681836-59-9Relevant 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.
RXR-LXR heterodimer modulators for the potential treatment of dyslipidemia
Lagu, Bharat,Pio, Barbara,Lebedev, Rimma,Yang, Maria,Pelton, Patricia D.
, p. 3497 - 3503 (2008/02/09)
A number of RXR agonists were synthesized and screened in functional assays. The synthesis and the structure-activity relationship (SAR) within the series of compounds will be presented. Some in vivo data in rodent models for dyslipidemia and diabetes wil
Heterocyclic amide derivatives as RXR agonists for the treatment of dyslipidemia, hypercholesterolemia and diabetes
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Page/Page column 29, (2010/11/26)
The present invention relates to compounds of Formula (I), methods for preparing these compounds, compositions, intermediates and derivatives thereof and for treating RXR mediated disorders. More particularly, the compounds of the present invention are RXR agonists useful for treating RXR mediated disorders.
2,4,6-Triaminopyrimidines for the treatment of depression and/or anxiety
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, (2010/02/06)
This invention is directed to pyrimidine derivatives which are selective antagonists for the GalR3 receptor. The invention provides a pharmaceutical composition comprising a therapeutically effective amount of a compound of the invention and a pharmaceuti
