Derivatives of pyrazolo 3,4-d pyrimidine as irreversible inhibitors of tyrosine kinase Bruton (BTK)

摘要

The present Invention relates to Derivatives of pyrazolo [3,4-d] pyrimidine of formula (i) wherein: L1 is u2013n (R2) C (o) - or - C (o) n (R2); r1 is aryl C6 C12, among others; R2 is H or c1-c4 alkyl h; R4 is C1 - C6 alkyl, cycloalkyl, among others; R5 is C3, C8, among others, R10 is Halogen, among others; M is 1 or 2, N is 0 OR 1; and P is 0, 1 or 2.Preferred compounds are: (R, e) - 4 - (4 - amino - 1 - (1 - (4 - ((but Cyclopropyl methyl) amino) - 2 - enoil) pyrrolidin-3-yl) - 1H pyrazolo [3,4-d] - 3 - il pyrimidin-2-yl) - N - (4 - metilpiridin - 2 - il) benzamide (R, e) - 4 - (4 - amino - 1 - (1 - (4 - ((but Cyclopropyl methyl) amino) - 2 - enoil) pyrrolidin-3-yl) - 1H pyrazolo [3,4-d] pyrimidine - 3 - il) - N - (4 - (TRIF Luorometil) pyridin-2-yl) benzamide, among others.These derivatives act as irreversible inhibitors of tyrosine kinase Bruton (BTK) being useful in the treatment of autoimmune diseases, heteroinmunitarias, cancer, including lymphoma and inflammatory diseases