2-chloro-1-(1-cyclohexyl-7-isopropyl-3,4-dihydroisoquinolin-2(1H)-yl)ethanone | 1085538-99-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: 2-chloro-1-(1-cyclohexyl-7-isopropyl-3,4-dihydroisoquinolin-2(1H)-yl)ethanone
• 英文别名: 2-(chloroacetyl)-1-cyclohexyl-7-isopropyl-1,2,3,4-tetrahydroisoquinoline；2-chloro-1-(1-cyclohexyl-7-propan-2-yl-3,4-dihydro-1H-isoquinolin-2-yl)ethanone
• CAS: 1085538-99-3
• 化学式: C₂₀H₂₈ClNO
• 分子量: 333.901
• InChiKey: HKFSUYADTPWEOF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (R)-(-)-1-氨基-2-丙醇 、 2-chloro-1-(1-cyclohexyl-7-isopropyl-3,4-dihydroisoquinolin-2(1H)-yl)ethanone 、 草酸 在 potassium carbonate 作用下， 以 乙腈 、 异丙醇 为溶剂， 反应 6.0h， 以69%的产率得到1-(1-cyclohexyl-7-isopropyl-3,4-dihydroisoquinolin-2(1H)-yl)-2-{[(2R)-2-hydroxypropyl]amino}ethanone oxalate
  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：

  在 甲醇 、 potassium fluoride 、 四(三苯基膦)钯 、 硫酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲苯 为溶剂， 反应 50.25h， 生成 2-chloro-1-(1-cyclohexyl-7-isopropyl-3,4-dihydroisoquinolin-2(1H)-yl)ethanone
  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

• 1-SUBSTITUTED TETRAHYDROISOQUINOLINE COMPOUND
  申请人：Astellas Pharma Inc.

  公开号：EP2149560B1

  公开（公告）日：2015-05-13
• US8263607B2
  申请人：——

  公开号：US8263607B2

  公开（公告）日：2012-09-11