Technologies targeting cell states

A compound of Formula I:

• or a pharmaceutically acceptable salt thereof, wherein;
• PBM is a KAT2 protein binding moiety, or is
• linker is an optional linking moiety, or is a covalent bond or an optionally substituted bivalent C1-C20 hydrocarbon chain, wherein one or more methylene units are optionally and independently replaced by —O—, —S—, —N(R)—, —N═N—, —C(O)—, —C(S)—, —C(NR)—, —C(NOR)—, —C(NNR2)—, —OC(O)—, —C(O)O—, —C(O)N(R)—, —N(R)C(O)—, —C(NR)O—, —OC(NR)—, —C(NR)NR—, —N(R)C(NR)—, —N(R)C(O)N(R)—, —N(R)C(O)O—, —OC(O)N(R)—, —N(R)C(O)S—, —SC(O)N(R)—, —N(R)C(NR)N(R)—, —S(O)—, —SO2—, —SO2N(R)—, —N(R)SO2—, or -Cy-;
• and
• LBM is an E3 ubiquitin ligase binding moiety, or is
• wherein:
• Ring A is selected from:
• Ring B is an optionally substituted 5- to 6-membered heterocyclyl having 1-2 heteroatoms independently selected from N, O, and S;
• L1 is a covalent bond or an optionally substituted bivalent C1-3 hydrocarbon chain;
• each R1 is independently —R;
• n is 0, 1, 2, 3, or 4;
• Z is N or CR3;
• R2 is halogen, —CN, or —R;
• each R3 is independently halogen, —CN, or —R;
• R4 is —R′;
• R5 is halogen, —CN, or —R, or
• R2 and R5, together with the atoms to which they are attached, combine to form an optionally substituted 5- to 6-membered ring having 0-2 heteroatoms independently selected from N, O, and S;
• R6 is —R′;
• X is O or NR7;
• R7 is —R′, or
• R4 and R7, together with the atoms to which they are attached, combine to form an optionally substituted 5- to 6-membered ring having 2-3 heteroatoms independently selected from N, O, and S;
• L3, L4, and L5 are each independently a covalent bond or an optionally substituted bivalent C1-6 hydrocarbon chain;
• each R8 is independently —R′;
• R9 is —R′;
• each Cy is independently an optionally substituted, 3- to 16-membered bivalent ring having 0-6 heteroatoms independently selected from N, O, and S;
• each of Ring C and Ring F is independently an optionally substituted 3- to 16-membered ring having 0-6 heteroatoms independently selected from N, O, and S;
• each Rb is independently halogen, —CN, —R′ or —OR;
• t is 0, 1, 2, 3, or 4;
• L2 is a covalent bond or an optionally substituted C1-3 hydrocarbon chain, wherein one or more methylene units are optionally and independently replaced by —O—, —S—, —N(R)—, —N═N—, —C(O)—, —C(S)—, —C(NR)—, —C(NOR)—, —C(NNR2)—, —OC(O)—, —C(O)O—, —C(O)N(R)—, —N(R)C(O)—, —C(NR)O—, —OC(NR)—, —C(NR)NR—, —N(R)C(NR)—, —N(R)C(O)N(R)—, —N(R)C(O)O—, —OC(O)N(R)—, —N(R)C(O)S—, —SC(O)N(R)—, —N(R)C(NR)N(R)—, —S(O)—, —SO2—, —SO2N(R)—, —N(R)SO2—, or -Cy-;
• Ring E is
• or an optionally substituted group selected from
• Y is N or CH;
• each Ra is independently halogen, —CN or —R′;
• linker is attached to the bracketed moiety at one of Rd, Re, Rf, or Rg, or linker is attached to the bracketed moiety at one Ri or the ring formed when two Ri groups are taken together;
• each Rd that is not the point of attachment for the linker is independently —R′, or
• two Rd, together with the atom to which they are attached, combine to form an optionally substituted 5- to 6-membered ring having 1-3 heteroatoms independently selected from N, O, and S and optionally fused to a phenyl or 5- to 6-membered heteroaryl ring having 1-3 heteroatoms independently selected from N, O, and S;
• each Re that is not the point of attachment for the linker is independently —R;
• Rf, when it is not the point of attachment for the linker, is —R;
• each Rg that is not the point of attachment for the linker is independently halogen, —CN, R or —OR;
• p is 0, 1, 2, or 3;
• Rh is halogen, or —R;
• each Ri that is not the point of attachment of the linker is independently halogen, —R, —C(O)N(R′)2, or —N(R)C(O)R, or
• two Ri groups, together with the atoms to which they are attached, combine to form an optionally substituted phenyl or 5- to 6-membered ring having 1-3 heteroatoms independently selected from N, O, and S;
• Rj is —R, or
• Rj combines with one instance of Ri, together with their intervening atoms, to form an optionally substituted 5- to 7-membered ring having 1-2 heteroatoms independently selected from N, O, and S;
• Rk is —R;
• r is 1, 2, 3, 4, or 5;
• q is 1 or 2;
• Rm is —R;
• each of Rn, Rp, Rq, Rr, Rs, and Ru is independently halogen, —CN, —R or —OR;
• s is 0, 1, 2, 3, 4, or 5;
• t is 0, 1, 2, 3, 4, or 5;
• each u is independently 0, 1, 2, 3, 4, or 5;
• each Rt is independently R, or
• both Rt groups, together with the atom to which they are attached, combine to form an optionally substituted 3- to 7-membered ring having 0-2 heteroatoms independently selected from N, O, and S;
• each Rv is independently halogen, —CN, —R or —OR, or
• one instance of Ru and Rv, together with their intervening atoms, combine to form an optionally substituted 3- to 7-membered ring having 0-2 heteroatoms independently selected from N, O, and S;
• each Rw is independently halogen, —CN, —R or —OR, or
• one instance of Ru and Rw, together with their intervening atoms, combine to form an optionally substituted 3- to 7-membered ring having 0-2 heteroatoms independently selected from N, O, and S;
• each v is independently 0, 1, 2, 3, 4, or 5;
• each R′ is independently —R, —C(O)R, or —S(O)2R, or two R′ attached to the same atom, together with the atom to which they are attached, combine to form an optionally substituted 3- to 16-membered ring having 1-5 heteroatoms independently selected from N, O, and S;
• and
• each R is independently hydrogen or an optionally substituted group selected from C1-8 aliphatic, C3-10 cycloaliphatic, C1-C8 heteroaliphatic having 1-3 heteroatoms independently selected from N, O, and S, C6-10 aryl, 5- to 10-membered heteroaryl having 1-5 heteroatoms independently selected from N, O, and S, and 3- to 10-membered monocyclic heterocyclyl having 1-5 heteroatoms independently selected from N, O, and S.

The compound of any one of the preceding claims, wherein the linker is less than 14 atoms in length, or wherein the linker is less than 11 atoms in length;

• and/or
• wherein the shortest-path length of linker is about or no more than 14 atoms, or wherein the shortest-path length of linker is about or no more than 10 atoms;
• and/or wherein the number of non-ring consecutive sp3 atoms in the shortest path chain of linker is about or no more than about 5, 4, 3, 2 or 1;
• and/or wherein the number of non-ring consecutive sp3 atoms in the shortest path chain of linker is about or no more than about 2;
• and/or wherein the number of bonds between two non-ring sp3 atoms in the shortest path chain of linker is about or no more than 5, 4, 3, 2 or 1;
• and/or wherein the number of bonds between two non-ring sp3 atoms in the shortest path chain of linker is about or no more than 1;
• and/or wherein the number of non-ring sp3 C, O, and S atoms in the shortest path chain of linker is about or no more than about 5, 4, 3, 2 or 1;
• and/or wherein the number of non-ring sp3 atoms in the shortest path chain of linker is about or no more than about 5, 4, 3, 2 or 1;
• and/or wherein the number of non-ring sp3 atoms in the shortest path chain of linker is about or no more than about 1;
• and/or wherein the number of non-ring atoms in the shortest path chain of linker is about or no more than about 5, 4, 3, 2 or 1;
• and/or wherein the number of non-ring atoms in the shortest path chain of linker is about or no more than about 1.