Therapeutic piperazines

摘要

The invention includes a compound of formula I:;
wherein R1, Y, A, n, R4 and Z have any of the values described herein, as well as salts of such compounds, compositions comprising such compounds, and therapeutic methods that comprise the administration of such compounds. The compounds are inhibitors of PDE4 function and are useful for improving cognitive function and/or treating cognitive disorders or impairment, traumatic and/or ischemic injuries of the central and peripheral nervous system and/or psychiatric disorders in animals, especially humans.

主权项

1. A method
of improving cognitive function in an animal comprising administering to the animal an effective amount of a compound of formula (I): or a pharmaceutically acceptable salt thereof, wherein: R1 is (C1-C6)alkyl or aryl(C1-C6)alkyl; Y is —(C═O); n is an integer from 0 to 6 inclusive; A is —(CRcRd)—; R4 is aryl or heteroaryl; Z is a phenyl ring substituted with one or more substituents independently selected from the group consisting of halogen, (C1-C6)alkyl, halo(C1-C6)alkyl, (C3-C8)cycloalkyl, (C3-C8)cycloalkyl(C1-C6)alkyl, (C1-C6)alkoxy, halo(C1-C6)alkoxy, (C3-C8)cycloalkoxy, (C3-C8)cycloalkyl(C1-C6)alkoxy, piperidinyloxy, piperidinyloxy(C1-C6)alkyl, and cyano; and each Rc and Rd is independently H (hydrogen), OH, NH2, or (C1-C6)alkyl, or optionally Rc and Rd taken together with the carbon to which they are attached is a 3 to 5 member ring consisting of C (carbon) atoms and optionally one or more O (oxygen) atoms and/or N(X) group, wherein X is absent, H (hydrogen), O (oxygen), OH, (C1-C4)alkyl, phenyl or benzyl, wherein any aryl, or heteroaryl of R1 or R4 is optionally substituted with one or more substituents independently selected from the group consisting of (C1-C6)alkyl, hydroxy, hydroxy(C1-C6)alkyl, halo(C1-C6)alkyl, phenyl, (C1-C6)alkoxy, (C1-C6)alkanoyl, (C1-C6)alkoxycarbonyl, (C1-C6)alkanoyloxy, (C3-C8)cycloalkyl, (C3-C8)cycloalkyl(C1-C6)alkoxy, halo(C1-C6)alkoxy, cyano, nitro, halo, (C1-C6)carboxy, and NRcRd; and wherein the piperazine core ring of formula (I) is optionally substituted at one or more carbon atoms with one or more substituents independently selected from the group consisting of oxo, halogen, (C1-C6)alkyl, and (C1-C6)alkoxy.