7-(4-methoxyphenyl)-6-heptenoic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 7-(4-methoxyphenyl)-6-heptenoic acid
• 英文别名: 7-(4-methoxyphenyl)hept-6-enoic acid
• 化学式: C₁₄H₁₈O₃
• 分子量: 234.295
• InChiKey: DORRNSYZGSHRDC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.35
• 重原子数：
  17.0
• 可旋转键数：
  7.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  46.53
• 氢给体数：
  1.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  7-(4-methoxyphenyl)-6-heptenoic acid 在 palladium on activated charcoal 氢气 、 三乙胺 作用下， 反应 0.75h， 生成 Ethoxycarbonyl 7-(4-methoxyphenyl)heptanoate
  参考文献：
  名称：

  在犬第二代幼虫中与哌酰胺有关的芳烷基和芳烯基酰胺的合成和杀线活性。

  摘要：

  合成了与哌啶相关的79个芳烷基和芳烯基酰胺，并研究了它们对犬round虫Toxocara canis的第二级幼虫的杀线虫活性。活性很大程度上取决于烷基链的长度和胺部分的性质，但是几乎不受链中是否存在双键的影响。在一系列同系物中表现出最强活性的烷基链长，对于吡咯烷酰胺为m = 11，对于N-甲基哌嗪酰胺为m = 13。尽管在所测试的同系物中，哌啶（3，4-亚甲基二氧苯基同系物）显示出最强的活性，但是芳环上的甲氧基取代基对该活性没有太大影响。然而，甲氧基向羟基的转化大大降低了活性并缩短了链长，从而提供了最强的活性。计算出的非酚芳基哌啶的log P值在3.5至4.5范围内，而羟苯基哌啶的log P值较小，表明酚和非酚化合物的杀线活性涉及不同的机理。

  DOI：

  10.1248/cpb.45.685
• 作为产物：
  描述：

  6-溴己酸 在 potassium tert-butylate 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 20.0h， 生成 7-(4-methoxyphenyl)-6-heptenoic acid
  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

• Synthesis, biological evaluation, and structure activity relationship (SAR) study of pyrrolidine amide derivatives as <i>N</i>-acylethanolamine acid amidase (NAAA) inhibitors
  作者：Pan Zhou、Lei Xiang、Dongsheng Zhao、Jie Ren、Yan Qiu、Yuhang Li

  DOI：10.1039/c8md00432c

  日期：——

  N-Acylethanolamine acid amidase (NAAA) is one of the key enzymes involved in the degradation of fatty acid ethanolamides (FAEs), especially for palmitoylethanolamide (PEA). Pharmacological blockage of NAAA restores PEA levels, providing therapeutic benefits in the management of inflammation and pain. In the current work, we showed the structure-activity relationship (SAR) studies for pyrrolidine amide

  N-酰基乙醇胺酸酰胺酶（NAAA）是参与脂肪酸乙醇酰胺（FAE）降解的关键酶之一，尤其是对于棕榈酰乙醇酰胺（PEA）而言。NAAA的药理学阻断作用可恢复PEA水平，从而在炎症和疼痛的治疗中提供治疗益处。在当前的工作中，我们显示了吡咯烷酰胺衍生物作为NAAA抑制剂的结构-活性关系（SAR）研究。检查了吡咯烷酰胺的末端苯基的一系列芳族取代基或取代基。SAR数据表明，较小的亲脂性3-苯基取代基对于最佳效用是优选的。构象柔性的接头增加了吡咯烷酰胺衍生物的抑制能力，但降低了其对脂肪酸酰胺水解酶（FAAH）的选择性。构象上受限的接头没有增强抑制剂对NAAA的效力，但是改善了对FAAH的选择性。开发了几种低微摩尔有效的NAAA抑制剂，其中包括带有刚性4-苯基肉桂酰基的4g。透析和动力学分析表明4g通过竞争和可逆的机制抑制NAAA。此外，4g在脂多糖（LPS）诱导的急性肺损伤（ALI）模型中显示出较高的抗
• Anodic coupling of carboxylic acids to electron-rich double bonds: A surprising non-Kolbe pathway to lactones
  作者：Robert J Perkins、Hai-Chao Xu、John M Campbell、Kevin D Moeller

  DOI：10.3762/bjoc.9.186

  日期：——

  Carboxylic acids have been electro-oxidatively coupled to electron-rich olefins to form lactones. Kolbe decarboxylation does not appear to be a significant competing pathway. Experimental results indicate that oxidation occurs at the olefin and that the reaction proceeds through a radical cation intermediate.

  羧酸已与富电子烯烃电氧化偶联以形成内酯。Kolbe 脱羧似乎不是一个重要的竞争途径。实验结果表明氧化发生在烯烃处，反应通过自由基阳离子中间体进行。
• 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.
• Crude Drugs Effective on Visceral Larva Migrans. Part XVIII. Synthesis and Nematocidal Activity of Aralkyl- and Aralkenylamides Related to Piperamide on Second-Stage Larvae of Toxocara canis.
  作者：Fumiyuki KIUCHI、Norio NAKAMURA、Makiko SAITOH、Kazue KOMAGOME、Hirokuni HIRAMATSU、Noriaki TAKIMOTO、Nobuaki AKAO、Kaoru KONDO、Yoshisuke TSUDA

  DOI：10.1248/cpb.45.685

  日期：——

  piperamides (3,4-methylenedioxyphenyl homologues) showed the strongest activity among the homologues tested, methoxy substituent(s) on the aromatic ring did not have much effect on the activity. However, conversion of the methoxy group to a hydroxy group greatly decreased the activity and shortened the chain length giving the strongest activity. Calculated log P values of non-phenolic aryl-piperamides fell

  合成了与哌啶相关的79个芳烷基和芳烯基酰胺，并研究了它们对犬round虫Toxocara canis的第二级幼虫的杀线虫活性。活性很大程度上取决于烷基链的长度和胺部分的性质，但是几乎不受链中是否存在双键的影响。在一系列同系物中表现出最强活性的烷基链长，对于吡咯烷酰胺为m = 11，对于N-甲基哌嗪酰胺为m = 13。尽管在所测试的同系物中，哌啶（3，4-亚甲基二氧苯基同系物）显示出最强的活性，但是芳环上的甲氧基取代基对该活性没有太大影响。然而，甲氧基向羟基的转化大大降低了活性并缩短了链长，从而提供了最强的活性。计算出的非酚芳基哌啶的log P值在3.5至4.5范围内，而羟苯基哌啶的log P值较小，表明酚和非酚化合物的杀线活性涉及不同的机理。