Claims
- 1. A compound of the formula (I)
- 2. A compound as in claim 1 wherein
R1 is selected from the group consisting of aryl, aralkyl and heteroaryl; wherein the aryl, aralkyl or heteroaryl group is optionally substituted with one or more substituents independently selected from halogen, hydroxy, alkyl, alkoxy, trihalomethyl, trihalomethoxy, amino, alkylamino or di(alkyl)amino; R2 is selected from the group consisting of aryl, aralkyl and heteroaryl; wherein the aryl, aralkyl or heteroaryl group is optionally substituted with one or more substituents independently selected from halogen, hydroxy, alkyl, alkoxy, trihalomethyl, trihalomethoxy, amino, alkylamino or di(alkyl)amino; R3 is selected from the group consisting of hydrogen and alkyl; R4 is selected from the group consisting of aryl, aralkyl and heteroaryl; wherein the aryl, aralkyl or heteroaryl group is optionally substituted with one or more substituents independently selected from halogen, hydroxy, alkyl, alkoxy, trihalomethyl, trihaomethoxy, amino, alkylamino or di(alkyl)amino; provided that when R1 is phenyl, chlorophenyl or benzyl, R2 is phenyl or benzothienyl and R4 is phenyl or aralkyl, then R3 is selected from the group consisting of alkyl; provided further that when R1 is benzyl or methylphenyl, R2 is phenyl or methylphenyl and R4 is methylphenyl or 4-methoxyphenyl, then R3 is selected from the group consisting of alkyl; provided further that when R1 is phenyl, R2 is phenyl and R4 is phenyl, then R3 is selected from the group consisting of C3-8alkyl; and pharmaceutically acceptable salts thereof.
- 3. A compound as in claim 2 wherein
R1 is aryl; wherein aryl group is optionally substituted with one to two substituents independently selected from halogen, alkyl and alkoxy; R2 is aryl; wherein the aryl group is optionally substituted with one to two substituents independently selected from alkyl and alkoxy; R3 is selected from the group consisting of hydrogen and alkyl; R4 is selected from the group consisting of aryl, aralkyl, and heteroaryl; wherein the aryl or aralkyl group is optionally substituted with one to two substituents independently selected from halogen, alkyl and alkoxy; provided that when R1 is phenyl or chlorophenyl, R2 is phenyl and R4 is phenyl or aralkyl, then R3 is selected from the group consisting of alkyl; provided further that when R1 is methylphenyl, R2 is phenyl and R4 is methylphenyl or 4-methoxyphenyl, then R3 is selected from the group consisting of alkyl; provided further that when R1 is phenyl, R2 is phenyl and R4 is phenyl, then R3 is selected from the group consisting of C3-8alkyl; and pharmaceutically acceptable salts thereof.
- 4. A compound as in claim 3 wherein
R1 is selected from the group consisting of phenyl, 2-chlorophenyl, 4-chlorophenyl, 2-methylphenyl, 4-methylphenyl, 2-methoxyphenyl and 4-methoxyphenyl, R2 is selected from the group consisting of phenyl, 4-methylphenyl, 2-methoxyphenyl and 4-methoxyphenyl; R3 is selected from the group consisting of hydrogen and methyl; R4 is selected from the group consisting of phenyl, 2-chlorophenyl, 4-chlorophenyl, 4-bromophenyl, 2-methylphenyl, 4-methylphenyl, 2-methoxyphenyl, 4-methoxyphenyl, benzyl, 2-chlorobenzyl, 4-chlorobenzyl, 2-methylbenzyl, 4-methylbenzyl, 2-methoxybenzyl, 4-methoxybenzyl, 2,6-difluorophenyl, 3,5-difluorophenyl, 2-chloro-6-methylphenyl and 3-pridyl; provided that when R1 is phenyl or chlorophenyl, R2 is phenyl and R4 is phenyl or benzyl, then R3 is selected from the group consisting of alkyl; provided further that when R1 is methylphenyl, R2 is phenyl and R4 is methylphenyl or 4-methoxyphenyl, then R3 is selected from the group consisting of alkyl; provided further that R1, R2 and R4 cannot each be phenyl; and pharmaceutically acceptable salts thereof.
- 5. A compound as in claim 4, selected from the group consisting of
2-(2-methoxyphenyl)-3-(2-methoxyphenyl)-5-phenylamino-[1,2,4]-thiadiazol-2-ium; 2-(2-methoxyphenyl)-3-(2-methoxyphenyl)-5-(2-methoxyphenylamino)-[1,2,4]-thiadiazol-2-ium; 2-(2-methoxyphenyl)-3-(2-methoxyphenyl)-5-(4-tolylamino)-[1,2,4]-thiadiazol-2ium; 2-(2-methoxyphenyl)-3-phenyl-5-(4-methoxyphenylamino)-[1,2,4]-thiadiazol-2-ium; 2-(2-methoxyphenyl)-3-phenyl-5-(4-tolylamino)-[1,2,4]-thiadiazol-2-ium; 2-(2-methoxyphenyl)-3-phenyl-5-(2-tolylamino)-[1,2,4]-thiadiazol-2-ium; and pharmaceutically acceptable salts thereof.
- 6. The compound of claim 5 selected from 2-(2-methoxyphenyl)-3-(2-methoxyphenyl)-5-phenylamino-[1,2,4]thiadiazol-2-ium or a pharmaceutically acceptable salt thereof.
- 7. A pharmaceutical composition comprising a compound as claimed in claim 1 and a pharmaceutically acceptable carrier.
- 8. A method of making a pharmaceutical composition comprising mixing a compound of claim 1 with a pharmaceutically acceptable carrier.
- 9. A pharmaceutical composition made by mixing a compound of claim 1 and a pharmaceutically acceptable carrier.
- 10. A method of treating a disorder mediated by a melanocortin receptor comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula (I)
- 11. A method as in claim 10 wherein
R1 is selected from the group consisting of aryl, aralkyl and heteroaryl; wherein the aryl, aralkyl or heteroaryl group is optionally substituted with one or more substituents independently selected from halogen, hydroxy, alkyl, alkoxy, trihalomethyl, trihalomethoxy, amino, alkylamino or di(alkyl)amino; R2 is selected from the group consisting of aryl, aralkyl and heteroaryl; wherein the aryl, aralkyl or heteroaryl group is optionally substituted with one or more substituents independently selected from halogen, hydroxy, alkyl, alkoxy, trihalomethyl, trihalomethoxy, amino, alkylamino or di(alkyl)amino; R3 is selected from the group consisting of hydrogen and alkyl; R4 is selected from the group consisting of aryl, aralkyl and heteroaryl; wherein the aryl, aralkyl or heteroaryl group is optionally substituted with one or more substituents independently selected from halogen, hydroxy, alkyl, alkoxy, trihalomethyl, trihaomethoxy, amino, alkylamino or di(alkyl)amino; and pharmaceutically acceptable salts thereof.
- 12. A method as in claim 11 wherein
R1 is aryl; wherein aryl group is optionally substituted with one to two substituents independently selected from halogen, alkyl and alkoxy; R2 is aryl; wherein the aryl group is optionally substituted with one to two substituents independently selected from alkyl and alkoxy; R3 is selected from the group consisting of hydrogen and alkyl; R4 is selected from the group consisting of aryl, aralkyl, and heteroaryl; wherein the aryl or aralkyl group is optionally substituted with one to two substituents independently selected from halogen, alkyl and alkoxy; and pharmaceutically acceptable salts thereof.
- 13. A method as in claim 12 wherein the compound is selected from the group consisting of
2-(2-methoxyphenyl)-3-(2-methoxyphenyl)-5-phenylamino-[1,2,4]-thiadiazol-2-ium; 2-(2-methoxyphenyl)-3-(2-methoxyphenyl)-5-(2-methoxyphenylamino)-[1,2,4]-thiadiazol-2-ium; 2-(2-methoxyphenyl)-3-(2-methoxyphenyl)-5-(4-tolylamino)-[1,2,4]-thiadiazol-2-ium; 2-(2-methoxyphenyl)-3-phenyl-5-(4-methoxyphenylamino)-[1,2,4]-thiadiazol-2-ium; 2-(2-methoxyphenyl)-3-phenyl-5-(4-tolylamino)-[1,2,4]-thiadiazol-2-ium; 2-(2-methoxyphenyl)-3-phenyl-5-(2-tolylamino)-[1,2,4]-thiadiazol-2-ium; and pharmaceutically acceptable salts thereof.
- 14. The method of claim 10, wherein the disorder mediated by a melanocortin receptor is selected from the group consisting of metabolic disorders, CNS disorders and dermatological disorders.
- 15. The method of claim 10, wherein the disorder mediated by a melanocortin receptor is selected from the group consisting of obesity, impaired oral glucoase tolerance, elevated blood glucose levels, type II diabetes, Syndrome X, diabetic retinopathy, acute neurodegenerative disorders, chronic neurodegenerative disorders, plexopathies, male erectile dysfunction, dry eyes, acne, dry skin, aged skin, seborrheic dermatitis, rosacea, excessive ear wax, meibomian gland disorder, pseudofolliculitis, yeast infections, dandruff, hiradenitis suppurativa, ocular rosacea and eccrine gland disorder.
- 16. The method of claim 10, wherein the disorder mediated by a melanocortin receptor is selected from the group consisting of obesity, impaired oral glucose tolerance, elevated blood glucose levels, type II diabetes and Syndrome X.
- 17. The method of claim 10, wherein the disorder mediated by a melanocortin receptor is selected from the group consisting of acne, dry skin and seborrheic dermatitis.
- 18. The method of claim 10, wherein the melanocortin receptor is a selected from the group consisting of the melanocortin-3 receptor, the melanocortin-4 receptor and the melanocortin-5 receptor.
CROSS REFERENCE TO RELATED APPLICATION
[0001] This application claims the benefit of U.S. Provisional Application No. 60/337,762, filed on Nov. 8, 2001, which is incorporated by reference herein in its entirety.
Provisional Applications (1)
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Number |
Date |
Country |
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60337762 |
Nov 2001 |
US |