1-(3-hydroxyphenyl)-1H-pyrrole-3-carboxylic acid | 1245740-11-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 1-(3-hydroxyphenyl)-1H-pyrrole-3-carboxylic acid
• 英文别名: 1-(3-hydroxy-phenyl)-1H-pyrrole-3-carboxylic acid；1-(3-hydroxyphenyl)pyrrole-3-carboxylic acid
• CAS: 1245740-11-7
• 化学式: C₁₁H₉NO₃
• 分子量: 203.197
• InChiKey: FAZPMZAHJWIEIG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  62.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(3-hydroxyphenyl)-1H-pyrrole-3-carboxylic acid 在 氯化亚砜 、 ammonium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 7.0h， 以57%的产率得到1‐(3‐hydroxyphenyl)‐1H‐pyrrole‐3‐carboxamide
  参考文献：
  名称：

  [EN] CARBAMATE DERIVATIVES IN PARTICULAR FOR THE TREATMENT OF NEUROLOGICAL DISORDERS
  [FR] DÉRIVÉS CARBAMATES EN PARTICULIER POUR LE TRAITEMENT DE TROUBLES NEUROLOGIQUES

  摘要：

  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。

  公开号：

  WO2010105930A1
• 作为产物：
  描述：

  2,5-二甲氧基-3-四氢呋喃缩醛 在 silver nitrate 、 溶剂黄146 、 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 1.25h， 生成 1-(3-hydroxyphenyl)-1H-pyrrole-3-carboxylic acid
  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

• 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。
• Pioneering first‐in‐class FAAH‐HDAC inhibitors as potential multitarget neuroprotective agents
  作者：Alessandro Papa、Ilaria Cursaro、Luca Pozzetti、Chiara Contri、Martina Cappello、Silvia Pasquini、Gabriele Carullo、Anna Ramunno、Sandra Gemma、Katia Varani、Stefania Butini、Giuseppe Campiani、Fabrizio Vincenzi

  DOI：10.1002/ardp.202300410

  日期：2023.12

  epigenetic machinery, we selected the fatty acid amide hydrolase (FAAH) and histone deacetylase (HDAC) enzymes as desired targets to develop potential neuroprotective multitarget-directed ligands (MTDLs), expecting to achieve an additive or synergistic therapeutic effect in oxidative stress-related conditions. We herein report the design, synthesis, and biological evaluation of the first-in-class FAAH-HDAC

  为了同时调节内源性大麻素系统（ECS）功能和表观遗传机制，我们选择脂肪酸酰胺水解酶（FAAH）和组蛋白脱乙酰酶（HDAC）作为所需靶标，以开发潜在的神经保护性多靶点定向配体（MTDL），期望在氧化应激相关病症中实现附加或协同治疗效果。我们在此报告了一流的 FAAH-HDAC 多靶点抑制剂的设计、合成和生物学评价。应用药效团合并策略，产生基于 1-苯基吡咯的化合物4a–j 。使用 1321N1人星形细胞瘤细胞和 SHSY5人神经元细胞，在氧化应激模型中测试了性能最佳的化合物（ 4c 、 4f和4h ）的神经保护特性。在我们的初步研究中，化合物4h脱颖而出，对所选靶点表现出平衡的纳摩尔抑制活性，并且在体外优于标准抗氧化剂N-乙酰半胱氨酸。与4f一起， 4h还能够保护 1321N1 细胞免受叔丁基过氧化氢或谷氨酸损伤。我们的研究可能为开发针对 ECS 和表观遗传酶的新型 MTDL 提供基础。
• [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。
• Discovery of Potent Inhibitors of Human and Mouse Fatty Acid Amide Hydrolases
  作者：Stefania Butini、Margherita Brindisi、Sandra Gemma、Patrizia Minetti、Walter Cabri、Grazia Gallo、Silvia Vincenti、Emanuela Talamonti、Franco Borsini、Antonio Caprioli、Maria Antonietta Stasi、Stefano Di Serio、Sindu Ros、Giuseppe Borrelli、Samuele Maramai、Filomena Fezza、Giuseppe Campiani、Mauro Maccarrone

  DOI：10.1021/jm300689c

  日期：2012.8.9

  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.