USP30 inhibitors and uses thereof

A compound of formula I′:

• or a pharmaceutically acceptable salt thereof, wherein:
• Ring A is phenyl, a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic aryl or heteroaryl ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• L1 is a C1-3 bivalent hydrocarbon chain wherein one methylene unit of the chain is replaced by —C(O)N(R)—, —N(R)C(O)—, —S(O)—, —S(O)2—, —S(O)N(R)—, —S(O)2N(R)—, or —S(O)(R)═N—;
• each R is independently hydrogen or an optionally substituted C1-3 aliphatic group;
• or:
• two R groups on the same nitrogen are optionally 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, or sulfur;
• or
• an R group and R1 on the same nitrogen are optionally 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, or sulfur;
• R1 is an optionally substituted group selected from C1-6 aliphatic, a 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring, a 5-8 membered saturated or partially unsaturated bridged bicyclic carbocyclic ring, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• each R2 is independently halogen, —CF3, —CN, —C(O)NHR, —NO2, —NHR, —NHC(O)R, —NHS(O)2R, —N(R)2, or —OR, or a C1-6 aliphatic group;
• or
• two R2 on the same carbon are optionally taken together to form ═O;
• or
• two R2 groups are optionally taken together with their intervening atoms to form a 5-8 membered partially unsaturated fused ring having 0-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• L2 is —C(O)N(R′)—;
• R′ is hydrogen or a C1-3 aliphatic group;
• L3 is —C(O)N(R″)—;
• R″ is hydrogen or a C1-3 aliphatic group;
• R3 is hydrogen or C1-3 aliphatic;
• R4 is hydrogen;
• R5 is hydrogen;
• Ring B is phenyl, a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic aryl or heteroaryl ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• each R6 is independently halogen, —CN, —NO2, —NHR, —N(R)2, —OR, or an optionally substituted C1-6 aliphatic group;
• or:
• two R6 on the same carbon are optionally taken together to form ═O;
• an R6 group and R′ group are optionally taken together with their intervening atoms to form a 5-8 membered partially unsaturated fused ring having 0-2 heteroatoms, in addition to the nitrogen, independently selected from nitrogen, oxygen, or sulfur;
• an R6 group and R3 group are optionally taken together with their intervening atoms to form a 5-8 membered partially unsaturated spiro-fused ring having 0-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• or
• an R6 group and R″ group are optionally taken together with their intervening atoms to form a 5-8 membered partially unsaturated fused ring having 0-2 heteroatoms, in addition to the nitrogen, independently selected from nitrogen, oxygen, or sulfur;
• Ring C is phenyl, a 3-8 membered saturated or partially unsaturated carbocyclic ring, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic aryl or heteroaryl ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• each R7 is independently halogen, —CN, —NO2, —NHR, —N(R)2, —OR, or an C1-6 aliphatic group;
• or
• two R7 on the same carbon are optionally taken together to form ═O;
• or
• an R7 group and R″ group are optionally taken together with their intervening atoms to form a 5-8 membered partially unsaturated fused ring having 0-2 heteroatoms, in addition to the nitrogen, independently selected from nitrogen, oxygen, or sulfur;
• and
• each of m, n, and p is independently 0, 1, 2, or 4;
• provided that R1 is other than isopropyl, t-butyl, 1-methylcyclopropyl, 1-fluoromethylcyclopropyl, 1-difluoromethylcyclopropyl, 1-trifluoromethylcyclopropyl, or 3-methyl-3-oxetanyl when L1 is —S(O)2N(R)—;
• R1 is other than ethyl when L1 is —S(O)2N(R)— and Ring A is naphthyl;
• and
• the compound is other than