The identification of potent and selective imidazole-based inhibitors of B-Raf kinase

Bioorganic & Medicinal Chemistry Letters - Tập 16 - Trang 378-381 - 2006
Andrew K. Takle1, Murray J.B. Brown2, Susannah Davies1, David K. Dean1, Gerraint Francis1, Alessandra Gaiba1, Alex W. Hird1, Frank D. King1, Peter J. Lovell1, Antoinette Naylor1, Alastair D. Reith3, Jon G. Steadman1, David M. Wilson1
1Department of Medicinal Chemistry, Neurology and GI Centre of Excellence for Drug Discovery, GlaxoSmithKline Pharmaceuticals, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK
2Department of Screening and Compound Profiling, GlaxoSmithKline Pharmaceuticals, Medicines R&D Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK
3Department of High Throughput Biology, GlaxoSmithKline Pharmaceuticals, Medicines R&D Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK

Tài liệu tham khảo

Pearson, 2001, Endocr. Rev., 22, 153, 10.1210/er.22.2.153 Davies, 2002, Nature, 417, 949, 10.1038/nature00766 Chang, 2003, Int. J. Oncol., 22, 469 Hilger, 2002, Onkologie, 25, 511, 10.1159/000068621 Irving, 2000, Mol. Brain Res., 77, 65, 10.1016/S0169-328X(00)00043-7 Namura, 2001, Proc. Natl. Acad. Sci. U.S.A, 98, 11569, 10.1073/pnas.181213498 Wang, 2003, J. Pharmacol. Exp. Ther., 304, 172, 10.1124/jpet.102.040246 Heimbrook, D. C.; Huber, H. E.; Stirdivant, S. M.; Patrick, D. R.; Claremon, D.; Liverton, N.; Selnick, H.; Ahern, J.; Conroy, R.; Drakas, R.; Falconi, N.; Hancock, P.; Robinson, R.; Smith, G.; Olif, A. American Association for Cancer Research, New Orleans, April 1998 poster #3793. Compound activity is determined as either the ability of test compounds to inhibit B-Raf mediated phosphorylation of kinase dead MEK (data expressed as IC50) or as a B-Raf-binding affinity derived from the fluorescent ligand displacement assay (FP, data expressed as Kd). For assay details, see Dean, D. K.; Takle, A. K.; Wilson, D. M. PCT Int. Appl. WO 02/24680. Adams, 2001, Prog. Med. Chem., 38, 1, 10.1016/S0079-6468(08)70091-2 Davies, 2000, Biochem. J., 351, 95, 10.1042/0264-6021:3510095 Gallagher, 1997, Bioorg. Med. Chem., 5, 49, 10.1016/S0968-0896(96)00212-X