undec-10-yn-1-yl isocyanate | 1245740-29-7

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: undec-10-yn-1-yl isocyanate
• 英文别名: 11-isocyanatoundec-1-yne；11-Isocyanato-undec-1-yne
• CAS: 1245740-29-7
• 化学式: C₁₂H₁₉NO
• 分子量: 193.289
• InChiKey: QMTBATGUEDMBPU-UHFFFAOYSA-N

物化性质

• 沸点：
  265.5±13.0 °C(Predicted)
• 密度：
  0.85±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  14
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  29.4
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1‐(3‐hydroxyphenyl)‐1H‐pyrrole‐3‐carboxamide 、 undec-10-yn-1-yl isocyanate 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 以78%的产率得到ST3911
  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：

  undec-10-yn-1-yl methanesulfonate 在 iron(III) chloride 、 sodium azide 、 碳酸氢钠 、 sodium iodide 作用下， 以 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 5.42h， 生成 undec-10-yn-1-yl isocyanate
  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。
• Development of Potent Inhibitors of Fatty Acid Amide Hydrolase Useful for the Treatment of Neuropathic Pain
  作者：Margherita Brindisi、Giuseppe Borrelli、Simone Brogi、Alessandro Grillo、Samuele Maramai、Marco Paolino、Mascia Benedusi、Alessandra Pecorelli、Giuseppe Valacchi、Lorenzo Di Cesare Mannelli、Carla Ghelardini、Marco Allarà、Alessia Ligresti、Patrizia Minetti、Giuseppe Campiani、Vincenzo di Marzo、Stefania Butini、Sandra Gemma

  DOI：10.1002/cmdc.201800397

  日期：2018.10.8

  6‐oxo‐5,6‐dihydro‐4H‐benzo[f]pyrrolo[1,2‐a][1,4]diazepin‐9‐yl‐6‐phenylhexylcarbamate (5 h) and 4‐oxo‐5,6‐dihydro‐4H‐benzo[f]pyrrolo[1,2‐a][1,4]diazepin‐9‐yl‐(6‐phenylhexyl)carbamate (5 i) (nanomolar FAAH inhibitors, the latter of which also shows micromolar affinity at the CB1R), were selected for further studies. Results of cell‐based studies on a neuroblastoma cell line (IMR32) demonstrated 5 h, 5 i, and

  脂肪酸酰胺水解酶（FAAH）在终止内源性大麻素（EC）信号传导中的独特作用支持了其作为治疗靶标的相关性。EC代谢酶的抑制引起大麻素受体（CBR）的间接激动作用，并且缺乏精神治疗作用。基于我们以前的配体，并针对发现新的选择性FAAH抑制剂，我们开发了一系列以功能化三环骨架为特征的12种新化合物。所有已开发的化合物对单酰基甘油脂肪酶（MAGL）和CBR的活性均可以忽略不计。新开发的系列中最有效的FAAH抑制剂6-氧代-5,6-二氢-4 H-苯并[ f ]吡咯并[1,2- a ] [1,4]二氮杂pin-9-基-6-苯基己基氨基甲酸酯（5小时）和4-氧代-5,6-二氢-4 H-苯并[ f ]吡咯并[1,2- a ] [1,4]二氮杂pin-9-基-（6-苯基己基）氨基甲酸酯（5 i）（纳摩尔选择FAAH抑制剂（后者在CB 1 R处也显示微摩尔亲和力）进行进一步研究。对神经母细胞瘤细胞系（IMR32）进行的基于细胞的研究结果表明，5
• 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。
• 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.