Serotonergic 5HT7 receptor compounds for treating ocular and CNS disorders

A compound of the formula:

• R3, R4 are independently H, C1-3alkyl, or C1-3alkyl substituted optionally with OH or OC1-3alkyl;
• R7, R8 are together with the nitrogen atom to which they are attached incorporated into a heterocyclic ring selected from the group consisting of pyrrolidine, piperidine, Δ3-piperidein, piperazine, morpholine or thiomorpholine which can be unsubstituted or substituted on carbon with one or more substituents optionally selected from C1-3alkyl, C1-3alkyl substituted optionally with OH, OC1-3alkyl, phenyl which can be unsubstituted or substituted optionally with halogen, CF3, OC1-3alkyl, or C1-3alkyl, or substituted on nitrogen with C1-4alkoxy or phenyl which can be unsubstituted or substituted optionally with halogen, CF3, OC1-3alkyl, or C1-3alkyl;
• R11 is C1-3alkyl, phenyl or a monocyclic heteroaromatic ring which can be unsubstituted or substituted with C1-4alkyl, halogen, OC1-4alkyl;
• R12 is C1-4alkyl or a fused bicyclic heteroaromatic ring selected from the group consisting of thieno[3,2-e]-1,2-thiazine, and 1,2-benzothiazine, or R12 can be joined to R11 to form 2,3-dihydro-benzo[c]isoxazole;
• n is 2 to 4
• or a pharmaceutically acceptable salt thereof.

A method for lowering IOP which comprises administering to a person in need thereof, a composition comprising an effective amount of a compound of the formula:

• R3, R4 are independently H, C1-3alkyl, or C1-3alkyl substituted optionally with OH or OC1-3alkyl;
• R7, R8 are together with the nitrogen atom to which they are attached incorporated into a heterocyclic ring selected from the group consisting of pyrrolidine, piperidine, Δ3-piperidein, piperazine, morpholine or thiomorpholine which can be unsubstituted or substituted on carbon with one or more substituents optionally selected from C1-3alkyl, C1-3alkyl substituted optionally with OH, OC1-3alkyl, phenyl which can be unsubstituted or substituted optionally with halogen, CF3, OC1-3alkyl, or C1-3alkyl, or substituted on nitrogen with C1-4alkoxy or phenyl which can be unsubstituted or substituted optionally with halogen, CF3, OC1-3alkyl, or C1-3alkyl;
• R11 is C1-3alkyl, phenyl or a monocyclic heteroaromatic ring which can be unsubstituted or substituted with C1-4alkyl, halogen, OC1-4alkyl;
• R12 is C1-4alkyl or a fused bicyclic heteroaromatic ring selected from the group consisting of thieno[3,2-e]-1,2-thiazine, and 1,2-benzothiazine, or R12 can be joined to R11 to form 2,3-dihydro-benzo[c]isoxazole;
• n is 2 to 4
• or a pharmaceutically acceptable salt thereof.

A method for improving blood flow to the optic nerve head and the retina which comprises administering to a person in need thereof, a composition comprising an effective amount of a compound of the formula:

• R3, R4 are independently H, C1-3alkyl, or C1-3alkyl substituted optionally with OH or OC1-3alkyl;
• R7, R8 are together with the nitrogen atom to which they are attached incorporated into a heterocyclic ring selected from the group consisting of pyrrolidine, piperidine, Δ3-piperidein, piperazine, morpholine or thiomorpholine which can be unsubstituted or substituted on carbon with one or more substituents optionally selected from C1-3alkyl, C1-3alkyl substituted optionally with OH, OC1-3alkyl, phenyl which can be unsubstituted or substituted optionally with halogen, CF3, OC1-3alkyl, or C1-3alkyl, or substituted on nitrogen with C1-4alkoxy or phenyl which can be unsubstituted or substituted optionally with halogen, CF3, OC1-3alkyl, or C1-3alkyl;
• R11 is C1-3alkyl, phenyl or a monocyclic heteroaromatic ring which can be unsubstituted or substituted with C1-4alkyl, halogen, OC1-4alkyl;
• R12 is C1-4alkyl or a fused bicyclic heteroaromatic ring selected from the group consisting of thieno[3,2-e]-1,2-thiazine, and 1,2-benzothiazine, or R12 can be joined to R11 to form 2,3-dihydro-benzo[c]isoxazole;
• n is 2 to 4
• or a pharmaceutically acceptable salt thereof.

A method for treating retinal diseases which comprises administering to a person in need thereof, a composition comprising an effective amount of a compound of the formula:

• R3, R4 are independently H, C1-3alkyl, or C1-3alkyl substituted optionally with OH or OC1-3alkyl;
• R7, R8 are together with the nitrogen atom to which they are attached incorporated into a heterocyclic ring selected from the group consisting of pyrrolidine, piperidine, Δ3-piperidein, piperazine, morpholine or thiomorpholine which can be unsubstituted or substituted on carbon with one or more substituents optionally selected from C1-3alkyl, C1-3alkyl substituted optionally with OH, OC1-3alkyl, phenyl which can be unsubstituted or substituted optionally with halogen, CF3, OC1-3alkyl, or C1-3alkyl, or substituted on nitrogen with C1-4alkoxy or phenyl which can be unsubstituted or substituted optionally with halogen, CF3, OC1-3alkyl, or C1-3alkyl;
• R11 is C1-3alkyl, phenyl or a monocyclic heteroaromatic ring which can be unsubstituted or substituted with C1-4 alkyl, halogen, OC1-4alkyl;
• R12 is C1-4alkyl or a fused bicyclic heteroaromatic ring selected from the group consisting of thieno[3,2-e]-1,2-thiazine, and 1,2-benzothiazine, or R12 can be joined to R11 to form a 2,3-dihydro-benzo[c]isoxazole;
• n is 2 to 4
• or a pharmaceutically acceptable salt thereof.

A method for treating persons suffering from a sleeping disorder, depression, schizophrenia, anxiety, obsessive compulsive disorder, circadian rhythm disorders, and centrally and peripherally mediated hypertension which comprises, administering a composition comprising a pharmaceutically effective amount of a compound of the formula:

• R3, R4 are independently H, C1-3alkyl, or C1-3alkyl substituted optionally with OH or OC1-3alkyl;
• R7, R8 are together with the nitrogen atom to which they are attached incorporated into a heterocyclic ring selected from the group consisting of pyrrolidine, piperidine, Δ3-piperidein, piperazine, morpholine or thiomorpholine which can be unsubstituted or substituted on carbon with one or more substituents optionally selected from C1-3alkyl, C1-3alkyl substituted optionally with OH, OC1-3alkyl, phenyl which can be unsubstituted or substituted optionally with halogen, CF3, OC1-3alkyl, or C1-3alkyl, or substituted on nitrogen with C1-4alkoxy or phenyl which can be unsubstituted or substituted optionally with halogen, CF3, OC1-3alkyl, or C1-3alkyl;
• R11 is C1-3alkyl, phenyl or a monocyclic heteroaromatic ring which can be unsubstituted or substituted with C1-4 alkyl, halogen, OC1-4alkyl;
• R12 is C1-4alkyl or a fused bicyclic heteroaromatic ring selected from the group consisting of thieno[3,2-e]-1,2-thiazine, and 1,2-benzothiazine, or R12 can be joined to R11 to form 2,3-dihydro-benzo[c]isoxazole;
• n is 2 to 4
• or a pharmaceutically acceptable salt thereof.

A composition comprising a pharmaceutically effective amount of a compound of the formula:

• R3, R4 are independently H, C1-3alkyl, or C1-3alkyl substituted optionally with OH or OC1-3alkyl;
• R7, R8 are together with the nitrogen atom to which they are attached incorporated into a heterocyclic ring selected from the group consisting of pyrrolidine, piperidine, Δ3-piperidein, piperazine, morpholine or thiomorpholine which can be unsubstituted or substituted on carbon with one or more substituents optionally selected from C1-3alkyl, C1-3alkyl substituted optionally with OH, OC1-3alkyl, phenyl which can be unsubstituted or substituted optionally with halogen, CF3, OC1-3alkyl, or C1-3alkyl, or substituted on nitrogen with C1-4alkoxy or phenyl which can be unsubstituted or substituted optionally with halogen, CF3, OC1-3alkyl, or C1-3alkyl;
• R11 is C1-3alkyl, phenyl or a monocyclic heteroaromatic ring which can be unsubstituted or substituted with C1-4alkyl, halogen, OC1-4alkyl;
• R12 is C1-4alkyl or a fused bicyclic heteroaromatic ring selected from the group consisting of thieno[3,2-e]-1,2-thiazine, and 1,2-benzothiazine, or R12 can be joined to R11 to form 2,3-dihydro-benzo[c]isoxazole;
• n is 2 to 4
• or a pharmaceutically acceptable salt thereof.