Inhibitors of cyclin-dependent kinase 7 (CDK7)

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);
• each instance of RA1 is independently selected from the group consisting of 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 the group consisting of 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 the group consisting of 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 the group consisting of N and CH, wherein at least one X is N;
• W is selected from the group consisting of N and C(R1a);
• each of R1a, if present, and R1b is independently selected from the group consisting of 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(R7)—;
• R3 is selected from the group consisting of 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(R7)—, or —S(O)2—;
• R4 is selected from the group consisting of —NH2, —NH—C(O)—(CH2)3—N(CH3)2, —NH—C(O)—CH2—CH(OH)—CH2—N(CH3)2,
• —NH—CH3, and —NH—C(O)—C(O)—NH2;
• each R5, if present, is independently selected from the group consisting of 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;
• each R6, if present, is independently selected from the group consisting of 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, ═O, CN, ORC1, —N(RC1)2, and —SRC1, wherein each occurrence of RC1 is independently selected from the group consisting of hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, a nitrogen protecting group when attached to a nitrogen atom, an oxygen protecting group when attached to an oxygen atom, and a sulfur protecting group when attached to a sulfur atom, or two RC1 groups are joined to form an optionally substituted heterocyclic ring;
• or
• two R6 are taken together to form a first 5-7 membered optionally substituted, heterocyclyl or carbocyclyl ring fused to the ring to which the R6 are bound;
• wherein two substituents on the substituted heterocyclyl or carbocyclyl ring, or one substituent on the substituted heterocyclyl or carbocyclyl ring and a third R6 may be taken together with the atoms to which they are bound to form a second optionally substituted, heterocyclyl or carbocyclyl ring fused to the ring to the first optionally substituted, heterocyclyl or carbocyclyl ring and/or the ring to which the third R6 is bound;
• each R7 is independently selected from the group consisting of hydrogen and optionally substituted —C1-C6 alkyl;
• n is 0, 1, 2, 3, 4, 5 or 6;
• and
• p is 0, 1, 2 or 3,
• wherein the compound is other than
• and stereoisomers and enantiomers thereof.