On March 11, 2015, Morrison, Angus; Carswell, Emma; Armer, Richard; Pesnot, Thomas; Bingham, Matilda; Bhamra, Inder; Kirkham, James; Colbon, Paul; Avery, Craig; McCarroll, Andrew; Testar, Richard published a patent.Category: pyrazoles-derivatives The title of the patent was Preparation of triazole derivatives as inhibitors of Raf kinases. And the patent contained the following:
Triazolyl compounds of formula [I; A = a 5-membered heterocyclic moiety; B = C6-14 aryl or C5-14 heteroaryl; L = ·SO 2 NRa , where Ra = H, C1-4 alkyl or C1-4 haloalkyl; R1 = C1-6 alkyl, C1-6 alkenyl, C1-6 alkynyl, C3-14 carbocyclyl or C3-14 heterocyclyl, each optionally substituted with 1-5 substituents selected from halo, ORb , SRb , NRbRc, NO, oxo, cyano, C1-4 acyl, C1-6 alkyl, C1-6 haloalkyl, C3-8 cycloalkyl, C(O)Rb and C(O)ORb ; R2 = H, halo, C1-4 alkyl or C1-4 haloalkyl; R3 = H, C1-6 alkyl, C1-6 haloalkyl, C3-8 cycloalkyl, or C3-8 heterocycloalkyl; R4 = H, halo, OR5 , SR5 , NR5R6, NO, oxo, cyano, acyl, C(O)ORb , C(O)NRbRc , C1-6 alkyl, C3-14 carbocyclyl or C3·14 heterocyclyl; R5 and R6 are H, C(O)Rb, C1-4 alkyl, C1-4 haloalkyl, C3-8 carbocyclyl or C3-8 heterocyclyl; Rb, Rc = H, C1-4 alkyl, C1-4 haloalkyl, C1-4 acyl, C3-7 cycloalkyl or C3-7 halocycloalkyl; m = 0-3; n = 0-2] are prepared These compounds may be useful as inhibitors of Raf kinases, e.g. B-Raf and C-Raf. The invention also contemplates the use of the compounds for treating conditions treatable by the inhibition of Raf kinases, for example cancer, including lymphoma, leukemia and melanoma. Thus, N-[3-(5-bromo-2-tert-butyltriazol-4-yl)-2-fluorophenyl]-2,5-difluorobenzenesulfonamide was coupled with a mixture of 3-methoxy-1-tetrahydropyran-2-yl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole and 5-methoxy-1-tetrahydropyran-2-yl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole in the presence of tripotassium phosphate, tricyclohexylphosphine, and tris(dibenzylideneacetone)dipalladium(0) in DMF and water under heating in a microwave at 130° for 3 h to give N-[3-[2-tert-butyl-5-(3-methoxy-1-tetrahydropyran-2-ylpyrazol-4-yl)triazol-4-yl]-2-fluorophenyl]-2,5-difluorobenzenesulfonamide and N-[3-[2-tert-butyl-5-(5-methoxy-1-tetrahydropyran-2-ylpyrazol-4-yl)triazol-4-yl]-2-fluorophenyl]-2,5-difluorobenzenesulfonamide as an inseparable mixture which was stirred p-toluenesulfonic acid monohydrate in methanol for a total of 72 h to give N-[3-[2-tert-butyl-5-(3-methoxy-1H-pyrazol-4-yl)triazol-4-yl]-2-fluorophenyl]-2,5-difluorobenzenesulfonamide (II). II showed IC50 of <15 nM against B-Raf and C-Raf kinase, resp. The experimental process involved the reaction of 5-Methoxy-1H-pyrazole(cas: 215610-30-3).Category: pyrazoles-derivatives
The Article related to triazole preparation inhibitor raf kinase, pyrazolyltriazolylphenylbenzenesulfonamide preparation inhibitor raf kinase, cancer lymphoma leukemia melanoma treatment triazole preparation and other aspects.Category: pyrazoles-derivatives
Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics