Claims
- 1. A compound of Formula I or a pharmaceutically acceptable salt thereof
- 2. A compound of claim 1 where R3 is hydrogen and m is 1.
- 3. A compound of claim 2 where R4 is methyl.
- 4. A compound of claim 3 selected from the following group:
2-[2-(4-morpholinyl)ethyl]-N-[1-[3-(3-pyridinyl)phenyl]ethyl]-4-(trifluoromethyl)-5-thiazolecarboxamide; N-[1-[3-(dimethylamino)phenyl]ethyl]-2-[2-(1-pyrrolidinyl)ethyl]-4-(trifluoromethyl)-5-thiazolecarboxamide; 2-[2-(1-pyrrolidinyl)ethyl]-4-(trifluoromethyl)-N-[1-[3-(trifluoromethyl)phenyl]ethyl]-5-thiazolecarboxamide; 2-[2-[(2-furanylmethyl)methylamino]ethyl]-N-[(1S)-1-[3-(4-morpholinyl)phenyl]ethyl]-4-(trifluoromethyl)-5-thiazolecarboxamide; 2-[2-[(2-furanylmethyl)methylamino]ethyl]-N-[1-[3-(3-pyridinyl)phenyl]ethyl]-4-(trifluoromethyl)-5-thiazolecarboxamide; 2-[2-(1-pyrrolidinyl)ethyl]-N-[1-[3-(trifluoromethoxy)phenyl]ethyl]-4-(trifluoromethyl)-5-thiazolecarboxamide; 2-[2-[(2-furanylmethyl)methylamino]ethyl]-N-[1-[3-(trifluoromethoxy)phenyl]ethyl]-4-(trifluoromethyl)-5-thiazolecarboxamide; 2-[2-(diethylamino)ethyl]-N-[1-[3-(trifluoromethoxy)phenyl]ethyl]-4-(trifluoromethyl)-5-thiazolecarboxamide; 2-[2-(diethylamino)ethyl]-N-[1-[3-(dimethylamino)phenyl]ethyl]-4-(trifluoromethyl)-5-thiazolecarboxamide; 2-[2-[ethyl(4-pyridinylmethyl)amino]ethyl]-4-(trifluoromethyl)-N-[1-[3-(trifluoromethyl)phenyl]ethyl]-5-thiazolecarboxamide; 2-[2-(4-thiomorpholinyl)ethyl]-4-(trifluoromethyl)-N-[1-[3-(trifluoromethyl)phenyl]ethyl]-5-thiazolecarboxamide; 2-[2-[[2-(dimethylamino)ethyl]methylamino]ethyl]-N-[1-[3-(trifluoromethoxy)phenyl]ethyl]-4-(trifluoromethyl )-5-thiazolecarboxamide; 2-[2-[[2-(dimethylamino)ethyl]methylamino]ethyl]-4-(trifluoromethyl)-N-[1-[3-(trifluoromethyl)phenyl]ethyl]-5-thiazolecarboxamide; 2-[2-(4-methyl-1-piperazinyl)ethyl]-N-[1-[3-(trifluoromethoxy)phenyl]ethyl]-4-(trifluoromethyl)-5-thiazolecarboxamide; 2-[2-(1-piperidinyl)ethyl]-N-[1-[3-(trifluoromethoxy)phenyl]ethyl]-4-(trifluoromethyl)-5-thiazolecarboxamide; N-[1-[3-(dimethylamino)phenyl]ethyl]-2-[2-(1-piperidinyl)ethyl]-4-(trifluoromethyl)-5-thiazolecarboxamide; 2-[2-(1-piperidinyl)ethyl]-4-(trifluoromethyl)-N-[1-[3-(trifluoromethyl)phenyl]ethyl]-5-thiazolecarboxamide; N-[(1S)-1-[3-(4-morpholinyl)phenyl]ethyl]-2-[2-(1-piperidinyl)ethyl]-4-(trifluoromethyl)-5-thiazolecarboxamide; 2-[2-(4-hydroxy-1-piperidinyl)ethyl]-N-[1-[3-(trifluoromethoxy)phenyl]ethyl]-4-(trifluoromethyl)-5-thiazolecarboxamide; 2-[2-(4-hydroxy-1-piperidinyl)ethyl]-4-(trifluoromethyl)-N-[1-[3-(trifluoromethyl)phenyl]ethyl]-5-thiazolecarboxamide; 2-[2-[(cyclopropylmethyl)propylamino]ethyl]-N-[1-[3-(trifluoromethoxy)phenyl]ethyl]-4-(trifluoromethyl)-5-thiazolecarboxamide; 2-[2-[(cyclopropylmethyl)propylamino]ethyl]-N-[1-[3-(dimethylamino)phenyl]ethyl]-4-(trifluoromethyl)-5-thiazolecarboxamide; 2-[2-[(cyclopropylmethyl)propylamino]ethyl]-4-(trifluoromethyl)-N-[1-[3-(trifluoromethyl)phenyl]ethyl]-5-thiazolecarboxamide; 2-[2-(diethylamino)ethyl]-N-[(1S)-1-[3-(3-pyridinyl)phenyl]ethyl]-4-(trifluoromethyl)-5-thiazolecarboxamide; 2-[2-(1-piperidinyl)ethyl]-N-[(1S)-1-[3-(3-pyridinyl)phenyl]ethyl]-4-(trifluoromethyl)-5-thiazolecarboxamide; 2-[2-[(1-ethylpropyl)amino]ethyl]-N-[1-[3-(trifluoromethoxy)phenyl]ethyl]-4-(trifluoromethyl)-5-thiazolecarboxamide; 2-[2-[(1-ethylpropyl)amino]ethyl]-4-(trifluoromethyl)-N-[1-[3-(trifluoromethyl)phenyl]ethyl]-5-thiazolecarboxamide; 2-[2-[(2-furanylmethyl)amino]ethyl]-N-[(1S)-1-[3-(3-pyridinyl)phenyl]ethyl]-4-(trifluoromethyl)-5-thiazolecarboxamide; 2-[2-(cyclopentylamino)ethyl]-N-[1-[3-(trifluoromethoxy)phenyl]ethyl]-4-(trifluoromethyl)-5-thiazolecarboxamide; 2-[2-(cyclopentylamino)ethyl]-N-[(1S)-1-[3-(3-pyridinyl)phenyl]ethyl]-4-(trifluoromethyl)-5-thiazolecarboxamide; 2-[2-[bis(2-methoxyethyl)amino]ethyl]-N-[1-[3-(trifluoromethoxy)phenyl]ethyl]-4-(trifluoromethyl)-5-thiazolecarboxamide; 2-[2-[bis(2-methoxyethyl)amino]ethyl]-4-(trifluoromethyl)-N-[1-[3-(trifluoromethyl)phenyl]ethyl]-5-thiazolecarboxamide; 2-[2-[bis(2-methoxyethyl)amino]ethyl]-N-[(1S)-1-[3-(3-pyridinyl)phenyl]ethyl]-4-(trifluoromethyl )-5-thiazolecarboxamide; 2-[2-(4-morpholinyl)ethyl]-N-[(1S)-1-[3-(4-morpholinyl)phenyl]ethyl]-4-(trifluoromethyl)-5-thiazolecarboxamide; N-[1-[3-(dimethylamino)phenyl]ethyl]-2-[2-(4-thiomorpholinyl)ethyl]-4-(trifluoromethyl)-5-thiazolecarboxamide; 2-[2-[[2-(dimethylamino)ethyl]methylamino]ethyl]-N-[1-[3-(dimethylamino)phenyl]ethyl]-4-(trifluoromethyl)-5-thiazolecarboxamide; and 2-[2-(4-methyl-1-piperazinyl)ethyl]-N-[(1S)-1-[3-(4-morpholinyl)phenyl]ethyl]-4-(trifluoromethyl)-5-thiazolecarboxamide.
- 5. A compound of claim 1 where R3 is hydroxy and m is 1.
- 6. A compound of claim 5 where R4 is methyl.
- 7. A compound of claim 6 selected from the following group:
2-[1-hydroxy-2-(1-piperidinyl)ethyl]-N-[1-[3-(trifluoromethoxy)phenyl]ethyl]-4-(trifluoromethyl)-5-thiazolecarboxamide; 2-[1-hydroxy-2-(1-pyrrolidinyl)ethyl]-4-(trifluoromethyl)-N-[1-[3-(trifluoromethyl)phenyl]ethyl]-5-thiazolecarboxamide; 2-[2-[(2-furanylmethyl)methylamino]-1-hydroxyethyl]-4-(trifluoromethyl)-N-[1-[3-(trifluoromethyl)phenyl]ethyl]-5-thiazolecarboxamide; 2-[2-[(cyclopropylmethyl)propylamino]-1-hydroxyethyl]-N-[1-[3-(trifluoromethoxy)phenyl]ethyl]-4-(trifluoromethyl)-5-thiazolecarboxamide; 2-[2-(diethylamino)-1-hydroxyethyl]-N-[(1S)-1-[3-(4-morpholinyl)phenyl]ethyl]-4-(trifluoromethyl)-5-thiazolecarboxamide; 2-[2-(diethylamino)-1-hydroxyethyl]-N-[(1S)-1-[3-(3-pyridinyl)phenyl]ethyl]-4-(trifluoromethyl)-5-thiazolecarboxamide; 2-[1-hydroxy-2-(4-morpholinyl)ethyl]-N-[1-[3-(trifluoromethoxy)phenyl]ethyl]-4-(trifluoromethyl)-5-thiazolecarboxamide; 2-[1-hydroxy-2-(4-morpholinyl)ethyl]-4-(trifluoromethyl)-N-[1-[3-(trifluoromethyl )phenyl]ethyl]-5-thiazolecarboxamide; 2-[1-hydroxy-2-(4-methyl-1-piperazinyl)ethyl]-4-(trifluoromethyl)-N-[1-[3-(trifluoromethyl)phenyl]ethyl]-5-thiazolecarboxamide; 2-[1-hydroxy-2-(4-methyl-1-piperazinyl)ethyl]-N-[(1S)-1-[3-(4-morpholinyl)phenyl]ethyl]-4-(trifluoromethyl)-5-thiazolecarboxamide; 2-[1-hydroxy-2-(4-methyl-1-piperazinyl)ethyl]-N-[(1S)-1-[3-(3-pyridinyl)phenyl]ethyl]-4-(trifluoromethyl)-5-thiazolecarboxamide; 2-[1-hydroxy-2-(1-piperidinyl)ethyl]-4-(trifluoromethyl)-N-[1-[3-(trifluoromethyl )phenyl]ethyl]-5-thiazolecarboxamide; 2-[1-hydroxy-2-(1-pyrrolidinyl)ethyl]-N-[1-[3-(trifluoromethoxy)phenyl]ethyl]-4-(trifluoromethyl)-5-thiazolecarboxamide; N-[1-[3-(dimethylamino)phenyl]ethyl]-2-[1-hydroxy-2-(1-pyrrolidinyl)ethyl]-4-(trifluoromethyl)-5-thiazolecarboxamide; 2-[1-hydroxy-2-(1-pyrrolidinyl)ethyl]-N-[(1S)-1-[3-(4-morpholinyl)phenyl]ethyl]-4-(trifluoromethyl)-5-thiazolecarboxamide; 2-[2-[(cyclopropylmethyl)propylamino]-1-hydroxyethyl]-4-(trifluoromethyl)-N-[1-[3-(trifluoromethyl )phenyl]ethyl]-5-thiazolecarboxamide; and 2-[2-(4-acetyl-1-piperazinyl)-1-hydroxyethyl]-4-(trifluoromethyl)-N-[1-[3-(trifluoromethyl)phenyl]ethyl]-5-thiazolecarboxamide.
- 8. A compound of claim 1 where the structure is that of Formula Ie.
- 9. A compound of claim 1 where the structure has the stereochemical configuration of Formula Id.
- 10. A pharmaceutical composition comprising a compound of Formula I and a pharmaceutically acceptable carrier.
- 11. A method for the treatment of disorders responsive to opening of the KCNQ potassium channels in a mammal in need thereof, which comprises administering to said mammal a therapeutically effective amount of the compound of claim 1.
- 12. The method of claim 11 wherein said disorders are acute and chronic pain, migraine, neuropathic pain, bipolar disorders, convulsions, mania, epilepsy, anxiety, depression and neurodegenerative disorders.
- 13. The method of claim 11 wherein said disorder is migraine.
- 14. The method of claim 11 wherein said disorder is bipolar disorders.
- 15. The method of claim 11 wherein said disorder is neuropathic pain.
- 16. The method of claim 11 wherein said disorder is anxiety.
REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit of U.S. provisional application No. 60/435971, filed Dec. 20, 2002.
Provisional Applications (1)
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Number |
Date |
Country |
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60435971 |
Dec 2002 |
US |