IP Library › Granted Patent US 7,238,696
Granted Patent B2
US 7,238,696 · App. 10/778,427 · Granted Jul 3, 2007

Heterocyclyl-3-sulfonylindazoles as 5-hydroxytryptamine-6 ligands

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Quick Facts
Patent No.
US 7,238,696
App. No.
10/778,427
Granted
Jul 3, 2007
Kind
B2
Abstract

The present invention provides a compound of formula I and the use thereof in the therapeutic treatment of disorders related to or affected by the 5-HT6 receptor

Claims (130)

1. A compound of formula I

wherein

A is N;

R 1 is H, halogen, CN, OR 17 or a C 1 –C 6 alkyl, or C 3 –C 7 cycloalkyl group each optionally substituted;

R 2 is an optionally substituted C 1 –C 6 alkyl, C 3 –C 7 cycloalkyl, aryl, or heteroaryl group

R 3 is H or a C 1 –C 6 alkyl, or C 3 –C 7 cycloalkyl group each optionally substituted;

R 4 is H or a C 1 –C 6 alkyl or C 3 –C 7 cycloalkyl group each optionally substituted;

R 5 , R 6 and R 7 are each independently H or a C 1 –C 6 alkyl or C 3 –C 7 cycloalkyl group each optionally substituted;

m and p are each independently an integer of 1, 2 or 3;

n is an integer of 1;

R 17 is H or a C 1 –C 6 alkyl, C 2 –C 6 alkenyl, C 2 –C 6 alkynyl, or C 3 –C 6 cycloalkyl group each optionally substituted; and

represents a single bond; or

the stereoisomers thereof or the pharmaceutically acceptable salts thereof.

2. The compound according to claim 1 wherein R 4 is H or an optionally substituted C 1 –C 4 alkyl group.

3. The compound according to claim 1 wherein R 2 is an optionally substituted phenyl, naphthyl or heteroaryl group.

4. The compound according to claim 1 wherein the 6-membered azacyclic ring is attached to the indazole in the 5 or 7 position.

5. The compound according to claim 4 wherein R 4 is H or an optionally substituted C 1 –C 4 alkyl group.

6. The compound according to claim 1 wherein R 2 is an optionally substituted phenyl, naphthyl or heteroaryl group.

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

5-(4-methylpiperazin-1-yl)-3-(1-naphthylsulfonyl)-1H-indazole;

3-(1-naphthylsulfonyl)-5-piperazin-1-yl-1H-indazole;

3-(1-naphthylsulfonyl)-7-piperazin-1-yl-1H-indazole;

1-(3-chlorobenzyl)-5-(4-methylpiperazin-1-yl)-3-(1-naphthylsulfonyl)-1H-indazole;

7-(4-methylpiperazin-1-yl)-3-(phenylsulfonyl)-1H-indazole;

3-(phenylsulfonyl)-7-(4-propylpiperazin-1-yl)-1H-indazole;

3-(phenylsulfonyl)-7-piperazin-1-yl-1H-indazole;

5-(4-methylpiperazin-1-yl)-3-(phenylsulfonyl)-1H-indazole;

3-(phenylsulfonyl)-5-(4-propylpiperazin-1-yl)-1H-indazole;

3-(phenylsulfonyl)-5-piperazin-1-yl-1H-indazole;

5-piperazin-1-yl-3-[(3-cyanophenyl)sulfonyl]-1H-indazole;

7-(4-methylpiperazin-1-yl)-3-[(2-phenethyl)sulfonyl]-1H-indazole;

3-(1-naphthylsulfonyl)-7-(4-propylpiperazin-1-yl)-1H-indazole;

5-(4-phenethylpiperazin-1-yl)-3-(1-naphthylsulfonyl)-1H-indazole;

5-(4-methylpiperazin-1-yl)-3-(2-naphthylsulfonyl)-1H-indazole;

3-[(2-chloro-4-fluorophenyl)sulfonyl]-5-piperazin-1-yl-1H-indazole;

1-methyl-3-(phenylsulfonyl)-5-piperazin-1-yl-1H-indazole;

1-phenyl-3-(phenylsulfonyl)-5-piperazin-1-yl-1H-indazole;

1-methyl-3-(phenylsulfonyl)-7-piperazin-1-yl -1H-indazole;

1-phenyl-3-(phenylsulfonyl)-7-piperazin-1-yl-1H-indazole;

7-piperazin-1-yl-3-[(3-fluorophenyl)sulfonyl]-1H-indazole;

3-[(4-fluorophenyl)sulfonyl]-7-(4-methylpiperazin-1-yl)-1H-indazole;

3-[(2-chlorophenyl)sulfonyl]-7-piperazin-1-yl-1H-indazole;

3-[(4-aminophenyl)sulfonyl]-7-piperazin-1-yl-1H-indazole;

5-piperazin-1-yl-3-[(3-fluorophenyl)sulfonyl]-1H-indazole;

3-[(4-fluorophenyl)sulfonyl]-5-(4-methylpiperazin-1-yl)-1H-indazole;

3-[(2-chlorophenyl)sulfonyl]-5-(4-propylpiperazin-1-yl)-1H-indazole;

3-[(4-aminophenyl)sulfonyl]-5-piperazin-1-yl-1H-indazole;

3-[(5-chlorothien-2-yl )sulfonyl]-5-piperazin-1-yl-1H-indazole;

3-[(5-chlorothien-2-yl)sulfonyl]-7-piperazin-1-yl-1H-indazole;

4-chloro-3-(phenylsulfonyl)-7-piperazin-1-yl-1H-indazole;

5-fluoro-3-(phenylsulfonyl)-7-piperazin-1-yl-1H-indazole;

6-fluoro-3-(phenylsulfonyl)-7-piperazin-1-yl-1H-indazole;

4-chloro-3-(phenylsulfonyl)-5-piperazin-1-yl-1H-indazole;

7-fluoro-3-(phenylsulfonyl)-5-piperazin-1-yl-1H-indazole;

6-fluoro-3-(phenylsulfonyl)-5-piperazin-1-yl-1H-indazole;

6-(4-phenethylpiperazin-1-yl)-3-(phenylsulfonyl)-1H-indazole;

6-(4-methylpiperazin-1-yl)-3-(phenylsulfonyl)-1H-indazole;

6-(4-propylpiperazin-1-yl)-3-(phenylsulfonyl)-1H-indazole;

3-(phenylsulfonyl)-6-piperazin-1-yl-1H-indazole;

4-piperazin-1-yl-3-(phenylsulfonyl)-1H-indazole;

4-(4-methylpiperazin-1-yl )-3-(phenylsulfonyl)-1H-indazole;

4-(4-propylpiperazin-1-yl)-3-(phenylsulfonyl)-1H-indazole;

3-(phenylsulfonyl)-4-piperazin-1-yl-1H-indazole;

the stereoisomers thereof; and

the pharmaceutically acceptable salts thereof.

8. A pharmaceutical composition which comprises at least one pharmaceutically acceptable carrier and an effective amount of compound of formula I

wherein

A is N;

R 1 is H, halogen, CN, OR 17 or a C 1 –C 6 alkyl, or C 3 –C 7 cycloalkyl group each optionally substituted;

R 2 is an optionally substituted C 1 –C 6 alkyl, C 3 –C 7 cycloalkyl, aryl, or heteroaryl group

R 3 is H or a C 1 –C 6 alkyl, or C 3 –C 7 cycloalkyl group each optionally substituted;

R 4 is H or a C 1 –C 6 alkyl or C 3 –C 7 cycloalkyl group each optionally substituted;

R 5, R 6 and R 7 are each independently H or a C 1 –C 6 alkyl or C 3 –C 7 cycloalkyl group each optionally substituted;

m and p are each independently an integer of 1, 2 or 3;

n is an integer of 1;

R 17 is H or a C 1 –C 6 alkyl, C 2 –C 6 alkenyl, C 2 –C 6 alkynyl, or C 3 –C 6 cycloalkyl group each optionally substituted; and

represents a single bond; or

the stereoisomers thereof or the pharmaceutically acceptable salts thereof.

9. The composition according to claim 8 having a formula I compound wherein R 4 is H or an optionally substituted C 1 –C 4 alkyl group.

10. The composition according to claim 9 having a formula I compound wherein R 2 is an optionally substituted phenyl, naphthyl or heteroaryl group.

11. The composition according to claim 10 having a formula I compound wherein the 6-membered azacyclic ring is attached to the indazole in the 5 or 7 position.

12. The composition according to claim 8 having a formula I compound selected from the group consisting of:

5-(4-methylpiperazin-1-yl)-3-(1-naphthylsulfonyl)-1H-indazole;

3-(1-naphthylsulfonyl)-5-piperazin-1-yl-1H-indazole;

3-(1-naphthylsulfonyl)-7-piperazin-1-yl-1H-indazole;

1-(3-chlorobenzyl)-5-(4-methylpiperazin-1-yl)-3-(1-naphthylsulfonyl)-1H-indazole;

7-(4-methylpiperazin-1-yl)-3-(phenylsulfonyl)-1H-indazole;

3-(phenylsulfonyl)-7-(4-propylpiperazin-1-yl)-1H-indazole;

3-(phenylsulfonyl)-7-piperazin-1-yl-1H-indazole;

5-(4-methylpiperazin-1-yl)-3-(phenylsulfonyl)-1H-indazole;

3-(phenylsulfonyl)-5-(4-propylpiperazin-1-yl)-1H-indazole;

3-(phenylsulfonyl)-5-piperazin-1-yl-1H-indazole;

5-piperazin-1-yl-3-[(3-cyanophenyl)sulfonyl]-1H-indazole;

7-(4-methylpiperazin-1-yl)-3-[(2-phenethyl)sulfonyl]-1H-indazole;

3-(1-naphthylsulfonyl)-7-(4-propylpiperazin-1-yl)-1H-indazole;

5-(4-phenethylpiperazin-1-yl)-3-(1-naphthylsulfonyl)-1H-indazole;

5-(4-methylpiperazin-1-yl)-3-(2-naphthylsulfonyl)-1H-indazole;

3-[(2-chloro-4-fluorophenyl)sulfonyl]-5-piperazin-1-yl-1H-indazole;

1-methyl-3-(phenylsulfonyl)-5-piperazin-1-yl-1H-indazole;

1-phenyl-3-(phenylsulfonyl)-5-piperazin-1-yl-1H-indazole;

1-methyl-3-(phenylsulfonyl)-7-piperazin-1-yl-1H-indazole;

1-phenyl-3-(phenylsulfonyl)-7-piperazin-1-yl-1H-indazole;

7-piperazin-1-yl-3-[(3-fluorophenyl)sulfonyl]-1H-indazole;

3-[(4-fluorophenyl)sulfonyl]-7-(4-methylpiperazin-1-yl)-1H-indazole;

3-[(2-chlorophenyl)sulfonyl]-7-piperazin-1-yl-1H-indazole;

3-[(4-aminophenyl)sulfonyl]-7-piperazin-1-yl-1H-indazole;

5-piperazin-1-yl-3-[(3-fluorophenyl)sulfonyl]-1H-indazole;

3-[(4-fluorophenyl)sulfonyl]-5-(4-methylpiperazin-1-yl)-1H-indazole;

3-[(2-chlorophenyl)sulfonyl]-5-(4-propylpiperazin-1-yl)-1H-indazole;

3-[(4-aminophenyl)sulfonyl]-5-piperazin-1-yl-1H-indazole;

3-[(5-chlorothien-2-yl)sulfonyl]-5-piperazin-1-yl-1H-indazole;

3-[(5-chlorothien-2-yl)sulfonyl]-7-piperazin-1-yl-1H-indazole;

4-chloro-3-(phenylsulfonyl)-7-piperazin-1-yl-1H-indazole;

5-fluoro-3-(phenylsulfonyl)-7-piperazin-1-yl-1H-indazole;

6-fluoro-3-(phenylsulfonyl)-7-piperazin-1-yl-1H-indazole;

4-chloro-3-(phenylsulfonyl)-5-piperazin-1-yl-1H-indazole;

7-fluoro-3-(phenylsulfonyl)-5-piperazin-1-yl-1H-indazole;

6-fluoro-3-(phenylsulfonyl)-5-piperazin-1-yl-1H-indazole;

6-(4-phenethylpiperazin-1-yl)-3-(phenylsulfonyl)-1H-indazole;

6-(4-methylpiperazin-1-yl)-3-(phenylsulfonyl)-1H-indazole;

6-(4-propylpiperazin-1-yl)-3-(phenylsulfonyl)-1H-indazole;

3-(phenylsulfonyl)-6-piperazin-1-yl-1H-indazole;

4-piperazin-1-yl-3-(phenylsulfonyl)-1H-indazole;

4-(4-methylpiperazin-1-yl)-3-(phenylsulfonyl)-1H-indazole;

4-(4-propylpiperazin-1-yl)-3-(phenylsulfonyl)-1H-indazole;

3-(phenylsulfonyl)-4-piperazin-1-yl-1H-indazole;

the stereoisomers thereof; and

the pharmaceutically acceptable salts thereof.

13. 3-(1-naphthylsulfonyl)-5-piperazinyl-1H-indazole or a pharmaceutically acceptable salt thereof.

14. A pharmaceutical composition which comprises at least one pharmaceutically acceptable carrier and an effective amount of 3-(1-naphthylsulfonyl)-5-piperazinyl-1H-indazole or a pharmaceutically acceptable salt thereof.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 13, 2004
From: BERNOTAS, RONALD CHARLES; YAN, YINFA; ROBICHAUD, ALBERT JEAN; LIU, GUANGCHENG
To: WYETH
Reel/Frame 014997/0433 →