PRMT5 inhibitors and uses thereof

A compound having the structure of Formula II:

• or a pharmaceutically acceptable salt thereof,
• wherein:
• in each instance is independently a double bond or a single bond;
• R1 is H, halogen, C1-C4 alkyl, C2-C4 alkenyl, —O(Ra), C3-C6 cycloalkyl, C3-C7 heterocyclyl or N(Ra)2;
• R2 is H, halogen, hydroxyl, cyano, —C(O)NH2, —C(O)N(Ra)2, —C(O)O(Ra), —C(O)Ra, —N(Ra)2, —O(Ra), C3-C6 cycloalkyl, C3-C7 heterocyclyl, optionally substituted C1-C4 alkyl or optionally substituted C2-C6 alkenyl;
• W is C(Rb) or C(O), with the proviso that V is NH and the between W and V is a single bond when W is C(O);
• V is CH, NH or N, with the proviso that W is C(Rb) and the between W and V is a double bond when V is CH or N;
• X1 and X2 are each independently CH or N;
• Y1 is (CH2), or C(O), with the proviso that Y1 cannot be C(O) when Y2 or Y3 is C(O);
• Y2 is CH2, C(O), S, SO2, O or NRa, with the provisos that:
• Y2 cannot be C(O) when Y1 or Y3 is C(O);
• and
• the between Y2 and Y3 is a single bond;
• Y3 is CH2 or C(O), with the provisos that:
• Y3 cannot be C(O) when Y1 or Y2 is C(O);
• and
• the between Y2 and Y3 is a single bond;
• or
• Y2 and Y3 are CH and the between Y2 and Y3 is a double bond;
• Z is CH2, O, S or NH;
• Ra in each instance is independently H, C1-C4 alkyl or C3-C6 cycloalkyl;
• Rb is H, halogen, hydroxyl, cyano, —C(O)NH2, —C(O)N(Ra)2, —C(O)O(Ra), —C(O)Ra, —N(Ra)2, —O(Ra), C3-C6 cycloalkyl, C3-C7 heterocyclyl, optionally substituted C1-C4 alkyl or optionally substituted C2-C6 alkenyl;
• m is 0, 1, 2 or 3;
• and
• n is 1 or 2.