Heterocyclylindazole and -azaindazole compounds as 5-hydroxytryptamine-6 ligands

1 . A compound of formula I

wherein

Q is SO 2 , CO, CONR 24 , CSNR 25 or CH 2 ;

W is N or CR 6 ;

X is N or CR 7 ;

Y is NR 8 or CR 9 R 10 ;

n is 0or an integer of 2;

Z is NR 11 or CR 12 R 13 with the proviso that when Y is NR 8 then Z must be CR 12 R 13 and at least one of Y and Z must be NR 8 or NR 11 ;

R 1 , R 2 and R 7 are each independently H, halogen, CN, OCO 2 R 14 , CO 2 R 15 , CONR 29 R 30 , CNR 16 NR 17 R 18 , SO m R 19 , NR 20 R 21 , OR 22 , COR 23 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 3 , R 4 , R 9 , R 10 , R 12 and R 13 are each independently H or an optionally substituted C 1 -C 6 alkyl group;

R 5 is an optionally substituted C 1 -C 6 alkyl, aryl or heteroaryl group;

m is 0 or an integer of 1 or 2;

R 6 is H, halogen, or an optionally substituted C 1 -C 6 alkyl, C 1 -C 6 alkoxy, aryl or heteroaryl group;

R 8 and R 11 are each independently H, CNR 26 NR 27 R 28 or a C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, cycloheteralkyl, aryl or heteroaryl group each optionally substituted;

R 14 , R 15 , R 22 and R 23 are each independently H or an optionally substituted 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;

R 16 , R 17 , R 18 , R 20 , R 21 , R 26 , R 27 , R 28 , R 29 and R 30 are each independently H or C 1 -C 4 alkyl;

R 19 is an optionally substituted C 1 -C 6 alkyl, aryl or heteroaryl group;

R 24 and R 25 are each independently H or an optionally substituted C 1 -C 6 alkyl, aryl or heteroaryl group; and

represents a single bond or a double bond; or the stereoisomers thereof or the pharmaceutically acceptable salts thereof.

2 . The compound according to claim 1 wherein Y is NR 8 .

3 . (canceled)

4 . The compound according to claim 1 wherein W is N.

5 . (canceled)

6 . The compound according to claim 4 wherein Z is NR 11 .

7 . The compound according to claim 2 wherein Q is SO 2 and R 5 is an optionally substituted aryl or heteroaryl group.

8 . The compound according to claim 7 wherein X is CH and represents a single bond.

9 . The compound according to claim 1 selected from the group consisting of:

1-phenylsulfonyl-3-(1-methylazepan-4-yl)-1H-pyrrolo[2,3-b]pyridine;

1-phenylsulfonyl-3-(1-methylazepan-4-yl)-1H-indole;

1-phenylsulfonyl-5-fluoro-3-(1-methylazepan-4-yl)-1H-indole;

1-phenylsulfonyl-3-(1-methyl-2,3,6,7-tetrahydro-1H-azepin-4-yl)-1H-indole;

1-phenylsulfonyl-3-(1-methyl-2,5,6,7-tetrahydro-1H-azepin-4-yl)-1H-indole;

1-phenylsulfonyl-3-(1-methyl-2,3,6,7-tetrahydro-1H-azepin-4-yl)-1H-pyrrolo[2,3-b]pyridine;

1-phenylsulfonyl-5-fluoro-3-(1-methyl-2,3,6,7-tetrahydro-1H-azepin-4-yl)-1H-indole;

1-phenylsulfonyl-5-fluoro-3-( 1-methyl-2,5,6,7-tetrahydro-1H-azepin-4-yl)-1H-indole;

3-(1-methylazepan-4-yl)-1-(naphth-1-yl-sulfonyl)-1H-pyrrolo[2,3-b]pyridine;

3-(1-methylazepan-4-yl)-1-(naphth-1-yl-sulfonyl)-1H-indole;

1-(benzo[b]thien-4-ylsulfonyl)-5-fluoro-3-( 1-methylazepan-4-yl)-1H-indole;

8-[3-(1-methyl-2,3,6,7-tetrahydro-1H-azepin-4-yl)-indole-1-sulfonyl]-quinoline;

3-(1-methyl-2,5,6,7-tetrahydro-1H-azepin-4-yl)-1-(naphth-1-ylsulfonyl)-1H-indole;

8-[3-(1-methyl-2,3,6,7-tetrahydro-1H-azepin-4-yl)-pyrrolo[2,3-b]pyridine-1-sulfonyl]-quinoline;

8-[5-fluoro-3-(1-methyl-2,3,6,7-tetrahydro-1H-azepin-4-yl)-indole-1-sulfonyl]-quinoline;

5-fluoro-3-(1-methyl-2,5,6,7-tetrahydro-1H-azepin-4-yl)-1-(naphth-1-ylsulfonyl)-1H-indole;

1-(naphth-1-ylsulfonyl)-3-(1-phenethyl-azepan-4-yl)-1H-pyrrolo[2,3-b]pyridine;

3-azepan-4-yl-1-(naphth-1-ylsulfonyl)-1H-indole;

3-azepan-4-yl-1-(3-chloro-5-methyl-benzo[b]thien-2-ylsulfonyl)-5-fluoro-1H-indole;

8-[3-(1-phenethyl-2,3,6,7-tetrahydro-1H-azepin-4-yl)-indole-1-sulfonyl]-quinoline;

3-[1-(3,3-dimethylbutyl)-2,5,6,7-tetrahydro-1H-azepin-4-yl]-1-(naphth-2-ylsulfonyl)-1H-indole;

1-(2,3-dichlorophenylsulfonyl)-3-( 1-methyl-2,3,6,7-tetrahydro-1H-azepin-4-yl)-1H-pyrrolo[2,3-]pyridine;

1-[(3-chloro-5-methoxyphenylsulfonyl)]-3-(2,2-dimethyl-2,3,6,7-tetrahydro-1H-azepin-4-yl)-5-fluoro-1H-indole;

3-azepan-4-yl-5-fluoro-1-(naphth-2-ylsulfonyl)-1H-indole;

10 . A method for the treatment of a disorder of the central nervous system related to or affected by the 5-HT6 receptor in a patient in need thereof which comprises

providing said patient with a therapeutically effective amount of a compound of formula I

wherein

Q is SO 2 , CO, CONR 24 , CSNR 25 or CH 2 ;

W is N or CR 6 ;

X is N or CR 7 ;

Y is NR 8 or CR 9 R 10 ;

n is 0or an integer of 1 or 2;

Z is NR 1 , or CR 12 R 13 with the proviso that when n is 1, Q is SO 2 , CO or CH 2 and W is CR 6 then Z must be CR 12 R 13 and with the further provisos that when Y is NR 8 then Z must be CR 12 R 13 and at least one of Y and Z must be NR 8 or NR 11 ;

R 1 , R 2 and R 7 are each independently H, halogen, CN, OCO 2 R 14 , CO 2 R 15 , CONR 29 R 30 , CNR 16 NR 17 R 18 , SO m R 19 , NR 20 R 21 , OR 22 , COR 23 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 3 , R 4 , R 9 , R 10 , R 12 and R 13 are each independently H or an optionally substituted C 1 -C 6 alkyl group;

R 5 is an optionally substituted C 1 -C 6 alkyl, aryl or heteroaryl group;

m is 0 or an integer of 1 or 2;

R 6 is H, halogen, or an optionally substituted C 1 -C 6 alkyl, C 1 -C 6 alkoxy, aryl or heteroaryl group;

R 8 and R 11 are each independently H, CNR 26 NR 27 R 28 or a C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, cycloheteralkyl, aryl or heteroaryl group each optionally substituted;

R 14 , R, 5 , R 22 and R 23 are each independently H or an optionally substituted 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;

R 16 , R 17 , R 18 , R 20 , R 21 , R 26 , R 27 , R 28 , R29 and R 30 are each independe C 4 alkyl;

R 19 is an optionally substituted C 1 -C 6 alkyl, aryl or heteroaryl group;

R 24 and R 25 are each independently H or an optionally substituted C 1 -C 6 alkyl, aryl or heteroaryl group; and

represents a single bond or a double bond; or the stereoisomers thereof or the pharmaceutically acceptable salts thereof.

11 . The method according to claim 10 wherein said disorder is a mood disorder, a motor disorder, or a cognitive disorder.

12 . The method according to claim 10 wherein said disorder is schizophrenia.

13 . The method according to claim 11 wherein said disorder is anxiety or depression.

14 . The method according to claim 11 wherein said disorder is memory loss or attention deficit disorder.

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

wherein

Q is SO 2 , CO, CONR 24 , CSNR 25 or CH 2 ;

W is N or CR 6 ;

X is N or CR 7 ;

Y is NR 8 or CR 9 R 10 ;

n is an integer of 2;

Z is NR 11 or CR 12 R 13 with the proviso that when Y is NR 8 then Z must be CR 12 R 13 and at least one of Y and Z must be NR 8 or NR 11 ;

R 1 , R 2 and R 7 are each independently H, halogen, CN, OCO 2 R 14 , CO 2 R 15 , CONR n R 30 , CNR 16 NR 17 R, 8 , SO m R 19 , NR 20 R 21 , OR 22 , COR 23 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 3 , R 4 , R 9 , R 10 , R 12 and R 13 are each independently H or an optionally substituted C 1 -C 6 alkyl group;

R 5 is an optionally substituted C 1 -C 6 alkyl, aryl or heteroaryl group;

m is 0 or an integer of 1 or 2;

R 6 is H, halogen, or an optionally substituted C 1 -C 6 alkyl, C 1 -C 6 alkoxy, aryl or heteroaryl group;

R 8 and R 11 are each independently H, CNR 26 NR 27 R 28 or a C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, cycloheteralkyl, aryl or heteroaryl group each optionally substituted;

R 14 , R 15 , R 22 and R 23 are each independently H or an optionally substituted 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;

R 16 , R 17 , R 18 , R 20 , R 21 , R 26 , R 27 , R 28 , R 29 and R 30 are each independently H or C 1 -C 4 alkyl;

R 19 is an optionally substituted C 1 -C 6 alkyl, aryl or heteroaryl group;

R 24 and R 25 are each independently H or an optionally substituted C 1 -C 6 alkyl, aryl or heteroaryl group; and

represents a single bond or a double bond; or the stereoisomers thereof or the pharmaceutically acceptable salts thereof.

16 . The composition according to claim 15 having a formula I compound wherein Q is SO 2 ; Y is NR 8 ; and X is CR 7 .

17 . The composition according to claim 15 having a formula I compound wherein Q is SO 2 ; X is CR 7 ; and Z is NR 11 .

18 . The composition according to claim 16 having a formula I compound wherein R 5 is an optionally substituted aryl group and represents a single bond.

19 . The composition according to claim 15 having a formula I compound selected from the group consisting of:

1-phenylsulfonyl-3-(1-methylazepan-4-yl)-1H-pyrrolo[2,3-b]pyridine;

1-phenylsulfonyl-3-(1-methylazepan-4-yl)-1H-indole;

1-phenylsulfonyl-5-fluoro-3-(1-methylazepan-4-yl)-1H-indole;

1-phenylsulfonyl-3-(1-methyl-2,3,6,7-tetrahydro-1H-azepin-4-yl)-1H-indole;

1-phenylsulfonyl-3-(1-methyl-2,5,6,7-tetrahydro-1H-azepin-4-yl)-1H-indole;

1-phenylsulfonyl-3-(1-methyl-2,3,6,7-tetrahydro-1H-azepin-4-yl)-1H-pyrrolo[2,3-b]pyridine;

1-phenylsulfonyl-5-fluoro-3-(1-methyl-2,3,6,7-tetrahydro-1H-azepin-4-yl)-1H-indole;

1-phenylsulfonyl-5-fluoro-3-(1-methyl-2,5,6,7-tetrahydro-1H-azepin-4-yl)-1H-indole;

3-(1-methylazepan-4-yl)-1-(naphth-1-yl-sulfonyl)-1H-pyrrolo[2,3-b]pyridine;

3-(1-methylazepan-4-yl)-1-(naphth-1-yl-sulfonyl)-1H-indole;

1-(benzo[b]thien-4-ylsulfonyl)-5-fluoro-3-(1-methylazepan-4-yl)-1H-indole;

8-[3-(1-methyl-2,3,6,7-tetrahydro-1H-azepin-4-yl)-indole-1-sulfonyl]-quinoline;

3-(1-methyl-2,5,6,7-tetrahydro-1H-azepin-4-yl)-1-(naphth-1-ylsulfonyl)-1H-indole;

8-[3-(1-methyl-2,3,6,7-tetrahydro-1H-azepin-4-yl)-pyrrolo[2,3-b]pyridine-1-sulfonyl]-quinoliene;

8-[5-fluoro-3-( 1-methyl-2,3,6,7-tetrahydro-1H-azepin-4-yl)-indole-1-sulfonyl]-quinoline;

5-fluoro-3-(1-methyl-2,5,6,7-tetrahydro-1H-azepin-4-yl)-1-(naphth-1-ylsulfonyl)-1H-indoline;

1-(naphth-1-ylsulfonyl)-3-(1-phenethyl-azepan-4-yl)-1H-pyrrolo[2,3-b]pyridine;

3-azepan-4-yl-1-(naphth-1-ylsulfonyl)-1H-indole;

3-azepan-4-yl-1-(3-chloro-5-methyl-benzo[b]thien-2-ylsulfonyl)-5-fluoro-1H-indole;

8-[3-(1-phenethyl-2,3,6,7-tetrahydro-1H-azepin-4-yl)-indole-1-sulfonyl]-quinoline;

3-[1-(3,3-dimethylbutyl)-2,5,6,7-tetrahydro-1H-azepin-4-yl]-1-(naphth-2-ylsulfonyl)-1H-indole;

1-(2,3-dichlorophenylsulfonyl)-3-( 1-methyl-2,3,6,7-tetrahydro-1H-azepin-4-yl)-1H-pyrrolo[2,3-]pyridine;

1-[(3-chloro-5-methoxyphenylsulfonyl)]-3-(2,2-dimethyl-2,3,6,7-tetrahydro-1H-azepin-4-yl)-5-fluoro-1H-indole;

3-azepan-4-yl-5-fluoro-1-(naphth-2-ylsulfonyl)-1H-indole; and

the pharmaceutically acceptable salts thereof.

20 . A process for the preparation of a compound of formula If

wherein

W is N or CR 6 ;

X is N or CR 7 ;

Y is NR 8 or CR 9 R 10 ;

n is an integer of 2;

Z is NR 1 , or CR 12 R 13 with the proviso that when Y is NR 8 then Z must be CR 12 R 13 and at least one of Y and Z must be NR 8 or NR 11 ;

R 1 , R 2 and R 7 are each independently H, halogen, CN, OCO 2 R 14 , CO 2 R 15 , CONR 29 R 30 , CONR 29 R 30 , CNR 16 NR 17 R 18 , SO m R 19 , NR 20 R 21 , OR 22 , COR 23 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 3 , R 4 , R 9 , R 10 , R 12 and R 13 are each independently H or an optionally substituted C 1 -C 6 alkyl group;

R 5 is an optionally substituted C 1 -C 6 alkyl, aryl or heteroaryl group;

m is 0 or an integer of 1 or 2;

R 6 is H, halogen, or an optionally substituted C 1 -C 6 alkyl, C 1 -C 6 alkoxy, aryl or heteroaryl group;

R 8 and R 1 are each independently H, CNR 26 NR 27 R 28 or a C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, cycloheteralkyl, aryl or heteroaryl group each optionally substituted;

R 14 , R 15 , R 22 and R 23 are each independently H or an optionally substituted 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;

R 16 , R 17 , R 18 , R 20 , R 21 , R 26 , R 27 , R 28 , R 29 and R 30 are each independently H or C 1 -C 4 alkyl;

R 19 is an optionally substituted C 1 -C 6 alkyl, aryl or heteroaryl group; and

represents a single bond or a double bond which process comprises reacting a compound of formula IVa

wherein W, X, Y, Z, n, R 1 , R 2 , R 3 and R 4 are as defined above with a sulfonyl chloride, R 5 SO 2 Cl, wherein R 5 is defined above in the presence of a base