N-substituted spiropiperidine compounds as ligands for ORL-1 receptor

A compound of the following formula I

• 10
• or a pharmaceutically acceptable salt or solvate thereof, wherein
• R1 through R12 are independently selected from the group consisting of hydrogen;
• halo;
• hydroxy;
• cyano;
• (C1-C6)alkyl;
• (C1-C6)alkyl substituted with one to five halo which may be same or different;
• (C1-C6)alkyl substituted with one to five substituents independently selected from the group consisting of hydroxy, amino, [(C1-C6)alkyl]NH—, [(C1-C6)alkyl]2N—, H2NC(═O)—, [(C1-C6)alkyl]NHC(═O)—, [(C1-C6)alkyl]2NC(═O)—, (C1-C6)alkoxy and a fully saturated five to six membered heterocyclyl containing one to two hetero atoms independently selected from nitrogen and oxygen;
• (C1-C6)alkoxy;
• (C1-C6)alkoxy substituted with one to five halo which may be same or different;
• (C1-C6)alkoxy substituted with one to five substituents independently selected from the group consisting of hydroxy, amino, [(C1-C6)alkyl]NH—, [(C1-C6)alkyl]2N—, H2NC(═O)—, [(C1-C6)alkyl]NHC(═O)— and [(C1-C6)alkyl]2NC(═O)—;
• amino;
• [(C1-C6)alkyl]NH—;
• [(C1-C6)alkyl]2N—;
• carboxy;
• [(C1-C6)alkoxy]C(═O)—;
• H2NC(═O)—;
• [(C1-C6)alkyl]NHC(═O)—;
• [(C1-C6)alkyl]NHC(═O)— wherein said (C1-C6)alkyl is substituted with one hydroxy;
• [(C1-C6)alkyl]2NC(═O)—;
• [(C1-C6)alkyl]2NC(═O)—wherein either or both of (C1-C6)alkyl is substituted with one hydroxy;
• aryl selected from phenyl and naphthyl;
• and four- to eight-membered heterocyclyl containing one to four hetero atoms in the ring independently selected from nitrogen, oxygen and sulfur;
• or two of R1, R2, R3 and R4 groups taken together form —CH2— or —(CH2)2— and the remaining two groups are defined as above;
• X1 and X2 are independently selected from CH2;
• CH-hydroxy;
• O;
• NH;
• S;
• C(═O);
• SO2;
• and [(C1-C6)alkyl]N;
• or X1 and X2 taken together form CH═CH;
• R13 is selected from the group consisting of hydrogen;
• hydroxy;
• (C1-C6)alkyl;
• (C1-C6)alkyl substituted with one to five halo which may be same or different;
• and (C1-C6)alkyl substituted with one to five substituents independently selected from the group consisting of hydroxy, amino, [(C1-C6)alkyl]NH—, [(C1-C6)alkyl]2N—, H2NC(═O)—, [(C1-C6)alkyl]NHC(═O)—, [(C1-C6)alkyl]2NC(═O)—, (C1-C6)alkoxy and a fully saturated five to six membered heterocyclyl containing one to two hetero atoms independently selected from nitrogen and oxygen;
• or
• R12 and R13 taken together with the three ring atoms of the dihydro- or tetrahydro-quinoline ring separating said substituents form a five to seven membered ring which is partially or fully unsaturated, wherein the ring atom not shared with the dihydro- or tetrahydroquinoline ring and adjacent to the nitrogen atom in the dihydro- or tetrahydroquinoline ring is a carbon atom;
• the remaining one to three ring atoms not shared with the dihydro- or tetrahydroquinoline ring are carbon atoms, one of said carbon atoms being optionally replaced with a nitrogen, oxygen or sulfur atom;
• and one or two of the carbon and nitrogen atoms not shared with the dihydro- or tetrahydro-quinoline ring are optionally substituted with substituents independently selected from oxo;
• hydroxy;
• (C1-C6)alkyl;
• (C1-C6)alkyl substituted with one to five halo which may be same or different;
• (C1-C6)alkyl substituted with one to five substituents independently selected from the group consisting of hydroxy, amino, [(C1-C6)alkyl]NH—, [(C1-C6)alkyl]2N—, H2NC(═O)—, [(C1-C6)alkyl]NHC(═O)—, [(C1-C6)alkyl]2NC(═O)—, (C1-C6)alkoxy and a fully saturated five to six membered heterocyclyl containing one to two hetero atoms independently selected from nitrogen and oxygen;
• (C1-C6)alkoxy;
• (C1-C6)alkoxy substituted with one to five halo which may be same or different;
• (C1-C6)alkoxy substituted with one to five substituents independently selected from the group consisting of hydroxy, amino, [(C1-C6)alkyl]NH—, [(C1-C6)alkyl]2N—, H2NC(═O)—, [(C1-C6)alkyl]NHC(═O)— and [(C1-C6)alkyl]2NC(═O)—;
• amino;
• [(C1-C6)alkyl]NH—;
• and [(C1-C6)alkyl]2N—;
• both R14 and R15 are hydrogen or taken together form oxo;
• and
• the dotted line represents a single or double bond.