Carm1 inhibitors and uses thereof

A compound of Formula (I):

• or a pharmaceutically acceptable salt thereof,
• wherein:
• X is —O—, —S—, or —CH2—;
• R1 is hydrogen or optionally substituted C1-4 aliphatic;
• R1a is hydrogen;
• each of R2a, R2b, R2c, and R2d is independently hydrogen, halogen, —CN, —NO2, —C(═O)RA2, —C(═O)ORA2, —C(═O)N(RA2)2, —ORA2, —SRA2, —N(RA2)2, —S(═O)RA2, —S(═O)2RA2, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, wherein each instance of RA2 is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl, or two RA2 groups attached to the same nitrogen atom are joined to form an optionally substituted heterocyclyl or optionally substituted heteroaryl ring;
• Ring HET is a 6-membered monocyclic heteroaryl ring system of the Formula:
• wherein:
• G8 is C—R8 or N;
• G10 is C—R10 or N;
• G11 is C—R11 or N;
• G12 is C—R12 or N;
• provided at least one instance of G8, G10, G11, or G12 is N;
• each instance of R8, R10, R11, and R12 is independently selected from the group consisting of hydrogen, halo, —CN, —NO2, —C(═O)R′, —C(═O)OR′, —C(═O)N(R′)2, optionally substituted alkyl, and -L1-R3;
• each instance of R′ is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl, or two R′ groups attached to the same nitrogen are joined to form an optionally substituted heterocyclyl ring or optionally substituted heteroaryl ring;
• each instance of L1 and L2 is independently a bond, —O—, —N(RL)—, —S—, —C(O)—, —C(O)O—, —C(O)S—, —C(O)N(RL)—, —C(O)N(RL)N(RL)—, —OC(O)—, —OC(O)N(RL)—, —NRLC(O)—, —NRLC(O)N(RL)—, —NRLC(O)N(RL)N(RL)—, —NRLC(O)O—, —SC(O)—, —C(═NRL)—, —C(═NNRL)—, —C(═NORL)—, —C(═NRL)N(RL)—, —NRLC(═NRL)—, —C(S)—, —C(S)N(RL)—, —NRLC(S)—, —S(O)—, —OS(O)2—, —S(O)2O—, —SO2—, —N(RL)SO2—, —SO2N(RL)—, —N(RL)SO2N(RL)—, an optionally substituted C1-10 saturated or unsaturated hydrocarbon chain, wherein one or more moieties selected from the group consisting of —O—, —N(RL)—, —S—, —C(O)—, —C(O)O—, —C(O)S—, —C(O)N(RL)—, —C(O)N(RL)N(RL)—, —OC(O)—, —OC(O)N(RL)—, —NRLC(O)—, —NRLC(O)N(RL)—, —NRLC(O)N(RL)N(RL)—, —NRLC(O)O—, —SC(O)—, —C(═NRL)—, —C(═NNRL)—, —C(═NORL)—, —C(═NRL)N(RL)—, —NRLC(═NRL)—, —C(S)—, —C(S)N(RL)—, —NRLC(S)—, —S(O)—, —OS(O)2—, —S(O)2O—, —SO2—, —N(RL)SO2—, —SO2N(RL)—, and —N(RL)SO2N(RL)— is optionally and independently present between two carbon atoms of the hydrocarbon chain, and optionally and independently present at one or both ends of the hydrocarbon chain;
• each RL is independently hydrogen, optionally substituted alkyl, or a nitrogen protecting group, or RL and R3 taken together form an optionally substituted heterocyclyl or optionally substituted heteroaryl ring, or RL and R13 taken together form an optionally substituted heterocyclyl or optionally substituted heteroaryl ring;
• R3 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl, provided when R3 is hydrogen, then L1 is not a bond;
• and
• R13 is optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl, 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 4n+2 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.