cyclohexylcarbamic acid 3′-acetyl-6-benzyloxybiphenyl-3-yl ester | 1446086-60-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: cyclohexylcarbamic acid 3′-acetyl-6-benzyloxybiphenyl-3-yl ester
• 英文别名: [3-(3-acetylphenyl)-4-phenylmethoxyphenyl] N-cyclohexylcarbamate
• CAS: 1446086-60-7
• 化学式: C₂₈H₂₉NO₄
• 分子量: 443.543
• InChiKey: SHJCRAREHXJBNJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  cyclohexylcarbamic acid 3′-acetyl-6-benzyloxybiphenyl-3-yl ester 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 、 乙酸乙酯 为溶剂， 反应 4.0h， 以50%的产率得到cyclohexylcarbamic acid 6-hydroxy-3′-(1-hydroxyethyl)-biphenyl-3-yl ester
  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：

  4-苄氧基-3-溴苯酚 在 四(三苯基膦)钯 、 sodium carbonate 、 三乙胺 作用下， 以 甲苯 、 乙腈 为溶剂， 反应 17.0h， 生成 cyclohexylcarbamic acid 3′-acetyl-6-benzyloxybiphenyl-3-yl ester
  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

• 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.