Fused bicyclic compounds for the treatment of disease

1. A compound having the structure of Formula (IV), or a pharmaceutically acceptable salt thereof:

wherein:

—X—Y—Z— is selected from

R 1 is selected from the group consisting of hydrogen, optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted C 3 -C 8 cycloalkyl, optionally substituted aryl, optionally substituted —(C 1 -C 2 alkylene)-(aryl), optionally substituted C 2 -C 9 heterocycloalkyl, optionally substituted heteroaryl, and optionally substituted —(C 1 -C 2 alkylene)-(heteroaryl);

R 2 is selected from the group consisting of —CN, —C(═O)OR 25 , —C(═O)N(R 25 )R 26 ,

 or R 1 and R 2 together with the carbon atoms to which they are attached, form an optionally substituted C 2 -C 9 heterocycloalkyl ring or an optionally substituted heteroaryl ring;

R 3 is —C(═O)R 20 or —S(═O) 2 R 20 ;

R 4 and R 5 are each independently selected from the group consisting of hydrogen, halogen, optionally substituted C 1 -C 6 alkyl, optionally substituted C 1 -C 6 alkoxy, optionally substituted C 2 -C 6 alkenyl, and optionally substituted C 2 -C 6 alkynyl; or R 4 and R 5 together with the carbon atom to which they are attached, form an optionally substituted C 3 -C 6 cycloalkyl ring or an optionally substituted C 2 -C 7 heterocycloalkyl ring;

R 6 is selected from the group consisting of hydrogen, halogen, optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, and —C(═O)N(R 27 )R 28 ;

R 7 is selected from the group consisting of hydrogen, halogen, optionally substituted C 1 -C 6 alkyl, optionally substituted C 1 -C 6 alkoxy, optionally substituted C 2 -C 6 alkenyl, and optionally substituted C 2 -C 6 alkynyl;

each R 12 is independently selected from the group consisting of hydrogen and C 1 -C 6 alkyl;

each R 13 and R 14 are each independently selected from the group consisting of hydrogen and C 1 -C 6 alkyl; or R 13 and R 14 together with the nitrogen atom to which they are attached, form an optionally substituted C 2 -C 9 heterocycloalkyl ring;

each R 39 is independently selected from the group consisting of hydrogen, halogen, —CN, amino, alkylamino, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, C 3 -C 8 cycloalkyl, C 2 -C 9 heterocycloalkyl, aryl, heteroaryl, —C(═O)OR 12 , and —C(═O)N(R 13 )R 14 ;

R 20 is selected from the group consisting of —R 34 R 35 or —R 31 ;

R 34 is selected from the group consisting of optionally substituted C 1 -C 6 alkyl, optionally substituted C 3 -C 10 cycloalkyl, optionally substituted aryl, optionally substituted —(C 1 -C 2 alkylene)-(aryl), optionally substituted heteroaryl, optionally substituted C 2 -C 9 heterocycloalkyl, and optionally substituted —(C 1 -C 2 alkylene)-(heteroaryl);

R 35 is —(C 1 -C 6 alkyl)-R 30 , —O(C 2 -C 6 alkyl)-R 30 , or —N(R 12 )(C 2 -C 6 alkyl)-R 30 ;

R 30 is R 36a , R 36b , or R 36c ;

R 31 is R 36a or R 36c ;

R 36a is

R 36b is

R 36c is

R 17a is C 1 -C 6 alkyl;

R 17b is C 1 -C 6 alkyl optionally substituted with phenyl, —C(═O)OH or —S(═O) 2 OH;

R 18 is hydrogen, —OH, —(C 0 -C 6 alkyl)-C(═O)OH, or C 1 -C 6 alkyl;

R 25 and R 26 are each independently selected from the group consisting of hydrogen, optionally substituted C 1 -C 6 alkyl, optionally substituted C 3 -C 8 cycloalkyl, optionally substituted aryl, optionally substituted —(C 1 -C 2 alkylene)-(aryl), optionally substituted C 2 -C 9 heterocycloalkyl, optionally substituted heteroaryl, and optionally substituted —(C 1 -C 2 alkylene)-(heteroaryl); and

R 27 and R 28 are each independently selected from the group consisting of hydrogen, optionally substituted C 1 -C 6 alkyl, optionally substituted C 3 -C 8 cycloalkyl, optionally substituted aryl, optionally substituted —(C 1 -C 2 alkylene)-(aryl), optionally substituted C 2 -C 9 heterocycloalkyl, optionally substituted heteroaryl, and optionally substituted —(C 1 -C 2 alkylene)-(heteroaryl); or R 27 and R 28 together with the nitrogen atom to which they are attached, form an optionally substituted C 2 -C 9 heterocycloalkyl ring.

2. The compound of claim 1 having the structure of Formula (IVc), or a pharmaceutically acceptable salt thereof:

3. The compound of claim 2 , or a pharmaceutically acceptable salt thereof, wherein R 3 is —C(═O)R 20 .

4. The compound of claim 3 , or a pharmaceutically acceptable salt thereof, wherein R 20 is —R 34 R 35 .

5. The compound of claim 4 , or a pharmaceutically acceptable salt thereof, wherein R 34 is selected from the group consisting of optionally substituted C 1 -C 6 alkyl, optionally substituted C 3 -C 10 cycloalkyl, and optionally substituted aryl.

6. The compound of claim 5 , or a pharmaceutically acceptable salt thereof, wherein R 34 is optionally substituted aryl and R 35 is —O(C 2 -C 6 alkyl)—R 30 .

7. The compound of claim 6 , or a pharmaceutically acceptable salt thereof, wherein R 30 is R 36b or R 36c .

8. The compound of claim 7 , or a pharmaceutically acceptable salt thereof, wherein R 36b is

9. The compound of claim 2 , or a pharmaceutically acceptable salt thereof, wherein R 39 is selected from the group consisting of hydrogen, C 1 -C 6 alkyl, and C 1 -C 6 haloalkyl.

10. The compound of claim 2 , or a pharmaceutically acceptable salt thereof, wherein R 1 , R 6 , R 7 , and R 12 are each hydrogen.

11. The compound of claim 2 , or a pharmaceutically acceptable salt thereof, wherein R 4 and R 5 are methyl.

12. The compound of claim 2 , or a pharmaceutically acceptable salt thereof, wherein R 2 is —C(O)OR 25 .

13. The compound of claim 12 , or a pharmaceutically acceptable salt thereof, wherein R 25 is optionally substituted C 1 -C 6 alkyl.

14. The compound of claim 12 , or a pharmaceutically acceptable salt thereof, wherein R 25 is isopropyl.

15. A pharmaceutical composition comprising a pharmaceutically acceptable diluent, excipient or binder, and a compound of claim 2 ; or a pharmaceutically acceptable salt thereof.

16. A compound having the structure:

or a pharmaceutically acceptable salt thereof.