A compound of formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, tautomer, nitrogen oxide, metabolite, prodrug, or mixture thereof:
- wherein,
- W is —N(R1a)—, —O—, —S—, —S(═O)1-2—, —C(═O)—, —(C(R2a)(R2b))1-4—, —N(R1a)(C(R2a)(R2b))1-4—, —N(R1a)C(═O)—, or —O(C(R2a)(R2b))1-4—;
- each of Arl and Ar2 is independently five-membered heteroaryl, wherein Ar1 and Ar2 are each optionally substituted with 1, 2, or 3 R2;
- Ar3 is aryl, or heteroaryl, wherein Ar3 is optionally substituted with 1, 2, 3, or 4 R3;
- Cy is cycloalkyl, heterocyclyl, spiro bicyclic, spiro heterobicyclic, fused bicyclic, fused heterobicyclic, bridged cyclic, bridged heterocyclic, aryl, or heteroaryl, wherein Cy is optionally substituted with 1, 2, 3, or 4 R4;
- Y is -(L1-W1)m-L2-;
- L1 is absent, or L1 is —O—, —C(═O)—, —N(Ri)—, —N(Rh)C(O)—, or —S(═O)0-2—;
- W1 is C1-4 alkylene, wherein C1-4 alkylene is optionally substituted with 1, 2, 3, or 4 groups independently selected from H, F, Cl, Br, I, —OH, —NH2, —NO2, —CN, or C1-6 alkoxy;
- L2 is absent, or L2 is —O—, —C(═O)—, —OC(═O)—, —C(═O)O—, —C(═O)—C(═O)—, —C(═O)—C(═O)N(Ra)—, —N(Rb)—, —C(═O)N(Rc)—, —N(Rc)C(═O)—, —C(═O)N(Rc)—R15—C(═O)O—, —C(═O)N(Rc)—R15—C(═O)N(Ra)—, —N(Rd)C(═O)N(Rc)—, —N(Rg)C(═O)O—, —S(═O)0-2—, —S(═O)1-2N(Re)—, —N(Rf)S(═O)1-2—, or —N(Rf)S(═O)1-2—R15—N(Ra)—;
- Z is H, —CN, alkyl, alkenyl, alkynyl, haloalkyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, cycloalkylalkyl, spiro bicyclic, spiro heterobicyclic, fused bicyclic, fused heterobicyclic, bridged cyclic, bridged heterocyclic, aryl, or heteroaryl, wherein each of alkyl, alkenyl, alkynyl, haloalkyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, cycloalkylalkyl, spiro bicyclic, spiro heterobicyclic, fused bicyclic, fused heterobicyclic, bridged cyclic, bridged heterocyclic, aryl, and heteroaryl is optionally substituted with one or more R5;
- R1 is alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, or heterocyclyl, wherein R1 is optionally substituted with 1, 2, 3, or 4 R6;
- each R2 is independently H, —CN, —NO2, —OH, —NH2, F, Cl, Br, I, alkyl, alkenyl, alkynyl, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxy, alkoxyalkyl, aralkoxyalkyl, aryloxyalkyl, haloalkoxy, —S(═O)0-2R7, —C(═O)R8, —C(═O)R8a, —OS(═O)1-2R7a, —OC(═O)OR8a, —N(R9a)C(═O)R9, —OC(═O)NR10R10a, —NR11R11a, —N(R12)S(═O)1-2R12a, —N(R13)C(═O)NR13aR13b, —R14—S(═O)0-2R7, —R14—C(═O)R8, —R14—OS(═O)1-2R7a, —R14—OC(═O)R8a, —R14—N(R9a)C(═O)R9, —R14—OC(═O)NR10R10a, —R14—NR11R11a, —R14—N(R12)S(═O)1-2R12a, or —R14—N(R13)C(═O)NR13aR13b;
- each of R2a and R2b is independently H, —CN, —OH, —NH2, F, Cl, Br, I, alkyl, alkenyl, alkynyl, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyl, haloalkoxy, aryl, aralkyl, heteroaryl, or heteroarylalkyl;
- each R3 is independently H, —CN, —NO2, —OH, —NH2, F, Cl, Br, I, alkyl, alkenyl, alkynyl, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyl, haloalkoxy, —S(═O)0-2R7, —C(═O)R8, —OS(═O)1-2R7a, —OC(═O)R8a, —C(═O)OR8a, —N(R9a)C(═O)R9, —OC(═O)NR10R10a, —NR11R11a, —N(R12)S(═O)1-2R12a, —N(R13)C(═O)NR13aR13b, —R14—S(═O)0-2R7, —R14—C(═O)R8, —R14—OS(═O)1-2R7a, —R14—OC(═O)R8a, —R14—N(R9a)C(═O)R9, —R14—OC(═O)NR10R10a, —R14—NR11R11a, —R14—N(R12)S(═O)1-2R12a, or —R14—N(R13)C(═O)NR13aR13b;
- each R4 is independently H, oxo (C═O), —CN, —NO2, —OH, —NH2, F, Cl, Br, I, alkyl, alkenyl, alkynyl, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyl, haloalkoxy, —S(═O)0-2R7, —C(═O)R8, —OS(═O)1-2R7a, —C(═O)OR8a, —OC(═O)R8a, —N(R9a)C(═O)R9, —C(═O)NR9aR9, —OC(═O)NR10R10a, —NR11R11a, —N(R12)S(═O)1-2R12a, —N(R13)C(═O)NR13aR13b, —R14—S(═O)0-2R7, —R14—C(═O)R8, —R14—OS(═O)1-2R7a, —R14—OC(═O)R8a, —R14—N(R9a)C(═O)R9, —R14—OC(═O)NR10R10a, —R14—NR11R11a, —R14—N(R12)S(═O)1-2R12a, or —R14—N(R13)C(═O)NR13aR13b;
- each R5 is independently H, oxo (C═O), —CN, —NO2, —OH, —NH2, F, Cl, Br, I, alkyl, alkenyl, alkynyl, alkylamino, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyl, haloalkoxy, aryl, aralkyl, —S(═O)0-2R7, —C(═O)R8, —OS(═O)1-2R7a, —OC(═O)R8a, —C(═O)OR8a, —N(R9a)C(═O)R9, —OC(═O)NR10R10a, —NR11R11a, —N(R12)S(═O)1-2R12a, —N(R13)C(═O)NR13aR13b, —R14—S(═O)0-2R7, —R14—C(═O)R8, —R14—OS(═O)1-2R7a, —R14—OC(═O)R8a, —R14—N(R9a)C(═O)R9, —R14—OC(═O)NR10R10a, —R14—NR11R11a, —R14—N(R12)S(═O)1-2R12a, or —R14—N(R13)C(═O)NR13aR13b;
- each R6 is independently H, —CN, —NO2, —OH, —NH2, F, Cl, Br, I, alkyl, alkenyl, alkynyl, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyl, haloalkoxy, —S(═O)0-2R7, —C(═O)R8, —OS(═O)1-2R7a, —OC(═O)R8a, —C(═O)OR8a, —N(R9a)C(═O)R9, —OC(═O)NR10R10a, —NR11R11a, —N(R12)S(═O)1-2R12a, —N(R13)C(═O)NR13aR13b, —R14—S(═O)0-2R7, —R14—C(═O)R8, —R14—OS(═O)1-2R7a, —R14—OC(═O)R8a, —R14—N(R9a)C(═O)R9, —R14—OC(═O)NR10R10a, —R14—NR11R11a, —R14—N(R12)S(═O)1-2R12a, or —R14—N(R13)C(═O)NR13aR13b;
- R7, R7a, R8, R8a, R9, and R12a are, independently in each instance, H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 cyanoalkyl, aryl, aralkyl, heteroaryl, heteroarylalkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, or heterocyclylalkyl;
- R9a, R10, and R10a are, independently in each instance, H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 cyanoalkyl, or C1-6 haloalkyl;
- R11 and R11a are, independently in each instance, H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 cyanoalkyl, or aralkyl;
- R12, R13, R13a, and R13b are, independently in each instance, H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 cyanoalkyl, or C1-6 haloalkyl;
- R1a is independently H, alkyl, alkenyl, alkynyl, haloalkyl, cyanoalkyl, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, aryl, or aralkyl;
- Ra, Rb, Rc, Rd, Re, Rf, Rg, Rh, and Ri are, independently in each instance, H, alkyl, alkenyl, alkynyl, cyanoalkyl, hydroxyalkyl, haloalkyl, R16—C(═O)—, or cycloalkylalkyl;
- R14 and R15 are, independently in each instance, alkylene, alkenylene, alkynylene, cyanoalkylene, or haloalkylene;
- R16 is H, C1-6 alkyl, or C1-6 haloalkyl;
- and
- m is 0, 1, or 2.