444731-74-2Relevant articles and documents
Discovery of Novel Pazopanib-Based HDAC and VEGFR Dual Inhibitors Targeting Cancer Epigenetics and Angiogenesis Simultaneously
Zang, Jie,Liang, Xuewu,Huang, Yongxue,Jia, Yuping,Li, Xiaoyang,Xu, Wenfang,Chou, C. James,Zhang, Yingjie
, p. 5304 - 5322 (2018)
Herein a novel series of pazopanib hybrids as polypharmacological antitumor agents were developed based on the crosstalk between histone deacetylases (HDACs) and vascular endothelial growth factor (VEGF) pathway. Among them, one ortho-aminoanilide 6d and one hydroxamic acid 13f exhibited considerable total HDACs and VEGFR-2 inhibitory activities. The HDAC inhibitory activities endowed 6d and 13f with potent antiproliferative activities, which was not observed in the approved VEGFR inhibitor pazopanib. Compounds 6d and 13f possessed comparable HDAC isoform selectivity profiles to the clinical class I HDAC inhibitor MS-275 and the approved pan-HDAC inhibitor SAHA, respectively. 6d and 13f also exhibited uncompromised multiple tyrosine kinases inhibitory activities relative to pazopanib. The intracellular dual inhibition to HDAC and VEGFR of 6d and 13f was validated by Western blot analysis. In both HUVECs tube formation assay and rat thoracic aorta rings assay, 6d and 13f showed comparable antiangiogenic potencies to pazopanib. What's more, 6d possessed desirable pharmacokinetic profiles with the oral bioavailability of 72% in SD rats and considerable in vivo antitumor efficacy in a human colorectal adenocarcinoma (HT-29) xenograft model.
Preparation, biological & cheminformatics-based assessment of N2,N4-diphenylpyrimidine-2,4-diamine as potential Kinase-targeted antimalarials
Toviwek, Borvornwat,Phuangsawai, Oraphan,Konsue, Adchatawut,Hannongbua, Supa,Riley, Jennifer,Mutter, Nicole,Anderson, Mark,Webster, Lauren,Hallyburton, Irene,Read, Kevin D,Gleeson, M. Paul
, (2021/09/04)
Twenty eight new N2,N4-diphenylpyrimidine-2,4-diamines have been prepared in order to expand our understanding of the anti-malarial SAR of the scaffold. The aim of the study was to make structural modifications to improve the overall
Synthesis and characterization of four process impurities in pazopanib
Yuan, Jian-Yong,Zhang, Di,Hu, Xiang-Nan,Wang, Hua-Jun,Ran, Dong-Zhi,Shang, Su-Qing,Gan, Zong-Jie
, p. 494 - 497 (2018/09/29)
Pazopanib (trade name Votrient) is a potent and selective multi-targeted tyrosine kinase inhibitor that blocks tumor growth and inhibits angiogenesis. Based on a recently reported procedure, we herein report the first synthesis of four potential process impurities generated in the production of pazopanib. The structure of these impurities were synthesized and characterized by 1H NMR, 13C NMR and HRMS data. The possible formation mechanisms of these impurities were also elucidated. These findings should be useful for the quality control of pazopanib in manufacture.