2,5-dimethoxytetrahydrofuran-3-carbonitrile | 81644-23-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氧唑烯
• 英文名称: 2,5-dimethoxytetrahydrofuran-3-carbonitrile
• 英文别名: 2,5-dimethoxyoxolane-3-carbonitrile
• CAS: 81644-23-7
• 化学式: C₇H₁₁NO₃
• 分子量: 157.169
• InChiKey: DPQYTBQXZDLFLQ-UHFFFAOYSA-N

物化性质

• 沸点：
  262.8±40.0 °C(Predicted)
• 密度：
  1.11±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  51.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2,5-dimethoxytetrahydrofuran-3-carbonitrile 在 盐酸 、 双氧水 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 为溶剂， 反应 28.0h， 生成 (3-(3-carbamoyl-1H-pyrrol-1-yl)phenoxycarbonyl)(2-(2-phenoxyethoxy)ethyl)amine
  参考文献：
  名称：

  Discovery of Potent Inhibitors of Human and Mouse Fatty Acid Amide Hydrolases

  摘要：

  Fatty acid amide hydrolase (FAAH, EC 3.5.1.99) is the main enzyme catabolizing endocannabinoid fatty acid amides. FAAH inactivation promotes beneficial effects upon pain and anxiety without the side effects accompanying agonists of type-1 cannabinoid receptors. Aiming at discovering new selective FAAH inhibitors, we developed a series of compounds (5a-u) characterized by a functionalized heteroaromatic scaffold. Particularly, 5c and 5d were identified as extremely potent, noncompetitive, and reversible FAAH inhibitors endowed with a remarkable selectivity profile and lacking interaction with the hERG channels. In vivo antinociceptive activity was demonstrated for 5c, 5d, and 5n at a dose much lower than that able to induce either striatal and limbic stereotypies or anxiolytic activity, thus outlining their potential to turn into optimum preclinical candidates. Aiming at improving pharmacokinetic properties and metabolic stability of 5d, we developed a subset of nanomolar dialyzable FAAH inhibitors (5v-z), functionalized by specific polyethereal lateral chains and fluorinated aromatic rings.

  DOI：

  10.1021/jm300689c
• 作为产物：
  描述：

  2,5-二甲氧基-3-四氢呋喃缩醛 在 ammonium hydroxide 作用下， 以 四氢呋喃 为溶剂， 以36 %的产率得到2,5-dimethoxytetrahydrofuran-3-carbonitrile
  参考文献：
  名称：

  WO2023/72913

  摘要：

  公开号：

文献信息

• Selective Fatty Acid Amide Hydrolase Inhibitors as Potential Novel Antiepileptic Agents
  作者：Alessandro Grillo、Filomena Fezza、Giulia Chemi、Roberto Colangeli、Simone Brogi、Domenico Fazio、Stefano Federico、Alessandro Papa、Nicola Relitti、Roberto Di Maio、Gianluca Giorgi、Stefania Lamponi、Massimo Valoti、Beatrice Gorelli、Simona Saponara、Mascia Benedusi、Alessandra Pecorelli、Patrizia Minetti、Giuseppe Valacchi、Stefania Butini、Giuseppe Campiani、Sandra Gemma、Mauro Maccarrone、Giuseppe Di Giovanni

  DOI：10.1021/acschemneuro.1c00192

  日期：2021.5.5

  antiepileptic effects, devoid of psychotropic effects. We herein report the discovery of selective anandamide catabolic enzyme fatty acid amide hydrolase (FAAH) inhibitors with promising antiepileptic efficacy, starting from a further investigation of our prototypical inhibitor 2a. When tested in two rodent models of epilepsy, 2a reduced the severity of the pilocarpine-induced status epilepticus and the elongation

  颞叶癫痫是癫痫的最常见形式，目前的抗癫痫药对许多患者无效。内源性大麻素系统与癫痫发作的按需保护反应有关。阻断内源性大麻素分解代谢将引起抗癫痫作用，而没有精神作用。我们从对我们的原型抑制剂2a的进一步研究开始，报告了发现具有前途抗癫痫功效的选择性anandamide分解代谢酶脂肪酸酰胺水解酶（FAAH）抑制剂的发现。在两个啮齿动物癫痫模型中进行测试时，2a降低了毛果芸香碱引起的癫痫持续状态的严重性以及海马最大齿状激活的延长。值得注意的是，2a没有影响海马齿状回的长期突触可塑性。这些数据促使我们进一步努力，旨在发现新的抗癫痫药，开发出一套新的FAAH抑制剂（3a – m）。生物学研究强调3h和3m是表现最好的类似物，有待进一步研究。在基于细胞的研究中，使用成神经细胞瘤细胞系3h和3m可以通过降低NF-kB p65的DNA结合活性来减少恶性炎症状态，而没有细胞毒性作用。在3小时内排除了有害的心脏
• Identification of a novel arylpiperazine scaffold for fatty acid amide hydrolase inhibition with improved drug disposition properties
  作者：Stefania Butini、Sandra Gemma、Margherita Brindisi、Samuele Maramai、Patrizia Minetti、Diana Celona、Raffaella Napolitano、Franco Borsini、Walter Cabri、Filomena Fezza、Lucio Merlini、Sabrina Dallavalle、Giuseppe Campiani、Mauro Maccarrone

  DOI：10.1016/j.bmcl.2012.11.035

  日期：2013.1

  We herein describe the systematic approach used to develop new analogues of compound 2, recently identified as a potent and selective fatty acid amide hydrolase (FAAH) inhibitor. Aiming at identifying new scaffolds endowed with improved drug disposition properties with respect to the phenylpyrrole-based lead, we subjected it to two different structural modification strategies. This process allowed the identification of derivatives 4b and 5c as potent, reversible and non-competitive FAAH inhibitors. (C) 2012 Published by Elsevier Ltd.