CXCR4 inhibitors and uses thereof

A method of treating a CXCR4-mediated disease, disorder, or condition, comprising administering to a patient in need thereof a compound of Formula I:

• or a pharmaceutically acceptable salt thereof, wherein the compound inhibits CXCR4 and the disease, disorder, or condition is treated by inhibition of CXCR4, wherein:
• Ring A is a 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring, phenyl, an 8-10 membered bicyclic aromatic carbocyclic ring, a 4-8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• each R1 is independently —R, halogen, —CN, —OR, —N(R)2, —NO2, —N3, —SR, or -L1-R6;
• each R is independently hydrogen or an optionally substituted group selected from C1-6 aliphatic, a 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring, phenyl, an 8-10 membered bicyclic aromatic carbocyclic ring, a 4-8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• each L1 and L2 is independently a covalent bond or a C1-8 bivalent straight or branched hydrocarbon chain wherein 1, 2, or 3 methylene units of the chain are independently and optionally replaced with —O—, —C(O)—, —C(O)O—, —OC(O)—, —N(R)—, —C(O)N(R)—, —(R)NC(O)—, —OC(O)N(R)—, —(R)NC(O)O—, —N(R)C(O)N(R)—, —S—, —SO—, —SO2—, —SO2N(R)—, —(R)NSO2—, —C(S)—, —C(S)O—, —OC(S)—, —C(S)N(R)—, —(R)NC(S)—, —(R)NC(S)N(R)—, or -Cy-;
• each -Cy- is independently a bivalent optionally substituted 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring, optionally substituted phenylene, an optionally substituted 4-8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, an optionally substituted 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, an optionally substituted 8-10 membered bicyclic or bridged bicyclic saturated or partially unsaturated heterocyclic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an optionally substituted 8-10 membered bicyclic or bridged bicyclic heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• R2 is hydrogen, halogen, —CN, —OR, —N(R)2, —NO2, —N3, —SR, -L2-R6, or optionally substituted C1-8 aliphatic;
• R3 is hydrogen, optionally substituted C1-6 aliphatic, or -L3-R6;
• L3 is a C1-6 bivalent straight or branched hydrocarbon chain wherein 1, 2, or 3 methylene units of the chain are independently and optionally replaced with —O—, —C(O)—, —C(O)O—, —OC(O)—, —N(R)—, —C(O)N(R)—, —(R)NC(O)—, —S—, —SO—, —SO2—, —C(S)—, or -Cy-;
• each R4 is independently hydrogen, deuterium, halogen, —CN, —OR6, or C1-4 alkyl, or two R4 groups on the same carbon are optionally taken together to form ═NR6, ═NOR6, ═O, or ═S;
• each R5 is independently R, halogen, —CN, —OR, —N(R)2, —NO2, —N3, —SR, or -L1-R6, or two R5 groups on the same saturated carbon atom are optionally taken together to form ═NR, ═NOR, ═O, ═S, or a spirocyclic 3-6 membered carbocyclic ring;
• each R6 is independently hydrogen or C1-6 alkyl optionally substituted with 1, 2, 3, 4, 5, or 6 deuterium or halogen atoms;
• m is 0, 1, 2, 3, or 4;
• n is 0, 1, 2, 3, or 4;
• and
• p is 0, 1, 2, 3, or 4.