Piperidine derivatives as serotonine reuptake inhibitors

A method of inhibiting the reuptake of serotonin and antagonizing the 5-HT1A receptor which comprises administering to a subject in need of such treatment an effective amount of a compound of the formula:

• wherein:
• X represents O or S;
• Y represents —C(═O)—, —CH(OH)—, —CH2—, S, SO, or SO2;
• represents a single or a double bond;
• n is 1, 2, 3 or 4;
• R1a, R1b, R1c, and R2 are each independently H, F, Cl, Br, I, OH, C1-C6 alkyl, C1-C6 alkoxy, halo(C1-C6)alkyl, phenyl, NO2, —NR7R8, CN or phenyl substituted with from 1 to 3 substituents selected from the group consisting of F, Cl, Br, I, OH, C1-C6 alkyl, C1-C6 alkoxy, halo(C1-C6)alkyl, phenyl, NO2, NH2, or CN;
• R3 represents H, OH, hydroxy(C1-C6)alkyl, C1-C6 alkyl, or C1-C6 alkoxy;
• R4 represents aryl, heterocycle, C3-C8 cycloalkyl, aryl substituted with from 1 to 3 substituents selected from the group consisting of F, Cl, Br, I, OH, C1-C6 alkyl, C1-C6 alkoxy, halo(C1-C6)alkyl, phenyl, NO2, NH2, or CN;
• or heterocycle substituted with from 1 to 3 substituents selected from the group consisting of F, Cl, Br, I, OH, C1-C6 alkyl, C1-C6 alkoxy, halo(C1-C6)alkyl, phenyl, NO2, NH2, or CN;
• R5 represents aryl, heterocycle, C3-C8 cycloalkyl, aryl substituted with from 1 to 3 substituents selected from the group consisting of F, Cl, Br, I, OH, C1-C6 alkyl, C1-C6 alkoxy, hydroxy(C1-C6)alkyl, halo(C1-C(,)alkyl, phenyl, NO2, NH2, or CN;
• heterocycle substituted with from 1 to 3 substituents selected from the group consisting of F, Cl, Br, I, OH, C1-C6 alkyl,C1-C6 alkoxy, hydroxy(C1-C6)alkyl, halo(C1-C6)alkyl, phenyl, NO2, NH2, or CN;
• or C3-C8 cycloalkyl substituted with C1-C4 alkyl;
• R6a and R6b are each independently H or C1-C3 alkyl;
• R7 and R8 are each independently H, C1-C6 alkyl, aryl or aryl substituted with from 1 to 3 substituents selected from the group consisting of F, Cl, Br, I, OH, C1-C6 alkyl, C1-C6 alkoxy, halo(C1-C6)alkyl, phenyl, NO2, NH2, or CN;
• or a pharmaceutically acceptable salt thereof.

A method of potentiating the action of a serotonin reuptake inhibitor comprising administering to a subject in of such treatment a compound formula:

• wherein:
• X represents O or S;
• Y represents —C(═O)—, —CH(OH)—, —CH2—, S, SO, or SO2;
• represents a single or a double bond;
• n is 1, 2, 3 or 4;
• R1a, R1b, R1c, and R2 are each independently H, F, Cl, Br, I, OH, C1-C6 alkyl, C1-C6 alkoxy, halo(C1-C6)alkyl, phenyl, NO2, —NR7R8, CN or phenyl substituted with from 1 to 3 substituents selected from the group consisting of F, Cl, Br, I, OH, C1-C6 alkyl, C1-C6 alkoxy, halo(C1-C6)alkyl, phenyl, NO2, NH2, or CN;
• R3 represents H, OH, hydroxy(C1-C6)alkyl, C1-C6 alkyl, or C1-C6 alkoxy;
• R4 represents aryl, heterocycle, C3-C8 cycloalkyl, aryl substituted with from 1 to 3 substituents selected from the group consisting of F, Cl, Br, I, OH, C1-C6 alkyl, C1-C6 alkoxy, halo(C1-C6)alkyl, phenyl, NO2, NH2, or CN;
• or heterocycle substituted with from 1 to 3 substituents selected from the group consisting of F, Cl, Br, I, OH, C1-C6 alkyl, C1-C6 alkoxy, halo(C1-C6)alkyl, phenyl, NO2, NH2, or CN;
• R5 represents aryl, heterocycle, C3-C8 cycloalkyl, aryl substituted with from 1 to 3 substituents selected from the group consisting of F, Cl, Br, I, OH, C1-C6 alkyl, C1-C6 alkoxy, hydroxy(C1-C6)alkyl, halo(C1-C6)alkyl, phenyl, NO2, NH2, or CN;
• heterocycle substituted with from 1 to 3 substituents selected from the group consisting of F, Cl, Br, I, OH, C1-C6 alkyl,C1-C6 alkoxy, hydroxy(C1-C6)alkyl, halo(C1-C6)alkyl, phenyl, NO2, NH2, or CN;
• or C3-C8 cycloalkyl substituted with C1-C4 alkyl;
• R6a and R6b are each independently H or C1-C3 alkyl;
• R7 and R8 are each independently H, C1-C6 alkyl, aryl or aryl substituted with from 1 to 3 substituents selected from the group consisting of F, Cl, Br, I, OH, C1-C6 alkyl, C1-C6 alkoxy, halo(C1-C6)alkyl, phenyl, NO2, NH2, or CN;
• or a pharmaceutically acceptable salt thereof.

A method of treating depression comprising administering to a subject in need thereof an effective amount of a compound of formula:

• wherein:
• X represents O or S;
• Y represents —C(═O)—, —CH(OH)—, —CH2—, S, SO, or SO2;
• represents a single or a double bond;
• n is 1, 2, 3 or 4;
• R1a, R1b, R1c, and R2 are each independently H, F, Cl, Br, I, OH, C1-C6 alkyl, C1-C6 alkoxy, halo(C1-C6)alkyl, phenyl, NO2, —NR7R8, CN or phenyl substituted with from 1 to 3 substituents selected from the group consisting of F, Cl, Br, I, OH, C1-C6 alkyl, C1-C6 alkoxy, halo(C1-C6)alkyl, phenyl, NO2, NH2, or CN;
• R3 represents H, OH, hydroxy(C1-C6)alkyl, C1-C6 alkyl, or C1-C6 alkoxy;
• R4 represents aryl, heterocycle, C3-C8 cycloalkyl, aryl substituted with from 1 to 3 substituents selected from the group consisting of F, Cl, Br, I, OH, C1-C6 alkyl, C1-C6 alkoxy, halo(C1-C6)alkyl, phenyl, NO2, NH2, or CN;
• or heterocycle substituted with from 1 to 3 substituents selected from the group consisting of F, Cl, Br, I, OH, C1-C6 alkyl, C1-C6 alkoxy, halo(C1-C6)alkyl, phenyl, NO2, NH2, or CN;
• R5 represents aryl, heterocycle, C3-C8 cycloalkyl, aryl substituted with from 1 to 3 substituents selected from the group consisting of F, Cl, Br, I, OH, C1-C6 alkyl, C1-C6 alkoxy, hydroxy(C1-C6)alkyl, halo(C1-C6)alkyl, phenyl, NO2, NH2, or CN;
• heterocycle substituted with from 1 to 3 substituents selected from the group consisting of F, Cl, Br, I, OH, C1-C6 alkyl,C1-C6 alkoxy, hydroxy(C1-C6)alkyl, halo(C1-C6)alkyl, phenyl, NO2, NH2, or CN;
• or C3-C8 cycloalkyl substituted with C1-C4 alkyl;
• R6a and R6b are each independently H or C1-C3 alkyl;
• R7 and R8 are each independently H, C1-C6 alkyl, aryl or aryl substituted with from 1 to 3 substituents selected from the group consisting of F, Cl, Br, I, OH, C1-C6 alkyl, C1-C6 alkoxy, halo(C1-C6)alkyl, phenyl, NO2, NH2, or CN;
• or a pharmaceutically acceptable salt thereof.