Detalle de: 1-Aryl-3-(4-methoxybenzyl)ureas as potentially irreversible glycogen synthase kinase 3 inhibitors: Synthesis and biological evaluation
| Title | 1-Aryl-3-(4-methoxybenzyl)ureas as potentially irreversible glycogen synthase kinase 3 inhibitors: Synthesis and biological evaluation |
| Abstract |
Glycogen synthase kinase 3 (GSK-3) has become known for its multifactorial involvement in the pathogenesis of Alzheimer's disease. In this study, a benzothiazole- and benzimidazole set of 1-aryl-3-(4-methoxybenzyl)ureas were synthesised as proposed Cys199-targeted covalent inhibitors of GSK-3β, through the incorporation of an electrophilic warhead onto their ring scaffolds. The nitrile-substituted benzimidazolylurea 2b (IC 50 = 0.086 ± 0.023 µM) and halomethylketone-substituted benzimidazolylurea 9b (IC 50 = 0.13 ± 0.060 µM) displayed high GSK-3β inhibitory activity, in comparison to reference inhibitor AR-A014418 (1, IC 50 = 0.072 ± 0.043) in our assay. The results suggest further investigation of 2b and 9b as potential covalent inhibitors of GSK-3β, since a targeted interaction might provide improved kinase-selectivity. |
| Apa Reference | Venter, J., Perez, C., van Otterlo, W. A. L., Martínez, A., & Blackie, M. A. L. (2019). 1-Aryl-3-(4-methoxybenzyl)ureas as potentially irreversible glycogen synthase kinase 3 inhibitors: Synthesis and biological evaluation. Bioorganic & Medicinal Chemistry Letters, 29(13), 1597–1600. 10.1016/j.bmcl.2019.04.049 |
| Doi | 10.1016/j.bmcl.2019.04.049 |
| Publication Date | Jul 2019 |
| Publication Type | Article |
| Researcher | Ana Martínez |
| Ontology | Genome Assembly, Drug Discovery and design |
| Research Groups | Translational Medicinal and Biological Chemistry |
| Tools |