Quinolinone, benzoxazinone, and quinoline compounds and uses thereof

Abstract

Provided herein are quinolinone, benzoxazinone, and quinoline compounds for modulating muscle myosin to treat obesity and related disorders such as cardiovascular diseases, type 2 diabetes, obstructive sleep apnea, cancer, and osteoarthritis

Description

QUINOLINONE, BENZOXAZINONE, AND QUINOLINE COMPOUNDS AND USES THEREOFCROSS-REFERENCE

[0001] This application claims the benefit of U.S. Provisional Application No. 63 / 570,078 filed March 26, 2024, and U.S. Provisional Application No. 63 / 702,567 filed October 2, 2024, which is hereby incorporated by reference in its entirety herein.BACKGROUND OF THE INVENTION

[0002] Obesity is a medical condition involving excess body fat accumulated to such an extent that it can potentially have negative effects on health. Obesity is a major cause of disability and is correlated with various diseases and conditions, particularly cardiovascular diseases, type 2 diabetes, obstructive sleep apnea, certain types of cancer, and osteoarthritis. Obesity is a leading preventable cause of death worldwide, with increasing rates in adults and children. In 2022, over 1 billion people were obese worldwide. Excess body fat underlies 64% of cases of diabetes in men and 77% of cases in women.SUMMARY OF THE INVENTION

[0003] In an aspect, the present disclosure provides a compound represented by Formula (I):(I); or a salt thereof, wherein: X1, X2, X3and X4are independently selected from C(R0) and N; Y is selected from C(R6)(R6a) and O; each R0is independently selected from: hydrogen, halogen, -NO2, -CN, -N3, -OR8, -SR8, -N(R8)2, -C(O)R8, -C(O)N(R8)2, -N(R8)C(O)R8, -N(R8)C(O)N(R8)2, -OC(O)N(R8)2, -N(R8)C(O)OR8, -C(O)OR8, -OC(O)R8, -S(O)R8, and -S(O)2R8; and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR8, -SR8, -N(R8)2, -C(O)R8, -C(O)N(R8)2, -N(R8)C(O)R8;-C(O)OR8, -OC(O)R8, -N(R8)C(O)N(R8)2, -OC(O)N(R8)2, -N(R8)C(O)OR8, -S(O)R8, -S(O)2R8, -NO2, =O, =S, =N(R8), -CN, C3-10carbocycle and 3- to 10-membered heterocycle, wherein the C3-10carbocycle and 3- to 10- membered heterocycle are each optionally substituted with one or more R7; and C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or moresubstituents independently selected from halogen, -OR8, -SR8, -N(R8)2, -C(O)R8, -C(O)N(R8)2, - N(R8)C(O)R8, -N(R8)C(O)N(R8)2, -OC(O)N(R8)2, -N(R8)C(O)OR8, -C(O)OR8, -OC(O)R8, - S(O)R8, -S(O)2R8, -NO2, =O-, =S, =N(R8), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R7; R1is selected from: C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR8a, -SR8a, - N(R8a)2, -C(O)R8a, -C(O)N(R8a)2, -N(R8a)C(O)R8a, -C(O)OR8a, -OC(O)R8a, -N(R8a)C(O)N(R8a)2, - OC(O)N(R8a)2, -N(R8a)C(O)OR8a, -S(O)R8a, -S(O)2R8a, -NO2, =O, =S, =N(R8a), -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10- membered heterocycle, are each optionally substituted with one or more R7a;R2is selected from: C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR8b, -SR8b, - N(R8b)2, -C(O)R8b, -C(O)N(R8b)2, -N(R8b)C(O)R8b-C(O)OR8b, -OC(O)R8b, -N(R8b)C(O)N(R8b)2, -OC(O)N(R8b)2, -N(R8b)C(O)OR8b, -S(O)R8b, -S(O)2R8b, -NO2, =O, =S, =N(R8b), -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10- membered heterocycle, are each optionally substituted with one or more R7b; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR8b, -SR8b, -N(R8b)2, -C(O)R8b, - C(O)N(R8b)2, -N(R8b)C(O)R8b-N(R8b)C(O)N(R8b)2, -OC(O)N(R8b)2, -N(R8b)C(O)OR8b, -C(O)OR8b, -OC(O)R8b, -S(O)R8b, -S(O)2R8b, -NO2, =O-, =S, =N(R8b), -CN, - N3, C3-10carbocycle, and 3- to 10-membered heterocycle, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein the C3-10carbocycle, 3- to 10-membered heterocycle, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R7b; or R1together with R2form a C3-10cycloalkyl, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR8b, -SR8b, - N(R8b)2, -C(O)R8b, -C(O)N(R8b)2, -N(R8b)C(O)R8b-N(R8b)C(O)N(R8b)2, -OC(O)N(R8b)2, - N(R8b)C(O)OR8b, -C(O)OR8b, -OC(O)R8b, -S(O)R8b, -S(O)2R8b, -NO2, =O-, =S, =N(R8b), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R7b;R3is selected from: hydrogen and C1-6alkyl optionally substituted with one or more one or more R7C; and R2together with R3form a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR8c, -SR8c, -N(R8c)2, -C(O)R8c, -C(O)N(R8c)2, -N(R8c)C(O)R8c, - N(R8c)C(O)N(R8c)2, -OC(O)N(R8c)2, -N(R8c)C(O)OR8c, -C(O)OR8c, -OC(O)R8c, -S(O)R8c, -S(O)2R8c, -NO2, =O- =S, =N(R8c), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R7c; R4is independently selected from: hydrogen, halogen, -OR8d, -SR8d, -N(R8d)2, -NO2, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR8d, -SR8d, -N(R8d)2, -NO2, and -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with one or more R7d; R4ais independently selected from: hydrogen, halogen, -OR8e, -SR8e, - N(R8e)2, -NO2, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR8e, -SR8e, -N(R8e)2, -NO2, and -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with one or more R7e; and R4together with R4aform a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR8e, -SR8e, - N(R8e)2, -C(O)R8e, -C(O)N(R8e)2, -N(R8e)C(O)R8e, -N(R8e)C(O)N(R8e)2, -OC(O)N(R8e)2, - N(R8e)C(O)OR8e, -C(O)OR8e, -OC(O)R8e, -S(O)R8e, -S(O)2R8e, -NO2, =O-, =S, =N(R8e), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R7e; each R5and R5ais selected independently from: hydrogen, halogen, -OR8f, -SR8f, -N(R8f)2, -NO2, -CN, C1-6alkyl, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C1-6alkyl, C3-10carbocycle, and 3- to 10- membered heterocycle are each optionally substituted with one or more R7f; or R5together with R5aform a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR8f, -SR8f, - N(R8f)2, -C(O)R8f, -C(O)N(R8f)2, -N(R8f)C(O)R8f, -N(R8f)C(O)N(R8f)2, -OC(O)N(R8f)2, - N(R8f)C(O)OR8f, -C(O)OR8f, -OC(O)R8f, -S(O)R8f, -S(O)2R8f, -NO2, =O-, =S, =N(R8f), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R7f; each R6and R6ais selected independently from: hydrogen, halogen, -OR8g, -SR8g, -N(R8g)2, -NO2, -CN, C1-6alkyl, C3-10carbocycle, and 3- to 10- membered heterocycle, wherein the C1-6alkyl, C3-10carbocycle, and 3- to 10- membered heterocycle are each optionally substituted with one or more R7g; or R6together with R5form an -O- bridge, an -NR7g- bridge, a C1-5alkylene bridge, or a 1- to 5-membered heteroalkylene bridge, wherein each of the C1-5alkylene bridge, or 1- to 5-membered heteroalkylene bridge is optionally substituted with one or more substituents independently selected from halogen, -OR8g, -SR8g, -N(R8g)2, -C(O)R8g, -C(O)N(R8g)2, -N(R8g)C(O)R8g-N(R8g)C(O)N(R8g)2, -OC(O)N(R8g)2, -N(R8g)C(O)OR8g, -C(O)OR8g, -OC(O)R8g, -S(O)R8g, -S(O)2R8g, -NO2, =O-, =S, =N(R8g), -CN,C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R7g; each R7, R7a, R7b, R7c, R7d, R7e, R7f, and R7gis independently selected from: hydrogen, halogen, -CN, -OH, -SH, -NO2, -NH2, -O-C1-6alkyl, -S- C1-6alkyl, -N(C1-6alkyl)2, and -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10-membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl; each R8, R8a, R8b, R8c, R8d, R8e, R8f, and R8gis independently selected from: hydrogen, halogen, -CN, - OH, -SH, -NO2, -NH2, -O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, and -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, - CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0004] In an aspect, the present disclosure provides a compound represented by Formula (II): ; or a salt thereof, wherein: X5, X6, X7and X8areindependently selected from C(R10) and N; each R10is independently selected from: hydrogen, halogen, -NO2, -CN, -N3, -OR18, -SR18, -N(R18)2, -C(O)R18, -C(O)N(R18)2, -N(R18)C(O)R18, - N(R18)C(O)N(R18)2, -OC(O)N(R18)2, -N(R18)C(O)OR18, -C(O)OR18, -OC(O)R18, -S(O)R18, and - S(O)2R18; and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR18, -SR18, -N(R18)2, -C(O)R18, -C(O)N(R18)2, -N(R18)C(O)R18, -C(O)OR18, -OC(O)R18, -N(R18)C(O)N(R18)2, -OC(O)N(R18)2, -N(R18)C(O)OR18, -S(O)R18, -S(O)2R18, -NO2, =O, =S, =N(R18), -CN, C3-10carbocycle and 3- to 10-membered heterocycle, wherein the C3-10carbocycle and 3- to 10- membered heterocycle are each optionally substituted with one or more R17; and C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR18, -SR18, -N(R18)2, -C(O)R18, - C(O)N(R18)2, -N(R18)C(O)R18, -N(R18)C(O)N(R18)2, -OC(O)N(R18)2, -N(R18)C(O)OR18, -C(O)OR18, -OC(O)R18, -S(O)R18, -S(O)2R18, -NO2, =O-, =S, =N(R18), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R17; R11is selected from: C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR18a, -SR18a, -N(R18a)2, -C(O)R18a, -C(O)N(R18a)2, - N(R18a)C(O)R18a, -C(O)OR18a, -OC(O)R18a, -N(R18a)C(O)N(R18a)2, -OC(O)N(R18a)2, - N(R18a)C(O)OR18a, -S(O)R18a, -S(O)2R18a, -NO2, =O, =S, =N(R18a), -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with one or more R17a; R12is selected from: C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR18b, -SR18b, -N(R18b)2, -C(O)R18b, -C(O)N(R18b)2, - N(R18b)C(O)R18b-C(O)OR18b, -OC(O)R18b, -N(R18b)C(O)N(R18b)2, -OC(O)N(R18b)2, - N(R18b)C(O)OR18b, -S(O)R18b, -S(O)2R18b, -NO2, =O, =S, =N(R18b), -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with one or more R7b; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR18b, -SR18b, -N(R18b)2, -C(O)R18b, -C(O)N(R18b)2, - N(R18b)C(O)R18b-N(R18b)C(O)N(R18b)2, -OC(O)N(R18b)2, -N(R18b)C(O)OR18b, -C(O)OR18b, - OC(O)R18b, -S(O)R18b, -S(O)2R18b, -NO2, =O-, =S, =N(R18b), -CN, -N3, C3-10carbocycle, and 3- to 10-membered heterocycle, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein the C3-10carbocycle, 3- to 10-membered heterocycle, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R7b; or R11together with R12form a C3-10cycloalkyl, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR18b, -SR18b, -N(R18b)2, -C(O)R18b, - C(O)N(R18b)2, -N(R18b)C(O)R18b-N(R18b)C(O)N(R18b)2, -OC(O)N(R18b)2, -N(R18b)C(O)OR18b, -C(O)OR18b, -OC(O)R18b, -S(O)R18b, -S(O)2R18b, -NO2, =O-, =S, =N(R18b), - CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R17b;R13is selected from: hydrogen and C1-6alkyl optionally substituted with one or more one or more R17C; and R12together with R13form a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR18c, -SR18c, -N(R18c)2, -C(O)R18c, -C(O)N(R18c)2, -N(R18c)C(O)R18c, - N(R18c)C(O)N(R18c)2, -OC(O)N(R18c)2, -N(R18c)C(O)OR18c, -C(O)OR18c, -OC(O)R18c, -S(O)R18c, -S(O)2R18c, -NO2, =O-, =S, =N(R18c), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R17c;R14is independently selected from: hydrogen, halogen, -OR18d, -SR18d, -N(R18d)2, -NO2, and - CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR18d, -SR18d, -N(R18d)2, -NO2, and -CN, C3-10carbocycle, and 3- to 10- membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with one or more R17d; R14ais independently selected from: hydrogen, halogen, -OR18e, -SR18e, -N(R18e)2, -NO2, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR18e, -SR18e, -N(R18e)2, -NO2, and - CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with one or more R17e; and R4together with R4aform a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR18e, -SR18e, -N(R18e)2, -C(O)R18e, -C(O)N(R18e)2, -N(R18e)C(O)R18e, -N(R18e)C(O)N(R18e)2, - OC(O)N(R18e)2, -N(R18e)C(O)OR18e, -C(O)OR18e, -OC(O)R18e, -S(O)R18e, -S(O)2R18e, -NO2, =O- , =S, =N(R18e), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R17e; R15is selected from: hydrogen and C1-6alkyl optionally substituted with one or more one or more R17f; each R17, R17a, R17b, R17C, R17d, R17e, and R17fis independently selected from: hydrogen, halogen, -CN, -OH, - SH, -NO2, -NH2, -O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, and -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10-membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, - OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, - NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl; each R18, R18a, R18b, R18c, R18d, and R18eis independently selected from: hydrogen, halogen, -CN, -OH, -SH, -NO2, -NH2, -O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, and -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, - NH(C1-6alkyl), C3-10carbocycle, 3- to 10-membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0005] In an aspect, the present disclosure provides a compound represented by Formula (III):; or a salt thereof, wherein:X9, X10, X11and X12are independently selected from C(R20) and N wherein at least one of X9, X10, X11and X12is N and no more than two of X9, X10, X11and X12are N; each R20is independently selected from: hydrogen, halogen, -NO2, -CN, -N3, -OR28, -SR28, -N(R28)2, -C(O)R28, -C(O)N(R28)2, -N(R28)C(O)R28, -N(R28)C(O)N(R28)2, -OC(O)N(R28)2, - N(R28)C(O)OR28, -C(O)OR28, -OC(O)R28, -S(O)R28, and -S(O)2R28; and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR28, -SR28, -N(R28)2, -C(O)R28, -C(O)N(R28)2, - N(R28)C(O)R28-C(O)OR28, -OC(O)R28, -N(R28)C(O)N(R28)2, -OC(O)N(R28)2, - N(R28)C(O)OR28, -S(O)R28, -S(O)2R28, -NO2, =O, =S, =N(R28), -CN, C3-10carbocycle and 3- to 10-membered heterocycle, wherein the C3-10carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more R27; and C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR28, -SR28, -N(R28)2, -C(O)R28, -C(O)N(R28)2, -N(R28)C(O)R28, - N(R28)C(O)N(R28)2, -OC(O)N(R28)2, -N(R28)C(O)OR28, -C(O)OR28, -OC(O)R28, -S(O)R28, - S(O)2R28, -NO2, =O-, =S, =N(R28), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R27; R21is selected from: C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR28a, -SR28a, - N(R28a)2, -C(O)R28a, -C(O)N(R28a)2, -N(R28a)C(O)R28a, -C(O)OR28a, -OC(O)R28a, - N(R28a)C(O)N(R28a)2, -OC(O)N(R28a)2, -N(R28a)C(O)OR28a, -S(O)R28a, -S(O)2R28a, -NO2, =O, =S,=N(R28a), -CN, C3-10 carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with one or more R27a;R22is selected from: C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR28b, -SR28b, - N(R28b)2, -C(O)R28b, -C(O)N(R28b)2, -N(R28b)C(O)R28b-C(O)OR28b, -OC(O)R28b, - N(R28b)C(O)N(R28b)2, -OC(O)N(R28b)2, -N(R28b)C(O)OR28b, -S(O)R28b, -S(O)2R28b, -NO2, =O, =S, =N(R28b), -CN, C3-10 carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with one or more R27b; and C3-10 carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR28b, -SR28b, - N(R28b)2, -C(O)R28b, -C(O)N(R28b)2, -N(R28b)C(O)R28b-N(R28b)C(O)N(R28b)2, -OC(O)N(R28b)2, - N(R28b)C(O)OR28b, -C(O)OR28b, -OC(O)R28b, -S(O)R28b, -S(O)2R28b, -NO2, =O-, =S, =N(R28b), - CN, -N3, C3-10carbocycle, and 3- to 10-membered heterocycle, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R27b; or R21together with R22form a C3-10cycloalkyl, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR28b, -SR28b, -N(R28b)2, -C(O)R28b, -C(O)N(R28b)2, - N(R28b)C(O)R28b-N(R28b)C(O)N(R28b)2, -OC(O)N(R28b)2, -N(R28b)C(O)OR28b, -C(O)OR28b, - OC(O)R28b, -S(O)R28b, -S(O)2R28b, -NO2, =O-, =S, =N(R28b), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R27b;R23is selected from: hydrogen and C1-6alkyl optionally substituted with one or more one or more R27C; and R22together with R23form a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR28c, -SR28c, -N(R28c)2, -C(O)R28c, -C(O)N(R28c)2, -N(R28c)C(O)R28c, - N(R28c)C(O)N(R28c)2, -OC(O)N(R28c)2, -N(R28c)C(O)OR28c, -C(O)OR28c, -OC(O)R28c, -S(O)R28c, -S(O)2R28c, -NO2, =O-, =S, =N(R28c), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R27c;R24is independently selected from: hydrogen, halogen, -OR28d, -SR28d, -N(R28d)2, -NO2, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR28d, -SR28d, -N(R28d)2, -NO2, and -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with one or more R27d; R24ais independently selected from: hydrogen,halogen, -OR28e, -SR28e, -N(R28e)2, -NO2, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR28e, -SR28e, -N(R28e)2, -NO2, and - CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with one or more R27e; and R23together with R24aform a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR28e, -SR28e, -N(R28e)2, -C(O)R28e, -C(O)N(R28e)2, -N(R28e)C(O)R28e, - N(R28e)C(O)N(R28e)2, -OC(O)N(R28e)2, -N(R28e)C(O)OR28e, -C(O)OR28e, -OC(O)R28e, -S(O)R28e, -S(O)2R28e, -NO2, =O-, =S, =N(R28e), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R27e; R25is selected from: hydrogen and C1-6alkyl optionally substituted with one or more one or more R27f; each R27, R27a, R27b, R27c, R27d, R27eand R27fis independently selected from: hydrogen, halogen, - CN, -OH, -SH, -NO2, -NH2, -O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, and -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, - NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10-membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -SO2- C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl; each R28, R28a, R28b, R28c, R28d, R28eis independently selected from: hydrogen, halogen, -CN, -OH, -SH, -NO2, -NH2, -O-C1-6alkyl, -S- C1-6alkyl, -N(C1-6alkyl)2, and -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3- 10 carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10-membered heterocycle; and C3- 10 carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0006] In an aspect, the present disclosure provides a compound represented by Formula (IV):; or a salt thereof, wherein: X13, X14, X15,X16and X17are independently selected from C(R32) and N wherein at least one of X13, X14, X15, X16and X17is N; n is selected from 1, 2, 3, and 4; each R30is independently selected from: hydrogen, halogen, -NO2, -CN, -N3, -OR38, -SR38, -N(R38)2, -C(O)R38, -C(O)N(R38)2, - N(R38)C(O)R38-N(R38)C(O)N(R38)2, -OC(O)N(R38)2, -N(R38)C(O)OR38, -C(O)OR38, - OC(O)R38, -S(O)R38, and -S(O)2R38; and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR38, -SR38, -N(R38)2, -C(O)R38, -C(O)N(R38)2, -N(R38)C(O)R38, -C(O)OR38, -OC(O)R38, - N(R38)C(O)N(R38)2, -OC(O)N(R38)2, -N(R38)C(O)OR38, -S(O)R38, -S(O)2R38, -NO2, =O, =s, =N(R38), -CN, C3-10 carbocycle and 3- to 10-membered heterocycle, wherein the C3-10carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more R371; and C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR38, -SR38, -N(R38)2, -C(O)R38, -C(O)N(R38)2, -N(R38)C(O)R38, -N(R38)C(O)N(R38)2, -OC(O)N(R38)2, - N(R38)C(O)OR38, -C(O)OR38, -OC(O)R38, -S(O)R38, -S(O)2R38, -NO2, =O-, =S, =N(R38), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R371; R31is selected from: C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR38a, -SR38a, -N(R38a)2, -C(O)R38a, -C(O)N(R38a)2, - N(R38a)C(O)R38a, -C(O)OR38a, -OC(O)R38a, -N(R38a)C(O)N(R38a)2, -OC(O)N(R38a)2, - N(R38a)C(O)OR38a, -S(O)R38a, -S(O)2R38a, -NO2, =O, =S, =N(R38a), -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with one or more R37'; each R32is independently selected from: hydrogen, halogen, -NO2, -CN, -N3, -OR38b, -SR38b, -N(R38b)2, -C(O)R38b, -C(O)N(R38b)2, - N(R38b)C(O)R38b-N(R38b)C(O)N(R38b)2, -OC(O)N(R38b)2, -N(R38b)C(O)OR38b, -C(O)OR38b, - OC(O)R38b, -S(O)R38b, and -S(O)2R38b; and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR38b, -SR38b, -N(R38b)2, -C(O)R38b, -C(O)N(R38b)2, -N(R38b)C(O)R38b-C(O)OR38b, - OC(O)R38b, -N(R38b)C(O)N(R38b)2, -OC(O)N(R38b)2, -N(R38b)C(O)OR38b, -S(O)R38b, -S(O)2R38b,-NO2, =O, =S, =N(R38b), -CN, C3-10carbocycle and 3- to 10-membered heterocycle, wherein the C3-10carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more R37b; and C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR38b, -SR38b, - N(R38b)2, -C(O)R38b, -C(O)N(R38b)2, -N(R38b)C(O)R38b-N(R38b)C(O)N(R38b)2, -OC(O)N(R38b)2, - N(R38b)C(O)OR38b, -C(O)OR38b, -OC(O)R38b, -S(O)R38b, -S(O)2R38b, -NO2, =O-, =S, =N(R38b), - CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R37b; R33is selected from: hydrogen and C1-6alkyl optionally substituted with one or more one or more R37c; R34is independently selected from: hydrogen, halogen, -OR38c, -SR38c, -N(R38c)2, -NO2, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR38c, -SR38c, - N(R38c)2, -NO2, and -CN, C3-10 carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with one or more R37d; R34ais independently selected from: hydrogen, halogen, -OR38d, -SR38d, -N(R38d)2, -NO2, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR38d, -SR38d, -N(R38d)2, -NO2, and -CN, C3-10carbocycle, and 3- to 10- membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with one or more R37e; and R34together with R34aform a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR38d, -SR38d, -N(R38d)2, -C(O)R38d, -C(O)N(R38d)2, -N(R38d)C(O)R38d-N(R38d)C(O)N(R38d)2, -OC(O)N(R38d)2, - N(R38d)C(O)OR38d, -C(O)OR38d, -OC(O)R38d, -S(O)R38d, -S(O)2R38d, -NO2, =O-, =S, =N(R38d), - CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R37e; each R35and R35ais independently selected from: hydrogen, halogen, -OR38e, -SR38e, -N(R38e)2, - NO2, -CN, C1-6alkyl, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C1-6alkyl, C3-10carbocycle, and 3- to 10- membered heterocycle are each optionally substituted with one or more R37f; or R35together with R35aform a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR38e, -SR38e, -N(R38e)2, -C(O)R38e, -C(O)N(R38e)2, - N(R38e)C(O)R38e, -N(R38e)C(O)N(R38e)2, -OC(O)N(R38e)2, -N(R38e)C(O)OR38e, -C(O)OR38e, - OC(O)R38e, -S(O)R38e, -S(O)2R38e, -NO2, =O-, =S, =N(R38e), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R37f; each R36and R36ais independently selected from: hydrogen, halogen, -OR38f, -SR38f, -N(R38f)2, -NO2, -CN, C1-6alkyl, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C1-6alkyl, C3-10carbocycle, and 3- to 10- membered heterocycle are each optionally substituted with one or more R37g; or R36together with R36aform a C3-10carbocycle, or 3- to 10- membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR38f, -SR38f, -N(R38f)2, -C(O)R38f, - C(O)N(R38f)2, -N(R38f)C(O)R38f, -N(R38f)C(O)N(R38f)2, -OC(O)N(R38f)2, -N(R38f)C(O)OR38f, -C(O)OR38f, -OC(O)R38f, -S(O)R38f, -S(O)2R38f, -NO2, =O-, =S, =N(R38f), - CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R37g; each R36and R36ais independently selected from: hydrogen, halogen, -OR38g, -SR38g, -N(R38g)2, -NO2, -CN, C1-6alkyl, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C1-6alkyl, C3-10carbocycle, and 3- to 10- membered heterocycle are each optionally substituted with one or more R37h; or R36together with R36aform a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR38g, -SR38g, - N(R38g)2, -C(O)R38g, -C(O)N(R38g)2, -N(R38g)C(O)R38g-N(R38g)C(O)N(R38g)2, -OC(O)N(R38g)2, - N(R38g)C(O)OR38g, -C(O)OR38g, -OC(O)R38g, -S(O)R38g, -S(O)2R38g, -NO2, =O-, =S, =N(R38g), - CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R37h; each R371, R37', R37b, R37c, R37d, R37e, R37f, R37g, and R37his independently selected from: hydrogen, halogen, -CN, -OH, -SH, -NO2, -NH2, -O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, and -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10-membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, - OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, - NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl; each R38, R38a, R38b, R38c, R38d, R38e, R38f, and R38gis independently selected from: hydrogen, halogen, -CN, -OH, -SH, -NO2, -NH2, -O-C1-6alkyl, -S- C1-6alkyl, -N(C1-6alkyl)2, and -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10-membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted withone or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0007] In an aspect, the present disclosure provides a compound represented by Formula (V): ; or a salt thereof, wherein: XA, XB, Xcand XDare independently selected from C(R40) and N; each R40is independently selected from: hydrogen, halogen, -NO2, -CN, -N3, -OR48, -SR48, -N(R48)2, -C(O)R48, -C(O)N(R48)2, - N(R48)C(O)R48-N(R48)C(O)N(R48)2, -OC(O)N(R48)2, -N(R48)C(O)OR48, -C(O)OR48, - OC(O)R48, -S(O)R48, and -S(O)2R48; and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR48, -SR48, -N(R48)2, -C(O)R48, -C(O)N(R48)2, -N(R48)C(O)R48, -C(O)OR48, -OC(O)R48, - N(R48)C(O)N(R48)2, -OC(O)N(R48)2, -N(R48)C(O)OR48, -S(O)R48, -S(O)2R48, -NO2, =O, =s, =N(R48), -CN, C3-10carbocycle and 3- to 10-membered heterocycle, wherein the C3-10carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more R47; and C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR48, -SR48, -N(R48)2, -C(O)R48, -C(O)N(R48)2, -N(R48)C(O)R48, -N(R48)C(O)N(R48)2, -OC(O)N(R48)2, - N(R48)C(O)OR48, -C(O)OR48, -OC(O)R48, -S(O)R48, -S(O)2R48, -NO2, =O-, =S, =N(R48), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R47; R41is selected from: halogen, -NO2, -CN, -N3, -OR48a, -SR48a, -N(R48a)2, -C(O)R48a, -C(O)N(R48a)2, -N(R48a)C(O)R48a, -N(R48a)C(O)N(R48a)2, - OC(O)N(R48a)2, -N(R48a)C(O)OR48a, -C(O)OR48a, -OC(O)R48a, -S(O)R48a, and -S(O)2R48a; and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR48a, -SR48a, -N(R48a)2, -C(O)R48a, - C(O)N(R48a)2, -N(R48a)C(O)R48a, -C(O)OR48a, -OC(O)R48a, -N(R48a)C(O)N(R48a)2, - OC(O)N(R48a)2, -N(R48a)C(O)OR48a, -S(O)R48a, -S(O)2R48a, -NO2, =O, =S, =N(R48a), -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10- membered heterocycle, are each optionally substituted with one or more R47a; R42is selected from: C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR48b, -SR48b, -N(R48b)2, -C(O)R48b,-C(O)N(R48b)2, -N(R48b)C(O)R48b-C(O)OR48b, -OC(O)R48b, -N(R48b)C(O)N(R48b)2, - OC(O)N(R48b)2, -N(R48b)C(O)OR48b, -S(O)R48b, -S(O)2R48b, -NO2, =O, =S, =N(R48b), -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10- membered heterocycle, are each optionally substituted with one or more R47b; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR48b, -SR48b, -N(R48b)2, -C(O)R48b, -C(O)N(R48b)2, -N(R48b)C(O)R48b-N(R48b)C(O)N(R48b)2, -OC(O)N(R48b)2, - N(R48b)C(O)OR48b, -C(O)OR48b, -OC(O)R48b, -S(O)R48b, -S(O)2R48b, -NO2, =O-, =S, =N(R48b), - CN, -N3, C3-10carbocycle, and 3- to 10-membered heterocycle, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein the C3-10carbocycle, 3- to 10-membered heterocycle, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R47b; or R41together with R42form a C3-10cycloalkyl, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR48b, -SR48b, - N(R48b)2, -C(O)R48b, -C(O)N(R48b)2, -N(R48b)C(O)R48b-N(R48b)C(O)N(R48b)2, -OC(O)N(R48b)2, - N(R48b)C(O)OR48b, -C(O)OR48b, -OC(O)R48b, -S(O)R48b, -S(O)2R48b, -NO2, =O-, =S, =N(R48b), - CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R47b; R43is selected from: hydrogen and C1-6alkyl optionally substituted with one or more one or more R47c; and R42together with R43form a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR48c, -SR48c, -N(R48c)2, -C(O)R48c, -C(O)N(R48c)2, -N(R48c)C(O)R48c, -N(R48c)C(O)N(R48c)2, -OC(O)N(R48c)2, - N(R48c)C(O)OR48c, -C(O)OR48c, -OC(O)R48c, -S(O)R48c, -S(O)2R48c, -NO2, =O-, =S, =N(R48c), - CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R47c;R44is independently selected from: hydrogen, halogen, -OR48d, -SR48d, -N(R48d)2, -NO2, and - CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR48d, -SR48d, -N(R48d)2, -NO2, and -CN, C3-10carbocycle, and 3- to 10- membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with one or more R47d; R44ais independently selected from: hydrogen, halogen, -OR48e, -SR48e, -N(R48e)2, -NO2, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR48e, -SR48e, -N(R48e)2, -NO2, and - CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with one or more R47e; and R44together with R44aform a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each ofwhich is optionally substituted with one or more substituents independently selected from halogen, -OR48e, -SR48e, -N(R48e)2, -C(O)R48e, -C(O)N(R48e)2, -N(R48e)C(O)R48e, - N(R48e)C(O)N(R48e)2, -OC(O)N(R48e)2, -N(R48e)C(O)OR48e, -C(O)OR48e, -OC(O)R48e, -S(O)R48e, -S(O)2R48e, -NO2, =O- =S, =N(R48e), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R47e; R45is selected independently from: hydrogen, halogen, -NO2, -CN, -N3, -OR48f, -SR48f, - N(R48f)2, -C(O)R48f, -C(O)N(R48f)2, -N(R48f)C(O)R48f, -N(R48f)C(O)N(R48f)2, -OC(O)N(R48f)2, - N(R48f)C(O)OR48f, -C(O)OR48f, -OC(O)R48f, -S(O)R48f, and -S(O)2R48f; and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR48f, -SR48f, -N(R48f)2, -C(O)R48f, -C(O)N(R48f)2, - N(R48f)C(O)R48f, -C(O)OR48f, -OC(O)R48f, -N(R48f)C(O)N(R48f)2, -OC(O)N(R48f)2, - N(R48f)C(O)OR48f, -S(O)R48f, -S(O)2R48f, -NO2, =O, =S, =N(R48f), -CN, C3-10carbocycle and 3- to 10-membered heterocycle, wherein the C3-10carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more R47f; and C3-10carbocycle and 3- to 10- membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR48f, -SR48f, -N(R48f)2, -C(O)R48f, -C(O)N(R48f)2, - N(R48f)C(O)R48f, -N(R48f)C(O)N(R48f)2, -OC(O)N(R48f)2, -N(R48f)C(O)OR48f, -C(O)OR48f, - OC(O)R48f, -S(O)R48f, -S(O)2R48f, -NO2, =O-, =S, =N(R48f), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R47f; each R46and R46ais selected independently from: hydrogen, halogen, -OR48g, -SR48g, -N(R48g)2, - NO2, -CN, C1-6alkyl, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C1-6alkyl, C3-10carbocycle, and 3- to 10- membered heterocycle are each optionally substituted with one or more R47g; or R46together with R45form an -O- bridge, an -NR7g- bridge, a C1-5alkylene bridge, or a 1- to 5-membered heteroalkylene bridge, wherein each of the C1-5alkylene bridge, or 1- to 5-membered heteroalkylene bridge is optionally substituted with one or more substituents independently selected from halogen, -OR48g, -SR48g, -N(R48g)2, -C(O)R48g, -C(O)N(R48g)2, - N(R48g)C(O)R48g-N(R48g)C(O)N(R48g)2, -OC(O)N(R48g)2, -N(R48g)C(O)OR48g, -C(O)OR48g, - OC(O)R48g, -S(O)R48g, -S(O)2R48g, -NO2, =O-, =S, =N(R48g), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R47g; each R47, R47a, R47b, R47c, R47d, R47e, R47f, and R47gis independently selected from: hydrogen, halogen, -CN, -OH, -SH, -NO2, -NH2, -O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, and -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected fromhalogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, - NH(C1-6alkyl), C3-10carbocycle, 3- to 10-membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl; each R48, R48a, R48b, R48c, R48d, R48e, R48f, and R48gis independently selected from: hydrogen, halogen, -CN, -OH, -SH, -NO2, - NH2, -O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, and -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, - O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10-membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, - OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, - NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0008] In an aspect, the present disclosure provides a compound represented by Formula (VI): ; or a salt thereof, wherein: XE, XF, X°and XHareindependently selected from C(R50) and N; each R50is independently selected from: hydrogen, halogen, -NO2, -CN, -N3, -OR58, -SR58, -N(R58)2, -C(O)R58, -C(O)N(R58)2, -N(R58)C(O)R58, - N(R58)C(O)N(R58)2, -OC(O)N(R58)2, -N(R58)C(O)OR58, -C(O)OR58, -OC(O)R58, -S(O)R58, and -S(O)2R58; and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR58, -SR58, -N(R58)2, -C(O)R58, -C(O)N(R58)2, -N(R58)C(O)R58, -C(O)OR58, -OC(O)R58, -N(R58)C(O)N(R58)2, -OC(O)N(R58)2, -N(R58)C(O)OR58, -S(O)R58, -S(O)2R58, -NO2, =O, =S, =N(R58), -CN, C3-10carbocycle and 3- to 10-membered heterocycle, wherein the C3-10carbocycle and 3- to 10- membered heterocycle are each optionally substituted with one or more R57; and C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR58, -SR58, -N(R58)2, -C(O)R58, - C(O)N(R58)2, -N(R58)C(O)R58, -N(R58)C(O)N(R58)2, -OC(O)N(R58)2, -N(R58)C(O)OR58, -C(O)OR58, -OC(O)R58, -S(O)R58, -S(O)2R58, -NO2, =O-, =S, =N(R58), -CN,C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R57; R51is selected from: C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR58a, -SR58a, -N(R58a)2, -C(O)R58a, -C(O)N(R58a)2, - N(R58a)C(O)R58a, -C(O)OR58a, -OC(O)R58a, -N(R58a)C(O)N(R58a)2, -OC(O)N(R58a)2, - N(R58a)C(O)OR58a, -S(O)R58a, -S(O)2R58a, -NO2, =O, =S, =N(R58a), -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with one or more R57a; R52is selected from: C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR58b, -SR58b, -N(R58b)2, -C(O)R58b, -C(O)N(R58b)2, - N(R58b)C(O)R58b-C(O)OR58b, -OC(O)R58b, -N(R58b)C(O)N(R58b)2, -OC(O)N(R58b)2, - N(R58b)C(O)OR58b, -S(O)R58b, -S(O)2R58b, -NO2, =O, =S, =N(R58b), -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with one or more R57b; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR58b, -SR58b, -N(R58b)2, -C(O)R58b, - C(O)N(R58b)2, -N(R58b)C(O)R58b-N(R58b)C(O)N(R58b)2, -OC(O)N(R58b)2, - N(R58b)C(O)OR58b, -C(O)OR58b, -OC(O)R58b, -S(O)R58b, -S(O)2R58b, -NO2, =O-, =S, =N(R58b), - CN, -N3, C3-10carbocycle, and 3- to 10-membered heterocycle, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein the C3-10carbocycle, 3- to 10-membered heterocycle, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R57b; or R51together with R52form a C3-10cycloalkyl, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR58b, -SR58b, - N(R58b)2, -C(O)R58b, -C(O)N(R58b)2, -N(R58b)C(O)R58b-N(R58b)C(O)N(R58b)2, -OC(O)N(R58b)2, - N(R58b)C(O)OR58b, -C(O)OR58b, -OC(O)R58b, -S(O)R58b, -S(O)2R58b, -NO2, =O-, =S, =N(R58b), - CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R57b; R53is selected from: hydrogen and C1-6alkyl optionally substituted with one or more one or more R57c; andR52together with R53form a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR58c, -SR58c, -N(R58c)2, -C(O)R58c, -C(O)N(R58c)2, -N(R58c)C(O)R58c, - N(R58c)C(O)N(R58c)2, -OC(O)N(R58c)2, -N(R58c)C(O)OR58c, -C(O)OR58c, -OC(O)R58c, -S(O)R58c, -S(O)2R58c, -NO2, =O-, =S, =N(R58c), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R57c; R54isindependently selected from: hydrogen, halogen, -OR58d, -SR58d, -N(R58d)2, -NO2, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR58d, -SR58d, -N(R58d)2, -NO2, and -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with one or more R57d; R54ais independently selected from: halogen, - OR58e, -SR58e, -N(R58e)2, -NO2, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR58e, -SR58e, -N(R58e)2, -NO2, and -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10- membered heterocycle, are each optionally substituted with one or more R57e; and R54together with R54aform a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR58e, -SR58e, -N(R58e)2, -C(O)R58e, -C(O)N(R58e)2, -N(R58e)C(O)R58e, -N(R58e)C(O)N(R58e)2, - OC(O)N(R58e)2, -N(R58e)C(O)OR58e, -C(O)OR58e, -OC(O)R58e, -S(O)R58e, -S(O)2R58e, -NO2, =O- , =S, =N(R58e), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R57e; R55is selected from: hydrogen, -F, -Br, -I, -OR58f, -SR58f, -N(R58f)2, -NO2, -CN, C1-6alkyl, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C1-6alkyl, C3-10carbocycle, and 3- to 10- membered heterocycle are each optionally substituted with one or more R57f; each R57, R57a, R57b, R57c, R57d, R57e, and R57fis independently selected from: hydrogen, halogen, -CN, -OH, -SH, -NO2, -NH2, - O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, and -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10-membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, - OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, - NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl; each R58, R58a, R58b, R58c, R58d, R58e, and R58fis independently selected from: hydrogen, halogen, -CN, -OH, -SH, -NO2, -NH2, -O-C1-6alkyl, -S-C1-6alkyl, - N(C1-6alkyl)2, and -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10-membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or moresubstituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.INCORPORATION BY REFERENCE

[0009] 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

[0010] While preferred embodiments of the present invention 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 now occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention. It is intended that the following claims define the scope of the invention and that methods and structures within the scope of these claims and their equivalents be covered thereby.Definitions

[0011] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of skill in the art to which this invention belongs.

[0012] As used in the specification and claims, the singular form “a”, “an” and “the” includes plural references unless the context clearly dictates otherwise.

[0013] The term “Cx-y” or “Cx-Cy” (e.g., when used in conjunction with a chemical moiety, such as alkyl, alkenyl, or alkynyl) is meant to include groups that comprise a number of carbon atoms greater than or equal to x carbon atoms and less than or equal to y carbon atoms in the chemical moiety, subject to the following. The term “Cx-y” or “Cx-Cy” is not meant to limit the number of carbon atoms which may be attached to the chemical moiety when the chemical moiety is substituted with a second chemical moiety. For example, the term “C1-6alkyl” or “C1to C6alkyl” refers to saturated, substituted or unsubstituted, hydrocarbon groups, including straight- chain alkyl groups (e.g., linear alkyl groups) and branched alkyl groups that contain 1, 2, 3, 4, 5, or 6 carbon atoms, plus however many carbon atoms may be present in any substituents of the C1-6alkyl. For example, if a C1-6alkyl is optionally substituted with a second chemical moiety comprising two carbon atoms, then it will be understood that the C1-6alkyl can include between 1 and 8 carbon atoms.

[0014] The terms “Cx-yalkenyl” and “Cx-yalkynyl” refer to substituted or unsubstituted unsaturated aliphatic groups analogous in length and possible substitution to the alkyls described above, but that contain at least one double or triple bond, respectively.

[0015] " Amino" refers to the -NH2moiety.

[0016] "Cyano" refers to the -CN moiety.

[0017] "Nitro" refers to the -NO2moiety.

[0018] " Oxa" refers to the -O- moiety.

[0019] " Oxo" refers to the =O moiety.

[0020] " Thioxo" refers to the =S moiety.

[0021] " Imino" refers to the =N-H moiety.

[0022] " Oximo" refers to the =N-OH moiety.

[0023] "Hydrazino" refers to the =N-NH2moiety.

[0024] "Alkyl" refers to a straight (e.g., linear) or branched (e.g., nonlinear) hydrocarbon moiety consisting solely of carbon and hydrogen atoms, fully saturated. In certain embodiments, “alkyl” comprises one to fifteen carbon atoms (e.g., C1-C15alkyl). In certain embodiments, an alkyl comprises one to thirteen carbon atoms (e.g., C1-C13alkyl). In certain embodiments, an alkyl comprises one to eight carbon atoms (e.g., C1-C8alkyl). In certain embodiments, an alkyl comprises one to six carbon atoms (e.g., C1-C6alkyl). In other embodiments, an alkyl comprises one to five carbon atoms (e.g., C1-C5alkyl). In other embodiments, an alkyl comprises one to four carbon atoms (e.g., C1-C4alkyl). In other embodiments, an alkyl comprises one to three carbon atoms (e.g., C1-C3alkyl). In other embodiments, an alkyl comprises one to two carbon atoms (e.g., C1-C2alkyl). In other embodiments, an alkyl comprises one carbon atom (e.g., C1alkyl, e.g., methyl). In other embodiments, an alkyl comprises five to fifteen carbon atoms (e.g., C5-C15alkyl). In other embodiments, an alkyl comprises five to eight carbon atoms (e.g., C5-C8alkyl). In other embodiments, an alkyl comprises two to five carbon atoms (e.g., C2-C5alkyl). In other embodiments, an alkyl comprises three to five carbon atoms (e.g., C3-C5alkyl). In other embodiments, the alkyl group is selected from methyl, ethyl, 1 -propyl (n -propyl), 1 -methylethyl (2 -propyl, iso-propyl), 1 -butyl (n -butyl), 1 -methylpropyl (sec-butyl), 2-methylpropyl (iso-butyl), 1,1 -dimethylethyl (tert-butyl), and 1 -pentyl (n -pentyl). The alkyl is attached to the rest of the molecule by a single bond.

[0025] “Aminoalkyl” refers to a moiety boded through a nitrogen atom of the form -N(H)(alkyl) or N(alkyl)(alkyl), wherein when the moiety is N(alkyl)(alkyl), the two alkyl groups bonded to nitrogen can be the same alkyl groups or different alkyl groups.

[0026] "Alkoxy" refers to a moiety bonded through an oxygen atom of the formula -O-alkyl, where alkyl is an alkyl chain as defined above.

[0027] "Alkenyl" refers to a straight (e.g., linear) or branched (e.g., nonlinear) hydrocarbon moiety consisting solely of carbon and hydrogen atoms, the moiety comprising at least one carbon-carbon double bond. In certain embodiments, an alkenyl comprises two to twelve carbon atoms. In certain embodiments, an alkenyl comprises two to eight carbon atoms. In other embodiments, an alkenyl comprises two to four carbon atoms. The alkenyl is attached to the rest of the molecule by a single bond, for example, ethenyl (e.g., vinyl), prop-1-enyl (e.g., allyl), but-1-enyl, pent-1-enyl, penta- 1,4-dienyl, and the like.

[0028] "Alkynyl" refers to a straight (e.g., linear) or branched (e.g., nonlinear) hydrocarbon moiety consisting solely of carbon and hydrogen atoms, the moiety comprising at least one carbon-carbon triple bond. In some embodiments, an alkynyl comprises from two to twelve carbon atoms. In some embodiments, an alkynyl optionally further comprises at least one carbon-carbon double bond. In certain embodiments, an alkynyl comprises two to eight carbon atoms. In other embodiments, an alkynyl comprises two to six carbon atoms. In other embodiments, an alkynyl comprises two to four carbon atoms. The alkynyl is attached to the rest of the molecule by a single bond, for example, ethynyl, propynyl, butynyl, pentynyl, hexynyl, and the like.

[0029] “Alkylene” or “alkylene chain” refers to a linear (e.g., straight), or branched (e.g., nonlinear), divalent, hydrocarbon moiety. An “alkylene” or “alkylene chain” can link a portion of the molecule to a second moiety. An “alkylene” or “alkylene chain” consists solely of carbon and hydrogen atoms (substitution of an alkylene with one or more substituents comprising atoms other than hydrogen, such as N, O, and S, may be specified). An “alkylene” or “alkylene chain” can contain no unsaturation (notwithstanding the points of attachment of an alkylene to the rest of the molecule). In certain embodiments, the “alkylene” or “alkylene chain” and comprises one to twelve carbon atoms, for example, methylene, ethylene, propylene, n-butylene, and the like. The alkylene chain can be attached to the portion of the molecule through a single bond and to the second moiety through a single bond. The points of attachment of an alkylene chain to the rest of the molecule and to the second moiety can be through one carbon atom in the alkylene chain or can be through any two carbon atoms within the alkylene. In certain embodiments, an alkylene comprises one to eight carbon atoms (e.g., C1-C8alkylene). In other embodiments, an alkylene comprises one to five carbon atoms (e.g., C1-C5alkylene). In other embodiments, an alkylene comprises one to four carbon atoms (e.g., C1-C4alkylene). In other embodiments, an alkylene comprises one to three carbon atoms (e.g., C1-C3alkylene). In other embodiments, analkylene comprises one to two carbon atoms (e.g., C1-C2alkylene). In other embodiments, an alkylene comprises one carbon atom (e.g., C1alkylene). In other embodiments, an alkylene comprises five to eight carbon atoms (e.g., C5-C8alkylene). In other embodiments, an alkylene comprises two to five carbon atoms (e.g., C2-C5alkylene). In other embodiments, an alkylene comprises three to five carbon atoms (e.g., C3-C5alkylene).

[0030] "Alkenylene" or "alkenylene chain" refers to a linear (e.g., straight), or branched, divalent, hydrocarbon moiety. An "alkenylene" or "alkenylene chain" can link a portion of the molecule to a second moiety. An "alkenylene" or "alkenylene chain" consists solely of carbon and hydrogen atoms (substitution of an alkenylene with one or more substituents comprising atoms other than hydrogen, such as N, O, and S, may be specified). An "alkenylene" or "alkenylene chain" comprises at least one carbon-carbon double bond. In certain embodiments, an "alkenylene" or "alkenylene chain" comprises from two to twelve carbon atoms. The alkenylene chain can be attached to the portion of the molecule through a single bond and to the second moiety through a single bond. The points of attachment of an alkenylene chain to the rest of the molecule and to the second moiety can be through one carbon atom in the alkenylene chain or through any two carbon atoms within the alkenylene chain. In certain embodiments, an alkenylene comprises two to eight carbon atoms (e.g., C2-C8alkenylene). In other embodiments, an alkenylene comprises two to five carbon atoms (e.g., C2-C5alkenylene). In other embodiments, an alkenyl ene comprises two to four carbon atoms (e.g., C2-C4alkenylene). In other embodiments, an alkenylene comprises two to three carbon atoms (e.g., C2- C3alkenylene). In other embodiments, an alkenylene comprises five to eight carbon atoms (e.g., C5-C8alkenylene). In other embodiments, an alkenyl ene comprises two to five carbon atoms (e.g., C2- C5alkenylene). In other embodiments, an alkenyl ene comprises three to five carbon atoms (e.g., C3-C5alkenylene).

[0031] "Alkynylene" or "alkynylene chain" refers to a linear (e.g., straight), or branched, divalent, hydrocarbon moiety. An “alkynylene" or "alkynylene chain" can link a portion of the molecule to a second moiety. An “alkynylene" or "alkynylene chain" consists solely of carbon and hydrogen (substitution of an alkynylene with one or more substituents comprising atoms other than hydrogen, such as N, O, and S, may be specified). An “alkynylene" or "alkynylene chain" comprises at least one carbon-carbon triple bond. In certain embodiments, an “alkynylene" or "alkynylene chain" comprises from two to twelve carbon atoms. An alkynylene chain can be attached to the portion of the molecule through a single bond and to the second moiety through a single bond. The points of attachment of an alkynylene chain to the rest of the molecule and to the second moiety can be through one carbon atom in the alkynylene chain orthrough any two carbon atoms within the alkynylene chain. In certain embodiments, an alkynylene comprises two to eight carbon atoms (e.g., C2-C8alkynylene). In other embodiments, an alkynylene comprises two to five carbon atoms (e.g., C2-C5alkynylene). In other embodiments, an alkynylene comprises two to four carbon atoms (e.g., C2-C4alkynylene). In other embodiments, an alkynylene comprises two to three carbon atoms (e.g., C2-C3alkynylene). In other embodiments, an alkynylene comprises two carbon atoms (e.g., C2alkynylene). In other embodiments, an alkynylene comprises five to eight carbon atoms (e.g., C5-C8alkynylene). In other embodiments, an alkynylene comprises three to five carbon atoms (e.g., C3-C5alkynylene).

[0032] The term “carbocycle” as used herein refers to a saturated or unsaturated (e.g., aromatic or nonaromatic unsaturated) ring or ring system in which each atom of the ring is carbon. The term “carbocycle” comprises “aryls,” “cycloalkenyls,” and “cycloalkyls.” For example, the term “carbocycle” includes 3- to 12-membered monocyclic rings (e.g., 3- to 10- membered monocyclic rings) and 4- to 20-membered polycyclic ring systems (e.g., 5- to 15-membered spiro polycyclic ring systems, 5- to 15-membered bridged polycyclic ring systems, or 4- to 15- membered fused polycyclic ring systems). For example, carbocycle includes 4- to 15-membered bicyclic rings (e.g., 5- to 15-membered spiro bicycles, 5- to 15-membered bridged bicyclic ring systems, or 4- to 15-membered fused bicyclic ring systems). For example, carbocycle includes tricyclic ring systems, which may be bridged, fused, spiro, or a combination thereof. For example, carbocycle includes tetracyclic ring systems, which may be bridged, fused, spiro, or a combination thereof. For example, carbocycle includes ring systems that are both fused and bridged; ring systems that are both fused and spiro; ring systems that are both bridged and spiro; and ring systems that are both fused and bridged and are also spiro. Each ring of a polycyclic carbocycle may be selected from saturated and unsaturated (e.g., aromatic or nonaromatic unsaturated) rings. In an exemplary embodiment, an aromatic ring (e.g., phenyl) of a polycyclic carbocycle may be fused to a saturated or unsaturated ring (e.g., cyclohexane, cyclopentane, cyclohexene, or phenyl). A polycyclic carbocycle includes any combination of saturated and unsaturated (e.g., aromatic or nonaromatic unsaturated)rings, as valence permits. For example, polycyclic carbocycles can be spiro bicyclic rings, such as spiropentane. For example, a polycyclic carbocycle includes any combination of ring sizes such as 2-2 spiro ring systems (e.g., spiro[2.2]pentane), 3-3 spiro ring systems, 4-4 spiro ring systems, 4-5 fused ring systems (e.g., bicyclo[4.5.0] fused ring systems), 5-5 fused ring systems, 5-6 fused ring systems, 6-6 fused ring systems (e.g., naphthalene), 5-7 fused ring systems, 6-7 fused ring systems, 5-8 fused ring systems, and 6-8 fused ring systems. Exemplary carbocycles include cyclopentyl, cyclohexyl,cyclohexenyl, adamantyl, phenyl, indanyl, naphthyl, trans-bicyclo[4.4.0]decane, cis- bicylo[4.4.0]decane, spiro[3.4]octane, fluoranthene, and bicyclo[l. l.l]pentanyl.

[0033] The term “aryl” refers to an aromatic monocyclic or aromatic polycyclic hydrocarbon ring system comprising at least one cyclic, delocalized (4n+2) π-electronic system, wherein n is an integer greater than or equal to 0, in accordance with Hückel theory. In some embodiments, the aromatic monocyclic or aromatic polycyclic hydrocarbon ring system comprises only hydrogen atoms and carbon atoms. In some embodiments, the aromatic monocyclic or polycyclic system contains from three to twenty carbon atoms. In some embodiments, at least one of the rings in the polycyclic aromatic ring system is aromatic. In some embodiments, the aromatic monocyclic or aromatic polycyclic hydrocarbon ring system comprises a cyclic, delocalized (4n+2) ^-electronic system in accordance with Hückel theory. In some embodiments, the ring system from which aryl groups are derived include, but are not limited to, groups such as benzene, fluorene, indane, indene, anthracene, tetralin, and naphthalene. In some embodiments, the aryl substituent is not charged (e.g., neutral). In some embodiments, the aryl substituent bears no charges. In some embodiments, the aryl substituent bears no net charge. In some embodiments, the aryl substituent bears no net charge and is not zwitterionic. In some embodiments, none of the carbon atoms of the aryl substituent are charged. In some embodiments, none of the carbon atoms of the aryl substituent are charged.

[0034] The term "cycloalkyl" refers to a saturated ring in which each atom of the ring is carbon. Cycloalkyl may include monocyclic and polycyclic rings such as 3- to 10-membered monocyclic rings, 5- to 12-membered bicyclic rings, 5- to 12-membered spiro bicycles, and 5- to 12- membered bridged rings. In certain embodiments, a cycloalkyl comprises three to ten carbon atoms. In other embodiments, a cycloalkyl comprises three to seven carbon atoms. In other embodiments, a cycloalkyl comprises five to seven carbon atoms. The cycloalkyl may be attached to the rest of the molecule by a single bond. Examples of monocyclic cycloalkyls include, e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Examples of polycyclic cycloalkyls include, but are not limited to, adamantyl, spiropentane, norbomyl (e.g., bicyclo[2.2.1]heptanyl), decalinyl, 7,7 dimethyl bicyclo[2.2.1]heptanyl, bicyclo[1.1.1]pentanyl, spiropentane, and the like.

[0035] The term "cycloalkenyl" refers to a saturated ring in which each atom of the ring is carbon and there is at least one double bond between two ring carbon atoms. Cycloalkenyl may include monocyclic and polycyclic rings, such as 3- to 10-membered monocyclic rings and 4- to 12-membered bicyclic rings (e.g., 5- to 12-membered bridged bicyclic rings, fused 4- to 12- membered bicyclic rings, and spiro 5- to 12-membered bicyclic rings). In other embodiments, acycloalkenyl comprises five to seven carbon atoms. The cycloalkenyl may be attached to the rest of the molecule by a single bond. Examples of monocyclic cycloalkenyls include, e.g., cyclopentenyl, cyclohexenyl, cycloheptenyl, and cyclooctenyl.

[0036] The term “halo” or, alternatively, “halogen” or “halide,” means fluoro, chloro, bromo or iodo. In some embodiments, a halo is fluoro, chloro, or bromo. In some embodiments, a halo is a fluoro or a chloro. In some embodiments, a halo is a fluoro. In some embodiments, a halo is a chloro.

[0037] The term “haloalkyl” refers to an alkyl, as defined above, that is substituted by one or more halogens, for example, trifluoromethyl, dichloromethyl, bromomethyl, 2,2,2-trifluoroethyl, 1-chloromethyl-2-fluoroethyl, and the like. In some embodiments, the alkyl part of the haloalkyl is optionally further substituted as described herein.

[0038] The term “heterocycle” as used herein refers to a saturated or unsaturated (e.g., aromatic or nonaromatic unsaturated) ring or ring system in which one or more heteroatom(s) is(are) member(s) of the ring or ring system. Exemplary heteroatoms include N, O, Si, P, B, and S atoms. For example, heterocycles include 3- to 12-membered monocyclic rings (e.g., 3- to 10- membered monocyclic rings) and 4- to 20-membered polycyclic ring systems (e.g., 4- to 15- membered fused poly ring systems, 5- to 15-membered spiro polycyclic ring systems, and 5- to 15-membered bridged polycyclic ring systems). For example, heterocycles include 4- to 20- membered bicyclic ring systems (e.g., 4- to 15-membered fused bicyclic ring systems, 5- to 15- membered spiro bicyclic ring systems, and 5- to 15-membered bridged bicyclic ring systems). For example, heterocycle includes tricyclic ring systems, which may be bridged, fused, spiro, or a combination thereof. For example, heterocycle includes tetracyclic ring systems, which may be bridged, fused, spiro, or a combination thereof. For example, heterocycle includes ring systems that are both fused and bridged; ring systems that are both fused and spiro; ring systems that are both bridged and spiro; and ring systems that are both fused and bridged and are also spiro. Each ring of a polycyclic heterocycle may be selected from saturated and unsaturated (e.g., aromatic or nonaromatic unsaturated) rings. A polycyclic heterocycle includes any combination of saturated, and unsaturated (e.g., aromatic or nonaromatic unsaturated) rings, as valence permits. In an exemplary embodiment, an aromatic ring, e.g., pyridyl or phenyl, may be fused to a saturated or unsaturated ring, e.g., cyclohexane, cyclopentane, morpholine, piperidine or cyclohexene, in a heterocycle, as long as at least one atom in the resulting fused ring system is a heteroatom. A polycyclic heterocycle includes any combination of ring sizes such as 3-3 spiro, 4-5 fused ring systems, 5-5 fused ring systems, 5-6 fused ring systems, 6-6 fused ring systems, 5- 7 fused ring systems, 6-7 fused ring systems, 5-8 fused ring systems, and 6-8 fused ring systems.A bicyclic heterocycle further includes spiro bicyclic rings, e.g., 5 to 12-membered spiro bicycles, such as 2-oxa-6-azaspiro[3.3]heptane. In some embodiments, a heterocycle comprises multiple heteroatoms. In some embodiments, a heterocycle comprises an atom selected from nitrogen, oxygen, and sulfur. In some embodiments, a heterocycle comprises multiple atoms selected from nitrogen, oxygen, and sulfur. In some embodiments, a heterocycle comprises one or more atom(s) selected from nitrogen, oxygen, and sulfur. In some embodiments, a heterocycle comprises one or more atom(s) selected from nitrogen and oxygen. In some embodiments, a heterocycle comprises one or more atom(s) selected from nitrogen and sulfur. In some embodiments, a heterocycle comprises one or more atom(s) selected from oxygen and sulfur. In some embodiments, a heterocycle comprises one or more atom(s) selected from nitrogen. In some embodiments, a heterocycle comprises one or more atom(s) selected from oxygen. In some embodiments, a heterocycle comprises one or more atom(s) selected from sulfur. In some embodiments, a heterocycle does not comprise Boron in the ring. In some embodiments, a heterocycle does not comprise Phosphorus in the ring. In some embodiments, a heterocycle does not comprise Sulfur in the ring. In some embodiments, a heterocycle does not comprise Oxygen in the ring. In some embodiments, a heterocycle does not comprise Nitrogen in the ring. In some embodiments, a heterocycle comprises only heteroatoms selected from nitrogen, oxygen, and sulfur in the ring, and the heterocycle comprises no other heteroatoms in the ring. Nonlimiting examples of heterocycles include pyridine, pyrrole, indole, carbazole, piperidine, oxazole, morpholine, thiophene, benzothiophene, furan, tetrahydrofuran, and pyran. Nonlimiting examples of heterocycles include azepinyl, acridinyl, benzimidazolyl, benzindolyl, 1,3 -benzodi oxolyl, benzofuranyl, benzoxazolyl, benzo[d]thiazolyl, benzothiadiazolyl, benzo[b ][1,4]dioxepinyl, benzo[b][l,4]oxazinyl, 1,4-benzodioxanyl, benzonaphthofuranyl, benzoxazolyl, benzodioxolyl, benzodioxinyl, benzopyranyl, benzopyranonyl, benzofuranyl, benzofuranonyl, benzothienyl (benzothiophenyl), benzothieno[3,2-d]pyrimidinyl, benzotriazolyl, benzo[4,6]imidazo[1,2-a]pyridinyl, carbazolyl, cinnolinyl, cyclopenta[d]pyrimidinyl,6.7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidinyl, 5,6-dihydrobenzo[h]quinazolinyl, 5,6-dihydrobenzo[h]cinnolinyl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[l,2-c]pyridazinyl, dibenzofuranyl, dibenzothiophenyl, furanyl, furanonyl, furo[3,2-c]pyridinyl,5.6.7.8.9.10-hexahydrocycloocta[d]pyrimidinyl, 5,6,7,8,9,10-hexahydrocycloocta[d]pyridazinyl,5.6.7.8.9.10-hexahydrocycloocta[d]pyridinyl, isothiazolyl, imidazolyl, indazolyl, indolyl, indazolyl, isoindolyl, indolinyl, isoindolinyl, isoquinolyl, indolizinyl, isoxazolyl,5.8-methano-5,6,7,8-tetrahydroquinazolinyl, naphthyridinyl, 1,6-naphthyridinonyl, oxadiazolyl, 2-oxoazepinyl, oxazolyl, oxiranyl, 5,6,6a,7,8,9,10,10a-octahydrobenzo[h]quinazolinyl,1 -phenyl- 1H -pyrrolyl, phenazinyl, phenothiazinyl, phenoxazinyl, phthalazinyl, pteridinyl, purinyl, pyrrolyl, pyrazolyl, pyrazolo[3,4-d]pyrimidinyl, pyridinyl, pyrido[3,2-d]pyrimidinyl, pyrido[3,4-d]pyrimidinyl, pyrazinyl, pyrimidinyl, pyridazinyl, pyrrolyl, quinazolinyl, quinoxalinyl, quinolinyl, isoquinolinyl, tetrahydroquinolinyl, 5,6,7,8-tetrahydroquinazolinyl,5.6.7.8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidinyl,6.7.8.9-tetrahydro-5H-cyclohepta[4,5]thieno[2,3-d]pyrimidinyl, 5,6,7,8-tetrahydropyrido[4,5-c]pyridazinyl, thiazolyl, thiadiazolyl, triazolyl, tetrazolyl, triazinyl, thieno[2,3-d]pyrimidinyl, thieno[3,2-d]pyrimidinyl, thieno[2,3-c]pyridinyl, and thiophenyl (e.g., thienyl).

[0039] In some embodiments, a heterocycle is attached to the molecule by a carbon atom. In some embodiments, the heterocycle is attached to the molecule by a nitrogen atom.

[0040] In some embodiments, a heterocycle comprises a moiety selected from a heteroaryl, a heterocycloalkyl, and a heterocycloalkenyl. In some embodiments, the heterocycle is a heteroaryl. In some embodiments, the heterocycle is a heterocycloalkyl. In some embodiments, the heterocycle is a heterocycloalkenyl.

[0041] In some embodiments, a heterocycle comprises an atom selected from nitrogen and oxygen. In some embodiments, a heterocycle comprises an atom selected from nitrogen and sulfur. In some embodiments, a heterocycle comprises an atom selected from oxygen and sulfur. In some embodiments, a heterocycle comprises an atom selected from nitrogen. In some embodiments, a heterocycle comprises an atom selected from oxygen. In some embodiments, a heterocycle comprises an atom selected from sulfur.

[0042] In some embodiments, a heterocycle comprises 1 to 8 heteroatoms. In some embodiments, the heterocycle comprises 1 to 5 heteroatoms. In some embodiments, the heterocycle comprises 1 to 3 heteroatoms. In some embodiments, the heterocycle comprises 1 to2 heteroatoms. In some embodiments, the heterocycle comprises 1 heteroatom. In some embodiments, the heterocycle comprises 2 heteroatoms. In some embodiments, the heterocycle comprises 3 heteroatoms. In some embodiments, the heterocycle comprises 4 heteroatoms. In some embodiments, the heterocycle comprises 5 heteroatoms. In some embodiments, the heterocycle comprises 6 heteroatoms.

[0043] In some embodiments, a heterocycle comprises a 3-memberd ring, 4-membered ring, 5- membered ring, 6-membered ring, 7-membered ring, 8-membered ring, 9-membered ring, 10- membered ring, 11 -membered ring, 12-membered ring, 13 -membered ring, 14-membered ring, or 15-20 membered ring. In some embodiments, a heterocycle is 3- to 10-membered. In some embodiments, a heterocycle is 3- to 6-membered. In some embodiments, a heterocycle is 5- to 6-membered. In some embodiments, a heterocycle is 9- to 10-membered. In some embodiments, a heterocycle is 9- to 11 -membered. In some embodiments, a heterocycle is 9- to 15-membered.

[0044] In some embodiments, the heterocycle is monosubstituted, di substituted, tri substituted, tetrasubstituted, or pentasubstituted (e.g., with further substituents in addition to the point of attachment). In some embodiments, the total number of substituents (e.g., atoms other than hydrogen) on the heterocycle (e.g., bonded to the ring of the heterocycle) is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more.

[0045] In some embodiments, in the molecule or moiety (e.g., in a heterocycle), one or more nitrogen atoms, if present, can be optionally quaternized. In some embodiments, the heterocycle substituent is positively charged, some embodiments, the heterocycle moiety is neutral. In some embodiments, the heterocycle substituent is zwitterionic. Alternatively, or in addition, in some embodiments, the heterocycle substituent is not charged. In some embodiments, the heterocycle substituent bears no charges. In some embodiments, the heterocycle substituent bears no net charge. In some embodiments, no atoms within the heterocycle substituent bear any net charge. In some embodiments, the heterocycle substituent bears no net charge and is not zwitterionic. The term "heteroaryl" refers to a moiety derived from an aromatic monocyclic or aromatic polycyclic ring system, in which one or more heteroatom(s) is(are) member(s) of the ring system, and the ring system comprises at least one cyclic, delocalized (4n+2) π-electronic system, wherein n is an integer greater than or equal to 0, in accordance with Hückel theory. In some embodiments, one or more heteroatom(s) is(are) member(s) of the ring system comprising the cyclic, delocalized (4n+2) π-electronic system (e.g., the ring with aromaticity). Exemplary heteroatoms include N, O, Si, P, B, and S atoms. In some embodiments, a heteroaryl comprises an aromatic ring, in which one or more heteroatom(s) is(are) member(s) of the ring system, to which one or more nonaromatic rings, each of which may or may not comprise one or more heteroatom(s), may be fused. In some embodiments, a heteroaryl includes one or more heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, a heteroaryl includes multiple heteroatoms selected from nitrogen, oxygen, and sulfur. In certain embodiments, “heteroaryl” includes rings and ring systems comprising 3 to 20 atoms. In some embodiments, “heteroaryl” includes rings and ring systems that comprise two to seventeen carbon atoms and from one to six heteroatoms selected from nitrogen, oxygen and sulfur. As used herein, the heteroaryl moiety is a monocyclic or polycyclic (e.g., bicyclic, tricyclic or tetracyclic) ring system, wherein at least one of the rings in the ring system is aromatic, e.g., it contains a cyclic, delocalized (4n+2) π-electron system in accordance with the Hückel theory. Heteroaryl includes fused, bridged, and spiro ring systems. The heteroatom(s) in the heteroarylmoiety is(are) optionally oxidized. One or more nitrogen atom(s), if present, is(are) optionally quaternized. The heteroaryl is attached to the rest of the molecule through any atom of the ring(s). Examples of heteroaryls include, but are not limited to, acridinyl, benzimidazolyl, benzindolyl, 1,3-benzodioxolyl, benzofuranyl, benzoxazolyl, benzo[d]thiazolyl, benzothiadiazolyl, benzo[b][1,4]dioxepinyl, benzo[b][l,4]oxazinyl, 1,4-benzodioxanyl, benzonaphthofuranyl, benzoxazolyl, benzodi oxolyl, benzodioxinyl, benzopyranyl, benzopyranonyl, benzofuranyl, benzofuranonyl, benzothienyl (benzothiophenyl), benzothieno[3,2-d]pyrimidinyl, benzotriazolyl, benzo[4,6]imidazo[1,2-a]pyridinyl, carbazolyl, cinnolinyl, cyclopenta[d]pyrimidinyl, 6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidinyl,5.6-dihydrobenzo[h]quinazolinyl, 5,6-dihydrobenzo[h]cinnolinyl, 6,7-dihydro-5H- benzo[6,7]cyclohepta[1,2-c]pyridazinyl, dibenzofuranyl, dibenzothiophenyl, furanyl, furo[3,2-c]pyridinyl, 5,6,7,8,9,10-hexahydrocycloocta[d]pyrimidinyl, 5,6,7,8,9,10-hexahydrocycloocta[d]pyridazinyl, 5,6,7,8,9,10-hexahydrocycloocta[d]pyridinyl, isothiazolyl, imidazolyl, indazolyl, indolyl, isoindolyl, indolinyl, isoindolinyl, isoquinolyl, indolizinyl, isoxazolyl, 5,8-methano-5,6,7,8-tetrahydroquinazolinyl, naphthyridinyl,1.6-naphthyri dinonyl, oxadiazolyl, oxazolyl, 5,6,6a,7,8,9,10,10a-octahydrobenzo[h]quinazolinyl, 1 -phenyl- 1H-pyrrolyl, phenazinyl, phenothiazinyl, phenoxazinyl, phthalazinyl, pteridinyl, purinyl, pyrrolyl, pyrazolyl, pyrazolo[3,4-d]pyrimidinyl, pyridinyl, pyrido[3,2-d]pyrimidinyl, pyrido[3,4-d]pyrimidinyl, pyrazinyl, pyrimidinyl, pyridazinyl, pyrrolyl, quinazolinyl, quinoxalinyl, quinolinyl, isoquinolinyl, tetrahydroquinolinyl, 5,6,7,8-tetrahydroquinazolinyl,5.6.7.8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidinyl,6.7.8.9-tetrahydro-5H-cyclohepta[4,5]thieno[2,3-d]pyrimidinyl, 5,6,7,8-tetrahydropyrido[4,5-c]pyridazinyl, thiazolyl, thiadiazolyl, triazolyl, tetrazolyl, triazinyl, thieno[2,3-d]pyrimidinyl, thieno[3,2-d]pyrimidinyl, thieno[2,3-c]pyridinyl, and thiophenyl (e.g., thienyl). In some embodiments, further examples of “heteroaryl” include 5, 6,7,8- tetrahydroquinoline; 1,2,3,4-tetrahydro-1,8-naphthyridine; 6,7-dihydro-5H- cyclopenta[b]pyridine; 2,3-dihydro-1H-pyrrolo[2,3-b]pyridine; 4,5,6,7-tetrahydrobenzofuran; 4,5,6,7-tetrahydrofuro[2,3-b]pyridine; 5,6-dihydro-4H-cyclopenta[b]furan; 4,5- dihydrothieno[2,3-b]furan. In some embodiments, the heteroaryl substituent is positively or negatively charged. In some embodiments, the heteroaryl substituent is neutral. In some embodiments, the heteroaryl substituent is zwitterionic; alternatively, or in addition, in some embodiments, the heteroaryl substituent is not charged. In some embodiments, the heteroaryl substituent bears no charges. In some embodiments, the heteroaryl substituent bears no netcharge. In some embodiments, the heteroaryl substituent bears no net charge and is not zwitterionic.

[0046] The term “heterocycle” comprises “heteroaryls,” “heterocycloalkenyls,” and “heterocycloalkyls.”

[0047] The term "heterocycloalkyl" refers to a moiety comprising a saturated ring (e.g., a ring with only single bonds connecting the members of the ring), wherein the saturated ring comprises carbon atom(s) and one or more heteroatom(s) as member(s) of the saturated ring, and wherein the saturated ring may be optionally fused, bridged with, or spiro to an additional ring, wherein the additional ring may comprise only carbon atoms as members of the additional ring or wherein the additional ring may comprise one or more heteroatom(s) as member(s) of the additional ring. In some embodiments, a heterocycloalkyl may be covalently bound to one or more carbocycle(s) or heterocycle(s). Exemplary heteroatoms include N, O, Si, P, B, and S atoms. Heterocycloalkyl may include monocyclic and polycyclic rings such as 3- to 10- membered monocyclic rings, 6- to 12-membered bicyclic rings, 5- to 12-membered spiro bicycles, or 5- to 12-membered bridged rings. The heteroatoms in the heterocycloalkyl radical are optionally oxidized. One or more nitrogen atoms, if present, are optionally quaternized. The heterocycloalkyl is attached to the rest of the molecule through any atom of the heterocycloalkyl, valence permitting, such as any carbon or nitrogen atoms of the heterocycloalkyl. Examples of heterocycloalkyl radicals include, but are not limited to, dioxolanyl, thienyl[l,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, 2-oxa-6-azaspiro[3.3]heptane, and 1,1-dioxo-thiomorpholinyl. In some embodiments, a heterocycloalkyl comprises one heteroatom. In some embodiments, a heterocycloalkyl comprises one heteroatom selected from N, O, and S. In some embodiments, a heterocycloalkyl comprises multiple heteroatoms. In some embodiments, a heterocycloalkyl comprises multiple heteroatoms selected from N, O, and S.

[0048] The term "heterocycloalkenyl" refers to a moiety comprising an unsaturated ring (e.g., a ring with either single bonds or double bonds connecting the members of the ring): wherein the unsaturated ring comprises carbon atoms and one or more heteroatom(s); wherein the unsaturated ring may be optionally fused, bridged with, or spiro to an additional ring, wherein the additional ring may comprise only carbon atoms as members of the additional ring or wherein the additional ring may comprise one or more heteroatom(s) as member(s) of theadditional ring; and wherein there is at least one double bond between two ringcarbon atoms (e.g., carbon atoms that are members of the unsaturated ring). Heterocycloalkenyl does not include heteroaryl rings. Exemplary heteroatoms include N, O, Si, P, B, and S atoms. Heterocycloalkenyl may include monocyclic and polycyclic rings such as 3- to 10-membered monocyclic rings, 6- to 12-membered bicyclic rings, and 5- to 12-membered bridged rings. In other embodiments, a heterocycloalkenyl comprises five to seven ring atoms. The heterocycloalkenyl may be attached to the rest of the molecule by a single bond. Examples of monocyclic cycloalkenyls include, e.g., pyrroline (dihydropyrrole), pyrazoline (dihydropyrazole), imidazoline (dihydroimidazole), triazoline (dihydrotriazole), dihydrofuran, dihydrothiophene, oxazoline (dihydrooxazole), isoxazoline (dihydroisoxazole), thiazoline (dihydrothiazole), isothiazoline (dihydroisothiazole), oxadiazoline (dihydrooxadiazole), thiadiazoline (dihydrothiadiazole), dihydropyridine, tetrahydropyridine, dihydropyridazine, tetrahydropyridazine, dihydropyrimidine, tetrahydropyrimidine, dihydropyrazine, tetrahydropyrazine, pyran, dihydropyran, thiopyran, dihydrothiopyran, dioxine, dihydrodioxine, oxazine, dihydrooxazine, thiazine, and dihydrothiazine.

[0049] A “spirocyclic” moiety (e.g., a “spiro” moiety) (e.g., a spirocyclic heterocycle, a spirocyclic heterocycloalkenyl, a spirocyclic carbocycle, a spirocyclic heterocycloalkyl, a spirocyclic cycloalkenyl, or a spirocyclic cycloalkyl) is a polycyclic system (e.g., bicyclic, tricyclic, tetracyclic) system wherein two rings share exactly one atom. Examples of spirocyclic moi eties include, but are not limited to:, and.

[0050] A spirocyclic heterocycle comprises a spirocyclic moiety that comprises at least one heteroatom in the ring system of the spirocyclic moiety. Examples of spirocyclic heterocyclesinclude, but are not limited to:

[0051] A spirocyclic carbocycle comprises a spirocyclic moiety that comprises only carbon atoms in the ring system of the spirocyclic moiety. Examples of spirocyclic carbocycles include, but are not limited to:

[0052] A “fused” moiety (e.g., a fused heterocycle, a fused carbocycle, a fused heterocycloalkyl, or a fused cycloalkyl) is a polycyclic system (e.g., bicyclic, tricyclic, tetracyclic) wherein two rings share exactly two atoms. Examples of fused moieties include, but are not limited to:

[0053] A “fused” heterocycle comprises a fused moiety that comprises at least one heteroatom in the ring system of the fused moiety. Examples of fused heterocycles include, but are not limited to:

[0054] A “fused” carbocycle comprises a fused moiety that comprises only carbon atoms in the ring system of the fused moiety. Examples of fused carbocycles include, but are not limited to:

[0055] A “bridged” moiety (e.g., a bridged heterocycle, a bridged carbocycle, a bridged heterocycloalkyl, a bridged heterocycloalkenyl, or a bridged cycloalkyl) is a polycyclic system (e.g., bicyclic, tricyclic, tetracyclic) which comprises two or more bridgeheads, wherein in at least one combination of two bridgeheads, each bridgehead in the combination of two bridgeheads is separated from the other bridgehead in the combination of two bridgeheads by three bridges, each bridge comprising at least one atom, wherein each of the three bridges does not contain any of the same atoms as either of the other two bridges.

[0056] In some embodiments, a “bridged” moiety (e.g., a bridged heterocycle, a bridged carbocycle, a bridged heterocycloalkyl, a bridged heterocycloalkenyl, or a bridged cycloalkyl) is a polycyclic system (e.g., bicyclic, tricyclic, tetracyclic) which comprises two or more bridgeheads, wherein in at least one pair of bridgeheads, each bridgehead in the pair is separated from the other bridgehead in the pair by three bridges, each bridge comprising at least one atom, wherein each of the three bridges does not contain any of the same atoms as either of the other two bridges.

[0057] In some embodiments, a bridgehead atom is a sp3-hybridized carbon or nitrogen atom that forms a nexus between two or more rings. In some embodiments, a bridge comprises one or more atom(s) connecting two bridgehead atoms.

[0058] Examples of bridged moi eties include, but are not limited to:(bicyclofl. l. l]pentane),(bicyclo[2.1.1]hexane), norbornanenorbornene, 2-oxa-5-azabicyclo[2.2. l]heptane , 7-oxabicyclo[2.2.1]heptane, 7-azabicyclo[2.2.1]heptanebicyclo[3.1.1]heptane, bicyclo[2.2.2]octane, twistane, isotwistanespiro[bicyclo[2.2.1]heptane-7,1'-cyclopropane],spiro[bicyclo[2.2.1]heptane-

[0059] A “bridged” carbocycle comprises a bridged moiety that comprises only carbon atoms in the ring system of the bridged moiety. Examples of bridged carbocycles include, but are not limited to: (bicyclo[1.1.1]pentane),(bicyclo[2.1.1]hexane), norbornane (norbomenebicyclo[3.1.1]heptanebicyclo[2.2.2]octane, twistanespiro[bicyclo[2.2.1]heptane-7,1'-cyclopropane], andspiro[bicyclo[2.2.1]heptane-2,1'- cyclopropane],

[0060] A “bridged” heterocycle comprises a bridged moiety that comprises at least one heteroatom in the ring system of the bridged moiety. Examples of bridged heterocycles include, but are not limited to:

[0061] The term “substituted” refers to moieties having substituents replacing a hydrogen on one or more carbon atom(s) or substitutable heteroatoms, e.g., an NH or NH2of a compound. It will be understood that “substitution” or “substituted with” includes the implicit proviso that such substitution is in accordance with permitted valence of the substituted atom and the substituent and further includes the proviso that the substitution results in a stable compound, e.g., a compound which does not rapidly undergo rearrangement, cyclization, elimination, etc. In certain embodiments, substituted refers to moieties having substituents replacing two hydrogen atoms on the same carbon atom, such as substituting the two hydrogen atoms on a single carbon atom with an oxo, imino, oxime, hydrazone, or thioxo group. As used herein, the term“substituted” is contemplated to include all permissible substituents of organic compounds. In a broad aspect, the permissible substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and non-aromatic substituents of organic compounds. The permissible substituents can be one or more and the same or different for appropriate organic compounds.

[0062] In some embodiments, the term “one or more substituents” may refer to one substituent, or two substituents, or three substituents, or four substituents, or five substituents, or six substituents, or more than six substituents. In some embodiments, the term “one or more substituents” may refer to one substituent. In some embodiments, the term “one or more substituents” may refer to two substituents. In some embodiments, the term “one or more substituents” may refer to three substituents. In some embodiments, the term “one or more substituents” may refer to four substituents. In some embodiments, the term “one or more substituents” may refer to five substituents. In some embodiments, the term “one or more substituents” may refer to more than five substituents. In some embodiments, the term “one or more substituents” may refer to 1 substituent to 10 substituents. In some embodiments, the term “one or more substituents” may refer to at least 1 substituent. In some embodiments, the term “one or more substituents” may refer to at most 10 substituents. In some embodiments, the term “one or more substituents” may refer to at most 5 substituents. In some embodiments, the term “one or more substituents” may refer to at most 2 substituents. In some embodiments, the term “one or more substituents” may refer to 1 substituent to 2 substituents. In some embodiments, the term “one or more substituents” may refer to 1 substituent to 1 substituent. 1 substituent to 3 substituents, 1 substituent to 4 substituents, 1 substituent to 5 substituents, 1 substituent to 6 substituents, 1 substituent to 7 substituents, 1 substituent to 10 substituents, 2 substituents to 3 substituents, 2 substituents to 4 substituents, 2 substituents to 5 substituents, 2 substituents to 6 substituents, 2 substituents to 7 substituents, 2 substituents to 10 substituents, 3 substituents to 4 substituents, 3 substituents to 5 substituents, 3 substituents to 6 substituents, 3 substituents to 7 substituents, 3 substituents to 10 substituents, 4 substituents to 5 substituents, 4 substituents to 6 substituents, 4 substituents to 7 substituents, 4 substituents to 10 substituents, 5 substituents to 6 substituents, 5 substituents to 7 substituents, 5 substituents to 10 substituents, 6 substituents to 7 substituents, 6 substituents to 10 substituents, or 7 substituents to 10 substituents. In some embodiments, the term “one or more substituents” may refer to 1 substituent, 2 substituents, 3 substituents, 4 substituents, 5 substituents, 6 substituents, 7 substituents, or 10 substituents.

[0063] In some embodiments, substituents may include any substituents described herein, for example: halogen, hydroxy, oxo (=O), thioxo (=S), cyano (-CN), nitro (-NO2), imino (=N-H),oximo (=N-OH), hydrazino (=N-NH2), -Rb-ORa, -Rb-OC(O)-Ra, -Rb-OC(O)-ORa, - Rb-OC(O)-N(Ra)2, -Rb-N(Ra)2, -Rb-C(O)Ra, -Rb-C(O)ORa, -Rb-C(O)N(Ra)2, - Rb-O-Rc-C(O)N(Ra)2, -Rb-N(Ra)C(O)ORa, -Rb-N(Ra)C(O)Ra, -Rb-N(Ra)S(O)tRa(where t is 1 or 2), -Rb-S(O)tRa(where t is 1 or 2), -Rb-S(O)tORa(where t is 1 or 2), and -Rb-S(O)tN(Ra)2(where t is 1 or 2); and alkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, aralkynyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, and heteroarylalkyl, any of which may be optionally substituted by alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo (=O), thioxo (=S), cyano (-CN), nitro (-NO2), imino (=N-H), oximo (=N-OH), hydrazine (=N-NH2), -Rb-ORa, -Rb-OC(O)-Ra, -Rb-OC(O)-ORa, -Rb-OC(O)-N(Ra)2, -Rb-N(Ra)2, - Rb-C(O)Ra, -Rb-C(O)ORa, -Rb-C(O)N(Ra)2, -Rb-O-Rc-C(O)N(Ra)2, -Rb-N(Ra)C(O)ORa, - Rb-N(Ra)C(O)Ra, -Rb-N(Ra)S(O)tRa(where t is 1 or 2), -Rb-S(O)tRa(where t is 1 or 2), - Rb-S(O)tORa(where t is 1 or 2) and -Rb-S(O)tN(Ra)2(where t is 1 or 2); wherein each Rais independently selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, or heteroarylalkyl, wherein each Ra, valence permitting, may be optionally substituted with alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo (=O), thioxo (=S), cyano (-CN), nitro (-NO2), imino (=N-H), oximo (=N-OH), hydrazine (=N-NH2), -Rb-ORa, -Rb-OC(O)-Ra, -Rb-OC(O)-ORa, - Rb-OC(O)-N(Ra)2, -Rb-N(Ra)2, -Rb-C(O)Ra, -Rb-C(O)ORa, -Rb-C(O)N(Ra)2, - Rb-O-Rc-C(O)N(Ra)2, -Rb-N(Ra)C(O)ORa, -Rb-N(Ra)C(O)Ra, -Rb-N(Ra)S(O)tRa(where t is 1 or 2), -Rb-S(O)tRa(where t is 1 or 2), -Rb-S(O)tORa(where t is 1 or 2) and -Rb-S(O)tN(Ra)2(where t is 1 or 2); and wherein each Rbis independently selected from a direct bond or a straight or branched alkylene, alkenylene, or alkynylene chain, and each Rcis a straight or branched alkylene, alkenylene or alkynylene chain.

[0064] Double bonds to oxygen atoms, such as oxo groups, are represented herein as both “=O” and “(O)”. Double bonds to nitrogen atoms are represented as both “=NR” and “(NR)”- Double bonds to sulfur atoms are represented as both “=S” and “(S)”.

[0065] The phrases “parenteral administration” and “administered parenterally” as used herein means modes of administration other than enteral and topical administration, usually by injection, and includes, without limitation, intravenous, intramuscular, intra-arterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, subcuticular, intraarticular, subcapsular, subarachnoid, intraspinal and intrasternal injection and infusion.

[0066] The phrase “pharmaceutically acceptable” is employed herein to refer to those compounds, materials, compositions, and / or dosage forms which are, within the scope of soundmedical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit / risk ratio.

[0067] The phrase “pharmaceutically acceptable excipient” or “pharmaceutically acceptable carrier” as used herein 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. Some examples of materials which can serve as pharmaceutically acceptable carriers include: (1) sugars, such as lactose, glucose and sucrose; (2) starches, such as com starch and potato starch; (3) cellulose, and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; (4) powdered tragacanth; (5) malt; (6) gelatin; (7) talc; (8) excipients, such as cocoa butter and suppository waxes; (9) oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, com oil and soybean oil; (10) glycols, such as propylene glycol; (11) polyols, such as glycerin, sorbitol, mannitol and polyethylene glycol; (12) esters, such as ethyl oleate and ethyl laurate; (13) agar; (14) buffering agents, such as magnesium hydroxide and aluminum hydroxide; (15) alginic acid; (16) pyrogen- free water; (17) isotonic saline; (18) Ringer's solution; (19) ethyl alcohol; (20) phosphate buffer solutions; and (21) other non-toxic compatible substances employed in pharmaceutical formulations.

[0068] The term “salt” or “pharmaceutically acceptable salt” refers to salts derived from a variety of organic and inorganic counter ions well known in the art. Pharmaceutically acceptable acid addition salts can be formed with inorganic acids and / or organic acids. Inorganic acids from which salts can be derived include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like. Organic acids from which salts can be derived include, for example, acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, and the like. Pharmaceutically acceptable base addition salts can be formed with inorganic and / or organic bases. Inorganic bases from which salts can be derived include, for example, sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum, and the like. Organic bases from which salts can be derived include, for example, primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines, basic ion exchange resins, and the like, specifically such as isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, and ethanolamine.In some embodiments, the pharmaceutically acceptable base addition salt is selected from ammonium, potassium, sodium, calcium, and magnesium salts.

[0069] As used herein, “treatment” or “treating” refers to an approach for obtaining beneficial or desired results with respect to a disease, disorder, or medical condition including but not limited to a therapeutic benefit and / or a prophylactic benefit. A therapeutic benefit can include, for example, the eradication or amelioration of the underlying disorder being treated. Also, a therapeutic benefit can include, for example, the eradication or amelioration of one or more of the physiological symptoms associated with the underlying disorder such that an improvement is observed in the subject, notwithstanding that the subject may still be afflicted with the underlying disorder. In certain embodiments, for prophylactic benefit, the compositions are administered to a subject at risk of developing a particular disease, or to a subject reporting one or more of the physiological symptoms of a disease, even though a diagnosis of this disease may not have been made. Treatment via administration of a compound described herein does not require the involvement of a medical professional.

[0070] Chemical entities having carbon-carbon double bonds or carbon-nitrogen double bonds may exist in Z- or E- form (or cis- or trans- form). Furthermore, some chemical entities may exist in various tautomeric forms. Unless otherwise specified, all structures described herein are intended to disclose, implicitly or explicitly, all Z-, E- and tautomeric forms as well.

[0071] A “tautomer” refers to a molecule wherein a proton shift from one atom of a molecule to another atom of the same molecule is possible. The compounds presented herein, in certain embodiments, exist as tautomers. In circumstances where tautomerization is possible, a chemical equilibrium of the tautomers will exist. The exact ratio of the tautomers depends on several factors, including physical state, temperature, solvent, and pH. Some examples of tautomeric equilibria include, but are not limited to:

[0072] The compounds disclosed herein, in some embodiments, are used in different enriched isotopic forms, e.g., enriched in the content of2H,3H,11C,13C and / or14C. In one particular embodiment, the compound is deuterated in at least one position. Such deuterated forms can be made by the procedure described in U.S. Patent Nos. 5,846,514 and 6,334,997. As described in U.S. Patent Nos. 5,846,514 and 6,334,997, deuteration can improve the metabolic stability and or efficacy of drugs, thus increasing the duration of action of drugs.

[0073] Unless otherwise stated, compounds described herein are intended to include compounds which differ only in the presence of one or more isotopically enriched atoms. For example, compounds having the present structures except for the replacement of one or more proton(s) by one or more deuterium(deuteria) or tritium(tritia), or combinations thereof, or except for the replacement of one or more12C atom(s) in the structure by one or more13C atom(s), one or more14C atom(s), or combinations thereof, in the structure are within the scope of the present disclosure.

[0074] The compounds of the present disclosure optionally comprise unnatural proportions of atomic isotopes at one or more atom(s) that constitute such compounds. For example, the compounds may be labeled with one or more isotope(s), such as for example, deuterium (2H), tritium (3H), iodine-125 (125I) or carbon-14 (14C). Isotopic substitution with2H,3H,nC,13C,14C,15C,12N,13N,15N,16N,17O,18O,14F,15F,16F,17F,18F,33S,34S,35S,36S,35C1,37C1,79Br,81Br, and125I are all contemplated. All isotopic variations of the compounds of the present invention, whether radioactive or not, are encompassed within the scope of the present invention.

[0075] In certain embodiments, the compounds disclosed herein have some or all of the1H atoms replaced with2H atoms. The methods of synthesis for deuterium-containing compoundsare known in the art and include, by way of non-limiting example only, the following synthetic methods.

[0076] Deuterium-substituted compounds are synthesized using various methods such as described in: Dean, Dennis C.; Editor. Recent Advances in the Synthesis and Applications of Radiolabeled Compounds for Drug Discovery and Development. [In: Curr., Pharm. Des., 2000; 6(10)] 2000, 110 pp; George W.; Varma, Rajender S. The Synthesis of Radiolabeled Compounds via Organometallic Intermediates, Tetrahedron, 1989, 45(21), 6601-21; and Evans, E. Anthony. Synthesis of radiolabeled compounds, J. Radioanal. Chem., 1981, 64(1-2), 9-32.

[0077] Deuterated starting materials are readily available and are subjected to the synthetic methods described herein to provide for the synthesis of deuterium-containing compounds. Large numbers of deuterium-containing reagents and building blocks are available commercially from chemical vendors, such as MilliporeSigma.

[0078] Included in the present disclosure are salts, particularly pharmaceutically acceptable salts, of the compounds described herein. The compounds of the present disclosure that comprise one or more sufficiently acidic functional group(s), one or more sufficiently basic functional group(s), or both one or more sufficiently acidic functional group(s) and one or more sufficiently basic functional group(s) to form a salt (particularly a pharmaceutically acceptable salt), can react with any of a number of inorganic organic bases or inorganic or organic acids, to form a salt. ; combinations thereof); or combinations thereof. Alternatively, compounds that are inherently charged, such as those with a quaternary nitrogen, can form a salt with an appropriate counterion.

[0079] The compounds and salts described herein may in some cases exist as diastereomers, enantiomers, or other stereoisomeric forms. Unless otherwise specified (e.g., in tables of biological data), the structures disclosed herein are intended to include, explicitly or implicitly, disclosure of all diastereomeric (e.g., epimeric) and enantiomeric forms as well as mixtures thereof. Separation of stereoisomers may be performed by chromatography or by forming diastereomers and separating by recrystallization, or chromatography, or any combination thereof. (Jean Jacques, Andre Collet, Samuel H. Wilen, “Enantiomers, Racemates and Resolutions”, John Wiley And Sons, Inc., 1981, herein incorporated by reference for this disclosure). Stereoisomers may also be obtained by stereoselective synthesis.

[0080] In certain embodiments, the compounds or salts of the compounds may be prodrugs. For example, in some embodiments, a hydroxyl in the parent compound is presented as an ester or a carbonate, or carboxylic acid present in the parent compound is presented as an ester. The term “prodrug” is intended to encompass compounds which, under physiologic conditions, areconverted into pharmaceutical agents of the present disclosure. One method for making a prodrug is to include one or more selected moieties which are hydrolyzed under physiologic conditions to reveal the desired molecule. In other embodiments, the prodrug is converted by an enzymatic activity of the host animal such as specific target cells in the host animal. For example, esters or carbonates (e.g., esters or carbonates of alcohols or carboxylic acids and esters of phosphonic acids) may be prodrugs of the present disclosure. In some embodiments, a prodrug for an amine might rely on enzymatic activation. In some embodiments, a prodrug for an amine might rely on physiological chemical conditions for release of the drugs. In some embodiments, a prodrug for an amine may be selected from an amide, a carbonate, an N-acyloxy alkyl derivative, an N-acyloxy carbonyl derivative, a beta-aminoketone, an(oxodi oxolenyl)methyl derivative, an N-Mannich base, an imine (e.g., a Schiff base), an enamine, an enaminone, an azo compound, a system capable of undergoing lactonization, a tetrahydrothiadiazine-2-thione, a redox system, or a PEG.

[0081] Prodrug forms of the herein described compounds, wherein the prodrug is metabolized in vivo to produce a compound as set forth herein are included within the scope of the claims. In some cases, some of the herein-described compounds may be a prodrug for another derivative or active compound.

[0082] Prodrugs are often useful because, in some situations, they may be easier to administer than the parent drug. They may, for instance, be bioavailable by oral administration whereas the parent is not. Prodrugs may help enhance the cell permeability of a compound relative to the parent drug. The prodrug may also have improved solubility in pharmaceutical compositions over the parent drug. Prodrugs may be designed as reversible drug derivatives, for use as modifiers to enhance drug transport to site-specific tissues or to increase drug residence inside of a cell.

[0083] In some embodiments, the design of a prodrug increases the lipophilicity of the pharmaceutical agent. In some embodiments, the design of a prodrug increases the effective water solubility. See, e.g., Fedorak et al., Am. J. Physiol., 269:G210-218 (1995); McLoed et al., Gastroenterol, 106:405-413 (1994); Hochhaus et al., Biomed. Chrom., 6:283-286 (1992); J. Larsen and H. Bundgaard, Int. J. Pharmaceutics, 37, 87 (1987); J. Larsen et al., Int. J.Pharmaceutics, 47, 103 (1988); Sinkula et al., J. Pharm. Sci., 64:181-210 (1975); T. Higuchi and V. Stella, Pro-drugs as Novel Delivery Systems, Vol. 14 of the A.C.S. Symposium Series; and Edward B. Roche, Bioreversible Carriers in Drug Design, American Pharmaceutical Association and Pergamon Press, 1987, all incorporated herein for such disclosure). According to another embodiment, the present disclosure provides methods of producing the above-definedcompounds. The compounds may be synthesized using conventional techniques.Advantageously, these compounds are conveniently synthesized from readily available starting materials.

[0084] Synthetic chemistry transformations and methodologies useful in synthesizing the compounds described herein are known in the art and include, for example, those described in R. Larock, Comprehensive Organic Transformations (1989); T. W. Greene and P. G. M.Wuts, Protective Groups in Organic Synthesis, 2d. Ed. (1991); L. Fieser and M. Fieser, Fieser and Fieser ’s Reagents for Organic Synthesis (1994); and L. Paquette, ed., Encyclopedia of Reagents for Organic Synthesis (1995).Compounds

[0085] The following is a discussion of compounds and salts thereof that may be used in the methods of the disclosure. In certain embodiments, the compounds and salts are described in Formulas (I), (II), (III), (IV), (V), and (VI).

[0086] In an aspect, the present disclosure provides a compound represented by Formula (I): or a salt thereof, wherein:X1, X2, X3and X4are independently selected from C(R0) and N;Y is selected from C(R6)(R6a) and O; each R0is independently selected from: hydrogen, halogen, -NO2, -CN, -N3, -OR8, -SR8, -N(R8)2, -C(O)R8, - C(O)N(R8)2, -N(R8)C(O)R8-N(R8)C(O)N(R8)2, -OC(O)N(R8)2, - N(R8)C(O)OR8, -C(O)OR8, -OC(O)R8, -S(O)R8, and -S(O)2R8; and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR8, -SR8, -N(R8)2, -C(O)R8, -C(O)N(R8)2, -N(R8)C(O)R8, -C(O)OR8, -OC(O)R8, - N(R8)C(O)N(R8)2, -OC(O)N(R8)2, -N(R8)C(O)OR8, -S(O)R8, -S(O)2R8, -NO2, =O, =S, =N(R8), -CN, C3-10 carbocycle and 3- to 10-membered heterocycle, wherein the C3-10carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more R7; and C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected fromhalogen, -OR8, -SR8, -N(R8)2, -C(O)R8, -C(O)N(R8)2, -N(R8)C(O)R8, - N(R8)C(O)N(R8)2, -OC(O)N(R8)2, -N(R8)C(O)OR8, -C(O)OR8, -OC(O)R8, -S(O)R8, - S(O)2R8, -NO2, =O-, =S, =N(R8), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R7;R1is selected from: C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR8a, -SR8a, -N(R8a)2, -C(O)R8a, -C(O)N(R8a)2, -N(R8a)C(O)R8a, -C(O)OR8a, - OC(O)R8a, -N(R8a)C(O)N(R8a)2, -OC(O)N(R8a)2, -N(R8a)C(O)OR8a, -S(O)R8a, - S(O)2R8a, -NO2, =O, =S, =N(R8a), -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with one or more R7a;R2is selected from: C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR8b, -SR8b, -N(R8b)2, -C(O)R8b, -C(O)N(R8b)2, -N(R8b)C(O)R8b-C(O)OR8b, - OC(O)R8b, -N(R8b)C(O)N(R8b)2, -OC(O)N(R8b)2, -N(R8b)C(O)OR8b, -S(O)R8b, - S(O)2R8b, -NO2, =O, =S, =N(R8b), -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with one or more R7b; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR8b, -SR8b, -N(R8b)2, -C(O)R8b, -C(O)N(R8b)2, -N(R8b)C(O)R8b- N(R8b)C(O)N(R8b)2, -OC(O)N(R8b)2, -N(R8b)C(O)OR8b, -C(O)OR8b, -OC(O)R8b, - S(O)R8b, -S(O)2R8b, -NO2, =O-, =S, =N(R8b), -CN, -N3, C3-10carbocycle, and 3- to 10-membered heterocycle, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein the C3-10carbocycle, 3- to 10-membered heterocycle, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R7b; orR1together with R2form a C3-10cycloalkyl, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR8b, -SR8b, -N(R8b)2, -C(O)R8b, - C(O)N(R8b)2, -N(R8b)C(O)R8b-N(R8b)C(O)N(R8b)2, -OC(O)N(R8b)2, - N(R8b)C(O)OR8b, -C(O)OR8b, -OC(O)R8b, -S(O)R8b, -S(O)2R8b, -NO2, =O-, =S,=N(R8b), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R7b;R3is selected from: hydrogen and C1-6alkyl optionally substituted with one or more one or more R7C; andR2together with R3form a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR8c, -SR8c, -N(R8c)2, -C(O)R8c, - C(O)N(R8c)2, -N(R8c)C(O)R8c, -N(R8c)C(O)N(R8c)2, -OC(O)N(R8c)2, - N(R8c)C(O)OR8c, -C(O)OR8c, -OC(O)R8c, -S(O)R8c, -S(O)2R8c, -NO2, =O-, =S, =N(R8c), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R7c;R4is independently selected from: hydrogen, halogen, -OR8d, -SR8d, -N(R8d)2, -NO2, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR8d, -SR8d, -N(R8d)2, -NO2, and -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with one or more R7d;R4ais independently selected from: hydrogen, halogen, -OR8e, -SR8e, -N(R8e)2, -NO2, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR8e, -SR8e, -N(R8e)2, -NO2, and -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with one or more R7e; andR4together with R4aform a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR8e, -SR8e, -N(R8e)2, -C(O)R8e, - C(O)N(R8e)2, -N(R8e)C(O)R8e, -N(R8e)C(O)N(R8e)2, -OC(O)N(R8e)2, - N(R8e)C(O)OR8e, -C(O)OR8e, -OC(O)R8e, -S(O)R8e, -S(O)2R8e, -NO2, =O-, =S, =N(R8e), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R7e; each R5and R5ais selected independently from: hydrogen, halogen, -OR8f, -SR8f, -N(R8f)2, -NO2, -CN, C1-6alkyl, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C1-6alkyl, C3-10carbocycle, and 3- to 10- membered heterocycle are each optionally substituted with one or more R7f; orR5together with R5aform a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR8f, -SR8f, -N(R8f)2, -C(O)R8f, - C(O)N(R8f)2, -N(R8f)C(O)R8f, -N(R8f)C(O)N(R8f)2, -OC(O)N(R8f)2, - N(R8f)C(O)OR8f, -C(O)OR8f, -OC(O)R8f, -S(O)R8f, -S(O)2R8f, -NO2, =O-, =S, =N(R8f), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R7f; each R6and R6ais selected independently from: hydrogen, halogen, -OR8g, -SR8g, -N(R8g)2, -NO2, -CN, C1-6alkyl, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C1-6alkyl, C3-10carbocycle, and 3- to 10- membered heterocycle are each optionally substituted with one or more R7g; orR6together with R5form an -O- bridge, an -NR7g- bridge, a C1-5alkylene bridge, or a 1- to 5-membered heteroalkylene bridge, wherein each of the C1-5alkylene bridge, or 1- to 5-membered heteroalkylene bridge is optionally substituted with one or more substituents independently selected from halogen, -OR8g, -SR8g, - N(R8g)2, -C(O)R8g, -C(O)N(R8g)2, -N(R8g)C(O)R8g-N(R8g)C(O)N(R8g)2, - OC(O)N(R8g)2, -N(R8g)C(O)OR8g, -C(O)OR8g, -OC(O)R8g, -S(O)R8g, -S(O)2R8g, - NO2, =O-, =S, =N(R8g), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R7g; each R7, R7a, R7b, R7c, R7d, R7e, R7f, and R7gis independently selected from: hydrogen, halogen, -CN, -OH, -SH, -NO2, -NH2, -O-C1-6alkyl, -S-C1-6alkyl, - N(C1-6alkyl)2, and -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10-membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl; each R8, R8a, R8b, R8c, R8d, R8e, R8f, and R8gis independently selected from: hydrogen, halogen, -CN, -OH, -SH, -NO2, -NH2, -O-C1-6alkyl, -S-C1-6alkyl, - N(C1-6alkyl)2, and -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10-membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0087] In some embodiments, for a compound or salt of Formula (I), X1, X2, X3, and X4are each independently selected from C(R0). In some embodiments, for a compound or salt of Formula (I), at least one of X1, X2, X3, and X4need not be N.

[0088] In some embodiments, for a compound or salt of Formula (I), X1, X2, X3, and X4are each independently selected from C(R0) and N. In some embodiments, for a compound or salt of Formula (I), at least one of X1, X2, X3, and X4is N. In some embodiments, for a compound or salt of Formula (I), at least two of X1, X2, X3, and X4are N. In some embodiments, for a compound or salt of Formula (I), X1is N. In some embodiments, for a compound or salt of Formula (I), X2is N. In some embodiments, for a compound or salt of Formula (I), X3is N. In some embodiments, for a compound or salt of Formula (I), X4is N.

[0089] In some embodiments, for a compound or salt of Formula (I), Y is independently selected from: O and C(R6)(R6a). In some embodiments, for a compound or salt of Formula (I), Y is O. In some embodiments, for a compound or salt of Formula (I), Y is C(R6)(R6a).

[0090] In some embodiments, for a compound or salt of Formula (I), each R0is independently selected from: hydrogen, halogen, -NO2, -CN, -N3, -OR8, -SR8, -N(R8)2, -C(O)R8, - C(O)N(R8)2, -N(R8)C(O)R8-OC(O)N(R8)2, -C(O)OR8, -OC(O)R8, and -S(O)2R8; C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR8, -SR8, -N(R8)2, -C(O)R8, -C(O)N(R8)2, -N(R8)C(O)R8, -C(O)OR8, -OC(O)R8, -N(R8)C(O)N(R8)2, -OC(O)N(R8)2, -N(R8)C(O)OR8, -S(O)R8, -S(O)2R8, =O, =S, -CN, C3-10carbocycle and 3- to 10-membered heterocycle; and C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR8, -SR8, -N(R8)2, -C(O)R8, -C(O)N(R8)2, -N(R8)C(O)R8, -C(O)OR8, - OC(O)R8, -N(R8)C(O)N(R8)2, -OC(O)N(R8)2, -N(R8)C(O)OR8, -S(O)R8, -S(O)2R8, =O, =S, -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more substituents independently selected from R7.

[0091] In some embodiments, for a compound or salt of Formula (I), each R0is independently selected from: hydrogen, -F, -Cl, -Br, -I, -NO2, -CN, -N3, -OR8, -SR8, -N(R8)2, -C(O)R8, - C(O)N(R8)2, -N(R8)C(O)R8-OC(O)N(R8)2, -C(O)OR8, -OC(O)R8, and -S(O)2R8.

[0092] In some embodiments, for a compound or salt of Formula (I), each R0is independently selected from: hydrogen, -F, -Cl, -Br, -I, -NO2, -CN, -N3, -OC1-6alkyl, -SC1-6alkyl, -N(C1-6alkyl)2, -C(O)C1-6alkyl, -C(O)N(C1-6alkyl)2, -N(C1-6alkyl)C(O)C1-6alkyl, -OC(O)N(C1-6alkyl)2, -C(O)OC1-6alkyl, -OC(O)C1-6alkyl, and -S(O)2C1-6alkyl.

[0093] In some embodiments, for a compound or salt of Formula (I), each R1is independently selected from: C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, - OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10-membered heterocycle.

[0094] In some embodiments, for a compound or salt of Formula (I), R1together with R2form a C3-6carbocycle, or 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR8a, -N(R8a)2, -C(O)R8a, - C(O)N(R8a)2, -N(R8a)C(O)R8a, -C(O)OR8a, -OC(O)R8a, -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more substituents independently selected from R7a.

[0095] In some embodiments, for a compound or salt of Formula (I), R1is selected from: methyl, ethyl, n-propyl, and isopropyl. In some embodiments, for a compound or salt of Formula (I), R1is hydrogen. In some embodiments, for a compound or salt of Formula (I), R1is methyl.

[0096] In some embodiments, for a compound or salt of Formula (I), R2is selected from: hydrogen; C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR8b, -N(R8b)2, -C(O)R8b, -C(O)N(R8b)2, -N(R8b)C(O)R8b-C(O)OR8b, -OC(O)R8b, - S(O)2R8b, -NO2, =O, -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with one or more substituents independently selected from R7b; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR8b, -N(R8b)2, -C(O)R8b, -C(O)N(R8b)2, -N(R8b)C(O)R8b-C(O)OR8b, - OC(O)R8b, -S(O)2R8b, -NO2, =O, -CN, -N3, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle and 3- to 10-membered heterocycle, wherein C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle and 3- to 10-membered heterocycle, are each optionally substituted with one or more substituents independently selected from R7b; orR2together with R3form a C3-10carbocycle, or 3- to 15-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR8b, -N(R8b)2, -C(O)R8b, -C(O)N(R8b)2, - N(R8b)C(O)R8b-C(O)OR8b, -OC(O)R8b, -S(O)2R8b, -NO2, =O, -CN, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle and 3- to 10-membered heterocycle, wherein C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle and 3- to 10-membered heterocycle, are each optionally substituted with one or more substituents independently selected from R7b.

[0097] In some embodiments, for a compound or salt of Formula (I), R2is selected from: C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR8b, -N(R8b)2, -C(O)R8b, -C(O)N(R8b)2, - N(R8b)C(O)R8b-C(O)OR8b, -OC(O)R8b, -S(O)2R8b, -NO2, =O, -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with one or more substituents independently selected from R7b.

[0098] In some embodiments, for a compound or salt of Formula (I), R2together with R3form a C3-12 carbocycle, or 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR8b, -N(R8b)2, -C(O)R8b, - C(O)N(R8b)2, =O, -CN, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle and 3- to 6- membered heterocycle, wherein C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle and 3- to 6-membered heterocycle, are each optionally substituted with one or more substituents independently selected from R7b.

[0099] In some embodiments, for a compound or salt of Formula (I), R2is selected from: C3-6carbocycle, and 3- to 6-membered heterocycle, each of which is optionally substituted with oneor more substituents independently selected from halogen, -OR8b, -N(R8b)2, -C(O)R8b, - C(O)N(R8b)2, -N(R8b)C(O)R8b-C(O)OR8b, -OC(O)R8b, -S(O)2R8b, -NO2, =O, -CN, -N3, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle and 3- to 10-membered heterocycle. In some embodiments, for a compound or salt of Formula (I), R2is selected from: phenyl, pyridyl, pyrimidyl, pyridazinyl, pyrimidinyl, and pyrazinyl, wherein each phenyl, pyridyl, pyrimidyl, pyridazinyl, pyrimidinyl, and pyrazinyl is optionally substituted with one or more substituents independently selected from halogen, -CN, and C1-6alkyl, wherein C1-6alkyl is optionally substituted with one or more R8b. In some embodiments for a compound or salt of Formula (I),R2is selected from

[0100] In some embodiments, for a compound or salt of Formula (I), R3is selected from: hydrogen; and C1-6alkyl optionally substituted with one or more one or more substituents independently selected from R7c. In some embodiments, for a compound or salt of Formula (I), R3is selected from hydrogen, methyl, ethyl, n-propyl, and isopropyl. In some embodiments, for a compound or salt of Formula (I), R3is hydrogen.

[0101] In some embodiments, for a compound or salt of Formula (I), R4is independently selected from: hydrogen; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OC1-6alkyl, -N(C1-6alkyl)2, -C(O)C1-6alkyl, -C(O)N(C1-6alkyl)2, C2-6alkenyl, C2-6alkynyl, -CN, C3-6carbocycle, and 3- to 6-membered heterocycle, wherein the C3-6carbocycle, and 3- to 6-membered heterocycle, are each optionally substituted with one or more halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl; andR4together with R4aform a C3-10carbocycle, or 3- to 6-membered heterocycloalkyl.

[0102] In some embodiments, for a compound or salt of Formula (I), R4is independently selected from: hydrogen; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OC1-6alkyl, -N(C1-6alkyl)2, -C(O)C1-6alkyl, -C(O)N(C1-6alkyl)2, C2-6alkenyl, C2-6alkynyl, -CN, C3-6carbocycle, and 3- to 6-membered heterocycle, wherein the C3-6carbocycle, and 3- to 6-membered heterocycle, are eachoptionally substituted with one or more halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl.

[0103] In some embodiments, for a compound or salt of Formula (I), R4is independently selected from: hydrogen; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OC1-6alkyl, -N(C1-6alkyl)2, -C(O)C1-6alkyl, -C(O)N(C1-6alkyl)2, C2-6alkenyl, C2-6alkynyl, and -CN. In some embodiments, for a compound or salt of Formula (I), R4is independently selected from: hydrogen, C1-6alkyl, and C1-6haloalkyl. In some embodiments, for a compound or salt of Formula (I), R4is independently selected from: hydrogen and C1-6alkyl. In some embodiments, for a compound or salt of Formula (I), R4is hydrogen.

[0104] In some embodiments, for a compound or salt of Formula (I), R4ais independently selected from: hydrogen; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OC1-6alkyl, -N(C1-6alkyl)2, -C(O)C1-6alkyl, -C(O)N(C1-6alkyl)2, C2-6alkenyl, C2-6alkynyl, -CN, C3-6carbocycle, and 3- to 6-membered heterocycle, wherein the C3-6carbocycle, and 3- to 6-membered heterocycle, are each optionally substituted with one or more halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl; andR4together with R4aform a C3-10carbocycle, or 3- to 6-membered heterocycloalkyl.

[0105] In some embodiments, for a compound or salt of Formula (I), R4ais independently selected from: C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OC1-6alkyl, -N(C1-6alkyl)2, -C(O)C1-6alkyl, -C(O)N(C1-6alkyl)2, C2-6alkenyl, C2-6alkynyl, -CN, C3-6carbocycle, and 3- to 6-membered heterocycle, wherein the C3-6carbocycle, and 3- to 6-membered heterocycle, are each optionally substituted with one or more halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl. In some embodiments, for a compound or salt of Formula (I), R4ais C1-6alkyl optionally substituted with C3-6carbocycle. In some embodiments, for a compound or salt of Formula (I), R4ais C1-6alkyl optionally substituted with C6carbocycle. In some embodiments, for a compound or salt of Formula (I), R4ais C1-6alkyl optionally substituted with phenyl. In some embodiments, for a compound or salt of Formula (I), R4ais C1-3alkyl optionally substituted with phenyl. In some embodiments, for a compound or salt of Formula (I), R4ais methyl optionally substituted with phenyl. In someembodiments, for a compound or salt of Formula (I), R4ais. In some embodiments, for a compound or salt of Formula (I), R4ais C1-6alkyl optionally substituted with a 3- to 6-membered heterocycle. In some embodiments, for a compound or salt of Formula (I), R4ais C1-6alkyl optionally substituted with a 6-membered heterocycle. In some embodiments, for a compound or salt of Formula (I), R4ais C1-6alkyl optionally substituted with a morpholino. In some embodiments, for a compound or salt of Formula (I), R4ais C1-3alkyl optionally substituted with a morpholino. In some embodiments, for a compound or salt of Formula (I), R4ais methyl optionally substituted with a morpholino. In some embodiments, for a compound or salt ofFormula (I), R4ais

[0106] In some embodiments, for a compound or salt of Formula (I), R4together with R4aform a C3-10carbocycle, or 3- to 6-membered heterocycloalkyl. In some embodiments, for a compound or salt of Formula (I), R4together with R4aform 3- to 6-membered heterocycloalkyl. In some embodiments, for a compound or salt of Formula (I), R4together with R4aform a C3-10carbocycle. In some embodiments, for a compound or salt of Formula (I), R4together with R4aform a C3-6carbocycle, In some embodiments, for a compound or salt of Formula (I), R4together with R4aform a C3carbocycle,

[0107] In some embodiments, for a compound or salt of Formula (I), R5is independently selected from: hydrogen, C1-6alkyl, C3-6carbocycle, and 3- to 6-membered heterocycle; or R5together with R5aform a C3-10carbocycle, or 3- to 6-membered heterocycloalkyl.

[0108] In some embodiments, for a compound or salt of Formula (I), R5ais independently selected from: hydrogen, C1-6alkyl, C3-6carbocycle, and 3- to 6-membered heterocycle; or R5together with R5aform a C3-10carbocycle, or 3- to 6-membered heterocycloalkyl.

[0109] In some embodiments, for a compound or salt of Formula (I), R6is independently selected from:hydrogen, -OC1-6alkyl, -SC1-6alkyl, -N(C1-6alkyl)2, -NO2, -CN, C1-6alkyl, C2- 6 alkenyl, and C2-6alkynyl, C3-6carbocycle, and 3- to 6-membered heterocycle, wherein the C1-6alkyl, C3-10carbocycle, and 3- to 10- membered heterocycle are each optionally substituted with one or more halogen, -OC1-6alkyl, -SC1-6alkyl, -N(C1-6alkyl)2, -NO2, -CN, C1-6alkyl.

[0110] In some embodiments, for a compound or salt of Formula (I), R6is hydrogen. In some embodiments, for a compound or salt of Formula (I), R6is methyl.

[0111] In some embodiments, for a compound or salt of Formula (I), R6ais independently selected from: hydrogen, -OC1-6alkyl, -SC1-6alkyl, -N(C1-6alkyl)2, -NO2, -CN, C1-6alkyl, C2- 6 alkenyl, and C2-6alkynyl, C3-6carbocycle, and 3- to 6-membered heterocycle, wherein the C1-6alkyl, C3-10carbocycle, and 3- to 10- membered heterocycle are each optionally substituted with one or more halogen, -OC1-6alkyl, -SC1-6alkyl, -N(C1-6alkyl)2, -NO2, -CN, C1-6alkyl; orR6atogether with R5form an -O- bridge, an -NH- bridge, an -NC1-6- bridge, a C1-5alkylene bridge, or a 1- to 5-membered heteroalkylene bridge, wherein each of the C1-5alkylene bridge, or 1- to 5-membered heteroalkylene bridge is optionally substituted with one or more substituents independently selected from halogen, -OC1-6alkyl, -SC1-6alkyl, -N(C1-6alkyl)2, -C(O)C1-6alkyl, -C(O)N(C1-6alkyl)2, -N(C1-6alkyl)C(O)C1-6alkyl, -C(O)OC1-6alkyl, -OC(O)C1-6alkyl, -S(O)C1-6alkyl, -S(O)2C1-6alkyl, -NO2, =O-,=N(C1-6alkyl), -CN, -N3, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl.

[0112] In some embodiments, for a compound or salt of Formula (I), R6atogether with R5form an -O- bridge, an -NH- bridge, an -NC1-6- bridge, a C1-5alkylene bridge. In some embodiments, for a compound or salt of Formula (I), R6atogether with R5form a C1-5alkylene bridge. In some embodiments, for a compound or salt of Formula (I), R6atogether with R5form a Ci alkylene bridge. In some embodiments, for a compound or salt of Formula (I), R6atogether with R5form a C2alkylene bridge.

[0113] In some embodiments, for a compound or salt of Formula (I), R7is independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0114] In some embodiments, for a compound or salt of Formula (I), R7ais independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0115] In some embodiments, for a compound or salt of Formula (I), R7bis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0116] In some embodiments, for a compound or salt of Formula (I), R7cis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0117] In some embodiments, for a compound or salt of Formula (I), R7dis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10-membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0118] In some embodiments, for a compound or salt of Formula (I), R7eis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0119] In some embodiments, for a compound or salt of Formula (I), R7fis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0120] In some embodiments, for a compound or salt of Formula (I), R7gis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0121] In some embodiments, for a compound or salt of Formula (I), R8is independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which isoptionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0122] In some embodiments, for a compound or salt of Formula (I), R8ais independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0123] In some embodiments, for a compound or salt of Formula (I), R8bis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0124] In some embodiments, for a compound or salt of Formula (I), R8cis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0125] In some embodiments, for a compound or salt of Formula (I), R8dis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0126] In some embodiments, for a compound or salt of Formula (I), R8eis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0127] In some embodiments, for a compound or salt of Formula (I), R8fis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0128] In some embodiments, for a compound or salt of Formula (I), R8gis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0129] In some embodiments, for a compound or salt of Formula (I), the compound is selectedor a salt of any onethereof.

[0130] In an aspect, the present disclosure provides a compound represented by Formula (II):or a salt thereof, wherein:X5, X6, X7and X8are independently selected from C(R10) and N; each R10is independently selected from: hydrogen, halogen, -NO2, -CN, -N3, -OR18, -SR18, -N(R18)2, -C(O)R18, - C(O)N(R18)2, -N(R18)C(O)R18, -N(R18)C(O)N(R18)2, -OC(O)N(R18)2, - N(R18)C(O)OR18, -C(O)OR18, -OC(O)R18, -S(O)R18, and -S(O)2R18; andC1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR18, -SR18, -N(R18)2, -C(O)R18, -C(O)N(R18)2, -N(R18)C(O)R18, -C(O)OR18, - OC(O)R18, -N(R18)C(O)N(R18)2, -OC(O)N(R18)2, -N(R18)C(O)OR18, -S(O)R18, - S(O)2R18, -NO2, =O, =S, =N(R18), -CN, C3-10carbocycle and 3- to 10-membered heterocycle, wherein the C3-10carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more R17; and C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR18, -SR18, -N(R18)2, -C(O)R18, -C(O)N(R18)2, -N(R18)C(O)R18, - N(R18)C(O)N(R18)2, -OC(O)N(R18)2, -N(R18)C(O)OR18, -C(O)OR18, -OC(O)R18, - S(O)R18, -S(O)2R18, -NO2, =O-, =S, =N(R18), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R17;R11is selected from: C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR18a, -SR18a, -N(R18a)2, -C(O)R18a, -C(O)N(R18a)2, -N(R18a)C(O)R18a, -C(O)OR18a, - OC(O)R18a, -N(R18a)C(O)N(R18a)2, -OC(O)N(R18a)2, -N(R18a)C(O)OR18a, -S(O)R18a, - S(O)2R18a, -NO2, =O, =S, =N(R18a), -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with one or more R17a;R12is selected from: C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR18b, -SR18b, -N(R18b)2, -C(O)R18b, -C(O)N(R18b)2, -N(R18b)C(O)R18b-C(O)OR18b, - OC(O)R18b, -N(R18b)C(O)N(R18b)2, -OC(O)N(R18b)2, -N(R18b)C(O)OR18b, -S(O)R18b, - S(O)2R18b, -NO2, =O, =S, =N(R18b), -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with one or more R7b; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR18b, -SR18b, -N(R18b)2, -C(O)R18b, -C(O)N(R18b)2, -N(R18b)C(O)R18b- N(R18b)C(O)N(R18b)2, -OC(O)N(R18b)2, -N(R18b)C(O)OR18b, -C(O)OR18b, -OC(O)R18b, -S(O)R18b, -S(O)2R18b, -NO2, =O- =S, =N(R18b), -CN, -N3, C3-10carbocycle, and 3- to 10-membered heterocycle, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein the C3-10carbocycle, 3- to 10-membered heterocycle, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R7b; orR11together with R12form a C3-10cycloalkyl, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR18b, -SR18b, - N(R18b)2, -C(O)R18b, -C(O)N(R18b)2, -N(R18b)C(O)R18b-N(R18b)C(O)N(R18b)2, - OC(O)N(R18b)2, -N(R18b)C(O)OR18b, -C(O)OR18b, -OC(O)R18b, -S(O)R18b, -S(O)2R18b, -NO2, =O-, =S, =N(R18b), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R17b;R13is selected from: hydrogen and C1-6alkyl optionally substituted with one or more one or more R17c; andR12together with R13form a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR18c, -SR18c, - N(R18c)2, -C(O)R18c, -C(O)N(R18c)2, -N(R18c)C(O)R18c, -N(R18c)C(O)N(R18c)2, - OC(O)N(R18c)2, -N(R18c)C(O)OR18c, -C(O)OR18c, -OC(O)R18c, -S(O)R18c, -S(O)2R18c, -NO2, =O-, =S, =N(R18c), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R17c;R14is independently selected from: hydrogen, halogen, -OR18d, -SR18d, -N(R18d)2, -NO2, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR18d, -SR18d, -N(R18d)2, -NO2, and -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10- membered heterocycle, are each optionally substituted with one or more R17d;R14ais independently selected from: hydrogen, halogen, -OR18e, -SR18e, -N(R18e)2, -NO2, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR18e, -SR18e, -N(R18e)2, -NO2, and -CN, C3-10carbocycle,and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10- membered heterocycle, are each optionally substituted with one or more R17e; andR4together with R4aform a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR18e, -SR18e, - N(R18e)2, -C(O)R18e, -C(O)N(R18e)2, -N(R18e)C(O)R18e, -N(R18e)C(O)N(R18e)2, - OC(O)N(R18e)2, -N(R18e)C(O)OR18e, -C(O)OR18e, -OC(O)R18e, -S(O)R18e, -S(O)2R18e, -NO2, =O-, =S, =N(R18e), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R17e;R15is selected from: hydrogen and C1-6alkyl optionally substituted with one or more one or more R17f; each R17, R17a, R17b, R17c, R17d, R17e, and R17fis independently selected from: hydrogen, halogen, -CN, -OH, -SH, -NO2, -NH2, -O-C1-6alkyl, -S-C1-6alkyl, - N(C1-6alkyl)2, and -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10-membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl. each R18, R18a, R18b, R18c, R18d, and R18eis independently selected from: hydrogen, halogen, -CN, -OH, -SH, -NO2, -NH2, -O-C1-6alkyl, -S-C1-6alkyl, - N(C1-6alkyl)2, and -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10-membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected fromhalogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0131] In some embodiments, for a compound or salt of Formula (II), X5, X6, X7, and X8are each independently selected from C(R10). In some embodiments, for a compound or salt of Formula (II), at least one of X5, X6, X7, and X8need not be N.

[0132] In some embodiments, for a compound or salt of Formula (II), X5, X6, X7, and X8are each independently selected from C(R10) and N. In some embodiments, for a compound or salt of Formula (II), at least one of X5, X6, X7, and X8is N. In some embodiments, for a compound or salt of Formula (II), at least two of X5, X6, X7, and X8are N. In some embodiments, for a compound or salt of Formula (II), X5is N. In some embodiments, for a compound or salt of Formula (II), X6is N. In some embodiments, for a compound or salt of Formula (II), X7is N. In some embodiments, for a compound or salt of Formula (II), X8is N.

[0133] In some embodiments, for a compound or salt of Formula (II), X5, X6, X7, and X8are each independently selected from C(R10) and N. In some embodiments, for a compound or salt of Formula (II), at least one of X5, X6, X7, and X8is N. In some embodiments, for a compound or salt of Formula (II), at least two of X5, X6, X7, and X8are N. In some embodiments, for a compound or salt of Formula (II), X5is N. In some embodiments, for a compound or salt of Formula (II), X6is N. In some embodiments, for a compound or salt of Formula (II), X7is N. In some embodiments, for a compound or salt of Formula (II), X8is N.

[0134] In some embodiments, for a compound or salt of Formula (II), each R10is independently selected from: hydrogen, halogen, -NO2, -CN, -N3, -OR18, -SR18, -N(R18)2, -C(O)R18, - C(O)N(R18)2, -N(R18)C(O)R18, -OC(O)N(R18)2, -C(O)OR18, -OC(O)R18, and - S(O)2R18; C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR18, -SR18, -N(R18)2, -C(O)R18, -C(O)N(R18)2, -N(R18)C(O)R18, -C(O)OR18, - OC(O)R18, -N(R18)C(O)N(R18)2, -OC(O)N(R18)2, -N(R18)C(O)OR18, -S(O)R18, - S(O)2R18, =O, =S, -CN, C3-10 carbocycle and 3- to 10-membered heterocycle; and C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR18, -SR18, -N(R18)2, -C(O)R18, -C(O)N(R18)2, - N(R18)C(O)R18-C(O)OR18, -OC(O)R18, -N(R18)C(O)N(R18)2, -OC(O)N(R18)2, -N(R18)C(O)OR18, -S(O)R18, -S(O)2R18, =O, =S, -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more substituents independently selected from R17.

[0135] In some embodiments, for a compound or salt of Formula (II), each R10is independently selected from: hydrogen, -F, -Cl, -Br, -I, -NO2, -CN, -N3, -OR18, -SR18, -N(R18)2, -C(O)R18, - C(O)N(R18)2, -N(R18)C(O)R18, -OC(O)N(R18)2, -C(O)OR18, -OC(O)R18, and -S(O)2R18.

[0136] In some embodiments, for a compound or salt of Formula (II), each R10is independently selected from: hydrogen, -F, -Cl, -Br, -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl. In some embodiments, for a compound or salt of Formula (II), R10is selected from: methyl, ethyl, n- propyl, and isopropyl. In some embodiments, for a compound or salt of Formula (II), R10is hydrogen.

[0137] In some embodiments, for a compound or salt of Formula (II), R11is independently selected from: hydrogen;C11-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR18a, -N(R18a)2, -C(O)R18a, -C(O)N(R18a)2, -N(R18a)C(O)R18a, -C(O)OR18a, - OC(O)R18a, -CN, C3-6carbocycle, and 3- to 6-membered heterocycle, wherein the C3- 6 carbocycle, and 3- to 6-membered heterocycle, are each optionally substituted with one or more substituents independently selected from R17a; and C3-6carbocycle, and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR18a, -N(R18a)2, -C(O)R18a, -C(O)N(R18a)2, -N(R18a)C(O)R18a, -C(O)OR18a, -OC(O)R18a, -CN, C11-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein Cn-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more substituents independently selected from R17a.

[0138] In some embodiments, for a compound or salt of Formula (II), R11together with R12form a C3-6cycloalkyl, or 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR18a, -N(R18a)2, -C(O)R18a, - C(O)N(R18a)2, -N(R18a)C(O)R18a, -C(O)OR18a, -OC(O)R18a, -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more substituents independently selected from R17a.

[0139] In some embodiments, for a compound or salt of Formula (II), R11is independently selected from: methyl, ethyl, n-propyl, and isopropyl. In some embodiments, for a compound orsalt of Formula (II), R11is hydrogen. In some embodiments, for a compound or salt of Formula (II), R11is methyl.

[0140] In some embodiments, for a compound or salt of Formula (II), R12is selected from: hydrogen; C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR18b, -SR18b, -N(R18b)2, -C(O)R18b, -C(O)N(R18b)2, -C(O)OR18b, -S(O)2R18b, =O, =S, -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with one or more substituents independently selected from R17b; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR18b, -SR18b, -N(R18b)2, -C(O)R18b, -C(O)N(R18b)2, -C(O)OR18b, - S(O)2R18b, =O, =S, -CN, -N3, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, C3-10carbocycle and 3- to 10-membered heterocycle, wherein C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle and 3- to 10-membered heterocycle, are each optionally substituted with one or more substituents independently selected from R17b; orR12together with R13form a C3-10carbocycle, or 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR18b, -SR18b, -N(R18b)2, -C(O)R18b, - C(O)N(R18b)2, -C(O)OR18b, -S(O)2R18b, =O, =S, -CN, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle and 3- to 10-membered heterocycle, wherein C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle and 3- to 10-membered heterocycle, are each optionally substituted with one or more substituents independently selected from R17b;

[0141] In some embodiments, for a compound or salt of Formula (II), R12is selected from: C3-6carbocycle, and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -NH2, =O, -O-C1-6alkyl, - N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10-membered heterocycle. In some embodiments, for a compound or salt of Formula (II), R12is selected from: phenyl, pyridyl, pyrimidyl, pyridazinyl, pyrimidinyl, and pyrazinyl, wherein each phenyl, pyridyl, pyrimidyl, pyridazinyl, pyrimidinyl, and pyrazinyl is optionally substituted with one or more substituents independently selected from halogen, -CN, and C1-6alkyl. In some embodiments, for a compound or salt of Formula (II), R12is pyridyl. In some embodiments, for a compound or saltof Formula (II), R12is phenyl. In some embodiments, for a compound or salt of Formula (II), R12is. In some embodiments, for a compound or salt of Formula (II), R12is

[0142] In some embodiments, for a compound or salt of Formula (II), R13is selected from: hydrogen; and C1-6alkyl optionally substituted with one or more one or more substituents independently selected from R17c. In some embodiments, for a compound or salt of Formula (II), R13is selected from hydrogen, methyl, ethyl, n-propyl, and isopropyl. In some embodiments, for a compound or salt of Formula (II), R13is hydrogen.

[0143] In some embodiments, for a compound or salt of Formula (II), R14is selected from: hydrogen, C1-6alkyl, C3-10carbocycle, and 3- to 10-membered heterocycle. In some embodiments, for a compound or salt of Formula (II), R14is selected from: methyl, ethyl, n- propyl, and isopropyl. In some embodiments, for a compound or salt of Formula (II), R14is hydrogen.

[0144] In some embodiments, for a compound or salt of Formula (II), R14ais selected from: hydrogen, C1-6alkyl, C3-10carbocycle, and 3- to 10-membered heterocycle. In some embodiments, for a compound or salt of Formula (II), R14ais selected from: methyl, ethyl, n- propyl, and isopropyl. In some embodiments, for a compound or salt of Formula (II), R14ais hydrogen.

[0145] In some embodiments, for a compound or salt of Formula (II), R15is selected from: hydrogen; and C1-6alkyl optionally substituted with one or more one or more substituents independently selected from R17f. In some embodiments, for a compound or salt of Formula (II), R15is selected from hydrogen, methyl, ethyl, n-propyl, and isopropyl. In some embodiments, for a compound or salt of Formula (II), R15is hydrogen.

[0146] In some embodiments, for a compound or salt of Formula (II), R17is independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0147] In some embodiments, for a compound or salt of Formula (II), R17ais independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0148] In some embodiments, for a compound or salt of Formula (II), R17bis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0149] In some embodiments, for a compound or salt of Formula (II), R17cis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0150] In some embodiments, for a compound or salt of Formula (II), R17dis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10-membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0151] In some embodiments, for a compound or salt of Formula (II), R17eis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0152] In some embodiments, for a compound or salt of Formula (II), R17fis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0153] In some embodiments, for a compound or salt of Formula (II), R18is independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0154] In some embodiments, for a compound or salt of Formula (II), R18ais independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which isoptionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0155] In some embodiments, for a compound or salt of Formula (II), R18bis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0156] In some embodiments, for a compound or salt of Formula (II), R18cis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0157] In some embodiments, for a compound or salt of Formula (II), R18dis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0158] In some embodiments, for a compound or salt of Formula (II), R18eis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0159] In some embodiments, for a compound or salt of Formula (II), R18fis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0160] In some embodiments, for a compound or salt of Formula (II), the compound is selected from:

[0161] In an aspect, the present disclosure provides a compound represented by Formula (III):or a salt thereof, wherein:X9, X10, X11and X12are independently selected from C(R20) and N wherein at least one of X9, X10, X11and X12is N and no more than two of X9, X10, X11and X12are N; each R20is independently selected from: hydrogen, halogen, -NO2, -CN, -N3, -OR28, -SR28, -N(R28)2, -C(O)R28, - C(O)N(R28)2, -N(R28)C(O)R28, -N(R28)C(O)N(R28)2, -OC(O)N(R28)2, - N(R28)C(O)OR28, -C(O)OR28, -OC(O)R28, -S(O)R28, and -S(O)2R28; and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR28, -SR28, -N(R28)2, -C(O)R28, -C(O)N(R28)2, -N(R28)C(O)R28, -C(O)OR28, - OC(O)R28, -N(R28)C(O)N(R28)2, -OC(O)N(R28)2, -N(R28)C(O)OR28, -S(O)R28, - S(O)2R28, -NO2, =O, =S, =N(R28), -CN, C3-10carbocycle and 3- to 10-membered heterocycle, wherein the C3-10carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more R27; and C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR28, -SR28, -N(R28)2, -C(O)R28, -C(O)N(R28)2, -N(R28)C(O)R28, -N(R28)C(O)N(R28)2, -OC(O)N(R28)2, -N(R28)C(O)OR28, -C(O)OR28, -OC(O)R28, - S(O)R28, -S(O)2R28, -NO2, =O- =S, =N(R28), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R27;R21is selected from: C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR28a, -SR28a, -N(R28a)2, -C(O)R28a, -C(O)N(R28a)2, -N(R28a)C(O)R28a, -C(O)OR28a, - OC(O)R28a, -N(R28a)C(O)N(R28a)2, -OC(O)N(R28a)2, -N(R28a)C(O)OR28a, -S(O)R28a, - S(O)2R28a, -NO2, =O, =S, =N(R28a), -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with one or more R27a;R22is selected from: C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR28b, -SR28b, -N(R28b)2, -C(O)R28b, -C(O)N(R28b)2, -N(R28b)C(O)R28b-C(O)OR28b, - OC(O)R28b, -N(R28b)C(O)N(R28b)2, -OC(O)N(R28b)2, -N(R28b)C(O)OR28b, -S(O)R28b, - S(O)2R28b, -NO2, =O, =S, =N(R28b), -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with one or more R27b; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR28b, -SR28b, -N(R28b)2, -C(O)R28b, -C(O)N(R28b)2, -N(R28b)C(O)R28b- N(R28b)C(O)N(R28b)2, -OC(O)N(R28b)2, -N(R28b)C(O)OR28b, -C(O)OR28b, - OC(O)R28b, -S(O)R28b, -S(O)2R28b, -NO2, =O-, =S, =N(R28b), -CN, -N3, C3-10carbocycle, and 3- to 10-membered heterocycle, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R27b; orR21together with R22form a C3-10cycloalkyl, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR28b, -SR28b, -N(R28b)2, -C(O)R28b, -C(O)N(R28b)2, -N(R28b)C(O)R28b-N(R28b)C(O)N(R28b)2, - OC(O)N(R28b)2, -N(R28b)C(O)OR28b, -C(O)OR28b, -OC(O)R28b, -S(O)R28b, -S(O)2R28b, -NO2, =O-, =S, =N(R28b), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R27b;R23is selected from: hydrogen and C1-6alkyl optionally substituted with one or more one or more R27C; andR22together with R23form a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR28c, -SR28c, - N(R28c)2, -C(O)R28c, -C(O)N(R28c)2, -N(R28c)C(O)R28c, -N(R28c)C(O)N(R28c)2, - OC(O)N(R28c)2, -N(R28c)C(O)OR28c, -C(O)OR28c, -OC(O)R28c, -S(O)R28c, -S(O)2R28c, -NO2, =O-, =S, =N(R28c), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R27C;R24is independently selected from: hydrogen, halogen, -OR28d, -SR28d, -N(R28d)2, -NO2, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR28d, -SR28d, -N(R28d)2, -NO2, and -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10- membered heterocycle, are each optionally substituted with one or more R27d;R24ais independently selected from: hydrogen, halogen, -OR28e, -SR28e, -N(R28e)2, -NO2, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR28e, -SR28e, -N(R28e)2, -NO2, and -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10- membered heterocycle, are each optionally substituted with one or more R27e; andR23together with R24aform a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR28e, -SR28e, - N(R28e)2, -C(O)R28e, -C(O)N(R28e)2, -N(R28e)C(O)R28e, -N(R28e)C(O)N(R28e)2, - OC(O)N(R28e)2, -N(R28e)C(O)OR28e, -C(O)OR28e, -OC(O)R28e, -S(O)R28e, -S(O)2R28e, -NO2, =O-, =S, =N(R28e), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R27e;R25is selected from:hydrogen and C1-6alkyl optionally substituted with one or more one or more R27f; each R27, R27a, R27b, R27c, R27d, R27eand R27fis independently selected from: hydrogen, halogen, -CN, -OH, -SH, -NO2, -NH2, -O-C1-6alkyl, -S-C1-6alkyl, - N(C1-6alkyl)2, and -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10-membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl. each R28, R28a, R28b, R28c, R28d, R28eis independently selected from: hydrogen, halogen, -CN, -OH, -SH, -NO2, -NH2, -O-C1-6alkyl, -S-C1-6alkyl, - N(C1-6alkyl)2, and -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10-membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0162] In some embodiments, for a compound or salt of Formula (III), each X9, X10, X11and X12are independently selected from C(R20) and N, wherein at least one of X9, X10, X11and X12is N and no more than two of X9, X10, X11and X12are N. In some embodiments, for a compound or salt of Formula (III), X9is N. In some embodiments, for a compound or salt of Formula (III), X10is N. In some embodiments, for a compound or salt of Formula (III), X11is N. In some embodiments, for a compound or salt of Formula (III), X12is N.

[0163] In some embodiments, for a compound or salt of Formula (III), each R20is independently selected from: hydrogen;C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR28, -N(R28)2, -C(O)R28, -C(O)N(R28)2, -N(R28)C(O)R28, -C(O)OR28, -OC(O)R28, - S(O)2R28, -NO2, =O, -CN, C3-10carbocycle and 3- to 10-membered heterocycle, wherein the C3-10carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents independently selected from R27; and C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen-OR28, -N(R28)2, -C(O)R28, -C(O)N(R28)2, -N(R28)C(O)R28, -C(O)OR28, - OC(O)R28, -S(O)2R28, -NO2, =O, -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more substituents independently selected from R27.

[0164] In some embodiments, for a compound or salt of Formula (III), each R20is independently selected from: -F, -Cl, -Br, -OR28, -N(R28)2, -C(O)R28.

[0165] In some embodiments, for a compound or salt of Formula (III), each R20is independently selected from: C1-6alkyl optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -OR28, -N(R28)2, -C(O)R28; and C3-6carbocycle and 3- to 6-membered heterocycle optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -OR28, -N(R28)2, -C(O)R28.

[0166] In some embodiments, for a compound or salt of Formula (III), R21is independently selected from: hydrogen; C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR28a, -N(R28a)2, -C(O)R28a, -C(O)N(R28a)2, -N(R28a)C(O)R28a, -C(O)OR28a, - OC(O)R28a, -CN, C3-6carbocycle, and 3- to 6-membered heterocycle, wherein the C3- 6 carbocycle, and 3- to 6-membered heterocycle, are each optionally substituted with one or more substituents independently selected from R27a; and C3-6carbocycle, and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR28a, -N(R28a)2, -C(O)R28a, -C(O)N(R28a)2, -N(R28a)C(O)R28a, -C(O)OR28a, -OC(O)R28a, -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more substituents independently selected from R27a.

[0167] In some embodiments, for a compound or salt of Formula (III), R21together with R22form a C3-6cycloalkyl, or 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR28a, -N(R28a)2, -C(O)R28a, -C(O)N(R28a)2, -N(R28a)C(O)R28a, -C(O)OR28a, -OC(O)R28a, -CN, C21-6alkyl, C2-6alkenyl, and C2- 6 alkynyl, wherein C21-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more substituents independently selected from R27a.

[0168] In some embodiments, for a compound or salt of Formula (III), R21is independently selected from: methyl, ethyl, n-propyl, and isopropyl. In some embodiments, for a compound or salt of Formula (III), R21is hydrogen. In some embodiments, for a compound or salt of Formula (III), R21is methyl.

[0169] In some embodiments, for a compound or salt of Formula (III), R22is independently selected from: hydrogen; C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR28a, -N(R28a)2, -C(O)R28a, -C(O)N(R28a)2, -N(R28a)C(O)R28a, -C(O)OR28a, - OC(O)R28a, -CN, C3-6carbocycle, and 3- to 6-membered heterocycle, wherein the C3- 6 carbocycle, and 3- to 6-membered heterocycle, are each optionally substituted with one or more substituents independently selected from R27a; and C3-6carbocycle, and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR28a, -N(R28a)2, -C(O)R28a, -C(O)N(R28a)2, -N(R28a)C(O)R28a, -C(O)OR28a, -OC(O)R28a, -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more substituents independently selected from R27a.

[0170] In some embodiments, for a compound or salt of Formula (III), R22together with R23form a C3-10carbocycle, or 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR28a, - N(R28a)2, -C(O)R28a, -C(O)N(R28a)2, -N(R28a)C(O)R28a, -N(R28a)C(O)N(R28a)2, -OC(O)N(R28a)2, - N(R28a)C(O)OR28a, -C(O)OR28a, -OC(O)R28a, -S(O)2R28a, =O-,-CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more substituents independently selected from R27b.

[0171] In some embodiments, for a compound or salt of Formula (III), R22is independently selected from: C3-6carbocycle and 3- to 6-membered heterocycle, each of which is optionallysubstituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, -NH2, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10-membered heterocycle. In some embodiments, for a compound or salt of Formula (III), R12is selected from: phenyl, pyridyl, pyrimidyl, pyridazinyl, pyrimidinyl, and pyrazinyl, wherein each phenyl, pyridyl, pyrimidyl, pyridazinyl, pyrimidinyl, and pyrazinyl is optionally substituted with one or more substituents independently selected from halogen, -CN, and C1-6alkyl. In some embodiments, for a compound or salt of Formula (III), R22is pyrimidyl. In some embodiments, for a compound or salt of Formula (III), R12is pyridyl. In some embodiments, for a compound or salt of Formula (II), R12is phenyl. In some embodiments, for a compound or salt of Formula(III), R22is

[0172] In some embodiments, for a compound or salt of Formula (III), R23is selected from: hydrogen; and C1-6alkyl optionally substituted with one or more one or more substituents independently selected from R27c. In some embodiments, for a compound or salt of Formula (III), R23is selected from hydrogen, methyl, ethyl, n-propyl, and isopropyl. In some embodiments, for a compound or salt of Formula (III), R23is hydrogen.

[0173] In some embodiments, for a compound or salt of Formula (III), R24is selected from: hydrogen, C1-6alkyl, C3-10carbocycle, and 3- to 10-membered heterocycle. In some embodiments, for a compound or salt of Formula (III), R24is selected from: methyl, ethyl, n- propyl, and isopropyl. In some embodiments, for a compound or salt of Formula (III), R24is hydrogen.

[0174] In some embodiments, for a compound or salt of Formula (III), R24ais selected from: hydrogen, C1-6alkyl, C3-10carbocycle, and 3- to 10-membered heterocycle. In some embodiments, for a compound or salt of Formula (III), R24ais selected from: methyl, ethyl, n- propyl, and isopropyl. In some embodiments, for a compound or salt of Formula (III), R24ais hydrogen.

[0175] In some embodiments, for a compound or salt of Formula (III), R25is selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, C3-6carbocycle, and 3- to 6-membered heterocycle. In some embodiments, for a compound or salt of Formula (III), R25is methyl. In some embodiments, for a compound or salt of Formula (III), R25is hydrogen.

[0176] In some embodiments, for a compound or salt of Formula (III), R26is selected from: hydrogen, methyl, ethyl, n-propyl, and isopropyl. In some embodiments, for a compound or salt of Formula (III), R26is methyl. In some embodiments, for a compound or salt of Formula (III), R26is hydrogen.

[0177] In some embodiments, for a compound or salt of Formula (III), R27is independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0178] In some embodiments, for a compound or salt of Formula (III), R27ais independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0179] In some embodiments, for a compound or salt of Formula (III), R27bis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0180] In some embodiments, for a compound or salt of Formula (III), R27cis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0181] In some embodiments, for a compound or salt of Formula (III), R27dis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0182] In some embodiments, for a compound or salt of Formula (III), R27eis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0183] In some embodiments, for a compound or salt of Formula (III), R27fis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0184] In some embodiments, for a compound or salt of Formula (III), R28is independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10-membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0185] In some embodiments, for a compound or salt of Formula (III), R28ais independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0186] In some embodiments, for a compound or salt of Formula (III), R28bis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0187] In some embodiments, for a compound or salt of Formula (III), R28cis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0188] In some embodiments, for a compound or salt of Formula (III), R28dis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which isoptionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0189] In some embodiments, for a compound or salt of Formula (III), R28eis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0190] In some embodiments, for a compound or salt of Formula (III), the compound is selected from:or a salt of any one thereof.

[0191] In an aspect, the present disclosure provides a compound represented by Formula (IV):or a salt thereof, wherein:X13, X14, X15, X16and X17are independently selected from C(R32) and N wherein at least one of X13, X14, X15, X16and X17is N; n is selected from 1, 2, 3, and 4; each R30is independently selected from: hydrogen, halogen, -NO2, -CN, -N3, -OR38, -SR38, -N(R38)2, -C(O)R38, - C(O)N(R38)2, -N(R38)C(O)R38, -N(R38)C(O)N(R38)2, -OC(O)N(R38)2, - N(R38)C(O)OR38, -C(O)OR38, -OC(O)R38, -S(O)R38, and -S(O)2R38; and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR38, -SR38, -N(R38)2, -C(O)R38, -C(O)N(R38)2, -N(R38)C(O)R38, -C(O)OR38, - OC(O)R38, -N(R38)C(O)N(R38)2, -OC(O)N(R38)2, -N(R38)C(O)OR38, -S(O)R38, - S(O)2R38, -NO2, =O, =S, =N(R38), -CN, C3-10carbocycle and 3- to 10-membered heterocycle, wherein the C3-10carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more R371; and C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR38, -SR38, -N(R38)2, -C(O)R38, -C(O)N(R38)2, -N(R38)C(O)R38, - N(R38)C(O)N(R38)2, -OC(O)N(R38)2, -N(R38)C(O)OR38, -C(O)OR38, -OC(O)R38, - S(O)R38, -S(O)2R38, -NO2, =O-, =S, =N(R38), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R371;R31is selected from: C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR38a, -SR38a, -N(R38a)2, -C(O)R38a, -C(O)N(R38a)2, -N(R38a)C(O)R38a, -C(O)OR38a, - OC(O)R38a, -N(R38a)C(O)N(R38a)2, -OC(O)N(R38a)2, -N(R38a)C(O)OR38a, -S(O)R38a, - S(O)2R38a, -NO2, =O, =S, =N(R38a), -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with one or more R37'; each R32is independently selected from: hydrogen, halogen, -NO2, -CN, -N3, -OR38b, -SR38b, -N(R38b)2, -C(O)R38b, - C(O)N(R38b)2, -N(R38b)C(O)R38b-N(R38b)C(O)N(R38b)2, -OC(O)N(R38b)2, - N(R38b)C(O)OR38b, -C(O)OR38b, -OC(O)R38b, -S(O)R38b, and -S(O)2R38b; andC1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR38b, -SR38b, -N(R38b)2, -C(O)R38b, -C(O)N(R38b)2, -N(R38b)C(O)R38b-C(O)OR38b, - OC(O)R38b, -N(R38b)C(O)N(R38b)2, -OC(O)N(R38b)2, -N(R38b)C(O)OR38b, -S(O)R38b, - S(O)2R38b, -NO2, =O, =S, =N(R38b), -CN, C3-10carbocycle and 3- to 10-membered heterocycle, wherein the C3-10carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more R37b; and C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR38b, -SR38b, -N(R38b)2, -C(O)R38b, -C(O)N(R38b)2, -N(R38b)C(O)R38b- N(R38b)C(O)N(R38b)2, -OC(O)N(R38b)2, -N(R38b)C(O)OR38b, -C(O)OR38b, - OC(O)R38b, -S(O)R38b, -S(O)2R38b, -NO2, =O-, =S, =N(R38b), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R37b;R33is selected from: hydrogen and C1-6alkyl optionally substituted with one or more one or moreR37C;R34is independently selected from: hydrogen, halogen, -OR38c, -SR38c, -N(R38c)2, -NO2, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR38c, -SR38c, -N(R38c)2, -NO2, and -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10- membered heterocycle, are each optionally substituted with one or more R37d;R34ais independently selected from: hydrogen, halogen, -OR38d, -SR38d, -N(R38d)2, -NO2, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR38d, -SR38d, -N(R38d)2, -NO2, and -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10- membered heterocycle, are each optionally substituted with one or more R37e; andR34together with R34aform a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR38d, -SR38d, -N(R38d)2, -C(O)R38d, -C(O)N(R38d)2, -N(R38d)C(O)R38d-N(R38d)C(O)N(R38d)2, - OC(O)N(R38d)2, -N(R38d)C(O)OR38d, -C(O)OR38d, -OC(O)R38d, -S(O)R38d, -S(O)2R38d,-NO2, =O- =S, =N(R38d), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R37e; each R35and R35ais independently selected from: hydrogen, halogen, -OR38e, -SR38e, -N(R38e)2, -NO2, -CN, C1-6alkyl, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C1-6alkyl, C3-10carbocycle, and 3- to 10- membered heterocycle are each optionally substituted with one or more R37f; orR35together with R35aform a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR38e, -SR38e, - N(R38e)2, -C(O)R38e, -C(O)N(R38e)2, -N(R38e)C(O)R38e, -N(R38e)C(O)N(R38e)2, - OC(O)N(R38e)2, -N(R38e)C(O)OR38e, -C(O)OR38e, -OC(O)R38e, -S(O)R38e, -S(O)2R38e, -NO2, =O-, =S, =N(R38e), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R37f; each R36and R36ais independently selected from: hydrogen, halogen, -OR38f, -SR38f, -N(R38f)2, -NO2, -CN, C1-6alkyl, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C1-6alkyl, C3-10carbocycle, and 3- to 10- membered heterocycle are each optionally substituted with one or more R37g; orR36together with R36aform a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR38f, -SR38f, - N(R38f)2, -C(O)R38f, -C(O)N(R38f)2, -N(R38f)C(O)R38f, -N(R38f)C(O)N(R38f)2, - OC(O)N(R38f)2, -N(R38f)C(O)OR38f, -C(O)OR38f, -OC(O)R38f, -S(O)R38f, -S(O)2R38f, - NO2, =O-, =S, =N(R38f), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R37g; each R37and R37ais independently selected from: hydrogen, halogen, -OR38g, -SR38g, -N(R38g)2, -NO2, -CN, C1-6alkyl, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C1-6alkyl, C3-10carbocycle, and 3- to 10- membered heterocycle are each optionally substituted with one or more R37h; orR37together with R37aform a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR38g, -SR38g, - N(R38g)2, -C(O)R38g, -C(O)N(R38g)2, -N(R38g)C(O)R38g-N(R38g)C(O)N(R38g)2, - OC(O)N(R38g)2, -N(R38g)C(O)OR38g, -C(O)OR38g, -OC(O)R38g, -S(O)R38g, -S(O)2R38g, -NO2, =O-, =S, =N(R38g), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R37h; each R371, R37->, R37b, R37c, R37d, R37e, R37f, R37g, and R37his independently selected from: hydrogen, halogen, -CN, -OH, -SH, -NO2, -NH2, -O-C1-6alkyl, -S-C1-6alkyl, - N(C1-6alkyl)2, and -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10-membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl; each R38, R38a, R38b, R38c, R38d, R38e, R38f, and R38gis independently selected from: hydrogen, halogen, -CN, -OH, -SH, -NO2, -NH2, -O-C1-6alkyl, -S-C1-6alkyl, - N(C1-6alkyl)2, and -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10-membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0192] In some embodiments, for a compound or salt of Formula (IV), n is selected from 1, 2, and 3. In some embodiments, for a compound or salt of Formula (IV), n is 1. In someembodiments, for a compound or salt of Formula (IV), n is 2. In some embodiments, for a compound or salt of Formula (IV), n is 3.

[0193] In some embodiments, for a compound or salt of Formula (IV), X13, X14, X15, X16, and X17are each independently selected from C(R32) and N. In some embodiments, for a compound or salt of Formula (IV), at least one of X13, X14, X15, X16, and X17is N. In some embodiments, for a compound or salt of Formula (IV), at least two of X13, X14, X15, X16, and X17are N. In some embodiments, for a compound or salt of Formula (IV), X13is N. In some embodiments, for a compound or salt of Formula (IV), X14is N. In some embodiments, for a compound or salt of Formula (IV), X15is N. In some embodiments, for a compound or salt of Formula (IV), X16is N. In some embodiments, for a compound or salt of Formula (IV), X17is N. In some embodiments, for a compound or salt of Formula (IV), both X13and X14are N. In some embodiments, for a compound or salt of Formula (IV), both X13and X15are N. In some embodiments, for a compound or salt of Formula (IV), both X13and X16are N. In some embodiments, for a compound or salt of Formula (IV), both X13and X17are N.

[0194] In some embodiments, for a compound or salt of Formula (IV), each R30is independently selected from: hydrogen; C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR38, -N(R38)2, -C(O)R38, -C(O)N(R38)2, -N(R38)C(O)R38, -C(O)OR38, -OC(O)R38, - S(O)2R38, -NO2, =O, -CN, C3-10carbocycle and 3- to 10-membered heterocycle, wherein the C3-10carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents independently selected from R371; and C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen-OR38, -N(R38)2, -C(O)R38, -C(O)N(R38)2, -N(R38)C(O)R38, -C(O)OR38, - OC(O)R38, -S(O)2R38, -NO2, =O, -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more substituents independently selected from R371.

[0195] In some embodiments, for a compound or salt of Formula (IV), each R30is independently selected from: C1-6alkyl optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -OR38, -N(R38)2, -C(O)R38; and C3-6carbocycle and 3- to 6-membered heterocycle optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -OR38, -N(R38)2, -C(O)R38.

[0196] In some embodiments, for a compound or salt of Formula (IV), R31is independently selected from: C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR38a, -SR38a, -N(R38a)2, -C(O)R38a, -C(O)N(R38a)2, -N(R38a)C(O)R38a, -C(O)OR38a, - OC(O)R38a, -N(R38a)C(O)N(R38a)2, -OC(O)N(R38a)2, -N(R38a)C(O)OR38a, -S(O)R38a, - S(O)2R38a, -NO2, =O, =S, =N(R38a), -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with one or more R37'.

[0197] In some embodiments, for a compound or salt of Formula (IV), R31is independently selected from: methyl, ethyl, n-propyl, and isopropyl. In some embodiments, for a compound or salt of Formula (IV), R31is methyl.

[0198] In some embodiments, for a compound or salt of Formula (IV), each R32is independently selected from: hydrogen; C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR38b, -N(R38b)2, -C(O)R38b, -C(O)N(R38b)2, -N(R38b)C(O)R38b-C(O)OR38b, - OC(O)R38b, -S(O)2R38b, -NO2, =O, -CN, C3-10carbocycle and 3- to 10-membered heterocycle, wherein the C3-10carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents independently selected from R37b; and C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen-OR38b, -N(R38b)2, -C(O)R38b, -C(O)N(R38b)2, -N(R38b)C(O)R38b-C(O)OR38b, - OC(O)R38b, -S(O)2R38b, -NO2, =O, -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more substituents independently selected from R37b.

[0199] In some embodiments, for a compound or salt of Formula (IV), each R32is independently selected from: C1-6alkyl optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -OR38b, -N(R38b)2, -C(O)R38b; and C3-6carbocycle and 3- to 6- membered heterocycle optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -OR38b, -N(R38b)2, -C(O)R38b. In some embodiments, for a compoundor salt of Formula (IV), R32is -F. In some embodiments, for a compound or salt of Formula (IV), R32is -CN.

[0200] In some embodiments, for a compound or salt of Formula (IV), R33is selected from: hydrogen; and C1-6alkyl optionally substituted with one or more one or more substituents independently selected from R37c. In some embodiments, for a compound or salt of Formula (IV), R33is selected from hydrogen, methyl, ethyl, n-propyl, and isopropyl. In some embodiments, for a compound or salt of Formula (IV), R33is hydrogen.

[0201] In some embodiments, for a compound or salt of Formula (IV), R34is selected from: hydrogen, C1-6alkyl, C3-10carbocycle, and 3- to 10-membered heterocycle. In some embodiments, for a compound or salt of Formula (IV), R34is selected from: methyl, ethyl, n- propyl, and isopropyl. In some embodiments, for a compound or salt of Formula (IV), R34is hydrogen.

[0202] In some embodiments, for a compound or salt of Formula (IV), R34ais selected from: hydrogen, C1-6alkyl, C3-10carbocycle, and 3- to 10-membered heterocycle. In some embodiments, for a compound or salt of Formula (IV), R34ais selected from: methyl, ethyl, n- propyl, and isopropyl. In some embodiments, for a compound or salt of Formula (IV), R34ais hydrogen.

[0203] In some embodiments, for a compound or salt of Formula (IV), R34together with R34aform a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl. In some embodiments, for a compound or salt of Formula (IV), R34together with R34aform a C3-6carbocycle, or 3- to 6- membered heterocycloalkyl. In some embodiments, for a compound or salt of Formula (IV), R34and R34aform a C3carbocycle. In some embodiments, for a compound or salt of Formula (IV), R34and R34aform a C4 carbocycle. In some embodiments, for a compound or salt of Formula (IV), R34and R34aform a C5carbocycle. In some embodiments, for a compound or salt of Formula (IV), R34and R34aform a C6carbocycle.

[0204] In some embodiments, for a compound or salt of Formula (IV), R35is independently selected from: methyl, ethyl, n-propyl, and isopropyl. In some embodiments, for a compound or salt of Formula (IV), R35is hydrogen. In some embodiments, for a compound or salt of Formula (IV), R35is methyl.

[0205] In some embodiments, for a compound or salt of Formula (IV), R35ais independently selected from: methyl, ethyl, n-propyl, and isopropyl. In some embodiments, for a compound or salt of Formula (IV), R35ais hydrogen. In some embodiments, for a compound or salt of Formula (IV), R35ais methyl.

[0206] In some embodiments, for a compound or salt of Formula (IV), R35together with R35aform a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl. In some embodiments, for a compound or salt of Formula (IV), R35together with R35aform a C3-10carbocycle. In some embodiments, for a compound or salt of Formula (IV), R35together with R35aform a 3- to 10- membered heterocycloalkyl.

[0207] In some embodiments, for a compound or salt of Formula (IV), R35together with R35aform a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR38e, -SR38e, - N(R38e)2, -C(O)R38e, -C(O)N(R38e)2, -N(R38e)C(O)R38e, -N(R38e)C(O)N(R38e)2, -OC(O)N(R38e)2, - N(R38e)C(O)OR38e, -C(O)OR38e, -OC(O)R38e, -S(O)R38e, -S(O)2R38e, -NO2, =O-, =S, =N(R38e), - CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R37f. In some embodiments, for a compound or salt of Formula (IV), R35together with R35aform a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR38e, -SR38e, -N(R38e)2, -C(O)R38e, -C(O)N(R38e)2, -CN, C1-6alkyl, and C1-6haloalkyl. In some embodiments, for a compound or salt of Formula (IV), R35together with R35aform a C3-10carbocycle. In some embodiments, for a compound or salt of Formula (IV), R35together with R35aform a C3-6carbocycle. In some embodiments, for a compound or salt of Formula (IV), R35together with R35aform a C3carbocycle.

[0208] In some embodiments, for a compound or salt of Formula (IV), R36is independently selected from: methyl, ethyl, n-propyl, and isopropyl. In some embodiments, for a compound or salt of Formula (IV), R36is hydrogen. In some embodiments, for a compound or salt of Formula (IV), R36is methyl.

[0209] In some embodiments, for a compound or salt of Formula (IV), R36ais independently selected from: methyl, ethyl, n-propyl, and isopropyl. In some embodiments, for a compound or salt of Formula (IV), R36ais hydrogen. In some embodiments, for a compound or salt of Formula (IV), R36ais methyl.

[0210] In some embodiments, for a compound or salt of Formula (IV), R36together with R36aform a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl.

[0211] In some embodiments, for a compound or salt of Formula (IV), R37is independently selected from: methyl, ethyl, n-propyl, and isopropyl. In some embodiments, for a compound or salt of Formula (IV), R37is hydrogen. In some embodiments, for a compound or salt of Formula (IV), R37is methyl.

[0212] In some embodiments, for a compound or salt of Formula (IV), R37ais independently selected from: methyl, ethyl, n-propyl, and isopropyl. In some embodiments, for a compound or salt of Formula (IV), R37ais hydrogen. In some embodiments, for a compound or salt of Formula (IV), R37ais methyl.

[0213] In some embodiments, for a compound or salt of Formula (IV), R37together with R37aform a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl.

[0214] In some embodiments, for a compound or salt of Formula (IV), R371is independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0215] In some embodiments, for a compound or salt of Formula (IV), R37' is independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0216] In some embodiments, for a compound or salt of Formula (IV), R37bis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0217] In some embodiments, for a compound or salt of Formula (IV), R37cis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0218] In some embodiments, for a compound or salt of Formula (IV), R37dis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0219] In some embodiments, for a compound or salt of Formula (IV), R37eis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0220] In some embodiments, for a compound or salt of Formula (IV), R37fis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0221] In some embodiments, for a compound or salt of Formula (IV), R37gis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0222] In some embodiments, for a compound or salt of Formula (IV), R37his independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0223] In some embodiments, for a compound or salt of Formula (IV), each R38, R38a, R38b, R38c, R38d, R38e, R38f, and R38gis independently selected from hydrogen, halogen, -CN, -OH, -NH2, and -O-CH3.

[0224] In some embodiments, for a compound or salt of Formula (IV), R38is independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0225] In some embodiments, for a compound or salt of Formula (IV), R38ais independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0226] In some embodiments, for a compound or salt of Formula (IV), R38bis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0227] In some embodiments, for a compound or salt of Formula (IV), R38cis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0228] In some embodiments, for a compound or salt of Formula (IV), R38dis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0229] In some embodiments, for a compound or salt of Formula (IV), R38eis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0230] In some embodiments, for a compound or salt of Formula (IV), R38fis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0231] In some embodiments, for a compound or salt of Formula (IV), R38gis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0232] In some embodiments, for a compound or salt of Formula (IV), the compound is selected from:or a salt of any one thereof.

[0233] In an aspect, the present disclosure provides a compound represented by Formula (V): compound represented by Formula (V):or a salt thereof, wherein:XA, XB, Xcand XDare independently selected from C(R40) and N; each R40is independently selected from: hydrogen, halogen, -NO2, -CN, -N3, -OR48, -SR48, -N(R48)2, -C(O)R48, - C(O)N(R48)2, -N(R48)C(O)R48, -N(R48)C(O)N(R48)2, -OC(O)N(R48)2, - N(R48)C(O)OR48, -C(O)OR48, -OC(O)R48, -S(O)R48, and -S(O)2R48; andC1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR48, -SR48, -N(R48)2, -C(O)R48, -C(O)N(R48)2, -N(R48)C(O)R48, -C(O)OR48, - OC(O)R48, -N(R48)C(O)N(R48)2, -OC(O)N(R48)2, -N(R48)C(O)OR48, -S(O)R48, - S(O)2R48, -NO2, =O, =S, =N(R48), -CN, C3-10carbocycle and 3- to 10-membered heterocycle, wherein the C3-10carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more R47; and C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR48, -SR48, -N(R48)2, -C(O)R48, -C(O)N(R48)2, -N(R48)C(O)R48, - N(R48)C(O)N(R48)2, -OC(O)N(R48)2, -N(R48)C(O)OR48, -C(O)OR48, -OC(O)R48, - S(O)R48, -S(O)2R48, -NO2, =O-, =S, =N(R48), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R47;R41is selected from: halogen, -NO2, -CN, -N3, -OR48a, -SR48a, -N(R48a)2, -C(O)R48a, -C(O)N(R48a)2, -N(R48a)C(O)R48a-N(R48a)C(O)N(R48a)2, -OC(O)N(R48a)2, - N(R48a)C(O)OR48a, -C(O)OR48a, -OC(O)R48a, -S(O)R48a, and -S(O)2R48a; and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR48a, -SR48a, -N(R48a)2, -C(O)R48a, -C(O)N(R48a)2, -N(R48a)C(O)R48a, -C(O)OR48a, - OC(O)R48a, -N(R48a)C(O)N(R48a)2, -OC(O)N(R48a)2, -N(R48a)C(O)OR48a, -S(O)R48a, - S(O)2R48a, -NO2, =O, =S, =N(R48a), -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with one or more R47a;R42is selected from: C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR48b, -SR48b, -N(R48b)2, -C(O)R48b, -C(O)N(R48b)2, -N(R48b)C(O)R48b-C(O)OR48b, - OC(O)R48b, -N(R48b)C(O)N(R48b)2, -OC(O)N(R48b)2, -N(R48b)C(O)OR48b, -S(O)R48b, - S(O)2R48b, -NO2, =O, =S, =N(R48b), -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with one or more R47b; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR48b, -SR48b, -N(R48b)2, -C(O)R48b, -C(O)N(R48b)2, -N(R48b)C(O)R48b-N(R48b)C(O)N(R48b)2, -OC(O)N(R48b)2, -N(R48b)C(O)OR48b, -C(O)OR48b, - OC(O)R48b, -S(O)R48b, -S(O)2R48b, -NO2, =O- =S, =N(R48b), -CN, -N3, C3-10carbocycle, and 3- to 10-membered heterocycle, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein the C3-10carbocycle, 3- to 10-membered heterocycle, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R47b; or R41together with R42form a C3-10cycloalkyl, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR48b, -SR48b, - N(R48b)2, -C(O)R48b, -C(O)N(R48b)2, -N(R48b)C(O)R48b-N(R48b)C(O)N(R48b)2, - OC(O)N(R48b)2, -N(R48b)C(O)OR48b, -C(O)OR48b, -OC(O)R48b, -S(O)R48b, -S(O)2R48b, -NO2, =O-, =S, =N(R48b), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R47b;R43is selected from: hydrogen and C1-6alkyl optionally substituted with one or more one or more R47C; andR42together with R43form a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR48c, -SR48c, - N(R48c)2, -C(O)R48c, -C(O)N(R48c)2, -N(R48c)C(O)R48c, -N(R48c)C(O)N(R48c)2, - OC(O)N(R48c)2, -N(R48c)C(O)OR48c, -C(O)OR48c, -OC(O)R48c, -S(O)R48c, -S(O)2R48c, -NO2, =O-, =S, =N(R48c), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R47C;R44is independently selected from: hydrogen, halogen, -OR48d, -SR48d, -N(R48d)2, -NO2, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR48d, -SR48d, -N(R48d)2, -NO2, and -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10- membered heterocycle, are each optionally substituted with one or more R47d;R44ais independently selected from: hydrogen, halogen, -OR48e, -SR48e, -N(R48e)2, -NO2, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR48e, -SR48e, -N(R48e)2, -NO2, and -CN, C3-10carbocycle,and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10- membered heterocycle, are each optionally substituted with one or more R47e; andR44together with R44aform a C3-10 carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR48e, -SR48e, - N(R48e)2, -C(O)R48e, -C(O)N(R48e)2, -N(R48e)C(O)R48e, -N(R48e)C(O)N(R48e)2, - OC(O)N(R48e)2, -N(R48e)C(O)OR48e, -C(O)OR48e, -OC(O)R48e, -S(O)R48e, -S(O)2R48e, -NO2, =O-, =S, =N(R48e), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R47e;R45is selected independently from: hydrogen, halogen, -NO2, -CN, -N3, - OR48f, -SR48f, -N(R48f)2, -C(O)R48f, -C(O)N(R48f)2, -N(R48f)C(O)R48f, - N(R48f)C(O)N(R48f)2, -OC(O)N(R48f)2, -N(R48f)C(O)OR48f, -C(O)OR48f, -OC(O)R48f, - S(O)R48f, and -S(O)2R48f; and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR48f, -SR48f, -N(R48f)2, -C(O)R48f, -C(O)N(R48f)2, -N(R48f)C(O)R48f, -C(O)OR48f, - OC(O)R48f, -N(R48f)C(O)N(R48f)2, -OC(O)N(R48f)2, -N(R48f)C(O)OR48f, -S(O)R48f, - S(O)2R48f, -NO2, =O, =S, =N(R48f), -CN, C3-10carbocycle and 3- to 10-membered heterocycle, wherein the C3-10carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more R47f; and C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR48f, -SR48f, -N(R48f)2, -C(O)R48f, -C(O)N(R48f)2, -N(R48f)C(O)R48f, - N(R48f)C(O)N(R48f)2, -OC(O)N(R48f)2, -N(R48f)C(O)OR48f, -C(O)OR48f, -OC(O)R48f, - S(O)R48f, -S(O)2R48f, -NO2, =O-, =S, =N(R48f), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R47f; each R46and R46ais selected independently from: hydrogen, halogen, -OR48g, -SR48g, -N(R48g)2, -NO2, -CN, C1-6alkyl, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C1-6alkyl, C3-10carbocycle, and 3- to 10- membered heterocycle are each optionally substituted with one or more R47g; orR46together with R45form an -O- bridge, an -NR7g- bridge, a C1-5alkylene bridge, or a 1- to 5-membered heteroalkylene bridge, wherein each of the C1-5alkylene bridge, or 1- to 5-membered heteroalkylene bridge is optionally substituted with one or more substituents independently selected from halogen, -OR48g, -SR48g, - N(R48g)2, -C(O)R48g, -C(O)N(R48g)2, -N(R48g)C(O)R48g-N(R48g)C(O)N(R48g)2, - OC(O)N(R48g)2, -N(R48g)C(O)OR48g, -C(O)OR48g, -OC(O)R48g, -S(O)R48g, -S(O)2R48g, -NO2, =O-, =S, =N(R48g), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R47g; each R47, R47a, R47b, R47c, R47d, R47e, R47f, and R47gis independently selected from: hydrogen, halogen, -CN, -OH, -SH, -NO2, -NH2, -O-C1-6alkyl, -S-C1-6alkyl, - N(C1-6alkyl)2, and -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10-membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl; each R48, R48a, R48b, R48c, R48d, R48e, R48f, and R48gis independently selected from: hydrogen, halogen, -CN, -OH, -SH, -NO2, -NH2, -O-C1-6alkyl, -S-C1-6alkyl, - N(C1-6alkyl)2, and -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10-membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0234] In some embodiments, for a compound or salt of Formula (V), XA, XB, Xcand XDare each independently selected from C(R40) and N. In some embodiments, for a compound or salt of Formula (V), at least one of XA, XB, Xcand XDis N. In some embodiments, for a compound or salt of Formula (V), at least two of XA, XB, Xcand XDis N. In some embodiments, for a compound or salt of Formula (V), XBis N. In some embodiments, for a compound or salt of Formula (V), XAis N In some embodiments, for a compound or salt of Formula (V), Xcis N In some embodiments, for a compound or salt of Formula (V), XDis N. In some embodiments, for a compound or salt of Formula (V), XA, XB, and Xcare each C(R40).

[0235] In some embodiments, for a compound or salt of Formula (V), R40is independently selected from: hydrogen; C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR48, -SR48, -N(R48)2, -C(O)R48, -C(O)N(R48)2, -N(R48)C(O)R48, -C(O)OR48, - OC(O)R48, -S(O)2R48, -NO2, =O, -CN, C3-10carbocycle and 3- to 10-membered heterocycle, wherein the C3-10carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more R47; and C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR48, -SR48, -N(R48)2, -C(O)R48, -C(O)N(R48)2, - N(R48)C(O)R48-C(O)OR48, -OC(O)R48, -S(O)2R48, -NO2, =O-,-CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R47.

[0236] In some embodiments, for a compound or salt of Formula (V), R40is independently selected from hydrogen, halogen, -NO2, -CN, -OR48, -SR48, -N(R48)2, -C(O)R48, -C(O)OR48, C1-6alkyl, and C1-6haloalkyl. In some embodiments, for a compound or salt of Formula (V), each R40is independently selected from hydrogen, halogen, and methyl. In some embodiments, for a compound or salt of Formula (V), each R40is independently selected from hydrogen and methyl.

[0237] In some embodiments, for a compound or salt of Formula (V), R41is selected from: halogen, -NO2, -CN, -N3, -OR48a, -SR48a, -N(R48a)2, -C(O)R48a, -C(O)N(R48a)2, -N(R48a)C(O)R48a-C(O)OR48a, -OC(O)R48a, and -S(O)2R48a; and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR48a, -SR48a, -N(R48a)2, -C(O)R48a, -C(O)N(R48a)2, -N(R48a)C(O)R48a, -C(O)OR48a, -OC(O)R48a, -S(O)2R48a, -NO2, =O, -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with one or more R47a;

[0238] In some embodiments, for a compound or salt of Formula (V), R41is selected from: C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR48a, -SR48a, -N(R48a)2, -C(O)R48a, -C(O)N(R48a)2, -N(R48a)C(O)R48a, -C(O)OR48a, - OC(O)R48a, -S(O)2R48a, -NO2, =O, and -CN.

[0239] In some embodiments, for a compound or salt of Formula (V), R41is selected from: methyl, ethyl, n-propyl, and isopropyl. In some embodiments, for a compound or salt of Formula (V), R41is methyl.

[0240] In some embodiments, for a compound or salt of Formula (V), R42is selected from: C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR48b, -SR48b, -N(R48b)2, -C(O)R48b, -C(O)N(R48b)2, -N(R48b)C(O)R48b-C(O)OR48b, - OC(O)R48b, -S(O)2R48b, -NO2, =O, -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with one or more R47b; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR48b, -SR48b, -N(R48b)2, -C(O)R48b, -C(O)N(R48b)2, - N(R48b)C(O)R48b-C(O)OR48b, -OC(O)R48b, -S(O)2R48b, -NO2, =O-, -CN, -N3, C3-10carbocycle, and 3- to 10-membered heterocycle, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein the C3-10carbocycle, 3- to 10-membered heterocycle, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R47b; orR41together with R42form a C3-10cycloalkyl, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR48b, -SR48b, -N(R48b)2, -C(O)R48b, -C(O)N(R48b)2, -N(R48b)C(O)R48b-C(O)OR48b, -OC(O)R48b, - S(O)2R48b, -NO2, =O-,-CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R47b.

[0241] In some embodiments, for a compound or salt of Formula (V), R42is selected from:C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR48b, -SR48b, -N(R48b)2, -C(O)R48b, -C(O)N(R48b)2, - N(R48b)C(O)R48b-C(O)OR48b, -OC(O)R48b, -S(O)2R48b, -NO2, =O-, -CN, -N3, C3-10carbocycle, and 3- to 10-membered heterocycle, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein the C3-10carbocycle, 3- to 10-membered heterocycle, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R47b; or R41together with R42form a C3-10cycloalkyl, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR48b, -SR48b, - N(R48b)2, -C(O)R48b, -C(O)N(R48b)2, -N(R48b)C(O)R48b-C(O)OR48b, -OC(O)R48b, - S(O)2R48b, -NO2, =O-,-CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R47b

[0242] In some embodiments, for a compound or salt of Formula (V), R42is selected from: C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, - OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10- membered heterocycle, and C1-6haloalkyl; orR41together with R42form a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, halogen, -OC1-6alkyl, -SC1-6alkyl, -N(C1-6alkyl)2, -C(O)C1-6alkyl, -C(O)N(C1-6alkyl)2, -N(C1-6alkyl)C(O)C1-6alkyl, -C(O)OC1-6alkyl, -OC(O)C1-6alkyl, -S(O)C1-6alkyl, -S(O)2C1-6alkyl, -NO2, =O-,=N(C1-6alkyl), - CN, -N3, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl.

[0243] In some embodiments, for a compound or salt of Formula (V), R42is selected from: C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, - OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10- membered heterocycle, and C1-6haloalkyl.

[0244] In some embodiments, for a compound or salt of Formula (V), R42is selected from 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituentsindependently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0245] In some embodiments, for a compound or salt of Formula (V), R42is selected from 5- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0246] In some embodiments, for a compound or salt of Formula (V), R42is pyridinyl optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - OCH3, -C(O)OMe, -CN, -N3, methyl, ethyl, propyl, and isopropyl. In some embodiments, for a compound or salt of Formula (V), R42is pyridinyl optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -OCH3, -CN, methyl, and ethyl. In some embodiments, for a compound or salt of Formula (V), R42is pyridinyl optionally substituted with one or more substituents independently selected from -F, and -CN.

[0247] In some embodiments, for a compound or salt of Formula (V), R42isoptionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - OCH3, -C(O)OMe, -CN, -N3, methyl, ethyl, propyl, and isopropyl. In some embodiments, for a compound or salt of Formula (V), R42isoptionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -OCH3, -CN, methyl, and ethyl. In some embodiments, for a compound or salt of Formula (V), R42isoptionally substituted with one or more substituents independently selected from -F and -CN.

[0248] In some embodiments, for a compound or salt of Formula (V), R42is

[0249] In some embodiments, for a compound or salt of Formula (V), R43is selected from: hydrogen and C1-6alkyl optionally substituted with one or more halogen, -CN, - OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10-membered heterocycle; andR42together with R43form a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, halogen, -OC1-6alkyl, -SC1-6alkyl, -N(C1-6alkyl)2, -C(O)C1-6alkyl, -C(O)N(C1-6alkyl)2, -N(C1-6alkyl)C(O)C1-6alkyl, -C(O)OC1-6alkyl, -OC(O)C1-6alkyl, -S(O)C1-6alkyl, -S(O)2C1-6alkyl, -NO2, =O-,=N(C1-6alkyl), - CN, -N3, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl.

[0250] In some embodiments, for a compound or salt of Formula (V), R43is selected from hydrogen, methyl, ethyl, propyl, and isopropyl. In some embodiments, for a compound or salt of Formula (V), R43is hydrogen.

[0251] In some embodiments, for a compound or salt of Formula (V), wherein R44and R44aare each independently selected from: hydrogen; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OC1-6alkyl, -N(C1-6alkyl)2, -CN, C3-6carbocycle, and 3- to 6- membered heterocycle, wherein the C3-6carbocycle, and 3- to 6-membered heterocycle, are each optionally substituted with one or more halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl; andR44together with R44aform a C3-10 carbocycle, or 3- to 6-membered heterocycloalkyl.

[0252] In some embodiments, for a compound or salt of Formula (V), R44together with R44aform a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR48e, -SR48e, - N(R48e)2, -C(O)R48e, -C(O)N(R48e)2, -N(R48e)C(O)R48e, -N(R48e)C(O)N(R48e)2, -OC(O)N(R48e)2, - N(R48e)C(O)OR48e, -C(O)OR48e, -OC(O)R48e, -S(O)R48e, -S(O)2R48e, -NO2, =O- =S, =N(R48e), - CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R47e. In some embodiments, for a compound or salt of Formula (V), R44together with R44aform a C3-10 carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR48e, -SR48e, -N(R48e)2, -C(O)R48e, -C(O)N(R48e)2, - N(R48e)C(O)R48e, -C(O)OR48e, -OC(O)R48e, -S(O)2R48e, -NO2, =O-,-CN, C1-6alkyl, wherein C1-6alkyl is optionally substituted with one or more R47e.

[0253] In some embodiments, for a compound or salt of Formula (V), R44together with R44aform a C3-10carbocycle, optionally substituted with one or more substituents independently selected from halogen, -OR48e, -SR48e, -N(R48e)2, -C(O)R48e, -C(O)N(R48e)2, -N(R48e)C(O)R48e, -C(O)OR48e, -OC(O)R48e, -S(O)2R48e, -NO2, =O-,-CN, C1-6alkyl, wherein C1-6alkyl is optionally substituted with one or more R47e. In some embodiments, for a compound or salt of Formula (V), R44together with R44aform a C3-6carbocycle, optionally substituted with one or more substituents independently selected from halogen, -OR48e, -SR48e, - N(R48e)2, -C(O)R48e, -C(O)N(R48e)2, -N(R48e)C(O)R48e, -C(O)OR48e, -OC(O)R48e, -S(O)2R48e, - NO2, =O-,-CN, C1-6alkyl, wherein C1-6alkyl is optionally substituted with one or more R47e. In some embodiments, for a compound or salt of Formula (V), R44together with R44aform a C3-6carbocycle, optionally substituted with one or more substituents independently selected from halogen, -OR48e, -SR48e, -N(R48e)2, -C(O)R48e, =O-,-CN, C1-6alkyl, and C1-6haloalkyl is optionally substituted with one or more R47e.

[0254] In some embodiments, for a compound or salt of Formula (V), R44together with R44aform a C3-6carbocycle. In some embodiments, for a compound or salt of Formula (V), R44together with R44aform a C3carbocycle.

[0255] In some embodiments, for a compound or salt of Formula (V), R45is selected independently from: hydrogen, halogen, -NO2, -CN, -N3, -OR48f, -SR48f, -N(R48f)2, -C(O)R48f, - C(O)N(R48f)2, -N(R48f)C(O)R48f, -N(R48f)C(O)N(R48f)2, -OC(O)N(R48f)2, - N(R48f)C(O)OR48f, -C(O)OR48f, -OC(O)R48f, -S(O)R48f, and -S(O)2R48f; and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR48f, -SR48f, -N(R48f)2, -C(O)R48f, -C(O)N(R48f)2, -N(R48f)C(O)R48f, -C(O)OR48f, - OC(O)R48f, -N(R48f)C(O)N(R48f)2, -OC(O)N(R48f)2, -N(R48f)C(O)OR48f, -S(O)R48f, - S(O)2R48f, -NO2, =O, =S, =N(R48f), -CN, C3-10carbocycle and 3- to 10-membered heterocycle, wherein the C3-10carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more R47f.

[0256] In some embodiments, for a compound or salt of Formula (V), R45is selected independently from: hydrogen, halogen, -NO2, -CN, -N3, -OR48f, -SR48f, -N(R48f)2, -C(O)R48f, - C(O)N(R48f)2, -N(R48f)C(O)R48f, -C(O)OR48f, -OC(O)R48f, and -S(O)2R48f; and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR48f, -SR48f, -N(R48f)2, -C(O)R48f, -C(O)N(R48f)2, -N(R48f)C(O)R48f, -C(O)OR48f, - OC(O)R48f, -S(O)2R48f, -NO2, =O, -CN, C3-10carbocycle and 3- to 10-memberedheterocycle, wherein the C3-10carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more R47f.

[0257] In some embodiments, for a compound or salt of Formula (V), R45is selected independently from: hydrogen, halogen, -NO2, -CN, -N3, -OR48f, -SR48f, -N(R48f)2, -C(O)R48f, - C(O)N(R48f)2, -N(R48f)C(O)R48f, -C(O)OR48f, -OC(O)R48f, and -S(O)2R48f

[0258] In some embodiments, for a compound or salt of Formula (V), R45is selected independently from: hydrogen, methyl, ethyl, propyl, and isopropyl. In some embodiments, for a compound or salt of Formula (V), R45is hydrogen.

[0259] In some embodiments, for a compound or salt of Formula (V), each R46and R46ais selected independently from hydrogen, halogen, -OC1-6alkyl, -SC1-6alkyl, -N(C1-6alkyl)2, -NO2, -CN, C1-6alkyl, C3-6carbocycle, and 3- to 6-membered heterocycle, wherein the C1-6alkyl, C3-10carbocycle, and 3- to 10- membered heterocycle are each optionally substituted with one or more halogen, -OC1-6alkyl, -SC1-6alkyl, -N(C1-6alkyl)2, -NO2, -CN, C1-6alkyl. In some embodiments, for a compound or salt of Formula (V), each R46and R46ais selected independently from hydrogen, halogen, -OC1-6alkyl, -SC1-6alkyl, -N(C1-6alkyl)2, -NO2, -CN, C1-6alkyl, and C1-6haloalkyl. In some embodiments, for a compound or salt of Formula (V), each R46and R46ais selected independently from hydrogen, methyl, ethyl, propyl, and isopropyl. In some embodiments, for a compound or salt of Formula (V), R46and R46aare each hydrogen.

[0260] In some embodiments, for a compound or salt of Formula (V), R47is independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0261] In some embodiments, for a compound or salt of Formula (V), R47ais independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0262] In some embodiments, for a compound or salt of Formula (V), R47bis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0263] In some embodiments, for a compound or salt of Formula (V), R47cis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0264] In some embodiments, for a compound or salt of Formula (V), R47dis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0265] In some embodiments, for a compound or salt of Formula (V), R47eis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10-membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0266] In some embodiments, for a compound or salt of Formula (V), R47fis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0267] In some embodiments, for a compound or salt of Formula (V), R47gis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0268] In some embodiments, for a compound or salt of Formula (V), R48is independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0269] In some embodiments, for a compound or salt of Formula (V), R48ais independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which isoptionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0270] In some embodiments, for a compound or salt of Formula (V), R48bis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0271] In some embodiments, for a compound or salt of Formula (V), R48cis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0272] In some embodiments, for a compound or salt of Formula (V), R48dis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0273] In some embodiments, for a compound or salt of Formula (V), R48eis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0274] In some embodiments, for a compound or salt of Formula (V), R48fis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0275] In some embodiments, for a compound or salt of Formula (V), R48gis independently selected from: hydrogen, -F, -Cl, -Br, -I, -CN, -OH, -NO2, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -OH, =O, -O-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10- membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, - I, -CN, -OH, =O, =S, -O-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0276] In some embodiments, for a compound or salt of Formula (V), the compound is selectedany one thereof.

[0277] In an aspect, the present disclosure provides a compound represented by Formula (VI):or a salt thereof, wherein:XE, XF, XGand XHare independently selected from C(R50) and N; each R50is independently selected from: hydrogen, halogen, -NO2, -CN, -N3, -OR58, -SR58, -N(R58)2, -C(O)R58, - C(O)N(R58)2, -N(R58)C(O)R58, -N(R58)C(O)N(R58)2, -OC(O)N(R58)2, - N(R58)C(O)OR58, -C(O)OR58, -OC(O)R58, -S(O)R58, and -S(O)2R58; and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR58, -SR58, -N(R58)2, -C(O)R58, -C(O)N(R58)2, -N(R58)C(O)R58, -C(O)OR58, - OC(O)R58, -N(R58)C(O)N(R58)2, -OC(O)N(R58)2, -N(R58)C(O)OR58, -S(O)R58, - S(O)2R58, -NO2, =O, =S, =N(R58), -CN, C3-10carbocycle and 3- to 10-membered heterocycle, wherein the C3-10carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more R57; and C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR58, -SR58, -N(R58)2, -C(O)R58, -C(O)N(R58)2, -N(R58)C(O)R58, - N(R58)C(O)N(R58)2, -OC(O)N(R58)2, -N(R58)C(O)OR58, -C(O)OR58, -OC(O)R58, - S(O)R58, -S(O)2R58, -NO2, =O-, =S, =N(R58), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R57;R51is selected from: C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR58a, -SR58a, -N(R58a)2, -C(O)R58a, -C(O)N(R58a)2, -N(R58a)C(O)R58a, -C(O)OR58a, - OC(O)R58a, -N(R58a)C(O)N(R58a)2, -OC(O)N(R58a)2, -N(R58a)C(O)OR58a, -S(O)R58a, - S(O)2R58a, -NO2, =O, =S, =N(R58a), -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with one or more R57a;R52is selected from:C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR58b, -SR58b, -N(R58b)2, -C(O)R58b, -C(O)N(R58b)2, -N(R58b)C(O)R58b-C(O)OR58b, - OC(O)R58b, -N(R58b)C(O)N(R58b)2, -OC(O)N(R58b)2, -N(R58b)C(O)OR58b, -S(O)R58b, - S(O)2R58b, -NO2, =O, =S, =N(R58b), -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with one or more R57b; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR58b, -SR58b, -N(R58b)2, -C(O)R58b, -C(O)N(R58b)2, -N(R58b)C(O)R58b- N(R58b)C(O)N(R58b)2, -OC(O)N(R58b)2, -N(R58b)C(O)OR58b, -C(O)OR58b, - OC(O)R58b, -S(O)R58b, -S(O)2R58b, -NO2, =O-, =S, =N(R58b), -CN, -N3, C3-10carbocycle, and 3- to 10-membered heterocycle, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein the C3-10carbocycle, 3- to 10-membered heterocycle, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R57b; orR51together with R52form a C3-10cycloalkyl, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR58b, -SR58b, -N(R58b)2, -C(O)R58b, -C(O)N(R58b)2, -N(R58b)C(O)R58b-N(R58b)C(O)N(R58b)2, - OC(O)N(R58b)2, -N(R58b)C(O)OR58b, -C(O)OR58b, -OC(O)R58b, -S(O)R58b, -S(O)2R58b, -NO2, =O-, =S, =N(R58b), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R57b;R53is selected from: hydrogen and C1-6alkyl optionally substituted with one or more one or more R57c; andR52together with R53form a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR58c, -SR58c, - N(R58c)2, -C(O)R58c, -C(O)N(R58c)2, -N(R58c)C(O)R58c, -N(R58c)C(O)N(R58c)2, - OC(O)N(R58c)2, -N(R58c)C(O)OR58c, -C(O)OR58c, -OC(O)R58c, -S(O)R58c, -S(O)2R58c, -NO2, =O-, =S, =N(R58c), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R57c;R54is independently selected from: hydrogen, halogen, -OR58d, -SR58d, -N(R58d)2, -NO2, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR58d, -SR58d, -N(R58d)2, -NO2, and -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10- membered heterocycle, are each optionally substituted with one or more R57d;R54ais independently selected from: halogen, -OR58e, -SR58e, -N(R58e)2, -NO2, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR58e, -SR58e, -N(R58e)2, -NO2, and -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10- membered heterocycle, are each optionally substituted with one or more R57e; andR54together with R54aform a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR58e, -SR58e, - N(R58e)2, -C(O)R58e, -C(O)N(R58e)2, -N(R58e)C(O)R58e, -N(R58e)C(O)N(R58e)2, - OC(O)N(R58e)2, -N(R58e)C(O)OR58e, -C(O)OR58e, -OC(O)R58e, -S(O)R58e, -S(O)2R58e, -NO2, =O-, =S, =N(R58e), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R57e;R55is selected from: hydrogen, -F, -Br, -I, -OR58f, -SR58f, -N(R58f)2, -NO2, -CN, C1-6alkyl, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C1-6alkyl, C3-10carbocycle, and 3- to 10- membered heterocycle are each optionally substituted with one or more R57f; each R57, R57a, R57b, R57c, R57d, R57e, and R57fis independently selected from: hydrogen, halogen, -CN, -OH, -SH, -NO2, -NH2, -O-C1-6alkyl, -S-C1-6alkyl, - N(C1-6alkyl)2, and -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10-membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected fromhalogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl; each R58, R58a, R58b, R58c, R58d, R58e, and R58fis independently selected from: hydrogen, halogen, -CN, -OH, -SH, -NO2, -NH2, -O-C1-6alkyl, -S-C1-6alkyl, - N(C1-6alkyl)2, and -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10-membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

[0278] In some embodiments, for a compound or salt of Formula (VI), XE, XF, XGand XHare each independently selected from C(R50). In some embodiments, for a compound or salt of Formula (II), at least one XE, XF, XGand XHneed not be N.

[0279] In some embodiments, for a compound or salt of Formula (VI), each R50is independently selected from: hydrogen, halogen, -NO2, -CN, -N3, -OR58, -SR58, -N(R58)2, -C(O)R58, - C(O)N(R58)2, -N(R58)C(O)R58, -C(O)OR58, -OC(O)R58, and -S(O)2R58; and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR58, -SR58, -N(R58)2, -C(O)R58, -C(O)N(R58)2, -N(R58)C(O)R58, -C(O)OR58, - OC(O)R58, -S(O)2R58, -NO2, =O, -CN, C3-10carbocycle and 3- to 10-membered heterocycle, wherein the C3-10carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more R57; and C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR58, -SR58, -N(R58)2, -C(O)R58, -C(O)N(R58)2, -N(R58)C(O)R58-C(O)OR58, -OC(O)R58, -S(O)R58, -S(O)2R58, -NO2, =O-,-CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R57.

[0280] In some embodiments, for a compound or salt of Formula (VI), each R50is independently selected from: hydrogen, halogen, -NO2, -CN, -N3, -OR58, -SR58, -N(R58)2, -C(O)R58, - C(O)N(R58)2, -N(R58)C(O)R58, -C(O)OR58, -OC(O)R58, and -S(O)2R58; and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR58, -SR58, -N(R58)2, -C(O)R58, -C(O)N(R58)2, -N(R58)C(O)R58, -C(O)OR58, - OC(O)R58, -S(O)2R58, -NO2, =O, -CN, C3-10carbocycle and 3- to 10-membered heterocycle, wherein the C3-10carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more R57.

[0281] In some embodiments, for a compound or salt of Formula (VI), each R50is independently selected from: hydrogen, halogen, -NO2, -CN, -N3, -OR58, -SR58, -N(R58)2, -C(O)R58, - C(O)N(R58)2, -N(R58)C(O)R58, -C(O)OR58, -OC(O)R58, and -S(O)2R58, C1-6alkyl, and C1-6haloalkyl. In some embodiments, for a compound or salt of Formula (VI), each R50is independently selected from hydrogen, -F, -Cl, -Br, -OCH3, -CN, and -CH3. In some embodiments, for a compound or salt of Formula (VI), each R50is independently selected from hydrogen, -F, -Cl, and -Br. In some embodiments, for a compound or salt of Formula (VI), each R50is independently selected from hydrogen and -F.

[0282] In some embodiments, for a compound or salt of Formula (VI), R51is selected from C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR58a, -SR58a, -N(R58a)2, -C(O)R58a, - C(O)N(R58a)2, -N(R58a)C(O)R58a, -C(O)OR58a, -OC(O)R58a, -S(O)2R58a, -NO2, =O, and -CN.

[0283] In some embodiments, for a compound or salt of Formula (VI), R51is selected from C1-6alkyl, optionally substituted with one or more substituents independently selected from halogen, -OR58a, -SR58a, -N(R58a)2, -C(O)R58a, -C(O)N(R58a)2, -N(R58a)C(O)R58a, -C(O)OR58a, -OC(O)R58a, -S(O)2R58a, -NO2, =O, and -CN. In some embodiments, for a compound or salt of Formula (VI), R51is selected from C1-3 alkyl, optionally substituted with one or more substituents independently selected from halogen, -OR58a, -SR58a, -N(R58a)2, -C(O)R58a, -C(O)N(R58a)2, - N(R58a)C(O)R58a, -C(O)OR58a, -OC(O)R58a, -S(O)2R58a, -NO2, =O, and -CN.

[0284] In some embodiments, for a compound or salt of Formula (VI), R51is selected from: methyl, ethyl, propyl, and isopropyl. In some embodiments, for a compound or salt of Formula (VI), R51is methyl.

[0285] In some embodiments, for a compound or salt of Formula (VI), R52is selected from:C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR58b, -SR58b, -N(R58b)2, -C(O)R58b, -C(O)N(R58b)2, -N(R58b)C(O)R58b-C(O)OR58b, - OC(O)R58b, -S(O)2R58b, -NO2, =O, -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with one or more R57b; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR58b, -SR58b, -N(R58b)2, -C(O)R58b, -C(O)N(R58b)2, - N(R58b)C(O)R58b-C(O)OR58b, -OC(O)R58b, -S(O)2R58b, -NO2, =O-,-CN, -N3, C3-10carbocycle, 3- to 10-membered heterocycle, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein the C3-10carbocycle, 3- to 10-membered heterocycle, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R57b; or

[0286] In some embodiments, for a compound or salt of Formula (VI), R52is selected from: C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, - NH(C1-6alkyl), C3-10carbocycle, 3- to 10-membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, - OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10- membered heterocycle, and C1-6haloalkyl.

[0287] In some embodiments, for a compound or salt of Formula (VI), R52is selected from: C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, - OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10- membered heterocycle, and C1-6haloalkyl.

[0288] In some embodiments, for a compound or salt of Formula (VI), R52is selected from: 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, and C1-6haloalkyl.

[0289] In some embodiments, for a compound or salt of Formula (VI), R52is selected from: 5- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, and C1-6haloalkyl.

[0290] In some embodiments, for a compound or salt of Formula (VI), R52is selected from: 5- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected firom-F, -Cl, -Br, -OCH3, -CN, and -CH3.

[0291] In some embodiments, for a compound or salt of Formula (VI), R52is pyridinyl, optionally substituted with one or more substituents independently selected from-F, -Cl, -Br, - OCH3, -CN, and -CH3.

[0292] In some embodiments, for a compound or salt of Formula (VI), R52isoptionally substituted with one or more substituents independently selected from-F, -Cl, -Br, - OCH3, -CN, and -CH3.

[0293] In some embodiments, for a compound or salt of Formula (VI), R52is

[0294] In some embodiments, for a compound or salt of Formula (VI), R53is selected from hydrogen and C1-6alkyl optionally substituted with one or more one or more R57c. In some embodiments, for a compound or salt of Formula (VI), R53is selected from hydrogen, C1-6alkyl and C1-6haloalkyl. In some embodiments, for a compound or salt of Formula (VI), R53is selected from hydrogen, methyl, ethyl, propyl, and isopropyl. In some embodiments, for a compound or salt of Formula (VI), R53is hydrogen.

[0295] In some embodiments, for a compound or salt of Formula (VI), R54is independently selected from: hydrogen, halogen, -OR58d, -SR58d, -N(R58d)2, -NO2, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR58d, -SR58d, -N(R58d)2, -NO2, and -CN.

[0296] In some embodiments, for a compound or salt of Formula (VI), R54is independently selected from hydrogen and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OC1-6alkyl, -N(C1-6alkyl)2, and -CN. In some embodiments, for a compound or salt of Formula (VI), R54is independently selected from hydrogen and C1-6alkyl. In some embodiments, for a compound or salt of Formula (VI), R54isindependently selected from hydrogen methyl, ethyl, propyl, and isopropyl. In some embodiments, for a compound or salt of Formula (VI), R54is hydrogen.

[0297] In some embodiments, for a compound or salt of Formula (VI), R54ais independently selected from: halogen, -OR58e, -SR58e, -N(R58e)2, -NO2, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR58e, -SR58e, -N(R58e)2, -NO2, and -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10- membered heterocycle, are each optionally substituted with one or more R57e; andR54together with R54aform a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR58e, -SR58e, - N(R58e)2, -C(O)R58e, -C(O)N(R58e)2, -N(R58e)C(O)R58e, -C(O)OR58e, -OC(O)R58e, - S(O)2R58e, -NO2, =O-,-CN, C1-6alkyl, wherein C1-6alkyl is optionally substituted with one or more R57e.

[0298] In some embodiments, for a compound or salt of Formula (VI), R54ais independently selected from: halogen, -OR58e, -SR58e, -N(R58e)2, -NO2, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR58e, -SR58e, -N(R58e)2, -NO2, and -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10- membered heterocycle, are each optionally substituted with one or more R57e.

[0299] In some embodiments, for a compound or salt of Formula (VI), R54ais independently selected from: halogen, -OR58e, -SR58e, -N(R58e)2, -NO2, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR58e, -SR58e, -N(R58e)2, -NO2, and -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with halogen, -OC1-6alkyl, -N(C1-6alkyl)2, -C(O)C1-6alkyl, -C(O)N(C1-6alkyl)2, -CN.

[0300] In some embodiments, for a compound or salt of Formula (VI), R54ais independently selected from: C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR58e, -SR58e, -N(R58e)2, -NO2, and -CN, C3-10carbocycle, and 3- to 10- membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, areeach optionally substituted with halogen, -OC1-6alkyl, -N(C1-6alkyl)2, -C(O)C1-6alkyl, - C(O)N(C1-6alkyl)2, -CN.

[0301] In some embodiments, for a compound or salt of Formula (VI), R54ais independently selected from: C1-6alkyl optionally substituted with one or more substituents independently selec...

Claims

1. CLAIMSWHAT IS CLAIMED IS:

1. A compound represented by Formula (I):or a salt thereof, wherein:X1, X2, X3and X4are independently selected from C(R0) and N;Y is selected from C(R6)(R6a) and O; each R0is independently selected from: hydrogen, halogen, -NO2, -CN, -N3, -OR8, -SR8, -N(R8)2, -C(O)R8, - C(O)N(R8)2, -N(R8)C(O)R8-N(R8)C(O)N(R8)2, -OC(O)N(R8)2, - N(R8)C(O)OR8, -C(O)OR8, -OC(O)R8, -S(O)R8, and -S(O)2R8; and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR8, -SR8, -N(R8)2, -C(O)R8, -C(O)N(R8)2, -N(R8)C(O)R8, -C(O)OR8, -OC(O)R8, - N(R8)C(O)N(R8)2, -OC(O)N(R8)2, -N(R8)C(O)OR8, -S(O)R8, -S(O)2R8, -NO2, =O, =S, =N(R8), -CN, C3-10 carbocycle and 3- to 10-membered heterocycle, wherein the C3-10carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more R7; and C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR8, -SR8, -N(R8)2, -C(O)R8, -C(O)N(R8)2, -N(R8)C(O)R8, - N(R8)C(O)N(R8)2, -OC(O)N(R8)2, -N(R8)C(O)OR8, -C(O)OR8, -OC(O)R8, -S(O)R8, - S(O)2R8, -NO2, =O-, =S, =N(R8), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R7;R1is selected from: C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR8a, -SR8a, -N(R8a)2, -C(O)R8a, -C(O)N(R8a)2, -N(R8a)C(O)R8a, -C(O)OR8a, - OC(O)R8a, -N(R8a)C(O)N(R8a)2, -OC(O)N(R8a)2, -N(R8a)C(O)OR8a, -S(O)R8a, -S(O)2R8a, -NO2, =O, =S, =N(R8a), -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with one or more R7a;R2is selected from: C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR8b, -SR8b, -N(R8b)2, -C(O)R8b, -C(O)N(R8b)2, -N(R8b)C(O)R8b-C(O)OR8b, - OC(O)R8b, -N(R8b)C(O)N(R8b)2, -OC(O)N(R8b)2, -N(R8b)C(O)OR8b, -S(O)R8b, - S(O)2R8b, -NO2, =O, =S, =N(R8b), -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with one or more R7b; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR8b, -SR8b, -N(R8b)2, -C(O)R8b, -C(O)N(R8b)2, -N(R8b)C(O)R8b- N(R8b)C(O)N(R8b)2, -OC(O)N(R8b)2, -N(R8b)C(O)OR8b, -C(O)OR8b, -OC(O)R8b, - S(O)R8b, -S(O)2R8b, -NO2, =O-, =S, =N(R8b), -CN, -N3, C3-10carbocycle, and 3- to 10-membered heterocycle, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein the C3-10carbocycle, 3- to 10-membered heterocycle, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R7b; orR1together with R2form a C3-10cycloalkyl, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR8b, -SR8b, -N(R8b)2, -C(O)R8b, - C(O)N(R8b)2, -N(R8b)C(O)R8b-N(R8b)C(O)N(R8b)2, -OC(O)N(R8b)2, - N(R8b)C(O)OR8b, -C(O)OR8b, -OC(O)R8b, -S(O)R8b, -S(O)2R8b, -NO2, =O-, =S, =N(R8b), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R7b;R3is selected from: hydrogen and C1-6alkyl optionally substituted with one or more one or more R7c; andR2together with R3form a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR8c, -SR8c, -N(R8c)2, -C(O)R8c, - C(O)N(R8c)2, -N(R8c)C(O)R8c, -N(R8c)C(O)N(R8c)2, -OC(O)N(R8c)2, - N(R8c)C(O)OR8c, -C(O)OR8c, -OC(O)R8c, -S(O)R8c, -S(O)2R8c, -NO2, =O-, =s,=N(R8c), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R7c;R4is independently selected from: hydrogen, halogen, -OR8d, -SR8d, -N(R8d)2, -NO2, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR8d, -SR8d, -N(R8d)2, -NO2, and -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with one or more R7d;R4ais independently selected from: hydrogen, halogen, -OR8e, -SR8e, -N(R8e)2, -NO2, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR8e, -SR8e, -N(R8e)2, -NO2, and -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with one or more R7e; andR4together with R4aform a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR8e, -SR8e, -N(R8e)2, -C(O)R8e, - C(O)N(R8e)2, -N(R8e)C(O)R8e, -N(R8e)C(O)N(R8e)2, -OC(O)N(R8e)2, - N(R8e)C(O)OR8e, -C(O)OR8e, -OC(O)R8e, -S(O)R8e, -S(O)2R8e, -NO2, =O-, =S, =N(R8e), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R7e; each R5and R5ais selected independently from: hydrogen, halogen, -OR8f, -SR8f, -N(R8f)2, -NO2, -CN, C1-6alkyl, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C1-6alkyl, C3-10carbocycle, and 3- to 10- membered heterocycle are each optionally substituted with one or more R7f; orR5together with R5aform a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR8f, -SR8f, -N(R8f)2, -C(O)R8f, - C(O)N(R8f)2, -N(R8f)C(O)R8f, -N(R8f)C(O)N(R8f)2, -OC(O)N(R8f)2, - N(R8f)C(O)OR8f, -C(O)OR8f, -OC(O)R8f, -S(O)R8f, -S(O)2R8f, -NO2, =O-, =S, =N(R8f), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R7f; each R6and R6ais selected independently from:hydrogen, halogen, -OR8g, -SR8g, -N(R8g)2, -NO2, -CN, C1-6alkyl, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C1-6alkyl, C3-10carbocycle, and 3- to 10- membered heterocycle are each optionally substituted with one or more R7g; orR6together with R5form an -O- bridge, an -NR7g- bridge, a C1-5alkylene bridge, or a 1- to 5-membered heteroalkylene bridge, wherein each of the C1-5alkylene bridge, or 1- to 5-membered heteroalkylene bridge is optionally substituted with one or more substituents independently selected from halogen, -OR8g, -SR8g, - N(R8g)2, -C(O)R8g, -C(O)N(R8g)2, -N(R8g)C(O)R8g-N(R8g)C(O)N(R8g)2, - OC(O)N(R8g)2, -N(R8g)C(O)OR8g, -C(O)OR8g, -OC(O)R8g, -S(O)R8g, -S(O)2R8g, - NO2, =O-, =S, =N(R8g), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R7g; each R7, R7a, R7b, R7c, R7d, R7e, R7f, and R7gis independently selected from: hydrogen, halogen, -CN, -OH, -SH, -NO2, -NH2, -O-C1-6alkyl, -S-C1-6alkyl, - N(C1-6alkyl)2, and -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10-membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl: each R8, R8a, R8b, R8c, R8d, R8e, R8f, and R8gis independently selected from: hydrogen, halogen, -CN, -OH, -SH, -NO2, -NH2, -O-C1-6alkyl, -S-C1-6alkyl, - N(C1-6alkyl)2, and -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10-membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected fromhalogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

2. The compound or salt of claim 1, wherein X1, X2, X3, and X4are each C(R0).

3. The compound or salt of claim 1 or 2, wherein Y is O.

4. The compound or salt of any one of claims 1 or 2, wherein Y is C(R6)(R6a).

5. The compound or salt of any one of claims 1 to 4, wherein each R0is independently selected from: hydrogen, halogen, -CN, -OH, -SH, -NO2, -NH2, -O-C1-6alkyl, -S-C1-6alkyl, - N(C1-6alkyl)2, and -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10-membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

6. The compound or salt of claim 5, wherein each R0is independently selected from: -H, -F, - Cl, -Br, -I, -CN, -OR8, -N(R8)2, -C(O)R8, -C(O)N(R8)2, -CF3, methyl, ethyl, cyclopropyl, - CCMe, -CCH, phenyl, N-morpholinyl, and N-pyrrolidinyl.

7. The compound or salt of claim 6, wherein each R0is independently selected from: -H, -F, - Cl, -CN, -CF3, and methyl.

8. The compound or salt of any one of claims 1 to 7, wherein R1is selected from: C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10-membered heterocycle.

9. The compound or salt of any one of claims 1 to 8, wherein R1is selected from: methyl, ethyl, propyl, and isopropyl.

10. The compound or salt of any one of claims 1 to 9, wherein R2is selected from: C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected fromhalogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-e alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl; orR1together with R2form a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, halogen, -OC1-6alkyl, -SC1-6alkyl, -N(C1-6alkyl)2, -C(O)C1-6alkyl, -C(O)N(C1-6alkyl)2, -N(C1-6alkyl)C(O)C1-6alkyl, -C(O)OC1-6alkyl, -OC(O)C1-6alkyl, -S(O)C1-6alkyl, -S(O)2C1-6alkyl, -NO2, =O-,=N(C1-6alkyl), -CN, -N3, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl.

11. The compound or salt of claim 10, wherein R2is selected from phenyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -OCH3, -C(O)0Me, -CN, -N3, methyl, ethyl, propyl, and isopropyl.

12. The compound or salt of claim 11, wherein R2is selected from:

13. The compound or salt of any one of claims 1 to 12, wherein R3is selected from: hydrogen and C1-6alkyl optionally substituted with one or more halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10-membered heterocycle; andR2together with R3form a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, halogen, -OC1-6alkyl, -SC1-6alkyl, -N(C1-6alkyl)2, -C(O)C1-6alkyl, -C(O)N(C1-6alkyl)2, -N(C1-6alkyl)C(O)C1-6alkyl, -C(O)OC1-6alkyl, -OC(O)C1-6alkyl, -S(O)C1-6alkyl, -S(O)2C1-6alkyl, -NO2, =O-,=N(C1-6alkyl), -CN, -N3, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl.

14. The compound or salt of claim 13, wherein R3is selected from hydrogen, methyl, ethyl, propyl, and isopropyl.

15. The compound or salt of claim 14, wherein R3is hydrogen.

16. The compound or salt of any one of claims 1 to 15, wherein R4and R4aare each independently selected from: hydrogen; andC1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OC1-6alkyl, -N(C1-6alkyl)2, -C(O)C1-6alkyl, -C(O)N(C1-6alkyl)2, C2-6alkenyl, C2-6alkynyl, -CN, C3-6carbocycle, and 3- to 6-membered heterocycle, wherein the C3-6carbocycle, and 3- to 6-membered heterocycle, are each optionally substituted with one or more halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl; andR4together with R4aform a C3-10carbocycle, or 3- to 6-membered heterocycloalkyl.

17. The compound or salt of claim 16, wherein R4and R4aform a C3-6carbocycle.

18. The compound or salt of claim 16, wherein R4and R4aare each independently selected from hydrogen and C1-6alkyl optionally substituted with one or more substituents independently selected from 3- to 6-membered heterocycle.

19. The compound or salt of claim 18, wherein R is hydrogen and R4ais . Thecompound or salt of claim 16, wherein R4and R4aare hydrogen.

20. The compound or salt of any one of claims 1 to 19, wherein R5and R5aare each independently selected from: hydrogen, C1-6alkyl, C3-6carbocycle, and 3- to 6-membered heterocycle; or R5together with R5aform a C3-10carbocycle, or 3- to 6-membered heterocycloalkyl.

21. The compound or salt of claim 20, wherein R5and R5aare hydrogen.

22. The compound or salt of claim 4, wherein R6and R6aare each independently selected from: hydrogen, -OC1-6alkyl, -SC1-6alkyl, -N(C1-6alkyl)2, -NO2, -CN, C1-6alkyl, C2- 6 alkenyl, and C2-6alkynyl, C3-6carbocycle, and 3- to 6-membered heterocycle, wherein the C1-6alkyl, C3-10carbocycle, and 3- to 10- membered heterocycle are each optionally substituted with one or more halogen, -OC1-6alkyl, -SC1-6alkyl, -N(C1-6alkyl)2, -NO2, -CN, C1-6alkyl; orR6together with R5form an -O- bridge, an -NH- bridge, an -NC1-6- bridge, a C1-5alkylene bridge, or a 1- to 5-membered heteroalkylene bridge, wherein each of the C1-5alkylene bridge, or 1- to 5-membered heteroalkylene bridge is optionally substituted with one or more substituents independently selected from halogen, -OC1-6alkyl, -SC1-6alkyl, -N(C1-6alkyl)2, -C(O)C1-6alkyl, -C(O)N(C1-6alkyl)2, -N(C1-6alkyl)C(O)C1-6alkyl, -C(O)OC1-6alkyl, -OC(O)C1-6alkyl, -S(O)C1-6alkyl, -S(O)2C1-6alkyl, -NO2, =O-,=N(C1-6alkyl), -CN, -N3, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl.

23. The compound or salt of claim 22, wherein R6and R6aare each hydrogen.

24. The compound or salt of claim 22, wherein R6and R5form a C1-3 alkylene bridge.

25. The compound or salt of any one of claims 1 to 24, wherein each R7, R7a, R7b, R7c, R7d, R7e, R7f, and R7gis independently selected from hydrogen, halogen, -CN, -OH, -NH2, and -O- CH3.

26. The compound or salt of any one of claims 1 to 25, wherein each R8, R8a, R8b, R8c, R8d, R8e, R8f, and R8gis independently selected from hydrogen, halogen, -CN, -OH, -NH2, and -O- CH3.

27. The compound of claim 1, selected from:thereof.

28. A compound represented by Formula (II):or a salt thereof, wherein:X5, X6, X7and X8are independently selected from C(R10) and N; each R10is independently selected from: hydrogen, halogen, -NO2, -CN, -N3, -OR18, -SR18, -N(R18)2, -C(O)R18, - C(O)N(R18)2, -N(R18)C(O)R18, -N(R18)C(O)N(R18)2, -OC(O)N(R18)2, - N(R18)C(O)OR18, -C(O)OR18, -OC(O)R18, -S(O)R18, and -S(O)2R18; and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR18, -SR18, -N(R18)2, -C(O)R18, -C(O)N(R18)2, -N(R18)C(O)R18, -C(O)OR18, - OC(O)R18, -N(R18)C(O)N(R18)2, -OC(O)N(R18)2, -N(R18)C(O)OR18, -S(O)R18, - S(O)2R18, -NO2, =O, =S, =N(R18), -CN, C3-10carbocycle and 3- to 10-memberedheterocycle, wherein the C3-10carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more R17; and C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR18, -SR18, -N(R18)2, -C(O)R18, -C(O)N(R18)2, -N(R18)C(O)R18, - N(R18)C(O)N(R18)2, -OC(O)N(R18)2, -N(R18)C(O)OR18, -C(O)OR18, -OC(O)R18, - S(O)R18, -S(O)2R18, -NO2, =O-, =S, =N(R18), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R17;R11is selected from: C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR18a, -SR18a, -N(R18a)2, -C(O)R18a, -C(O)N(R18a)2, -N(R18a)C(O)R18a, -C(O)OR18a, - OC(O)R18a, -N(R18a)C(O)N(R18a)2, -OC(O)N(R18a)2, -N(R18a)C(O)OR18a, -S(O)R18a, - S(O)2R18a, -NO2, =O, =S, =N(R18a), -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with one or more R17a;R12is selected from: C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR18b, -SR18b, -N(R18b)2, -C(O)R18b, -C(O)N(R18b)2, -N(R18b)C(O)R18b-C(O)OR18b, - OC(O)R18b, -N(R18b)C(O)N(R18b)2, -OC(O)N(R18b)2, -N(R18b)C(O)OR18b, -S(O)R18b, - S(O)2R18b, -NO2, =O, =S, =N(R18b), -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with one or more R7b; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR18b, -SR18b, -N(R18b)2, -C(O)R18b, -C(O)N(R18b)2, -N(R18b)C(O)R18b- N(R18b)C(O)N(R18b)2, -OC(O)N(R18b)2, -N(R18b)C(O)OR18b, -C(O)OR18b, - OC(O)R18b, -S(O)R18b, -S(O)2R18b, -NO2, =O-, =S, =N(R18b), -CN, -N3, C3-10carbocycle, and 3- to 10-membered heterocycle, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein the C3-10carbocycle, 3- to 10-membered heterocycle, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R7b; orR11together with R12form a C3-10cycloalkyl, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR18b, -SR18b, - N(R18b)2, -C(O)R18b, -C(O)N(R18b)2, -N(R18b)C(O)R18b-N(R18b)C(O)N(R18b)2, - OC(O)N(R18b)2, -N(R18b)C(O)OR18b, -C(O)OR18b, -OC(O)R18b, -S(O)R18b, -S(O)2R18b, -NO2, =O-, =S, =N(R18b), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R17b;R13is selected from: hydrogen and C1-6alkyl optionally substituted with one or more one or more R17c; andR12together with R13form a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR18c, -SR18c, - N(R18c)2, -C(O)R18c, -C(O)N(R18c)2, -N(R18c)C(O)R18c, -N(R18c)C(O)N(R18c)2, - OC(O)N(R18c)2, -N(R18c)C(O)OR18c, -C(O)OR18c, -OC(O)R18c, -S(O)R18c, -S(O)2R18c, -NO2, =O-, =S, =N(R18c), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R17c;R14is independently selected from: hydrogen, halogen, -OR18d, -SR18d, -N(R18d)2, -NO2, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR18d, -SR18d, -N(R18d)2, -NO2, and -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10- membered heterocycle, are each optionally substituted with one or more R17d;R14ais independently selected from: hydrogen, halogen, -OR18e, -SR18e, -N(R18e)2, -NO2, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR18e, -SR18e, -N(R18e)2, -NO2, and -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10- membered heterocycle, are each optionally substituted with one or more R17e; andR4together with R4aform a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR18e, -SR18e, -N(R18e)2, -C(O)R18e, -C(O)N(R18e)2, -N(R18e)C(O)R18e, -N(R18e)C(O)N(R18e)2, - OC(O)N(R18e)2, -N(R18e)C(O)OR18e, -C(O)OR18e, -OC(O)R18e, -S(O)R18e, -S(O)2R18e, -NO2, =O- =S, =N(R18e), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R17e;R15is selected from: hydrogen and C1-6alkyl optionally substituted with one or more one or more R17f; each R17, R17a, R17b, R17c, R17d, R17e, and R17fis independently selected from: hydrogen, halogen, -CN, -OH, -SH, -NO2, -NH2, -O-C1-6alkyl, -S-C1-6alkyl, - N(C1-6alkyl)2, and -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10-membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl. each R18, R18a, R18b, R18c, R18d, and R18eis independently selected from: hydrogen, halogen, -CN, -OH, -SH, -NO2, -NH2, -O-C1-6alkyl, -S-C1-6alkyl, - N(C1-6alkyl)2, and -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10-membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

29. The compound or salt of claim 28, wherein one of X5, X6, X7and X8is N.

30. The compound or salt of claim 28, wherein X5, X6, X7and X8are C(R10).

31. The compound or salt of claim 30, wherein R10is selected from hydrogen, -F, -Cl, -Br, - OCH3, -CN, and -CH3.

32. The compound or salt of any one of claims 28 to 31, wherein R11is selected from: methyl, ethyl, propyl, and isopropyl.

33. The compound or salt of any one of claims 28 to 32, wherein R12is selected from: C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10-membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.R12together with R13form a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, halogen, -OC1-6alkyl, -SC1-6alkyl, -N(C1-6alkyl)2, -C(O)C1-6alkyl, -C(O)N(C1-6alkyl)2, -N(C1-6alkyl)C(O)C1-6alkyl, -C(O)OC1-6alkyl, -OC(O)C1-6alkyl, -S(O)C1-6alkyl, -S(O)2C1-6alkyl, -NO2, =O-,=N(C1-6alkyl), -CN, -N3, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl.

34. The compound or salt of claim 33, wherein R12is selected from:

35. The compound or salt of any one of claims 28 to 34, wherein R13is selected from hydrogen, methyl, ethyl, propyl, and isopropyl.

36. The compound or salt of any one of claims 28 to 35, wherein R14and R14aare each independently selected from: hydrogen; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OC1-6alkyl, -N(C1-6alkyl)2, -C(O)C1-6alkyl, -C(O)N(C1-6alkyl)2, -CN; andR14together with R14aform a C3-10carbocycle, or 3- to 6-membered heterocycloalkyl.

37. The compound or salt of any one of claims 28 to 36, wherein R15is selected from hydrogen, methyl, ethyl, propyl, and isopropyl.

38. The compound or salt of claim 28, selected from:

39. A compound represented by Formula (III):or a salt thereof, wherein:X9, X10, X11and X12are independently selected from C(R20) and N wherein at least one of X9, X10, X11and X12is N and no more than two of X9, X10, X11and X12are N; each R20is independently selected from: hydrogen, halogen, -NO2, -CN, -N3, -OR28, -SR28, -N(R28)2, -C(O)R28, - C(O)N(R28)2, -N(R28)C(O)R28, -N(R28)C(O)N(R28)2, -OC(O)N(R28)2, - N(R28)C(O)OR28, -C(O)OR28, -OC(O)R28, -S(O)R28, and -S(O)2R28; and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR28, -SR28, -N(R28)2, -C(O)R28, -C(O)N(R28)2, -N(R28)C(O)R28, -C(O)OR28, - OC(O)R28, -N(R28)C(O)N(R28)2, -OC(O)N(R28)2, -N(R28)C(O)OR28, -S(O)R28, - S(O)2R28, -NO2, =O, =S, =N(R28), -CN, C3-10carbocycle and 3- to 10-membered heterocycle, wherein the C3-10carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more R27; and C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR28, -SR28, -N(R28)2, -C(O)R28, -C(O)N(R28)2, -N(R28)C(O)R28, - N(R28)C(O)N(R28)2, -OC(O)N(R28)2, -N(R28)C(O)OR28, -C(O)OR28, -OC(O)R28, - S(O)R28, -S(O)2R28, -NO2, =O-, =S, =N(R28), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R27;R21is selected from: C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR28a, -SR28a, -N(R28a)2, -C(O)R28a, -C(O)N(R28a)2, -N(R28a)C(O)R28a, -C(O)OR28a, - OC(O)R28a, -N(R28a)C(O)N(R28a)2, -OC(O)N(R28a)2, -N(R28a)C(O)OR28a, -S(O)R28a, - S(O)2R28a, -NO2, =O, =S, =N(R28a), -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with one or more R27a;R22is selected from: C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR28b, -SR28b, -N(R28b)2, -C(O)R28b, -C(O)N(R28b)2, -N(R28b)C(O)R28b-C(O)OR28b, - OC(O)R28b, -N(R28b)C(O)N(R28b)2, -OC(O)N(R28b)2, -N(R28b)C(O)OR28b, -S(O)R28b, - S(O)2R28b, -NO2, =O, =S, =N(R28b), -CN, C3-10carbocycle, and 3- to 10-memberedheterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with one or more R27b; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR28b, -SR28b, -N(R28b)2, -C(O)R28b, -C(O)N(R28b)2, -N(R28b)C(O)R28b- N(R28b)C(O)N(R28b)2, -OC(O)N(R28b)2, -N(R28b)C(O)OR28b, -C(O)OR28b, - OC(O)R28b, -S(O)R28b, -S(O)2R28b, -NO2, =O-, =S, =N(R28b), -CN, -N3, C3-10carbocycle, and 3- to 10-membered heterocycle, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R27b; orR21together with R22form a C3-10cycloalkyl, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR28b, -SR28b, -N(R28b)2, -C(O)R28b, -C(O)N(R28b)2, -N(R28b)C(O)R28b-N(R28b)C(O)N(R28b)2, - OC(O)N(R28b)2, -N(R28b)C(O)OR28b, -C(O)OR28b, -OC(O)R28b, -S(O)R28b, -S(O)2R28b, -NO2, =O-, =S, =N(R28b), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R27b;R23is selected from: hydrogen and C1-6alkyl optionally substituted with one or more one or more R27c; andR22together with R23form a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR28c, -SR28c, -N(R28c)2, -C(O)R28c, -C(O)N(R28c)2, -N(R28c)C(O)R28c, -N(R28c)C(O)N(R28c)2, - OC(O)N(R28c)2, -N(R28c)C(O)OR28c, -C(O)OR28c, -OC(O)R28c, -S(O)R28c, -S(O)2R28c, -NO2, =O-, =S, =N(R28c), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R27c;R24is independently selected from: hydrogen, halogen, -OR28d, -SR28d, -N(R28d)2, -NO2, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR28d, -SR28d, -N(R28d)2, -NO2, and -CN, C3-10carbocycle,and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10- membered heterocycle, are each optionally substituted with one or more R27d;R24ais independently selected from: hydrogen, halogen, -OR28e, -SR28e, -N(R28e)2, -NO2, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR28e, -SR28e, -N(R28e)2, -NO2, and -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10- membered heterocycle, are each optionally substituted with one or more R27e; and R23together with R24aform a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR28e, -SR28e, - N(R28e)2, -C(O)R28e, -C(O)N(R28e)2, -N(R28e)C(O)R28e, -N(R28e)C(O)N(R28e)2, - OC(O)N(R28e)2, -N(R28e)C(O)OR28e, -C(O)OR28e, -OC(O)R28e, -S(O)R28e, -S(O)2R28e, -NO2, =O-, =S, =N(R28e), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R27e;R25is selected from: hydrogen and C1-6alkyl optionally substituted with one or more one or more R27f; each R27, R27a, R27b, R27c, R27d, R27eand R27fis independently selected from: hydrogen, halogen, -CN, -OH, -SH, -NO2, -NH2, -O-C1-6alkyl, -S-C1-6alkyl, - N(C1-6alkyl)2, and -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10-membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl. each R28, R28a, R28b, R28c, R28d, R28eis independently selected from: hydrogen, halogen, -CN, -OH, -SH, -NO2, -NH2, -O-C1-6alkyl, -S-C1-6alkyl, - N(C1-6alkyl)2, and -NH(C1-6alkyl); andC1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10-membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

40. The compound or salt of claim 39, wherein X9is N.

41. The compound or salt of any one of claims 39 to 40, wherein R20is selected from hydrogen, - F, -Cl, -Br, -OCH3, -CN, and -CH3.

42. The compound or salt of any one of claims 39 to 41, wherein R21is selected from: methyl, ethyl, propyl, and isopropyl.

43. The compound or salt of any one of claims 39 to 42, wherein R22is selected from: C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10-membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl;R22together with R23form a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, halogen, -OC1-6alkyl, -SC1-6alkyl, -N(C1-6alkyl)2, -C(O)C1-6alkyl, -C(O)N(C1-6alkyl)2, -N(C1-6alkyl)C(O)C1-6alkyl, -C(O)OC1-6alkyl, -OC(O)C1-6alkyl, -S(O)C1-6alkyl, -S(O)2C1-6alkyl, -NO2, =O-,=N(C1-6alkyl), -CN, -N3, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl.

44. The compound or salt of claim 43, wherein R22is selected from: phenyl, 7V-morpholinyl, and N-pyrrolidinyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -NO2, -O-C1-6alkyl, and -N(C1-6alkyl)2.

45. The compound or salt of any one of claims 39 to 44, wherein R22is46. The compound or salt of any one of claims 39 to 45, wherein R23is selected from hydrogen, methyl, ethyl, propyl, and isopropyl.

47. The compound or salt of any one of claims 39 to 46, wherein R24and R24aare each independently selected from: hydrogen; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OC1-6alkyl, -N(C1-6alkyl)2, -C(O)C1-6alkyl, -C(O)N(C1-6alkyl)2, -CN; andR24together with R24aform a C3-10carbocycle, or 3- to 6-membered heterocycloalkyl.

48. The compound or salt of any one of claims 39 to 47, wherein R25is selected from hydrogen, methyl, ethyl, propyl, and isopropyl.

49. The compound or salt of any one of claims 39 to 48, wherein R26is selected from hydrogen, methyl, ethyl, propyl, and isopropyl.

50. The compound or salt of claim 39, selected from:or a salt of any one thereof.

51. A compound represented by Formula (IV):or a salt thereof, wherein:X13, X14, X15, X16and X17are independently selected from C(R32) and N; wherein at least one of X13, X14, X15, X16and X17is N; n is selected from 1, 2, 3, and 4; each R30is independently selected from: hydrogen, halogen, -NO2, -CN, -N3, -OR38, -SR38, -N(R38)2, -C(O)R38, - C(O)N(R38)2, -N(R38)C(O)R38, -N(R38)C(O)N(R38)2, -OC(O)N(R38)2, - N(R38)C(O)OR38, -C(O)OR38, -OC(O)R38, -S(O)R38, and -S(O)2R38; and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR38, -SR38, -N(R38)2, -C(O)R38, -C(O)N(R38)2, -N(R38)C(O)R38, -C(O)OR38, - OC(O)R38, -N(R38)C(O)N(R38)2, -OC(O)N(R38)2, -N(R38)C(O)OR38, -S(O)R38, - S(O)2R38, -NO2, =O, =S, =N(R38), -CN, C3-10carbocycle and 3- to 10-membered heterocycle, wherein the C3-10carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more R371; and C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR38, -SR38, -N(R38)2, -C(O)R38, -C(O)N(R38)2, -N(R38)C(O)R38, - N(R38)C(O)N(R38)2, -OC(O)N(R38)2, -N(R38)C(O)OR38, -C(O)OR38, -OC(O)R38, - S(O)R38, -S(O)2R38, -NO2, =O-, =S, =N(R38), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R371;R31is selected from: C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR38a, -SR38a, -N(R38a)2, -C(O)R38a, -C(O)N(R38a)2, -N(R38a)C(O)R38a, -C(O)OR38a, - OC(O)R38a, -N(R38a)C(O)N(R38a)2, -OC(O)N(R38a)2, -N(R38a)C(O)OR38a, -S(O)R38a, - S(O)2R38a, -NO2, =O, =S, =N(R38a), -CN, C3-10carbocycle, and 3- to 10-memberedheterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with one or more R37j; each R32is independently selected from: hydrogen, halogen, -NO2, -CN, -N3, -OR38b, -SR38b, -N(R38b)2, -C(O)R38b, - C(O)N(R38b)2, -N(R38b)C(O)R38b-N(R38b)C(O)N(R38b)2, -OC(O)N(R38b)2, - N(R38b)C(O)OR38b, -C(O)OR38b, -OC(O)R38b, -S(O)R38b, and -S(O)2R38b; and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR38b, -SR38b, -N(R38b)2, -C(O)R38b, -C(O)N(R38b)2, -N(R38b)C(O)R38b-C(O)OR38b, - OC(O)R38b, -N(R38b)C(O)N(R38b)2, -OC(O)N(R38b)2, -N(R38b)C(O)OR38b, -S(O)R38b, - S(O)2R38b, -NO2, =O, =S, =N(R38b), -CN, C3-10carbocycle and 3- to 10-membered heterocycle, wherein the C3-10carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more R37b; and C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR38b, -SR38b, -N(R38b)2, -C(O)R38b, -C(O)N(R38b)2, -N(R38b)C(O)R38b- N(R38b)C(O)N(R38b)2, -OC(O)N(R38b)2, -N(R38b)C(O)OR38b, -C(O)OR38b, - OC(O)R38b, -S(O)R38b, -S(O)2R38b, -NO2, =O-, =S, =N(R38b), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R37b;R33is selected from: hydrogen and C1-6alkyl optionally substituted with one or more one or moreR37c;R34is independently selected from: hydrogen, halogen, -OR38c, -SR38c, -N(R38c)2, -NO2, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR38c, -SR38c, -N(R38c)2, -NO2, and -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10- membered heterocycle, are each optionally substituted with one or more R37d;R34ais independently selected from: hydrogen, halogen, -OR38d, -SR38d, -N(R38d)2, -NO2, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR38d, -SR38d, -N(R38d)2, -NO2, and -CN, C3-10carbocycle,and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10- membered heterocycle, are each optionally substituted with one or more R37e; andR34together with R34aform a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR38d, -SR38d, - N(R38d)2, -C(O)R38d, -C(O)N(R38d)2, -N(R38d)C(O)R38d-N(R38d)C(O)N(R38d)2, - OC(O)N(R38d)2, -N(R38d)C(O)OR38d, -C(O)OR38d, -OC(O)R38d, -S(O)R38d, -S(O)2R38d, -NO2, =O-, =S, =N(R38d), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R37e; each R35and R35ais independently selected from: hydrogen, halogen, -OR38e, -SR38e, -N(R38e)2, -NO2, -CN, C1-6alkyl, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C1-6alkyl, C3-10carbocycle, and 3- to 10- membered heterocycle are each optionally substituted with one or more R37f; orR35together with R35aform a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR38e, -SR38e, - N(R38e)2, -C(O)R38e, -C(O)N(R38e)2, -N(R38e)C(O)R38e, -N(R38e)C(O)N(R38e)2, - OC(O)N(R38e)2, -N(R38e)C(O)OR38e, -C(O)OR38e, -OC(O)R38e, -S(O)R38e, -S(O)2R38e, -NO2, =O-, =S, =N(R38e), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R37f; each R36and R36ais independently selected from: hydrogen, halogen, -OR38f, -SR38f, -N(R38f)2, -NO2, -CN, C1-6alkyl, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C1-6alkyl, C3-10carbocycle, and 3- to 10- membered heterocycle are each optionally substituted with one or more R37g; orR36together with R36aform a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR38f, -SR38f, - N(R38f)2, -C(O)R38f, -C(O)N(R38f)2, -N(R38f)C(O)R38f, -N(R38f)C(O)N(R38f)2, - OC(O)N(R38f)2, -N(R38f)C(O)OR38f, -C(O)OR38f, -OC(O)R38f, -S(O)R38f, -S(O)2R38f, - NO2, =O-, =S, =N(R38f), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R37g; each R37and R37ais independently selected from: hydrogen, halogen, -OR38g, -SR38g, -N(R38g)2, -NO2, -CN, C1-6alkyl, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C1-6alkyl, C3-10carbocycle, and 3- to 10- membered heterocycle are each optionally substituted with one or more R37h; orR37together with R37aform a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR38g, -SR38g, - N(R38g)2, -C(O)R38g, -C(O)N(R38g)2, -N(R38g)C(O)R38g-N(R38g)C(O)N(R38g)2, - OC(O)N(R38g)2, -N(R38g)C(O)OR38g, -C(O)OR38g, -OC(O)R38g, -S(O)R38g, -S(O)2R38g, -NO2, =O-, =S, =N(R38g), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R37h; each R37i, R37j, R37b, R37c, R37d, R37e, R37f, R37g, and R37his independently selected from: hydrogen, halogen, -CN, -OH, -SH, -NO2, -NH2, -O-C1-6alkyl, -S-C1-6alkyl, - N(C1-6alkyl)2, and -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10-membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl; each R38, R38a, R38b, R38c, R38d, R38e, R38f, and R38gis independently selected from: hydrogen, halogen, -CN, -OH, -SH, -NO2, -NH2, -O-C1-6alkyl, -S-C1-6alkyl, - N(C1-6alkyl)2, and -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10-membered heterocycle; andC3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-e alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

52. The compound or salt of claim 51, wherein X13is N.

53. The compound or salt of any one of claims 51 to 52, wherein R30is selected from hydrogen, - F, -Cl, -Br, -OCH3, -CN, and -CH3.

54. The compound or salt of any one of claims 51 to 53, wherein R31is selected from: methyl, ethyl, propyl, and isopropyl.

55. The compound or salt of any one of claims 51 to 54, wherein R32is selected from hydrogen, - F, -Cl, -Br, -OCH3, -CN, and -CH3.

56. The compound or salt of any one of claims 51 to 55, wherein n is selected from 0, 1, and 2.

57. The compound or salt of any one of claims 51 to 56, wherein R33is selected from: hydrogen, methyl, ethyl, propyl, and isopropyl; andR33together with R30form a C1-3 carbocycle, which is optionally substituted with substituents independently selected from halogen, -OR38d, -SR38d, - N(R38d)2, -C(O)R38d, -C(O)N(R38d)2, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl.

58. The compound or salt of claim 57, wherein R33is selected from hydrogen, methyl, ethyl, propyl, and isopropyl.

59. The compound or salt of any one of claims 51 to 58, wherein R34and R34aare each independently selected from: hydrogen; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OC1-6alkyl, -N(C1-6alkyl)2, -C(O)C1-6alkyl, -C(O)N(C1-6alkyl)2, -CN; andR34together with R34aform a C3-10carbocycle, or 3- to 6-membered heterocycloalkyl; andR34together with R35form a C3-10carbocycle, or 3- to 6-membered heterocycloalkyl.

60. The compound or salt of any one of claims 51 to 59, wherein R35and R35aare each independently selected from: hydrogen; andC1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OC1-6alkyl, -N(C1-6alkyl)2, -C(O)C1-6alkyl, -C(O)N(C1-6alkyl)2, -CN; andR35together with R35aform a C3-10carbocycle, or 3- to 6-membered heterocycloalkyl; andR35together with R36form a C3-10carbocycle, or 3- to 6-membered heterocycloalkyl; andR35together with R37form a C3-10carbocycle, or 3- to 6-membered heterocycloalkyl.

61. The compound or salt of claim 60, wherein R35together with R35aform a C3-6carbocycle optionally substituted with one or more substituents independently selected from halogen, - OR38e, -SR38e, -N(R38e)2, -C(O)R38e, -C(O)N(R38e)2, -N(R38e)C(O)R38e, -C(O)OR38e, -NO2, =O-,-CN, C1-6alkyl, and C1-6haloalkyl.

62. The compound or salt of any one of claims 51 to 61, wherein R36and R36aare each independently selected from: hydrogen; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OC1-6alkyl, -N(C1-6alkyl)2, -C(O)C1-6alkyl, -C(O)N(C1-6alkyl)2, -CN;R36together with R36aform a C3-10carbocycle, or 3- to 6-membered heterocycloalkyl.

63. The compound or salt of any one of claims 51 to 62, wherein R37and R37aare each independently selected from: hydrogen; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OC1-6alkyl, -N(C1-6alkyl)2, -C(O)C1-6alkyl, -C(O)N(C1-6alkyl)2, -CN; andR37together with R37aform a C3-10carbocycle, or 3- to 6-membered heterocycloalkyl.

64. The compound or salt of any one of claims 51 to 63, wherein R37and R37aare each independently selected from: hydrogen; andC1-3 alkyl optionally substituted with one or more substituents independently selected from halogen, -OMe, -OH, -N(Me)2, and -CN; andR37together with R37aform a C3-10carbocycle, or 3- to 6-membered heterocycloalkyl.

65. The compound or salt of claim 51, selected from:any one thereof.

66. A compound represented by Formula (V):or a salt thereof, wherein:XA, XB, Xcand XDare independently selected from C(R40) and N; each R40is independently selected from: hydrogen, halogen, -NO2, -CN, -N3, -OR48, -SR48, -N(R48)2, -C(O)R48, - C(O)N(R48)2, -N(R48)C(O)R48, -N(R48)C(O)N(R48)2, -OC(O)N(R48)2, - N(R48)C(O)OR48, -C(O)OR48, -OC(O)R48, -S(O)R48, and -S(O)2R48; andC1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR48, -SR48, -N(R48)2, -C(O)R48, -C(O)N(R48)2, -N(R48)C(O)R48, -C(O)OR48, - OC(O)R48, -N(R48)C(O)N(R48)2, -OC(O)N(R48)2, -N(R48)C(O)OR48, -S(O)R48, - S(O)2R48, -NO2, =O, =S, =N(R48), -CN, C3-10carbocycle and 3- to 10-membered heterocycle, wherein the C3-10carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more R47; and C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR48, -SR48, -N(R48)2, -C(O)R48, -C(O)N(R48)2, -N(R48)C(O)R48, - N(R48)C(O)N(R48)2, -OC(O)N(R48)2, -N(R48)C(O)OR48, -C(O)OR48, -OC(O)R48, - S(O)R48, -S(O)2R48, -NO2, =O-, =S, =N(R48), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R47;R41is selected from: halogen, -NO2, -CN, -N3, -OR48a, -SR48a, -N(R48a)2, -C(O)R48a, -C(O)N(R48a)2, -N(R48a)C(O)R48a-N(R48a)C(O)N(R48a)2, -OC(O)N(R48a)2, -N(R48a)C(O)OR48a, -C(O)OR48a, -OC(O)R48a, -S(O)R48a, and -S(O)2R48a; and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR48a, -SR48a, -N(R48a)2, -C(O)R48a, -C(O)N(R48a)2, -N(R48a)C(O)R48a, -C(O)OR48a, - OC(O)R48a, -N(R48a)C(O)N(R48a)2, -OC(O)N(R48a)2, -N(R48a)C(O)OR48a, -S(O)R48a, - S(O)2R48a, -NO2, =O, =S, =N(R48a), -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with one or more R47a;R42is selected from: C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR48b, -SR48b, -N(R48b)2, -C(O)R48b, -C(O)N(R48b)2, -N(R48b)C(O)R48b-C(O)OR48b, - OC(O)R48b, -N(R48b)C(O)N(R48b)2, -OC(O)N(R48b)2, -N(R48b)C(O)OR48b, -S(O)R48b, - S(O)2R48b, -NO2, =O, =S, =N(R48b), -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with one or more R47b; andC3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR48b, -SR48b, -N(R48b)2, -C(O)R48b, -C(O)N(R48b)2, -N(R48b)C(O)R48b- N(R48b)C(O)N(R48b)2, -OC(O)N(R48b)2, -N(R48b)C(O)OR48b, -C(O)OR48b, - OC(O)R48b, -S(O)R48b, -S(O)2R48b, -NO2, =O-, =S, =N(R48b), -CN, -N3, C3-10carbocycle, and 3- to 10-membered heterocycle, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein the C3-10carbocycle, 3- to 10-membered heterocycle, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R47b; orR41together with R42form a C3-10cycloalkyl, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR48b, -SR48b, -N(R48b)2, -C(O)R48b, -C(O)N(R48b)2, -N(R48b)C(O)R48b-N(R48b)C(O)N(R48b)2, - OC(O)N(R48b)2, -N(R48b)C(O)OR48b, -C(O)OR48b, -OC(O)R48b, -S(O)R48b, -S(O)2R48b, -NO2, =O-, =S, =N(R48b), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R47b;R43is selected from: hydrogen and C1-6alkyl optionally substituted with one or more one or more R47c; andR42together with R43form a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR48c, -SR48c, -N(R48c)2, -C(O)R48c, -C(O)N(R48c)2, -N(R48c)C(O)R48c, -N(R48c)C(O)N(R48c)2, - OC(O)N(R48c)2, -N(R48c)C(O)OR48c, -C(O)OR48c, -OC(O)R48c, -S(O)R48c, -S(O)2R48c, -NO2, =O-, =S, =N(R48c), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R47c;R44is independently selected from: hydrogen, halogen, -OR48d, -SR48d, -N(R48d)2, -NO2, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR48d, -SR48d, -N(R48d)2, -NO2, and -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10- membered heterocycle, are each optionally substituted with one or more R47d;R44ais independently selected from:hydrogen, halogen, -OR48e, -SR48e, -N(R48e)2, -NO2, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR48e, -SR48e, -N(R48e)2, -NO2, and -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10- membered heterocycle, are each optionally substituted with one or more R47e; andR44together with R44aform a C3-10 carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR48e, -SR48e, - N(R48e)2, -C(O)R48e, -C(O)N(R48e)2, -N(R48e)C(O)R48e, -N(R48e)C(O)N(R48e)2, - OC(O)N(R48e)2, -N(R48e)C(O)OR48e, -C(O)OR48e, -OC(O)R48e, -S(O)R48e, -S(O)2R48e, -NO2, =O-, =S, =N(R48e), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R47e;R45is selected independently from: hydrogen, halogen, -NO2, -CN, -N3, - OR48f, -SR48f, -N(R48f)2, -C(O)R48f, -C(O)N(R48f)2, -N(R48f)C(O)R48f, - N(R48f)C(O)N(R48f)2, -OC(O)N(R48f)2, -N(R48f)C(O)OR48f, -C(O)OR48f, -OC(O)R48f, - S(O)R48f, and -S(O)2R48f; and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR48f, -SR48f, -N(R48f)2, -C(O)R48f, -C(O)N(R48f)2, -N(R48f)C(O)R48f, -C(O)OR48f, - OC(O)R48f, -N(R48f)C(O)N(R48f)2, -OC(O)N(R48f)2, -N(R48f)C(O)OR48f, -S(O)R48f, - S(O)2R48f, -NO2, =O, =S, =N(R48f), -CN, C3-10carbocycle and 3- to 10-membered heterocycle, wherein the C3-10carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more R47f; and C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR48f, -SR48f, -N(R48f)2, -C(O)R48f, -C(O)N(R48f)2, -N(R48f)C(O)R48f, - N(R48f)C(O)N(R48f)2, -OC(O)N(R48f)2, -N(R48f)C(O)OR48f, -C(O)OR48f, -OC(O)R48f, - S(O)R48f, -S(O)2R48f, -NO2, =O-, =S, =N(R48f), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R47f; each R46and R46ais selected independently from: hydrogen, halogen, -OR48g, -SR48g, -N(R48g)2, -NO2, -CN, C1-6alkyl, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C1-6alkyl, C3-10carbocycle, and 3- to 10- membered heterocycle are each optionally substituted with one or more R47g; orR46together with R45form an -O- bridge, an -NR7g- bridge, a C1-5alkylene bridge, or a 1- to 5-membered heteroalkylene bridge, wherein each of the C1-5alkylene bridge, or 1- to 5-membered heteroalkylene bridge is optionally substituted with one or more substituents independently selected from halogen, -OR48g, -SR48g, - N(R48g)2, -C(O)R48g, -C(O)N(R48g)2, -N(R48g)C(O)R48g-N(R48g)C(O)N(R48g)2, - OC(O)N(R48g)2, -N(R48g)C(O)OR48g, -C(O)OR48g, -OC(O)R48g, -S(O)R48g, -S(O)2R48g, -NO2, =O-, =S, =N(R48g), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R47g; each R47, R47a, R47b, R47c, R47d, R47e, R47f, and R47gis independently selected from: hydrogen, halogen, -CN, -OH, -SH, -NO2, -NH2, -O-C1-6alkyl, -S-C1-6alkyl, - N(C1-6alkyl)2, and -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10-membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl; each R48, R48a, R48b, R48c, R48d, R48e, R48f, and R48gis independently selected from: hydrogen, halogen, -CN, -OH, -SH, -NO2, -NH2, -O-C1-6alkyl, -S-C1-6alkyl, - N(C1-6alkyl)2, and -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10-membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

67. The compound or salt of claim 66, wherein at least one of XA, XB, Xcand XDis N.

68. The compound or salt of claim 67, wherein XBis N.

69. The compound or salt of any one of claims 66-68, wherein XA, XB, and Xcare each C(R40).

70. The compound or salt of claim 69, wherein XAis C(R40).

71. The compound or salt of claims 69 or 70, wherein each R40is independently selected from hydrogen, halogen, -NO2, -CN, -OR48, -SR48, -N(R48)2, -C(O)R48, -C(O)OR48, C1-6alkyl and C1-6haloalkyl.

72. The compound or salt of claim 71, wherein each R40is independently selected from hydrogen, halogen, and methyl.

73. The compound or salt of any one of claims 66-72, wherein R41is selected from: methyl, ethyl, propyl, and isopropyl.

74. The compound or salt of any one of claims 66-73, wherein R42is selected from: C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, - OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10- membered heterocycle, and C1-6haloalkyl; orR41together with R42form a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, halogen, -OC1-6alkyl, -SC1-6alkyl, -N(C1-6alkyl)2, -C(O)C1-6alkyl, -C(O)N(C1-6alkyl)2, -N(C1-6alkyl)C(O)C1-6alkyl, -C(O)OC1-6alkyl, -OC(O)C1-6alkyl, -S(O)C1-6alkyl, -S(O)2C1-6alkyl, -NO2, =O-,=N(C1-6alkyl), - CN, -N3, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl.

75. The compound or salt of claim 74, wherein R42is selected from 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S- C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

76. The compound or salt of claim 75, wherein R42is pyridinyl optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, -OCH3, -C(O)0Me, -CN, -N3, methyl, ethyl, propyl, and isopropyl.

77. The compound or salt of claim 76, wherein R42is78. The compound or salt of any one of claims 66-77, wherein R43is selected from: hydrogen and C1-6alkyl optionally substituted with one or more halogen, -CN, - OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10-membered heterocycle; andR42together with R43form a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, halogen, -OC1-6alkyl, -SC1-6alkyl, -N(C1-6alkyl)2, -C(O)C1-6alkyl, -C(O)N(C1-6alkyl)2, -N(C1-6alkyl)C(O)C1-6alkyl, -C(O)OC1-6alkyl, -OC(O)C1-6alkyl, -S(O)C1-6alkyl, -S(O)2C1-6alkyl, -NO2, =O-,=N(C1-6alkyl), - CN, -N3, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl.

79. The compound or salt of claim 78, wherein R43is selected from hydrogen, methyl, ethyl, propyl, and isopropyl.

80. The compound or salt of claim 79, wherein R43is hydrogen.

81. The compound or salt of any one of claims 66-80, wherein R44and R44aare each independently selected from: hydrogen; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OC1-6alkyl, -N(C1-6alkyl)2, -CN, C3-6carbocycle, and 3- to 6- membered heterocycle, wherein the C3-6carbocycle, and 3- to 6-membered heterocycle, are each optionally substituted with one or more halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl; andR44together with R44aform a C3-10 carbocycle, or 3- to 6-membered heterocycloalkyl.

82. The compound or salt of claim 81, wherein R44and R44aform a C3-6carbocycle.

83. The compound or salt of claim 82, wherein R44and R44aform a cyclopropyl.

84. The compound or salt of any one of claims 66-83, wherein R45is selected independently from: hydrogen, halogen, -NO2, -CN, -N3, -OR48f, -SR48f, -N(R48f)2, -C(O)R48f, - C(O)N(R48f)2, -N(R48f)C(O)R48f, -N(R48f)C(O)N(R48f)2, -OC(O)N(R48f)2, - N(R48f)C(O)OR48f, -C(O)OR48f, -OC(O)R48f, -S(O)R48f, and -S(O)2R48f; andC1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR48f, -SR48f, - N(R48f)2, -C(O)R48f, -C(O)N(R48f)2, -N(R48f)C(O)R48f, -C(O)OR48f, -OC(O)R48f, - N(R48f)C(O)N(R48f)2, -OC(O)N(R48f)2, -N(R48f)C(O)OR48f, -S(O)R48f, -S(O)2R48f, -NO2, =O, =S, =N(R48f), -CN, C3-10carbocycle and 3- to 10-membered heterocycle, wherein the C3-10carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more R47f.

85. The compound or salt of claim 84, wherein R45is selected from hydrogen, methyl, ethyl, propyl, and isopropyl.

86. The compound or salt of any one of claims 66-85, wherein each R46and R46ais selected independently from hydrogen, halogen, -OC1-6alkyl, -SC1-6alkyl, -N(C1-6alkyl)2, -NO2, -CN, C1-6alkyl, C3-6carbocycle, and 3- to 6-membered heterocycle, wherein the C1-6alkyl, C3-10carbocycle, and 3- to 10- membered heterocycle are each optionally substituted with one or more halogen, -OC1-6alkyl, -SC1-6alkyl, -N(C1-6alkyl)2, -NO2, -CN, C1-6alkyl.

87. The compound or salt of claim 86, wherein R46and R46aare each hydrogen.

88. The compound or salt of claim 66, selected fromand89. A compound represented by Formula (VI):or a salt thereof, wherein:XE, XF, XGand XHare independently selected from C(R50) and N; each R50is independently selected from: hydrogen, halogen, -NO2, -CN, -N3, -OR58, -SR58, -N(R58)2, -C(O)R58, - C(O)N(R58)2, -N(R58)C(O)R58, -N(R58)C(O)N(R58)2, -OC(O)N(R58)2, -N(R58)C(O)OR58, -C(O)OR58, -OC(O)R58, -S(O)R58, and -S(O)2R58; andC1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR58, -SR58, -N(R58)2, -C(O)R58, -C(O)N(R58)2, -N(R58)C(O)R58, -C(O)OR58, - OC(O)R58, -N(R58)C(O)N(R58)2, -OC(O)N(R58)2, -N(R58)C(O)OR58, -S(O)R58, - S(O)2R58, -NO2, =O, =S, =N(R58), -CN, C3-10carbocycle and 3- to 10-membered heterocycle, wherein the C3-10carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more R57; and C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR58, -SR58, -N(R58)2, -C(O)R58, -C(O)N(R58)2, -N(R58)C(O)R58, - N(R58)C(O)N(R58)2, -OC(O)N(R58)2, -N(R58)C(O)OR58, -C(O)OR58, -OC(O)R58, - S(O)R58, -S(O)2R58, -NO2, =O-, =S, =N(R58), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R57;R51is selected from: C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR58a, -SR58a, -N(R58a)2, -C(O)R58a, -C(O)N(R58a)2, -N(R58a)C(O)R58a, -C(O)OR58a, - OC(O)R58a, -N(R58a)C(O)N(R58a)2, -OC(O)N(R58a)2, -N(R58a)C(O)OR58a, -S(O)R58a, - S(O)2R58a, -NO2, =O, =S, =N(R58a), -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with one or more R57a;R52is selected from: C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR58b, -SR58b, -N(R58b)2, -C(O)R58b, -C(O)N(R58b)2, -N(R58b)C(O)R58b-C(O)OR58b, - OC(O)R58b, -N(R58b)C(O)N(R58b)2, -OC(O)N(R58b)2, -N(R58b)C(O)OR58b, -S(O)R58b, - S(O)2R58b, -NO2, =O, =S, =N(R58b), -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with one or more R57b; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR58b, -SR58b, -N(R58b)2, -C(O)R58b, -C(O)N(R58b)2, -N(R58b)C(O)R58b- N(R58b)C(O)N(R58b)2, -OC(O)N(R58b)2, -N(R58b)C(O)OR58b, -C(O)OR58b, -OC(O)R58b, -S(O)R58b, -S(O)2R58b, -NO2, =O- =S, =N(R58b), -CN, -N3, C3-10carbocycle, and 3- to 10-membered heterocycle, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein the C3-10carbocycle, 3- to 10-membered heterocycle, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R57b; orR51together with R52form a C3-10cycloalkyl, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR58b, -SR58b, - N(R58b)2, -C(O)R58b, -C(O)N(R58b)2, -N(R58b)C(O)R58b-N(R58b)C(O)N(R58b)2, - OC(O)N(R58b)2, -N(R58b)C(O)OR58b, -C(O)OR58b, -OC(O)R58b, -S(O)R58b, -S(O)2R58b, -NO2, =O-, =S, =N(R58b), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R57b;R53is selected from: hydrogen and C1-6alkyl optionally substituted with one or more one or more R57c; andR52together with R53form a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR58c, -SR58c, - N(R58c)2, -C(O)R58c, -C(O)N(R58c)2, -N(R58c)C(O)R58c, -N(R58c)C(O)N(R58c)2, - OC(O)N(R58c)2, -N(R58c)C(O)OR58c, -C(O)OR58c, -OC(O)R58c, -S(O)R58c, -S(O)2R58c, -NO2, =O-, =S, =N(R58c), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R57c;R54is independently selected from: hydrogen, halogen, -OR58d, -SR58d, -N(R58d)2, -NO2, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR58d, -SR58d, -N(R58d)2, -NO2, and -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10- membered heterocycle, are each optionally substituted with one or more R57d;R54ais independently selected from: halogen, -OR58e, -SR58e, -N(R58e)2, -NO2, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR58e, -SR58e, -N(R58e)2, -NO2, and -CN, C3-10carbocycle,and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10- membered heterocycle, are each optionally substituted with one or more R57e; andR54together with R54aform a C3-10carbocycle, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR58e, -SR58e, - N(R58e)2, -C(O)R58e, -C(O)N(R58e)2, -N(R58e)C(O)R58e, -N(R58e)C(O)N(R58e)2, - OC(O)N(R58e)2, -N(R58e)C(O)OR58e, -C(O)OR58e, -OC(O)R58e, -S(O)R58e, -S(O)2R58e, -NO2, =O-, =S, =N(R58e), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more R57e;R55is selected from: hydrogen, -F, -Br, -I, -OR58f, -SR58f, -N(R58f)2, -NO2, -CN, C1-6alkyl, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C1-6alkyl, C3-10carbocycle, and 3- to 10- membered heterocycle are each optionally substituted with one or more R57f; each R57, R57a, R57b, R57c, R57d, R57e, and R57fis independently selected from: hydrogen, halogen, -CN, -OH, -SH, -NO2, -NH2, -O-C1-6alkyl, -S-C1-6alkyl, - N(C1-6alkyl)2, and -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10-membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl; each R58, R58a, R58b, R58c, R58d, R58e, and R58fis independently selected from: hydrogen, halogen, -CN, -OH, -SH, -NO2, -NH2, -O-C1-6alkyl, -S-C1-6alkyl, - N(C1-6alkyl)2, and -NH(C1-6alkyl); and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C3-10carbocycle, 3- to 10-membered heterocycle; andC3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10-membered heterocycle, and C1-6haloalkyl.

90. The compound or salt of claim 89, wherein XE, XF, XGand XHare each C(R50).

91. The compound or salt of claim 90, wherein each R50is independently selected from hydrogen, -F, -Cl, -Br, -OCH3, -CN, and -CH3.

92. The compound or salt of any one of claims 89-91, wherein R51is selected from: methyl, ethyl, propyl, and isopropyl.

93. The compound or salt of any one of claims 89-92, wherein R52is selected from: C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C3-10carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -N(C1-6alkyl)2, - NH(C1-6alkyl), C3-10carbocycle, 3- to 10-membered heterocycle; and C3-10carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, - OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S-C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10carbocycle, 3- to 10- membered heterocycle, and C1-6haloalkyl.

94. The compound or salt of claim 93, wherein R52is selected from 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C1-6alkyl, -S- C1-6alkyl, -SO2-C1-6alkyl, -N(C1-6alkyl)2, -NH(C1-6alkyl), C1-6alkyl, and C1-6haloalkyl.

95. The compound or salt of claim 94, wherein R52is pyridinyl optionally substituted with -F, - Cl, -Br, -OCH3, -CN, and -CH3.

96. The compound or salt of any one of claims 89-95, wherein R53is selected from hydrogen, methyl, ethyl, propyl, and isopropyl.

97. The compound or salt of any one of claims 89-96, wherein R54is independently selected from hydrogen and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OC1-6alkyl, -N(C1-6alkyl)2, and -CN.

98. The compound or salt of any one of claims 89-97, wherein R54ais independently selected from halogen, -OR58e, -SR58e, -N(R58e)2, -NO2, and -CN; andC1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR58e, -SR58e, -N(R58e)2, -NO2, and -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with halogen, -OC1-6alkyl, -N(C1-6alkyl)2, -C(O)C1-6alkyl, -C(O)N(C1-6alkyl)2, -CN.

99. The compound or salt of claim 98, wherein R54ais independently selected from C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, - OR58e, -SR58e, -N(R58e)2, -NO2, and -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10carbocycle, and 3- to 10-membered heterocycle, are each optionally substituted with halogen, -OC1-6alkyl, -N(C1-6alkyl)2, -C(O)C1-6alkyl, - C(O)N(C1-6alkyl)2, -CN.

100. The compound or salt of claim 99, wherein R54ais101. The compound or salt of any one of claims 89-100, wherein R55is selected from hydrogen, methyl, ethyl, propyl, and isopropyl.

103. A pharmaceutical composition comprising a compound or salt of any one of claims 1 to 102 and a pharmaceutically acceptable excipient.

104. A method of treating a metabolic disease, a neuromuscular condition, a skeletal muscular condition, sarcopenia, muscle wasting, muscle spasm, inducing weight loss, or of inducingmuscle gain, the method comprising administering to a patient in need thereof a compound or salt of any one of claims 1 to 102 or the pharmaceutical composition of claim 103.

105. The method of claim 104, wherein the metabolic disease is selected from obesity, morbid obesity, super morbid obesity, pre-diabetes, diabetes, or a metabolic syndrome.

106. The method of claim 105, wherein metabolic disease is obesity.

107. The method of claim 105, wherein diabetes is selected from type 1 diabetes and type 2 diabetes.

108. The method of claim 105, wherein the metabolic syndrome is selected from high blood pressure, high blood sugar, excess body fat around the waist, or irregular cholesterol levels.

109. The method of claim 104, further comprising the administration of a second therapeutic agent.

110. The method of claim 109, wherein the second therapeutic agent comprises a GLP-1 modulator or SGLT2 modulator, GIP modulator, a secretagogue, or alpha-glucosidase modulator.

111. The method of claim 110, wherein the second therapeutic agent comprises Dulaglutide, Exenatide, Semaglutide, Liraglutide, Lixisenatide, or Tirzepatide.

112. A method of extending the amount of time muscle fibers reside in a DRX state or increasing the population of muscle fibers residing in the DRX state, the method comprising administering to a patient in need thereof a compound or salt of any one of claims 1 to 102 or the pharmaceutical composition of claim 103.

113. The method of claim 112, wherein the amount of time muscle fibers reside in a DRX state is increased by 5% or more.

114. The method of claim 112, wherein the population of muscle fibers residing in the DRX state is increased by 5% or more.

115. The method of claim 112, wherein the resting energy consumption rate of the subject is increased 5% or more.

116. A method of modulating myosin, the method comprising administering a therapeutically effective amount of a compound or salt of any one of claims 1 to 102 or the pharmaceutical composition of claim 103.

117. The method of claim 116, wherein the myosin is skeletal myosin or cardiac myosin.

118. The method of claim 117, wherein the myosin is skeletal myosin, and the modulation is activation or inhibition.

119. The method of claim 118, wherein the myosin is skeletal myosin, and the modulation is activation.

120. The method of claim 118, wherein the myosin is skeletal myosin, and the modulation is inhibition.

121. The method of claim 116, wherein the myosin is cardiac myosin, and the modulation is activation or inhibition.

122. The method of claim 121, wherein the myosin is cardiac myosin, and the modulation is activation.

123. The method of claim 121, wherein the myosin is cardiac myosin, and the modulation is inhibition.

124. The method of claim 119, wherein the modulation is skeletal activation, and the method is for inducing weight loss; inducing muscle gain; extending the amount of time muscle fibers reside in a DRX state; increasing the population of muscle fibers residing in the DRX state; or treating a condition selected from: a metabolic disease, activity-induced muscle damage, a neuromuscular condition, a skeletal muscular condition, sarcopenia, muscle wasting, and muscle spasm.

125. The method of claim 124, wherein the method is for treating obesity.

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