N(4)-Aryl-6-substitutedphenylmethyl-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamines as receptor tyrosine kinase inhibitors.
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Gangjee A, Kurup S, Ihnat MA, Thorpe JE, Disch B
N(4)-Aryl-6-substitutedphenylmethyl-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamines as receptor tyrosine kinase inhibitors.
Bioorg Med Chem. 2012 Jan 15;20(2):910-4. doi: 10.1016/j.bmc.2011.11.058. Epub 2011 Dec 8.
- PubMed ID
- 22204741 [ View in PubMed]
- Abstract
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-beta (PDGFR-beta) 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.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Erlotinib Epidermal growth factor receptor IC 50 (nM) 1200 N/A N/A Details Semaxanib Vascular endothelial growth factor receptor 2 IC 50 (nM) 12000 N/A N/A Details Sunitinib Platelet-derived growth factor receptor beta IC 50 (nM) 12200 N/A N/A Details Sunitinib Vascular endothelial growth factor receptor 2 IC 50 (nM) 18900 N/A N/A Details