Heteroaromatic compounds useful for the treatment of proliferative diseases

A compound having the structural formula I:

• or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein:
• ring A is an optionally substituted heteroaryl ring of any one of the Formulae (i-1)-(i-6):
• wherein:
• each instance of V1, V2, V3, V4, V5, V6, V7, V8, V9, V10, V11, V12, V13, V14 and V15 is independently O, S, N, N(RA1), C, or C(RA2), and wherein at least one ring atom in ring A is selected from O, S or N;
• each instance of RA1 is independently selected from hydrogen, deuterium, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl;
• each instance of RA2 is independently selected from hydrogen, deuterium, halogen, —CN, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, —ORA2a, —N(RA2a)2, and —SRA2a wherein each occurrence of RA2a is independently selected from hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or
• any two RA1, any two RA2, or one RA1 and one RA2 are joined to form an optionally substituted carbocyclic, optionally substituted heterocyclic, optionally substituted aryl, or optionally substituted heteroaryl ring;
• each X is independently selected from N and CH, wherein at least one X is N;
• W is selected from N and C(R1a);
• each of R1a, if present, and R1b is independently selected from hydrogen, deuterium, halogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, —CN, —ORB1a, —N(RB1a)2, and —SRB1a, wherein each occurrence of RB1a is independently selected from hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or
• R1a and R1b are joined to form an optionally substituted carbocyclic, optionally substituted heterocyclic, optionally substituted aryl, or optionally substituted heteroaryl ring;
• R2 is an optionally substituted C1-C4 alkylene or an optionally substituted C2-C4 alkenylene or alkynylene, wherein one or more methylene units of the alkylene, alkenylene or alkynylene are optionally and independently replaced with —O—, —S—, or —N(R6)—;
• Q is selected from:
• and a 4-14 membered, divalent, fused or spirofused bicyclic ring system comprising a total of 0 to 4 ring heteroatoms independently selected from N, O and S, and optionally substituted with 1 to 6 independently selected R3, wherein:
• each ring in the bicyclic ring system is independently selected from heterocyclyl, carbocyclyl, aromatic or heteroaromatic,
• one atom in each ring of the bicyclic ring system is attached to the rest of the compound, and
• t is 0, 1, 2, 3, or 4;
• wherein each represents a portion of Q bound to the rest of the compound;
• and “*” represents a portion of Q bound to R2;
• each instance of R3, if present, is independently selected from deuterium, halogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, —ORC1, —N(RC1)2, and —SRC1, wherein each occurrence of RC1 is independently selected from hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or
• two R3 groups bound to the same ring carbon atom are taken together to form ═O, or
• two R3 groups bound to the same or different ring carbon atoms are joined to form an optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl ring;
• R4 is selected from a bond, an optionally substituted C1-C4 alkylene, and an optionally substituted C2-C4 alkenylene or alkynylene, wherein:
• one or more methylene units of the alkylene, alkenylene or alkynylene other than a methylene unit bound to a nitrogen atom is optionally and independently replaced with —O—, —S—, —N(R6)—, or —S(═O)2—, and
• two substituents on either the same or adjacent carbon atoms in the alkylene, alkenylene or alkynylene are taken together to form an optionally substituted carbocyclic or optionally substituted heterocyclic ring;
• R5 is selected from a bond, an optionally substituted C1-C4 alkylene, and an optionally substituted C2-C4 alkenylene or alkynylene, wherein:
• one or more methylene units of the alkylene, alkenylene or alkynylene is optionally and independently replaced with —O—, —S—, —N(R6)—, or —S(═O)2—, and
• two substituents on either the same or adjacent carbon atoms in the alkylene, alkenylene or alkynylene are optionally taken together to form an optionally substituted carbocyclic or optionally substituted heterocyclic ring;
• each R6 is independently selected from hydrogen, and —C1-C6 alkyl;
• R7 is any one of the Formulae (ii-1)-(ii-20):
• wherein:
• R7 and Q are para or meta to each other;
• L3 is a bond, an optionally substituted C1-C7 alkylene, or an optionally substituted C2-C5 alkenylene or alkynylene, wherein one or more methylene units of the alkylene, alkenylene or alkynylene are optionally and independently replaced with —O—, —S—, —S(O)—, —S(O)2, or —N(R6)—;
• L4 is a bond, an optionally substituted C1-C4 alkylene, or an optionally substituted C2-C4 alkenylene or alkynylene;
• each of RE1, RE2 and RE3 is independently selected from hydrogen, deuterium, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, —CH2OR9, —CH2N(R9)2, —CH2SR9, —CN, —OR9, —N(R9)2, and —SR9, wherein each occurrence of R9 is independently selected from hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or
• RE1 and RE3, or RE2 and RE3, or RE1 and RE2 are joined to form an optionally substituted carbocyclic or optionally substituted heterocyclic ring;
• RE4 is a leaving group;
• RE5 is selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, —CN, —CH2ORE5a, —CH2N(RE5a)2, —CH2SRE5a, —ORE5a, —N(RE5a)2, and —SRE5a, wherein each occurrence of RE5a is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or two RE5a groups are joined to form an optionally substituted heterocyclic ring;
• Y is O, S, or N(RE6);
• wherein RE6 is hydrogen, substituted or unsubstituted C1-6 alkyl, or a nitrogen protecting group;
• z is 0, 1, 2, 3, 4, 5, or 6;
• a is 1 or 2;
• each instance of R8, if present, is independently selected from deuterium, halogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, —ORD1, —N(RD1)2, and —SRD1, wherein each occurrence of RD1 is independently selected from hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, and optionally substituted aryl, optionally substituted heteroaryl, or
• two R8 groups are joined to form an optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl ring;
• m is 0, 1, 2, 3 or 4;
• n is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14;
• and
• wherein the compound is other than:

A compound of Formula (II):

• and pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers, and isotopically labeled derivatives thereof, wherein:
• ring A is an optionally substituted heteroaryl ring of any one of the Formulae (i-1)-(i-6):
• wherein:
• each instance of V1, V2, V3, V4, V5, V6, V7, V8, V9, V10, V11, V12, V13, V14 and V15 is independently O, S, N, N(RA1), C, or C(RA2), and wherein at least one ring atom in ring A is selected from O, S or N;
• each instance of RA1 is independently selected from hydrogen, deuterium, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl;
• each instance of RA2 is independently selected from hydrogen, deuterium, halogen, —CN, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, —ORA2, —N(RA2a)2, and —SRA2a, wherein each occurrence of RA2a is independently selected from hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or
• any two RA1, any two RA2, or one RA1 and one RA2 are joined to form an optionally substituted carbocyclic, optionally substituted heterocyclic, optionally substituted aryl, or optionally substituted heteroaryl ring;
• each X is independently selected from N and CH, wherein at least one X is N;
• W is selected from N and C(R1a);
• each of R1a, if present, and R1b is independently selected from hydrogen, deuterium, halogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, —CN, —ORB1a, —N(RB1a)2, and —SRB1a, wherein each occurrence of RB1a is independently selected from hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or
• R1a and R1b are joined to form an optionally substituted carbocyclic, optionally substituted heterocyclic, optionally substituted aryl, or optionally substituted heteroaryl ring;
• R2 is an optionally substituted C1-C4 alkylene or an optionally substituted C2-C4 alkenylene or alkynylene, wherein one or more methylene units of the alkylene, alkenylene or alkynylene are optionally and independently replaced with —O—, —S—, or —N(R6)—;
• Q is selected from:
• R5,
• and a 4-14 membered, divalent, fused or spirofused bicyclic ring system comprising a total of 0 to 4 ring heteroatoms independently selected from N, O and S, and optionally substituted with 1 to 6 independently selected R3, wherein:
• each ring in the bicyclic ring system is independently selected from heterocyclyl, carbocyclyl, aromatic or heteroaromatic,
• one atom in each ring of the bicyclic ring system is attached to the rest of the compound, and
• t is 0, 1, 2, 3, or 4;
• wherein each represents a portion of Q bound to the rest of the compound;
• and “*” represents a portion of Q bound to R2;
• each instance of R3, if present, is independently selected from deuterium, halogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, —ORC1, —N(RC1)2, and —SRC1 wherein each occurrence of RC1 is independently selected from hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or
• two R3 groups bound to the same ring carbon atom are taken together to form ═O, or two R3 groups bound to the same or different ring carbon atoms are joined to form an optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl ring;
• R4 is selected from a bond, an optionally substituted C1-C4 alkylene, and an optionally substituted C2-C4 alkenylene or alkynylene, wherein:
• one or more methylene units of the alkylene, alkenylene or alkynylene other than a methylene unit bound to a nitrogen atom is optionally and independently replaced with —O—, —S—, —N(R6)—, or —S(═O)2—, and
• two substituents on either the same or adjacent carbon atoms in the alkylene, alkenylene or alkynylene are taken together to form an optionally substituted carbocyclic or optionally substituted heterocyclic ring;
• R5 is selected from a bond, an optionally substituted C1-C4 alkylene, and an optionally substituted C2-C4 alkenylene or alkynylene, wherein:
• one or more methylene units of the alkylene, alkenylene or alkynylene is optionally and independently replaced with —O—, —S—, —N(R6)—, or —S(═O)2—, and
• two substituents on either the same or adjacent carbon atoms in the alkylene, alkenylene or alkynylene are optionally taken together to form an optionally substituted carbocyclic or optionally substituted heterocyclic ring;
• each R6 is independently selected from hydrogen, and —C1-C6 alkyl;
• and
• R14 is selected from —C1-C8 alkyl, —O—C1-C8 alkyl, —NH2, —NH(C1-C8 alkyl), —N(C1-C8 alkyl)2, wherein each alkyl in R14 is independently selected and optionally and independently substituted.