Tryptanthrin derivative and application thereof

Abstract

The present disclosure provides tryptanthrin derivatives as IDO2 modulators, as well as pharmaceutical compositions comprising these compounds. The present disclosure also provides methods of using these compounds in the treatment of diseases.

Description

[0001] Cross-references

[0002] This patent application claims the benefit of U.S. Provisional Patent Application No. 63 / 334,878, filed on April 26, 2022, which is incorporated herein by reference in its entirety. Background Art

[0003] Indole-2,3-dioxygenase 1 ("IDO1") and indole-2,3-dioxygenase 2 ("IDO2") are two closely related enzymes encoded by linked genes. IDO1 and IDO2 are heme-containing enzymes that constitute the rate-limiting enzymes in the tryptophan metabolic pathway in mammals. IDO enzymes catalyze the oxidation of the essential amino acid tryptophan to produce N-formylkynurenine and are responsible for the catabolism of tryptophan in the body. By degrading tryptophan, IDO enzymes create a tryptophan-deficient microenvironment in the body, potentially leading to various diseases, including cancer, cataracts, and neurological disorders.

[0004] The IDO pathway also has immunomodulatory effects, and IDO1 is a well-characterized mediator of tumor immune escape. Because IDO2 is homologous to IDO1, IDO2 is thought to have similar immunomodulatory functions, and it has been shown that IDO2, like IDO1, is required for the differentiation of regulatory T cells in vitro. However, in vivo studies have shown that IDO2 has different functions compared to IDO1. Experiments in preclinical models of autoimmune arthritis have shown that IDO2 plays a pro-inflammatory role in mediating B cell and T cell activation, thereby driving autoimmune diseases. Because the IDO enzyme is associated with a variety of different diseases, including cancer, there is still a need for highly effective IDO inhibitors, including those that are selective between IDO1 and IDO2. Summary of the Invention

[0005] In one aspect, the present disclosure provides compounds of formula (I):

[0006]

[0007] or a pharmaceutically acceptable salt thereof; wherein

[0008] R 1 Selected from fluorine, chlorine, bromine, hydroxyl, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -OC 1-6 Alkyl, -OC 1-6 Haloalkyl, -OR 12 、-SR 11 、-N(R 13 )2、-C(O)R 11 、-C(O)OR 11、-OC(O)R 11 、-OC(O)N(R 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-N(R 11 )C(O)OR 11 、-N(R 11 )C(O)N(R 11 )2、-N(R 11 )S(O)2(R 11 )、-S(O)2R 11 、-S(O)2N(R 11 )2, -NO2, -N3 and -CN;

[0009] When R 1 When it is hydroxyl, -O-C1 alkyl or -NO2, R 2 Selected from

[0010] Fluorine, bromine, iodine, -OR 22 SR 21 、-N(R 21 )2、-C(O)R 21 、-OC(O)R 21 、-OC(O)N(R 21 )2、-N(R 21 )C(O)R 21 、-N(R 21 )C(O)OR 21 、-N(R 21 )C(O)N(R 21 )2、-N(R 21 )S(O)2(R 21 )、-N(R 21 )SO2N(R 21 )、-N(R 21 )P(O)(OR 21 )R 21 、-S(O)2R 21 、-S(O)2N(R 21 )2, -NO2 and -CN;

[0011] Optionally, one or more independently selected from R 30 Substituents substituted C 1-6 Alkyl; and

[0012] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 30 Substituents substituted;

[0013] When R 1 When it is fluorine, R 2 Selected from

[0014] Bromine, OR 23 、-N(H)R 23 、-C(O)R 23 、-C(O)N(R 23 )2、-C(O)OR 23 、-OC(O)R 23 、-OC(O)N(R 23 )2、-N(R 23 )C(O)R 23 、-N(R 23 )C(O)OR 23 、-N(R 23 )C(O)N(R 23 )2、-N(R 23 )S(O)2R 23 、-N(R 23 )SO2N(R 23 )、-N(R 23 )P(O)(OR 23 )R 23 、-S(O)2R 23 、-S(O)2N(R 23 )2, -NO2 and -CN;

[0015] Optionally, one or more independently selected from R 30 Substituents substituted C 1-6 Alkyl; and

[0016] C 3-6 Carbocyclic ring, 3- to 4-membered heterocyclic ring, Any one of which is optionally replaced by one or more independently selected from R 30 Substituents substituted;

[0017] When R 1 When R is C1 alkyl, -O-C1 haloalkyl, hydroxyl, chlorine or bromine, 2 Selected from:

[0018] Iodine, -OR 25 、-C(O)R 24 、-C(O)OR 25 、-OC(O)R 24 、-OC(O)N(R 24 )2、-C(O)N(R 24 )2、-N(R 24 )C(O)R 24 、-N(R 24)C(O)OR 24 、-N(R 24 )C(O)N(R 24 )2、-N(R 24 )S(O)2(R 24 )、N(R 24 )SO2N(R 24 )、-N(R 24 )P(O)(OR 24 )R 24 、-S(O)R 24 、-S(O)2R 24 、-S(O)2N(R 24 )2, -NO2 and -CN;

[0019] Optionally, one or more independently selected from R 30 Substituents substituted C 2-6 alkyl;

[0020] C 3-6 Carbocyclic and 3 to 5 membered heterocyclic rings, any of which are optionally substituted by one or more independently selected R 30 and

[0021] When R 1 When R is selected from bromine, hydroxyl and C1 alkyl, 2 further selected from fluorine;

[0022] When R 1 C 2-6 Alkyl, C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 2-6 Haloalkyl, -OR 12 、-SR 11 、-N(R 13 )2、-C(O)R 11 、-C(O)OR 11 、-OC(O)R 11 、-OC(O)N(R 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-N(R 11 )C(O)OR 11 、-N(R 11 )C(O)N(R 11 )2、-N(R 11 )S(O)2(R 11 )、-S(O)2R 11 、-S(O)2N(R 11)2, -N3 or -CN, R 2 Selected from

[0023] Halogen, -OR 26 、-SR 26 、-N(R 26 )2、-C(O)R 26 、-C(O)OR 26 、-OC(O)R 26 、-OC(O)N(R 26 )2、-C(O)N(R 26 )2、-N(R 26 )C(O)R 26 、-N(R 26 )C(O)OR 26 、-N(R 26 )C(O)N(R 26 )2、-N(R 26 )S(O)2(R 26 )、N(R 26 )SO2N(R 26 )、-N(R 26 )P(O)(OR 26 )R 26 、-S(O)R 26 、-S(O)2R 26 、-S(O)2N(R 26 )2, -NO2 and -CN;

[0024] Optionally, one or more independently selected from R 30 Substituents substituted C 1-6 Alkyl; and

[0025] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 30 Substituents substituted;

[0026] The condition is that when R 1 -C(O)OR 11 When R 2 It cannot be a substituted 6-membered heterocycle; R 3 and R 4 Each occurrence is independently selected from

[0027] Halogen, -OR 14 、-SR 14 、-N(R 14 )2、-N(R 14 )C(O)R 14 、-C(O)R 14 、-C(O)OR14 、-C(O)N(R 14 )2, -NO2 and -CN;

[0028] C 1-4 Alkyl, which is optionally substituted by one or more independently selected from halogen, -OR 14 、-SR 14 、-N(R 14 )2、-N(R 14 )C(O)R 14 、-C(O)R 14 、-C(O)OR 14 、-C(O)N(R 14 )2, -NO2 and -CN; and

[0029] C 3-4 Carbocyclic and 3 to 4 membered heterocyclic rings, any of which are optionally substituted by one or more independently selected from halogen, -OR 14 、-SR 14 、-N(R 14 )2、-N(R 14 )C(O)R 14 、-C(O)R 14 、-C(O)OR 14 、-C(O)N(R 14 )2, -NO2 and -CN substituents;

[0030] R 5 and R 5’ are each independently selected from hydrogen and hydroxy; or R 5 and R 5’ Together = O;

[0031] R 6 and R 6’ are each independently selected from hydrogen and hydroxy; or R 6 and R 6’ Together they are =O, =N-OR 26 or =NR 26 ;

[0032] m is selected from 0, 1, 2 and 3;

[0033] n is selected from 0, 1, 2 and 3;

[0034] R 11 and R 14 Each occurrence is independently selected from

[0035] hydrogen;

[0036] Optionally, one or more independently selected from R 31 Substituents substituted C1-6 Alkyl; and

[0037] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 31 Substituents substituted;

[0038] R 12 Each time it appears, select

[0039] One or more independently selected from R 32 Substituents substituted C 1-6 Alkyl; and C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 33 Substituents substituted;

[0040] R 13 Each time it appears, select

[0041] hydrogen;

[0042] Optionally, one or more independently selected from R 34 Substituents substituted C 1-6 Alkyl; and

[0043] C 3-5 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 34 Substituents substituted;

[0044] R 21 、R 23 、R 24 and R 26 Each occurrence is independently selected from

[0045] hydrogen;

[0046] Optionally, one or more independently selected from R 34 Substituents substituted C 1-6 Alkyl; and

[0047] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which are optionally substituted by one or more independently selected C 1-4 Alkyl, C 1-4 Haloalkyl and R 34 Substituents substituted;

[0048] R 22 and R 25 Each occurrence is independently selected from C 2-6 Alkyl, C 2-6 Halogenated alkyl, C 2-6 hydroxyalkyl; and

[0049] R 30 、R 31 、R 33 and R 34 Each occurrence is independently selected from

[0050] Halogen, -OR 41 、-SR 41 、-N(R 41 )2、-C(O)R 41 、-C(O)OR 41 、-OC(O)R 41 、-OC(O)N(R 41 )2、-C(O)N(R 41 )2、-N(R 41 )C(O)R 41 、-N(R 41 )C(O)OR 41 、-N(R 41 )C(O)N(R 41 )2、-N(R 41 )S(O)2(R 41 )、-N(R 41 )SO2N(R 41 )、-N(R 41 )P(O)(OR 41 )R 41 、-S(O)R 41 、-S(O)2R 41 、-S(O)2N(R 41 )2, -NO2, =O, =S, -CN, C 3-6 Carbocyclic and 3- to 7-membered heterocyclic rings;

[0051] R 32 independently selected at each occurrence

[0052] -OR 41 、-SR 41 、-N(R 41 )2、-C(O)R 41 、-C(O)OR 41 、-OC(O)R 41 、-OC(O)N(R 41 )2、-C(O)N(R 41 )2、-N(R 41 )C(O)R 41 、-N(R 41 )C(O)OR 41 、-N(R 41 )C(O)N(R 41)2、-N(R 41 )S(O)2(R 41 )、-N(R 41 )SO2N(R 41 )、-N(R 41 )P(O)(OR 41 )R 41 、-S(O)R 41 、-S(O)2R 41 、-S(O)2N(R 41 )2, -NO2, =O, =S and -CN; and

[0053] R 41 independently selected at each occurrence from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl and C 1-6 Hydroxyalkyl.

[0054] In some embodiments, R 1 Selected from fluorine, chlorine, bromine, hydroxyl, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -OC 1-6 Alkyl, -OC 1-6 Haloalkyl, -OR 12 、-N(R 13 )2、-C(O)OR 11 、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-N(R 11 )S(O)2(R 11 )、-S(O)2R 11 、-S(O)2N(R 11 )2, -NO2, -N3 and -CN. In some embodiments, R 1 Selected from fluorine, -C 1-6 Haloalkyl, -OC 1-6 Haloalkyl, -N(R 13 )2、-C(O)OR 11 、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-S(O)2R 11 , -NO2, -N3 and -CN. In some embodiments, R 1 is hydroxy, -O-C1 alkyl or -NO2; and R 2 Selected from fluorine, bromine, iodine, -OR 22 SR 21 、-N(R 21)2、-C(O)R 21 、-OC(O)R 21 、-OC(O)N(R 21 )2、-N(R 21 )C(O)R 21 、-N(R 21 )C(O)OR 21 、-N(R 21 )C(O)N(R 21 )2、-N(R 21 )S(O)2(R 21 )、-N(R 21 )SO2N(R 21 )、-N(R 21 )P(O)(OR 21 )R 21 、-S(O)2R 21 、-S(O)2N(R 21 )2, -NO2, -CN and optionally substituted C 1-6 In some embodiments, R 1 For NO2.

[0055] In some embodiments, R 2 Selected from fluorine, bromine, -N(R 21 )2、-N(R 21 )C(O)R 21 、-N(R 21 )C(O)OR 21 , -NO2, -CN and optionally substituted C 1-6 In some embodiments, R 1 is fluorine; and R 2 Selected from bromine, OR 23 、-N(H)R 23 、-C(O)R 23 、-C(O)N(R 23 )2、-C(O)OR 23 、-OC(O)R 23 、-OC(O)N(R 23 )2、-N(R 23 )C(O)R 23 、-N(R 23 )C(O)OR 23 、-N(R 23 )C(O)N(R 23 )2、-N(R 23 )S(O)2R 23 、-N(R 23 )SO2N(R 23 )、-N(R23 )P(O)(OR 23 )R 23 、-S(O)2R 23 、-S(O)2N(R 23 )2, -NO2, -CN, and optionally substituted C 1-6 In some embodiments, R 2 Selected from bromine, OR 23 、-N(H)R 23 、-N(R 23 )C(O)R 23 、-N(R 23 )C(O)OR 23 , -NO2, -CN and optionally substituted C 1-6 In some embodiments, R 1 is C1 alkyl, -O-C1 haloalkyl, hydroxy, chlorine or bromine; and R 2 Selected from iodine, -OR 25 、-C(O)R 24 、-C(O)OR 25 、-OC(O)R 24 、-OC(O)N(R 24 )2、-C(O)N(R 24 )2、-N(R 24 )C(O)R 24 、-N(R 24 )C(O)OR 24 、-N(R 24 )C(O)N(R 24 )2、-N(R 24 )S(O)2(R 24 )、N(R 24 )SO2N(R 24 )、-N(R 24 )P(O)(OR 24 )R 24 、-S(O)R 24 、-S(O)2R 24 、-S(O)2N(R 24 )2, -NO2, -CN and optionally substituted C 2-6 In some embodiments, R 1 is -O-C1 haloalkyl, chlorine or bromine; and R 2 Select from -OR 25 、-C(O)OR 25 、-C(O)N(R 24 )2、-N(R 24 )C(O)R 24、-N(R 24 )C(O)OR 24 , -NO2, -CN and optionally substituted C 2-6 alkyl.

[0056] In some embodiments, R 1 Selected from C 2-6 Alkyl, C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 2-6 Haloalkyl, -OR 12 、-SR 11 、-N(R 13 )2、-C(O)R 11 、-OC(O)R 11 、-OC(O)N(R 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-N(R 11 )C(O)OR 11 、-N(R 11 )C(O)N(R 11 )2、-N(R 11 )S(O)2(R 11 )、-S(O)2R 11 、-S(O)2N(R 11 )2, -N3 and -CN; and R 2 Selected from halogen, -OR 26 、-SR 26 、-N(R 26 )2、-C(O)R 26 、-C(O)OR 26 、-OC(O)R 26 、-OC(O)N(R 26 )2、-C(O)N(R 26 )2、-N(R 26 )C(O)R 26 、-N(R 26 )C(O)OR 26 、-N(R 26 )C(O)N(R 26 )2、-N(R 26 )S(O)2(R 26 )、-N(R 26 )SO2N(R 26 )、-N(R 26 )P(O)(OR 26 )R 26 、-S(O)R26 、-S(O)2R 26 、-S(O)2N(R 26 )2, -NO2, -CN and optionally substituted C 1-6 In some embodiments, R 1 Selected from C 2-6 Alkyl, C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 2-6 Haloalkyl, -OR 12 、-N(R 13 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-N(R 11 )C(O)OR 11 、-S(O)2R 11 、-S(O)2N(R 11 )2, -N3 and -CN. In some embodiments, R 1 Selected from -N(R 13 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-S(O)2R 11 , -N3 and -CN. In some embodiments, R 1 In some embodiments, R 2 Selected from halogen, -OR 26 、-SR 26 、-N(R 26 )2、-C(O)R 26 、-C(O)OR 26 、-C(O)N(R 26 )2、-N(R 26 )C(O)R 26 、-N(R 26 )C(O)OR 26 、-N(R 26 )S(O)2(R 26 )、-S(O)2R 26 、-S(O)2N(R 26 )2, -NO2, -CN and optionally substituted C 1-6 alkyl.

[0057] In some embodiments, R 5 and R 5’ Together they are =0. In some embodiments, R 6 and R 6’Together they are =0. In some embodiments, R 6 and R 6’ Together =N-OR 26 In some embodiments, m is 0 or 1; and n is 0 or 1.

[0058] In some embodiments, R 11 and R 14 is independently selected at each occurrence from hydrogen and optionally substituted C 1-6 Alkyl; R 12 is independently selected at each occurrence from optionally substituted C 1-6 alkyl; and R 13 is independently selected at each occurrence from hydrogen and optionally substituted C 1-6 In some embodiments, R 21 、R 23 、R 24 and R 26 are independently selected at each occurrence from hydrogen, optionally substituted C 1-6 In some embodiments, R 22 and R 25 Each occurrence is independently selected from C 3-6 Alkyl and C 3-6 Halogenated alkyl.

[0059] In some embodiments, R 30 、R 31 、R 33 and R 34 is independently selected at each occurrence from halogen, -OR 41 、-N(R 41 )2、-OC(O)N(R 41 )2、-C(O)N(R 41 )2、-N(R 41 )C(O)R 41 、-N(R 41 )C(O)OR 41 、-N(R 41 )C(O)N(R 41 )2、-N(R 41 )S(O)2(R 41 )、-N(R 41 )SO2N(R 41 )、-N(R 41 )P(O)(OR 41 )R 41 、-S(O)R 41 、-S(O)2R 41 , =O and -CN. In some embodiments, R30 、R 31 、R 33 and R 34 Each occurrence is independently selected from halogen, -N(R 41 )2、-N(R 41 )S(O)2(R 41 )、-N(R 41 )SO2N(R 41 )、-N(R 41 )P(O)(OR 41 )R 41 、-S(O)2R 41 and =0. In some embodiments, R 32 is independently selected at each occurrence from halogen, -N(R 41 )2、-N(R 41 )S(O)2(R 41 )、-N(R 41 )SO2N(R 41 )、-N(R 41 )P(O)(OR 41 )R 41 、-S(O)2R 41 and =0. In some embodiments, R 41 independently selected at each occurrence from hydrogen and C 1-6 alkyl.

[0060] In another aspect, the present disclosure provides compounds of formula (II):

[0061]

[0062] or a pharmaceutically acceptable salt thereof; wherein

[0063] R 51 Selected from fluorine, chlorine, bromine, iodine, hydroxyl, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -N(R 61 )2、-OR 61 、-SR 61 、-C(O)R 61 、-C(O)OR 61 、-OC(O)R 61 、-OC(O)N(R 61 )2、-C(O)N(R 61 )2、-N(R 61 )C(O)R 61 、-N(R 61 )C(O)OR 61 、-N(R 61 )C(O)N(R61 )2、-N(R 61 )S(O)2(R 61 )、-S(O)2R 61 、-S(O)2N(R 61 )2, -NO2 and -CN;

[0064] When R 51 When it is fluorine, chlorine or iodine, R 52 Selected from

[0065] Bromine, iodine, -N(R 71 )2、-OR 71 、-SR 71 、-C(O)R 71 、-C(O)OR 71 、-OC(O)R 71 、-OC(O)N(R 71 )2、-C(O)N(R 71 )2、-N(R 71 )C(O)R 71 、-N(R 71 )C(O)OR 71 、-N(R 71 )C(O)N(R 71 )2、-N(R 71 )S(O)2(R 71 )、N(R 71 )SO2N(R 71 )、-N(R 71 )P(O)(OR 71 )R 71 、-S(O)R 71 、-S(O)2R 71 、-S(O)2N(R 71 )2, -NO2 and -CN;

[0066] One or more independently selected from R 80 a C1 alkyl group substituted with a substituent, and

[0067] Optionally, one or more independently selected from R 80 Substituents substituted C 2-6 Alkyl; and

[0068] C 3-6 Carbocyclic and 3 to 5 membered heterocyclic rings, any of which are optionally substituted by one or more independently selected R 80 Substituents substituted;

[0069] When R 51 When it is C1 alkyl or -NO2, R 52 Selected from

[0070] Fluorine, iodine, -OR 72 、-SR 72 、-N(R 72 )2、-C(O)R 72 、-C(O)OR 72 、-OC(O)R 72 、-OC(O)N(R 72 )2、-C(O)N(R 72 )2、-N(R 72 )C(O)R 72 、-N(R 72 )C(O)OR 72 、-N(R 72 )C(O)N(R 72 )2、-N(R 72 )S(O)2(R 72 )、-N(R 72 )SO2N(R 72 )、-N(R 72 )P(O)(OR 72 )R 72 、-S(O)R 72 、-S(O)2R 72 、-S(O)2N(R 72 )2, -NO2 and -CN;

[0071] Optionally, one or more independently selected from R 80 Substituents substituted C 1-6 Alkyl; and

[0072] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 80 Substituents substituted;

[0073] When R 51 Selected from bromine, hydroxyl, -C 2-6 Alkyl, -C 1-6 Haloalkyl, -N(R 61 )2、-OR 61 、-SR 61 、-C(O)R 61 、-C(O)OR 61 、-OC(O)R 61 、-OC(O)N(R 61 )2、-C(O)N(R 61 )2、-N(R 61 )C(O)R 61 、-N(R 61 )C(O)OR61 、-N(R 61 )C(O)N(R 61 )2、-N(R 61 )S(O)2(R 61 )、-S(O)2R 61 、-S(O)2N(R 61 )2 and -CN,

[0074] R 52 Selected from

[0075] Halogen, -OR 73 、-SR 73 、-N(R 73 )2、-C(O)R 73 、-C(O)OR 73 、-OC(O)R 73 、-OC(O)N(R 73 )2、-C(O)N(R 73 )2、-N(R 73 )C(O)R 73 、-N(R 73 )C(O)OR 73 、-N(R 73 )C(O)N(R 73 )2、-N(R 73 )S(O)2(R 73 )、-N(R 73 )SO2N(R 73 )、-N(R 73 )P(O)(OR 73 )R 73 、-S(O)R 73 、-S(O)2R 73 、-S(O)2N(R 73 )2, -NO2 and -CN;

[0076] Optionally, one or more independently selected from R 80 Substituents substituted C 1-6 Alkyl; and

[0077] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 80 Substituents substituted;

[0078] R 53 and R 54 Each occurrence is independently selected from

[0079] Halogen, -OR 64 、-SR64 、-N(R 64 )2、-N(R 64 )C(O)R 64 、-C(O)R 64 、-C(O)OR 64 、-C(O)N(R 64 )2, -NO2 and -CN;

[0080] C 1-4 Alkyl, which is optionally substituted by one or more independently selected from halogen, -OR 64 、-SR 64 、-N(R 64 )2、-N(R 64 )C(O)R 64 、-C(O)R 64 、-C(O)OR 64 、-C(O)N(R 64 ) substituted with 2-NO2 and -CN; and

[0081] C 3-4 Carbocyclic and 3 to 4 membered heterocyclic rings, any of which are optionally substituted by one or more independently selected from halogen, -OR 64 、-SR 64 、-N(R 64 )2、-N(R 64 )C(O)R 64 、-C(O)R 64 、-C(O)OR 64 、-C(O)N(R 64 )2, -NO2 and -CN substituents;

[0082] R 55 and R 55 ' are each independently selected from hydrogen and hydroxy; or R 55 and R 55 'Together for =O;

[0083] R 56 and R 56 ' are each independently selected from hydrogen and hydroxy; or R 56 and R 56 'Together = O, = N-OR 64 or =NR 64 ;

[0084] p is selected from 0, 1, 2 and 3;

[0085] q is selected from 0, 1, 2 and 3;

[0086] R 61 and R 64Each occurrence is independently selected from

[0087] hydrogen;

[0088] Optionally, one or more independently selected from R 81 Substituents substituted C 1-6 Alkyl; and

[0089] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 81 Substituents substituted;

[0090] R 71 、R 72 and R 73 Each occurrence is independently selected from

[0091] hydrogen;

[0092] Optionally, one or more independently selected from R 82 Substituents substituted C 1-6 Alkyl; and

[0093] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which are optionally substituted by one or more independently selected C 1-4 Alkyl, C 1-4 Haloalkyl and R 82 Substituents substituted;

[0094] R 80 、R 81 and R 82 Each occurrence is independently selected from

[0095] Halogen, -OR 91 、-SR 91 、-N(R 91 )2、-C(O)R 91 、-C(O)OR 91 、-OC(O)R 91 、-OC(O)N(R 91 )2、-C(O)N(R 91 )2、-N(R 91 )C(O)R 91 、-N(R 91 )C(O)OR 91 、-N(R 91 )C(O)N(R 91 )2、-N(R 91 )S(O)2(R 91 )、-N(R 91 )SO2N(R 91)、-N(R 91 )P(O)(OR 91 )R 91 、-S(O)R 91 、-S(O)2R 91 、-S(O)2N(R 91 )2, -NO2, =O, =S, -CN, C 3-6 carbocyclic and 3- to 7-membered heterocyclic rings; and

[0096] R 91 independently selected at each occurrence from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl and C 1-6 Hydroxyalkyl.

[0097] In some embodiments, R 51 Selected from fluorine, chlorine, bromine, hydroxyl, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -N(R 61 )2、-OR 61 、-C(O)R 61 、-C(O)OR 61 、-C(O)N(R 61 )2、-N(R 61 )C(O)R 61 -N(R 61 )S(O)2(R 61 )、-S(O)2R 61 、-S(O)2N(R 61 )2, -NO2 and -CN. In some embodiments, R 51 Selected from -C(O)R 61 、-C(O)OR 61 、-C(O)N(R 61 )2 and -NO2. In some embodiments, R 51 is fluorine, chlorine or iodine. In some embodiments, R 51 is C1 alkyl or -NO2; and R 52 Selected from fluorine, iodine, -OR 72 、-SR 72 、-N(R 72 )2、-C(O)R 72 、-C(O)OR 72 、-OC(O)R 72 、-OC(O)N(R 72 )2、-C(O)N(R 72 )2、-N(R 72 )C(O)R 72 、-N(R 72)C(O)OR 72 、-N(R 72 )C(O)N(R 72 )2、-N(R 72 )S(O)2(R 72 )、-N(R 72 )SO2N(R 72 )、-N(R 72 )P(O)(OR 72 )R 72 、-S(O)R 72 、-S(O)2R 72 、-S(O)2N(R 72 )2, -NO2, -CN and optionally substituted C 1-6 In some embodiments, R 51 In some embodiments, R 52 Selected from fluorine, -OR 72 , -NO2, -CN and optionally substituted C 1-6 alkyl.

[0098] In some embodiments, R 51 Selected from bromine, hydroxyl, -C 2-6 Alkyl, -C 1-6 Haloalkyl, -N(R 61 )2、-OR 61 、-SR 61 、-C(O)R 61 、-C(O)OR 61 、-OC(O)R 61 、-OC(O)N(R 61 )2、-C(O)N(R 61 )2、-N(R 61 )C(O)R 61 、-N(R 61 )C(O)OR 61 、-N(R 61 )C(O)N(R 61 )2、-N(R 61 )S(O)2(R 61 )、-S(O)2R 61 、-S(O)2N(R 61 )2 and -CN. In some embodiments, R 51 Select from -OR 61 、-C(O)R 61 、-C(O)OR 61 、-C(O)N(R 61 )2 and -CN; and R 52 Selected from halogen, -OR73 、-SR 73 、-N(R 73 )2、-C(O)R 73 、-C(O)OR 73 、-N(R 73 )C(O)R 73 、-N(R 73 )C(O)OR 73 、-N(R 73 )C(O)N(R 73 )2、-N(R 73 )S(O)2(R 73 )、-N(R 73 )SO2N(R 73 )、-N(R 73 )P(O)(OR 73 )R 73 、-S(O)R 73 、-S(O)2R 73 、-S(O)2N(R 73 )2, -NO2 and -CN. In some embodiments, R 51 Selected from -C(O)R 61 、-C(O)OR 61 and -C(O)N(R 61 )2. In some embodiments, R 52 In some embodiments, R 52 For chlorine.

[0099] In some embodiments, R 53 and R 54 is independently selected from halogen at each occurrence. In some embodiments, R 53 is independently selected from halogen at each occurrence. In some embodiments, R 55 and R 55 ' together is =0. In some embodiments, R 56 and R 56 ' together is =0. In some embodiments, R 56 and R 56 'Together =N-OR 64 In some embodiments, p is selected from 0 and 1. In some embodiments, q is 0.

[0100] In some embodiments, R 61 and R 64 are independently selected at each occurrence from hydrogen, optionally substituted C 1-6 In some embodiments, R 80 、R81 and R 82 Each occurrence is independently selected from -N(R 91 )2、-C(O)OR 91 and -N(R 91 )SO2N(R 91 ). In some embodiments, R 91 independently selected at each occurrence from hydrogen and C 1-6 alkyl.

[0101] In another aspect, the present disclosure provides compounds of formula (III):

[0102]

[0103] or a pharmaceutically acceptable salt thereof; wherein

[0104] R 101 Selected from fluorine, chlorine, bromine, hydroxyl, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -OC 1-6 Alkyl, -OC 1-6 Haloalkyl, -N(R 111 )2、-OR 112 、-SR 111 、-C(O)R 111 、-C(O)OR 111 、-OC(O)R 111 、-OC(O)N(R 111 )2、-C(O)N(R 111 )2、-N(R 111 )C(O)R 111 、-N(R 111 )C(O)OR 111 、-N(R 111 )C(O)N(R 111 )2、-N(R 111 )S(O)2(R 111 )、-S(O)2R 111 、-S(O)2N(R 111 )2, -NO2 and -CN;

[0105] When R 101 When it is fluorine, R 102 Selected from

[0106] Chlorine, bromine, iodine, -N(R 121 )2、-OR 122 、-SR 121 、-C(O)R 121 、-C(O)OR 121 、-OC(O)R121 、-OC(O)N(R 121 )2、-C(O)N(R 121 )2、-N(R 121 )C(O)R 121 、-N(R 21 )C(O)OR 121 、-N(R 121 )C(O)N(R 121 )2、-N(R 121 )S(O)2(R 121 )、-N(R 121 )SO2N(R 121 )、-N(R 121 )P(O)(OR 121 )R 121 、-S(O)R 121 、-S(O)2R 121 、-S(O)2N(R 121 )2, -NO2 and -CN;

[0107] One or more independently selected from R 123 C1 alkyl substituted with a substituent, and optionally substituted with one or more independently selected from R 130 Substituents substituted C 2-6 alkyl;

[0108] as well as

[0109] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 130 Substituents substituted;

[0110] When R 101 Bromine, iodine, hydroxyl, -O-C1 alkyl, -C(O)OR 111 、-C(O)N(H)(C2 alkyl)、-S(O)2R 111 or -S(O)2N(R 111 )2, R 102 Selected from

[0111] Fluorine, -N(R 124 )2、-OR 125 、-SR 124 、-C(O)R 124 、-C(O)OR 124 、-OC(O)R 124 、-OC(O)N(R 124 )2、-C(O)N(R 124 )2、-N(R 124 )C(O)R124 、-N(R 124 )C(O)OR 124 、-N(R 124 )C(O)N(R 124 )2、-N(R 124 )S(O)2(R 124 )、-N(R 124 )SO2N(R 124 )、-N(R 124 )P(O)(OR 124 )R 124 、-S(O)R 124 、-S(O)2R 124 、-S(O)2N(R 124 )2, -NO2 and -CN;

[0112] Optionally, one or more independently selected from R 130 Substituents substituted C 1-6 Alkyl; and

[0113] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 130 Substituents substituted;

[0114] When R 101 Chloro, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 1-6 Haloalkyl, -OR 112 、-SR 111 、-N(R 111 )2、-C(O)R 111 、-OC(O)R 111 、-C(O)N(R 113 )2、-OC(O)N(R 111 )2、-N(R 111 )C(O)R 111 、-N(R 111 )C(O)OR 111 、-N(R 111 )C(O)N(R 111 )2、-N(R 111 )S(O)2(R 111 ), -NO2 or -CN; R 102 Selected from halogen, -OR 126 、-SR 126 、-N(R 126 )2、-C(O)R 126、-C(O)OR 126 、-OC(O)R 126 、-OC(O)N(R 126 )2、-C(O)N(R 126 )2、-N(R 126 )C(O)R 126 、-N(R 126 )C(O)OR 126 、-N(R 126 )C(O)N(R 126 )2、-N(R 126 )S(O)2(R 126 )、-N(R 126 )SO2N(R 126 )、-N(R 126 )P(O)(OR 126 )R 126 、-S(O)R 126 、-S(O)2R 126 、-S(O)2N(R 126 )2, -NO2 and -CN;

[0115] Optionally, one or more independently selected from R 130 Substituents substituted C 1-6 Alkyl; and

[0116] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 130 Substituents substituted;

[0117] The condition is (i) when R 101 When it is NO2, R 102 cannot be methyl; (ii) when R 101 When it is methyl, R 102 cannot be chlorine; and (iii) when R 101 When it is chlorine, R 102 Cannot be bromine; R 103 and R 104 Each occurrence is independently selected from

[0118] Halogen, -OR 114 、-SR 114 、-N(R 114 )2、-N(R 114 )C(O)R 114 、-C(O)R 114 、-C(O)OR 114 、-C(O)N(R 114 )2, -NO2 and -CN;

[0119] C 1-4 Alkyl, which is optionally substituted by one or more independently selected from halogen, -OR 114 、-SR 114 、-N(R 114 )2、-N(R 114 )C(O)R 114 、-C(O)R 114 、-C(O)OR 114 、-C(O)N(R 114 )2, -NO2 and -CN; and

[0120] C 3-4 Carbocyclic and 3 to 4 membered heterocyclic rings, any of which are optionally substituted by one or more independently selected from halogen, -OR 114 、-SR 114 、-N(R 114 )2、-N(R 114 )C(O)R 114 、-C(O)R 114 、-C(O)OR 114 、-C(O)N(R 114 )2, -NO2 and -CN substituents;

[0121] R 105 and R 105’ are each independently selected from hydrogen and hydroxy; or R 105 and R 105’ Together = O;

[0122] R 106 and R 106’ are each independently selected from hydrogen and hydroxy; or R 106 and R 106’ Together they are =O, =N-OR 114 or =NR 114 ;

[0123] r is selected from 0, 1, 2 and 3;

[0124] s is selected from 0, 1, 2 and 3;

[0125] R 111 and R 114 Each occurrence is independently selected from

[0126] hydrogen;

[0127] Optionally, one or more independently selected from R 131 Substituents substituted C 1-6 Alkyl; and

[0128] C 3-6Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 131 Substituents substituted;

[0129] R 112 Each time it appears, select

[0130] One or more independently selected from R 132 Substituents substituted C 1-6 Alkyl; and

[0131] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 133 Substituents substituted;

[0132] R 113 Each time it appears, select

[0133] hydrogen;

[0134] Optionally, one or more independently selected from R 134 Substituents substituted C1 alkyl and C 3-6 Alkyl, and one or more independently selected from R 134 a C2 alkyl group substituted with a substituent of

[0135] C 3-5 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 134 Substituents substituted;

[0136] R 121 、R 124 and R 126 Each occurrence is independently selected from

[0137] hydrogen;

[0138] Optionally, one or more independently selected from R 134 Substituents substituted C 1-6 Alkyl; and

[0139] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which are optionally substituted by one or more independently selected C 1-4 Alkyl, C 1-4 Haloalkyl and R 134 Substituents substituted;

[0140] R 122 and R 125 Each occurrence is independently selected from

[0141] Optionally, one or more independently selected from R 134Substituents substituted C 2-6 Alkyl; and

[0142] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which are optionally substituted by one or more independently selected C 1-4 Alkyl, C 1-4 Haloalkyl and R 134 Substituents substituted;

[0143] R 123 independently selected at each occurrence

[0144] hydrogen;

[0145] Optionally, one or more independently selected from R 134 Substituents substituted C 1-6 alkyl

[0146] base; and

[0147] C 3-5 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which are optionally substituted by one or more independently selected C 1-4 Alkyl, C 1-4 Haloalkyl and R 134 Substituents substituted;

[0148] R 130 、R 131 、R 132 、R 133 and R 134 Each occurrence is independently selected from

[0149] Halogen, -OR 141 、-SR 141 、-N(R 141 )2、-C(O)R 141 、-C(O)OR 141 、-OC(O)R 141 、-OC(O)N(R 141 )2、-C(O)N(R 141 )2、-N(R 141 )C(O)R 141 、-N(R 141 )C(O)OR 141 、-N(R 141 )C(O)N(R 141 )2、-N(R 141 )S(O)2(R 141 )、-N(R 141 )SO2N(R 141 )、-N(R 141 )P(O)(OR141 )R 141 、-S(O)R 141 、-S(O)2R 141 、-S(O)2N(R 141 )2, -NO2, =O, =S, -CN, C 3-6 carbocyclic and 3- to 7-membered heterocyclic rings; and

[0150] R 141 independently selected at each occurrence from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl and C 1-6 Hydroxyalkyl.

[0151] In some embodiments, R 101 Selected from fluorine, chlorine, bromine, hydroxyl, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -OC 1-6 Alkyl, -OC 1-6 Haloalkyl, -N(R 111 )2、-OR 112 、C(O)R 111 、-C(O)OR 111 、C(O)N(R 111 )2、N(R 111 )S(O)2(R 111 )、-S(O)2R 111 、-S(O)2N(R 111 )2, -NO2 and -CN. In some embodiments, R 101 is selected from fluorine, -NO2 and -CN. In some embodiments, R 101 In some embodiments, R 102 Selected from chlorine, bromine, iodine, -N(R 121 )2、-OR 122 、-C(O)R 121 、-C(O)OR 121 、-C(O)N(R 121 )2、-N(R 121 )C(O)R 121 、-N(R 121 )S(O)2(R 121 )、-S(O)2R 121 、-S(O)2N(R 121 )2, -NO2 and -CN. In some embodiments, R 102 In some embodiments, R 101 Selected from bromine, iodine, hydroxyl, -O-C1 alkyl, -C(O)OR 111、-C(O)N(H)(C2 alkyl)、-S(O)2R 111 and -S(O)2N(R 111 )2. In some embodiments, R 101 Selected from chlorine, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 1-6 Haloalkyl, -OR 112 、-SR 111 、-N(R 111 )2、-C(O)R 111 、-OC(O)R 111 、-C(O)N(R 113 )2、-OC(O)N(R 111 )2、-N(R 111 )C(O)R 111 、-N(R 111 )C(O)OR 111 、-N(R 111 )C(O)N(R 111 )2、-N(R 111 )S(O)2(R 111 ), -NO2 and -CN. In some embodiments, R 101 In some embodiments, R 102 is selected from halogen and optionally substituted C 1-6 alkyl.

[0152] In some embodiments, R 103 and R 104 is independently selected at each occurrence from halogen and C 1-4 In some embodiments, R 105 and R 105’ Together they are =0. In some embodiments, R 106 and R 106’ Together they are =0. In some embodiments, R 106 and R 106’ Together =N-OR 114 In some embodiments, r is selected from 0 and 1. In some embodiments, s is 0.

[0153] In another aspect, the present disclosure provides compounds of formula (IV):

[0154]

[0155] or a pharmaceutically acceptable salt thereof; wherein

[0156] R151 Selected from fluorine, bromine, -N(R 161 )2、-C(O)R 161 、-C(O)OR 161 、-OC(O)R 161 、-OC(O)N(R 161 )2、-C(O)N(R 161 )2、-N(R 161 )C(O)R 161 、-N(R 161 )C(O)OR 161 、-N(R 161 )C(O)N(R 161 )2、-N(R 161 )S(O)2(R 161 )、-N(R 161 )S(O)2N(R 161 )2、-SR 161 、-S(O)R 161 、-S(O)2R 161 、-S(O)2N(R 161 )2、-CN、-NO2、-C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 1-6 Haloalkyl, -OR 3-6 Carbocyclic ring and -OR 3-6 heterocyclic rings; and

[0157]

[0158] wherein each is optionally replaced by one or more independently selected R 171 Substituents substituted;

[0159] When R 151 When it is fluorine, R 152 Selected from

[0160] Iodine, -NHR 192 、-OR 171 、-SR 171 、-C(=NR 196 )N(R 196 )2、-C(O)R 171 、-C(O)OR 171 、-OC(O)R 171 、-OC(O)N(R 171 )2、-C(O)N(R 171 )2、-N(R 193 )C(O)R 171 、-N(H)C(O)R 194 、-N(R193 )C(O)OR 171 、-N(R 171 )C(O)N(R 171 )2、-N(R 171 )S(O)2(R 171 )、-N(R 171 )SO2N(R 171 )2、-N(R 171 )P(O)(OR 171 )R 171 、-S(O)R 171 、-S(O)2R 171 、-S(O)2N(R 171 )2、-NR 196 (C=NR 196 )N(R 196 )2, -N3 and -CN;

[0161] One or more independently selected from R 195 C1 alkyl substituted with a substituent, and optionally substituted with one or more independently selected from R 180 Substituents substituted C 2-6 alkyl;

[0162] as well as

[0163] C 3-6 Carbocyclic ring, 3-membered heterocyclic ring, 4-membered heterocyclic ring, and 6-membered heterocyclic rings, any of which is optionally replaced by one or more independently selected R 180 Substituents substituted;

[0164] When R 151 for -SR 161 、-S(O)R 161 、-S(O)2R 161 or -S(O)2N(R 161 ) or -CN, R 152 Selected from

[0165] Halogen, -N(R 174 )2、-OR 174 、-SR 174 、-C(O)R 174 、-C(O)OR 174 、-OC(O)R 174 、-OC(O)N(R 174 )2、-C(O)N(R 174 )2、-N(R 174 )C(O)R 174 、-N(R174 )C(O)OR 174 、-N(R 174 )C(O)N(R 174 )2、-N(R 174 )S(O)2(R 174 )、-N(R 124 )SO2N(R 174 )2、-N(R 174 )P(O)(OR 174 )R 174 、-S(O)R 174 、-S(O)2R 174 、-S(O)2N(R 174 )2, -NO2 and -CN;

[0166] Optionally, one or more independently selected from R 180 Substituents substituted C 1-6 Alkyl; and

[0167] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 180 Substituents substituted;

[0168] When R 151 When it is bromine or -NO2, R 152 Selected from

[0169] Iodine, -OR 197 、-SR 176 、-NHR 178 、-C(O)R 176 、-C(O)OR 176 、-OC(O)R 176 、-OC(O)N(R 176 )2、-C(O)N(R 176 )2、-N(R 176 )C(O)R 176 、-N(R 176 )C(O)OR 176 、-N(R 176 )C(O)N(R 176 )2、-N(R 176 )S(O)2(R 176 )、-N(R 176 )SO2N(R 176 )2、-N(R 176 )P(O)(OR 176 )R 176 、-S(O)R 176 、-S(O)2R 176、-S(O)2N(R 176 )2, -NO2 and -CN;

[0170] One or more independently selected from R 180 C1 alkyl substituted by one or more independently selected from R 198 C1 alkyl substituted with a substituent, and optionally substituted with one or more independently selected from R 180 Substituents substituted C 2-6 alkyl;

[0171] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 180 and

[0172] The condition is (i) when R 151 When it is NO2, R 152 cannot be one or more independently selected from R 180 and (ii) when R 151 When it is NO2, R 152

[0173] It cannot be ethyl;

[0174] When R 151 -C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 1-6 Haloalkyl, -OR 3-6 Carbocyclic ring, -OR 3-6 Heterocyclic, -N(R 161 )2、-C(O)R 161 、-OC(O)R 161 、-C(O)N(R 161 )2、-OC(O)N(R 161 )2、-N(R 161 )C(O)R 161 、-N(R 161 )C(O)OR 161 、-N(R 161 )C(O)N(R 161 )2、-N(R 161 )S(O)2(R 161 ) or -N(R 161 )S(O)2N(R 161 )2, R 152 Selected from

[0175] Halogen, -OR 176 、-SR 176 、-N(R176 )2、-C(O)R 176 、-C(O)OR 176 、-OC(O)R 176 、-OC(O)N(R 176 )2、-C(O)N(R 176 )2、-N(R 176 )C(O)R 176 、-N(R 176 )C(O)OR 176 、-N(R 176 )C(O)N(R 176 )2、-N(R 176 )S(O)2(R 176 )、-N(R 176 )SO2N(R 176 )2、-N(R 176 )P(O)(OR 176 )R 176 、-S(O)R 176 、-S(O)2R 176 、-S(O)2N(R 176 )2, -NO2 and -CN;

[0176] Optionally, one or more independently selected from R 177 Substituents substituted C 1-6 Alkyl; and

[0177] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 177 Substituents substituted;

[0178] R 153 and R 154 Each occurrence is independently selected from

[0179] Halogen, -OR 164 、-NHR 178 、-N(R 164 )C(O)R 164 、-C(O)R 164 、-C(O)OR 164 、-C(O)N(R 164 )2, -NO2 and -CN;

[0180] C 1-4 Alkyl, which is optionally substituted by one or more independently selected from halogen, -OR 164 、-SR 164 、-N(R 164 )2、-N(R 164)C(O)R 164 、-C(O)R 164 、-C(O)OR 164 、-C(O)N(R 164 )2, -NO2 and -CN; and

[0181] C 3-6 Carbocyclic and 3 to 5 membered heterocyclic rings, any of which are optionally substituted by one or more independently selected from halogen, -OR 164 、-SR 164 、-N(R 164 )2、-N(R 164 )C(O)R 164 、-C(O)R 164 、-C(O)OR 164 、-C(O)N(R 164 )2, -NO2 and -CN substituents;

[0182] R 155 and R 155’ are each independently selected from hydrogen, hydroxy and methyl; or R 155 and R 155’ Together = O;

[0183] R 156 and R 156’ are each independently selected from hydrogen, hydroxy and methyl; or R 156 and R 156’ Together they are =O, =N-OR 171 or =NR 171 ;

[0184] t is selected from 0, 1, 2, and 3;

[0185] u is selected from 0, 1, 2 and 3;

[0186] R 161 and R 164 Each occurrence is independently selected from

[0187] hydrogen;

[0188] Optionally, one or more independently selected from R 177 Substituents substituted C 1-6 Alkyl; and

[0189] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 177 Substituents substituted;

[0190] R 171 、R 174 and R176 Each occurrence is independently selected from

[0191] hydrogen;

[0192] Optionally, one or more independently selected from R 180 Substituents substituted C 1-6 Alkyl; and

[0193] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which are optionally substituted by one or more independently selected C 1-4 Alkyl, C 1-4 Haloalkyl and R 180 Substituents substituted;

[0194] R 177 and R 180 Each occurrence is independently selected from

[0195] Halogen, -OR 191 、-SR 191 、-N(R 191 )2、-C(O)R 191 、-C(O)OR 191 、-OC(O)R 191 、-OC(O)N(R 191 )2、-C(O)N(R 191 )2、-N(R 191 )C(O)R 191 、-N(R 191 )C(O)OR 191 、-N(R 191 )C(O)N(R 191 )2、-N(R 191 )S(O)2(R 191 )、-N(R 191 )SO2N(R 191 )2、-N(R 191 )P(O)(OR 191 )R 191 、-NR 196 (C=NR 196 )N(R 196 )2、-S(O)R 191 、-S(O)2R 191 、-S(O)2N(R 191 )2, -NO2, =O, =S, -CN, C 1-6 Alkyl, C 3-6 Carbocyclic and 3- to 7-membered heterocyclic rings;

[0196] R 178 Each time it appears, select

[0197] Optionally, one or more independently selected from R 180 Substituents substituted C 1-6 Alkyl; and

[0198] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 180 Substituents substituted;

[0199] R 191 independently selected at each occurrence from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl and C 1-6 Hydroxyalkyl.

[0200] R 192 Each time it appears, select

[0201] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 180 Substituents substituted;

[0202] R 193 Each time it appears, select

[0203] Optionally, one or more independently selected from R 180 Substituents substituted C 1-6 Alkyl; and

[0204] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which are optionally substituted by one or more independently selected C 1-4 Alkyl, C 1-4 Haloalkyl and R 180 Substituents substituted;

[0205] R 194 Each time it appears, select

[0206] One or more independently selected from R 180 Substituents substituted C 1-6 alkyl;

[0207] R 195 independently selected at each occurrence

[0208] Halogen, -NH2, -NHR 192 、-NR 196 (C=NR 196 )N(R 196 )2、-OR 171 、-SR 171 、-C(O)R 171、-C(O)OR 171 、-OC(O)R 171 、-OC(O)N(R 171 )2、-C(O)N(R 171 )2、-N(R 171 )C(O)R 171 、-N(R 171 )C(O)R 171 、-N(R 193 )C(O)OR 171 、-N(R 171 )C(O)N(R 171 )2、-N(R 171 )S(O)2(R 171 )、-N(R 171 )S(O)2N(R 171 )2、-N(R 171 )P(O)(OR 171 )R 171 、-S(O)R 171 、-S(O)2R 171 and -S(O)2N(R 171 )2;

[0209] Optionally, one or more independently selected from R 180 Substituents substituted C 1-6 Alkyl; and

[0210] C 5-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which are optionally substituted by one or more independently selected C 1-4 Alkyl, C 1-4 Haloalkyl and R 180 Substituents substituted;

[0211] R 196 Each time it appears, select

[0212] Hydrogen, -CN, and OR 171 ;

[0213] Optionally, one or more independently selected from R 180 Substituents substituted C 1-6 Alkyl; and

[0214] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which are optionally substituted by one or more independently selected C 1-4 Alkyl, C 1-4 Haloalkyl and R 180 Substituents substituted;

[0215] R 197Each time it appears, select

[0216] hydrogen;

[0217] Optionally, one or more independently selected from R 180 Substituents substituted C 2-6 alkyl

[0218] base; and

[0219] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which are optionally substituted by one or more independently selected C 1-4 Alkyl, C 1-4 Haloalkyl and R 180 Substituents substituted;

[0220] R 198 independently selected at each occurrence

[0221] Fluorine, chlorine, iodine, -NH2, -NHR 192 、-NR 196 (C=NR 196 )N(R 196 )2、-OR 171 、-SR 171 、-C(O)R 171 、-C(O)OR 171 、-OC(O)R 171 、-OC(O)N(R 171 )2、-C(O)N(R 171 )2、-N(R 171 )C(O)R 171 、-N(R 171 )C(O)R 171 、-N(R 193 )C(O)OR 171 、-N(R 171 )C(O)N(R 171 )2、-N(R 171 )S(O)2(R 171 )、-N(R 171 )SO2N(R 171 )2、-N(R 171 )P(O)(OR 171 )R 171 、-S(O)R 171 、-S(O)2R 171 and -S(O)2N(R 171 )2;

[0222] Optionally, one or more independently selected from R 180 Substituents substituted C 2-6Alkyl; and

[0223] C 5-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which are optionally substituted by one or more independently selected C 1-4 Alkyl, C 1-4 Haloalkyl and R 180 Substituents substituted;

[0224] In some embodiments, R 151 Selected from fluorine, bromine, -C(O)R 161 、-C(O)OR 161 、-C(O)N(R 161 )2、-N(R 161 )C(O)R 161 、-N(R 161 )S(O)2(R 161 ),-SR 161 、-S(O)R 161 、-S(O)2R 161 、-S(O)2N(R 161 )2、-CN、-NO2、-C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 1-6 Haloalkyl and In some embodiments, R 151 Selected from fluorine, bromine, -C(O)R 161 、-C(O)OR 161 、-C(O)N(R 161 )2、-N(R 161 )C(O)R 161 、-SR 161 、-S(O)2R 161 、-S(O)2N(R 161 )2, -CN, -NO2 and In some embodiments, R 151 Selected from fluorine, bromine, -SR 161 、-S(O)2R 161 , -CN, -NO2 and In some embodiments, R 151 In some embodiments, R 152 Selected from -NHR 192 、-OR 171 、-SR 171 、-C(=NR 196 )N(R 196 )2、-C(O)R 171 、-C(O)OR 171 、-OC(O)R171 、-C(O)N(R 171 )2、-N(H)C(O)R 194 、-N(R 171 )S(O)2(R 171 )、-S(O)2R 171 、-S(O)2N(R 171 )2、-NR 196 (C=NR 196 )N(R 196 )2, -N3, -CN, one or more independently selected from R 195 C1 alkyl substituted with a substituent, In some embodiments, R 152 Selected from -NHR 192 、-C(=NR 196 )N(R 196 )2、-C(O)R 171 、-C(O)OR 171 、-C(O)N(R 171 )2、-N(H)C(O)R 194 、-NR 196 (C=NR 196 )N(R 196 )2, -N3, -CN, one or more independently selected from R 195 C1 alkyl substituted with a substituent,

[0225] In some embodiments, R 151 Selected from-SR 161 、-S(O)2R 161 , -CN and In some embodiments, R 152 Selected from halogen, -N(R 174 )2、-OR 174 、-SR 174 、-C(O)R 174 、-C(O)OR 174 、-OC(O)R 174 、-C(O)N(R 174 )2、-N(R 174 )C(O)R 174 、-N(R 174 )C(O)OR 174 、-N(R 174 )S(O)2(R 174 )、-S(O)2R 174 、-S(O)2N(R 174 )2, -NO2, -CN, optionally one or more independently selected from R180 Substituents substituted C 1-6 alkyl, and optionally substituted by one or more independently selected R 180 In some embodiments, R 152 Selected from halogen, -N(R 174 )2、-OR 174 、-C(O)N(R 174 )2、-N(R 174 )C(O)R 174 、-N(R 174 )C(O)OR 174 , -NO2, -CN, optionally one or more independently selected from R 180 Substituents substituted C 1-6 alkyl, and optionally substituted by one or more independently selected R 180 In some embodiments, R 152 Selected from -C(O)N(R 174 )2、-N(R 174 )C(O)R 174 、-N(R 174 )C(O)OR 174 , optionally one or more independently selected from R 180 Substituents substituted C 1-6 alkyl, and optionally substituted by one or more independently selected R 180 A 5-membered heterocyclic ring substituted with a substituent.

[0226] In some embodiments, R 151 In some embodiments, R 152 Select from -OR 197 、-SR 176 、-NHR 178 、-C(O)R 176 、-C(O)OR 176 、-C(O)N(R 176 )2、-N(R 176 )C(O)R 176 、-N(R 176 )S(O)2(R 176 )、-S(O)2R 176 、-S(O)2N(R 176 )2, -NO2, -CN, one or more independently selected from R 180 C1 alkyl substituted by one or more independently selected from R 198 C1 alkyl substituted with a substituent and optionally substituted with one or more independently selected from R 180Substituents substituted C 2-6 alkyl, provided that (i) when R 151 When it is NO2, R 152 cannot be one or more independently selected from R 180 and (ii) when R 151 When it is NO2, R 152 In some embodiments, R 152 Selected from one or more independently selected from R 180 C1 alkyl substituted by one or more independently selected from R 198 C1 alkyl substituted with a substituent and optionally substituted with one or more independently selected from R 180 Substituents substituted C 2-6 alkyl, provided that (i) when R 151 When it is NO2, R 152 cannot be one or more independently selected from R 180 and (ii) when R 151 When it is NO2, R 152 In some embodiments, R 151 is bromine and R 152 is one or more independently selected from R 180 In some embodiments, R 151 is -NO2 and R 152 is one or more independently selected from R 198 A C1 alkyl group substituted with a substituent.

[0227] In some embodiments, R 153 and R 154 is independently selected at each occurrence from halogen and C 1-4 In some embodiments, R 155 and R 155’ Together they are =0. In some embodiments, R 156 and R 156’ Together they are =0. In some embodiments, R 156 and R 156’ Together =N-OR 171 In some embodiments, R 156 and R 156’ In some embodiments, t is selected from the group consisting of 0 and 1. In some embodiments, u is 0.

[0228] In another aspect, the present disclosure provides a pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of Formula (I), (II), (III) or (IV).

[0229] In another aspect, the present disclosure provides a method of modulating indoleamine 2,3-dioxygenase 2 (IDO2) in a subject in need thereof, comprising administering to the subject a compound or salt of Formula (I), (II), (III) or (IV), or a pharmaceutical composition comprising a compound or salt of Formula (I), (II), (III) or (IV) and a pharmaceutically acceptable excipient.

[0230] Incorporation by reference

[0231] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. DETAILED DESCRIPTION

[0232] Provided herein are IDO2 modulators that can be used to treat a variety of diseases or conditions, including cancer and autoimmune diseases. The disclosure also provides tryptanthrin analogs, which are effective IDO2 modulators with different selectivity characteristics. In some embodiments, the disclosure provides modulators of IDO1 and IDO2. In some embodiments, the disclosure provides IDO2 / IDO1 dual modulators. In some embodiments, the disclosure provides selective IDO2 modulators that preferentially regulate the activity of IDO2 rather than IDO1.

[0233] definition

[0234] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention belongs. All patents and publications cited herein are incorporated by reference. As used in the specification and claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.

[0235] "Alkyl" refers to a straight or branched hydrocarbon chain monovalent group consisting solely of carbon and hydrogen atoms, having no unsaturation and preferably having 1 to 12 carbon atoms (i.e., C1-C 12 Alkyl). The alkyl group is connected to the rest of the molecule by a single bond. In certain embodiments, the alkyl group contains 1 to 12 carbon atoms (i.e., C1-C 12In certain embodiments, the alkyl group comprises 1 to 8 carbon atoms (i.e., C1-C8 alkyl). In other embodiments, the alkyl group comprises 1 to 5 carbon atoms (i.e., C1-C5 alkyl). In other embodiments, the alkyl group comprises 1 to 4 carbon atoms (i.e., C1-C4 alkyl). In other embodiments, the alkyl group comprises 1 to 3 carbon atoms (i.e., C1-C3 alkyl). In other embodiments, the alkyl group comprises 1 to 2 carbon atoms (i.e., C1-C2 alkyl). In other embodiments, the alkyl group comprises 1 carbon atom (i.e., C1 alkyl). In other embodiments, the alkyl group comprises 5 to 15 carbon atoms (i.e., C5-C 15 In some embodiments, the alkyl group comprises 5 to 8 carbon atoms (i.e., C5-C8 alkyl). In other embodiments, the alkyl group comprises 2 to 5 carbon atoms (i.e., C2-C5 alkyl). In other embodiments, the alkyl group comprises 3 to 5 carbon atoms (i.e., C3-C5 alkyl). For example, the alkyl group can be connected to the rest of the molecule by a single bond, such as methyl, ethyl, 1-propyl (n-propyl), 1-methylethyl (isopropyl), 1-butyl (n-butyl), 1-methylpropyl (sec-butyl), 2-methylpropyl (isobutyl), 1,1-dimethylethyl (tert-butyl), 1-pentyl (n-pentyl), etc.

[0236] "Alkenyl" refers to a straight or branched hydrocarbon chain group (i.e., C2-C 12 In some embodiments, the alkenyl group comprises 2 to 8 carbon atoms (i.e., C2-C8 alkenyl). In some embodiments, the alkenyl group comprises 2 to 6 carbon atoms (i.e., C2-C6 alkenyl). In other embodiments, the alkenyl group comprises 2 to 4 carbon atoms (i.e., C2-C4 alkenyl). The alkenyl group is connected to the rest of the molecule by a single bond, such as ethenyl (i.e., vinyl), prop-1-enyl (i.e., allyl), but-1-enyl, pent-1-enyl, penta-1,4-dienyl, etc.

[0237] "Alkynyl" refers to a straight or branched hydrocarbon chain group (i.e., C2-C 12 In certain embodiments, the alkynyl group comprises 2 to 8 carbon atoms (i.e., C2-C8 alkynyl). In other embodiments, the alkynyl group comprises 2 to 6 carbon atoms (i.e., C2-C6 alkynyl). In other embodiments, the alkynyl group comprises 2 to 4 carbon atoms (i.e., C2-C4 alkynyl). The alkynyl group is connected to the rest of the molecule by a single bond, for example, ethynyl, propynyl, butynyl, pentynyl, hexynyl, etc.

[0238] "Alkylene" refers to a straight divalent hydrocarbon chain that connects the rest of the molecule to a group, the chain consisting only of carbon and hydrogen, having no unsaturation, and preferably having 1 to 12 carbon atoms, such as methylene, ethylene, propylene, butylene, etc. The alkylene chain is connected to the rest of the molecule by a single bond and to the group by a single bond. The connection points of the alkylene chain to the rest of the molecule and the group are respectively through the terminal carbon. The alkylene chain can be optionally substituted with one or more substituents, such as those described herein. In certain embodiments, the alkylene group contains 1 to 10 carbon atoms (i.e., C1-C 10 In certain embodiments, the alkylene group comprises 1 to 8 carbon atoms (i.e., C1-C8 alkylene). In other embodiments, the alkylene group comprises 1 to 5 carbon atoms (i.e., C1-C5 alkylene). In other embodiments, the alkylene group comprises 1 to 4 carbon atoms (i.e., C1-C4 alkylene). In other embodiments, the alkylene group comprises 1 to 3 carbon atoms (i.e., C1-C3 alkylene). In other embodiments, the alkylene group comprises 1 to 2 carbon atoms (i.e., C1-C2 alkylene). In other embodiments, the alkylene group comprises 1 carbon atom (i.e., C1 alkylene). In other embodiments, the alkylene group comprises 5 to 8 carbon atoms (i.e., C5-C8 alkylene). In other embodiments, the alkylene group comprises 2 to 5 carbon atoms (i.e., C2-C5 alkylene). In other embodiments, the alkylene group comprises 3 to 5 carbon atoms (i.e., C3-C5 alkylene).

[0239] "Alkenylene" refers to a straight divalent hydrocarbon chain that connects the rest of the molecule to a group, the chain consisting only of carbon and hydrogen, containing at least one carbon-carbon double bond, and preferably having 2 to 12 carbon atoms. The alkenylene chain is connected to the rest of the molecule by a single bond and to the group by a single bond. The connection points of the alkenylene chain to the rest of the molecule and the group are respectively through the terminal carbon. The alkenylene chain can be optionally substituted with one or more substituents, such as those described herein. In certain embodiments, the alkenylene group comprises 2 to 10 carbon atoms (i.e., C2-C 10 In certain embodiments, the alkenylene group comprises 2 to 8 carbon atoms (i.e., C2-C8 alkenylene). In other embodiments, the alkenylene group comprises 2 to 5 carbon atoms (i.e., C2-C5 alkenylene). In other embodiments, the alkenylene group comprises 2 to 4 carbon atoms (i.e., C2-C4 alkenylene). In other embodiments, the alkenylene group comprises 2 to 3 carbon atoms (i.e., C2-C3 alkenylene). In other embodiments, the alkenylene group comprises 2 carbon atoms (i.e., C2 alkenylene). In other embodiments, the alkenylene group comprises 5 to 8 carbon atoms (i.e., C5-C8 alkenylene). In other embodiments, the alkenylene group comprises 3 to 5 carbon atoms (i.e., C3-C5 alkenylene).

[0240] "Alkynylidene" refers to a straight divalent hydrocarbon chain that connects the rest of the molecule to a radical, the chain consisting solely of carbon and hydrogen, containing at least one carbon-carbon triple bond, and preferably having 2 to 12 carbon atoms. The alkynylene chain is connected to the rest of the molecule by a single bond and to the radical by a single bond. The points of attachment of the alkynylene chain to the rest of the molecule and to the radical are respectively through the terminal carbons. The alkynylene chain may optionally be substituted with one or more substituents, such as those described herein. In certain embodiments, the alkynylene group comprises 2 to 10 carbon atoms (i.e., C2-C 10 In certain embodiments, the alkynylene group comprises 2 to 8 carbon atoms (i.e., C2-C8 alkynylene). In other embodiments, the alkynylene group comprises 2 to 5 carbon atoms (i.e., C2-C5 alkynylene). In other embodiments, the alkynylene group comprises 2 to 4 carbon atoms (i.e., C2-C4 alkynylene). In other embodiments, the alkynylene group comprises 2 to 3 carbon atoms (i.e., C2-C3 alkynylene). In other embodiments, the alkynylene group comprises 2 carbon atoms (i.e., C2 alkynylene). In other embodiments, the alkynylene group comprises 5 to 8 carbon atoms (i.e., C5-C8 alkynylene). In other embodiments, the alkynylene group comprises 3 to 5 carbon atoms (i.e., C3-C5 alkynylene).

[0241] The term "C x-y " when used in conjunction with a chemical moiety such as an alkyl, alkenyl, or alkynyl group, is intended to include groups containing from x to y carbons in the chain. For example, the term "C 1-6 "Alkyl" refers to substituted or unsubstituted saturated hydrocarbon groups, including straight-chain and branched-chain alkyl groups containing 1 to 6 carbon atoms. The term -C x-y Alkylene- refers to a substituted or unsubstituted alkylene chain having from x to y carbons in the alkylene chain. For example, -C 1-6 Alkylene- may be selected from methylene, ethylene, propylene, butylene, pentylene and hexylene, any of which is optionally substituted.

[0242] The term "C x-y Alkenyl" and "C x-y "Alkynyl" refers to an unsaturated aliphatic group similar in length and possible substitution to the alkyl groups described above, but containing at least one double or triple bond, respectively. The term -C x-y Alkenylene- refers to a substituted or unsubstituted alkenylene chain having from x to y carbons in the alkenylene chain. For example, -C 2-6 Alkenylene- may be selected from ethenylene, propenylene, butenylene, pentenylene and hexenylene, any of which is optionally substituted. The alkenylene chain may have one double bond or more than one double bond in the alkenylene chain. The term -C x-y Alkyne- refers to a substituted or unsubstituted alkynylene chain having from x to y carbon atoms in the alkynylene chain. For example, -C 2-6Alkynylene- may be selected from ethynylene, propynylene, butynylene, pentynylene and hexynylene, any of which is optionally substituted. The alkynylene chain may have one triple bond or more than one triple bond in the alkynylene chain.

[0243] As used herein, the term "carbocycle" refers to a saturated, unsaturated, or aromatic ring in which each atom of the ring is carbon. Carbocycles include 3-10 membered monocycles and 6-12 membered bicyclic rings. Each ring of a bicyclic carbocycle can be selected from a saturated ring, an unsaturated ring, and an aromatic ring. The bicyclic carbocycle can be a fused, bridged, or spirocyclic ring system. In some embodiments, the carbocycle is an aryl group. In some embodiments, the carbocycle is a cycloalkyl group. In some embodiments, the carbocycle is a cycloalkenyl group. In exemplary embodiments, an aromatic ring, such as a phenyl group, can be fused to a saturated or unsaturated ring, such as cyclohexane, cyclopentane, or cyclohexene. Any combination of saturated, unsaturated, and aromatic bicyclic rings, as long as the valence number permits, is included in the definition of carbocycle. Exemplary carbocycles include cyclopentyl, cyclohexyl, cyclohexenyl, adamantyl, phenyl, indanyl, and naphthyl. The carbocycle can optionally be substituted with one or more substituents, such as those described herein.

[0244] "Cycloalkyl" refers to a stable, fully saturated monocyclic or polycyclic hydrocarbon radical consisting solely of carbon and hydrogen atoms, including fused or bridged ring systems, and preferably having from 3 to 12 carbon atoms (i.e., C 3-12 In certain embodiments, the cycloalkyl group contains 3 to 10 carbon atoms (i.e., C 3-10 In other embodiments, the cycloalkyl group contains 5 to 7 carbon atoms (i.e., C 5-7 Cycloalkyl). The cycloalkyl group may be connected to the rest of the molecule by a single bond. Examples of monocyclic cycloalkyl groups include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Polycyclic cycloalkyl groups include, for example, adamantyl, norbornyl (i.e., bicyclo[2.2.1]heptyl), norbornenyl, decalinyl, 7,7-dimethylbicyclo[2.2.1]heptyl, and the like. The cycloalkyl group may be optionally substituted with one or more substituents, such as those described herein.

[0245] "Cycloalkenyl" refers to a stable, unsaturated, non-aromatic monocyclic or polycyclic hydrocarbon radical consisting solely of carbon and hydrogen atoms, including fused or bridged ring systems, preferably having from 3 to 12 carbon atoms and containing at least one double bond (i.e., C 3-12 In certain embodiments, a cycloalkenyl group contains 3 to 10 carbon atoms (i.e., C 3-10 In other embodiments, the cycloalkenyl group contains 5 to 7 carbon atoms (i.e., C 5-7Cycloalkenyl). The cycloalkenyl group can be connected to the rest of the molecule by a single bond. Examples of monocyclic cycloalkenyl groups include, for example, cyclopentenyl, cyclohexenyl, cycloheptenyl, and cyclooctenyl. The cycloalkenyl group can be optionally substituted with one or more substituents, such as those described herein.

[0246] "Aryl" refers to a group derived from an aromatic monocyclic or polycyclic hydrocarbon ring system by removing hydrogen atoms from ring carbon atoms. The aromatic monocyclic or polycyclic hydrocarbon ring system contains only hydrogen and carbon and 5 to 18 carbon atoms, wherein at least one ring in the ring system is aromatic, i.e., according to Hückel theory, it contains a cyclic, delocalized (4n+2) π-electron system. Ring systems from which aryl groups are derived include, but are not limited to, groups such as benzene, fluorene, indane, indene, tetralin, and naphthalene. The aryl group may be optionally substituted with one or more substituents, such as those described herein.

[0247] “C x-y Carbocycle is intended to include groups containing x to y carbon atoms in the ring. For example, the term "C 3-6 A "carbocycle" may be a saturated, unsaturated, or aromatic ring system containing from 3 to 6 carbon atoms - any of which is optionally substituted as provided herein.

[0248] The term "heterocycle" as used herein refers to a saturated, unsaturated, non-aromatic or aromatic ring containing one or more heteroatoms. Exemplary heteroatoms include N, O, Si, P, B and S atoms. Heterocycle includes 3 to 10-membered monocycles and 6 to 12-membered bicyclic rings. Each ring of the bicyclic heterocycle can be selected from a saturated ring, an unsaturated ring and an aromatic ring. In some embodiments, the heterocycle includes at least one heteroatom selected from oxygen, nitrogen, sulfur or any combination thereof. In some embodiments, the heterocycle includes at least one heteroatom selected from oxygen, nitrogen or any combination thereof. In some embodiments, the heterocycle includes at least one heteroatom selected from oxygen, sulfur or any combination thereof. In some embodiments, the heterocycle includes at least one heteroatom selected from nitrogen, sulfur or any combination thereof. The heterocycle can be connected to the rest of the molecule by any atom of the heterocycle (as long as the valence number allows) such as a carbon atom or nitrogen atom of the heterocycle. In some embodiments, the heterocycle is a heteroaryl. In some embodiments, the heterocycle is a heterocycloalkyl. Exemplary heterocycles include pyrrolidinyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, piperidinyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, thienyl, oxazolyl, thiazolyl, morpholinyl, indazolyl, indolyl and quinolyl. Heterocycle can be optionally substituted by one or more substituents (such as those described herein). Bicyclic heterocycle can be fused, bridged or spirocyclic system. In exemplary embodiments, heterocycle, such as pyridyl, can be fused to saturated or unsaturated ring, such as cyclohexane, cyclopentane or cyclohexene. Heterocycle can be optionally substituted by one or more substituents (such as those described herein).

[0249] "Heterocycloalkyl" refers to a stable 3 to 12 membered non-aromatic ring radical comprising 2 to 12 carbon atoms and at least one heteroatom, wherein each heteroatom may be selected from N, O, Si, P, B, and S atoms. In some embodiments, heterocycloalkyl comprises at least one heteroatom selected from oxygen, nitrogen, sulfur, or any combination thereof. In some embodiments, heterocycloalkyl comprises at least one heteroatom selected from oxygen, nitrogen, or any combination thereof. In some embodiments, heterocycloalkyl comprises at least one heteroatom selected from oxygen, sulfur, or any combination thereof. In some embodiments, heterocycloalkyl comprises at least one heteroatom selected from nitrogen, sulfur, or any combination thereof. Heterocycloalkyl may be selected from monocyclic or bicyclic and fused or bridged ring systems. The heteroatoms in heterocycloalkyl are optionally oxidized. If present, one or more nitrogen atoms are optionally quaternized. Heterocycloalkyl is partially or completely saturated. Heterocycloalkyl is connected to the remainder of the molecule by any atom of heterocycloalkyl (as long as the valence number allows), such as any carbon atom or nitrogen atom of heterocycloalkyl. Examples of heterocycloalkyl groups include, but are not limited to, dioxolanyl, thienyl[1,3]dithianyl, decahydroisoquinolinyl, imidazolinyl, imidazolidinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, piperidinyl, piperazinyl, 4-piperidonyl, pyrrolidinyl, pyrazolidinyl, quinuclidinyl, thiazolidinyl, tetrahydrofuranyl, trithianyl, tetrahydropyranyl, thiomorpholinyl, thiamorpholinyl, 1-oxothiomorpholinyl, and 1,1-dioxothiomorpholinyl. Heterocycloalkyl groups may be optionally substituted with one or more substituents, such as those described herein.

[0250] The term "heteroaryl" refers to a group derived from a 3 to 12-membered aromatic ring group comprising 1 to 11 carbon atoms and at least one heteroatom, wherein each heteroatom can be selected from N, O and S. In some embodiments, the heteroaryl group comprises at least one heteroatom selected from oxygen, nitrogen, sulfur or any combination thereof. In some embodiments, the heteroaryl group comprises at least one heteroatom selected from oxygen, nitrogen or any combination thereof. In some embodiments, the heteroaryl group comprises at least one heteroatom selected from oxygen, sulfur or any combination thereof. In some embodiments, the heteroaryl group comprises at least one heteroatom selected from nitrogen, sulfur or any combination thereof. As used herein, the heteroaryl ring can be selected from a monocyclic or bicyclic ring and a fused or bridged ring system ring, wherein at least one ring in the ring system is aromatic, i.e., according to Hückel theory, it contains a cyclic, delocalized (4n+2) π-electron system. The one or more heteroatoms in the heteroaryl group can be optionally oxidized. If present, one or more nitrogen atoms are optionally quaternized. Heteroaryl can be connected to the rest of the molecule by any atom of the heteroaryl (as long as the valence number allows), such as a carbon atom or nitrogen atom of the heteroaryl. Heteroaryl includes aromatic monocyclic structures, preferably 5 to 6 membered rings, whose ring structure includes at least one heteroatom, preferably 1 to 4 heteroatoms, more preferably 1 or 2 heteroatoms. Heteroaryl includes, for example, pyrrole, furan, thiophene, imidazole, oxazole, thiazole, pyrazole, pyridine, pyrazine, pyridazine and pyrimidine. Heteroaryl can optionally be substituted with one or more substituents (such as those described herein). Heteroaryl also includes a polycyclic ring system with two or more rings, wherein two or more atoms are shared by two adjacent rings, wherein at least one ring is heteroaromatic, for example, other rings can be aromatic or non-aromatic carbocyclic or heterocyclic. Heteroaryl can optionally be substituted with one or more substituents (such as those described herein).

[0251] "X-membered heterocycle" refers to the number of atoms (ie, X) in the ring. For example, a 5-membered heteroaryl ring or a 5-membered aromatic heterocycle has 5 atoms in the ring, such as triazole, oxazole, thiophene, etc.

[0252] "Alkoxy" refers to a group bonded through an oxygen atom of the formula -O-alkyl where alkyl is an alkyl chain as defined above.

[0253] "Halo" or "halogen" refers to halogen substituents such as bromo, chloro, fluoro, and iodo substituents.

[0254] As used herein, the term "haloalkyl" or "haloalkane" refers to an alkyl group as defined above that is substituted with one or more halogen groups, for example, trifluoromethyl, dichloromethyl, bromomethyl, 2,2,2-trifluoroethyl, 1-fluoromethyl-2-fluoroethyl, etc. In some embodiments, the alkyl portion of the fluoroalkyl group is optionally further substituted. Examples of halogen-substituted alkanes ("haloalkanes") include halogenated methanes (e.g., chloromethane, bromomethane, fluoromethane, iodomethane), dihalogenated methanes and trihalogenated methanes (e.g., chloroform, bromomethane, trifluoromethane, iodomethane), 1-haloethane, 2-haloethane, 1,2-dihaloethane, 1-halopropane, 2-halopropane, 3-halopropane, 1,2-dihalopropane, 1,3-dihalopropane, 2,3-dihalopropane, 1,2,3-trihalopropane, and any other suitable combination of an alkane (or substituted alkane) and a halogen (e.g., Cl, Br, F, and I). When an alkyl group is substituted with more than one halogen group, each halogen can be independently selected, for example, 1-chloro, 2-fluoroethane.

[0255] The term "substituted" refers to a moiety having a substituent that replaces hydrogen on one or more carbons or substitutable heteroatoms (such as NH or NH2) of a compound. It should be understood that "substituted" or "substituted by ... " include implicit conditions, i.e., such substitutions meet the allowed valences of the substituted atoms and substituents, and substitutions produce stable compounds, i.e., compounds that do not spontaneously undergo conversion (such as by rearrangement, cyclization, elimination, etc.). In certain embodiments, substitution refers to a moiety with a substituent that replaces two hydrogen atoms on the same carbon atom, such as replacing two hydrogen atoms on a single carbon with an oxo, imino, or thio group. As used herein, the term "substituted" is intended to include all substituents allowed of an organic compound. In a broad sense, the substituents allowed include acyclic and cyclic, branched and straight-chain, carbocyclic and heterocyclic, aromatic and non-aromatic substituents of an organic compound. For appropriate organic compounds, the substituents allowed can be one or more and can be identical or different.

[0256] In some embodiments, the substituents may include any of the substituents described herein, for example, halogen, hydroxy, oxo (=O), thio (=S), cyano (-CN), nitro (-NO2), imino (=NH), oxime (=N-OH), hydrazine (=N-NH2), -R b -OR a 、-R b -OC(O)-R a 、-R b -OC(O)-OR a 、-R b -OC(O)-N(R a )2. -R b -N(Ra )2. -R b -C(O)R a 、-R b -C(O)OR a 、-R b -C(O)N(R a )2. -R b -OR c -C(O)N(R a )2. -R b -N(R a )C(O)OR a 、-R b -N(R a )C(O)R a 、-R b -N(R a )S(O) t R a (where t is 1 or 2), -R b -S(O) t R a (where t is 1 or 2), -R b -S(O) t OR a (where t is 1 or 2) and -R b -S(O) t N(R a )2 (wherein t is 1 or 2); and alkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, aralkynyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl and heteroarylalkyl, any of which may be optionally replaced by alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo (=O), thio (=S), cyano (-CN), nitro (-NO2), imino (=NH), oxime (=N-OH), hydrazine (=N-NH2), -R b -OR a 、-R b -OC(O)-R a 、-R b -OC(O)-OR a 、-R b -OC(O)-N(R a )2. -R b -N(R a )2. -R b -C(O)R a 、-R b -C(O)OR a 、-R b -C(O)N(R a )2. -R b-OR c -C(O)N(R a )2. -R b -N(R a )C(O)OR a 、-R b -N(R a )C(O)R a 、-R b -N(R a )S(O) t R a (where t is 1 or 2), -R b -S(O) t R a (where t is 1 or 2), -R b -S(O) t OR a (where t is 1 or 2) and -R b -S(O) t N(R a )2 (wherein t is 1 or 2) substituted; wherein each R a are independently selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl or heteroarylalkyl, wherein each R a (If the valence permits) may be optionally replaced by alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo (=O), thio (=S), cyano (-CN), nitro (-NO2), imino (=NH), oxime (=N-OH), hydrazine (=N-NH2), -R b -OR a 、-R b -OC(O)-R a 、-R b -OC(O)-OR a 、-R b -OC(O)-N(R a )2. -R b -N(R a )2. -R b -C(O)R a 、-R b -C(O)OR a 、-R b -C(O)N(R a )2. -R b -OR c -C(O)N(R a )2. -R b -N(R a )C(O)OR a 、-R b-N(R a )C(O)R a 、-R b -N(R a )S(O) t R a (where t is 1 or 2), -R b -S(O) t R a (where t is 1 or 2), -R b -S(O) t OR a (where t is 1 or 2) and -R b -S(O) t N(R a )2 (wherein t is 1 or 2) substituted; wherein each R b are independently selected from a direct bond or a straight or branched alkylene, alkenylene or alkynylene chain, and each R c It will be understood by those skilled in the art that the substituents themselves may be substituted where appropriate.

[0257] The term "salt" or "pharmaceutically acceptable salt" refers to salts derived from various organic and inorganic counterions known in the art. Pharmaceutically acceptable acid addition salts can be formed with inorganic and organic acids. Pharmaceutically acceptable base addition salts can be formed with inorganic and organic bases.

[0258] As used herein, the phrase "pharmaceutically acceptable" refers to those compounds, materials, compositions and / or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit / risk ratio.

[0259] As used herein, the phrases "pharmaceutically acceptable excipient" or "pharmaceutically acceptable carrier" refer to a pharmaceutically acceptable material, composition, or vehicle, such as a liquid or solid filler, diluent, excipient, solvent, or encapsulating material. Each carrier must be "acceptable" in the sense of being compatible with the other ingredients of the formulation and not injurious to the patient.

[0260] The terms "subject," "individual," and "patient" are used interchangeably and refer to humans as well as non-human mammals (e.g., non-human primates, canines, equines, felines, porcines, bovines, ungulates, lagomorphs, etc.). In various embodiments, the subject can be a human (e.g., an adult male, adult female, adolescent male, adolescent female, boy, girl) who is receiving care from a physician or other health worker in a hospital, as an outpatient, or in other clinical settings. In certain embodiments, the subject may not be receiving care or prescribing guidance from a physician or other health worker.

[0261] As used herein, the phrase "a subject in need thereof" refers to a subject having or at risk for a pathology to be treated prophylactically or therapeutically with a compound or salt described herein.

[0262] The terms "administer," "administered," "administers," and "administering" are defined as providing a composition to a subject by routes known in the art, including, but not limited to, intravenous, intraarterial, oral, parenteral, buccal, topical, transdermal, rectal, intramuscular, subcutaneous, intraosseous, transmucosal, or intraperitoneal administration. In certain embodiments, an oral route of administration of the composition may be used. The terms "administer," "administered," "administers," and "administering" a compound should be understood to mean providing a compound of the invention or a prodrug of a compound of the invention to an individual in need thereof.

[0263] As used herein, "treatment" or "treating" refers to a method for obtaining a beneficial or desired result about a disease, disorder or medical condition, including but not limited to therapeutic benefit and / or preventive benefit. In certain embodiments, treatment or treating involves administering a compound or composition disclosed herein to a subject. Therapeutic benefit can include eradicating or improving the underlying condition being treated. In addition, therapeutic benefit can be achieved by eradicating or improving one or more physiological symptoms associated with the underlying condition, such as observing improvement in the subject, although the subject may still be suffering from the underlying condition. In certain embodiments, for preventive benefit, the composition is administered to a subject at risk of developing a specific disease, or to a subject reporting one or more physiological symptoms of the disease, even if a diagnosis of the disease may not yet be made. Treating can include, for example, reducing, delaying or alleviating the severity of one or more symptoms of a disease or condition, or it can include reducing the frequency with which a patient experiences symptoms of a disease, defect, disorder or adverse condition, etc. Treating can be used herein to refer to a method for treating or improving a certain degree of a disease or condition, and a range of results for this purpose can be considered, including but not limited to preventing the condition completely.

[0264] In certain embodiments, the terms "prevent" or "preventing" in relation to a disease or condition may refer to a compound that reduces the occurrence of the disease or condition in a treated sample relative to an untreated control sample, or delays the onset of or reduces the severity of one or more symptoms of the disease or condition relative to an untreated control sample.

[0265] As used herein, the term "therapeutic effect" encompasses therapeutic benefits and / or prophylactic benefits as described above. A prophylactic effect includes delaying or eliminating the appearance of a disease or condition, delaying or eliminating the onset of a disease or condition, slowing, stopping, or reversing the progression of a disease or condition, or any combination thereof.

[0266] Compound

[0267] In one aspect, provided herein are compounds having the structure of Formula (I):

[0268]

[0269] or a pharmaceutically acceptable salt thereof; wherein

[0270] R 1 Selected from fluorine, chlorine, bromine, hydroxyl, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -OC 1-6 Alkyl, -OC 1-6 Haloalkyl, -OR12 、-SR 11 、-N(R 13 )2、-C(O)R 11 、-C(O)OR 11 、-OC(O)R 11 、-OC(O)N(R 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-N(R 11 )C(O)OR 11 、-N(R 11 )C(O)N(R 11 )2、-N(R 11 )S(O)2(R 11 )、-S(O)2R 11 、-S(O)2N(R 11 )2, -NO2, -N3 and -CN;

[0271] When R 1 When it is hydroxyl, -O-C1 alkyl or -NO2, R 2 Selected from

[0272] Fluorine, bromine, iodine, -OR 22 、-SR 21 、-N(R 21 )2、-C(O)R 21 、-OC(O)R 21 、-OC(O)N(R 21 )2、-N(R 21 )C(O)R 21 、-N(R 21 )C(O)OR 21 、-N(R 21 )C(O)N(R 21 )2、-N(R 21 )S(O)2(R 21 )、-N(R 21 )SO2N(R 21 )、-N(R 21 )P(O)(OR 21 )R 21 、-S(O)2R 21 、-S(O)2N(R 21 )2, -NO2 and -CN;

[0273] Optionally, one or more independently selected from R 30 Substituents substituted C 1-6 Alkyl; and

[0274] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 30 Substituents substituted;

[0275] When R 1 When it is fluorine, R 2 Selected from

[0276] Bromine, -OR 23 、-N(H)R 23 、-C(O)R 23 、-C(O)N(R 23 )2、-C(O)OR 23 、-OC(O)R 23 、-OC(O)N(R 23 )2、-N(R 23 )C(O)R 23 、-N(R 23 )C(O)OR 23 、-N(R 23 )C(O)N(R 23 )2、-N(R 23 )S(O)2R 23 、-N(R 23 )SO2N(R 23 )、-N(R 23 )P(O)(OR 23 )R 23 、-S(O)2R 23 、-S(O)2N(R 23 )2, -NO2 and -CN;

[0277] Optionally, one or more independently selected from R 30 Substituents substituted C 1-6 Alkyl; and

[0278] C 3-6 Carbocyclic and 3- to 4-membered heterocyclic rings, Any one of which is optionally replaced by one or more independently selected from R 30 Substituents substituted;

[0279] When R 1 When R is C1 alkyl, -O-C1 haloalkyl, hydroxyl, chlorine or bromine, 2 Selected from:

[0280] Iodine, -OR 25 、-C(O)R 24 、-C(O)OR 25 、-OC(O)R 24 、-OC(O)N(R24 )2、-C(O)N(R 24 )2、-N(R 24 )C(O)R 24 、-N(R 24 )C(O)OR 24 、-N(R 24 )C(O)N(R 24 )2、-N(R 24 )S(O)2(R 24 )、N(R 24 )SO2N(R 24 )、-N(R 24 )P(O)(OR 24 )R 24 、-S(O)R 24 、-S(O)2R 24 、-S(O)2N(R 24 )2, -NO2 and -CN;

[0281] Optionally, one or more independently selected from R 30 Substituents substituted C 2-6 alkyl;

[0282] C 3-6 Carbocyclic and 3 to 5 membered heterocyclic rings, any of which are optionally substituted by one or more independently selected R 30 and

[0283] When R 1 When R is selected from bromine, hydroxyl and C1 alkyl, 2 further selected from fluorine;

[0284] When R 1 C 2-6 Alkyl, C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 2-6 Haloalkyl, -OR 12 、-SR 11 、-N(R 13 )2、-C(O)R 11 、-C(O)OR 11 、-OC(O)R 11 、-OC(O)N(R 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-N(R 11 )C(O)OR 11 、-N(R 11 )C(O)N(R11 )2、-N(R 11 )S(O)2(R 11 )、-S(O)2R 11 、-S(O)2N(R 11 )2, -N3 or -CN, R 2 Selected from

[0285] Halogen, -OR 26 、-SR 26 、-N(R 26 )2、-C(O)R 26 、-C(O)OR 26 、-OC(O)R 26 、-OC(O)N(R 26 )2、-C(O)N(R 26 )2、-N(R 26 )C(O)R 26 、-N(R 26 )C(O)OR 26 、-N(R 26 )C(O)N(R 26 )2、-N(R 26 )S(O)2(R 26 )、N(R 26 )SO2N(R 26 )、-N(R 26 )P(O)(OR 26 )R 26 、-S(O)R 26 、-S(O)2R 26 、-S(O)2N(R 26 )2, -NO2 and -CN;

[0286] Optionally, one or more independently selected from R 30 Substituents substituted C 1-6 Alkyl; and

[0287] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 30 Substituents substituted;

[0288] The condition is that when R 1 -C(O)OR 11 When R 2 It cannot be a substituted 6-membered heterocycle;

[0289] R 3 and R 4 Each occurrence is independently selected from

[0290] Halogen, -OR 14 、-SR 14 、-N(R 14 )2、-N(R 14 )C(O)R 14 、-C(O)R 14 、-C(O)OR 14 、-C(O)N(R 14 )2, -NO2 and -CN;

[0291] C 1-4 Alkyl, which is optionally substituted by one or more independently selected from halogen, -OR 14 、-SR 14 、-N(R 14 )2、-N(R 14 )C(O)R 14 、-C(O)R 14 、-C(O)OR 14 、-C(O)N(R 14 )2, -NO2 and -CN substituents;

[0292] C 3-4 Carbocyclic and 3 to 4 membered heterocyclic rings, any of which are optionally substituted by one or more independently selected from halogen, -OR 14 、-SR 14 、-N(R 14 )2、-N(R 14 )C(O)R 14 、-C(O)R 14 、-C(O)OR 14 、-C(O)N(R 14 )2, -NO2 and -CN substituents;

[0293] R 5 and R 5’ are each independently selected from hydrogen and hydroxy; or R 5 and R 5’ Together = O;

[0294] R 6 and R 6’ are each independently selected from hydrogen and hydroxy; or R 6 and R 6’ Together they are =O, =N-OR 26 or =NR 26 ;

[0295] m is selected from 0, 1, 2 and 3;

[0296] n is selected from 0, 1, 2 and 3;

[0297] R 11and R 14 Each occurrence is independently selected from

[0298] hydrogen;

[0299] Optionally, one or more independently selected from R 31 Substituents substituted C 1-6 alkyl;

[0300] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 31 Substituents substituted;

[0301] R 12 Each time it appears, select

[0302] One or more independently selected from R 32 Substituents substituted C 1-6 alkyl;

[0303] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which are optionally replaced by one or more

[0304] Independently selected from R 33 Substituents substituted;

[0305] R 13 Each time it appears, select

[0306] hydrogen;

[0307] Optionally, one or more independently selected from R 34 Substituents substituted C 1-6 alkyl;

[0308] C 3-5 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 34 Substituents substituted;

[0309] R 21 、R 23 、R 24 and R 26 Each occurrence is independently selected from

[0310] hydrogen;

[0311] Optionally, one or more independently selected from R 34 Substituents substituted C 1-6 alkyl;

[0312] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which are optionally replaced by one or more

[0313] Independently selected from C 1-4 Alkyl, C 1-4 Haloalkyl and R 34 Substituents substituted;

[0314] R 22 and R 25 Each occurrence is independently selected from C 2-6 Alkyl, C 2-6 Haloalkyl and C 2-6 hydroxyalkyl;

[0315] R 30 、R 31 、R 33 and R 34 Each occurrence is independently selected from

[0316] Halogen, -OR 41 、-SR 41 、-N(R 41 )2、-C(O)R 41 、-C(O)OR 41 、-OC(O)R 41 、-OC(O)N(R 41 )2、-C(O)N(R 41 )2、-N(R 41 )C(O)R 41 、-N(R 41 )C(O)OR 41 、-N(R 41 )C(O)N(R 41 )2、-N(R 41 )S(O)2(R 41 )、-N(R 41 )SO2N(R 41 )、-N(R 41 )P(O)(OR 41 )R 41 、-S(O)R 41 、-S(O)2R 41 、-S(O)2N(R 41 )2, -NO2, =O, =S, -CN, C 3-6 Carbocyclic and 3- to 7-membered heterocyclic rings;

[0317] R 32 independently selected at each occurrence

[0318] -OR 41 、-SR 41 、-N(R 41 )2、-C(O)R 41 、-C(O)OR41 、-OC(O)R 41 、-OC(O)N(R 41 )2、-C(O)N(R 41 )2、-N(R 41 )C(O)R 41 、-N(R 41 )C(O)OR 41 、-N(R 41 )C(O)N(R 41 )2、-N(R 41 )S(O)2(R 41 )、-N(R 41 )SO2N(R 41 )、-N(R 41 )P(O)(OR 41 )R 41 、-S(O)R 41 、-S(O)2R 41 、-S(O)2N(R 41 )2, -NO2, =O, =S and -CN; and

[0319] R 41 independently selected at each occurrence from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl and C 1-6 Hydroxyalkyl.

[0320] In some embodiments, for the compound or salt of formula (I),

[0321] R 1 Selected from fluorine, -C 1-6 Haloalkyl, -OC 1-6 Haloalkyl, -SR 11 、-N(R 13 )2、-C(O)OR 11 、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-S(O)2R 11 , -NO2, -N3 and -CN;

[0322] When R 1 When it is -NO2, R 2 Selected from: fluorine, bromine, iodine, -OR 22 、-N(R 21 )2、-C(O)R 23 、-C(O)N(R 23 )2、-C(O)OR 23 、-OC(O)R 23、-OC(O)N(R 23 )2、-N(R 23 )C(O)R 23 ;-N(R 21 )C(O)OR 21 , -NO2, -CN and optionally one or more independently selected from R 30 Substituents substituted C 1-6 alkyl.

[0323] When R 1 When it is fluorine, R 2 Selected from: Bromine, OR 23 、-N(H)R 23 、-C(O)R 23 、-C(O)N(R 23 )2、-C(O)OR 23 、-OC(O)R 23 、-OC(O)N(R 23 )2、-N(R 23 )C(O)R 23 、-NO2、-CN、 and optionally one or more independently selected from R 30 Substituents substituted C 1-6 alkyl.

[0324] When R 1 When it is -O-C1 haloalkyl, R 2 Selected from: iodine, -OR 25 、-C(O)R 24 、-C(O)OR 25 、-OC(O)R 24 、-C(O)N(R 24 )2、-N(R 24 )C(O)R 24 , -NO2, -CN and optionally one or more independently selected from R 30 Substituents substituted C 2-6 alkyl;

[0325] When R 1 When R is selected from bromine, hydroxyl and C1 alkyl, 2 further selected from fluorine;

[0326] When R 1 For-SR 11 、-N(R 13 )2、-C(O)R 11 、-C(O)OR 11 、-C(O)N(R 11 )2、-N(R 11 )C(O)R11 、-S(O)2R 11 、-S(O)2N(R 11 )2, -N3 or -CN, R 2 Selected from halogen, -OR 26 、-N(R 26 )2、-C(O)R 26 、-C(O)OR 26 、-OC(O)R 26 、-C(O)N(R 26 )2、-N(R 26 )C(O)R 26 , -NO2, -CN, optionally one or more independently selected from R 30 Substituents substituted C 1-6 alkyl;

[0327] R 3 and R 4 is independently selected at each occurrence from halogen, -OR 14 、-N(R 14 )2, -NO2 and -CN; R 5 and R 5’ are each independently selected from hydrogen and hydroxy; or R 5 and R 5’ Together = O; R 6 and R 6’ are each independently selected from hydrogen and hydroxy; or R 6 and R 6’ Together they are =O, =N-OR 26 or =NR 26 ; m is selected from 0 and 1; n is selected from 0 and 1;

[0328] R 11 and R 14 are each independently selected at each occurrence from hydrogen; optionally replaced by one or more independently selected from R 31 Substituents substituted C 1-6 Alkyl; and optionally one or more independently selected from R 31 A 3- to 6-membered heterocyclic ring substituted with a substituent; R 12 is selected at each occurrence from one or more independently selected from R 32 Substituents substituted C 1-6 Alkyl; R 13 at each occurrence selected from hydrogen;

[0329] R 21 、R 23 、R 24 and R 26are each independently selected at each occurrence from hydrogen; optionally replaced by one or more independently selected from R 34 Substituents substituted C 1-6 Alkyl; and optionally one or more independently selected from C 1-4 Alkyl and C 1-4 a 3- to 6-membered heterocyclic ring substituted with a haloalkyl substituent; R 22 and R 25 Each occurrence is independently selected from C 2-6 alkyl;

[0330] R 30 、R 31 、R 33 and R 34 is independently selected at each occurrence from halogen, -OR 41 、-N(R 41 )2、-C(O)OR 41 、-OC(O)R 41 、-C(O)N(R 41 )2、-N(R 41 )C(O)R 41 、-N(R 41 )S(O)2(R 41 )、-N(R 41 )SO2N(R 41 )、-N(R 41 )P(O)(OR 41 )R 41 , =O, -CN and C 3-6 Carbon ring; R 32 In each occurrence, independently selected from -OR 41 、-SR 41 、-N(R 41 )2, =O and -CN; and

[0331] R 41 independently selected at each occurrence from hydrogen and C 1-6 alkyl.

[0332] In some embodiments, for the compound or salt of Formula (I), R 1 Selected from fluorine, chlorine, bromine, hydroxyl, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -OC 1-6 Alkyl, -OC 1-6 Haloalkyl, -OR 12 、-SR 11 、-N(R 13 )2、-C(O)R 11 、-C(O)OR 11 、-OC(O)R11 、-OC(O)N(R 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-N(R 11 )C(O)OR 11 、-N(R 11 )C(O)N(R 11 )2、-N(R 11 )S(O)2(R 11 )、-S(O)2R 11 、-S(O)2N(R 11 )2, -NO2, -N3 and -CN. In some embodiments, R 1 Selected from fluorine, chlorine, bromine, hydroxyl, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -OC 1-6 Alkyl, -OC 1-6 Haloalkyl, -OR 12 、-SR 11 、-N(R 13 )2、-C(O)R 11 、-C(O)OR 11 、-OC(O)R 11 、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-N(R 11 )S(O)2(R 11 )、-S(O)2R 11 、-S(O)2N(R 11 )2, -NO2, -N3 and -CN. In some embodiments, R 1 Selected from fluorine, chlorine, bromine, hydroxyl, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -OC 1-6 Alkyl, -OC 1-6 Haloalkyl, -OR 12 、-SR 11 、-N(R 13 )2、-C(O)R 11 、-C(O)OR 11 、-OC(O)R 11 、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-N(R 11 )S(O)2(R 11)、-S(O)2R 11 , -NO2, -N3 and -CN. In some embodiments, R 1 Selected from fluorine, chlorine, bromine, hydroxyl, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -OC 1-6 Alkyl, -OC 1-6 Haloalkyl, -OR 12 、-SR 11 、-N(R 13 )2、-C(O)OR 11 、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-S(O)2R 11 , -NO2, -N3 and -CN. In some embodiments, R 1 Selected from fluorine, chlorine, bromine, hydroxyl, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -OC 1-6 Alkyl, -OC 1-6 Haloalkyl, -SR 11 、-N(R 13 )2、-C(O)OR 11 、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-S(O)2R 11 , -NO2, -N3 and -CN. In some embodiments, R 1 Selected from fluorine, chlorine, bromine, -C 1-6 Haloalkyl, -OC 1-6 Haloalkyl, -SR 11 、-N(R 13 )2、-C(O)OR 11 、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-S(O)2R 11 , -NO2, -N3 and -CN. In some embodiments, R 1 Selected from fluorine, -C 1-6 Haloalkyl, -OC 1-6 Haloalkyl, -SR 11 、-N(R 13 )2、-C(O)OR 11 、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11、-S(O)2R 11 , -NO2, -N3 and -CN.

[0333] In some embodiments, for the compound or salt of Formula (I), R 1 Selected from fluorine, chlorine, bromine, hydroxyl, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -OC 1-6 Alkyl, -OC 1-6 Haloalkyl, -OR 12 、-SR 11 、-N(R 13 )2、-C(O)OR 11 、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-N(R 11 )C(O)OR 11 、-N(R 11 )S(O)2(R 11 )、-S(O)2R 11 、-S(O)2N(R 11 )2, -NO2, -N3 and -CN. In some embodiments, R 1 Selected from fluorine, chlorine, bromine, hydroxyl, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -OC 1-6 Haloalkyl, -SR 11 、-N(R 13 )2、-C(O)R 11 、-C(O)OR 11 、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-N(R 11 )C(O)OR 11 、-N(R 11 )S(O)2(R 11 )、-S(O)2R 11 、-S(O)2N(R 11 )2, -NO2, -N3 and -CN. In some embodiments, R 1 Selected from fluorine, chlorine, bromine, hydroxyl, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -OC 1-6 Haloalkyl, -SR 11 、-N(R 13 )2、-C(O)R 11 、-C(O)OR 11、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-S(O)2R 11 , -NO2, -N3 and -CN. In some embodiments, R 1 Selected from fluorine, chlorine, bromine, hydroxyl, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -OC 1-6 Alkyl, -OC 1-6 Haloalkyl, -OR 12 , -NO2, -N3 and -CN.

[0334] In some embodiments, for the compound or salt of Formula (I), R 1 In some embodiments, R 1 Selected from -C 1-6 Alkyl and -C 1-6 In some embodiments, R 1 Selected from hydroxyl, -OC 1-6 Alkyl, -OC 1-6 Haloalkyl, -OR 12 、-OC(O)R 11 and -OC(O)N(R 11 )2. In some embodiments, R 1 In some embodiments, R 1 Selected from -N(R 13 )2、-N(R 11 )C(O)R 11 、-N(R 11 )C(O)OR 11 、-N(R 11 )S(O)2(R 11 ) and -N(R 11 )C(O)N(R 11 )2. In some embodiments, R 1 Selected from -C(O)R 11 、-C(O)OR 11 and -C(O)N(R 11 )2. In some embodiments, R 1 Selected from-SR 11 、-S(O)2R 11 and -S(O)2N(R 11 )2.

[0335] In some embodiments, for the compound or salt of Formula (I), R 1 In some embodiments, R1 -C 1-6 In some embodiments, R 1 For-OC 1-6 In some embodiments, R 1 For-SR 11 In some embodiments, R 1 -N(R 13 )2. In some embodiments, R 1 -C(O)OR 11 In some embodiments, R 1 -C(O)N(R 11 )2. In some embodiments, R 1 -N(R 11 )C(O)R 11 In some embodiments, R 1 is -S(O)2R 11 In some embodiments, R 1 In some embodiments, R 1 In some embodiments, R 1 It is -N3.

[0336] In some embodiments, for the compound or salt of Formula (I), R 1 is hydroxy, -O-C1 alkyl, -NO2, fluorine, C1 alkyl, -O-C1 haloalkyl, hydroxy, chlorine or bromine. In some embodiments, R 1 is hydroxy, -O-C1 alkyl or -NO2. In some embodiments, R 1 In some embodiments, R 1 is C1 alkyl, -O-C1 haloalkyl, hydroxy, chlorine or bromine. In some embodiments, R 1 is hydroxy, -O-C1 alkyl, -NO2 or fluorine. In some embodiments, R 1 In some embodiments, R 1 is hydroxy, -O-C1 alkyl, -NO2, C1 alkyl, -O-C1 haloalkyl, hydroxy, chlorine or bromine. In some embodiments, R 1 In some embodiments, R 1 is fluorine, C1 alkyl, -O-C1 haloalkyl, hydroxy, chlorine or bromine. In some embodiments, R 1 is fluorine or -O-C1 haloalkyl.

[0337] In some embodiments, for the compound or salt of Formula (I), when R 1When it is hydroxyl, -O-C1 alkyl or -NO2, R 2 Selected from

[0338] Fluorine, bromine, iodine, -OR 22 SR 21 、-N(R 21 )2、-C(O)R 21 、-OC(O)R 21 、-OC(O)N(R 21 )2、-N(R 21 )C(O)R 21 、-N(R 21 )C(O)OR 21 、-N(R 21 )C(O)N(R 21 )2、-N(R 21 )S(O)2(R 21 )、-N(R 21 )SO2N(R 21 )、-N(R 21 )P(O)(OR 21 )R 21 、-S(O)2R 21 、-S(O)2N(R 21 )2, -NO2 and -CN;

[0339] Optionally, one or more independently selected from R 30 Substituents substituted C 1-6 Alkyl; and

[0340] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 30 substituted by a substituent.

[0341] In some embodiments, for compounds or salts of formula (I), when R 1 When it is hydroxyl, -O-C1 alkyl or -NO2, R 2 Selected from fluorine, bromine, iodine, -OR 22 、-SR 21 、-N(R 21 )2、-C(O)R 21 、-OC(O)R 21 、-OC(O)N(R 21 )2、-N(R 21 )C(O)R 21 、-N(R 21 )C(O)OR 21 、-N(R 21 )C(O)N(R 21)2、-N(R 21 )S(O)2(R 21 )、-N(R 21 )SO2N(R 21 )、-N(R 21 )P(O)(OR 21 )R 21 、-S(O)2R 21 、-S(O)2N(R 21 )2, -NO2, -CN and optionally one or more independently selected from R 30 Substituents substituted C 1-6 In some embodiments, when R 1 When it is hydroxyl, -O-C1 alkyl or -NO2; R 2 Selected from fluorine, bromine, iodine, -OR 22 、-N(R 21 )2、-C(O)R 21 、-OC(O)R 21 、-OC(O)N(R 21 )2、-N(R 21 )C(O)R 21 、-N(R 21 )C(O)OR 21 、-N(R 21 )S(O)2(R 21 )、-S(O)2R 21 、-S(O)2N(R 21 )2, -NO2, -CN and optionally one or more independently selected from R 30 Substituents substituted C 1-6 In some embodiments, when R 1 When it is hydroxyl, -O-C1 alkyl or -NO2; R 2 Selected from fluorine, bromine, iodine, -OR 22 、-N(R 21 )2、-C(O)R 21 、-N(R 21 )C(O)R 21 、-N(R 21 )C(O)OR 21 、-N(R 21 )S(O)2(R 21 )、-NO2、-CN、C 1-6 Alkyl and C 1-6 In some embodiments, when R 1 When it is hydroxyl, -O-C1 alkyl or -NO2; R 2 Selected from fluorine, bromine, iodine, -OR 22 、-N(R21 )2、-N(R 21 )C(O)OR 21 , -NO2, -CN and C 1-6 In some embodiments, when R 1 When it is hydroxyl, -O-C1 alkyl or -NO2; R 2 Selected from fluorine, bromine, iodine, -N(R 21 )2、-N(R 21 )C(O)OR 21 and C 1-6 In some embodiments, when R 1 When it is hydroxyl, -O-C1 alkyl or -NO2; R 2 Selected from fluorine, -N(R 21 )2、-N(R 21 )C(O)OR 21 and C 1-6 alkyl.

[0342] In some embodiments, for compounds or salts of formula (I), when R 1 When it is -NO2; R 2 Selected from fluorine, bromine, iodine, -OR 22 、-SR 21 、-N(R 21 )2、-C(O)R 21 、-OC(O)R 21 、-OC(O)N(R 21 )2、-N(R 21 )C(O)R 21 、-N(R 21 )C(O)OR 21 、-N(R 21 )C(O)N(R 21 )2、-N(R 21 )S(O)2(R 21 )、-N(R 21 )SO2N(R 21 )、-N(R 21 )P(O)(OR 21 )R 21 、-S(O)2R 21 、-S(O)2N(R 21 )2, -NO2, -CN and optionally one or more independently selected from R 30 Substituents substituted C 1-6 In some embodiments, when R 1 When it is -NO2; R 2 Selected from fluorine, bromine, iodine, -OR 22 、-N(R21 )2、-C(O)R 21 、-OC(O)R 21 、-OC(O)N(R 21 )2、-N(R 21 )C(O)R 21 、-N(R 21 )C(O)OR 21 、-N(R 21 )S(O)2(R 21 )、-S(O)2R 21 、-S(O)2N(R 21 )2, -NO2, -CN and optionally one or more independently selected from R 30 Substituents substituted C 1-6 In some embodiments, when R 1 When it is -NO2; R 2 Selected from fluorine, bromine, iodine, -OR 22 、-N(R 21 )2、-C(O)R 21 、-N(R 21 )C(O)R 21 、-N(R 21 )C(O)OR 21 、-N(R 21 )S(O)2(R 21 )、-NO2、-CN、C 1-6 Alkyl and C 1-6 In some embodiments, when R 1 When it is -NO2; R 2 Selected from fluorine, bromine, iodine, -OR 22 、-N(R 21 )2、-N(R 21 )C(O)OR 21 , -NO2, -CN and C 1-6 In some embodiments, when R 1 When it is -NO2; R 2 Selected from fluorine, bromine, iodine, -N(R 21 )2、-N(R 21 )C(O)OR 21 and C 1-6 In some embodiments, when R 1 When it is -NO2; R 2 Selected from fluorine, -N(R 21 )2、-N(R 21 )C(O)OR 21 and C 1-6 alkyl.

[0343] In some embodiments, for the compound or salt of Formula (I), when R 1 When fluorine is present; R 2 Selected from:

[0344] Bromine, -OR 23 、-N(H)R 23 、-C(O)R 23 、-C(O)N(R 23 )2、-C(O)OR 23 、-OC(O)R 23 、-OC(O)N(R 23 )2、-N(R 23 )C(O)R 23 、-N(R 23 )C(O)OR 23 、-N(R 23 )C(O)N(R 23 )2、-N(R 23 )S(O)2R 23 、-N(R 23 )SO2N(R 23 )、-N(R 23 )P(O)(OR 23 )R 23 、-S(O)2R 23 、-S(O)2N(R 23 )2, -NO2 and -CN;

[0345] Optionally, one or more independently selected from R 30 Substituents substituted C 1-6 Alkyl; and

[0346] C 3-6 Carbocyclic ring, 3- to 4-membered heterocyclic ring, Any one of which is optionally replaced by one or more independently selected from R 30 substituted by a substituent.

[0347] In some embodiments, for compounds or salts of formula (I), when R 1 When fluorine is present; R 2 Selected from bromine, -OR 23 、-N(H)R 23 、-C(O)R 23 、-C(O)N(R 23 )2、-C(O)OR 23 、-OC(O)R 23 、-OC(O)N(R 23 )2、-N(R 23 )C(O)R 23、-N(R 23 )C(O)OR 23 、-N(R 23 )C(O)N(R 23 )2、-N(R 23 )S(O)2R 23 、-N(R 23 )SO2N(R 23 )、-N(R 23 )P(O)(OR 23 )R 23 、-S(O)2R 23 、-S(O)2N(R 23 )2, -NO2, -CN, and optionally one or more independently selected from R 30 Substituents substituted C 1-6 In some embodiments, when R 1 When fluorine is present; R 2 Selected from bromine, -OR 23 、-N(H)R 23 、-C(O)R 23 、-C(O)N(R 23 )2、-C(O)OR 23 、-OC(O)R 23 、-OC(O)N(R 23 )2、-N(R 23 )C(O)R 23 、-NO2、-CN、 and optionally one or more independently selected from R 30 Substituents substituted C 1-6 In some embodiments, when R 1 When fluorine is present; R 2 Selected from bromine, -OR 23 、-N(H)R 23 、-C(O)R 23 、-C(O)N(R 23 )2、-C(O)OR 23 、-NO2、-CN、 and optionally one or more independently selected from R 30 Substituents substituted C 1-6 In some embodiments, when R 1 When fluorine is present; R 2 Selected from bromine, -OR 23 、-N(H)R 23 、-C(O)R 23 、-C(O)N(R 23)2、-C(O)OR 23 、-NO2、-CN、 and optionally one or more independently selected from R 30 Substituents substituted C 1-6 In some embodiments, when R 1 When fluorine is present; R 2 Selected from bromine, -OR 23 、-N(H)R 23 、-NO2、-CN、 and optionally one or more independently selected from R 30 Substituents substituted C 1-6 In some embodiments, when R 1 When fluorine is present; R 2 Selected from bromine, -OR 23 、-N(H)R 23 、 and optionally one or more independently selected from R 30 Substituents substituted C 1-6 In some embodiments, when R 1 When fluorine is present; R 2 Selected from optionally one or more independently selected from R 30 Substituents substituted C 1-6 alkyl.

[0348] In some embodiments, for the compound or salt of Formula (I), when R 1 When R is C1 alkyl, -O-C1 haloalkyl, hydroxyl, chlorine or bromine; 2 Selected from:

[0349] Iodine, -OR 25 、-C(O)R 24 、-C(O)OR 25 、-OC(O)R 24 、-OC(O)N(R 24 )2、-C(O)N(R 24 )2、-N(R 24 )C(O)R 24 、-N(R 24 )C(O)OR 24 、-N(R 24 )C(O)N(R 24 )2、-N(R 24 )S(O)2(R 24 )、N(R 24 )SO2N(R 24 )、-N(R 24 )P(O)(OR 24 )R24 、-S(O)R 24 、-S(O)2R 24 、-S(O)2N(R 24 )2, -NO2 and -CN;

[0350] Optionally, one or more independently selected from R 30 Substituents substituted C 2-6 alkyl;

[0351] C 3-6 Carbocyclic and 3 to 5 membered heterocyclic rings, any of which are optionally substituted by one or more independently selected R 30 and

[0352] When R 1 When R is selected from bromine, hydroxyl and C1 alkyl, 2 Further selected from fluorine.

[0353] In some embodiments, for the compound or salt of Formula (I), when R 1 When R is C1 alkyl, -O-C1 haloalkyl, hydroxyl, chlorine or bromine; 2 Selected from:

[0354] Iodine, -OR 25 、-C(O)R 24 、-C(O)OR 25 、-OC(O)R 24 、-OC(O)N(R 24 )2、-C(O)N(R 24 )2、-N(R 24 )C(O)R 24 、-N(R 24 )C(O)OR 24 、-N(R 24 )C(O)N(R 24 )2、-N(R 24 )S(O)2(R 24 )、N(R 24 )SO2N(R 24 )、-N(R 24 )P(O)(OR 24 )R 24 、-S(O)R 24 、-S(O)2R 24 、-S(O)2N(R 24 )2, -NO2 and -CN;

[0355] Optionally, one or more independently selected from R 30 Substituents substituted C 2-6 alkyl; and

[0356] When R 1 When R is selected from bromine, hydroxyl and C1 alkyl, 2 Further selected from fluorine.

[0357] In some embodiments, for the compound or salt of Formula (I), when R 1 When R is C1 alkyl, -O-C1 haloalkyl, hydroxyl, chlorine or bromine, 2 Selected from: iodine, -OR 25 、-C(O)R 24 、-C(O)OR 25 、-OC(O)R 24 、-OC(O)N(R 24 )2、-C(O)N(R 24 )2、-N(R 24 )C(O)R 24 、-N(R 24 )C(O)OR 24 、-N(R 24 )C(O)N(R 24 )2、-N(R 24 )S(O)2(R 24 )、N(R 24 )SO2N(R 24 )、-N(R 24 )P(O)(OR 24 )R 24 、-S(O)R 24 、-S(O)2R 24 、-S(O)2N(R 24 )2, -NO2 and -CN; and when R 1 When R is selected from bromine, hydroxyl and C1 alkyl, 2 Further selected from fluorine. In some embodiments, when R 1 When R is C1 alkyl, -O-C1 haloalkyl, hydroxyl, chlorine or bromine; 2 Selected from: iodine, -OR 25 、-C(O)R 24 、-C(O)OR 25 、-OC(O)R 24 、-OC(O)N(R 24 )2、-C(O)N(R 24 )2、-N(R 24 )C(O)R 24 、-N(R 24 )S(O)2(R 24 )、-S(O)2R 24 , -NO2 and -CN; and when R 1When R is selected from bromine, hydroxyl and C1 alkyl, 2 Further selected from fluorine.

[0358] In some embodiments, when R 1 When R is C1 alkyl, -O-C1 haloalkyl, hydroxyl, chlorine or bromine; 2 Selected from: iodine, -OR 25 、-C(O)R 24 、-C(O)OR 25 、-C(O)N(R 24 )2、-N(R 24 )C(O)R 24 、-N(R 24 )S(O)2(R 24 )、-S(O)2R 24 , -NO2 and -CN; and when R 1 When R is selected from bromine, hydroxyl and C1 alkyl, 2 Further selected from fluorine. In some embodiments, when R 1 When R is C1 alkyl, -O-C1 haloalkyl, hydroxyl, chlorine or bromine; 2 Selected from: iodine, -OR 25 、-OC(O)R 24 、-OC(O)N(R 24 )2、-C(O)N(R 24 )2、-N(R 24 )C(O)R 24 、-N(R 24 )S(O)2(R 24 )、-S(O)2R 24 , -NO2 and -CN; and when R 1 When R is selected from bromine, hydroxyl and C1 alkyl, 2 Further selected from fluorine. In some embodiments, when R 1 When R is C1 alkyl, -O-C1 haloalkyl, hydroxyl, chlorine or bromine; 2 Selected from: iodine, -OR 25 、-C(O)R 24 、-C(O)OR 25 、-OC(O)R 24 、-OC(O)N(R 24 )2、-C(O)N(R 24 )2、-S(O)2R 24 , -NO2 and -CN; and when R 1 When R is selected from bromine, hydroxyl and C1 alkyl, 2 Further selected from fluorine.

[0359] In some embodiments, when R1 When R is C1 alkyl, -O-C1 haloalkyl, hydroxyl, chlorine or bromine; 2 Selected from: iodine, -OR 25 、-C(O)R 24 、-S(O)2R 24 , -NO2 and -CN; and when R 1 When R is selected from bromine, hydroxyl and C1 alkyl, 2 Further selected from fluorine. In some embodiments, when R 1 When R is C1 alkyl, -O-C1 haloalkyl, hydroxyl, chlorine or bromine; 2 Selected from: Iodine, OR 25 , -NO2 and -CN; and when R 1 When R is selected from bromine, hydroxyl and C1 alkyl, 2 Further selected from fluorine. In some embodiments, when R 1 When R is C1 alkyl, -O-C1 haloalkyl, hydroxyl, chlorine or bromine; 2 Selected from: iodine, -NO2 and -CN; In some embodiments, when R 1 When R is C1 alkyl, -O-C1 haloalkyl, hydroxyl, chlorine or bromine; 2 Selected from: -NO2, -CN; and when R 1 When R is selected from bromine, hydroxyl and C1 alkyl, 2 Further selected from fluorine.

[0360] In some embodiments, for compounds or salts of formula (I), when R 1 When it is -O-C1 haloalkyl, hydroxyl or bromine; R 2 Selected from:

[0361] Fluorine, iodine, -OR 25 、-C(O)R 24 、-C(O)OR 25 、-OC(O)R 24 、-OC(O)N(R 24 )2、-C(O)N(R 24 )2、-N(R 24 )C(O)R 24 、-N(R 24 )C(O)OR 24 、-N(R 24 )C(O)N(R 24 )2、-N(R 24 )S(O)2(R 24 )、-N(R 24 )SO2N(R 24 )、-N(R 24 )P(O)(OR 24)R 24 、-S(O)R 24 、-S(O)2R 24 、-S(O)2N(R 24 )2, -NO2 and -CN;

[0362] Optionally, one or more independently selected from R 30 Substituents substituted C 2-6 alkyl;

[0363] C 3-6 Carbocyclic and 3 to 5 membered heterocyclic rings, any of which are optionally substituted by one or more independently selected R 30 substituted by a substituent.

[0364] In some embodiments, for compounds or salts of formula (I), when R 1 When it is -O-C1 haloalkyl, hydroxyl or bromine; R 2 Selected from: fluorine, iodine, -OR 25 、-C(O)R 24 、-C(O)OR 25 、-OC(O)R 24 、-OC(O)N(R 24 )2、-C(O)N(R 24 )2、-N(R 24 )C(O)R 24 、-N(R 24 )C(O)OR 24 、-N(R 24 )C(O)N(R 24 )2、-N(R 24 )S(O)2(R 24 )、-N(R 24 )SO2N(R 24 )、-N(R 24 )P(O)(OR 24 )R 24 、-S(O)R 24 、-S(O)2R 24 、-S(O)2N(R 24 )2, -NO2, -CN and optionally one or more independently selected from R 30 Substituents substituted C 2-6 alkyl.

[0365] In some embodiments, for compounds or salts of formula (I), when R 1 When it is -O-C1 haloalkyl, hydroxyl or bromine; R 2 Selected from: fluorine, iodine, -OR 25 、-C(O)R 24、-C(O)OR 25 、-OC(O)R 24 、-OC(O)N(R 24 )2、-C(O)N(R 24 )2、-N(R 24 )C(O)R 24 、-N(R 24 )C(O)OR 24 、-N(R 24 )C(O)N(R 24 )2、-N(R 24 )S(O)2(R 24 )、-N(R 24 )SO2N(R 24 )、-N(R 24 )P(O)(OR 24 )R 24 、-S(O)R 24 、-S(O)2R 24 、-S(O)2N(R 24 )2, -NO2 and -CN. In some embodiments, when R 1 When it is -O-C1 haloalkyl, hydroxyl or bromine; R 2 Selected from: fluorine, iodine, -OR 25 、-C(O)R 24 、-C(O)OR 25 、-OC(O)R 24 、-C(O)N(R 24 )2、-N(R 24 )C(O)R 24 、-N(R 24 )S(O)2(R 24 ),-S(O)R 24 、-S(O)2R 24 、-S(O)2N(R 24 )2, -NO2 and -CN. In some embodiments, when R 1 When it is -O-C1 haloalkyl, hydroxyl or bromine; R 2 Selected from: fluorine, iodine, -OR 25 、-OC(O)R 24 、-C(O)N(R 24 )2、-N(R 24 )C(O)R 24 、-N(R 24 )S(O)2(R 24 ),-S(O)R 24 、-S(O)2R 24 、-S(O)2N(R 24)2, -NO2 and -CN. In some embodiments, when R 1 When it is -O-C1 haloalkyl, hydroxyl or bromine; R 2 Selected from: fluorine, iodine, -OR 25 、-C(O)R 24 、-C(O)OR 25 、-C(O)N(R 24 )2、-N(R 24 )C(O)R 24 、-N(R 24 )S(O)2(R 24 ),-S(O)R 24 、-S(O)2R 24 、-S(O)2N(R 24 )2, -NO2 and -CN. In some embodiments, when R 1 When it is -O-C1 haloalkyl, hydroxyl or bromine; R 2 Selected from: fluorine, iodine, -OR 25 、-C(O)R 24 、-C(O)OR 25 、-OC(O)R 24 、-C(O)N(R 24 )2、-S(O)R 24 、-S(O)2R 24 、-S(O)2N(R 24 )2, -NO2 and -CN. In some embodiments, when R 1 When it is -O-C1 haloalkyl, hydroxyl or bromine; R 2 Selected from: fluorine, iodine, -OR 25 、-C(O)R 24 、-C(O)OR 25 、-OC(O)R 24 、-OC(O)N(R 24 )2、-C(O)N(R 24 )2、-N(R 24 )C(O)R 24 、-N(R 24 )S(O)2(R 24 ), -NO2 and -CN.

[0366] In some embodiments, for the compound or salt of Formula (I), when R 1 When it is -O-C1 haloalkyl, hydroxyl or bromine; R 2 Selected from: fluorine, iodine, -OR 25 、-C(O)R 24 、-C(O)OR 25 、-OC(O)R 24、-C(O)N(R 24 )2、-N(R 24 )C(O)R 24 、-N(R 24 )S(O)2(R 24 )、-S(O)2R 24 , -NO2 and -CN. In some embodiments, when R 1 When it is -O-C1 haloalkyl, hydroxyl or bromine; R 2 Selected from: fluorine, iodine, -OR 25 、-C(O)R 24 、-S(O)2R 24 , -NO2 and -CN. In some embodiments, when R 1 When it is -O-C1 haloalkyl, hydroxyl or bromine; R 2 Selected from: fluorine, iodine, -OR 25 、-C(O)R 24 , -NO2 and -CN. In some embodiments, when R 1 When it is -O-C1 haloalkyl, hydroxyl or bromine; R 2 Selected from: fluorine, iodine, -OR 25 , -NO2 and -CN. In some embodiments, when R 1 When it is -O-C1 haloalkyl, hydroxyl or bromine; R 2 Selected from: fluorine, iodine, -NO2 and -CN. In some embodiments, when R 1 When it is -O-C1 haloalkyl, hydroxyl or bromine; R 2 Selected from: fluorine, -OR 25 , -NO2 and -CN. In some embodiments, when R 1 When it is -O-C1 haloalkyl, hydroxyl or bromine; R 2 Selected from: fluorine, -NO2 and -CN. In some embodiments, when R 1 When it is -O-C1 haloalkyl, hydroxyl or bromine; R 2 In some embodiments, for compounds or salts of formula (I), when R 1 When it is -O-C1 haloalkyl, hydroxyl or bromine; R 2 In some embodiments, when R 1 When it is -O-C1 haloalkyl, hydroxyl or bromine; R 2 For fluorine.

[0367] In some embodiments, for compounds or salts of formula (I), when R 1 When it is -O-C1 haloalkyl or bromine; R 2 Selected from:

[0368] Fluorine, iodine, -OR 25 、-C(O)R 24 、-C(O)OR 25 、-OC(O)R 24 、-OC(O)N(R 24 )2、-C(O)N(R 24 )2、-N(R 24 )C(O)R 24 、-N(R 24 )C(O)OR 24 、-N(R 24 )C(O)N(R 24 )2、-N(R 24 )S(O)2(R 24 )、-N(R 24 )SO2N(R 24 )、-N(R 24 )P(O)(OR 24 )R 24 、-S(O)R 24 、-S(O)2R 24 、-S(O)2N(R 24 )2, -NO2 and -CN;

[0369] Optionally, one or more independently selected from R 30 The substituents replace C 2-6 alkyl;

[0370] C 3-6 Carbocyclic and 3 to 5 membered heterocyclic rings, any of which are optionally substituted by one or more independently selected R 30 substituted by a substituent.

[0371] In some embodiments, for compounds or salts of formula (I), when R 1 When it is -O-C1 haloalkyl or bromine; R 2 Selected from: fluorine, iodine, -OR 25 、-C(O)R 24 、-C(O)OR 25 、-OC(O)R 24 、-OC(O)N(R 24 )2、-C(O)N(R 24 )2、-N(R 24 )C(O)R 24 、-N(R 24 )C(O)OR 24 、-N(R 24 )C(O)N(R 24 )2、-N(R 24 )S(O)2(R 24)、-N(R 24 )SO2N(R 24 )、-N(R 24 )P(O)(OR 24 )R 24 、-S(O)R 24 、-S(O)2R 24 、-S(O)2N(R 24 )2, -NO2, -CN and optionally one or more independently selected from R 30 Substituents substituted C 2-6 alkyl.

[0372] In some embodiments, for the compound or salt of Formula (I), when R 1 When it is -O-C1 haloalkyl or bromine; R 2 Selected from: fluorine, iodine, -OR 25 、-C(O)R 24 、-C(O)OR 25 、-OC(O)R 24 、-OC(O)N(R 24 )2、-C(O)N(R 24 )2、-N(R 24 )C(O)R 24 、-N(R 24 )C(O)OR 24 、-N(R 24 )C(O)N(R 24 )2、-N(R 24 )S(O)2(R 24 )、-N(R 24 )SO2N(R 24 )、-N(R 24 )P(O)(OR 24 )R 24 、-S(O)R 24 、-S(O)2R 24 、-S(O)2N(R 24 )2, -NO2 and -CN. In some embodiments, when R 1 When it is -O-C1 haloalkyl or bromine; R 2 Selected from: fluorine, iodine, -OR 25 、-C(O)R 24 、-C(O)OR 25 、-OC(O)R 24 、-C(O)N(R 24 )2、-N(R 24 )C(O)R 24 、-N(R 24 )S(O)2(R24 ),-S(O)R 24 、-S(O)2R 24 、-S(O)2N(R 24 )2, -NO2 and -CN. In some embodiments, when R 1 When it is -O-C1 haloalkyl or bromine; R 2 Selected from: fluorine, iodine, -OR 25 、-OC(O)R 24 、-C(O)N(R 24 )2、-N(R 24 )C(O)R 24 、-N(R 24 )S(O)2(R 24 ),-S(O)R 24 、-S(O)2R 24 、-S(O)2N(R 24 )2, -NO2 and -CN. In some embodiments, when R 1 When it is -O-C1 haloalkyl or bromine; R 2 Selected from: fluorine, iodine, -OR 25 、-C(O)R 24 、-C(O)OR 25 、-C(O)N(R 24 )2、-N(R 24 )C(O)R 24 、-N(R 24 )S(O)2(R 24 ),-S(O)R 24 、-S(O)2R 24 、-S(O)2N(R 24 )2, -NO2 and -CN. In some embodiments, when R 1 When it is -O-C1 haloalkyl or bromine; R 2 Selected from: fluorine, iodine, -OR 25 、-C(O)R 24 、-C(O)OR 25 、-OC(O)R 24 、-C(O)N(R 24 )2、-S(O)R 24 、-S(O)2R 24 、-S(O)2N(R 24 )2, -NO2 and -CN. In some embodiments, when R 1 When it is -O-C1 haloalkyl or bromine; R 2 Selected from: fluorine, iodine, -OR 25 、-C(O)R 24 、-C(O)OR25 、-OC(O)R 24 、-OC(O)N(R 24 )2、-C(O)N(R 24 )2、-N(R 24 )C(O)R 24 、-N(R 24 )S(O)2(R 24 ), -NO2 and -CN.

[0373] In some embodiments, for the compound or salt of Formula (I), when R 1 When it is -O-C1 haloalkyl or bromine; R 2 Selected from: fluorine, iodine, -OR 25 、-C(O)R 24 、-C(O)OR 25 、-OC(O)R 24 、-C(O)N(R 24 )2、-N(R 24 )C(O)R 24 、-N(R 24 )S(O)2(R 24 )、-S(O)2R 24 , -NO2 and -CN. In some embodiments, when R 1 When it is -O-C1 haloalkyl or bromine; R 2 Selected from: fluorine, iodine, -OR 25 、-C(O)R 24 、-S(O)2R 24 , -NO2 and -CN. In some embodiments, when R 1 When it is -O-C1 haloalkyl or bromine; R 2 Selected from: fluorine, iodine, -OR 25 、-C(O)R 24 , -NO2 and -CN. In some embodiments, when R 1 When it is -O-C1 haloalkyl or bromine; R 2 Selected from: fluorine, iodine, -OR 25 , -NO2 and -CN. In some embodiments, when R 1 When it is -O-C1 haloalkyl or bromine; R 2 Selected from: fluorine, iodine, -NO2 and -CN. In some embodiments, when R 1 When it is -O-C1 haloalkyl or bromine; R 2 Selected from: fluorine, -OR 25 , -NO2 and -CN. In some embodiments, when R 1 When it is -O-C1 haloalkyl or bromine; R 2Selected from: fluorine, -NO2 and -CN. In some embodiments, when R 1 When it is -O-C1 haloalkyl or bromine; R 2 In some embodiments, when R 1 When it is -O-C1 haloalkyl or bromine; R 2 In some embodiments, when R 1 When it is -O-C1 haloalkyl or bromine; R 2 For fluorine.

[0374] In some embodiments, for the compound or salt of Formula (I), when R 1 C 2-6 Alkyl, C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 2-6 Haloalkyl, -OR 12 、-SR 11 、-N(R 13 )2、-C(O)R 11 、-C(O)OR 11 、-OC(O)R 11 、-OC(O)N(R 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-N(R 11 )C(O)OR 11 、-N(R 11 )C(O)N(R 11 )2、-N(R 11 )S(O)2(R 11 )、-S(O)2R 11 、-S(O)2N(R 11 )2, -N3 or -CN; R 2 Selected from:

[0375] Halogen, -OR 26 、-SR 26 、-N(R 26 )2、-C(O)R 26 、-C(O)OR 26 、-OC(O)R 26 、-OC(O)N(R 26 )2、-C(O)N(R 26 )2、-N(R 26 )C(O)R 26 、-N(R 26 )C(O)OR 26 、-N(R26 )C(O)N(R 26 )2、-N(R 26 )S(O)2(R 26 )、N(R 26 )SO2N(R 26 )、-N(R 26 )P(O)(OR 26 )R 26 、-S(O)R 26 、-S(O)2R 26 、-S(O)2N(R 26 )2, -NO2 and -CN;

[0376] Optionally, one or more independently selected from R 30 Substituents substituted C 1-6 Alkyl; and

[0377] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 30 Substituents substituted;

[0378] The condition is that when R 1 -C(O)OR 11 When R 2 It cannot be a substituted 6-membered heterocycle.

[0379] In some embodiments, for the compound or salt of Formula (I), when R 1 C 2-6 Alkyl, C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 2-6 Haloalkyl, -OR 12 、-SR 11 、-N(R 13 )2、-C(O)R 11 、-C(O)OR 11 、-OC(O)R 11 、-OC(O)N(R 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-N(R 11 )C(O)OR 11 、-N(R 11 )C(O)N(R 11 )2、-N(R 11 )S(O)2(R 11 )、-S(O)2R 11 、-S(O)2N(R11 )2, -N3 or -CN; R 2 Selected from:

[0380] Halogen, -OR 26 、-SR 26 、-N(R 26 )2、-C(O)R 26 、-C(O)OR 26 、-OC(O)R 26 、-OC(O)N(R 26 )2、-C(O)N(R 26 )2、-N(R 26 )C(O)R 26 、-N(R 26 )C(O)OR 26 、-N(R 26 )C(O)N(R 26 )2、-N(R 26 )S(O)2(R 26 )、-N(R 26 )SO2N(R 26 )、-N(R 26 )P(O)(OR 26 )R 26 、-S(O)R 26 、-S(O)2R 26 、-S(O)2N(R 26 )2, -NO2 and -CN;

[0381] Optionally, one or more independently selected from R 30 Substituents substituted C 1-6 alkyl.

[0382] In some embodiments, for the compound or salt of Formula (I), when R 1 C 2-6 Alkyl, C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 2-6 Haloalkyl, -OR 12 、-SR 11 、-N(R 13 )2、-C(O)R 11 、-C(O)OR 11 、-OC(O)R 11 、-OC(O)N(R 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-N(R 11)C(O)OR 11 、-N(R 11 )C(O)N(R 11 )2、-N(R 11 )S(O)2(R 11 )、-S(O)2R 11 、-S(O)2N(R 11 )2, -N3 or -CN; R 2 Selected from: halogen, -OR 26 、-SR 26 、-N(R 26 )2、-C(O)R 26 、-C(O)OR 26 、-OC(O)R 26 、-OC(O)N(R 26 )2、-C(O)N(R 26 )2、-N(R 26 )C(O)R 26 、-N(R 26 )C(O)OR 26 、-N(R 26 )C(O)N(R 26 )2、-N(R 26 )S(O)2(R 26 )、-N(R 26 )SO2N(R 26 )、-N(R 26 )P(O)(OR 26 )R 26 、-S(O)R 26 、-S(O)2R 26 、-S(O)2N(R 26 )2, -NO2, -CN and optionally one or more independently selected from R 30 Substituents substituted C 2-6 alkyl.

[0383] In some embodiments, for the compound or salt of Formula (I), when R 1 C 2-6 Alkyl, C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 2-6 Haloalkyl, -OR 12 、-SR 11 、-N(R 13 )2、-C(O)R 11 、-C(O)OR 11 、-OC(O)R 11 、-OC(O)N(R 11)2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-N(R 11 )C(O)OR 11 、-N(R 11 )C(O)N(R 11 )2、-N(R 11 )S(O)2(R 11 )、-S(O)2R 11 、-S(O)2N(R 11 )2, -N3 or -CN; R 2 Selected from: halogen, -OR 26 、-SR 26 、-N(R 26 )2、-C(O)R 26 、-C(O)OR 26 、-OC(O)R 26 、-C(O)N(R 26 )2、-N(R 26 )C(O)R 26 、-N(R 26 )S(O)2(R 26 )、-S(O)2R 26 , -NO2, -CN and optionally one or more independently selected from R 30 Substituents substituted C 1-6 In some embodiments, when R 1 C 2-6 Alkyl, C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 2-6 Haloalkyl, -OR 12 、-SR 11 、-N(R 13 )2、-C(O)R 11 、-C(O)OR 11 、-OC(O)R 11 、-OC(O)N(R 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-N(R 11 )C(O)OR 11 、-N(R 11 )C(O)N(R 11 )2、-N(R 11 )S(O)2(R 11 )、-S(O)2R 11、-S(O)2N(R 11 )2, -N3 or -CN; R 2 Selected from: halogen, -OR 26 、-SR 26 、-N(R 26 )2、-C(O)R 26 、-C(O)OR 26 、-OC(O)R 26 、-C(O)N(R 26 )2、-N(R 26 )C(O)R 26 、-N(R 26 )S(O)2(R 26 )、-S(O)2R 26 , -NO2, -CN and optionally one or more independently selected from R 30 Substituents substituted C 1-6 alkyl.

[0384] In some embodiments, for the compound or salt of Formula (I), when R 1 C 2-6 Alkyl, C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 2-6 Haloalkyl, -OR 12 、-SR 11 、-N(R 13 )2、-C(O)R 11 、-C(O)OR 11 、-OC(O)R 11 、-OC(O)N(R 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-N(R 11 )C(O)OR 11 、-N(R 11 )C(O)N(R 11 )2、-N(R 11 )S(O)2(R 11 )、-S(O)2R 11 、-S(O)2N(R 11 )2, -N3 or -CN; R 2 Selected from: halogen, -OR 26 、-N(R 26 )2、-C(O)R 26 、-C(O)OR 26 、-OC(O)R 26 、-C(O)N(R26 )2、-N(R 26 )C(O)R 26 、-N(R 26 )S(O)2(R 26 ), -NO2, -CN and optionally one or more independently selected from R 30 Substituents substituted C 1-6 In some embodiments, when R 1 C 2-6 Alkyl, C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 2-6 Haloalkyl, -OR 12 、-SR 11 、-N(R 13 )2、-C(O)R 11 、-C(O)OR 11 、-OC(O)R 11 、-OC(O)N(R 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-N(R 11 )C(O)OR 11 、-N(R 11 )C(O)N(R 11 )2、-N(R 11 )S(O)2(R 11 )、-S(O)2R 11 、-S(O)2N(R 11 )2, -N3 or -CN; R 2 Selected from: halogen, -OR 26 、-SR 26 、-N(R 26 )2、-OC(O)R 26 、-N(R 26 )C(O)R 26 、-N(R 26 )S(O)2(R 26 )、-S(O)2R 26 , -NO2, -CN and optionally one or more independently selected from R 30 Substituents substituted C 1-6 In some embodiments, when R 1 C 2-6 Alkyl, C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 2-6 Haloalkyl, -OR12 、-SR 11 、-N(R 13 )2、-C(O)R 11 、-C(O)OR 11 、-OC(O)R 11 、-OC(O)N(R 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-N(R 11 )C(O)OR 11 、-N(R 11 )C(O)N(R 11 )2、-N(R 11 )S(O)2(R 11 )、-S(O)2R 11 、-S(O)2N(R 11 )2, -N3 or -CN, R 2 Selected from: halogen, -OR 26 、-SR 26 、-N(R 26 )2、-C(O)N(R 26 )2、-N(R 26 )C(O)R 26 、-N(R 26 )S(O)2(R 26 )、-S(O)2R 26 , -NO2, -CN and optionally one or more independently selected from R 30 Substituents substituted C 1-6 In some embodiments, when R 1 C 2-6 Alkyl, C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 2-6 Haloalkyl, -OR 12 、-SR 11 、-N(R 13 )2、-C(O)R 11 、-C(O)OR 11 、-OC(O)R 11 、-OC(O)N(R 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-N(R 11 )C(O)OR 11 、-N(R 11 )C(O)N(R11 )2、-N(R 11 )S(O)2(R 11 )、-S(O)2R 11 、-S(O)2N(R 11 )2, -N3 or -CN; R 2 Selected from: halogen, -OR 26 、-SR 26 、-N(R 26 )2、-C(O)R 26 、-C(O)OR 26 、-OC(O)R 26 、-C(O)N(R 26 )2、-S(O)2R 26 , -NO2, -CN and optionally one or more independently selected from R 30 Substituents substituted C 1-6 In some embodiments, when R 1 C 2-6 Alkyl, C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 2-6 Haloalkyl, -OR 12 、-SR 11 、-N(R 13 )2、-C(O)R 11 、-C(O)OR 11 、-OC(O)R 11 、-OC(O)N(R 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-N(R 11 )C(O)OR 11 、-N(R 11 )C(O)N(R 11 )2、-N(R 11 )S(O)2(R 11 )、-S(O)2R 11 、-S(O)2N(R 11 )2, -N3 or -CN; R 2 Selected from: halogen, -OR 26 、-SR 26 、-N(R 26 )2、-C(O)R 26 、-C(O)OR 26 、-OC(O)R 26 、-C(O)N(R 26 )2、-S(O)2R26 , -NO2, -CN and C 1-6 alkyl.

[0385] In some embodiments, for the compound or salt of Formula (I), when R 1 C 2-6 Alkyl, C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 2-6 Haloalkyl, -OR 12 、-SR 11 、-N(R 13 )2、-C(O)R 11 、-C(O)OR 11 、-OC(O)R 11 、-OC(O)N(R 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-N(R 11 )C(O)OR 11 、-N(R 11 )C(O)N(R 11 )2、-N(R 11 )S(O)2(R 11 )、-S(O)2R 11 、-S(O)2N(R 11 )2, -N3 or -CN; R 2 Selected from: halogen, -OR 26 、-SR 26 、-N(R 26 )2、-C(O)R 26 、-C(O)OR 26 、-C(O)N(R 26 )2、-S(O)2R 26 , -NO2, -CN and optionally one or more independently selected from R 30 Substituents substituted C 1-6 In some embodiments, when R 1 C 2-6 Alkyl, C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 2-6 Haloalkyl, -OR 12 、-SR 11 、-N(R 13 )2、-C(O)R 11 、-C(O)OR 11 、-OC(O)R 11、-OC(O)N(R 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-N(R 11 )C(O)OR 11 、-N(R 11 )C(O)N(R 11 )2、-N(R 11 )S(O)2(R 11 )、-S(O)2R 11 、-S(O)2N(R 11 )2, -N3 or -CN; R 2 Selected from: halogen, -OR 26 、-SR 26 、-N(R 26 )2、-C(O)R 26 、-S(O)2R 26 , -NO2, -CN and optionally one or more independently selected from R 30 Substituents substituted C 1-6 In some embodiments, when R 1 C 2-6 Alkyl, C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 2-6 Haloalkyl, -OR 12 、-SR 11 、-N(R 13 )2、-C(O)R 11 、-C(O)OR 11 、-OC(O)R 11 、-OC(O)N(R 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-N(R 11 )C(O)OR 11 、-N(R 11 )C(O)N(R 11 )2、-N(R 11 )S(O)2(R 11 )、-S(O)2R 11 、-S(O)2N(R 11 )2, -N3 or -CN; R 2 Selected from: halogen, -OR 26 、-SR 26 、-N(R 26)2, -NO2, -CN and optionally one or more independently selected from R 30 Substituents substituted C 1-6 In some embodiments, when R 1 C 2-6 Alkyl, C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 2-6 Haloalkyl, -OR 12 、-SR 11 、-N(R 13 )2、-C(O)R 11 、-C(O)OR 11 、-OC(O)R 11 、-OC(O)N(R 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-N(R 11 )C(O)OR 11 、-N(R 11 )C(O)N(R 11 )2、-N(R 11 )S(O)2(R 11 )、-S(O)2R 11 、-S(O)2N(R 11 )2, -N3 or -CN; R 2 Selected from: halogen, -OR 26 , -NO2, -CN and optionally one or more independently selected from R 30 Substituents substituted C 1-6 In some embodiments, when R 1 C 2-6 Alkyl, C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 2-6 Haloalkyl, -OR 12 、-SR 11 、-N(R 13 )2、-C(O)R 11 、-C(O)OR 11 、-OC(O)R 11 、-OC(O)N(R 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-N(R 11 )C(O)OR 11 、-N(R 11)C(O)N(R 11 )2、-N(R 11 )S(O)2(R 11 )、-S(O)2R 11 、-S(O)2N(R 11 )2, -N3 or -CN; R 2 Selected from: halogen, -OR 26 , -NO2, -CN and C 1-6 alkyl.

[0386] In some embodiments, for the compound or salt of Formula (I), when R 1 C 2-6 Alkyl, C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 2-6 Haloalkyl, -OR 12 、-SR 11 、-N(R 13 )2、-C(O)R 11 、-C(O)OR 11 、-OC(O)R 11 、-OC(O)N(R 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-N(R 11 )C(O)OR 11 、-N(R 11 )C(O)N(R 11 )2、-N(R 11 )S(O)2(R 11 )、-S(O)2R 11 、-S(O)2N(R 11 )2, -N3 or -CN; R 2 Selected from: halogen, -NO2, -CN and optionally one or more independently selected from R 30 Substituents substituted C 1-6 In some embodiments, for compounds or salts of formula (I), when R 1 C 2-6 Alkyl, C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 2-6 Haloalkyl, -OR 12 、-SR 11 、-N(R 13 )2、-C(O)R 11 、-C(O)OR 11 、-OC(O)R11 、-OC(O)N(R 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-N(R 11 )C(O)OR 11 、-N(R 11 )C(O)N(R 11 )2、-N(R 11 )S(O)2(R 11 )、-S(O)2R 11 、-S(O)2N(R 11 )2, -N3 or -CN; R 2 Selected from: halogen, -NO2, -CN and C 1-6 In some embodiments, when R 1 C 2-6 Alkyl, C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 2-6 Haloalkyl, -OR 12 、-SR 11 、-N(R 13 )2、-C(O)R 11 、-C(O)OR 11 、-OC(O)R 11 、-OC(O)N(R 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-N(R 11 )C(O)OR 11 、-N(R 11 )C(O)N(R 11 )2、-N(R 11 )S(O)2(R 11 )、-S(O)2R 11 、-S(O)2N(R 11 )2, -N3 or -CN; R 2 Selected from: halogen, -CN and optionally one or more independently selected from R 30 Substituents substituted C 1-6 In some embodiments, when R 1 C 2-6 Alkyl, C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 2-6 Haloalkyl, -OR 12 、-SR11 、-N(R 13 )2、-C(O)R 11 、-C(O)OR 11 、-OC(O)R 11 、-OC(O)N(R 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-N(R 11 )C(O)OR 11 、-N(R 11 )C(O)N(R 11 )2、-N(R 11 )S(O)2(R 11 )、-S(O)2R 11 、-S(O)2N(R 11 )2, -N3 or -CN; R 2 Selected from: halogen and optionally one or more independently selected from R 30 Substituents substituted C 1-6 In some embodiments, when R 1 C 2-6 Alkyl, C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 2-6 Haloalkyl, -OR 12 、-SR 11 、-N(R 13 )2、-C(O)R 11 、-C(O)OR 11 、-OC(O)R 11 、-OC(O)N(R 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-N(R 11 )C(O)OR 11 、-N(R 11 )C(O)N(R 11 )2、-N(R 11 )S(O)2(R 11 )、-S(O)2R 11 、-S(O)2N(R 11 )2, -N3 or -CN; R 2 Selected from: halogen and C 1-6 alkyl.

[0387] In some embodiments, for the compound or salt of Formula (I), when R1 For-SR 11 、-N(R 13 )2、-C(O)R 11 、-C(O)OR 11 、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-S(O)2R 11 、-S(O)2N(R 11 )2 or -CN; R 2 Selected from:

[0388] Halogen, -OR 26 、-SR 26 、-N(R 26 )2、-C(O)R 26 、-C(O)OR 26 、-OC(O)R 26 、-OC(O)N(R 26 )2、-C(O)N(R 26 )2、-N(R 26 )C(O)R 26 、-N(R 26 )C(O)OR 26 、-N(R 26 )C(O)N(R 26 )2、-N(R 26 )S(O)2(R 26 )、N(R 26 )SO2N(R 26 )、-N(R 26 )P(O)(OR 26 )R 26 、-S(O)R 26 、-S(O)2R 26 、-S(O)2N(R 26 )2, -NO2 and -CN;

[0389] Optionally, one or more independently selected from R 30 The substituents replace C 1-6 Alkyl; and

[0390] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 30 Substituents substituted;

[0391] The condition is that when R 1 -C(O)OR 11 When R 2 It cannot be a substituted 6-membered heterocycle.

[0392] In some embodiments, for the compound or salt of Formula (I), when R 1 For-SR 11 、-N(R 13 )2、-C(O)R 11 、-C(O)OR 11 、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-S(O)2R 11 、-S(O)2N(R 11 )2 or -CN; R 2 Selected from:

[0393] Halogen, -OR 26 、-SR 26 、-N(R 26 )2、-C(O)R 26 、-C(O)OR 26 、-OC(O)R 26 、-OC(O)N(R 26 )2、-C(O)N(R 26 )2、-N(R 26 )C(O)R 26 、-N(R 26 )C(O)OR 26 、-N(R 26 )C(O)N(R 26 )2、-N(R 26 )S(O)2(R 26 )、-N(R 26 )SO2N(R 26 )、-N(R 26 )P(O)(OR 26 )R 26 、-S(O)R 26 、-S(O)2R 26 、-S(O)2N(R 26 )2, -NO2 and -CN;

[0394] Optionally, one or more independently selected from R 30 Substituents substituted C 1-6 alkyl.

[0395] In some embodiments, for the compound or salt of Formula (I), when R 1 For-SR 11 、-N(R 13 )2、-C(O)R 11 、-C(O)OR11 、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-S(O)2R 11 、-S(O)2N(R 11 )2 or -CN; R 2 Selected from: halogen, -OR 26 、-SR 26 、-N(R 26 )2、-C(O)R 26 、-C(O)OR 26 、-OC(O)R 26 、-OC(O)N(R 26 )2、-C(O)N(R 26 )2、-N(R 26 )C(O)R 26 、-N(R 26 )C(O)OR 26 、-N(R 26 )C(O)N(R 26 )2、-N(R 26 )S(O)2(R 26 )、-N(R 26 )SO2N(R 26 )、-N(R 26 )P(O)(OR 26 )R 26 、-S(O)R 26 、-S(O)2R 26 、-S(O)2N(R 26 )2, -NO2, -CN and optionally one or more independently selected from R 30 Substituents substituted C 1-6 alkyl.

[0396] In some embodiments, for the compound or salt of Formula (I), when R 1 For-SR 11 、-N(R 13 )2、-C(O)R 11 、-C(O)OR 11 、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-S(O)2R 11 、-S(O)2N(R 11 )2 or -CN; R 2 Selected from: halogen, -OR 26 、-SR 26 、-N(R26 )2、-C(O)R 26 、-C(O)OR 26 、-OC(O)R 26 、-C(O)N(R 26 )2、-N(R 26 )C(O)R 26 、-N(R 26 )S(O)2(R 26 )、-S(O)2R 26 , -NO2, -CN and optionally one or more independently selected from R 30 Substituents substituted C 1-6 In some embodiments, when R 1 For-SR 11 、-N(R 13 )2、-C(O)R 11 、-C(O)OR 11 、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-S(O)2R 11 、-S(O)2N(R 11 )2 or -CN; R 2 Selected from: halogen, -OR 26 、-SR 26 、-N(R 26 )2、-C(O)R 26 、-C(O)OR 26 、-OC(O)R 26 、-C(O)N(R 26 )2、-N(R 26 )C(O)R 26 、-N(R 26 )S(O)2(R 26 )、-S(O)2R 26 , -NO2, -CN and optionally one or more independently selected from R 30 Substituents substituted C 1-6 alkyl.

[0397] In some embodiments, for the compound or salt of Formula (I), when R 1 For-SR 11 、-N(R 13 )2、-C(O)R 11 、-C(O)OR 11 、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11、-S(O)2R 11 、-S(O)2N(R 11 )2 or -CN; R 2 Selected from: halogen, -OR 26 、-N(R 26 )2、-C(O)R 26 、-C(O)OR 26 、-OC(O)R 26 、-C(O)N(R 26 )2、-N(R 26 )C(O)R 26 、-N(R 26 )S(O)2(R 26 ), -NO2, -CN and optionally one or more independently selected from R 30 Substituents substituted C 1-6 In some embodiments, when R 1 For-SR 11 、-N(R 13 )2、-C(O)R 11 、-C(O)OR 11 、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-S(O)2R 11 、-S(O)2N(R 11 )2 or -CN; R 2 Selected from: halogen, -OR 26 、-SR 26 、-N(R 26 )2、-OC(O)R 26 、-N(R 26 )C(O)R 26 、-N(R 26 )S(O)2(R 26 )、-S(O)2R 26 , -NO2, -CN and optionally one or more independently selected from R 30 Substituents substituted C 1-6 In some embodiments, when R 1 For-SR 11 、-N(R 13 )2、-C(O)R 11 、-C(O)OR 11 、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-S(O)2R 11 、-S(O)2N(R11 )2 or -CN; R 2 Selected from: halogen, -OR 26 、-SR 26 、-N(R 26 )2、-C(O)N(R 26 )2、-N(R 26 )C(O)R 26 、-N(R 26 )S(O)2(R 26 )、-S(O)2R 26 , -NO2, -CN and optionally one or more independently selected from R 30 Substituents substituted C 1-6 In some embodiments, when R 1 For-SR 11 、-N(R 13 )2、-C(O)R 11 、-C(O)OR 11 、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-S(O)2R 11 、-S(O)2N(R 11 )2 or -CN; R 2 Selected from: halogen, -OR 26 、-SR 26 、-N(R 26 )2、-C(O)R 26 、-C(O)OR 26 、-OC(O)R 26 、-C(O)N(R 26 )2、-S(O)2R 26 , -NO2, -CN and optionally one or more independently selected from R 30 Substituents substituted C 1-6 In some embodiments, when R 1 For-SR 11 、-N(R 13 )2、-C(O)R 11 、-C(O)OR 11 、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-S(O)2R 11 、-S(O)2N(R 11 )2 or -CN; R 2 Selected from: halogen, -OR 26 、-SR 26、-N(R 26 )2、-C(O)R 26 、-C(O)OR 26 、-OC(O)R 26 、-C(O)N(R 26 )2、-S(O)2R 26 , -NO2, -CN and C 1-6 alkyl.

[0398] In some embodiments, for the compound or salt of Formula (I), when R 1 For-SR 11 、-N(R 13 )2、-C(O)R 11 、-C(O)OR 11 、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-S(O)2R 11 、-S(O)2N(R 11 )2 or -CN; R 2 Selected from: halogen, -OR 26 、-SR 26 、-N(R 26 )2、-C(O)R 26 、-C(O)OR 26 、-C(O)N(R 26 )2、-S(O)2R 26 , -NO2, -CN and optionally one or more independently selected from R 30 Substituents substituted C 1-6 In some embodiments, when R 1 For-SR 11 、-N(R 13 )2、-C(O)R 11 、-C(O)OR 11 、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-S(O)2R 11 、-S(O)2N(R 11 )2 or -CN; R 2 Selected from: halogen, -OR 26 、-SR 26 、-N(R 26 )2、-C(O)R 26 、-S(O)2R 26 , -NO2, -CN and optionally one or more independently selected from R 30Substituents substituted C 1-6 In some embodiments, when R 1 For-SR 11 、-N(R 13 )2、-C(O)R 11 、-C(O)OR 11 、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-S(O)2R 11 、-S(O)2N(R 11 )2 or -CN; R 2 Selected from: halogen, -OR 26 、-SR 26 、-N(R 26 )2, -NO2, -CN and optionally one or more independently selected from R 30 Substituents substituted C 1-6 In some embodiments, when R 1 For-SR 11 、-N(R 13 )2、-C(O)R 11 、-C(O)OR 11 、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-S(O)2R 11 、-S(O)2N(R 11 )2 or -CN; R 2 Selected from: halogen, -OR 26 , -NO2, -CN and optionally one or more independently selected from R 30 Substituents substituted C 1-6 In some embodiments, when R 1 For-SR 11 、-N(R 13 )2、-C(O)R 11 、-C(O)OR 11 、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-S(O)2R 11 、-S(O)2N(R 11 )2 or -CN; R 2 Selected from: halogen, -OR 26 , -NO2, -CN and C 1-6 alkyl.

[0399] In some embodiments, for the compound or salt of Formula (I), when R 1 For-SR 11 、-N(R 13 )2、-C(O)R 11 、-C(O)OR 11 、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-S(O)2R 11 、-S(O)2N(R 11 )2 or CN; R 2 Selected from: halogen, -NO2, -CN and optionally one or more independently selected from R 30 Substituents substituted C 1-6 In some embodiments, for compounds or salts of formula (I), when R 1 For-SR 11 、-N(R 13 )2、-C(O)R 11 、-C(O)OR 11 、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-S(O)2R 11 、-S(O)2N(R 11 )2 or -CN; R 2 Selected from: halogen, -NO2, -CN and C 1-6 In some embodiments, when R 1 For-SR 11 、-N(R 13 )2、-C(O)R 11 、-C(O)OR 11 、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-S(O)2R 11 、-S(O)2N(R 11 )2 or -CN; R 2 Selected from: halogen, -CN and optionally one or more independently selected from R 30 Substituents substituted C 1-6 In some embodiments, when R 1 For-SR 11 、-N(R 13 )2、-C(O)R 11 、-C(O)OR 11 、-C(O)N(R 11)2、-N(R 11 )C(O)R 11 、-S(O)2R 11 、-S(O)2N(R 11 )2 or -CN; R 2 Selected from: halogen and optionally one or more independently selected from R 30 Substituents substituted C 1-6 In some embodiments, when R 1 For-SR 11 、-N(R 13 )2、-C(O)R 11 、-C(O)OR 11 、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-S(O)2R 11 、-S(O)2N(R 11 )2 or -CN; R 2 Selected from: halogen and C 1-6 alkyl.

[0400] In some embodiments, for the compound or salt of Formula (I), R 3 and R 4 Each occurrence is independently selected from:

[0401] Halogen, -OR 14 、-SR 14 、-N(R 14 )2、-N(R 14 )C(O)R 14 、-C(O)R 14 、-C(O)OR 14 、-C(O)N(R 14 )2, -NO2 and -CN; and

[0402] C 1-4 Alkyl, which is optionally substituted by one or more independently selected from halogen, -OR 14 、-SR 14 、-N(R 14 )2、-N(R 14 )C(O)R 14 、-C(O)R 14 、-C(O)OR 14 、-C(O)N(R 14 )2, -NO2 and -CN substituents.

[0403] In some embodiments, for the compound or salt of Formula (I), R 3 and R4 Each occurrence is independently selected from:

[0404] Halogen, -OR 14 、-SR 14 、-N(R 14 )2、-N(R 14 )C(O)R 14 、-C(O)R 14 、-C(O)OR 14 、-C(O)N(R 14 )2, -NO2 and -CN; and

[0405] C 1-4 Alkyl, which is optionally substituted by one or more independently selected from halogen, -OR 14 、-N(R 14 )2, -NO2 and -CN substituents.

[0406] In some embodiments, for the compound or salt of Formula (I), R 3 and R 4 Each occurrence is independently selected from:

[0407] Halogen, -OR 14 、-N(R 14 )2, -NO2 and -CN; and

[0408] C 1-4 Alkyl, which is optionally substituted by one or more independently selected from halogen, -OR 14 、-N(R 14 )2, -NO2 and -CN substituents.

[0409] In some embodiments, for the compound or salt of Formula (I), R 3 and R 4 is independently selected at each occurrence from: halogen, -OR 14 、-SR 14 、-N(R 14 )2、-N(R 14 )C(O)R 14 、-C(O)R 14 、-C(O)OR 14 、-C(O)N(R 14 )2、-NO2、-CN、C 1-4 Alkyl and C 1-4 In some embodiments, R 3 and R 4 is independently selected at each occurrence from: halogen, -OR 14 、-N(R 14)2、-N(R 14 )C(O)R 14 、-C(O)R 14 、-C(O)OR 14 、-C(O)N(R 14 )2、-NO2、-CN、C 1-4 Alkyl and C 1-4 In some embodiments, R 3 and R 4 is independently selected at each occurrence from: halogen, -OR 14 、-N(R 14 )2、-N(R 14 )C(O)R 14 、-NO2、-CN、C 1-4 Alkyl and C 1-4 In some embodiments, R 3 and R 4 is independently selected at each occurrence from: halogen, -OR 14 、-N(R 14 )2、-C(O)R 14 、-C(O)OR 14 、-NO2、-CN、C 1-4 Alkyl and C 1-4 In some embodiments, R 3 and R 4 is independently selected at each occurrence from: halogen, -OR 14 、-N(R 14 )2、-NO2、-CN、C 1-4 Alkyl and C 1-4 In some embodiments, R 3 and R 4 is independently selected at each occurrence from: halogen, -OR 14 、-N(R 14 )2, -CN, C 1-4 Alkyl and C 1-4 In some embodiments, R 3 and R 4 is independently selected at each occurrence from: halogen, -OR 14 、-CN、C 1-4 Alkyl and C 1-4 In some embodiments, R 3 and R 4 Each occurrence is independently selected from: halogen, -CN, C 1-4 Alkyl and C 1-4 In some embodiments, R 3and R 4 Each occurrence is independently selected from: halogen, C 1-4 Alkyl and C 1-4 In some embodiments, R 3 and R 4 Each occurrence is independently selected from halogen.

[0410] In some embodiments, for the compound or salt of Formula (I), R 5 and R 5’ are each independently selected from hydrogen and hydroxy; or R 5 and R 5’ Together they are =0. In some embodiments, R 5 and R 5’ are each independently selected from hydrogen; or R 5 and R 5’ Together they are =0. In some embodiments, R 5 and R 5’ are each independently selected from hydrogen and hydroxy. 5 and R 5’ Together they are =0. In some embodiments, R 5 and R 5’ Each is hydrogen.

[0411] In some embodiments, for the compound or salt of Formula (I), R 6 and R 6’ are each independently selected from hydrogen and hydroxy; or R 6 and R 6’ Together they are =O, =N-OR 26 or =NR 26 In some embodiments, R 6 and R 6’ are each independently selected from hydrogen; or R 6 and R 6’ Together = O or = N-OR 23 In some embodiments, R 6 and R 6’ are each independently selected from hydrogen and hydroxy. 6 and R 6’ Together they are =0. In some embodiments, R 6 and R 6’ Together =N-OR 26 In some embodiments, R 6 and R 6’ Each is hydrogen.

[0412] In some embodiments, for the compound or salt of Formula (I), m is selected from 0, 1, 2, and 3. In some embodiments, m is selected from 0, 1, and 2. In some embodiments, m is selected from 0 and 1. In some embodiments, m is selected from 1 and 2. In some embodiments, m is 0. In some embodiments, m is 1. In some embodiments, m is 2.

[0413] In some embodiments, for the compound or salt of Formula (I), n is selected from 0, 1, 2, and 3. In some embodiments, n is selected from 0, 1, and 2. In some embodiments, n is selected from 0 and 1. In some embodiments, n is selected from 1 and 2. In some embodiments, n is 0. In some embodiments, n is 1. In some embodiments, n is 2.

[0414] In some embodiments, for the compound or salt of Formula (I), R 11 and R 14 Each occurrence is independently selected from:

[0415] hydrogen;

[0416] Optionally, one or more independently selected from R 31 Substituents substituted C 1-6 alkyl;

[0417] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 31 substituted by a substituent.

[0418] In some embodiments, for the compound or salt of Formula (I), R 11 and R 14 are independently selected at each occurrence from: hydrogen; optionally substituted by one or more independently selected from R 31 Substituents substituted C 1-6 Alkyl; and 3 to 6 membered heterocyclic ring, any one of which is optionally substituted by one or more independently selected from R 31 In some embodiments, R 11 and R 14 Each occurrence is independently selected from: hydrogen, C 1-6 Alkyl, C 3-6 In some embodiments, R 11 and R 14 Each occurrence is independently selected from: hydrogen, C 1-6 alkyl and 3- to 6-membered heterocyclic rings.

[0419] In some embodiments, R 11 and R 14is independently selected at each occurrence from: hydrogen and optionally substituted by one or more independently selected from R 31 Substituents substituted C 1-6 In some embodiments, R 11 and R 14 Each occurrence is independently selected from hydrogen and C 1-6 In some embodiments, R 11 and R 14 is independently selected at each occurrence from hydrogen and optionally substituted by one or more independently selected from R 31 In some embodiments, R 11 and R 14 and R at each occurrence is independently selected from hydrogen and a 3- to 6-membered heterocyclic ring.

[0420] In some embodiments, for the compound or salt of Formula (I), R 11 and R 14 Each occurrence is independently selected from:

[0421] hydrogen;

[0422] C optionally substituted by one or more substituents independently selected from the following 1-6 alkyl:

[0423] Halogen, -OR 41 、-SR 41 、-N(R 41 )2、-C(O)R 41 、-C(O)OR 41 、-OC(O)R 41 、-OC(O)N(R 41 )2、-C(O)N(R 41 )2、-N(R 41 )C(O)R 41 、-N(R 41 )C(O)OR 41 、-N(R 41 )C(O)N(R 41 )2、-N(R 41 )S(O)2(R 41 )、-N(R 41 )SO2N(R 41 )、-N(R 41 )P(O)(OR 41 )R 41 、-S(O)R 41 、-S(O)2R 41 、-S(O)2N(R 41)2, -NO2, =O, =S, -CN, C 3-6 Carbocyclic and 3- to 7-membered heterocyclic rings;

[0424] C 3-6 carbocyclic and 3- to 6-membered heterocyclic rings, any of which are optionally substituted with one or more substituents independently selected from:

[0425] Halogen, -OR 41 、-SR 41 、-N(R 41 )2、-C(O)R 41 、-C(O)OR 41 、-OC(O)R 41 、-OC(O)N(R 41 )2、-C(O)N(R 41 )2、-N(R 41 )C(O)R 41 、-N(R 41 )C(O)OR 41 、-N(R 41 )C(O)N(R 41 )2、-N(R 41 )S(O)2(R 41 )、-N(R 41 )SO2N(R 41 )、-N(R 41 )P(O)(OR 41 )R 41 、-S(O)R 41 、-S(O)2R 41 、-S(O)2N(R 41 )2, -NO2, =O, =S, -CN, C 3-6 carbocyclic rings and 3- to 7-membered heterocyclic rings.

[0426] In some embodiments, for the compound or salt of Formula (I), R 11 and R 14 Each occurrence is independently selected from:

[0427] hydrogen;

[0428] C optionally substituted by one or more substituents independently selected from the following 1-6 alkyl:

[0429] Halogen, -OR 41 、-N(R 41 )2、-C(O)OR 41 、-C(O)N(R 41 )2、-N(R 41 )C(O)R 41、-N(R 41 )SO2N(R 41 )、-N(R 41 )P(O)(OR 41 )R 41 、-S(O)2R 41 , =O, -CN and C 3-6 carbon ring;

[0430] C 3-6 carbocyclic and 3- to 6-membered heterocyclic rings, any of which are optionally substituted with one or more substituents independently selected from:

[0431] Halogen, -OR 41 、-N(R 41 )2、-C(O)R 41 、-C(O)OR 41 、-C(O)N(R 41 )2、-N(R 41 )C(O)R 41 、、-N(R 41 )S(O)2(R 41 )、-N(R 41 )SO2N(R 41 )、-N(R 41 )P(O)(OR 41 )R 41 、-S(O)2R 41 , =O, -CN and C 3-6 Carbon ring.

[0432] In some embodiments, for the compound or salt of Formula (I), R 11 and R 14 Each occurrence is independently selected from:

[0433] hydrogen;

[0434] C optionally substituted by one or more substituents independently selected from the following 1-6 alkyl:

[0435] Halogen, -OR 41 、-N(R 41 )2、-C(O)OR 41 -N(R 41 )SO2N(R 41 )、-N(R 41 )P(O)(OR 41 )R 41 , =O, -CN and C 3-6 carbon ring;

[0436] C 3-6carbocyclic and 3- to 6-membered heterocyclic rings, any of which are optionally substituted with one or more substituents independently selected from:

[0437] Halogen, -OR 41 、-N(R 41 )2、-C(O)OR 41 -N(R 41 )SO2N(R 41 )、-N(R 41 )P(O)(OR 41 )R 41 , =O, -CN and C 3-6 Carbon ring.

[0438] In some embodiments, for the compound or salt of Formula (I), R 12 Each time it appears, select

[0439] One or more independently selected from R 32 Substituents substituted C 1-6 alkyl;

[0440] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 33 substituted by a substituent.

[0441] In some embodiments, for the compound or salt of Formula (I), R 12 is selected at each occurrence from one or more independently selected from R 32 Substituents substituted C 1-6 In some embodiments, R 12 is selected at each occurrence from optionally one or more independently selected from R 32 Substituents substituted C 1-6 In some embodiments, R 12 Select C at each occurrence 1-6 alkyl.

[0442] In some embodiments, for the compound or salt of Formula (I), R 12 is selected at each occurrence from C substituted with one or more substituents independently selected from 1-6 Alkyl: -OR 41 、-SR 41 、-N(R 41 )2、-C(O)R 41 、-C(O)OR 41 、-OC(O)R 41 、-OC(O)N(R 41 )2、-C(O)N(R 41)2、-N(R 41 )C(O)R 41 、-N(R 41 )C(O)OR 41 、-N(R 41 )C(O)N(R 41 )2、-N(R 41 )S(O)2(R 41 )、-N(R 41 )SO2N(R 41 )、-N(R 41 )P(O)(OR 41 )R 41 、-S(O)R 41 、-S(O)2R 41 、-S(O)2N(R 41 )2, -NO2, =O, =S and -CN. In some embodiments, R 12 is selected at each occurrence from C substituted with one or more substituents independently selected from 1-6 Alkyl: -OR 41 、-N(R 41 )2、-C(O)R 41 、-C(O)OR 41 、-OC(O)R 41 、-C(O)N(R 41 )2、-N(R 41 )C(O)R 41 、-N(R 41 )S(O)2(R 41 )、-N(R 41 )SO2N(R 41 )、-N(R 41 )P(O)(OR 41 )R 41 、-S(O)2N(R 41 )2, -NO2, =O and -CN. In some embodiments, R 12 is selected at each occurrence from C substituted with one or more substituents independently selected from 1-6 Alkyl: -OR 41 、-N(R 41 )2、-C(O)R 41 、-C(O)OR 41 、-C(O)N(R 41 )2、-N(R 41 )C(O)R 41 , =O and -CN. In some embodiments, R 12 is selected at each occurrence from C substituted with one or more substituents independently selected from1-6 Alkyl: -OR 41 、-N(R 41 )2, =O and -CN.

[0443] In some embodiments, for the compound or salt of Formula (I), R 13 Each time it appears, select

[0444] hydrogen;

[0445] Optionally, one or more independently selected from R 34 Substituents substituted C 1-6 alkyl;

[0446] C 3-5 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 34 substituted by a substituent.

[0447] In some embodiments, for the compound or salt of Formula (I), R 13 At each occurrence, selected from hydrogen, C 1-6 Alkyl, C 3-5 In some embodiments, R 13 is selected at each occurrence from hydrogen and optionally substituted by one or more independently selected from R 34 Substituents substituted C 1-6 In some embodiments, R 13 At each occurrence selected from hydrogen and C 1-6 In some embodiments, R 13 At each occurrence, selected from hydrogen, C 3-5 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 34 In some embodiments, R 13 At each occurrence, selected from hydrogen, C 3-5 In some embodiments, R 13 At each occurrence, is selected from hydrogen.

[0448] In some embodiments, for the compound or salt of Formula (I), R 13 independently selected at each occurrence from:

[0449] hydrogen;

[0450] C optionally substituted by one or more substituents independently selected from the following 1-6 alkyl:

[0451] Halogen, -OR 41 、-SR 41 、-N(R41 )2、-C(O)R 41 、-C(O)OR 41 、-OC(O)R 41 、-OC(O)N(R 41 )2、-C(O)N(R 41 )2、-N(R 41 )C(O)R 41 、-N(R 41 )C(O)OR 41 、-N(R 41 )C(O)N(R 41 )2、-N(R 41 )S(O)2(R 41 )、-N(R 41 )SO2N(R 41 )、-N(R 41 )P(O)(OR 41 )R 41 、-S(O)R 41 、-S(O)2R 41 、-S(O)2N(R 41 )2, -NO2, =O, =S, -CN, C 3-6 Carbocyclic and 3- to 7-membered heterocyclic rings;

[0452] C 3-6 carbocyclic and 3- to 6-membered heterocyclic rings, any of which are optionally substituted with one or more substituents independently selected from:

[0453] Halogen, -OR 41 、-SR 41 、-N(R 41 )2、-C(O)R 41 、-C(O)OR 41 、-OC(O)R 41 、-OC(O)N(R 41 )2、-C(O)N(R 41 )2、-N(R 41 )C(O)R 41 、-N(R 41 )C(O)OR 41 、-N(R 41 )C(O)N(R 41 )2、-N(R 41 )S(O)2(R 41 )、-N(R 41 )SO2N(R 41 )、-N(R 41 )P(O)(OR 41 )R 41、-S(O)R 41 、-S(O)2R 41 、-S(O)2N(R 41 )2, -NO2, =O, =S, -CN, C 3-6 carbocyclic rings and 3- to 7-membered heterocyclic rings.

[0454] In some embodiments, for the compound or salt of Formula (I), R 13 independently selected at each occurrence from:

[0455] hydrogen;

[0456] C optionally substituted by one or more substituents independently selected from the following 1-6 alkyl:

[0457] Halogen, -OR 41 、-N(R 41 )2、-C(O)OR 41 、-C(O)N(R 41 )2、-N(R 41 )C(O)R 41 、-N(R 41 )SO2N(R 41 )、-N(R 41 )P(O)(OR 41 )R 41 、-S(O)2R 41 , =O, -CN and C 3-6 carbon ring;

[0458] C 3-6 carbocyclic and 3- to 6-membered heterocyclic rings, any of which are optionally substituted with one or more substituents independently selected from:

[0459] Halogen, -OR 41 、-N(R 41 )2、-C(O)R 41 、-C(O)OR 41 、-C(O)N(R 41 )2、-N(R 41 )C(O)R 41 、、-N(R 41 )S(O)2(R 41 )、-N(R 41 )SO2N(R 41 )、-N(R 41 )P(O)(OR 41 )R 41 、-S(O)2R 41 , =O, -CN and C 3-6 Carbon ring.

[0460] In some embodiments, for the compound or salt of Formula (I), R 13 independently selected at each occurrence from:

[0461] hydrogen;

[0462] C optionally substituted by one or more substituents independently selected from the following 1-6 alkyl:

[0463] Halogen, -OR 41 、-N(R 41 )2、-C(O)OR 41 -N(R 41 )SO2N(R 41 )、-N(R 41 )P(O)(OR 41 )R 41 , =O, -CN and C 3-6 carbon ring;

[0464] C 3-6 carbocyclic and 3- to 6-membered heterocyclic rings, any of which are optionally substituted with one or more substituents independently selected from:

[0465] Halogen, -OR 41 、-N(R 41 )2、-C(O)OR 41 -N(R 41 )SO2N(R 41 )、-N(R 41 )P(O)(OR 41 )R 41 , =O, -CN and C 3-6 Carbon ring.

[0466] In some embodiments, for the compound or salt of Formula (I), R 21 、R 23 、R 24 and R 26 Each occurrence is independently selected from:

[0467] hydrogen;

[0468] Optionally, one or more independently selected from R 34 Substituents substituted C 1-6 alkyl;

[0469] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which are optionally substituted by one or more independently selected C 1-4 Alkyl, C 1-4 Haloalkyl and R 34 substituted by a substituent.

[0470] In some embodiments, for the compound or salt of Formula (I), R 21 、R 23 、R 24 and R 26 Each occurrence is independently selected from:

[0471] hydrogen;

[0472] Optionally, one or more independently selected from R 34 Substituents substituted C 1-6 alkyl;

[0473] 3 to 6 membered heterocyclic rings, any one of which is optionally replaced by one or more independently selected C 1-4 Alkyl, C 1-4 Haloalkyl and R 34 substituted by a substituent.

[0474] In some embodiments, for the compound or salt of Formula (I), R 21 、R 23 、R 24 and R 26 is independently selected at each occurrence from: hydrogen and optionally substituted by one or more independently selected from R 34 Substituents substituted C 1-6 In some embodiments, for the compound or salt of formula (I), R 21 、R 23 、R 24 and R 26 Each occurrence is independently selected from: hydrogen and optionally one or more independently selected from C 1-4 Alkyl, C 1-4 Haloalkyl and R 34 In some embodiments, R 21 、R 23 、R 24 and R 26 Each occurrence is independently selected from: hydrogen, C 1-6 alkyl and 3- to 6-membered heterocyclic rings.

[0475] In some embodiments, for the compound or salt of Formula (I), R 21 、R 23 、R 24 and R 26 Each occurrence is independently selected from:

[0476] hydrogen;

[0477] C optionally substituted by one or more substituents independently selected from the following1-6 alkyl:

[0478] Halogen, -OR 41 、-SR 41 、-N(R 41 )2、-C(O)R 41 、-C(O)OR 41 、-OC(O)R 41 、-OC(O)N(R 41 )2、-C(O)N(R 41 )2、-N(R 41 )C(O)R 41 、-N(R 41 )C(O)OR 41 、-N(R 41 )C(O)N(R 41 )2、-N(R 41 )S(O)2(R 41 )、-N(R 41 )SO2N(R 41 )、-N(R 41 )P(O)(OR 41 )R 41 、-S(O)R 41 、-S(O)2R 41 、-S(O)2N(R 41 )2, -NO2, =O, =S, -CN, C 3-6 Carbocyclic and 3- to 7-membered heterocyclic rings;

[0479] C 3-6 carbocyclic and 3- to 6-membered heterocyclic rings, any of which are optionally substituted with one or more substituents independently selected from:

[0480] C 1-4 Alkyl, C 1-4 Haloalkyl, halogen, -OR 41 、-SR 41 、-N(R 41 )2、-C(O)R 41 、-C(O)OR 41 、-OC(O)R 41 、-OC(O)N(R 41 )2、-C(O)N(R 41 )2、-N(R 41 )C(O)R 41 、-N(R 41 )C(O)OR 41 、-N(R 41 )C(O)N(R 41 )2、-N(R41 )S(O)2(R 41 )、-N(R 41 )SO2N(R 41 )、-N(R 41 )P(O)(OR 41 )R 41 、-S(O)R 41 、-S(O)2R 41 、-S(O)2N(R 41 )2, -NO2, =O, =S, -CN, C 3-6 carbocyclic rings and 3- to 7-membered heterocyclic rings.

[0481] In some embodiments, for the compound or salt of Formula (I), R 21 、R 23 、R 24 and R 26 Each occurrence is independently selected from:

[0482] hydrogen;

[0483] C optionally substituted by one or more substituents independently selected from the following 1-6 alkyl:

[0484] Halogen, -OR 41 、-N(R 41 )2、-C(O)R 41 、-C(O)OR 41 、-OC(O)R 41 、-C(O)N(R 41 )2、-N(R 41 )C(O)R 41 、-N(R 41 )S(O)2(R 41 )、-N(R 41 )SO2N(R 41 )、-N(R 41 )P(O)(OR 41 )R 41 、-S(O)2R 41 、-S(O)2N(R 41 )2, -NO2, =O, -CN and C 3-6 carbon rings; and

[0485] C 3-6 carbocyclic and 3- to 6-membered heterocyclic rings, any of which are optionally substituted with one or more substituents independently selected from:

[0486] C 1-4 Alkyl, C 1-4 Haloalkyl, halogen, -OR41 、-N(R 41 )2、-C(O)R 41 、-C(O)OR 41 、-OC(O)R 41 、-C(O)N(R 41 )2、-N(R 41 )C(O)R 41 、-N(R 41 )S(O)2(R 41 )、-N(R 41 )SO2N(R 41 )、-N(R 41 )P(O)(OR 41 )R 41 、-S(O)2R 41 、-S(O)2N(R 41 )2, -NO2, =O, -CN and C 3-6 Carbon ring.

[0487] In some embodiments, for the compound or salt of Formula (I), R 21 、R 23 、R 24 and R 26 Each occurrence is independently selected from:

[0488] hydrogen;

[0489] C optionally substituted by one or more substituents independently selected from the following 1-6 alkyl:

[0490] Halogen, -OR 41 、-N(R 41 )2、-C(O)R 41 、-C(O)OR 41 、-C(O)N(R 41 )2、-N(R 41 )C(O)R 41 、--N(R 41 )SO2N(R 41 )、-N(R 41 )P(O)(OR 41 )R 41 , =O, -CN and C 3-6 carbon ring;

[0491] C 3-6 carbocyclic and 3- to 6-membered heterocyclic rings, any of which are optionally substituted with one or more substituents independently selected from:

[0492] C 1-4 Alkyl, C 1-4Haloalkyl, halogen, -OR 41 、-N(R 41 )2、-C(O)R 41 、-C(O)OR 41 、-C(O)N(R 41 )2、-N(R 41 )C(O)R 41 、-N(R 41 )SO2N(R 41 )、-N(R 41 )P(O)(OR 41 )R 41 , =O, -CN and C 3-6 Carbon ring.

[0493] In some embodiments, for the compound or salt of Formula (I), R 22 and R 25 Each occurrence is independently selected from C 2-6 Alkyl, C 2-6 Haloalkyl and C 2-6 In some embodiments, for compounds or salts of formula (I), R 22 and R 25 Each occurrence is independently selected from hydrogen, C 2-6 Alkyl, C 2-6 Haloalkyl and C 2-6 In some embodiments, for compounds or salts of formula (I), R 22 and R 25 Each occurrence is independently selected from C 2-6 Alkyl and C 2-6 In some embodiments, for the compound or salt of formula (I), R 22 and R 25 Each occurrence is independently selected from C 2-6 In some embodiments, for the compound or salt of formula (I), R 22 and R 25 Each occurrence is independently selected from C 2-6 Halogenated alkyl.

[0494] In some embodiments, for the compound or salt of Formula (I), R 30 、R 31 、R 33 and R 34 is independently selected at each occurrence from: halogen, -OR 41 、-SR 41 、-N(R 41 )2、-C(O)R 41 、-C(O)OR41 、-OC(O)R 41 、-OC(O)N(R 41 )2、-C(O)N(R 41 )2、-N(R 41 )C(O)R 41 、-N(R 41 )C(O)OR 41 、-N(R 41 )C(O)N(R 41 )2、-N(R 41 )S(O)2(R 41 )、-N(R 41 )SO2N(R 41 )、-N(R 41 )P(O)(OR 41 )R 41 、-S(O)R 41 、-S(O)2R 41 、-S(O)2N(R 41 )2, -NO2, =O, =S, -CN, C 3-6 In some embodiments, R 30 、R 31 、R 33 and R 34 is independently selected at each occurrence from: halogen, -OR 41 、-SR 41 、-N(R 41 )2、-C(O)R 41 、-C(O)OR 41 、-OC(O)R 41 、-OC(O)N(R 41 )2、-C(O)N(R 41 )2、-N(R 41 )C(O)R 41 、-N(R 41 )S(O)2(R 41 )、-N(R 41 )SO2N(R 41 )、-N(R 41 )P(O)(OR 41 )R 41 、-S(O)R 41 、-S(O)2R 41 、-S(O)2N(R 41 )2, -NO2, =O, =S, -CN, C 3-6 In some embodiments, R 30 、R 31 、R33 and R 34 is independently selected at each occurrence from: halogen, -OR 41 、-N(R 41 )2、-C(O)R 41 、-C(O)OR 41 、-OC(O)R 41 、-OC(O)N(R 41 )2、-C(O)N(R 41 )2、-N(R 41 )C(O)R 41 、-N(R 41 )S(O)2(R 41 )、-N(R 41 )SO2N(R 41 )、-N(R 41 )P(O)(OR 41 )R 41 、-S(O)R 41 、-S(O)2R 41 、-S(O)2N(R 41 )2、-NO2、=O、-CN、C 3-6 In some embodiments, R 30 、R 31 、R 33 and R 34 is independently selected at each occurrence from: halogen, -OR 41 、-N(R 41 )2、-C(O)R 41 、-C(O)OR 41 、-OC(O)R 41 、-OC(O)N(R 41 )2、-C(O)N(R 41 )2、-N(R 41 )C(O)R 41 、-N(R 41 )S(O)2(R 41 )、-N(R 41 )SO2N(R 41 )、-N(R 41 )P(O)(OR 41 )R 41 、-S(O)R 41 、-S(O)2R 41 、-S(O)2N(R 41 )2, -NO2, =O, -CN and C 3-6 Carbon ring.

[0495] In some embodiments, for the compound or salt of Formula (I), R 30 、R 31 、R 33 and R 34 is independently selected at each occurrence from: halogen, -OR 41 、-N(R 41 )2、-C(O)R 41 、-C(O)OR 41 、-C(O)N(R 41 )2、-N(R 41 )C(O)R 41 、-N(R 41 )S(O)2(R 41 )、-N(R 41 )SO2N(R 41 )、-N(R 41 )P(O)(OR 41 )R 41 、-S(O)2R 41 、-S(O)2N(R 41 )2, -NO2, =O, -CN and C 3-6 In some embodiments, R 30 、R 31 、R 33 and R 34 is independently selected at each occurrence from: halogen, -OR 41 、-N(R 41 )2、-C(O)R 41 、-C(O)OR 41 、-C(O)N(R 41 )2、-N(R 41 )C(O)R 41 、-N(R 41 )S(O)2(R 41 )、-N(R 41 )SO2N(R 41 )、-N(R 41 )P(O)(OR 41 )R 41 , =O, -CN and C 3-6 In some embodiments, R 30 、R 31 、R 33 and R 34 is independently selected at each occurrence from: halogen, -OR 41 、-N(R 41 )2、-C(O)R 41 、-C(O)OR 41 、-C(O)N(R41 )2、-N(R 41 )SO2N(R 41 )、-N(R 41 )P(O)(OR 41 )R 41 , =O, -CN and C 3-6 In some embodiments, R 30 、R 31 、R 33 and R 34 is independently selected at each occurrence from: halogen, -OR 41 、-N(R 41 )2、-C(O)OR 41 、-N(R 41 )SO2N(R 41 )、-N(R 41 )P(O)(OR 41 )R 41 , =O, -CN and C 3-6 In some embodiments, R 30 、R 31 、R 33 and R 34 Each occurrence is independently selected from: -N(R 41 )2、-C(O)OR 41 、-N(R 41 )SO2N(R 41 )、-N(R 41 )P(O)(OR 41 )R 41 and C 3-6 Carbon ring.

[0496] In some embodiments, for the compound or salt of Formula (I), R 32 independently selected at each occurrence from: -OR 41 、-SR 41 、-N(R 41 )2、-C(O)R 41 、-C(O)OR 41 、-OC(O)R 41 、-OC(O)N(R 41 )2、-C(O)N(R 41 )2、-N(R 41 )C(O)R 41 、-N(R 41 )C(O)OR 41 、-N(R 41 )C(O)N(R 41 )2、-N(R 41)S(O)2(R 41 )、-N(R 41 )SO2N(R 41 )、-N(R 41 )P(O)(OR 41 )R 41 、-S(O)R 41 、-S(O)2R 41 、-S(O)2N(R 41 )2, -NO2, =O, =S and -CN. In some embodiments, R 32 independently selected at each occurrence from: -OR 41 、-SR 41 、-N(R 41 )2、-C(O)R 41 、-C(O)OR 41 、-OC(O)R 41 、-C(O)N(R 41 )2、-N(R 41 )C(O)R 41 、-N(R 41 )S(O)2(R 41 )、-S(O)2R 41 、-S(O)2N(R 41 )2, -NO2, =O, =S and -CN. In some embodiments, R 32 independently selected at each occurrence from: -OR 41 、-N(R 41 )2、-C(O)R 41 、-C(O)OR 41 、-OC(O)R 41 、-C(O)N(R 41 )2、-N(R 41 )C(O)R 41 、-N(R 41 )S(O)2(R 41 )、-S(O)2R 41 、-S(O)2N(R 41 )2, =O and -CN. In some embodiments, R 32 independently selected at each occurrence from: -OR 41 、-N(R 41 )2、-C(O)R 41 、-C(O)OR 41 、-OC(O)R 41 、-C(O)N(R 41 )2、-N(R 41 )C(O)R 41, =O and -CN. In some embodiments, R 32 independently selected at each occurrence from: -OR 41 、-N(R 41 )2, =O and -CN.

[0497] In some embodiments, for the compound or salt of Formula (I), R 41 independently selected at each occurrence from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl and C 1-6 In some embodiments, R 41 independently selected at each occurrence from hydrogen, C 1-6 Alkyl and C 1-6 In some embodiments, R 41 independently selected at each occurrence from hydrogen, C 1-6 Alkyl and C 1-6 In some embodiments, R 41 independently selected at each occurrence from hydrogen and C 1-6 In some embodiments, R 41 In each occurrence, independently selected from C 1-6 In some embodiments, R 41 is independently selected at each occurrence from hydrogen.

[0498] In one aspect, provided herein are compounds having the structure of Formula (II):

[0499]

[0500] or a pharmaceutically acceptable salt or solvate thereof, wherein

[0501] R 51 Selected from fluorine, chlorine, bromine, iodine, hydroxyl, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -N(R 61 )2、-OR 61 、-SR 61 、-C(O)R 61 、-C(O)OR 61 、-OC(O)R 61 、-OC(O)N(R 61 )2、-C(O)N(R 61 )2、-N(R 61 )C(O)R 61 、-N(R 61 )C(O)OR 61 、-N(R 61 )C(O)N(R 61)2、-N(R 61 )S(O)2(R 61 )、-S(O)2R 61 、-S(O)2N(R 61 )2, -NO2 and -CN;

[0502] When R 51 When it is fluorine, chlorine or iodine, R 52 Selected from

[0503] Bromine, iodine, -N(R 71 )2、-OR 71 、-SR 71 、-C(O)R 71 、-C(O)OR 71 、-OC(O)R 71 、-OC(O)N(R 71 )2、-C(O)N(R 71 )2、-N(R 71 )C(O)R 71 、-N(R 71 )C(O)OR 71 、-N(R 71 )C(O)N(R 71 )2、-N(R 71 )S(O)2(R 71 )、N(R 71 )SO2N(R 71 )、-N(R 71 )P(O)(OR 71 )R 71 、-S(O)R 71 、-S(O)2R 71 、-S(O)2N(R 71 )2, -NO2 and -CN;

[0504] One or more independently selected from R 80 a C1 alkyl group substituted with a substituent, and

[0505] Optionally, one or more independently selected from R 80 Substituents substituted C 2-6 Alkyl; and

[0506] C 3-6 Carbocyclic and 3 to 5 membered heterocyclic rings, any of which are optionally substituted by one or more independently selected R 80 Substituents substituted;

[0507] When R 51 When it is C1 alkyl or -NO2, R 52 Selected from

[0508] Fluorine, iodine, -OR 72 、-SR 72 、-N(R 72 )2、-C(O)R 72 、-C(O)OR 72 、-OC(O)R 72 、-OC(O)N(R 72 )2、-C(O)N(R 72 )2、-N(R 72 )C(O)R 72 、-N(R 72 )C(O)OR 72 、-N(R 72 )C(O)N(R 72 )2、-N(R 72 )S(O)2(R 72 )、-N(R 72 )SO2N(R 72 ),

[0509] -N(R 72 )P(O)(OR 72 )R 72 、-S(O)R 72 、-S(O)2R 72 、-S(O)2N(R 72 )2, -NO2

[0510] and -CN;

[0511] Optionally, one or more independently selected from R 80 Substituents substituted C 1-6 Alkyl; and

[0512] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 80 Substituents substituted;

[0513] When R 51 Selected from bromine, hydroxyl, -C 2-6 Alkyl, -C 1-6 Haloalkyl, -N(R 61 )2、-OR 61 、-SR 61 、-C(O)R 61 、-C(O)OR 61 、-OC(O)R 61 、-OC(O)N(R 61 )2、-C(O)N(R 61 )2、-N(R 61 )C(O)R61 、-N(R 61 )C(O)OR 61 、-N(R 61 )C(O)N(R 61 )2、-N(R 61 )S(O)2(R 61 )、-S(O)2R 61 、-S(O)2N(R 61 )2 and -CN,

[0514] R 52 Selected from

[0515] Halogen, -OR 73 、-SR 73 、-N(R 73 )2、-C(O)R 73 、-C(O)OR 73 、-OC(O)R 73 、-OC(O)N(R 73 )2、-C(O)N(R 73 )2、-N(R 73 )C(O)R 73 、-N(R 73 )C(O)OR 73 、-N(R 73 )C(O)N(R 73 )2、-N(R 73 )S(O)2(R 73 )、-N(R 73 )SO2N(R 73 )、-N(R 73 )P(O)(OR 73 )R 73 、-S(O)R 73 、-S(O)2R 73 、-S(O)2N(R 73 )2, -NO2 and -CN;

[0516] Optionally, one or more independently selected from R 80 Substituents substituted C 1-6 Alkyl; and

[0517] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which are optionally replaced by one or more

[0518] Independently selected from R 80 Substituents substituted;

[0519] R 53 and R 54Each occurrence is independently selected from

[0520] Halogen, -OR 64 、-SR 64 、-N(R 64 )2、-N(R 64 )C(O)R 64 、-C(O)R 64 、-C(O)OR 64 、-C(O)N(R 64 )2, -NO2 and -CN;

[0521] C 1-4 Alkyl, which is optionally substituted by one or more independently selected from halogen, -OR 64 、-SR 64 、-N(R 64 )2、-N(R 64 )C(O)R 64 、-C(O)R 64 、-C(O)OR 64 、-C(O)N(R 64 )2, -NO2 and -CN substituents;

[0522] C 3-4 Carbocyclic and 3 to 4 membered heterocyclic rings, any of which are optionally substituted by one or more independently selected from halogen, -OR 64 、-SR 64 、-N(R 64 )2、-N(R 64 )C(O)R 64 、-C(O)R 64 、-C(O)OR 64 、-C(O)N(R 64 )2, -NO2 and -CN substituents;

[0523] R 55 and R 55’ are each independently selected from hydrogen and hydroxy; or R 55 and R 55’ Together = O;

[0524] R 56 and R 56’ are each independently selected from hydrogen and hydroxy; or R 56 and R 56’ Together they are =O, =N-OR 64 or =NR 64 ;

[0525] p is selected from 0, 1, 2 and 3;

[0526] q is selected from 0, 1, 2 and 3;

[0527] R 61 and R 64 Each occurrence is independently selected from

[0528] hydrogen;

[0529] Optionally, one or more independently selected from R 81 Substituents substituted C 1-6 alkyl;

[0530] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 81 Substituents substituted;

[0531] R 71 、R 72 and R 73 Each occurrence is independently selected from

[0532] hydrogen;

[0533] Optionally, one or more independently selected from R 82 Substituents substituted C 1-6 alkyl;

[0534] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which are optionally substituted by one or more independently selected C 1-4 Alkyl, C 1-4 Haloalkyl and R 82 Substituents substituted;

[0535] R 80 、R 81 and R 82 Each occurrence is independently selected from

[0536] Halogen, -OR 91 、-SR 91 、-N(R 91 )2、-C(O)R 91 、-C(O)OR 91 、-OC(O)R 91 、-OC(O)N(R 91 )2、-C(O)N(R 91 )2、-N(R 91 )C(O)R 91 、-N(R 91 )C(O)OR 91 、-N(R 91 )C(O)N(R 91 )2、-N(R 91 )S(O)2(R91 )、-N(R 91 )SO2N(R 91 )、-N(R 91 )P(O)(OR 91 )R 91 、-S(O)R 91 、-S(O)2R 91 、-S(O)2N(R 91 )2, -NO2, =O, =S, -CN, C 3-6 carbocyclic and 3- to 7-membered heterocyclic rings; and

[0537] R 91 independently selected at each occurrence from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl and C 1-6 Hydroxyalkyl.

[0538] In some embodiments, for the compound or salt of formula (II), R 51 Selected from fluorine, chlorine, bromine, iodine, hydroxyl, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -N(R 61 )2、-OR 61 、-SR 61 、-C(O)R 61 、-C(O)OR 61 、-OC(O)R 61 、-OC(O)N(R 61 )2、-C(O)N(R 61 )2、-N(R 61 )C(O)R 61 、-N(R 61 )C(O)OR 61 、-N(R 61 )C(O)N(R 61 )2、-N(R 61 )S(O)2(R 61 )、-S(O)2R 61 、-S(O)2N(R 61 )2, -NO2 and -CN. In some embodiments, R 51 Selected from fluorine, chlorine, bromine, iodine, hydroxyl, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -N(R 61 )2、-OR 61 、-SR 61 、-C(O)R 61 、-C(O)OR 61 、-OC(O)R 61、-C(O)N(R 61 )2、-N(R 61 )C(O)R 61 、-N(R 61 )S(O)2(R 61 )、-S(O)2R 61 、-S(O)2N(R 61 )2, -NO2 and -CN. In some embodiments, R 51 Selected from fluorine, chlorine, bromine, iodine, hydroxyl, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -N(R 61 )2、-OR 61 、-SR 61 、-C(O)R 61 、-C(O)OR 61 、-OC(O)R 61 、-C(O)N(R 61 )2、-N(R 61 )C(O)R 61 , -NO2 and -CN. In some embodiments, R 51 Selected from fluorine, chlorine, bromine, iodine, hydroxyl, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -N(R 61 )2、-OR 61 、-C(O)R 61 、-C(O)OR 61 、-OC(O)R 61 、-C(O)N(R 61 )2、-N(R 61 )C(O)R 61 , -NO2 and -CN. In some embodiments, R 51 Selected from fluorine, chlorine, bromine, iodine, hydroxyl, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -N(R 61 )2、-OR 61 、-C(O)R 61 、-C(O)OR 61 、-C(O)N(R 61 )2, -NO2 and -CN. In some embodiments, R 51 Selected from fluorine, chlorine, bromine, iodine, hydroxyl, -N(R 61 )2、-OR 61 、-C(O)R 61 、-C(O)OR 61 、-C(O)N(R 61)2, -NO2 and -CN. In some embodiments, R 51 Selected from fluorine, chlorine, bromine, iodine, hydroxyl, -C(O)R 61 、-C(O)OR 61 、-C(O)N(R 61 )2, -NO2 and -CN. In some embodiments, R 51 Selected from fluorine, chlorine, bromine, -C(O)R 61 、-C(O)OR 61 、-C(O)N(R 61 )2, -NO2 and -CN. In some embodiments, R 51 Selected from fluorine, -C(O)R 61 、-C(O)OR 61 、-C(O)N(R 61 )2, -NO2 and -CN. In some embodiments, R 51 Selected from -C(O)R 61 、-C(O)OR 61 、-C(O)N(R 61 )2 and -NO2.

[0539] In some embodiments, for the compound or salt of formula (II), R 51 is fluorine, chlorine or iodine. In some embodiments, R 51 is C1 alkyl or -NO2. In some embodiments, R 51 Selected from bromine, hydroxyl, -C 2-6 Alkyl, -C 1-6 Haloalkyl, -N(R 61 )2、-OR 61 、-SR 61 、-C(O)R 61 、-C(O)OR 61 、-OC(O)R 61 、-OC(O)N(R 61 )2、-C(O)N(R 61 )2、-N(R 61 )C(O)R 61 、-N(R 61 )C(O)OR 61 、-N(R 61 )C(O)N(R 61 )2、-N(R 61 )S(O)2(R 61 )、-S(O)2R 61 、-S(O)2N(R 61 )2 and -CN. In some embodiments, for the compound or salt of formula (II), R 51is selected from fluorine, chlorine, iodine, C1 alkyl or -NO2.

[0540] In some embodiments, for the compound or salt of formula (II), R 51 Selected from fluorine, chlorine, iodine, bromine, hydroxyl, -C 2-6 Alkyl, -C 1-6 Haloalkyl, -N(R 61 )2、-OR 61 、-SR 61 、-C(O)R 61 、-C(O)OR 61 、-OC(O)R 61 、-OC(O)N(R 61 )2、-C(O)N(R 61 )2、-N(R 61 )C(O)R 61 、-N(R 61 )C(O)OR 61 、-N(R 61 )C(O)N(R 61 )2、-N(R 61 )S(O)2(R 61 )、-S(O)2R 61 、-S(O)2N(R 61 )2 and -CN. In some embodiments, R 51 Selected from fluorine, chlorine, iodine, bromine, hydroxyl, -C 2-6 Alkyl, -C 1-6 Haloalkyl, -N(R 61 )2、-OR 61 、-SR 61 、-C(O)R 61 、-C(O)OR 61 、-C(O)N(R 61 )2、-N(R 61 )S(O)2(R 61 )、-S(O)2R 61 、-S(O)2N(R 61 )2 and -CN. In some embodiments, R 51 Selected from fluorine, chlorine, iodine, bromine, hydroxyl, -C 2-6 Alkyl, -C 1-6 Haloalkyl, -N(R 61 )2、-OR 61 、-SR 61 、-C(O)R 61 、-C(O)OR 61 、-C(O)N(R 61 )2 and -CN. In some embodiments, R51 Selected from -C(O)R 61 、-C(O)OR 61 、-C(O)N(R 61 )2 and -CN.

[0541] In some embodiments, for the compound or salt of formula (II), R 51 Selected from C1 alkyl, -NO2, bromine, hydroxyl, -C 2-6 Alkyl, -C 1-6 Haloalkyl, -N(R 61 )2、-OR 61 、-SR 61 、-C(O)R 61 、-C(O)OR 61 、-OC(O)R 61 、-OC(O)N(R 61 )2、-C(O)N(R 61 )2、-N(R 61 )C(O)R 61 、-N(R 61 )C(O)OR 61 、-N(R 61 )C(O)N(R 61 )2、-N(R 61 )S(O)2(R 61 )、-S(O)2R 61 、-S(O)2N(R 61 )2 and -CN. In some embodiments, R 51 Selected from C1 alkyl, -NO2, bromine, hydroxyl, -C 2-6 Alkyl, -C 1-6 Haloalkyl, -N(R 61 )2、-OR 61 、-SR 61 、-C(O)R 61 、-C(O)OR 61 、-OC(O)R 61 、-C(O)N(R 61 )2、-N(R 61 )C(O)R 61 In some embodiments, R 51 Selected from -NO2, -C(O)R 61 、-C(O)OR 61 and -C(O)N(R 61 )2.

[0542] In some embodiments, for the compound or salt of formula (II), R 51 Selected from bromine, hydroxyl, -C1-6 Alkyl, -C 1-6 Haloalkyl, -N(R 61 )2、-OR 61 、-SR 61 、-C(O)R 61 、-C(O)OR 61 、-OC(O)R 61 、-OC(O)N(R 61 )2、-C(O)N(R 61 )2、-N(R 61 )C(O)R 61 、-N(R 61 )C(O)OR 61 、-N(R 61 )C(O)N(R 61 )2、-N(R 61 )S(O)2(R 61 )、-S(O)2R 61 、-S(O)2N(R 61 )2, -NO2 and -CN. In some embodiments, R 51 Selected from fluorine, chlorine, bromine, iodine, hydroxyl, -C 2-6 Alkyl, -C 1-6 Haloalkyl, -N(R 61 )2、-OR 61 、-SR 61 、-C(O)R 61 、-C(O)OR 61 、-OC(O)R 61 、-OC(O)N(R 61 )2、-C(O)N(R 61 )2、-N(R 61 )C(O)R 61 、-N(R 61 )C(O)OR 61 、-N(R 61 )C(O)N(R 61 )2、-N(R 61 )S(O)2(R 61 )、-S(O)2R 61 、-S(O)2N(R 61 )2 and -CN. In some embodiments, R 51 is selected from the group consisting of fluorine, chlorine, iodine, -C1 alkyl and -NO2. In some embodiments, R 51 In some embodiments, R 51 In some embodiments, R 51 Selected from bromine, hydroxyl, -C2-6 Alkyl, -C 1-6 Haloalkyl, -N(R 61 )2、-OR 61 、-SR 61 、-C(O)R 61 、-C(O)OR 61 、-OC(O)R 61 、-OC(O)N(R 61 )2、-C(O)N(R 61 )2、-N(R 61 )C(O)R 61 、-N(R 61 )C(O)OR 61 、-N(R 61 )C(O)N(R 61 )2、-N(R 61 )S(O)2(R 61 )、-S(O)2R 61 、-S(O)2N(R 61 )2 and -CN.

[0543] In some embodiments, for the compound or salt of formula (II), when R 51 When R is fluorine, chlorine or iodine, 52 Selected from

[0544] Bromine, iodine, -N(R 71 )2、-OR 71 、-SR 71 、-C(O)R 71 、-C(O)OR 71 、-OC(O)R 71 、-OC(O)N(R 71 )2、-C(O)N(R 71 )2、-N(R 71 )C(O)R 71 、-N(R 71 )C(O)OR 71 、-N(R 71 )C(O)N(R 71 )2、-N(R 71 )S(O)2(R 71 )、N(R 71 )SO2N(R 71 )、-N(R 71 )P(O)(OR 71 )R 71 、-S(O)R 71 、-S(O)2R 71 、-S(O)2N(R 71)2, -NO2 and -CN;

[0545] One or more independently selected from R 80 C1 alkyl substituted with a substituent, and optionally substituted with one or more independently selected from R 80 Substituents substituted C 2-6 Alkyl; and

[0546] C 3-6 Carbocyclic and 3 to 5 membered heterocyclic rings, any of which are optionally substituted by one or more independently selected R 80 substituted by a substituent.

[0547] In some embodiments, for the compound or salt of formula (II), when R 51 When R is fluorine, chlorine or iodine, 52 Selected from bromine, iodine, -N(R 71 )2、-OR 71 、-SR 71 、-C(O)R 71 、-C(O)OR 71 、-OC(O)R 71 、-OC(O)N(R 71 )2、-C(O)N(R 71 )2、-N(R 71 )C(O)R 71 、-N(R 71 )C(O)OR 71 、-N(R 71 )C(O)N(R 71 )2、-N(R 71 )S(O)2(R 71 )、N(R 71 )SO2N(R 71 )、-N(R 71 )P(O)(OR 71 )R 71 、-S(O)R 71 、-S(O)2R 71 、-S(O)2N(R 71 )2, -NO2, -CN, one or more independently selected from R 80 C1 alkyl substituted with a substituent and optionally substituted with one or more independently selected from R 80 Substituents substituted C 2-6 In some embodiments, when R 51 When R is fluorine, chlorine or iodine, 52 Selected from bromine, iodine, -N(R 71 )2、-OR 71 、-SR 71、-C(O)R 71 、-C(O)OR 71 、-OC(O)R 71 、-C(O)N(R 71 )2、-N(R 71 )C(O)R 71 , -NO2, -CN, one or more independently selected from R 80 C1 alkyl substituted with a substituent and optionally substituted with one or more independently selected from R 80 Substituents substituted C 2-6 In some embodiments, when R 51 When R is fluorine, chlorine or iodine, 52 Selected from bromine, iodine, -N(R 71 )2、-OR 71 、-SR 71 、-C(O)R 71 、-C(O)OR 71 、-OC(O)R 71 、-C(O)N(R 71 )2、-N(R 71 )C(O)R 71 , -NO2 and -CN. In some embodiments, when R 51 When R is fluorine, chlorine or iodine, 52 Selected from bromine, iodine, -N(R 71 )2、-OR 71 , -NO2 and -CN.

[0548] In some embodiments, for the compound or salt of formula (II), when R 51 When it is C1 alkyl or -NO2, R 52 Selected from

[0549] Fluorine, iodine, -OR 72 、-SR 72 、-N(R 72 )2、-C(O)R 72 、-C(O)OR 72 、-OC(O)R 72 、-OC(O)N(R 72 )2、-C(O)N(R 72 )2、-N(R 72 )C(O)R 72 、-N(R 72 )C(O)OR 72 、-N(R 72 )C(O)N(R 72 )2、-N(R 72 )S(O)2(R 72)、N(R 72 )SO2N(R 72 )、-N(R 72 )P(O)(OR 72 )R 72 、-S(O)R 72 、-S(O)2R 72 、-S(O)2N(R 72 )2, -NO2 and -CN;

[0550] Optionally, one or more independently selected from R 80 Substituents substituted C 1-6 Alkyl; and

[0551] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 80 substituted by a substituent.

[0552] In some embodiments, for the compound or salt of formula (II), when R 51 When it is C1 alkyl or -NO2, R 52 Selected from: fluorine, iodine, -OR 72 、-SR 72 、-N(R 72 )2、-C(O)R 72 、-C(O)OR 72 、-OC(O)R 72 、-OC(O)N(R 72 )2、-C(O)N(R 72 )2、-N(R 72 )C(O)R 72 、-N(R 72 )C(O)OR 72 、-N(R 72 )C(O)N(R 72 )2、-N(R 72 )S(O)2(R 72 )、N(R 72 )SO2N(R 72 )、-N(R 72 )P(O)(OR 72 )R 72 、-S(O)R 72 、-S(O)2R 72 、-S(O)2N(R 72 )2, -NO2, -CN and optionally one or more independently selected from R 80 Substituents substituted C 1-6 In some embodiments, when R 51When it is C1 alkyl or -NO2, R 52 Selected from: fluorine, iodine, -OR 72 、-SR 72 、-N(R 72 )2、-C(O)R 72 、-C(O)OR 72 、-OC(O)R 72 、-OC(O)N(R 72 )2、-C(O)N(R 72 )2、-N(R 72 )C(O)R 72 、-S(O)R 72 、-S(O)2R 72 、-S(O)2N(R 72 )2, -NO2, -CN and optionally one or more independently selected from R 80 Substituents substituted C 1-6 In some embodiments, when R 51 When it is C1 alkyl or -NO2, R 52 Selected from fluorine, iodine, -OR 72 、-SR 72 、-N(R 72 )2、-C(O)R 72 、-C(O)OR 72 、-OC(O)R 72 、-C(O)N(R 72 )2、-N(R 72 )C(O)R 72 , -NO2, -CN and optionally one or more independently selected from R 80 Substituents substituted C 1-6 In some embodiments, when R 51 When it is C1 alkyl or -NO2, R 52 Selected from fluorine, iodine, -OR 72 、-SR 72 、-N(R 72 )2、-C(O)R 72 、-C(O)OR 72 、-OC(O)R 72 、-C(O)N(R 72 )2、-N(R 72 )C(O)R 72 , -NO2, -CN and optionally one or more independently selected from R 80 Substituents substituted C 1-6 In some embodiments, when R 51 When it is C1 alkyl or -NO2, R 52Selected from fluorine, iodine, -OR 72 、-N(R 72 )2、-C(O)R 72 、-C(O)OR 72 、C(O)N(R 72 )2, -NO2, -CN and optionally one or more independently selected from R 80 Substituents substituted C 1-6 In some embodiments, when R 51 When it is C1 alkyl or -NO2, R 52 Selected from fluorine, iodine, -OR 72 、-N(R 72 )2、-C(O)R 72 、-C(O)OR 72 、C(O)N(R 72 )2, -NO2, -CN and C 1-6 In some embodiments, when R 51 When it is C1 alkyl or -NO2, R 52 Selected from fluorine, iodine, -OR 72 、-N(R 72 )2, NO2, -CN and optionally one or more independently selected from R 80 Substituents substituted C 1-6 In some embodiments, when R 51 When it is C1 alkyl or -NO2, R 52 Selected from fluorine, iodine, -OR 72 、-N(R 72 )2, NO2, -CN and C 1-6 In some embodiments, when R 51 When it is C1 alkyl or -NO2, R 52 selected from fluorine and optionally substituted by one or more independently selected from R 80 Substituents substituted C 1-6 In some embodiments, when R 51 When it is C1 alkyl or -NO2, R 52 Selected from fluorine and C 1-6 alkyl.

[0553] In some embodiments, for the compound or salt of formula (II), when R 51 When it is -NO2, R 52 Selected from:

[0554] Fluorine, iodine, -OR 72 、-SR 72 、-N(R 72 )2、-C(O)R 72 、-C(O)OR72 、-OC(O)R 72 、-OC(O)N(R 72 )2、-C(O)N(R 72 )2、-N(R 72 )C(O)R 72 、-N(R 72 )C(O)OR 72 、-N(R 72 )C(O)N(R 72 )2、-N(R 72 )S(O)2(R 72 )、N(R 72 )SO2N(R 72 )、-N(R 72 )P(O)(OR 72 )R 72 、-S(O)R 72 、-S(O)2R 72 、-S(O)2N(R 72 )2, -NO2 and -CN;

[0555] Optionally, one or more independently selected from R 80 Substituents substituted C 1-6 Alkyl; and

[0556] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 80 substituted by a substituent.

[0557] In some embodiments, for the compound or salt of formula (II), when R 51 When it is -NO2, R 52 Selected from fluorine, iodine, -OR 72 、-SR 72 、-N(R 72 )2、-C(O)R 72 、-C(O)OR 72 、-OC(O)R 72 、-OC(O)N(R 72 )2、-C(O)N(R 72 )2、-N(R 72 )C(O)R 72 、-N(R 72 )C(O)OR 72 、-N(R 72 )C(O)N(R 72 )2、-N(R 72 )S(O)2(R 72 )、N(R72 )SO2N(R 72 )、-N(R 72 )P(O)(OR 72 )R 72 、-S(O)R 72 、-S(O)2R 72 、-S(O)2N(R 72 )2, -NO2, -CN and optionally one or more independently selected from R 80 Substituents substituted C 1-6 In some embodiments, when R 51 When it is -NO2, R 52 Selected from fluorine, iodine, -OR 72 、-SR 72 、-N(R 72 )2、-C(O)R 72 、-C(O)OR 72 、-OC(O)R 72 、-OC(O)N(R 72 )2、-C(O)N(R 72 )2、-N(R 72 )C(O)R 72 、-S(O)R 72 、-S(O)2R 72 、-S(O)2N(R 72 )2, -NO2, -CN and optionally one or more independently selected from R 80 Substituents substituted C 1-6 In some embodiments, when R 51 When it is -NO2, R 52 Selected from fluorine, iodine, -OR 72 、-SR 72 、-N(R 72 )2、-C(O)R 72 、-C(O)OR 72 、-OC(O)R 72 、-C(O)N(R 72 )2、-N(R 72 )C(O)R 72 , -NO2, -CN and optionally one or more independently selected from R 80 Substituents substituted C 1-6 In some embodiments, when R 51 When it is -NO2, R 52 Selected from fluorine, iodine, -OR 72 、-SR 72 、-N(R 72 )2、-C(O)R72 、-C(O)OR 72 、-OC(O)R 72 、-C(O)N(R 72 )2、-N(R 72 )C(O)R 72 , -NO2, -CN and optionally one or more independently selected from R 80 Substituents substituted C 1-6 In some embodiments, when R 51 When it is -NO2, R 52 Selected from fluorine, iodine, -OR 72 、-N(R 72 )2、-C(O)R 72 、-C(O)OR 72 、C(O)N(R 72 )2, -NO2, -CN and optionally one or more independently selected from R 80 Substituents substituted C 1-6 In some embodiments, when R 51 When it is -NO2, R 52 Selected from fluorine, iodine, -OR 72 、-N(R 72 )2, NO2, -CN and optionally one or more independently selected from R 80 Substituents substituted C 1-6 In some embodiments, when R 51 When it is -NO2, R 52 selected from fluorine and optionally substituted by one or more independently selected from R 80 Substituents substituted C 1-6 In some embodiments, when R 51 When it is -NO2, R 52 Selected from fluorine and C 1-6 alkyl.

[0558] In some embodiments, for the compound or salt of formula (II), when R 51 Selected from bromine, hydroxyl, -C 2-6 Alkyl, -C 1-6 Haloalkyl, -N(R 61 )2、-OR 61 、-SR 61 、-C(O)R 61 、-C(O)OR 61 、-OC(O)R 61 、-OC(O)N(R 61 )2、-C(O)N(R 61 )2、-N(R 61 )C(O)R61 、-N(R 61 )C(O)OR 61 、-N(R 61 )C(O)N(R 61 )2、-N(R 61 )S(O)2(R 61 )、-S(O)2R 61 、-S(O)2N(R 61 )2 and -CN; R 52 Selected from halogen, -OR 73 、-SR 73 、-N(R 73 )2、-C(O)R 73 、-C(O)OR 73 、-OC(O)R 73 、-OC(O)N(R 73 )2、-C(O)N(R 73 )2、-N(R 73 )C(O)R 73 、-N(R 73 )C(O)OR 73 、-N(R 73 )C(O)N(R 73 )2、-N(R 73 )S(O)2(R 73 )、N(R 73 )SO2N(R 73 )、-N(R 73 )P(O)(OR 73 )R 73 、-S(O)R 73 、-S(O)2R 73 、-S(O)2N(R 73 )2, -NO2 and -CN; optionally one or more independently selected from R 80 Substituents substituted C 1-6 Alkyl; and C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 80 substituted by a substituent.

[0559] In some embodiments, for the compound or salt of formula (II), when R 51 Selected from bromine, hydroxyl, -C 2-6 Alkyl, -C 1-6 Haloalkyl, -N(R 61 )2、-OR 61 、-SR 61 、-C(O)R 61 、-C(O)OR61 、-OC(O)R 61 、-OC(O)N(R 61 )2、-C(O)N(R 61 )2、-N(R 61 )C(O)R 61 、-N(R 61 )C(O)OR 61 、-N(R 61 )C(O)N(R 61 )2、-N(R 61 )S(O)2(R 61 )、-S(O)2R 61 、-S(O)2N(R 61 )2 and -CN, R 52 Selected from halogen, -OR 73 、-SR 73 、-N(R 73 )2、-C(O)R 73 、-C(O)OR 73 、-OC(O)R 73 、-C(O)N(R 73 )2、-N(R 73 )C(O)R 73 , -NO2 and -CN; optionally one or more independently selected from R 80 Substituents substituted C 1-6 Alkyl; and C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 80 In some embodiments, when R 51 Selected from bromine, hydroxyl, -C 2-6 Alkyl, -C 1-6 Haloalkyl, N(R 61 )2、-OR 61 、-SR 61 、-C(O)R 61 、-C(O)OR 61 、-OC(O)R 61 、-OC(O)N(R 61 )2、-C(O)N(R 61 )2、-N(R 61 )C(O)R 61 、-N(R 61 )C(O)OR 61 、-N(R 61 )C(O)N(R 61 )2、-N(R 61 )S(O)2(R 61)、-S(O)2R 61 、-S(O)2N(R 61 )2 and -CN, R 52 Selected from halogen, -OR 73 、-N(R 73 )2、-C(O)R 73 , -NO2 and -CN; optionally one or more independently selected from R 80 Substituents substituted C 1-6 Alkyl; and C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 80 In some embodiments, when R 51 Selected from bromine, hydroxyl, -C 2-6 Alkyl, -C 1-6 Haloalkyl, -N(R 61 )2、-OR 61 、-SR 61 、-C(O)R 61 、-C(O)OR 61 、-OC(O)R 61 、-OC(O)N(R 61 )2、-C(O)N(R 61 )2、-N(R 61 )C(O)R 61 、-N(R 61 )C(O)OR 61 、-N(R 61 )C(O)N(R 61 )2、-N(R 61 )S(O)2(R 61 )、-S(O)2R 61 、-S(O)2N(R 61 )2 and -CN, R 52 Selected from halogen, -OR 73 、-N(R 73 )2、-C(O)R 73 , -NO2 and -CN and optionally one or more independently selected from R 80 Substituents substituted C 1-6 In some embodiments, when R 51 Selected from bromine, hydroxyl, -C 2-6 Alkyl, -C 1-6 Haloalkyl, -N(R 61 )2、-OR 61 、-SR 61 、-C(O)R 61 、-C(O)OR 61、-OC(O)R 61 、-OC(O)N(R 61 )2、-C(O)N(R 61 )2、-N(R 61 )C(O)R 61 、-N(R 61 )C(O)OR 61 、-N(R 61 )C(O)N(R 61 )2、-N(R 61 )S(O)2(R 61 )、-S(O)2R 61 、-S(O)2N(R 61 )2 and -CN, R 52 Selected from halogen, -OR 73 、-N(R 73 )2 and optionally one or more independently selected from R 80 Substituents substituted C 1-6 In some embodiments, when R 51 Selected from bromine, hydroxyl, -C 2-6 Alkyl, -C 1-6 Haloalkyl, -N(R 61 )2、-OR 61 、-SR 61 、-C(O)R 61 、-C(O)OR 61 、-OC(O)R 61 、-OC(O)N(R 61 )2、-C(O)N(R 61 )2、-N(R 61 )C(O)R 61 、-N(R 61 )C(O)OR 61 、-N(R 61 )C(O)N(R 61 )2、-N(R 61 )S(O)2(R 61 )、-S(O)2R 61 、-S(O)2N(R 61 )2 and -CN, R 52 It is a halogen.

[0560] In some embodiments, for the compound or salt of formula (II), when R 51 Selected from bromine, hydroxyl, -C 2-6 Alkyl, -C 1-6 Haloalkyl, -N(R 61 )2、-OR 61 、-SR61 、-C(O)R 61 、-C(O)OR 61 、-OC(O)R 61 、-OC(O)N(R 61 )2、-C(O)N(R 61 )2 and -CN, R 52 Selected from

[0561] Halogen, -OR 73 、-SR 73 、-N(R 73 )2、-C(O)R 73 、-C(O)OR 73 、-OC(O)R 73 、-OC(O)N(R 73 )2、-C(O)N(R 73 )2、-N(R 73 )C(O)R 73 、-N(R 73 )C(O)OR 73 、-N(R 73 )C(O)N(R 73 )2、-N(R 73 )S(O)2(R 73 )、N(R 73 )SO2N(R 73 )、-N(R 73 )P(O)(OR 73 )R 73 、-S(O)R 73 、-S(O)2R 73 、-S(O)2N(R 73 )2, -NO2 and -CN;

[0562] Optionally, one or more independently selected from R 80 Substituents substituted C 1-6 Alkyl; and

[0563] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 80 substituted by a substituent.

[0564] In some embodiments, for the compound or salt of formula (II), when R 51 Selected from bromine, hydroxyl, -C 2-6 Alkyl, -C 1-6 Haloalkyl, -N(R 61 )2、-OR 61 、-SR 61 、-C(O)R61 、-C(O)OR 61 、-OC(O)R 61 、-OC(O)N(R 61 )2、-C(O)N(R 61 )2 and -CN, R 52 Selected from halogen, -OR 73 、-SR 73 、-N(R 73 )2、-C(O)R 73 、-C(O)OR 73 、-OC(O)R 73 、-C(O)N(R 73 )2、-N(R 73 )C(O)R 73 , -NO2 and -CN; optionally one or more independently selected from R 80 Substituents substituted C 1-6 Alkyl; and C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 80 In some embodiments, when R 51 Selected from bromine, hydroxyl, -C 2-6 Alkyl, -C 1-6 Haloalkyl, -N(R 61 )2、-OR 61 、-SR 61 、-C(O)R 61 、-C(O)OR 61 、-OC(O)R 61 、-OC(O)N(R 61 )2、-C(O)N(R 61 )2 and -CN, R 52 Selected from halogen, -OR 73 、-N(R 73 )2、-C(O)R 73 , -NO2 and -CN; optionally one or more independently selected from R 80 Substituents substituted C 1-6 Alkyl; and C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 80 In some embodiments, when R 51 Selected from bromine, hydroxyl, -C 2-6 Alkyl, -C 1-6 Haloalkyl, -N(R 61 )2、-OR 61 、-SR 61、-C(O)R 61 、-C(O)OR 61 、-OC(O)R 61 、-OC(O)N(R 61 )2、-C(O)N(R 61 )2 and -CN, R 52 Selected from halogen, -OR 73 、-N(R 73 )2、-C(O)R 73 , -NO2 and -CN, and optionally one or more independently selected from R 80 Substituents substituted C 1-6 In some embodiments, when R 51 Selected from bromine, hydroxyl, -C 2-6 Alkyl, -C 1-6 Haloalkyl, -N(R 61 )2、-OR 61 、-SR 61 、-C(O)R 61 、-C(O)OR 61 、-OC(O)R 61 、-OC(O)N(R 61 )2、-C(O)N(R 61 )2 and -CN, R 52 Selected from halogen, -OR 73 、-N(R 73 )2 and optionally one or more independently selected from R 80 Substituents substituted C 1-6 In some embodiments, when R 51 Selected from bromine, hydroxyl, -C 2-6 Alkyl, -C 1-6 Haloalkyl, -N(R 61 )2、-OR 61 、-SR 61 、-C(O)R 61 、-C(O)OR 61 、-OC(O)R 61 、-OC(O)N(R 61 )2、-C(O)N(R 61 )2 and -CN, R 52 It is a halogen.

[0565] In some embodiments, for the compound or salt of formula (II), when R 51 Selected from bromine, hydroxyl, -C 2-6 Alkyl, -N(R 61 )2、-OR 61 、-SR 61、-C(O)R 61 、-C(O)OR 61 、-C(O)N(R 61 )2 and -CN, R 52 Selected from

[0566] Halogen, -OR 73 、-SR 73 、-N(R 73 )2、-C(O)R 73 、-C(O)OR 73 、-OC(O)R 73 、-OC(O)N(R 73 )2、-C(O)N(R 73 )2、-N(R 73 )C(O)R 73 、-N(R 73 )C(O)OR 73 、-N(R 73 )C(O)N(R 73 )2、-N(R 73 )S(O)2(R 73 )、N(R 73 )SO2N(R 73 )、-N(R 73 )P(O)(OR 73 )R 73 、-S(O)R 73 、-S(O)2R 73 、-S(O)2N(R 73 )2, -NO2 and -CN;

[0567] Optionally, one or more independently selected from R 80 Substituents substituted C 1-6 Alkyl; and

[0568] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 80 substituted by a substituent.

[0569] In some embodiments, for the compound or salt of formula (II), when R 51 Selected from bromine, hydroxyl, -C 2-6 Alkyl, -N(R 61 )2、-OR 61 、-SR 61 、-C(O)R 61 、-C(O)OR 61 、-C(O)N(R 61 )2 and -CN, R 52Selected from halogen, -OR 73 、-SR 73 、-N(R 73 )2、-C(O)R 73 、-C(O)OR 73 、-OC(O)R 73 、-C(O)N(R 73 )2、-N(R 73 )C(O)R 73 , -NO2 and -CN; optionally one or more independently selected from R 80 Substituents substituted C 1-6 Alkyl; and C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 80 In some embodiments, when R 51 Selected from bromine, hydroxyl, -C 2-6 Alkyl, -N(R 61 )2、-OR 61 、-SR 61 、-C(O)R 61 、-C(O)OR 61 、-C(O)N(R 61 )2 and -CN, R 52 Selected from halogen, -OR 73 、-N(R 73 )2、-C(O)R 73 , -NO2 and -CN; optionally one or more independently selected from R 80 Substituents substituted C 1-6 Alkyl; and C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 80 In some embodiments, when R 51 Selected from bromine, hydroxyl, -C 2-6 Alkyl, -N(R 61 )2、-OR 61 、-SR 61 、-C(O)R 61 、-C(O)OR 61 、-C(O)N(R 61 )2 and -CN, R 52 Selected from halogen, -OR 73 、-N(R 73 )2、-C(O)R 73 , -NO2 and -CN and optionally one or more independently selected from R 80 Substituents substituted C 1-6In some embodiments, when R 51 Selected from bromine, hydroxyl, -C 2-6 Alkyl, -N(R 61 )2、-OR 61 、-SR 61 、-C(O)R 61 、-C(O)OR 61 、-C(O)N(R 61 )2 and -CN, R 52 Selected from halogen, -OR 73 、-N(R 73 )2 and optionally one or more independently selected from R 80 Substituents substituted C 1-6 In some embodiments, when R 51 Selected from bromine, hydroxyl, -C 2-6 Alkyl, -N(R 61 )2、-OR 61 、-SR 61 、-C(O)R 61 、-C(O)OR 61 、-C(O)N(R 61 )2 and -CN, R 52 Selected from halogen.

[0570] In some embodiments, for the compound or salt of formula (II), when R 51 Selected from -C(O)R 61 、-C(O)OR 61 and -C(O)N(R 61 )2, R 52 Selected from

[0571] Halogen, -OR 73 、-SR 73 、-N(R 73 )2、-C(O)R 73 、-C(O)OR 73 、-OC(O)R 73 、-OC(O)N(R 73 )2、-C(O)N(R 73 )2、-N(R 73 )C(O)R 73 、-N(R 73 )C(O)OR 73 、-N(R 73 )C(O)N(R 73 )2、-N(R 73 )S(O)2(R 73 )、N(R 73 )SO2N(R73 )、-N(R 73 )P(O)(OR 73 )R 73 、-S(O)R 73 、-S(O)2R 73 、-S(O)2N(R 73 )2, -NO2 and -CN;

[0572] Optionally, one or more independently selected from R 80 Substituents substituted C 1-6 Alkyl; and C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 80 substituted by a substituent.

[0573] In some embodiments, for the compound or salt of formula (II), when R 51 Selected from -C(O)R 61 、-C(O)OR 61 and -C(O)N(R 61 )2, R 52 Selected from halogen, -OR 73 、-SR 73 、-N(R 73 )2、-C(O)R 73 、-C(O)OR 73 、-OC(O)R 73 、-C(O)N(R 73 )2、-N(R 73 )C(O)R 73 , -NO2 and -CN; optionally one or more independently selected from R 80 Substituents substituted C 1-6 Alkyl; and C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 80 In some embodiments, when R 51 Selected from -C(O)R 61 、-C(O)OR 61 and -C(O)N(R 61 )2, R 52 Selected from halogen, -OR 73 、-N(R 73 )2、-C(O)R 73 , -NO2 and -CN; optionally one or more independently selected from R 80 Substituents substituted C 1-6 Alkyl; and C 3-6Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 80 In some embodiments, when R 51 Selected from -C(O)R 61 、-C(O)OR 61 and -C(O)N(R 61 )2, R 52 Selected from halogen, -OR 73 、-N(R 73 )2、-C(O)R 73 , -NO2 and -CN and optionally one or more independently selected from R 80 Substituents substituted C 1-6 In some embodiments, when R 51 Selected from -C(O)R 61 、-C(O)OR 61 and -C(O)N(R 61 )2, R 52 Selected from halogen, -OR 73 、-N(R 73 )2 and optionally one or more independently selected from R 80 Substituents substituted C 1-6 In some embodiments, when R 51 Selected from -C(O)R 61 、-C(O)OR 61 and -C(O)N(R 61 )2, R 52 Selected from halogen, -OR 73 、-N(R 73 )2 and C 1-6 In some embodiments, when R 51 Selected from -C(O)R 61 、-C(O)OR 61 and -C(O)N(R 61 )2, R 52 It is a halogen.

[0574] In some embodiments, for the compound or salt of formula (II), R 53 and R 54 Each occurrence is independently selected from

[0575] Halogen, -OR 64 、-SR 64 、-N(R 64 )2、-N(R 64 )C(O)R 64 、-C(O)R 64 、-C(O)OR64 、-C(O)N(R 64 )2, -NO2 and -CN;

[0576] C 1-4 Alkyl, which is optionally substituted by one or more independently selected from halogen, -OR 64 、-SR 64 、-N(R 64 )2、-N(R 64 )C(O)R 64 、-C(O)R 64 、-C(O)OR 64 、-C(O)N(R 64 )2, -NO2 and -CN; and

[0577] and C 3-4 Carbocyclic and 3 to 4 membered heterocyclic rings, any of which are optionally substituted by one or more independently selected from halogen, -OR 64 、-SR 64 、-N(R 64 )2、-N(R 64 )C(O)R 64 、-C(O)R 64 、-C(O)OR 64 、-C(O)N(R 64 )2, -NO2 and -CN substituents.

[0578] In some embodiments, for the compound or salt of formula (II), R 53 and R 54 is independently selected at each occurrence from halogen, -OR 64 、-SR 64 、-N(R 64 )2、-N(R 64 )C(O)R 64 、-C(O)R 64 、-C(O)OR 64 、-C(O)N(R 64 )2, -NO2, -CN and C 1-4 Alkyl, the C 1-4 Alkyl is optionally substituted by one or more independently selected from halogen, -OR 64 、-SR 64 、-N(R 64 )2、-N(R 64 )C(O)R 64 、-C(O)R 64 、-C(O)OR 64 、-C(O)N(R 64)2, -NO2 and -CN. In some embodiments, R 53 and R 54 is independently selected at each occurrence from halogen, -OR 64 、-SR 64 、-N(R 64 )2、-C(O)R 64 , -NO2, -CN and C 1-4 Alkyl, the C 1-4 Alkyl is optionally substituted by one or more independently selected from halogen, -OR 64 、-SR 64 、-N(R 64 )2、-N(R 64 )C(O)R 64 、-C(O)R 64 、-C(O)OR 64 、-C(O)N(R 64 )2, -NO2, -CN. In some embodiments, R 53 and R 54 is independently selected at each occurrence from halogen, -OR 64 、-SR 64 、-N(R 64 )2、-C(O)R 64 , -NO2 and -CN. In some embodiments, R 53 and R 54 is independently selected at each occurrence from halogen, -OR 64 、-N(R 64 )2, -NO2 and -CN. In some embodiments, R 53 and R 54 Each occurrence is independently selected from halogen.

[0579] In some embodiments, for the compound or salt of formula (II), R 55 and R 55’ are each independently selected from hydrogen and hydroxy; or R 55 and R 55’ Together they are =0. In some embodiments, R 55 and R 55’ Together they are =O.

[0580] In some embodiments, for the compound or salt of formula (II), R 56 and R 56’ are each independently selected from hydrogen and hydroxy; or R 56 and R 56’ Together they are =O, =N-OR 64 or =NR 64In some embodiments, R 56 and R 56’ are each independently selected from hydrogen and hydroxy. 56 and R 56’ Together they are =0. In some embodiments, R 56 and R 56’ Together =N-OR 64 .

[0581] In some embodiments, for the compound or salt of Formula (II), p is selected from 0, 1, 2, and 3. In some embodiments, p is selected from 0 and 1.

[0582] In some embodiments, for the compound or salt of formula (II), R 61 and R 64 Each occurrence is independently selected from

[0583] hydrogen;

[0584] Optionally, one or more independently selected from R 81 Substituents substituted C 1-6 Alkyl; and

[0585] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 81 substituted by a substituent.

[0586] In some embodiments, for the compound or salt of formula (II), R 61 and R 64 Each occurrence is independently selected from

[0587] hydrogen;

[0588] Optionally, one or more independently selected from R 81 Substituents substituted C 1-6 Alkyl; and

[0589] 3 to 6 membered heterocyclic ring, which is optionally substituted by one or more independently selected from R 81 substituted by a substituent.

[0590] In some embodiments, for the compound or salt of formula (II), R 61 and R 64 Each occurrence is independently selected from

[0591] hydrogen;

[0592] C 1-6 Alkyl; and

[0593] 3 to 6 membered heterocyclic ring, which is optionally substituted by one or more independently selected from R 81 substituted by a substituent.

[0594] In some embodiments, for the compound or salt of formula (II), R 71 、R 72 and R 73 Each occurrence is independently selected from

[0595] hydrogen;

[0596] Optionally, one or more independently selected from R 82 Substituents substituted C 1-6 Alkyl; and

[0597] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which are optionally substituted by one or more independently selected C 1-4 Alkyl, C 1-4 Haloalkyl and R 82 substituted by a substituent.

[0598] In some embodiments, R 71 、R 72 and R 73 is independently selected at each occurrence from hydrogen and optionally substituted by one or more independently selected from R 82 Substituents substituted C 1-6 In some embodiments, R 71 、R 72 and R 73 Each occurrence is independently selected from optionally one or more independently selected from R 82 Substituents substituted C 1-6 In some embodiments, R 71 、R 72 and R 73 is independently selected at each occurrence from hydrogen. In some embodiments, R 71 、R 72 and R 73 Each occurrence is independently selected from C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which are optionally substituted by one or more independently selected C 1-4 Alkyl, C 1-4 Haloalkyl and R 8 In some embodiments, R 71 、R 72 and R 73 Each occurrence is independently selected from C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which are optionally substituted by one or more independently selected C1-4 Alkyl and R 8 In some embodiments, R 71 、R 72 and R 73 Each occurrence is independently selected from C 3-6 carbocyclic rings and 3- to 6-membered heterocyclic rings.

[0599] In some embodiments, for the compound or salt of formula (II), R 80 、R 81 and R 82 is independently selected at each occurrence from halogen, -OR 91 、-SR 91 、-N(R 91 )2、-C(O)R 91 、-C(O)OR 91 、-OC(O)R 91 、-OC(O)N(R 91 )2、-C(O)N(R 91 )2、-N(R 91 )C(O)R 91 、-N(R 91 )C(O)OR 91 、-N(R 91 )C(O)N(R 91 )2、-N(R 91 )S(O)2(R 91 )、-N(R 91 )SO2N(R 91 )、-N(R 91 )P(O)(OR 91 )R 91 、-S(O)R 91 、-S(O)2R 91 、-S(O)2N(R 91 )2, -NO2, =O, =S, -CN, C 3-6 In some embodiments, R 80 、R 81 and R 82 is independently selected at each occurrence from halogen, -OR 91 、-SR 91 、-N(R 91 )2、-C(O)R 91 、-C(O)OR 91 、-OC(O)R 91 、-OC(O)N(R 91 )2、-C(O)N(R 91 )2、-N(R91 )C(O)R 91 、-N(R 91 )S(O)2(R 91 )、-N(R 91 )SO2N(R 91 ),-S(O)R 91 、-S(O)2R 91 、-S(O)2N(R 91 )2, -NO2, =O, =S, -CN, C 3-6 In some embodiments, R 80 、R 81 and R 82 is independently selected at each occurrence from halogen, -OR 91 、-SR 91 、-N(R 91 )2、-C(O)R 91 、-C(O)OR 91 、-OC(O)R 91 、-OC(O)N(R 91 )2、-C(O)N(R 91 )2、-N(R 91 )C(O)R 91 、-N(R 91 )SO2N(R 91 )、-NO2、=O、-CN、C 3-6 In some embodiments, R 80 、R 81 and R 82 is independently selected at each occurrence from halogen, -OR 91 、-SR 91 、-N(R 91 )2、-C(O)R 91 、-C(O)OR 91 、-N(R 91 )SO2N(R 91 )、-NO2、=O、-CN、C 3-6 In some embodiments, R 80 、R 81 and R 82 is independently selected at each occurrence from halogen, -OR 91 、-SR 91 、-N(R 91 )2、-C(O)R 91 、-C(O)OR 91 、-N(R 91 )SO2N(R 91), -NO2, =O and -CN. In some embodiments, R 80 、R 81 and R 82 is independently selected at each occurrence from halogen, -OR 91 、-N(R 91 )2、-C(O)OR 91 、-N(R 91 )SO2N(R 91 ), -NO2, =O and -CN. In some embodiments, R 80 、R 81 and R 82 Each occurrence is independently selected from -N(R 91 )2、-C(O)OR 91 and -N(R 91 )SO2N(R 91 ).

[0600] In some embodiments, for the compound or salt of formula (II), R 91 independently selected at each occurrence from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl and C 1-6 In some embodiments, R 91 independently selected at each occurrence from hydrogen, C 1-6 Alkyl and C 1-6 In some embodiments, R 91 independently selected at each occurrence from hydrogen, C 1-6 Alkyl and C 1-6 In some embodiments, R 91 independently selected at each occurrence from hydrogen and C 1-6 alkyl.

[0601] In one aspect, provided herein are compounds having the structure of Formula (III):

[0602]

[0603] or a pharmaceutically acceptable salt thereof; wherein

[0604] R 101 Selected from fluorine, chlorine, bromine, hydroxyl, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -OC 1-6 Alkyl, -OC 1-6 Haloalkyl, -N(R 111 )2、-OR 112 、-SR 111 、-C(O)R 111、-C(O)OR 111 、-OC(O)R 111 、-OC(O)N(R 111 )2、-C(O)N(R 111 )2、-N(R 111 )C(O)R 111 、-N(R 111 )C(O)OR 111 、-N(R 111 )C(O)N(R 111 )2、-N(R 111 )S(O)2(R 111 )、-S(O)2R 111 、-S(O)2N(R 111 )2, -NO2 and -CN;

[0605] When R 101 When it is fluorine, R 102 Selected from

[0606] Chlorine, bromine, iodine, -N(R 121 )2、-OR 122 、-SR 121 、-C(O)R 121 、-C(O)OR 121 、-OC(O)R 121 、-OC(O)N(R 121 )2、-C(O)N(R 121 )2、-N(R 121 )C(O)R 121 、-N(R 21 )C(O)OR 121 、-N(R 121 )C(O)N(R 121 )2、-N(R 121 )S(O)2(R 121 )、-N(R 121 )SO2N(R 121 )、-N(R 121 )P(O)(OR 121 )R 121 、-S(O)R 121 、-S(O)2R 121 、-S(O)2N(R 121 )2, -NO2 and -CN;

[0607] One or more independently selected from R 123 C1 alkyl substituted with a substituent, and optionally substituted with one or more independently selected from R 130 Substituents substituted C 2-6alkyl;

[0608] as well as

[0609] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 130 Substituents substituted;

[0610] When R 101 Bromine, iodine, hydroxyl, -O-C1 alkyl, -C(O)OR 111 、-C(O)N(H)(C2 alkyl)、-S(O)2R 111 or -S(O)2N(R 111 )2, R 102 Selected from

[0611] Fluorine, -N(R 124 )2、-OR 125 、-SR 124 、-C(O)R 124 、-C(O)OR 124 、-OC(O)R 124 、-OC(O)N(R 124 )2、-C(O)N(R 124 )2、-N(R 124 )C(O)R 124 、-N(R 124 )C(O)OR 124 、-N(R 124 )C(O)N(R 124 )2、-N(R 124 )S(O)2(R 124 )、-N(R 124 )SO2N(R 124 )、-N(R 124 )P(O)(OR 124 )R 124 、-S(O)R 124 、-S(O)2R 124 、-S(O)2N(R 124 )2, -NO2 and -CN;

[0612] Optionally, one or more independently selected from R 130 Substituents substituted C 1-6 Alkyl; and

[0613] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 130 Substituents substituted;

[0614] When R101 Chloro, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 1-6 Haloalkyl, -OR 112 、-SR 111 、-N(R 111 )2、-C(O)R 111 、-OC(O)R 111 、-C(O)N(R 113 )2、-OC(O)N(R 111 )2、-N(R 111 )C(O)R 111 、-N(R 111 )C(O)OR 111 、-N(R 111 )C(O)N(R 111 )2、-N(R 111 )S(O)2(R 111 ), -NO2 or -CN; R 102 Selected from halogen, -OR 126 、-SR 126 、-N(R 126 )2、-C(O)R 126 、-C(O)OR 126 、-OC(O)R 126 、-OC(O)N(R 126 )2、-C(O)N(R 126 )2、-N(R 126 )C(O)R 126 、-N(R 126 )C(O)OR 126 、-N(R 126 )C(O)N(R 126 )2、-N(R 126 )S(O)2(R 126 )、-N(R 126 )SO2N(R 126 )、-N(R 126 )P(O)(OR 126 )R 126 、-S(O)R 126 、-S(O)2R 126 、-S(O)2N(R 126 )2, -NO2 and -CN;

[0615] Optionally, one or more independently selected from R 130 Substituents substituted C 1-6 Alkyl; and

[0616] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 130 Substituents substituted;

[0617] The condition is (i) when R 101 When it is NO2, R 102 cannot be methyl; (ii) when R 101 When it is methyl, R 102 cannot be chlorine; and (iii) when R 101 When it is chlorine, R 102 It cannot be bromine;

[0618] R 103 and R 104 Each occurrence is independently selected from

[0619] Halogen, -OR 114 、-SR 114 、-N(R 114 )2、-N(R 114 )C(O)R 114 、-C(O)R 114 、-C(O)OR 114 、-C(O)N(R 114 )2, -NO2 and -CN;

[0620] C 1-4 Alkyl, which is optionally substituted by one or more independently selected from halogen, -OR 114 、-SR 114 、-N(R 114 )2、-N(R 114 )C(O)R 114 、-C(O)R 114 、-C(O)OR 114 、-C(O)N(R 114 )2, -NO2 and -CN substituents;

[0621] C 3-4 Carbocyclic and 3 to 4 membered heterocyclic rings, any of which are optionally substituted by one or more independently selected from halogen, -OR 114 、-SR 114 、-N(R 114 )2、-N(R 114 )C(O)R 114 、-C(O)R 114 、-C(O)OR 114 、-C(O)N(R 114 )2, -NO2 and -CN substituents;

[0622] R 105 and R 105’ are each independently selected from hydrogen and hydroxy; or R 105 and R 105’ Together = O;

[0623] R 106 and R 106’ are each independently selected from hydrogen and hydroxy; or R 106 and R 106’ Together they are =O, =N-OR 114 or =NR 114 ;

[0624] r is selected from 0, 1, 2 and 3;

[0625] s is selected from 0, 1, 2 and 3;

[0626] R 111 and R 114 Each occurrence is independently selected from

[0627] hydrogen;

[0628] Optionally, one or more independently selected from R 131 Substituents substituted C 1-6 alkyl;

[0629] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 131 Substituents substituted;

[0630] R 112 Each time it appears, select

[0631] One or more independently selected from R 132 Substituents substituted C 1-6 alkyl;

[0632] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 133 Substituents substituted;

[0633] R 113 Each time it appears, select

[0634] hydrogen;

[0635] Optionally, one or more independently selected from R 134 Substituents substituted C1 alkyl and C 3-6 Alkyl, and one or more independently selected from R 134 a C2 alkyl group substituted with a substituent;

[0636] C 3-5 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 134 Substituents substituted;

[0637] R 121 、R 124 and R 126 Each occurrence is independently selected from

[0638] hydrogen;

[0639] Optionally, one or more independently selected from R 134 Substituents substituted C 1-6 alkyl;

[0640] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which are optionally substituted by one or more independently selected C 1-4 Alkyl, C 1-4 Haloalkyl and R 134 Substituents substituted;

[0641] R 122 and R 125 Each occurrence is independently selected from

[0642] Optionally, one or more independently selected from R 134 Substituents substituted C 2-6 alkyl;

[0643] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which are optionally substituted by one or more independently selected C 1-4 Alkyl, C 1-4 Haloalkyl and R 134 Substituents substituted;

[0644] R 123 independently selected at each occurrence

[0645] hydrogen;

[0646] Optionally, one or more independently selected from R 134 Substituents substituted C 1-6 alkyl;

[0647] C 3-5 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which are optionally substituted by one or more independently selected C 1-4 Alkyl, C 1-4 Haloalkyl and R 134 Substituents substituted;

[0648] R 130 、R131 、R 132 、R 133 and R 134 Each occurrence is independently selected from

[0649] Halogen, -OR 141 、-SR 141 、-N(R 141 )2、-C(O)R 141 、-C(O)OR 141 、-OC(O)R 141 、-OC(O)N(R 141 )2、-C(O)N(R 141 )2、-N(R 141 )C(O)R 141 、-N(R 141 )C(O)OR 141 、-N(R 141 )C(O)N(R 141 )2、-N(R 141 )S(O)2(R 141 )、-N(R 141 )SO2N(R 141 )、-N(R 141 )P(O)(OR 141 )R 141 、-S(O)R 141 、-S(O)2R 141 、-S(O)2N(R 141 )2, -NO2, =O, =S, -CN, C 3-6 Carbocyclic and 3- to 7-membered heterocyclic rings;

[0650] and

[0651] R 141 independently selected at each occurrence from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl and C 1-6 Hydroxyalkyl.

[0652] In some embodiments, for the compound or salt of (III), R 101 In some embodiments, for the compound or salt of (III), R 101 Bromine, iodine, hydroxyl, -O-C1 alkyl, -C(O)OR 111 、-C(O)N(H)(C2 alkyl)、-S(O)2R 111 or -S(O)2N(R 111 ) 2. In some embodiments, for the compound or salt of (III), R 101 Chloro, -C1-6 Alkyl, -C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 1-6 Haloalkyl, -OR 112 、-SR 111 、-N(R 111 )2、-C(O)R 111 、-OC(O)R 111 、-C(O)N(R 113 )2、-OC(O)N(R 111 )2、-N(R 111 )C(O)R 111 、-N(R 111 )C(O)OR 111 、-N(R 111 )C(O)N(R 111 )2、-N(R 111 )S(O)2(R 111 ), -NO2 or -CN.

[0653] In some embodiments, for the compound or salt of (III), R 101 is fluorine, bromine, iodine, hydroxyl, -O-C1 alkyl, -C(O)OR 111 、-C(O)N(H)(C2 alkyl)、-S(O)2R 111 or -S(O)2N(R 111 )2. In some embodiments, R 101 is fluorine, bromine, iodine, hydroxyl, -O-C1 alkyl, -C(O)OR 111 or -C(O)N(H)(C2 alkyl). In some embodiments, R 101 is fluorine, bromine, iodine, hydroxy or -O-C1 alkyl.

[0654] In some embodiments, for the compound or salt of (III), R 101 For fluorine, chlorine, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 1-6 Haloalkyl, -OR 112 、-SR 111 、-N(R 111 )2、-C(O)R 111 、-OC(O)R 111 、-C(O)N(R 113 )2、-OC(O)N(R 111 )2、-N(R 111 )C(O)R 111 、-N(R111 )C(O)OR 111 、-N(R 111 )C(O)N(R 111 )2、-N(R 111 )S(O)2(R 111 ), -NO2 or -CN. In some embodiments, R 101 For fluorine, chlorine, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 1-6 Haloalkyl, -OR 112 、-SR 111 、-N(R 111 )2、-C(O)R 111 、-OC(O)R 111 、-C(O)N(R 113 )2、-OC(O)N(R 111 )2、-N(R 111 )C(O)R 111 , -NO2 or -CN. In some embodiments, R 101 For fluorine, chlorine, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OR 112 、-SR 111 、-N(R 111 )2、-C(O)R 111 , -NO2 or -CN. In some embodiments, R 101 It is fluorine, -NO2 or -CN.

[0655] In some embodiments, for the compound or salt of (III), R 101 Bromine, iodine, hydroxyl, -O-C1 alkyl, -C(O)OR 111 、-C(O)N(H)(C2 alkyl)、-S(O)2R 111 or -S(O)2N(R 111 )2, chlorine, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 1-6 Haloalkyl, -OR 112 、-SR 111 、-N(R 111 )2、-C(O)R 111 、-OC(O)R 111 、-C(O)N(R 113 )2、-OC(O)N(R111 )2、-N(R 111 )C(O)R 111 、-N(R 111 )C(O)OR 111 、-N(R 111 )C(O)N(R 111 )2、-N(R 111 )S(O)2(R 111 ), -NO2 or -CN. In some embodiments, R 101 Bromine, iodine, hydroxyl, -O-C1 alkyl, -C(O)OR 111 、-C(O)N(H)(C2 alkyl)、-S(O)2R 111 or -S(O)2N(R 111 )2, chlorine, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 1-6 Haloalkyl, -OR 112 、-SR 111 、-N(R 111 )2、-C(O)R 111 、-OC(O)R 111 、-C(O)N(R 113 )2、--N(R 111 )C(O)R 111 , -NO2 or -CN. In some embodiments, R 101 Bromine, iodine, hydroxyl, -O-C1 alkyl, -C(O)OR 111 、-C(O)N(H)(C2 alkyl)、-S(O)2R 111 or -S(O)2N(R 111 )2, chlorine, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OR 112 、-SR 111 、-N(R 111 )2、-C(O)R 111 、-OC(O)R 111 、-C(O)N(R 113 )2、--N(R 111 )C(O)R 111 , -NO2 or -CN. In some embodiments, R 101 Bromine, iodine, hydroxyl, -O-C1 alkyl, -C(O)OR 111 、-C(O)N(H)(C2 alkyl)、-S(O)2R 111or -S(O)2N(R 111 )2, chlorine, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OR 112 、-SR 111 、-N(R 111 )2, -NO2 or -CN. In some embodiments, R 101 Bromine, iodine, hydroxyl, -O-C1 alkyl, -C(O)OR 111 、-C(O)N(H)(C2 alkyl)、-S(O)2R 111 or -S(O)2N(R 111 )2, -NO2 or -CN. In some embodiments, R 101 It is bromine, iodine, hydroxyl, -O-C1 alkyl, -NO2 or -CN.

[0656] In some embodiments, for the compound or salt of (III), R 101 Selected from fluorine, chlorine, bromine, hydroxyl, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -OC 1-6 Alkyl, -OC 1-6 Haloalkyl, -N(R 111 )2、-OR 112 、-SR 111 、-C(O)R 111 、-C(O)OR 111 、-OC(O)R 111 、-OC(O)N(R 111 )2、-C(O)N(R 111 )2、-N(R 111 )C(O)R 111 、-N(R 111 )C(O)OR 111 、-N(R 111 )C(O)N(R 111 )2、-N(R 111 )S(O)2(R 111 )、-S(O)2R 111 、-S(O)2N(R 111 )2, -NO2 and -CN. In some embodiments, R 101 Selected from fluorine, chlorine, bromine, hydroxyl, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -OC 1-6 Alkyl, -OC 1-6 Haloalkyl, -N(R 111 )2、-OR112 、-SR 111 、-C(O)R 111 、-C(O)OR 111 、-OC(O)R 111 、-C(O)N(R 111 )2、-N(R 111 )C(O)R 111 、N(R 111 )S(O)2(R 111 )、-S(O)2R 111 、-S(O)2N(R 111 )2, -NO2 and -CN. In some embodiments, R 101 Selected from fluorine, chlorine, bromine, hydroxyl, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -OC 1-6 Alkyl, -OC 1-6 Haloalkyl, -N(R 111 )2、-OR 112 、-SR 111 、-C(O)R 111 、-C(O)OR 111 、-OC(O)R 111 、-C(O)N(R 111 )2、-N(R 111 )C(O)R 111 、N(R 111 )S(O)2(R 111 )、-S(O)2R 111 、-S(O)2N(R 111 )2, -NO2 and -CN. In some embodiments, R 101 Selected from fluorine, chlorine, bromine, hydroxyl, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -OC 1-6 Alkyl, -OC 1-6 Haloalkyl, -N(R 111 )2、-OR 112 、-C(O)R 111 、-C(O)OR 111 、-OC(O)R 111 、-C(O)N(R 111 )2、-N(R 111 )C(O)R 111 、-S(O)2R 111 , -NO2 and -CN. In some embodiments, R 101 Selected from fluorine, chlorine, bromine, hydroxyl, -C 1-6 Alkyl, -C 1-6Haloalkyl, -OC 1-6 Alkyl, -N(R 111 )2、-OR 112 、-C(O)R 111 、-C(O)OR 111 、-OC(O)R 111 、-C(O)N(R 111 )2、-N(R 111 )C(O)R 111 , -NO2 and -CN. In some embodiments, R 101 Selected from fluorine, chlorine, bromine, hydroxyl, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -OC 1-6 Alkyl, -N(R 111 )2、-OR 112 、-C(O)R 111 、-C(O)OR 111 , -NO2 and -CN. In some embodiments, R 101 Selected from fluorine, chlorine, bromine, hydroxyl, -C 1-6 Alkyl, -OC 1-6 Alkyl, -N(R 111 )2、-OR 112 , -NO2 and -CN. In some embodiments, R 101 Selected from fluorine, -NO2 and -CN.

[0657] In some embodiments, for the compound or salt of formula (III), when R 101 When it is fluorine, R 102 Selected from

[0658] Chlorine, bromine, iodine, -N(R 121 )2、-OR 122 、-SR 121 、-C(O)R 121 、-C(O)OR 121 、-OC(O)R 121 、-OC(O)N(R 121 )2、-C(O)N(R 121 )2、-N(R 121 )C(O)R 121 、-N(R 21 )C(O)OR 121 、-N(R 121 )C(O)N(R 121 )2、-N(R 121 )S(O)2(R 121 )、N(R 121 )SO2N(R 121)、-N(R 121 )P(O)(OR 121 )R 121 、-S(O)R 121 、-S(O)2R 121 、-S(O)2N(R 121 )2, -NO2 and -CN;

[0659] One or more independently selected from R 123 C1 alkyl substituted with a substituent, and optionally substituted with one or more independently selected from R 130 Substituents substituted C 2-6 Alkyl; and

[0660] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 130 substituted by a substituent.

[0661] In some embodiments, for the compound or salt of formula (III), when R 101 When it is fluorine, R 102 Selected from chlorine, bromine, iodine, -N(R 121 )2、-OR 122 、-SR 121 、-C(O)R 121 、-C(O)OR 121 、-OC(O)R 121 、-OC(O)N(R 121 )2、-C(O)N(R 121 )2、-N(R 121 )C(O)R 121 、-N(R 21 )C(O)OR 121 、-N(R 121 )C(O)N(R 121 )2、-N(R 121 )S(O)2(R 121 )、N(R 121 )SO2N(R 121 )、-N(R 121 )P(O)(OR 121 )R 121 、-S(O)R 121 、-S(O)2R 121 、-S(O)2N(R 121 )2, -NO2 and -CN. In some embodiments, when R 101 When it is fluorine, R 102 Selected from chlorine, bromine, iodine, -N(R 121 )2、-OR122 、-SR 121 、-C(O)R 121 、-C(O)OR 121 、-OC(O)R 121 、-OC(O)N(R 121 )2、-C(O)N(R 121 )2、-N(R 121 )C(O)R 121 、-N(R 21 )C(O)OR 121 、-N(R 121 )C(O)N(R 121 )2、-N(R 121 )S(O)2(R 121 )、N(R 121 )SO2N(R 121 )、-N(R 121 )P(O)(OR 121 )R 121 、-S(O)R 121 、-S(O)2R 121 、-S(O)2N(R 121 )2, -NO2 and -CN. In some embodiments, when R 101 When it is fluorine, R 102 Selected from chlorine, bromine, iodine, -N(R 121 )2、-OR 122 、-SR 121 、-C(O)R 121 、-C(O)OR 121 、-OC(O)R 121 、-C(O)N(R 121 )2、-N(R 121 )C(O)R 121 、-N(R 121 )S(O)2(R 121 )、N(R 121 )SO2N(R 121 )、-N(R 121 )P(O)(OR 121 )R 121 、-S(O)R 121 、-S(O)2R 121 、-S(O)2N(R 121 )2, -NO2 and -CN. In some embodiments, when R 101 When it is fluorine, R 102 Selected from chlorine, bromine, iodine, -N(R 121 )2、-OR 122 、-SR 121、-C(O)R 121 、-C(O)OR 121 、-OC(O)R 121 、-C(O)N(R 121 )2、-N(R 121 )C(O)R 121 、-S(O)R 121 、-S(O)2R 121 、-S(O)2N(R 121 )2, -NO2 and -CN. In some embodiments, when R 101 When it is fluorine, R 102 Selected from chlorine, bromine, iodine, -N(R 121 )2、-OR 122 、-SR 121 、-C(O)R 121 、-C(O)OR 121 、-OC(O)R 121 、-C(O)N(R 121 )2、-N(R 121 )C(O)R 121 , -NO2 and -CN. In some embodiments, when R 101 When it is fluorine, R 102 Selected from chlorine, bromine, iodine, -N(R 121 )2、-OR 122 、-SR 121 、-C(O)R 121 、-C(O)OR 121 、-OC(O)R 121 、-C(O)N(R 121 )2, -NO2 and -CN. In some embodiments, when R 101 When it is fluorine, R 102 Selected from chlorine, bromine, iodine, -N(R 121 )2、-OR 122 、-C(O)R 121 、-C(O)OR 121 、-OC(O)R 121 、-C(O)N(R 121 )2, -NO2 and -CN. In some embodiments, when R 101 When it is fluorine, R 102 Selected from chlorine, bromine, iodine, -N(R 121 )2、-OR 122 、-C(O)R 121 , -NO2 and -CN. In some embodiments, when R 101 When it is fluorine, R 102 Selected from chlorine, bromine, iodine, -N(R 121)2、-OR 122 , -NO2 and -CN. In some embodiments, when R 101 When it is fluorine, R 102 is selected from the group consisting of chlorine, bromine, iodine, -NO2 and -CN. In some embodiments, when R 101 When it is fluorine, R 102 In some embodiments, when R 101 When it is fluorine, R 102 For bromine.

[0662] In some embodiments, for the compound or salt of formula (III), when R 101 Bromine, iodine, hydroxyl, -O-C1 alkyl, -C(O)OR 111 、-C(O)N(H)(C2 alkyl)、-S(O)2R 111 or -S(O)2N(R 111 )2, R 102 Selected from

[0663] Fluorine, -N(R 124 )2、-OR 125 、-SR 124 、-C(O)R 124 、-C(O)OR 124 、-OC(O)R 124 、-OC(O)N(R 124 )2、-C(O)N(R 124 )2、-N(R 124 )C(O)R 124 、-N(R 124 )C(O)OR 124 、-N(R 124 )C(O)N(R 124 )2、-N(R 124 )S(O)2(R 124 )、N(R 124 )SO2N(R 124 )、-N(R 124 )P(O)(OR 124 )R 124 、-S(O)R 124 、-S(O)2R 124 、-S(O)2N(R 124 )2, -NO2 and -CN;

[0664] Optionally, one or more independently selected from R 130 Substituents substituted C 1-6 Alkyl; and

[0665] C 3-6Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 130 substituted by a substituent.

[0666] In some embodiments, for the compound or salt of formula (III), when R 101 Bromine, iodine, hydroxyl, -O-C1 alkyl, -C(O)OR 111 、-C(O)N(H)(C2 alkyl)、-S(O)2R 111 or -S(O)2N(R 111 )2, R 102 Selected from fluorine, -N(R 124 )2、-OR 125 、-SR 124 、-C(O)R 124 、-C(O)OR 124 、-OC(O)R 124 、-OC(O)N(R 124 )2、-C(O)N(R 124 )2、-N(R 124 )C(O)R 124 、-N(R 124 )C(O)OR 124 、-N(R 124 )C(O)N(R 124 )2、-N(R 124 )S(O)2(R 124 )、N(R 124 )SO2N(R 124 )、-N(R 124 )P(O)(OR 124 )R 124 、-S(O)R 124 、-S(O)2R 124 、-S(O)2N(R 124 )2, -NO2 and -CN; optionally one or more independently selected from R 130 Substituents substituted C 1-6 Alkyl; and C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 130 In some embodiments, when R 101 Bromine, iodine, hydroxyl, -O-C1 alkyl, -C(O)OR 111 、-C(O)N(H)(C2 alkyl)、-S(O)2R 111 or -S(O)2N(R 111 )2, R 102 Selected from fluorine, -N(R 124)2、-OR 125 、-SR 124 、-C(O)R 124 、-C(O)OR 124 、-OC(O)R 124 、-OC(O)N(R 124 )2、-C(O)N(R 124 )2、-N(R 124 )C(O)R 124 、-N(R 124 )C(O)OR 124 、-N(R 124 )C(O)N(R 124 )2、-N(R 124 )S(O)2(R 124 )、N(R 124 )SO2N(R 124 )、-N(R 124 )P(O)(OR 124 )R 124 、-S(O)R 124 、-S(O)2R 124 、-S(O)2N(R 124 )2, -NO2 and -CN; optionally one or more independently selected from R 130 Substituents substituted C 1-6 Alkyl; and C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 130 In some embodiments, when R 101 Bromine, iodine, hydroxyl, -O-C1 alkyl, -C(O)OR 111 、-C(O)N(H)(C2 alkyl)、-S(O)2R 111 or -S(O)2N(R 111 )2, R 102 Selected from fluorine, -N(R 124 )2、-OR 125 、-SR 124 、-C(O)R 124 、-C(O)OR 124 、-OC(O)R 124 、-OC(O)N(R 124 )2、-C(O)N(R 124 )2、-N(R 124 )C(O)R 124 、-N(R 124 )C(O)OR 124 、-N(R 124 )C(O)N(R124 )2、-N(R 124 )S(O)2(R 124 )、N(R 124 )SO2N(R 124 )、-N(R 124 )P(O)(OR 124 )R 124 、-S(O)R 124 、-S(O)2R 124 、-S(O)2N(R 124 )2, -NO2, -CN, optionally one or more independently selected from R 130 Substituents substituted C 1-6 alkyl.

[0667] In some embodiments, for the compound or salt of formula (III), when R 101 Bromine, iodine, hydroxyl, -O-C1 alkyl, -C(O)OR 111 、-C(O)N(H)(C2 alkyl)、-S(O)2R 111 or -S(O)2N(R 111 )2, R 102 Selected from fluorine, -N(R 124 )2、-OR 125 、-SR 124 、-C(O)R 124 、-C(O)OR 124 、-OC(O)R 124 、-C(O)N(R 124 )2、-N(R 124 )C(O)R 124 、-N(R 124 )S(O)2(R 124 )、N(R 124 )SO2N(R 124 )、-N(R 124 )P(O)(OR 124 )R 124 、-S(O)R 124 、-S(O)2R 124 、-S(O)2N(R 124 )2, -NO2, -CN, optionally one or more independently selected from R 130 Substituents substituted C 1-6 In some embodiments, when R 101 Bromine, iodine, hydroxyl, -O-C1 alkyl, -C(O)OR 111 、-C(O)N(H)(C2 alkyl)、-S(O)2R 111 or -S(O)2N(R111 )2, R 102 Selected from fluorine, -N(R 124 )2、-OR 125 、-SR 124 、-C(O)R 124 、-C(O)OR 124 、-OC(O)R 124 、-C(O)N(R 124 )2、-N(R 124 )C(O)R 124 、-S(O)R 124 、-S(O)2R 124 、-S(O)2N(R 124 )2, -NO2, -CN, optionally one or more independently selected from R 130 Substituents substituted C 1-6 In some embodiments, when R 101 Bromine, iodine, hydroxyl, -O-C1 alkyl, -C(O)OR 111 、-C(O)N(H)(C2 alkyl)、-S(O)2R 111 or -S(O)2N(R 111 )2, R 102 Selected from fluorine, -N(R 124 )2、-OR 125 、-C(O)R 124 、-C(O)OR 124 、-OC(O)R 124 、-C(O)N(R 124 )2、-N(R 124 )C(O)R 124 、-S(O)R 124 , -NO2, -CN, optionally one or more independently selected from R 130 Substituents substituted C 1-6 In some embodiments, when R 101 Bromine, iodine, hydroxyl, -O-C1 alkyl, -C(O)OR 111 、-C(O)N(H)(C2 alkyl)、-S(O)2R 111 or -S(O)2N(R 111 )2, R 102 Selected from fluorine, -N(R 124 )2、-OR 125 、-C(O)R 124 、-C(O)OR 124 、-OC(O)R 124 , -NO2, -CN, optionally one or more independently selected from R 130Substituents substituted C 1-6 In some embodiments, when R 101 Bromine, iodine, hydroxyl, -O-C1 alkyl, -C(O)OR 111 、-C(O)N(H)(C2 alkyl)、-S(O)2R 111 or -S(O)2N(R 111 )2, R 102 Selected from fluorine, -N(R 124 )2、-OR 125 , -NO2, -CN, optionally one or more independently selected from R 130 Substituents substituted C 1-6 In some embodiments, when R 101 Bromine, iodine, hydroxyl, -O-C1 alkyl, -C(O)OR 111 、-C(O)N(H)(C2 alkyl)、-S(O)2R 111 or -S(O)2N(R 111 )2, R 102 Selected from fluorine, -N(R 124 )2、-OR 125 、-NO2、-CN、C 1-6 In some embodiments, when R 101 Bromine, iodine, hydroxyl, -O-C1 alkyl, -C(O)OR 111 、-C(O)N(H)(C2 alkyl)、-S(O)2R 111 or -S(O)2N(R 111 )2, R 102 Selected from fluorine, -NO2, -CN, C 1-6 In some embodiments, when R 101 Bromine, iodine, hydroxyl, -O-C1 alkyl, -C(O)OR 111 、-C(O)N(H)(C2 alkyl)、-S(O)2R 111 or -S(O)2N(R 111 )2, R 102 Selected from fluorine, -NO2 and -CN.

[0668] In some embodiments, for the compound or salt of formula (III), when R 101 Bromine, iodine, hydroxyl, -O-C1 alkyl, -C(O)OR 111 or -C(O)N(H)(C2 alkyl), R 102 Selected from fluorine, -N(R 124 )2、-OR 125 、-SR 124 、-C(O)R 124、-C(O)OR 124 、-OC(O)R 124 、-OC(O)N(R 124 )2、-C(O)N(R 124 )2、-N(R 124 )C(O)R 124 、-N(R 124 )C(O)OR 124 、-N(R 124 )C(O)N(R 124 )2、-N(R 124 )S(O)2(R 124 )、N(R 124 )SO2N(R 124 )、-N(R 124 )P(O)(OR 124 )R 124 、-S(O)R 124 、-S(O)2R 124 、-S(O)2N(R 124 )2, -NO2 and -CN;

[0669] Optionally, one or more independently selected from R 130 Substituents substituted C 1-6 Alkyl; and

[0670] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 130 substituted by a substituent.

[0671] In some embodiments, for the compound or salt of formula (III), when R 101 Bromine, iodine, hydroxyl, -O-C1 alkyl, -C(O)OR 111 or -C(O)N(H)(C2 alkyl), R 102 Selected from fluorine, -N(R 124 )2、-OR 125 、-SR 124 、-C(O)R 124 、-C(O)OR 124 、-OC(O)R 124 、-OC(O)N(R 124 )2、-C(O)N(R 124 )2、-N(R 124 )C(O)R 124 、-N(R 124 )C(O)OR 124 、-N(R 124 )C(O)N(R 124)2、-N(R 124 )S(O)2(R 124 )、N(R 124 )SO2N(R 124 )、-N(R 124 )P(O)(OR 124 )R 124 、-S(O)R 124 、-S(O)2R 124 、-S(O)2N(R 124 )2, -NO2 and -CN; optionally one or more independently selected from R 130 Substituents substituted C 1-6 Alkyl; and C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 130 In some embodiments, when R 101 Bromine, iodine, hydroxyl, -O-C1 alkyl, -C(O)OR 111 or -C(O)N(H)(C2 alkyl), R 102 Selected from fluorine, -N(R 124 )2、-OR 125 、-SR 124 、-C(O)R 124 、-C(O)OR 124 、-OC(O)R 124 、-OC(O)N(R 124 )2、-C(O)N(R 124 )2、-N(R 124 )C(O)R 124 、-N(R 124 )C(O)OR 124 、-N(R 124 )C(O)N(R 124 )2、-N(R 124 )S(O)2(R 124 )、N(R 124 )SO2N(R 124 )、-N(R 124 )P(O)(OR 124 )R 124 、-S(O)R 124 、-S(O)2R 124 、-S(O)2N(R 124 )2, -NO2 and -CN; optionally one or more independently selected from R 130 Substituents substituted C 1-6 Alkyl; and C 3-6Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 130 substituted by a substituent.

[0672] In some embodiments, for the compound or salt of formula (III), when R 101 Bromine, iodine, hydroxyl, -O-C1 alkyl, -C(O)OR 111 or -C(O)N(H)(C2 alkyl), R 102 Selected from fluorine, -N(R 124 )2、-OR 125 、-SR 124 、-C(O)R 124 、-C(O)OR 124 、-OC(O)R 124 、-OC(O)N(R 124 )2、-C(O)N(R 124 )2、-N(R 124 )C(O)R 124 、-N(R 124 )C(O)OR 124 、-N(R 124 )C(O)N(R 124 )2、-N(R 124 )S(O)2(R 124 )、N(R 124 )SO2N(R 124 )、-N(R 124 )P(O)(OR 124 )R 124 、-S(O)R 124 、-S(O)2R 124 、-S(O)2N(R 124 )2, -NO2, -CN, optionally one or more independently selected from R 130 Substituents substituted C 1-6 In some embodiments, when R 101 Bromine, iodine, hydroxyl, -O-C1 alkyl, -C(O)OR 111 or -C(O)N(H)(C2 alkyl), R 102 Selected from fluorine, -N(R 124 )2、-OR 125 、-SR 124 、-C(O)R 124 、-C(O)OR 124 、-OC(O)R 124 、-C(O)N(R 124 )2、-N(R 124 )C(O)R 124、-N(R 124 )S(O)2(R 124 )、N(R 124 )SO2N(R 124 )、-N(R 124 )P(O)(OR 124 )R 124 、-S(O)R 124 、-S(O)2R 124 、-S(O)2N(R 124 )2, -NO2, -CN, optionally one or more independently selected from R 130 Substituents substituted C 1-6 In some embodiments, when R 101 Bromine, iodine, hydroxyl, -O-C1 alkyl, -C(O)OR 111 or -C(O)N(H)(C2 alkyl), R 102 Selected from fluorine, -N(R 124 )2、-OR 125 、-SR 124 、-C(O)R 124 、-C(O)OR 124 、-OC(O)R 124 、-C(O)N(R 124 )2、-N(R 124 )C(O)R 124 、-S(O)R 124 、-S(O)2R 124 、-S(O)2N(R 124 )2, -NO2, -CN, optionally one or more independently selected from R 130 Substituents substituted C 1-6 In some embodiments, when R 101 Bromine, iodine, hydroxyl, -O-C1 alkyl, -C(O)OR 111 or -C(O)N(H)(C2 alkyl), R 102 Selected from fluorine, -N(R 124 )2、-OR 125 、-C(O)R 124 、-C(O)OR 124 、-OC(O)R 124 、-C(O)N(R 124 )2、-N(R 124 )C(O)R 124 、-S(O)R 124 , -NO2, -CN, optionally one or more independently selected from R 130 Substituents substituted C 1-6In some embodiments, when R 101 Bromine, iodine, hydroxyl, -O-C1 alkyl, -C(O)OR 111 or -C(O)N(H)(C2 alkyl), R 102 Selected from fluorine, -N(R 124 )2、-OR 125 、-C(O)R 124 、-C(O)OR 124 、-OC(O)R 124 , -NO2, -CN, optionally one or more independently selected from R 130 Substituents substituted C 1-6 In some embodiments, when R 101 Bromine, iodine, hydroxyl, -O-C1 alkyl, -C(O)OR 111 or -C(O)N(H)(C2 alkyl), R 102 Selected from fluorine, -N(R 124 )2、-OR 125 , -NO2, -CN, optionally one or more independently selected from R 130 Substituents substituted C 1-6 In some embodiments, when R 101 Bromine, iodine, hydroxyl, -O-C1 alkyl, -C(O)OR 111 or -C(O)N(H)(C2 alkyl), R 102 Selected from fluorine, -N(R 124 )2、-OR 125 、-NO2、-CN、C 1-6 In some embodiments, when R 101 Bromine, iodine, hydroxyl, -O-C1 alkyl, -C(O)OR 111 , or -C(O)N(H)(C2 alkyl), R 102 Selected from fluorine, -NO2, -CN, C 1-6 In some embodiments, when R 101 Bromine, iodine, hydroxyl, -O-C1 alkyl, -C(O)OR 111 , or -C(O)N(H)(C2 alkyl), R 102 Selected from fluorine, -NO2 and -CN.

[0673] In some embodiments, for the compound or salt of formula (III), when R 101 When R is bromine, iodine or hydroxyl, 102 Selected from

[0674] Fluorine, -N(R 124 )2、-OR 125 、-SR124 、-C(O)R 124 、-C(O)OR 124 、-OC(O)R 124 、-OC(O)N(R 124 )2、-C(O)N(R 124 )2、-N(R 124 )C(O)R 124 、-N(R 124 )C(O)OR 124 、-N(R 124 )C(O)N(R 124 )2、-N(R 124 )S(O)2(R 124 )、N(R 124 )SO2N(R 124 )、-N(R 124 )P(O)(OR 124 )R 124 、-S(O)R 124 、-S(O)2R 124 、-S(O)2N(R 124 )2, -NO2 and -CN;

[0675] Optionally, one or more independently selected from R 130 Substituents substituted C 1-6 Alkyl; and

[0676] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 130 substituted by a substituent.

[0677] In some embodiments, for the compound or salt of formula (III), when R 101 When R is bromine, iodine or hydroxyl, 102 Selected from fluorine, -N(R 124 )2、-OR 125 、-SR 124 、-C(O)R 124 、-C(O)OR 124 、-OC(O)R 124 、-OC(O)N(R 124 )2、-C(O)N(R 124 )2、-N(R 124 )C(O)R 124 、-N(R 124 )C(O)OR 124 、-N(R 124 )C(O)N(R 124 )2、-N(R124 )S(O)2(R 124 )、N(R 124 )SO2N(R 124 )、-N(R 124 )P(O)(OR 124 )R 124 、-S(O)R 124 、-S(O)2R 124 、-S(O)2N(R 124 )2, -NO2 and -CN; optionally one or more independently selected from R 130 Substituents substituted C 1-6 Alkyl; and C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 130 In some embodiments, when R 101 When R is bromine, iodine or hydroxyl, 102 Selected from fluorine, -N(R 124 )2、-OR 125 、-SR 124 、-C(O)R 124 、-C(O)OR 124 、-OC(O)R 124 、-OC(O)N(R 124 )2、-C(O)N(R 124 )2、-N(R 124 )C(O)R 124 、-N(R 124 )C(O)OR 124 、-N(R 124 )C(O)N(R 124 )2、-N(R 124 )S(O)2(R 124 )、N(R 124 )SO2N(R 124 )、-N(R 124 )P(O)(OR 124 )R 124 、-S(O)R 124 、-S(O)2R 124 、-S(O)2N(R 124 )2, -NO2 and -CN; optionally one or more independently selected from R 130 The substituents replace C 1-6 Alkyl; and C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 130 In some embodiments, when R 101When R is bromine, iodine or hydroxyl, 102 Selected from fluorine, -N(R 124 )2、-OR 125 、-SR 124 、-C(O)R 124 、-C(O)OR 124 、-OC(O)R 124 、-OC(O)N(R 124 )2、-C(O)N(R 124 )2、-N(R 124 )C(O)R 124 、-N(R 124 )C(O)OR 124 、-N(R 124 )C(O)N(R 124 )2、-N(R 124 )S(O)2(R 124 )、N(R 124 )SO2N(R 124 )、-N(R 124 )P(O)(OR 124 )R 124 、-S(O)R 124 、-S(O)2R 124 、-S(O)2N(R 124 )2, -NO2, -CN, optionally one or more independently selected from R 130 Substituents substituted C 1-6 In some embodiments, when R 101 When R is bromine, iodine or hydroxyl, 102 Selected from fluorine, -N(R 124 )2、-OR 125 、-SR 124 、-C(O)R 124 、-C(O)OR 124 、-OC(O)R 124 、-C(O)N(R 124 )2、-N(R 124 )C(O)R 124 、-N(R 124 )S(O)2(R 124 )、N(R 124 )SO2N(R 124 )、-N(R 124 )P(O)(OR 124 )R 124 、-S(O)R 124 、-S(O)2R 124 、-S(O)2N(R 124)2, -NO2, -CN, optionally one or more independently selected from R 130 Substituents substituted C 1-6 In some embodiments, when R 101 When R is bromine, iodine or hydroxyl, 102 Selected from fluorine, -N(R 124 )2、-OR 125 、-SR 124 、-C(O)R 124 、-C(O)OR 124 、-OC(O)R 124 、-C(O)N(R 124 )2、-N(R 124 )C(O)R 124 、-S(O)R 124 、-S(O)2R 124 、-S(O)2N(R 124 )2, -NO2, -CN, optionally one or more independently selected from R 130 Substituents substituted C 1-6 In some embodiments, when R 101 When R is bromine, iodine or hydroxyl, 102 Selected from fluorine, -N(R 124 )2、-OR 125 、-C(O)R 124 、-C(O)OR 124 、-OC(O)R 124 、-C(O)N(R 124 )2、-N(R 124 )C(O)R 124 、-S(O)R 124 , -NO2, -CN, optionally one or more independently selected from R 130 Substituents substituted C 1-6 In some embodiments, when R 101 When R is bromine, iodine or hydroxyl, 102 Selected from fluorine, -N(R 124 )2、-OR 125 、-C(O)R 124 、-C(O)OR 124 、-OC(O)R 124 , -NO2, -CN, optionally one or more independently selected from R 130 Substituents substituted C 1-6 In some embodiments, when R 101 When R is bromine, iodine or hydroxyl, 102 Selected from fluorine, -N(R 124 )2、-OR125 , -NO2, -CN, optionally one or more independently selected from R 130 Substituents substituted C 1-6 In some embodiments, when R 101 When R is bromine, iodine or hydroxyl, 102 Selected from fluorine, -N(R 124 )2、-OR 125 、-NO2、-CN、C 1-6 In some embodiments, when R 101 When R is bromine, iodine or hydroxyl, 102 Selected from fluorine, -NO2, -CN, C 1-6 In some embodiments, when R 101 When R is bromine, iodine or hydroxyl, 102 Selected from fluorine, -NO2 and -CN.

[0678] In some embodiments, for the compound or salt of formula (III), when R 101 Chloro, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 1-6 Haloalkyl, -OR 112 、-SR 111 、-N(R 111 )2、-C(O)R 111 、-OC(O)R 111 、-C(O)N(R 113 )2、-OC(O)N(R 111 )2、-N(R 111 )C(O)R 111 、-N(R 111 )C(O)OR 111 、-N(R 111 )C(O)N(R 111 )2、-N(R 111 )S(O)2(R 111 ), -NO2 or -CN; R 102 Selected from

[0679] Halogen, -OR 126 、-SR 126 、-N(R 126 )2、-C(O)R 126 、-C(O)OR 126 、-OC(O)R 126 、-OC(O)N(R 126 )2、-C(O)N(R 126 )2、-N(R126 )C(O)R 126 、-N(R 126 )C(O)OR 126 、-N(R 126 )C(O)N(R 126 )2、-N(R 126 )S(O)2(R 126 )、N(R 126 )SO2N(R 126 )、-N(R 126 )P(O)(OR 126 )R 126 、-S(O)R 126 、-S(O)2R 126 、-S(O)2N(R 126 )2, -NO2 and -CN;

[0680] Optionally, one or more independently selected from R 130 Substituents substituted C 1-6 Alkyl; and

[0681] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 130 Substituents substituted;

[0682] The condition is (i) when R 101 When it is NO2, R 102 cannot be methyl; (ii) when R 101 When it is methyl, R 102 cannot be chlorine; and (iii) when R 101 When it is chlorine, R 102 It cannot be bromine;

[0683] In some embodiments, for the compound or salt of formula (III), when R 101 Chloro, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 1-6 Haloalkyl, -OR 112 、-SR 111 、-N(R 111 )2、-C(O)R 111 、-OC(O)R 111 、-C(O)N(R 113 )2、-OC(O)N(R 111 )2、-N(R 111 )C(O)R 111 、-N(R 111 )C(O)OR111 、-N(R 111 )C(O)N(R 111 )2、-N(R 111 )S(O)2(R 111 ), -NO2 or -CN; R 102 Selected from halogen, -OR 126 、-SR 126 、-N(R 126 )2、-C(O)R 126 、-C(O)OR 126 、-OC(O)R 126 、-OC(O)N(R 126 )2、-C(O)N(R 126 )2、-N(R 126 )C(O)R 126 、-N(R 126 )C(O)OR 126 、-N(R 126 )C(O)N(R 126 )2、-N(R 126 )S(O)2(R 126 )、N(R 126 )SO2N(R 126 )、-N(R 126 )P(O)(OR 126 )R 126 、-S(O)R 126 、-S(O)2R 126 、-S(O)2N(R 126 )2, -NO2, -CN and optionally one or more independently selected from R 130 Substituents substituted C 1-6 alkyl; provided that (i) when R 101 When it is NO2, R 102 cannot be methyl; (ii) when R 101 When it is methyl, R 102 cannot be chlorine; and (iii) when R 101 When it is chlorine, R 102 In some embodiments, for compounds or salts of formula (III), when R 101 Chloro, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 1-6 Haloalkyl, -OR 112 、-SR 111 、-N(R 111 )2、-C(O)R 111 、-OC(O)R111 、-C(O)N(R 113 )2、-OC(O)N(R 111 )2、-N(R 111 )C(O)R 111 、-N(R 111 )C(O)OR 111 、-N(R 111 )C(O)N(R 111 )2、-N(R 111 )S(O)2(R 111 ), -NO2 or -CN; R 102 Selected from halogen, -OR 126 、-SR 126 、-N(R 126 )2、-C(O)R 126 、-C(O)OR 126 、-OC(O)R 126 、-C(O)N(R 126 )2、-N(R 126 )C(O)R 126 、-N(R 126 )S(O)2(R 126 )、N(R 126 )SO2N(R 126 ),-S(O)R 126 、-S(O)2R 126 、-S(O)2N(R 126 )2, -NO2, -CN and optionally one or more independently selected from R 130 Substituents substituted C 1-6 alkyl; provided that (i) when R 101 When it is NO2, R 102 cannot be methyl; (ii) when R 101 When it is methyl, R 102 cannot be chlorine; and (iii) when R 101 When it is chlorine, R 102 In some embodiments, for compounds or salts of formula (III), when R 101 Chloro, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 1-6 Haloalkyl, -OR 112 、-SR 111 、-N(R 111 )2、-C(O)R 111 、-OC(O)R 111 、-C(O)N(R 113)2、-OC(O)N(R 111 )2、-N(R 111 )C(O)R 111 、-N(R 111 )C(O)OR 111 、-N(R 111 )C(O)N(R 111 )2、-N(R 111 )S(O)2(R 111 ), -NO2 or -CN; R 102 Selected from halogen, -OR 126 、-N(R 126 )2、-C(O)R 126 、-C(O)OR 126 、-OC(O)R 126 、-C(O)N(R 126 )2、-N(R 126 )C(O)R 126 , -NO2, -CN and optionally one or more independently selected from R 130 Substituents substituted C 1-6 alkyl; provided that (i) when R 101 When it is NO2, R 102 cannot be methyl; (ii) when R 101 When it is methyl, R 102 cannot be chlorine; and (iii) when R 101 When it is chlorine, R 102 In some embodiments, for compounds or salts of formula (III), when R 101 Chloro, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 1-6 Haloalkyl, -OR 112 、-SR 111 、-N(R 111 )2、-C(O)R 111 、-OC(O)R 111 、-C(O)N(R 113 )2、-OC(O)N(R 111 )2、-N(R 111 )C(O)R 111 、-N(R 111 )C(O)OR 111 、-N(R 111 )C(O)N(R 111 )2、-N(R 111 )S(O)2(R 111), -NO2 or -CN; R 102 Selected from halogen, -OR 126 、-N(R 126 )2, -NO2, -CN and optionally one or more independently selected from R 130 Substituents substituted C 1-6 alkyl; provided that (i) when R 101 When it is NO2, R 102 cannot be methyl; (ii) when R 101 When it is methyl, R 102 cannot be chlorine; and (iii) when R 101 When it is chlorine, R 102 In some embodiments, for compounds or salts of formula (III), when R 101 Chloro, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 1-6 Haloalkyl, -OR 112 、-SR 111 、-N(R 111 )2、-C(O)R 111 、-OC(O)R 111 、-C(O)N(R 113 )2、-OC(O)N(R 111 )2、-N(R 111 )C(O)R 111 、-N(R 111 )C(O)OR 111 、-N(R 111 )C(O)N(R 111 )2、-N(R 111 )S(O)2(R 111 ), -NO2 or -CN; R 102 selected from halogen and optionally substituted by one or more independently selected from R 130 Substituents substituted C 1-6 alkyl; provided that (i) when R 101 When it is NO2, R 102 cannot be methyl; (ii) when R 101 When it is methyl, R 102 cannot be chlorine; and (iii) when R 101 When it is chlorine, R 102 In some embodiments, for compounds or salts of formula (III), when R 101 Chloro, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -OC 2-6Alkyl, -OC 1-6 Haloalkyl, -OR 112 、-SR 111 、-N(R 111 )2、-C(O)R 111 、-OC(O)R 111 、-C(O)N(R 113 )2、-OC(O)N(R 111 )2、-N(R 111 )C(O)R 111 、-N(R 111 )C(O)OR 111 、-N(R 111 )C(O)N(R 111 )2、-N(R 111 )S(O)2(R 111 ), -NO2 or -CN; R 102 Selected from halogen and C 1-6 alkyl; provided that (i) when R 101 When it is NO2, R 102 cannot be methyl; (ii) when R 101 When it is methyl, R 102 cannot be chlorine; and (iii) when R 101 When it is chlorine, R 102 It cannot be bromine.

[0684] In some embodiments, for the compound or salt of formula (III), when R 101 Chloro, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OR 112 、-SR 111 、-N(R 111 )2、-C(O)R 111 、-OC(O)R 111 、-C(O)N(R 113 )2、-OC(O)N(R 111 )2、-N(R 111 )C(O)R 111 , -NO2 or -CN; R 102 Selected from

[0685] Halogen, -OR 126 、-SR 126 、-N(R 126 )2、-C(O)R 126 、-C(O)OR 126 、-OC(O)R 126 、-OC(O)N(R126 )2、-C(O)N(R 126 )2、-N(R 126 )C(O)R 126 、-N(R 126 )C(O)OR 126 、-N(R 126 )C(O)N(R 126 )2、-N(R 126 )S(O)2(R 126 )、N(R 126 )SO2N(R 126 )、-N(R 126 )P(O)(OR 126 )R 126 、-S(O)R 126 、-S(O)2R 126 、-S(O)2N(R 126 )2, -NO2 and -CN;

[0686] Optionally, one or more independently selected from R 130 Substituents substituted C 1-6 Alkyl; and

[0687] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 130 Substituents substituted;

[0688] The condition is (i) when R 101 When it is NO2, R 102 cannot be methyl; (ii) when R 101 When it is methyl, R 102 cannot be chlorine; and (iii) when R 101 When it is chlorine, R 102 It cannot be bromine;

[0689] In some embodiments, for the compound or salt of formula (III), when R 101 Chloro, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OR 112 、-SR 111 、-N(R 111 )2、-C(O)R 111 、-OC(O)R 111 、-C(O)N(R 113 )2、-OC(O)N(R 111 )2、-N(R 111 )C(O)R 111, -NO2 or -CN; R 102 Selected from halogen, -OR 126 、-SR 126 、-N(R 126 )2、-C(O)R 126 、-C(O)OR 126 、-OC(O)R 126 、-OC(O)N(R 126 )2、-C(O)N(R 126 )2、-N(R 126 )C(O)R 126 、-N(R 126 )C(O)OR 126 、-N(R 126 )C(O)N(R 126 )2、-N(R 126 )S(O)2(R 126 )、N(R 126 )SO2N(R 126 )、-N(R 126 )P(O)(OR 126 )R 126 、-S(O)R 126 、-S(O)2R 126 、-S(O)2N(R 126 )2, -NO2, -CN and optionally one or more independently selected from R 130 Substituents substituted C 1-6 alkyl; provided that (i) when R 101 When it is NO2, R 102 cannot be methyl; (ii) when R 101 When it is methyl, R 102 cannot be chlorine; and (iii) when R 101 When it is chlorine, R 102 In some embodiments, for compounds or salts of formula (III), when R 101 Chloro, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OR 112 、-SR 111 、-N(R 111 )2、-C(O)R 111 、-OC(O)R 111 、-C(O)N(R 113 )2、-OC(O)N(R 111 )2、-N(R 111 )C(O)R 111 , -NO2 or -CN; R102 Selected from halogen, -OR 126 、-SR 126 、-N(R 126 )2、-C(O)R 126 、-C(O)OR 126 、-OC(O)R 126 、-C(O)N(R 126 )2、-N(R 126 )C(O)R 126 、-N(R 126 )S(O)2(R 126 )、N(R 126 )SO2N(R 126 ),-S(O)R 126 、-S(O)2R 126 、-S(O)2N(R 126 )2, -NO2, -CN and optionally one or more independently selected from R 130 Substituents substituted C 1-6 alkyl; provided that (i) when R 101 When it is NO2, R 102 cannot be methyl; (ii) when R 101 When it is methyl, R 102 cannot be chlorine; and (iii) when R 101 When it is chlorine, R 102 In some embodiments, for compounds or salts of formula (III), when R 101 Chloro, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OR 112 、-SR 111 、-N(R 111 )2、-C(O)R 111 、-OC(O)R 111 、-C(O)N(R 113 )2、-OC(O)N(R 111 )2、-N(R 111 )C(O)R 111 , -NO2 or -CN; R 102 Selected from halogen, -OR 126 、-N(R 126 )2、-C(O)R 126 、-C(O)OR 126 、-OC(O)R 126 、-C(O)N(R 126 )2、-N(R 126 )C(O)R 126, -NO2, -CN and optionally one or more independently selected from R 130 Substituents substituted C 1-6 alkyl; provided that (i) when R 101 When it is NO2, R 102 cannot be methyl; (ii) when R 101 When it is methyl, R 102 cannot be chlorine; and (iii) when R 101 When it is chlorine, R 102 In some embodiments, for compounds or salts of formula (III), when R 101 Chloro, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OR 112 、-SR 111 、-N(R 111 )2、-C(O)R 111 、-OC(O)R 111 、-C(O)N(R 113 )2、-OC(O)N(R 111 )2、-N(R 111 )C(O)R 111 , -NO2 or -CN; R 102 Selected from halogen, -OR 126 、-N(R 126 )2, -NO2, -CN and optionally one or more independently selected from R 130 Substituents substituted C 1-6 Alkyl; provided that (I) when R 101 When it is NO2, R 102 Cannot be methyl; (II) When R 101 When it is methyl, R 102 cannot be chlorine; and (iii) when R 101 When it is chlorine, R 102 In some embodiments, for compounds or salts of formula (III), when R 101 Chloro, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OR 112 、-SR 111 、-N(R 111 )2、-C(O)R 111 、-OC(O)R 111 、-C(O)N(R 113 )2、-OC(O)N(R 111 )2、-N(R 111)C(O)R 111 , -NO2 or -CN; R 102 selected from halogen and optionally substituted by one or more independently selected from R 130 Substituents substituted C 1-6 alkyl; provided that (i) when R 101 When it is NO2, R 102 cannot be methyl; (ii) when R 101 When it is methyl, R 102 cannot be chlorine; and (iii) when R 101 When it is chlorine, R 102 In some embodiments, for compounds or salts of formula (III), when R 101 Chloro, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OR 112 、-SR 111 、-N(R 111 )2、-C(O)R 111 、-OC(O)R 111 、-C(O)N(R 113 )2、-OC(O)N(R 111 )2、-N(R 111 )C(O)R 111 , -NO2 or -CN; R 102 Selected from halogen and C 1-6 alkyl; provided that (i) when R 101 When it is NO2, R 102 cannot be methyl; (ii) when R 101 When it is methyl, R 102 cannot be chlorine; and (iii) when R 101 When it is chlorine, R 102 It cannot be bromine.

[0690] In some embodiments, for the compound or salt of formula (III), when R 101 Chloro, -C 1-6 Alkyl, -OC 2-6 Alkyl, -OR 112 、-N(R 111 )2, -NO2 or -CN; R 102 Selected from

[0691] Halogen, -OR 126 、-SR 126 、-N(R 126 )2、-C(O)R 126 、-C(O)OR 126 、-OC(O)R126 、-OC(O)N(R 126 )2、-C(O)N(R 126 )2、-N(R 126 )C(O)R 126 、-N(R 126 )C(O)OR 126 、-N(R 126 )C(O)N(R 126 )2、-N(R 126 )S(O)2(R 126 )、N(R 126 )SO2N(R 126 )、-N(R 126 )P(O)(OR 126 )R 126 、-S(O)R 126 、-S(O)2R 126 、-S(O)2N(R 126 )2, -NO2 and -CN;

[0692] Optionally, one or more independently selected from R 130 Substituents substituted C 1-6 Alkyl; and

[0693] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 130 Substituents substituted;

[0694] The condition is (i) when R 101 When it is NO2, R 102 cannot be methyl; (ii) when R 101 When it is methyl, R 102 cannot be chlorine; and (iii) when R 101 When it is chlorine, R 102 It cannot be bromine;

[0695] In some embodiments, for the compound or salt of formula (III), when R 101 Chloro, -C 1-6 Alkyl, -OC 2-6 Alkyl, -OR 112 、-N(R 111 )2, -NO2 or -CN; R 102 Selected from halogen, -OR 126 、-SR 126 、-N(R 126 )2、-C(O)R 126 、-C(O)OR 126 、-OC(O)R 126、-OC(O)N(R 126 )2、-C(O)N(R 126 )2、-N(R 126 )C(O)R 126 、-N(R 126 )C(O)OR 126 、-N(R 126 )C(O)N(R 126 )2、-N(R 126 )S(O)2(R 126 )、N(R 126 )SO2N(R 126 )、-N(R 126 )P(O)(OR 126 )R 126 、-S(O)R 126 、-S(O)2R 126 、-S(O)2N(R 126 )2, -NO2, -CN and optionally one or more independently selected from R 130 Substituents substituted C 1-6 alkyl; provided that (i) when R 101 When it is NO2, R 102 cannot be methyl; (ii) when R 101 When it is methyl, R 102 cannot be chlorine; and (iii) when R 101 When it is chlorine, R 102 In some embodiments, for compounds or salts of formula (III), when R 101 Chloro, -C 1-6 Alkyl, -OC 2-6 Alkyl, -OR 112 、-N(R 111 )2, -NO2 or -CN; R 102 Selected from halogen, -OR 126 、-SR 126 、-N(R 126 )2、-C(O)R 126 、-C(O)OR 126 、-OC(O)R 126 、-C(O)N(R 126 )2、-N(R 126 )C(O)R 126 、-N(R 126 )S(O)2(R 126 )、N(R 126 )SO2N(R 126 ),-S(O)R 126 、-S(O)2R 126、-S(O)2N(R 126 )2, -NO2, -CN and optionally one or more independently selected from R 130 Substituents substituted C 1-6 alkyl; provided that (i) when R 101 When it is NO2, R 102 cannot be methyl; (ii) when R 101 When it is methyl, R 102 cannot be chlorine; and (iii) when R 101 When it is chlorine, R 102 In some embodiments, for compounds or salts of formula (III), when R 101 Chloro, -C 1-6 Alkyl, -OC 2-6 Alkyl, -OR 112 、-N(R 111 )2, -NO2 or -CN; R 102 Selected from halogen, -OR 126 、-N(R 126 )2、-C(O)R 126 、-C(O)OR 126 、-OC(O)R 126 、-C(O)N(R 126 )2、-N(R 126 )C(O)R 126 , -NO2, -CN and optionally one or more independently selected from R 130 Substituents substituted C 1-6 alkyl; provided that (i) when R 101 When it is NO2, R 102 cannot be methyl; (ii) when R 101 When it is methyl, R 102 cannot be chlorine; and (iii) when R 101 When it is chlorine, R 102 In some embodiments, for compounds or salts of formula (III), when R 101 Chloro, -C 1-6 Alkyl, -OC 2-6 Alkyl, -OR 112 、-N(R 111 )2, -NO2 or -CN; R 102 Selected from halogen, -OR 126 、-N(R 126 )2, -NO2, -CN and optionally one or more independently selected from R 130 Substituents substituted C 1-6 alkyl; provided that (i) when R 101 When it is NO2, R102 cannot be methyl; (ii) when R 101 When it is methyl, R 102 cannot be chlorine; and (iii) when R 101 When it is chlorine, R 102 In some embodiments, for compounds or salts of formula (III), when R 101 Chloro, -C 1-6 Alkyl, -OC 2-6 Alkyl, -OR 112 、-N(R 111 )2, -NO2 or -CN; R 102 selected from halogen and optionally substituted by one or more independently selected from R 130 Substituents substituted C 1-6 alkyl; provided that (i) when R 101 When it is NO2, R 102 cannot be methyl; (ii) when R 101 When it is methyl, R 102 cannot be chlorine; and (iii) when R 101 When it is chlorine, R 102 In some embodiments, for compounds or salts of formula (III), when R 101 Chloro, -C 1-6 Alkyl, -OC 2-6 Alkyl, -OR 112 、-N(R 111 )2, -NO2 or -CN; R 102 Selected from halogen and C 1-6 alkyl; provided that (i) when R 101 When it is NO2, R 102 cannot be methyl; (ii) when R 101 When it is methyl, R 102 cannot be chlorine; and (iii) when R 101 When it is chlorine, R 102 It cannot be bromine.

[0696] In some embodiments, for the compound or salt of formula (III), R 103 and R 104 Each occurrence is independently selected from

[0697] Halogen, -OR 114 、-SR 114 、-N(R 114 )2、-N(R 114 )C(O)R 114 、-C(O)R 114 、-C(O)OR 114 、-C(O)N(R114 )2, -NO2 and -CN;

[0698] C 1-4 Alkyl, which is optionally substituted by one or more independently selected from halogen, -OR 114 、-SR 114 、-N(R 114 )2、-N(R 114 )C(O)R 114 、-C(O)R 114 、-C(O)OR 114 、-C(O)N(R 114 )2, -NO2 and -CN; and

[0699] C 3-4 Carbocyclic and 3 to 4 membered heterocyclic rings, any of which are optionally substituted by one or more independently selected from halogen, -OR 114 、-SR 114 、-N(R 114 )2、-N(R 114 )C(O)R 114 、-C(O)R 114 、-C(O)OR 114 、-C(O)N(R 114 )2, -NO2 and -CN substituents.

[0700] In some embodiments, for the compound or salt of formula (III), R 103 and R 104 Each occurrence is independently selected from

[0701] Halogen, -OR 114 、-SR 114 、-N(R 114 )2、-N(R 114 )C(O)R 114 、-C(O)R 114 、-C(O)OR 114 、-C(O)N(R 114 )2, -NO2 and -CN;

[0702] C 1-4 Alkyl, which is optionally substituted by one or more independently selected from halogen, -OR 114 、-SR 114 、-N(R 114 )2、-N(R 114 )C(O)R 114 、-C(O)R 114 、-C(O)OR 114 、-C(O)N(R 114)2, -NO2 and -CN; and

[0703] C 3-4 carbocyclic and 3- to 4-membered heterocyclic rings.

[0704] In some embodiments, for the compound or salt of formula (III), R 103 and R 104 is independently selected at each occurrence from halogen, -OR 114 、-SR 114 、-N(R 114 )2、-N(R 114 )C(O)R 114 、-C(O)R 114 、-C(O)OR 114 、-C(O)N(R 114 )2, -NO2, -CN and C 1-4 Alkyl, the C 1-4 Alkyl is optionally substituted by one or more independently selected from halogen, -OR 114 、-SR 114 、-N(R 114 )2、-N(R 114 )C(O)R 114 、-C(O)R 114 、-C(O)OR 114 、-C(O)N(R 114 )2, -NO2 and -CN. In some embodiments, R 103 and R 104 is independently selected at each occurrence from halogen, -OR 114 、-SR 114 、-N(R 114 )2、-C(O)R 114 , -NO2, -CN and C 1-4 Alkyl, the C 1-4 Alkyl is optionally substituted by one or more independently selected from halogen, -OR 114 、-SR 114 、-N(R 114 )2、-N(R 114 )C(O)R 114 、-C(O)R 114 、-C(O)OR 114 、-C(O)N(R 114 )2, -NO2 and -CN. In some embodiments, R 103 and R 104 is independently selected at each occurrence from halogen, -OR 114 、-N(R 114)2, -NO2, -CN and C 1-4 Alkyl, the C 1-4 Alkyl is optionally substituted by one or more independently selected from halogen, -OR 114 、-SR 114 、-N(R 114 )2、-N(R 114 )C(O)R 114 、-C(O)R 114 、-C(O)OR 114 、-C(O)N(R 114 )2, -NO2 and -CN. In some embodiments, R 103 and R 104 is independently selected at each occurrence from halogen and C 1-4 Alkyl, the C 1-4 Alkyl is optionally substituted by one or more independently selected from halogen, -OR 114 、-SR 114 、-N(R 114 )2、-N(R 114 )C(O)R 114 、-C(O)R 114 、-C(O)OR 114 、-C(O)N(R 114 )2, -NO2 and -CN. In some embodiments, R 103 and R 104 is independently selected at each occurrence from halogen and C 1-4 Alkyl, the C 1-4 Alkyl is optionally substituted by one or more independently selected from halogen, -OR 114 、-SR 114 、-N(R 114 )2, -NO2 and -CN. In some embodiments, R 103 and R 104 is independently selected at each occurrence from halogen and C 1-4 Alkyl, the C 1-4 Alkyl is optionally substituted by one or more independently selected from halogen, -OR 114 、-N(R 114 )2, -NO2 and -CN. In some embodiments, R 103 and R 104 is independently selected at each occurrence from halogen and C 1-4 alkyl.

[0705] In some embodiments, for the compound or salt of formula (III), R 105 and R 105’are each independently selected from hydrogen and hydroxy; or R 105 and R 105’ In some embodiments, for the compound or salt of formula (III), R 105 and R 105’ are each independently selected from hydrogen and hydroxy. 105 and R 105’ Together they are =O.

[0706] In some embodiments, for the compound or salt of formula (III), R 106 and R 106’ are each independently selected from hydrogen and hydroxy; or R 106 and R 106’ Together they are =O, =N-OR 114 or =NR 114 In some embodiments, for the compound or salt of formula (III), R 106 and R 106’ are each independently selected from hydrogen and hydroxy. 106 and R 106’ Together they are =0. In some embodiments, R 106 and R 106’ Together =N-OR 114 .

[0707] In some embodiments, for the compound or salt of formula (III), r is selected from 0, 1, 2, and 3. In some embodiments, r is selected from 0 and 1.

[0708] In some embodiments, for the compound or salt of formula (III), s is selected from 0, 1, 2, and 3. In some embodiments, s is 0.

[0709] In some embodiments, for the compound or salt of formula (III), R 111 and R 114 Each occurrence is independently selected from

[0710] hydrogen;

[0711] Optionally, one or more independently selected from R 131 Substituents substituted C 1-6 Alkyl; and

[0712] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 131 substituted by a substituent.

[0713] In some embodiments, for the compound or salt of formula (III), R 111 and R114 Each occurrence is independently selected from

[0714] hydrogen;

[0715] Optionally, one or more independently selected from R 131 Substituents substituted C 1-6 Alkyl; and

[0716] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 131 substituted by a substituent.

[0717] In some embodiments, R 111 and R 114 are each independently selected at each occurrence from hydrogen; optionally replaced by one or more independently selected from R 131 Substituents substituted C 1-6 Alkyl; C 3-6 In some embodiments, R 111 and R 114 is independently selected at each occurrence from hydrogen and optionally substituted by one or more independently selected from R 131 Substituents substituted C 1-6 In some embodiments, R 111 and R 114 Each occurrence is independently selected from hydrogen and C 1-6 In some embodiments, R 111 and R 114 Each is hydrogen.

[0718] In some embodiments, for the compound or salt of formula (III), R 112 Each time it appears, select

[0719] One or more independently selected from R 132 Substituents substituted C 1-6 Alkyl; and

[0720] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 133 substituted by a substituent.

[0721] In some embodiments, for the compound or salt of formula (III), R 112 is selected at each occurrence from one or more independently selected from R 132 Substituents substituted C 1-6 Alkyl; and C 3-6Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 133 In some embodiments, R 112 is independently selected at each occurrence from one or more independently selected from R 132 Substituents substituted C 1-6 Alkyl; and C 3-6 In some embodiments, R 112 is one or more independently selected from R 132 Substituents substituted C 1-6 In some embodiments, R 112 It is C 1-6 alkyl.

[0722] In some embodiments, for the compound or salt of formula (III), R 113 Each time it appears, select

[0723] hydrogen;

[0724] Optionally, one or more independently selected from R 134 Substituents substituted C1 alkyl and C 3-6 Alkyl, and one or more independently selected from R 134 a C2 alkyl group substituted with a substituent of

[0725] C 3-5 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 134 substituted by a substituent.

[0726] In some embodiments, for the compound or salt of formula (III), R 113 Each time it appears, select

[0727] hydrogen;

[0728] Optionally, one or more independently selected from R 134 Substituents substituted C1 alkyl and C 3-6 Alkyl, and one or more independently selected from R 134 a C2 alkyl group substituted with a substituent of

[0729] C 3-5 carbocyclic rings and 3- to 6-membered heterocyclic rings.

[0730] In some embodiments, for the compound or salt of formula (III), R 113 is selected at each occurrence from hydrogen, optionally substituted by one or more independently selected from R 134 Substituents substituted C1 alkyl and C 3-6Alkyl, and one or more independently selected from R 134 In some embodiments, R 113 is selected at each occurrence from hydrogen, optionally substituted by one or more independently selected from R 134 C1 alkyl substituted with a substituent, and substituted with one or more independently selected from R 134 In some embodiments, R 113 is selected at each occurrence from hydrogen, optionally substituted by one or more independently selected from R 134 In some embodiments, R 113 is selected from hydrogen, C1 alkyl and C2 alkyl at each occurrence. In some embodiments, R 113 is selected from hydrogen and C1 alkyl at each occurrence. In some embodiments, R 113 For hydrogen.

[0731] In some embodiments, for the compound or salt of formula (III), R 121 、R 124 and R 126 Each occurrence is independently selected from

[0732] hydrogen;

[0733] Optionally, one or more independently selected from R 134 Substituents substituted C 1-6 Alkyl; and

[0734] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which are optionally substituted by one or more independently selected C 1-4 Alkyl, C 1-4 Haloalkyl and R 134 substituted by a substituent.

[0735] In some embodiments, for the compound or salt of formula (III), R 121 、R 124 and R 126 Each occurrence is independently selected from

[0736] hydrogen;

[0737] Optionally, one or more independently selected from R 134 Substituents substituted C 1-6 Alkyl; and

[0738] C 3-6 carbocyclic rings and 3- to 6-membered heterocyclic rings.

[0739] In some embodiments, for the compound or salt of formula (III), R121 、R 124 and R 126 is independently selected at each occurrence from hydrogen and optionally substituted by one or more independently selected from R 134 Substituents substituted C 1-6 In some embodiments, R 121 、R 124 and R 126 Each occurrence is independently selected from hydrogen and C 1-6 In some embodiments, R 121 、R 124 and R 126 Each is hydrogen.

[0740] In some embodiments, for the compound or salt of formula (III), R 122 and R 125 Each occurrence is independently selected from

[0741] Optionally, one or more independently selected from R 134 Substituents substituted C 2-6 Alkyl; and

[0742] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which are optionally substituted by one or more independently selected C 1-4 Alkyl, C 1-4 Haloalkyl and R 13 substituted by a substituent.

[0743] In some embodiments, for the compound or salt of formula (III), R 122 and R 125 Each occurrence is independently selected from optionally one or more independently selected from R 134 Substituents substituted C 2-6 Alkyl; and C 3-6 In some embodiments, R 122 and R 125 Each is optionally selected from one or more independently selected R 134 Substituents substituted C 2-6 In some embodiments, R 122 and R 125 Each is C 2-6 alkyl.

[0744] In some embodiments, for the compound or salt of formula (III), R 123 independently selected at each occurrence

[0745] hydrogen;

[0746] Optionally, one or more independently selected from R 134 Substituents substituted C 1-6 Alkyl; and

[0747] C 3-5 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which are optionally substituted by one or more independently selected C 1-4 Alkyl, C 1-4 Haloalkyl and R 134 Substituents substituted;

[0748] In some embodiments, for the compound or salt of formula (III), R 123 independently selected at each occurrence

[0749] hydrogen;

[0750] Optionally, one or more independently selected from R 134 Substituents substituted C 1-6 Alkyl; and

[0751] C 3-5 Carbocyclic and 3- to 6-membered heterocyclic rings;

[0752] In some embodiments, for the compound or salt of formula (III), R 123 is independently selected at each occurrence from hydrogen and optionally substituted by one or more independently selected from R 134 Substituents substituted C 1-6 In some embodiments, R 123 independently selected at each occurrence from hydrogen and C 1-6 alkyl.

[0753] In some embodiments, for the compound or salt of formula (III), R 130 、R 131 、R 132 、R 133 and R 134 Each occurrence is independently selected from

[0754] Halogen, -OR 141 、-SR 141 、-N(R 141 )2、-C(O)R 141 、-C(O)OR 141 、-OC(O)R 141 、-OC(O)N(R 141 )2、-C(O)N(R 141 )2、-N(R 141 )C(O)R 141 、-N(R 141 )C(O)OR 141、-N(R 141 )C(O)N(R 141 )2、-N(R 141 )S(O)2(R 141 )、-N(R 141 )SO2N(R 141 )、-N(R 141 )P(O)(OR 141 )R 141 、-S(O)R 141 、-S(O)2R 141 、-S(O)2N(R 141 )2, -NO2, =O, =S, -CN, C 3-6 carbocyclic rings and 3- to 7-membered heterocyclic rings.

[0755] In some embodiments, for the compound or salt of formula (III), R 130 、R 131 、R 132 、R 133 and R 134 is independently selected at each occurrence from halogen, -OR 141 、-SR 141 、-N(R 141 )2、-C(O)R 141 、-C(O)OR 141 、-OC(O)R 141 、-OC(O)N(R 141 )2、-C(O)N(R 141 )2、-N(R 141 )C(O)R 141 、-N(R 141 )C(O)OR 141 、-N(R 141 )C(O)N(R 141 )2、-N(R 141 )S(O)2(R 141 )、-N(R 141 )SO2N(R 141 )、-N(R 141 )P(O)(OR 141 )R 141 、-S(O)R 141 、-S(O)2R 141 、-S(O)2N(R 141 )2, -NO2, =O, =S and -CN. In some embodiments, R 130 、R 131 、R 132 、R 133 and R 134is independently selected at each occurrence from halogen, -OR 141 、-SR 141 、-N(R 141 )2、-C(O)R 141 、-C(O)OR 141 、-OC(O)R 141 、-C(O)N(R 141 )2、-N(R 141 )C(O)R 141 、-N(R 141 )S(O)2(R 141 )、-N(R 141 )SO2N(R 141 )、-N(R 141 )P(O)(OR 141 )R 141 、-S(O)R 141 、-S(O)2R 141 、-S(O)2N(R 141 )2, -NO2, =O, =S and -CN. In some embodiments, R 130 、R 131 、R 132 、R 133 and R 134 is independently selected at each occurrence from halogen, -OR 141 、-SR 141 、-N(R 141 )2、-C(O)R 141 、-C(O)OR 141 、-OC(O)R 141 、-C(O)N(R 141 )2、-N(R 141 )C(O)R 141 、-S(O)R 141 、-S(O)2R 141 、-S(O)2N(R 141 )2, -NO2, =O, =S and -CN. In some embodiments, R 130 、R 131 、R 132 、R 133 and R 134 is independently selected at each occurrence from halogen, -OR 141 、-SR 141 、-N(R 141 )2、-C(O)R 141 、-C(O)OR 141 、-OC(O)R 141 、-C(O)N(R 141)2、-N(R 141 )C(O)R 141 , -NO2, =O, =S and -CN. In some embodiments, R 130 、R 131 、R 132 、R 133 and R 134 is independently selected at each occurrence from halogen, -OR 141 、-SR 141 、-N(R 141 )2, -NO2, =O, =S and -CN. In some embodiments, R 130 、R 131 、R 132 、R 133 and R 134 is independently selected at each occurrence from halogen, -OR 141 、-SR 141 、-N(R 141 )2, -NO2, =O and -CN. In some embodiments, R 130 、R 131 、R 132 、R 133 and R 134 is independently selected at each occurrence from halogen, -OR 141 、-N(R 141 )2, -NO2, =O and -CN. In some embodiments, R 130 、R 131 、R 132 、R 133 and R 134 is independently selected at each occurrence from halogen, -OR 141 、-N(R 141 )2, -NO2 and -CN. In some embodiments, R 130 、R 131 、R 132 、R 133 and R 134 is independently selected at each occurrence from halogen, -NO2 and -CN.

[0756] In some embodiments, for the compound or salt of formula (III), R 141 independently selected at each occurrence from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl and C 1-6 In some embodiments, R 141 independently selected at each occurrence from hydrogen, C 1-6 Alkyl and C 1-6In some embodiments, R 141 independently selected at each occurrence from hydrogen, C 1-6 Alkyl and C 1-6 In some embodiments, R 141 independently selected at each occurrence from hydrogen and C 1-6 In some embodiments, R 141 At each occurrence, hydrogen.

[0757] In one aspect, provided herein are compounds having the structure of Formula (IV):

[0758]

[0759] or a pharmaceutically acceptable salt thereof; wherein

[0760] R 151 Selected from fluorine, bromine, -N(R 161 )2、-C(O)R 161 、-C(O)OR 161 、-OC(O)R 161 、-OC(O)N(R 161 )2、-C(O)N(R 161 )2、-N(R 161 )C(O)R 161 、-N(R 161 )C(O)OR 161 、-N(R 161 )C(O)N(R 161 )2、-N(R 161 )S(O)2(R 161 )、-N(R 161 )S(O)2N(R 161 )2、-SR 161 、-S(O)R 161 、-S(O)2R 161 、-S(O)2N(R 161 )2、-CN、-NO2、-C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 1-6 Haloalkyl, -OR 3-6 Carbocyclic ring and -OR 3-6 heterocyclic rings; and

[0761]

[0762] wherein each is optionally replaced by one or more independently selected R 171 Substituents substituted;

[0763] When R151 When it is fluorine, R 152 Selected from

[0764] Iodine, -NHR 192 、-OR 171 、-SR 171 、-C(=NR 196 )N(R 196 )2、-C(O)R 171 、-C(O)OR 171 、-OC(O)R 171 、-OC(O)N(R 171 )2、-C(O)N(R 171 )2、-N(R 193 )C(O)R 171 、-N(H)C(O)R 194 、-N(R 193 )C(O)OR 171 、-N(R 171 )C(O)N(R 171 )2、-N(R 171 )S(O)2(R 171 )、-N(R 171 )SO2N(R 171 )2、-N(R 171 )P(O)(OR 171 )R 171 、-S(O)R 171 、-S(O)2R 171 、-S(O)2N(R 171 )2、-NR 196 (C=NR 196 )N(R 196 )2, -N3 and -CN;

[0765] One or more independently selected from R 195 C1 alkyl substituted with a substituent, and optionally substituted with one or more independently selected from R 180 Substituents substituted C 2-6 alkyl;

[0766] as well as

[0767] C 3-6 Carbocyclic ring, 3-membered heterocyclic ring, 4-membered heterocyclic ring,

[0768] and 6-membered heterocyclic rings, any of which is optionally replaced by one or more independently selected R 180 Substituents substituted;

[0769] When R 151 for -SR 161 、-S(O)R 161 、-S(O)2R 161 or -S(O)2N(R 161 )2 or -CN, R 152 Selected from

[0770] Halogen, -N(R 174 )2、-OR 174 、-SR 174 、-C(O)R 174 、-C(O)OR 174 、-OC(O)R 174 、-OC(O)N(R 174 )2、-C(O)N(R 174 )2、-N(R 174 )C(O)R 174 、-N(R 174 )C(O)OR 174 、-N(R 174 )C(O)N(R 174 )2、-N(R 174 )S(O)2(R 174 )、-N(R 124 )SO2N(R 174 )2、-N(R 174 )P(O)(OR 174 )R 174 、-S(O)R 174 、-S(O)2R 174 、-S(O)2N(R 174 )2, -NO2 and -CN;

[0771] Optionally, one or more independently selected from R 180 Substituents substituted C 1-6 Alkyl; and

[0772] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 180 Substituents substituted;

[0773] When R 151 When it is bromine or -NO2, R 152 Selected from

[0774] Iodine, -OR 197 、-SR 176 、-NHR 178 、-C(O)R 176 、-C(O)OR 176 、-OC(O)R176 、-OC(O)N(R 176 )2、-C(O)N(R 176 )2、-N(R 176 )C(O)R 176 、-N(R 176 )C(O)OR 176 、-N(R 176 )C(O)N(R 176 )2、-N(R 176 )S(O)2(R 176 )、-N(R 176 )SO2N(R 176 )2、-N(R 176 )P(O)(OR 176 )R 176 、-S(O)R 176 、-S(O)2R 176 、-S(O)2N(R 176 )2, -NO2 and -CN;

[0775] One or more independently selected from R 180 C1 alkyl substituted by one or more independently selected from R 198 C1 alkyl substituted with a substituent and optionally substituted with one or more independently selected from R 180 Substituents substituted C 2-6 alkyl;

[0776] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 180 and

[0777] The condition is (i) when R 151 When it is NO2, R 152 cannot be one or more independently selected from R 180 and (ii) when R 151 When it is NO2, R 152

[0778] It cannot be ethyl;

[0779] When R 151 -C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 1-6 Haloalkyl, -OR 3-6 Carbocyclic ring, -OR 3-6 Heterocyclic, -N(R 161 )2、-C(O)R 161 、-OC(O)R161 、-C(O)N(R 161 )2、-OC(O)N(R 161 )2、-N(R 161 )C(O)R 161 、-N(R 161 )C(O)OR 161 、-N(R 161 )C(O)N(R 161 )2、-N(R 161 )S(O)2(R 161 ) or -N(R 161 )S(O)2N(R 161 )2, R 152 Selected from

[0780] Halogen, -OR 176 、-SR 176 、-N(R 176 )2、-C(O)R 176 、-C(O)OR 176 、-OC(O)R 176 、-OC(O)N(R 176 )2、-C(O)N(R 176 )2、-N(R 176 )C(O)R 176 、-N(R 176 )C(O)OR 176 、-N(R 176 )C(O)N(R 176 )2、-N(R 176 )S(O)2(R 176 )、-N(R 176 )SO2N(R 176 )2、-N(R 176 )P(O)(OR 176 )R 176 、-S(O)R 176 、-S(O)2R 176 、-S(O)2N(R 176 )2, -NO2 and -CN;

[0781] Optionally, one or more independently selected from R 177 Substituents substituted C 1-6 Alkyl; and

[0782] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 177 Substituents substituted;

[0783] R153 and R 154 Each occurrence is independently selected from

[0784] Halogen, -OR 164 、-NHR 178 、-N(R 164 )C(O)R 164 、-C(O)R 164 、-C(O)OR 164 、-C(O)N(R 164 )2, -NO2 and -CN;

[0785] C 1-4 Alkyl, optionally substituted with one or more substituents independently selected from the group consisting of halogen, -OR 164 、-SR 164 、-N(R 164 )2、-N(R 164 )C(O)R 164 、-C(O)R 164 、-C(O)OR 164 、-C(O)N(R 164 )2, -NO2 and -CN; and

[0786] C 3-6 Carbocyclic and 3 to 5 membered heterocyclic rings, any of which are optionally substituted by one or more substituents independently selected from the group consisting of halogen, -OR 164 、-SR 164 、-N(R 164 )2.

[0787] -N(R 164 )C(O)R 164 、-C(O)R 164 、-C(O)OR 164 、-C(O)N(R 164 )2, -NO2 and -CN;

[0788] R 155 and R 155’ are each independently selected from hydrogen, hydroxy and methyl; or R 155 and R 155’ Together = O;

[0789] R 156 and R 156’ are each independently selected from hydrogen, hydroxy and methyl; or R 156 and R 156’ Together they are =O, =N-OR 171 or =NR 171 ;

[0790] t is selected from 0, 1, 2, and 3;

[0791] u is selected from 0, 1, 2 and 3;

[0792] R 161 and R 164 Each occurrence is independently selected from

[0793] hydrogen;

[0794] Optionally, one or more independently selected from R 177 Substituents substituted C 1-6 Alkyl; and

[0795] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected R 177 Substituents substituted;

[0796] R 171 、R 174 and R 176 Each occurrence is independently selected from

[0797] hydrogen;

[0798] Optionally, one or more independently selected from R 180 Substituents substituted C 1-6 Alkyl; and

[0799] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which are optionally substituted by one or more independently selected C 1-4 Alkyl, C 1-4 Haloalkyl and R 180 Substituents substituted;

[0800] R 177 and R 180 Each occurrence is independently selected from

[0801] Halogen, -OR 191 、-SR 191 、-N(R 191 )2、-C(O)R 191 、-C(O)OR 191 、-OC(O)R 191 、-OC(O)N(R 191 )2、-C(O)N(R 191 )2、-N(R 191 )C(O)R 191 、-N(R 191 )C(O)OR 191 、-N(R 191 )C(O)N(R191 )2、-N(R 191 )S(O)2(R 191 )、-N(R 191 )SO2N(R 191 )2、-N(R 191 )P(O)(OR 191 )R 191 、-NR 196 (C=NR 196 )N(R 196 )2、-S(O)R 191 、-S(O)2R 191 、-S(O)2N(R 191 )2, -NO2, =O, =S, -CN, C 1-6 Alkyl, C 3-6 Carbocyclic and 3- to 7-membered heterocyclic rings;

[0802] R 178 Each time it appears, select

[0803] Optionally, one or more independently selected from R 180 Substituents substituted C 1-6 alkyl

[0804] base; and

[0805] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which are optionally replaced by one or more

[0806] Independently selected from R 180 Substituents substituted;

[0807] R 191 independently selected at each occurrence from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl and C 1-6 Hydroxyalkyl.

[0808] R 192 Each time it appears, select

[0809] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which are optionally replaced by one or more

[0810] Independently selected from R 180 Substituents substituted;

[0811] R 193 Each time it appears, select

[0812] Optionally, one or more independently selected from R 180 Substituents substituted C 1-6 alkyl

[0813] base; and

[0814] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which are optionally substituted by one or more independently selected C 1-4 Alkyl, C 1-4 Haloalkyl and R 180 Substituents substituted;

[0815] R 194 Each time it appears, select

[0816] One or more independently selected from R 180 Substituents substituted C 1-6 alkyl;

[0817] R 195 independently selected at each occurrence

[0818] Halogen, -NH2, -NHR 192 、-NR 196 (C=NR 196 )N(R 196 )2、-OR 171 、-SR 171 、-C(O)R 171 、-C(O)OR 171 、-OC(O)R 171 、-OC(O)N(R 171 )2、-C(O)N(R 171 )2、-N(R 171 )C(O)R 171 、-N(R 171 )C(O)R 171 、-N(R 193 )C(O)OR 171 、-N(R 171 )C(O)N(R 171 )2、-N(R 171 )S(O)2(R 171 )、-N(R 171 )S(O)2N(R 171 )2、-N(R 171 )P(O)(OR 171 )R 171 、-S(O)R 171 、-S(O)2R 171 and -S(O)2N(R 171 )2;

[0819] Optionally, one or more independently selected from R 180 Substituents substituted C1-6 Alkyl; and

[0820] C 5-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which are optionally substituted by one or more independently selected C 1-4 Alkyl, C 1-4 Haloalkyl and R 180 Substituents substituted;

[0821] R 196 Each time it appears, select

[0822] Hydrogen, -CN, and OR 171 ;

[0823] Optionally, one or more independently selected from R 180 Substituents substituted C 1-6 Alkyl; and

[0824] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which are optionally substituted by one or more independently selected C 1-4 Alkyl, C 1-4 Haloalkyl and R 180 Substituents substituted;

[0825] R 197 Each time it appears, select

[0826] hydrogen;

[0827] Optionally, one or more independently selected from R 180 Substituents substituted C 2-6 Alkyl; and

[0828] C 3-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which are optionally substituted by one or more independently selected C 1-4 Alkyl, C 1-4 Haloalkyl and R 180 Substituents substituted;

[0829] R 198 independently selected at each occurrence

[0830] Fluorine, chlorine, iodine, -NH2, -NHR 192 、-NR 196 (C=NR 196 )N(R 196 )2、-OR 171 、-SR 171 、-C(O)R 171 、-C(O)OR 171 、-OC(O)R 171 、-OC(O)N(R171 )2、-C(O)N(R 171 )2、-N(R 171 )C(O)R 171 、-N(R 171 )C(O)R 171 、-N(R 193 )C(O)OR 171 、-N(R 171 )C(O)N(R 171 )2、-N(R 171 )S(O)2(R 171 )、-N(R 171 )SO2N(R 171 )2、-N(R 171 )P(O)(OR 171 )R 171 、-S(O)R 171 、-S(O)2R 171 and -S(O)2N(R 171 )2;

[0831] Optionally, one or more independently selected from R 180 Substituents substituted C 2-6 Alkyl; and

[0832] C 5-6 Carbocyclic and 3 to 6 membered heterocyclic rings, any of which are optionally substituted by one or more independently selected C 1-4 Alkyl, C 1-4 Haloalkyl and R 180 Substituents substituted;

[0833] In some embodiments, for the compound or salt of (IV), R 151 Fluorine, bromine, -C(O)R 161 、-C(O)OR 161 、-C(O)N(R 161 )2、-N(R 161 )C(O)R 161 、-N(R 161 )S(O)2(R 161 ),-SR 161 、-S(O)R 161 、-S(O)2R 161 、-S(O)2N(R 161 )2、-CN、-NO2、-C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 1-6 haloalkyl or In some embodiments, for the compound or salt of (IV), R151 Fluorine, bromine, -C(O)R 161 、-C(O)OR 161 、-C(O)N(R 161 )2、-N(R 161 )C(O)R 161 、-SR 161 、-S(O)2R 161 、-S(O)2N(R 161 )2, -CN, -NO2 or In some embodiments, for the compound or salt of (IV), R 151 For fluorine, bromine, -SR 161 、-S(O)2R 161 , -CN, -NO2 or In some embodiments, for the compound or salt of (IV), R 151 In some embodiments, for the compound or salt of (IV), when R 151 When it is fluorine, R 152 Selected from -NHR 192 、-OR 171 、-SR 171 、-C(=NR 196 )N(R 196 )2、-C(O)R 171 、-C(O)OR 171 、-OC(O)R 171 、-C(O)N(R 171 )2、-N(H)C(O)R 194 、-N(R 171 )S(O)2(R 171 )、-S(O)2R 171 、-S(O)2N(R 171 )2、-NR 196 (C=NR 196 )N(R 196 )2, -N3, -CN, one or more independently selected from R 195 C1 alkyl substituted with a substituent, In some embodiments, for the compound or salt of (IV), when R 151 When it is fluorine, R 152 Selected from -NHR 192 、-C(=NR 196 )N(R 196 )2、-C(O)R 171 、-C(O)OR 171 、-C(O)N(R 171 )2、-N(H)C(O)R194 、-NR 196 (C=NR 196 )N(R 196 )2, -N3, -CN, one or more independently selected from R 195 C1 alkyl substituted with a substituent, In some embodiments, for the compound or salt of (IV), when R 151 When it is fluorine, R 152 Selected from NHR 192 、-C(=NR 196 )N(R 196 )2、-C(O)R 171 、-C(O)OR 171 、-NR 196 (C=NR 196 )N(R 196 )2, -N3, -CN, one or more independently selected from R 195 C1 alkyl substituted with a substituent, In some embodiments, for the compound or salt of (IV), when R 151 When it is fluorine, R 152 Selected from -NHR 192 、-C(=NR 196 )N(R 196 )2、-C(O)R 171 、-C(O)OR 171 and -NR 196 (C=NR 196 )N(R 196 ) 2. In some embodiments, for the compound or salt of (IV), when R 151 When it is fluorine, R 152 Selected from -N3, -CN, one or more independently selected from R 195 C1 alkyl substituted with a substituent, In some embodiments, for the compound or salt of (IV), when R 151 When it is fluorine, R 152 Selected from -NHR 192 、-C(=NR 196 )N(R 196 )2、-C(O)R 171 、-C(O)OR 171 and -NR 196 (C=NR 196 )N(R 196 ) 2. In some embodiments, for the compound or salt of (IV), when R 151 When it is fluorine, R 152 Selected from -NHR192 、-C(=NR 196 )N(R 196 )2 and -NR 196 (C=NR 196 )N(R 196 ) 2. In some embodiments, for the compound or salt of (IV), when R 151 When it is fluorine, R 152 Selected from -NHR 192 、-C(O)R 171 and -C(O)OR 171 In some embodiments, for the compound or salt of (IV), when R 151 When it is fluorine, R 152 NHR 192 In some embodiments, for the compound or salt of (IV), when R 151 When it is fluorine, R 152 -C(=NR 196 )N(R 196 ) 2. In some embodiments, for the compound or salt of (IV), when R 151 When it is fluorine, R 152 -C(O)R 171 In some embodiments, for the compound or salt of (IV), when R 151 When it is fluorine, R 152 -C(O)OR 171 In some embodiments, for the compound or salt of (IV), when R 151 When it is fluorine, R 152 -NR 196 (C=NR 196 )N(R 196 ) 2. In some embodiments, for the compound or salt of (IV), when R 151 When it is fluorine, R 152 Selected from one or more independently selected from R 195 C1 alkyl substituted with a substituent, In some embodiments, for the compound or salt of (IV), when R 151 When it is fluorine, R 152 In some embodiments, for the compound or salt of (IV), when R 151 When it is fluorine, R 152 In some embodiments, for the compound or salt of (IV), when R 151 When it is fluorine, R 152 is one or more independently selected from R 195In some embodiments, for the compound or salt of (IV), when R 151 When it is fluorine, R 152 for In some embodiments, for the compound or salt of (IV), when R 151 When it is fluorine, R 152 for

[0834] In some embodiments, for the compound or salt of (IV), R 151 for -SR 161 、-S(O)R 161 、-S(O)2R 161 、-S(O)2N(R 161 )2 or -CN. In some embodiments, for the compound or salt of (IV), R 151 For-SR 161 、-S(O)2R 161 , -CN or In some embodiments, for the compound or salt of (IV), R 151 For-SR 161 In some embodiments, for the compound or salt of (IV), R 151 is -S(O)2R 161 In some embodiments, for the compound or salt of (IV), R 151 In some embodiments, for the compound or salt of (IV), R 151 for In some embodiments, for the compound or salt of (IV), when R 151 For-SR 161 、-S(O)2R 161 , -CN or When R 152 Selected from halogen, -N(R 174 )2、-OR 174 、-SR 174 、-C(O)R 174 、-C(O)OR 174 、-OC(O)R 174 、-C(O)N(R 174 )2、-N(R 174 )C(O)R 174 、-N(R 174 )C(O)OR 174 、-N(R 174 )S(O)2(R 174 )、-S(O)2R174 、-S(O)2N(R 174 )2, -NO2, -CN, optionally one or more independently selected from R 180 Substituents substituted C 1-6 alkyl and optionally one or more independently selected from R 180 In some embodiments, for the compound or salt of (IV), when R 151 For-SR 161 、-S(O)2R 161 , -CN or When R 152 Selected from halogen, -N(R 174 )2、-OR 174 、-C(O)N(R 174 )2、-N(R 174 )C(O)R 174 、-N(R 174 )C(O)OR 174 , -NO2, -CN, optionally one or more independently selected from R 180 Substituents substituted C 1-6 alkyl and optionally one or more independently selected from R 180 In some embodiments, for the compound or salt of (IV), when R 151 For-SR 161 、-S(O)2R 161 , -CN or When R 152 Selected from -C(O)N(R 174 )2、-N(R 174 )C(O)R 174 、-N(R 174 )C(O)OR 174 , optionally one or more independently selected from R 180 Substituents substituted C 1-6 alkyl and optionally one or more independently selected from R 180 In some embodiments, for the compound or salt of (IV), when R 151 For-SR 161 When R 152 Selected from -C(O)N(R 174 )2、-N(R 174 )C(O)R 174 、-N(R 174 )C(O)OR 174 , optionally one or more independently selected from R 180 Substituents substituted C1-6 alkyl and optionally one or more independently selected from R 180 In some embodiments, for the compound or salt of (IV), when R 151 is -S(O)2R 161 When R 152 Selected from -C(O)N(R 174 )2、-N(R 174 )C(O)R 174 、-N(R 174 )C(O)OR 174 , optionally one or more independently selected from R 180 Substituents substituted C 1-6 alkyl and optionally one or more independently selected from R 180 In some embodiments, for the compound or salt of (IV), when R 151 When it is -CN, R 152 Selected from -C(O)N(R 174 )2、-N(R 174 )C(O)R 174 、-N(R 174 )C(O)OR 174 , optionally one or more independently selected from R 180 Substituents substituted C 1-6 alkyl and optionally one or more independently selected from R 180 In some embodiments, for the compound or salt of (IV), when R 151 for When R 152 Selected from -C(O)N(R 174 )2、-N(R 174 )C(O)R 174 、-N(R 174 )C(O)OR 174 , optionally one or more independently selected from R 180 Substituents substituted C 1-6 alkyl and optionally one or more independently selected from R 180 A 5-membered heterocyclic ring substituted with a substituent.

[0835] In some embodiments, for the compound or salt of (IV), R 151 is bromine or -NO2. In some embodiments, for the compound or salt of (IV), R 151 In some embodiments, for the compound or salt of (IV), R 151In some embodiments, for the compound or salt of (IV), when R 151 When it is bromine or -NO2, R 152 Select from -OR 197 、-SR 176 、-NHR 178 、-C(O)R 176 、-C(O)OR 176 、-C(O)N(R 176 )2、-N(R 176 )C(O)R 176 、-N(R 176 )S(O)2(R 176 )、-S(O)2R 176 、-S(O)2N(R 176 )2, -NO2, -CN, one or more independently selected from R 180 C1 alkyl substituted by one or more independently selected from R 198 C1 alkyl substituted with a substituent and optionally substituted with one or more independently selected from R 180 Substituents substituted C 2-6 alkyl, provided that (i) when R 151 When it is NO2, R 152 cannot be one or more independently selected from R 180 and (ii) when R 151 When it is NO2, R 152 In some embodiments, for the compound or salt of (IV), when R 151 When it is bromine or -NO2, R 152 Selected from one or more independently selected from R 180 C1 alkyl substituted by one or more independently selected from R 198 C1 alkyl substituted with a substituent and optionally substituted with one or more independently selected from R 180 Substituents substituted C 2-6 alkyl, provided that (i) when R 151 When it is NO2, R 152 cannot be one or more independently selected from R 180 and (ii) when R 151 When it is NO2, R 152 In some embodiments, for the compound or salt of (IV), R 151 is bromine and R 152 is one or more independently selected from R 180In some embodiments, for the compound or salt of (IV), R 151 is -NO2 and R 152 is one or more independently selected from R 198 In some embodiments, for the compound or salt of (IV), when R 151 When it is bromine, R 152 Select from -OR 197 、-SR 176 、-NHR 178 、-C(O)R 176 、-C(O)OR 176 、-C(O)N(R 176 )2、-N(R 176 )C(O)R 176 、-N(R 176 )S(O)2(R 176 )、-S(O)2R 176 、-S(O)2N(R 176 )2, -NO2, -CN, one or more independently selected from R 180 C1 alkyl substituted by one or more independently selected from R 198 C1 alkyl substituted with a substituent and optionally substituted with one or more independently selected from R 180 Substituents substituted C 2-6 In some embodiments, for the compound or salt of (IV), when R 151 When it is -NO2, R 152 Select from -OR 197 、-SR 176 、-NHR 178 、-C(O)R 176 、-C(O)OR 176 、-C(O)N(R 176 )2、-N(R 176 )C(O)R 176 、-N(R 176 )S(O)2(R 176 )、-S(O)2R 176 、-S(O)2N(R 176 )2, -NO2, -CN, one or more independently selected from R 180 C1 alkyl substituted by one or more independently selected from R 198 C1 alkyl substituted with a substituent and optionally substituted with one or more independently selected from R 180 Substituents substituted C 2-6 alkyl, provided that (i) R 152cannot be one or more independently selected from R 180 C1 alkyl substituted with a substituent; and (ii) R 152 It cannot be ethyl.

[0836] In some embodiments, for the compound or salt of (IV), R 153 and R 154 is independently selected at each occurrence from halogen and C 1-4 In some embodiments, for the compound or salt of (IV), R 155 and R 155’ Together they are =0. In some embodiments, for the compound or salt of (IV), R 156 and R 156’ Together they are =0. In some embodiments, for the compound or salt of (IV), R 156 and R 156’ Together =N-OR 171 In some embodiments, for the compound or salt of (IV), R 156 and R 156’ Each is independently selected from hydroxyl and methyl. In some embodiments, for the compound or salt of (IV), t is selected from 0 and 1. In some embodiments, for the compound or salt of (IV), u is 0.

[0837] In some aspects, the compound is any compound shown in Table 1, or a pharmaceutically acceptable salt or solvate thereof.

[0838] Table 1

[0839]

[0840]

[0841]

[0842]

[0843]

[0844]

[0845]

[0846]

[0847]

[0848]

[0849]

[0850]

[0851]

[0852]

[0853]

[0854]

[0855]

[0856]

[0857]

[0858]

[0859]

[0860]

[0861] Although preferred embodiments of the present invention have been shown and described herein, it will be apparent to those skilled in the art that these embodiments are provided by way of example only. Many variations, modifications, and substitutions will now occur to those skilled in the art without departing from the present invention. It will be understood that various alternatives to the embodiments of the present invention described herein may be employed in practicing the present invention. The following claims are intended to define the scope of the present invention and are intended to encompass methods and structures within the scope of these claims and their equivalents.

[0862] Chemical entities having carbon-carbon double bonds or carbon-nitrogen double bonds can exist in the Z form or the E form (or cis or trans). In addition, some chemical entities can exist in various tautomeric forms. Unless otherwise indicated, the compounds or salts of formula (I), (II), (III) and (IV) are also intended to include all Z forms, E forms and tautomeric forms.

[0863] "Isomers" are different compounds with the same molecular formula. "Stereoisomers" are isomers that differ only in the way their atoms are arranged in space. "Enantiomers" are a pair of stereoisomers that are non-superimposable mirror images of each other. A 1:1 mixture of a pair of enantiomers is a "racemic" mixture. The term "(±)" is used to denote a racemic mixture where appropriate. "Diastereomers" or "diastereomers" are stereoisomers that have at least two asymmetric atoms but are not mirror images of each other. Absolute stereochemistry is designated according to the Cahn-Ingold-Prelog R-S system. When a compound is a pure enantiomer, the stereochemistry of each chiral carbon can be designated as R or S. Resolved compounds whose absolute configuration is unknown can be designated as (+) or (-) based on the direction (right- or left-handed) that they rotate plane-polarized light at the wavelength of the sodium D line. Certain compounds described herein contain one or more asymmetric centers and can therefore produce enantiomers, diastereomers, and other stereoisomeric forms, whose asymmetric centers can be defined as CAN- or (S)- in terms of absolute stereochemistry. The chemical entities, pharmaceutical compositions, and methods of the present invention are intended to include all such possible stereoisomers, including racemic mixtures, optically pure forms, diastereomeric mixtures, and intermediate mixtures. Optically active CAN- and (S)-isomers can be prepared using chiral synthons or chiral reagents, or resolved using conventional techniques. The optical activity of the compounds can be analyzed by any suitable method, including but not limited to chiral chromatography and optical rotation, and the degree of dominance of one stereoisomer over another can be determined.

[0864] In some cases, the compounds or salts of formula (I), (II), (III) and (IV) herein may exist as diastereomers, enantiomers or other stereoisomeric forms. The compounds provided herein include all diastereomers, enantiomers and epimers as well as racemates, diastereomeric mixtures and other mixtures thereof, as long as they can be prepared by ordinary skill in the art by routine experimentation. The separation of stereoisomers can be carried out by chromatography or by forming diastereomers and separating by recrystallization or chromatography or any combination thereof. (Jean Jacques, Andre Collet, Samuel H. Wilen, "Enantiomers, Racemates and Resolutions", John Wiley And Sons, Inc., 1981, incorporated herein by reference for use in this disclosure). Stereoisomers can also be obtained by stereoselective synthesis. In addition, a mixture of two enantiomers enriched in one of the two enantiomers can be purified by recrystallization and / or grinding to provide a further optically enriched form of the major enantiomer.

[0865] In certain embodiments, the compound or salt of Formula (I), (II), (III) and (IV) may comprise two or more enantiomers or diastereomers of the compound, wherein a single enantiomer or diastereomer comprises at least about 70% by weight, at least about 80% by weight, at least about 90% by weight, at least about 98% by weight, or at least about 99% by weight or more of the total weight of all stereoisomers. Methods for producing substantially pure enantiomers are well known to those skilled in the art. For example, a single stereoisomer, such as an enantiomer, which is substantially free of its stereoisomers, can be obtained by resolving a racemic mixture using methods such as those for forming diastereomers using optically active resolving agents (Stereochemistry of Carbon Compounds, (1962), EL Elliel, McGraw Hill; Lochmuller (1975) J. Chromatogr., 113(3): 283-302). Racemic mixtures of chiral compounds can be separated and isolated by any suitable method, including, but not limited to: (1) formation of ionic diastereomeric salts with chiral compounds and separation by fractional crystallization or other methods, (2) formation of diastereomeric compounds with chiral derivatizing reagents, separation of the diastereomers, and conversion to pure stereoisomers, and (3) direct separation of substantially pure or enriched stereoisomers under chiral conditions. Another method for separating enantiomers is to use a Diacel chiral column and elution with an organic mobile phase, such as is available on a fee-for-service basis from Chiral Technologies (www.chiraltech.com).

[0866] "Tautomers" refer to molecules in which a proton can be transferred from one atom of a molecule to another atom of the same molecule. In certain embodiments, the compounds or salts of Formula (I), (II), (III), and (IV) exist as tautomers. Where tautomerism is possible, a chemical equilibrium of tautomers may exist. The exact ratio of tautomers depends on several factors, including physical state, temperature, solvent, and pH. Some non-limiting examples of tautomeric equilibria include:

[0867]

[0868] In some embodiments, the compounds disclosed herein are in different isotopically enriched forms, e.g., 2 H. 3 H. 11 C. 13 C and / or 14In a specific embodiment, the compound is deuterated at at least one position. This deuterated form can be prepared by the methods described in U.S. Patent Nos. 5,846,514 and 6,334,997. As described in U.S. Patent Nos. 5,846,514 and 6,334,997, deuteration can improve metabolic stability and / or efficacy, thereby increasing the duration of action of the drug.

[0869] In certain embodiments, some or all of the compounds disclosed herein 1 H atoms are 2 H atom substitution. Methods for the synthesis of deuterium-containing compounds are known in the art and include, by way of non-limiting example only, the following synthetic methods.

[0870] Deuterium-substituted compounds are synthesized using various methods, such as those described in Dean, Dennis C.; ed. Recent Advances in the Synthesis and Applications of Radiolabeled Compounds for Drug Discovery and Development. [In: Curr., Pharm. Des., 2000; 6(10)] 2000, 110 pp; George W.; Varma, Rajender S. The Synthesis of Radiolabeled Compounds via Organometallic Intermediates, Tetrahedron, 1989, 45(21), 6601-21; and Evans, E. Anthony. Synthesis of radiolabeled compounds, J. Radioanal. Chem., 1981, 64(1-2), 9-32.

[0871] Deuterated starting materials are readily available and are subjected to the synthetic methods described herein to provide the synthesis of deuterium-containing compounds. A large number of deuterium-containing reagents and building blocks are commercially available from chemical suppliers such as Aldrich Chemical Co.

[0872] Unless otherwise stated, the compounds described herein are intended to include compounds that differ only in the presence of one or more isotopically enriched atoms. For example, a compound having the disclosed structures, except for the replacement of hydrogen by deuterium or tritium, or by 13 C or 14 All other carbon-rich carbon substitutions are within the scope of the present disclosure.

[0873] The compounds of the present disclosure optionally contain unnatural proportions of atomic isotopes at one or more of the atoms that constitute such compounds. For example, the compounds may be labeled with an isotope, such as deuterium ( 2 H), tritium ( 3 H), iodine-125 ( 125 I) or carbon 14 ( 14 C). 2 H. 11 C. 13 C. 14 C. 15 C. 12 N. 13 N. 15 N. 16 N. 16 O. 17 O. 14 F. 15 F. 16 F. 17 F. 18 F. 33 S. 34 S. 35 S. 36 S. 35 Cl, 37 Cl, 79 Br, 81 Br and 125 Isotopic substitutions of I are contemplated. All isotopic variations of the compounds of the present invention, whether radioactive or not, are encompassed within the scope of the present invention.

[0874] The present disclosure includes salts of compounds of formula (I), (II), (III) and (IV), particularly pharmaceutically acceptable salts. The compounds of the present disclosure may have sufficient acidity, sufficient basicity or both functional groups to react with any of a number of inorganic bases and inorganic and organic acids to form salts. Alternatively, inherently charged compounds (such as compounds with quaternary ammonium nitrogen) may form salts with appropriate counterions (e.g., halides such as bromide, chloride or fluoride, particularly bromide).

[0875] The methods and compositions of Formula (I), (II), (III) and (IV) include the use of amorphous forms as well as crystalline forms (also known as polymorphs). The compounds described herein may be in the form of pharmaceutically acceptable salts. Likewise, in some embodiments, active metabolites of these compounds having the same type of activity are also included within the scope of this disclosure. In addition, the compounds described herein may exist in unsolvated forms as well as solvated forms with pharmaceutically acceptable solvents such as water, ethanol, etc. The solvated forms of the compounds provided herein are also considered to be disclosed herein.

[0876] Compounds of Formula (I), (II), (III) and (IV) also include crystalline and amorphous forms of those compounds, pharmaceutically acceptable salts and active metabolites of these compounds having the same type of activity, including, for example, polymorphs, pseudopolymorphs, solvates, hydrates, unsolvated polymorphs (including anhydrates), conformational polymorphs and amorphous forms of the compounds, and mixtures thereof.

[0877] The present disclosure includes salts of compounds represented by formula (I), (II), (III) and (IV), particularly pharmaceutically acceptable salts. The compounds of the present invention have sufficient acidity, sufficient basicity or both functional groups to react with any of a number of inorganic bases and inorganic and organic acids to form salts. Alternatively, inherently charged compounds (such as compounds with quaternary ammonium nitrogen) can form salts with appropriate counterions (e.g., halides, such as bromide, chloride or fluoride, particularly bromide).

[0878] In certain embodiments, the compound or salt of formula (I), (II), (III) and (IV) can be a prodrug, for example, wherein the hydroxyl group in the parent compound exists in the form of an ester or carbonate, or the carboxylic acid present in the parent compound exists in the form of an ester. The term "prodrug" is intended to include compounds that are converted into the medicament of the present disclosure under physiological conditions. A method of making a prodrug is to include one or more selected parts that are hydrolyzed under physiological conditions to display the desired molecule. In other embodiments, the prodrug is converted by the enzymatic activity of a host animal (such as a specific target cell in a host animal). For example, esters or carbonates (for example, esters or carbonates of an alcohol or carboxylic acid and phosphonates) are preferred prodrugs of the present disclosure.

[0879] Prodrugs are often useful because, in some cases, they may be easier to administer than the parent drug. For example, they may be bioavailable by oral administration, whereas the parent drug is not. Prodrugs may help enhance the cell permeability of the compound relative to the parent drug. Prodrugs may also have improved solubility in pharmaceutical compositions compared to the parent drug. Prodrugs can be designed as reversible drug derivatives, used as modifiers to enhance drug transport to site-specific tissues or increase drug residence time within cells.

[0880] In certain embodiments, the prodrug can be converted to the parent compound by enzymatic or chemical means under intracellular conditions. In certain embodiments, the parent compound comprises an acidic portion, such as an acidic portion produced by hydrolysis of the prodrug, which can be charged under intracellular conditions. In certain embodiments, the prodrug is converted to the parent compound once it passes through the cell membrane and enters the cell. In certain embodiments, the parent compound has reduced cell membrane permeability relative to the prodrug, such as reduced lipophilicity and increased hydrophilicity.

[0881] In some embodiments, the design of the prodrug increases the lipophilicity of the agent. In some embodiments, the design of the prodrug increases the effective water solubility. See, e.g., Fedorak et al., Am. J. Physiol., 269:G210-218 (1995); McLoed et al., Gastroenterol, 106:405-413 (1994); Hochhaus et al., Biomed. Chrom., 6:283-286 (1992); J. Larsen and H. Bundgaard, Int. J. Pharmaceutics, 37, 87 (1987); J. Larsen et al., Int. J. Pharmaceutics, 47, 103 (1988); Sinkula et al., J. Pharm. Sci., 64:181-210 (1975); T. Higuchi and V. Stella, Pro-drugs as Novel Delivery Systems, ACS Symposium Series Vol. 14; and Edward B. Roche, Bioreversible Carriers in Drug Delivery Systems. Design, American Pharmaceutical Association and Pergamon Press, 1987, both incorporated herein for such disclosure). According to another embodiment, the present disclosure provides methods for producing the compounds defined above. The compounds can be synthesized using conventional techniques. Advantageously, these compounds can be conveniently synthesized from readily available starting materials.

[0882] Synthetic chemistry transformations and methods useful for synthesizing the compounds described herein are known in the art and include, for example, those described in R. Larock, Comprehensive Organic Transformations (1989); T. W. Greene and PGM Wuts, Protective Groups in Organic Synthesis, 2nd ed. (1991); L. Fieser and M. Fieser, Fieser and Fieser's Reagents for Organic Synthesis (1994); and L. Paquette, ed., Encyclopedia of Reagents for Organic Synthesis (1995).

[0883] pharmaceutical preparations

[0884] In some aspects, the present disclosure provides a pharmaceutical composition comprising a compound or salt of Formula (I), (II), (III), or (IV) and at least one pharmaceutically acceptable excipient.

[0885] Pharmaceutical compositions can be formulated using one or more physiologically acceptable carriers (including excipients and adjuvants). Formulations can be modified according to the selected route of administration. Pharmaceutical compositions comprising compounds, salts or conjugates can be manufactured by, for example, lyophilizing compounds, salts or conjugates, mixing, dissolving, emulsifying, encapsulating or embedding conjugates. Pharmaceutical compositions can also include compounds, salts or conjugates in the form of free bases or pharmaceutically acceptable salts.

[0886] The method for preparing the conjugate can include preparing any one of the compound, salt or conjugate with one or more inert, pharmaceutically acceptable excipients or carriers to form a solid, semisolid or liquid composition. Solid compositions can include, for example, powders, tablets, dispersible particles and capsules, and in some aspects, solid compositions also contain non-toxic auxiliary substances, such as wetting agents or emulsifiers, pH buffers and other pharmaceutically acceptable additives. Alternatively, the compound, salt or conjugate can be lyophilized or in powder form for reconstitution with a suitable vehicle (e.g., sterile pyrogen-free water) before use.

[0887] The pharmaceutical composition can comprise at least one active ingredient (e.g., a compound, salt, or conjugate). The active ingredi...

Claims

1. A compound of formula (I): or a pharmaceutically acceptable salt thereof; wherein R 1 Selected from fluorine, chlorine, bromine, hydroxyl, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -OC 1-6 Alkyl, -OC 1-6 Haloalkyl, -OR 12 、-SR 11 、-N(R 13 )2. -C(O)R 11 、-C(O)OR 11 、-OC(O)R 11 、-OC(O)N(R 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-N(R 11 )C(O)OR 11 、-N(R 11 )C(O)N(R 11 )2、-N(R 11 )S(O)2(R 11 )、-S(O)2R 11 、-S(O)2N(R 11 )2, -NO2, -N3 and -CN; When R 1 When it is hydroxyl, -O-C1 alkyl or -NO2, R 2 Selected from Fluorine, bromine, iodine, -OR 22 , SR 21 、-N(R 21 )2. -C(O)R 21 、-OC(O)R 21 , -OC(O)N(R 21 )2, -N(R 21 )C(O)R 21 , -N(R 21 )C(O)OR 21 , -N(R 21 )C(O)N(R 21 )2, -N(R 21 )S(O)2(R 21 ), -N(R 21 )SO2N(R 21 ), -N(R 21 )P(O)(OR 21 )R 21 ), -S(O)2R 21 ), -S(O)2N(R 21 )2, -NO2 and -CN; Optionally one or more independently selected from R 30 Substituents substituted with C 1-6 Alkyl; and C 3-6 carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected from R 30 Substituents are substituted; When R 1 When it is fluorine, R 2 Selected from bromine, OR 23 -N(H)R 23 -C(O)R 23 -C(O)N(R 23 )2, -C(O)OR 23 , -OC(O)R 23 ,-OC(O)N(R 23 )2, -N(R 23 )C(O)R 23 , -N(R 23 )C(O)OR 23 , -N(R 23 )C(O)N(R 23 )2, -N(R 23 )S(O)2R 23 , -N(R 23 )SO2N(R 23 )2, -N(R 23 )P(O)(OR 23 )R 23 , -S(O)2R 23 , -S(O)2N(R 23 )2, -NO2 and -CN; Optionally one or more independently selected from R 30 Substituents substituted with C 1-6 Alkyl; and C 3-6 Carbocyclic ring, 3- to 4-membered heterocyclic ring, Any one of which is optionally selected from one or more independently selected from R 30 Substituents are substituted; When R 1 When R is C1 alkyl, -O-C1 haloalkyl, hydroxyl, chlorine or bromine, 2 Selected from: iodine, -OR 25 , -C(O)R 24 , -C(O)OR 25 , -OC(O)R 24 , -OC(O)N(R 24 )2, -C(O)N(R 24 )2, -N(R 24 )C(O)R 24 , -N(R 24 )C(O)OR 24 , -N(R 24 )C(O)N(R 24 )2, -N(R 24 )S(O)2(R 24 ), N(R 24 )SO2N(R 24 )2, -N(R 24 )P(O)(OR 24 )R 24 , -S(O)R 24 , -S(O)2R 24 , -S(O)2N(R 24 )2, -NO2 and -CN; Optionally one or more independently selected from R 30 Substituents substituted with C 2-6 alkyl; C 3-6 carbocyclic and 3 to 5 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected from R 30 substituted with a substituent; and When R 1 When R is selected from bromine, hydroxyl and C1 alkyl, 2 further selected from fluorine; When R 1 C 2-6 Alkyl, C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 2-6 Haloalkyl, -OR 12 、-SR 11 、-N(R 13 )2. -C(O)R 11 、-C(O)OR 11 、-OC(O)R 11 、-OC(O)N(R 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-N(R 11 )C(O)OR 11 、-N(R 11 )C(O)N(R 11 )2、-N(R 11 )S(O)2(R 11 )、-S(O)2R 11 、-S(O)2N(R 11 )2, -N3 or -CN, R 2 Selected from Halogen, -OR 26 , -SR 26 , -N(R 26 )2, -C(O)R 26 , -C(O)OR 26 , -OC(O)R 26 , -OC(O)N(R 26 )2, -C(O)N(R 26 )2, -N(R 26 )C(O)R 26 , -N(R 26 )C(O)OR 26 , -N(R 26 )C(O)N(R 26 )2, -N(R 26 )S(O)2(R 26 ), N(R 26 )SO2N(R 26 ), 2, -N(R 26 )P(O)(OR 26 )R 26 , -S(O)R 26 , -S(O)2R 26 , -S(O)2N(R 26 )2, -NO2 and -CN; Optionally one or more independently selected from R 30 Substituents substituted with C 1-6 Alkyl; and C 3-6 carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected from R 30 Substituents are substituted; The condition is that when R 1 -C(O)OR 11 When R 2 It cannot be a substituted 6-membered heterocyclic ring; R 3 and R 4 In each occurrence, each is independently selected from halogen, -OR 14 , -SR 14 , -N(R 14 )2, -N(R 14 )C(O)R 14 , -C(O)R 14 , -C(O)OR 14 , -C(O)N(R 14 )2, -NO2 and -CN; C 1-4 Alkyl, which is optionally substituted by one or more independently selected from halogen, -OR 14 、-SR 14 、-N(R 14 )2、-N(R 14 )C(O)R 14 、-C(O)R 14 、-C(O)OR 14 、-C(O)N(R 14 )2. -NO2 and -CN substituents; and C 3-4 carbocyclic and 3 to 4 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected from halogen, -OR 14 、-SR 14 、-N(R 14 )2、-N(R 14 )C(O)R 14 、-C(O)R 14 、-C(O)OR 14 、-C(O)N(R 14 )2, -NO2 and -CN substituents; R 5 and R 5’ are each independently selected from hydrogen and hydroxy; or R 5 and R 5’ Together = O; R 6 and R 6’ are each independently selected from hydrogen and hydroxy; or R 6 and R 6’ Together they are =O, =N-OR 26 or =NR 26 ; m is selected from 0, 1, 2 and 3; n is selected from 0, 1, 2 and 3; R 11 and R 14 In each occurrence, each is independently selected from hydrogen; Optionally one or more independently selected from R 31 Substituents substituted with C 1-6 Alkyl; and C 3-6 carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected from R 31 Substituents are substituted; R 12 Select from each occurrence One or more independently selected from R 32 Substituents substituted with C 1-6 Alkyl; and C 3-6 carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected from R 33 Substituents are substituted; R 13 Select from each occurrence hydrogen; Optionally one or more independently selected from R 34 Substituents substituted with C 1-6 Alkyl; and C 3-5 carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected from R 34 Substituents are substituted; R 21 , R 23 , R 24 and R 26 In each occurrence, each is independently selected from hydrogen; Optionally one or more independently selected from R 34 Substituents substituted with C 1-6 Alkyl; and C 3-6 carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected from C 1-4 Alkyl, C 1-4 Haloalkyl and R 34 Substituents are substituted; R 22 and R 25 Each occurrence is independently selected from C 2-6 Alkyl, C 2-6 Haloalkyl, C 2-6 hydroxyalkyl; and R 30 , R 31 , R 33 and R 34 In each occurrence, each is independently selected from halogen, -OR 41 , -SR 41 , -N(R 41 )2, -C(O)R 41 , -C(O)OR 41 , -OC(O)R 41 , -OC(O)N(R 41 )2、-C(O)N(R 41 )2、-N(R 41 )C(O)R 41 、-N(R 41 )C(O)OR 41 、-N(R 41 )C(O)N(R 41 )2、-N(R 41 )S(O)2(R 41 )、-N(R 41 )SO2N(R 41 )2、-N(R 41 )P(O)(OR 41 )R 41 、-S(O)R 41 、-S(O)2R 41 、-S(O)2N(R 41 )2, -NO2, =O, =S, -CN, C 3-6 Carbocyclic and 3- to 7-membered heterocyclic rings; R 32 In each occurrence, independently selected -OR 41 、-SR 41 、-N(R 41 )2、-C(O)R 41 、-C(O)OR 41 、-OC(O)R 41 、 -OC(O)N(R 41 )2, -C(O)N(R 41 )2, -N(R 41 )C(O)R 41 , -N(R 41 )C(O)OR 41 , -N(R 41 )C(O)N(R 41 )2, -N(R 41 )S(O)2(R 41 ), -N(R 41 )SO2N(R 41 ), -N(R 41 )P(O)(OR 41 )R 41 , -S(O)R 41 , -S(O)2R 41 , -S(O)2N(R 41 )2, -NO2, =O, =S and -CN; and R 41 is independently selected at each occurrence from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl and C 1-6 Hydroxyalkyl.

2. The compound or salt according to claim 1, wherein R 1 Selected from fluorine, chlorine, bromine, hydroxyl, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -OC 1-6 Alkyl, -OC 1-6 Haloalkyl, -OR 12 、-N(R 13 )2. -C(O)OR 11 、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-N(R 11 )S(O)2(R 11 )、-S(O)2R 11 、-S(O)2N(R 11 )2, -NO2, -N3 and -CN.

3. The compound or salt according to claim 2, wherein R 1 Selected from fluorine, -C 1-6 Haloalkyl, -OC 1-6 Haloalkyl, -N(R 13 )2. -C(O)OR 11 、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-S(O)2R 11 , -NO2, -N3 and -CN.

4. The compound or salt according to claim 1, wherein R 1 is hydroxyl, -O-C1 alkyl or -NO2; and R 2 Selected from fluorine, bromine, iodine, -OR 22 , SR 21 、-N(R 21 )2. -C(O)R 21 、-OC(O)R 21 、-OC(O)N(R 21 )2、-N(R 21 )C(O)R 21 、-N(R 21 )C(O)OR 21 、-N(R 21 )C(O)N(R 21 )2、-N(R 21 )S(O)2(R 21 )、-N(R 21 )SO2N(R 21 )2、-N(R 21 )P(O)(OR 21 )R 21 、-S(O)2R 21 、-S(O)2N(R 21 )2, -NO2, -CN and optionally substituted C 1-6 alkyl.

5. The compound or salt according to any one of claims 1 to 4, wherein R 1 For NO2.

6. The compound or salt according to claim 4 or 5, wherein R 2 Selected from fluorine, bromine, -N(R 21 )2、-N(R 21 )C(O)R 21 、-N(R 21 )C(O)OR 21 , -NO2, -CN and optionally substituted C 1-6 alkyl.

7. The compound or salt according to claim 1, wherein R 1 is fluorine; and R 2 Selected from bromine, OR 23 、-N(H)R 23 、-C(O)R 23 、-C(O)N(R 23 )2. -C(O)OR 23 、-OC(O)R 23 、-OC(O)N(R 23 )2、-N(R 23 )C(O)R 23 、-N(R 23 )C(O)OR 23 、-N(R 23 )C(O)N(R 23 )2、-N(R 23 )S(O)2R 23 、-N(R 23 )SO2N(R 23 )2、-N(R 23 )P(O)(OR 23 )R 23 、-S(O)2R 23 、-S(O)2N(R 23 )2, -NO2, -CN, and optionally substituted C 1-6 alkyl.

8. The compound or salt according to claim 7, wherein R 2 Selected from bromine, OR 23 、-N(H)R 23 、-N(R 23 )C(O)R 23 、-N(R 23 )C(O)OR 23 、-NO2、-CN、 and optionally substituted C 1-6 alkyl.

9. The compound or salt according to claim 1, wherein R 1 is C1 alkyl, -O-C1 haloalkyl, hydroxy, chlorine or bromine; and R 2 Selected from iodine, -OR 25 、-C(O)R 24 、-C(O)OR 25 、-OC(O)R 24 、-OC(O)N(R 24 )2、-C(O)N(R 24 )2、-N(R 24 )C(O)R 24 、-N(R 24 )C(O)OR 24 、-N(R 24 )C(O)N(R 24 )2、-N(R 24 )S(O)2(R 24 )、N(R 24 )SO2N(R 24 )2、-N(R 24 )P(O)(OR 24 )R 24 、-S(O)R 24 、-S(O)2R 24 、-S(O)2N(R 24 )2, -NO2, -CN and optionally substituted C 2-6 alkyl.

10. The compound or salt according to claim 1 or claim 9, wherein R 1 is -O-C1 haloalkyl, chlorine or bromine; and R 2 Select from -OR 25 、-C(O)OR 25 、-C(O)N(R 24 )2、-N(R 24 )C(O)R 24 、-N(R 24 )C(O)OR 24 , -NO2, -CN and optionally substituted C 2-6 alkyl.

11. The compound or salt according to claim 1, wherein R 1 Selected from C 2-6 Alkyl, C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 2-6 Haloalkyl, -OR 12 、-SR 11 、-N(R 13 )2. -C(O)R 11 、-OC(O)R 11 、-OC(O)N(R 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-N(R 11 )C(O)OR 11 、-N(R 11 )C(O)N(R 11 )2、-N(R 11 )S(O)2(R 11 )、-S(O)2R 11 、-S(O)2N(R 11 )2, -N3 and -CN; and R 2 Selected from halogen, -OR 26 、-SR 26 、-N(R 26 )2. -C(O)R 26 、-C(O)OR 26 、-OC(O)R 26 、-OC(O)N(R 26 )2、-C(O)N(R 26 )2、-N(R 26 )C(O)R 26 、-N(R 26 )C(O)OR 26 、-N(R 26 )C(O)N(R 26 )2、-N(R 26 )S(O)2(R 26 )、-N(R 26 )SO2N(R 26 )2、-N(R 26 )P(O)(OR 26 )R 26 、-S(O)R 26 、-S(O)2R 26 、-S(O)2N(R 26 )2, -NO2, -CN and optionally substituted C 1-6 alkyl.

12. The compound or salt according to claim 1 or claim 11, wherein R 1 Selected from C 2-6 Alkyl, C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 2-6 Haloalkyl, -OR 12 、-N(R 13 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-N(R 11 )C(O)OR 11 、-S(O)2R 11 、-S(O)2N(R 11 )2, -N3 and -CN.

13. The compound or salt according to claim 1 or claim 12, wherein R 1 Selected from -N(R 13 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 、-S(O)2R 11 , -N3 and -CN.

14. The compound or salt according to claim 1 or claim 13, wherein R 1 It is -CN.

15. A compound or salt according to any one of claims 11 to 14, wherein R 2 Selected from halogen, -OR 26 、-SR 26 、-N(R 26 )2. -C(O)R 26 、-C(O)OR 26 、-C(O)N(R 26 )2、-N(R 26 )C(O)R 26 、-N(R 26 )C(O)OR 26 、-N(R 26 )S(O)2(R 26 )、-S(O)2R 26 、-S(O)2N(R 26 )2, -NO2, -CN and optionally substituted C 1-6 alkyl.

16. A compound or salt according to any one of claims 1 to 15, wherein R 3 and R 4 is independently selected at each occurrence from halogen, -OR 14 、-N(R 14 )2、-N(R 14 )C(O)R 14 、-C(O)OR 14 、-C(O)N(R 14 )2, -NO2 and -CN and optionally substituted C 1-4 alkyl.

17. A compound or salt according to any one of claims 1 to 16, wherein R 5 and R 5’ Together they are =O.

18. A compound or salt according to any one of claims 1 to 17, wherein R 6 and R 6’ Together they are =O.

19. A compound or salt according to any one of claims 1 to 17, wherein R 6 and R 6’ Together = N-OR 26 .

20. The compound or salt of any one of claims 1 to 19, wherein m is 0 or 1; and n is 0 or 1.

21. A compound or salt according to any one of claims 1 to 20, wherein R 11 and R 14 is independently selected at each occurrence from hydrogen and optionally substituted C 1-6 alkyl; R 12 is independently selected at each occurrence from optionally substituted C 1-6 Alkyl; and R 13 is independently selected at each occurrence from hydrogen and optionally substituted C 1-6 alkyl.

22. A compound or salt according to any one of claims 1 to 21, wherein R 21 , R 23 , R 24 and R 26 is independently selected at each occurrence from hydrogen, optionally substituted C 1-6 alkyl and optionally substituted 3- to 6-membered heterocyclic ring.

23. A compound or salt according to any one of claims 1 to 22, wherein R 22 and R 25 Each occurrence is independently selected from C 3-6 Alkyl and C 3-6 Halogenated alkyl.

24. A compound or salt according to any one of claims 1 to 23, wherein R 30 , R 31 , R 33 and R 34 is independently selected at each occurrence from halogen, -OR 41 、-N(R 41 )2、-OC(O)N(R 41 )2、-C(O)N(R 41 )2、-N(R 41 )C(O)R 41 、-N(R 41 )C(O)OR 41 、-N(R 41 )C(O)N(R 41 )2、-N(R 41 )S(O)2(R 41 )、-N(R 41 )SO2N(R 41 )2、-N(R 41 )P(O)(OR 41 )R 41 、-S(O)R 41 、-S(O)2R 41 , =O and -CN.

25. The compound or salt according to claim 24, wherein R 30 , R 31 , R 33 and R 34 is independently selected at each occurrence from halogen, -N(R 41 )2、-N(R 41 )S(O)2(R 41 )、-N(R 41 )SO2N(R 41 )2、-N(R 41 )P(O)(OR 41 )R 41 、-S(O)2R 41 And = O.

26. A compound or salt according to any one of claims 1 to 25, wherein R 32 is independently selected at each occurrence from halogen, -N(R 41 )2、-N(R 41 )S(O)2(R 41 )、-N(R 41 )SO2N(R 41 )2、-N(R 41 )P(O)(OR 41 )R 41 、-S(O)2R 41 And = O.

27. A compound or salt according to any one of claims 1 to 26, wherein R 41 is independently selected at each occurrence from hydrogen and C 1-6 alkyl.

28. The compound or salt according to claim 1, wherein the compound or salt of formula (I) is selected from: or a pharmaceutically acceptable salt thereof.

29. A compound of formula (II): or a pharmaceutically acceptable salt thereof; wherein R 51 Selected from fluorine, chlorine, bromine, iodine, hydroxyl, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -N(R 61 )2.-OR 61 、-SR 61 、-C(O)R 61 、-C(O)OR 61 、-OC(O)R 61 、-OC(O)N(R 61 )2、-C(O)N(R 61 )2、-N(R 61 )C(O)R 61 、-N(R 61 )C(O)OR 61 、-N(R 61 )C(O)N(R 61 )2、-N(R 61 )S(O)2(R 61 )、-S(O)2R 61 、-S(O)2N(R 61 )2, -NO2 and -CN; When R 51 When it is fluorine, chlorine or iodine, R 52 Selected from Bromine, iodine, -N(R 71 )2, -OR 71 , -SR 71 , -C(O)R 71 , -C(O)OR 71 , -OC(O)R 71 , -OC(O)N(R 71 )2, -C(O)N(R 71 )2, -N(R 71 )C(O)R 71 、-N(R 71 )C(O)OR 71 、-N(R 71 )C(O)N(R 71 )2、-N(R 71 )S(O)2(R 71 )、N(R 71 )SO2N(R 71 )2、-N(R 71 )P(O)(OR 71 )R 71 、-S(O)R 71 、-S(O)2R 71 、-S(O)2N(R 71 )2、-NO2 and -CN; One or more independently selected from R 80 C1 alkyl substituted with a substituent, and optionally substituted with one or more independently selected from R 80 Substituents substituted with C 2-6 Alkyl; and C 3-6 carbocyclic and 3 to 5 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected from R 80 Substituents are substituted; When R 51 When it is C1 alkyl or -NO2, R 52 Selected from F, I, -OR 72 , -SR 72 , -N(R 72 )2, -C(O)R 72 , -C(O)OR 72 , -OC(O)R 72 , -OC(O)N(R 72 )2, -C(O)N(R 72 )2, -N(R 72 )C(O)R 72 、-N(R 72 )C(O)OR 72 、-N(R 72 )C(O)N(R 72 )2、-N(R 72 )S(O)2(R 72 )、-N(R 72 )SO2N(R 72 )2、-N(R 72 )P(O)(OR 72 )R 72 、-S(O)R 72 、-S(O)2R 72 、-S(O)2N(R 72 )2、-NO2 and -CN; Optionally one or more independently selected from R 80 Substituents substituted with C 1-6 Alkyl; and C 3-6 carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected from R 80 Substituents are substituted; When R 51 Selected from bromine, hydroxyl, -C 2-6 Alkyl, -C 1-6 Haloalkyl, -N(R 61 )2.-OR 61 、-SR 61 、-C(O)R 61 、-C(O)OR 61 、-OC(O)R 61 、-OC(O)N(R 61 )2、-C(O)N(R 61 )2、-N(R 61 )C(O)R 61 、-N(R 61 )C(O)OR 61 、-N(R 61 )C(O)N(R 61 )2、-N(R 61 )S(O)2(R 61 )、-S(O)2R 61 、-S(O)2N(R 61 )2 and -CN, R 52 Selected from Halogen, -OR 73 , -SR 73 , -N(R 73 )2, -C(O)R 73 , -C(O)OR 73 , -OC(O)R 73 , -OC(O)N(R 73 )2, -C(O)N(R 73 )2, -N(R 73 )C(O)R 73 , -N(R 73 )C(O)OR 73 , -N(R 73 )C(O)N(R 73 )2, -N(R 73 )S(O)2(R 73 ), -N(R 73 )SO2N(R 73 ), 2, -N(R 73 )P(O)(OR 73 )R 73 , -S(O)R 73 , -S(O)2R 73 , -S(O)2N(R 73 )2, -NO2 and -CN; Optionally one or more independently selected from R 80 Substituents substituted with C 1-6 Alkyl; and C 3-6 carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected from R 80 Substituents are substituted; R 53 and R 54 In each occurrence, each is independently selected from halogen, -OR 64 , -SR 64 , -N(R 64 )2, -N(R 64 )C(O)R 64 , -C(O)R 64 , -C(O)OR 64 , -C(O)N(R 64 )2, -NO2 and -CN; C 1-4 Alkyl, which is optionally substituted by one or more independently selected from halogen, -OR 64 、-SR 64 、-N(R 64 )2、-N(R 64 )C(O)R 64 、-C(O)R 64 、-C(O)OR 64 、-C(O)N(R 64 )2, -NO2 and -CN; and C 3-4 carbocyclic and 3 to 4 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected from halogen, -OR 64 、-SR 64 、-N(R 64 )2、-N(R 64 )C(O)R 64 、-C(O)R 64 、-C(O)OR 64 、-C(O)N(R 64 )2, -NO2 and -CN substituents; R 55 and R 55’ are each independently selected from hydrogen and hydroxy; or R 55 and R 55’ Together = O; R 56 and R 56’ are each independently selected from hydrogen and hydroxy; or R 56 and R 56’ Together they are =O, =N-OR 64 or =NR 26 ; p is selected from 0, 1, 2 and 3; q is selected from 0, 1, 2 and 3; R 61 and R 64 In each occurrence, each is independently selected from hydrogen; Optionally one or more independently selected from R 81 Substituents substituted with C 1-6 Alkyl; and C 3-6 carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected from R 81 Substituents are substituted; R 71 , R 72 and R 73 In each occurrence, each is independently selected from hydrogen; Optionally one or more independently selected from R 82 Substituents substituted with C 1-6 Alkyl; and C 3-6 carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected from C 1-4 Alkyl, C 1-4 Haloalkyl and R 82 Substituents are substituted; R 80 , R 81 and R 82 In each occurrence, each is independently selected from halogen, -OR 91 , -SR 91 , -N(R 91 )2, -C(O)R 91 , -C(O)OR 91 , -OC(O)R 91 , -OC(O)N(R 91 )2、-C(O)N(R 91 )2、-N(R 91 )C(O)R 91 、-N(R 91 )C(O)OR 91 、-N(R 91 )C(O)N(R 91 )2、-N(R 91 )S(O)2(R 91 )、-N(R 91 )SO2N(R 91 )2、-N(R 91 )P(O)(OR 91 )R 91 、-S(O)R 91 、-S(O)2R 91 、-S(O)2N(R 91 )2, -NO2, =O, =S, -CN, C 3-6 Carbocyclic rings and 3 to 7 membered heterocyclic rings; and R 91 is independently selected at each occurrence from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl and C 1-6 Hydroxyalkyl.

30. The compound or salt according to claim 29, wherein R 51 Selected from fluorine, chlorine, bromine, hydroxyl, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -N(R 61 )2.-OR 61 、-C(O)R 61 、-C(O)OR 61 、-C(O)N(R 61 )2、-N(R 61 )C(O)R 61 -N(R 61 )S(O)2(R 61 )、-S(O)2R 61 、-S(O)2N(R 61 )2, -NO2 and -CN.

31. The compound or salt according to claim 30, wherein R 51 Selected from -C(O)R 61 、-C(O)OR 61 、-C(O)N(R 61 )2 and -NO2.

32. The compound or salt of claim 29, wherein R 51 It is fluorine, chlorine or iodine.

33. The compound or salt according to claim 29, wherein R 51 is C1 alkyl or -NO2; and R 52 Selected from fluorine, iodine, -OR 72 、-SR 72 、-N(R 72 )2. -C(O)R 72 、-C(O)OR 72 、-OC(O)R 72 、-OC(O)N(R 72 )2、-C(O)N(R 72 )2、-N(R 72 )C(O)R 72 、-N(R 72 )C(O)OR 72 、-N(R 72 )C(O)N(R 72 )2、-N(R 72 )S(O)2(R 72 )、-N(R 72 )SO2N(R 72 )2、-N(R 72 )P(O)(OR 72 )R 72 、-S(O)R 72 、-S(O)2R 72 、-S(O)2N(R 72 )2, -NO2, -CN and optionally substituted C 1-6 alkyl.

34. A compound or salt according to any one of claims 29 to 33, wherein R 51 It is -NO2.

35. A compound or salt according to claim 33 or claim 34, wherein R 52 Selected from fluorine, -OR 72 , -NO2, -CN and optionally substituted C 1-6 alkyl.

36. The compound or salt of claim 29, wherein R 51 Selected from bromine, hydroxyl, -C 2-6 Alkyl, -C 1-6 Haloalkyl, -N(R 61 )2.-OR 61 、-SR 61 、-C(O)R 61 、-C(O)OR 61 、-OC(O)R 61 、-OC(O)N(R 61 )2、-C(O)N(R 61 )2、-N(R 61 )C(O)R 61 、-N(R 61 )C(O)OR 61 、-N(R 61 )C(O)N(R 61 )2、-N(R 61 )S(O)2(R 61 )、-S(O)2R 61 、-S(O)2N(R 61 )2 and -CN.

37. A compound or salt according to claim 29 or claim 36, wherein R 51 Select from -OR 61 、-C(O)R 61 、-C(O)OR 61 、-C(O)N(R 61 )2 and -CN; and R 52 Selected from halogen, -OR 73 、-SR 73 、-N(R 73 )2. -C(O)R 73 、-C(O)OR 73 、-N(R 73 )C(O)R 73 、-N(R 73 )C(O)OR 73 、-N(R 73 )C(O)N(R 73 )2、-N(R 73 )S(O)2(R 73 )、-N(R 73 )SO2N(R 73 )2、-N(R 73 )P(O)(OR 73 )R 73 、-S(O)R 73 、-S(O)2R 73 、-S(O)2N(R 73 )2, -NO2 and -CN.

38. A compound or salt according to claim 29 or claim 36, wherein R 51 Selected from -C(O)R 61 、-C(O)OR 61 and -C(O)N(R 61 )2.

39. A compound or salt according to any one of claims 36 to 38, wherein R 52 Selected from halogen.

40. The compound or salt of claim 39, wherein R 52 For chlorine.

41. A compound or salt according to any one of claims 29 to 40, wherein R 53 and R 54 Each occurrence is independently selected from halogen.

42. A compound or salt according to any one of claims 29 to 41, wherein R 53 is independently selected at each occurrence from halogen.

43. A compound or salt according to any one of claims 29 to 42, wherein R 55 and R 55’ Together they are =O.

44. A compound or salt according to any one of claims 29 to 43, wherein R 56 and R 56’ Together they are =O.

45. A compound or salt according to any one of claims 29 to 43, wherein R 56 and R 56’ Together = N-OR 64 .

46. ​​A compound or salt according to any one of claims 29 to 45, wherein p is selected from 0 and 1.

47. A compound or salt according to any one of claims 29 to 46, wherein q is 0.

48. A compound or salt according to any one of claims 29 to 47, wherein R 61 and R 64 is independently selected at each occurrence from hydrogen, optionally substituted C 1-6 alkyl and optionally substituted 3- to 6-membered heterocyclic ring.

49. A compound or salt according to any one of claims 29 to 48, wherein R 80 , R 81 and R 82 Each occurrence is independently selected from -N(R 91 )2. -C(O)OR 91 and -N(R 91 )SO2N(R 91 )2.

50. A compound or salt according to any one of claims 29 to 49, wherein R 91 is independently selected at each occurrence from hydrogen and C 1-6 alkyl.

51. The compound or salt according to claim 29, wherein the compound or salt of formula (II) is selected from: or a pharmaceutically acceptable salt thereof.

52. A compound of formula (III): or a pharmaceutically acceptable salt thereof, wherein R 101 Selected from fluorine, chlorine, bromine, hydroxyl, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -OC 1-6 Alkyl, -OC 1-6 Haloalkyl, -N(R 111 )2.-OR 112 、-SR 111 、-C(O)R 111 、-C(O)OR 111 、-OC(O)R 111 、-OC(O)N(R 111 )2、-C(O)N(R 111 )2、-N(R 111 )C(O)R 111 、-N(R 111 )C(O)OR 111 、-N(R 111 )C(O)N(R 111 )2、-N(R 111 )S(O)2(R 111 )、-S(O)2R 111 、-S(O)2N(R 111 )2, -NO2 and -CN; When R 101 When it is fluorine, R 102 Selected from chlorine, bromine, iodine, -N(R 121 )2, -OR 122 , -SR 121 , -C(O)R 121 , -C(O)OR 121 , -OC(O)R 121 , -OC(O)N(R 121 )2, -C(O)N(R 121 )2, -N(R 121 )C(O)R 121 , -N(R 21 )C(O)OR 121 , -N(R 121 )C(O)N(R 121 )2, -N(R 121 )S(O)2(R 121 , -N(R 121 )SO2N(R 121 )2, -N(R 121 )P(O)(OR 121 )R 121 , -S(O)R 121 , -S(O)2R 121 , -S(O)2N(R 121 )2, -NO2 and -CN; One or more independently selected from R 123 C1 alkyl substituted with a substituent, and optionally substituted with one or more independently selected from R 130 Substituents substituted with C 2-6 Alkyl; and C 3-6 carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected from R 130 Substituents are substituted; When R 101 Bromine, iodine, hydroxyl, -O-C1 alkyl, -C(O)OR 111 、-C(O)N(H)(C2 alkyl)、-S(O)2R 111 or -S(O)2N(R 111 )2, R 102 Selected from F, -N(R 124 )2, -OR 125 , -SR 124 , -C(O)R 124 , -C(O)OR 124 , -OC(O)R 124 , -OC(O)N(R 124 )2, -C(O)N(R 124 )2, -N(R 124 )C(O)R 124 , -N(R 124 )C(O)OR 124 , -N(R 124 )C(O)N(R 124 )2, -N(R 124 )S(O)2(R 124 , -N(R 124 )SO2N(R 124 )2, -N(R 124 )P(O)(OR 124 )R 124 , -S(O)R 124 , -S(O)2R 124 , -S(O)2N(R 124 )2, -NO2 and -CN; Optionally one or more independently selected from R 130 Substituents substituted with C 1-6 Alkyl; and C 3-6 carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected from R 130 Substituents are substituted; When R 101 Chlorine, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 1-6 Haloalkyl, -OR 112 、-SR 111 、-N(R 111 )2. -C(O)R 111 、-OC(O)R 111 、-C(O)N(R 113 )2、-OC(O)N(R 111 )2、-N(R 111 )C(O)R 111 、-N(R 111 )C(O)OR 111 、-N(R 111 )C(O)N(R 111 )2、-N(R 111 )S(O)2(R 111 ), -NO2 or -CN, R 102 Selected from halogen, -OR 126 , -SR 126 , -N(R 126 )2, -C(O)R 126 , -C(O)OR 126 , -OC(O)R 126 , -OC(O)N(R 126 )2, -C(O)N(R 126 )2, -N(R 126 )C(O)R 126 , -N(R 126 )C(O)OR 126 , -N(R 126 )C(O)N(R 126 )2, -N(R 126 )S(O)2(R 126 , -N(R 126 )SO2N(R 126 )2, -N(R 126 )P(O)(OR 126 )R 126 , -S(O)R 126 , -S(O)2R 126 , -S(O)2N(R 126 )2, -NO2 and -CN; Optionally one or more independently selected from R 130 Substituents substituted with C 1-6 Alkyl; and C 3-6 carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected from R 130 Substituents are substituted; The condition is (i) when R 101 When it is NO2, R 102 cannot be methyl; (ii) when R 101 When it is methyl, R 102 cannot be chlorine; and (iii) when R 101 When it is chlorine, R 102 It cannot be bromine; R 103 and R 104 In each occurrence, each is independently selected from halogen, -OR 114 , -SR 114 , -N(R 114 )2, -N(R 114 )C(O)R 114 , -C(O)R 114 , -C(O)OR 114 , -C(O)N(R 114 )2, -NO2 and -CN; C 1-4 Alkyl, which is optionally substituted by one or more independently selected from halogen, -OR 114 , -SR 114 、-N(R 114 )2、-N(R 114 )C(O)R 114 、-C(O)R 114 、-C(O)OR 114 、-C(O)N(R 114 )2, -NO2 and -CN; and C 3-4 carbocyclic and 3 to 4 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected from halogen, -OR 114 、-SR 114 、-N(R 114 )2、-N(R 114 )C(O)R 114 、-C(O)R 114 、-C(O)OR 114 、-C(O)N(R 114 )2, -NO2 and -CN substituents; R 105 and R 105’ are each independently selected from hydrogen and hydroxy; or R 105 and R 105’ Together = O; R 106 and R 106’ are each independently selected from hydrogen and hydroxy; or R 106 and R 106’ Together they are =O, =N-OR 114 or =NR 114 ; r is selected from 0, 1, 2 and 3; s is selected from 0, 1, 2 and 3; R 111 and R 114 In each occurrence, each is independently selected from hydrogen; Optionally one or more independently selected from R 131 Substituents substituted with C 1-6 Alkyl; and C 3-6 carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected from R 131 Substituents are substituted; R 112 Select from each occurrence One or more independently selected from R 132 Substituents substituted with C 1-6 Alkyl; and C 3-6 carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected from R 133 Substituents are substituted; R 113 Select from each occurrence hydrogen; Optionally one or more independently selected from R 134 Substituents substituted C1 alkyl and C 3-6 alkyl, and one or more independently selected from R 134 C2 alkyl substituted with a substituent; and C 3-5 carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected from R 134 Substituents are substituted; R 121 , R 124 and R 126 In each occurrence, each is independently selected from hydrogen; Optionally one or more independently selected from R 134 Substituents substituted with C 1-6 Alkyl; and C 3-6 carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected from C 1-4 Alkyl, C 1-4 Haloalkyl and R 134 Substituents are substituted; R 122 and R 125 In each occurrence, each is independently selected from Optionally one or more independently selected from R 134 Substituents substituted with C 2-6 Alkyl; and C 3-6 carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected from C 1-4 Alkyl, C 1-4 Haloalkyl and R 134 Substituents are substituted; R 123 In each occurrence, independently selected hydrogen; Optionally one or more independently selected from R 134 Substituents substituted with C 1-6 Alkyl; and C 3-5 carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected from C 1-4 Alkyl, C 1-4 Haloalkyl and R 134 Substituents are substituted; R 130 , R 131 , R 132 , R 133 and R 134 In each occurrence, each is independently selected from halogen, -OR 141 , -SR 141 , -N(R 141 )2, -C(O)R 141 , -C(O)OR 141 , -OC(O)R 141 , -OC(O)N(R 141 )2, -C(O)N(R 141 )2, -N(R 141 )C(O)R 141 , -N(R 141 )C(O)OR 141 , -N(R 141 )C(O)N(R 141 )2, -N(R 141 )S(O)2(R 141 , -N(R 141 )SO2N(R 141 )2, -N(R 141 )P(O)(OR 141 )R 141 , -S(O)R 141 , -S(O)2R 141 , -S(O)2N(R 141 )2, -NO2, =O, =S, -CN, C 3-6 Carbocyclic rings and 3 to 7 membered heterocyclic rings; and R 141 is independently selected at each occurrence from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl and C 1-6 Hydroxyalkyl.

53. The compound or salt of claim 52, wherein R 101 Selected from fluorine, chlorine, bromine, hydroxyl, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -OC 1-6 Alkyl, -OC 1-6 Haloalkyl, -N(R 111 )2.-OR 112 、C(O)R 111 、-C(O)OR 111 、C(O)N(R 111 )2、N(R 111 )S(O)2(R 111 )、-S(O)2R 111 、-S(O)2N(R 111 )2, -NO2 and -CN.

54. The compound or salt of claim 53, wherein R 101 Selected from fluorine, -NO2 and -CN.

55. The compound or salt of claim 52, wherein R 101 For fluorine.

56. The compound or salt of claim 55, wherein R 102 Selected from chlorine, bromine, iodine, -N(R 121 )2.-OR 122 、-C(O)R 121 、-C(O)OR 121 、-C(O)N(R 121 )2、-N(R 121 )C(O)R 121 、-N(R 121 )S(O)2(R 121 )、-S(O)2R 121 、-S(O)2N(R 121 )2, -NO2 and -CN.

57. A compound or salt according to claim 55 or claim 56, wherein R 102 Chlorine or bromine.

58. The compound or salt of claim 52, wherein R 101 Selected from bromine, iodine, hydroxyl, -O-C1 alkyl, -C(O)OR 111 、-C(O)N(H)(C2 alkyl)、-S(O)2R 111 and -S(O)2N(R 111 )2.

59. The compound or salt of claim 52, wherein R 101 Selected from chlorine, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 1-6 Haloalkyl, -OR 112 、-SR 111 、-N(R 111 )2. -C(O)R 111 、-OC(O)R 111 、-C(O)N(R 113 )2、-OC(O)N(R 111 )2、-N(R 111 )C(O)R 111 、-N(R 111 )C(O)OR 111 、-N(R 111 )C(O)N(R 111 )2、-N(R 111 )S(O)2(R 111 ), -NO2 and -CN.

60. The compound or salt of claim 59, wherein R 101 Selected from -NO2 and -CN.

61. A compound or salt according to claim 59 or claim 60, wherein R 102 is selected from halogen and optionally substituted C 1-6 alkyl.

62. A compound or salt according to any one of claims 52 to 61, wherein R 103 and R 104 is independently selected at each occurrence from halogen and C 1-4 alkyl.

63. A compound or salt according to any one of claims 52 to 62, wherein R 105 and R 105’ Together they are =O.

64. A compound or salt according to any one of claims 52 to 62, wherein R 106 and R 106’ Together they are =O.

65. A compound or salt according to any one of claims 52 to 62, wherein R 106 and R 106’ Together = N-OR 114 .

66. A compound or salt according to any one of claims 52 to 65, wherein r is selected from 0 and 1.

67. A compound or salt according to any one of claims 52 to 66, wherein s is 0.

68. A compound or salt according to claim 52, wherein the compound of formula (III) is selected from: or a pharmaceutically acceptable salt thereof.

69. A compound of formula (IV): or a pharmaceutically acceptable salt thereof; wherein R 151 Selected from fluorine, bromine, -N(R 161 )2. -C(O)R 161 、-C(O)OR 161 、-OC(O)R 161 、-OC(O)N(R 161 )2、-C(O)N(R 161 )2、-N(R 161 )C(O)R 161 、-N(R 161 )C(O)OR 161 、-N(R 161 )C(O)N(R 161 )2、-N(R 161 )S(O)2(R 161 )、-N(R 161 )S(O)2N(R 161 )2. -SR 161 、-S(O)R 161 、-S(O)2R 161 、-S(O)2N(R 161 )2, -CN, -NO2, -C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 1-6 Haloalkyl, -OR 3-6 Carbon ring and -OR 3-6 Heterocyclic rings; and wherein each is optionally selected from one or more independently selected from R 171 Substituents are substituted; When R 151 When it is fluorine, R 152 Selected from Iodine, -NHR 192 , -OR 171 , -SR 171 , -C(=NR 196 )N(R 196 )2, -C(O)R 171 , -C(O)OR 171 , -OC(O)R 171 , -OC(O)N(R 171 )2, -C(O)N(R 171 )2, -N(R 193 )C(O)R 171 , -N(H)C(O)R 194 , -N(R 193 )C(O)OR 171 , -N(R 171 )C(O)N(R 171 )2, -N(R 171 )S(O)2(R 171 , -N(R 171 )SO2N(R 171 )2, -N(R 171 )P(O)(OR 171 )R 171 , -S(O)R 171 , -S(O)2R 171 , -S(O)2N(R 171 )2, -NR 196 (C=NR 196 )N(R 196 )2, -N3 and -CN; One or more independently selected from R 195 C1 alkyl substituted with a substituent, and optionally substituted with one or more independently selected from R 180 Substituents substituted with C 2-6 Alkyl; and C 3-6 Carbocyclic ring, 3-membered heterocyclic ring, 4-membered heterocyclic ring, and a 6-membered heterocyclic ring, any of which is optionally replaced by one or more independently selected from R 180 Substituents are substituted; When R 151 for SR 161 、-S(O)R 161 、-S(O)2R 161 、-S(O)2N(R 161 ) or -CN, R 152 Selected from halogen, -N(R 174 )2, -OR 174 , -SR 174 , -C(O)R 174 , -C(O)OR 174 , -OC(O)R 174 , -OC(O)N(R 174 )2, -C(O)N(R 174 )2, -N(R 174 )C(O)R 174 , -N(R 174 )C(O)OR 174 , -N(R 174 )C(O)N(R 174 )2, -N(R 174 )S(O)2(R 174 , -N(R 124 )SO2N(R 174 )2, -N(R 174 )P(O)(OR 174 )R 174 , -S(O)R 174 , -S(O)2R 174 , -S(O)2N(R 174 )2, -NO2 and -CN; Optionally one or more independently selected from R 180 Substituents substituted with C 1-6 Alkyl; and C 3-6 carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected from R 180 Substituents are substituted; When R 151 When it is bromine or -NO2, R 152 Selected from iodine, -OR 197 , -SR 176 , -NHR 178 , -C(O)R 176 , -C(O)OR 176 , -OC(O)R 176 , -OC(O)N(R 176 )2、-C(O)N(R 176 )2、-N(R 176 )C(O)R 176 、-N(R 176 )C(O)OR 176 、-N(R 176 )C(O)N(R 176 )2、-N(R 176 )S(O)2(R 176 )、-N(R 176 )SO2N(R 176 )2、-N(R 176 )P(O)(OR 176 )R 176 、-S(O)R 176 、-S(O)2R 176 、 -S(O)2N(R 176 )2, -NO2 and -CN; One or more independently selected from R 180 C1 alkyl substituted with a substituent, substituted with one or more independently selected from R 198 The substituents are C1 alkyl substituted with one or more independently selected from R 180 Substituents substituted with C 2-6 alkyl; C 3-6 carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected from R 180 substituted with a substituent; and The condition is (i) when R 151 When it is NO2, R 152 cannot be one or more independently selected from R 180 and (ii) when R 151 When it is NO2, R 152 It cannot be ethyl; When R 151 For -C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 1-6 Haloalkyl, -OR 3-6 Carbon ring, -OR 3-6 Heterocyclic, -N(R 161 )2. -C(O)R 161 、-OC(O)R 161 、-C(O)N(R 161 )2、-OC(O)N(R 161 )2、-N(R 161 )C(O)R 161 、-N(R 161 )C(O)OR 161 、-N(R 161 )C(O)N(R 161 )2、-N(R 161 )S(O)2(R 161 ) or -N(R 161 )S(O)2N(R 161 )2, R 152 Selected from halogen, -OR 176 , -SR 176 , -N(R 176 )2, -C(O)R 176 , -C(O)OR 176 , -OC(O)R 176 , -OC(O)N(R 176 )2, -C(O)N(R 176 )2, -N(R 176 )C(O)R 176 , -N(R 176 )C(O)OR 176 , -N(R 176 )C(O)N(R 176 )2, -N(R 176 )S(O)2(R 176 , -N(R 176 )SO2N(R 176 )2, -N(R 176 )P(O)(OR 176 )R 176 , -S(O)R 176 , -S(O)2R 176 , -S(O)2N(R 176 )2, -NO2 and -CN; Optionally one or more independently selected from R 177 Substituents substituted with C 1-6 Alkyl; and C 3-6 carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected from R 177 Substituents are substituted; R 153 and R 154 In each occurrence, each is independently selected from Halogen, -OR 164 、-NHR 178 、-N(R 164 )C(O)R 164 、-C(O)R 164 、-C(O)OR 164 、-C(O)N(R 164 )2, -NO2 and -CN; C 1-4 Alkyl, which is optionally substituted by one or more independently selected from halogen, -OR 164 , -SR 164 、-N(R 164 )2、-N(R 164 )C(O)R 164 、-C(O)R 164 、-C(O)OR 164 、-C(O)N(R 164 )2, -NO2 and -CN; and C 3-6 carbocyclic and 3 to 5 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected from halogen, -OR 164 、-SR 164 、-N(R 164 )2、-N(R 164 )C(O)R 164 、-C(O)R 164 、-C(O)OR 164 、-C(O)N(R 164 )2, -NO2 and -CN substituents; R 155 and R 155’ are each independently selected from hydrogen, hydroxyl and methyl; or R 155 and R 155’ Together = O; R 156 and R 156’ are each independently selected from hydrogen, hydroxyl and methyl; or R 156 and R 156’ Together they are =O, =N-OR 171 or =NR 171 ; t is selected from 0, 1, 2 and 3; u is selected from 0, 1, 2 and 3; R 161 and R 164 In each occurrence, each is independently selected from hydrogen; Optionally one or more independently selected from R 177 Substituents substituted with C 1-6 Alkyl; and C 3-6 carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected from R 177 Substituents are substituted; R 171 , R 174 and R 176 In each occurrence, each is independently selected from hydrogen; Optionally one or more independently selected from R 180 Substituents substituted with C 1-6 Alkyl; and C 3-6 carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected from C 1-4 Alkyl, C 1-4 Haloalkyl and R 180 Substituents are substituted; R 177 and R 180 In each occurrence, each is independently selected from halogen, -OR 191 , -SR 191 , -N(R 191 )2, -C(O)R 191 , -C(O)OR 191 , -OC(O)R 191 , -OC(O)N(R 191 )2, -C(O)N(R 191 )2, -N(R 191 )C(O)R 191 , -N(R 191 )C(O)OR 191 , -N(R 191 )C(O)N(R 191 )2, -N(R 191 )S(O)2(R 191 , -N(R 191 )SO2N(R 191 )2, -N(R 191 )P(O)(OR 191 )R 191 , -NR 196 (C=NR 196 )N(R 196 )2, -S(O)R 191 , -S(O)2R 191 , -S(O)2N(R 191 )2, -NO2, =O, =S, -CN, C 1-6 Alkyl, C 3-6 Carbocyclic and 3- to 7-membered heterocyclic rings; R 178 Select from each occurrence Optionally one or more independently selected from R 180 Substituents substituted with C 1-6 Alkyl; and C 3-6 carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected from R 180 Substituents are substituted; R 191 is independently selected at each occurrence from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl and C 1-6 Hydroxyalkyl; R 192 Select from each occurrence C 3-6 carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected from R 180 Substituents are substituted; R 193 Select from each occurrence Optionally one or more independently selected from R 180 Substituents substituted with C 1-6 Alkyl; and C 3-6 carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected from C 1-4 Alkyl, C 1-4 Haloalkyl and R 180 Substituents are substituted; R 194 Select from each occurrence One or more independently selected from R 180 Substituents substituted with C 1-6 alkyl; R 195 In each occurrence, independently selected Halogen, -NH2, -NHR 192 、-NR 196 (C=NR 196 )N(R 196 )2.-OR 171 、-SR 171 , -C(O)R 171 、-C(O)OR 171 、-OC(O)R 171 、-OC(O)N(R 171 )2、-C(O)N(R 171 )2、 -N(R 171 )C(O)R 171 、-N(R 171 )C(O)R 171 、-N(R 193 )C(O)OR 171 、-N(R 171 )C(O)N(R 171 )2、-N(R 171 )S(O)2(R 171 )、-N(R 171 )S(O)2N(R 171 )2、 -N(R 171 )P(O)(OR 171 )R 171 、-S(O)R 171 、-S(O)2R 171 和-S(O)2N(R 171 )2; Optionally one or more independently selected from R 180 Substituents substituted with C 1-6 Alkyl; and C 5-6 carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected from C 1-4 Alkyl, C 1-4 Haloalkyl and R 180 Substituents are substituted; R 196 Select from each occurrence Hydrogen, -CN and OR 171 ; Optionally one or more independently selected from R 180 Substituents substituted with C 1-6 Alkyl; and C 3-6 carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected from C 1-4 Alkyl, C 1-4 Haloalkyl and R 180 Substituents are substituted; R 197 Select from each occurrence hydrogen; Optionally one or more independently selected from R 180 Substituents substituted with C 2-6 Alkyl; and C 3-6 carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected from C 1-4 Alkyl, C 1-4 Haloalkyl and R 180 Substituents are substituted; R 198 In each occurrence, independently selected F, Cl, I, -NH2, -NHR 192 , -NR 196 (C=NR 196 )N(R 196 )2, -OR 171 , -SR 171 , -C(O)R 171 , -C(O)OR 171 , -OC(O)R 171 , -OC(O)N(R 171 )2, -C(O)N(R 171 )2, -N(R 171 )C(O)R 171 , -N(R 171 )C(O)R 171 , -N(R 193 )C(O)OR 171 , -N(R 171 )C(O)N(R 171 )2, -N(R 171 )S(O)2(R 171 , -N(R 171 )SO2N(R 171 )2, -N(R 171 )P(O)(OR 171 )R 171 , -S(O)R 171 , -S(O)2R 171 and -S(O)2N(R 171 )2; Optionally one or more independently selected from R 180 Substituents substituted with C 2-6 Alkyl; and C 5-6 carbocyclic and 3 to 6 membered heterocyclic rings, any of which is optionally substituted by one or more independently selected from C 1-4 Alkyl, C 1-4 Haloalkyl and R 180 substituted by a substituent.

70. The compound or salt of claim 69, wherein R 151 Selected from fluorine, bromine, -C(O)R 161 、-C(O)OR 161 、-C(O)N(R 161 )2、-N(R 161 )C(O)R 161 、-N(R 161 )S(O)2(R 161 ),-SR 161 、-S(O)R 161 、-S(O)2R 161 、-S(O)2N(R 161 )2, -CN, -NO2, -C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 1-6 Haloalkyl and 71. A compound or salt according to claim 69 or claim 70, wherein R 151 Selected from fluorine, bromine, -C(O)R 161 、-C(O)OR 161 、-C(O)N(R 161 )2、-N(R 161 )C(O)R 161 、-SR 161 、-S(O)2R 161 、-S(O)2N(R 161 )2, -CN, -NO2 and 72. A compound or salt according to any one of claims 69 to 71, wherein R 151 Selected from fluorine, bromine, -SR 161 、-S(O)2R 161 , -CN, -NO2 and 73. A compound or salt according to any one of claims 69 to 72, wherein R 151 For fluorine.

74. The compound or salt of claim 73, wherein R 152 Selected from -NHR 192 、-OR 171 、-SR 171 、-C(=NR 196 )N(R 196 )2. -C(O)R 171 、-C(O)OR 171 、-OC(O)R 171 、-C(O)N(R 171 )2, -N(H)C(O)R 194 、-N(R 171 )S(O)2(R 171 )、-S(O)2R 171 、-S(O)2N(R 171 )2.-NR 196 (C=NR 196 )N(R 196 )2, -N3, -CN, one or more independently selected from R 195 C1 alkyl substituted with a substituent, 75. A compound or salt according to claim 73 or claim 74, wherein R 152 Selected from -NHR 192 、-C(=NR 196 )N(R 196 )2. -C(O)R 171 、-C(O)OR 171 、-C(O)N(R 171 )2, -N(H)C(O)R 194 、-NR 196 (C=NR 196 )N(R 196 )2, -N3, -CN, one or more independently selected from R 195 C1 alkyl substituted with a substituent, 76. A compound or salt according to any one of claims 69 to 72, wherein R 151 Selected from -SR 161 、-S(O)2R 161 , -CN and 77. The compound or salt of claim 76, wherein R 152 Selected from halogen, -N(R 174 )2.-OR 174 、-SR 174 、-C(O)R 174 、-C(O)OR 174 、-OC(O)R 174 、-C(O)N(R 174 )2、-N(R 174 )C(O)R 174 、-N(R 174 )C(O)OR 174 、-N(R 174 )S(O)2(R 174 )、-S(O)2R 174 、-S(O)2N(R 174 )2, -NO2, -CN, optionally one or more independently selected from R 180 Substituents substituted with C 1-6 alkyl, and optionally one or more independently selected from R 180 A 5-membered heterocyclic ring substituted with a substituent.

78. A compound or salt according to claim 76 or claim 77, wherein R 152 Selected from halogen, -N(R 174 )2.-OR 174 、-C(O)N(R 174 )2、-N(R 174 )C(O)R 174 、-N(R 174 )C(O)OR 174 , -NO2, -CN, optionally one or more independently selected from R 180 Substituents substituted with C 1-6 alkyl, and optionally one or more independently selected from R 180 A 5-membered heterocyclic ring substituted with a substituent.

79. A compound or salt according to any one of claims 76 to 78, wherein R 152 Selected from -C(O)N(R 174 )2、-N(R 174 )C(O)R 174 、-N(R 174 )C(O)OR 174 , optionally one or more independently selected from R 180 Substituents substituted with C 1-6 alkyl, and optionally one or more independently selected from R 180 A 5-membered heterocyclic ring substituted with a substituent.

80. A compound or salt according to any one of claims 69 to 72, wherein R 151 Selected from bromine and -NO2.

81. The compound or salt of claim 80, wherein R 152 Select from -OR 197 、-SR 176 、-NHR 178 、-C(O)R 176 、-C(O)OR 176 、-C(O)N(R 176 )2、-N(R 176 )C(O)R 176 、-N(R 176 )S(O)2(R 176 )、-S(O)2R 176 、-S(O)2N(R 176 )2, -NO2, -CN, one or more independently selected from R 180 C1 alkyl substituted with a substituent, substituted with one or more independently selected from R 198 The substituents are C1 alkyl substituted with one or more independently selected from R 180 Substituents substituted with C 2-6 alkyl, provided that (i) when R 151 When it is NO2, R 152 cannot be one or more independently selected from R 180 and (ii) when R 151 When it is NO2, R 152 It cannot be ethyl.

82. A compound or salt according to claim 80 or claim 81, wherein R 152 is selected from one or more independently selected from R 180 C1 alkyl substituted with a substituent, substituted with one or more independently selected from R 198 The substituents are C1 alkyl substituted with one or more independently selected from R 180 Substituents substituted with C 2-6 alkyl, provided that (i) when R 151 When it is NO2, R 152 cannot be one or more independently selected from R 180 and (ii) when R 151 When it is NO2, R 152 It cannot be ethyl.

83. A compound or salt according to any one of claims 69 or claims 80 to 82, wherein R 151 is bromine and R 152 is one or more independently selected from R 180 The substituent is a C1 alkyl substituted with a substituent.

84. A compound or salt according to any one of claims 69 or claims 80 to 82, wherein R 151 is -NO2 and R 152 is one or more independently selected from R 198 The substituent is a C1 alkyl substituted with a substituent.

85. A compound or salt according to any one of claims 69 to 84, wherein R 153 and R 154 is independently selected at each occurrence from halogen and C 1-4 alkyl.

86. A compound or salt according to any one of claims 69 to 85, wherein R 155 and R 155’ Together they are =O.

87. A compound or salt according to any one of claims 69 to 86, wherein R 156 and R 156’ Together they are =O.

88. The compound or salt of any one of claims 69 to 86, wherein R 156 and R 156’ Together = N-OR 171 .

89. A compound or salt according to any one of claims 69 to 86, wherein R 156 and R 156’ Each is independently selected from hydroxy and methyl.

90. The compound or salt of any one of claims 69 to 89, wherein t is selected from 0 and 1.

91. A compound or salt according to any one of claims 69 to 90, wherein u is 0.

92. The compound or salt of claim 69, wherein the compound of formula (IV) is selected from: or a pharmaceutically acceptable salt thereof.

93. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound or salt according to any one of claims 1 to 92.

94. A method of modulating indoleamine 2,3-dioxygenase 2 (IDO2) in a subject in need thereof, comprising administering to the subject a compound or salt according to any one of claims 1 to 92 or a pharmaceutical composition according to claim 93.

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