Heterobifunctional compounds and methods of treating disease

A compound represented by Formula I:

• or a pharmaceutically acceptable salt thereof, wherein:
• R1 is —(C1-3 alkylene)-C(O)N(R6)2;
• R2, R3, R5, and R6 are independently hydrogen or C1-4 alkyl;
• R4 is hydrogen, C1-4 alkyl, or halo;
• R7 represents independently for each occurrence halo or C1-4 alkyl;
• A1 is a pyrimidinylene, pyridazinylene, pyrazinylene, pyridinylene, or phenylene, each of which is substituted with n occurrences of R7;
• L is a linker;
• and
• A2 is one of the following:
• R1A is C1-4 alkyl or C3-4 cycloalkyl;
• R2A represents independently for each occurrence C1-4 alkyl or C3-4 cycloalkyl;
• R3A is phenyl substituted with 1, 2, or 3 substituents independently selected from halo, C1-C4 alkyl, or C1-C4 haloalkyl;
• R4A is —(C1-6 alkylene)-C(O)N(R5A)(R6A), —(C1-6 alkylene)-N(R5A)C(O)R7A, —(C1-6 alkylene)-CO2R7A, —(C1-6 alkylene)-OC(O)R7A, C1-6 alkyl, or —(C0-6 alkylene)-(5-6 membered heteroaryl containing 1, 2, or 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur);
• R5A and R6A are independently hydrogen, C1-6 alkyl, or C3-6 cycloalkyl;
• or R5A and R6A are taken together with the nitrogen atom to which they are attached to form a 3-7 membered ring containing 1 nitrogen atom;
• R7A is C1-6 alkyl, —(C1-6 alkylene)-(C3-6 cycloalkyl), or C3-6 cycloalkyl;
• R1B represents independently for each occurrence halo, C1-4 alkyl, or C1-4 haloalkyl;
• R2B is hydrogen, halo, C1-4 alkyl, or C1-4 haloalkyl;
• R3B is —N(R8B)SO2R9B, —SO2N(R8B)2, —SO2R9B, —(C1-6 alkylene)-SO2R9B, C1-6 hydroxyalkyl, or a 4-7 membered saturated carbocyclic ring in which one CH2 is replaced with SO2;
• R4B is hydrogen, halo, or C1-4 alkyl;
• R5B is C1-4 alkyl or C3-4 cycloalkyl;
• R6B is hydrogen, C1-4 alkyl, or C3-4 cycloalkyl;
• R7B represents independently for each occurrence C1-4 alkyl or C3-4 cycloalkyl;
• R8B represents independently for each occurrence hydrogen or C1-4 alkyl;
• or two occurrences of R8B are taken together with the nitrogen atom to which they are attached to form a 3-7 membered heterocyclic ring containing 1 or 2 heteroatoms independently selected from nitrogen and oxygen;
• or R8B and R9B are taken together with their intervening atoms to a form a 5-7 membered ring containing 1, 2, or 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• R9B is C1-6 alkyl, C1-6 haloalkyl, —(C1-6 alkylene)-(C3-6 cycloalkyl), or C3-6 cycloalkyl;
• A3 is phenylene, a 3-10 membered saturated monocyclic, bicyclic or spirocyclic carbocycylene, or C1-6 alkylene;
• and
• n, p, and t are independently 0, 1, or 2.