Spiro[isobenzofuran-1,4'-piperidin]-3-ones and 3H-spiroisobenzofuran-1,4'-piperidines

A compound of the formula:

• or a pharmaceutically acceptable salt or prodrug thereof, wherein:
• V, W, Y and Z are independently N or CR1;
• R1 is independently selected at each occurrence from:
• (i) hydrogen, halogen, hydroxy, amino, nitro, cyano, —C(═O)NH2 and —COOH;
• and
• (ii) L-RA-Q-G, wherein:
• L is a bond, —O—, —C(═O)—, —OC(═O)—, —C(═O)O—, —O—C(═O)O—, —S(O)n—, —NRB—, —C(═O)NHRB—, —NHRBC(═O)—, —NRBS(O)n— or —S(O)nNRB—;
• n is 0, 1 or 2;
• RA is (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8) (C3-C8) cycloalkyl, (C3-C8)cycloalkenyl, (C3-C8)cycloalkynyl or (C3-C8)heterocycloalkyl, each of which is optionally substituted with from 1 to 5 substituents independently selected from hydroxy, halogen, amino, cyano, nitro, (C1-C6)alkyl and halo(C1-C6)alkyl;
• Q is a bond, —O—, —C(═O)—, —OC(═O)—, —C(═O)O—, —O—C(═O)O—, —S(O)n—, —CHRB—, —NRB—, —C(═O)NHRB—, —NHRBC(═O)—, —NRBS(O)n— or —S(O)nNRB—;
• RB is independently selected at each occurrence from hydrogen, (C1-C8)alkyl, (C3-C8)cycloalkyl, (C3-C8)cycloalkyl(C1-C8)alkyl and (C1-C8)alkyl(C3-C8)cycloalkyl;
• and
• G is:
• hydrogen;
• or
• (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (C3-C8)cycloalkyl(C1-C8)alkyl or a 3- to 10-membered carbocyclic or heterocyclic group, each of which is optionally substituted with from 1 to 5 substituents independently selected from hydroxy, halogen, amino, cyano, nitro, (C1-C8)alkyl, halo(C1-C8)alkyl, (C1-C8)alkoxy, —NH(C1-C8)alkyl, —N((C1-C8)alkyl)2, —NHC(═O)(C1-C8)alkyl, —N(C1-C8) alkylC(═O)(alkyl), —NHS(O)s(C1-C8)alkyl, —S(O)s(C1-C8)alkyl, —S(O)sNH(C1-C8)alkyl and —S(O)sN((C1-C8)alkyl)2, wherein s is 0, 1 or 2;
• J is a bond or (C1-C6)alkyl;
• and
• RG is (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl or a 3- to 10-membered carbocyclic or heterocyclic group, each of which is optionally substituted with from 1 to 5 substituents independently selected from:
• (i) hydrogen, halogen, hydroxy, amino, nitro, cyano, —C(═O)NH2 and —COOH;
• and
• (ii) T-RC-U-M, wherein:
• T is a bond, —O—, —C(═O)—, —OC(═O)—, —C(═O)O—, —O—C(═O)O—, —S(O)n—, —NRD—, —C(═O)NHRD—, —NHRDC(═O)—, —NRDS(O)n— or —S(O)nNRD—;
• n is independently chosen at each occurrence from 0, 1 or 2;
• RC is (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl or a 3-to 10-membered carbocyclic or heterocyclic group, each of which is optionally substituted with from 1 to 5 substituents independently selected from hydroxy, halogen, amino, cyano, nitro, (C1-C6)alkyl and halo(C1-C6)alkyl;
• U is a bond, —O—, —C(═O)—, —OC(═O)—, —C(═O)O—, —O—C(═O)O—, —S(O)n—, —CHRD—, —NRD—, —C(═O)NHRD—, —NHRDC(═O)—, —NRDS(O)n— or —S(O)nNRD—;
• RD is independently selected at each occurrence from hydrogen, (C1-C8)alkyl, (C3-C8)cycloalkyl, (C3-C8)cycloalkyl(C1-C8)alkyl and (C1-C8) alkyl(C3-C8)cycloalkyl;
• and
• M is:
• hydrogen;
• or
• (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (C3-C8) cycloalkyl(C1-C8)alkyl or a 3- to 10-membered carbocyclic or heterocyclic group, each of which is optionally substituted with from 1 to 9 substituents independently selected from hydroxy, halogen, amino, cyano, nitro, (C1-C8)alkyl, (C3-C8)cycloalkyl, halo(C1-C8)alkyl, (C1-C8)alkoxy, —NH(C1-C8)alkyl, —N((C1-C8)alkyl)2, —NHC(═O)(C1-C8)alkyl, —N(C1-C8)alkylC(═O)(alkyl), —NHS(O)s(C1-C8)alkyl, —S(O)s(C1-C8)alkyl, —S(O)sNH(C1-C8)alkyl and —S(O)sN((C1-C8)alkyl)2, wherein s is 0, 1 or 2;
• with the proviso that if RG, M or both are aromatic, then J is (C1-C6)alkyl.