Substituted Benzamides Containing Azaspiro Rings as Upregulators of Apolipoprotein A-I Transcription

Molecules

Yu Du¹  Yuan Yang¹  Wei Jiang¹  Li Wang¹  Xiao-Jian Jia¹  Shu-Yi Si¹  Xiao-Fang Chen¹ 

[1] Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Tian Tan Xi Li 1#, Beijing 100050, China

关键词: apolipoprotein A-I;    transcriptional upregulator;    structure-activity relationship;    atherosclerosis;   

DOI  :  10.3390/molecules17067379

来源: mdpi

【 摘 要 】

Apolipoprotein A-I (Apo A-I) is the principal protein component of high density lipoprotein (HDL), which is generally considered as a potential therapeutic target against atherosclerosis. The understanding of the Apo A-I regulation mechanism has fuelled the development of novel HDL targeted therapeutic approaches. To identify novel agents that can upregulate Apo A-I expression, we performed a cell-based reporter assay to screen 25,600 small molecules. Based on the dataset obtained from screening, a series of novel analogs of substituted benzamides containing azaspiro rings were assessed for their ability to induce the transcription of the Apo A-I gene, and the structure-activity relationship (SAR) around these analogs was also proposed. The results indicated that the trifluoromethyl substituted benzamide containing an azaspiro ring is a promising backbone for designing Apo A-I transcriptional upregulator and could be viable leads for development of new drugs to prevent and treat atherosclerosis in the future.

【 授权许可】

CC BY   
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.