Phenylethynyl and styryl derivatives of imidazole and fused ring heterocycles

1. A method of treating Alzheimer's disease comprising administering to a person in need of such treatment a therapeutically effective amount of a compound of the formula

wherein

R 1 , R 2 , R 3 , R 4 and R 5 are independently selected from the group consisting of —(CH 2 ) n -halogen, lower alkoxy, —(CH 2 ) n —NRR′, —(CH 2 ) n —N(R)—C(O)-lower alkyl, aryl, unsubstituted heteroaryl or heteroaryl substituted by one or more lower alkyl;

R, R′ and R″ are independently selected from the group consisting of hydrogen or lower alkyl;

A is selected from the group consisting of —CH═CH— and —C≡C—; and

B is selected from the group consisting of

wherein

R 6 is selected from the group consisting of lower alkyl, —(CH 2 ) n —C(O)OR and halogen;

R 7 is selected from the group consisting of lower alkyl, —(CH 2 ) n —C(O)OR′, halogen, nitro, unsubstituted heteroaryl and heteroaryl substituted by lower alkyl or cycloalkyl;

R 8 is selected from the group consisting of lower alkyl, —(CH 2 ) n —OH, —(CH 2 ) n —C(O)OR″ and aryl;

R 9 is lower alkyl;

R 10 is selected from the group consisting of lower alkyl and halogen;

R 11 is alkyl;

R 21 is lower alkyl;

R 22 is from the group consisting of lower alkyl and lower alkyl carrying at least one substituent selected from hydroxy and halogen;

R 23 is selected from the group consisting of lower alkyl, lower alkanoyl and nitro;

R 24 , R 25 and R 26 are each independently lower alkyl; and

n is 0, 1, 2, 3, 4, 5 or 6;

or a pharmaceutically acceptable salt thereof.

2. A method of treating Alzheimer's disease comprising administering to a person in need of such treatment a therapeutically effective amount of a compound of the formula

wherein

R 1 , R 2 , R 3 , R 4 and R 5 are independently selected from the group consisting of —(CH 2 ) n -halogen, lower alkoxy, —(CH 2 ) n —NRR′, —(CH 2 ) n —N(R)—C(O)-lower alkyl, aryl, unsubstituted heteroaryl and heteroaryl substituted by one or more lower alkyl;

R, R′ and R″ are independently selected from the group consisting of, hydrogen or lower alkyl; and

B is selected from the group consisting of

wherein

R 6 is selected from the group consisting of lower alkyl, —(CH 2 ) n —C(O)OR and halogen;

R 7 is selected from the group consisting of lower alkyl, —(CH 2 ) n —C(O)OR′, halogen, nitro, unsubstituted heteroaryl and heteroaryl substituted by lower alkyl or cycloalkyl;

R 8 is selected from the group consisting of lower alkyl, —(CH 2 ) n —OH, —(CH 2 ) n —C(O)OR″ and aryl;

R 9 is lower alkyl;

R 10 is selected from the group consisting of lower alkyl and halogen;

R 11 is alkyl;

R 21 is lower alkyl:

R 22 is selected from the group consisting of lower alkyl and lower alkyl carrying at least one substituent selected from hydroxy and halogen;

R 23 is selected from the group consisting of lower alkyl, lower alkanoyl and nitro;

R 24 , R 25 and R 26 are each independently lower alkyl; and

n is 0, 1, 2, 3, 4, 5 or 6;

or a pharmaceutically acceptable salt thereof.

3. A method of treating pain comprising administering to a person in need of such treatment a therapeutically effective amount of a compound of formula

wherein

R 1 , R 2 , R 3 , R 4 and R 5 are independently selected from the group consisting of hydrogen —(CH 2 ) n -halogen, lower alkoxy, —(CH 2 ) n —NRR′, —(CH 2 ) n —N(R)—C(O)-lower alkyl, aryl, unsubstituted heteroaryl and heteroaryl substituted by one or more lower alkyl;

R, R′ and R″ are independently selected from the group consisting of hydrogen and lower alkyl;

A is selected from the group consisting of —CH═CH— and —C≡C—; and

B is selected from the group consisting of

wherein

R 6 is selected from the group consisting of lower alkyl, —(CH 2 ) n —C(O)OR and halogen;

R 7 is selected from the group consisting of lower alkyl, —(CH 2 ) n —C(O)OR′, halogen, nitro, unsubstituted heteroaryl and heteroaryl substituted by lower alkyl or cycloalkyl;

R 8 is selected from the group consisting of lower alkyl, —(CH 2 ) n —OH, —(CH 2 ) n —C(O)OR″ and aryl;

R 9 is lower alkyl;

R 10 is selected from the group consisting of lower alkyl and halogen;

R 11 is alkyl;

R 21 is lower alkyl;

R 22 is selected from the group consisting of lower alkyl and lower alkyl carrying at least one substituent selected from hydroxy and halogen;

R 23 is selected from the group consisting of lower alkyl, lower alkanoyl and nitro;

R 24 , R 25 and R 26 are each independently lower alkyl; and

n is 0, 1, 2, 3, 4, 5 or 6;

or a pharmaceutically acceptable salt thereof.

4. A method of treating anxiety or depression comprising administering to a person in need of such treatment a therapeutically effective amount of a compound of formula

wherein

R 1 , R 2 , R 3 , R 4 and R 5 are independently selected from the group consisting of —(CH 2 ) n -halogen, lower alkoxy, —(CH 2 ) n —NRR′, —(CH 2 ) n —N(R)—C(O)-lower alkyl, aryl, unsubstituted heteroaryl and heteroaryl substituted by one or more lower alkyl;

R, R′ and R″ are independently selected from the group consisting of hydrogen and lower alkyl;

A is selected from the group consisting of —CH═CH— and —C≡C—; and

B is selected from the group consisting of

wherein

R 6 is selected from the group consisting of lower alkyl, —(CH 2 ) n —C(O)OR and halogen;

R 7 is selected from the group consisting of lower alkyl, —(CH 2 ) n —C(O)OR′, halogen, nitro, unsubstituted heteroaryl and heteroaryl substituted by lower alkyl or cycloalkyl;

R 8 is selected from the group consisting of lower alkyl, —(CH 2 ) n —OH, —(CH 2 ) n —C(O)OR″ and aryl;

R 9 is lower alkyl;

R 10 is selected from the group consisting of lower alkyl and halogen;

R 11 is alkyl;

R 21 is lower alkyl;

R 22 is selected from the group consisting of lower alkyl carrying at least one substituent selected from hydroxy and halogen;

R 23 is selected from the group consisting of lower alkyl, lower alkanoyl and nitro;

R 24 , R 25 and R 26 are each independently lower alkyl; and

n is 0, 1, 2, 3, 4, 5 or 6;

or a pharmaceutically acceptable salt thereof.

5. A method of treating pain comprising administering to a person in need of such treatment a therapeutically effective amount of a compound of the formula

wherein

R 1 , R 2 , R 3 , R 4 and R 5 are independently selected from the group consisting of —(CH 2 ) n -halogen, lower alkoxy, —(CH 2 ) n NRR′, —(CH 2 ) n —N(R)—C(O)-lower alkyl, aryl, unsubstituted heteroaryl and heteroaryl substituted by one or more lower alkyl;

R, R′ and R″ are independently selected from the group consisting of hydrogen or lower alkyl; and

B is selected from the group consisting of

wherein

R 6 is selected from the group consisting of lower alkyl, —(CH 2 ) n —C(O)OR and halogen;

R 7 is selected from the group consisting of lower alkyl, —(CH 2 ) n —C(O)OR′, halogen, nitro or unsubstituted heteroaryl and heteroaryl substituted by lower alkyl or cycloalkyl;

R 8 is selected from the group consisting of lower alkyl, —(CH 2 ) n —OH, —(CH 2 ) n —C(O)OR″ and aryl;

R 9 is lower alkyl;

R 10 is selected from the group consisting of lower alkyl and halogen;

R 11 is alkyl;

R 21 is lower alkyl;

R 22 is from the group consisting of lower alkyl and lower alkyl carrying least one substituent selected from hydroxy and halogen;

R 23 is selected from the group consisting of lower alkyl, alkanoyl and nitro;

R 24 , R 25 and R 26 are each independently lower alkyl; and

n is 0, 1, 2, 3, 4, 5 or 6;

or a pharmaceutically acceptable salt thereof.

6. A method of treating anxiety or depression comprising administering to a person in need of such treatment a therapeutically effective amount of a compound of the formula

wherein

R 1 , R 2 , R 3 , R 4 and R 5 are independently selected from the group consisting of —(CH 2 ) n -halogen, lower alkoxy, —(CH 2 ) n —NRR′, —(CH 2 ) n —N(R)—C(O)-lower alkyl, aryl, unsubstituted heteroaryl and heteroaryl substituted by one or more lower alkyl;

R, R′ and R″ are independently selected from the group consisting of hydrogen or lower alkyl; and

B is selected from the group consisting of

wherein

R 6 is selected from the group consisting of lower alkyl, —(CH 2 ) n —C(O)OR and halogen;

R 7 is selected from the group consisting of lower alkyl, —(CH 2 ) n —C(O)OR′, halogen, nitro or unsubstituted heteroaryl and heteroaryl substituted by lower alkyl or cycloalkyl;

R 8 is selected from the group consisting of lower alkyl, —(CH 2 ) n —OH, —(CH 2 ) n —C(O)OR″ and aryl;

R 9 is lower alkyl;

R 10 is selected from the group consisting of lower alkyl and halogen;

R 11 is alkyl;

R 21 is lower alkyl;

R 22 is selected from the group consisting of lower alkyl and lower alkyl carrying at least one substituent selected from hydroxy and halogen;

R 23 is selected from the group consisting of lower alkyl, lower alkanoyl and nitro;

R 24 , R 25 and R 26 are each independently lower alkyl; and

n is 0, 1, 2, 3, 4, 5 or 6;

or a pharmaceutically acceptable salt thereof.

7. A method of treating Alzheimer's disease comprising administering to the person in need of such treatment a therapeutically effective amount of a compound of the compound of formula

wherein

R 1 , R 2 , R 3 , R 4 and R 5 are independently selected from the group consisting of —(CH 2 ) n -halogen, lower alkoxy, —(CH 2 ) n —NRR′, —(CH 2 ) n —N(R)—C(O)-lower alkyl, aryl, unsubstituted heteroaryl and heteroaryl substituted by one or more lower alkyl residues;

R, R′ and R″ are independently selected from the group consisting of hydrogen and lower alkyl; and

B is selected from the group consisting of

wherein

R 6 is selected from the group consisting of lower alkyl, —(CH 2 ) n —C(O)OR and halogen;

R 7 is selected from the group consisting of lower alkyl, —(CH 2 ) n —C(O)OR′, halogen, nitro, and unsubstituted heteroaryl and heteroaryl substituted by lower alkyl or cycloalkyl;

R 8 is selected from the group consisting of lower alkyl, —(CH 2 ) n —OH, —(CH 2 ) n —C(O)OR″ and aryl;

R 9 is lower alkyl;

R 10 is selected from the group consisting of lower alkyl and halogen;

R 11 is alkyl;

R 21 is lower alkyl;

R 22 is selected from the group consisting of lower alkyl and lower alkyl carrying at least one substituent selected from hydroxy and halogen;

R 23 is selected from the group consisting of lower alkyl, lower alkanoyl and nitro;

R 24 , R 25 and R 26 are each independently lower alkyl; and

n is 0, 1, 2, 3, 4, 5 or 6;

or a pharmaceutically acceptable salt thereof.

8. A method of treating pain comprising administering to a person in need of such treatment a therapeutically effective amount of a compound of formula

wherein

R 1 , R 2 , R 3 , R 4 and R 5 are independently selected from the group consisting of —(CH 2 ) n -halogen, lower alkoxy, —(CH 2 ) n —NRR′, —(CH 2 ) n —N(R)—C(O)-lower alkyl, aryl, unsubstituted heteroaryl and heteroaryl substituted by one or more lower alkyl;

R, R′ and R″ are independently selected from the group consisting of hydrogen and lower alkyl; and

B is selected from the group consisting of

wherein

R 6 is selected from the group consisting of lower alkyl, —(CH 2 ) n —C(O)OR and halogen;

R 7 is selected from the group consisting of lower alkyl, —(CH 2 ) n —C(O)OR′, halogen, nitro, unsubstituted heteroaryl and heteroaryl substituted by lower alkyl or cycloalkyl;

R 8 is selected from the group consisting of lower alkyl, —(CH 2 ) n —OH, —(CH 2 ) n —C(O)OR″ and aryl;

R 9 is lower alkyl;

R 10 is selected from the group consisting of lower alkyl and halogen;

R 11 is alkyl;

R 21 is lower alkyl;

R 22 is selected from the group consisting of lower alkyl and lower alkyl carrying at least one substituent selected from hydroxy and halogen;

R 23 is selected from the group consisting of lower alkyl, lower alkanoyl and nitro;

R 24 , R 25 and R 26 are each independently lower alkyl; and

n is 0, 1, 2, 3, 4, 5 or 6;

or a pharmaceutically acceptable salt thereof.

9. A method of treating anxiety or depression comprising administering to a person in need of such treatment a therapeutically effective amount of a compound of formula

wherein

R 1 , R 2 , R 3 , R 4 and R 5 are independently selected from the group consisting of —(CH 2 ) n -halogen, lower alkoxy, —(CH 2 ) n —NRR′, —(CH 2 ) n —N(R)—C(O)-lower alkyl, aryl, unsubstituted heteroaryl and heteroaryl substituted by one or more lower alkyl;

R, R′ and R″ are independently selected from the group consisting of hydrogen and lower alkyl; and

B is selected from the group consisting of

wherein

R 6 is selected from the group consisting of lower alkyl, —(CH 2 ) n —C(O)OR and halogen;

R 7 is selected from the group consisting of lower alkyl, —(CH 2 ) n —C(O)OR′, halogen, nitro, unsubstituted heteroaryl and heteroaryl substituted by lower alkyl or cycloalkyl;

R 8 is selected from the group consisting of lower alkyl, —(CH 2 ) n —OH, —(CH 2 ) n —C(O)OR″ and aryl;

R 9 is lower alkyl;

R 10 is selected from the group consisting of lower alkyl and halogen;

R 11 is alkyl;

R 21 is lower alkyl;

R 22 is from the group consisting of lower alkyl and lower alkyl carrying at least one substituent selected from hydroxy and halogen:

R 23 is selected from the group consisting of lower alkyl, lower alkanoyl and nitro;

R 24 , R 25 and R 26 are each independently lower alkyl; and

n is 0, 1, 2, 3, 4, 5 or 6;

or a pharmaceutically acceptable salt thereof.

10. A method of treating pain comprising administering to a person in need of such treatment a compound of formula

wherein

R 1 , R 2 , R 3 , R 4 and R 5 are independently selected from the group consisting of —(CH 2 ) n -halogen, lower alkoxy, —(CH 2 ) n —NRR′, —(CH 2 ) n —N(R)—C(O)-lower alkyl, aryl, unsubstituted heteroaryl and heteroaryl substituted by at least one lower alkyl;

R, R′ and R″ are independently selected from the group consisting of hydrogen and lower alkyl;

R 6 is selected from the group consisting of lower alkyl, —(CH 2 ) n —C(O)OR and halogen;

R 7 is selected from the group consisting of lower alkyl, —(CH 2 ) n —C(O)OR′, halogen, nitro, unsubstituted heteroaryl and heteroaryl substituted by lower alkyl or cycloalkyl; and

R 8 is selected from the group consisting of lower alkyl, —(CH 2 ) n —OH, —(CH 2 ) n —C(O)OR″ and aryl;

or a pharmaceutically acceptable salt thereof.

11. A method of treating anxiety or depression comprising administering to a person in need of such treatment a compound of formula

wherein

R 1 , R 2 , R 3 , R 4 and R 5 are independently selected from the group consisting of —(CH 2 ) n -halogen, lower alkoxy, —(CH 2 ) n —NRR′, —(CH 2 ) n —N(R)—C(O)-lower alkyl, aryl, unsubstituted heteroaryl and heteroaryl substituted by at least one lower alkyl;

R, R′ and R″ are independently selected from the group consisting of hydrogen and lower alkyl;

R 6 is selected from the group consisting of lower alkyl, —(CH 2 ) n —C(O)OR and halogen;

R 7 is selected from the group consisting of lower alkyl, —(CH 2 ) n —C(O)OR′, halogen, nitro, unsubstituted heteroaryl and heteroaryl substituted by lower alkyl or cycloalkyl; and

R 8 is selected from the group consisting of lower alkyl, —(CH 2 ) n —OH, —(CH 2 ) n —C(O)OR″ and aryl;

or a pharmaceutically acceptable salt thereof.

12. A method of treating pain comprising administering to a person in need of such treatment a therapeutically effective amount of a compound of formula

wherein

R 1 , R 2 , R 3 , R 4 and R 5 are independently selected from the group consisting of —(CH 2 ) n -halogen, lower alkoxy, —(CH 2 ) n —NRR′, —(CH 2 ) n —N(R)—C(O)-lower alkyl, aryl, unsubstituted heteroaryl and heteroaryl substituted by at least one lower alkyl residues;

R and R′ are selected from the group consisting of hydrogen or lower alkyl;

R 9 is lower alkyl;

R 10 is halogen; and

R 11 is or a pharmaceutically acceptable salt thereof.

13. A method of treating anxiety or depression comprising administering to a person in need of such treatment a therapeutically effective amount of a compound of formula

wherein

R 1 , R 2 , R 3 , R 4 and R 5 are independently selected from the group consisting of —(CH 2 ) n -halogen, lower alkoxy, —(CH 2 ) n —NRR′, —(CH 2 ) n —N(R)—C(O)-lower alkyl, aryl, unsubstituted heteroaryl and heteroaryl substituted by at least one lower alkyl residues;

R and R′ are selected from the group consisting of hydrogen or lower alkyl;

R 9 is lower alkyl;

R 10 is halogen; and

R 11 is alkyl;

or a pharmaceutically acceptable salt thereof.

14. A method of treating Alzheimer's disease comprising administering to a person in need of such treatment a compound of formula

wherein

R 1 , R 2 , R 3 , R 4 and R 5 are independently selected from the group consisting of —(CH 2 ) n -halogen, lower alkoxy, —(CH 2 ) n —NRR′, —(CH 2 ) n —N(R)—C(O)-lower alkyl, aryl, unsubstituted heteroaryl and heteroaryl substituted by at least one lower alkyl;

R, R′ and R″ are independently selected from the group consisting of hydrogen and lower alkyl;

R 6 is selected from the group consisting of lower alkyl, —(CH 2 ) n —C(O)OR and halogen;

R 7 is selected from the group consisting of lower alkyl, —(CH 2 ) n —C(O)OR′, halogen, nitro, unsubstituted heteroaryl and heteroaryl substituted by lower alkyl or cycloalkyl; and

R 8 is selected from the group consisting of lower alkyl, —(CH 2 ) n —OH, —(CH 2 ) n —C(O)OR″ and aryl;

or a pharmaceutically acceptable salt thereof.

15. A method of treating Alzheimer's disease comprising administering to a person in need of such treatment a therapeutically effective amount of a compound of formula

wherein

R 1 , R 2 , R 3 , R 4 and R 5 are independently selected from the group consisting of —(CH 2 ) n -halogen, lower alkoxy, —(CH 2 ) n —NRR′, —(CH 2 ) n —N(R)—C(O)-lower alkyl, aryl, unsubstituted heteroaryl and heteroaryl substituted by at least one lower alkyl residues;

R and R′ are selected from the group consisting of hydrogen or lower alkyl;

R 9 is lower alkyl;

R 10 is halogen; and

R 11 is or a pharmaceutically acceptable salt thereof.