Use of benzimidazole-proline derivatives
The present invention relates to compounds of the formula (I) wherein Ar 1 and Ar 2 are as described in the description and to their use as pharmaceuticals for the treatment of sundown syndrome. The invention also relates to the preparation of such compounds and of pharmaceutically acceptable salts thereof.
1. A method of treatment of sundown syndrome, comprising administering to a patient in need thereof a compound of the formula (I):
in free or pharmaceutically acceptable salt form,
wherein the compound of formula (I) is in absolute configuration (S);
Ar 1 represents
and Ar 2 represents
2. The method according to claim 1 , wherein the compound is:
[(S)-2-(5-Chloro-4-methyl-1H-benzoimidazol-2-yl)-2-methyl-pyrrolidin-1-yl]-(5-methyl-2-pyrimidin-2-yl-phenyl)-methanone;
[(S)-2-(5-Bromo-7-methyl-1H-benzoimidazol-2-yl)-2-methyl-pyrrolidin-1-yl]-(5-methyl-2-[1,2,3]triazol-2-yl-phenyl)-methanone;
[(S)-2-(5-Bromo-7-methyl-1H-benzoimidazol-2-yl)-2-methyl-pyrrolidin-1-yl]-(5-methyl-2-pyrimidin-2-yl-phenyl)-methanone;
[(S)-2-(5-Chloro-4-methyl-1H-benzoimidazol-2-yl)-2-methyl-pyrrolidin-1-yl]-(5-methoxy-2-[1,2,3]triazol-2-yl-phenyl)-methanone;
[(S)-2-(6-Bromo-5-fluoro-1H-benzoimidazol-2-yl)-2-methyl-pyrrolidin-1-yl]-(5-methyl-2-[1,2,3]triazol-2-yl-phenyl)-methanone;
[(S)-2-(5,6-Dimethoxy-1H-benzoimidazol-2-yl)-2-methyl-pyrrolidin-1-yl]-(5-methyl-2-[1,2,3]triazol-2-yl-phenyl)-methanone;
[(S)-2-(5,6-Dimethoxy-1H-benzoimidazol-2-yl)-2-methyl-pyrrolidin-1-yl]-(5-methyl-2-pyrazol-1-yl-phenyl)-methanone;
[(S)-2-(5,6-Dimethoxy-1H-benzoimidazol-2-yl)-2-methyl-pyrrolidin-1-yl]-(5-methoxy-2-[1,2,3]triazol-2-yl-phenyl)-methanone;
[(S)-2-(6-Chloro-5-trifluoromethyl-1H-benzoimidazol-2-yl)-2-methyl-pyrrolidin-1-yl]-(5-methyl-2-[1,2,3]triazol-2-yl-phenyl)-methanone;
(5-Methyl-2-[1,2,3]triazol-2-yl-phenyl)-[(S)-2-methyl-2-(5-trifluoromethyl-1H-benzoimidazol-2-yl)-pyrrolidin-1-yl]-methanone; or
(5-Methyl-2-[1,2,3]triazol-2-yl-phenyl)-[(S)-2-methyl-2-(5-trifluoromethoxy-1H-benzoimidazol-2-yl)-pyrrolidin-1-yl]-methanone,
in free or pharmaceutically acceptable salt form.
3. The method according to claim 1 , wherein the compound is:
[(S)-2-(5-Bromo-7-methyl-1H-benzoimidazol-2-yl)-2-methyl-pyrrolidin-1-yl]-(5-methyl-2-pyrimidin-2-yl-phenyl)-methanone,
in free or pharmaceutically acceptable salt form.
4. The method according to claim 1 , wherein the compound is:
[(S)-2-(5-Chloro-4-methyl-1H-benzoimidazol-2-yl)-2-methyl-pyrrolidin-1-yl]-(5-methoxy-2-[1,2,3]triazol-2-yl-phenyl)-methanone,
in free or pharmaceutically acceptable salt form.
5. The method according to claim 1 , wherein said patient has a dementia of Alzheimer's type.
6. The method of claim 5 , wherein the patient has middle stage Alzheimer dementia.
7. The method of claim 5 , wherein the sundown syndrome is afternoon sundown syndrome.
8. The method according to claim 4 , wherein said patient has a dementia of Alzheimer's type.
9. The method of claim 8 , wherein the patient has middle stage Alzheimer dementia.
10. The method of claim 8 , wherein the sundown syndrome is afternoon sundown syndrome.
11. The method of claim 4 , wherein what is treated is increased agitation.
12. The method of claim 8 , wherein what is treated is increased agitation.
13. The method of claim 9 , wherein what is treated is increased agitation.
14. The method of claim 10 , wherein what is treated is increased agitation.