N-containing heterocyclic compounds

摘要

The present invention relates to N-containing heterocyclic compounds that are inhibitors of protein kinases including JAK kinases. In particular, the compounds are selective for JAK1, JAK2, JAK3 or TYK2 kinases and combinations thereof such as JAK1 and JAK2. The kinase inhibitors can be used in the treatment of kinase associated diseases such as immunological and inflammatory diseases including organ transplants; hyperproliferative diseases including cancer and myeloproliferative diseases; viral diseases; metabolic diseases; and vascular diseases.

主权项

1. A method of inhibiting a kinase in a cell comprising contacting the cell with the compound of formula 1b wherein Z is NR2 or S; A and B are independently absent or substituted or unsubstituted C1-6alkylene wherein one or more carbon atoms can be optionally replaced with O, CO, NR2, NR2CO, CONR2, NR2SO2, SO2NR2, S and/or S(O)n; R1 is independently selected from the group consisting of H, substituted or unsubstituted C1-6alkyl, substituted or unsubstituted C2-6alkenyl, substituted or unsubstituted C2-6alkynyl, substituted or unsubstituted C1-6alkoxy, OH, halogen, CN, NO2, NR2R3, So2R3, SO2NR2R3, CF3, OCF3, NR2SO2R3, CO2R3, COSR3, CSR3, COR3, NR2, CSR3, NR2CSR3, CONR2R3, NR2COR3, NR2CONR2R3, SO3R3, substituted or unsubstituted C3-8cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl having up to 3 heteroatoms selected from N, O, S and SO2; R is selected from the group consisting of H, substituted or unsubstituted C1-6alkyl, substituted or unsubstituted C2-6alkenyl, substituted or unsubstituted C2-6alkynyl, substituted or unsubstituted C1-6alkoxy, OH, halogen, CN, NO2, CO2R3, CONR2R3, NR2COR3, SO3R3, C3-8cycloalkyl, aryl and heterocyclyl having up to 3 heteroatoms selected from N, O, S and SO2, each of which may be substituted with up to 3 substituents independently selected from the group consisting of substituted or unsubstituted C1-6alkyl, substituted or unsubstituted C2-6alkenyl, substituted or unsubstituted C2-6alkynyl, substituted or unsubstituted C1-6alkoxy, OH, OCF3, halogen, CN, NO2, NR2R3, S02R3, SO2NR2R3, NR2SO2R3, CO2R3, COR3, NR2COR3, R2NHCO2R3, CONR2R3, NR2CONR2R3 and substituted or unsubstituted heterocyclyl having up to 3 heteroatoms selected from N, O, S and SO2; R2 and R3 are independently selected from the group consisting of H, substituted or unsubstituted C1-6alkyl, substituted or unsubstituted C2-6alkenyl, substituted or unsubstituted C2-6alkynyl, substituted or unsubstituted C1-6alkoxy, CN, substituted or unsubstituted C3-8cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl having up to 3 heteroatoms selected from N, O, S and SO2; m is 1 to 3; and n is 1 or 2; and salts or stereoisomers thereof.