Arginine methyltransferase inhibitors and uses thereof

A compound of Formula (VI):

• or a pharmaceutically acceptable salt thereof,
• wherein X is N, Z is NR4, and Y is CR5;
• or
• X is NR4, Z is N, and Y is CR5;
• or
• X is CR5, Z is NR4, and Y is N;
• or
• X is CR5, Z is N, and Y is NR4;
• Rx is optionally substituted C1-4 alkyl or optionally substituted C3-4 cycloalkyl;
• L1 is a bond, —O—, —N(RB)—, —S—, —C(O)—, —C(O)O—, —C(O)S—, —C(O)N(RB)—, —C(O)N(RB)N(RB)—, —OC(O)—, —OC(O)N(RB)—, —NRBC(O)—, —NRBC(O)N(RB)—, —NRBC(O)N(RB)N(RB)—, —NRBC(O)O—, —SC(O)—, —C(═NRB)—, —C(═NNRB)—, —C(═NORA)—, —C(═NRB)N(RB)—, —NRBC(═NRB)—, —C(S)—, —C(S)N(RB)—, —NRBC(S)—, —S(O)—, —OS(O)2—, —S(O)2O—, —SO2—, —N(RB)SO2—, —SO2N(RB)—, or an optionally substituted C1-6 saturated or unsaturated hydrocarbon chain, wherein one or more methylene units of the hydrocarbon chain is optionally and independently replaced with —O—, —N(RB)—, —S—, —C(O)—, —C(O)O—, —C(O)S—, —C(O)N(RB)—, —C(O)N(RB)N(RB)—, —OC(O)—, —OC(O)N(RB)—, —NRBC(O)—, —NRBC(O)N(RB)—, —NRBC(O)N(RB)N(RB)—, —NRBC(O)O—, —SC(O)—, —C(═NRB)—, —C(═NNRB)—, —C(═NORA)—, —C(═NRB)N(RB)—, —NRBC(═NRB)—, —C(S)—, —C(S)N(RB)—, —NRBC(S)—, —S(O)—, —OS(O)2—, —S(O)2O—, —SO2—, —N(RB)SO2—, or —SO2N(RB)—;
• each RA is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, and a sulfur protecting group when attached to a sulfur atom;
• each RB is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, and a nitrogen protecting group, or an RB and RW on the same nitrogen atom may be taken together with the intervening nitrogen to form an optionally substituted heterocyclic ring;
• Ring A is optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl;
• R3 is hydrogen, C1-4 alkyl, or C3-4 cycloalkyl;
• R4 is hydrogen, optionally substituted C1-6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, optionally substituted C3-7 cycloalkyl, optionally substituted 4-to 7-membered heterocyclyl;
• or optionally substituted C1-4 alkyl-Cy;
• Cy is optionally substituted C3-7 cycloalkyl, optionally substituted 4-to 7-membered heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl;
• and
• R5 is hydrogen, halo, —CN, optionally substituted C1-4 alkyl, or optionally substituted C3-4 cycloalkyl;
• wherein, and unless otherwise specified,
• heterocyclyl or heterocyclic refers to a radical of a 3-10 membered non-aromatic ring system having ring carbon atoms and 1-4 ring heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur;
• carbocyclyl or carbocyclic refers to a radical of a non-aromatic cyclic hydrocarbon group having from 3 to 10 ring carbon atoms and zero heteroatoms in the non-aromatic ring system;
• aryl refers to a radical of a monocyclic or polycyclic aromatic ring system having 6-14 ring carbon atoms and zero heteroatoms provided in the aromatic ring system;
• and
• heteroaryl refers to a radical of a 5-10 membered monocyclic or bicyclic 4n+2 aromatic ring system having ring carbon atoms and 1-4 ring heteroatoms provided in the aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen and sulfur.