Pfizer Inc.
PYRAZOLO[1,5-A]PYRAZIN-4-YL DERIVATIVES

Abstract:

A compound having the structure: ##STR00001## 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.dbd.O, C--R' or N--R'', where R' and R'' may independently be H, amino, --NR.sub.7COR.sub.6, COR.sup.6, --CONR.sub.7R.sub.8, C.sub.1-C.sub.6 alkyl, or hydroxy(C.sub.1-C.sub.6 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.dbd.O; R.sub.0 and R are independently H, Br, Cl, F, or C.sub.1-C.sub.6 alkyl; R.sub.1 is H, C.sub.1-C.sub.6 alkyl, or hydroxy(C.sub.1-C.sub.6 alkyl); R.sub.2 is selected from the group consisting of H, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy, hydroxy(C.sub.1-C.sub.6 alkyl), phenyl(C.sub.1-C.sub.6 alkyl), formyl, heteroaryl, heterocyclic, --COR.sub.6, --OCOR.sub.6, --COOR.sub.6, --NR.sub.7COR.sub.6, --CONR.sub.7R.sub.8, and --(CH.sub.2).sub.n--W, where W is cyano, hydroxy, C.sub.3-C.sub.8 cycloalkyl, --SO.sub.2NR.sub.7R.sub.8, and --SO.sub.2--R.sub.9, where R.sub.9 is C.sub.1-C.sub.6 alkyl, C.sub.3-C.sub.8 cycloalkyl, heteroaryl, or heterocyclic; wherein each of said alkyl, cycloalkyl, heterocyclic, or heteroaryl may be unsubstituted or substituted by halo, cyano, hydroxy, or C.sub.1-C.sub.6 alkyl; X is C--R.sub.3 or N, where R.sub.3 may be H or C.sub.1-C.sub.6 alkyl; R.sub.4 and R.sub.5 are independently H, amino, C.sub.1-C.sub.6 alkyl, or hydroxy(C.sub.1-C.sub.6 alkyl); R.sub.6, R.sub.7 and R.sub.8 are each independently H, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.4 alkoxy(C.sub.1-C.sub.6 alkyl), or C.sub.3-C.sub.8 cycloalkyl, said C.sub.1-C.sub.6 alkyl is optionally substituted by halo, CN or hydroxy; or, R.sub.7 and R.sub.8 together with the atom bonded thereto form a 5- or 6-membered ring, said ring being optionally substituted by halo, hydroxy, CN, or C.sub.1-C.sub.6alkyl; 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.