Spirocyclic tetrahydroquinazolines

1. A compound of Formula VII:

wherein:

Z is

X represents a 6- to 12-membered monocyclic or bicyclic heterocyclo;

R 1 is selected from the group consisting of —C(═O)R 1a , —C(═O)—CR 4a ═CR 4b R 4c , —C(═O)—C≡CR 5a , —S(═O) 2 CR 4e ═CR 4f R 4g , and —S(═O) 2 —C≡CR 5b ;

R 1a is selected from the group consisting of C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, and C 3 -C 6 cycloalkyl;

R 4a , R 4b , and R 4c are independently selected from the group consisting of hydrogen, halogen, C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, (amino)C 1 -C 4 alkyl, (hydroxy)C 1 -C 4 alkyl, (alkoxy)C 1 -C 4 alkyl, and (optionally substituted heterocyclo)C 1 -C 4 alkyl;

R 5a is selected from the group consisting of hydrogen, halogen, C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, (amino)C 1 -C 4 alkyl, (hydroxy)C 1 -C 4 alkyl, (alkoxy)C 1 -C 4 alkyl, and (optionally substituted heterocyclo)C 1 -C 4 alkyl;

R 4e , R 4f , and R 4g are independently selected from the group consisting of hydrogen, halogen, C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, (amino)C 1 -C 4 alkyl, (hydroxy)C 1 -C 4 alkyl, (alkoxy)C 1 -C 4 alkyl, and (optionally substituted heterocyclo)C 1 -C 4 alkyl;

R 5b is selected from the group consisting of hydrogen, halogen, C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, (amino)C 1 -C 4 alkyl, (hydroxy)C 1 -C 4 alkyl, (alkoxy)C 1 -C 4 alkyl, and (optionally substituted heterocyclo)C 1 -C 4 alkyl;

R 2a is selected from the group consisting of hydrogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, (cyano)C 1 -C 4 alkyl, (hydroxy)C 1 -C 4 alkyl, (alkoxy)C 1 -C 4 alkyl, (amino)C 1 -C 4 alkyl, (optionally substituted heterocyclo)C 1 -C 4 alkyl, (optionally substituted aryl)C 1 -C 4 alkyl, (optionally substituted hetereoaryl)C 1 -C 4 alkyl, C 2 -C 4 alkynyl, heteroalkyl, cyano, —C(═O)OR 5c , —C(═O)NR 5d R 5e , and —NR 5f R 5g ;

R 2b and R 2c are independently selected from the group consisting of hydrogen and C 1 -C 4 alkyl; or

R 2b and R 2c are attached to the same carbon atom and are taken together to form a —C(═O)— group;

R 5c is selected from the group consisting hydrogen and C 1 -C 4 alkyl;

R 5d and R 5e are independently selected from the group consisting hydrogen and C 1 -C 4 alkyl; or

R 5d and R 5e taken together with the nitrogen atom to which they are attached form an optionally substituted 4- to 8-membered heterocyclo;

R 5f and R 5g are independently selected from the group consisting hydrogen and C 1 -C 4 alkyl; or

R 5f and R 5g taken together with the nitrogen atom to which they are attached form an optionally substituted 4- to 8-membered heterocyclo;

L is selected from the group consisting of —O—, —S—, and —N(R 7 )—; or L is a bond;

R 7 is selected from the group consisting of hydrogen and C 1 -C 4 alkyl;

R 3 is selected from the group consisting of hydrogen, C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, (amino)C 1 -C 4 alkyl, (hydroxy)C 1 -C 4 alkyl, (alkoxy)C 1 -C 4 alkyl, (carboxamido)C 1 -C 4 alkyl, (optionally substituted heterocyclo)C 1 -C 4 alkyl, (optionally substituted aryl)C 1 -C 4 alkyl, and (optionally substituted hetereoaryl)C 1 -C 4 alkyl;

A is —CH 2 —;

E is —CH 2 —;

E 1 is —CH 2 —;

E 2 is —O—;

Q is selected from the group consisting of ═C(R 10 )— and ═N—;

R 10 is selected from the group consisting of hydrogen, C 1 -C 4 alkyl and C 3 -C 6 cycloalkyl; and

R 11a , R 11b , R 11c , and R 11d are independently selected from the group consisting of hydrogen, halo, cyano, hydroxy, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 3 -C 6 cycloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, and (hydroxy)C 1 -C 4 alkyl,

or a pharmaceutically acceptable salt or solvate thereof.

2. The compound of claim 1 of Formula VIII:

or a pharmaceutically acceptable salt or solvate thereof.

3. The compound of claim 1 of Formula IX:

or a pharmaceutically acceptable salt or solvate thereof.

4. The compound of claim 1 , wherein Q is ═N—; and L is —O—, or a pharmaceutically acceptable salt or solvate thereof.

5. The compound of claim 1 , wherein R 3 is selected from the group consisting of (amino)C 1 -C 4 alkyl, (carboxamido)C 1 -C 4 alkyl, and (optionally substituted heterocyclo)C 1 -C 4 alkyl, or a pharmaceutically acceptable salt or solvate thereof.

6. The compound of claim 1 , wherein R 3 is:

wherein:

X is selected from the group consisting of —O— and —CR 18a R 18b ;

each R 17 is independently selected from the group consisting of halo, C 1 -C 3 alkyl, C 1 -C 3 haloalkyl, and (hydroxyl)C 1 -C 3 alkyl;

R 18a and R 18b are each independently selected from the group consisting of hydrogen, halo, C 1 -C 3 alkyl, C 1 -C 3 haloalkyl, and (hydroxyl)C 1 -C 3 alkyl; or

R 18a and R 18b taken together with the carbon atom to which they are attached form an optionally substituted 3- to 6-membered cycloalkyl;

u is 1, 2, or 3; and

v is 0, 1, or 2,

with the proviso that u is 2 or 3 when X is —O—.

7. The compound of claim 1 , wherein R 3 is selected from the group consisting of:

or a pharmaceutically acceptable salt or solvate thereof.

8. The compound of claim 1 , wherein Z is selected from the group consisting of:

wherein R 2a is —CH 2 CN, or a pharmaceutically acceptable salt or solvate thereof.

9. The compound of claim 1 , wherein R 1 is selected from the group consisting of —C(═O)—CR 4a ═CHR 4b , —C(═O)—CCR 5a , and —S(═O) 2 CH═CHR 4f , or a pharmaceutically acceptable salt or solvate thereof.

10. The compound of claim 1 , wherein R 1 is selected from the group consisting of:

or a pharmaceutically acceptable salt or solvate thereof.

11. A pharmaceutical composition comprising the compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable carrier.

12. The compound of claim 5 , wherein R 3 is (optionally substituted heterocyclo)C 1 -C 4 alkyl, or a pharmaceutically acceptable salt or solvate thereof.

13. The compound of claim 10 , wherein R 1 is:

or a pharmaceutically acceptable salt or solvate thereof.

14. A compound selected from the group consisting of:

or a pharmaceutically acceptable salt or solvate thereof.