N-[2-(2-methoxyphenyl)ethyl]cyclohexanecarboxamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: N-[2-(2-methoxyphenyl)ethyl]cyclohexanecarboxamide
• 化学式: C₁₆H₂₃NO₂
• mdl: MFCD08724034
• 分子量: 261.364
• InChiKey: AZORKGXHEFBRJM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-[2-(2-methoxyphenyl)ethyl]cyclohexanecarboxamide 在 四磷十氧化物 、 三氯氧磷 作用下， 以 甲苯 为溶剂， 反应 5.0h， 以36%的产率得到1-cyclohexyl-5-methoxy-3,4-dihydroisoquinoline
  参考文献：
  名称：

  Discovery of an 8-methoxytetrahydroisoquinoline derivative as an orally active N-type calcium channel blocker for neuropathic pain without CYP inhibition liability

  摘要：

  In lead optimization efforts starting from the tetrahydroisoquinoline (S)-1, we identified 2-{[(2R)-2-hydroxypropyl]amino}-1-[(1S)-8-methoxy-1-phenyl-3,4-dihydroisoquinolin-2(1H)-yl]ethanone((1S)-8t) as a novel orally active small-molecule N-type calcium channel blocker without CYP inhibition liability. CYP3A4 inhibition profile was improved by reducing the lipophilicity of compound (S)-1. Moreover, introduction of a methoxy group to the C-8 position of tetrahydroisoquinoline led to identification of (1S)-8t, which eliminated CYP2D6 inhibition liability. Oral administration of (1S)-8t exerted efficacy in a rat spinal nerve ligation (SNL) model of neuropathic pain with an ED50 value of 2.8 mg/kg. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.05.053
• 作为产物：
  描述：

  环己甲酰氯 、 2-甲氧基苯乙胺 在 碳酸氢钠 作用下， 以 水 、 乙酸乙酯 为溶剂， 反应 3.0h， 以91%的产率得到N-[2-(2-methoxyphenyl)ethyl]cyclohexanecarboxamide
  参考文献：
  名称：

  Discovery of an 8-methoxytetrahydroisoquinoline derivative as an orally active N-type calcium channel blocker for neuropathic pain without CYP inhibition liability

  摘要：

  In lead optimization efforts starting from the tetrahydroisoquinoline (S)-1, we identified 2-{[(2R)-2-hydroxypropyl]amino}-1-[(1S)-8-methoxy-1-phenyl-3,4-dihydroisoquinolin-2(1H)-yl]ethanone((1S)-8t) as a novel orally active small-molecule N-type calcium channel blocker without CYP inhibition liability. CYP3A4 inhibition profile was improved by reducing the lipophilicity of compound (S)-1. Moreover, introduction of a methoxy group to the C-8 position of tetrahydroisoquinoline led to identification of (1S)-8t, which eliminated CYP2D6 inhibition liability. Oral administration of (1S)-8t exerted efficacy in a rat spinal nerve ligation (SNL) model of neuropathic pain with an ED50 value of 2.8 mg/kg. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.05.053

文献信息

• Discovery of an 8-methoxytetrahydroisoquinoline derivative as an orally active N-type calcium channel blocker for neuropathic pain without CYP inhibition liability
  作者：Takashi Ogiyama、Koichi Yonezawa、Makoto Inoue、Naoko Katayama、Toshihiro Watanabe、Seiji Yoshimura、Takayasu Gotoh、Tetsuo Kiso、Akiko Koakutsu、Shuichiro Kakimoto、Jun-ichi Shishikura

  DOI：10.1016/j.bmc.2015.05.053

  日期：2015.8

  In lead optimization efforts starting from the tetrahydroisoquinoline (S)-1, we identified 2-[(2R)-2-hydroxypropyl]amino}-1-[(1S)-8-methoxy-1-phenyl-3,4-dihydroisoquinolin-2(1H)-yl]ethanone((1S)-8t) as a novel orally active small-molecule N-type calcium channel blocker without CYP inhibition liability. CYP3A4 inhibition profile was improved by reducing the lipophilicity of compound (S)-1. Moreover, introduction of a methoxy group to the C-8 position of tetrahydroisoquinoline led to identification of (1S)-8t, which eliminated CYP2D6 inhibition liability. Oral administration of (1S)-8t exerted efficacy in a rat spinal nerve ligation (SNL) model of neuropathic pain with an ED50 value of 2.8 mg/kg. (C) 2015 Elsevier Ltd. All rights reserved.