Synthesis and Biological Evaluation of Sigma-1 (σ1) Receptor Ligands Based on Phenyl-1,2,4-oxadiazole Derivatives

Article abstract of DOI:10.1002/cbdv.201800599

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 σ₁ receptor and selectivity for the σ₂ 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.

Full text of DOI:10.1002/cbdv.201800599

Title: Synthesis and Biological Evaluation of σ1 Receptor Ligands
Based on Phenyl-1,2,4-oxadiazole Derivatives
Authors: Xudong Cao, Zhongyuan Yao, Fei Dou, Yifang Zhang, Yinli
Qiu, Song Zhao, Xiangqing Xu, Xin Liu, Bi-Feng Liu, Yin
Chen, and Guisen Zhang
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To be cited as: Chem. Biodiversity 10.1002/cbdv.201800599
Link to VoR: http://dx.doi.org/10.1002/cbdv.201800599

10.1002/cbdv.201800599
Chemistry & Biodiversity
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10.1002/cbdv.201800599
Chemistry & Biodiversity
This article is protected by copyright. All rights reserved.

10.1002/cbdv.201800599
Chemistry & Biodiversity
This article is protected by copyright. All rights reserved.

10.1002/cbdv.201800599
Chemistry & Biodiversity
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10.1002/cbdv.201800599
Chemistry & Biodiversity
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10.1002/cbdv.201800599
Chemistry & Biodiversity
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10.1002/cbdv.201800599
Chemistry & Biodiversity
This article is protected by copyright. All rights reserved.

10.1002/cbdv.201800599
Chemistry & Biodiversity
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Mechanical allodynia (von Frey test)
55
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45
40
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25
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15
10
Basel
CCI
CCI+Cmpd 39
**
*
##
##
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Normal
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Control
25 mg/kg
50 mg/kg
100 mg/kg
This article is protected by copyright. All rights reserved.

10.1002/cbdv.201800599
Chemistry & Biodiversity
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10.1002/cbdv.201800599
Chemistry & Biodiversity
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10.1002/cbdv.201800599
Chemistry & Biodiversity
(
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10.1002/cbdv.201800599
Chemistry & Biodiversity
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10.1002/cbdv.201800599
Chemistry & Biodiversity
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10.1002/cbdv.201800599
Chemistry & Biodiversity
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10.1002/cbdv.201800599
Chemistry & Biodiversity
2
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10.1002/cbdv.201800599
Chemistry & Biodiversity
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10.1002/cbdv.201800599
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10.1002/cbdv.201800599
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10.1002/cbdv.201800599
Chemistry & Biodiversity
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