PRMT5 inhibitors and uses thereof

A compound of Formula (A):

• or a pharmaceutically acceptable salt thereof;
• wherein:
• R12 is hydrogen, and —R13 is halogen;
• or
• R12 is hydrogen, and R13 is —OR1;
• R1 is hydrogen, Rz, or —C(O)Rz, wherein Rz is optionally substituted C1-6 alkyl;
• Lz is —C(O)N(R)— or —XA—C(R2A)(R3A)C(═O)N(R)—, wherein XA is —CR4AR5A—, and each instance of R2A, R3A, R4A, and R5A is hydrogen;
• R is hydrogen or optionally substituted C1-6 aliphatic;
• Ring Z is a monocyclic or bicyclic aromatic ring having 0-4 heteroatoms selected from nitrogen, wherein Ring Z is substituted with 0, 1, 2, 3, 4, or 5 Ry groups, as valency permits;
• each Ry is independently selected from the group consisting of halo, —CN, —NO2, optionally substituted aliphatic, optionally substituted carbocyclyl, optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted heteroaryl, —ORA, —N(RB)2, —SRA, —C(═O)RA, —C(O)ORA, —C(O)SRA, —C(O)N(RB)2, —C(O)N(RB)N(RB)2, —OC(O)RA, —OC(O)N(RB)2, —NRBC(O)RA, —NRBC(O)N(RB)2, —NRBC(O)N(RB)N(RB)2, —NRBC(O)ORA, —SC(O)RA, —C(═NRB)RA, —C(═NNRB)RA, —C(═NORA)RA, —C(═NRB)N(RB)2, —NRBC(═NRB)RB, —C(═S)RA, —C(═S)N(RB)2, —NRBC(═S)RA, —S(O)RA, —OS(O)2RA, —SO2RA, —NRBSO2RA, and —SO2N(RB)2;
• each RA is independently selected from the group consisting of hydrogen, optionally substituted aliphatic, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl;
• each RB is independently selected from the group consisting of hydrogen, optionally substituted aliphatic, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or two RB groups are taken together with their intervening atoms to form an optionally substituted heterocyclic ring;
• R21, R22, R23, and R24 are each independently hydrogen, halo, or optionally substituted aliphatic;
• each Rx is independently selected from the group consisting of halo, —CN, optionally substituted aliphatic, and —OR′;
• R′ is hydrogen or optionally substituted aliphatic;
• n is 0, 1, 2, 3, 4, 5, 6, 7, or 8;
• and
• x is 1, and y is 1;
• or
• x is 0, and y is 2, 3, or 4;
• or
• x is 1, and y is 3.