Arginine methyltransferase inhibitors and uses thereof

A method of therapeutically treating cancer, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of Formula (I):

• 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;
• RW is optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl;
• provided that when L1 is a bond, RW is not 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 the cancer is selected from the group consisting of breast cancer, prostate cancer, lung cancer, colorectal cancer, bladder cancer, and leukemia.