Synthesis and Analgesic Activity of Novel Open-chained Epibatidine Analogues

Abstract

Abstract: Based on the structure of the leading compound ABT-594 and the bioisosteric replancement rule,ten new open-chain EP analogues were designed and synthesized by the PTC and Mitsunobo reactions.Their structures were confirmed by ¹H and ¹³C NMR,elemental analysis,MS or HRMS.All the target compounds were evaluated for their analgesic activity in vivo.The result revealed that most of them showed some activity.Though their analgesic activity was not so satisfactory,some interesting SAR was found.The compounds containing furan ring exhibited a higher activity than others.Replaced 2-chloropyridine in ABT-594 with 2-methyl-5-nitroimidazole or 5-methyl tetrazole,and(or) instead of the CH₂O with CH₂ as linking arm,the analgesic activity didn't obviously decrease.Additionally,the toxicity of all tested compounds was lower than epibatidine itself significantly.

Key words: Epibatidine, ABT-594, Open-chain EP analogue, Synthesis, Analgesic activity

CLC Number:

O621

TrendMD:

ZHANG Chuan-Xin, ZHANG Hong-Mei, LI Chang-Ling, GE Ze-Mei, CHENG Tie-Ming, LI Run-Tao . Synthesis and Analgesic Activity of Novel Open-chained Epibatidine Analogues[J]. Chem. J. Chinese Universities, 2005, 26(10): 1840.

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Synthesis and Analgesic Activity of Novel Open-chained Epibatidine Analogues

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