3,4-DIAMINO-3-CYCLOBUTENE-1,2-DIONE DERIVATIVES AS POTASSIUM CHANNEL OPENERS

Abstract

The present invention is directed to novel 3,4-diamino-3-cyclobutene-1,2-dione derivatives, pharmaceutical compositions containing them and their use in the treatment of disorders related to potassium channel.

Description

Claims

1. A compound of formula (I)

2. A compound as in claim 1, wherein n is an integer from 0 to 2;R1 is selected from the group consisting of cycloalkyl, aryl and 5- to 6 membered heteroaryl;wherein the aryl or heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, amino, C1-4alkylamino, di(C1-4alkyl)amino, cyano, nitro, C1-4alkyl and fluorine substituted C1-4alkyl;or a pharmaceutically acceptable salt thereof.

3. A compound as in claim 2, wherein n is an integer from 0 to 2;R1 is selected from the group consisting of cycloalkyl, phenyl and 6-membered heteroaryl; wherein the aryl or heteroaryl is optionally substituted with one to three substituents independently selected from the group consisting of halogen, C1-4alkyl, fluorine substituted C1-4alkyl and cyano;or a pharmaceutically acceptable salt thereof.

4. A compound as in claim 3, wherein n is an integer from 0 to 2;R1 is selected from the group consisting of cyclohexyl, 1-adamantyl, phenyl, 4-chlorophenyl, 3,4-dichloro-phenyl, 2-fluorophenyl, 2-trifluoromethyl-phenyl, 3-trifluoromethyl-phenyl, 3,5-bis(trifluoromethyl)-phenyl, 2-ethyl-4-cyano-phenyl, 2,4-dichloro-6-methyl-phenyl and 5-cyano-pyrid-2-yl;or a pharmaceutically acceptable salt thereof.

5. A compound as in claim 4, wherein n is an integer from 0 to 1;R1 is selected from the group consisting of phenyl, 4-chlorophenyl, 3-trifluoromethyl-phenyl, 2-ethyl-4-cyano-phenyl and 2,4-dichloro-6-methyl-phenyl;or a pharmaceutically acceptable salt thereof.

6. A compound as in claim 4, selected from the group consisting of 3-ethyl-4-[[2-(1-oxaspiro[4.4]non-6-ylamino)-3,4-dioxo-1-cyclobutene-1-yl]amino]-benzonitrile and pharmaceutically acceptable salts thereof.

7. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of claim 1.

8. A method of treating a disorder related to ion channels, comprising administering, to a subject in need thereof, a therapeutically effective amount of the compound of claim 1.

9. The method of claim 8, wherein the ion channel is a potassium ion channel.

10. The method of claim 9, wherein the ion channel is an ATP-sensitive potassium ion channel.

11. The method of claim 8, wherein the disorder related to ion channels is selected from the group consisting of urinary incontinence, overactive bladder, hypertension, erectile dysfunction, female sexual disorders, dysmenorrhea, irritable bowl syndrome, airway hyperactivity, epilepsy, stroke, Alzheimer's disease, Parkinson's disease, myocardial injury, coronary artery disease, hair loss and baldness.

12. The method of claim 8, wherein the disorder related to ion channels is selected from the group consisting of urinary incontinence and overactive bladder.

13. A method of treating a disorder selected from the group consisting of urinary incontinence, overactive bladder, hypertension, erectile dysfunction, female sexual disorders, dysmenorrhea, irritable bowl syndrome, airway hyperactivity, epilepsy, stroke, Alzheimer's disease, Parkinson's disease, myocardial injury, coronary artery disease, hair loss and baldness, comprising administering, to a subject in need thereof, a therapeutically effective amount of the composition of claim 7.