title: Diarylureas and Diarylamides with Oxazolo[5,4-d]pyrimidine Scaffold as Angiogenesis Inhibitors.
abstract: A series of oxazolopyrimidine-based ureas and amides were designed, synthesized, and biologically evaluated for their antiproliferative and antiangiogenic activities. These compounds were identified to exhibit inhibitory activities against human umbilical vein endothelial cells (HUVEC) in vitro. Among these compounds, compound 22 effectively inhibited the migration and capillary-like tube formation of human umbilical vein endothelial cells. It also exhibited a concentration-dependent inhibition on capillary sprouting from the rat aorta rings. Preliminary mechanistic studies revealed that compound 22 suppressed protein kinases activation, by decreasing PI3K and ERK 1/2 phosphorylation. These results support the further investigation of this class of compounds as potential anticancer agents.
authors.affiliation: Jiangsu Key Laboratory of Drug Design & Optimization, China Pharmaceutical University, Nanjing, 210009, P. R. China.|Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing, 210009, P. R. China.
authors.forename: Ya-Hui
authors.initials: YH
authors.lastname: Deng
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, P. R. China.
authors.forename: Ji-Ping
authors.initials: JP
authors.lastname: Liu
authors.affiliation: Jiangsu Key Laboratory of Drug Design & Optimization, China Pharmaceutical University, Nanjing, 210009, P. R. China.|Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing, 210009, P. R. China.
authors.forename: Yi-Juan
authors.initials: YJ
authors.lastname: Cheng
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, P. R. China. liuyuyaoda@163.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Jiangsu Key Laboratory of Drug Design & Optimization, China Pharmaceutical University, Nanjing, 210009, P. R. China. chslp@cpu.edu.cn.|Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing, 210009, P. R. China. chslp@cpu.edu.cn.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Sun
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects; D002196:Capillaries / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects*; D006801:Humans; D015394:Molecular Structure; D010080:Oxazoles / Q000737:chemistry / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011494:Protein Kinases / Q000378:metabolism*; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000577:Amides; D020533:Angiogenesis Inhibitors; D010080:Oxazoles; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; C000613494:oxazolo(5,4-d)pyrimidine; D014508:Urea; D011494:Protein Kinases
keywords: Amides; Antiangiogenesis; Anticancer agents; Antiproliferative activity; Oxazolopyrimidines; Ureas