Substituted 3,4,6,7-tetrahydro-5

1. A compound of the formula:

wherein:

R 1a and R 1b are independently selected from the group consisting of hydrogen, C 1-6 alkyl, 1-hydroxy-1-methylethyl, 1-(methylsulfonylamino)-1-methylethyl, 3-(methylsulfonylamino)propyl and 1-fluoro-1-methylethyl; or R 1a and R 1b , together with the carbon atom to which they are attached, form a ring selected from the group consisting of cyclopropane, cyclobutane, cyclopentane, cyclohexane, oxetane, tetrahydrofuran, and tetrahydropyran;

R 1c is selected from the group consisting of:

—X—R 4 ,

—X—Y—R 4 ,

—X—Y—X′—Y—R 4 , and

—X—R 5 ;

R 2 is selected from the group consisting of hydrogen, alkyl, alkoxyalkyl, and hydroxyalkyl;

X is alkylene optionally interrupted by one or more —O— groups, and optionally substituted by a hydroxy or methoxy group;

X′ is selected from the group consisting of alkylene, arylene, heteroarylene, and heterocyclylene wherein the alkylene group can be optionally interrupted or terminated by arylene, heteroarylene or heterocyclylene and optionally interrupted by one or more —O— groups;

Y is selected from the group consisting of:

—O—,

—S(O) 0-2 —,

—S(O) 2 —N(R 8 )—,

—C(R 6 )—,

—C(R 6 )—O—,

—O—C(R 6 )—,

—O—C(O)—O—,

—N(R 8 )-Q-,

—C(R 6 )—N(R 8 )—,

—O—C(R 6 )—N(R 8 )—,

—C(R 6 )—N(OR 9 )—,

—O—N(R 8 )-Q-,

—O—N═C(R 4 )—,

—C(═N—O—R 8 )—, and

—CH(—N(—O—R 8 )-Q-R 4 )—,

R 4 is selected from the group consisting of hydrogen, alkyl, aryl, arylalkylenyl, aryloxyalkylenyl, alkylarylenyl, heteroaryl, heteroarylalkylenyl, heteroaryloxyalkylenyl, alkylheteroarylenyl, and heterocyclyl wherein the alkyl, aryl, arylalkylenyl, aryloxyalkylenyl, alkylarylenyl, heteroaryl, heteroarylalkylenyl, heteroaryloxyalkylenyl, alkylheteroarylenyl, and heterocyclyl groups can be unsubstituted or substituted by one or more substituents independently selected from the group consisting of alkyl; alkoxy; hydroxyalkyl; haloalkyl; haloalkoxy; halogen; hydroxy; mercapto; cyano; aryl; aryloxy; arylalkyleneoxy; heteroaryl; heteroaryloxy; heteroarylalkyleneoxy; heterocyclyl; amino; alkylamino; dialkylamino; (dialkylamino)alkyleneoxy; and, in the case of alkyl and heterocyclyl, oxo; with the proviso that when R 4 is aryl, arylalkylenyl, heteroaryl, or heteroarylalkylenyl, then the one or more substituents may also be independently selected from the group consisting of arylalkylenyl, alkylarylenyl, alkoxyarylenyl, haloarylenyl, alkylsulfonylamino, arylsulfonylamino, alkylcarbonylamino, arylcarbonylamino, alkylaminocarbonylamino, arylaminocarbonylamino, heteroarylsulfonylamino, heteroarylcarbonylamino, heteroarylaminocarbonylamino, alkoxycarbonylamino, and aryloxycarbonylamino; and with the further proviso that when R 4 is heterocyclyl, then the one or more substituents may also be independently selected from the group consisting of arylalkylenyl, and aminocarbonyl;

R 5 is selected from the group consisting of:

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

R 7 is C 2-7 alkylene;

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

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

R 10 is C 3-8 alkylene;

A is selected from the group consisting of —CH 2 —, —O—, —C(O)—, —S(O) 0-2 —, and —N(-Q-R 4 )—;

A′ is selected from the group consisting of —O—, —S(O) 0-2 —, —N(-Q-R 4 )—, and —CH 2 —;

Q is selected from the group consisting of a bond, —C(R 6 )—, —C(R 6 )—C(R 6 )—, —S(O) 2 —, —C(R 6 )—N(R 8 )—W—, —S(O) 2 —N(R 8 )—, —C(R 6 )—O—, —C(R 6 )—S—, and —C(R 6 )—N(OR 9 )—;

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 —;

W is selected from the group consisting of a bond, —C(O)—, and —S(O) 2 —; and

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

with the proviso that X can also be a bond when:

R 4 is bonded to X; or

Y is bonded to X and Y is —C(R 6 )—, —C(R 6 )—O—, —C(R 6 )—N(R 8 )—, —C(R 6 )—N(OR 9 )—, —C(═N—O—R 8 )—, or —CH(—N(—O—R 8 )-Q-R 4 )—; or

R 5 is bonded to X and R 5 is

wherein V is —C(R 6 )— or

or a pharmaceutically acceptable salt thereof.

2. The compound or salt of claim 1 wherein R 1a and R 1b are independently selected from the group consisting of hydrogen, C 1-6 alkyl, 1-hydroxy-1-methylethyl, 1-(methylsulfonylamino)-1-methylethyl, 3-(methylsulfonylamino)propyl and 1-fluoro-1-methylethyl.

3. The compound or salt of claim 1 wherein R 1a and R 1b join together to form a ring selected from the group consisting of cyclopropane, cyclobutane, cyclopentane, cyclohexane, oxetane, tetrahydrofuran, and tetrahydropyran.

4. The compound or salt of claim 1 wherein R 1c is selected from the group consisting of —X—R 4 , —X—Y—R 4 and —X—Y—X′—Y′—R 4 .

5. The compound or salt of claim 1 wherein R 2 is selected from the group consisting of hydrogen, alkyl, alkoxyalkyl, and hydroxyalkyl.

6. The compound or salt of claim 4 wherein R 1c is —X—R 4 .

7. The compound or salt of claim 6 wherein R 4 in —X—R 4 is alkyl which is unsubstituted or substituted by one or more substituents selected from the group consisting of halogen, hydroxy, and alkoxy.

8. The compound or salt of claim 5 wherein R 2 is selected from the group consisting of methyl, ethyl, n-propyl, n-butyl, ethoxymethyl, hydroxymethyl, and 2-methoxyethyl).

9. A pharmaceutical composition comprising a therapeutically effective amount of a compound or salt of claim 1 and a pharmaceutically acceptable carrier.

10. 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.

11. A compound of the formula:

wherein:

R 1a and R 1b are independently selected from the group consisting of hydrogen, C 1-6 alkyl, 1-hydroxy-1-methylethyl, 1-(methylsulfonylamino)-1-methylethyl, 3-(methylsulfonylamino)propyl and 1-fluoro-1-methylethyl; or R 1a and R 1b , together with the carbon atom to which they are attached, form a ring selected from the group consisting of cyclopropane, cyclobutane, cyclopentane, cyclohexane, oxetane, tetrahydrofuran, and tetrahydropyran;

R 1c is selected from the group consisting of:

—X—R 4 ,

—X—Y—R 4 ,

—X—Y—X′—Y—R 4 , and

—X—R 5 ;

R 2 is selected from the group consisting of hydrogen, alkyl, alkoxyalkyl, and hydroxyalkyl;

X is alkylene optionally interrupted by one or more —O— groups, and optionally substituted by a hydroxy or methoxy group;

X′ is selected from the group consisting of alkylene, arylene, heteroarylene, and heterocyclylene wherein the alkylene group can be optionally interrupted or terminated by arylene, heteroarylene or heterocyclylene and optionally interrupted by one or more —O— groups;

Y is selected from the group consisting of:

—O—,

—S(O) 0-2 ,

—S(O) 2 —N(R 8 )—,

—C(R 6 )—,

—C(R 6 )—O—,

—O—C(R 6 )—,

—O—C(O)—O—,

—N(R 8 )-Q-,

—C(R 6 )—N(R 8 )—,

—O—C(R 6 )—N(R 8 )—,

—C(R 6 )—N(OR 9 )—,

—O—N(R 8 )-Q-,

—O—N═C(R 4 )—,

—C(═N—O—R 8 )—, and

—CH(—N(—O—R 8 )-Q-R 4 )—,

R 4 is selected from the group consisting of hydrogen, alkyl, aryl, arylalkylenyl, aryloxyalkylenyl, alkylarylenyl, heteroaryl, heteroarylalkylenyl, heteroaryloxyalkylenyl, alkylheteroarylenyl, and heterocyclyl wherein the alkyl, aryl, arylalkylenyl, aryloxyalkylenyl, alkylarylenyl, heteroaryl, heteroarylalkylenyl, heteroaryloxyalkylenyl, alkylheteroarylenyl, and heterocyclyl groups can be unsubstituted or substituted by one or more substituents independently selected from the group consisting of alkyl; alkoxy; hydroxyalkyl; haloalkyl; haloalkoxy; halogen; hydroxy; mercapto; cyano; aryl; aryloxy; arylalkyleneoxy; heteroaryl; heteroaryloxy; heteroarylalkyleneoxy; heterocyclyl; amino; alkylamino; dialkylamino; (dialkylamino)alkyleneoxy; and, in the case of alkyl and heterocyclyl, oxo; with the proviso that when R 4 is aryl, arylalkylenyl, heteroaryl, or heteroarylalkylenyl, then the one or more substituents may also be independently selected from the group consisting of arylalkylenyl, alkylarylenyl, alkoxyarylenyl, haloarylenyl, alkylsulfonylamino, arylsulfonylamino, alkylcarbonylamino, arylcarbonylamino, alkylaminocarbonylamino, arylaminocarbonylamino, heteroarylsulfonylamino, heteroarylcarbonylamino, heteroarylaminocarbonylamino, alkoxycarbonylamino, and aryloxycarbonylamino; and with the further proviso that when R 4 is heterocyclyl, then the one or more substituents may also be independently selected from the group consisting of arylalkylenyl, and aminocarbonyl;

R 5 is selected from the group consisting of:

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

R 7 is C 2-7 alkylene;

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

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

R 10 is C 3-8 alkylene;

A is selected from the group consisting of —CH 2 —, —O—, —C(O)—, —S(O) 0-2 —, and —N(-Q-R 4 )—;

A′ is selected from the group consisting of —O—, —S(O) 0-2 —, —N(-Q-R 4 )—, and —CH 2 —;

Q is selected from the group consisting of a bond, —C(R 6 )—, —C(R 6 )—C(R 6 )—, —S(O) 2 —, —C(R 6 )—N(R 8 )—W—, —S(O) 2 —N(R 8 )—, —C(R 6 )—O—, —C(R 6 )—S—, and —C(R 6 )—N(OR 9 )—;

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 —;

W is selected from the group consisting of a bond, —C(O)—, and —S(O) 2 —; and

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

with the proviso that X can also be a bond when:

R 4 is bonded to X; or

Y is bonded to X and Y is —C(R 6 )—, —C(R 6 )—O—, —C(R 6 )—N(R 8 )—, —C(R 6 )—N(OR 9 )—, —C(═N—O—R 8 )—, or —CH(—N(—O—R 8 )-Q-R 4 )—; or

R 5 is bonded to X and R 5 is

wherein V is —C(R 6 )— or

or a pharmaceutically acceptable salt thereof.

12. The compound or salt of claim 11 wherein R 1a and R 1b are independently selected from the group consisting of hydrogen, C 1-6 alkyl, 1-hydroxy-1-methylethyl, 1-(methylsulfonylamino)-1-methylethyl, 3-(methylsulfonylamino)propyl and 1-fluoro-1-methylethyl.

13. The compound or salt of claim 11 wherein R 1a and R 1b join together to form a ring selected from the group consisting of cyclopropane, cyclobutane, cyclopentane, cyclohexane, oxetane, tetrahydrofuran, and tetrahydropyran.

14. The compound or salt of claim 11 wherein R 1c is selected from the group consisting of —X—R 4 , —X—Y—R 4 and —X—Y—X′—Y′—R 4 .

15. The compound or salt of claim 11 wherein R 2 is selected from the group consisting of hydrogen, alkyl, alkoxyalkyl, and hydroxyalkyl.

16. The compound or salt of claim 14 wherein R 1c is —X—R 4 .

17. The compound or salt of claim 16 wherein R 4 in —X—R 4 is alkyl which is unsubstituted or substituted by one or more substituents selected from the group consisting of halogen, hydroxy, and alkoxy.

18. The compound or salt of claim 15 wherein R 2 is selected from the group consisting of methyl, ethyl, n-propyl, n-butyl, ethoxymethyl, hydroxymethyl, and 2-methoxyethyl.

19. A pharmaceutical composition comprising a therapeutically effective amount of a compound or salt of claim 11 and a pharmaceutically acceptable carrier.

20. A method of inducing cytokine biosynthesis in an animal comprising administering an effective amount of a compound or salt of claim 11 to the animal.