The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.
N-(5-Chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5- (tetrahydro-2 H-pyran-4-yloxy)quinazolin-4-amine, a Novel, Highly Selective, Orally Available, Dual-Specific c-Src/Abl Kinase Inhibitor
Open accessAbstract
Src family kinases (SFKs) are nonreceptor tyrosine kinases that are reported to be critical for cancer progression. We report here a novel subseries of C-5-substituted anilinoquinazolines that display high affinity and specificity for the tyrosine kinase domain of the c-Src and Abl enzymes. These compounds exhibit high selectivity for SFKs over a panel of recombinant protein kinases, excellent pharmacokinetics, and in vivo activity following oral dosing. N-(5-Chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5-(tetrahydro-2H-pyran-4-yloxy)quinazolin-4-amine (AZD0530) inhibits c-Src and Abl enzymes at low nanomolar concentrations and is highly selective over a range of kinases. AZD0530 displays excellent pharmacokinetic parameters in animal preclinically and in man (t(1/2) = 40 h). AZD0530 is a potent inhibitor of tumor growth in a c-Src-transfected 3T3-fibroblast xenograft model in vivo and led to a significant increase in survival in a highly aggressive, orthotopic model of human pancreatic cancer when dosed orally once daily. AZD0530 is currently undergoing clinical evaluation in man.
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Patient-derived models of acquired resistance can identify effective drug combinations for cancer
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Metadata
- Authors
- Hennequin, L. F., Allen, J., Breed, J., Curwen, J., Fennell, M., Green, T. P., Lambert-van der Brempt, C., Morgentin, R., Norman, R. A., Olivier, A., Otterbein, L., Plé, P. A., Warin, N., & Costello, G.
- Venue
- Journal of Medicinal Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2006-10-04
- Volume
- 49
- Issue
- 22
- Pages
- 6465-6488
- ISSN
- 0022-2623 (ISSN-L)
- 1520-4804
- OpenAlex
- W2024262880
- Cited by
- 364
- References
- 46
- FWCI
- 13.36
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: N-(5-Chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5- (tetrahydro-2 H-pyran-4-yloxy)quinazolin-4-amine, a Novel, Highly Selective, Orally Available, Dual-Specific c-Src/Abl Kinase Inhibitor. https://app.cochat.ai/papers/10.1021/jm060434q
- The paper
- Hennequin, L. F., Allen, J., Breed, J., Curwen, J., Fennell, M., Green, T. P., Lambert-van der Brempt, C., Morgentin, R., Norman, R. A., Olivier, A., Otterbein, L., Plé, P. A., Warin, N., & Costello, G. (2006). N-(5-Chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5- (tetrahydro-2 H-pyran-4-yloxy)quinazolin-4-amine, a Novel, Highly Selective, Orally Available, Dual-Specific c-Src/Abl Kinase Inhibitor. Journal of Medicinal Chemistry. https://doi.org/10.1021/jm060434q
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
