| 摘要 |
The present invention relates to pharmaceutical compounds, compositions and methods, especially as they are related to compositions and methods for the treatment and/or prevention of a proliferation disorder, a cancer, a tumor, an inflammatory disease, an autoimmune disease, psoriasis, dry eye or an immunologically related disease, and in some embodiments diseases or disorders related to the dysregulation of kinase such as, but not limited to, EGFR (including HER), Alk, PDGFR, BLK, BMX/ETK, FLT3(D835Y), ITK, TEC, TXK, BTK, or JAK, and the respective pathways. |
| 主权项 |
1. A compound of Formula (Ia): wherein R1 is H, or
NRcRd wherein
Rc is H, C1-4 alkyl, C1-4 alkenyl, or 3-7 member cyclic ring, said C1-4 alkyl, C1-4 alkenyl, or 3-7 member cyclic ring being optionally substituted with OZ or NR11R12, wherein Z, R11, R12 are independently H or C1-4 alkyl, or said 3-7 member cyclic ring being optionally substituted with C1-4 alkyl that is further optionally substituted with OZ or NR11R12, wherein Z, R11, R12 are independently H or C1-4 alkyl, or said 3-7 member cyclic ring being optionally substituted with SO2(CH2)qH, wherein q is 1-4, or said 3-7 member cyclic ring being optionally substituted with C1-4 alkyl that is further optionally substituted with SO2(CH2)qH, wherein q is 1-4, or said 3-7 member cyclic ring being optionally substituted with R8CO, wherein R8 is C1-4 alkyl, andRd is H, C1-4 alkyl, C1-4 alkenyl, or 3-7 member cyclic ring, said C1-4 alkyl, C1-4 alkenyl or 3-7 member cyclic ring being optionally substituted with OZ or NR11R12, wherein Z, R11, R12 are independently H or C1-4 alkyl; or3-7 member cyclic ring substituted with Ra wherein Ra is C1-8 alkyl optionally substituted with halo, C1-4 alkoxy or SO2(CH2)qH, wherein q is 1-4; orO(CH2)mSO2(CH2)nH, wherein m is 1-4 and n is 1-4; R2 is absent, H, halo, C1-4 alkyl, C1-4 alkoxy, or alkylamine (NR11R12), wherein R11 and R12 are independently H or C1-4 alkyl; R3 is H, hydroxyl, halo, C1-4 alkyl, C1-4 alkoxy, or alkylamine (NR11R12), wherein R11 and R12 are independently H or C1-4 alkyl; R5 is absent, H, halo, C1-4 alkyl, C1-4 alkoxy, or alkylamine (NR11R12), wherein R11 and R12 are independently H or C1-4 alkyl; R6 is H, halo, C1-4 alkyl, C1-4 alkoxy; or alkylamine (NR11R12), wherein R11 and R12 are independently H or C1-4 alkyl; R7 is H, halo, C1-4 alkyl, C1-4 alkoxy, or alkylamine (NR11R12), wherein R11 and R12 are independently H or C1-4 alkyl; R9 is H, hydroxyl, halo, C1-4 alkyl, C1-4 alkoxy, or alkylamine (NR11R12), wherein R11 and R12 are independently H or C1-4 alkyl; R10 is H, hydroxyl, halo, C1-4 alkyl, C1-4 alkoxy, or alkylamine (NR11R12), wherein R11 and R12 are independently H or C1-4 alkyl; or R1 and R5 are part of 3-7 member cyclic ring, said 3-7 member cyclic being optionally substituted with C1-4 alkyl optionally substituted with OZ or NR11R12 wherein Z, R11 and R12 are independently H or C1-4 alkyl, or said 3-7 member cyclic being optionally substituted with R8CO, wherein R8 is C1-4 alkyl, or said 3-7 member cyclic being optionally substituted with SO2(CH2)qH, wherein q is 1-4; or R1 and R2 are part of 3-7 member cyclic ring, optionally substituted with C1-4 alkyl, said C1-4 alkyl further optionally substituted with halo, OZ, or NR11R12 wherein Z, R11 and R12 are independently H or C1-4 alkyl, or one or more members of said 3-7 member cyclic ring is optionally part of a carbonyl group or a sulfonyl group; or R2 and R6 are part of 3-7 member cyclic ring, optionally substituted with C1-4 alkyl optionally substituted with OZ or NR11R12 wherein Z, R11 and R12 are independently H or C1-4 alkyl; R4 is C2 alkenyl optionally substituted with C1-4 alkyl, —CH2OCH3, or —CH2N(CH3)2; X is O, C1-4 alkyl optionally substituted with halo, or Rb, wherein Rb is H, or C1-8 alkyl optionally substituted with halo; Y is C, CH optionally substituted with halo, or N; A is C, CH optionally substituted with halo or N; and wherein at least one of R2, R3, R5 and R6 is not H; or a pharmaceutically acceptable salt thereof. |
