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Papers of the Week

Papers: 22 Feb 2020 - 28 Feb 2020

Animal Studies, Pharmacology/Drug Development

2020 Feb 14

Eur J Med Chem


Piperidine propionamide as a scaffold for potent sigma-1 receptor antagonists and mu opioid receptor agonists for treating neuropathic pain.


Xiong J, Jin J, Gao L, Hao C, Liu X, Liu B-F, Chen Y, Zhang G
Eur J Med Chem. 2020 Feb 14; 191:112144.
PMID: 32087465.


We designed and synthesized a novel series of piperidine propionamide derivatives as potent sigma-1 (σ) receptor antagonists and mu (μ) opioid receptor agonists, and measured their affinity for σ and μ receptors in vitro through binding assays. The basic scaffold of the new compounds contained a 4-substituted piperidine ring and N-aryl propionamide. Compound 44, N-(2-(4-(4-fluorobenzyl) piperidin-1-yl) ethyl)-N-(4-methoxy-phenyl) propionamide, showed the highest affinity for σ receptor (K σ = 1.86 nM) and μ receptor (K μ = 2.1 nM). It exhibited potent analgesic activity in the formalin test (ED = 15.1 ± 1.67 mg/kg) and had equivalent analgesic effects to S1RA (σ antagonist) in a CCI model. Therefore, Compound 44, which has mixed σ/μ receptor profiles, may be a potential candidate for treating neuropathic pain.