BROWN, Matthew Frank,DERMENCI, Alpay,FENSOME, Andrew,GERSTENBERGER, Brian Stephen,HAYWARD, Matthew Merrill,OWEN, Dafydd Rhys,WRIGHT, Stephen Wayne,XING, Li Huang,YANG, Xiaojing
申请号：
PH12018501788
公开号：
PH12018501788A1
申请日:
2018.08.23
申请国别(地区):
PH
年份:
2019
代理人:
摘要：
A compound compound having the structure (I) or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate of said compound or pharmaceutically acceptable salt, wherein A, A' and A" are independently O, C=O, C-R' or N-R", where R' and R" may independently be H, amino, -NR7COR6, COR6, -CONR7R8, C1-C6 alkyl, or hydroxy(C1-C6 alkyl), and R" may be present or absent, and is present where the rules of valency permit, and where not more than one of A, A' and A" is O or C=0； R0 and R are independently H, Br, CI, F, or C1-C6 alkyl； R1 is H, C1-C6 alkyl, or hydroxy(C1-C6 alkyl)； R2 is selected from the group consisting of H, C1-C6 alkyl, C1-C6 alkoxy, hydroxy(C1-C6 alkyl), phenyl(C1-C6 alkyl), formyl, heteroaryl, heterocyclic, -COR6, -OCOR6, -COOR6, -NR7COR6, -CONR7R8, and -(CH2)n-W, where W is cyano, hydroxy, C3-C8 cycloalkyl, -SO2NR7R8, and -SO2-R9, where R9 is C1-C6 alkyl, C3-C8 cycloalkyl, heteroaryl, or heterocyclic； wherein each of said alkyl, cycloalkyl, heterocyclic, or heteroaryl may be unsubstituted or substituted by halo, cyano, hydroxy, or C1-C6 alkyl； X is C-R3 or N, where R3 may be H or C1-C6 alkyl； R4 and R5 are independently H, amino, C1-C6 alkyl, or hydroxy(C1-C6 alkyl)； R6, R7 and R8 are each independently H, C1-C6 alkyl, C1-C4 alkoxy(C1-C6 alkyl), or C3-C8 cycloalkyl, said C1- C6 alkyl is optionally substituted by halo, CN or hydroxy； or, R7 and R8 together with the atom bonded thereto form a 5- or 6-membered ring, said ring being optionally substituted by halo, hydroxy, CN, or C1-C6 alkyl； and, n is 0, 1, 2 or 3. Also provided are methods of treatment as Janus Kinase inhibitors and pharmaceutical compositions containing the compounds of the invention and combinations thereof with other therapeutic agents.
