ABSTRACT
We report herein the design and synthesis of novel 4-aminoquinazoline derivatives based on the inhibitors of VEGFR-2 tyrosine kinases. The VEGFR-2 inhibitory activities of these newly synthesized compounds were also evaluated and compared with that of ZD6474. We found that most of target compounds had good inhibitory potency. In particular, compounds 1h, 1n and 1o were found to be 6, 2 and 2-fold more potent than the positive control ZD6474. The leading compound 1h also showed an in vivo activity against HepG2 human tumor xenograft model in BALB/c-nu mice.
Subject(s)
Chemistry, Pharmaceutical/methods , Quinazolines/pharmacology , Vascular Endothelial Growth Factor Receptor-2/antagonists & inhibitors , Animals , Antineoplastic Agents/pharmacology , Drug Design , Drug Screening Assays, Antitumor/methods , Enzyme Inhibitors/pharmacology , Hep G2 Cells , Humans , Inhibitory Concentration 50 , Mice , Mice, Nude , Models, Chemical , Neoplasm Transplantation , Piperidines/pharmacology , Quinazolines/chemical synthesis , Vascular Endothelial Growth Factor Receptor-2/chemistryABSTRACT
Heavy metal concentrations of Cd, Cu, Pb and Zn were monitored during 10 rainfall runoff events occurred on a representative expressway road in Nanjing. Discharge rule of metal pollution, event mean concentrations (EMC) and the effect of hydrologic characteristics were evaluated. The results indicated that the discharge characteristics were various in different types of rainfall events. The metal concentrations fluctuated in the range of comparatively high levels during the events with short duration, light rainfall and low intensity. In the events with long duration, heavy rainfall and initial high intensity, the initial metal concentrations were high and metal exhibited a pronounced first flush. Second flush effect existed in the events with short duration, medium rainfall and double intensity peaks. The EMCs of Cd, Cu, Pb and Zn were 1.43 microg x L(-1), 0.092 mg x L(-1), 38.6 microg x L(-1) and 0.51 mg x L(-1), respectively. EMCs showed that the pollution extent of Pb was serious. Pollution of Cd, Cu and Pb were similar to other domestic reports, but Pb was lower than those studies. Cu and Zn were similar to related foreign studies, but Cd and Pb were lower. Correlation analysis suggested that the influence of rainfall on the discharge of Cu and the influence of antecedent dry period on the accumulation of Zn were significant.
