【摘 要】
：
Due to ineffectiveness and side effects of existing analgesics, chronic pain has become one of the most complex and difficult problems in the clinic.Monoacylglycerol lipase (MAGL) is an essential hydrolase in the endocannabinoid system and has been identi
【机 构】
：
Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 211
论文部分内容阅读
Due to ineffectiveness and side effects of existing analgesics, chronic pain has become one of the most complex and difficult problems in the clinic.Monoacylglycerol lipase (MAGL) is an essential hydrolase in the endocannabinoid system and has been identified as a potential target for the treatment of pain.In the present study, we designed and synthesized twelve tanshinone IIA analogs and screened their activity against MAGL.Selected compounds were tested for analgesic activity in vivo, with the acetic acid writhing test model.Among the test compounds, compound Ⅲ-3 (IC50 120 nmol.L-1) showed significant activity against MAGL and ameliorated the clinical progression in the mouse pain model.Additionally, compound Ⅲ-3, substitution with N-methyl-2-morpholinoacetamide, demonstrated improved solubility relative to tanshinone ⅡA.
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