Pyrido[3,4-d]pyrimidinone and pyrimdllne aryl hydrocarbon receptor antagonists and uses thereof

A compound, or pharmaceutically acceptable salt thereof, having a structure of Formula (I) or Formula (II):

• L is a bond, C(O), C2-3alkenylene, or C2-3alkynylene;
• Ar1 is phenyl, C3-8cycloalkyl, or 4-8 membered aromatic or non-aromatic heterocyclyl having 1-3 ring heteroatoms selected from O, N, and S;
• each RA is independently halo, OH, ═O, CN, C1-6alkyl, C1-6haloalkyl, C1-6hydroxyalkyl, C1-6alkoxy, C1-6haloalkoxy, cyclopropyl, NRNRN, C(O)NRNRN, CO2RN, C(O)RN, or SO2—C1-6alkyl;
• each RN is independently H or C1-6alkyl;
• Ar2 is 5-10 membered aromatic or non-aromatic ring having 0-3 ring heteroatoms selected from O, N, and S;
• each RB is independently halo, CN, C1-6alkyl, OH, ═O, C1-6hydroxyalkyl, C(O)RN, CO2RN, C(O)NRNRN, Het, C(O)—C0-2alkylene-Het, or N(RN)—C0-3alkylene-C(O)—C0-3alkylene-Het;
• Het is a 4-8-membered aromatic or non-aromatic ring having 0-3 ring heteroatoms selected from N, O, and S, and is optionally substituted with 1, 2, or 3 RC;
• each RC is independently halo, OH, ═O, CN, C1-6alkyl, C1-6haloalkyl, C1-6hydroxyalkyl, C1-6alkoxy, C1-6haloalkoxy, NRNRN, C(O)NRNRN, CO2RN, C(O)RN, or SO2—C1-6alkyl;
• R1 is C1-6alkyl, C1-6alkylene-RD, C1-6alkylene-C(O)RD, C1-6alkylene-NHSO2cyclopropyl, or C1-6alkylene-NRN—C(O)RN;
• and
• RD is ORN or NRNRN,
• with the proviso that
• (i) for compounds of Formula (I), when L is a bond, then (a) Ar2 is substituted with at least one RB selected from Het, C(O)—C0-2alkylene-Het, and N(RN)—C0-3alkylene-C(O)—C0-3alkylene-Het or (b) Ar2 comprises a 8-10-membered bicyclic aromatic or non-aromatic ring having 1-3 ring heteroatoms and is substituted with 0-3 RB;
• and
• (ii) for compounds of Formula (II), when L is a bond, Ar2 is phenyl or a 6-membered aromatic heterocyclyl, Ar2 is substituted with 1 RB, and RB is Het, then (a) Het is attached to Ar2 via a carbon ring atom of Het or (b) Het is substituted with 1, 2, or 3 RC.