title: Design, synthesis and biological evaluation of pazopanib derivatives as antitumor agents.
abstract: A novel series of pazopanib derivatives were designed, synthesized, and evaluated for their inhibitory activity against a series of kinases including VEGFR-2, EGFR, AKT1, ALK1, and ABL1. The anti-angiogenic activities ex vivo of some compounds were also investigated. Compounds P2d and P2e demonstrated outstanding inhibitory activity against VEGFR-2 and ABL1 and higher anti-angiogenic activity compared with Pazopanib, the reference standard. These two compounds (P2d and P2e) could be used as novel lead compounds for further development of anticancer agents.
authors.affiliation: Shandong Institute of Pharmaceutical Industry, Ji'nan, Shandong, 250101, China.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Jia
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Jinhong
authors.initials: J
authors.lastname: Feng
authors.forename: Fuming
authors.initials: F
authors.lastname: Xu
authors.forename: Huili
authors.initials: H
authors.lastname: Pan
authors.forename: Wenfang
authors.initials: W
authors.lastname: Xu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D015195:Drug Design; D004789:Enzyme Activation / Q000187:drug effects; D007191:Indazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016315:Proto-Oncogene Proteins c-abl / Q000037:antagonists & inhibitors / Q000378:metabolism; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000096926:Benzenesulfonamides
chemical_list: D000970:Antineoplastic Agents; D007191:Indazoles; D047428:Protein Kinase Inhibitors; D016315:Proto-Oncogene Proteins c-abl; D011743:Pyrimidines; D013449:Sulfonamides; D040301:Vascular Endothelial Growth Factor Receptor-2; C000592739:4-((4-((2,3-dimethyl-2H-indazole-6-yl)(methyl)amino)pyrimidin-2-yl)amino)-N-(4,6-dimethylpyrimidin-2-yl)benzenesulfonamide; D000096926:Benzenesulfonamides; C000592738:4-((4-((2,3-dimethyl-2H-indazole-6-yl)(methyl)amino)pyrimidin-2-yl)amino)-N-(4-methylpyrimidin-2-yl)benzenesulfonamide; C516667:pazopanib
keywords: anti-angiogenesis; antitumor agent; pazopanib derivatives; synthesis