Synthesis of benzimidazole and benzothiazole derivatives as a sirtuins 2 inhibitor

VernacularTitle:苯并咪唑和苯并噻唑类衍生物的合成及其sirtuins抑制活性评价
Author: Yu-mei ZHOU ¹ ; Hua-qing CUI ² ; Xiao-ming YU ² ; Shou-guo ZHANG ³ ; Tao PENG ³ ; Gang WANG ³ ; Xiao-xue WEN ³ ; Yun-bo SUN ³ ; Shu-chen LIU ³ ; Lin WANG ¹
Author Information

1. College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124, China
2. Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
3. Institute of Radiation Medicine, Academy of Military Medical Sciences, Beijing 100850, China
Publication Type:ORIGINAL ARTICLES
Keywords: design and synthesis; benzimidazole; benzothiazole; sirtuins inhibitor
From: Acta Pharmaceutica Sinica 2017;52(5):773-778
CountryChina
Language:Chinese
Abstract: 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 IC₅₀ 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).