1-aryl-or 1-alkylsulfonylbenzazole derivatives as 5-hydroxytryptamine-6 ligands

1. A compound of formula I

wherein

W is SO 2 , CO, CONH, CSNH or CH 2 ;

X is CR 7 or N;

Y is CR 8 ;

Z is O, SO p or NR 9 ;

R 1 and R 2 are each independently H or C 1 -C 6 alkyl;

n is an integer of 2, 3 or 4;

R 3 and R 4 are taken together with the atom to which they are attached to form an optionally substituted 3- to 6-membered ring optionally containing an additional heteroatom selected from O, N or S;

R 5 is H, halogen, CN, OR 13 , CO 2 R 14 , CONR 15 R 16 , CNR 17 NR 18 R 19 , SO 2 NR 20 R 21 , SO q R 22 or a C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, cycloheteroalkyl, phenyl or heteroaryl group each optionally substituted;

m is an integer of 1, 2 or 3;

p and q are each independently 0 or an integer of 1 or 2;

R 6 is an optionally substituted heteroaryl group or an optionally substituted 8- to 13-membered bicyclic or tricyclic ring system having a N atom at the bridgehead and optionally containing 1, 2 or 3 additional heteroatoms selected from N, O or S;

R 7 and R 8 are each independently H, halogen or a C 1 -C 6 alkyl, aryl, heteroaryl or C 1 - C 6 alkoxy group each optionally substituted;

R 9 is H or a C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted;

R 15 , R 16 , R 17 , R 18 and R 19 are each independently H or C 1 -C 4 alkyl;

R 13 is H, COR 23 or a C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, aryl or heteroaryl group each optionally substituted;

R 14 is H or a C 1 -C 6 alkyl, aryl or heteroaryl group each optionally substituted;

R 20 and R 21 are each independently H or a C 1 -C 6 alkyl, aryl or heteroaryl group each optionally substituted; and

R 22 and R 23 are each independently an optionally substituted C 1 -C 6 alkyl, aryl or heteroaryl group; or

a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 wherein W is SO 2 .

3. The compound according to claim 1 wherein Z is O.

4. The compound according to claim 1 wherein n is 2.

5. The compound according to claim 1 wherein R 6 is an optionally substituted thienyl or imidazothiazolyl group.

6. The compound according to claim 1 wherein X is CR 7 and R 5 and R 7 are H.

7. The compound according to claim 2 wherein R 1 and R 2 are H; Z is O; and n is 2.

8. The compound according to claim 6 wherein W is SO 2 ; Z is O; and R 3 and R 4 are taken together with the atom to which they are attached to form a 5- or 6-membered ring optionally containing one oxygen atom.

9. The compound according to claim 6 selected from the group consisting of:

1-[(5-chlorothien-2-yl)sulfonyl]-5-[2-(piperidin-1-yl)ethoxy]-1H-indole;

1-[(4, 5-dichlorothien-2-yl)sulfonyl]-5-[2-(piperidin-1-yl)ethoxy]-1H-indole;

1-[(6-chloroimidazo[2,1-b][1,3]thiazol-5-yl)sulfonyl]-5-[2-(piperidin-1-yl)ethoxy]-1H-indole;

1-[(5-chloro-3-methyl-1-benzothien-2-yl)sulfonyl]-5-[2-(piperidin-1-yl)ethoxy]-1H-indole;

1-[(5-chloro-3-methyl-1-benzothien-2-yl)sulfonyl]-4-[2-(piperidin-1-yl)ethoxy]-1H-indole; and

a pharmaceutically acceptable salt thereof.

10. A pharmaceutical composition which comprises a pharmaceutically acceptable carrier and an effective amount of a compound of formula I

wherein

W is SO 2 , CO, CONH, CSNH or CH 2 ;

X is CR 7 or N;

Y is CR 8 ;

Z is O, SO p or NR 9 ;

R 1 and R 2 are each independently H or C 1 -C 6 alkyl;

n is an integer of 2, 3 or 4;

R 3 and R 4 are taken together with the atom to which they are attached to form an optionally substituted 3- to 6-membered ring optionally containing an additional heteroatom selected from O, N or S;

R 5 is H, halogen, CN, OR 13 , CO 2 R 14 , CONR 15 R 16 , CNR 17 NR 18 R 19 , SO 2 NR 20 R 21 , SO q R 22 or a C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, cycloheteroalkyl, phenyl or heteroaryl group each optionally substituted;

m is an integer of 1, 2 or 3;

p and q are each independently 0 or an integer of 1 or 2;

R 6 is an optionally substituted heteroaryl group or an optionally substituted 8- to 13-membered bicyclic or tricyclic ring system having a N atom at the bridgehead and optionally containing 1, 2 or 3 additional heteroatoms selected from N, O or S;

R 7 and R 8 are each independently H, halogen or a C 1 -C 6 alkyl, aryl, heteroaryl or C 1 -C 6 alkoxy group each optionally substituted;

R 9 is H or a C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted;

R 15 , R 16 , R 17 , R 18 and R 19 are each independently H or C 1 -C 4 alkyl;

R 13 is H, COR 23 or a C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, aryl or heteroaryl group each optionally substituted;

R 14 is H or a C 1 -C 6 alkyl, aryl or heteroaryl group each optionally substituted;

R 20 and R 21 , are each independently H or a C 1 -C 6 alkyl, aryl or heteroaryl group each optionally substituted; and

R 22 and R 23 are each independently an optionally substituted C 1 -C 6 alkyl, aryl or heteroaryl group; or

a pharmaceutically acceptable salt thereof.

11. The composition according to claim 10 wherein W is SO 2 ; Z is O; and n is 2.

12. The composition according to claim 11 wherein R 6 is an optionally substituted thienyl or imidazothiazolyl group.

13. The composition according to claim 12 wherein X is CR 7 and R 1 , R 2 , R 5 , and R 7 are H.

14. The composition according to claim 10 having a formula I compound selected from the group consisting of:

1-[(5-chlorothien-2-yl)sulfonyl]-5-[2-(piperidin-1-yl)ethoxy]-1H-indole;

1-[(4,5-dichlorothien-2-yl)sulfonyl]-5-[2-(piperidin-1-yl)ethoxy]-1H-indole;

1-[(6-chloroimidazo[2,1-b][1,3]thiazol-5-yl)sulfonyl]-5-[2-(piperidin-1-yl)ethoxy]-1H-indole;

1-[(5-chloro-3-methyl-1-benzothien-2-yl)sulfonyl]-5-[2-(piperidin-1-yl)ethoxy]-1H-indole;

1-[(5-chloro-3-methyl-1-benzothien-2-yl)sulfonyl]-4-[2-(piperidin-1-yl)ethoxy]-1H-indole; and

a pharmaceutically acceptable salt thereof.

15. The compound according to claim 1 of formula I

wherein

W is SO 2 ;

X is CR 7 or N;

Y is CR 8 ;

Z is O;

R 1 and R 2 are each independently H or C 1 -C 6 alkyl;

n is an integer of 2, 3 or 4;

R 3 and R 4 are taken together with the atom to which they are attached to form an optionally substituted 3-to 6-membered ring optionally containing an additional heteroatom selected from O, N or S;

R 5 is H, halogen, CN, OR 13 , or a C 1 -C 6 alkyl group optionally substituted with halo;

m is an integer of 1, 2or 3;

R 6 is an optionally substituted heteroaryl group or an optionally substituted 8-to 13-membered bicyclic or tricyclic ring system having a N atom at the bridgehead and optionally containing 1, 2 or 3 additional heteroatoms selected from N, O or S;

R 7 and R 8 are each independently H, halogen or a C 1 -C 6 alkyl optionally substituted with halo;

R 13 is H, COR 23 or a C 1 -C 6 alkyl optionally substituted with halo;

R 23 is C 1 -C 6 alkyl optionally substituted with halo; or

a pharmaceutically acceptable salt thereof.

16. The compound according to claim 15 of formula I

wherein

W is SO 2 ;

X is CR 7 or N;

Y is CR 8 ;

Z is O;

R 1 and R 2 are each independently H;

n is 2;

R 3 and R 4 are taken together with the atom to which they are attached to form an optionally substituted 3-to 6-membered ring optionally containing an additional heteroatom selected from O, N or S;

R 5 is H, halogen, —CN, —OH, —O(C 1 -C 6 alkyl), or C 1 -C 6 alkyl;

m is 1;

R 6 is an optionally substituted heteroaryl group or an optionally substituted 8-to 13-membered bicyclic or tricyclic ring system having a N atom at the bridgehead and optionally containing 1, 2 or 3 additional heteroatoms selected from N, O or S;

R 7 and R 8 are each independently H, halogen or C 1 -C 6 alkyl; or

a pharmaceutically acceptable salt thereof.

17. The compound according to claim 16 wherein X is CR 7 .

18. The compound according to claim 16 wherein X is N.

19. A method for the treatment of schizophrenia or depression in a patient in need thereof which comprises providing to said patient a therapeutically effective amount of a compound of claim 1 .

20. A method for the treatment of Alzheimer's disease or Parkinson's disease in a patient in need thereof which comprises providing to said patient a therapeutically effective amount of a compound of claim 1 .