2-oxo-1,3-oxazolidinyl imidazothiadiazole derivatives
The present invention relates to 2-oxo-1,3-oxazolidinyl imidazothiadiazole derivatives, processes for preparing them, pharmaceutical compositions containing them and their use as pharmaceuticals.
1. A compound having formula (I), or a geometrical isomer, enantiomer, diastereomer, isotope or mixture thereof, or a pharmaceutically acceptable salt thereof,
wherein
R 1 is a C 1-4 alkyl optionally substituted by one or more halogen substituents;
R 2 is a halogen atom, or a C 1-4 alkyl optionally substituted by one or more halogen atoms;
R 3 is a C 1-4 alkyl substituted by an alkoxy substituent.
2. A compound according to claim 1 , wherein R 1 is an i-butyl, a n-propyl, a 2,2-difluoropropyl, a 2-chloro-2,2-difluoroethyl, a 2,2-difluoroethyl, a 2,2,2-trifluoroethyl or a 2-fluoroethyl moiety.
3. A compound according to claim 1 , wherein R 1 is n-propyl, a 2,2-difluoropropyl, or a 2,2,2-trifluoroethyl moiety.
4. A compound according to claim 1 , wherein R 2 is a chlorine atom, a difluoromethyl moiety, or a trifluoromethyl moiety.
5. A compound according to claim 1 , wherein R 2 is a difluoromethyl moiety or a trifluoromethyl moiety.
6. A compound according to claim 1 , wherein R 3 is a methoxymethyl, a [( 2 H 3 )methyloxy]methyl, a methoxy( 2 H 2 )methyl, or a [( 2 H 3 )methyloxy]( 2 H 2 )methyl moiety.
7. A compound according to claim 1 , wherein
R 1 is a n-propyl, a 2,2-difluoropropyl or a 2,2,2-trifluoroethyl moiety;
R 2 is a difluoromethyl or a trifluoromethyl moiety;
R 3 is a methoxymethyl, a [( 2 H 3 )methoxy]methyl, a [( 2 H 3 )methoxy] ( 2 H 2 ) methyl or a methoxy( 2 H 2 ) methyl moiety.
8. A compound according to claim 1 which is:
(+)-3-[[2-(methoxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl]-5-propyl-oxazolidin-2-one;
(−)-3-[[2-(methoxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl]-5-propyl-oxazolidin-2-one;
(+)-3-[[6-(difluoromethyl)-2-(methoxymethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl]-5-propyl-oxazolidin-2-one;
(−)-3-[[6-(difluoromethyl)-2-(methoxymethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl]-5-propyl-oxazolidin-2-one;
(+)-3-[[2-[dideuterio(methoxy)methyl]-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl]-5-propyl-oxazolidin-2-one;
(−)-3-[[2-[dideuterio(methoxy)methyl]-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl]-5-propyl-oxazolidin-2-one;
(+)-3-[[2-[dideuterio(trideuteriomethoxy)methyl]-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl]-5-propyl-oxazolidin-2-one;
(−)-3-[[2-[dideuterio(trideuteriomethoxy)methyl]-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl]-5-propyl-oxazolidin-2-one;
(+)-3-[[2-(methoxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl]-5-(2,2,2-trifluoroethyl)oxazolidin-2-one;
(−)-3-[[2-(methoxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl]-5-(2,2,2-trifluoroethyl)oxazolidin-2-one;
(+)-3-[[6-(difluoromethyl)-2-(methoxymethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl]-5-(2,2,2-trifluoroethyl)oxazolidin-2-one;
(−)-3-[[6-(difluoromethyl)-2-(methoxymethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl]-5-(2,2,2-trifluoroethyl)oxazolidin-2-one;
(−)-5-(2,2-difluoropropyl)-3-[[2-(methoxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl]oxazolidin-2-one;
(+)-5-(2,2-difluoropropyl)-3-[[2-(methoxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl]oxazolidin-2-one;
3-[[6-(difluoromethyl)-2-(methoxymethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl]-5-(2,2-difluoropropyl)oxazolidin-2-one, enantiomer 1;
3-[[6-(difluoromethyl)-2-(methoxymethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl]-5-(2,2-difluoropropyl)oxazolidin-2-one, enantiomer 2.
9. A pharmaceutical composition comprising an effective amount of a compound according to claim 1 in combination with a pharmaceutically acceptable diluent or carrier.
10. A method for the treatment of epilepsy, epileptogenesis, seizure disorders, or convulsions, comprising administering to a patient in need thereof an effective amount of a compound or salt according to claim 1 .
11. A method according to claim 9 , wherein the treatment is for refractory seizures.
12. A compound according to claim 2 , wherein R 2 is a chlorine atom, a difluoromethyl moiety, or a trifluoromethyl moiety.
13. A compound according to claim 3 , wherein R 2 is a difluoromethyl moiety or a trifluoromethyl moiety.
14. A compound according to claim 2 , wherein R 3 is a methoxymethyl, a [( 2 H 3 )methyloxy]methyl, a methoxy( 2 H 2 )methyl, or a [( 2 H 3 )methyloxy]( 2 H 2 )methyl moiety.
15. A compound according to claim 4 , wherein R 3 is a methoxymethyl, a [( 2 H 3 )methyloxy]methyl, a methoxy( 2 H 2 )methyl, or a [( 2 H 3 )methyloxy]( 2 H 2 )methyl moiety.