Ether substituted imidazopyridines

1. A compound of the Formula (I-2):

wherein:

X is —CH(R 5 )—, —CH(R 5 )-alkylene-, —CH(R 5 )-alkenylene-, or CH(R 5 )-alkylene-Y-alkylene-;

R 1-2 is selected from the group consisting of:

—R 6 —N(R 9 )—SO 2 —R 8 -alkyl;

—R 6 —N(R 9 )—SO 2 —R 8 -alkenyl;

—R 6 —N(R 9 )—SO 2 —R 8 -aryl;

—R 6 —N(R 9 )—SO 2 —R 8 -heteroaryl;

—R 6 —N(R 9 )—SO 2 —R 8 -heterocyclyl;

—R 6 —N(R 9 )—SO 2 —R 10 ;

—R 6 —N(R 9 )—SO 2 —N(R 5 )—R 8 -alkyl;

—R 6 —N(R 9 )—SO 2 —N(R 5 )—R 8 -alkenyl;

—R 6 —N(R 9 )—SO 2 —N(R 5 )—R 8 -aryl;

—R 6 —N(R 9 )—SO 2 —N(R 5 )—R 8 -heteroaryl;

—R 6 —N(R 9 )—SO 2 —N(R 5 )—R 8 -heterocyclyl; and

—R 6 —N(R 9 )—SO 2 —NH 2 ;

R 2 is selected from the group consisting of:

-hydrogen;

-alkyl;

-alkenyl;

-aryl;

-heteroaryl;

-heterocyclyl;

-alkylene-Y-alkyl;

-alkylene-Y-alkenyl;

-alkylene-Y-aryl; and

-alkyl or alkenyl substituted by one or more substituents selected from the group consisting of:

—OH;

-halogen;

—N(R 5 ) 2 ;

—C(O)—C 1-10 alkyl;

—C(O)—O—C 1-10 alkyl;

—N 3 ;

-aryl;

-heteroaryl;

-heterocyclyl;

—C(O)-aryl; and

—C(O)-heteroaryl;

Y is —O— or —S(O) 0-2 —;

R 3 and R4 are independently selected from the group consisting of hydrogen, C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, C 1-10 alkoxy, C 1-10 alkylthio, amino, alkylamino, dialkylamino, halogen, and nitro;

each R 5 is independently hydrogen, C 1-10 alkyl, or C 2-10 alkenyl;

R 6 is alkylene, alkenylene, or alkynylene, which may be interrupted by one or more —O— groups;

R 8 is a bond, alkylene, alkenylene, or alkynylene which may be interrupted by one or more —O— groups;

R 9 is hydrogen, C 1-10 alkyl, or arylalkyl; or R 9 can join together with any carbon atom of R 6 to form a ring of the formula

R 10 is hydrogen or C 1-10 alkyl; or R 9 and R 10 can join together to form a ring selected from

R 12 is C 2-7 alkylene which is straight chain or branched, wherein the branching does not prevent formation of the ring;

or a pharmaceutically acceptable salt thereof.

2. A compound or salt of claim 1 wherein R 3 and R 4 are both methyl.

3. A compound or salt of claim 1 wherein R 1-2 is —R 6 —N(R 9 )—SO 2 —R 8 -alkyl.

4. A compound or salt of claim 1 wherein R 1-2 is —R 6 —N(R 9 )—SO 2 —R 10 .

5. A compound or salt of claim 4 wherein R 9 and R 10 join to form the ring.

6. A compound of the Formula (I-3):

wherein:

X is —CH(R 5 )—, —CH(R 5 )-alkylene-, —CH(R 5 )-alkenylene-, or CH(R 5 )-alkylene-Y-alkylene-;

R 1-3 is selected from the group consisting of:

—R 6 —N(R 9 )—C(R 7 )—N(R 5 )-Q-R 8 -alkyl;

—R 6 —N(R 9 )—C(R 7 )—N(R 5 )-Q-R 8 -alkenyl;

—R 6 —N(R 9 )—C(R 7 )—N(R 5 )-Q-R 8 -aryl;

—R 6 —N(R 9 )—C(R 7 )—N(R 5 )-Q-R 8 -heteroaryl;

—R 6 —N(R 9 )—C(R 7 )—N(R 5 )-Q-R 8 -heterocyclyl;

—R 6 —N(R 9 )—C(R 7 )—N(R 5 ) 2 ;

—R 6 —N(R 9 )—C(R 7 )—N(R 11 )-Q-R 8 -alkyl;

—R 6 —N(R 9 )—C(R 7 )—N(R 11 )-Q-R 8 -alkenyl;

—R 6 —N(R 9 )—C(R 7 )—N(R 11 )-Q-R 8 -aryl;

—R 6 —N(R 9 )—C(R 7 )—N(R 11 )-Q-R 8 -heteroaryl;

—R 6 —N(R 9 )—C(R 7 )—N(R 11 )-Q-R 8 -heterocyclyl; and

—R 6 —N(R 9 )—C(R 7 )—N(R 11 )H;

R 2 is selected from the group consisting of:

-hydrogen;

-alkyl;

-alkenyl;

-aryl;

-heteroaryl;

-heterocyclyl;

-alkylene-Y-alkyl;

-alkylene-Y-alkenyl;

-alkylene-Y-aryl; and

-alkyl or alkenyl substituted by one or more substituents selected from the group consisting of:

—OH;

-halogen;

—N(R 5 ) 2 ;

—C(O)—C 1-10 alkyl;

—C(O)—O—C 1-10 alkyl;

—N 3 ;

-aryl;

-heteroaryl;

-heterocyclyl;

—C(O)-aryl; and

—C(O)-heteroaryl;

Y is —O— or —S(O) 0-2 —;

Q is a bond, —C(O)—, or —SO 2 —; and

A represents the atoms necessary to provide a 5- or 6-membered heterocyclic or heteroaromatic ring that contains up to three heteroatoms;

R 3 and R 4 are independently selected from the group consisting of hydrogen, C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, C 1-10 alkoxy, C 1-10 alkylthio, amino, alkylamino, dialkylamino, halogen, and nitro;

each R 5 is independently hydrogen, C 1-10 alkyl, or C 2-10 alkenyl;

R 6 is alkylene, alkenylene, or alkynylene, which may be interrupted by one or more —O— groups;

each R 7 is ═O or ═S;

R 8 is a bond, alkylene, alkenylene, or alkynylene, which may be interrupted by one or more —O— groups;

R 9 is hydrogen, C 1-10 alkyl, or arylalkyl; or R 9 can join together with any carbon atom of R 6 to form a ring of the formula

R 11 is C 1-10 alkyl; or R 9 and R 11 can join together to form a ring having the structure

or a pharmaceutically acceptable salt thereof.

7. A compound or salt of claim 6 wherein R 3 and R 4 are methyl.

8. A compound or salt of claim 6 wherein R 1-3 is

9. A compound or salt of claim 6 wherein R 1-3 is —R 6 —N(R 9 )—C(R 7 )—N(R 5 )-Q-R 8 -alkyl.

10. A compound or salt of claim 6 wherein Q is a bond.

11. A compound or salt of claim 6 wherein R 7 is ═O.

12. A compound of the Formula (I-4):

wherein:

X is —CH(R 5 )—, —CH(R 5 )-alkylene-, —CH(R 5 )-alkenylene-, or CH(R 5 )-alkylene-Y-alkylene-;

R 1-4 is selected from the group consisting of:

-alkenyl;

-aryl; and

—R 6 -aryl;

R 2 is selected from the group consisting of:

-hydrogen;

-alkyl;

-alkenyl;

-aryl;

-heteroaryl;

-heterocyclyl;

-alkylene-Y-alkyl;

-alkylene-Y-alkenyl;

-alkylene-Y-aryl; and

-alkyl or alkenyl substituted by one or more substituents selected from the group consisting of:

—OH;

-halogen;

—N(R 5 ) 2 ;

—C(O)—C 1-10 alkyl;

—C(O)—O—C 1-10 alkyl;

—N 3 ;

-aryl;

-heteroaryl;

-heterocyclyl;

—C(O)-aryl; and

—C(O)-heteroaryl;

Y is —O— or —S(O) 0-2 —;

R 3 and R 4 are independently selected from the group consisting of hydrogen, C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, C 1-10 alkoxy, C 1-10 alkylthio, amino, alkylamino, dialkylamino, halogen, and nitro;

each R 5 is independently hydrogen, C 1-10 alkyl, or C 2-10 alkenyl; and

R 6 is alkylene, alkenylene, or alkynylene, which may be interrupted by one or more —O— groups;

or a pharmaceutically acceptable salt thereof.

13. A compound or salt of claim 12 wherein R 3 and R 4 are both methyl.

14. A compound or salt of claim 12 wherein R 1-4 is -aryl or —R 6 -aryl.

15. A compound or salt of claim 14 wherein aryl is phenyl or substituted phenyl.

16. A compound or salt of claim 12 wherein R 6 is —(CH 2 ) 1-4 —.

17. A compound of the Formula (I-5):

wherein:

X is —CH(R 5 )—, —CH(R 5 )-alkylene-, —CH(R 5 )-alkenylene-, or CH(R 5 )-alkylene-Y-alkylene-;

R 1-5 is selected from the group consisting of:

-heteroaryl;

-heterocyclyl;

—R 6 -heteroaryl; and

—R 6 -heterocyclyl;

R 2 is selected from the group consisting of:

-hydrogen;

-alkyl;

-alkenyl;

-aryl;

-heteroaryl;

-heterocyclyl;

-alkylene-Y-alkyl;

-alkylene-Y-alkenyl;

-alkylene-Y-aryl; and

-alkyl or alkenyl substituted by one or more substituents selected from the group consisting of:

—OH;

-halogen;

—N(R 5 ) 2 ;

—C(O)—C 1-10 alkyl;

—C(O)—O—C 1-10 alkyl;

—N 3 ;

-aryl;

-heteroaryl;

-heterocyclyl;

—C(O)-aryl; and

—C(O)-heteroaryl;

Y is —O— or —S(O) 0-2 —;

R 3 and R 4 are independently selected from the group consisting of hydrogen, C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, C 1-10 alkoxy, C 1-10 alkylthio, amino, alkylamino, dialkylamino, halogen, and nitro;

each R 5 is independently hydrogen, C 1-10 alkyl, or C 2-10 alkenyl; and

R 6 is alkylene, alkenylene, or alkynylene, which may be interrupted by one or more —O— groups;

or a pharmaceutically acceptable salt thereof.

18. A compound or salt of claim 17 wherein R 3 and R 4 are both methyl.

19. A compound or salt of claim 17 wherein R 1-5 is -heteroaryl or —R 6 -heteroaryl.

20. A compound or salt of claim 17 wherein R 1-5 is -heterocyclyl or —R 6 -heterocyclyl.

21. A compound or salt of claim 17 wherein R 6 is —(CH 2 ) 1-4 —.

22. A pharmaceutical composition comprising a pharmaceutically effective amount of a compound of claim 1 in combination with a pharmaceutically acceptable carrier.

23. A pharmaceutical composition comprising a pharmaceutically effective amount of a compound of claim 6 in combination with a pharmaceutically acceptable carrier.

24. A pharmaceutical composition comprising a pharmaceutically effective amount of a compound of claim 12 in combination with a pharmaceutically acceptable carrier.

25. A pharmaceutical composition comprising a pharmaceutically effective amount of a compound of claim 17 in combination with a pharmaceutically acceptable carrier.

26. A method of inducing cytokine biosynthesis in an animal wherein the cytokine is interferon alpha and/or tumor necrosis factor alpha comprising administering an effective amount of a compound of claim 1 to the animal.

27. A method of inducing cytokine biosynthesis in an animal wherein the cytokine is interferon alpha and/or tumor necrosis factor alpha comprising administering an effective amount of a compound of claim 6 to the animal.

28. A method of inducing cytokine biosynthesis in an animal wherein the cytokine is interferon alpha and/or tumor necrosis factor alpha comprising administering an effective amount of a compound of claim 12 to the animal.

29. A method of inducing cytokine biosynthesis in an animal wherein the cytokine is interferon alpha and/or tumor necrosis factor alpha comprising administering an effective amount of a compound of claim 17 to the animal.

30. A compound or salt of claim 1 wherein R 2 is hydrogen, alkyl, or -alkylene-O-alkyl.

31. A compound or salt of claim 6 wherein R 2 is hydrogen, alkyl, or -alkylene-O-alkyl.

32. A compound or salt of claim 12 wherein R 2 is hydrogen, alkyl, or -alkylene-O-alkyl.

33. A compound or salt of claim 17 wherein R 2 is hydrogen, alkyl, or -alkylene-O-alkyl.