Amides of acetic and propionic acids

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):

wherein:

R 1 represents a 1-azabicyclo[m.n.p]alkyl radical having 7 to 11 ring atoms, wherein the bicycloalkyl radical is optionally substituted by (C 1 -C 6 )-alkyl;

m represents a value of 2 or 3;

n represents a value of 2 or 3;

p represents a value of 1, 2, or 3;

A represents a methylene or an ethylene;

R 2 represents a 8- to 10-membered ring comprising heteroaryl, naphthyl, or azulenyl, wherein the ring is optionally substituted by a radical 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, wherein the R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 and R 11 independently represent hydrogen, (C 1 -C 6 )-alkyl, phenyl, or benzyl; and

R 3 represents a hydrogen or (C 1 -C 6 )-alkyl; or

a physiological acceptable salt, enantiomer, or diastereomer thereof.

2. The method of claim 1 , wherein the cognitive impairment is Alzheimer's disease.

3. The method of claim 2 , wherein R 1 represents 1-azabicyclo[2.2.2]oct-3-yl.

4. The method of claim 3 , wherein:

A represents a methylene;

R 2 represents indolyl, benzoimidazolyl, benzotriazolyl, benzothiophenyl, benzofuranyl, quinolinyl, isoquinolyl, benzopyrazinyl, benzoprimidinyl, benzopyridizanyl or naphthyl, wherein 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, and (C 1 -C 4 )-alkylthio; and

R 3 represents hydrogen.

5. The method of claim 3 , wherein:

A represents a methylene;

R 2 represents benzotriazolyl, benzothiophenyl, quinolinyl, benzopyrazinyl, or naphthyl, wherein the ring is 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.

6. The method of claim 3 , wherein:

A represents a methylene;

R 2 represents benzothiophenyl, quinolinyl, or naphthyl, wherein the ring is optionally substituted by 1 to 2 radicals selected from the group of hydrogen, fluorine, chlorine, bromine, nitro; and

R 3 represents hydrogen.

7. The method of claim 1 , wherein the compound represented by Formula (I) is selected from the group consisting of: 2-(1-Azabicyclo[2.2.2]oct-3-yl)-N-(7-bromo-1-benzothien-2-yl)acetamide hydrochloride, 2-(3-Azabicyclo[2.2.2]oct-3-yl)-N-(6-bromo-1-benzothien-2-yl)acetamide hydrochloride, 2-(1-Azabicyclo[2.2.2]oct-3-yl)-N-(7-quinolinyl)acetamide hydrochloride, 2-(1-Azabicyclo[2.2.2]oct-3-yl)-N-(2-naphthyl)acetamide hydrochloride, and 2-(1-Azabicyclo[2.2.2]oct-3-yl)-N-(8-nitro-2-naphthyl)acetamide hydrochloride.

8. The method of claim 7 , wherein the cognitive impairment is Alzheimer's disease.

9. 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):

wherein:

R 1 represents a 1-azabicyclo[m.n.p]alkyl radical having 7 to 11 ring atoms, wherein the bicycloalkyl radical is optionally substituted by (C 1 -C 6 )-alkyl;

m represents a value of 2 or 3;

n represents a value of 2 or 3;

p represents a value of 1, 2, or 3;

A represents a methylene or an ethylene;

R 2 represents a 8- to 10-membered ring comprising heteroaryl, naphthyl, or azulenyl, wherein the ring is optionally substituted by a radical 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, wherein the R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 and R 11 independently represent hydrogen, (C 1 -C 6 )-alkyl, phenyl, or benzyl; and

R 3 represents a hydrogen or (C 1 -C 6 )-alkyl; or

a physiological acceptable salt, enantiomer, or diastereomer thereof;

and ii) one or more pharmaceutically acceptable carriers or excipients.

10. The method of claim 9 , wherein the cognitive impairment is Alzheimer's disease.

11. The method of claim 10 , wherein R 1 represents 1-azabicyclo[2.2.2]oct-3-yl.

12. The method of claim 11 , wherein:

A represents a methylene;

R 2 represents indolyl, benzoimidazolyl, benzotriazolyl, benzothiophenyl, benzofuranyl, quinolinyl, isoquinolyl, benzopyrazinyl, benzoprimidinyl, benzopyridizanyl or naphthyl, wherein 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, and (C 1 -C 4 )-alkylthio; and

R 3 represents hydrogen.

13. The method of claim 11 , wherein:

A represents a methylene;

R 2 represents benzotriazolyl, benzothiophenyl, quinolinyl, benzopyrazinyl, or naphthyl, wherein the ring is 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.

14. The method of claim 11 , wherein:

A represents a methylene,

R 2 represents benzothiophenyl, quinolinyl, or naphthyl, wherein the ring is optionally substituted by 1 to 2 radicals selected from the group of hydrogen, fluorine, chlorine, bromine, nitro; and

R 3 represents hydrogen.

15. The method of claim 11 , wherein the compound represented by Formula (I) is selected from the group consisting of: 2-(1-Azabicyclo[2.2.2]oct-3-yl)-N-(7-bromo-1-benzothien-2-yl)acetamide hydrochloride, 2-(3-Azabicyclo[2.2.2]oct-3-yl)-N-(6-bromo-1-benzothien-2-yl)acetamide hydrochloride, 2-(1-Azabicyclo[2.2.2]oct-3-yl)-N-(7-quinolinyl)acetamide hydrochloride, 2-(1-Azabicyclo[2.2.2]oct-3-yl)-N-(2-naphthyl)acetamide hydrochloride, and 2-(1-Azabicyclo[2.2.2]oct-3-yl)-N-(8-nitro-2-naphthyl)acetamide hydrochloride.

16. The method of claim 9 , wherein the cognitive impairment is Alzheimer's disease.