Show simple item record

dc.contributor.authorNiculescu-Duvaz, D
dc.contributor.authorNiculescu-Duvaz, I
dc.contributor.authorSuijkerbuijk, B
dc.contributor.authorMénard, D
dc.contributor.authorZambon, A
dc.contributor.authorDavies, L
dc.contributor.authorPons, J
dc.contributor.authorWhittaker, S
dc.contributor.authorMarais, Richard
dc.contributor.authorSpringer, C
dc.date.accessioned2013-04-05T13:01:26Z
dc.date.available2013-04-05T13:01:26Z
dc.date.issued2013-03-01
dc.identifier.citationPotent BRAF kinase inhibitors based on 2,4,5-trisubstituted imidazole with naphthyl and benzothiophene 4-substituents. 2013, 21 (5):1284-304 Bioorg Med Chemen_GB
dc.identifier.issn1464-3391
dc.identifier.pmid23376011
dc.identifier.doi10.1016/j.bmc.2012.12.035
dc.identifier.urihttp://hdl.handle.net/10541/279093
dc.description.abstractThe RAS-RAF-MEK-ERK pathway is hyperactivated in 30% of human cancers. BRAF is a serine-threonine kinase, belonging to this pathway that is mutated with high frequency in human melanoma and other cancers thus BRAF is an important therapeutic target in melanoma. We have designed inhibitors of BRAF based on 2,4,5-trisubstituted imidazoles with naphthyl and benzothiophene-4-substituents. Two compounds were discovered to be potent BRAF inhibitors: 1-(6-{2-[4-(2-dimethylamino-ethoxy)phenyl]-5-(pyridin-4-yl)-1H-imidazol-4-yl} benzo[b]thiophen-3-yl)-2,2,2-trifluoroethanol (1i) with BRAF IC(50)=190 nM and with cellular GI(50)=2100 nM, and 6-{2-[4-(2-dimethylamino-ethoxy)-phenyl]-5-pyridin-4-yl-3H-imidazol-4-yl}-naphthalen-1-ol (1q) with IC(50)=9 nM and GI(50)=220 nM.
dc.language.isoenen
dc.rightsArchived with thanks to Bioorganic & medicinal chemistryen_GB
dc.titlePotent BRAF kinase inhibitors based on 2,4,5-trisubstituted imidazole with naphthyl and benzothiophene 4-substituents.en
dc.typeArticleen
dc.contributor.departmentThe Institute of Cancer Research, Cancer Research UK Cancer Therapeutics Unit, Division of Cancer Therapeutics, 15 Cotswold Road, Sutton, Surrey SM2 5NG, United Kingdom.en_GB
dc.identifier.journalBioorganic & Medicinal Chemistryen_GB
html.description.abstractThe RAS-RAF-MEK-ERK pathway is hyperactivated in 30% of human cancers. BRAF is a serine-threonine kinase, belonging to this pathway that is mutated with high frequency in human melanoma and other cancers thus BRAF is an important therapeutic target in melanoma. We have designed inhibitors of BRAF based on 2,4,5-trisubstituted imidazoles with naphthyl and benzothiophene-4-substituents. Two compounds were discovered to be potent BRAF inhibitors: 1-(6-{2-[4-(2-dimethylamino-ethoxy)phenyl]-5-(pyridin-4-yl)-1H-imidazol-4-yl} benzo[b]thiophen-3-yl)-2,2,2-trifluoroethanol (1i) with BRAF IC(50)=190 nM and with cellular GI(50)=2100 nM, and 6-{2-[4-(2-dimethylamino-ethoxy)-phenyl]-5-pyridin-4-yl-3H-imidazol-4-yl}-naphthalen-1-ol (1q) with IC(50)=9 nM and GI(50)=220 nM.


Files in this item

This item appears in the following Collection(s)

Show simple item record