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 compound of formula I: wherein:
R1 is (C1-C6)alkyl, halo(C1-C6)alkyl, RaRbN(C1-C6)alkyl, hydroxy(C1-C6)alkyl, alkoxy(C1-C6)alkyl, het(C1-C6)alkyl, het(C1-C6)haloalkyl, aryl(C1-C6)alkyl, aryl(C1-C6)haloalkyl, aryl-(C═O)—, or het-(C═O)—;Y is a direct bond, —CH2—, or —(C═O)—;n is an integer from 0 to 6 inclusive;each of the n instances of A is independently a direct bond or —(CRcRd)—;R4 is aryl or heteroaryl;Z is a phenyl ring substituted with one or more substituents independently selected from 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, and (C3-C8)cycloalkyl(C1-C6)alkoxy; piperidinyloxy, piperidinyloxy (C1-C6)alkyl, or cyano;each Ra and Rb is independently H, (C1-C6)alkyl, aryl, aryl(C1-C6)alkyl, het, or het(C1-C6)alkyl;each Rc and Rd is independently H, OH, NH2, (C1-C6)alkyl, or Rc and Rd taken together may join to form a 3- to 5-member ring consisting of C atoms and optionally one or more O atom(s) and/or N(X), wherein X is absent, H, O, OH, (C1-C4)alkyl, phenyl or benzyl;wherein any phenyl, aryl, het or heteroaryl of R1 or R4 is optionally substituted at any position with one or more substituents independently selected from (C1-C6)alkyl, hydroxy, hydroxy(C1-C6)alkyl, phenyl, (C1-C6)alkoxy, (C1-C6)alkanoyl, (C1-C6)alkoxycarbonyl, (C1-C6)alkanoyloxy, (C3-C8)cycloalkyl, (C3-C8)cycloalkyl(C1-C6)alkyl, halo(C1-C6)alkyl, (C3-C8)cycloalkyloxy, (C3-C8)cycloalkyl(C1-C6)alkoxy, halo(C1-C6)alkoxy, cyano, nitro, halo, (C1-C6)carboxy or NRcRd; and wherein the piperazine core ring of compound I is optionally substituted at one or more carbon atom(s) with one or more substituents independently selected from oxo, halogen, (C1-C6)alkyl or (C1-C6)alkoxy;and when R1 is C1alkyl, Y-(A)n-R4 taken together is not aryl(C1-C6)alkyl or hydroxy(C1-C6)alkyl;or a pharmaceutically acceptable salt thereof.