Synthesis and pharmacological evaluation of carbamic acid 1-phenyl-3-(4-phenyl-piperazine-1-yl)-propyl ester derivatives as new analgesic agents

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• 作者：Eunhee Chae ; ^{Eunhee.chae@sk.com} ; Hanju Yi ; Yeonjung Choi ; Hyeon Cho ; Kiho Lee ; Hongsik Moon
• 关键词：Arylpiperazine ; Analgesic ; Anti-nociceptive ; 5-HT2A antagonism
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2012
• 期刊代码：10_0960894x
• 类别：ch
• 出版时间：1 April, 2012
• 卷：22
• 期：7
• 页码：2434-2439
• 文件大小：282 K

摘要

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.