Bicyclic heteroaryl inhibitors of PDE4

1. A compound of structural Formula IV

or a salt thereof, wherein:

R 1 and R 2 are independently selected from the group consisting of —(CH 2 ) s G 1 G 2 G 3 , acyl, acylalkyl, carboxyalkyl, cyanoalkyl, alkoxy, alkoxyalkyl, amidoalkyl, amino, alkyl, alkylalkoxy, aminoalkyl, alkenyl, alkynyl, carboxyl, carboxyalkyl, ether, heteroalkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, aralkyl, aryl, guanidine, heteroaryl, heteroaralkyl, and hydroxyalkyl, any of which may be optionally substituted;

s is 0-8;

G 1 is selected from the group consisting of alkoxy, amino, amido, carbonyl, hydroxy, ether, an amino acid, and null;

G 2 is selected from the group consisting of alkyl, alkoxy, amino, aryl, halo, haloalkyl, heterocycloalkyl, heteroaryl, carboxylalkylamino, guanidine, an amino acid, and null, any of which may be optionally substituted;

G 3 is selected from the group consisting of alkyl, alkoxy, amino, hydroxy, ether, carboxyl, hydroxamic acid, an amino acid, phosphonate, phosphoamide, and null, any of which may be optionally substituted;

when s is 0, G 1 , G 2 , and G 3 may not all together be null;

R 3 and R 4 are independently selected from the group consisting of alkoxy, lower alkyl, halogen and hydrogen;

R 5 is selected from the group consisting of (CH 2 ) p , C(O)NH, N(R 7 ) and S(O) q ;

p is 1,2,3 or 4;

q is 0, 1 or 2;

R 6 is selected from the group consisting of aryl heteroaryl, either of which may be optionally substituted;

R 7 selected from the group consisting of hydrogen and optionally substituted lower alkyl; R 17 is selected from the group consisting of hydrogen, halogen, hydroxyl, lower alkyl, hydroxyalkyl, haloalkyl, alkoxy, haloalkoxy, amino, aminoalkyl and aminoalkoxy.

2. The compound as recited in claim 1 , wherein

R 17 is selected from the group consisting of hydrogen, halogen, lower alkyl, haloalkyl, alkoxy, haloalkoxy, amino, aminoalkyl and aminoalkoxy.

3. The compound as recited in claim 2 , wherein R 17 is hydrogen.

4. The compound as recited in claim 3 , wherein R 6 is selected from the group consisting of phenyl, pyridine, pyrimidine, pyridazine, and pyrazine, any of which may be optionally substituted.

5. The compound as recited in claim 4 , wherein R 3 and R 4 are both hydrogen.

6. The compound as recited in claim 5 , wherein:

R 5 N(R 7 ); and

R 7 hydrogen.

7. The compound as recited in claim 6 , wherein R 2 is lower alkyl.

8. The compound as recited in claim 7 , wherein:

R 1 is selected from the group consisting of —(CH 2 ) s G 1 G 2 G 3 , lower alkyl, cycloalkyl, cycloalkylalkyl, and heterocycloalkyl, any of which may be optionally substituted;

s is 1-6;

G 1 is selected from the group consisting of amino, amido, and null;

G 2 is selected from the group consisting of alkoxy, aryl, halo, heterocycloalkyl, and null, any of which may be optionally substituted; and

G 3 is selected from the group consisting of alkyl, carboxyl, and null, any of which may be optionally substituted.

9. The compound as recited in claim 8 , wherein R 2 is methyl.

10. The compound as recited in claim 9 , wherein R 6 has a formula selected from the group consisting of:

R 19 , R 20 , R 21 , R 22 , and R 23 are independently selected from the group consisting of hydrogen, halogen, hydroxyl, lower alkyl, lower alkoxy, lower haloalkyl, lower haloalkoxy, amino, and carboxyl.

11. A compound of structural Formula VI

or a salt thereof, wherein:

R 1 and R 2 are independently selected from the group consisting of —(CH 2 ) s G 1 G 2 G 3 , acyl, acylalkyl, carboxyalkyl, cyanoalkyl, alkoxy, alkoxyalkyl, amidoalkyl, amino, alkyl, alkylalkoxy, aminoalkyl, alkenyl, alkynyl, carboxyl, carboxyalkyl, ether, heteroalkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, aralkyl, aryl, guanidine, heteroaryl, heteroaralkyl and hydroxyalkyl, any of which may be optionally substituted;

s is 1-8;

G 1 is selected from the group consisting of alkoxy, acyl, amino, amido, carbonyl, ether, an amino acid, and null;

G 2 is selected from the group consisting of alkyl, alkoxy, acyl, amino, aryl, halo, haloalkyl, heterocycloalkyl, heteroaryl, carboxylalkylamino, guanidine, an amino acid, and null, any of which may be optionally substituted;

G 3 is selected from the group consisting of alkyl, alkoxy, amino, hydroxy, ether, carboxyl, hydroxamic acid, an amino acid, phosphonate, phosphoamide, and null, any of which may be optionally substituted;and

R 19 and R 23 are independently selected from the group consisting of hydrogen, halogen, hydroxyl, lower alkyl, lower alkoxy, lower haloalkyl, lower haloalkoxy, amino, and carboxyl.

12. The compound as recited in claim 11 , wherein R 19 and R 23 are independently selected from the group consisting of hydrogen, halogen, and lower alkyl.

13. The compound as recited in claim 12 , wherein R 2 is lower alkyl.

14. The compound as recited in claim 13 , wherein:

R 1 is selected from the group consisting of —(CH 2 ) s G 1 G 2 G 3 , lower alkyl, cycloalkyl, cycloalkylalkyl, and heterocycloalkyl, any of which may be optionally substituted;

s is 1-6;

G 1 is selected from the group consisting of amino, amido, and null;

G 2 is selected from the group consisting of alkoxy, aryl, halo, heterocycloalkyl, and null, any of which may be optionally substituted; and

G 3 is selected from the group consisting of alkyl, carboxyl, and null, any of which may be optionally substituted.

15. The compound as recited in claim 14 , wherein R 2 is methyl.

16. A compound of structural Formula VII

or a salt thereof, wherein:

R 1 and R 2 are independently selected from the group consisting of —(CH 2 ) s G 1 G 2 G 3 , acyl, acylalkyl, carboxyalkyl, cyanoalkyl, alkoxy, alkoxyalkyl, amidoalkyl, amino, alkyl, alkylalkoxy, aminoalkyl, alkenyl, alkynyl, carboxyl, carboxyalkyl, ether, heteroalkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, aralkyl, aryl, guanidine, heteroaryl, heteroaralkyl and hydroxyalkyl, any of which may be optionally substituted;

s is 1-8; G 1 is selected from the group consisting of alkoxy, acyl, amino, amido, carbonyl, ether, an amino acid, and null; G 2 is selected from the group consisting of alkyl, alkoxy, acyl, amino, aryl, halo, haloalkyl, heterocycloalkyl, heteroaryl, carboxylalkylamino, guanidine, an amino acid, and null, any of which may be optionally substituted; G 3 is selected from the group consisting of alkyl, alkoxy, amino, hydroxy, ether, carboxyl, hydroxamic acid, an amino acid, phosphonate, phosphoamide, and null, any of which may be optionally substituted; and

R 19 , R 21, and R 23 are independently selected from the group consisting of hydrogen, halogen, hydroxyl, lower alkyl, lower alkoxy, lower haloalkyl, lower haloalkoxy, amino, and carboxyl.

17. The compound as recited in claim 16 , wherein R 19 , R 21 , and R 23 are independently selected from the group consisting of hydrogen, halogen, and lower alkyl.

18. The compound as recited in claim 17 , wherein R 2 is lower alkyl.

19. The compound as recited in claim 18 , wherein:

R 1 is selected from the group consisting of —(CH 2 ) s G 1 G 2 G 3 , ower alkyl, cycloalkyl, cycloalkylalkyl, and heterocycloalkyl, any of which may be optionally substituted;

s is 1-6;

G 1 is selected from the group consisting of amino, amido, and null;

G 2 is selected from the group consisting of alkoxy, aryl, halo, heterocycloalkyl, and null, any of which may be optionally substituted; and

G 3 is selected from the group consisting of alkyl, carboxyl, and null, any of which may be optionally substituted.

20. The compound as recited in claim 19 , wherein R 2 is methyl.

21. A compound selected from the group consisting of Examples 1 to 105.

22. A pharmaceutical composition comprising a compound as recited in claim 1 together with a pharmaceutically acceptable carrier.