Aryl- or heteroaryl-substituted benzene compounds

1. A compound of Formula (I) or a pharmaceutically acceptable salt thereof:

wherein

X 1 is N or CR 11 ;

X 2 is N or CR 13 ;

Z is NR 7 R 8 , OR 7 , S(O) n R 7 , or CR 7 R 8 R 14 , in which n is 0, 1, or 2;

each of R 1 , R 5 , R 9 , and R 10 , independently, is H or C 1 -C 6 alkyl optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, COOH, C(O)O—C 1 -C 6 alkyl, cyano, C 1 -C 6 alkoxyl, amino, mono-C 1 -C 6 alkylamino, di-C 1 -C 6 alkylamino, C 3 -C 8 cycloalkyl, C 6 -C 10 aryl, 4 to 12-membered heterocycloalkyl, and 5- or 6-membered heteroaryl;

each of R 2 , R 3 , and R 4 , independently, is -Q 1 -T 1 , in which Q 1 is a bond or C 1 -C 3 alkyl linker optionally substituted with halo, cyano, hydroxyl or C 1 -C 6 alkoxy, and T 1 is H, halo, hydroxyl, COOH, cyano, or R S1 , in which R S1 is C 1 -C 3 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 alkoxyl, C(O)O—C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, C 6 -C 10 aryl, amino, mono-C 1 -C 6 alkylamino, di-C 1 -C 6 alkylamino, 4 to 12-membered heterocycloalkyl, or 5- or 6-membered heteroaryl, and R S1 is optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, oxo, COOH, C(O)O—C 1 -C 6 alkyl, cyano, C 1 -C 6 alkoxyl, amino, mono-C 1 -C 6 alkylamino, di-C 1 -C 6 alkylamino, C 3 -C 8 cycloalkyl, C 6 -C 10 aryl, 4 to 12-membered heterocycloalkyl, and 5- or 6-membered heteroaryl;

R 6 is C 6 -C 10 aryl or 5- or 6-membered heteroaryl, each of which is optionally substituted with one or more -Q 2 -T 2 , wherein Q 2 is a bond or C 1 -C 3 alkyl linker optionally substituted with halo, cyano, hydroxyl or C 1 -C 6 alkoxy, and T 2 is H, halo, cyano, —OR a , —NR a R b , —(NR a R b R c ) + A − , —C(O)R a , —C(O)OR a , —C(O)NR a R b , —NR b C(O)R a , —NR b C(O)OR a , —S(O) 2 R a , —S(O) 2 NR a R b , or R S2 , in which each of R a , R b , and R c , independently is H or R S3 , A − is a pharmaceutically acceptable anion, each of R S2 and R S3 , independently, is C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, C 6 -C 10 aryl, 4 to 12-membered heterocycloalkyl, or 5- or 6-membered heteroaryl, or R a and R b , together with the N atom to which they are attached, form a 4 to 12-membered heterocycloalkyl ring having 0 or 1 additional heteroatom, and each of R S2 , R S3 , and the 4 to 12-membered heterocycloalkyl ring formed by R a and R b , is optionally substituted with one or more -Q 3 -T 3 , wherein Q 3 is a bond or C 1 -C 3 alkyl linker each optionally substituted with halo, cyano, hydroxyl or C 1 -C 6 alkoxy, and T 3 is selected from the group consisting of halo, cyano, C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, C 6 -C 10 aryl, 4 to 12-membered heterocycloalkyl, 5- or 6-membered heteroaryl, OR d , COOR d , —S(O) 2 R d , —NR d R e , and —C(O)NR d R e , each of R d and R e independently being H or C 1 -C 6 alkyl, or -Q 3 -T 3 is oxo; or any two neighboring -Q 2 -T 2 , together with the atoms to which they are attached form a 5- or 6-membered ring optionally containing 1-4 heteroatoms selected from N, O and S and optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, COOH, C(O)O—C 1 -C 6 alkyl, cyano, C 1 -C 6 alkoxyl, amino, mono-C 1 -C 6 alkylamino, di-C 1 -C 6 alkylamino, C 3 -C 8 cycloalkyl, C 6 -C 10 aryl, 4 to 12-membered heterocycloalkyl, and 5- or 6-membered heteroaryl;

R 7 is -Q 4 -T 4 , in which Q 4 is a bond, C 1 -C 4 alkyl linker, or C 2 -C 4 alkenyl linker, each linker optionally substituted with halo, cyano, hydroxyl or C 1 -C 6 alkoxy, and T 4 is H, halo, cyano, NR f R g , —OR f , —C(O)R f , —C(O)OR f , —C(O)NR f R g , —C(O)NR f OR g , —NR f C(O)R g , —S(O) 2 R f , or R S4 , in which each of R f and R g , independently is H or R S5 , each of R S4 and R S5 , independently is C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 8 cycloalkyl, C 6 -C 10 aryl, 4 to 12-membered heterocycloalkyl, or 5- or 6-membered heteroaryl, and each of R S4 and R S5 is optionally substituted with one or more -Q 5 -T 5 , wherein Q 5 is a bond, C(O), C(O)NR k , NR k C(O), S(O) 2 , or C 1 -C 3 alkyl linker, R k being H or C 1 -C 6 alkyl, and T 5 is H, halo, C 1 -C 6 alkyl, hydroxyl, cyano, C 1 -C 6 alkoxyl, amino, mono-C 1 -C 6 alkylamino, di-C 1 -C 6 alkylamino, C 3 -C 8 cycloalkyl, C 6 -C 10 aryl, 4 to 12-membered heterocycloalkyl, 5- or 6-membered heteroaryl, or S(O) q R q in which q is 0, 1, or 2 and R q is C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 8 cycloalkyl, C 6 -C 10 aryl, 4 to 12-membered heterocycloalkyl, or 5- or 6-membered heteroaryl, and T 5 is optionally substituted with one or more substituents selected from the group consisting of halo, C 1 -C 6 alkyl, hydroxyl, cyano, C 1 -C 6 alkoxyl, amino, mono-C 1 -C 6 alkylamino, di-C 1 -C 6 alkylamino, C 3 -C 8 cycloalkyl, C 6 -C 10 aryl, 4 to 12-membered heterocycloalkyl, and 5- or 6-membered heteroaryl except when T 5 is H, halo, hydroxyl, or cyano; or -Q 5 -T 5 is oxo;

each of R 8 , R 11 , and R 13 , independently, is H, halo, hydroxyl, COOH, cyano, R S6 , OR S6 , or COOR S6 , in which R S6 is C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 8 cycloalkyl, 4 to 12-membered heterocycloalkyl, amino, mono-C 1 -C 6 alkylamino, or di-C 1 -C 6 alkylamino, and R S6 is optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, COOH, C(O)O—C 1 -C 6 alkyl, cyano, C 1 -C 6 alkoxyl, amino, mono-C 1 -C 6 alkylamino, and di-C 1 -C 6 alkylamino; or R 7 and R 8 , together with the N atom to which they are attached, form a 4 to 11-membered heterocycloalkyl ring having 0 to 2 additional heteroatoms, or R 7 and R 8 , together with the C atom to which they are attached, form C 3 -C 8 cycloalkyl or a 4 to 11-membered heterocycloalkyl ring having 1 to 3 heteroatoms, and each of the 4 to 11-membered heterocycloalkyl rings or C 3 -C 8 cycloalkyl formed by R 7 and R 8 is optionally substituted with one or more Q 6 -T 6 , wherein Q 6 is a bond, C(O), C(O)NR m , NR m C(O), S(O) 2 , or C 1 -C 3 alkyl linker, R m being H or C 1 -C 6 alkyl, and T 6 is H, halo, C 1 -C 6 alkyl, hydroxyl, cyano, C 1 -C 6 alkoxyl, amino, mono-C 1 -C 6 alkylamino, di-C 1 -C 6 alkylamino, C 3 -C 8 cycloalkyl, C 6 -C 10 aryl, 4 to 12-membered heterocycloalkyl, 5- or 6-membered heteroaryl, or S(O) p R p in which p is 0, 1, or 2 and R p is C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 8 cycloalkyl, C 6 -C 10 aryl, 4 to 12-membered heterocycloalkyl, or 5- or 6-membered heteroaryl, and T 6 is optionally substituted with one or more substituents selected from the group consisting of halo, C 1 -C 6 alkyl, hydroxyl, cyano, C 1 -C 6 alkoxyl, amino, mono-C 1 -C 6 alkylamino, di-C 1 -C 6 alkylamino, C 3 -C 8 cycloalkyl, C 6 -C 10 aryl, 4 to 12-membered heterocycloalkyl, and 5- or 6-membered heteroaryl except when T 6 is H, halo, hydroxyl, or cyano; or -Q 6 -T 6 is oxo;

R 12 is halo, hydroxyl, COOH, cyano, R S6 , OR S6 , or COOR S6 , in which R S6 is C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 8 cycloalkyl, 4 to 12-membered heterocycloalkyl, amino, mono-C 1 -C 6 alkylamino, or di-C 1 -C 6 alkylamino, and R S6 is optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, COOH, C(O)O—C 1 -C 6 alkyl, cyano, C 1 -C 6 alkoxyl, amino, mono-C 1 -C 6 alkylamino, and di-C 1 -C 6 alkylamino; and

R 14 is absent, H, or C 1 -C 6 alkyl optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, COOH, C(O)O—C 1 -C 6 alkyl, cyano, C 1 -C 6 alkoxyl, amino, mono-C 1 -C 6 alkylamino, di-C 1 -C 6 alkylamino, C 3 -C 8 cycloalkyl, C 6 -C 10 aryl, 4 to 12-membered heterocycloalkyl, and 5- or 6-membered heteroaryl.

2. The compound of claim 1 , wherein R 6 is phenyl substituted with one or more -Q 2 -T 2 .

3. The compound of claim 1 , wherein R 6 is 5- or 6-membered heteroaryl containing 1-3 additional heteroatoms selected from N, O, and S and optionally substituted with one or more -Q 2 -T 2 .

4. The compound of claim 1 , wherein R 7 is C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl or 4 to 12-membered heterocycloalkyl, each optionally substituted with one or more -Q 5 -T 5 .

5. The compound of claim 1 , wherein each of R 1 and R 11 is H and each of R 2 and R 4 , independently is H or C 1 -C 6 alkyl optionally substituted with amino, mono-C 1 -C 6 alkylamino, di-C 1 -C 6 alkylamino, or C 6 -C 10 aryl.

6. The compound of claim 1 , wherein R 12 is methyl, ethyl, ethenyl, or halo; and R 8 is H, methyl, or ethyl.

7. The compound of claim 1 , wherein X 1 is CR 11 and X 2 is CR 13 .

8. The compound of claim 1 , wherein X 1 is CR 11 and X 2 is N.

9. The compound of claim 1 , wherein X 1 is N and X 2 is CR 13 .

10. The compound of claim 1 , wherein X 1 is N and X 2 is N.

11. The compound of claim 1 , wherein Z is NR 7 R 8 .

12. The compound of claim 1 , wherein Z is CR 7 R 8 R 14 .

13. The compound of claim 1 , wherein Z is OR 7 .

14. The compound of claim 1 , wherein Z is SR 7 .

15. A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

16. The compound of claim 1 , wherein R 6 is C 6 -C 10 aryl or 5- or 6-membered heteroaryl, each of which is unsubstituted or substituted with one or more -Q 2 -T 2 , in which Q 2 is a bond or methyl or ethyl linker and T 2 is H, halo, —OR a , —NR a R b , —(NR a R b R c ) + A − , —S(O) 2 R a , or —S(O) 2 NR a R b .

17. The compound of claim 1 , wherein the compound is of Formula (Ig) or a pharmaceutically acceptable salt thereof:

in which R 6 is phenyl or 5- or 6-membered heteroaryl, each of which is unsubstituted or substituted with one or more -Q 2 -T 2 , in which Q 2 is a bond or C 1 -C 3 alkyl linker optionally substituted with halo or hydroxyl, and T 2 is H, halo, —OR a , —NR a R b , —(NR a R b R c ) + A − , —S(O) 2 R a , or —S(O) 2 NR a R b , and R 7 is piperidinyl, tetrahydropyran, cyclopentyl, or cyclohexyl, each optionally substituted with one -Q 5 -T 5 .

18. The compound of claim 17 , wherein R 6 is phenyl or 5- or 6-membered heteroaryl, each of which is unsubstituted or substituted with one or more -Q 2 -T 2 , in which Q 2 is a bond or methyl linker, and T 2 is —OR a , —NR a R b , —(NR a R b R c ) + A − , or —S(O) 2 R a .

19. The compound of claim 17 , wherein Q 5 is a bond and T 5 is amino, mono-C 1 -C 6 alkylamino, di-C 1 -C 6 alkylamino.

20. The compound of claim 17 , wherein R 6 is phenyl or 5- or 6-membered heteroaryl, each of which is unsubstituted or substituted with one or more -Q 2 -T 2 , in which Q 2 is a bond or methyl linker, and T 2 is —OR a or —S(O) 2 R a , in which R a is H or C 1 -C 6 alkyl optionally substituted with one or more -Q 3 -T 3 .