Pyrimidine, pyridine and pyrazine amide derivatives substituted with thiazole or imidazole and related compounds such as inhibitors of ABL1, ABL2 and BCR-ABL1 for the treatment of cancer, specific viral infections and specific CNS disorders

摘要

A compound of the formula (I): ** Formula ** wherein: Y in each presentation is independently selected from N and CH; Y1 is selected from N and CR5; wherein R5 is selected from hydrogen, methoxy and imidazolyl; wherein the imidazolyl is unsubstituted or substituted with methyl; R1 is a 5- to 9-membered heteroaryl ring that incorporates one to four nitrogen, oxygen or sulfur atoms, wherein no more than one of the atoms is selected from an oxygen or sulfur; wherein the heteroaryl of R1 is unsubstituted or substituted with 1 to 3 R6 groups; R2 is selected from hydrogen, halogen, hydroxyl, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, methoxycarbonyl, 3,6-dihydro-2H-pyran-4-yl, tetrahydro- 2H-pyran-4-yl, tetrahydro-2H-pyran-4-yloxy and cyclobutyl; wherein this alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, cyclobutyl or tetrahydro-2Hpiran-4-yl of R2 may be unsubstituted or substituted with 1 to 3 groups independently selected from halogen, hydroxyl , cyano, alkoxy of 1 to 4 carbon atoms, morpholino, piperazinyl and NR5aR5b; wherein R5a is selected from hydrogen and alkyl of 1 to 4 carbon atoms; and R5b is selected from hydroxy-ethyl; wherein the R2 piperazinyl substituent may be unsubstituted or additionally substituted with alkyl of 1 to 4 carbon atoms; R3 is selected from hydrogen and halogen; R4 is selected from -SF5 and -Y2-CF2-Y3; R6 in each presentation is independently selected from hydrogen, hydroxyl, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, cyano, trifluoro-methyl, halogen, amino, methyl-carbonyl, methoxy carbonyl, cyclopropyl and pyrrolidinyl methyl; wherein this alkyl of 1 to 4 carbon atoms, or alkoxy of 1 to 4 carbon atoms of R6 is unsubstituted or substituted with 1 to 3 groups independently selected from halogen and hydroxyl; Y2 is selected from CF2, O and S (O) 0-2; and Y3 is selected from hydrogen, halogen, methyl, difluoro-methyl and trifluoro-methyl; Y4 is selected from N and CR2; Y5 and Y6 are independently selected from N, CR5 or CF; wherein R5 is selected from hydrogen and halogen; with the proviso that, when Y4 is N, Y5, Y6 and Y1 are each CR5; or pharmaceutically acceptable salts thereof; with the proviso that the compounds of the formula I do not include 3- (2-amino-quinazolin-6- yl) -4-methyl-N- (4- (trifluoro-methoxy) -phenyl) -benzamide and 3- ( 2-amino-quinazolin-6-yl) -5-bromo-N- (4- (trifluoro-methoxy) -phenyl) -benzamide, for use in the treatment of cancer, a virus infection selected from a smallpox virus and an Ebola virus infection or a c-ABL-mediated CNS disorder selected from Alzheimer's and Pick's disease.