CHEN, WEI,WANG, LONGCHENG,LOURY, DAVID J.,JIA, ZHAOZHONG J.
申请号：
PE0004272016
公开号：
PE05602016A1
申请日:
2014.09.29
申请国别(地区):
PE
年份:
2016
代理人:
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 diseasesLa presente invencion se refiere a derivados de pirazolo[3,4-d]pirimidin de formula (I), en donde: L1 es –N(R2)C(O)- o –C(O)N(R2)- R1 es arilo C6-C12, entre otros R2 es H o alquilo C1-C4 R4 es H, alquilo C1-C6, entre otros R5 es cicloalquilo C3-C8, entre otros R10 es halogeno, entre otros m es 1 o 2 n es 0 o 1 y p es 0, 1 o 2. Son compuestos preferidos: (R,E)-4-(4-amino-1-(1-(4-(ciclopropil(metil)amino)but-2-enoil)pirrolidin-3-il)- 1H-pirazolo[3,4-d]pirimidin-3-il)-N-(4-metilpiridin-2-il)benzamida (R,E)-4-(4-amino-1-(1-(4-(ciclopropil(metil)amino)but-2-enoil)pirrolidin-3-il)- 1H-pirazolo[3,4-d]pirimidin-3-il)-N-(4-(trifluorometil)piridin-2-il)benzamida, entre otros. Estos derivados actuan como inhibidores irreversibles de la Tirosina Cinasa de Bruton (Btk) siendo utiles en el tratamiento de enfermedades autoinmunitarias, heteroinmunitarias, cancer, inclusive linfoma y enfermedades inflamatorias
