IP Library › Granted Patent US 7,723,329

Granted Patent B2

US 7,723,329 · App. 11/504,350 · Granted May 25, 2010

Substituted-3-sulfonylindazole derivatives as 5-hydroxytryptamine-6 ligands

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Quick Facts

Patent No.: US 7,723,329
App. No.: 11/504,350
Granted: May 25, 2010
Kind: B2

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USPTO Patent Center↗ Full Patent PDF↗

Abstract

The present invention provides a compound of formula I and the use thereof for the treatment of a central nervous system disorder related to or affected by the 5-HT6 receptor.

Claims (285)

1. A compound of formula I

wherein

X is O or S;

n is an integer of 2, 3, 4, 5 or 6;

R 1 is H or an alkyl, cycloalkyl, aryl or heteroaryl group each optionally substituted;

R 2 is an optionally substituted cycloalkyl or aryl group;

R 3 and R 4 are each independently H, or an optionally substituted alkyl group;

R 5 and R 6 are each independently H, or an alkyl, alkenyl, alkynyl, or cycloalkyl, group each optionally substituted;

R 7 is H, halogen, CN, OR 8 , CO 2 R 9 , CONR 10 R 11 , or an alkyl, alkenyl, alkynyl, cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted;

m is an integer of 1, 2 or 3;

R 8 is H, COR 12 or an alkyl, alkenyl, alkynyl, aryl or heteroaryl group each optionally substituted;

R 9 is H or a C 1 -C 6 alkyl, aryl or heteroaryl group each optionally substituted;

R 10 and R 11 are each independently H or an optionally substituted alkyl group; and

R 12 is an optionally substituted C 1 -C 6 alkyl, cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group; or

a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 wherein X is O.

3. The compound according to claim 1 wherein n is 2 or 3.

4. The compound according to claim 2 wherein R 2 is an optionally substituted aryl.

5. The compound according to claim 3 wherein X is O.

6. The compound according to claim 5 wherein R 5 and R 6 are each independently H or C 1 -C 4 alkyl.

7. The compound according to claim 5 wherein R 2 is an optionally substituted naphthyl group.

8. The compound according to claim 7 wherein R 2 is naphthyl and n is 3.

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

N,N-Dimethyl-3-{[3-(1-naphthylsulfonyl)-1H-indazol-5-yl]oxy}propan-1-amine;

N,N-Dimethyl-2-{[3-(phenylsulfonyl)-1H-indazol-5-yl]oxy}ethanamine;

N,N-Dimethyl-2-{[3-(1-naphthylsulfonyl)-1H-indazol-5-yl]oxy}ethanamine;

N-(2-{[3-(1-Naphthylsulfonyl)-1H-indazol-5-yl]oxy}ethyl)cyclopentanamine;

N-Ethyl-N-methyl-2-{[3-(1-naphthylsulfonyl)-1H-indazol-5-yl]oxy}ethanamine;

N-(2-{[3-(1-Naphthylsulfonyl)-1H-indazol-5-yl]oxy}ethyl)butan-1-amine;

N-Ethyl-2-{[3-(phenylsulfonyl)-1H-indazol-5-yl]oxy}ethanamine;

N-(2-{[3-(Phenylsulfonyl)-1H-indazol-5-yl]oxy}ethyl) propan-2-amine;

N-(2-{[3-(1-Naphthylsulfonyl)-1H-indazol-5-yl]oxy}ethyl)propan-2-amine;

N-Ethyl-2-{[3-(1-naphthylsulfonyl)-1H-indazol-5-yl]oxy}ethanamine;

N-Methyl-2-{[3-(1-naphthylsulfonyl)-1H-indazol-5-yl]oxy}ethanamine;

N,N-Diethyl-2-{[3-(1-naphthylsulfonyl)-1H-indazol-5-yl]oxy}ethanamine;

N-(2-{[3-(1-Naphthylsulfonyl)-1H-indazol-5-yl]oxy}ethyl)cyclopropanamine;

(2-{[1-(3-Chlorobenzyl)-3-(1-naphthylsulfonyl)-1H-indazol-7-yl]oxy}ethyl)amine;

N-(2-{[3-(Phenylsulfonyl)-1H-indazol-5-yl]oxy}ethyl)cyclopentanamine;

N-Methyl-2-{[3-(phenylsulfonyl)-1H-indazol-5-yl]oxy}ethanamine;

N-Methyl-2-{[1-methyl-3-(phenylsulfonyl)-1H-indazol-7-yl]oxy}ethanamine;

(2-{[1-(3-Chlorobenzyl)-3-(phenylsulfonyl)-1H-indazol-7-yl]oxy}ethyl)methylamine;

(2-{[1-(3-Chlorobenzyl)-3-(phenylsulfonyl)-1H-indazol-7-yl]oxy}ethyl)ethylamine;

N-Methyl-2-{[3-(phenylsulfonyl)-1H-indazol-7-yl]oxy}ethanamine;

(2-{[1-(3-Chlorobenzyl)-3-(1-naphthylsulfonyl)-1H-indazol-7-yl]oxy}ethyl)ethylamine;

(2-{[1-(3-Chlorobenzyl )-3-(1-naphthylsulfonyl)-1H-indazol-7-yl]oxy}ethyl)methylamine;

N-Ethyl-2-{[3-(phenylsulfonyl)-1H-indazol-7-yl]oxy}ethanamine;

N,N-Diethyl-2-{[3-(phenylsulfonyl)-1H-indazol-7-yl]oxy}ethanamine;

N-(2-{[3-(Phenylsulfonyl)-1H-indazol-7-yl]oxy}ethyl) butan-1-amine;

N,N-Diethyl-2-{[1-methyl-3-(1-naphthylsulfonyl)-1H-indazol-7-yl]oxy}ethanamine;

N-Ethyl-2-{[1-methyl-3-(1-naphthylsulfonyl)-1H-indazol-7-yl]oxy}ethanamine;

N-Ethyl-2-{[3-(1-naphthylsulfonyl)-1H-indazol-7-yl]oxy}ethanamine;

(2-{[3-(1-Naphthylsulfonyl)-1H-indazol-7-yl]oxy}ethyl)amine;

(2-{[1-(3-Chlorobenzyl)-5-fluoro-3-(1-naphthylsulfonyl)-1H-indazol-7-yl]oxy}ethyl)-dimethylamine;

(2-{[1-Benzyl-3-(1-naphthylsulfonyl)-1H-indazol-5-yl]oxy}ethyl)methylamine;

(2-{[1-Benzyl-3-(1-naphthylsulfonyl)-1H-indazol-5-yl]oxy}ethyl)dimethylamine;

(2-{[1-Benzyl-3-(1-naphthylsulfonyl)-1H-indazol-5-yl]oxy}ethyl)ethylamine;

N-Methyl-2-{[3-(1-naphthylsulfonyl)-1H-indazol-7-yl]oxy}ethanamine;

N,N-Dimethyl-2-{[3-(1-naphthylsulfonyl)-1H-indazol-7-yl]oxy}ethanamine;

N,N-Diethyl-2-{[5-fluoro-3-(1-naphthylsulfonyl)-1H-indazol-7-yl]oxy}ethanamine;

(2-{[5-Fluoro-3-(1-naphthylsulfonyl)-1H-indazol-7-yl]oxy}ethyl)dimethylamine;

N-Ethyl-2-{[5-fluoro-3-(1-naphthylsulfonyl)-1H-indazol-7-y]oxy}ethanamine;

(2-{[1-(3-Chlorobenzyl)-3-(1-naphthylsulfonyl)-1H-indazol-5-yl]oxy}ethyl)-dimethylamine;

N-Methyl-3-{[3-(1-naphthylsulfonyl)-1H-indazol-5-yl]oxy}propan-1-amine;

N-Ethyl-N-methyl-3-{[3-(1-naphthylsulfonyl)-1H-indazol-5-yl]oxy}propan-1-amine;

N,N-Dimethyl-3-{[3-(1-naphthylsulfonyl)-1H-indazol-5-yl]oxy}propan-1-amine;

N,N-Diethyl-3-{[3-(1-naphthylsulfonyl)-1H-indazol-5-yl]oxy}propan-1-amine;

N-(3-{[3-(1-Naphthylsulfonyl)-1H-indazol-5-yl]oxy}propyl)butan-1-amine;

(2-{[5-Methoxy-3-(1-naphthylsulfonyl)-1H-indazol-7-yl]oxy}ethyl)methylamine;

(2-{[5-Methoxy-3-(1-naphthylsulfonyl)-1H-indazol-7-yl]oxy}ethyl)dimethylamine;

(2-{[1-(3-Chlorobenzyl)-3-(1-naphthylsulfonyl)-1H-indazol -5-yl]oxy}ethyl)ethylamine;

(3-{[1-(3-Chlorobenzyl)-3-(1-naphthylsulfonyl)-1H-indazol-7-yl]oxy}propyl)-diethylamine;

N-Methyl-3-{[3-(1-naphthylsulfonyl)-1H-indazol-7-yl]oxy}propan-1-amine;

N,N-Diethyl-3-{[3-(1-naphthylsulfonyl)-1H-indazol-7-yl]oxy}propan-1-amine;

N-Methyl-2-{[1-methyl-3-(1-naphthylsulfonyl)-1H-indazol-5-yl]oxy}ethanamine;

N,N-Dimethyl-2-{[1-methyl-3-(1-naphthylsulfonyl)-1H-indazol-5-yl]oxy}ethanamine;

N-Ethyl-N-methyl-2-{[1-methyl-3-(1-naphthylsulfonyl)-1H-indazol-5-yl]oxy}ethanamine;

N-Ethyl-2-{[1-methyl-3-(1-naphthylsulfonyl)-1H-indazol-5-yl]oxy}ethanamine;

N,N-Diethyl-2-{[1-methyl-3-(1-naphthylsulfonyl)-1H-indazol-5-yl]oxy}ethanamine;

N-(2-{[1-Methyl-3-(1-naphthylsulfonyl)-1H-indazol-5-yl]oxy}ethyl)propan-2-amine;

(2-{[1-Methyl-3-(1-naphthylsulfonyl)-1H-indazol-7-yl]oxy}ethyl)amine;

N-Ethyl-3-{[3-(1-naphthylsulfonyl)-1H-indazol-5-yl]oxy}propan-1-amine;

N-Isopropyl-3-{[3-(1-naphthylsulfonyl)-1H-indazol-5-yl]oxy}propan-1-amine;

N-(3-{[3-(1-Naphthylsulfonyl)-1H-indazol-5-yl]oxy}propyl)cyclopentanamine;

N-(3-{[3-(1-Naphthylsulfonyl)-1H-indazol-5-yl]oxy}propyl)cyclopropanamine;

(3-{[3-(1-Naphthylsulfonyl)-1H-indazol-5-yl]oxy}propyl)amine;

N-Methyl-4-{[3-(1-naphthylsulfonyl)-1H-indazol-5-yl]oxy}butan-1-amine

N,N-Dimethyl-4-{[3-(1-naphthylsulfonyl)-1H-indazol-5-yl]oxy}butan-1-amine;

N-Ethyl-4-{[3-(1-naphthylsulfonyl)-1H-indazol-5-yl]oxy}butan-1-amine;

N,N-Diethyl-4-{[3-(1-naphthylsulfonyl)-1H-indazol-5-yl]oxy}butan-1-amine;

N-Methyl-4-{[3-(1-naphthylsulfonyl)-1H-indazol-5-yl]oxy}-N-propylbutan-1-amine;

(4-{[3-(1-Naphthylsulfonyl)-1H-indazol-5-yl]oxy}butyl)amine;

(2-{[5-Fluoro-3-(1-naphthylsulfonyl)-1H-indazol-7-yl]oxy}ethyl)methylamine;

(2-{[3-(1-Naphthylsulfonyl)-1H-indazol-5-yl]oxy}ethyl)amine;

2-{[5-Fluoro-3-(phenysulfonyl)-1H-indazol-7-yl]oxy}ethanamine;

2-{[3-(Phenylsulfonyl)-1H-indazol-7-yl]oxy}ethanamine;

N,N-Dimethyl-2-{[3-(1-naphthylsulfonyl)-1H-indazol-4-yl]oxy}ethanamine;

2-{[3-(1-Naphthylsulfonyl)-1H-indazol-4-yl]oxy}ethanamine;

N-Methyl-{[3-(1-naphthylsulfonyl)-1H-indazol-6-yl]oxy}ethanamine;

2-{[3-(1-Naphthylsulfonyl)-1H-indazol-6-yl]oxy}ethanamine;

a stereoisomer thereof; 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

X is O;

n is an integer of 2, 3, 4, 5 or 6;

R 1 is H or an alkyl, cycloalkyl, aryl or heteroaryl group each optionally substituted;

R 2 is an optionally substituted cycloalkyl or aryl group

R 3 and R 4 are each independently H, or an optionally substituted alkyl group;

R 5 and R 6 are each independently H, or an alkyl, alkenyl, alkynyl, or cycloalkyl, group each optionally substituted,

R 7 is H, halogen, CN, OR 8 , CO 2 R 9 , CONR 10 R 11 , or an alkyl, alkenyl, alkynyl, cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted;

m is an integer of 1, 2 or 3;

R 8 is H, COR 12 or an alkyl, alkenyl, alkynyl, aryl or heteroaryl group each optionally substituted;

R 9 is H or a C 1 -C 6 alkyl, aryl or heteroaryl group each optionally substituted;

R 10 and R 11 are each independently H or an optionally substituted alkyl group; and

R 12 is an optionally substituted C 1 -C 6 alkyl, cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group; or a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

11. The composition according to claim 10 having a formula I compound wherein X is O.

12. The composition according to claim 11 having a formula I compound wherein n is 2 or 3.

13. The composition according to claim 12 having a formula I compound wherein X is O; R 2 is an optionally substituted phenyl or naphthyl or group; and n is 3.

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