Aryl hydrocarbon receptor agonist prodrugs and methods of use thereof

A compound having a structure of Formula (I):

• wherein:
• A is —Y1—Z1 or a fused bicyclic heteroaryl group having 8-10 total ring atoms and 1, 2, or 3 heteroatoms selected from N, O, or S, and the heteroaryl is optionally substituted with 1, 2, or 3 Ra;
• Y1 is
• O, S, SO, or SO2;
• Z1 is phenyl or a 5- to 6-membered heteroaryl having 1, 2, or 3 heteroatoms selected from N, O, and S, and the phenyl or heteroaryl is optionally substituted with 1, 2, or 3 Ra;
• X1 is N, CR3 or C—O-L-R2;
• R1 is C1-45alkyl, C1-5haloalkyl, C1-5hydroxyalkyl, C3-5cycloalkyl, OC1-5alkyl, N(RN)2, C(═O)C1-4 alkyl, or C(═CH)C1-4alkyl;
• each R2 independently is SO2—R4, PO(R4)2, CO2H, N(RN)2, N(H)—C2-6alkylene-N(RN)2, N(H)—C2-6polyoxyalkylene-N(RN)2, NHCH(R5)CO2H, NH—C1-5alkylene-CH(NH2)CO2H, a saccharide, or NH-phenyl wherein the phenyl is optionally substituted with 1, 2, or 3 Rb;
• R3 is halo, C1-6alkoxy, OH, or N(RN)2;
• each L independently is C(O), C(O)—Wn—C(O), C(O)—Wn, or C(O)NH—Wn, or when R2 is SO2—R4, PO(R4)2, or a saccharide, L can be a bond;
• each W independently is CH2, C2-3alkylene-O, or O—C2-3alkylene;
• n is 1, 2, 3, 4, 5, or 6;
• each R4 independently is OH or NH2;
• each R5 independently is H, C1-5alkyl, or C1-5alkylene-R6;
• each R6 independently is CO2H, CO2C1-3alkyl, CON(RN)2, OH, OCH3, N(RN)2, NHC(NH)NH2, heteroaryl comprising 5 or 6 total ring atoms and 1, 2, or 3 heteroatoms selected from N, O, and S, or phenyl, wherein the heteroaryl or phenyl is optionally substituted with 1, 2, 3, 4, or 5 C0-2alkylene-Rb substituents;
• each Ra independently is halo, C1-5alkyl, CO2H, CO2C1-3alkyl, CON(RN)2, OH, OC1-3alkyl, or N(RN)2;
• each Rb independently is CO2H, CO2C1-3alkyl, or OH;
• and
• each RN independently is H or C1-3alkyl;
• or a pharmaceutically acceptable salt thereof,
• provided that when Y1 is
• Z1 is unsubstituted phenyl, and R1 is isopropyl, then X1 is N or CR3, and R3 is halo, C1-6alkoxy, or N(RN)2.