Synthesis and pharmacological evaluation of carbamic acid 1-phenyl-3-(4-phenyl-piperazine-1-yl)-propyl ester derivatives as new analgesic agents
作者: Eunhee ChaeHanju YiYeonjung ChoiHyeon ChoKiho LeeHongsik Moon
作者单位: 1Life Science Division, SK Biopharmaceuticals, Daejeon 305-712, Republic of Korea
刊名: Bioorganic & Medicinal Chemistry Letters, 2012, Vol.22 (7), pp.2434-2439
来源数据库: Elsevier Journal
DOI: 10.1016/j.bmcl.2012.02.023
关键词: ArylpiperazineAnalgesicAnti-nociceptive5-HT 2A antagonism
英文摘要: Abstract(#br)A series of carbamic acid 1-phenyl-3-(4-phenyl-piperazine-1-yl)-propyl ester derivatives were synthesized through discovery strategies for balancing target-based in vitro screening and phenotypic in vivo screening. All the newly synthesized compounds were screened for their analgesic activities and compared with standard drug morphine. Among them, compound 44r , a potent analgesic agent that has favorable pharmacokinetic properties in rats and most importantly, has a wide safety margin. We demonstrated with in vitro and in vivo functional assays that its analgesic activity might be through 5-HT 2A antagonism to some extent. Hence, it is concluded that there is ample scope for further study in developing compound 44r as a good lead candidate for an analgesic agent.
全文获取路径: Elsevier  (合作)
影响因子:2.338 (2012)

  • piperazine 哌嗪
  • ester 
  • analgesic 镇痛药
  • phenyl 苯基
  • nociceptive 感受伤害的
  • antagonism 对抗酌
  • carbamic 氨基甲酸的
  • propyl 丙基
  • derivatives 派生物
  • evaluation 评价