Pyrazolo[1,5-a]pyrazin-4-yl derivatives

Abstract

A compound compound having the structure: 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, —NRCOR, COR, —CONRR, C-Calkyl, or hydroxy(C-Calkyl), 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═O; Rand R are independently H, Br, Cl, F, or C-Calkyl; Ris H, C-Calkyl, or hydroxy(C-Calkyl); Ris selected from the group consisting of H, C-Calkyl, C-Calkoxy, hydroxy(C-Calkyl), phenyl(C-Calkyl), formyl, heteroaryl, heterocyclic, —COR, —OCOR, —COOR, —NRCOR, —CONRR, and —(CH)—W, where W is cyano, hydroxy, C-Ccycloalkyl, —SONRR, and —SO—R, where Ris C-Calkyl, C-Ccycloalkyl, heteroaryl, or heterocyclic; wherein each of said alkyl, cycloalkyl, heterocyclic, or heteroaryl may be unsubstituted or substituted by halo, cyano, hydroxy, or C-Calkyl; X is C—Ror N, where Rmay be H or C-Calkyl; Rand Rare independently H, amino, C-Calkyl, or hydroxy(C-Calkyl); R, Rand Rare each independently H, C-Calkyl, C-Calkoxy(C-Calkyl), or C-Ccycloalkyl, said C-Calkyl is optionally substituted by halo, CN or hydroxy; or, Rand Rtogether with the atom bonded thereto form a 5- or 6-membered ring, said ring being optionally substituted by halo, hydroxy, CN, or C-Calkyl; 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.