3-(3,5-dibenzyloxyphenyl)benzamide | 1425459-47-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-(3,5-dibenzyloxyphenyl)benzamide
• 英文别名: 3-(3,5-Dibenzyloxyphenyl)benzamide；3-[3,5-bis(phenylmethoxy)phenyl]benzamide
• CAS: 1425459-47-7
• 化学式: C₂₇H₂₃NO₃
• 分子量: 409.485
• InChiKey: XXYVIVXHJDQNDT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  61.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(3,5-dibenzyloxyphenyl)benzamide 在 palladium 10% on activated carbon 、 copper(l) chloride 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 、 环己烯 为溶剂， 反应 2.5h， 生成 [3-(3-carbamoylphenyl)-5-hydroxy-phenyl]-N-cyclohexylcarbamate
  参考文献：
  名称：

  Synthesis and Structure–Activity Relationship Studies of O-Biphenyl-3-yl Carbamates as Peripherally Restricted Fatty Acid Amide Hydrolase Inhibitors

  摘要：

  The peripherally restricted fatty acid amide hydrolase (FAAH) inhibitor URB937 (3, cyclohexylcarbamic acid 3'-carbamoyl-6-hydroxybiphenyl-3-yl ester) is extruded from the brain and spinal cord by the Abcg2 efflux transporter. Despite its inability to enter the central nervous system (CNS), 3 exerts profound antinociceptive effects in mice and rats, which result from the inhibition of FAAH in peripheral tissues and the consequent enhancement of anandamide signaling at CB1 cannabinoid receptors localized on sensory nerve endings. In the present study, we examined the structure-activity relationships (SAP.) for the biphenyl region of compound 3, focusing on the carbamoyl and hydroxyl groups in the distal and proximal phenyl rings. Our SAR studies generated a new series of peripherally restricted FAAH inhibitors and identified compound 35 (cyclohexylcarbamic acid 3'-carbamoyl-5-hydroxybiphenyl-3-yl ester) as the most potent brain-impermeant FAAH inhibitor disclosed to date.

  DOI：

  10.1021/jm4007017
• 作为产物：
  描述：

  1-溴-3,5-二氟苯 在 palladium diacetate 、 potassium carbonate 、 sodium t-butanolate 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.33h， 生成 3-(3,5-dibenzyloxyphenyl)benzamide
  参考文献：
  名称：

  Synthesis and Structure–Activity Relationship Studies of O-Biphenyl-3-yl Carbamates as Peripherally Restricted Fatty Acid Amide Hydrolase Inhibitors

  摘要：

  The peripherally restricted fatty acid amide hydrolase (FAAH) inhibitor URB937 (3, cyclohexylcarbamic acid 3'-carbamoyl-6-hydroxybiphenyl-3-yl ester) is extruded from the brain and spinal cord by the Abcg2 efflux transporter. Despite its inability to enter the central nervous system (CNS), 3 exerts profound antinociceptive effects in mice and rats, which result from the inhibition of FAAH in peripheral tissues and the consequent enhancement of anandamide signaling at CB1 cannabinoid receptors localized on sensory nerve endings. In the present study, we examined the structure-activity relationships (SAP.) for the biphenyl region of compound 3, focusing on the carbamoyl and hydroxyl groups in the distal and proximal phenyl rings. Our SAR studies generated a new series of peripherally restricted FAAH inhibitors and identified compound 35 (cyclohexylcarbamic acid 3'-carbamoyl-5-hydroxybiphenyl-3-yl ester) as the most potent brain-impermeant FAAH inhibitor disclosed to date.

  DOI：

  10.1021/jm4007017

文献信息

• META-SUBSTITUTED BIPHENYL PERIPHERALLY RESTRICTED FAAH INHIBITORS
  申请人：The Regents of the University of California

  公开号：US20140288170A1

  公开（公告）日：2014-09-25

  The present invention provides methods of making and using peripherally restricted inhibitors of fatty acid amide hydrolase (FAAH). The present invention provides compounds and compositions that suppress FAAH activity and increases anandamide levels outside the central nervous system (CNS). The present invention also sets forth methods for inhibiting FAAH as well as methods for treating conditions such as, but not limited to, pain, inflammation, immune disorders, dermatitis, mucositis, the over reactivity of peripheral sensory neurons, neurodermatitis, and an overactive bladder. Accordingly, the invention also provides compounds, methods, and pharmaceutical compositions for treating conditions in which the selective inhibition of peripheral FAAH (as opposed to CNS FAAH) would be of benefit.

  本发明提供了制备和使用周边限制性脂肪酸酰胺水解酶（FAAH）抑制剂的方法。本发明提供了抑制FAAH活性并增加中枢神经系统（CNS）外的芳香酰胺水平的化合物和组合物。本发明还提出了抑制FAAH的方法以及治疗疼痛、炎症、免疫紊乱、皮炎、口腔炎、周围感觉神经过度反应、神经性皮炎和过度活跃膀胱等疾病的方法。因此，本发明还提供了用于治疗选择性抑制周围FAAH（而不是CNS FAAH）将有益的情况下的化合物、方法和制药组合物。
• [EN] META-SUBSTITUTED BIPHENYL PERIPHERALLY RESTRICTED FAAH INHIBITORS<br/>[FR] INHIBITEURS DE LA FAAH RESTREINTS DE MANIÈRE PÉRIPHÉRIQUE SUBSTITUÉS EN POSITION MÉTA PAR UN BIPHÉNYLE
  申请人：UNIV CALIFORNIA

  公开号：WO2013028570A3

  公开（公告）日：2013-04-18
• Synthesis and Structure–Activity Relationship Studies of <i>O</i>-Biphenyl-3-yl Carbamates as Peripherally Restricted Fatty Acid Amide Hydrolase Inhibitors
  作者：Guillermo Moreno-Sanz、Andrea Duranti、Laurin Melzig、Claudio Fiorelli、Gian Filippo Ruda、Giampiero Colombano、Paola Mestichelli、Silvano Sanchini、Andrea Tontini、Marco Mor、Tiziano Bandiera、Rita Scarpelli、Giorgio Tarzia、Daniele Piomelli

  DOI：10.1021/jm4007017

  日期：2013.7.25

  The peripherally restricted fatty acid amide hydrolase (FAAH) inhibitor URB937 (3, cyclohexylcarbamic acid 3'-carbamoyl-6-hydroxybiphenyl-3-yl ester) is extruded from the brain and spinal cord by the Abcg2 efflux transporter. Despite its inability to enter the central nervous system (CNS), 3 exerts profound antinociceptive effects in mice and rats, which result from the inhibition of FAAH in peripheral tissues and the consequent enhancement of anandamide signaling at CB1 cannabinoid receptors localized on sensory nerve endings. In the present study, we examined the structure-activity relationships (SAP.) for the biphenyl region of compound 3, focusing on the carbamoyl and hydroxyl groups in the distal and proximal phenyl rings. Our SAR studies generated a new series of peripherally restricted FAAH inhibitors and identified compound 35 (cyclohexylcarbamic acid 3'-carbamoyl-5-hydroxybiphenyl-3-yl ester) as the most potent brain-impermeant FAAH inhibitor disclosed to date.