Substituted indoles with inhibitory activity

A compound having a structure according to Formula T-A

• wherein
• X1 is selected from CR5 or N,
• X2, X3, X4, and X5 are independently selected from CH, CL2R3, CR4, or N,
• L1 is a linker selected from a bond, —C1-C6 alkylene-, —C2-C6 alkenylene-, —C2-C6 alkynylene-, —C1-C6 haloalkylene-, —C2-C6 haloalkenylene-, —C2-C6 haloalkynylene-, —C1-C6 alkoxy-, —C1-C6 alkenyleneoxy-, —C1-C6 alkylamine-, —C1-C6 alkylamide-, —C1-C6 alkylsulfide-, —C1-C6 alkylthiol-, —C1-C6 alkylsulfoxide-, —C1-C6 alkylsulfonyl-, —C1-C6 alkylsulfonamide-, —C1-C6 alkylsulfoximine-, —C1-C6 alkyl sulfur diimide-, —C3-C7 cycloalkyl-, —C2-C7 heterocycloalkyl-, —C5-C7 aryl-, —C2-C7 heteroaryl-, —R′CO2R″—, —C(O)R″—, —R′CONHR″—, —R′CONR″R′″—, wherein R′, R″, and R′″ are independently absent or selected from a bond, C1-C6 alkyl, C2-C6alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C1-C6 haloalkyl, cycloalkyl, alkyl cycloalkyl, cycloalkenyl, alkyl cycloalkenyl, heterocycloalkyl, alkyl heterocycloalkyl, cycloheteroalkenyl, aryl, alkylaryl, heteroaryl or two or more of R′, R″, and R′″ can combine and form a ring, and wherein L1 is optionally substituted with one or more groups;
• L2 is a linker selected from a bond, —C1-C6 alkylene-, —C2-C6 alkenylene-, —C2-C6 alkynylene-, —C1-C6 haloalkylene-, —C2-C6 haloalkenylene-, —C2-C6 haloalkynylene-, —C1-C6 alkoxy-, —C1-C6 alkenyleneoxy-, —C1-C6 alkylamine-, —C1-C6 alkylamide-, —C1-C6 alkylsulfide-, —C1-C6 alkylthiol-, —C1-C6 alkylsulfoxide-, —C1-C6 alkylsulfonyl-, —C1-C6 alkylsulfonamide-, —C1-C6 alkylsulfoximine-, —C1-C6 alkyl sulfur diimide-, —C3-C7 cycloalkyl-, —C2-C7 heterocycloalkyl-, —C5-C7 aryl-, —C2-C7 heteroaryl-, —R′CO2R″—, —C(O)R″—, —R′CONHR″—, —R′CONR″R′″—, wherein R′, R″, and R′″ are independently absent or selected from a bond, C1-C6 alkyl, C2-C6alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C1-C6 haloalkyl, cycloalkyl, alkyl cycloalkyl, cycloalkenyl, alkyl cycloalkenyl, heterocycloalkyl, alkyl heterocycloalkyl, cycloheteroalkenyl, aryl, alkylaryl, heteroaryl or two or more of R′, R″, and R′″ can combine and form a ring, and wherein L2 is optionally substituted with one or more groups;
• R1 is selected from hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C2-C6 haloalkenyl, C2-C6 haloalkynyl, C1-C6alkoxy, C1-C6 haloalkoxy, C1-C6 alkylamine, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, wherein R1 is optionally substituted or unsubstituted;
• R2 is selected from hydrogen, cycloalkyl, cycloalkenyl, heterocycloalkyl, heteroalkyl, cycloheteroalkenyl, aryl, or heteroaryl, wherein R2 is optionally substituted with one or more groups selected from halogen, alkyl, haloalkyl, heteroalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkoxy, haloalkoxy, amine, alkylamine, amide, alkylamide, hydroxyl, cycloalkyl, heterocycloalkyl, cyano, nitro, —R′CO2H, —CO2R″, —R′CO2R″, —CONH2, —R′CONH2, —CONHR″, —R′CONHR″, —CONR″R′″, —R′CONR″R′″, —CONHOH, —R′CONHOH, —R′CONHCN, —NR′C(═O)—R″, —SR″, —SO—R″, —SO2—R″, —R′SO3R″, —R′SO2NHCOR″, —R′CONHSO2R″, —SO2NR′R″, —R′SO2NR′R″, —NR′SO2R″, —OCONR′R″, —NR′CO2—R″, —OCO2—R″, —NHCONH—R″, —OCO—R″, or —NR′R″, —SF5, wherein R′, R″, and R′″ are independently selected from hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C1-C6 haloalkyl, cycloalkyl, alkyl cycloalkyl, cycloalkenyl, alkyl cycloalkenyl, heterocycloalkyl, alkyl heterocycloalkyl, cycloheteroalkenyl, aryl, alkyl aryl, heteroaryl, or alkyl heteroaryl or two or more of R′, R″, and R′″ can combine and form a ring;
• R3 is selected from a metal (for e.g., Zn) chelating group, an acid group, or an acid isostere, such as —R′CO2H, —CO2R″, —R′CO2R″, —R′COR″, —COR″, —CONH2, —R′CONH2, —CONHR″, —R′CONHR″, —CONR″R′″, —R′CONR″R′″, —R′CONHOH, —N(OH)COR″, —R′N(OH)COR″, —CONH(OR″), —R′CONH(OR″), —ONH(COR″), —R′ONH(COR″), —R′CONHCN, —NR′C(═O)—R″, —R′SO2NHCOR″, —R′CONHSO2R″, —SR″, —SOR″, —SO2—R″, —R′SO2—R″, —SO(OR″), —R′SO(OR″), —SO2(OR″), —R′SO2(OR″), —SO2NR′R″, —R′SO2NR′R″, —NR′SO2R″, —CONR′SO2R″, —CONR′SO2NR″R′″, —NR′SO2(OR″), —C(O)N(CH2R′)—OR″, —O—NR′—COR″, —OCONR′R″, —NR′CO(OR″), —OCO(OR″), —NHCONH—R″, —NHCONHCO—R″, —NHCONHSO2—R″, —OCO—R″, —NR′R″, —PO(OR″)(R′″), —PO(OR″)(OR′″), —R′PO(OR″)(OR′″), —C(O)-haloalkyl, substituted cycloalkenyl, substituted or unsubstituted dioxocyclopentyl, heterocycloalkyl, heteroalkyl, heterocycloalkenyl, aryl, or heteroaryl, wherein R′, R″, and R′″ are independently selected from hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C1-C6 haloalkyl, cycloalkyl, alkyl cycloalkyl, cycloalkenyl, alkyl cycloalkenyl, heterocycloalkyl, alkyl heterocycloalkyl, cycloheteroalkenyl, substituted or unsubstituted aryl, alkyl aryl, substituted or unsubstituted heteroaryl, or alkyl heteroaryl or two or more of R′, R″, and R′″ can combine and form a ring, and wherein R3 is optionally substituted with one or more groups, wherein R3 is not hydroxamic acid;
• R4 is selected from hydrogen, halogen, alkyl, haloalkyl, heteroalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkoxy, haloalkoxy, amine, alkylamine, amide, alkylamide, hydroxyl, cycloalkyl, heterocycloalkyl, cyano, nitro, —R′CO2H, —CO2R″, —R′CO2R″, —CONH2, —R′CONH2, —CONHR″, —R′CONHR″, —CONR″R′″, —R′CONR″R′″, —CONHOH, —R′CONHOH, —R′CONHCN, —NR′C(═O)—R″, —SR″, —SO—R″, —SO2—R″, —R′SO3R″, —R′SO2NHCOR″, —R′CONHSO2R″, —SO2NR′R″, —R′SO2NR′R″, —NR′SO2R″, —OCONR′R″, —NR′CO2—R″, —OCO2—R″, —NHCONH—R″, —OCO—R″, —NR′R″, cycloalkyl, cycloalkenyl, heterocycloalkyl, heteroalkyl, cycloheteroalkenyl, aryl, or heteroaryl, SF5, wherein R′, R″, and R′″ are independently selected from hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C1-C6 haloalkyl, cycloalkyl, alkyl cycloalkyl, cycloalkenyl, alkyl cycloalkenyl, heterocycloalkyl, alkyl heterocycloalkyl, cycloheteroalkenyl, aryl, alkylaryl, heteroaryl, alkylheteroaryl or two or more of R′, R″, and R′″ can combine and form a ring, and wherein R4 is optionally substituted with one or more groups;
• R5 when present, is selected from hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 heteroalkyl, C1-C6 alkylamine, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or —Y2—R6;
• wherein Y2 is selected from C1-C6 alkylene, C1-C6 haloalkylene, C2-C6 alkenylene, or C2-C6 heteroalkylene;
• R6 is selected from hydrogen, halogen, cyano, hydroxy, amino, C1-C6 alkylamino, C1-C6 alkoxy, C3-C8 cycloalkyl, substituted or unsubstituted C2-C8 heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or —Y3—R7;
• Y3 is a bond, —O—, —S—, —SO—, —SO2—, —NR′—, —CO—, —C(O)O—, —OC(O)—, NHC(O)—, —C(O)NR′—, —SO2NR′—, —NHSO2—, —OC(O)NR′—, —NHC(O)O—, —OC(O)O—, —NHC(O)NR′—;
• wherein R′ is selected from hydrogen and C1-C4 alkyl;
• and R7 is selected from hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl,
• is a bond that can be present or absent;
• or a pharmaceutically acceptable salt, ester, or prodrug thereof.