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Synthesis and Biological Evaluation of Sigma‐1 (σ 1 ) Receptor Ligands Based on Phenyl‐1,2,4‐oxadiazole Derivatives
Author(s) -
Cao Xudong,
Yao Zhongyuan,
Dou Fei,
Zhang Yifang,
Qiu Yinli,
Zhao Song,
Xu Xiangqing,
Liu Xin,
Liu BiFeng,
Chen Yin,
Zhang Guisen
Publication year - 2019
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.201800599
Subject(s) - neuropathic pain , chemistry , oxadiazole , pharmacology , receptor , allodynia , sigma 1 receptor , piperidine , selectivity , stereochemistry , hyperalgesia , nociception , biochemistry , medicine , organic chemistry , agonist , catalysis
In this study, a series of phenyl‐1,2,4‐oxadiazole derivatives were synthesized and evaluated for anti‐allodynic activity. Structure–activity relationship studies identified 1‐{4‐[3‐(2,4‐dichlorophenyl)‐1,2,4‐oxadiazol‐5‐yl]butyl}piperidine ( 39 ) with excellent affinity for the σ 1 receptor and selectivity for the σ 2 receptor, with poor activity to other central nervous system neurotransmitter receptors and transporters associated with pain. Compound 39 exhibited dose‐dependent efficacy in suppressing the formalin‐induced flinching and attenuating mechanical allodynia in chronic constriction injury‐induced neuropathic rats. These results suggest that compound 39 exerts potent antihyperalgesic activity and could be considered as a promising candidate for treating neuropathic pain.