摘要
设计合成新型结构sirtuins抑制剂并评价其对SIRT1~SIRT3的抑制活性。基于已报道的sirtuins抑制剂结构和药效团特征,设计了一系列苯并咪唑和苯并噻唑类化合物。以乙基黄原酸钾为起始原料,经3步反应合成了16个未见文献报道的目标化合物,目标化合物的结构经1H NMR、HR-MS确证。对目标化合物进行SIRT1~SIRT3的抑制活性评价,其中苯并咪唑类化合物对SIRT2具有选择性的抑制活性。
A series of novel benzimidazole and benzothiazole derivatives were designed and synthesized as inhibitors of SIRT1-SIRT3. The target compounds were synthesized from potassium O-ethyldithiocarbonate through a three-step route. The structures of the obtained compounds were elucidated by 1H NMR and HR-MS. Of all compounds, six showed potent SIRT2-inhibitory activities with ICs0 values ranging from 2.8 to 21.2 μmol.L^-1. Among them, compound 10c displayed the most potent SIRT2-inhibitory activities （IC50=2.8 μmol·L^-1）, with more than 35-fold selectivity over SIRT1 and SIRT3 （IC50〉 100 μmol·L^-1）.
出处
《药学学报》
CAS
CSCD
北大核心
2017年第5期773-778,共6页
Acta Pharmaceutica Sinica
基金
国家自然科学基金资助项目(81273431)
