2-oxo-1-imidazolidinyl imidazothiadiazole derivatives
View Patent ↗The present invention relates to 2-oxo-1-imidazolidinyl imidazothiadiazole derivatives, processes for preparing them, pharmaceutical compositions containing them and their use as pharmaceuticals.
1. A compound of formula (I), a geometrical isomer, an enantiomer, a diastereomer, or mixtures thereof, or a pharmaceutically acceptable salt thereof,
wherein
R 1 is a C 1-4 alkyl or a C 2-4 alkenyl optionally substituted by one or more halogen substituents;
R 2 is either a halogen or a C 1-4 alkyl containing at least one halogen substituent;
R 3 is a C 1-4 alkyl containing at least one hydroxy or an alkoxy substituent;
R 4 is either hydrogen or a methyl group.
2. A compound of formula (I-A) according to claim 1 , wherein
wherein
R 1 is a C 1-4 alkyl optionally substituted by one or more halogen substituents;
R 2 is either a halogen or a C 1-4 alkyl containing at least one halogen substituent;
R 3 is a C 1-4 alkyl containing at least one hydroxy or an alkoxy substituent.
3. A compound of formula (IB) according to claim 1 , wherein
wherein
R 1 is a C 1-4 alkyl or a C 2-4 alkenyl optionally substituted by one or more halogen substituents;
R 2 is either a halogen or a C 1-4 alkyl containing at least one halogen substituent;
R 3 is a C 1-4 alkyl containing at least one hydroxy (OH) or an alkoxy substituent.
4. A compound according to claim 1 , wherein R 1 is an i-butyl, n-propyl, 2,2-difluoropropyl, a 2-chloro-2,2-difluoroethyl, a 2,2-difluoroethyl, a 2,2,2-trifluoroethyl, a 3,3,3-trifluoropropyl, a 2-fluoroethyl or a 2,2-difluoroethenyl moiety.
5. A compound according to claim 1 , wherein R 1 is an i-butyl, n-propyl, 2,2-difluoropropyl, a 2-chloro-2,2-difluoroethyl, a 2,2-difluoroethyl, a 2,2,2-trifluoroethyl, a 3,3,3-trifluoropropyl or a 2-fluoroethyl moiety.
6. A compound according to claim 1 , wherein R 2 is a chloro, a difluoromethyl or a trifluoromethyl moiety.
7. A compound according to claim 1 , wherein R 3 is either a hydroxymethyl, a methoxymethyl, a [( 2 H 3 )methyloxy]methyl, a methoxy( 2 H 2 ) methyl, a (2,2,2-trifluoroethoxy)methyl or a 2-methoxyethyl moiety.
8. A compound according to claim 1 , wherein
R 1 is a i-butyl, n-propyl, a 2-chloro-2,2-difluoroethyl, a 2,2,2-trifluoroethyl or a 3,3,3-trifluoropropyl moiety;
R 2 is a chloro or a trifluoromethyl moiety;
R 3 is a methoxymethyl moiety.
9. A compound according to claim 1 selected from the group consisting of:
1-{[2-(methoxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}-4-(2-methylpropyl)imidazolidin-2-one;
(−)-1-{[2-(methoxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}-4-(2-methylpropyl)imidazolidin-2-one;
(+)-1-{[2-(methoxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}-4-(2-methylpropyl)imidazolidin-2-one;
1-{[2-(methoxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}-4-propylimidazolidin-2-one;
(−)-1-{[2-(methoxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}-4-propylimidazolidin-2-one;
(+)-1-{[2-(methoxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}-4-propylimidazolidin-2-one;
1-{[2-(methoxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}-4-(3,3,3-trifluoropropyl)imidazolidin-2-one;
(−)-1-{[2-(methoxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}-4-(3,3,3-trifluoropropyl)imidazolidin-2-one;
(+)-1-{[2-(methoxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}-4-(3,3,3-trifluoropropyl)imidazolidin-2-one;
1-{[6-chloro-2-(methoxymethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}- 4 -(3,3,3-trifluoropropyl)imidazolidin-2-one;
(−)-1-{[6-chloro-2-(methoxymethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}-4-(3,3,3-trifluoropropyl)imidazolidin-2-one;
(+)-1-{[6-chloro-2-(methoxymethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}-4-(3,3,3-trifluoropropyl)imidazolidin-2-one;
1-{[2-(methoxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}-4-(2,2,2-trifluoroethyl)imidazolidin-2-one;
(+)-1-{[2-(methoxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}-4-(2,2,2-trifluoroethyl)imidazolidin-2-one;
(−)-1-{[2-(methoxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}-4-(2,2,2-trifluoroethyl)imidazolidin-2-one;
4-(2-chloro-2,2-difluoroethyl)-1-{[2-(methoxymethyl)-6-(trifluoromethyl)-imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}imidazolidin-2-one;
(+)-4-(2-chloro-2,2-difluoroethyl)-1-{[2-(methoxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}imidazolidin-2-one;
(−)-4-(2-chloro-2,2-difluoroethyl)-1-{[2-(methoxymethyl)-6-(trifluoro-methyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}imidazolidin-2-one;
4-(2,2-difluoroethenyl)-1-{[2-(methoxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}imidazolidin-2-one;
4-(2-chloro-2,2-difluoroethyl)-1-{[2-(hydroxymethyl)-6-(trifluoromethyl)-imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}imidazolidin-2-one;
1-{[2-(hydroxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}-4-(2,2,2-trifluoroethyl)imidazolidin-2-one;
(+)-4-(2-chloro-2,2-difluoroethyl)-1-{[2-(methoxymethyl)-6-(trifluoromethyl)-imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}-3-methylimidazolidin-2-one; and
(−)-4-(2-chloro-2,2-difluoroethyl)-1-{[2-(methoxymethyl)-6-(trifluoromethyl)-imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}-3-methylimidazolidin-2-one.
10. A pharmaceutical composition comprising an effective amount of a compound according to claim 1 in combination with a pharmaceutically acceptable diluent or carrier.