Bifunctional agents for protein recruitment and/or degradation

A compound of the general formula (A) K-L-Q, or a salt, enantiomer, stereoisomer, polymorph, or N-oxide thereof, wherein:

• A is a compound that binds to an E3 ubiquitin ligase and has a structure of Formula III
• Q is a moiety that binds to a target protein which is sequestered to the E3 ubiquitin ligase and/or degraded upon interaction with the E3 ubiquitin ligase, wherein Q is selected from the group consisting of trimethoprim, vorinostat, tamoxifen, JQ1, Nutlin 3, afatinib, chloroalkane, dasatinib, BIRB796, FK-506, simvastatin, rapamycin, and sorafenib;
• L is a linker;
• each A is covalently linked to the L as allowed by valence;
• R3 is cyano, aryl, —NH—(C3-C10)heteroaryl, or —N(R5)—(CH2)m—X—(CH2)n—R6, any of which may be optionally substituted with 1 or more Rw groups as allowed by valence;
• R5 at each occurrence is independently H, (C1-C3)alkyl, (C3-C10)heterocyclo, (C3-C10)cycloalkyl, —(CH2)n—(C3-C10) cycloalkyl, —(CH2)n—(C3-C10)heterocyclo, —(CH2)n-aryl, —(CH2)n-heteroaryl, aryl, or heteroaryl, any of which may be optionally substituted with 1 or more Rw groups as allowed by valence;
• R6 at each occurrence is independently OH, (C1-C3)alkyl, —(C1-C3)alkoxy, (C3-C10)heterocyclo, (C3-C10)cycloalkyl, —(CH2)n—(C3-C10)cycloalkyl, —(CH2)n—(C3-C10)heterocyclo, —(CH2)n-aryl, —(CH2)n-heteroaryl, aryl, heteroaryl, or R5 and R6 taken together with the atoms they are attached to forming a nitrogen containing (C3-C10)heterocyclic ring, any of which may be optionally substituted with 1 or more Rw groups as allowed by valence;
• Rw at each occurrence is independently H, halo, cyano, nitro, oxo, alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclo, aryl, heteroaryl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkyl, wherein said alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclo, aryl, heteroaryl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkyl groups may be further independently substituted with one or more groups selected from the group consisting of halo, cyano, oxo(C3-C10)heterocyclo, (C3-C10)cycloalkyl, —(CH2)n—(C3-C10)cycloalkyl, —(CH2)n—(C3-C10)heterocyclo, —(CH2)n-aryl, —(CH2)n-heteroaryl, aryl, and heteroaryl;
• X is a bond, —SO2—, —(CH2)nC(O)(CH2)m—, —C(O)NH—, —C(O)N(Rw)—, —NHC (O)NH—, or —(CH2)n—;
• m is 0, 1, 2, 3, or 4;
• k is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10;
• and
• n is 0, 1, 2, 3, or 4.