53811-70-4Relevant academic research and scientific papers
Discovery and Characterization of Benzimidazole Derivative XY123 as a Potent, Selective, and Orally Available RORγ Inverse Agonist
Wu, Xishan,Shen, Hui,Zhang, Yan,Wang, Chao,Li, Qiu,Zhang, Cheng,Zhuang, Xiaoxi,Li, Chenchang,Shi, Yudan,Xing, Yanli,Xiang, Qiuping,Xu, Jinxin,Wu, Donghai,Liu, Jinsong,Xu, Yong
, p. 8775 - 8797 (2021/06/30)
Receptor-related orphan receptor γ (RORγ) has emerged as an attractive therapeutic target for the treatment of cancer and inflammatory diseases. Herein, we report our effort on the discovery, optimization, and evaluation of benzothiazole and benzimidazole derivatives as novel inverse agonists of RORγ. The representative compound27h(designated as XY123) potently inhibited the RORγ transcription activity with a half-maximal inhibitory concentration (IC50) value of 64 nM and showed excellent selectivity against other nuclear receptors.27halso potently suppressed cell proliferation, colony formation, and the expression of androgen receptor (AR)-regulated genes in AR-positive prostate cancer cell lines. In addition,27hdemonstrated good metabolic stability and a pharmacokinetic property with reasonable oral bioavailability (32.41%) and moderate half-life (t1/2= 4.98 h). Significantly, oral administration of compound27hachieved complete and long-lasting tumor regression in the 22Rv1 xenograft tumor model in mice. Compound27hmay serve as a new valuable lead compound for further development of drugs for the treatment of prostate cancer.
Benzimidazole compound with endothelial lipase inhibition effect and application of benzimidazole compound
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Paragraph 0097; 0206; 0212-0214; 0247, (2020/12/09)
The invention discloses a benzimidazole compound with an endothelial lipase inhibition effect and application of the benzimidazole compound, and belongs to the technical field of medicines. The benzimidazole compound has an excellent inhibition effect on endothelial lipase, can effectively treating atherosclerosis and sequelae thereof, such as coronary heart disease, and also promotes treatment onmetabolic syndrome and sequelae thereof, such as diabetes. The benzimidazole compound provided by the invention has good solubility in an aqueous medium, also has good biological activity and metabolic stability, and shows advantages in the aspect of serum stability.
