AMINE-SUBSTITUTED HETEROCYCLIC COMPOUNDS AS EHMT2 INHIBITORS AND METHODS OF USE THEREOF

1 . A compound of Formula (I0), (II0), (III0), or (IV0):

or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein

X 1 is N or CR 2 ;

X 2 is N or CR 3 ;

X 3 is N or CR 4 ;

X 4 is N or CR 5 ;

X 5 is N or CH;

X 6 is N or CR 15 ;

X 7 is N or CH;

X 8 is NR 13 or CR 11 R 12 ;

one of X 13 and X 14 independently is NR 8 R 9 , and the other is R 10 ;

B is C 6 -C 10 aryl or 5- to 10-membered heteroaryl optionally substituted with one or more R 15 ;

R 1 is H or C 1 -C 4 alkyl;

each of R 2 , R 3 , R 4 , and R 5 , independently is selected from the group consisting of H, halo, cyano, C 1 -C 6 alkoxyl, C 6 -C 10 aryl, OH, NR a R b , C(O)NR a R b , NR a C(O)R b , C(O)OR a , OC(O)R a , OC(O)NR a R b , NR a C(O)OR b , C 3 -C 8 cycloalkyl, 4- to 7-membered heterocycloalkyl, 5- to 6-membered heteroaryl, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, and C 2 -C 6 alkynyl, wherein the C 6 -C 10 aryl, C 3 -C 8 cycloalkyl, 4- to 7-membered heterocycloalkyl, 5- to 6-membered heteroaryl, C 1 -C 6 alkoxyl, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, and C 2 -C 6 alkynyl, are each optionally substituted with one or more of halo, OR a , or NR a R b , in which each of R a and R b independently is H or C 1 -C 6 alkyl;

R 6 is -Q 5 -T 5 , in which Q 1 is a bond, or C 1 -C 6 alkylene, C 2 -C 6 alkenylene, or C 2 -C 6 alkynylene linker each optionally substituted with one or more of halo, cyano, hydroxyl, oxo, or C 1 -C 6 alkoxyl, and T 1 is H, halo, cyano, or R St , in which R S1 is C 3 -C 8 cycloalkyl, phenyl, 4- to 12-membered heterocycloalkyl containing 1-4 heteroatoms selected from N, O, and S, or a 5- or 6-membered heteroaryl and R S1 is optionally substituted with one or more of halo, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, hydroxyl, oxo, —C(O)R c , —C(O)OR c , —SO 2 R c , —SO 2 N(R) 2 , —NR c C(O)R d , —C(O)NR c R d , —NR c C(O)OR d , —OC(O)NR c R d , NR c R d , or C 1 -C 6 alkoxyl, in which each of R c and R d independently is H or C 1 -C 6 alkyl;

R 7 is -Q 2 -T 2 , in which Q 2 is a bond, C(O)NR e , or NR e C(O), R being H or C 1 -C 6 alkyl and T 2 is 5- to 10-membered heteroaryl or 4- to 12-membered heterocycloalkyl, and wherein the 5- to 10-membered heteroaryl or 4- to 12-membered heterocycloalkyl is optionally substituted with one or more -Q 3 -T 3 , wherein each Q 3 independently is a bond or C 1 -C 3 alkylene linker each optionally substituted with one or more of halo, cyano, hydroxyl, or C 1 -C 6 alkoxy, and each T 3 independently is selected from the group consisting of H, halo, cyano, 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 containing 1-4 heteroatoms selected from N, O, and S, 5- to 6-membered heteroaryl, OR f , C(O)R f , C(O)OR f , OC(O)R f , S(O) 2 R f , NR f R g , OC(O)NR f R g , NR f C(O)OR g , C(O)NR f R g , and NR f C(O)R g , each of R f and R g independently being H, C 3 -C 8 cycloalkyl, or C 1 -C 6 alkyl optionally substituted with C 3 -C 8 cycloalkyl, in which the C 3 -C 8 cycloalkyl, C 6 -C 10 aryl, 4- to 7-membered heterocycloalkyl or 5- to 6-membered heteroaryl is optionally substituted with one or more halo, cyano, hydroxyl, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, or C 1 -C 6 alkoxy; or -Q 3 -T 3 is oxo;

R 8 is H or C 1 -C 6 alkyl;

R 9 is -Q 4 -T 4 , in which Q 4 is a bond or C 1 -C 6 alkylene, C 2 -C 6 alkenylene, or C 2 -C 6 alkynylene linker each optionally substituted with one or more of halo, cyano, hydroxyl, or C 1 -C 6 alkoxyl, and T 1 is H, halo, OR h , NR h R i , NR h C(O)R i , C(O)NR h R i , C(O)R h , C(O)OR h , NR j C(O)OR i , OC(O)NR h R i , S(O) 2 R h , S(O) 2 NR h R i , or R S2 , in which each of R h and R i independently is H or C 1 -C 6 alkyl, and R S2 is C 3 -C 8 cycloalkyl, C 6 -C 10 aryl, 4- to 12-membered heterocycloalkyl containing 1-4 heteroatoms selected from N, O, and S, or a 5- to 10-membered heteroaryl, and R S2 is optionally substituted with one or more -Q 5 -T 5 , wherein each Q 1 independently is a bond or C 1 -C 3 alkylene linker each optionally substituted with one or more of halo, cyano, hydroxyl, or C 1 -C 6 alkoxy, and each T 5 independently is selected from the group consisting of H, halo, cyano, 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 containing 1-4 heteroatoms selected from N, O, and S, 5- to 6-membered heteroaryl, OR j , C(O)R j , C(O)OR j , OC(O)R j , S(O) 2 j R, NR j R k , OC(O)NR j R k , NR j C(O)OR k , C(O)NR j R k , and NR j C(O)R k , each of R j and R k independently being H or C 1 -C 6 alkyl; or -Q 5 -T 5 is oxo;

R 10 is halo, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 8 cycloalkyl, or 4- to 12-membered heterocycloalkyl containing 1-4 heteroatoms selected from N, O, and S, wherein each of the C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 8 cycloalkyl, and 4- to 12-membered heterocycloalkyl is optionally substituted with one or more halo, cyano, hydroxyl, oxo, amino, mono- or di-alkylamino, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 alkoxy, C(O)NR j R k , or NR j C(O)R k ;

R 11 and R 12 together with the carbon atom to which they are attached form a C 3 -C 12 cycloalkyl or 4- to 12-membered heterocycloalkyl containing 1-4 heteroatoms selected from N, O, and S, wherein the C 3 -C 12 cycloalkyl or 4- to 12-membered heterocycloalkyl is optionally substituted with one or more of halo, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, hydroxyl, oxo, amino, mono- or di-alkylamino, or C 1 -C 6 alkoxyl;

R 13 is H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 12 cycloalkyl, or 4- to 12-membered heterocycloalkyl containing 1-4 heteroatoms selected from N, O, and S;

R 14 is H, halo, cyano, P(O)R l R m , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 12 cycloalkyl, 4- to 7-membered heterocycloalkyl, 5- to 6-membered heteroaryl, or —OR 6 , wherein the C 1 -C 6 alkyl, C 2 -C 6 alkenyl, or C 2 -C 6 alkynyl is optionally substituted with one or more of halo or OR 6 , and each of R l and R m independently is C 1 -C 6 alkyl; and

R is is H, halo, cyano, or —OR 6 .

2 . The compound of claim 1 , being of Formula (I), (II), or (III):

or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein

X 1 is N or CR 2 ;

X 2 is N or CR 3 ;

X 3 is N or CR 4 ;

X 4 is N or CR 5 ;

X 5 is N or CH;

X 6 is N or CR 15 ;

X 7 is N or CH;

one of X 13 and X 14 independently is NR 8 R 9 , and the other is R 10 ;

B is C 6 -C 10 aryl or 5- to 10-membered heteroaryl optionally substituted with one or more R 15 ;

R 1 is H or C 1 -C 4 alkyl;

each of R 2 , R 3 , R 4 , and R 5 , independently is selected from the group consisting of H, halo, cyano, C 1 -C 6 alkoxyl, C 6 -C 10 aryl, OH, NR a R b , C(O)NR a R b , NR a C(O)R b , C(O)OR a , OC(O)R a , OC(O)NR a R b , NR a C(O)OR b , C 3 -C 8 cycloalkyl, 4- to 7-membered heterocycloalkyl, 5- to 6-membered heteroaryl, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, and C 2 -C 6 alkynyl, wherein the C 6 -C 10 aryl, C 3 -C 8 cycloalkyl, 4- to 7-membered heterocycloalkyl, 5- to 6-membered heteroaryl, C 1 -C 6 alkoxyl, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, and C 2 -C 6 alkynyl, are each optionally substituted with one or more of halo, OR a , or NR a R b , in which each of R a and R b independently is H or C 1 -C 6 alkyl;

R 6 is -Q 1 -T 1 , in which Q 1 is a bond, or C 1 -C 6 alkylene, C 2 -C 6 alkenylene, or C 2 -C 6 alkynylene linker each optionally substituted with one or more of halo, cyano, hydroxyl, oxo, or C 1 -C 6 alkoxyl, and T 1 is H, halo, cyano, or R S1 , in which R S1 is C 3 -C 8 cycloalkyl, phenyl, 4- to 12-membered heterocycloalkyl containing 1-4 heteroatoms selected from N, O, and S, or a 5- or 6-membered heteroaryl and R S1 is optionally substituted with one or more of halo, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, hydroxyl, oxo, —C(O)R c , —C(O)OR c , —SO 2 R c , —SO 2 N(R) 2 , —NR c C(O)R d , —C(O)NR c R d , —NR c C(O)OR d , —OC(O)NR c R d , NR c R d , or C 1 -C 6 alkoxyl, in which each of R c and R d independently is H or C 1 -C 6 alkyl;

R 1 is -Q 2 -T 2 , in which Q 2 is a bond, C(O)NR e , or NR e C(O), R e being H or C 1 -C 6 alkyl and T 2 is 5- to 10-membered heteroaryl or 4- to 12-membered heterocycloalkyl, and wherein the 5- to 10-membered heteroaryl or 4- to 12-membered heterocycloalkyl is optionally substituted with one or more -Q 3 -T 3 , wherein each Q 3 independently is a bond or C 1 -C 3 alkylene linker each optionally substituted with one or more of halo, cyano, hydroxyl, or C 1 -C 6 alkoxy, and each T 3 independently is selected from the group consisting of H, halo, cyano, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 8 cycloalkyl, C 1 -C 10 aryl, 4- to 7-membered heterocycloalkyl containing 1-4 heteroatoms selected from N, O, and S, 5- to 6-membered heteroaryl, OR f , C(O)R f , C(O)OR f , OC(O)R f , S(O) 2 R f , NR f R g , OC(O)NR f R g , NR f C(O)OR g , C(O)NR f R g , and NR f C(O)R g , each of R f and R g independently being H, C 3 -C 8 cycloalkyl, or C 1 -C 6 alkyl optionally substituted with C 3 -C 8 cycloalkyl, in which the C 3 -C 8 cycloalkyl, C 6 -C 10 aryl, 4- to 7-membered heterocycloalkyl or 5- to 6-membered heteroaryl is optionally substituted with one or more halo, cyano, hydroxyl, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, or C 1 -C 6 alkoxy; or -Q 3 -T 3 is oxo;

R 8 is H or C 1 -C 6 alkyl;

R 9 is -Q 4 -T 4 , in which Q 4 is a bond or C 1 -C 6 alkylene, C 2 -C 6 alkenylene, or C 2 -C 6 alkynylene linker each optionally substituted with one or more of halo, cyano, hydroxyl, or C 1 -C 6 alkoxyl, and T 4 is H, halo, OR h , NR h R i , NR h C(O)R i , C(O)NR h R i , C(O)R h , C(O)OR h , NR h C(O)OR i , OC(O)NR h R i , S(O) 2 R h , S(O) 2 NR h R i , or R S2 , in which each of R h and R i independently is H or C 1 -C 6 alkyl, and R S2 is C 3 -C 8 cycloalkyl, C 6 -C 10 aryl, 4- to 12-membered heterocycloalkyl containing 1-4 heteroatoms selected from N, O, and S, or a 5- to 10-membered heteroaryl, and R S2 is optionally substituted with one or more -Q 5 -T 5 , wherein each Q 5 independently is a bond or C 1 -C 3 alkylene linker each optionally substituted with one or more of halo, cyano, hydroxyl, or C 1 -C 6 alkoxy, and each T 5 independently is selected from the group consisting of H, halo, cyano, 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 containing 1-4 heteroatoms selected from N, O, and S, 5- to 6-membered heteroaryl, OR j , C(O)R j , C(O)OR j , OC(O)R j , S(O) 2 R, NR j R k , OC(O)NR j R k , NR j C(O)OR k , C(O)NR j R k , and NR j C(O)R k , each of R j and R k independently being H or C 1 -C 6 alkyl; or -Q 5 -T 5 is oxo;

R 10 is halo, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 8 cycloalkyl, or 4- to 12-membered heterocycloalkyl containing 1-4 heteroatoms selected from N, O, and S, wherein each of the C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 8 cycloalkyl, and 4- to 12-membered heterocycloalkyl is optionally substituted with one or more halo, cyano, hydroxyl, oxo, amino, mono- or di-alkylamino, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 alkoxy, C(O)NR j R k , or NR j C(O)R k ;

R 11 and R 12 together with the carbon atom to which they are attached form a C 3 -C 12 cycloalkyl or 4- to 12-membered heterocycloalkyl containing 1-4 heteroatoms selected from N, O, and S, wherein the C 3 -C 12 cycloalkyl or 4- to 12-membered heterocycloalkyl is optionally substituted with one or more of halo, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, hydroxyl, oxo, amino, mono- or di-alkylamino, or C 1 -C 6 alkoxyl; and

R 15 is H, halo, cyano, or —OR 6 .

3 . The compound of claim 1 , wherein the compound is of Formula (I0) or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer.

4 . The compound any one of the preceding claims, wherein

is

5 . The compound any one of the preceding claims, wherein

is

6 . The compound any one of the preceding claims, wherein ring B is C 6 -C 10 aryl or 5- to 10-membered heteroaryl.

7 . The compound any one of the preceding claims, wherein

is

8 . The compound any one of the preceding claims, being of any one of Formulae (I0a)-(I0l):

or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer.

9 . The compound any one of the preceding claims, wherein ring B is C 6 -C 10 aryl or 5- to 10-membered heteroaryl substituted with one R 15 .

10 . The compound any one of the preceding claims, wherein

is

11 . The compound any one of the preceding claims, being of any one of Formulae (I0a′)-(I0i′):

or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer.

12 . The compound of claim 2 , being of Formula (I) or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer.

13 . The compound any one of the preceding claims, wherein

14 . The compound any one of the preceding claims, being of Formula (Ia)-(Il):

or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer.

15 . The compound any one of the preceding claims, wherein

is

16 . The compound any one of the preceding claims, being of Formula (Ia′)-(Ii′):

or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer.

17 . The compound of any one of the preceding claims, wherein at least one of X 1 , X 2 , X 3 and X 4 is N.

18 . The compound of any one of the preceding claims, wherein X 1 and X 3 are N.

19 . The compound of any one of the preceding claims, wherein X 1 and X 3 are N, X 2 is CR 3 and X 4 is CR 5 .

20 . The compound of any one of the preceding claims, wherein R 1 is C 1 -C 4 alkyl.

21 . The compound of any one of the preceding claims, wherein R 1 is H.

22 . The compound of any one of the preceding claims, wherein at most one of R 3 and R 5 is not H.

23 . The compound of any one of the preceding claims, wherein R 3 is H or halo.

24 . The compound of any one of the preceding claims, wherein R 3 is H.

25 . The compound of any one of the preceding claims, wherein R 5 is C 1 -C 6 alkyl.

26 . The compound of any one of the preceding claims, wherein at most one of R 4 and R 5 is not H.

27 . The compound of any one of the preceding claims, wherein at least one of R 4 and R 5 is not H.

28 . The compound of any one of the preceding claims, wherein R 4 is H, C 1 -C 6 alkyl, or halo.

29 . The compound of any one of the preceding claims, wherein at most one of R 2 and R 5 is not H.

30 . The compound of any one of the preceding claims, wherein at least one of R 2 and R 5 is not H.

31 . The compound of any one of the preceding claims, wherein R 2 is H, C 1 -C 6 alkyl, or halo.

32 . The compound of any one of the preceding claims, wherein R 5 is C 1 -C 6 alkyl.

33 . The compound of any one of the preceding claims, wherein R 6 is -Q 1 -T 1 , in which Q 1 is a bond or C 1 -C 6 alkylene linker optionally substituted with one or more of halo, and T 1 is H, halo, cyano, or R S1 , in which R S1 is C 3 -C 8 cycloalkyl, phenyl, 4- to 12-membered heterocycloalkyl containing 1-4 heteroatoms selected from N, O, and S, or a 5- or 6-membered heteroaryl and R S1 is optionally substituted with one or more of halo, C 1 -C 6 alkyl, hydroxyl, oxo, NR c R d , or C 1 -C 6 alkoxyl.

34 . The compound of any one of the preceding claims, wherein R 6 is C 1 -C 6 alkyl optionally substituted with one or more of halo, cyano, hydroxyl, or C 1 -C 6 alkoxyl.

35 . The compound of any one of the preceding claims, wherein R 6 is unsubstituted C 1 -C 6 alkyl.

36 . The compound of any one of the preceding claims, wherein R 7 is -Q 2 -T 2 , in which Q 2 is a bond or C(O)NR e , and T 2 is 5- to 10-membered heteroaryl or 4- to 12-membered heterocycloalkyl, wherein the 5- to 10-membered heteroaryl or 4- to 12-membered heterocycloalkyl is optionally substituted with one or more -Q 3 -T 3 .

37 . The compound of any one of the preceding claims, wherein R 7 is -Q 2 -T 2 , in which Q 2 is a bond, and T 2 is 5- to 10-membered heteroaryl or 4- to 12-membered heterocycloalkyl, wherein the 5- to 10-membered heteroaryl or 4- to 12-membered heterocycloalkyl is optionally substituted with one or more -Q 3 -T 3 .

38 . The compound of any one of the preceding claims, wherein T 2 is 4- to 12-membered heterocycloalkyl containing 1-4 heteroatoms selected from N, O, and S, which is optionally substituted with one or more -Q 3 -T 3 .

39 . The compound of any one of the preceding claims, wherein T 2 is 8- to 12-membered bicyclic heterocycloalkyl that comprises a 5- or 6-membered aryl or heteroaryl ring fused with a non-aromatic ring.

40 . The compound of any one of the preceding claims, wherein T 2 is 8- to 12-membered bicyclic heterocycloalkyl that comprises a 5- or 6-membered aryl or heteroaryl ring fused with a non-aromatic ring, in which the 5- or 6-membered aryl or heteroaryl ring is connected to Q 2 .

41 . The compound of any one of the preceding claims, wherein T 2 is 5- to 10-membered heteroaryl.

42 . The compound of any one of the preceding claims, wherein T 2 is selected from

and tautomers thereof, each of which is optionally substituted with one or more -Q 3 -T 3 , wherein X 8 is NH, O, or S, each of X 9 , X 10 , X 11 , and X 12 is independently CH or N, and at least one of X 9 , X 10 , X 11 , and X 12 is N, and ring A is a C 5 -C 8 cycloalkyl, phenyl, 6-membered heteroaryl, or 4- to 8-membered heterocycloalkyl containing 1-4 heteroatoms selected from N, O, and S.

43 . The compound of any one of the preceding claims, wherein T 2 is selected from

and tautomers thereof, each of which is optionally substituted with one or more -Q 3 -T 3 .

44 . The compound of any one of the preceding claims, wherein T 2 is selected from

and tautomers thereof, each of which is optionally substituted with one or more -Q 3 -T 3 .

45 . The compound of any one of the preceding claims, wherein T 2 is selected from

and tautomers thereof, each of which is optionally substituted with one or more -Q 3 -T 3 .

46 . The compound of any one of the preceding claims, wherein each Q 3 independently is a bond or C 1 -C 3 alkylene linker each optionally substituted with one or more of halo, cyano, hydroxyl, or C 1 -C 6 alkoxy, and each T 3 independently is selected from the group consisting of H, C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, 4- to 7-membered heterocycloalkyl, OR f , C(O)R f , C(O)OR f , NR f R g , C(O)NR f R g , and NR f C(O)R g , in which the C 3 -C 8 cycloalkyl or 4- to 7-membered heterocycloalkyl is optionally substituted with one or more halo, cyano, hydroxyl, C 1 -C 6 alkyl or C 1 -C 6 alkoxy.

47 . The compound of any one of the preceding claims, wherein each Q 3 independently is a C 1 -C 3 alkylene linker, and each T 3 independently is NR f R g , each of R f and R g independently being H, C 3 -C 8 cycloalkyl, or C 1 -C 6 alkyl optionally substituted with C 3 -C 8 cycloalkyl, in which the C 3 -C 8 cycloalkyl, C 6 -C 10 aryl, 4- to 7-membered heterocycloalkyl or 5- to 6-membered heteroaryl is optionally substituted with one or more halo, cyano, hydroxyl, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, or C 1 -C 6 alkoxy.

48 . The compound of any one of the preceding claims, wherein at least one of R 8 and R 9 is H.

49 . The compound of any one of the preceding claims, wherein each of R 8 and R 9 is H.

50 . The compound of any one of the preceding claims, wherein R 8 is H.

51 . The compound of any one of the preceding claims, wherein R 9 is -Q 4 -T 4 , in which Q 4 is a bond or C 1 -C 6 alkylene linker optionally substituted with one or more of halo, cyano, hydroxyl, or C 1 -C 6 alkoxyl, and T 4 is H, halo, OR h , NR h R i , NR h C(O)R i , C(O)NR h R i , C(O)R h , C(O)OR h , or R 2 , in which R S2 is C 3 -C 8 cycloalkyl or 4- to 7-membered heterocycloalkyl, and R S2 is optionally substituted with one or more -Q 5 -T 5 .

52 . The compound of any one of the preceding claims, wherein Q 4 is C 1 -C 6 alkylene, and T 1 is H.

53 . The compound of any one of the preceding claims, wherein each Q 5 independently is a bond or C 1 -C 3 alkylene linker.

54 . The compound of any one of the preceding claims, wherein each T 5 independently is selected from the group consisting of H, halo, cyano, C 1 -C 6 alkyl, OR j , C(O)R, C(O)OR, NR j R k , C(O)NR j R k , and NR j C(O)R k .

55 . The compound of any one of the preceding claims, wherein R 9 is C 1 -C 3 alkyl.

56 . The compound of any one of the preceding claims, wherein R 14 is H, halo, or C 1 -C 6 alkyl.

57 . The compound of any one of the preceding claims, wherein R 14 is halo or —OR 6 .

58 . The compound of any one of the preceding claims, wherein R 14 is halo.

59 . The compound of any one of the preceding claims, wherein R 14 is —OR 6 .

60 . The compound of any one of the preceding claims, wherein R 15 is H or halo.

61 . The compound of any one of the preceding claims, wherein R 15 is H.

62 . The compound of any one of the preceding claims, wherein R 15 is H or halo.

63 . The compound of any one of the preceding claims, wherein R 14 is halo, and R 15 is H.

64 . The compound of any one of the preceding claims, wherein R 14 is —OR 6 , and R 15 is H.

65 . The compound of any one of the preceding claims, wherein R 14 is halo, and R 15 is halo.

66 . The compound of any one of the preceding claims, wherein R 14 is —OR 6 , and R 15 is halo.

67 . The compound of claim 1 , being of Formula (II0) or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer.

68 . The compound of any one of the preceding claims, being of Formulae (II0a) or (II0b):

or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer.

69 . The compound of claim 2 , wherein the compound is of Formula (II), or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer.

70 . The compound of any one of the preceding claims, being of Formula (IIa) or (IIb):

or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer.

71 . The compound of any one of the preceding claims, wherein each of X 5 , X 6 and X 7 is CH.

72 . The compound of any one of the preceding claims, wherein at least one of X 5 , X 6 and X 7 is N.

73 . The compound of any one of the preceding claims, wherein at most one of X 5 , X 6 and X 7 is N.

74 . The compound of any one of the preceding claims, wherein R 10 is optionally substituted 4- to 7-membered heterocycloalkyl containing 1-4 heteroatoms selected from N, O, and S.

75 . The compound of any one of the preceding claims, wherein R 0 is connected to the bicyclic group of Formula (II) via a carbon-carbon bond.

76 . The compound of any one of the preceding claims, wherein R 10 is connected to the bicyclic group of Formula (II) via a carbon-nitrogen bond.

77 . The compound of claim 1 , wherein the compound is of Formula (III0) or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer.

78 . The compound of any one of the preceding claims, being of Formula (III0a) or (III0b):

or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer.

79 . The compound of claim 2 , being of Formula (III) or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer.

80 . The compound of any one of the preceding claims, wherein R 11 and R 12 together with the carbon atom to which they are attached form a 4- to 7-membered heterocycloalkyl containing 1-4 heteroatoms selected from N, O, and S, wherein the 4- to 7-membered heterocycloalkyl is optionally substituted with one or more of halo, C 1 -C 6 alkyl, hydroxyl, oxo, amino, mono- or dialkylamino, or C 1 -C 6 alkoxyl.

81 . The compound of any one of the preceding claims, wherein R 11 and R 12 together with the carbon atom to which they are attached form a C 4 -C 8 cycloalkyl which is optionally substituted with one or more of halo, C 1 -C 6 alkyl, hydroxyl, oxo, amino, mono- or di-alkylamino, or C 1 -C 6 alkoxyl.

82 . The compound of any one of the preceding claims, wherein each of X 5 and X 6 is CH.

83 . The compound of any one of the preceding claims, wherein each of X 5 and X 6 is N.

84 . The compound of any one of the preceding claims, wherein one of X 5 and X 6 is CH and the other is CH.

85 . The compound of claim 1 , being of Formula (IV0) or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer.

86 . The compound of any one of the preceding claims, being of Formula (IV0a) or (IV0b):

or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer.

87 . The compound of any one of the preceding claims, wherein the compound is selected from those in Table 1 and pharmaceutically acceptable salts thereof.

88 . The compound of any one of the preceding claims, wherein the compound inhibits a kinase with an enzyme inhibition IC 50 value of about 100 nM or greater, 1 μM or greater, 10 μM or greater, 100 μM or greater, or 1000 μM or greater.

89 . The compound of any one of the preceding claims, wherein the compound inhibits a kinase with an enzyme inhibition IC 50 value of about 1 mM or greater.

90 . The compound of any one of the preceding claims, wherein the compound inhibits a kinase with an enzyme inhibition IC 50 value of 1 μM or greater, 2 μM or greater, 5 μM or greater, or 10 μM or greater, wherein the kinase is one or more of the following: AbI, AurA, CHK1, MAP4K, IRAK4, JAK3, EphA2, FGFR3, KDR, Lck, MARK1, MNK2, PKCb2, SIK, and Src.

91 . A pharmaceutical composition comprising a compound of any one of the preceding claims and a pharmaceutically acceptable carrier.

92 . A method of preventing or treating a blood disorder via inhibition of a methyltransferase enzyme selected from EHMT1 and EHMT2, the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of any one of the preceding claims.

93 . The method of any one of the preceding claims, wherein the blood disorder is sickle cell anemia or β-thalassemia.

94 . The method of any one of the preceding claims, wherein the blood disorder is a hematological cancer.

95 . A method of preventing or treating a cancer via inhibition of a methyltransferase enzyme selected from EHMT1 and EHMT2, the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of any one of the preceding claims.

96 . The method of claim 95 , wherein the cancer is lymphoma, leukemia, melanoma, breast cancer, ovarian cancer, hepatocellular carcinoma, prostate carcinoma, lung cancer, brain cancer, or hematological cancer.

97 . The method of any one of the preceding claims, wherein the hematological cancer is acute myeloid leukemia (AML) or chronic lymphocytic leukemia (CLL).

98 . The method claim 96 , wherein the lymphoma is diffuse large B-cell lymphoma, follicular lymphoma, Burkitt's lymphoma or Non-Hodgkin's Lymphoma.

99 . The method of claim 95 , wherein the cancer is chronic myelogenous leukemia (CML), acute myeloid leukemia, acute lymphocytic leukemia or mixed lineage leukemia, or myelodysplastic syndromes (MDS).

100 . The method of any one of the preceding claims, wherein a compound of any of Formulae (I0)-(IV0) or (I)-(III) is a selective inhibitor of EHMT2.

101 . A compound of any one of the preceding claims for use in preventing or treating a blood disorder via inhibition of a methyltransferase enzyme selected from EHMT1 and EHMT2.

102 . The compound of any one of the preceding claims, wherein the blood disorder is sickle cell anemia or β-thalassemia.

103 . The compound of any one of the preceding claims, wherein the blood disorder is a hematological cancer.

104 . A compound of any one of the preceding claims for use in preventing or treating a cancer via inhibition of a methyltransferase enzyme selected from EHMT1 and EHMT2.

105 . The compound of any one of the preceding claims, wherein the cancer is lymphoma, leukemia, melanoma, breast cancer, ovarian cancer, hepatocellular carcinoma, prostate carcinoma, lung cancer, brain cancer, or hematological cancer.

106 . The compound of any one of the preceding claims, wherein the hematological cancer is acute myeloid leukemia (AML) or chronic lymphocytic leukemia (CLL).

107 . The compound of any one of the preceding claims, wherein the lymphoma is diffuse large B-cell lymphoma, follicular lymphoma, Burkitt's lymphoma or Non-Hodgkin's Lymphoma.

108 . The compound of any one of the preceding claims, wherein the cancer is chronic myelogenous leukemia (CML), acute myeloid leukemia, acute lymphocytic leukemia or mixed lineage leukemia, or myelodysplastic syndromes (MDS).

109 . The compound of any one of the preceding claims, wherein the compound of any of Formulae (I0)-(IV0) or (I)-(III) is a selective inhibitor of EHMT2.

110 . Use of a compound of any one of the preceding claims in manufacture of a medicament for preventing or treating a blood disorder via inhibition of a methyltransferase enzyme selected from EHMT1 and EHMT2.

111 . The use of any one of the preceding claims, wherein the blood disorder is sickle cell anemia or 3-thalassemia.

112 . The use of any one of the preceding claims, wherein the blood disorder is a hematological cancer.

113 . Use of a compound of any one of the preceding claims in manufacture of a medicament for preventing or treating a cancer via inhibition of a methyltransferase enzyme selected from EHMT1 and EHMT2.

114 . The use of any one of the preceding claims, wherein the cancer is lymphoma, leukemia, melanoma, breast cancer, ovarian cancer, hepatocellular carcinoma, prostate carcinoma, lung cancer, brain cancer, or hematological cancer.

115 . The use of any one of the preceding claims, wherein the hematological cancer is acute myeloid leukemia (AML) or chronic lymphocytic leukemia (CLL).

116 . The use of any one of the preceding claims, wherein the lymphoma is diffuse large B-cell lymphoma, follicular lymphoma, Burkitt's lymphoma or Non-Hodgkin's Lymphoma.

117 . The use of any one of the preceding claims, wherein the cancer is chronic myelogenous leukemia (CML), acute myeloid leukemia, acute lymphocytic leukemia or mixed lineage leukemia, or myelodysplastic syndromes (MDS).

118 . The use of any one of the preceding claims, wherein the compound of any of Formulae (I0)-(IV0) or (I)-(III) is a selective inhibitor of EHMT2.