyond FAAH.

  DOI：

  10.1021/ja064522b
• 作为试剂：
  描述：

  2-(1-(tert-butyldimethylsilyloxy)-7-phenylheptyl)oxazole-5-carboxylic acid 、 甲苯 、 三甲基硅烷化重氮甲烷 、 溶剂黄146 在 乙酸乙酯 、 碳酸氢钠 、 氯化钠 、 Sodium sulfate-III 、 2-[1-(tert-butyldimethylsilyloxy)-7-phenylheptyl]oxazole-5-carboxylic acid methyl ester 、 EtOAc hexanes 作用下， 以 甲醇 为溶剂， 反应 0.5h， 以to afford the pure ester as a clear oil (225 mg, 78%)的产率得到2-[1-(tert-butyldimethylsilyloxy)-7-phenylheptyl]oxazole-5-carboxylic acid methyl ester
  参考文献：
  名称：

  Substituted oxazole ketone modulators of fatty acid amide hydrolase

  摘要：

  本文描述了某些噁唑酮化合物，这些化合物可用作FAAH抑制剂。这些化合物可以用于制备药物组合物和治疗由脂肪酸酰胺水解酶（FAAH）活性介导的疾病状态、紊乱和病况的方法。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（如多发性硬化等）。

  公开号：

  US20100075931A1

文献信息

• Potent and Selective α-Ketoheterocycle-Based Inhibitors of the Anandamide and Oleamide Catabolizing Enzyme, Fatty Acid Amide Hydrolase
  作者：F. Anthony Romero、Wu Du、Inkyu Hwang、Thomas J. Rayl、F. Scott Kimball、Donmienne Leung、Heather S. Hoover、Richard L. Apodaca、J. Guy Breitenbucher、Benjamin F. Cravatt、Dale L. Boger

  DOI：10.1021/jm0611509

  日期：2007.3.1

  with these studies, the effect of substitution on the pyridine ring of 2f was also examined. A series of small, nonaromatic C5-substituents was also explored and revealed that the K(i) follows a well-defined correlation with the Hammett sigma(p) constant (rho = 3.01, R2 = 0.91) in which electron-withdrawing substituents enhance potency, leading to inhibitors with K(i)s as low as 400 pM (20n). Proteomic-wide

  针对2f（OL-135）（一种有效的脂肪酸酰胺水解酶（FAAH）抑制剂）的结构-活性关系（SAR）进行了详细研究，其目标是恶唑的5位。对一系列取代苯衍生物（12-14）的研究表明，最佳取代位置是间位，所选成员的效价接近或超过2f。与这些研究同时，还研究了取代对2f的吡啶环的影响。还研究了一系列小的非芳香族C5取代基，发现K（i）与Hammett sigma（p）常数（rho = 3.01，R2 = 0.91）具有明确定义的相关性，吸电子取代基增强效力，导致抑制剂的K（i）s低至400 pM（20n）。
• WO2008/30532
  申请人：——

  公开号：——

  公开（公告）日：——
• Delineation of a Fundamental α-Ketoheterocycle Substituent Effect for Use in the Design of Enzyme Inhibitors
  作者：F. Anthony Romero、Inkyu Hwang、Dale L. Boger

  DOI：10.1021/ja064522b

  日期：2006.11.1

  The synthesis and examination of a systematic series of 5-substituted 2-keto oxazoles as inhibitors of fatty acid amide hydrolase (FAAH) defined a fundamental substituent effect that led to the discovery of inhibitors with Ki's as low as 400 pM. The intrinsic basis of the relationship (-log Ki vs sigmap), which relates Ki with the Hammett sigmap constant of the substituent, the magnitude of the effect (rho = 3.01), and its predictive value (R2 = 0.91) suggest a widespread applicability in studies beyond FAAH.
• Substituted oxazole ketone modulators of fatty acid amide hydrolase
  申请人：Boger Dale L.

  公开号：US20100075931A1

  公开（公告）日：2010-03-25

  Certain oxazole ketone compounds are described, which are useful as FAAH inhibitors. Such compounds may be used in pharmaceutical compositions and methods for the treatment of 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).

  本文描述了某些噁唑酮化合物，这些化合物可用作FAAH抑制剂。这些化合物可以用于制备药物组合物和治疗由脂肪酸酰胺水解酶（FAAH）活性介导的疾病状态、紊乱和病况的方法。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（如多发性硬化等）。