Amides of acetic and propionic acids
View Patent ↗The invention relates to novel amides of acetic and propionic acids, methods for production and use thereof for the production of medicaments for the treatment and/or prophylaxis of diseases and for improving perception, concentration, learning ability and memory.
1. A method of treating a cognitive impairment in a patient in need thereof, comprising administering to the patient a compound represented by formula (I)
in which
R 1 is 1-azabicyclo[2.2.2]oct-3-yl optionally substituted by (C 1 -C 6 )-alkyl,
A is methylene or ethylene,
R 2 is benzothiophenyl optionally substituted by radicals selected from the group of halogen, formyl, —CO—NR 4 R 5 , —CO—OR 6 , —NR 7 R 8 , —NR 9 —CO—R 10 , cyano, trifluoromethyl, trifluoromethoxy, nitro, optionally hydroxyl-, amino-, —NH—CO—R 11 — or cyano-substituted (C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkoxy, (C 1 -C 6 )-alkylthio,
in which R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 and R 11 are independently of one another hydrogen, (C 1 -C 6 )-alkyl, phenyl or benzyl,
and
R 3 is hydrogen or (C 1 -C 6 )-alkyl,
or a salt thereof.
2. The method of claim 1 , wherein the cognitive impairment is Alzheimer's disease.
3. The method of claim 2 , wherein
R 1 is 1-azabicyclo[2.2.2]oct-3-yl,
and R 2 and R 3 have the meaning indicated in claim 1 ,
or a salt thereof.
4. The method of claim 3 , wherein
A represents a methylene;
R 2 represents benzotriazolyl optionally substituted by 1 to 3 radicals selected from the group of hydrogen, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, (C 1 -C 4 )-alkyl, (C 1 -C 4 )-alkoxy, (C 1 -C 4 )-alkylthio, and
R 3 represents hydrogen.
5. The method of claim 3 , where
R 1 is 1-azabicyclo[2.2.2]oct-3-yl,
A is methylene,
R 2 is benzothiophenyl where the rings are optionally substituted by 1 to 3 radicals selected from the group of hydrogen, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, (C 1 -C 4 )-alkyl, (C 1 -C 4 )-alkoxy, (C 1 -C 4 )-alkylthio,
and
R 3 is hydrogen,
or a salt thereof.
6. The method of claim 3 , where
R 1 is 1-azabicyclo[2.2.2)oct-3-yl,
A is methylene,
R 2 is benzothiophenyl, where the rings are optionally substituted by 1 to 2 radicals selected from the group of hydrogen, fluorine, chlorine, bromine, nitro
and
R 3 is hydrogen,
or a salt thereof.
7. A method of treating a cognitive impairment in a patient in need thereof, comprising administering to the patient a pharmaceutical composition comprising: i) a compound represented by formula (I)
in which
R 1 is 1-azabicyclo[2.2.2]oct-3-yl optionally substituted by (C 1 -C 6 )-alkyl,
A is methylene or ethylene,
R 2 is benzothiophenyl optionally substituted by radicals selected from the group of halogen, formyl, —CO—NR 4 R 5 , —CO—OR 6 , —NR 7 R 8 , —NR 9 —CO—R 10 , cyano, trifluoromethyl, trifluoromethoxy, nitro, optionally hydroxyl-, amino-, —NH—CO—R 11 — or cyano-substituted (C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkoxy, (C 1 -C 6 )-alkylthio,
in which R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 and R 11 are independently of one another hydrogen, (C 1 -C 6 )-alkyl, phenyl or benzyl,
and
R 3 is hydrogen or (C 1 -C 6 )-alkyl,
or a salt thereof; and
ii) one or more pharmaceutically acceptable carriers or excipients.
8. The method of claim 7 , wherein the cognitive impairment is Alzheimer's disease.
9. The method of claim 8 , wherein
R 1 is 1-azabicyclo[2.2.2]oct-3-yl,
and R 2 and R 3 have the meaning indicated in claim 7 ,
or a salt thereof.
10. The method of claim 9 , wherein
A represents a methylene;
R 2 represents benzotriazolyl optionally substituted by 1 to 3 radicals selected from the group of hydrogen, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, (C 1 -C 4 )-alkyl, (C 1 -C 4 )-alkoxy, (C 1 -C 4 )-alkylthio, and
R 3 represents hydrogen.
11. The method of claim 9 , where
R 1 is 1-azabicyclo[2.2.2]oct-3-yl,
A is methylene,
R 2 is benzothiophenyl, where the rings are optionally substituted by 1 to 3 radicals selected from the group of hydrogen, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, (C 1 -C 4 )-alkyl, (C 1 -C 4 )-alkoxy, (C 1 -C 4 )-alkylthio,
and
R 3 is hydrogen,
or a salt thereof.
12. The method of claim 9 , where
R 1 is 1-azabicyclo[2.2.2)oct-3-yl,
A is methylene,
R 2 is benzothiophenyl, where the rings are optionally substituted by 1 to 2 radicals selected from the group of hydrogen, fluorine, chlorine, bromine, nitro
and
R 3 is hydrogen,
or a salt thereof.