Tryptanthrin derivatives and uses thereof

Abstract

The present disclosure provides tryptanthrin derivatives that are modulators of IDO2, and pharmaceutical compositions that include these compounds. The present disclosure further provides methods of using these compounds in the treatment of diseases.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Patent Application No. 63 / 334,878, filed April 26, 2022, which is incorporated herein by reference in its entirety. [Background technology]

[0002] 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 mammalian tryptophan metabolic pathway. The IDO enzyme catalyzes the oxidation of the essential amino acid tryptophan to produce N-formylkynurenine, responsible for tryptophan catabolism in vivo. By degrading tryptophan, the IDO enzyme generates a tryptophan-depleted microenvironment in vivo, which may contribute to various diseases, including cancer, cataracts, and neurological disorders.

[0003] The IDO pathway is also an immunomodulator, and IDO1 is a well-characterized mediator of tumor immune evasion. Due to its homology to IDO1, IDO2 has been proposed to perform a similar immunomodulatory function, and, like IDO1, IDO2 has been demonstrated to be required for regulatory T cell differentiation in vitro. However, in vivo studies have demonstrated that the function of IDO2 differs compared to IDO1. Experiments with preclinical models of autoimmune arthritis support a proinflammatory role for IDO2 in mediating B and T cell activation leading to autoimmune disease. Because IDO enzymes are involved in several different diseases, including cancer, highly effective IDO inhibitors, including those selective for IDO1 versus IDO2, are needed. Summary of the Invention

[0004] In one aspect, the present disclosure provides a compound of formula (I):

[0005] [ka] or a pharmaceutically acceptable salt thereof, wherein R 1 is fluoro, chloro, bromo, 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)R 11 , -S(O)2N(R 11 )2, -NO2, -N3, and -CN; R 1 is hydroxyl, -O-C1 alkyl, or -NO2, R 2 teeth, Fluoro, bromo, iodo, -OR 22 , S.R. 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, R 30 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both are R 30 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; R 1 When is fluoro, R 2 teeth, Bromo, 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, R 30 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both are R 30 C optionally substituted with one or more substituents independently selected from 3-6 Carbocyclic rings, 3- to 4-membered heterocyclic rings,

[0006] [ka] is selected from R 1 is C1 alkyl, -O-C1 haloalkyl, hydroxy, chloro, or bromo, R 2 teeth, 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, R 30 C optionally substituted with one or more substituents independently selected from 2-6 Alkyl, and Both are R 30 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 5-membered heterocycles; R 1 is selected from bromo, hydroxy, and C alkyl, R 2is further selected from fluoro; R 1 But 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)R 11 , -S(O)2N(R 11 )2, -N3, or -CN, R 2 teeth, 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, R 30 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both are R 30 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; However, R 1 -C(O)OR 11 When R 2 provided that cannot be a substituted 6-membered heterocycle, R 3 and R 4 are each independently, for each occurrence, 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, 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 C optionally substituted with one or more substituents independently selected from —C, —NO, and —CN 1-4 Alkyl, and All 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 14C optionally substituted with one or more substituents independently selected from —C, —NO, and —CN 3-4 selected from carbocycles and 3- to 4-membered heterocycles; R 5 and R 5’ are each independently selected from hydrogen and hydroxyl, or R 5 and R 5’ are united as =O, R 6 and R 6’ are each independently selected from hydrogen and hydroxyl, or R 6 and R 6’ are combined =O, =N-OR 26 , or =NR 26 and m is selected from 0, 1, 2, and 3; n is selected from 0, 1, 2, and 3; R 11 and R 14 are each independently, for each occurrence, hydrogen, R 31 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both are R 31 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; R 12 For each occurrence, R 32 C substituted with one or more substituents independently selected from 1-6 Alkyl, and Both are R 33 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; R 13 For each occurrence, hydrogen, R 34C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both are R 34 C optionally substituted with one or more substituents independently selected from 3-5 selected from carbocycles and 3- to 6-membered heterocycles; R 21 , R 23 , R 24 , and R 26 are each independently, for each occurrence, hydrogen, R 34 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both C 1-4 Alkyl, C 1-4 haloalkyl, and R 34 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; R 22 and R 25 are independently, for each occurrence, C 2-6 Alkyl, C 2-6 Haloalkyl, C 2-6 hydroxyalkyl; R 30 , R 31 , R 33 , and R 34 are each independently, for each occurrence, 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(R41 )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 selected from a carbocycle and a 3- to 7-membered heterocycle; R 32 For each occurrence, -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; R 41 are independently hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and C 1-6 hydroxyalkyl, The present invention provides a compound or a pharmaceutically acceptable salt thereof.

[0007] In some embodiments, R 1 is fluoro, chloro, bromo, 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)R 11 , -S(O)2N(R 11 )2, —NO2, —N3, and —CN. In some embodiments, R 1 is fluoro, -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 hydroxyl, -O-C1 alkyl, or -NO2, and R 2 -Fluoro, bromo, iodo, -OR 22 , S.R. 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(R21 )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 is NO2.

[0008] In some embodiments, R 2 is fluoro, bromo, -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 fluoro and R 2 Bromo, 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,

[0009] [ka] and optionally substituted C 1-6 In some embodiments, R 2 Bromo, 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, hydroxyl, chloro, or bromo; R 2 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, chloro, or bromo, and R 2 -OR 25 , -C(O)OR 25 , -C(O)N(R 24 )2, -N(R 24 )C(O)R 24 , -N(R 24 )C(O)OR24 , -NO2, -CN, and optionally substituted C 2-6 alkyl.

[0010] In some embodiments, R 1 is 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)R 11 , -S(O)2N(R 11 )2, -N3, and -CN; R 2 is 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 )R26 , -S(O)R 26 , -S(O)2R 26 , -S(O)2N(R 26 )2, -NO2, -CN, and optionally substituted C 1-6 In some embodiments, R 1 is 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 is -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 is -CN. In some embodiments, R 2 is 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)R 26 , -S(O)2N(R 26 )2, -NO2, -CN, and optionally substituted C 1-6 alkyl.

[0011] In some embodiments, R 5 and R 5’ are taken together to be =O. In some embodiments, R 6 and R 6’ are taken together to be =O. 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.

[0012] In some embodiments, R 11 and R 14 is independently selected at each occurrence from hydrogen and optionally substituted C 1-6 alkyl, and R 12 independently, for each occurrence, optionally substituted C 1-6 alkyl, and R 13 independently, at each occurrence, hydrogen and optionally substituted C 1-6 In some embodiments, R 21 , R 23 , R 24 , and R 26 is, independently at each occurrence, hydrogen, optionally substituted C 1-6 alkyl, and optionally substituted 3- to 6-membered heterocycle. 22 and R 25 are independently, for each occurrence, C 3-6 Alkyl and C 3-6 haloalkyl.

[0013] In some embodiments, R 30 , R 31 , R 33 , and R 34 are each independently, at each occurrence, halogen, -OR 41 , -N(R 41 )2, -OC(O)N(R 41 )2, -C(O)N(R 41 )2, -N(R 41 )C(O)R41 , -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, R 30 , R 31 , R 33 , and R 34 are each independently, at each occurrence, 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 In some embodiments, R 32 are independently, at each occurrence, 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 In some embodiments, R 41 independently for each occurrence, hydrogen and C 1-6 alkyl.

[0014] In another aspect, the present disclosure provides a compound of formula (II):

[0015] [ka] or a pharmaceutically acceptable salt thereof, wherein R 51 is fluoro, chloro, bromo, iodo, 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)R 61 , -S(O)2N(R 61 )2, -NO2, and -CN; R 51 When is fluoro, chloro, or iodo, R 52 teeth, Bromo, iodo, -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, R 80 C alkyl substituted with one or more substituents independently selected from 80 C optionally substituted with one or more substituents independently selected from 2-6 Alkyl, and Both are R 80 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 5-membered heterocycles; R 51 is C1 alkyl or -NO2, R 52 teeth, Fluoro, 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, R 80 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both are R 80 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; R 51 But bromo, 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)R 61 , -S(O)2N(R 61 )2, and -CN, R 52 teeth, 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 )R73 , -S(O)R 73 , -S(O)2R 73 , -S(O)2N(R 73 )2, -NO2, and -CN, R 80 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both are R 80 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; R 53 and R 54 are each independently, for each occurrence, 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, 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 C optionally substituted with one or more substituents independently selected from —C, —NO, and —CN 1-4 Alkyl, and All 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 C optionally substituted with one or more substituents independently selected from —C, —NO, and —CN 3-4selected from carbocycles and 3- to 4-membered heterocycles; R 55 and R 55’ are each independently selected from hydrogen and hydroxyl, or R 55 and R 55’ are united as =O, R 56 and R 56’ are each independently selected from hydrogen and hydroxyl, or R 56 and R 56’ are combined =O, =N-OR 64 , or =NR 64 and p is selected from 0, 1, 2, and 3; q is selected from 0, 1, 2, and 3; R 61 and R 64 are each independently, for each occurrence, hydrogen, R 81 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both are R 81 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; R 71 , R 72 , and R 73 are each independently, for each occurrence, hydrogen, R 82 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both C 1-4 Alkyl, C 1-4 haloalkyl, and R 82 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; R 80 , R 81 , and R82 are each independently, for each occurrence, 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 selected from a carbocycle and a 3- to 7-membered heterocycle; R 91 are independently hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and C 1-6 hydroxyalkyl, The present invention provides a compound or a pharmaceutically acceptable salt thereof.

[0016] In some embodiments, R 51 is fluoro, chloro, bromo, 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(R61 )S(O)2(R 61 ), -S(O)R 61 , -S(O)2N(R 61 )2, —NO2, and —CN. In some embodiments, R 51 is -C(O)R 61 , -C(O)OR 61 , -C(O)N(R 61 )2, and —NO2. In some embodiments, R 51 is fluoro, chloro, or iodo. In some embodiments, is C alkyl or -NO, and R 52 -Fluoro, iodo, -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 is —NO. In some embodiments, R 52 Fluoro, -OR 72 , -NO2, -CN, and optionally substituted C 1-6 alkyl.

[0017] In some embodiments, R 51 is bromo, 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)R 61 , -S(O)2N(R 61 )2, and -CN. In some embodiments, R 51 -OR 61 , -C(O)R 61 , -C(O)OR 61 , -C(O)N(R 61 )2, and -CN, and R 52 is 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 ), -N(R 73 )P(O)(OR 73 )R 73 , -S(O)R 73 , -S(O)2R 73 , -S(O)2N(R73 )2, —NO2, and —CN. In some embodiments, R 51 is -C(O)R 61 , -C(O)OR 61 , and -C(O)N(R 61 In some embodiments, R 52 is selected from halogen. In some embodiments, R 52 is chloro.

[0018] In some embodiments, R 53 and R 54 is independently selected at each occurrence from halogen. 53 is independently selected at each occurrence from halogen. 55 and R 55’ are taken together to be =O. In some embodiments, R 56 and R 56’ are taken together to be =O. 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.

[0019] In some embodiments, R 61 and R 64 is, independently at each occurrence, hydrogen, optionally substituted C 1-6 alkyl, and optionally substituted 3- to 6-membered heterocycle. 80 , R 81 , and R 82 are each independently, for each occurrence, -N(R 91 )2, -C(O)OR 91 , and -N(R 91 )SO2N(R 91 In some embodiments, R 91 independently for each occurrence, hydrogen and C 1-6 alkyl.

[0020] In another aspect, the present disclosure provides a compound of formula (III):

[0021] [ka] or a pharmaceutically acceptable salt thereof, wherein R 101 is fluoro, chloro, bromo, 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)R 111 , -S(O)2N(R 111 )2, -NO2, and -CN; R 101 When is fluoro, R 102 teeth, Chloro, bromo, iodo, -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(R121 )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, R 123 C alkyl substituted with one or more substituents independently selected from 130 C optionally substituted with one or more substituents independently selected from 2-6 Alkyl, and Both are R 130 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; R 101 Bromo, iodo, hydroxyl, -O-C1 alkyl, -C(O)OR 111 , -C(O)N(H)(C2 alkyl), -S(O)2R 111 , or -S(O)N(R 111 )2, then R 102 teeth, Fluoro, -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, R 130 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both are R 130 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; R 101 But 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, and -CN, R 102 teeth, 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)R126 , -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, R 130 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both are R 130 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; However, (i) R 101 When is NO2, R 102 cannot be methyl, and (ii) R 101 When is methyl, R 102 cannot be chloro, and (iii) R 101 When is chloro, R 102 Assuming that it cannot be bromo, R 103 and R 104 are each independently, for each occurrence, 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, Halogen, -OR 114 , -SR 114 , -N(R 114 )2, -N(R114 )C(O)R 114 , -C(O)R 114 , -C(O)OR 114 , -C(O)N(R 114 C optionally substituted with one or more substituents independently selected from —C, —NO, and —CN 1-4 Alkyl, and All 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 C optionally substituted with one or more substituents independently selected from —C, —NO, and —CN 3-4 selected from carbocycles and 3- to 4-membered heterocycles; R 105 and R 105’ are each independently selected from hydrogen and hydroxyl, or R 105 and R 105’ are united as =O, R 106 and R 106’ are each independently selected from hydrogen and hydroxyl, or R 106 and R 106’ are combined =O, =N-OR 114 , or =NR 114 and r is selected from 0, 1, 2, and 3; s is selected from 0, 1, 2, and 3; R 111 and R 114 are each independently, for each occurrence, hydrogen, R 131 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both are R 131 C optionally substituted with one or more substituents independently selected from3-6 selected from carbocycles and 3- to 6-membered heterocycles; R 112 For each occurrence, R 132 C substituted with one or more substituents independently selected from 1-6 Alkyl, and Both are R 133 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; R 113 For each occurrence, hydrogen, R 134 C alkyl and C optionally substituted with one or more substituents independently selected from 3-6 Alkyl, and R 134 C alkyl optionally substituted with one or more substituents independently selected from Both are R 134 C optionally substituted with one or more substituents independently selected from 3-5 selected from carbocycles and 3- to 6-membered heterocycles; R 121 , R 124 , and R 126 are each independently, for each occurrence, hydrogen, R 134 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both C 1-4 Alkyl, C 1-4 haloalkyl, and R 134 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; R 122 and R 125 are each independently, for each occurrence, R 134C optionally substituted with one or more substituents independently selected from 2-6 Alkyl, and Both C 1-4 Alkyl, C 1-4 haloalkyl, and R 134 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; R 123 independently, for each occurrence, hydrogen, R 134 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both C 1-4 Alkyl, C 1-4 haloalkyl, and R 134 C optionally substituted with one or more substituents independently selected from 3-5 selected from carbocycles and 3- to 6-membered heterocycles; R 130 , R 131 , R 132 , R 133 , and R 134 are each independently, for each occurrence, 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 selected from a carbocycle and a 3- to 7-membered heterocycle; R 141 are independently hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and C 1-6 hydroxyalkyl, The present invention provides a compound or a pharmaceutically acceptable salt thereof.

[0022] In some embodiments, R 101 is fluoro, chloro, bromo, 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)R 111 , -S(O)2N(R 111 )2, —NO2, and —CN. In some embodiments, R 101 is selected from fluoro, —NO, and —CN. In some embodiments, R 101 is fluoro. In some embodiments, R 102 is chloro, bromo, iodo, -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)R 121, -S(O)2N(R 121 )2, —NO2, and —CN. In some embodiments, R 102 is chloro or bromo. In some embodiments, R 101 is bromo, iodo, hydroxyl, -O-C1 alkyl, -C(O)OR 111 , -C(O)N(H)(C2 alkyl), -S(O)2R 111 , and -S(O)N(R 111 In some embodiments, R 101 is 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 ), —NO, and —CN. In some embodiments, R 101 is selected from —NO and —CN. In some embodiments, R 102 is a halogen and optionally substituted C 1-6 alkyl.

[0023] In some embodiments, R 103 and R 104 are each independently, for each occurrence, halogen and C 1-4 In some embodiments, R 105 and R 105’ are taken together to be =O. In some embodiments, R 106 and R106’ are taken together to be =O. 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.

[0024] In another aspect, the present disclosure provides a compound of formula (IV):

[0025] [ka] or a pharmaceutically acceptable salt thereof, wherein R 151 is fluoro, bromo, -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 rings, and -OR 3-6 heterocycles, and 171 and optionally substituted with one or more substituents independently selected from

[0026] [ka] is selected from R 151 When is fluoro, R 152 teeth, 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, R 195 C alkyl substituted with one or more substituents independently selected from 180 C optionally substituted with one or more substituents independently selected from 2-6 Alkyl, and Both are R 180 C optionally substituted with one or more substituents independently selected from 3-6 Carbocycle, 3-membered heterocycle, 4-membered heterocycle,

[0027] [ka] and a 6-membered heterocycle; R 151 but,

[0028] [ka] -SR 161 , -S(O)R 161 , -S(O)2R 161 , or -S(O)N(R 161 )2, or -CN, R 152 teeth, 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 ), -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, R 180 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both are R 180 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; R 151 When is bromo or -NO2, R 152 teeth, 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, R 180 C alkyl substituted with one or more substituents independently selected from 198 C alkyl substituted with one or more substituents independently selected from 180 C optionally substituted with one or more substituents independently selected from 2-6 Alkyl, and Both are R 180 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; However, (i) R 151 When is NO2, R 152 is R 180 and (ii) R 151 When is NO2, R152 is assumed to be ethyl, R 151 But -C 1-6 Haloalkyl, -OC 2-6 Alkyl, -OC 1-6 Haloalkyl, -OR 3-6 Carbocyclic ring, -OR 3-6 Heterocycle, -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, then R 152 teeth, 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, R 177 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both are R 177 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; R 153 and R 154 are each independently, for each occurrence, 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, 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 C optionally substituted with one or more substituents independently selected from —C, —NO, and —CN 1-4 Alkyl, and All 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 C optionally substituted with one or more substituents independently selected from —C, —NO, and —CN 3-6 selected from carbocycles and 3- to 5-membered heterocycles; R 155 and R 155’are each independently selected from hydrogen, hydroxyl, and methyl, or R 155 and R 155’ are united as =O, R 156 and R 156’ are each independently selected from hydrogen, hydroxyl, and methyl, or R 156 and R 156’ are combined =O, =N-OR 171 , or =NR 171 and t is selected from 0, 1, 2, and 3; u is selected from 0, 1, 2, and 3; R 161 and R 164 are each independently, for each occurrence, hydrogen, R 177 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both are R 177 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; R 171 , R 174 , and R 176 are each independently, for each occurrence, hydrogen, R 180 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both C 1-4 Alkyl, C 1-4 haloalkyl, and R 180 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; R 177 and R 180 are each independently, for each occurrence, Halogen, -OR 191 , -SR191 , -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 selected from a carbocycle and a 3- to 7-membered heterocycle; R 178 For each occurrence, R 180 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both are R 180 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; R 191 are independently hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and C 1-6 hydroxyalkyl; R 192 For each occurrence, Both are R 180C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; R 193 For each occurrence, R 180 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both C 1-4 Alkyl, C 1-4 haloalkyl, and R 180 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; R 194 For each occurrence, R 180 C substituted with one or more substituents independently selected from 1-6 alkyl, R 195 independently, for each occurrence, Halogens, -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 )R171 , -S(O)R 171 , -S(O)2R 171 , and -S(O)N(R 171 )2, R 180 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both C 1-4 Alkyl, C 1-4 haloalkyl, and R 180 C optionally substituted with one or more substituents independently selected from 5-6 selected from carbocycles and 3- to 6-membered heterocycles; R 196 For each occurrence, Hydrogen, -CN, and OR 171 , R 180 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both C 1-4 Alkyl, C 1-4 haloalkyl, and R 180 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; R 197 For each occurrence, hydrogen, R 180 C optionally substituted with one or more substituents independently selected from 2-6 Alkyl, and Both C 1-4 Alkyl, C 1-4 haloalkyl, and R 180 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; R 198 independently, for each occurrence, Fluoro, chloro, iodo, -NH2, -NHR 192 , -NR 196 (C=NR196 )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)N(R 171 )2, R 180 C optionally substituted with one or more substituents independently selected from 2-6 Alkyl, and Both C 1-4 Alkyl, C 1-4 haloalkyl, and R 180 C optionally substituted with one or more substituents independently selected from 5-6 selected from carbocycles and 3- to 6-membered heterocycles; The present invention provides a compound or a pharmaceutically acceptable salt thereof.

[0029] In some embodiments, R 151 is fluoro, bromo, -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(R161 ), -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

[0030] [ka] In some embodiments, R 151 is fluoro, bromo, -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

[0031] [ka] In some embodiments, R 151 -Fluoro, bromo, -SR 161 , -S(O)2R 161 , -CN, -NO2, and

[0032] [ka] In some embodiments, R 151 is fluoro. In some embodiments, R 152 -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(R171 )2, -N(H)C(O)R 194 , -N(R 171 )S(O)2(R 171 ), -S(O)R 171 , -S(O)2N(R 171 )2, -NR 196 (C=NR 196 )N(R 196 )2, -N3, -CN, R 195 C alkyl substituted with one or more substituents independently selected from

[0033] [ka] In some embodiments, R 152 -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, R 195 C alkyl substituted with one or more substituents independently selected from

[0034] [ka] is selected from.

[0035] In some embodiments, R 151 -SR 161 , -S(O)2R 161 , -CN, and

[0036] [ka] In some embodiments, R 152 is a 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)R 174 , -S(O)2N(R 174 )2, -NO2, -CN, R 180 C optionally substituted with one or more substituents independently selected from 1-6 alkyl, and R 180 In some embodiments, R is selected from a 5-membered heterocycle optionally substituted with one or more substituents independently selected from 152 is a 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, R 180 C optionally substituted with one or more substituents independently selected from 1-6 alkyl, and R 180 In some embodiments, R is selected from a 5-membered heterocycle optionally substituted with one or more substituents independently selected from 152 is -C(O)N(R 174 )2, -N(R 174 )C(O)R 174 , -N(R 174 )C(O)OR 174 , R 180 C optionally substituted with one or more substituents independently selected from 1-6 alkyl, and R 180 and wherein the aryl group is a 5-membered heterocycle optionally substituted with one or more substituents independently selected from:

[0037] In some embodiments, R 151 is selected from bromo and —NO. 152 -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)R 176 , -S(O)2N(R 176 )2, -NO2, -CN, R 180 C alkyl substituted with one or more substituents independently selected from 198 C alkyl substituted with one or more substituents independently selected from 180 C optionally substituted with one or more substituents independently selected from 2-6 alkyl, with the proviso that (i) R 151 When is NO2, R 152 is R 180 and (ii) R 151 When is NO2, R 152 It is provided that R cannot be ethyl. 152 is R 180 C alkyl substituted with one or more substituents independently selected from 198 C alkyl substituted with one or more substituents independently selected from 180 C optionally substituted with one or more substituents independently selected from 2-6 alkyl, with the proviso that (i) R 151 When is NO2, R 152 is R 180 and (ii) R 151When is NO2, R 152 It is provided that R cannot be ethyl. 151 is bromo and R 152 is R 180 In some embodiments, R is a C alkyl substituted with one or more substituents independently selected from 151 is -NO2. R 152 is R 198 is a C alkyl substituted with one or more substituents independently selected from:

[0038] In some embodiments, R 153 and R 154 are each independently, for each occurrence, halogen and C 1-4 In some embodiments, R 155 and R 155’ are taken together to be =O. In some embodiments, R 156 and R 156’ are taken together to be =O. In some embodiments, R 156 and R 156’ together =N-OR 171 In some embodiments, R 156 and R 156’ are each independently selected from hydroxyl and methyl. In some embodiments, t is selected from 0 and 1. In some embodiments, u is 0.

[0039] In another aspect, the disclosure provides a pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of Formula (I), (II), (III), or (IV).

[0040] In another aspect, the 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 of Formula (I), (II), (III), or (IV) and a pharmaceutically acceptable excipient.

[0041] Incorporation by Reference 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 OF THE INVENTION

[0042] Provided herein are IDO2 modulators that are useful for treating several diseases or disorders, including cancer and autoimmune diseases. The present disclosure further provides tryptanthrin analogs, which are potent IDO2 modulators with distinct selectivity profiles. In some embodiments, the present disclosure provides modulators of IDO1 and IDO2. In some embodiments, the present disclosure provides dual IDO2 / IDO1 modulators. In some embodiments, the present disclosure provides selective IDO2 modulators that preferentially modulate IDO2 activity over IDO1 activity.

[0043] definition 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 this invention belongs. All patents and publications mentioned herein are incorporated by reference. As used in this specification and claims, the singular forms "a," "an," and "the" include the plural forms unless the context clearly dictates otherwise.

[0044] "Alkyl" refers to an alkyl group consisting solely of carbon and hydrogen atoms, without unsaturation, and preferably having 1 to 12 carbon atoms (e.g., C1-C 12 Alkyl) refers to a straight or branched hydrocarbon chain monovalent radical. An alkyl is attached to the rest of the molecule by a single bond. In certain embodiments, an alkyl contains 1 to 12 carbon atoms (i.e., C1-C 12In certain embodiments, alkyl contains 1 to 8 carbon atoms (i.e., C1-C8 alkyl). In other embodiments, alkyl contains 1 to 5 carbon atoms (i.e., C1-C5 alkyl). In other embodiments, alkyl contains 1 to 4 carbon atoms (i.e., C1-C4 alkyl). In other embodiments, alkyl contains 1 to 3 carbon atoms (i.e., C1-C3 alkyl). In other embodiments, alkyl contains 1 to 2 carbon atoms (i.e., C1-C2 alkyl). In other embodiments, alkyl contains 1 carbon atom (i.e., C1 alkyl). In other embodiments, alkyl contains 5 to 15 carbon atoms (i.e., C5-C 15 In other embodiments, alkyl contains 5 to 8 carbon atoms (i.e., C5-C8 alkyl). In other embodiments, alkyl contains 2 to 5 carbon atoms (i.e., C2-C5 alkyl). In other embodiments, alkyl contains 3 to 5 carbon atoms (i.e., C3-C5 alkyl). For example, alkyl groups may be attached to the remainder of the molecule by a single bond and include methyl, ethyl, 1-propyl (n-propyl), 1-methylethyl (iso-propyl), 1-butyl (n-butyl), 1-methylpropyl (sec-butyl), 2-methylpropyl (iso-butyl), 1,1-dimethylethyl (tert-butyl), 1-pentyl (n-pentyl), and the like.

[0045] "Alkenyl" refers to an alkyl group consisting solely of carbon and hydrogen atoms, containing at least one carbon-carbon double bond, and having 2 to 12 carbon atoms (i.e., C-C 12Alkenyl refers to a straight or branched hydrocarbon chain radical group. In certain embodiments, alkenyl contains 2 to 8 carbon atoms (i.e., C2-C8 alkenyl). In certain embodiments, alkenyl contains 2 to 6 carbon atoms (i.e., C2-C6 alkenyl). In other embodiments, alkenyl contains 2 to 4 carbon atoms (i.e., C2-C4 alkenyl). Alkenyl is attached to the remainder of the molecule by a single bond, and examples include ethenyl (i.e., vinyl), prop-1-enyl (i.e., allyl), but-1-enyl, pent-1-enyl, and penta-1,4-dienyl.

[0046] "Alkynyl" refers to an alkyl group consisting solely of carbon and hydrogen atoms, containing at least one carbon-carbon triple bond, and having 2 to 12 carbon atoms (i.e., C-C 12 Alkynyl refers to a straight or branched hydrocarbon chain radical group. In certain embodiments, alkynyl contains 2 to 8 carbon atoms (i.e., C2-C8 alkynyl). In other embodiments, alkynyl contains 2 to 6 carbon atoms (i.e., C2-C6 alkynyl). In other embodiments, alkynyl contains 2 to 4 carbon atoms (i.e., C2-C4 alkynyl). Alkynyl is attached to the rest of the molecule by a single bond, and examples include ethynyl, propynyl, butynyl, pentynyl, hexynyl, and the like.

[0047] "Alkylene" refers to a linear divalent hydrocarbon chain that links the rest of the molecule to a radical group, consisting solely of carbon and hydrogen, containing no unsaturation, and preferably having 1 to 12 carbon atoms, such as methylene, ethylene, propylene, n-butylene, and the like. The alkylene chain is attached to the rest of the molecule by a single bond and to the radical group by a single bond. The points of attachment of the alkylene chain to the rest of the molecule and to the radical group are through the terminal carbons, respectively. The alkylene chain can be optionally substituted with one or more substituents, such as those described herein. In certain embodiments, the alkylene contains 1 to 10 carbon atoms (i.e., C1-C 10alkylene). In certain embodiments, alkylene contains 1 to 8 carbon atoms (i.e., C1-C8 alkylene). In other embodiments, alkylene contains 1 to 5 carbon atoms (i.e., C1-C5 alkylene). In other embodiments, alkylene contains 1 to 4 carbon atoms (i.e., C1-C4 alkylene). In other embodiments, alkylene contains 1 to 3 carbon atoms (i.e., C1-C3 alkylene). In other embodiments, alkylene contains 1 to 2 carbon atoms (i.e., C1-C2 alkylene). In other embodiments, alkylene contains 1 carbon atom (i.e., C1 alkylene). In other embodiments, alkylene contains 5 to 8 carbon atoms (i.e., C5-C8 alkylene). In other embodiments, alkylene contains 2 to 5 carbon atoms (i.e., C2-C5 alkylene). In other embodiments, alkylene contains 3 to 5 carbon atoms (i.e., C3-C5 alkylene).

[0048] "Alkenylene" refers to a linear divalent hydrocarbon chain, consisting solely of carbon and hydrogen, containing at least one carbon-carbon double bond, and preferably having 2 to 12 carbon atoms, linking the rest of the molecule to a radical group. The alkenylene chain is attached to the rest of the molecule through a single bond and to the radical group through a single bond. The points of attachment of the alkenylene chain to the rest of the molecule and to the radical group are through the terminal carbons, respectively. The alkenylene chain can be optionally substituted with one or more substituents, such as those described herein. In certain embodiments, the alkenylene contains 2 to 10 carbon atoms (i.e., C2-C 10alkenylene). In certain embodiments, alkenylene contains 2 to 8 carbon atoms (i.e., C2-C8 alkenylene). In other embodiments, alkenylene contains 2 to 5 carbon atoms (i.e., C2-C5 alkenylene). In other embodiments, alkenylene contains 2 to 4 carbon atoms (i.e., C2-C4 alkenylene). In other embodiments, alkenylene contains 2 to 3 carbon atoms (i.e., C2-C3 alkenylene). In other embodiments, alkenylene contains 2 carbon atoms (i.e., C2 alkenylene). In other embodiments, alkenylene contains 5 to 8 carbon atoms (i.e., C5-C8 alkenylene). In other embodiments, alkenylene contains 3 to 5 carbon atoms (i.e., C3-C5 alkenylene).

[0049] "Alkynylene" refers to a linear divalent hydrocarbon chain, consisting solely of carbon and hydrogen, containing at least one carbon-carbon triple bond, and preferably having 2 to 12 carbon atoms, linking the rest of the molecule to a radical group. The alkynylene chain is attached to the rest of the molecule through a single bond and to the radical group through a single bond. The points of attachment of the alkynylene chain to the rest of the molecule and to the radical group are through the terminal carbons, respectively. The alkynylene chain can be optionally substituted with one or more substituents, such as those described herein. In certain embodiments, the alkynylene contains 2 to 10 carbon atoms (i.e., C2-C 10 alkynylene). In certain embodiments, alkynylene contains 2 to 8 carbon atoms (i.e., C2-C8 alkynylene). In other embodiments, alkynylene contains 2 to 5 carbon atoms (i.e., C2-C5 alkynylene). In other embodiments, alkynylene contains 2 to 4 carbon atoms (i.e., C2-C4 alkynylene). In other embodiments, alkynylene contains 2 to 3 carbon atoms (i.e., C2-C3 alkynylene). In other embodiments, alkynylene contains 2 carbon atoms (i.e., C2 alkynylene). In other embodiments, alkynylene contains 5 to 8 carbon atoms (i.e., C5-C8 alkynylene). In other embodiments, alkynylene contains 3 to 5 carbon atoms (i.e., C3-C5 alkynylene).

[0050] "C x-y The term "alkyl," when used with a chemical moiety such as alkyl, alkenyl, or alkynyl, is meant to include groups containing x to y carbons in the chain. For example, "C 1-6 The term "alkyl" refers to substituted or unsubstituted saturated hydrocarbon groups, including straight-chain alkyl and branched-chain alkyl groups, containing 1 to 6 carbons. x-y The term alkylene- refers to a substituted or unsubstituted alkylene chain having 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 one of which is optionally substituted.

[0051] "C x-y alkenyl" and "C x-y The term "alkynyl" refers to unsaturated aliphatic groups analogous in length and possible substitution to the alkyls described above, but which contain at least one double or triple bond respectively. x-y The term alkenylene- refers to a substituted or unsubstituted alkenylene chain having x to y carbons in the chain. For example, -C 2-6 Alkenylene- can be selected from ethenylene, propenylene, butenylene, pentenylene, and hexenylene, any one of which is optionally substituted. The alkenylene chain can have one double bond or more than one double bond in the alkenylene chain. The term -Cx-y alkynylene- refers to a substituted or unsubstituted alkynylene chain having x to y carbons in the alkynylene chain. For example, -C 2-6 Alkynylene- can be selected from ethynylene, propynylene, butynylene, pentynylene, and hexynylene, any one of which is optionally substituted. The alkynylene chain can have one triple bond or more than one triple bond along the alkynylene chain.

[0052] 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- to 10-membered monocyclic rings and 6- to 12-membered bicyclic rings. Each ring of a bicyclic carbocycle can be selected from saturated, unsaturated, and aromatic rings. A bicyclic carbocycle can be a fused, bridged, or spiro ring system. In some embodiments, a carbocycle is an aryl. In some embodiments, a carbocycle is a cycloalkyl. In some embodiments, a carbocycle is a cycloalkenyl. In exemplary embodiments, an aromatic ring, such as phenyl, can be fused to a saturated or unsaturated ring, such as cyclohexane, cyclopentane, or cyclohexene. All combinations of saturated, unsaturated, and aromatic bicyclic rings are included in the definition of carbocycle, if valences permit. Exemplary carbocycles include cyclopentyl, cyclohexyl, cyclohexenyl, adamantyl, phenyl, indanyl, and naphthyl. Carbocycles can be optionally substituted with one or more substituents such as those described herein.

[0053] "Cycloalkyl" refers to a group 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 Cycloalkyl) refers to a stable, fully saturated, monocyclic or polycyclic hydrocarbon radical. In certain embodiments, cycloalkyl contains 3 to 10 carbon atoms (i.e., C 3-10 In other embodiments, the cycloalkyl contains 5 to 7 carbon atoms (i.e., C 5-7Cycloalkyl). A cycloalkyl can be attached to the remainder of the molecule by a single bond. Examples of monocyclic cycloalkyls include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Polycyclic cycloalkyl radicals include, for example, adamantyl, norbornyl (i.e., bicyclo[2.2.1]heptanyl), norbornenyl, decalinyl, 7,7-dimethyl-bicyclo[2.2.1]heptanyl, and the like. A cycloalkyl can be optionally substituted with one or more substituents, such as those described herein.

[0054] "Cycloalkenyl" refers to a group 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., "C3-C 12 "cycloalkyl" refers to a stable, unsaturated, non-aromatic, monocyclic or polycyclic hydrocarbon radical. In certain embodiments, cycloalkenyl contains 3 to 10 carbon atoms (i.e., C 3-10 In other embodiments, the cycloalkenyl contains 5 to 7 carbon atoms (i.e., C 5-7 Cycloalkenyl). The cycloalkenyl may be attached to the rest of the molecule by a single bond. Examples of monocyclic cycloalkenyls include, for example, cyclopentenyl, cyclohexenyl, cycloheptenyl, and cyclooctenyl. The cycloalkenyl may be optionally substituted with one or more substituents, such as those described herein.

[0055] "Aryl" refers to a radical derived from an aromatic monocyclic or aromatic polycyclic hydrocarbon ring system by removing a hydrogen atom from a ring carbon atom. The aromatic monocyclic or aromatic polycyclic hydrocarbon ring system contains only hydrogen and carbon atoms of 5 to 18 carbon atoms, and at least one ring in the ring system is aromatic, i.e., contains a cyclic delocalized (4n+2) π-electron system according to Hückel's theory. Ring systems from which aryl groups are derived include, but are not limited to, groups such as benzene, fluorene, indane, indene, tetralin, and naphthalene. Aryl can be optionally substituted with one or more substituents, such as those described herein.

[0056] "C x-y "Carbocyclic" means a group containing x to y carbons in the ring. For example, "C 3-6 The term "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.

[0057] As used herein, the term "heterocycle" 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. Heterocycles include 3- to 10-membered monocyclic rings and 6- to 12-membered bicyclic rings. Each ring of a bicyclic heterocycle can be selected from a saturated ring, an unsaturated ring, and an aromatic ring. In some embodiments, a heterocycle contains at least one heteroatom selected from oxygen, nitrogen, sulfur, or any combination thereof. In some embodiments, a heterocycle contains at least one heteroatom selected from oxygen, nitrogen, or any combination thereof. In some embodiments, a heterocycle contains at least one heteroatom selected from oxygen, sulfur, or any combination thereof. In some embodiments, a heterocycle contains at least one heteroatom selected from nitrogen, sulfur, or any combination thereof. A heterocycle may be attached to the remainder of the molecule through any atom of the heterocycle, such as a carbon atom or nitrogen atom of the heterocycle, if valence allows. In some embodiments, the heterocycle is heteroaryl. In some embodiments, the heterocycle is heterocycloalkyl. Exemplary heterocycles include pyrrolidinyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, piperidinyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, thiophenyl, oxazolyl, thiazolyl, morpholinyl, indazolyl, indolyl, and quinolinyl. The heterocycle may be optionally substituted with one or more substituents, such as those described herein. Bicyclic heterocycles may be fused, bridged, or spirocyclic. In exemplary embodiments, the heterocycle, e.g., pyridyl, may be fused to a saturated or unsaturated ring, e.g., cyclohexane, cyclopentane, or cyclohexene. Heterocycles can be optionally substituted with one or more substituents such as those described herein.

[0058] "Heterocycloalkyl" refers to a stable 3- to 12-membered non-aromatic ring radical containing 2 to 12 carbon atoms and at least one heteroatom, where each heteroatom may be selected from N, O, Si, P, B, and S atoms. In some embodiments, a heterocycloalkyl contains at least one heteroatom selected from oxygen, nitrogen, sulfur, or any combination thereof. In some embodiments, a heterocycloalkyl contains at least one heteroatom selected from oxygen, nitrogen, or any combination thereof. In some embodiments, a heterocycloalkyl contains at least one heteroatom selected from oxygen, sulfur, or any combination thereof. In some embodiments, a heterocycloalkyl contains at least one heteroatom selected from nitrogen, sulfur, or any combination thereof. Heterocycloalkyls may be selected from monocyclic or bicyclic ring systems, and fused or bridged ring systems. The heteroatoms in a heterocycloalkyl are optionally oxidized. One or more nitrogen atoms, if present, are optionally quaternized. A heterocycloalkyl radical is partially or fully saturated. The heterocycloalkyl may be attached to the remainder of the molecule by any atom of the heterocycloalkyl, including any carbon or nitrogen atom of the heterocycloalkyl, if valence allows. Examples of heterocycloalkyl radicals include, but are not limited to, dioxolanyl, thienyl[1,3]dithianyl, decahydroisoquinolyl, imidazolinyl, imidazolidinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, piperidinyl, piperazinyl, 4-piperidonyl, pyrrolidinyl, pyrazolidinyl, quinuclidinyl, thiazolidinyl, tetrahydrofuryl, trithianyl, tetrahydropyranyl, thiomorpholinyl, thiamorpholinyl, 1-oxo-thiomorpholinyl, and 1,1-dioxo-thiomorpholinyl. Heterocycloalkyl can be optionally substituted with one or more substituents, such as those described herein.

[0059] The term "heteroaryl" refers to a radical derived from a 3- to 12-membered aromatic ring radical containing 1 to 11 carbon atoms and at least one heteroatom selected from N, O, and S. In some embodiments, a heteroaryl contains at least one heteroatom selected from oxygen, nitrogen, sulfur, or any combination thereof. In some embodiments, a heteroaryl contains at least one heteroatom selected from oxygen, nitrogen, or any combination thereof. In some embodiments, a heteroaryl contains at least one heteroatom selected from oxygen, sulfur, or any combination thereof. In some embodiments, a heteroaryl contains at least one heteroatom selected from nitrogen, sulfur, or any combination thereof. As used herein, a heteroaryl ring may be selected from monocyclic or bicyclic fused or bridged ring systems, wherein at least one of the rings in the ring system is aromatic, i.e., contains a cyclic delocalized (4n+2) π-electron system according to Hückel theory. The heteroatoms in a heteroaryl radical may be optionally oxidized. One or more nitrogen atoms, if present, are optionally quaternized. A heteroaryl can be attached to the remainder of the molecule by any atom of the heteroaryl, such as a carbon atom or nitrogen atom of the heteroaryl, if valence allows. A heteroaryl includes an aromatic monocyclic ring structure, preferably a 5- or 6-membered ring, whose ring structure contains at least one heteroatom, preferably 1 to 4 heteroatoms, and more preferably 1 or 2 heteroatoms. Examples of heteroaryl groups include pyrrole, furan, thiophene, imidazole, oxazole, thiazole, pyrazole, pyridine, pyrazine, pyridazine, and pyrimidine. A heteroaryl can be optionally substituted with one or more substituents, such as those described herein. A heteroaryl also includes polycyclic ring systems having two or more rings, in which two or more atoms are common to two adjacent rings, and at least one of the rings is heteroaromatic, e.g., the other ring(s) can be aromatic or non-aromatic, carbocyclic, or heterocyclic.The heteroaryl can be optionally substituted with one or more substituents such as those described herein.

[0060] An "X-membered heterocycle" refers to the number of ring atoms in the ring, i.e., X. For example, a 5-membered heteroaryl ring or a 5-membered heteroaromatic ring has 5 ring atoms, e.g., triazole, oxazole, thiophene, etc.

[0061] "Alkoxy" refers to a radical attached through an oxygen atom of the formula --O-alkyl, where alkyl is an alkyl chain as defined above.

[0062] "Halo" or "halogen" refers to halogen substituents such as bromo, chloro, fluoro, and iodo substituents.

[0063] As used herein, the term "haloalkyl" or "haloalkane" refers to an alkyl radical, as defined above, that is substituted with one or more halogen radicals, such as trifluoromethyl, dichloromethyl, bromomethyl, 2,2,2-trifluoroethyl, 1-fluoromethyl-2-fluoroethyl, etc. In some embodiments, the alkyl portion of the fluoroalkyl radical is optionally further substituted. Examples of halogen-substituted alkanes ("haloalkanes") include halomethanes (e.g., chloromethane, bromomethane, fluoromethane, iodomethane), ditrihalomethanes and trihalomethanes (e.g., trichloromethane, tribromomethane, trifluoromethane, triiodomethane), 1-haloethanes, 2-haloethanes, 1,2-dihaloethanes, 1-halopropanes, 2-halopropanes, 3-halopropanes, 1,2-dihalopropanes, 1,3-dihalopropanes, 2,3-dihalopropanes, 1,2,3-trihalopropanes, and other suitable combinations of alkanes (or substituted alkanes) and halogens (e.g., Cl, Br, F, and I). When an alkyl group is substituted with more than one halogen radical, each halogen can be independently selected from, for example, 1-chloro, 2-fluoroethane.

[0064] The term "substituted" refers to a moiety having substituents replacing hydrogen on one or more carbon or substitutable heteroatoms, such as the NH or NH of a compound. It is understood that "substituted" or "substituted with" includes the implicit proviso that such substitution is subject to the permissible valences of the substituted atom and substituent, and that the substitution results in a stable compound, i.e., a compound that does not spontaneously undergo transformation, such as rearrangement, cyclization, or excretion. In certain embodiments, substituted refers to a moiety having substituents replacing two hydrogen atoms on the same carbon atom, such as replacing two hydrogen atoms on a single carbon with an oxo, imino, or thioxo group. As used herein, the term "substituted" is intended to include all permissible substituents of organic compounds. In a broad aspect, permissible substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and nonaromatic substituents of organic compounds. The permissible substituents can be one or more and the same or different in appropriate organic compounds.

[0065] In some embodiments, a substituent may be any substituent described herein, for example, halogen, hydroxy, oxo (=O), thioxo (=S), cyano (-CN), nitro (-NO), imino (=NH), oximo (=N-OH), hydrazino (=N-NH), -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 (t is 1 or 2), -R b -S(O) t R a (t is 1 or 2), -R b -S(O) t OR a (t is 1 or 2), and -R b -S(O) t N(R a )2 (t is 1 or 2), as well as alkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, aralkynyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, and heteroaralkyl, any of which may include alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo (=O), thioxo (=S), cyano (-CN), nitro (-NO2), imino (=NH), oximo (=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(Ra )C(O)OR a , -R b -N(R a )C(O)R a , -R b -N(R a )S(O) t R a (t is 1 or 2), -R b -S(O) t R a (t is 1 or 2), -R b -S(O) t OR a (t is 1 or 2), and -R b -S(O) t N(R a )2 (t is 1 or 2), and each R a is independently selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, or heteroarylalkyl; and each R a is, as far as valence allows, alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo (=O), thioxo (=S), cyano (-CN), nitro (-NO2), imino (=NH), oximo (=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(Ra )C(O)OR a , -R b -N(R a )C(O)R a , -R b -N(R a )S(O) t R a (t is 1 or 2), -R b -S(O) t R a (t is 1 or 2), -R b -S(O) t OR a (t is 1 or 2), and -R b -S(O) t N(R a )2 (t is 1 or 2), and each R b are independently selected from a direct bond or a straight or branched alkylene, alkenylene, or alkynylene chain; c is a straight or branched alkylene, alkenylene, or alkynylene chain. Those skilled in the art will recognize that the substituents themselves can be substituted, if appropriate.

[0066] The term "salt" or "pharmaceutically acceptable salt" refers to salts derived from a variety of organic and inorganic counterions well 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.

[0067] The phrase "pharmaceutically acceptable" is used herein to refer to compounds, materials, compositions, and / or dosage forms that are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without undue toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit-risk ratio.

[0068] As used herein, the phrase "pharmaceutically acceptable excipient" or "pharmaceutically acceptable carrier" means 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.

[0069] The terms "subject," "individual," and "patient" are used interchangeably and can refer to humans as well as non-human mammals (e.g., non-human primates, dogs, horses, cats, pigs, cows, ungulates, rabbits, etc.). In various embodiments, a subject can be a human (e.g., an adult male, adult female, adolescent male, adolescent female, boy, girl) receiving care from a physician or other health worker while hospitalized, as an outpatient, or in other clinical settings. In certain embodiments, a subject may not be receiving care from or prescribed by a physician or other health worker.

[0070] As used herein, "a subject in need thereof" refers to a subject, as described below, suffering from or at risk for a condition to be treated prophylactically or therapeutically with a compound or salt described herein.

[0071] The terms "administer," "administered," "administers," and "administering" are defined as providing a composition to a subject via a route known in the art, including, but not limited to, intravenous, intraarterial, oral, parenteral, buccal, topical, transdermal, rectal, intramuscular, subcutaneous, intraosseous, oromucosal, or intraperitoneal routes of administration. In certain embodiments, the oral route of administering the composition can be used. The terms "administer," "administered," "administers," and "administering" 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.

[0072] As used herein, "treatment" or "treating" refers to an approach for obtaining a beneficial or desired result with respect to a disease, disorder, or condition, including, but not limited to, a therapeutic benefit and / or a preventative benefit. In certain embodiments, treating or treating includes administering a compound or composition disclosed herein to a subject. A "therapeutic benefit" can include eradication or amelioration of the underlying disorder being treated. A therapeutic benefit can also be achieved by eradicating or alleviating one or more physiological symptoms associated with the underlying disease, such as observing an improvement in a subject, even though the subject may still suffer from the underlying disease. In certain embodiments, for preventative benefit, a composition is administered to a subject who is at risk of developing a particular disease or who reports one or more physiological symptoms of the disease, even if the disease has not been diagnosed. Treating can include, for example, reducing, delaying, or alleviating one or more symptoms of a disease or condition, or can include reducing the frequency with which a patient experiences a disease, disorder, disorder, or adverse condition. Treating can be used herein to refer to a method of bringing about some level of treatment or amelioration of a disease or disorder, and can contemplate a range of end results, including, but not limited to, prevention of the disease altogether.

[0073] In certain embodiments, the terms "prevent" or "preventing" in relation to a disease or disorder may refer to a compound that, in a statistical sample, reduces the occurrence of the disorder or disease 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 disorder or disease relative to an untreated control sample.

[0074] A "therapeutic effect," as that term is used herein, encompasses the therapeutic and / or prophylactic benefits described above. A prophylactic effect includes delaying or eliminating the appearance of a disease or condition, delaying or eliminating the onset of symptoms of a disease or condition, slowing, halting, or reversing the progression of a disease or condition, or any combination thereof.

[0075] compound In one aspect herein, a compound of formula (I):

[0076] [ka] or a pharmaceutically acceptable salt thereof, wherein R 1 is fluoro, chloro, bromo, 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)R 11 , -S(O)2N(R 11 )2, -NO2, -N3, and -CN; R 1 is hydroxyl, -O-C1 alkyl, or -NO2, R 2 teeth, Fluoro, bromo, iodo, -OR 22 , -SR21 , -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, R 30 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both are R 30 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; R 1 When is fluoro, R 2 teeth, Bromo, -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, R 30 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both are R 30 C optionally substituted with one or more substituents independently selected from 3-6 Carbocyclic rings and 3- to 4-membered heterocyclic rings,

[0077] [ka] is selected from R 1 is C1 alkyl, -O-C1 haloalkyl, hydroxy, chloro, or bromo, R 2 teeth, 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, R 30C optionally substituted with one or more substituents independently selected from 2-6 Alkyl, and Both are R 30 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 5-membered heterocycles; R 1 is selected from bromo, hydroxy, and C alkyl, R 2 is further selected from fluoro; R 1 But 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)R 11 , -S(O)2N(R 11 )2, -N3, or -CN, R 2 teeth, 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)OR26 , -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, R 30 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both are R 30 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; However, R 1 -C(O)OR 11 When R 2 provided that cannot be a substituted 6-membered heterocycle, R 3 and R 4 are each independently, for each occurrence, 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, 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 14C optionally substituted with one or more substituents independently selected from —C, —NO, and —CN 1-4 Alkyl, All 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 C optionally substituted with one or more substituents independently selected from —C, —NO, and —CN 3-4 selected from carbocycles and 3- to 4-membered heterocycles; R 5 and R 5’ are each independently selected from hydrogen and hydroxyl, or R 5 and R 5’ are united as =O, R 6 and R 6’ are each independently selected from hydrogen and hydroxyl, or R 6 and R 6’ are combined =O, =N-OR 26 , or =NR 26 and m is selected from 0, 1, 2, and 3; n is selected from 0, 1, 2, and 3; R 11 and R 14 are each independently, for each occurrence, hydrogen, R 31 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, Both are R 31 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; R 12 For each occurrence, R 32C substituted with one or more substituents independently selected from 1-6 Alkyl, Both are R 33 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; R 13 For each occurrence, hydrogen, R 34 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, Both are R 34 C optionally substituted with one or more substituents independently selected from 3-5 selected from carbocycles and 3- to 6-membered heterocycles; R 21 , R 23 , R 24 , and R 26 are each independently, for each occurrence, hydrogen, R 34 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, Both C 1-4 Alkyl, C 1-4 haloalkyl, and R 34 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; R 22 and R 25 are independently, for each occurrence, C 2-6 Alkyl, C 2-6 Haloalkyl, and C 2-6 hydroxyalkyl; R 30 , R 31 , R 33 , and R 34 are each independently, for each occurrence, 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 selected from a carbocycle and a 3- to 7-membered heterocycle; R 32 For each occurrence, -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; R 41 are independently hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and C 1-6 hydroxyalkyl, A compound or a pharmaceutically acceptable salt thereof is provided. In some embodiments, in the compound or salt of Formula (I), R 1 is fluoro, -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; R 1 When is -NO2, R 2 -Fluoro, bromo, iodo, -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 ,R 30 C optionally substituted with one or more substituents independently selected from 1-6 alkyl, R 1 When is fluoro, R 2 , bromo, -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,

[0078] [ka] and R 30 C optionally substituted with one or more substituents independently selected from 1-6 alkyl, R 1 When is -O-C1 haloalkyl, R 2 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 ,R 30 C optionally substituted with one or more substituents independently selected from 2-6 alkyl, R 1 is selected from bromo, hydroxy, and C alkyl, R 2 is further selected from fluoro; R 1 But, -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, -N3, or -CN, R 2 is halogen, -OR 26 , -N(R 26 )2, -C(O)R 26 , -C(O)OR 26 , -OC(O)R26 , -C(O)N(R 26 )2, -N(R 26 )C(O)R 26 , -NO2, -CN, and ,R 30 C optionally substituted with one or more substituents independently selected from 1-6 alkyl, R 3 and R 4 are each independently, at each occurrence, halogen, -OR 14 , -N(R 14 )2, -NO2, and -CN; R 5 and R 5’ are each independently selected from hydrogen and hydroxyl, or R 5 and R 5’ are united = O and R 6 and R 6’ are each independently selected from hydrogen and hydroxyl, or R 6 and R 6’ are combined =O, =N-OR 26 , or =NR 26 wherein m is selected from 0 and 1, and n is selected from 0 and 1; R 11 and R 14 are each independently, for each occurrence, hydrogen, R 31 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and R 31 and R is selected from a 3- to 6-membered heterocycle optionally substituted with one or more substituents independently selected from 12 For each occurrence, R 32 C substituted with one or more substituents independently selected from 1-6 alkyl, and R 13 is selected from hydrogen for each occurrence, R 21 , R 23 , R 24 , and R 26 are each independently, for each occurrence, hydrogen, R 34C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and both C 1-4 Alkyl and C 1-4 haloalkyl; 22 and R 25 are independently, for each occurrence, C 2-6 alkyl, R 30 , R 31 , R 33 , and R 34 are each independently, at each occurrence, 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 carbocyclic rings, R 32 independently, for each occurrence, -OR 41 , -SR 41 , -N(R 41 )2, =O, and -CN; R 41 independently for each occurrence, hydrogen and C 1-6 alkyl.

[0079] In some embodiments, in the compound or salt of Formula (I), R 1 is fluoro, chloro, bromo, 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)R 11 , -S(O)2N(R 11 )2, —NO2, —N3, and —CN. In some embodiments, R 1 is fluoro, chloro, bromo, 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)R 11 , -S(O)2N(R 11 )2, —NO2, —N3, and —CN. In some embodiments, R 1 is fluoro, chloro, bromo, 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)R 11 , —NO2, —N3, and —CN. In some embodiments, R 1 is fluoro, chloro, bromo, 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 is fluoro, chloro, bromo, 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 is fluoro, chloro, bromo, -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 is fluoro, -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.

[0080] In some embodiments, in the compound or salt of Formula (I), R 1 is fluoro, chloro, bromo, 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 , -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)R 11 , -S(O)2N(R 11 )2, —NO2, —N3, and —CN. In some embodiments, R 1 is fluoro, chloro, bromo, 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(R11 )C(O)R 11 , -N(R 11 )C(O)OR 11 , -N(R 11 )S(O)2(R 11 ), -S(O)R 11 , -S(O)2N(R 11 )2, —NO2, —N3, and —CN. In some embodiments, R 1 is fluoro, chloro, bromo, 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 is fluoro, chloro, bromo, hydroxyl, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -OC 1-6 Alkyl, -OC 1-6 Haloalkyl, -OR 12 , —NO2, —N3, and —CN.

[0081] In some embodiments, in the compound or salt of Formula (I), R 1 is selected from fluoro, chloro, bromo, and hydroxyl. 1 -C 1-6 Alkyl and -C 1-6 In some embodiments, R is selected from haloalkyl. 1 is hydroxyl, -OC 1-6 Alkyl, -OC 1-6 Haloalkyl, -OR 12 , -OC(O)R 11 , and -OC(O)N(R 11 In some embodiments, R1 is selected from —NO and —CN. In some embodiments, R 1 is -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 In some embodiments, R 1 is -C(O)R 11 , -C(O)OR 11 , and -C(O)N(R 11 In some embodiments, R 1 is selected -SR 11 , -S(O)2R 11 , and -S(O)N(R 11 )2.

[0082] In some embodiments, in the compound or salt of Formula (I), R 1 is fluoro. In some embodiments, R 1 Ha-C 1-6 In some embodiments, R 1 Ha-OC 1-6 In some embodiments, R 1 Ha-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 is -C(O)N(R 11 )2. In some embodiments, R 1 -N(R 11 )C(O)R 11 In some embodiments, R 1 -S(O)2R 11 In some embodiments, R 1 is —NO. In some embodiments, R 1is -CN. In some embodiments, R 1 is -N3.

[0083] In some embodiments, in the compound or salt of Formula (I), R 1 is hydroxyl, —O—C1 alkyl, —NO2, fluoro, C1 alkyl, —O—C1 haloalkyl, hydroxy, chloro, or bromo. 1 is hydroxyl, —O—C alkyl, or —NO. In some embodiments, R 1 is fluoro. In some embodiments, R 1 is C alkyl, —O—C haloalkyl, hydroxy, chloro, or bromo. 1 is hydroxyl, —O—C alkyl, —NO, or fluoro. In some embodiments, R 1 is —NO or fluoro. In some embodiments, R 1 is hydroxyl, —O—C1 alkyl, —NO2, C1 alkyl, —O—C1 haloalkyl, hydroxy, chloro, or bromo. 1 is —NO or —O—C haloalkyl. In some embodiments, R 1 is fluoro, C alkyl, —O—C haloalkyl, hydroxy, chloro, or bromo. 1 is fluoro or —O—C1 haloalkyl.

[0084] In some embodiments, in the compound or salt of Formula (I), R 1 is hydroxyl, -O-C1 alkyl, or -NO2, R 2 teeth, Fluoro, bromo, iodo, -OR 22 , S.R. 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, R 30 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both are R 30 C optionally substituted with one or more substituents independently selected from 3-6 It is selected from carbocycles and 3- to 6-membered heterocycles.

[0085] In some embodiments, in the compound or salt of Formula (I), R 1 is hydroxyl, -O-C1 alkyl, or -NO2, R 2 -Fluoro, bromo, iodo, -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(R21 )2, -NO2, -CN, and R 30 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 1 is hydroxyl, -O-C1 alkyl, or -NO2, R 2 -Fluoro, bromo, iodo, -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)R 21 , -S(O)2N(R 21 )2, -NO2, -CN, and R 30 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 1 is hydroxyl, -O-C1 alkyl, or -NO2, R 2 -Fluoro, bromo, iodo, -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, R is selected from haloalkyl. 1 is hydroxyl, -O-C1 alkyl, or -NO2, R 2 -Fluoro, bromo, iodo, -OR 22 , -N(R 21 )2, -N(R 21 )C(O)OR21 , -NO2, -CN, and C 1-6 In some embodiments, R 1 is hydroxyl, -O-C1 alkyl, or -NO2, R 2 is fluoro, bromo, iodo, -N(R 21 )2, -N(R 21 )C(O)OR 21 , and C 1-6 In some embodiments, R 1 is hydroxyl, -O-C1 alkyl, or -NO2, R 2 is fluoro, -N(R 21 )2, -N(R 21 )C(O)OR 21 , and C 1-6 alkyl. In some embodiments, in the compound or salt of Formula (I), R 1 When is -NO2, R 2 -Fluoro, bromo, iodo, -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 R 30 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R1 When is -NO2, R 2 -Fluoro, bromo, iodo, -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)R 21 , -S(O)2N(R 21 )2, -NO2, -CN, and R 30 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 1 When is -NO2, R 2 -Fluoro, bromo, iodo, -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, R is selected from haloalkyl. 1 When is -NO2, R 2 -Fluoro, bromo, iodo, -OR 22 , -N(R 21 )2, -N(R 21 )C(O)OR 21 , -NO2, -CN, and C 1-6 In some embodiments, R 1 When is -NO2, R 2 is fluoro, bromo, iodo, -N(R 21 )2, -N(R 21 )C(O)OR 21 , and C1-6 In some embodiments, R 1 When is -NO2, R 2 is fluoro, -N(R 21 )2, -N(R 21 )C(O)OR 21 , and C 1-6 alkyl.

[0086] In some embodiments, in the compound or salt of Formula (I), R 1 When is fluoro, R 2 teeth, Bromo, -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, R 30 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both are R 30 C optionally substituted with one or more substituents independently selected from 3-6 Carbocyclic rings, 3- to 4-membered heterocyclic rings,

[0087] [ka] is selected from.

[0088] In some embodiments, in the compound or salt of Formula (I), R 1 When is fluoro, R 2 , bromo, -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,

[0089] [ka] and R 30 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 1 When is fluoro, R 2 , bromo, -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,

[0090] [ka] and R 30 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 1 When is fluoro, R 2 , bromo, -OR 23 , -N(H)R 23 , -C(O)R 23 , -C(O)N(R 23 )2, -C(O)OR 23 , -NO2, -CN,

[0091] [ka] and R 30 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 1 When is fluoro, R 2 , bromo, -OR 23 , -N(H)R 23 , -C(O)R 23 , -C(O)N(R 23 )2, -C(O)OR 23 , -NO2, -CN,

[0092] [ka] and R 30 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 1 When is fluoro, R 2 , bromo, -OR 23 , -N(H)R 23 , -NO2, -CN,

[0093] [ka] and R 30 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 1 When is fluoro, R 2 , bromo, -OR 23 , -N(H)R 23 ,

[0094] [ka] and R 30 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 1 When is fluoro, R 2 is R 30 C optionally substituted with one or more substituents independently selected from 1-6 alkyl.

[0095] In some embodiments, in the compound or salt of Formula (I), R 1 is C1 alkyl, -O-C1 haloalkyl, hydroxy, chloro, or bromo, R 2 teeth, 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(R24 )P(O)(OR 24 )R 24 , -S(O)R 24 , -S(O)2R 24 , -S(O)2N(R 24 )2, -NO2, and -CN, R 30 C optionally substituted with one or more substituents independently selected from 2-6 Alkyl, and Both are R 30 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 5-membered heterocycles; R 1 is selected from bromo, hydroxy, and C alkyl, R 2 is further selected from fluoro.

[0096] In some embodiments, in the compound or salt of Formula (I), R 1 is C1 alkyl, -O-C1 haloalkyl, hydroxy, chloro, or bromo, R 2 teeth, 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, R 30 C optionally substituted with one or more substituents independently selected from 2-6 alkyl, R 1 is selected from bromo, hydroxy, and C alkyl, R 2 is further selected from fluoro.

[0097] In some embodiments, in the compound or salt of Formula (I), R 1 is C1 alkyl, -O-C1 haloalkyl, hydroxy, chloro, or bromo, R 2 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; R 1 is selected from bromo, hydroxy, and C alkyl, R 2 is further selected from fluoro. 1 is C1 alkyl, -O-C1 haloalkyl, hydroxy, chloro, or bromo, R 2 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 ), -S(O)R 24 , -NO2, and -CN; R 1 is selected from bromo, hydroxy, and C alkyl, R 2 is further selected from fluoro.

[0098] In some embodiments, R 1 is C1 alkyl, -O-C1 haloalkyl, hydroxy, chloro, or bromo, R 2 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 , -NO2, and -CN; R 1 is selected from bromo, hydroxy, and C alkyl, R 2 is further selected from fluoro. 1 is C1 alkyl, -O-C1 haloalkyl, hydroxy, chloro, or bromo, R 2 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)R 24 , -NO2, and -CN; R 1is selected from bromo, hydroxy, and C alkyl, R 2 is further selected from fluoro. 1 is C1 alkyl, -O-C1 haloalkyl, hydroxy, chloro, or bromo, R 2 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; R 1 is selected from bromo, hydroxy, and C alkyl, R 2 is further selected from fluoro.

[0099] In some embodiments, R 1 is C1 alkyl, -O-C1 haloalkyl, hydroxy, chloro, or bromo, R 2 Iodine, -OR 25 , -C(O)R 24 , -S(O)2R 24 , -NO2, and -CN; R 1 is selected from bromo, hydroxy, and C alkyl, R 2 is further selected from fluoro. 1 is C1 alkyl, -O-C1 haloalkyl, hydroxy, chloro, or bromo, R 2 Iodine, -OR 25 , -NO2, and -CN; R 1 is selected from bromo, hydroxy, and C alkyl, R 2 is further selected from fluoro. 1 is C1 alkyl, -O-C1 haloalkyl, hydroxy, chloro, or bromo, R 2 is selected from iodine, -NO2, and -CN, and R 1is selected from bromo, hydroxy, and C alkyl, R 2 is further selected from fluoro. 1 is C1 alkyl, -O-C1 haloalkyl, hydroxy, chloro, or bromo, R 2 is selected from -NO2 and -CN, and R 1 is selected from bromo, hydroxy, and C alkyl, R 2 is further selected from fluoro.

[0100] In some embodiments, in the compound or salt of Formula (I), R 1 is —O—C1 haloalkyl, hydroxy, or bromo, R 2 teeth, Fluoro, 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, R 30 C optionally substituted with one or more substituents independently selected from 2-6 Alkyl, and Both are R 30 C optionally substituted with one or more substituents independently selected from 3-6It is selected from carbocycles and 3- to 5-membered heterocycles.

[0101] In some embodiments, in the compound or salt of Formula (I), R 1 is —O—C1 haloalkyl, hydroxy, or bromo, R 2 -Fluoro, iodo, -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 R 30 C optionally substituted with one or more substituents independently selected from 2-6 alkyl.

[0102] In some embodiments, in the compound or salt of Formula (I), R 1 is —O—C1 haloalkyl, hydroxy, or bromo, R 2 -Fluoro, iodo, -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(R24 )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, R 1 is —O—C1 haloalkyl, hydroxy, or bromo, R 2 -Fluoro, iodo, -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, R 1 is —O—C1 haloalkyl, hydroxy, or bromo, R 2 -Fluoro, iodo, -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, R 1 is —O—C1 haloalkyl, hydroxy, or bromo, R2 -Fluoro, iodo, -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, R 1 is —O—C1 haloalkyl, hydroxy, or bromo, R 2 -Fluoro, iodo, -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, R 1 is —O—C1 haloalkyl, hydroxy, or bromo, R 2 -Fluoro, iodo, -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.

[0103] In some embodiments, in the compound or salt of Formula (I), R 1 is —O—C1 haloalkyl, hydroxy, or bromo, R 2 -Fluoro, iodo, -OR 25 , -C(O)R24 , -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 , —NO2, and —CN. In some embodiments, R 1 is —O—C1 haloalkyl, hydroxy, or bromo, R 2 -Fluoro, iodo, -OR 25 , -C(O)R 24 , -S(O)2R 24 , —NO2, and —CN. In some embodiments, R 1 is —O—C1 haloalkyl, hydroxy, or bromo, R 2 -Fluoro, iodo, -OR 25 , -C(O)R 24 , —NO2, and —CN. In some embodiments, R 1 is —O—C1 haloalkyl, hydroxy, or bromo, R 2 -Fluoro, iodo, -OR 25 , —NO2, and —CN. In some embodiments, R 1 is —O—C1 haloalkyl, hydroxy, or bromo, R 2 is selected from fluoro, iodo, —NO, and —CN. 1 is —O—C1 haloalkyl, hydroxy, or bromo, R 2 -Fluoro, iodo, -OR 25 , —NO2, and —CN. In some embodiments, R 1 is —O—C1 haloalkyl, hydroxy, or bromo, R 2 is selected from fluoro, —NO, and —CN. In some embodiments, R 1 is —O—C1 haloalkyl, hydroxy, or bromo, R 2is selected from fluoro and —CN. In some embodiments, in the compound or salt of Formula (I), R 1 is —O—C1 haloalkyl, hydroxy, or bromo, R 2 is selected from fluoro and —NO. 1 is —O—C1 haloalkyl, hydroxy, or bromo, R 2 is fluoro,

[0104] In some embodiments, in the compound or salt of Formula (I), R 1 When is -O-C1 haloalkyl or bromo, R 2 teeth, Fluoro, 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, R 30 C optionally substituted with one or more substituents independently selected from 2-6 Alkyl, and Both are R 30 C optionally substituted with one or more substituents independently selected from 3-6 It is selected from carbocycles and 3- to 5-membered heterocycles.

[0105] In some embodiments, in the compound or salt of Formula (I), R 1 When is -O-C1 haloalkyl or bromo, R 2 -Fluoro, iodo, -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 R 30 C optionally substituted with one or more substituents independently selected from 2-6 alkyl. In some embodiments, in the compound or salt of Formula (I), R 1 When is -O-C1 haloalkyl or bromo, R 2 -Fluoro, iodo, -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(R24 )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, R 1 When is -O-C1 haloalkyl or bromo, R 2 -Fluoro, iodo, -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, R 1 When is -O-C1 haloalkyl or bromo, R 2 -Fluoro, iodo, -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, R 1 When is -O-C1 haloalkyl or bromo, R 2 -Fluoro, iodo, -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, R 1 When is -O-C1 haloalkyl or bromo, R 2 -Fluoro, iodo, -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, R 1 When is -O-C1 haloalkyl or bromo, R 2 -Fluoro, iodo, -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.

[0106] In some embodiments, in the compound or salt of Formula (I), R 1 When is -O-C1 haloalkyl or bromo, R 2 -Fluoro, iodo, -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(R24 )S(O)2(R 24 ), -S(O)R 24 , —NO2, and —CN. In some embodiments, R 1 When is -O-C1 haloalkyl or bromo, R 2 -Fluoro, iodo, -OR 25 , -C(O)R 24 , -S(O)2R 24 , —NO2, and —CN. In some embodiments, R 1 When is -O-C1 haloalkyl or bromo, R 2 -Fluoro, iodo, -OR 25 , -C(O)R 24 , —NO2, and —CN. In some embodiments, R 1 When is -O-C1 haloalkyl or bromo, R 2 -Fluoro, iodo, -OR 25 , —NO2, and —CN. In some embodiments, R 1 When is -O-C1 haloalkyl or bromo, R 2 is selected from fluoro, iodo, —NO, and —CN. 1 When is -O-C1 haloalkyl or bromo, R 2 -Fluoro, iodo, -OR 25 , —NO2, and —CN. In some embodiments, R 1 When is -O-C1 haloalkyl or bromo, R 2 is selected from fluoro, —NO, and —CN. In some embodiments, R 1 When is -O-C1 haloalkyl or bromo, R 2 is selected from fluoro and —CN. 1 When is -O-C1 haloalkyl or bromo, R 2 is selected from fluoro and —NO. 1 When is -O-C1 haloalkyl or bromo, R 2 is fluoro.

[0107] In some embodiments, in the compound or salt of Formula (I), R 1 But 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)R 11 , -S(O)2N(R 11 )2, -N3, or -CN, R 2 teeth, 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, R 30 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both are R 30 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; However, R 1 -C(O)OR 11 When R 2 It is provided that cannot be a substituted 6-membered heterocycle.

[0108] In some embodiments, in the compound or salt of Formula (I), R 1 But 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)R 11 , -S(O)2N(R 11 )2, -N3, or -CN, R 2 teeth, 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, R 30 C optionally substituted with one or more substituents independently selected from 1-6 alkyl.

[0109] In some embodiments, in the compound or salt of Formula (I), R 1 But 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)R 11 , -S(O)2N(R 11 )2, -N3, or -CN, R 2 is 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 R 30 C optionally substituted with one or more substituents independently selected from 1-6 alkyl.

[0110] In some embodiments, in the compound or salt of Formula (I), R 1 But 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)R 11 , -S(O)2N(R 11 )2, -N3, or -CN, R 2 is 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)R 26 , -NO2, -CN, and ,R 30 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 1 But 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)R 11 , -S(O)2N(R 11 )2, -N3, or -CN, R 2 is 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)R 26 , -NO2, -CN, and ,R 30 C optionally substituted with one or more substituents independently selected from 1-6 alkyl.

[0111] In some embodiments, in the compound or salt of Formula (I), R 1 But 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)R 11 , -S(O)2N(R 11 )2, -N3, or -CN, R 2 is 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 R 30 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 1 But 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)R 11 , -S(O)2N(R 11 )2, -N3, or -CN, R 2 is 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)R 26 , -NO2, -CN, and ,R 30C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 1 But 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)R 11 , -S(O)2N(R 11 )2, -N3, or -CN, R 2 is 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)R 26 , -NO2, -CN, and ,R 30 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 1 But 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)R 11 , -S(O)2N(R 11 )2, -N3, or -CN, R 2 is 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 ,R 30 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 1 But 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(R11 )S(O)2(R 11 ), -S(O)R 11 , -S(O)2N(R 11 )2, -N3, or -CN, R 2 is 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.

[0112] In some embodiments, in the compound or salt of Formula (I), R 1 But 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)R 11 , -S(O)2N(R 11 )2, -N3, or -CN, R 2 is halogen, -OR 26 , -SR 26 , -N(R 26 )2, -C(O)R 26 , -C(O)OR 26 , -C(O)N(R26 )2, -S(O)2R 26 , -NO2, -CN, and ,R 30 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 1 But 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)R 11 , -S(O)2N(R 11 )2, -N3, or -CN, R 2 is halogen, -OR 26 , -SR 26 , -N(R 26 )2, -C(O)R 26 , -S(O)2R 26 , -NO2, -CN, and ,R 30 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 1 But 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)R11 , -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)R 11 , -S(O)2N(R 11 )2, -N3, or -CN, R 2 is halogen, -OR 26 , -SR 26 , -N(R 26 )2, -NO2, -CN, and R 30 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 1 But 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)R 11 , -S(O)2N(R 11 )2, -N3, or -CN, R 2is halogen, -OR 26 , -NO2, -CN, and ,R 30 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 1 But 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)R 11 , -S(O)2N(R 11 )2, -N3, or -CN, R 2 is halogen, -OR 26 , -NO2, -CN, and C 1-6 alkyl.

[0113] In some embodiments, in the compound or salt of Formula (I), R 1 But 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(R11 )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)R 11 , -S(O)2N(R 11 )2, -N3, or -CN, R 2 is halogen, -NO2, -CN, and R 30 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, in the compound or salt of Formula (I), R 1 But 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)R 11 , -S(O)2N(R 11 )2, -N3, or -CN, R 2 are halogens, -NO2, -CN, and C 1-6 In some embodiments, R 1 But C 2-6 Alkyl, C 1-6 Haloalkyl, -OC 2-6Alkyl, -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)R 11 , -S(O)2N(R 11 )2, -N3, or -CN, R 2 is halogen, -CN, and R 30 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 1 But 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)R 11 , -S(O)2N(R 11)2, -N3, or -CN, R 2 is a halogen, and R 30 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 1 But 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)R 11 , -S(O)2N(R 11 )2, -N3, or -CN, R 2 is halogen and C 1-6 alkyl.

[0114] In some embodiments, in the compound or salt of Formula (I), R 1 But, -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 teeth, Halogen, -OR 26 , -SR26 , -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, R 30 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both are R 30 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; However, R 1 -C(O)OR 11 When R 2 It is provided that cannot be a substituted 6-membered heterocycle.

[0115] In some embodiments, in the compound or salt of Formula (I), R 1 But, -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 teeth, 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, R 30 C optionally substituted with one or more substituents independently selected from 1-6 alkyl.

[0116] In some embodiments, in the compound or salt of Formula (I), R 1 But, -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 is 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 R 30 C optionally substituted with one or more substituents independently selected from 1-6 alkyl. In some embodiments, in the compound or salt of Formula (I), R 1 But, -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 is 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(R26 ), -S(O)R 26 , -NO2, -CN, and ,R 30 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 1 But, -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 is 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)R 26 , -NO2, -CN, and ,R 30 C optionally substituted with one or more substituents independently selected from 1-6 alkyl.

[0117] In some embodiments, in the compound or salt of Formula (I), R 1 But, -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 is halogen, -OR26 , -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 R 30 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 1 But, -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 is 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)R 26 , -NO2, -CN, and ,R 30 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 1 But, -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 is 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)R 26 , -NO2, -CN, and ,R 30 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 1 But, -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 is 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 ,R 30 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 1 But, -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 is 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.

[0118] In some embodiments, in the compound or salt of Formula (I), R 1 But, -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 is 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 ,R 30 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 1 But, -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 2is halogen, -OR 26 , -SR 26 , -N(R 26 )2, -C(O)R 26 , -S(O)2R 26 , -NO2, -CN, and ,R 30 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 1 But, -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 is halogen, -OR 26 , -SR 26 , -N(R 26 )2, -NO2, -CN, and R 30 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 1 But, -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 is halogen, -OR 26 , -NO2, -CN, and ,R 30 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 1 But, -SR 11 , -N(R 13 )2, -C(O)R11 , -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 is halogen, -OR 26 , -NO2, -CN, and C 1-6 alkyl.

[0119] In some embodiments, in the compound or salt of Formula (I), R 1 But, -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 is halogen, -NO2, -CN, and R 30 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, in the compound or salt of Formula (I), R 1 But, -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 are halogens, -NO2, -CN, and C 1-6 In some embodiments, R 1 But, -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 is halogen, -CN, and R 30 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 1 But, -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 is a halogen, and R 30 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 1 But, -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 is halogen and C 1-6 alkyl.

[0120] In some embodiments, in the compound or salt of Formula (I), R 3 and R 4 are each independently, for each occurrence, 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 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 C optionally substituted with one or more substituents independently selected from —C, —NO, and —CN 1-4 alkyl.

[0121] In some embodiments, in the compound or salt of Formula (I), R 3 and R 4 are each independently, for each occurrence, 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 Halogen, -OR 14 , -N(R 14 C optionally substituted with one or more substituents independently selected from —C, —NO, and —CN 1-4 alkyl.

[0122] In some embodiments, in the compound or salt of Formula (I), R 3 and R 4 are each independently, for each occurrence, Halogen, -OR 14 , -N(R 14 )2, -NO2, and -CN, and Halogen, -OR 14 , -N(R 14 C optionally substituted with one or more substituents independently selected from —C, —NO, and —CN 1-4 alkyl.

[0123] In some embodiments, in the compound or salt of Formula (I), R 3 and R 4 are each independently, at each occurrence, 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 is selected from haloalkyl. 3 and R 4 are each independently, at each occurrence, 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 is selected from haloalkyl. 3 and R 4 are each independently, at each occurrence, 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 is selected from haloalkyl. 3 and R 4 are each independently, at each occurrence, halogen, -OR 14 , -N(R14 )2, -C(O)R 14 , -C(O)OR 14 , -NO2, -CN, C 1-4 Alkyl, and C 1-4 In some embodiments, R is selected from haloalkyl. 3 and R 4 are each independently, at each occurrence, halogen, -OR 14 , -N(R 14 )2, -NO2, -CN, C 1-4 Alkyl, and C 1-4 In some embodiments, R is selected from haloalkyl. 3 and R 4 are each independently, at each occurrence, halogen, -OR 14 , -N(R 14 )2, -CN, C 1-4 Alkyl, and C 1-4 In some embodiments, R is selected from haloalkyl. 3 and R 4 are each independently, at each occurrence, halogen, -OR 14 , -CN, C 1-4 Alkyl, and C 1-4 In some embodiments, R is selected from haloalkyl. 3 and R 4 are each independently, at each occurrence, halogen, -CN, C 1-4 Alkyl, and C 1-4 In some embodiments, R is selected from haloalkyl. 3 and R 4 are each independently, for each occurrence, halogen, C 1-4 Alkyl, and C 1-4 In some embodiments, R is selected from haloalkyl. 3 and R 4 is independently selected at each occurrence from halogen.

[0124] In some embodiments, in the compound or salt of Formula (I), R 5 and R 5’ are each independently selected from hydrogen and hydroxyl, or R5 and R 5’ are taken together to be =O. In some embodiments, R 5 and R 5’ are each independently selected from hydrogen or R 5 and R 5’ are taken together to be =O. In some embodiments, R 5 and R 5’ are each independently selected from hydrogen and hydroxyl. 5 and R 5’ are taken together to be =O. In some embodiments, R 5 and R 5’ are hydrogen atoms.

[0125] In some embodiments, in the compound or salt of Formula (I), R 6 and R 6’ are each independently selected from hydrogen and hydroxyl, or R 6 and R 6’ are combined =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’ =O or =N-OR together 23 In some embodiments, R 6 and R 6’ are each independently selected from hydrogen and hydroxyl. 6 and R 6’ are taken together to be =O. In some embodiments, R 6 and R 6’ together =N-OR 26 In some embodiments, R 6 and R 6’ are hydrogen atoms.

[0126] In some embodiments, in 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.

[0127] In some embodiments, in 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.

[0128] In some embodiments, in the compound or salt of Formula (I), R 11 and R 14 are each independently, for each occurrence, hydrogen, R 31 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both are R 31 C optionally substituted with one or more substituents independently selected from 3-6 It is selected from carbocycles and 3- to 6-membered heterocycles.

[0129] In some embodiments, in the compound or salt of Formula (I), R 11 and R 14 are each independently, for each occurrence, hydrogen, R 31 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and both R 31 In some embodiments, R is selected from a 3- to 6-membered heterocycle optionally substituted with one or more substituents independently selected from 11 and R14 are each independently hydrogen, C 1-6 Alkyl, C 3-6 In some embodiments, R is selected from the group consisting of a carbocycle, a 3- to 6-membered heterocycle, and a 3- to 6-membered heterocycle. 11 and R 14 are each independently hydrogen, C 1-6 It is selected from alkyl, and 3- to 6-membered heterocycle.

[0130] In some embodiments, R 11 and R 14 are each independently, at each occurrence, hydrogen, and R 31 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 11 and R 14 are each independently, for each occurrence, hydrogen and C 1-6 In some embodiments, R 11 and R 14 are each independently, at each occurrence, hydrogen, and R 31 In some embodiments, R is selected from a 3- to 6-membered heterocycle optionally substituted with one or more substituents independently selected from 11 and R 14 is independently selected at each occurrence from hydrogen and a 3- to 6-membered heterocycle.

[0131] In some embodiments, in the compound or salt of Formula (I), R 11 and R 14 are each independently, for each occurrence, hydrogen, 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)R41 , -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 C optionally substituted with one or more substituents independently selected from carbocycle, and 3- to 7-membered heterocycle 1-6 Alkyl, All 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 C optionally substituted with one or more substituents independently selected from carbocycle, and 3- to 7-membered heterocycle 3-6It is selected from carbocycles and 3- to 6-membered heterocycles.

[0132] In some embodiments, in the compound or salt of Formula (I), R 11 and R 14 are each independently, for each occurrence, hydrogen, 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 C optionally substituted with one or more substituents independently selected from carbocycles 1-6 Alkyl, All 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 C optionally substituted with one or more substituents independently selected from carbocycles 3-6 It is selected from carbocycles and 3- to 6-membered heterocycles.

[0133] In some embodiments, in the compound or salt of Formula (I), R 11 and R 14are each independently, for each occurrence, hydrogen, 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 C optionally substituted with one or more substituents independently selected from carbocycles 1-6 Alkyl, All 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 C optionally substituted with one or more substituents independently selected from carbocycles 3-6 It is selected from carbocycles and 3- to 6-membered heterocycles.

[0134] In some embodiments, in the compound or salt of Formula (I), R 12 For each occurrence, R 32 C substituted with one or more substituents independently selected from 1-6 Alkyl, Both are R 33 C optionally substituted with one or more substituents independently selected from 3-6 It is selected from carbocycles and 3- to 6-membered heterocycles.

[0135] In some embodiments, in the compound or salt of Formula (I), R 12 For each occurrence, R 32 C substituted with one or more substituents independently selected from 1-6 In some embodiments, R 12For each occurrence, R 32 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 12 For each occurrence, C 1-6 alkyl.

[0136] In some embodiments, in the compound or salt of Formula (I), R 12 For each occurrence, -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; 1-6 In some embodiments, R 12 For each occurrence, -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(R41 ), -N(R 41 )SO2N(R 41 ), -N(R 41 )P(O)(OR 41 )R 41 , -S(O)2N(R 41 )2, -NO2, =O, and C 3-6 C substituted with one or more substituents independently selected from carbocycles 1-6 In some embodiments, R 12 For each occurrence, -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 C substituted with one or more substituents independently selected from: ═O, ═O, and —CN; 1-6 In some embodiments, R 12 For each occurrence, -OR 41 , -N(R 41 )2, =O, and -CN; 1-6 alkyl.

[0137] In some embodiments, in the compound or salt of Formula (I), R 13 For each occurrence, hydrogen, R 34 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, Both are R 34 C optionally substituted with one or more substituents independently selected from 3-5 It is selected from carbocycles and 3- to 6-membered heterocycles.

[0138] In some embodiments, in the compound or salt of Formula (I), R 13 For each occurrence, hydrogen, C 1-6 Alkyl, C 3-5In some embodiments, R is selected from the group consisting of a carbocycle, a 3- to 6-membered heterocycle, and a 3- to 6-membered heterocycle. 13 is hydrogen, and R 34 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 13 independently for each occurrence, hydrogen and C 1-6 In some embodiments, R 13 For each occurrence, hydrogen and R 34 C optionally substituted with one or more substituents independently selected from 3-5 In some embodiments, R is selected from carbocycles and 3- to 6-membered heterocycles. 13 For each occurrence, hydrogen, C 3-5 In some embodiments, R is selected from the group consisting of a carbocycle, a 3- to 6-membered heterocycle, and a 3- to 6-membered heterocycle. 13 is selected from hydrogen at each occurrence.

[0139] In some embodiments, in the compound or salt of Formula (I), R 13 independently, for each occurrence, hydrogen, 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 C optionally substituted with one or more substituents independently selected from carbocycle, and 3- to 7-membered heterocycle 1-6 Alkyl, All 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 C optionally substituted with one or more substituents independently selected from carbocycle, and 3- to 7-membered heterocycle 3-6 It is selected from carbocycles and 3- to 6-membered heterocycles.

[0140] In some embodiments, in the compound or salt of Formula (I), R 13 independently, for each occurrence, hydrogen, Halogen, -OR 41 , -N(R 41 )2, -C(O)OR 41 , -C(O)N(R 41 )2, -N(R 41 )C(O)R41 , -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 C optionally substituted with one or more substituents independently selected from carbocycles 1-6 Alkyl, All 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 C optionally substituted with one or more substituents independently selected from carbocycles 3-6 It is selected from carbocycles and 3- to 6-membered heterocycles.

[0141] In some embodiments, in the compound or salt of Formula (I), R 13 independently, for each occurrence, hydrogen, 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 C optionally substituted with one or more substituents independently selected from carbocycles 1-6 Alkyl, All halogen, -OR41 , -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 C optionally substituted with one or more substituents independently selected from carbocycles 3-6 It is selected from carbocycles and 3- to 6-membered heterocycles.

[0142] In some embodiments, in the compound or salt of Formula (I), R 21 , R 23 , R 24 , and R 26 are each independently, for each occurrence, hydrogen, R 34 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both C 1-4 Alkyl, C 1-4 haloalkyl, and R 34 C optionally substituted with one or more substituents independently selected from 3-6 It is selected from carbocycles and 3- to 6-membered heterocycles.

[0143] In some embodiments, in the compound or salt of Formula (I), R 21 , R 23 , R 24 , and R 26 are each independently, for each occurrence, hydrogen, R 34 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both C 1-4 Alkyl, C 1-4 haloalkyl, and R 34 is selected from a 3- to 6-membered heterocycle optionally substituted with one or more substituents independently selected from:

[0144] In some embodiments, in the compound or salt of Formula (I), R 21 , R 23 , R 24 , and R 26 are each independently, at each occurrence, hydrogen, and R 34 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, in the compound or salt of Formula (I), R 21 , R 23 , R 24 , and R 26 are each independently, at each occurrence, hydrogen, and C 1-4 Alkyl, C 1-4 haloalkyl, and R 34 In some embodiments, R is selected from a 3- to 6-membered heterocycle optionally substituted with one or more substituents independently selected from 21 , R 23 , R 24 , and R 26 are each independently hydrogen, C 1-6 It is selected from alkyl, and 3- to 6-membered heterocycle.

[0145] In some embodiments, in the compound or salt of Formula (I), R 21 , R 23 , R 24 , and R 26 are each independently, for each occurrence, hydrogen, 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(R41 )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 C optionally substituted with one or more substituents independently selected from carbocycle, and 3- to 7-membered heterocycle 1-6 Alkyl, Both 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(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 C optionally substituted with one or more substituents independently selected from carbocycle, and 3- to 7-membered heterocycle 3-6 It is selected from carbocycles and 3- to 6-membered heterocycles.

[0146] In some embodiments, in the compound or salt of Formula (I), R 21 , R 23 , R 24 , and R 26 are each independently, for each occurrence, hydrogen, 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 C optionally substituted with one or more substituents independently selected from carbocycles 1-6 Alkyl, and Both C 1-4 Alkyl, C 1-4 Haloalkyl, 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 C optionally substituted with one or more substituents independently selected from carbocycles 3-6 It is selected from carbocycles and 3- to 6-membered heterocycles.

[0147] In some embodiments, in the compound or salt of Formula (I), R 21 , R 23 , R 24 , and R 26 are each independently, for each occurrence, hydrogen, 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 C optionally substituted with one or more substituents independently selected from carbocycles 1-6 Alkyl, Both C 1-4 Alkyl, C 1-4 Haloalkyl, 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 C optionally substituted with one or more substituents independently selected from carbocycles 3-6 It is selected from carbocycles and 3- to 6-membered heterocycles.

[0148] In some embodiments, in the compound or salt of Formula (I), R 22 and R 25 are independently, for each occurrence, C 2-6 Alkyl, C 2-6 Haloalkyl, and C 2-6 In some embodiments, in the compound or salt of Formula (I), R 22 and R 25 are each independently hydrogen, C 2-6 Alkyl, C 2-6 Haloalkyl, and C 2-6 In some embodiments, in the compound or salt of Formula (I), R 22 and R 25 are independently, for each occurrence, C 2-6 Alkyl and C 2-6 In some embodiments, in the compound or salt of Formula (I), R 22 and R 25 are independently, for each occurrence, C 2-6 In some embodiments, in the compound or salt of Formula (I), R 22 and R 25 are independently, for each occurrence, C 2-6 haloalkyl.

[0149] In some embodiments, in the compound or salt of Formula (I), R 30 , R 31 , R 33 , and R 34 are each independently, at each occurrence, 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)R41 , -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 are each independently, at each occurrence, 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 , R 33 , and R 34 are each independently, at each occurrence, 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 are each independently, at each occurrence, 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 Carbocycles are selected from:

[0150] In some embodiments, in the compound or salt of Formula (I), R 30 , R 31 , R 33 , and R 34 are each independently, at each occurrence, 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 are each independently, at each occurrence, 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 are each independently, at each occurrence, halogen, -OR 41 , -N(R 41)2, -C(O)R 41 , -C(O)OR 41 , -C(O)N(R 41 )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 are each independently, at each occurrence, 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 are each independently, for each occurrence, -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 Carbocycles are selected from:

[0151] In some embodiments, in the compound or salt of Formula (I), R 32 independently, for each occurrence, -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, for each occurrence, -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)R 41 , -S(O)2N(R 41 )2, —NO2, ═O, ═S, and —CN. In some embodiments, R 32 independently, for each occurrence, -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)R 41 , -S(O)2N(R 41 )2, ═O, and —CN. In some embodiments, R 32 independently, for each occurrence, -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, for each occurrence, -OR 41 , -N(R 41 )2, =O, and -CN.

[0152] In some embodiments, in the compound or salt of Formula (I), R 41 are each independently hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and C 1-6 In some embodiments, R 41 are each independently hydrogen, C 1-6 Alkyl, and C 1-6 In some embodiments, R is selected from haloalkyl. 41 are each independently hydrogen, C 1-6 Alkyl, and C 1-6 In some embodiments, R 41 independently for each occurrence, hydrogen and C 1-6 In some embodiments, R 41 independently, for each occurrence, C 1-6 In some embodiments, R 41 is independently selected at each occurrence from hydrogen.

[0153] In one aspect herein, a compound of formula (II):

[0154] [ka] or a pharmaceutically acceptable salt or solvate thereof, wherein: R51 is fluoro, chloro, bromo, iodo, 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)R 61 , -S(O)2N(R 61 )2, -NO2, and -CN; R 51 When is fluoro, chloro, or iodo, R 52 teeth, Bromo, iodo, -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, R 80 C alkyl substituted with one or more substituents independently selected from 80 C optionally substituted with one or more substituents independently selected from 2-6 Alkyl, and Both are R 80 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 5-membered heterocycles; R 51 is C1 alkyl or -NO2, R 52 teeth, Fluoro, 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, R 80 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both are R 80C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; R 51 But bromo, 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)R 61 , -S(O)2N(R 61 )2, and -CN, R 52 teeth, 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)R73 , -S(O)2R 73 , -S(O)2N(R 73 )2, -NO2, and -CN, R 80 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both are R 80 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; R 53 and R 54 are each independently, for each occurrence, 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, 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 C optionally substituted with one or more substituents independently selected from —C, —NO, and —CN 1-4 Alkyl, and All 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 C optionally substituted with one or more substituents independently selected from —C, —NO, and —CN 3-4 selected from carbocycles and 3- to 4-membered heterocycles; R 55 and R 55’ are each independently selected from hydrogen and hydroxyl, or R 55 and R 55’ are united as =O, R 56 and R 56’ are each independently selected from hydrogen and hydroxyl, or R 56 and R 56’ are combined =O, =N-OR 64 , or =NR 64 and p is selected from 0, 1, 2, and 3; q is selected from 0, 1, 2, and 3; R 61 and R 64 are each independently, for each occurrence, hydrogen, R 81 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both are R 81 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; R 71 , R 72 , and R 73 are each independently, for each occurrence, hydrogen, R 82 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both C 1-4 Alkyl, C 1-4 haloalkyl, and R 82 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; R 80 , R 81 , and R 82are each independently, for each occurrence, 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 selected from a carbocycle and a 3- to 7-membered heterocycle; R 91 are independently hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and C 1-6 hydroxyalkyl, A compound or a pharmaceutically acceptable salt or solvate thereof is provided.

[0155] In some embodiments, in the compound or salt of Formula (II), R 51 is fluoro, chloro, bromo, iodo, 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)R 61 , -S(O)2N(R 61 )2, —NO2, and —CN. In some embodiments, R 51 is fluoro, chloro, bromo, iodo, 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)R 61 , -S(O)2N(R 61 )2, —NO2, and —CN. In some embodiments, R 51 is fluoro, chloro, bromo, iodo, 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 is fluoro, chloro, bromo, iodo, hydroxyl, -C 1-6Alkyl, -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 is fluoro, chloro, bromo, iodo, 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 is fluoro, chloro, bromo, iodo, 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 is fluoro, chloro, bromo, iodo, hydroxyl, -C(O)R 61 , -C(O)OR 61 , -C(O)N(R 61 )2, —NO2, and —CN. In some embodiments, R 51 is fluoro, chloro, bromo, -C(O)R 61 , -C(O)OR 61 , -C(O)N(R 61 )2, —NO2, and —CN. In some embodiments, R 51 is fluoro, -C(O)R 61 , -C(O)OR 61 , -C(O)N(R 61 )2, —NO2, and —CN. In some embodiments, R 51 is -C(O)R61 , -C(O)OR 61 , -C(O)N(R 61 )2, and -NO2.

[0156] In some embodiments, in the compound or salt of Formula (II), R 51 is selected from fluoro, chloro, or iodo. 51 is C alkyl or -NO. In some embodiments, R 51 is bromo, 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)R 61 , -S(O)2N(R 61 In some embodiments, in the compound or salt of formula (II), R 51 is selected from fluoro, chloro, iodo, C1 alkyl, or -NO2.

[0157] In some embodiments, in the compound or salt of Formula (II), R 51 is fluoro, chloro, iodo, bromo, 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)R 61 , -S(O)2N(R 61 )2, and -CN. In some embodiments, R 51 is fluoro, chloro, iodo, bromo, 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)R 61 , -S(O)2N(R 61 )2, and -CN. In some embodiments, R 51 is fluoro, chloro, iodo, bromo, 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, —NO2, and —CN. In some embodiments, R 51 is -C(O)R 61 , -C(O)OR 61 , -C(O)N(R 61 )2, and -CN.

[0158] In some embodiments, in the compound or salt of Formula (II), R51 is C1 alkyl, -NO2, bromo, 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)R 61 , -S(O)2N(R 61 )2, and -CN. In some embodiments, R 51 is C1 alkyl, -NO2, bromo, 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 is selected from -CN. 51 -NO2, -C(O)R 61 , -C(O)OR 61 , and -C(O)N(R 61 )2 is selected.

[0159] In some embodiments, in the compound or salt of Formula (II), R 51 are bromo, iodo, hydroxyl, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -N(R61 )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)R 61 , -S(O)2N(R 61 )2, —NO2, and —CN. In some embodiments, R 51 is fluoro, chloro, bromo, iodo, 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)R 61 , -S(O)2N(R 61 )2, and -CN. In some embodiments, R 51 is selected from fluoro, chloro, iodo, -C1 alkyl, and -NO2. 51 is selected from fluoro, chloro, and iodo. 51is selected from C alkyl or —NO. In some embodiments, R 51 is bromo, 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)R 61 , -S(O)2N(R 61 )2, and -CN.

[0160] In some embodiments, in the compound or salt of Formula (II), R 51 When is fluoro, chloro, or iodo, R 52 teeth, Bromo, iodo, -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, R 80 C alkyl substituted with one or more substituents independently selected from 80 C optionally substituted with one or more substituents independently selected from 2-6 Alkyl, and Both are R 80 C optionally substituted with one or more substituents independently selected from 3-6 It is selected from carbocycles and 3- to 5-membered heterocycles.

[0161] In some embodiments, in the compound or salt of Formula (II), R 51 When is fluoro, chloro, or iodo, R 52 is bromo, iodo, -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, R 80C alkyl substituted with one or more substituents independently selected from, and R 80 C optionally substituted with one or more substituents independently selected from 2-6 In some embodiments, R 51 When is fluoro, chloro, or iodo, R 52 is bromo, iodo, -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, R 80 C alkyl substituted with one or more substituents independently selected from, and R 80 C optionally substituted with one or more substituents independently selected from 2-6 In some embodiments, R 51 When is fluoro, chloro, or iodo, R 52 is bromo, iodo, -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, R 51 When is fluoro, chloro, or iodo, R 52 are bromo, iodo, -N(R 71 )2, -OR 71 , —NO2, and —CN.

[0162] In some embodiments, in the compound or salt of Formula (II), R 51 When is C1 alkyl or -NO2, R 52teeth, Fluoro, 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, R 80 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both are R 80 C optionally substituted with one or more substituents independently selected from 3-6 It is selected from carbocycles and 3- to 6-membered heterocycles.

[0163] In some embodiments, in the compound or salt of Formula (II), R 51 When is C1 alkyl or -NO2, R 52 -Fluoro, iodo, -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(R72 )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 R 80 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 51 When is C1 alkyl or -NO2, R 52 -Fluoro, iodo, -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 R 80 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 51 When is C1 alkyl or -NO2, R 52 -Fluoro, iodo, -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 ,R 80 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 51 When is C1 alkyl or -NO2, R 52 -Fluoro, iodo, -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 ,R 80 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 51 When is C1 alkyl or -NO2, R 52 -Fluoro, iodo, -OR 72 , -N(R 72 )2, -C(O)R 72 , -C(O)OR 72 , C(O)N(R 72 )2, -NO2, -CN, and R 80 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 51 When is C1 alkyl or -NO2, R 52 -Fluoro, iodo, -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, R 51 When is C1 alkyl or -NO2, R52 -Fluoro, iodo, -OR 72 , -N(R 72 )2, -NO2, -CN, and R 80 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 51 When is C1 alkyl or -NO2, R 52 -Fluoro, iodo, -OR 72 , -N(R 72 )2, -NO2, -CN, and C 1-6 In some embodiments, R 51 When is C1 alkyl or -NO2, R 52 is fluoro, and R 80 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 51 When is C1 alkyl or -NO2, R 52 Fluoro, and C 1-6 alkyl.

[0164] In some embodiments, in the compound or salt of Formula (II), R 51 When is -NO2, R 52 teeth, Fluoro, 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(R72 ), -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, R 80 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both are R 80 C optionally substituted with one or more substituents independently selected from 3-6 It is selected from carbocycles and 3- to 6-membered heterocycles.

[0165] In some embodiments, in the compound or salt of Formula (II), R 51 When is -NO2, R 52 -Fluoro, iodo, -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 R 80 C optionally substituted with one or more substituents independently selected from 1-6In some embodiments, R 51 When is -NO2, R 52 -Fluoro, iodo, -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 R 80 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 51 When is -NO2, R 52 -Fluoro, iodo, -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 ,R 80 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 51 When is -NO2, R 52 -Fluoro, iodo, -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 ,R 80 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 51 When is -NO2, R 52 -Fluoro, iodo, -OR 72 , -N(R 72 )2, -C(O)R 72 , -C(O)OR 72 , C(O)N(R 72 )2, -NO2, -CN, and R 80 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 51 When is -NO2, R 52 -Fluoro, iodo, -OR 72 , -N(R 72 )2, -NO2, -CN, and R 80 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 51 When is -NO2, R 52 is fluoro, and R 80 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 51 When is -NO2, R 52 Fluoro, and C 1-6 alkyl.

[0166] In some embodiments, in the compound or salt of Formula (II), R 51 But bromo, 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(R61 )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)R 61 , -S(O)2N(R 61 )2, and -CN, R 52 is 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, R 80 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and both R 80 C optionally substituted with one or more substituents independently selected from 3-6 It is selected from carbocycles and 3- to 6-membered heterocycles.

[0167] In some embodiments, in the compound or salt of Formula (II), R51 But bromo, 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)R 61 , -S(O)2N(R 61 )2, and -CN, R 52 is 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, R 80 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and both R 80 C optionally substituted with one or more substituents independently selected from 3-6 In some embodiments, R is selected from carbocycles and 3- to 6-membered heterocycles. 51 But bromo, 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)R61 , -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)R 61 , -S(O)2N(R 61 )2, and -CN, R 52 is halogen, -OR 73 , -N(R 73 )2, -C(O)R 73 , -NO2, and -CN, R 80 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and both R 80 C optionally substituted with one or more substituents independently selected from 3-6 In some embodiments, R is selected from carbocycles and 3- to 6-membered heterocycles. 51 But bromo, 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)R 61 , -S(O)2N(R 61 )2, and -CN, R52 is halogen, -OR 73 , -N(R 73 )2, -C(O)R 73 , -NO2, and -CN, and R 80 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 51 But bromo, 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)R 61 , -S(O)2N(R 61 )2, and -CN, R 52 is halogen, -OR 73 , -N(R 73 )2, and R 80 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 51 But bromo, 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(R61 )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)R 61 , -S(O)2N(R 61 )2, and -CN, R 52 is a halogen.

[0168] In some embodiments, in the compound or salt of Formula (II), R 51 But bromo, 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 teeth, 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, R 80 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both are R 80 C optionally substituted with one or more substituents independently selected from 3-6 It is selected from carbocycles and 3- to 6-membered heterocycles. In some embodiments, in the compound or salt of Formula (II), R 51 But bromo, 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 is 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, R 80 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and both R 80 C optionally substituted with one or more substituents independently selected from 3-6 In some embodiments, R is selected from carbocycles and 3- to 6-membered heterocycles. 51 But bromo, hydroxyl, -C 2-6 Alkyl, -C1-6 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 is halogen, -OR 73 , -N(R 73 )2, -C(O)R 73 , -NO2, and -CN, R 80 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and both R 80 C optionally substituted with one or more substituents independently selected from 3-6 In some embodiments, R is selected from carbocycles and 3- to 6-membered heterocycles. 51 But bromo, 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 is halogen, -OR 73 , -N(R 73 )2, -C(O)R 73 , -NO2, and -CN, and R 80 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 51 But bromo, 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 is halogen, -OR 73 , -N(R 73 )2, and R 80 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 51 But bromo, 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 is a halogen.

[0169] In some embodiments, in the compound or salt of Formula (II), R 51 But bromo, hydroxyl, -C 2-6 Alkyl, -N(R 61 )2, -OR 61 , -SR 61 , -C(O)R 61 , -C(O)OR 61 , -OC(O)N(R 61 )2, and -CN, R 52 teeth, 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(R73 )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, R 80 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both are R 80 C optionally substituted with one or more substituents independently selected from 3-6 It is selected from carbocycles and 3- to 6-membered heterocycles. In some embodiments, in the compound or salt of Formula (II), R 51 But bromo, hydroxyl, -C 2-6 Alkyl, -N(R 61 )2, -OR 61 , -SR 61 , -C(O)R 61 , -C(O)OR 61 , -OC(O)N(R 61 )2, and -CN, R 52 is 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, R 80C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and both R 80 C optionally substituted with one or more substituents independently selected from 3-6 In some embodiments, R is selected from carbocycles and 3- to 6-membered heterocycles. 51 But bromo, hydroxyl, -C 2-6 Alkyl, -N(R 61 )2, -OR 61 , -SR 61 , -C(O)R 61 , -C(O)OR 61 , -OC(O)N(R 61 )2, and -CN, R 52 is halogen, -OR 73 , -N(R 73 )2, -C(O)R 73 , -NO2, and -CN, R 80 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and both R 80 C optionally substituted with one or more substituents independently selected from 3-6 In some embodiments, R is selected from carbocycles and 3- to 6-membered heterocycles. 51 But bromo, hydroxyl, -C 2-6 Alkyl, -N(R 61 )2, -OR 61 , -SR 61 , -C(O)R 61 , -C(O)OR 61 , -OC(O)N(R 61 )2, and -CN, R 52 is halogen, -OR 73 , -N(R 73 )2, -C(O)R 73 , -NO2, and -CN, and R 80 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 51 But bromo, hydroxyl, -C 2-6Alkyl, -N(R 61 )2, -OR 61 , -SR 61 , -C(O)R 61 , -C(O)OR 61 , -OC(O)N(R 61 )2, and -CN, R 52 is halogen, -OR 73 , -N(R 73 )2, and R 80 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 51 But bromo, hydroxyl, -C 2-6 Alkyl, -N(R 61 )2, -OR 61 , -SR 61 , -C(O)R 61 , -C(O)OR 61 , -OC(O)N(R 61 )2, and -CN, R 52 is a halogen.

[0170] In some embodiments, in the compound or salt of Formula (II), R 51 But -C(O)R 61 , -C(O)OR 61 , and -C(O)N(R 61 )2, R 52 teeth, 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(R73 ), 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, R 80 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and both R 80 C optionally substituted with one or more substituents independently selected from 3-6 It is selected from carbocycles and 3- to 6-membered heterocycles.

[0171] In some embodiments, in the compound or salt of Formula (II), R 51 But -C(O)R 61 , -C(O)OR 61 , and -C(O)N(R 61 )2, R 52 is 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, R 80 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and both R 80 C optionally substituted with one or more substituents independently selected from 3-6 In some embodiments, R is selected from carbocycles and 3- to 6-membered heterocycles. 51 But -C(O)R 61 , -C(O)OR 61 , and -C(O)N(R 61 )2, R 52is halogen, -OR 73 , -N(R 73 )2, -C(O)R 73 , -NO2, and -CN, R 80 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and both R 80 C optionally substituted with one or more substituents independently selected from 3-6 In some embodiments, R is selected from carbocycles and 3- to 6-membered heterocycles. 51 But -C(O)R 61 , -C(O)OR 61 , and -C(O)N(R 61 )2, R 52 is halogen, -OR 73 , -N(R 73 )2, -C(O)R 73 , -NO2, and -CN, and R 80 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 51 But -C(O)R 61 , -C(O)OR 61 , and -C(O)N(R 61 )2, R 52 is halogen, -OR 73 , -N(R 73 )2, and R 80 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 51 But -C(O)R 61 , -C(O)OR 61 , and -C(O)N(R 61 )2, R 52 is halogen, -OR 73 , -N(R 73 )2, and C 1-6 In some embodiments, R 51 But -C(O)R 61 , -C(O)OR 61, and -C(O)N(R 61 )2, R 52 is a halogen.

[0172] In some embodiments, in the compound or salt of Formula (II), R 53 and R 54 are each independently, for each occurrence, 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, 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 C optionally substituted with one or more substituents independently selected from —C, —NO, and —CN 1-4 Alkyl, and All 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 C optionally substituted with one or more substituents independently selected from —C, —NO, and —CN 3-4 It is selected from carbocycles and 3- to 4-membered heterocycles.

[0173] In some embodiments, in the compound or salt of Formula (II), R 53 and R 54 are each independently, at each occurrence, 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 halogens, -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 C optionally substituted with one or more substituents independently selected from —C, —NO, and —CN 1-4 In some embodiments, R 53 and R 54 are each independently, at each occurrence, halogen, -OR 64 , -SR 64 , -N(R 64 )2, -C(O)R 64 , -NO2, -CN, and halogens, -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 C optionally substituted with one or more substituents independently selected from —C, —NO, and —CN 1-4 In some embodiments, R 53 and R 54 are each independently, at each occurrence, halogen, -OR 64 , -SR 64 , -N(R 64 )2, -C(O)R 64 , —NO2, and —CN. In some embodiments, R 53 and R 54 are each independently, at each occurrence, halogen, -OR 64, -N(R 64 )2, —NO2, and —CN. In some embodiments, R 53 and R 54 is independently selected at each occurrence from halogen.

[0174] In some embodiments, in the compound or salt of Formula (II), R 55 and R 55’ are each independently selected from hydrogen and hydroxyl, or R 55 and R 55’ are taken together to be =O. In some embodiments, R 55 and R 55’ are united as =O.

[0175] In some embodiments, in the compound or salt of Formula (II), R 56 and R 56’ are each independently selected from hydrogen and hydroxyl, or R 56 and R 56’ are combined =O, =N-OR 64 , or =NR 64 In some embodiments, R 56 and R 56’ are each independently selected from hydrogen and hydroxyl. 56 and R 56’ are taken together to be =O. In some embodiments, R 56 and R 56’ together =N-OR 64 is.

[0176] In some embodiments, in 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.

[0177] In some embodiments, in the compound or salt of Formula (II), R 61 and R 64 are each independently, for each occurrence, hydrogen, R 81 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both are R 81 C optionally substituted with one or more substituents independently selected from 3-6 It is selected from carbocycles and 3- to 6-membered heterocycles.

[0178] In some embodiments, in the compound or salt of Formula (II), R 61 and R 64 are each independently, for each occurrence, hydrogen, R 81 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and R 81 is selected from a 3- to 6-membered heterocycle optionally substituted with one or more substituents independently selected from:

[0179] In some embodiments, in the compound or salt of Formula (II), R 61 and R 64 are each independently, for each occurrence, hydrogen, C 1-6 Alkyl, and R 81 is selected from a 3- to 6-membered heterocycle optionally substituted with one or more substituents independently selected from:

[0180] In some embodiments, in the compound or salt of Formula (II), R 71 , R 72 , and R 73 are each independently, for each occurrence, hydrogen, R 82 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both C 1-4 Alkyl, C 1-4haloalkyl, and R 82 C optionally substituted with one or more substituents independently selected from 3-6 It is selected from carbocycles and 3- to 6-membered heterocycles.

[0181] In some embodiments, R 71 , R 72 , and R 73 are each independently, at each occurrence, hydrogen, and R 82 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 71 , R 72 , and R 73 are each independently, for each occurrence, R 82 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 71 , R 72 , and R 73 is independently selected at each occurrence from hydrogen. 71 , R 72 , and R 73 are each independently, for each occurrence, C 1-4 Alkyl, C 1-4 haloalkyl, and R 8 C optionally substituted with one or more substituents independently selected from 3-6 In some embodiments, R is selected from carbocycles and 3- to 6-membered heterocycles. 71 , R 72 , and R 73 are each independently, for each occurrence, C 1-4 Alkyl and R 8 C optionally substituted with one or more substituents independently selected from 3-6 In some embodiments, R is selected from carbocycles and 3- to 6-membered heterocycles. 71 , R 72 , and R 73 are independently, for each occurrence, C 3-6It is selected from carbocycles and 3- to 6-membered heterocycles.

[0182] In some embodiments, in the compound or salt of Formula (II), R 80 , R 81 , and R 82 are each independently, at each occurrence, 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 are each independently, at each occurrence, 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 )S(O)2(R91 ), -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 are each independently, at each occurrence, 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, =S, -CN, C 3-6 In some embodiments, R 80 , R 81 , and R 82 are each independently, at each occurrence, 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, =S, -CN, C 3-6 In some embodiments, R 80 , R 81 , and R 82 are each independently, at each occurrence, halogen, -OR 91 , -SR 91 , -N(R 91 )2, -C(O)R 91 , -C(O)OR 91 , -N(R 91)SO2N(R 91 ), —NO, ═O, and —CN. In some embodiments, R 80 , R 81 , and R 82 are each independently, at each occurrence, halogen, -OR 91 , -N(R 91 )2, -C(O)OR 91 , -N(R 91 )SO2N(R 91 ), —NO, ═O, and —CN. In some embodiments, R 80 , R 81 , and R 82 are each independently, for each occurrence, -N(R 91 )2, -C(O)OR 91 , and -N(R 91 )SO2N(R 91 ) is selected.

[0183] In some embodiments, in the compound or salt of Formula (II), R 91 are each independently hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and C 1-6 In some embodiments, R 91 are each independently hydrogen, C 1-6 Alkyl, and C 1-6 In some embodiments, R is selected from haloalkyl. 91 are each independently hydrogen, C 1-6 Alkyl, and C 1-6 In some embodiments, R 91 independently for each occurrence, hydrogen and C 1-6 alkyl.

[0184] In one aspect herein, a compound of formula (III):

[0185] [ka] or a pharmaceutically acceptable salt thereof, wherein R 101 is fluoro, chloro, bromo, 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)R 111 , -S(O)2N(R 111 )2, -NO2, and -CN; R 101 When is fluoro, R 102 teeth, Chloro, bromo, iodo, -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(R121 )P(O)(OR 121 )R 121 , -S(O)R 121 , -S(O)2R 121 , -S(O)2N(R 121 )2, -NO2, and -CN, R 123 C alkyl substituted with one or more substituents independently selected from 130 C optionally substituted with one or more substituents independently selected from 2-6 Alkyl, and Both are R 130 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; R 101 Bromo, iodo, hydroxyl, -O-C1 alkyl, -C(O)OR 111 , -C(O)N(H)(C2 alkyl), -S(O)2R 111 , or -S(O)N(R 111 )2, then R 102 teeth, Fluoro, -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, R 130 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both are R 130 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; R 101 But 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, and -CN, R 102 teeth, 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, R 130 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both are R 130 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; However, (i) R 101 When is NO2, R 102 cannot be methyl, and (ii) R 101 When is methyl, R 102 cannot be chloro, and (iii) R 101 When is chloro, R 102 Assuming that it cannot be bromo, R 103 and R 104 are each independently, for each occurrence, 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, 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 114C optionally substituted with one or more substituents independently selected from —C, —NO, and —CN 1-4 Alkyl, All 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 C optionally substituted with one or more substituents independently selected from —C, —NO, and —CN 3-4 selected from carbocycles and 3- to 4-membered heterocycles; R 105 and R 105’ are each independently selected from hydrogen and hydroxyl, or R 105 and R 105’ are united as =O, R 106 and R 106’ are each independently selected from hydrogen and hydroxyl, or R 106 and R 106’ are combined =O, =N-OR 114 , or =NR 114 and r is selected from 0, 1, 2, and 3; s is selected from 0, 1, 2, and 3; R 111 and R 114 are each independently, for each occurrence, hydrogen, R 131 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, Both are R 131 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; R 112 For each occurrence, R 132C substituted with one or more substituents independently selected from 1-6 Alkyl, Both are R 133 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; R 113 For each occurrence, hydrogen, R 134 C alkyl and C optionally substituted with one or more substituents independently selected from 3-6 alkyl, and R 134 C alkyl substituted with one or more substituents independently selected from Both are R 134 C optionally substituted with one or more substituents independently selected from 3-5 selected from carbocycles and 3- to 6-membered heterocycles; R 121 , R 124 , and R 126 are each independently, for each occurrence, hydrogen, R 134 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, Both C 1-4 Alkyl, C 1-4 haloalkyl, and R 134 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; R 122 and R 125 are each independently, for each occurrence, R 134 C optionally substituted with one or more substituents independently selected from 2-6 Alkyl, Both C 1-4 Alkyl, C 1-4 haloalkyl, and R 134C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; R 123 independently, for each occurrence, hydrogen, R 134 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, Both C 1-4 Alkyl, C 1-4 haloalkyl, and R 134 C optionally substituted with one or more substituents independently selected from 3-5 selected from carbocycles and 3- to 6-membered heterocycles; R 130 , R 131 , R 132 , R 133 , and R 134 are each independently, for each occurrence, 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 3-6selected from a carbocycle and a 3- to 7-membered heterocycle; R 141 are independently hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and C 1-6 hydroxyalkyl, A compound or a pharmaceutically acceptable salt thereof is provided.

[0186] In some embodiments, in the compound or salt of Formula (III), R 101 is fluoro. In some embodiments, in the compound or salt of Formula (III), R 101 is bromo, iodo, hydroxyl, -O-C1 alkyl, -C(O)OR 111 , -C(O)N(H)(C2 alkyl), -S(O)2R 111 , or -S(O)N(R 111 )2. In some embodiments, in the compound or salt of formula (III), R 101 is 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.

[0187] In some embodiments, in the compound or salt of Formula (III), R 101 is fluoro, bromo, iodo, hydroxyl, -O-C1 alkyl, -C(O)OR111 , -C(O)N(H)(C2 alkyl), -S(O)2R 111 , or -S(O)N(R 111 )2. In some embodiments, R 101 is fluoro, bromo, iodo, hydroxyl, -O-C1 alkyl, -C(O)OR 111 or —C(O)N(H)(C alkyl). In some embodiments, R 101 is fluoro, bromo, iodo, hydroxyl, or —O—C1 alkyl.

[0188] In some embodiments, in the compound or salt of Formula (III), R 101 is fluoro, 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 ), —NO, or —CN. In some embodiments, R 101 is 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 , —NO, or —CN. In some embodiments, R 101 is fluoro, 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 , —NO, or —CN. In some embodiments, R 101 is fluoro, -NO2, or -CN.

[0189] In some embodiments, in the compound or salt of Formula (III), R 101 is bromo, iodo, hydroxyl, -O-C1 alkyl, -C(O)OR 111 , -C(O)N(H)(C2 alkyl), -S(O)2R 111 , or -S(O)N(R 111 )2, 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 ), —NO, or —CN. In some embodiments, R 101 is bromo, iodo, hydroxyl, -O-C1 alkyl, -C(O)OR 111 , -C(O)N(H)(C2 alkyl), -S(O)2R 111, or -S(O)N(R 111 )2, 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, --N(R 111 )C(O)R 111 , —NO, or —CN. In some embodiments, R 101 is bromo, iodo, hydroxyl, -O-C1 alkyl, -C(O)OR 111 , -C(O)N(H)(C2 alkyl), -S(O)2R 111 , or -S(O)N(R 111 )2, 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, --N(R 111 )C(O)R 111 , —NO, or —CN. In some embodiments, R 101 is bromo, iodo, hydroxyl, -O-C1 alkyl, -C(O)OR 111 , -C(O)N(H)(C2 alkyl), -S(O)2R 111 , or -S(O)N(R 111 )2, chloro, -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 101is bromo, iodo, hydroxyl, -O-C1 alkyl, -C(O)OR 111 , -C(O)N(H)(C2 alkyl), -S(O)2R 111 , or -S(O)N(R 111 )2, -NO2, or -CN. In some embodiments, R 101 is bromo, iodo, hydroxyl, -O-C1 alkyl, -NO2, or -CN.

[0190] In some embodiments, in the compound or salt of Formula (III), R 101 is fluoro, chloro, bromo, 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)R 111 , -S(O)2N(R 111 )2, —NO2, and —CN. In some embodiments, R 101 is fluoro, chloro, bromo, 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)R 111 , -S(O)2N(R 111 )2, —NO2, and —CN. In some embodiments, R 101 is fluoro, chloro, bromo, 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)R 111 , -S(O)2N(R 111 )2, —NO2, and —CN. In some embodiments, R 101 is fluoro, chloro, bromo, 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 is fluoro, chloro, bromo, hydroxyl, -C 1-6Alkyl, -C 1-6 Haloalkyl, -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 is fluoro, chloro, bromo, 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 is fluoro, chloro, bromo, hydroxyl, -C 1-6 Alkyl, -OC 1-6 Alkyl, -N(R 111 )2, -OR 112 , —NO2, and —CN. In some embodiments, R 101 is selected from fluoro, —NO 2 , and —CN.

[0191] In some embodiments, in the compound or salt of Formula (III), R 101 When is fluoro, R 102 teeth, Chloro, bromo, iodo, -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, R 123 C alkyl substituted with one or more substituents independently selected from 130 C optionally substituted with one or more substituents independently selected from 2-6 Alkyl, and Both are R 130 C optionally substituted with one or more substituents independently selected from 3-6 It is selected from carbocycles and 3- to 6-membered heterocycles.

[0192] In some embodiments, in the compound or salt of Formula (III), R 101 When is fluoro, R 102 is chloro, bromo, iodo, -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)(OR121 )R 121 , -S(O)R 121 , -S(O)2R 121 , -S(O)2N(R 121 )2, —NO2, and —CN. In some embodiments, R 101 When is fluoro, R 102 is chloro, bromo, iodo, -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, R 101 When is fluoro, R 102 is chloro, bromo, iodo, -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(R121 )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, R 101 When is fluoro, R 102 is chloro, bromo, iodo, -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, R 101 When is fluoro, R 102 is chloro, bromo, iodo, -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, R 101 When is fluoro, R 102 is chloro, bromo, iodo, -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, R 101 When is fluoro, R 102is chloro, bromo, iodo, -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, R 101 When is fluoro, R 102 is chloro, bromo, iodo, -N(R 121 )2, -OR 122 , -C(O)R 121 , —NO2, and —CN. In some embodiments, R 101 When is fluoro, R 102 is chloro, bromo, iodo, -N(R 121 )2, -OR 122 , —NO2, and —CN. In some embodiments, R 101 When is fluoro, R 102 is selected from chloro, bromo, iodo, —NO, and —CN. 101 When is fluoro, R 102 is selected from chloro, bromo, and iodo. 101 When is fluoro, R 102 is bromo.

[0193] In some embodiments, in the compound or salt of Formula (III), R 101 Bromo, iodo, hydroxyl, -O-C1 alkyl, -C(O)OR 111 , -C(O)N(H)(C2 alkyl), -S(O)2R 111 , or -S(O)N(R 111 )2, then R 102 teeth, Fluoro, -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, R 130 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both are R 130 C optionally substituted with one or more substituents independently selected from 3-6 It is selected from carbocycles and 3- to 6-membered heterocycles.

[0194] In some embodiments, in the compound or salt of Formula (III), R 101 Bromo, iodo, hydroxyl, -O-C1 alkyl, -C(O)OR 111 , -C(O)N(H)(C2 alkyl), -S(O)2R 111 , or -S(O)N(R 111 )2, then R 102 is fluoro, -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, R 130 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and both R 130 C optionally substituted with one or more substituents independently selected from 3-6 In some embodiments, R is selected from carbocycles and 3- to 6-membered heterocycles. 101 Bromo, iodo, hydroxyl, -O-C1 alkyl, -C(O)OR 111 , -C(O)N(H)(C2 alkyl), -S(O)2R 111 , or -S(O)N(R 111 )2, then R 102 is fluoro, -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)R124 , -S(O)2R 124 , -S(O)2N(R 124 )2, -NO2, and -CN, R 130 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and both R 130 C optionally substituted with one or more substituents independently selected from 3-6 In some embodiments, R is selected from carbocycles and 3- to 6-membered heterocycles. 101 Bromo, iodo, hydroxyl, -O-C1 alkyl, -C(O)OR 111 , -C(O)N(H)(C2 alkyl), -S(O)2R 111 , or -S(O)N(R 111 )2, then R 102 is fluoro, -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, R 130 C optionally substituted with one or more substituents independently selected from 1-6 alkyl.

[0195] In some embodiments, in the compound or salt of Formula (III), R 101 Bromo, iodo, hydroxyl, -O-C1 alkyl, -C(O)OR 111 , -C(O)N(H)(C2 alkyl), -S(O)2R 111 , or -S(O)N(R 111 )2, then R 102 is fluoro, -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, R 130 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 101 Bromo, iodo, hydroxyl, -O-C1 alkyl, -C(O)OR 111 , -C(O)N(H)(C2 alkyl), -S(O)2R 111 , or -S(O)N(R 111 )2, then R 102 is fluoro, -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, R 130 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 101 Bromo, iodo, hydroxyl, -O-C1 alkyl, -C(O)OR 111 , -C(O)N(H)(C2 alkyl), -S(O)2R 111 , or -S(O)N(R 111 )2, then R 102 is fluoro, -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, R 130 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 101 Bromo, iodo, hydroxyl, -O-C1 alkyl, -C(O)OR 111 , -C(O)N(H)(C2 alkyl), -S(O)2R 111 , or -S(O)N(R 111 )2, then R 102 is fluoro, -N(R 124 )2, -OR 125 , -C(O)R 124 , -C(O)OR 124 , -OC(O)R 124 , -NO2, -CN, R 130 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 101 Bromo, iodo, hydroxyl, -O-C1 alkyl, -C(O)OR 111, -C(O)N(H)(C2 alkyl), -S(O)2R 111 , or -S(O)N(R 111 )2, then R 102 is fluoro, -N(R 124 )2, -OR 125 , -NO2, -CN, R 130 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 101 Bromo, iodo, hydroxyl, -O-C1 alkyl, -C(O)OR 111 , -C(O)N(H)(C2 alkyl), -S(O)2R 111 , or -S(O)N(R 111 )2, then R 102 is fluoro, -N(R 124 )2, -OR 125 , -NO2, -CN, C 1-6 In some embodiments, R 101 Bromo, iodo, hydroxyl, -O-C1 alkyl, -C(O)OR 111 , -C(O)N(H)(C2 alkyl), -S(O)2R 111 , or -S(O)N(R 111 )2, then R 102 Fluoro, -NO2, -CN, and C 1-6 In some embodiments, R 101 Bromo, iodo, hydroxyl, -O-C1 alkyl, -C(O)OR 111 , -C(O)N(H)(C2 alkyl), -S(O)2R 111 , or -S(O)N(R 111 )2, then R 102 is selected from fluoro, —NO 2 , and —CN.

[0196] In some embodiments, in the compound or salt of Formula (III), R 101 Bromo, iodo, hydroxyl, -O-C1 alkyl, -C(O)OR 111 or -C(O)N(H)(C alkyl), R102 is fluoro, -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, R 130 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and both R 130 C optionally substituted with one or more substituents independently selected from 3-6 It is selected from carbocycles and 3- to 6-membered heterocycles.

[0197] In some embodiments, in the compound or salt of Formula (III), R 101 Bromo, iodo, hydroxyl, -O-C1 alkyl, -C(O)OR 111 or -C(O)N(H)(C alkyl), R 102 is fluoro, -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(R124 )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, R 130 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and both R 130 C optionally substituted with one or more substituents independently selected from 3-6 In some embodiments, R is selected from carbocycles and 3- to 6-membered heterocycles. 101 Bromo, iodo, hydroxyl, -O-C1 alkyl, -C(O)OR 111 or -C(O)N(H)(C alkyl), R 102 is fluoro, -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, R 130 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and both R 130 C optionally substituted with one or more substituents independently selected from 3-6 It is selected from carbocycles and 3- to 6-membered heterocycles.

[0198] In some embodiments, in the compound or salt of Formula (III), R 101 Bromo, iodo, hydroxyl, -O-C1 alkyl, -C(O)OR 111 or -C(O)N(H)(C alkyl), R 102 is fluoro, -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, R 130 C optionally substituted with one or more substituents independently selected from 1-6In some embodiments, R 101 Bromo, iodo, hydroxyl, -O-C1 alkyl, -C(O)OR 111 or -C(O)N(H)(C alkyl), R 102 is fluoro, -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, R 130 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 101 Bromo, iodo, hydroxyl, -O-C1 alkyl, -C(O)OR 111 or -C(O)N(H)(C alkyl), R 102 is fluoro, -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, R 130C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 101 Bromo, iodo, hydroxyl, -O-C1 alkyl, -C(O)OR 111 or -C(O)N(H)(C alkyl), R 102 is fluoro, -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, R 130 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 101 Bromo, iodo, hydroxyl, -O-C1 alkyl, -C(O)OR 111 or -C(O)N(H)(C alkyl), R 102 is fluoro, -N(R 124 )2, -OR 125 , -C(O)R 124 , -C(O)OR 124 , -OC(O)R 124 , -NO2, -CN, R 130 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 101 Bromo, iodo, hydroxyl, -O-C1 alkyl, -C(O)OR 111 or -C(O)N(H)(C alkyl), R 102 is fluoro, -N(R 124 )2, -OR 125 , -NO2, -CN, R 130 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R101 Bromo, iodo, hydroxyl, -O-C1 alkyl, -C(O)OR 111 or -C(O)N(H)(C alkyl), R 102 is fluoro, -N(R 124 )2, -OR 125 , -NO2, -CN, C 1-6 In some embodiments, R 101 Bromo, iodo, hydroxyl, -O-C1 alkyl, -C(O)OR 111 or -C(O)N(H)(C alkyl), R 102 Fluoro, -NO2, -CN, and C 1-6 In some embodiments, R 101 Bromo, iodo, hydroxyl, -O-C1 alkyl, -C(O)OR 111 or -C(O)N(H)(C alkyl), R 102 is selected from fluoro, —NO 2 , and —CN.

[0199] In some embodiments, in the compound or salt of Formula (III), R 101 is bromo, iodo, or hydroxyl, R 102 teeth, Fluoro, -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)(OR124 )R 124 , -S(O)R 124 , -S(O)2R 124 , -S(O)2N(R 124 )2, -NO2, and -CN, R 130 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both are R 130 C optionally substituted with one or more substituents independently selected from 3-6 It is selected from carbocycles and 3- to 6-membered heterocycles.

[0200] In some embodiments, in the compound or salt of Formula (III), R 101 is bromo, iodo, or hydroxyl, R 102 is fluoro, -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, R 130 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and both R 130C optionally substituted with one or more substituents independently selected from 3-6 In some embodiments, R is selected from carbocycles and 3- to 6-membered heterocycles. 101 is bromo, iodo, or hydroxyl, R 102 is fluoro, -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, R 130 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and both R 130 C optionally substituted with one or more substituents independently selected from 3-6 In some embodiments, R is selected from carbocycles and 3- to 6-membered heterocycles. 101 is bromo, iodo, or hydroxyl, R 102 is fluoro, -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, R 130 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 101 is bromo, iodo, or hydroxyl, R 102 is fluoro, -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, R 130 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 101is bromo, iodo, or hydroxyl, R 102 is fluoro, -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, R 130 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 101 is bromo, iodo, or hydroxyl, R 102 is fluoro, -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, R 130 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 101 is bromo, iodo, or hydroxyl, R 102 is fluoro, -N(R 124 )2, -OR 125 , -C(O)R 124 , -C(O)OR 124 , -OC(O)R 124 , -NO2, -CN, R 130 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 101is bromo, iodo, or hydroxyl, R 102 is fluoro, -N(R 124 )2, -OR 125 , -NO2, -CN, R 130 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 101 is bromo, iodo, or hydroxyl, R 102 is fluoro, -N(R 124 )2, -OR 125 , -NO2, -CN, C 1-6 In some embodiments, R 101 is bromo, iodo, or hydroxyl, R 102 Fluoro, -NO2, -CN, and C 1-6 In some embodiments, R 101 is bromo, iodo, or hydroxyl, R 102 is selected from fluoro, —NO 2 , and —CN.

[0201] In some embodiments, in the compound or salt of Formula (III), R 101 But 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, R102 teeth, 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, R 130 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both are R 130 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; However, (i) R 101 When is NO2, R 102 cannot be methyl, and (ii) R 101 When is methyl, R 102 cannot be chloro, and (iii) R 101 When is chloro, R 102 It is assumed that cannot be bromo.

[0202] In some embodiments, in the compound or salt of Formula (III), R 101 But chloro, -C 1-6Alkyl, -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 is 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 R 130 C optionally substituted with one or more substituents independently selected from 1-6 alkyl, with the proviso that (i) R 101When is NO2, R 102 cannot be methyl, and (ii) R 101 When is methyl, R 102 cannot be chloro, and (iii) R 101 When is chloro, R 102 In some embodiments, in the compound or salt of formula (III), R 101 But 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 is 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 R 130C optionally substituted with one or more substituents independently selected from 1-6 alkyl, with the proviso that (i) R 101 When is NO2, R 102 cannot be methyl, and (ii) R 101 When is methyl, R 102 cannot be chloro, and (iii) R 101 When is chloro, R 102 In some embodiments, in the compound or salt of formula (III), R 101 But 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 is 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 R 130 C optionally substituted with one or more substituents independently selected from 1-6 alkyl, with the proviso that (i) R 101 When is NO2, R102 cannot be methyl, and (ii) R 101 When is methyl, R 102 cannot be chloro, and (iii) R 101 When is chloro, R 102 In some embodiments, in the compound or salt of formula (III), R 101 But 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 is halogen, -OR 126 , -N(R 126 )2, -NO2, -CN, and R 130 C optionally substituted with one or more substituents independently selected from 1-6 alkyl, with the proviso that (i) R 101 When is NO2, R 102 cannot be methyl, and (ii) R 101 When is methyl, R 102 cannot be chloro, and (iii) R 101 When is chloro, R 102 In some embodiments, in the compound or salt of formula (III), R 101 But chloro, -C 1-6 Alkyl, -C1-6 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 is a halogen, and R 130 C optionally substituted with one or more substituents independently selected from 1-6 alkyl, with the proviso that (i) R 101 When is NO2, R 102 cannot be methyl, and (ii) R 101 When is methyl, R 102 cannot be chloro, and (iii) R 101 When is chloro, R 102 In some embodiments, in the compound or salt of formula (III), R 101 But 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 is halogen and C 1-6 alkyl, with the proviso that (i) R 101 When is NO2, R 102 cannot be methyl, and (ii) R 101 When is methyl, R 102 cannot be chloro, and (iii) R 101 When is chloro, R 102 It is assumed that cannot be bromo.

[0203] In some embodiments, in the compound or salt of Formula (III), R 101 But 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 teeth, 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, R 130 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both are R 130 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; However, (i) R 101 When is NO2, R 102 cannot be methyl, and (ii) R 101 When is methyl, R 102 cannot be chloro, and (iii) R 101 When is chloro, R 102 It is assumed that cannot be bromo.

[0204] In some embodiments, in the compound or salt of Formula (III), R 101 But 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 is halogen, -OR 126 , -SR 126 , -N(R126 )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 R 130 C optionally substituted with one or more substituents independently selected from 1-6 alkyl, with the proviso that (i) R 101 When is NO2, R 102 cannot be methyl, and (ii) R 101 When is methyl, R 102 cannot be chloro, and (iii) R 101 When is chloro, R 102 In some embodiments, in the compound or salt of formula (III), R 101 But 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 is 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 R 130 C optionally substituted with one or more substituents independently selected from 1-6 alkyl, with the proviso that (i) R 101 When is NO2, R 102 cannot be methyl, and (ii) R 101 When is methyl, R 102 cannot be chloro, and (iii) R 101 When is chloro, R 102 In some embodiments, in the compound or salt of formula (III), R 101 But 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 is halogen, -OR 126 , -N(R 126 )2, -C(O)R126 , -C(O)OR 126 , -OC(O)R 126 , -C(O)N(R 126 )2, -N(R 126 )C(O)R 126 , -NO2, -CN, and R 130 C optionally substituted with one or more substituents independently selected from 1-6 alkyl, with the proviso that (i) R 101 When is NO2, R 102 cannot be methyl, and (ii) R 101 When is methyl, R 102 cannot be chloro, and (iii) R 101 When is chloro, R 102 In some embodiments, in the compound or salt of formula (III), R 101 But 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 is halogen, -OR 126 , -N(R 126 )2, -NO2, -CN, and R 130 C optionally substituted with one or more substituents independently selected from 1-6 alkyl, with the proviso that (i) R 101 When is NO2, R 102 cannot be methyl, and (ii) R 101 When is methyl, R 102 cannot be chloro, and (iii) R 101 When is chloro, R 102In some embodiments, in the compound or salt of formula (III), R 101 But 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 is a halogen, and R 130 C optionally substituted with one or more substituents independently selected from 1-6 alkyl, with the proviso that (i) R 101 When is NO2, R 102 cannot be methyl, and (ii) R 101 When is methyl, R 102 cannot be chloro, and (iii) R 101 When is chloro, R 102 In some embodiments, in the compound or salt of formula (III), R 101 But 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 is halogen and C 1-6 alkyl, with the proviso that (i) R 101When is NO2, R 102 cannot be methyl, and (ii) R 101 When is methyl, R 102 cannot be chloro, and (iii) R 101 When is chloro, R 102 It is assumed that cannot be bromo.

[0205] In some embodiments, in the compound or salt of Formula (III), R 101 But chloro, -C 1-6 Alkyl, -OC 2-6 Alkyl, -OR 112 , -N(R 111 )2, -NO2, or -CN, R 102 teeth, 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, R 130 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both are R 130C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; However, (i) R 101 When is NO2, R 102 cannot be methyl, and (ii) R 101 When is methyl, R 102 cannot be chloro, and (iii) R 101 When is chloro, R 102 It is assumed that cannot be bromo.

[0206] In some embodiments, in the compound or salt of Formula (III), R 101 But chloro, -C 1-6 Alkyl, -OC 2-6 Alkyl, -OR 112 , -N(R 111 )2, -NO2, or -CN, R 102 is 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 R 130C optionally substituted with one or more substituents independently selected from 1-6 alkyl, with the proviso that (i) R 101 When is NO2, R 102 cannot be methyl, and (ii) R 101 When is methyl, R 102 cannot be chloro, and (iii) R 101 When is chloro, R 102 In some embodiments, in the compound or salt of formula (III), R 101 But chloro, -C 1-6 Alkyl, -OC 2-6 Alkyl, -OR 112 , -N(R 111 )2, -NO2, or -CN, R 102 is 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 R 130 C optionally substituted with one or more substituents independently selected from 1-6 alkyl, with the proviso that (i) R 101 When is NO2, R 102 cannot be methyl, and (ii) R 101 When is methyl, R 102 cannot be chloro, and (iii) R 101 When is chloro, R 102In some embodiments, in the compound or salt of formula (III), R 101 But chloro, -C 1-6 Alkyl, -OC 2-6 Alkyl, -OR 112 , -N(R 111 )2, -NO2, or -CN, R 102 is 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 R 130 C optionally substituted with one or more substituents independently selected from 1-6 alkyl, with the proviso that (i) R 101 When is NO2, R 102 cannot be methyl, and (ii) R 101 When is methyl, R 102 cannot be chloro, and (iii) R 101 When is chloro, R 102 In some embodiments, in the compound or salt of formula (III), R 101 But chloro, -C 1-6 Alkyl, -OC 2-6 Alkyl, -OR 112 , -N(R 111 )2, -NO2, or -CN, R 102 is halogen, -OR 126 , -N(R 126 )2, -NO2, -CN, and R 130 C optionally substituted with one or more substituents independently selected from 1-6 alkyl, with the proviso that (i) R 101 When is NO2, R 102 cannot be methyl, and (ii) R 101 When is methyl, R102 cannot be chloro, and (iii) R 101 When is chloro, R 102 In some embodiments, in the compound or salt of formula (III), R 101 But chloro, -C 1-6 Alkyl, -OC 2-6 Alkyl, -OR 112 , -N(R 111 )2, -NO2, or -CN, R 102 is a halogen, and R 130 C optionally substituted with one or more substituents independently selected from 1-6 alkyl, with the proviso that (i) R 101 When is NO2, R 102 cannot be methyl, and (ii) R 101 When is methyl, R 102 cannot be chloro, and (iii) R 101 When is chloro, R 102 In some embodiments, in the compound or salt of formula (III), R 101 But chloro, -C 1-6 Alkyl, -OC 2-6 Alkyl, -OR 112 , -N(R 111 )2, -NO2, or -CN, R 102 is halogen and C 1-6 alkyl, with the proviso that (i) R 101 When is NO2, R 102 cannot be methyl, and (ii) R 101 When is methyl, R 102 cannot be chloro, and (iii) R 101 When is chloro, R 102 It is assumed that cannot be bromo.

[0207] In some embodiments, in the compound or salt of Formula (III), R 103 and R 104are each independently, for each occurrence, 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, 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 C optionally substituted with one or more substituents independently selected from —C, —NO, and —CN 1-4 Alkyl, and All 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 C optionally substituted with one or more substituents independently selected from —C, —NO, and —CN 3-4 It is selected from carbocycles and 3- to 4-membered heterocycles.

[0208] In some embodiments, in the compound or salt of Formula (III), R 103 and R 104 are each independently, for each occurrence, 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, 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 C optionally substituted with one or more substituents independently selected from —C, —NO, and —CN 1-4 Alkyl, and C 3-4 It is selected from carbocycles and 3- to 4-membered heterocycles.

[0209] In some embodiments, in the compound or salt of Formula (III), R 103 and R 104 are each independently, at each occurrence, 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, as well as halogens, -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 C optionally substituted with one or more substituents independently selected from —C, —NO, and —CN 1-4 In some embodiments, R 103 and R 104 are each independently, at each occurrence, halogen, -OR 114 , -SR 114 , -N(R 114 )2, -C(O)R 114 , -NO2, -CN, and halogens, -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 C optionally substituted with one or more substituents independently selected from —C, —NO, and —CN 1-4 In some embodiments, R 103 and R 104 are each independently, at each occurrence, halogen, -OR 114 , -N(R 114 )2, -NO2, -CN, and halogens, -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 C optionally substituted with one or more substituents independently selected from —C, —NO, and —CN 1-4 In some embodiments, R 103 and R 104 are each independently, at each occurrence, a halogen, as well as a 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 C optionally substituted with one or more substituents independently selected from —C, —NO, and —CN 1-4 In some embodiments, R 103 and R 104 are each independently, at each occurrence, a halogen, as well as a halogen, -OR 114 , -SR 114 , -N(R 114C optionally substituted with one or more substituents independently selected from —C, —NO, and —CN 1-4 In some embodiments, R 103 and R 104 are each independently, at each occurrence, a halogen, as well as a halogen, -OR 114 , -N(R 114 C optionally substituted with one or more substituents independently selected from —C, —NO, and —CN 1-4 In some embodiments, R 103 and R 104 are each independently, for each occurrence, halogen and C 1-4 alkyl.

[0210] In some embodiments, in the compound or salt of Formula (III), R 105 and R 105’ are each independently selected from hydrogen and hydroxyl, or R 105 and R 105’ and together are =0. In some embodiments, in the compound or salt of formula (III), R 106 and R 106’ are each independently selected from hydrogen and hydroxyl. 105 and R 105’ are united as =O.

[0211] In some embodiments, in the compound or salt of Formula (III), R 106 and R 106’ are each independently selected from hydrogen and hydroxyl, or R 106 and R 106’ are combined =O, =N-OR 114 , or =NR 114 In some embodiments, in the compound or salt of formula (III), R 106 and R 106’ are each independently selected from hydrogen and hydroxyl. 106and R 106’ are taken together to be =O. In some embodiments, R 106 and R 106’ together =N-OR 114 is.

[0212] In some embodiments, in 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.

[0213] In some embodiments, in the compound or salt of Formula (III), s is selected from 0, 1, 2, and 3. In some embodiments, s is 0.

[0214] In some embodiments, in the compound or salt of Formula (III), R 111 and R 114 are each independently, for each occurrence, hydrogen, R 131 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both are R 131 C optionally substituted with one or more substituents independently selected from 3-6 It is selected from carbocycles and 3- to 6-membered heterocycles.

[0215] In some embodiments, in the compound or salt of Formula (III), R 111 and R 114 are each independently, for each occurrence, hydrogen, R 131 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both are R 131 C optionally substituted with one or more substituents independently selected from 3-6 It is selected from carbocycles and 3- to 6-membered heterocycles.

[0216] In some embodiments, R 111 and R 114 are each independently, for each occurrence, hydrogen, R 131 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, C 3-6 In some embodiments, R is selected from carbocycles and 3- to 6-membered heterocycles. 111 and R 114 are each independently, at each occurrence, hydrogen, and R 131 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 111 and R 114 are each independently, for each occurrence, hydrogen and C 1-6 In some embodiments, R 111 and R 114 are hydrogen atoms.

[0217] In some embodiments, in the compound or salt of Formula (III), R 112 For each occurrence, R 132 C substituted with one or more substituents independently selected from 1-6 Alkyl, and Both are R 133 C optionally substituted with one or more substituents independently selected from 3-6 It is selected from carbocycles and 3- to 6-membered heterocycles.

[0218] In some embodiments, in the compound or salt of Formula (III), R 112 For each occurrence, R 132 C substituted with one or more substituents independently selected from 1-6 Alkyl, and both R 133 C optionally substituted with one or more substituents independently selected from 3-6 In some embodiments, R is selected from carbocycles and 3- to 6-membered heterocycles. 112 For each occurrence, R 132C substituted with one or more substituents independently selected from 1-6 Alkyl, and C 3-6 In some embodiments, R is selected from carbocycles and 3- to 6-membered heterocycles. 112 For each occurrence, R 132 C substituted with one or more substituents independently selected from 1-6 In some embodiments, R 112 is C 1-6 It is alkyl.

[0219] In some embodiments, in the compound or salt of Formula (III), R 113 independently, for each occurrence, hydrogen, R 134 C alkyl and C optionally substituted with one or more substituents independently selected from 3-6 alkyl, and R 134 C alkyl substituted with one or more substituents independently selected from Both are R 134 C optionally substituted with one or more substituents independently selected from 3-5 It is selected from carbocycles and 3- to 6-membered heterocycles.

[0220] In some embodiments, in the compound or salt of Formula (III), R 113 independently, for each occurrence, hydrogen, R 134 C alkyl and C optionally substituted with one or more substituents independently selected from 3-6 alkyl, and R 134 C alkyl substituted with one or more substituents independently selected from C 3-5 It is selected from carbocycles and 3- to 6-membered heterocycles.

[0221] In some embodiments, in the compound or salt of Formula (III), R 113 are independently, for each occurrence, hydrogen, R 134C alkyl and C optionally substituted with one or more substituents independently selected from 3-6 Alkyl, and R 134 In some embodiments, R is selected from C alkyl optionally substituted with one or more substituents independently selected from 113 For each occurrence, hydrogen, R 134 C alkyl optionally substituted with one or more substituents independently selected from 134 In some embodiments, R is selected from C alkyl substituted with one or more substituents independently selected from 113 For each occurrence, hydrogen, R 134 In some embodiments, R is selected from C alkyl optionally substituted with one or more substituents independently selected from 113 is independently selected at each occurrence from hydrogen, C alkyl, and C alkyl. In some embodiments, R 113 At each occurrence, R is selected from hydrogen and C alkyl. 113 is hydrogen.

[0222] In some embodiments, in the compound or salt of Formula (III), R 121 , R 124 , and R 126 are each independently, for each occurrence, hydrogen, R 134 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both C 1-4 Alkyl, C 1-4 haloalkyl, and R 134 C optionally substituted with one or more substituents independently selected from 3-6 It is selected from carbocycles and 3- to 6-membered heterocycles.

[0223] In some embodiments, in the compound or salt of Formula (III), R 121 , R 124 , and R126 are each independently, for each occurrence, hydrogen, R 134 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and C 3-6 It is selected from carbocycles and 3- to 6-membered heterocycles.

[0224] In some embodiments, in the compound or salt of Formula (III), R 121 , R 124 , and R 126 are each independently, at each occurrence, hydrogen, and R 134 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 121 , R 124 , and R 126 are each independently, for each occurrence, hydrogen and C 1-6 In some embodiments, R 121 , R 124 , and R 126 are hydrogen atoms.

[0225] In some embodiments, in the compound or salt of Formula (III), R 122 and R 125 are each independently, for each occurrence, R 134 C optionally substituted with one or more substituents independently selected from 2-6 Alkyl, and Both C 1-4 Alkyl, C 1-4 haloalkyl, and R 13 C optionally substituted with one or more substituents independently selected from 3-6 It is selected from carbocycles and 3- to 6-membered heterocycles.

[0226] In some embodiments, in the compound or salt of Formula (III), R 122 and R125 are each independently, for each occurrence, R 134 C optionally substituted with one or more substituents independently selected from 2-6 Alkyl, and C 3-6 In some embodiments, R is selected from carbocycles and 3- to 6-membered heterocycles. 122 and R 125 are R 134 C optionally substituted with one or more substituents independently selected from 2-6 In some embodiments, R 122 and R 125 are C 2-6 It is alkyl.

[0227] In some embodiments, in the compound or salt of Formula (III), R 123 independently, for each occurrence, hydrogen, R 134 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both C 1-4 Alkyl, C 1-4 haloalkyl, and R 134 C optionally substituted with one or more substituents independently selected from 3-5 It is selected from carbocycles and 3- to 6-membered heterocycles.

[0228] In some embodiments, in the compound or salt of Formula (III), R 123 independently, for each occurrence, hydrogen, R 134 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and C 3-5 It is selected from carbocycles and 3- to 6-membered heterocycles.

[0229] In some embodiments, in the compound or salt of Formula (III), R 123are each independently, at each occurrence, hydrogen, and R 134 C optionally substituted with one or more substituents independently selected from 1-6 In some embodiments, R 123 independently for each occurrence, hydrogen and C 1-6 alkyl.

[0230] In some embodiments, in the compound or salt of Formula (III), R 130 , R 131 , R 132 , R 133 , and R 134 are each independently, at each occurrence, 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 It is selected from carbocycles and 3- to 7-membered heterocycles.

[0231] In some embodiments, in the compound or salt of Formula (III), R 130 , R 131 , R 132 , R 133 , and R134 are each independently, at each occurrence, 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 134 are each independently, at each occurrence, 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 are each independently, at each occurrence, 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 are each independently, at each occurrence, 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 , —NO, ═O, ═S, and —CN. In some embodiments, R 130 , R 131 , R 132 , R 133 , and R 134 are each independently, at each occurrence, 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 R134 are each independently, at each occurrence, 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 are each independently, at each occurrence, 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 are each independently, at each occurrence, 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, —NO 2 , and —CN.

[0232] In some embodiments, in the compound or salt of Formula (III), R 141 are each independently hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and C 1-6 In some embodiments, R 141 are each independently hydrogen, C 1-6 Alkyl, and C 1-6 In some embodiments, R is selected from haloalkyl. 141 are each independently hydrogen, C 1-6 Alkyl, and C 1-6 In some embodiments, R 141 independently for each occurrence, hydrogen and C 1-6In some embodiments, R 141 is hydrogen at each occurrence.

[0233] In one aspect herein, a compound of formula (IV):

[0234] [ka] or a pharmaceutically acceptable salt thereof, wherein R 151 is fluoro, bromo, -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 rings, and -OR 3-6 heterocycles, and each R 171 and optionally substituted with one or more substituents independently selected from

[0235] [ka] is selected from R 151 When is fluoro, R152 teeth, 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, R 195 C alkyl substituted with one or more substituents independently selected from 180 C optionally substituted with one or more substituents independently selected from 2-6 Alkyl, and Both are R 180 C optionally substituted with one or more substituents independently selected from 3-6 Carbocycle, 3-membered heterocycle, 4-membered heterocycle,

[0236] [ka] and a 6-membered heterocycle; R151 but,

[0237] [ka] -SR 161 , -S(O)R 161 , -S(O)2R 161 , or -S(O)N(R 161 )2, or -CN, R 152 teeth, 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 ), -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, R 180 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both are R 180 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; R 151 When is bromo or -NO2, R 152 teeth, Iodine, -OR197 , -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, R 180 C alkyl substituted with one or more substituents independently selected from 198 C alkyl substituted with one or more substituents independently selected from 180 C optionally substituted with one or more substituents independently selected from 2-6 Alkyl, Both are R 180 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; However, (i) R 151 When is NO2, R 152 is R 180 and (ii) R 151 When is NO2, R 152 is assumed to be ethyl, R 151 But -C 1-6Haloalkyl, -OC 2-6 Alkyl, -OC 1-6 Haloalkyl, -OR 3-6 Carbocyclic ring, -OR 3-6 Heterocycle, -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, then R 152 teeth, 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, R 177 C optionally substituted with one or more substituents independently selected from1-6 Alkyl, and Both are R 177 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; R 153 and R 154 are each independently, for each occurrence, 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, 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 C optionally substituted with one or more substituents independently selected from —C, —NO, and —CN 1-4 Alkyl, and All 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 C optionally substituted with one or more substituents independently selected from —C, —NO, and —CN 3-6 selected from carbocycles and 3- to 5-membered heterocycles; R 155 and R 155’ are each independently selected from hydrogen, hydroxyl, and methyl, or R 155 and R 155’ are united as =O, R 156and R 156’ are each independently selected from hydrogen, hydroxyl, and methyl, or R 156 and R 156’ are combined =O, =N-OR 171 , or =NR 171 and t is selected from 0, 1, 2, and 3; u is selected from 0, 1, 2, and 3; R 161 and R 164 are each independently, for each occurrence, hydrogen, R 177 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both are R 177 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; R 171 , R 174 , and R 176 are each independently, for each occurrence, hydrogen, R 180 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both C 1-4 Alkyl, C 1-4 haloalkyl, and R 180 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; R 177 and R 180 are each independently, for each occurrence, Halogen, -OR 191 , -SR 191 , -N(R 191 )2, -C(O)R 191 , -C(O)OR 191 , -OC(O)R 191 , -OC(O)N(R191 )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 , -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 selected from a carbocycle and a 3- to 6-membered heterocycle; R 178 For each occurrence, R 180 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both are R 180 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; R 191 are independently hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, and C 1-6 hydroxyalkyl; R 192 For each occurrence, 180 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; R 193 For each occurrence, R 180 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both C 1-4 Alkyl, C 1-4 haloalkyl, and R 180 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; R 194 For each occurrence, R 180 C substituted with one or more substituents independently selected from 1-6 alkyl, R 195 independently, for each occurrence, Halogens, -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)N(R 171 )2, R 180 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both C1-4 Alkyl, C 1-4 haloalkyl, and R 180 C optionally substituted with one or more substituents independently selected from 5-6 selected from carbocycles and 3- to 6-membered heterocycles; R 196 For each occurrence, Hydrogen, -CN, and OR 171 , R 180 C optionally substituted with one or more substituents independently selected from 1-6 Alkyl, and Both C 1-4 Alkyl, C 1-4 haloalkyl, and R 180 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; R 197 For each occurrence, hydrogen, R 180 C optionally substituted with one or more substituents independently selected from 2-6 Alkyl, and Both C 1-4 Alkyl, C 1-4 haloalkyl, and R 180 C optionally substituted with one or more substituents independently selected from 3-6 selected from carbocycles and 3- to 6-membered heterocycles; R 198 independently, for each occurrence, Fluoro, chloro, iodo, -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(R171 )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)N(R 171 )2, R 180 C optionally substituted with one or more substituents independently selected from 2-6 Alkyl, and Both C 1-4 Alkyl, C 1-4 haloalkyl, and R 180 C optionally substituted with one or more substituents independently selected from 5-6 selected from carbocycles and 3- to 6-membered heterocycles; A compound or a pharmaceutically acceptable salt thereof is provided.

[0238] In some embodiments, in the compound or salt of (IV), R 151 is fluoro, bromo, -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 1-6haloalkyl, or

[0239] [ka] In some embodiments, in the compound or salt of (IV), R 151 is fluoro, bromo, -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

[0240] [ka] In some embodiments, in the compound or salt of (IV), R 151 -Fluoro, bromo, -SR 161 , -S(O)2R 161 , -CN, -NO2, or

[0241] [ka] In some embodiments, in the compound or salt of (IV), R 151 is fluoro. In some embodiments, in the compound or salt of (IV), R 151 When is fluoro, R 152 -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)R171 , -S(O)2N(R 171 )2, -NR 196 (C=NR 196 )N(R 196 )2, -N3, -CN, R 195 C alkyl substituted with one or more substituents independently selected from

[0242] [ka] In some embodiments, in the compound or salt of (IV), R 151 When is fluoro, R 152 -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, R 195 C alkyl substituted with one or more substituents independently selected from

[0243] [ka] In some embodiments, in the compound or salt of (IV), R 151 When is fluoro, R 152 -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, R 195 C alkyl substituted with one or more substituents independently selected from

[0244] [ka] In some embodiments, in the compound or salt of (IV), R 151 When is fluoro, R 152 -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 In some embodiments, in the compound or salt of (IV), R 151 When is fluoro, R 152 -N3, -CN, R 195 C alkyl substituted with one or more substituents independently selected from

[0245] [ka] In some embodiments, in the compound or salt of (IV), R 151 When is fluoro, R 152 -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 In some embodiments, in the compound or salt of (IV), R 151 When is fluoro, R 152 -NHR 192 , -C(=NR 196 )N(R 196 )2, and -NR 196 (C=NR 196 )N(R 196 In some embodiments, in the compound or salt of (IV), R 151 When is fluoro, R 152-NHR 192 , -C(O)R 171 , and -C(O)OR 171 In some embodiments, in the compound or salt of (IV), R 151 When is fluoro, R 152 Ha-NHR 192 In some embodiments, in the compound or salt of (IV), R 151 When is fluoro, R 152 is -C(=NR 196 )N(R 196 )2. In some embodiments, in the compound or salt of (IV), R 151 When is fluoro, R 152 HA-C(O)R 171 In some embodiments, in the compound or salt of (IV), R 151 When is fluoro, R 152 -C(O)OR 171 In some embodiments, in the compound or salt of (IV), R 151 When is fluoro, R 152 Ha-NR 196 (C=NR 196 )N(R 196 )2. In some embodiments, in the compound or salt of (IV), R 151 When is fluoro, R 152 is R 195 C alkyl substituted with one or more substituents independently selected from

[0246] [ka] In some embodiments, in the compound or salt of (IV), R 151 When is fluoro, R 152 is -N3. In some embodiments, in the compound or salt of (IV), R 151 When is fluoro, R 152 is —CN. In some embodiments, in the compound or salt of (IV), R 151 When is fluoro, R152 is R 195 In some embodiments, in the compound or salt of (IV), R 151 When is fluoro, R 152 teeth,

[0247] [ka] In some embodiments, in the compound or salt of (IV), R 151 When is fluoro, R 152 teeth,

[0248] [ka] is.

[0249] In some embodiments, in the compound or salt of (IV), R 151 teeth,

[0250] [ka] -SR 161 , -S(O)R 161 , -S(O)2R 161 , -S(O)2N(R 161 )2, or —CN. In some embodiments, in the compound or salt of (IV), R 151 -SR 161 , -S(O)2R 161 , -CN, or

[0251] [ka] In some embodiments, in the compound or salt of (IV), R 151 Ha-SR 161 In some embodiments, in the compound or salt of (IV), R 151 -S(O)2R 161In some embodiments, in the compound or salt of (IV), R 151 is —CN. In some embodiments, in the compound or salt of (IV), R 151 teeth,

[0252] [ka] In some embodiments, in the compound or salt of (IV), R 151 But, -SR 161 , -S(O)2R 161 , -CN, or

[0253] [ka] When R 152 is a 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)R 174 , -S(O)2N(R 174 )2, -NO2, -CN, R 180 C optionally substituted with one or more substituents independently selected from 1-6 alkyl, and R 180 In some embodiments, in the compound or salt of (IV), R 151 But, -SR 161 , -S(O)2R 161 , -CN, or

[0254] [ka] When R 152 is a 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, R 180 C optionally substituted with one or more substituents independently selected from 1-6 alkyl, and R 180 In some embodiments, in the compound or salt of (IV), R 151 But, -SR 161 , -S(O)2R 161 , -CN, or

[0255] [ka] When R 152 is -C(O)N(R 174 )2, -N(R 174 )C(O)R 174 , -N(R 174 )C(O)OR 174 , R 180 C optionally substituted with one or more substituents independently selected from 1-6 alkyl, and R 180 In some embodiments, in the compound or salt of (IV), R 151 Ga-SR 161 When R 152 is -C(O)N(R 174 )2, -N(R 174 )C(O)R 174 , -N(R 174 )C(O)OR 174 , R 180 C optionally substituted with one or more substituents independently selected from1-6 alkyl, and R 180 In some embodiments, in the compound or salt of (IV), R 151 -S(O)2R 161 When R 152 is -C(O)N(R 174 )2, -N(R 174 )C(O)R 174 , -N(R 174 )C(O)OR 174 , R 180 C optionally substituted with one or more substituents independently selected from 1-6 alkyl, and R 180 In some embodiments, in the compound or salt of (IV), R 151 Ga-SR 161 When R 152 is -C(O)N(R 174 )2, -N(R 174 )C(O)R 174 , -N(R 174 )C(O)OR 174 , R 180 C optionally substituted with one or more substituents independently selected from 1-6 alkyl, and R 180 In some embodiments, in the compound or salt of (IV), R 151 but

[0256] [ka] When R 152 is -C(O)N(R 174 )2, -N(R 174 )C(O)R 174 , -N(R 174 )C(O)OR 174 , R 180C optionally substituted with one or more substituents independently selected from 1-6 alkyl, and R 180 and wherein the aryl group is a 5-membered heterocycle optionally substituted with one or more substituents independently selected from:

[0257] In some embodiments, in the compound or salt of (IV), R 151 is bromo or —NO. In some embodiments, in the compound or salt of (IV), R 151 is bromo. In some embodiments, in the compound or salt of (IV), R 151 is —NO. In some embodiments, in the compound or salt of (IV), R 151 When is bromo or -NO2, R 152 -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)R 176 , -S(O)2N(R 176 )2, -NO2, -CN, R 180 C alkyl substituted with one or more substituents independently selected from 198 C alkyl substituted with one or more substituents independently selected from 180 C optionally substituted with one or more substituents independently selected from 2-6 alkyl, with the proviso that (i) R 151 When is NO2, R 152 is R 180 and (ii) R 151 When is NO2, R 152It is provided that R cannot be ethyl. In some embodiments, in the compound or salt of (IV), R 151 When is bromo or -NO2, R 152 is R 180 C alkyl substituted with one or more substituents independently selected from 198 C alkyl substituted with one or more substituents independently selected from 180 C optionally substituted with one or more substituents independently selected from 2-6 alkyl, with the proviso that (i) R 151 When is NO2, R 152 is R 180 and (ii) R 151 When is NO2, R 152 It is provided that R cannot be ethyl. In some embodiments, in the compound or salt of (IV), R 151 is bromo and R 152 is R 180 In some embodiments, in the compound or salt of (IV), R 151 is -NO2 and R 152 is R 198 In some embodiments, in the compound or salt of (IV), R 151 When is bromo, R 152 -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)R 176 , -S(O)2N(R 176 )2, -NO2, -CN, R180 C alkyl substituted with one or more substituents independently selected from 198 C alkyl substituted with one or more substituents independently selected from 180 C optionally substituted with one or more substituents independently selected from 2-6 In some embodiments, in the compound or salt of (IV), R 151 When is -NO2, R 152 -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)R 176 , -S(O)2N(R 176 )2, -NO2, -CN, R 180 C alkyl substituted with one or more substituents independently selected from 198 C alkyl substituted with one or more substituents independently selected from 180 C optionally substituted with one or more substituents independently selected from 2-6 alkyl, with the proviso that (i) R 152 is R 180 and (ii) R 152 It is assumed that cannot be ethyl.

[0258] In some embodiments, in the compound or salt of (IV), R 153 and R 154 are each independently, for each occurrence, halogen and C 1-4 In some embodiments, in the compound or salt of (IV), R 155 and R 155’are taken together to be =O. In some embodiments, in the compound or salt of (IV), R 156 and R 156’ are taken together to be =O. In some embodiments, in the compound or salt of (IV), R 156 and R 156’ together =N-OR 171 In some embodiments, in the compound or salt of (IV), R 156 and R 156’ are each independently selected from hydroxyl and methyl. In some embodiments, in the compound or salt of (IV), t is selected from 0 and 1. In some embodiments, in the compound or salt of (IV), u is 0.

[0259] In some embodiments, the compound is any of the compounds represented in Table I, or a pharmaceutically acceptable salt or solvate thereof.

[0260] [Table 1-1]

[0261] [Table 1-2]

[0262] [Table 1-3]

[0263] [Table 1-4]

[0264] [Table 1-5]

[0265] [Table 1-6]

[0266]

Table 1-7

[0267]

Table 1-8

[0268]

Table 1-9

[0269]

Table 1-10

[0270]

Table 1-11

[0271]

Table 1-12

[0272]

Table 1-13

[0273]

Table 1-14

[0274]

Table 1-15

[0275]

Table 1-16

[0276] [Table 1-17]

[0277] [Table 1-18]

[0278] [Table 1-19]

[0279] [Table 1-20]

[0280] [Table 1-21]

[0281] While preferred embodiments of the present disclosure have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will occur to those skilled in the art without departing from the invention. It is understood that various alternatives to the embodiments of the invention described herein may be utilized in practicing the disclosure. The following claims define the scope of the invention, and it is intended that methods and structures within the scope of these claims and their equivalents be covered thereby.

[0282] Chemical entities having a carbon-carbon double bond or a carbon-nitrogen double bond can exist in the Z- or E-form (i.e., cis- or trans-form). Additionally, some chemical entities can exist in various tautomeric forms. Unless otherwise specified, compounds or salts of formulas (I), (II), (III), and (IV) are intended to include all Z-, E-, and tautomeric forms.

[0283] "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 designate a racemic mixture where appropriate. "Diastereoisomers" or "diastereomers" are stereoisomers that have at least two asymmetric atoms but are not mirror images of each other. Absolute stereochemistry is specified using the Cahn-Ingold-Prelog RS system. When a compound is a pure enantiomer, the stereochemistry of each chiral carbon can be specified as either R or S. Resolved compounds whose absolute configuration is unknown can be designated as (+) or (-) depending on the direction (dextrorotatory or levorotatory) 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 give rise to enantiomers, diastereomers, and other stereoisomeric forms, which can be defined in terms of absolute stereochemistry as C- or (S)-. The subject chemical entities, pharmaceutical compositions, and methods are intended to encompass all such possible stereoisomers, including racemic mixtures, optically pure forms, mixtures of diastereomers, and intermediate mixtures. Optically active C- and (S)-isomers can be prepared using chiral synthons or chiral reagents or resolved using conventional techniques. The optical activity of a compound can be analyzed by any suitable method, including, but not limited to, chiral chromatography and polarimetry, to determine the degree of predominance of one stereoisomer over another.

[0284] The compounds or salts of formulas (I), (II), (III), and (IV) herein may exist as diastereomers, enantiomers, or other stereoisomeric forms. The compounds presented herein include all diastereomeric, enantiomeric, and epimeric forms, as well as racemates, mixtures of diastereomers, and other mixtures thereof, to the extent that those skilled in the art can accomplish through routine experimentation. Separation of stereoisomers may be carried out by chromatography, or by forming diastereomers and separating them by recrystallization or chromatography, or any combination thereof ("Enantiomers, Racemates, and Resolutions" by Jean Jacques, Andre Collet, and Samuel H. Wilen, John Wiley and Sons, Inc., 1981, incorporated herein by reference in this disclosure). Stereoisomers may also be obtained by stereoselective synthesis. Furthermore, mixtures of two enantiomers enriched in one of the two can be purified to provide more optically enriched forms of the major enantiomer by recrystallization and / or trituration.

[0285] In certain embodiments, the compounds or salts of Formulas (I), (II), (III), and (IV) may contain two or more enantiomers or diastereomers of the compound, wherein one enantiomer or diastereomer accounts for at least about 70%, at least about 80%, at least about 90%, at least about 98%, 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, e.g., an enantiomer, substantially free of stereoisomers may be obtained by resolving a racemic mixture using methods such as the formation of diastereomers with an optically active resolving agent (E.L. Eliel, Stereochemistry of Carbon Compounds, (1962), 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 agents, separation of the diastereomers, and conversion to pure stereoisomers, and (3) separation of substantially pure or enriched stereoisomers directly under chiral conditions. Another approach for enantiomer separation is elution with an organic mobile phase using a Diacel chiral column, such as that offered as a fee-based service by Chiral Technologies (www.chiraltech.com).

[0286] "Tautomer" refers to a molecule capable of proton transfer from one atom of the molecule to another atom of the same molecule. In certain embodiments, compounds or salts of formulas (I), (II), (III), and (IV) exist as tautomers. In situations where tautomerization is possible, a chemical equilibrium of tautomers may exist. The exact ratio of tautomers depends on various factors, including physical conditions, temperature, solvent, and pH. Some non-limiting examples of tautomeric equilibrium include:

[0287] [ka] Examples include:

[0288] In some embodiments, the compounds disclosed herein are used in various enriched isotopic forms, e.g., 2 H, 3 H, 11 C. 13 C, and / or 14 In a particular embodiment, the compound is deuterated at at least one position. Such deuterated forms can be prepared by the procedures 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 increase the duration of action of a drug by improving metabolic stability or efficacy.

[0289] In certain embodiments, the compounds disclosed herein are 2 exchanged with H atoms 1 Some or all of the H atoms are present. Methods for synthesizing deuterium-containing compounds are known in the art, and non-limiting examples include the following synthesis methods:

[0290] Deuterium-substituted compounds are synthesized using a variety of methods, including 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, p. 110; 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.

[0291] Deuterated starting materials are readily available and amenable to the synthetic methods described herein to effect the synthesis of deuterated compounds. Many deuterated reagents and building blocks are commercially available from chemical suppliers such as Aldrich Chemical Co.

[0292] Unless otherwise specified, the compounds described herein are intended to include compounds that differ only in the presence of one or more isotopically enriched atoms. For example, the replacement of a hydrogen by deuterium or tritium, or 13 C or 14 Compounds having this structure, except for the replacement of a carbon with a C-rich carbon, are within the scope of this disclosure.

[0293] The compounds of the present disclosure may optionally contain unnatural proportions of atomic isotopes at one or more of the atoms that constitute such compounds. For example, the compounds may contain unnatural proportions of atomic isotopes, such as deuterium ( 2 H), tritium ( 3 H), iodine-125( 125 I), or carbon-14 (14 It may be labeled with an isotope such as 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 All isotopic substitutions at 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.

[0294] The present disclosure includes salts of compounds of formulas (I), (II), (III), and (IV), particularly pharmaceutically acceptable salts. Compounds of the present disclosure may have functional groups that are sufficiently acidic, sufficiently basic, or both, and can react with some inorganic bases, as well as inorganic and organic acids, to form salts. Alternatively, inherently charged compounds, such as those with tetravalent nitrogen, can form salts with a suitable counterion, for example, a halide, such as bromide, chloride, or fluoride, especially bromide.

[0295] The methods and compositions of Formulas (I), (II), (III), and (IV) encompass 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. Similarly, in some embodiments, active metabolites of these compounds having the same type of activity are included within the scope of the present disclosure. In addition, the compounds described herein can exist in unsolvated forms as well as solvated forms with pharmaceutically acceptable solvents, such as water and ethanol. Solvated forms of the compounds provided herein are also considered to be disclosed herein.

[0296] Compounds of Formulas (I), (II), (III), and (IV) also include crystalline and amorphous forms of these compounds, pharmaceutically acceptable salts and active metabolites of these compounds having the same type of activity, including, for example, polymorphs, pseudopolymorphs, solvates, hydrates, nonsolvated polymorphs (including anhydrates), conformational polymorphs, and amorphous forms of the compounds, as well as mixtures thereof.

[0297] The present disclosure includes salts of the compounds represented by formulas (I), (II), (III), and (IV), particularly pharmaceutically acceptable salts. Compounds of the present invention having functional groups that are sufficiently acidic, sufficiently basic, or both, can react with any of several inorganic bases, as well as inorganic and organic acids, to form salts. Alternatively, inherently charged compounds, such as those with tetravalent nitrogen, can form salts with a suitable counterion, for example, a halide, such as bromide, chloride, or fluoride, especially bromide.

[0298] In certain embodiments, the compounds or salts of formulas (I), (II), (III), and (IV) may be prodrugs, in which a hydroxyl in the parent compound is presented as an ester or carbonate, or a carboxylic acid in the parent compound is presented as an ester. The term "prodrug" is intended to encompass compounds that are converted to the pharmaceuticals of the present disclosure under physiological conditions. One method for making a prodrug is to include one or more selected moieties that are hydrolyzed under physiological conditions to reveal 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 the host animal. For example, esters or carbonates (e.g., esters or carbonates of alcohols or carboxylic acids, and esters of phosphonic acids) are preferred prodrugs of the present disclosure.

[0299] Prodrugs are often useful because they may be easier to administer than the parent drug in some situations. They may be bioavailable, for example, by oral administration, whereas the parent drug is not. Prodrugs can help enhance the cell permeability of compounds compared 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 to improve drug transport to site-specific tissues or to be used as modifiers to increase drug abundance inside cells.

[0300] In certain embodiments, the prodrug can be converted to the parent compound under intracellular conditions, for example, enzymatically or chemically. In certain embodiments, the parent compound includes an acidic moiety, such as that produced by hydrolysis of the prodrug, that can become charged under intracellular conditions. In certain embodiments, the prodrug is converted to the parent compound upon crossing the cell membrane and reaching the cell. In certain embodiments, the parent compound has reduced cell membrane permeability characteristics compared to the prodrug, for example, increased lipophilicity and decreased hydrophilicity.

[0301] In some embodiments, the design of the prodrug increases the lipophilicity of the pharmaceutical agent. In some embodiments, the design of the prodrug improves 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, Vol. 14 of the ACS Symposium, all of which are incorporated herein by reference). Series; Bioreversible Carriers in Drug Design by Edward B. Roche, American Pharmaceutical Association and Pergam on Press, 1987). According to another embodiment, the present disclosure provides a method for producing the compounds defined above. The compounds may be synthesized using conventional techniques. Advantageously, these compounds are conveniently synthesized from readily available starting materials.

[0302] Synthetic chemical transformations and methods useful for synthesizing the compounds described herein are known in the art and include, for example, those described in Comprehensive Organic Transformations by R. Larock (1989); Protective Groups in Organic Synthesis, 2d. Ed. by T.W. Greene and P.G.M. Buts (1991); Fieser and Fieser's Reagents for Organic Synthesis by L. Fieser and M. Fieser (1994); and Encyclopedia of Reagents for Organic Synthesis, edited by L. Paquette (1995).

[0303] Pharmaceutical preparations In another aspect, the disclosure provides a pharmaceutical composition comprising a compound or salt of Formula (I), (II), (III), or (IV) and a pharmaceutically acceptable excipient.

[0304] Pharmaceutical compositions can be formulated using one or more physiologically acceptable carriers, including excipients and auxiliary agents.The formulation can be modified according to the selected route of administration.Pharmaceutical compositions containing compounds, salts, or conjugates can be prepared, for example, by lyophilizing the compounds, salts, or conjugates, and then mixing, dissolving, emulsifying, encapsulating, or trapping the conjugates.Pharmaceutical compositions can also contain compounds, salts, or conjugates in free base form or in pharmaceutically acceptable salt form.

[0305] Methods for formulating conjugates can include formulating either the compound, salt, or conjugate with one or more inert and pharmaceutically acceptable excipients or carriers to form solid, semi-solid, or liquid compositions.Solid compositions can include, for example, powders, tablets, dispersible granules, and capsules, and in some embodiments, the solid compositions further contain non-toxic auxiliary substances, such as wetting or emulsifying agents, pH buffering agents, and other pharmaceutically acceptable additives.Alternatively, the compound, salt, or conjugate can be lyophilized or in powder form for reconstitution with a suitable vehicle, such as pyrogen-free distilled water, before use.

[0306] The pharmaceutical composition can include at least one active ingredient (e.g., a compound, salt, or conjugate). The active ingredient can be entrapped in microcapsules (e.g., hydroxymethylcellulose or gelatin microcapsules, and poly-(methyl methacrylate) microcapsules, respectively) prepared by coacervation techniques or interfacial polymerization, in colloidal drug delivery systems (e.g., liposomes, albumin microspheres, microemulsions, nanoparticles, and nanocapsules), or in macroemulsions.

[0307] Pharmaceutical compositions can often further comprise more than one active compound (e.g., compounds, salts, or conjugates, and other agents) as needed for the particular indication being treated. The active compounds may have complementary activities that do not adversely affect each other. For example, the composition can also include a chemotherapeutic agent, a cytotoxic agent, a cytokine, a growth inhibitory agent, an antihormonal agent, an antiangiogenic agent, and / or a cardioprotectant. Such molecules can be present in combination in amounts effective for the intended purpose.

[0308] The compositions and formulations can be sterilized. Sterilization can be accomplished, for example, by filtration by sterile filtration.

[0309] The composition can be formulated for administration as injection.Non-limiting examples of injection preparations can include sterile suspensions, solutions, or emulsions in oily or aqueous vehicles.Suitable oily vehicles can include, but are not limited to, lipophilic solvents or vehicles, such as fatty oils or synthetic fatty acid esters, or liposomes.Aqueous injection suspensions can contain substances that increase the viscosity of the suspension.Suspensions can also contain suitable stabilizers.Injections can be formulated for bolus injection or continuous infusion.Alternatively, the composition can be lyophilized or in powder form, to be reconstituted with a suitable vehicle, such as pyrogen-free distilled water, before use.

[0310] For parenteral administration, the compound, salt, or conjugate can be combined with a pharmaceutically acceptable parenteral vehicle and formulated into a unit-dose injectable form (e.g., solution, suspension, or emulsion). Such vehicles can be essentially non-toxic and non-therapeutic. Vehicles can be water, saline, Ringer's solution, dextrose solution, and 5% human serum albumin. Non-aqueous vehicles such as fixed oils and ethyl oleate can also be used. Liposomes can be used as carriers. Vehicles can contain small amounts of additives, such as substances that improve isotonicity and chemical stability (e.g., buffers or preservatives).

[0311] Sustained-release preparations can also be prepared.The example of sustained-release preparations can include the semipermeable matrix of solid hydrophobic polymer that can contain compound, salt or conjugate, and these matrices can be in the form of shaped articles (for example, film or microcapsule).The example of sustained-release matrix can include polyester, hydrogel (for example, poly(2-hydroxyethyl-methacrylate) or poly(vinyl alcohol)), polylactic acid, copolymer of L-glutamic acid and gamma ethyl-L-glutamate, non-degradable ethylene-vinyl acetate, degradable lactic acid-glycolic acid copolymer such as LUPRON DEPO (i.e., injectable microspheres composed of lactic acid-glycolic acid copolymer and leuprolide acetate), and poly-D-(-)-3-hydroxybutyric acid.

[0312] Pharmaceutical formulations can be prepared for storage by mixing the compound, salt, or conjugate with pharmaceutically acceptable carriers, excipients, and / or stabilizers. The formulation can be a lyophilized formulation or an aqueous solution. Acceptable carriers, excipients, and / or stabilizers can be nontoxic to recipients at the dosages and concentrations used. Acceptable carriers, excipients, and / or stabilizers can include buffers such as phosphate, citrate, and other organic acids; antioxidants including ascorbic acid and methionine; preservatives; polypeptides; proteins such as serum albumin and gelatin; hydrophilic polymers; amino acids; monosaccharides, disaccharides, and other carbohydrates, including glucose, mannose, or dextrin; chelating agents such as EDTA; sugars such as sucrose, mannitol, trehalose, or sorbitol; salt-forming counterions such as sodium; metal complexes; and / or nonionic surfactants or polyethylene glycol.

[0313] The compounds or salts of any one of Formulas (I), (II), (III), and (IV) may be formulated in any suitable pharmaceutical formulation. The pharmaceutical formulations of the present disclosure typically contain an active ingredient (e.g., a compound or salt of any one of Formulas (I), (II), (III), and (IV)) and one or more pharmaceutically acceptable excipients, including, but not limited to, inert solid excipients and fillers, diluents, sterile aqueous solutions and various organic solvents, penetration enhancers, antioxidants, solubilizers, and adjuvants.

[0314] In certain embodiments, the compound or salt of Formula (I), (II), (III), or (IV) is formulated with a chelating agent or other substance capable of binding metal ions, such as ethylenediaminetetraacetic acid (EDTA), which salt can enhance the stability of the compound or salt of Formula (I), (II), (III), or (IV).

[0315] Pharmaceutical formulations may be provided in any suitable form, which may depend on the route of administration. In some embodiments, the pharmaceutical compositions disclosed herein can be formulated into dosage forms for administration to a subject. In some embodiments, the pharmaceutical compositions are formulated for oral, intravenous, intraarterial, aerosol, parenteral, buccal, topical, transdermal, rectal, intramuscular, subcutaneous, intraosseous, intranasal, intrapulmonary, oral mucosal, inhalation, and / or intraperitoneal administration. In some embodiments, the dosage form is formulated for oral administration. For example, the pharmaceutical composition can be formulated in the form of a pill, tablet, capsule, inhaler, suspension, emulsion, gel, or powder. In some embodiments, the pharmaceutical composition can be formulated as a unit dose in the form of a liquid, gel, semi-liquid, semi-solid, or solid.

[0316] The amount of the compound or salt of Formula (I), (II), (III), and (IV) will depend on the mammal being treated, the severity of the disorder or disease, the rate of administ...

Claims

1. Equation (I): 【Chemistry 1】 A compound of or a pharmaceutically acceptable salt thereof, wherein the formula is R ２ , １１ , １１ , ２ , ２ is selected from fluoro, chloro, bromo, hydroxyl, -C １－６ alkyl, -C １－６ haloalkyl, -O-C １－６ alkyl, -O-C １－６ haloalkyl, -OR １２ , -SR １１ , -N(R １３ ), -C(O)R ２ , -C(O)OR １１ , -OC(O)R[[ID=2l]] １１ , -OC(O)N(R １１ ), -C(O)N(R １１ ), -N(R ２ ), -C(O)N(R １１ ), -N(R ２ [[ID=z2]], -N(R １１ [[ID=zq]], -N(R １１ , -N(R １１ , -N(R １１ , -N(R １１ ), -N(R １１ ), -N(R ２ ), -N(R １１ ), -S(O) ２ (R １１ ), -S(O) ２ R １１ , -S(O) ２ N(R １１ [[ID=6o]]), -NO ２ , -NO ２ , -N ３ , and -CN, R １ However, hydroxyl, -O-C １ Alkyl, or -NO ２ When R ２ teeth, Fluoro, bromo, iodine, -OR ２２ , SR ２１ , -N(R ２１ ) ２ , -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 ) SO ２ N(R) ２１ ), -N(R ２１ )P(O)(OR ２１ ) R ２１ , -S(O) ２ R ２１ , -S(O) ２ N(R) ２１ ) ２ , -NO ２ , and -CN, R ３０ C is optionally substituted with one or more substituents independently selected from １－６ Alkyl, and All are R ３０ C is optionally substituted with one or more substituents independently selected from ３－６ Selected from carbon rings and 3- to 6-membered heterocycles, R １ When R is fluoro, ２ teeth, ブロモ、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) ２ R ２３ 、-N(R ２３ )SO ２ N(R ２３ ) ２ 、-N(R ２３ )P(O)(OR ２３ )R ２３ 、-S(O) ２ R ２３ 、-S(O) ２ N(R ２３ ) ２ 、-NO ２ 、および-CN、 R ３０ C is optionally substituted with one or more substituents independently selected from １－６ Alkyl, and All are R ３０ C is optionally substituted with one or more substituents independently selected from ３－６ Carbon rings, 3-4 membered heterocycles, 【Chemistry 2】 Selected from, R １ C １ Alkyl, -O-C １ When R is a haloalkyl, hydroxy, chloro, or bromo, ２ teeth, ヨード、-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 )SO ２ N(R ２４ ) ２ 、-N(R ２４ )P(O)(OR ２４ )R ２４ 、-S(O)R ２４ 、-S(O) ２ R ２４ 、-S(O) ２ N(R ２４ ) ２ 、-NO ２ 、および-CN、 R ３０ C is optionally substituted with one or more substituents independently selected from ２－６ Alkyl, and All are R ３０ C is optionally substituted with one or more substituents independently selected from ３－６ Selected from carbon rings and 3- to 5-membered heterocycles, R １ is bromo, hydroxy, and C １ When selected from alkyl groups, R ２ Further selected from Fluor R １ However, C ２－６ Alkyl, C １－６ Haloalkyl, -O-C ２－６ Alkyl, -O-C 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) ２ R １１ , -S(O) ２ N(R) １１ ) ２ , -N ３ , or when it is -CN, R ２ teeth, ハロゲン、-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 )SO ２ N(R ２６ ) ２ 、-N(R ２６ )P(O)(OR ２６ )R ２６ 、-S(O)R ２６ 、-S(O) ２ R ２６ 、-S(O) ２ N(R ２６ ) ２ 、-NO ２ 、および-CN、 R ３０ C is optionally substituted with one or more substituents independently selected from １－６ Alkyl, and All are R ３０ C is optionally substituted with one or more substituents independently selected from ３－６ Selected from carbon rings and 3- to 6-membered heterocycles, However, R １ ga-C(O)OR １１ When R ２ Assuming that it cannot be a substituted six-member complex ring, R ３ and R ４ Each of them is independent, and each time it appears, 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 , -NO ２ , and -CN, 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 , -NO ２ , and C which is optionally substituted with one or more substituents independently selected from -CN. １－４ Alkyl, and Both are 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 , -NO ２ , and C which is optionally substituted with one or more substituents independently selected from -CN. ３－４ Selected from carbon rings and 3-4 membered heterocycles, R ５ and R ５’ These are independently selected from hydrogen and hydroxyl, or R ５ and R ５’ They are one and equal to O, R ６ and R ６’ These are independently selected from hydrogen and hydroxyl, or R ６ and R ６’ These are combined as =O, =N-OR ２６ , or = NR ２６ And, m is selected from 0, 1, 2, and 3. n is selected from 0, 1, 2, and 3. R １１ and R １４ Each of them is independent, and each time it appears, hydrogen, R ３１ C is optionally substituted with one or more substituents independently selected from １－６ Alkyl, and All are R ３１ C is optionally substituted with one or more substituents independently selected from ３－６ Selected from carbon rings and 3- to 6-membered heterocycles, R １２ Each time it appears, R ３２ C substituted with one or more substituents independently selected from １－６ Alkyl, and All are R ３３ C is optionally substituted with one or more substituents independently selected from ３－６ Selected from carbon rings and 3- to 6-membered heterocycles, R １３ Each time it appears, hydrogen, R ３４ C is optionally substituted with one or more substituents independently selected from １－６ Alkyl, and All are R ３４ C is optionally substituted with one or more substituents independently selected from ３－５ Selected from carbon rings and 3- to 6-membered heterocycles, R ２１ , R ２３ , R ２４ , and R ２６ Each of them is independent, and each time it appears, hydrogen, R ３４ C is optionally substituted with one or more substituents independently selected from １－６ Alkyl, and All are C １－４ Alkyl, C １－４ Haloalkyl and R ３４ C is optionally substituted with one or more substituents independently selected from ３－６ Selected from carbon rings and 3- to 6-membered heterocycles, R ２２ and R ２５ Each of them is independent, and each time it appears, C ２－６ Alkyl, C ２－６ Haloalkyl, C ２－６ Selected from hydroxyalkyl groups, R ３０ , R ３１ , R ３３ , and R ３４ Each of them is independent, and each time it appears, 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 ) SO ２ N(R) ４１ ) ２ , -N(R ４１ )P(O)(OR ４１ ) R ４１ , -S(O)R ４１ , -S(O) ２ R ４１ , -S(O) ２ N(R) ４１ ) ２ , -NO ２ , = S, -CN, C ３－６ Selected from carbon rings and 3- to 7-membered heterocycles, R ３２ Each time it appears, -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 )SO ２ N(R ４１ ) ２ 、-N(R ４１ )P(O)(OR ４１ )R ４１ 、-S(O)R ４１ 、-S(O) ２ R ４１ 、-S(O) ２ N(R ４１ ) ２ 、-NO ２ 、=O、=S, and -CN, selected from R ４１ Each of them is independent, and each time it appears, hydrogen, C １－６ Alkyl, C １－６ Haloalkyl and C １－６ Selected from hydroxyalkyl groups, A compound or a pharmaceutically acceptable salt thereof.

2. R １ However, fluoro, chloro, bromo, hydroxyl, -C １－６ Alkyl, -C １－６ Haloalkyl, -O-C １－６ Alkyl, -O-C 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) ２ R １１ , -S(O) ２ N(R) １１ ) ２ , -NO ２ , -N ３ A compound according to claim 1, selected from , and -CN, or a pharmaceutically acceptable salt thereof.

3. R １ However, fluoro, -C １－６ Haloalkyl, -O-C 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) ２ R １１ , -NO ２ , -N ３ A compound according to claim 2, selected from , and -CN, or a pharmaceutically acceptable salt thereof.

4. R １ However, hydroxyl, -O-C １ Alkyl, or -NO ２ And R ２ However, fluoro, bromo, 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 ) SO ２ N(R) ２１ ) ２ , -N(R ２１ )P(O)(OR ２１ ) R ２１ , -S(O) ２ R ２１ , -S(O) ２ N(R) ２１ ) ２ , -NO ２ , -CN, and optionally substituted C １－６ A compound according to claim 1, selected from alkyl groups, or a pharmaceutically acceptable salt thereof.

5. R １ NO ２ The compound according to claim 1 or a pharmaceutically acceptable salt thereof.

6. R ２ However, fluoro, bromo, -N(R ２１ ) ２ , -N(R ２１ ) C(O)R ２１ , -N(R ２１ ) C(O)OR ２１ , -NO ２ , -CN, and optionally substituted C １－６ A compound according to claim 1, selected from alkyl groups, or a pharmaceutically acceptable salt thereof.

7. R １ is fluoro, R ２ However, Bromo, 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) ２ R ２３ , -N(R ２３ ) SO ２ N(R) ２３ ) ２ , -N(R ２３ )P(O)(OR ２３ ) R ２３ , -S(O) ２ R ２３ , -S(O) ２ N(R) ２３ ) ２ , -NO ２ ,-CN, 【Transformation 3】 and C which is optionally replaced １－６ A compound according to claim 1, selected from alkyl groups, or a pharmaceutically acceptable salt thereof.

8. R ２ However, Bromo, OR ２３ , -N(H)R ２３ , -N(R ２３ ) C(O)R ２３ , -N(R ２３ ) C(O)OR ２３ , -NO ２ ,-CN, 【Chemistry 4】 and C which is optionally replaced １－６ A compound according to claim 7, selected from alkyl groups, or a pharmaceutically acceptable salt thereof.

9. R １ However, C １ Alkyl, -O-C １ It is a haloalkyl, hydroxyl, chloro, or bromo, R ２ However, 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 ) SO ２ N(R) ２４ ) ２ , -N(R ２４ )P(O)(OR ２４ ) R ２４ , -S(O)R ２４ , -S(O) ２ R ２４ , -S(O) ２ N(R) ２４ ) ２ , -NO ２ , -CN, and optionally substituted C ２－６ A compound according to claim 1, selected from alkyl groups, or a pharmaceutically acceptable salt thereof.

10. R １ However, -O-C １ It is a haloalkyl, chloro, or bromo, R ２ However, -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 , -NO ２ , -CN, and optionally substituted C ２－６ A compound according to claim 1, selected from alkyl groups, or a pharmaceutically acceptable salt thereof.

11. R １ However, C ２－６ Alkyl, C １－６ Haloalkyl, -O-C ２－６ Alkyl, -O-C 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) ２ R １１ , -S(O) ２ N(R) １１ ) ２ , -N ３ Selected from , and -CN, R ２ However, 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 ) SO ２ N(R) ２６ ) ２ , -N(R ２６ )P(O)(OR ２６ ) R ２６ , -S(O)R ２６ , -S(O) ２ R ２６ , -S(O) ２ N(R) ２６ ) ２ , -NO ２ , -CN, and optionally substituted C １－６ A compound according to claim 1, selected from alkyl groups, or a pharmaceutically acceptable salt thereof.

12. R １ However, C ２－６ Alkyl, C １－６ Haloalkyl, -O-C ２－６ Alkyl, -O-C 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) ２ R １１ , -S(O) ２ N(R) １１ ) ２ , -N ３ A compound according to claim 1, selected from , and -CN, or a pharmaceutically acceptable salt thereof.

13. R １ However, -N(R １３ ) ２ , -C(O)N(R １１ ) ２ , -N(R １１ ) C(O)R １１ , -S(O) ２ R １１ , -N ３ A compound according to claim 1, selected from , and -CN, or a pharmaceutically acceptable salt thereof.

14. R １ The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein is -CN.

15. R ２ However, 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) ２ R ２６ , -S(O) ２ N(R) ２６ ) ２ , -NO ２ , -CN, and optionally substituted C １－６ A compound according to claim 1, selected from alkyl groups, or a pharmaceutically acceptable salt thereof.

16. R ３ and R ４ However, each appears independently, with halogen, -OR １４ , -N(R １４ ) ２ , -N(R １４ ) C(O)R １４ , -C(O)OR １４ , -C(O)N(R １４ ) ２ , -NO ２ , and -CN, as well as C, which is optionally substituted. １－４ A compound according to any one of claims 1 to 15, selected from alkyl groups, or a pharmaceutically acceptable salt thereof.

17. R ５ and R ５’ A compound according to any one of claims 1 to 15 or a pharmaceutically acceptable salt thereof, wherein the compound and its constituent atoms together equal O.

18. R ６ and R ６’ A compound according to any one of claims 1 to 15 or a pharmaceutically acceptable salt thereof, wherein the compound and its constituent atoms together equal O.

19. R ６ and R ６’ However, as a whole = N - OR ２６ A compound according to any one of claims 1 to 15 or a pharmaceutically acceptable salt thereof.

20. A compound according to any one of claims 1 to 15 or a pharmaceutically acceptable salt thereof, wherein m is 0 or 1 and n is 0 or 1.

21. R １１ and R １４ However, each instance appears independently, with hydrogen and optionally substituted C. １－６ Selected from alkyl groups, R １２ Each instance of C is independently and selectively substituted. １－６ Selected from alkyl groups, R １３ Each instance independently includes hydrogen and optionally substituted C. １－６ A compound according to any one of claims 1 to 15, selected from alkyl groups, or a pharmaceutically acceptable salt thereof.

22. R ２１ , R ２３ , R ２４ , and R ２６ However, each instance appears independently, with hydrogen and optionally substituted C. １－６ A compound according to any one of claims 1 to 15, selected from alkyl groups and optionally substituted 3- to 6-membered heterocycles, or a pharmaceutically acceptable salt thereof.

23. R ２２ and R ２５ However, each independently, each time it appears, C ３－６ Alkyl and C ３－６ A compound according to any one of claims 1 to 15, selected from haloalkyls, or a pharmaceutically acceptable salt thereof.

24. R ３０ , R ３１ , R ３３ , and R ３４ However, each appears independently, with 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 ) SO ２ N(R) ４１ ) ２ , -N(R ４１ )P(O)(OR ４１ ) R ４１ , -S(O)R ４１ , -S(O) ２ R ４１ A compound according to any one of claims 1 to 15, selected from , and -CN, or a pharmaceutically acceptable salt thereof.

25. R ３０ , R ３１ , R ３３ , and R ３４ However, each appears independently, with halogen and -N(R) ４１ ) ２ , -N(R ４１ ) S(O) ２ (R ４１ ), -N(R ４１ ) SO ２ N(R) ４１ ) ２ , -N(R ４１ )P(O)(OR ４１ ) R ４１ , and -S(O) ２ A compound according to claim 24 or a pharmaceutically acceptable salt thereof, selected from R 41.

26. R ３２ Each of these appears independently, with halogen, -N(R) ４１ ) ２ , -N(R ４１ ) S(O) ２ (R ４１ ), -N(R ４１ ) SO ２ N(R) ４１ ) ２ , -N(R ４１ )P(O)(OR ４１ ) R ４１ , -S(O) ２ R ４１ A compound according to any one of claims 1 to 15, selected from , and =O, or a pharmaceutically acceptable salt thereof.

27. R ４１ Independently, each instance of hydrogen and C １－６ A compound according to any one of claims 1 to 15, selected from alkyl groups, or a pharmaceutically acceptable salt thereof.

28. The compound of formula (I) or a pharmaceutically acceptable salt thereof 【Transformation 5】 【Transformation 6】 【Transformation 7】 【Transformation 8】 【Chemistry 9】 【Chemistry 10】 The compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from among pharmaceutically acceptable salts thereof.

29. The compound of formula (I) or a pharmaceutically acceptable salt thereof 【Chemistry 11】 The compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from among pharmaceutically acceptable salts thereof.

30. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound according to any one of claims 1 to 15 or 28 to 29 or a pharmaceutically acceptable salt thereof.

31. Use of a compound according to any one of claims 1 to 15 or 28 to 29 or a pharmaceutically acceptable salt thereof in the manufacture of an agent for modulating indoleamine 2,3-dioxygenase 2 (IDO2) in subjects requiring regulation of IDO2.

32. The pharmaceutical composition according to claim 30, for use in the manufacture of a drug for regulating indoleamine 2,3-dioxygenase 2 (IDO2) in subjects requiring regulation of IDO2.

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