Piperidine propionamide as a scaffold for potent sigma-1 receptor antagonists and mu opioid receptor agonists for treating neuropathic pain.
Basic Information
ID: ALA4765270
Journal: Eur J Med Chem
Title: Piperidine propionamide as a scaffold for potent sigma-1 receptor antagonists and mu opioid receptor agonists for treating neuropathic pain.
Authors: Xiong J,Jin J,Gao L,Hao C,Liu X,Liu BF,Chen Y,Zhang G
Abstract: 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.
CiteXplore: 32087465
DOI: 10.1016/j.ejmech.2020.112144
Patent ID: ┄