ASH1L degraders and methods of treatment therewith

A compound having a structure of:

• wherein R1 is selected from H, alkyl, substituted alkyl, halogen substituted alkyl, branched alkyl, a substituted brached alkyl halogen substituted branched alkyl, alkoxy, amine, substituted amine, thioalkyl, ketone, amide, a substituted amide, cyano, sulfonyl, carboxy, dialkylphosphine oxide, a carbocyclic ring, a substituted carbocyclic ring, an aromatic ring, a substituted aromatic ring, a heterocyclic aromatic ring, a substituted heterocyclic aromatic ring, a substituted or non-substituted heterocyclic non-aromatic ring carbocyclic or heterocyclic aromatic ring fused to another aromatic ring, a hydrogen bond donor, a hydrogen bond acceptor, and combinations thereof;
• wherein R2, R3, R4, R5, and R7, when present, are independently selected from H, halogen, CH3, OH, SH, NH2, CN, CF3, CCl3, —CH2—CH3, —CH2—OH, —CH2NH2, CH3SH, CH2Cl, CH2Br, CH2F, CHF2, CH2CN, CH2CF3, CH2Cl3, alkyl, haloalkyl, and alcohol;
• and
• wherein R6 is selected from H, alkyl, substituted alkyl, halogen substituted alkyl, branched alkyl, a substituted brached alkyl halogen substituted branched alkyl hydroxy, alkoxy, amine, substituted amine, alkylamine, substituted alkylamine, thioalkyl, alkylthioalkyl, halogen, ketone, amide, a substituted amide, alkylamide, substituted alkylamide, cyano, sulfonyl, carboxy, dialkylphosphine oxide, a carbocyclic ring, substituted carbocyclic ring, an aromatic ring, a substituted aromatic ring, a heterocyclic aromatic ring, a substituted heterocyclic aromatic ring, a substituted or non-substituted heterocyclic non-aromatic ring, carbocyclic or heterocyclic aromatic ring fused to another aromatic ring, a hydrogen bond donor, a hydrogen bond acceptor, and combinations thereof;
• wherein X is CH or N;
• wherein Z is O or S;
• wherein A is a covalent bond or is selected from
• wherein one of X and Y is
• or
• and the other is H,
• wherein X and Y are independently CH or N,
• wherein erein X and Y are O, NH, or CH2, and
• wherein X and Y are independently N or CH, and wherein Z is O, NH, or CH2;
• wherein n, when present, is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15;
• wherein m, when present, is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 or ranges therebetween;
• wherein the Linker is selected from:
• wherein X, Y, and Z groups, when present are independently O, NH, or CH2, and do not need to be the same group when present in the same linker;
• wherein n, when present, is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15;
• wherein m, when present, is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 or ranges therebetween;
• wherein k, when present is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
• wherein l, when present is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
• wherein the Ligase Ligand is selected from:
• or a salt thereof.