Piperidines derivatives and their use as serotonin receptor antagonists

A compound of the formula:

• wherein
• B is selected from the group consisting of:
• represents a single or a double bond;
• X is hydrogen, OH or C1-C6 alkoxy whenrepresents a single bond in the piperidine ring, and X is nothing whenrepresents a double bond in the piperidine ring;
• Y is S or CH2;
• R1 is hydrogen, F, C1-C20 alkyl, —C(═O)NR8R9, or CN;
• R2 is hydrogen, F, Cl, Br, I, OH, C1-C6 alkyl or C1-C6 alkoxy;
• R3 and R4 are each independently hydrogen or C1-C4 alkyl;
• R5 and R6 are each independently hydrogen, F, Cl, Br, I, OH, C1-C6 alkyl, C1-C6 alkoxy, halo(C1-C6)alkyl, phenyl, —C(═O)NR8R9, NO2, NH2, 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, NO2, NH2, CN, and phenyl;
• R7 is hydrogen, F, Cl, Br, I, OH, C1-C6 alkyl or (C1-C6 alkyl)NR8R9;
• R8 and R9 are each independently hydrogen or C1-C10 alkyl;
• m is 0, 1, or 2;
• and
• n is 0, 1, or 2;
• or a pharmaceutically acceptable salt thereof.

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

• wherein
• A is hydrogen or OH:
• B is selected from the group consisting of:
• represents a single or a double bond;
• X is hydrogen, OH or C1-C6 alkoxy whenrepresents a single bond in the piperidine ring, and X is nothing whenrepresents a double bond piperidine ring;
• R1 is hydrogen, F, C1-C20 alkyl, —C(═O)NR8R9, or CN;
• R2 is hydrogen, F, Cl, Br, I, OH, C1-C6 alkyl or C1-C6 alkoxy;
• R3 and R4 are each independently hydrogen or C1-C4 alkyl;
• R5 and R6 are each independently hydrogen, F, Cl, Br, I, OH, C1-C6 alkyl, C1-C6 alkoxy, halo(C1-C6)alkyl, phenyl, —C(═O)NR8R9, NO2, NH2, 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, NO2, NH2, CN, and phenyl;
• R7 is hydrogen, F, Cl, Br, I, OH, C1-C6 alkyl or (C1-C6 alkyl)NR8R9;
• R8 and R9 are each independently hydrogen or C1-C10 alkyl;
• m is 0, 1, or 2;
• n is 0, 1, or 2;
• p is 0, 1, 2, 3 or 4;
• and
• q is 0, 1, 2 or 3;
• or a pharmaceutically acceptable salt thereof;
• with the proviso that if both R3 and R4 represent hydrogen, then R1 is F, C1-C20 alkyl, —C(═O)NR8R9, or CN.

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

• wherein
• A is hydrogen or OH:
• B is selected from the group consisting of:
• represents a single or a double bond;
• X is hydrogen, OH or C1-C6 alkoxy whenrepresents a single bond in the piperidine ring, and X is nothing whenrepresents a double bond piperidine ring;
• R1 is hydrogen, F, C1-C20 alkyl, —C(═O)NR8R9, or CN;
• R2 is hydrogen, F, Cl, Br, I, OH, C4-C6 alkyl or C1-C6 alkoxy;
• R3 and R1 are each independently hydrogen or C1-C4 alkyl;
• R5 and R6 are each independently hydrogen, F, Cl, Br, I, OH, C1-C6 alkyl, C1-C6 alkoxy, halo(C1-C6)alkyl, phenyl, —C(═O)NR8R9, NO2, NH2, 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, NO2, NH2, CN, and phenyl;
• R7 is hydrogen, F, Cl, Br, I, OH, C1-C6 alkyl or (C1-C6 alkyl)NR8R9;
• R8 and R9 are each independently hydrogen or C1-C10 alkyl;
• m is 0, 1, or 2;
• n is 0, 1, or 2;
• p is 0, 1, 2, 3 or 4;
• and
• q is 0, 1, 2 or 3;
• or a pharmaceutically acceptable salt thereof;
• with the proviso that if both R3 and R4 represent hydrogen, then R1 is F, C1-C20 alkyl, —C(═O)NR8R9, or CN.

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

• wherein
• A is hydrogen or OH:
• B is selected from the group consisting of:
• represents a single or a double bond;
• X is hydrogen, OH or C1-C6 alkoxy whenrepresents a single bond in the piperidine ring, and X is nothing whenrepresents a double bond piperidine ring;
• R1 is hydrogen, F, C1-C20 alkyl, —C(═O)NR8R9, or CN;
• R2 is hydrogen, F, Cl, Br, I, OH, C1-C6 alkyl or C1-C6 alkoxy;
• R3 and R4 are each independently hydrogen or C1-C4 alkyl;
• R5 and R6 are each independently hydrogen, F, Cl, Br, I, OH, C1-C6 alkyl, C1-C6 alkoxy, halo(C1-C6)alkyl, phenyl, —C(═O)NR8R9, NO2, NH2, 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, NO2, NH2, CN, and phenyl;
• R7 is hydrogen, F, Cl, Br, I, OH, C1-C6 alkyl or (C1-C6 alkyl)NR8R9;
• R8 and R9 are each independently hydrogen or C1-C10 alkyl;
• m is 0, 1, or 2;
• n is 0, 1, or 2;
• p is 0, 1, 2, 3 or 4;
• and
• q is 0, 1, 2 or 3;
• or a pharmaceutically acceptable salt thereof;
• with the proviso that if both R3 and R4 represent hydrogen, then R1 is F, C1-C20 alkyl, —C(═O)NR8R9, or CN.