PRMT5 inhibitors and uses thereof

A compound of Formula (I):

• or a pharmaceutically acceptable salt thereof,
• wherein:
• represents a single or double bond;
• R1 is hydrogen, Rz, or —C(O)Rz, wherein Rz is optionally substituted C1-6 alkyl;
• X is —O— or —N(R)—;
• each R is hydrogen;
• R2 and R3 are independently selected from the group consisting of hydrogen, halo, —CN, —NO2, optionally substituted aliphatic, optionally substituted carbocyclyl, optionally substituted phenyl, 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;
• or R2 and R3 are taken together with their intervening atoms to form an optionally substituted carbocyclic or heterocyclic ring;
• 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;
• R8, R9, R10, and R11 are independently hydrogen, halo, or optionally substituted aliphatic;
• Cy is a monocyclic or bicyclic, saturated, partially unsaturated, or aromatic ring system having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein Cy is substituted with 0, 1, 2, 3, or 4 Ry groups;
• 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;
• or an Ry group may be optionally taken together with R2 or R3 to form an optionally substituted 5- to 6-membered carbocyclic or heterocyclic ring fused to Cy;
• each Rx is independently selected from the group consisting of halo, —CN, optionally substituted aliphatic, —OR′, and —N(R″)2;
• R′ is hydrogen, or optionally substituted aliphatic;
• each R″ is independently hydrogen or optionally substituted aliphatic, or two R″ are taken together with their intervening atoms to form an optionally substituted heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• and
• n is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10, as valency permits;
• wherein each instance of aliphatic is independently an alkyl, alkenyl, alkynyl, cycloalkyl, or cycloalkenyl group.