zd-6474 and 4-aminoquinazoline

The 4-aminoquinazoline core is an interesting pharmacophore and its applications in medicinal chemistry are wide spread. The core has been used for making many kinase inhibitors in past few years. Many researcher demonstrated 4-aminoquinazoline derivatives as specific kinase inhibitors, including tyrosine kinase and serine/theronine kinases. A number of anticancer drugs with 4-aminoquinazoline core are in the market, e.g. gefitinib, erlotinib, afatinib, lapatinib, decomitinib etc. 4-aminoquinazoline derivatives are applied for target specific treatment of lung, breast, colon, prostate cancers. In this review, we discussed the current development of 4-aminoquinazoline derivatives as kinase inhibitors and their uses as anticancer agents in recent years.

Topics: Animals; Antineoplastic Agents; Chemistry Techniques, Synthetic; Humans; Neoplasms; Protein Kinase Inhibitors; Quinazolines

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.

Topics: Animals; Antineoplastic Agents; Chemistry, Pharmaceutical; Drug Design; Drug Screening Assays, Antitumor; Enzyme Inhibitors; Hep G2 Cells; Humans; Inhibitory Concentration 50; Mice; Mice, Nude; Models, Chemical; Neoplasm Transplantation; Piperidines; Quinazolines; Vascular Endothelial Growth Factor Receptor-2