Substituted [1,2,4]triazolo[1,5-
This invention relates to novel substituted [1,2,4]triazolo[1,5-a]pyrimidines and their use as modulators of potassium channels. In other aspects the invention relates to the use of these compounds, in a method for therapy and to pharmaceutical compositions comprising the compounds of the invention.
1. A compound of the formula (I)
a stereoisomer or a mixture of its stereoisomers, or a pharmaceutically acceptable addition salt thereof, wherein
R 1 and R 2 , independently of each other, are hydrogen, halogen, C 1-6 -alkyl, C 3-7 -cycloalkyl or C 1-6 -alkoxy;
R′ and R″, independently of each other, are hydrogen or C 1-6 -alkyl, and
R is hydrogen or C 1-6 -alkyl;
with the proviso that the compound is not N-{7-[1-(Phenoxy)ethyl]-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl}-N′-methoxy-formamidine.
2. A compound of the formula (I)
a stereoisomer or a mixture of its stereoisomers, or a pharmaceutically acceptable addition salt thereof, wherein
R 1 is hydrogen, halogen, C 1-6 -alkyl, C 3-7 -cycloalkyl or C 1-6 -alkoxy,
R 2 is halogen, C 1-6 -alkyl, C 3-7 -cycloalkyl or C 1-6 -alkoxy;
R′ and R″, independently of each other, are hydrogen or C 1-6 -alkyl, and R is hydrogen or C 1-6 -alkyl.
3. A compound of the formula (I),
a stereoisomer or a mixture of its stereoisomers, or a pharmaceutically acceptable addition salt thereof, wherein
R 1 and R 2 , independently of each other, are hydrogen, halogen, C 1-6 -alkyl, C 3-7 -cycloalkyl or C 1-6 -alkoxy;
R′ and R″, independently of each other, are hydrogen or C 1-6 -alkyl, and
R is hydrogen or C 2-6 -alkyl.
4. A compound of the formula (I)
a stereoisomer or a mixture of its stereoisomers, or a pharmaceutically acceptable addition salt thereof, wherein
R 1 and R 2 , independently of each other, are hydrogen, halogen, C 1-6 -alkyl, C 3-7 -cycloalkyl or C 1-6 -alkoxy;
R′ and R″, independently of each other, are hydrogen or C 2-6 -alkyl, or R′ and R″ both are hydrogen; or R′ and R″ both are methyl; and
R is hydrogen or C 1-6 -alkyl.
5. The compound according to claim 1 , which is:
N-{7-[1-(2-Methylphenoxy)ethyl]-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl}-N′-methoxy-formamidine;
or a stereoisomer or a mixture of its stereoisomers, or a pharmaceutically acceptable addition salt thereof.
6. A pharmaceutical composition comprising a therapeutically effective amount of the compound of the formula (I)
a stereoisomer or a mixture of its stereoisomers, or a pharmaceutically acceptable addition salt thereof, wherein
R 1 and R 2 , independently of each other, are hydrogen, halogen, C 1-6 -alkyl, C 3-7 -cycloalkyl or C 1-6 -alkoxy;
R′ and R″, independently of each other, are hydrogen or C 1-6 -alkyl, and
R is hydrogen or C 1-6 -alkyl.
7. The pharmaceutical composition according to claim 6 , wherein the compound is:
N-{7-[1-(Phenoxy)ethyl]-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl}-N′-methoxy-formamidine; or
N-{7-[1-(2-Methylphenoxy)ethyl]-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl}-N′-methoxy-formamidine;
or a stereoisomer or a mixture of its stereoisomers, or a pharmaceutically acceptable addition salt thereof.
8. A method of modulation of SK channels, which method comprises the step of contacting a cell with a compound of the formula (I)
a stereoisomer or a mixture of its stereoisomers, or a pharmaceutically acceptable addition salt thereof, wherein
R 1 and R 2 , independently of each other, are hydrogen, halogen, C 1-6 -alkyl, C 3-7 -cycloalkyl or C 1-6 -alkoxy;
R′ and R″, independently of each other, are hydrogen or C 1-6 -alkyl, and
R is hydrogen or C 1-6 -alkyl.
9. The method according to claim 8 , wherein the compound is:
N-{7-[1-(Phenoxy)ethyl]-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl}-N′-methoxy-formamidine, or
N-{7-[1-(2-Methylphenoxy)ethyl]-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl}-N′-methoxy-formamidine;
or a stereoisomer or a mixture of its stereoisomers, or a pharmaceutically acceptable addition salt thereof.
10. The method according to claim 8 , wherein the cell is contacted with the compound, its stereoisomer or a mixture of its stereoisomers, or a pharmaceutically acceptable addition salt thereof, in vitro.
11. A method of treatment or alleviation of a disease or a disorder or a condition of a human, which method comprises the step of administering to said human in need thereof, a therapeutically effective amount of the compound of claim 6 ,
wherein the disease or disorder is psychosis, schizophrenia, bipolar disorder, depression, epilepsy, Parkinson's disease or pain.
12. A method of treatment or alleviation of a disease or a disorder or a condition of a human, which method comprises the step of administering to said human in need thereof, a therapeutically effective amount of the compound of claim 6 ,
wherein the disease or disorder is epilepsy, seizures, stroke or traumatic brain injury.
13. A method of treatment or alleviation of a disease or a disorder or a condition of a human, which method comprises the step of administering to said human in need thereof, a therapeutically effective amount of the compound of claim 6 ,
wherein the disease or disorder is angina pectoris, arrhythmia, asthma or chronic obstructive pulmonary disease.