Hydroxylamine and oxime substituted imidazoquinolines, imidazopyridines, and imidazonaphthyridines

1. A compound of the Formula (II):

wherein:

Z is —C(═N—O—R 1-2 )—

X is:

—CH(R 9 )—, or

—CH(R 9 )-alkylene-;

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

hydrogen,

alkyl, and

aryl;

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

hydrogen,

alkyl,

heterocyclyl,

aryl,

heteroaryl, and

alkyl, heterocyclyl, aryl, or heteroaryl, substituted by one or more substituents selected from the group consisting of:

halogen,

cyano,

alkyl,

hydroxy,

hydroxyalkyl,

alkoxy,

dialkylamino,

heterocyclyl,

aryl, and

heteroaryl;

R is selected from the group consisting of:

halogen,

hydroxy,

alkyl,

alkenyl,

haloalkyl,

alkoxy,

alkylthio, and

—N(R 9 ) 2 ;

R 2 is selected from the group consisting of:

hydrogen;

alkyl;

alkoxyalkyl; and

hydroxyalkyl;

R 3 is selected from the group consisting of:

aryl,

heteroaryl, and

aryl and heteroaryl substituted by one or more of the groups selected from halogen, hydroxyl, alkoxy, hydroxyalkyl, cyano, dialkylamino, heterocyclyl, —C(O)NH 2 , —NHS(O) 2 -alkyl, —C(O)NH-alkyl, —NHC(O)-alkyl, —C(O)NH-heterocyclyl, and

R 6 is selected from the group consisting of ═O and ═S;

R 8 is selected from the group consisting of hydrogen, C 1-10 alkyl, C 2-10 alkenyl, C 1-10 alkoxy-C 1-10 alkylenyl, hydroxy-C 1-10 alkylenyl, heteroaryl-C 1-10 alkylenyl, and aryl-C 1-10 alkylenyl;

R 9 is selected from the group consisting of hydrogen and alkyl;

A is selected from the group consisting of —O—, —C(O)—, —S(O) 0-2 —, and —CH 2 —;

V is selected from the group consisting of —C(R 6 )—, —O—C(R 6 )—, —N(R 8 )—C(R 6 )—, and —S(O) 2 —;

a and b are each independently integers from 1 to 6 with the proviso that a+b is ≦7;

n′ is an integer from 0 to 4; and

m is 0 or 1; with the proviso that when m is 1, then n′ is 0 or 1;

or a pharmaceutically acceptable salt thereof.

2. The compound or salt of claim 1 wherein m is 0.

3. The compound or salt of claim 1 wherein n′ is 0.

4. The compound or salt of claim 2 wherein m and n′ are both 0.

5. The compound or salt of claim 1 , wherein R 3 is selected from the group consisting of pyridin-3-yl, pyridin-4-yl, 5-(hydroxymethyl)pyridin-3-yl, and 2-ethoxyphenyl.

6. The compound or salt of claim 1 wherein R 2 is selected from the group consisting of C 1-4 alkyl, and C 1-4 alkylenyl-O—C 1-4 alkyl.

7. The compound or salt of claim 1 wherein X is selected from the group consisting of —(CH 2 ) 1-6 —, —CH 2 C(CH 3 ) 2 —, and —CH 2 C(CH 3 ) 2 CH 2 —.

8. The compound or salt of claim 1 wherein R 1-1 is selected from the group consisting of hydrogen, C 1-4 alkyl, and phenyl.

9. The compound or salt of claim 1 wherein R 1-2 is selected from the group consisting of hydrogen, C 1-4 alkyl, benzyl, and pyridin-2-ylmethyl.

10. A pharmaceutical composition comprising a therapeutically effective amount of a compound or salt of claim 1 in combination with a pharmaceutically acceptable carrier.

11. A method of inducing cytokine biosynthesis in an animal comprising administering an effective amount of a compound or salt of claim 1 to the animal, wherein the cytokine induced is selected interferon or tumor necrosis factor alpha.

12. A compound of the Formula (IV):

wherein:

Z is —C(═N—O—R 1-2 )—

X is —CH(R 9 )— or —CH(R 9 )-alkylene-;

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

hydrogen,

alkyl, and

aryl;

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

hydrogen,

alkyl,

aryl, and

alkyl substituted by one or more substituents selected from the group consisting of aryl and heteroaryl;

R is selected from the group consisting of:

halogen,

hydroxy,

alkyl,

alkenyl,

haloalkyl,

alkoxy,

alkylthio, and

—N(R 9 ) 2 ;

R 2 is selected from the group consisting of:

hydrogen,

alkyl,

alkoxyalkyl, and

hydroxyalkyl;

R 3 is selected from the group consisting of:

halogen,

aryl,

heteroaryl, and

aryl and heteroaryl substituted by one or more of the groups selected from hydroxyl, —C(O)NH 2 , —NHS(O) 2 -alkyl, —C(O)NH-alkyl, —C(O)NH-heterocyclyl;

R 9 is selected from the group consisting of hydrogen and alkyl;

n′ is 0 or 1; and

m is 0 or 1;

or a pharmaceutically acceptable salt thereof.

13. A compound selected from the group consisting of:

5-(4-amino-7-phenyl-2-propyl-1H-imidazo[4,5-c]quinolin-1-yl)pentan-2-one-O-methyloximine;

4-(4-amino-2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)-1-phenylbutan-1-one-oxime;

4-(4-amino-2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)-1-phenylbutan-1-one-O-methyloxime;

5-(4-amino-2-methyl-1H-imidazo[4,5-c]quinolin-1-yl)pentan-2-one-oxime;

5-(4-amino-2-methyl-1H-imidazo[4,5-c]quinolin-1-yl)pentan-2-one-O-benzyloxime;

5-(4-amino-2-methyl-1H-imidazo[4,5-c]quinolin-1-yl)pentan-2-one-O-methyloxime;

5-(4-amino-2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)pentan-2-one-O-methyloxime;

5-(4-amino-2-ethoxymethyl-1H-imidazo[4,5-c]quinolin-1-yl)pentan-2-one-oxime;

5-(4-amino-2-ethoxymethyl-1H-imidazo[4,5-c]quinolin-1-yl)pentan-2-one-O-methyloxime hydrochloride;

5-(4-amino-2-ethoxymethyl-1H-imidazo[4,5-c]quinolin-1-yl)pentan-2-one-O-benzyloxime hydrochloride;

1-(4-amino-2-propyl-1H-imidazo[4,5-c]quinolin-1-yl)-6-methylheptan-4-one-oxime;

1-(4-amino-2-propyl-1H-imidazo[4,5-c]quinolin-1-yl)decan-4-one-oxime;

5-(4-amino-2-methyl-1H-imidazo[4,5-c]quinolin-1-yl)-4,4-dimethylpentan-2-one-O-methyloxime;

5-(4-amino-2-propyl-1H-imidazo[4,5-c]quinolin-1-yl)-4,4-dimethylpentan-2-one-O-methyloxime;

5-(4-amino-1H-imidazo-[4,5-c]quinolin-1-yl)-4,4-dimethylpentan-2-one-O-methyloxime;

(1E,Z)-4-(4-amino-2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)butanal-O-methyloxime;

4-(4-amino-2-methyl-1H-imidazo[4,5-c]quinolin-1-yl)butanal-O-methyloxime;

1-[4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butan-2-one-O-methyloxime;

or a pharmaceutically acceptable salt thereof.