化学
哌啶
Sigma-1受体
止痛药
阿片受体
ED50公司
药理学
西格玛受体
受体
神经病理性疼痛
敌手
立体化学
类阿片
δ-阿片受体
内在活性
兴奋剂
生物化学
医学
作者
Jiaying Xiong,Jian Jin,Lanchang Gao,Chao Hao,Xin Liu,Bi‐Feng Liu,Yin Chen,Guisen Zhang
标识
DOI:10.1016/j.ejmech.2020.112144
摘要
We designed and synthesized a novel series of piperidine propionamide derivatives as potent sigma-1 (σ1) receptor antagonists and mu (μ) opioid receptor agonists, and measured their affinity for σ1 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 σ1 receptor (Ki σ1 = 1.86 nM) and μ receptor (Ki μ = 2.1 nM). It exhibited potent analgesic activity in the formalin test (ED50 = 15.1 ± 1.67 mg/kg) and had equivalent analgesic effects to S1RA (σ1 antagonist) in a CCI model. Therefore, Compound 44, which has mixed σ1/μ receptor profiles, may be a potential candidate for treating neuropathic pain.
科研通智能强力驱动
Strongly Powered by AbleSci AI