Pyrimidine derivatives as inhibitors of the tyrosine kinase activity of Bruton (BTK)

摘要

Refers to Derivatives of pyrimidine compounds of formula (1) where Z1 and Z2 is cr is n or Z1 and Z2 is cr is n; is phenylene, piridilideno, 1.2 - 2 - oxo - dihidropiridinilo, among others, optionally substituted with Halo, CN, Nitro substituents, Oxo, among others; l is alquileno (C0 - C4), or - alquileno (C0 - Alquileno (C0 C4) - C4) (os), among others, optionally with sustiuidos Halo, CN, Nitro, Oxo,Among other substituents; G H, Halo, Hydroxy, alkoxy, Nitro (C1 - C20), among others; R and R1 are each H or alkyl (C1 - C6); W is piridilideno phenylene or optionally substituted alkyl, alkoxy (C1 - C6) (C1 - C6), Halo or Hydroxy q is a Compound of formula (i), (ii), among others, where R13, R14 And R15 are each h, alkyl (C1 - C6), haloalquilo (C1 - C6), phenylAmong others; R2 is an aryl or heteroaryl (c5-c6) of 5 to 7 members optionally substituted with Hydroxy, sulfonyl, Halo, (c1-c6 alkoxy substituents), among others.Preferred compounds are: 4 - Tert Butyl N - (2 - methyl - 3 - (2 - (4 - (2 - morpholino - 2-oxoethyl) phenylamino) pyrimidin-4-yl) phenyl) benzamide, 4 - Tert Butyl N - (2 - methyl - 3 - 2 - {[4 - (4 - (carbonyl) - phenylamino] pyrimidin-4-yl) - phenyl) - benzamide, {2 - methyl - 3 - [2 - (4 - metilcarbamoil - phenylamino) - pyrimidin-4-yl] - phenyl) - amide Acid 4 - ter - butilbenzoico, among others. It also relates to a Pharmaceutical composition.These compounds are inhibitors of the tyrosine kinase activity of Bruton (BTK) being useful in the treatment of cancer, Leukemia