2034-25-5Relevant academic research and scientific papers
Discovery of a flexible triazolylbutanoic acid as a highly potent uric acid transporter 1 (URAT1) inhibitor
Tian, He,Liu, Wei,Zhou, Zhixing,Shang, Qian,Liu, Yuqiang,Xie, Yafei,Liu, Changying,Xu, Weiren,Tang, Lida,Wang, Jianwu,Zhao, Guilong
, (2016/12/02)
In order to systematically explore and understand the structure-activity relationship (SAR) of a lesinurad-based hit (1c) derived from the replacement of the S atom in lesinurad with CH2, 18 compounds (1a-1r) were designed, synthesized and subjected to in vitro URAT1 inhibitory assay. The SAR exploration led to the discovery of a highly potent flexible URAT1 inhibitor, 1q, which was 31-fold more potent than parent lesinurad (IC50 = 0.23 μM against human URAT1 for 1q vs. 7.18 μM for lesinurad). The present study discovered a flexible molecular scaffold, as represented by 1q, which might serve as a promising prototype scaffold for further development of potent URAT1 inhibitors, and also demonstrated that the S atom in lesinurad was not indispensable for its URAT1 inhibitory activity.
Triazole derivatives: A series of Darapladib analogues as orally active Lp-PLA2 inhibitors
Wang, Kai,Xu, Wenwei,Zhang, Wei,Mo, Mingguang,Wang, Yiping,Shen, Jianhua
, p. 2897 - 2901 (2013/06/26)
This Letter reports our efforts towards the optimization of our previously identified series of imidazole and triazole derivatives that lead to the discovery of a series of orally active Lp-PLA2 inhibitors in C57 mice. These inhibitors are characterized by the presence of a diamine side chain in the molecules, such as 2c, 2f, and 4a. The introduction of the terminal-end amine succeeded in maintaining the in vitro activities at sub-nanomolar levels. The vivo activities could be greatly affected by variations in the two amines via modulating the metabolic stability and lipophilicity of the compounds.
