USE OF BENZO-HETEROARYL SULFAMIDE DERIVATIVES FOR THE TREATMENT OF SUBSTANCE ABUSE AND ADDICTION

Abstract

The present invention is a method for the treatment of substance abuse and/or addiction comprising administering to a subject in need thereof a therapeutically effective amount of one or more novel benzo-heteroaryl sulfamide derivatives of formula (I) as herein defined.

Description

Claims

1. A method of treating substance abuse or addiction comprising administering to a subject in need thereof a therapeutically effective amount of a compound of the formula (I)

2. The method of claim 1 wherein R1 is selected from the group consisting of hydrogen, halogen, trifluoromethyl, cyano and nitro;X—Y is selected from the group consisting of —S—CH—, —O—CH—, —O—C(CH3)—, —N(CH3)—CH— and —CH═CH—CH—;A is selected from the group consisting of —CH2— and —CH(CH3)—;R2 is selected from the group consisting of hydrogen and methyl;R3 and R4 are each independently selected from the group consisting of hydrogen, methyl and ethyl;or a pharmaceutically acceptable salt thereof.

3. The method of claim 2, wherein R1 is selected from the group consisting of hydrogen, halogen, trifluoromethyl and cyano;X—Y is selected from the group consisting of —S—CH—, —O—CH—, —O—C(CH3)—, —N(CH3)—CH— and —CH═CH—CH—;A is selected from the group consisting of —CH2— and —CH(CH3)—;R2 is hydrogen;R3 and R4 are each independently selected from the group consisting of hydrogen and ethyl;or a pharmaceutically acceptable salt thereof.

4. The method of claim 3, wherein R1 is selected from the group consisting of hydrogen, 5-chloro, 5-fluoro, 5-bromo, 4-bromo, 7-fluoro, 5-trifluoromethyl and 5-cyano;X—Y is selected from the group consisting of —S—CH—, —O—CH—, —O—C(CH3)—, —N(CH3)—CH— and —CH═CH—CH—;A is selected from the group consisting of —CH2— and —CH(CH3)—;R2 is hydrogen;R3 and R4 are each hydrogen; alternatively R3 is hydrogen and R4 is ethyl;or a pharmaceutically acceptable salt thereof.

5. The method of claim 1, wherein R1 is selected from the group consisting of hydrogen, halogen, trifluoromethyl and cyano;X—Y is selected from the group consisting of —S—CH—, —O—CH—, —O—C(CH3)—, —N(CH3)—CH— and —CH═CH—CH—;A is selected from the group consisting of —CH2— and —CH(CH3)—;R2 is selected from the group consisting of hydrogen and methyl;R3 and R4 are taken together with the nitrogen atom to which they are bound to form a 5 to 7 membered, saturated, partially unsaturated or aromatic ring structure, optionally containing one to two additional heteroatoms independently selected from the group consisting of O, N and S;or a pharmaceutically acceptable salt thereof.

6. The method of claim 5, wherein R1 is selected from the group consisting of hydrogen, halogen, trifluoromethyl and cyano;X—Y is selected from the group consisting of —S—CH—, —O—CH—, —O—C(CH3)—, —N(CH3)—CH— and —CH═CH—CH—;A is selected from the group consisting of —CH2— and —CH(CH3)—;R2 is selected from the group consisting of hydrogen and methyl;R3 and R4 are taken together with the nitrogen atom to which they are bound to form a 5 to 6 membered, saturated or aromatic ring structure, optionally containing one to two additional heteroatoms independently selected from the group consisting of O, N and S;or a pharmaceutically acceptable salt thereof.

7. The method of claim 6, wherein R1 is hydrogen;X—Y is —S—CH—;A is —CH2—;R2 is hydrogen;R3 and R4 are taken together with the nitrogen atom to which they are bound to form a 5 membered ring structure selected from the group consisting of pyrrolidinyl and imidazolyl;or a pharmaceutically acceptable salt thereof.

8. The method of claim 2, wherein the compound of formula (I) is selected from the group consisting of N-(benzo[b]thien-3-yl methyl )-sulfamide;N-[(5-chlorobenzo[b]thien-3-yl)methyl]-sulfamide;N-(3-benzofuranylmethyl)-sulfamide;N-[(5-fluorobenzo[b]thien-3-yl)methyl]-sulfamide;N-(1-benzo[b]thien-3-ylethyl)-sulfamide;N-(1-naphthalenylmethyl)-sulfamide;N-[(2-methyl-3-benzofuranyl)methyl]-sulfamide;N-[(5-bromobenzo[b]thien-3-yl)methyl]-sulfamide;N-[(4-bromobenzo[b]thien-3-yl)methyl]-sulfamide;N-[(7-fluorobenzo[b]thien-3-yl)methyl]-sulfamide;N-[(1-methyl-1H-indol-3-yl)methyl]-sulfamide;N-[(4-trifluoromethylbenzo[b]thien-3-yl)methyl]-sulfamide;N-[(4-cyanobenzo[b]thien-3-yl)methyl]-sulfamide;N-[(benzo[b]thien-3-yl)methyl]-sulfamoylpyrrolidine;N-[(benzo[b]thien-3-yl)methyl]-N′-ethylsulfamide;imidazole-1-sulfonic acid [(benzo[b]thien-3-yl)methyl]-amide;and pharmaceutically acceptable salts thereof.

9. The method of claim 1, wherein the compound of formula (I) is selected from the group consisting of N-(benzo[b]thien-3-ylmethyl)-sulfamide; N-[(5-fluorobenzo[b]thien-3-yl)methyl]-sulfamide; and pharmaceutically acceptable salts thereof.

10. A method of treating substance abuse or addiction comprising administering to a subject in need thereof a therapeutically effective amount of a compound selected from the group consisting of N-(benzo[b]thien-3-ylmethyl)-sulfamide and pharmaceutically acceptable salts thereof.

11. The method of claim 1 wherein the substance of abuse or addiction is selected from the group consisting of alcohol, cocaine, heroine, methamphetamine, ketamine, Ecstacy, nicotine, oxycontin/oxycodone, codeine and morphine.

12. The method of claim 1, wherein the substance of abuse or addiction is selected from the group consisting of alcohol, cocaine, heroine, methamphetamine and nicotine.

13. The method of claim 1, wherein the substance of abuse or addiction is alcohol or nicotine.

14. The method of claim 1, wherein the substance of abuse or addiction is alcohol.

15. The method of claim 10, wherein the substance of abuse or addiction is selected from the group consisting of alcohol, cocaine, heroine, methamphetamine, ketamine, Ecstacy, nicotine, oxycontin/oxycodone, codeine and morphine.

16. The method of claim 10, wherein the substance of abuse or addiction is selected from the group consisting of alcohol, cocaine, heroine, methamphetamine and nicotine.

17. The method of claim 10, wherein the substance of abuse or addiction is alcohol or nicotine.

18. The method of claim 10, wherein the substance of abuse or addiction is alcohol.