Substituted 6,5-fused bicyclic heteroaryl compounds

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

wherein

X 1 is NR 7 or CR 7 ;

X 2 is N, NR 8 , CR 8 , O, or S;

X 3 is NR 8 , CR 8 , O, or S;

X 4 is C;

Y 1 is CH;

Y 2 is CR 6 ;

Y 3 is N;

each of 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 R 6 independently is H, halo, OR a , —NR a R b , —C(O)R a , —C(O)OR a , —C(O)NR a R b , —NR b C(O)R a , —S(O) 2 R a , —S(O) 2 NR a R b , or R S2 , in which each of R a and R b , independently is H or R S3 and each of R S2 and R S3 , 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 7-membered heterocycloalkyl, or 5 to 6-membered heteroaryl; or R a and R b , together with the N atom to which they are attached, form a 4 to 7-membered heterocycloalkyl ring having 0 or 1 additional heteroatoms to the N atom; and each of R S2 , R S3 , and the 4 to 7-membered heterocycloalkyl ring containing R a and R b , is optionally substituted with one or more -Q 2 -T 2 , wherein Q 2 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 2 is H, halo, cyano, —OR c , —NR c R d , —(NR c R d R d′ ) + A − , —C(O)R c , —C(O)OR c , —C(O)NR c R d , —NR d C(O)R c , —NR d C(O)OR c , —S(O) 2 R c , —S(O) 2 NR c R d , or R S4 , in which each of R c , R d , and R d′ , independently is H or R S5 , A − is a pharmaceutically acceptable anion, each of R S4 and R S5 , independently, is C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, C 6 -C 10 aryl, 4 to 7-membered heterocycloalkyl, or 5 to 6-membered heteroaryl, or R c and R d , together with the N atom to which they are attached, form a 4 to 7-membered heterocycloalkyl ring having 0 or 1 additional heteroatoms to the N atom, and each of R S4 , R S5 , and the 4 to 7-membered heterocycloalkyl ring containing R c and R d , 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 H, halo, cyano, C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, C 6 -C 10 aryl, 4 to 7-membered heterocycloalkyl, 5 to 6-membered heteroaryl, OR e , COOR e , —S(O) 2 R e , —NR e R f , and —C(O)NR e R f , each of R e and R f independently being H or C 1 -C 6 alkyl optionally substituted with OH, O—C 1 -C 6 alkyl, or NH—C 1 -C 6 alkyl; or -Q 3 -T 3 is oxo; or -Q 2 -T 2 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 7-membered heterocycloalkyl, and 5 to 6-membered heteroaryl; provided that -Q 2 -T 2 is not H;

each R 7 independently 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 g R h , —OR g , —C(O)R g , —C(O)OR g , —C(O)NR g R h , —C(O)NR g OR h , —NR g C(O)R h , —S(O) 2 R g , or R S6 , in which each of R g and R h , independently is H or R S7 , each of R S6 and R S7 , independently is C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, C 6 -C 10 aryl, 4 to 7-membered heterocycloalkyl, or 5 to 6-membered heteroaryl, and each of R S6 and R S7 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), NR k , S(O) 2 , NR k 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, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, 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 7-membered heterocycloalkyl, or 5 to 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 7-membered heterocycloalkyl, and 5 to 6-membered heteroaryl except when T 5 is H, halo, hydroxyl, or cyano; or Q 5 -T 5 is oxo; provided that -Q 4 -T 4 is not H; and

each R 8 independently is H, halo, hydroxyl, COOH, cyano, R S8 , OR S8 , or COOR S8 , in which R S8 is C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, amino, mono-C 1 -C 6 alkylamino, or di-C 1 -C 6 alkylamino, and R S8 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;

X is a monocyclic or bicyclic 5 to 10-membered saturated, unsaturated, or aromatic ring containing 2-4 heteroatom ring members and optionally substituted with one or more -Q 7 -T 7 , wherein Q 7 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 7 is H, —OR n , —NR n R r , —C(O)R n , —C(O)OR n , —C(O)NR n R r , —S(O) 2 R n , —S(O) 2 NR n R r , or R S9 , in which each of R n and R r , independently is H or R S10 , each of R S9 and R S10 , 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 n and R r , 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 S9 , R S10 , and the 4 to 12-membered heterocycloalkyl ring formed by R n and R r , is optionally substituted with one or more -Q 8 -T 8 , wherein Q 8 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 8 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 s , COOR s , —S(O) 2 R s , —NR s R t , and —C(O)NR s R t , each of R s and R t independently being H or C 1 -C 6 alkyl, or -Q 8 -T 8 is oxo; or -Q 7 -T 7 is oxo; or any two neighboring -Q 7 -T 7 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; and

n is 3, 4, or 5;

provided that at most one of X 2 and X 3 is O or S, at least one of X 1 , X 2 , X 3 , X 4 , Y 2 , and Y 3 is N or NR 7 , and X 1 , X 2 , X 3 , X 4 , Y 1 , Y 2 , and Y 3 are assigned such that the

moiety in Formula (I) is a bicyclic heteroaryl system.

2. The compound of claim 1 , wherein the compound is of Formula (Ia):

wherein R 7 is -Q 4 -T 4 , wherein Q 4 is a bond or methyl linker, T 4 is C 1 -C 6 alkyl optionally substituted with one or more -Q 5 -T 5 , C 3 -C 8 cycloalkyl optionally substituted with one or more -Q 5 -T 5 , or 4- to 14-membered heterocycloalkyl optionally substituted with one or more -Q 5 -T 5 .

3. The compound of claim 2 , wherein R 7 is tetrahydropyranyl, piperidine substituted by 1, 2, or 3 C 1-4 alkyl groups, or cyclohexyl substituted by N(C 1-4 alkyl) 2 wherein one or both of the C 1-4 alkyl is optionally substituted with C 1-6 alkoxyl.

4. The compound of claim 1 , wherein R 7 is sec-butyl, cyclopentyl, or iso-propyl.

5. The compound claim 1 , wherein R 6 is

6. The compound of claim 1 , wherein X is

wherein

each of D 1 , D 2 , and D 3 , independently, is CR 901 or N, provided that at least one of D 1 , D 2 , and D 3 is N;

D 4 is O, S, or NR 902 ; and

each R 901 and R 902 , independently, is -Q 7 -T 7 , wherein Q 7 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 7 is H, —OR n , —NR n R r , —C(O)R n , —C(O)OR n , —C(O)NR n R r , —S(O) 2 R n , —S(O) 2 NR n R r , or R S9 , in which each of R n and R r , independently is H or R S10 , each of R S9 and R S10 , independently, is C 1 -C 8 alkyl, C 3 -C 8 cycloalkyl, C 8 -C 10 aryl, 4 to 12-membered heterocycloalkyl, or 5- or 6-membered heteroaryl, or R n and R r , 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 S9 , R S10 , and the 4 to 12-membered heterocycloalkyl ring formed by R n and R r , is optionally substituted with one or more -Q 8 -T 8 , wherein Q 8 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 8 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 s , COOR s , —S(O) 2 R s , —NR s R t , and —C(O)NR s R t , each of R s and R t independently being H or C 1 -C 6 alkyl, or -Q 8 -T 8 is oxo; or -Q 7 -T 7 is oxo; or any two neighboring -Q 7 -T 7 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.

7. The compound of claim 1 , wherein X is

wherein

each of E 1 , E 2 , and E 4 , independently, is CR 903 or N, provided that at least one of E 1 , E 2 , and E 4 is N;

E 3 is O, S, or NR 904 ; and

each of R 903 and R 904 , independently, is -Q 7 -T 7 , wherein Q 7 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 7 is H, —OR n , —NR n R r , —C(O)R n , —C(O)OR n , —C(O)NR n R r , —S(O) 2 R n , —S(O) 2 NR n R r , or R S9 , in which each of R n and R r , independently is H or R S10 , each of R S9 and R S10 , 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 n and R r , 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 S9 , R S10 , and the 4 to 12-membered heterocycloalkyl ring formed by R n and R r , is optionally substituted with one or more -Q 8 -T 8 , wherein Q 8 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 8 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 s , COOR s , —S(O) 2 R s , —NR s R t , and —C(O)NR s R t , each of R s and R t independently being H or C 1 -C 6 alkyl, or -Q 8 -T 8 is oxo; or -Q 7 -T 7 is oxo; or any two neighboring -Q 7 -T 7 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.

8. The compound of claim 1 , wherein X is

wherein

G 1 is O, S, or NR 907 ;

each of G 2 , G 3 , and G 4 , independently, is N or CR 908 , provided that at least one of G 2 , G 3 , and G 4 is N; and

each of R 905 , R 906 , R 907 , and R 908 , independently, is -Q 7 -T 7 , wherein Q 7 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 7 is H, —OR n , —NR n R r -C(O)R n , —C(O)OR n , —C(O)NR n R r , —S(O) 2 R n , —S(O) 2 NR n R r , or R S9 , in which each of R n and R r , independently is H or R S10 , each of R S9 and R S10 , 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 n and R r , 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 S9 , R S10 , and the 4 to 12-membered heterocycloalkyl ring formed by R n and R r , is optionally substituted with one or more -Q 8 -T 8 , wherein Q 8 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 8 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 s , COOR s , —S(O) 2 R s , —NR s R t , and —C(O)NR s R t , each of R s and R t independently being H or C 1 -C 6 alkyl, or -Q 8 -T 8 is oxo; or -Q 7 -T 7 is oxo; or any two neighboring -Q 7 -T 7 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.

9. The compound of claim 1 , wherein X is

wherein

each of J 1 , J 2 , J 3 , and J 4 , independently, is N or CR 911 , provided that at least one of J 1 , J 2 , J 3 , and J 4 is N; and

each of R 909 , R 910 , and R 911 , independently, is -Q 7 -T 7 , wherein Q 7 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 7 is H, —OR n , —NR n R r , —C(O)R n , —C(O)OR n , —C(O)NR n R r , —S(O) 2 R n , —S(O) 2 NR n R r , or R S9 , in which each of R n and R r , independently is H or R S10 , each of R S9 and R S10 , 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 n and R r , 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 S9 , R S10 , and the 4 to 12-membered heterocycloalkyl ring formed by R n and R r , is optionally substituted with one or more -Q 8 -T 8 , wherein Q s 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 8 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 s , COOR s , —S(O) 2 R s , —NR s R t , and —C(O)NR s R t , each of R s and R t independently being H or C 1 -C 6 alkyl, or -Q 8 -T 8 is oxo; or -Q 7 -T 7 is oxo; or any two neighboring -Q 7 -T 7 together with the atoms to which they are attached forma 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.

10. The compound of claim 1 , wherein X is

wherein

each of K 1 , K 2 , K 3 , and K 4 , independently, is N or CR 914 , provided that at least one of K 1 , K 2 , K 3 , and K 4 is N; and

each of R 912 , R 913 , and R 914 , independently, is -Q 7 -T 7 , wherein Q 7 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 7 is H, —OR n , —NR n R r , —C(O)R n , —C(O)OR n , —C(O)NR n R r , —S(O) 2 R n , —S(O) 2 NR n R r , or R S9 , in which each of R n and R r , independently is H or R S10 , each of R S9 and R S10 , 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 n and R r , 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 S9 , R S10 , and the 4 to 12-membered heterocycloalkyl ring formed by R n and R r , is optionally substituted with one or more -Q 8 -T 8 , wherein Q 8 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 8 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 s , COOR s , —S(O) 2 R s , —NR s R t , and —C(O)NR s R t , each of R s and R t independently being H or C 1 -C 6 alkyl, or -Q 8 -T 8 is oxo; or -Q 7 -T 7 is oxo; or any two neighboring -Q 7 -T 7 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.

11. The compound of claim 1 , wherein X is

wherein

each of U 1 , U 3 , and U 4 , independently, is N or CR 917 , provided that at least one of U 1 , U 3 , and U 4 is N;

U 2 is O, S, or NR 918 ; and

each of R 915 , R 916 , R 917 and R 918 , independently, is -Q 7 -T 7 , wherein Q 7 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 7 is H, —OR n , —NR n R r , —C(O)R n , —C(O)OR n , —C(O) NR n R r , —S(O) 2 R n , —S(O) 2 NR n R r , or R S9 , in which each of R n and R r , independently is H or R S10 , each of R S9 and R S10 , 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 n and R r , 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 S9 , R S10 , and the 4 to 12-membered heterocycloalkyl ring formed by R n and R r , is optionally substituted with one or more -Q 8 -T 8 , wherein Q s 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 8 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 s , COOR s , —S(O) 2 R s , —NR s R t , and —C(O)NR s R t , each of R s and R t independently being H or C 1 -C 6 alkyl, or -Q 8 -T 8 is oxo; or -Q 7 -T 7 is oxo; or any two neighboring -Q 7 -T 7 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.

12. The compound of claim 1 , wherein X is

wherein

each of V 1 and V 2 , independently, is N or CR 919 , provided that at least one of V 1 and V 2 is N; V 3 is O, S, or NR 920 ;

each of V 4 , V 5 , and V 6 is O, S, or NR 921 , or CR 922 R 923 ; and

each of R 919 , R 920 , R 921 , R 922 , and R 923 , independently, is -Q 7 -T 7 , wherein Q 7 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 7 is H, —OR n , —NR n R r , —C(O)R n , —C(O)OR n , —C(O) NR n R r , —S(O) 2 R n , —S(O) 2 NR n R r , or R S9 , in which each of R n and R r , independently is H or R S10 , each of R S9 and R S10 , 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 n and R r , 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 S9 , R S10 , and the 4 to 12-membered heterocycloalkyl ring formed by R n and R r , is optionally substituted with one or more -Q 8 -T 8 , wherein Q 8 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 8 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 s , COOR s , —S(O) 2 R s , —NR s R t , and —C(O)NR s R t , each of R s and R t independently being H or C 1 -C 6 alkyl, or -Q 8 -T 8 is oxo; or -Q 7 -T 7 is oxo; or any two neighboring -Q 7 -T 7 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.

13. The compound of claim 1 , wherein X is imidazol-2-yl, imidazol-4-yl, triazol-3-yl, 3H-imidazo[4,5-c]pyridin-7-yl, 1H-benzo[d]imidazol-4-yl, 1H-indazol-7-yl, isoxazol-3-yl, thiazol-2-yl, 1H-pyrazolo[4,3-c]pyridin-7-yl, imidazo[1,2-a]pyridin-8-yl, imidazo[1,2-c]pyrimidin-8-yl, 1,4,6,7-tetrahydropyrano[4,3-c]pyrazol-7-yl, 1,4,6,7-tetrahydropyrano[3,4-]imidazol-7-yl, or 4,5,6,7-tetrahydro-1H-benzo[d]imidazol-4-yl.

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

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

wherein

X 1 is NR 7 or CR 7 ;

X 2 is N, NR 8 , CR 8 , O, or S;

X 3 is NR 8 , CR 8 , O, or S;

X 4 is C;

Y 1 is CH;

Y 2 is CR 6 ;

Y 3 is N;

each of 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 R 6 independently is H, halo, OR a , —NR a R b , —C(O)R a , —C(O)OR a , —C(O)NR a R b , —NR b C(O)R a , —S(O) 2 R a , —S(O) 2 NR a R b , or R S2 , in which each of R a and R b , independently is H or R S3 and each of R S2 and R S3 , 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 7-membered heterocycloalkyl, or 5 to 6-membered heteroaryl; or R a and R b , together with the N atom to which they are attached, form a 4 to 7-membered heterocycloalkyl ring having 0 or 1 additional heteroatoms to the N atom; and each of R S2 , R S3 , and the 4 to 7-membered heterocycloalkyl ring containing R a and R b , is optionally substituted with one or more -Q 2 -T 2 , wherein Q 2 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 2 is H, halo, cyano, —OR c , —NR c R d , —(NR c R d R d′ ) + A − , —C(O)R c , —C(O)OR cc , —C(O)NR c R d , —NR d C(O)R c , —NR d C(O)OR c , —S(O) 2 R c , —S(O) 2 NR c R d , or R S4 , in which each of R c , R d , and R d′ , independently is H or R S5 , A − is a pharmaceutically acceptable anion, each of R S4 and R S5 , independently, is C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, C 6 -C 10 aryl, 4 to 7-membered heterocycloalkyl, or 5 to 6-membered heteroaryl, or R c and R d , together with the N atom to which they are attached, form a 4 to 7-membered heterocycloalkyl ring having 0 or 1 additional heteroatoms to the N atom, and each of R S4 , R S5 , and the 4 to 7-membered heterocycloalkyl ring containing R c and R d , 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 H, halo, cyano, C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, C 6 -C 10 aryl, 4 to 7-membered heterocycloalkyl, 5 to 6-membered heteroaryl, OR e , COOR e , —S(O) 2 R e , —NR e R f , and —C(O)NR e R f , each of R e and R f independently being H or C 1 -C 6 alkyl optionally substituted with OH, O—C 1 -C 6 alkyl, or NH—C 1 -C 6 alkyl; or -Q 3 -T 3 is oxo; or -Q 2 -T 2 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 7-membered heterocycloalkyl, and 5 to 6-membered heteroaryl; provided that -Q 2 -T 2 is not H;

each R 7 independently 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 g R h , —OR g , —C(O)R g , —C(O)OR g , —C(O)NR g R h , —C(O)NR g OR h , —NR g C(O)R h , —S(O) 2 R g , or R S6 , in which each of R g and R h , independently is H or R S7 , each of R S6 and R S7 , independently is C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, C 6 -C 10 aryl, 4 to 7-membered heterocycloalkyl, or 5 to 6-membered heteroaryl, and each of R S5 and R S7 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), NR k , S(O) 2 , NR k 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, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, 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 7-membered heterocycloalkyl, or 5 to 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 7-membered heterocycloalkyl, and 5 to 6-membered heteroaryl except when T 5 is H, halo, hydroxyl, or cyano; or -Q 5 -T 5 is oxo; provided that -Q 4 -T 4 is not H; and

each R 8 independently is H, halo, hydroxyl, COOH, cyano, R S8 , OR S8 , or COOR S8 , in which R S8 is C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, amino, mono-C 1 -C 6 alkylamino, or di-C 1 -C 6 alkylamino, and R S8 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;

X is a bicyclic 5 to 10-membered saturated, unsaturated, or aromatic ring containing 2-4 heteroatom ring members and optionally substituted with one or more -Q 7 -T 7 , wherein Q 7 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 7 is H, —OR n , —NR n R r , —C(O)R n , —C(O)Ok, —C(O)NR n R r , —S(O) 2 R n , —S(O) 2 NR n R r , or R S9 , in which each of R n and R r , independently is H or R S10 , each of R S9 and R S10 , 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 n and R r , 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 S9 , R S10 , and the 4 to 12-membered heterocycloalkyl ring formed by R n and R r , is optionally substituted with one or more -Q 8 -T 8 , wherein Q 8 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 8 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 s , COOR s , —S(O) 2 R s , —NR s R t , and —C(O)NR s R t , each of R s and R t independently being H or C 1 -C 6 alkyl, or -Q 8 -T 8 is oxo; or -Q 7 -T 7 is oxo; or any two neighboring -Q 7 -T 7 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; and

n is 0, 1, 2, 3, 4, or 5;

provided that at most one of X 2 and X 3 is O or S, at least one of X 1 , X 2 , X 3 , X 4 , Y 2 , and Y 3 is N or NR 7 , and X 1 , X 2 , X 3 , X 4 , Y 1 , Y 2 , and Y 3 are assigned such that the

moiety in Formula (I) is a bicyclic heteroaryl system.

16. The compound of claim 15 , wherein X is

wherein

G 1 is O, S, or NR 907 ;

each of G 2 , G 3 , and G 4 , independently, is N or CR 908 , provided that at least one of G 2 , G 3 , and G 4 is N; and

each of R 905 , R 906 , R 907 , and R 908 , independently, is -Q 7 -T 7 , wherein Q 7 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 7 is H, —OR n , —NR n R r , —C(O)R n , —C(O)OR n , —C(O)NR n R r , —S(O) 2 R n , —S(O) 2 NR n R r , or R S9 , in which each of R n and R r , independently is H or R S10 , each of R S9 and R S10 , 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 n and R r , 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 S9 , R S10 , and the 4 to 12-membered heterocycloalkyl ring formed by R n and R r , is optionally substituted with one or more -Q 8 -T 8 , wherein Q s 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 8 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 s , COOR s , —S(O) 2 R s , —NR s R t , and —C(O)NR s R t , each of R s and R t independently being H or C 1 -C 6 alkyl, or -Q 8 -T 8 is oxo; or -Q 7 -T 7 is oxo; or any two neighboring -Q 7 -T 7 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 5 alkylamino, C 3 -C 8 cycloalkyl, C 6 -C 10 aryl, 4 to 12-membered heterocycloalkyl, and 5- or 6-membered heteroaryl.

17. The compound of claim 15 , wherein X is

wherein

each of J 1 , J 2 , J 3 , and J 4 , independently, is N or CR 911 , provided that at least one of J 1 , J 2 , J 3 , and J 4 is N; and

each of R 909 , R 910 , and R 911 , independently, is -Q 7 -T 7 , wherein Q 7 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 7 is H, —OR n , —NR n R r , —C(O)R n , —C(O)OR n , —C(O)NR n R r , —S(O) 2 R n , —S(O) 2 NR n R r , or R S9 , in which each of R n and R r , independently is H or R S10 , each of R S9 and R S10 , 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 n and R r , 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 S9 , R S10 , and the 4 to 12-membered heterocycloalkyl ring formed by R n and R r , is optionally substituted with one or more -Q 8 -T 8 , wherein Q s is a bond or C 1 -C 3 alkyl linker each optionally substituted with halo, cyano, hydroxyl or C 1 -C 5 alkoxy, and T 8 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 s , COOR s , —S(O) 2 R s , —NR s R t , and —C(O)NR s R t , each of R s and R t independently being H or C 1 -C 6 alkyl, or -Q 8 -T 8 is oxo; or -Q 7 -T 7 is oxo; or any two neighboring -Q 7 -T 7 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.

18. The compound of claim 15 , wherein X is

wherein

each of K 1 , K 2 , K 3 , and K 4 , independently, is N or CR 914 , provided that at least one of K 1 , K 2 , K 3 , and K 4 is N; and

each of R 912 , R 913 , and R 914 , independently, is -Q 7 -T 7 , wherein Q 7 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 7 is H, —OR n , —NR n R r , —C(O)R n , —C(O)OR n , —C(O)NR n R r , —S(O) 2 R n , —S(O) 2 NR n R r , or R S9 , in which each of R n and R r , independently is H or R S10 , each of R S9 and R S10 , 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 n and R r , 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 S9 , R S10 , and the 4 to 12-membered heterocycloalkyl ring formed by R n and R r , is optionally substituted with one or more -Q 8 -T 8 , wherein Q 8 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 8 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 s , COOR s , —S(O) 2 R s , —NR s R t , and —C(O)NR s R t , each of R s and R t independently being H or C 1 -C 6 alkyl, or -Q 8 -T 8 is oxo; or -Q 7 -T 7 is oxo; or any two neighboring -Q 7 -T 7 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.

19. The compound of claim 15 , wherein X is

wherein

each of U 1 , U 3 , and U 4 , independently, is N or CR 917 , provided that at least one of U 1 , U 3 , and U 4 is N;

U 2 is O, S, or NR 918 ; and

each of R 915 , R 916 , R 917 and R 918 , independently, is -Q 7 -T 7 , wherein Q 7 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 7 is H, —OR n , —NR n R r , —C(O)R n , —C(O)OR n , —C(O) NR n R r , —S(O) 2 R n , —S(O) 2 NR n R r , or R S9 , in which each of R n and R r , independently is H or R S10 , each of R S9 and R S10 , 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 n and R r , 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 S9 , R S10 , and the 4 to 12-membered heterocycloalkyl ring formed by R n and R r , is optionally substituted with one or more -Q 8 -T 8 , wherein Q 8 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 8 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 s , COOR s , —S(O) 2 R s , —NR s R t , and —C(O)NR s R t , each of R s and R t independently being H or C 1 -C 6 alkyl, or -Q 8 -T 8 is oxo; or -Q 7 -T 7 is oxo; or any two neighboring -Q 7 -T 7 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.

20. The compound of claim 15 , wherein X is

wherein

each of V 1 and V 2 , independently, is N or CR 919 , provided that at least one of V 1 and V 2 is N; V 3 is O, S, or NR 920 ;

each of V 4 , V 5 , and V 6 is O, S, or NR 921 , or CR 922 R 923 ; and

each of R 919 , R 920 , R 921 , R 922 , and R 923 , independently, is -Q 7 -T 7 , wherein Q 7 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 7 is H, —OR n , —NR n R r , —C(O)R n , —C(O)OR n , —C(O) NR n R r , —S(O) 2 R n , —S(O) 2 NR n R r , or R S9 , in which each of R n and R r , independently is H or R S10 , each of R S9 and R S10 , 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 n and R r , 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 S9 , R S10 , and the 4 to 12-membered heterocycloalkyl ring formed by R n and R r , is optionally substituted with one or more -Q 8 -T 8 , wherein Q 8 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 8 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 s , COOR s , —S(O) 2 R s , —NR s R t , and —C(O)NR s R t , each of R s and R t independently being H or C 1 -C 6 alkyl, or -Q 8 -T 8 is oxo; or -Q 7 -T 7 is oxo; or any two neighboring -Q 7 -T 7 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.