N-(2-Arylethyl) benzylamines as antagonists of the 5-HT

1. A compound of the formula

wherein

X is —O—;

R 1 is selected from the group consisting of phenyl,

which phenyl is unsubstituted or substituted with one to three groups independently selected from the group consisting of hydrogen, hydroxy, C 1 –C 4 alkyl, halogen, benzyloxy, carboxy, C 1 –C 4 alkoxycarbonyl, amido, N—(C 1 –C 4 alkyl)amido, sulfonylamido, cyano, trifluoromethyl, trifluoromethoxy, nitro, and phenyl,

which phenyl is unsubstituted or substituted with C 1 –C 4 alkyl, C 1 –C 4 alkoxy, halogen, cyano, or trifluoromethyl;

and a radical of the formula

wherein Q 1 is —NR g — wherein R g is selected from the group consisting of hydrogen and C 1 –C 4 alkyl;

R d and R e are taken together with the atoms to which they are attached to form a benzo ring,

which benzo ring is unsubstituted or substituted with 1 to 4 substituents independently selected from the group consisting of hydrogen, hydroxy, C 1 –C 4 alkyl, C 1 –C 4 alkoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, trifluoromethyl, halogen, carboxy, C 1 –C 4 alkoxycarbonyl, amido, N—(C 1 –C 4 alkyl)amido, amino, (C 1 –C 4 alkyl)amino, acylamino wherein the acyl group is selected from the group consisting of C 1 –C 4 alkyl and phenyl; cyano, nitro, sulfonylamido, phenyl,

which phenyl is unsubstituted or substituted with C 1 –C 4 alkyl, C 1 –C 4 alkoxy, halogen, cyano, or trifluoromethyl;

phenoxy, benzyloxy, —NHS(O) 2 R h , wherein R h is selected from the group consisting of C 1 –C 4 alkyl and phenyl; and —S(O) p R i , wherein p is 0, 1, or 2 and R i is selected from the group consisting of C 1 –C 4 alkyl and phenyl,

which phenyl is unsubstituted or substituted with C 1 –C 4 alkyl, C 1 –C 4 alkoxy, halogen, cyano, or trifluoromethyl;

and R f is selected from the group consisting of hydrogen, C 1 –C 4 alkyl, C 1 –C 4 alkoxy, trifluoromethyl, and halogen;

R 2 is selected from the group consisting of hydrogen and C 1 –C 3 alkyl;

R 3 is selected from the group consisting of hydrogen, fluoro, and methyl;

R 4 is selected from the group consisting of C 2 –C 4 alkyl, and fluorinated C 2 –C 4 alkyl; and

pharmaceutically acceptable salts thereof.

2. The compound according to claim 1 wherein R 3 is hydrogen.

3. The compound according to claim 2 wherein R 1 is phenyl;

which phenyl is unsubstituted or substituted with one to three groups independently selected from the group consisting of hydrogen, hydroxy, C 1 –C 4 alkyl, halogen, benzyloxy, carboxy, C 1 –C 4 alkoxycarbonyl, amido, N—(C 1 –C 4 alkyl)amido, sulfonylamido, cyano, trifluoromethyl, trifluoromethoxy, nitro, and phenyl,

which phenyl is unsubstituted or substituted with C 1 –C 4 alkyl, C 1 –C 4 alkoxy, halogen, cyano, or trifluoromethyl.

4. The compound according to claim 2 wherein R 1 is a radical of the formula

wherein Q 1 is —NR g — wherein R g is selected from the group consisting of hydrogen and C 1 –C 4 alkyl;

R d and R e are taken together with the atoms to which they are attached to form a benzo ring,

which benzo ring is unsubstituted or substituted with 1 to 4 substituents independently selected from the group consisting of hydrogen, hydroxy, C 1 –C 4 alkyl, C 1 –C 4 alkoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, trifluoromethyl, halogen, carboxy, C 1 –C 4 alkoxycarbonyl, amido, N—(C 1 –C 4 alkyl)amido, amino, (C 1 –C 4 alkyl)amino, acylamino wherein the acyl group is selected from the group consisting of C 1 –C 4 alkyl and phenyl; cyano, nitro, sulfonylamido, phenyl,

which phenyl is unsubstituted or substituted with C 1 –C 4 alkyl, C 1 –C 4 alkoxy, halogen, cyano, or trifluoromethyl;

phenoxy, benzyloxy, —NHS(O) 2 R h , wherein R h is selected from the group consisting of C 1 –C 4 alkyl and phenyl; and —S(O) p R i , wherein p is 0, 1, or 2 and R i is selected from the group consisting of C 1 –C 4 alkyl and phenyl,

which phenyl is unsubstituted or substituted with C 1 –C 4 alkyl, C 1 –C 4 alkoxy, halogen, cyano, or trifluoromethyl;

and R f is selected from the group consisting of hydrogen, C 1 –C 4 alkyl, C 1 –C 4 alkoxy, trifluoromethyl, and halogen.

5. The compound according to claim 4 wherein R 4 is C 2 –C 4 fluorinated alkyl.

6. The compound of claim 1 wherein the compound is N-(2-(6-Fluoro-1H-indol-3-yl)ethyl)-3-(2,2,3,3-tetrafluoropropoxy)benzylamine.

7. The compound of claim 1 wherein the compound is N-(2-(6-Fluoro-1H-indol-3-yl)ethyl)-3-(2,2,3,3-tetrafluoropropoxy)benzylamine hydrochloride.

8. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable diluent.

9. A method of treating disorders associated with the 5-HT 6 receptor, wherein the disorder is selected from the group consisting of schizophrenia, anxiety, and Alzheimer's disease, comprising: administering to a patient in need thereof an effective amount of a compound of claim 1 .

10. A method for treating cognitive disorders associated with the 5-HT 6 receptor, wherein the cognitive disorder is selected from the group consisting of age-related cognitive decline, mild cognitive impairment, and dementia, comprising: administering to a patient in need thereof an effective amount of a compound of claim 1 .

11. The method of claim 10 comprising: administering to a patient in need thereof an effective amount of a compound of claim 6 .

12. The method of claim 10 comprising: administering to a patient in need thereof an effective amount of a compound of claim 7 .