1-(5-tert-butyl-2-phenyl-2H-pyrazol-3-yl)-3-[2-fluoro-4-(1-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-B]pyridin-7-yloxy)-phenyl]-urea and related compounds and their use in therapy

The present invention pertains generally to the field of therapeutic compds., and more specifically to certain compds. of the following formula (I) (for convenience, collectively referred to herein as "IP compds.")​, which, inter alia, are useful in the treatment of cancer, e.g., cancer characterized by (e.g., driven by) mutant RAS ("mutant RAS cancer")​. The present invention also pertains to pharmaceutical compns. comprising such compds., and the use of such compds. and compns. in the treatment of cancer, e.g., mutant RAS cancer

BRAF as a therapeutic target: A patent review (2006-2012)

Introduction: After its identification as an oncogene in 2002, mutant BRAF has become the target of a number of drug discovery programmes, primarily aimed at the treatment of late stage or unresectable melanoma. Some of the drugs thus developed, such as vemurafenib and dabrafenib, show impressive responses in melanoma patients harbouring a BRAF mutation. Areas covered: This review summarises the patent literature on BRAF from 2006 to 2012, focusing on the specific areas of inhibitors of mutant BRAF, drug combinations including BRAF inhibitors, diagnostic methods for use with mutant BRAF inhibitors & diagnosis and treatment of mutant BRAF cancers resistant to BRAF inhibitors. Expert opinion: Whilst these first-generation BRAF inhibitors initially mediate excellent responses in late stage or unresectable melanoma patients bearing the V600 mutation, resistance usually occurs and patients eventually relapse. The patent literature for new BRAF inhibitors and therapies reflects the desire to develop second-generation drugs able to overcome this resistance and combination treatments that increase the efficiency of current mutant BRAF inhibitors. \ua9 2013 Informa UK, Ltd

Preparation of 1-​(5-​tert-​butyl-​2-​aryl-​pyrazol-​3-​yl)​-​3-​[2-​fluoro-​4-​[(3-​oxo-​4H-​pyrido[2,​3-​b]​pyrazin-​8-​yl)​oxy]​phenyl]​urea derivatives as RAF inhibitors for treating cancer

The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain l-(5-tert-butyl-2-aryl-pyrazol-3-yl)- 3-[2-fluoro-4-[(3-oxo-4H-pyrido[2,3-b]pyrazin-8-yl)oxy]phenyl]urea compounds (referred herein as "TBAP compounds") that, inter alia, inhibit RAF (e.g., BRAF, CRAF, etc.). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit RAF (e.g., BRAF, CRAF, etc.); and to treat disorders including: proliferative disorders; cancer (including, e.g., malignant melanoma, colorectal carcinoma, pancreatic adenocarcinoma); inflammation; immunological disorders; viral infections; fibrotic disorders; disorders associated with a mutated form of RAF (e.g., BRAF, CRAF, etc.); disorders ameliorated by the inhibition of RAF (e.g., BRAF, CRAF, etc.); disorders ameliorated by the inhibition of mutant BRAF; disorders ameliorated by the inhibition of BRAF and CRAF; disorders associated with RAS mutations and/or MAPK pathway activation; disorders ameliorated by the inhibition of SRC, p38, FGFRA, VEGFR-2 (KDR), and/or LCK; etc

1 - ( 5 - TERT - BUTYL - 2 - ARYL - PYRAZOL - 3 - YL ) . 3 - 12 - FLUORO - 4 - [ ( 3 - OXO - 4H - PYRIDO [ 2 . 3 - BJPYRAZIN - 8 - YL ) OXY | PHENYLJUREA DERIVATIVES AS RAF INHIBITORS FOR THE TREATMENT OF CANCER

therapeutic compounds . More specifically the present invention pertains to certain 1 - ( 5 - tert - butyl - 2 - aryl - pyrazol - 3 - yl ) - 3 - [ 2 - fluoro - 4 - [ ( 3 - oxo 4H - pyrido [ 2 , 3 - b ] pyrazin - 8 - yl ) oxylphenyl ] urea compounds ( referred herein as “ TBAP compounds ” ) that , inter alia , inhibit RAF ( e . g . , BRAF , CRAF , etc . ) . The present invention also pertains to pharmaceutical com positions comprising such compounds , and the use of such compounds and compositions , both in vitro and in vivo , to inhibit RAF ( e . g . , BRAF , CRAF , etc . ) ; and to treat disorders including : proliferative disorders ; cancer ( including , e . g . , malignant melanoma , colorectal carcinoma , pancreatic adenocarcinoma ) ; inflammation ; immunological disorders ; viral infections ; fibrotic disorders ; disorders associated with a mutated form of RAF ( e . g . , BRAF , CRAF , etc . ) ; disorders ameliorated by the inhibition of RAF ( e . g . , BRAF , CRAF , etc . ) ; disorders ameliorated by the inhibition of mutant BRAF ; disorders ameliorated by the inhibition of BRAF and CRAF ; disorders associated with RAS mutations and / or MAPK pathway activation ; disorders ameliorated by the inhibition of SRC , p38 , FGFRA , VEGFR - 2 ( KDR ) , and / or LCK ; etc

1-(5-TERT-BUTYL-2-ARYL-PYRAZOL-3-YL)-3-2-FLUORO-4-(3-OXO-4H-PYRIDO2,3-BPYRAZIN-8-YL)OXYPHENYLUREA DERIVATIVES AS RAF INHIBITORS FOR THE TREATMENT OF CANCER

The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain 1-(5-tert-butyl-2-aryl-pyrazol-3-yl)- 3-2-fluoro-4-(3-oxo-4H-pyrido 2,3-bipyrazin-8-yl)oxy phenylurea compounds (referred herein as “TBAP compounds') that, inter alia, inhibit RAF (e.g., BRAF, CRAF, etc.). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of Such compounds and compositions, both in vitro and in vivo, to inhibit RAF (e.g., BRAF, CRAF, etc.); and to treat disorders including proliferative disorders; cancer (including, e.g., malignant melanoma, colorectal carcinoma, pancreatic adenocarcinoma); inflammation; immunological disorders; viral infections; fibrotic disorders; disorders associated with a mutated form of RAF (e.g. BRAF, CRAF, etc.); disorders ameliorated by the inhibition of RAF (e.g., BRAF. CRAF, etc.); disorders ameliorated by the inhibition of mutant BRAF; disorders ameliorated by the inhibition of BRAF and CRAF; disorders associated with RAS mutations and/or MAPK pathway activation; disorders ameliorated by the inhibition of SRC, p38, FGFRA, VEGFR-2 (KDR), and/or LCK; etc.(I