Protein degraders and uses thereof

A compound of formula I:

• or a pharmaceutically acceptable salt thereof, wherein:
• X1 is a bivalent moiety selected from a covalent bond, —CH2—, —C(O)—, —C(S)—, or
• R1 is hydrogen, halogen, —CN, —OR, —SR, —S(O)R, —S(O)2R, —NR2, or an optionally substituted C1-4 aliphatic;
• each R2 is independently hydrogen, —R6, halogen, —CN, —NO2, —OR, —SR, —NR2, —S(O)2R, —S(O)2NR2,
• —S(O)R, —C(O)R, —C(O)OR, —C(O)NR2, —C(O)N(R)OR, —OC(O)R, —OC(O)NR2, —N(R)C(O)OR,
• —N(R)C(O)R, —N(R)C(O)NR2, or —N(R)S(O)2R;
• Ring A is a bi- or tricyclic ring selected from
• Ring B is a fused ring selected from 6-membered aryl containing 0-2 nitrogen atoms, 5 to 7-membered partially saturated carbocyclyl, 5 to 7-membered partially saturated heterocyclyl with 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur, and a 5-membered heteroaryl with 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur;
• R3 is selected from hydrogen, halogen, ~OR, —NR2, or —SR;
• each R4 is independently hydrogen, —R6, halogen, —CN, —NO2, —OR, —SR, —NR2, —S(O)2R, —S(O)2NR2,
• —S(O)R, —C(O)R, —C(O) OR, —C(O) NR2, —C(O) N(R)OR, —OC(O)R, —OC(O)NR2, —N(R)C(O)OR,
• —N(R)C(O)R, —N(R)C(O)NR2, or —N(R)S(O)2R;
• R5 is hydrogen, C1-4 aliphatic, or —CN;
• each R6 is independently an optionally substituted group selected from C1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• L is a covalent bond or a bivalent, saturated or unsaturated, straight or branched C1-50 hydrocarbon chain, wherein 0-6 methylene units of L are independently replaced by -Cy-, —O—, —NR—, —S—, —OC(O)—, —C(O)O—, —C(O)—, —S(O)—, —S(O)2—, —NRS(O)2—, —S(O)2NR—, —NRC(O)—, —C(O)NR—, —OC(O)NR—, —NRC(O)O—,
• wherein:
• each -Cy- is independently an optionally substituted bivalent ring selected from phenylenyl, an 8-10 membered bicyclic arylenyl, a 4-7 membered saturated or partially unsaturated carbocyclylenyl, a 4-7 membered saturated or partially unsaturated spiro carbocyclylenyl, an 8-10 membered bicyclic saturated or partially unsaturated carbocyclylenyl, a 4-7 membered saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 4-7 membered saturated or partially unsaturated spiro heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, an 8-10 membered bicyclic saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5-6 membered heteroarylenyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and an 8-10 membered bicyclic heteroarylenyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• TBM is a target binding moiety, wherein the target binding moiety is an ABL binding moiety, and wherein the ABL binding moiety is ponatinib, masitinib, imatinib, nilotinib, dasatinib, XL228, pexmetinib (ARRY-614), ENMD-2076, PD180970, AG957, adaphostin (NSC 680410), PD173955, or asciminib (ABL001);
• m is 0, 1, 2, 3 or 4;
• each of n is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10;
• and
• each R is independently hydrogen, or an optionally substituted group selected from C1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or:
• two R groups on the same nitrogen are taken together with their intervening atoms to form a 4-7 membered saturated, partially unsaturated, or heteroaryl ring having 0-3 heteroatoms, in addition to the nitrogen, independently selected from nitrogen, oxygen, and sulfur.