title: Discovery of 4-amino-2-(thio)phenol derivatives as novel protein kinase and angiogenesis inhibitors for the treatment of cancer: synthesis and biological evaluation. Part II.
abstract: A novel series of 4-amino-2-(thio)phenol derivatives were well synthesized. The preliminary biological test revealed that several compounds displayed high specific protein kinase and angiogenesis inhibitory activities compared with previous work mainly because of the substitution of sulfonamide structure for amide fragment. Among which, compound 5i was identified to inhibit protein kinase B/AKT (IC₅₀ = 1.26 μM) and ABL tyrosine kinase (IC₅₀ = 1.50 μM) effectively. Meanwhile, compound 5i demonstrated competitive in vitro antiangiogenic activities to Pazopanib in both human umbilical vein endothelial cell (HUVEC) tube formation assay and the rat thoracic aorta rings test.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Shandong University, Ji'nan, Shandong 250012, PR China.
authors.forename: Fuming
authors.initials: F
authors.lastname: Xu
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Yuping
authors.initials: Y
authors.lastname: Jia
authors.forename: Xuejian
authors.initials: X
authors.lastname: Wang
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Li
authors.forename: Qingli
authors.initials: Q
authors.lastname: Wen
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Zhang
authors.forename: Wenfang
authors.initials: W
authors.lastname: Xu
mesh_terms: D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D008297:Male; D008958:Models, Molecular; D015394:Molecular Structure; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000201:enzymology; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016315:Proto-Oncogene Proteins c-abl / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000096926:Benzenesulfonamides
chemical_list: D020533:Angiogenesis Inhibitors; D047428:Protein Kinase Inhibitors; D016315:Proto-Oncogene Proteins c-abl; D051057:Proto-Oncogene Proteins c-akt; D013449:Sulfonamides; D014230:Triazoles; D040301:Vascular Endothelial Growth Factor Receptor-2; C000589299:N-(3-((1H-1,2,4-triazol-5-yl)thio)-4-hydroxyphenyl)-4-nitrobenzenesulfonamide; D000096926:Benzenesulfonamides
keywords: ABL; AKT; FHRYIUWAZBCUGX-UHFFFAOYSA-N; HUVECs; Protein kinase; Rat thoracic aorta rings