(3-bromo-4-phenylmethoxyphenyl) N-cyclohexylcarbamate | 1426068-24-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (3-bromo-4-phenylmethoxyphenyl) N-cyclohexylcarbamate
• CAS: 1426068-24-7
• 化学式: C₂₀H₂₂BrNO₃
• 分子量: 404.304
• InChiKey: CUFYJWRHZRPPEP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  47.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (3-bromo-4-phenylmethoxyphenyl) N-cyclohexylcarbamate 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以97%的产率得到cyclohexylcarbamic acid 3-bromo-4-hydroxyphenyl 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：

  环己基异氰酸酯 在 N-溴代丁二酰亚胺(NBS) 、 三乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 32.0h， 生成 (3-bromo-4-phenylmethoxyphenyl) N-cyclohexylcarbamate
  参考文献：
  名称：

  Development of a Multigram Synthesis of URB937, a Peripherally Restricted FAAH Inhibitor

  摘要：

  A new synthetic approach to URB937 was developed starting from the inexpensive and widely available 4-benzyloxyphenol. A reproducible four step procedure, requiring no chromatographic purifications, was optimized that allowed the preparation of 100 g of URB937 in 45% overall yield.

  DOI：

  10.1021/op300301u

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.
• Development of a Multigram Synthesis of URB937, a Peripherally Restricted FAAH Inhibitor
  作者：Claudio Fiorelli、Rita Scarpelli、Daniele Piomelli、Tiziano Bandiera

  DOI：10.1021/op300301u

  日期：2013.3.15

  A new synthetic approach to URB937 was developed starting from the inexpensive and widely available 4-benzyloxyphenol. A reproducible four step procedure, requiring no chromatographic purifications, was optimized that allowed the preparation of 100 g of URB937 in 45% overall yield.