undec-10-ynyl-1-(3-hydroxyphenyl)-1H-pyrrole-3-carboxylate | 1245740-27-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: undec-10-ynyl-1-(3-hydroxyphenyl)-1H-pyrrole-3-carboxylate
• 英文别名: 1-(3-hydroxy-phenyl)-1H-pyrrole-3-carboxylic acid undec-10-ynyl ester；undec-10-ynyl 1-(3-hydroxyphenyl)pyrrole-3-carboxylate
• CAS: 1245740-27-5
• 化学式: C₂₂H₂₇NO₃
• 分子量: 353.461
• InChiKey: GBSRMJBBZOHYDJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  26
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  51.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  undec-10-ynyl-1-(3-hydroxyphenyl)-1H-pyrrole-3-carboxylate 、 环己基异氰酸酯 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 以83%的产率得到(3-(3-((undec-10-ynyloxy)carbonyl)-1H-pyrrol-1-yl)phenoxycarbonyl)cyclohexylamine
  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 偶氮二甲酸二异丙酯 、 silver nitrate 、 溶剂黄146 、 三苯基膦 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 49.25h， 生成 undec-10-ynyl-1-(3-hydroxyphenyl)-1H-pyrrole-3-carboxylate
  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

文献信息

• [EN] CARBAMATE DERIVATIVES IN PARTICULAR FOR THE TREATMENT OF NEUROLOGICAL DISORDERS<br/>[FR] DÉRIVÉS CARBAMATES EN PARTICULIER POUR LE TRAITEMENT DE TROUBLES NEUROLOGIQUES
  申请人：SIGMA TAU IND FARMACEUTI

  公开号：WO2010105930A1

  公开（公告）日：2010-09-23

  The present invention relates to new carbamate derivatives of formula I, processes for their preparation, and to pharmaceutical compositions containing them for the treatment of neurological disorders, such as neuropathic pain and anxiety.

  本发明涉及一类新的氨基甲酸衍生物，其化学式为I，包括它们的制备方法，以及包含这些化合物的药物组合物，用于治疗神经系统疾病，如神经性疼痛和焦虑。
• CARBAMATE DERIVATIVES IN PARTICULAR FOR THE TREATMENT OF NEUROLOGICAL DISORDERS
  申请人：Cabri Walter

  公开号：US20120252865A1

  公开（公告）日：2012-10-04

  The present invention relates to new carbamate derivatives of formula I, processes for their preparation, and to pharmaceutical compositions containing them for the treatment of neurological disorders, such as neuropathic pain and anxiety.

  本发明涉及一种新的I式碳酸酯衍生物，其制备方法以及含有该衍生物的制药组合物，用于治疗神经系统疾病，如神经病性疼痛和焦虑症。