高等学校化学学报

高等学校化学学报 ›› 2002, Vol. 23 ›› Issue (4): 585.

• 研究论文 • 上一篇    下一篇

含(1-芳乙酰胺基-2-叔胺基)乙烷结构的六氢-1H-1,4-二氮(艹卓)类化合物的合成与镇痛活性

沈敬山, 雷厉军, 李剑峰, 嵇汝运   

  1. 中国科学院上海药物研究所, 上海 200031
  • 收稿日期:2000-12-22 出版日期:2002-04-24 发布日期:2002-04-24
  • 通讯作者: 沈敬山(1962年出生),男,博士,从事药物化学及合成工艺研究.
  • 基金资助:

    上海市科学技术发展基金(批准号:95QB14025)资助.

Synthesis of Hexahydro-1H-1,4-diazepine Analogues Carrying the Segment of(1-Arylacetamide-2-tertiary amide) Ethane and Their Analgesic Effects

SHEN Jing-Shan, LEI Li-Jun, LI Jian-Feng, JI Ru-Yun   

  1. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 200031, China
  • Received:2000-12-22 Online:2002-04-24 Published:2002-04-24

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摘要： 2-或5-取代的六氢-1H-1,4-二氮(艹卓)类化合物(1～3)经单酰化及酰化反应后,合成了16个带有(1-芳乙酰胺基-2-叔氨基)乙烷结构的六氢-1H-1,4-二氮(艹卓)类目标化合物(5～9,11～13,15～17,19～23),经元素分析、IR、MS和1H NMR确证了其组成和结构。对所有目标化合物都进行了豚鼠回肠试验,初步药理试验表明,16个化合物对受试标本显示不同程度的抑制作用,对抑制率较高的两个化合物5和7测试了IC50值。对在豚鼠回肠试验中显示较强激动作用的4个化合物进行了小鼠扭体法镇痛活性试验,测得了其ED50值。

关键词: 选择性kappa受体激动剂, 镇痛活性, 六氢-1H-1, 4-二氮(艹卓), (1-芳乙酰胺基-2-叔氨基)乙烷结构

Abstract: In order to get some selective κ-opioid receptor agonists, which can relieve pain while lackingserious side effects, 16 target compounds of hexahydro-1H-1, 4-diazepine analogues carrying the segmentof (1-arylacetamide-2-tertiary amide) ethane were synthesized through single amidation and amidation ofthe basic modified structures of compounds 1-3, 2-(5-) substituted hexahydro-1H-1, 4-diazepine.Thestructures of these products were characterized by IR, EIMS, elementary analysis and 1H NMR.All thetarget compounds were screened in vitro in the guinea pig ileum(GPI) for their receptor affinities.The pre-liminary pharmacology tests indicated that these compounds showed a certain agonist activity(presented inthe item of inhibition rate) respectively at 5 × 10-6mol/Llevel and the IC50 values(μmol/L) of compounds5, 7 were achieved.The antinociceptive potencies of the compounds with a higher potency(compounds 5,13, 22, 23) in the GPIstudy were further tested their in the mouse abdominal constriction model and their ED50 values(mg/kg, s.c.) were also obtained.

Key words: Selective κ-opioid receptor agonists, Analgesic effect, Hexahydro-1H-1, 4-diazepine ana-logues, (1-Arylacetamide-2-tertiary amide) ethane structure

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