782493-60-1Relevant articles and documents
AZETIDIN-3-YLMETHANOL DERIVATIVES AS CCR6 RECEPTOR MODULATORS
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Page/Page column 178, (2021/11/06)
The present invention relates to compounds of Formula (I), their synthesis and use as CCR6 receptor modulators for the treatment or prevention of various diseases, conditions or disorders.
Discovery of 1,2,4-oxadiazole-Containing hydroxamic acid derivatives as histone deacetylase inhibitors potential application in cancer therapy
Yang, Zhuang,Shen, Mingsheng,Tang, Minghai,Zhang, Wanhua,Cui, Xue,Zhang, Zihao,Pei, Heying,Li, Yong,Hu, Mengshi,Bai, Peng,Chen, Lijuan
, p. 116 - 130 (2019/06/11)
In this study, a series of novel HDAC inhibitors, using 1,2,4-oxadiazole-containing as the cap group, were synthesized and evaluated in vitro. Compound 14b, N-hydroxy-2-(methyl((3-(1-(4-methylbenzyl)piperidin-4-yl)-1,2,4-oxadiazol-5-yl)methyl)amino)pyrimidine-5-carboxamide, displayed the most potent histone deacetylase (HDAC) inhibition, especially against HDAC1, 2, and 3 with IC50 values of 1.8, 3.6 and 3.0 nM, respectively. In vitro antiproliferative studies confirmed that 14b was more potent than SAHA, with IC50 values against 12 types of cancer cell lines ranging from 9.8 to 44.9 nM. The results of Western blot assays showed that compound 14b can significantly up-regulate the acetylation of the biomarker his-H3 and molecular docking analyses revealed the mode of action of compound 14b against HDAC1. The results of flow-cytometry analysis suggested that compound 14b induces cell cycle arrest at the G1 phase and has apoptotic effects. Further investigation of the activity of 14b on the primary cells of three patients, showed IC50 values of 21.3, 61.1, and 77.4 nM. More importantly, an oral bioavailability of up to 53.52% was observed for 14b. An in vivo pharmacodynamic evaluation demonstrated that compound 14b can significantly inhibit tumor growth in a Daudi Burkitt's lymphoma xenograft model, with tumor inhibition rates of 53.8 and 46.1% observed at 20 and 10 mg/kg when administered p.o. and i.v., respectively. These results indicate that compound 14b may be a suitable lead for further evaluation and development as an HDAC inhibitor and a potent anticancer agent.
CYCLIC AMINE COMPOUND AND PEST CONTROL AGENT
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Paragraph 0450-0453, (2019/07/10)
A compound represented by a formula (I), or a salt thereof: wherein Ar1 is a substituted or unsubstituted C6-10 aryl group, or the like; the number of X1 groups that can be substituted on Ar1 is 5 or less; Xsup