Ethanediamine-heterocycle derivatives as inhibitors of protein arginine methyltransferases

A compound of structural Formula I

• or a salt thereof, wherein:
• A is a monocyclic heterocycloalkyl ring comprising 5 to 7 ring members including:
• X1 and X2,
• Z, which is chosen from —CH2—, —CHR3—, —C(R3)2—, —N(R5a)—, N(COR5a)—,
• N(CONR5aR5b)—, N(SO2R5a)—, —O—, and —SO2—, and
• all other ring members Y, which are chosen from —CH2—, —CHR2—, and —C(R2)2—;
• R1a, R1b, and R1c are independently chosen from H and CH3;
• either X1 is C and X2 is N, or X1 is N and X2 is C;
• each R2 and R3 is independently chosen from cyano, halo, hydroxy, C1-6alkyl,
• C1-6haloalkyl, C1-6hydroxyalkyl, (C1-6alkoxy)C1-6 alkyl;
• OR5a, C(O)R5a, C(O)OR5a, C(O)NR5aR5b, SO2R5a;
• SO2NR5aR5b, NR5aR5b, NR5aC(O)R5b, NR5cC(O)OR5b, NR5cC(O)NR5aR5b, and NR5aSO2R5b, or
• any two R2 or R3, when directly attached to the same atom, forms a 3-7 membered cycloalkyl or heterocycloalkyl ring;
• R4 is chosen from cycloalkyl, heterocycloalkyl, aryl and heteroaryl, any of which is optionally substituted with 1, 2, 3, or 4 R6 groups;
• each R5a and R5b is independently chosen from H, C1-6alkyl, cyanoC1-6alkyl, haloC1-6alkyl, hydroxyC1-6alkyl, (C1-6alkoxy)C1-6 alkyl;
• C3-6 cycloalkyl, cyanoC3-6 cycloalkyl, haloC3-6 cycloalkyl, hydroxyC3-6 cycloalkyl, and (C3-6 alkoxy)C3-6 cycloalkyl, or
• R5a and R5b, when directly attached to the same atom, forms a 3-7 membered cycloalkyl or heterocycloalkyl ring;
• R5c is chosen from H, C1-6alkyl, cyanoC1-6alkyl, haloC1-6alkyl, hydroxyC1-6alkyl, (C1-6 alkoxy)C1-6 alkyl;
• C3-6 cycloalkyl, cyanoC3-6 cycloalkyl, haloC3-6 cycloalkyl, hydroxyC3-6 cycloalkyl, and (C3-6 alkoxy)C3-6 cycloalkyl;
• each R6 is independently chosen from C1-6alkyl, cyanoC1-6alkyl, haloC1-6alkyl, hydroxyC1-6alkyl, (C1-6 alkoxy)C1-6 alkyl, (haloC1-6alkoxy)C1-6alkyl, C3-6 cycloalkyl, cyanoC3-6 cycloalkyl, haloC3-6 cycloalkyl, hydroxyC3-6 cycloalkyl, (C3-6 alkoxy)C3-6 cycloalkyl, (C3-6 cycloalkyl)C1-6alkyl, (heterocycloalkyl)C1-6alkyl, (aryl)C1-6alkyl, (heteroaryl)C1-6alkyl, ((C1-6alkyl)aryl)C1-6alkyl, ((C1-6alkyl)heteroaryl)C1-6alkyl, OR7, CH2OR7, CH2CH2OR7, COR7, COOH, COOR7, CONH2, CONHR7, CON(R7)2, NHCOR7, NR7COR7, NHCONH2, NHCONHR7, NHCON(R7)2, NR7CONH2, NR7CONHR7, NR7CON(R7)2, SO2R7, SO2NHR7, SO2N(R7)2, NHSO2R7, NR7SO2R7, carboxy, cyano, halo, hydroxy, and oxo;
• each R7 is independently chosen from C1-6alkyl, haloC1-6alkyl, aryl, heteroaryl, C3-6cycloalkyl, heterocycloalkyl, (aryl)C1-6alkyl, (heteroaryl)C1-6 alkyl, (cycloalkyl)C1-6alkyl, and (heterocycloalkyl)C1-6 alkyl, any of which is optionally substituted with 1 or 2 R8 groups;
• and
• each R8 is independently chosen from C1-6 alkyl, haloC1-6 alkyl, C3-6 cycloalkyl, and haloC3-6 cycloalkyl.