N 4-Aryl-6-substitutedphenylmethyl-7H-pyrrolo[2,3-d]pyrimidine-2, 4-diamines as receptor tyrosine kinase inhibitors
Bioorganic and Medicinal Chemistry
Pyrrolo[2, 3-d]pyrimidines, Receptor tyrosine kinase inhibitors
Six novel N 4-substitutedphenyl-6-substitutedphenylmethyl-7H- pyrrolo[2,3-d]pyrimidine-2,4-diamines were synthesized as multiple receptor tyrosine kinase (RTK) inhibitors and antitumor agents. An improvement in the inhibitory potency against epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor 1 (VEGFR-1) and vascular endothelial growth factor receptor 2 (VEGFR-2) assays and in the A431 cellular proliferation assay was observed for compounds 8-13 over the previously reported 5-7. Three compounds (8, 9 and 13) demonstrated potent, multiple RTK inhibition and were more potent or equipotent compared to the lead compounds 5 and 7 and the standard compounds. Compounds 10 and 12 showed potent inhibition of VEGFR-2 over EGFR, platelet-derived growth factor receptor-β (PDGFR-β) and VEGFR-1. The results indicate that the RTK inhibitory profile could be modulated with slight variations to the N 4-aryl-6-substitutedphenylmethyl-7H- pyrrolo[2,3-d]pyrimidine-2,4-diamino scaffold. © 2011 Elsevier Ltd. All rights reserved.
Gangjee, A., Kurup, S., Ihnat, M., Thorpe, J., & Disch, B. (2012). N 4-Aryl-6-substitutedphenylmethyl-7H-pyrrolo[2,3-d]pyrimidine-2, 4-diamines as receptor tyrosine kinase inhibitors. Bioorganic and Medicinal Chemistry, 20 (2), 910-914. https://doi.org/10.1016/j.bmc.2011.11.058