Salts of heterocyclic GLP1 receptor agonists and uses thereof

Abstract

The present application provides salts of GLP1 receptor agonists. Also provided are pharmaceutical compositions containing such salts. Methods of preparing these salts and compositions, and methods of using these salts and compositions to treat or prevent a disease or a condition mediated by GLP1, are also provided.

Description

Docket No. 43658-02205 (EXAV-024 / 001WO)SALTS OF HETEROCYCLIC GLP1 RECEPTOR AGONISTS AND USES THEREOF RELATED APPLICATIONS

[0001] This application is a PCT International Patent Application claiming the benefit of and priority to U.S. Provisional Application Nos. 63 / 779,524 filed March 28, 2025, 63 / 824,738 filed June 16, 2025, 63 / 910,443 filed November 3, 2025, and 63 / 960,878 filed January 15, 2026, which are incorporated herein by reference in their entireties.BACKGROUND

[0002] There is a need in the art for improved delivery of therapeutic agents, including small molecule heterocyclic GLP1 receptor agonists like orforglipron. More specifically, there is a need for extended-release salts that improve the pharmacokinetic profile, peak-to-trough exposure, bioavailability, tolerability, efficacy, and / or interval dosing of heterocyclic GLP1 receptor agonists like orforglipron. The present disclosure provides salts of heterocyclic GLP1 receptor agonists like orforglipron, as well as pharmaceutical compositions comprising these salts. Without wishing to be bound by theory, the salts and pharmaceutical compositions provided herein allow for sustained-release of heterocyclic GLP1 receptor agonists like orforglipron over extended time periods. Accordingly, the salts and compositions described herein are applicable to the treatment and prevention of a variety of different diseases and disorders, including, but not limited to type 2 diabetes, obesity, cardiovascular disease, heart failure, metabolic dysfunction-associated steatohepatitis (MASH; formerly known as NASH), chronic kidney disease, polycystic ovary syndrome, depression, and substance use disorders.SUMMARY

[0003] In some aspects, the present disclosure provides a salt comprising anion G-A-and a counterion, wherein:G is:1316435300Docket No. 43658-02205 (EXAV-024 / 001WO)a stereoisomer thereof, or a tautomer thereof;XG is — N= or — CRaG=; RaGis selected from a hydrogen atom, a halogen atom, and Ci- 6 alkyl;YG is selected from — C(=O) —, — -CHRG—, and — S(=O)2—; RGis a hydrogen atom or Ci-6 alkyl;QG1is C6-10 aryl or 5 to 10 membered heteroaryl, wherein the Ce-io aryl and 5 to 10 membered heteroaryl are optionally substituted with one to five substituents independently selected from a halogen atom, Ci-6 alkyl (wherein Ci-6 alkyl is optionally substituted with one or more halogen atoms), C3-6 cycloalkyl, and C1-6 alkoxy;QG2is 3 to 12 membered heterocyclyl or 5 to 10 membered heteroaryl, wherein the 3 to 12 membered heterocyclyl and 5 to 10 membered heteroaryl are optionally substituted with one to three substituents independently selected from a halogen atom, C1-6 alkyl (wherein Ci-6 alkyl is optionally substituted with one or more halogen atoms), C1-6 alkoxy, and ---NRQaRQb, and two Ci-6 alkyl groups together with a carbon atom to which they are attached may form C3- 8 carbocyclic ring; and RQaand RQbare independently selected from a hydrogen atom, Ci-6 alkyl, and (C1-6 alkyl)carbonyl;Z3, Z4, Z5, Ze, Z7, Zs, Z9, Z10, Z11, Z12 and Z13 are each independently selected from the group consisting of N and C;316435300Docket No. 43658-02205 (EXAV-024 / 001WO)RG1, RG2, RG3, RG1', RG2', and RG3'are each independently selected from a hydrogen atom, halogen atom, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 haloalkoxy, cycloalkyl, and heterocycloalkyl, wherein the Ci-6 alkyl, cycloalkyl, or heterocycloalkyl is optionally substituted by one or more substituents independently selected from a halogen atom, Ci-6 alkoxy, and hydroxy; or RG2and RG3together with the carbon atom to which they are attached form 4- to 8-membered heterocy cl oalky 1;RG4, RG5and RG6are independently selected from a hydrogen atom, a halogen atom, and Ci-6 alkyl;RG7and RG8are independently a hydrogen atom or Ci-6 alkyl, wherein the Ci-6 alkyl is optionally substituted with one or more substituents independently selected from a halogen atom and C3-15 cycloalkyl, or RG7and RG8together with a carbon atom to which they are attached may form C3-15 cycloalkane ring, wherein the C3-15 cycloalkane ring formed by RG7and RG8together is optionally substituted with one to three Ci-6 alkyl, wherein the Ci-6 alkyl is optionally substituted with one or more substituents independently selected from a halogen atom, hydroxy, ---NRG7aRG7b, Ci-6 alkoxy, and 3 to 12 membered heterocyclyl, and RG7aand RG7bare independently selected from a hydrogen atom, C1-6 alkyl, and (C1-6 alkyl)carbonyl; and any two C1-6 alkyl optionally together with the carbon atom to which they are attached form C3-15 carbocyclic ring;nGl is an integer of 0 to 3; nG2 is an integer of 0 to 5; nG3 is 0 or 1;ZG1is selected from the group consisting ofwherein Rzais selected from a hydrogen atom, C1-6 alkyl, and (C1-6 alkyl)carbonyl; Rzband Rzcare each independently a hydrogen atom or C1-6 alkyl; n4 is an integer of 1 to 3; n5 and n6 are independently an integer of 0 to 10 (* represents a binding position with a pyrazolopyridine structure, and ** represents a binding position with ZG2);316435300Docket No. 43658-02205 (EXAV-024 / 001WO)ZG2is selected from the group consisting of Ci-6 alkyl, C3-15 cycloalkyl, 3 to 12 membered heterocyclyl, Ce-io aryl, and 5 to 10 membered heteroaryl, wherein the C3-15 cycloalkyl, 3 to 12 membered heterocyclyl, C6-10 aryl, and 5 to 10 membered heteroaryl are optionally substituted with one to five substituents independently selected from Group A:Group A a) oxo,b) a halogen atom,c) cyano,d) — NRzdRze; wherein Rzdand Rzeare independently selected from a hydrogen atom, C1-6 alkyl and (C1-6 alkyl)carbonyl, wherein C1-6 alkyl is optionally substituted with one or more substituents independently selected from hydroxy, a halogen atom and C1-6 alkoxy,e) — C(=O) — NRzfRzg; wherein Rzfand Rzgare independently selected from a hydrogen atom, Ci-6 alkyl and (Ci-6alkyl)carbonyl, wherein C1-6 alkyl is optionally substituted with one or more substituents independently selected from hydroxy, a halogen atom and Ci-6 alkoxy,f) - -S(=O)n7 - Rzh; wherein n7 is an integer of 0 to 2; and Rzhis a hydrogen atom or C i-6 alkyl,g) C1-6 alkyl optionally substituted with one or more substituent independently selected from a halogen atom, hydroxy, — NRziRzj, C1-6 alkoxy, and 3 to 12 membered heterocyclyl, wherein Rziand Rzjare independently a hydrogen atom or C1-6 alkyl, and wherein 3 to 12 membered heterocyclyl is optionally substituted with one or more substituents independently selected from hydroxy, Ci-6 alkyl and 3 to 12 membered heterocyclyl,h) C1-6 alkoxy optionally substituted with one or more substituent independently selected from hydroxy, a halogen atom, and C1-6 alkoxy,i) 3 to 12 membered heterocyclyl optionally substituted with one or more substituents independently selected from C1-6 alkyl and (C1-6 alkyl)carbonyl, j) C6-10 aryl optionally substituted with one or more (C1-6 alkyl)carbonyl, k) 5 to 10 membered heteroaryl optionally substituted with one or more substituents independently selected from C1-6 alkyl, C1-6 alkoxy, - -NRzkRzl, and 3 to 12 membered heterocyclyl, wherein Rzkand Rzlare independently selected from4316435300Docket No. 43658-02205 (EXAV-024 / 001WO)a hydrogen atom, Ci-6 alkyl and (Ci-6 alkyl)carbonyl, and wherein 3 to 12 membered heterocyclyl is optionally substituted with one or more substituents independently selected from Ci-6 alkyl and (Ci-6 alkyl)carbonyl,l) — P(==O)(Rzm)(Rzn), wherein Rzmand Rznare each independently a hydrogen atom or Ci-6 alkyl;m) C3-C15 cycloalkyl optionally substituted with one or more substituents independently selected from the group consisting of halogen, oxo, C1-6 alkyl, Ci- 6 alkoxy and (C1-6 alkyl) carbonyl, wherein each of alkyl and alkoxy is optionally substituted with halogen; andn) C1-C6 alkyl-C3-C15 cycloalkyl wherein the cycloalkyl or alkyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, oxo, C1-6 alkyl, C1-6 alkoxy and (C1-6 alkyl) carbonyl, wherein each of alkyl and alkoxy is optionally substituted with halogen;wherein:RGA, Jisselected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, thio, C1-6 alkyl, C1-6 deuterated alkyl, C1-6 halogenated alkyl, C1-6 deuterated haloalkyl, Ci- 6 hydroxyalkyl, C1-6 deuterated hydroxyalkyl, C1-6 sulfanyl, Ci-e deuterated sulfanyl, C1-6 alkoxy, C1-6 deuterated alkoxy, C1-6 halogenated alkoxy, C1-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C’3-8 Cycloalkyl, 3-8 membered heterocyclyl, Ce-io aryl, and 5-10 membered heteroaryl, wherein the amino, C1-6 alkyl, C1-6 deuterated alkyl, C1-6 halogenated alkyl, C1-6 deuterated5316435300Docket No. 43658-02205 (EXAV-024 / 001WO)haloalkyl, Ci-6 hydroxyalkyl, Ci-6 deuterated hydroxyalkyl, Ci-6 sulfanyl, Ci-e deuterated sulfanyl, Ci-6 alkoxy, Ci-6 deuterated alkoxy, Ci-6 halogenated alkoxy, C1-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-8 Cycloalkyl, 3-8 membered heterocyclyl, C6-10 aryl, or 5-10 membered heteroaryl is optionally further substituted by deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, thio, C1-6 alkyl, C1-6 deuterated alkyl, C1-6 halogenated alkyl, C1-6 deuterated haloalkyl, C1-6 hydroxyalkyl, C1-6 deuterated hydroxyalkyl, Ci-6 sulfanyl, C1-6 deuterated sulfanyl, C1-6 alkoxy, C1-6 deuterated alkoxy, C1-6 halogenated alkoxy, C1-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, 3-8 membered heterocyclyl, Ce-io aryl, or 5-10 membered heteroaryl substituted by one or more substituents;LGA1, LGA2, and LGA3are each independently selected from a bond, C2-4 alkenylene, C2-4 alkynylidene and -(CH2)nGAi -;Ring AGAis selected from C3-14 cycloalkyl, 3-14 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl;Ring BGAis selected from C’3-12 cycloalkyl, 3-12 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl, wherein the C3-12 cycloalkyl, 3-12 membered heterocyclyl, C6-14 aryl, or 5-14 membered heteroaryl is optionally further substituted by deuterium, halogen, amino, nitro, hydroxyl, cyano, oxo, thiol, thio, C1-6 alkyl, C1-6 deuterated alkyl, C1-6 halogenated alkyl, C1-6 deuterated haloalkyl, C1-6 hydroxyalkyl, C1-6 deuterated hydroxyalkyl, C1-6 sulfanyl, C1-6 deuterated sulfanyl, Ci-6 alkoxy, C1-6 deuterated alkoxy, C1-6 haloalkoxy or C1-6 deuterated haloalkoxy substituted by one or more substituents;Ring DGAis selected from C3-12 cycloalkyl, 3-12 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl;Ring EGAis selected from C3-14 cycloalkyl, 3-14 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl, wherein the C3-14 cycloalkyl, 3-14 membered heterocyclyl, C6-14 aryl, or 5-14 membered heteroaryl is optionally further substituted by deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, thio, Ci-6 alkyl, C1-6 deuterated alkyl, C1-6 halogenated alkyl, Ci-6 deuterated haloalkyl, C1-6 hydroxyalkyl, C1-6 deuterated hydroxyalkyl, C1-6 sulfanyl, C1-6 deuterated sulfanyl, Ci-6 alkoxy, C1-6 deuterated alkoxy, C1-6 halogenated alkoxy, C1-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, 3-8 membered heterocyclyl, Ce-io aryl, or 5-10 membered heteroaryl substituted by one or more substituents;6316435300Docket No. 43658-02205 (EXAV-024 / 001WO) o..alternatively, ringEGA- is ’ optionally substituted with one or more substituents selected from the group consisting of methyl, ethyl, methoxy, and ethoxy;RGA1, RGA3, RGA4, RGA5, RGA6, RGA7, RGA8, RGA9, RGA14, RGA15, and RGA16eachindependently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, thio, Ci-6 alkyl, Ci-6 deuterated alkyl, Ci-6 halogenated alkyl, Ci-6 deuterated haloalkyl, Ci-6 hydroxyalkyl, Ci-6 deuterated hydroxyalkyl, Ci-6 sulfanyl, Ci-6 deuterated sulfanyl, Ci-6 alkoxy, Ci-6 deuterated alkoxy, Ci-6 halogenated alkoxy, Ci-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, 3-8 membered heterocyclyl, Ce-io aryl, 5-10 membered heteroaryl, - (CH2)mGAiORGAci, and (=C)RGAc3RGAc4, wherein the amino, Ci-6 alkyl, C1-6 deuterated alkyl, Ci-6 halogenated alkyl, C1-6 deuterated haloalkyl, C1-6 hydroxyalkyl, C1-6 deuterated hydroxyalkyl, C1-6 sulfanyl, C1-6 deuterated sulfanyl, C1-6 alkoxy, Ci-6 deuterated alkoxy, Ci-6 halogenated alkoxy, C1-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C’3-8 Cycloalkyl, 3-8 membered heterocyclyl, Ce-io aryl, 5-10 membered heteroaryl, -(CH2)mGAiORGAcl, or (=C)RGAc3RGAc4is optionally further substituted with deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, thio, C1-6 alkyl, C1-6 deuterated alkyl, Ci-6 halogenated alkyl, Ci-6 deuterated haloalkyl, C1-6 hydroxyalkyl, C1-6 deuterated hydroxyalkyl, C1-6 sulfanyl, C1-6 deuterated sulfanyl, C1-6 alkoxy, Ci-6 deuterated alkoxy, Ci-6 halogenated alkoxy, C1-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-8 Cycloalkyl, 3-8 membered heterocyclyl, C6-10 aryl, or 5-10 membered heteroaryl substituted by one or more substituents;RGAc1, RGAc3, and RGAc4are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, thio, C1-6 alkyl, C1-6 deuterated alkyl, C1-6 halogenated alkyl, C1-6 deuterated haloalkyl, C1-6 hydroxyalkyl, C1-6 deuterated hydroxyalkyl, Ci- 6 sulfanyl, C1-6 deuterated sulfanyl, C1-6 alkoxy, C1-6 deuterated alkoxy, C1-6 halogenated alkoxy, C1-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-8 Cycloalkyl, 3-8 membered heterocyclyl, Ce-io aryl, 5-10 membered heteroaryl,, -(CH2)mGA2ORGAc2, -(CH2)mGA3C(O)NRGAa1RGAb1, and -(CH2)mGA4C(O)ORGAa2, wherein the amino, C1-6 alkyl, C1-6 deuterated alkyl, C1-6 halogenated alkyl, Ci-6 deuterated haloalkyl, C1-6 hydroxyalkyl, C1-67316435300Docket No. 43658-02205 (EXAV-024 / 001WO)deuterated hydroxyalkyl, Ci-e sulfanyl, Ci-6 deuterated sulfanyl, Ci-6 alkoxy, Ci-6 deuterated alkoxy, Ci-6 halogenated alkoxy, Ci-6 deuterated haloalkoxy, C2-6 alkenyl, C2- 6 alkynyl, C3- s Cycloalkyl, 3-8 membered heterocyclyl, C6-10aryl, 5-10 membered heteroaryl, -(CH2)mGA2ORGAc2, -(CH2)mGA3C(O)NRGAa1RGAb1, or -(CH2)mGA4C(O)ORGAa2is optionally further substituted with deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, thio, C1-6 alkyl, C1-6 deuterated alkyl, C1-6 halogenated alkyl, C1-6 deuterated haloalkyl, C1-6 hydroxyalkyl, Ci-6 deuterated hydroxyalkyl, C1-6 sulfanyl, C1-6 deuterated sulfanyl, C1-6 alkoxy, C1-6 deuterated alkoxy, C1-6 halogenated alkoxy, Ci-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-8 Cycloalkyl, 3-8 membered heterocyclyl, Ce-io aryl, or 5-10 membered heteroaryl substituted by one or more substituents;RGAal, RGAa2, RGAbl, and RGAc2are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, thio, C1-6 alkyl, Ci-6 deuterated alkyl, C1-6 halogenated alkyl, C1-6 deuterated haloalkyl, C1-6 hydroxyalkyl, C1-6 deuterated hydroxyalkyl, Ci- 6 sulfanyl, C1-6 deuterated sulfanyl, C1-6 alkoxy, C1-6 deuterated alkoxy, C1-6 halogenated alkoxy, C1-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-8 Cycloalkyl, 3-8 membered heterocyclyl, C6-10aryl or 5-10 membered heteroaryl, wherein the amino, C1-6 alkyl, C1-6 deuterated alkyl, C1-6 halogenated alkyl, C1-6 deuterated haloalkyl, C1-6 hydroxyalkyl, C1-6 deuterated hydroxyalkyl, C1-6 sulfanyl, C1-6 deuterated sulfanyl, C1-6 alkoxy, C1-6 deuterated alkoxy, C1-6 halogenated alkoxy, C1-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, 3-8 membered heterocyclyl, Ce-io aryl, or 5-10 membered heteroaryl is optionally further substituted by deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C1-6 alkyl, Ci-e deuterated alkyl, C1-6 halogenated alkyl, Ci-6 deuterated haloalkyl, C1-6 hydroxyalkyl, C1-6 deuterated hydroxyalkyl, C1-6 sulfanyl, C1-6 deuterated sulfanyl, C1-6 alkoxy, C1-6 deuterated alkoxy, C1-6 halogenated alkoxy, C1-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, 3-8 membered heterocyclyl, Ce-io aryl, or 5-10 membered heteroaryl substituted by one or more substituents;or, RGA9and RGA16together with the atoms connected to them form C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-12 aryl or 5-12 membered heteroaryl;or, when nGA is not 1,RGA1and RGA1', RGA2and RGA2', RGA4and RGA5, RGA5and RGA6, RGA7and RGA8, together with the atoms connected to them, form C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-12 aryl,8316435300Docket No. 43658-02205 (EXAV-024 / 001WO)or 5-12 membered heteroaryl, optionally further substituted by deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, thio, Ci-6 alkyl, Ci-6 deuterated alkyl, Ci-6 halogenated alkyl, Ci-6 deuterated haloalkyl, Ci- 6-hydroxyalkyl, Ci-6 deuterated hydroxyalkyl, Ci-6 sulfanyl, Ci-6 deuterated sulfanyl, Ci-6 alkoxy, Ci-6 deuterated alkoxy, Ci- 6-halogenated alkoxy, Ci-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C’3-8 Cycloalkyl, 3-8 membered heterocyclyl, Ce-io aryl, or 5-10 membered heteroaryl substituted by one or more substituents; andnGA, nGAl, nGAl, mGA2, mGA3, and mGA4 are each independently selected from 0, 1, 2, 3, 4 or 5;(RGBe)qGB wherein:Ring AGBis selected from C3-15 carbocyclyl, 3-12 membered heterocyclyl, C6-14aryl, and 5-12 membered heteroaryl;Ring BGBis selected from 3-12 membered heterocyclyl, C6-14 aryl, and 5-12 membered heteroaryl;Ring CGBis 9-membered bicyclic heteroaryl;Ring DGBis selected from C3-15 carbocyclyl, 3-12 membered heterocyclyl, C6-14aryl, and 5-12 membered heteroaryl;Ring EBis selected from C3-15 carbocyclyl, 3-12 membered heterocyclyl, Cb-14 aryl, and 5-12 membered heteroaryl;each RGBais independently selected from hydrogen, deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -ORGBal, -S(O)RGBa!, -SO2(RGBal),-C(O)RGBal, -C(O)ORGBal, - OC(O)RGBal, -N(RGBal)(RGBa2), -C(O)N(RGBal)(RGBa2), -N(RGBal)C(O)RGBa29316435300Docket No. 43658-02205 (EXAV-024 / 001WO)S(O)N(RGBal)(RGBa2), -SO2N(RGBa1)(RGBa2), -N(RGBal)S(O)RGBa2, -N(RGBal)S(O)2RGBa2, and optionally replaced by one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) RGBa3substituted with the following groups: Ci-6 alkyl, Ci-6 alkoxy, Ci-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, or 5-12 membered heteroaryl;or two RGBa, together with the atoms to which they are attached, form a 3-10 membered heterocyclyl or 5-12 membered heteroaryl, wherein the 3-10 membered heterocyclyl or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, Ci-6 alkyl, C1-6 alkoxy, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14 aryl, or 5-12 membered heteroaryl;RGBa1and RGBa2are each independently selected from hydrogen, deuterium, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14 aryl, and 5-12 membered heteroaryl, wherein the C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14 aryl, or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, a 3-6 membered heterocyclyl, phenyl, or 5-6 membered heteroaryl; each RGBa3is independently selected from hydrogen, deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -RGBa4, -ORGBa4, -SRGBa4, -S(O)RGBa4, -S(O)2RGBa4, - C(O)RGBa4, -C(O)ORGBa4, -OC(O)RGBa4, -N(RGBa4)(RGBa5), -C(O)N(RGBa4)(RGBa5), - N(RGBa4)C(O)RGBa5, -S(O)N(RGBa4)(RGBa5), -S(O)2N(RGBa4)(RGBa5), -N(RGBa4)S(O)RGBa5, - N(RGBa4)S(O)2RGBa5;RGBa4and RGBa5are each independently selected from hydrogen, deuterium, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, and 5-12 membered heteroaryl, wherein the C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3- 10 cycloalkyl, 3-10 membered heterocyclyl, C6-14 aryl, or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, 3-7 membered heterocyclyl, phenyl, and 5-6 membered heteroaryl;RGBbis each independently selected from hydrogen, deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 alkylamino, C2-6 alkenyl, C2-610316435300Docket No. 43658-02205 (EXAV-024 / 001WO)alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, and 5-12 membered heteroaryl, wherein the C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C8-14 aryl, or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) RGBbl;or two RGBb, together with the atoms to which they are attached, form 3-10 membered heterocyclyl or 5-12 membered heteroaryl, wherein the 3-10 membered heterocyclyl or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) groups independently selected from deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, C1-6 alkoxy, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, and 5-12 membered heteroaryl;RGBblis each independently selected from deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -RGBb2, -ORGBb2, -SRGBb2, -S(O)RGBb2, -S(O)2RGBb2, -C(O)RGBb2, -C(O)ORGBb2, -OC(O)RGBb2, -N(RGBb2)(RGBb3), -C(O)N(RGBb2)(RGBb3), -N(RGBb2)C(O)RGBb3, -S(O)N(RGBb2)(RGBb3), -S(O)2N(RGBb2)(RGBb3), -N(RGBb2)S(O)RGBb3, and -N(RGBb2)S(O)2RGBb3;RGBb2and RGBb3are each independently selected from hydrogen, deuterium, Ci-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C’6-14 aryl, and 5-12 membered heteroaryl, wherein the Ci-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14 aryl, or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10cycloalkyl, 3-10 membered heterocyclyl, C6-14 aryl, and 5-12 membered heteroaryl;RGBcis each independently selected from hydrogen, deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, C1-6 alkoxy, Ci-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C’3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, and 5-12 membered heteroaryl, wherein the Ci-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) RGBcl;or two RGBe, together with the atoms to which they are attached, form 3-10 membered heterocyclyl or 5-12 membered heteroaryl, wherein the 3-10 membered heterocyclyl or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) groups11316435300Docket No. 43658-02205 (EXAV-024 / 001WO)independently selected from deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, Ci-6 alkyl, Ci-6 alkoxy, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, and 5-12 membered heteroaryl;RGBc1is each independently selected from deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -RGBc2, -ORGBc2, -SRGBc2, -S(O)RGBc2, -S(O)2RGBc2, -C(O)RGBc2, - C(O)ORGBc2, -OC(O)RGBC2, -N(RGBC2)(RGBC3), -C(O)N(RGBC2)(RGBC3), -N(RGBC2)C(O)RGBC3, -S(O)N(RGBC2)(RGBC3), -S(O)2N(RGBC2)(RGBC3), -N(RGBC2)S(O)RGBC3, -N(RGBC2)S(O)2RGBC3;RGBC2and RGBC3are each independently selected from hydrogen, deuterium, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14 aryl, and 5-12 membered heteroaryl, wherein the C1-6alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3- 10 cycloalkyl, 3-10 membered heterocyclyl, C6-14 aryl, or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14 aryl, and 5-12 membered heteroaryl;RGBdis each independently selected from hydrogen, deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -ORGBdl, -S(O)RGBdl, -S(O)2RGBdl, -C(O)RGBdl, - C(O)ORGBdl, -OC(O)RGBdl, -N(RGBdl)(RGBd2), -C(O)N(RGBdl)(RGBd2), -N(RGBdl)C(O)RGBd2, - S(O)N(RGBdl)(RGBd2), -S(O)2N(RGBdl)(RGBd2), -N(RGBdl)S(O)RGBd2, -N(RGBdl)S(O)2RGBd2, and optionally replaced by one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) RGBd3substituted with the following groups: Ci-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, or 5-12 membered heteroaryl;or two RGBd, together with the atoms to which they are attached, form 3-10 membered heterocyclyl, 3-7 membered cycloalkyl, or 5-12 membered heteroaryl, wherein the 3-10 membered heterocyclyl, 3-7 membered cycloalkyl, or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7, or 8) groups independently selected from deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, C1-6 alkoxy, C3- io cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, and 5-12 membered heteroaryl;RGBdland RGBd2are each independently selected from hydrogen, deuterium, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, and 5-12 membered heteroaryl, wherein the Ci-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-12316435300Docket No. 43658-02205 (EXAV-024 / 001WO)io cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, Ci-6 alkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, 3-6 membered heterocyclyl, phenyl, and 5-6 membered heteroaryl;RGBd3is each independently selected from hydrogen, deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -RGBd4, -ORGBd4, -SRGBd4, -S(O)RGBd4, -S(O)2RGBd4, - C(O)RGBd4, -C(O)ORGBd4, -OC(O)RGBd4, -N(RGBd4)(RGBd5), -C(O)N(RGBd4)(RGBd5), - N(RGBd4)C(O)RGBd5, -S(O)N(RGBd4)(RGBd5), -S(O)2N(RGBd4)(RGBd5), -N(RGBd4)S(O)RGBd5, and - N(RGBd4)S(O)2RGBd5;RGBd4and RGBd5are each independently selected from hydrogen, deuterium, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14 aryl, and 5-12 membered heteroaryl, wherein the C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3- 10 cycloalkyl, 3-10 membered heterocyclyl, C6-14 aryl, or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C’3-7 cycloalkyl, 3-7 membered heterocyclyl, phenyl, or 5-6 membered heteroaryl;RGBeis each independently selected from hydrogen, deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -ORGBel, -SRGBel, -S(O)RGBel, -S(O)2RGBel, -C(O)RGBel, -C(O)ORGBel, -OC(O)RGBel, -N(RGBel)(RGBe2), -C(O)N(RGBel)(RGBe2), -N(RGBel)C(O)RGBe2, - S(O)N(RGBel)(RGBe2), -S(O)2N(RGBel)(RGBe2), -N(RGBel)S(O)RGBe2, -N(RGBel)S(O)2RGBe2, - C(O)N(RGBel)S(O)2N(RGBel)(RGBe2), -C(O)N(RGBel)S(O)2RGBe2, -P(O)(RGBel)RGBe2, and optionally replaced by one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) RGBe3substituted with the following groups: C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, or 5-12 membered heteroaryl;or two RGBe, together with the atoms to which they are attached, form 3-10 membered heterocyclyl or 5-12 membered heteroaryl, wherein the 3-10 membered heterocyclyl or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) groups independently selected from deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, C1-6 alkoxy, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14 aryl, and 5-12 membered heteroaryl;13316435300Docket No. 43658-02205 (EXAV-024 / 001WO)RGBeland RGBe2are each independently selected from hydrogen, deuterium, Ci-6 alkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, and 5-12 membered heteroaryl, wherein the C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3- 10 cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from hydrogen, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, 3-6 membered heterocyclyl, phenyl, and 5-6 membered heteroaryl;RGBe3is each independently selected from hydrogen, deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -RGBe4, -ORGBe4, -SRGBe4, -S(O)RGBe4, -S(O)2RGBe4, - C(O)RGBe4, -C(O)ORGBe4, -OC(O)RGBe4, -N(RGBe4)(RGBe5), -C(O)N(RGBe4)(RGBe5), - N(RGBe4)C(O)RGBe5, -S(O)N(RGBe4)(RGBe5), -S(O)2N(RGBe4)(RGBe5), -N(RGBe4)S(O)RGBe5, - N(RGBe4)S(O)2RGBe5, -C(O)N(RGBe4)S(O)2N(RGBe4)(RGBe5), -C(O)N(RGBe4)S(O)2RGBe5, and - (O)(RGBe4)RGBe5;RGBe4and RGBe5are each independently selected from hydrogen, deuterium, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C’6-14 aryl, and 5-12 membered heteroaryl, wherein the C1-6 alkyl, Cue alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3- 10 cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, or 5-12 membered heteroaryl are optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, 3-7 membered heterocyclyl, phenyl, and 5-6 membered heteroaryl;RGB1and RGB2together with the atoms to which they are attached, form C3-15 carbocyclyl optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7, or 8) RGB3;RGB3is each independently selected from hydrogen, deuterium, halogen, hydroxyl, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C3-10 cycloalkyl, and 3-10 membered heterocyclyl, wherein the C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C3-10 cycloalkyl, or 3-10 membered heterocyclyl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from deuterium, halogen, hydroxyl, amino, cyano, oxo, C3-10 cycloalkyl, and 3-10 membered heterocyclyl;14316435300Docket No. 43658-02205 (EXAV-024 / 001WO)LGB1is selected from a bond, -C(RGBL1)2-, -O-, -C(RGBL1)2O-, -S-, -C(O)-, -C(O)O-, -OC(O)-, -N(RGBL1)C(O)-, -C(O)N(RGBL1)-, and -N(RGBL1)-;RGBL1is each independently selected from hydrogen, deuterium, Ci-6 alkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl, wherein the C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, or 3-10 membered heterocyclyl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from deuterium, halogen, hydroxyl, amino, nitro, mercapto, cyano, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl;LGB2 is selected from a bond, -C(RGBL2)2-, -O-, -C(RGBL2)2O-, -S-, -C(O)-, -C(O)O-, - OC(O)-, -N(RGBL2)C(O)-, -C(O)N(RGBL2)-, and -N(RGBL2)-;RGBL2are each independently selected from hydrogen, deuterium, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl, wherein the Ci-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, or 3-10 membered heterocyclyl are optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from deuterium, halogen, hydroxyl, amino, nitro, mercapto, cyano, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl;LGB3is selected from a bond, -C(RGBL3)2-, -O-, -S-, -C(O)-, -C(O)O-, -OC(O)-, - N(RGBL3)C(O)-, -C(O)N(RGBL3)-, and -N(RGBL3)-;RGBL3is each independently selected from hydrogen, deuterium, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl, wherein the Ci-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, or 3-10 membered heterocyclyl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from deuterium, halogen, hydroxyl, amino, nitro, mercapto, cyano, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl;LGB4is a bond, -LGB4x-C(RGBL4a)(RGBL4b)-LGB4y-, -LGB4x-O-LGB4y-, -LGB4x-S-LGB4y-, -LGB4x-C(O)-LGB4y-, -LGB4x-C(O)O-LGB4y-, -LGB4x-OC(O)-LGB4y-, -LGB4x-N(RGBL4a)C(O)-LGB4y-, -LGB4x-C(O)N(RGBL4a)-LGB4y-, -LGB4x-N(RGBL4a)-LGB4y-, -LGB4X -15316435300Docket No. 43658-02205 (EXAV-024 / 001WO)N(RGBL4a)C(O)N(RGBL4b)iGB4y„N(RGBL4a)C(S)N(RGBL4b)-LGB4y -, Of(RGBL4z)rGBLGB4X and LGB4V are each independently a bond or Ci-io alkylene, wherein the Ci-io alkylene is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from deuterium, halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, Ci-6 alkyl, Ct-6 alkoxy, Ci-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10cycloalkyl, and 3-10 membered heterocyclyl;RGBL4aand RGBL4bare independently selected from hydrogen, deuterium, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl, wherein the C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, or 3-10 membered heterocyclyl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from deuterium, halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, Ci-6 alkoxy, Ci-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 substituted by a cycloalkyl group or a 3-10 membered heterocyclyl;Ring LGB4Z is C3-15 carbocyclyl, 3-12 membered heterocyclyl, C6-14 aryl, or 5-12 membered heteroaryl;RGBL4zare each independently selected from hydrogen, deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl, wherein the C1-6 alkyl, C1-6 alkoxy, Ci-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, or 3-10 membered heterocyclyl are optionally substituted with one or more substituents independently selected from deuterium, halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, C1-6 alkoxy, Ci-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl;LGB.Xand LGBSY are each independently a bond or Ci-10 alkylene, wherein the Ci-io alkylene is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from deuterium, halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl;16316435300Docket No. 43658-02205 (EXAV-024 / 001WO)mGB, nGB, oGB, pGB, qGB, and rGB are each independently 0, 1, 2, or 3; unless otherwise specified, the heteroatoms in the above heterocyclyl and heteroaryl are independently selected from O, N or S, and the number of heteroatoms is 1, 2, 3 or 4; and wherein the definitions of the above variables are combined to form a stable chemical structure;(iv)(RGC3)pGCwherein:XGC1, XGC2, and XGC3are independently selected from the group consisting of N and C; rings AGC, BGC, and CGCare independently selected from the group consisting of Cs- io cycloalkyl, heterocyclyl, aryl, and heteroaryl;each RGC1is independently selected from the group consisting of hydrogen, halogen, Ci-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-10 cycloalkyl, C3-10 cycloalkyl-Ci-4 alkyl, heterocyclyl, heterocyclyl-Ci-4 alkyl, aryl, aryl-C 1-4 alkyl, heteroaryl, heteroaryl-Ci-4alkyl, — CN, — NO2, — NRGCA1RGCB1, ORGCA1, --C(O)RGCA1, C(O)ORGCA1, OC(O)RGCA1, ---C(O)NRGCA1RGCB1— NRGCA1C(O)RGCB1, — OC(O)NRGCA1RGCB1, — S(O)rGcRGCA1, — S(O)2ORGCA1, — OS(O)2RGCA1, — NRGCA1S(O)rGcRGCB1, — S(O)rGcNRGCA1RGCB1, — P(O)RGCA1RGCBi, and — P(O)(ORGCA1)(ORGCB1), wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is unsubstituted or substituted independently with at least one RGCX1;17316435300Docket No. 43658-02205 (EXAV-024 / 001WO)each RGC2is independently selected from the group consisting of hydrogen, halogen, Ci- 10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-10 cycloalkyl, C3-10 cycloalkyl-Ci-4 alkyl, heterocyclyl, heterocyclyl-C 1-4 alkyl, aryl, aryl-Ci-4 alkyl, heteroaryl, heteroaryl-Ci-4alkyl, — (CH2)SGCCF3, CN, — NO2, — -NRGCA2RGCB2, -— ORGCA2, — C(O)RGCA2, — C(O)ORGCA2, — OC(O)RGCA2.C(O)NRGCA2RGCB2, -NRGCA2C(O)RGCB2, -OC(O)NRGCA2NRGCA2C(O)ORGCB2,S(O)rGcRGCA2, — P(O)RGCA2RGCB2, — S(O)rGcNRGCA2RGCB2, and — P(O)(ORGCA2)(ORGCB2), wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is unsubstituted or substituted independently with at least one RGCX2;each RGC3is independently selected from the group consisting of hydrogen, halogen, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-10 cycloalkyl, C3-10 cycloalkyl-Ci-4 alkyl, heterocyclyl, heterocyclyl-Ci-4 alkyl, aryl, aryl-C 1-4 alkyl, heteroaryl, heteroaryl-Ci-4 alkyl, — CN, — NO2, — NRGCA3RGCB3, — ORGCA3, and — C(O)RGCA3, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is unsubstituted or substituted independently with at least one RGCX3; ortwo RGC3, together with the atom(s) to which they are attached, form a C3-10 cycloalkyl or 4- to 12-membered heterocyclyl containing 1, 2, or 3 heteroatoms, wherein the heteroatoms are independently selected from the group consisting of oxygen, sulfur, nitrogen, and phosphorus, and the ring thereof is unsubstituted or substituted independently with 1, 2, or 3 RGCX3;RGC4is selected from the group consisting of — C(O)OH, heterocyclyl, and heteroaryl; RGC5is selected from the group consisting of hydrogen and C1-6 alkyl;RGC6is selected from the group consisting of hydrogen, halogen, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-10 cycloalkyl, C3-10 cycloalkyl-Ci-4 alkyl, heterocyclyl, heterocyclyl-Ci-4 alkyl, aryl, aryl-C 1-4 alkyl, heteroaryl, heteroaryl-Ci-4 alkyl, ----CN, - — NO2, ------ NRGCA4RGCB4, ---ORGCA4, and — C(O)RGCA4, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, and, and heteroaryl is unsubstituted or substituted independently with at least one RGCX4;RGC7and RGC8, together with the atom to which they are attached, form a fragment, and RGC9and RGC10are independently selected from the group consisting of hydrogen, halogen, and C1-3 alkyl; or18316435300Docket No. 43658-02205 (EXAV-024 / 001WO)RGC9and RGC10, together with the atom to which they are attached, form a fragment■pGCand RGC7and RGC8are independently selected from the group consisting of hydrogen, halogen, and C1-3 alkyl; orRGC8and RGC9, together with the carbon atoms to which they are attached, form a0 11fragment, and RGC7and RGC10are independently selected from the group consisting of hydrogen, halogen, and C1-3 alkyl;rings TGC, T'GC, and WGCare independently selected from the group consisting of C3- 10 cycloalkyl, C3-8 cycloalkenyl, 3- to 12-membered heterocyclyl, and 5- to 6-membered heteroaryl, and the rings are unsubstituted or substituted independently with 1, 2, or 3 RGCX;“zr n;” is a single bond or a double bond; orRGC8and RGC6, together with the atoms to which they are attached, form a C3-10 cycloalkyl or 4- to 12-membered heterocyclyl containing 1, 2, or 3 heteroatoms, wherein the heteroatoms are independently selected from the group consisting of oxygen, sulfur, nitrogen, and phosphorus, and the ring thereof is unsubstituted or substituted with 1, 2, or 3 RGCX; and RGC7, RGC9, and RGC10are each independently selected from the group consisting of hydrogen, halogen, and Ci -3 alkyl; orRGC9and RGC10, together with the atoms to which they are attached, form a C3-10 cycloalkyl or 4- to 12-membered heterocyclyl containing 1, 2, or 3 heteroatoms, wherein the heteroatoms are independently selected from the group consisting of oxygen, sulfur, nitrogen, and phosphorus, and the ring thereof is unsubstituted or substituted independently with 1, 2, or 3 RGCX; and RGC7, RGC8, and RGC10are each independently selected from the group consisting of hydrogen, halogen, and C1-3 alkyl;each of RGCA1, RGCA2, RGCA3, RGCA4, RGCB1, RGCB2, RGCB3, and RGCB4is independently selected from the group consisting of hydrogen, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3- io cycloalkyl, C3-10cycloalkyl-Ci-4 alkyl, heterocyclyl, heterocyclyl-C 1-4 alkyl, aryl, aryl-Ci- 19316435300Docket No. 43658-02205 (EXAV-024 / 001WO)4 alkyl, heteroaryl, and heteroaryl -Ci -4 alkyl, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is unsubstituted or substituted with at least one substituent independently selected from the group consisting of hydroxyl, oxo, Ci-6 alkyl, C2- 6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, cyano, alkoxy, alkylamino, di(alkyl)amino, haloalkyl, acyl, sulfonyl, sulfonamido, and halogen; or“RGCA1and RGCB1” or “RGCA2and RGCB2” or “RGCA3and RGCB3”, together with single or multiple atom(s) to which they are attached, form a 4- to 12-membered heterocyclic ring containing 0, 1, or 2 additional heteroatoms independently selected from the group consisting of oxygen, sulfur, nitrogen, and phosphorus, and the ring is unsubstituted or substituted with 1, 2, or 3 substituents selected from the group consisting of hydroxyl, oxo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, cyano, alkoxy, alkylamino, di(alkyl)amino, haloalkyl, acyl, sulfonyl, sulfonamido, and halogen;each of RGCX, RGCX1, RGCX2, RGCX3, and RGCX4is independently selected from the group consisting of hydroxyl, oxo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, cyano, alkoxy, alkylamino, di(alkyl)amino, haloalkyl, acyl, sulfonyl, sulfonamido, and halogen;mGC, nGC, and pGC are independently selected from the group consisting of 0, 1, 2, and 3; andrGC and sGC are independently selected from the group consisting of 0, 1, and 2; or(v)(RGD2)mGDwherein:LGD1is selected from -CO-, -SO-, -SO2-, -NRciDa -and-CRGDaRGDb -;20316435300Docket No. 43658-02205 (EXAV-024 / 001WO)LGD2is selected from,, -RGDL-NRGDa -*, -RGDL-CO- NRGDa-*, -RGDL -NRGDa-CO-NRGDa-*, -RGDL-C(S)-NRGDa-*, -RGDL -NRGDa-C(S)-NRGDa-*, where the asterisk indicates a connection to the N atom in the central ring;Ring A is C3-10 cycloalkyl, C3-10 cycloalkenyl, 3-10 membered heterocyclic alkyl, 3-10 membered heterocyclic alkenyl, C6-10 aryl, or 5-10 membered heteroaryl each optionally substituted with one or more RGD3 groups, each RGD3 group being independently selected from halogen, cyano, hydroxyl, NRGDaRGDb C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkyl, C1-6 cyanoalkyl, C1-6 hydroxyalkyl, and (optionally selected independently by one or more halogens and C1-6 alkyl-substituted C3-10cycloalkyl)-RGDi-, or two of the RGD3S, together with the atoms they are attached to, form a 4- to 6-membered ring optionally containing one or more heteroatoms independently selected from N, O, or S, wherein the 4- to 6-membered ring is optionally substituted with one or more substituents independently selected from halogen, cyano, hydroxyl, oxo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 deuterated alkyl, C1-6 haloalkyl, Ci-6 cyanoalkyl and C1-6 hydroxyalkyl;Ring B is a naphthylene or an 8-10 membered bicyclic heteroarylene, each optionally substituted by one or more RGD4 groups, each RGD4 group independently selected from halogen, cyano, hydroxyl, NRGDaRGDb, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 alkylthio, Ci- 6 haloalkyl, Ci-e cyanoalkyl, Ci-6 hydroxyalkyl, (C3-10 cycloalkyl)-RGDL-, (5-10 membered heterocyclic alkyl)-RGDL-, (Cs-io aryl)-RGDL, and (5-10 membered heteroaryl)-RGDL-, wherein the cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents each independently selected from halogen, Ci-6 alkyl, or C1-6 alkoxy;Ring C is C3-10 cycloalkyl, C3-10 cycloalkenyl, 3-10 membered heterocyclic alkyl, 3-10 membered heterocyclic alkenyl, C6-10 aryl, or 5-10 membered heteroaryl optionally substituted by one or more substituents, wherein each substituent is independently selected from H, halogen, cyano, hydroxyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, (C1-6 alkoxy)-RGDL-, (C1-6 alkylthio)-RGDL-, C1-6 alkoxy-Ci-6 alkoxy-, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 cyanoalkyl, Ci-6 hydroxyalkyl, C1-6 alkyl, C1-6 halogenated alkyl, COOH, -CONH2, -CONH(CI-6 alkyl), -21316435300Docket No. 43658-02205 (EXAV-024 / 001WO)-O-P(=O)(ORGDa) C(=S)NH2, -C(=S)NH(C1-6 alkyl), -P(RGDa)(RGDb), -P(=O)(C1-6 alkyl)(C1-6 alkyl),ORGDb, Ci-6alkyl-C0-, (Ci-6 haloalkoxy)-RGDL-(C3-10 cycloalkyl optionally substituted with halogen or hydroxyl groups)-RGDL-, (C3-10 cycloalkyl)-C2-4 alkenyl-, (C3-10 cycloalkyl)-C2-4 a-ethynyl-, (C3-10 cycloalkyloxy)-RGDL-, (3-10 membered heterocyclic alkyl)-RGDL-, (3-10 membered heterocyclic alkyloxy)-RGDi,~, (C6-10 aryl)-RGDL-, (C6-10 aryloxy)-RGDL-, (C6-10 aryl-C1-6 alkyleneoxy)-RGDL-, (5-10 membered heteroaryl)-RGDL-, (5-10-membered heteroaryloxy)-RGDL-, NRGDaRGDb-(CRGDaRGDb)mGD-, NRGDaRGDb-CO- and RGD6, or two of these substituents together with the atoms they are attached to, form a 3- to 7-membered ring optionally containing one or more heteroatoms selected from N, O, or S, said ring optionally being substituted with one or more substituents each independently selected from oxo, halogen, cyano, C1-6 alkyl, Ci-6 haloalkyl, C3-10 cycloalkyl, 3-10 membered heterocyclic alkyl, Ce-io aryl, and 5-7 membered heteroaryl;Ring D is C3-10 cycloalkyl, C3-10 cycloalkenyl, 3-10 membered heterocyclic alkyl, 3-10 membered heterocyclic alkenyl, C6-10 aryl, or 5-10 membered heteroaryl;RGDI is each independently H, halogen, cyano, hydroxyl, mercapto, NRGDaRGDb, Ci-6 alkyl, C2-6 alkenyl, C1-6 deuterated alkyl, C1-6 haloalkyl, Ci-6 cyanoalkyl, C1-6 hydroxyalkyl, Ci-6 alkoxy, C1-6 alkylthio, C1-6 halogenated alkoxy, or C3-8 cycloalkyl, or two RGDI atoms together with the carbon atoms they are attached to form C3-4 cycloalkyl;RGD2 is each independently selected from H, halogen, cyano, OH, NRGDaRGDb, C1-6 alkyl, C2-6 alkenyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkyl, C1-6 halogenated alkoxy, optionally substituted with one or more substituents selected from C1-6 alkyl-substituted 5-10-membered heteroaryl, -P(O)(Ci-6 alkyl)(Ci-6 alkyl), -C(O)(Ci-6 alkyl), -S(O)(Ci-6 alkyl), -S(O)2(Ci-6 alkyl), -NRGDa-S(O)2-(C1-6 alkyl), -C(O)-(C3-10 cycloalkyl), -S(O)-(C3-10 cycloalkyl), -S(O)2-(C3-10 cycloalkyl), -S(=O)(=NRGDa)-(C3-10 cycloalkyl), or -C(=O)-N(RGDa)-(C3-10 cycloalkyl), or two of the RGD2 groups together with the atoms they are attached form a 6- membered aromatic ring or a 5-6 membered saturated, partially unsaturated, or aromatic heterocycle, wherein the ring is optionally substituted with a substituent selected from the following: halogen, oxo, (NRGDaRGDb)-RGDL-, C1-6 alkyl, C1-6 deuterated alkyl, Ci-6 haloalkyl, C1-6 cyanoalkyl, C1-6 hydroxyalkyl, (C1-6 alkoxy )-RGDL-, (C1-6 alkylthio)-RGDL-, (C3-10 cycloalkyl optionally substituted with one or more halogens, Ci-6 alkyl or C1-6 alkoxy)-RGDL- (3-1022316435300Docket No. 43658-02205 (EXAV-024 / 001WO)membered heterocyclic alkyl optionally substituted with one or more halogen, C1-6 alkyl, or Ci- 6 haloalky 1)-RGDL-, and (Ce-io aryl)-RGDL where C3-10 cycloalkyl groups can be monocyclic, bicyclic, spirocyclic, or bridged rings;RGD6 is a 5- or 6-membered partially unsaturated or aromatic heterocycle containing one or more heteroatoms independently selected from N, O, or S;RGDp is each independently halogen, cyano, hydroxyl, NH2, C1-6 alkyl, or absent;RGDa and RGDb is each independently H or C1-6 alkyl;RGDS and RGDI are each independently H, Ci-6 alkyl, Ci-6 haloalkyl, Ce-io aryl, or 5-10 membered heteroaryl;RGDL is each independently a bond; Ci-io alkylene optionally substituted with halogen, cyano, or hydroxyl; or Ci-4 deuterated alkylene;TGD is Ci-4 alkylene, C2-4 imidene, C2-4 acetylene, or C3-6 cycloalkylene group bonded to the rest of the molecule through two different ring carbon atoms;QGD is O or S;mGD is 0, 1, 2, 3, 4, or 5;nGD is 0, 1, or 2; andqGD is 0, 1, 2, or 3;N^N® NN|® N^N®N^ N® 0-4 y=N- s-4A“ isN N, O RA, or0, or a tautomer thereof;RAis selected from the group consisting of hydrogen, C1-6 alkyl and (C1-6 alkyl) carbonyl, wherein C1-6 alkyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen and C1-6 alkoxy;the counterion comprises an amine-containing polymer, a diamine or a conjugate thereof, a polyamine or a conjugate thereof, or Mh;23316435300Docket No. 43658-02205 (EXAV-024 / 001WO)RN1and RN2are each independently hydrogen or C1-C30 alkyl;Yi, Y2, Yi’, and Y2’ are each independently a bond, -O-, or -NH-;Li, L2, L3, Li’, and L2’ are each independently a bond, C1-C25 alkylene, or Ce-Cio arylene, wherein the alkylene and arylene are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, C6-C10 aryl, C1-C6 alkoxy, or Ci-Ce haloalkyl;Ri is C1-C30 alkyl, C2-C30 alkenyl, Ce-Cio aryl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl, wherein the alkyl, alkenyl, aryl, heterocyclyl, and heteroaryl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, C6-C10 aryl, Ci-Ce alkoxy, Ci-Ce haloalkyl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl; andm is 0 or 1.

[0004] In some aspects, the present disclosure provides a salt comprising anion G-A' and a counterion, wherein:G is:24316435300Docket No. 43658-02205 (EXAV-024 / 001WO)\, a stereoisomer thereof, or a tautomer thereof;XG is — N= or — CRaG=; RaGis selected from a hydrogen atom, a halogen atom, and Ci- 6 alkyl;YG is selected from — C(=O) -, CHRG, and - -S(=O)2 - -; RGis a hydrogen atom or Ci-6 alkyl;QG1is C6-10 aryl or 5 to 10 membered heteroaryl, wherein the Ce-io aryl and 5 to 10 membered heteroaryl are optionally substituted with one to five substituents independently selected from a halogen atom, Ci-6 alkyl (wherein Ci-6 alkyl is optionally substituted with one or more halogen atoms), C3-6 cycloalkyl, and C1-6 alkoxy;QG2is 3 to 12 membered heterocyclyl or 5 to 10 membered heteroaryl, wherein the 3 to 12 membered heterocyclyl and 5 to 10 membered heteroaryl are optionally substituted with one to three substituents independently selected from a halogen atom, C1-6 alkyl (wherein C1-6 alkyl is optionally substituted with one or more halogen atoms), C1-6 alkoxy, and — NRGQaRGQb, and two Ci-6 alkyl groups together with a carbon atom to which they are attached may form C3- 8 carbocyclic ring; and RQaand RQbare independently selected from a hydrogen atom, Ci-6 alkyl, and (Ci-6 alkyl)carbonyl;Z3, Z4, Z5, Ze, Z7, Zs, Z9, Z10, Z11, Z12 and Z13 are each independently selected from the group consisting of N and C;25316435300Docket No. 43658-02205 (EXAV-024 / 001WO)RG1, RG2, RG3, RG1', RG2', and RG3'are each independently selected from a hydrogen atom, halogen atom, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 haloalkoxy, cycloalkyl, and heterocycloalkyl, wherein the Ci-6 alkyl, cycloalkyl, or heterocycloalkyl is optionally substituted by one or more substituents independently selected from a halogen atom, Ci-6 alkoxy, and hydroxy; or RG2and RG3together with the carbon atom to which they are attached form 4- to 8-membered heterocy cl oalky 1;RG4, RG5and RG6are independently selected from a hydrogen atom, a halogen atom, and Ci-6 alkyl;RG7and RG8are independently a hydrogen atom or Ci-6 alkyl, wherein the Ci-6 alkyl is optionally substituted with one or more substituents independently selected from a halogen atom and C3-15 cycloalkyl, or RG7and RG8together with a carbon atom to which they are attached may form C3-15 cycloalkane ring, wherein the C3-15 cycloalkane ring formed by RG7and RG8together is optionally substituted with one to three Ci-6 alkyl, wherein the Ci-6 alkyl is optionally substituted with one or more substituents independently selected from a halogen atom, hydroxy, ---NRG7aRG7b, Ci-6 alkoxy, and 3 to 12 membered heterocyclyl, and RG7aand RG7bare independently selected from a hydrogen atom, C1-6 alkyl, and (C1-6 alkyl)carbonyl; and any two C1-6 alkyl optionally together with the carbon atom to which they are attached form C3-15 carbocyclic ring;nGl is an integer of 0 to 3; nG2 is an integer of 0 to 5; nG3 is 0 or 1;ZG1is selected from the group consisting ofwherein Rzais selected from a hydrogen atom, C1-6 alkyl, and (C1-6 alkyl)carbonyl; Rzband Rzcare each independently a hydrogen atom or C1-6 alkyl; n4 is an integer of 1 to 3; n5 and n6 are independently an integer of 0 to 10 (* represents a binding position with a pyrazolopyridine structure, and ** represents a binding position with ZG2);26316435300Docket No. 43658-02205 (EXAV-024 / 001WO)ZG2is selected from the group consisting of Ci-6 alkyl, C3-15 cycloalkyl, 3 to 12 membered heterocyclyl, Ce-io aryl, and 5 to 10 membered heteroaryl, wherein the C3-15 cycloalkyl, 3 to 12 membered heterocyclyl, C6-10 aryl, and 5 to 10 membered heteroaryl are optionally substituted with one to five substituents independently selected from Group A:Group A a) oxo,b) a halogen atom,c) cyano,d) — NRzdRze; wherein Rzdand Rzeare independently selected from a hydrogen atom, C1-6 alkyl and (C1-6 alkyl)carbonyl, wherein C1-6 alkyl is optionally substituted with one or more substituents independently selected from hydroxy, a halogen atom and C1-6 alkoxy,e) — C(=O) — NRzfRzg; wherein Rzfand Rzgare independently selected from a hydrogen atom, Ci-6 alkyl and (Ci-6alkyl)carbonyl, wherein C1-6 alkyl is optionally substituted with one or more substituents independently selected from hydroxy, a halogen atom and Ci-6 alkoxy,f) - -S(=O)n7 - Rzh; wherein n7 is an integer of 0 to 2; and Rzhis a hydrogen atom or C i-6 alkyl,g) C1-6 alkyl optionally substituted with one or more substituent independently selected from a halogen atom, hydroxy, — NRziRzj, C1-6 alkoxy, and 3 to 12 membered heterocyclyl, wherein Rziand Rzjare independently a hydrogen atom or C1-6 alkyl, and wherein 3 to 12 membered heterocyclyl is optionally substituted with one or more substituents independently selected from hydroxy, Ci-6 alkyl and 3 to 12 membered heterocyclyl,h) C1-6 alkoxy optionally substituted with one or more substituent independently selected from hydroxy, a halogen atom, and C1-6 alkoxy,i) 3 to 12 membered heterocyclyl optionally substituted with one or more substituents independently selected from C1-6 alkyl and (C1-6 alkyl)carbonyl, j) C6-10 aryl optionally substituted with one or more (C1-6 alkyl)carbonyl, k) 5 to 10 membered heteroaryl optionally substituted with one or more substituents independently selected from C1-6 alkyl, C1-6 alkoxy, - -NRzkRzl, and 3 to 12 membered heterocyclyl, wherein Rzkand Rzlare independently selected from27316435300Docket No. 43658-02205 (EXAV-024 / 001WO)a hydrogen atom, Ci-6 alkyl and (Ci-6 alkyl)carbonyl, and wherein 3 to 12 membered heterocyclyl is optionally substituted with one or more substituents independently selected from Ci-6 alkyl and (Ci-6 alkyl)carbonyl,l) — P(==O)(Rzm)(Rzn), wherein Rzmand Rznare each independently a hydrogen atom or Ci-6 alkyl;m) C3-C15 cycloalkyl optionally substituted with one or more substituents independently selected from the group consisting of halogen, oxo, C1-6 alkyl, Ci- 6 alkoxy and (C1-6 alkyl) carbonyl, wherein each of alkyl and alkoxy is optionally substituted with halogen; andn) C1-C6 alkyl-C3-C15 cycloalkyl wherein the cycloalkyl or alkyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, oxo, C1-6 alkyl, C1-6 alkoxy and (C1-6 alkyl) carbonyl, wherein each of alkyl and alkoxy is optionally substituted with halogen;wherein:RGA13isselected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, thio, Ci-6 alkyl, Ci-6 deuterated alkyl, C1-6 halogenated alkyl, C1-6 deuterated haloalkyl, Ci-6 hydroxyalkyl, C1-6 deuterated hydroxyalkyl, C1-6 sulfanyl, C1-6 deuterated sulfanyl, C1-6 alkoxy, Ci-6 deuterated alkoxy, Ci-6 halogenated alkoxy, C1-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-8 Cycloalkyl, 3-8 membered heterocyclyl, Ce-io aryl, and 5-10 membered heteroaryl, wherein the amino, C1-6 alkyl, C1-6 deuterated alkyl, C1-6 halogenated alkyl, C1-6 deuterated28316435300Docket No. 43658-02205 (EXAV-024 / 001WO)haloalkyl, Ci-6 hydroxyalkyl, Ci-6 deuterated hydroxyalkyl, Ci-6 sulfanyl, Ci-e deuterated sulfanyl, Ci-6 alkoxy, Ci-6 deuterated alkoxy, Ci-6 halogenated alkoxy, C1-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-8 Cycloalkyl, 3-8 membered heterocyclyl, C6-10 aryl, or 5-10 membered heteroaryl is optionally further substituted by deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, thio, C1-6 alkyl, C1-6 deuterated alkyl, C1-6 halogenated alkyl, C1-6 deuterated haloalkyl, C1-6 hydroxyalkyl, C1-6 deuterated hydroxyalkyl, Ci-6 sulfanyl, C1-6 deuterated sulfanyl, C1-6 alkoxy, C1-6 deuterated alkoxy, C1-6 halogenated alkoxy, C1-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, 3-8 membered heterocyclyl, Ce-io aryl, or 5-10 membered heteroaryl substituted by one or more substituents;LGA1, LGA2, and LGA3are each independently selected from a bond, C2-4 alkenylene, C2-4 alkynylidene and -(CH2)nGAi -;Ring AGAis selected from C3-14 cycloalkyl, 3-14 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl;Ring BGAis selected from C’3-12 cycloalkyl, 3-12 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl, wherein the C3-12 cycloalkyl, 3-12 membered heterocyclyl, C6-14 aryl, or 5-14 membered heteroaryl is optionally further substituted by deuterium, halogen, amino, nitro, hydroxyl, cyano, oxo, thiol, thio, C1-6 alkyl, C1-6 deuterated alkyl, C1-6 halogenated alkyl, C1-6 deuterated haloalkyl, C1-6 hydroxyalkyl, C1-6 deuterated hydroxyalkyl, C1-6 sulfanyl, C1-6 deuterated sulfanyl, Ci-6 alkoxy, C1-6 deuterated alkoxy, C1-6 haloalkoxy or C1-6 deuterated haloalkoxy substituted by one or more substituents;Ring DGAis selected from C3-12 cycloalkyl, 3-12 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl;Ring EGAis selected from C3-14 cycloalkyl, 3-14 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl, wherein the C3-14 cycloalkyl, 3-14 membered heterocyclyl, C6-14 aryl, or 5-14 membered heteroaryl is optionally further substituted by deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, thio, Ci-6 alkyl, C1-6 deuterated alkyl, C1-6 halogenated alkyl, Ci-6 deuterated haloalkyl, C1-6 hydroxyalkyl, C1-6 deuterated hydroxyalkyl, C1-6 sulfanyl, C1-6 deuterated sulfanyl, Ci-6 alkoxy, C1-6 deuterated alkoxy, C1-6 halogenated alkoxy, C1-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, 3-8 membered heterocyclyl, Ce-io aryl, or 5-10 membered heteroaryl substituted by one or more substituents;29316435300Docket No. 43658-02205 (EXAV-024 / 001WO) o..alternatively, ringEGA- is ’ optionally substituted with one or more substituents selected from the group consisting of methyl, ethyl, methoxy, and ethoxy;RGA1, RGA3, RGA4, RGA5, RGA6, RGA7, RGA8, RGA9, RGA14, RGA15, and RGA16eachindependently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, thio, Ci-6 alkyl, Ci-6 deuterated alkyl, Ci-6 halogenated alkyl, Ci-6 deuterated haloalkyl, Ci-6 hydroxyalkyl, Ci-6 deuterated hydroxyalkyl, Ci-6 sulfanyl, Ci-6 deuterated sulfanyl, Ci-6 alkoxy, Ci-6 deuterated alkoxy, Ci-6 halogenated alkoxy, Ci-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, 3-8 membered heterocyclyl, Ce-io aryl, 5-10 membered heteroaryl, - (CH2)mGAiORGAci, and (=C)RGAc3RGAc4, wherein the amino, Ci-6 alkyl, C1-6 deuterated alkyl, Ci-6 halogenated alkyl, C1-6 deuterated haloalkyl, C1-6 hydroxyalkyl, C1-6 deuterated hydroxyalkyl, C1-6 sulfanyl, C1-6 deuterated sulfanyl, C1-6 alkoxy, Ci-6 deuterated alkoxy, Ci-6 halogenated alkoxy, C1-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C’3-8 Cycloalkyl, 3-8 membered heterocyclyl, Ce-io aryl, 5-10 membered heteroaryl, -(CH2)mGAiORGAcl, or (=C)RGAc3RGAc4is optionally further substituted with deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, thio, C1-6 alkyl, C1-6 deuterated alkyl, Ci-6 halogenated alkyl, Ci-6 deuterated haloalkyl, C1-6 hydroxyalkyl, C1-6 deuterated hydroxyalkyl, C1-6 sulfanyl, C1-6 deuterated sulfanyl, C1-6 alkoxy, Ci-6 deuterated alkoxy, Ci-6 halogenated alkoxy, C1-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-8 Cycloalkyl, 3-8 membered heterocyclyl, C6-10 aryl, or 5-10 membered heteroaryl substituted by one or more substituents;RGAc1, RGAc3, and RGAc4are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, thio, C1-6 alkyl, C1-6 deuterated alkyl, C1-6 halogenated alkyl, C1-6 deuterated haloalkyl, C1-6 hydroxyalkyl, C1-6 deuterated hydroxyalkyl, Ci- 6 sulfanyl, C1-6 deuterated sulfanyl, C1-6 alkoxy, C1-6 deuterated alkoxy, C1-6 halogenated alkoxy, C1-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-8 Cycloalkyl, 3-8 membered heterocyclyl, Ce-io aryl, 5-10 membered heteroaryl,, -(CH2)mGA2ORGAc2, -(CH2)mGA3C(O)NRGAa1RGAb1, and -(CH2)mGA4C(O)ORGAa2, wherein the amino, C1-6 alkyl, C1-6 deuterated alkyl, C1-6 halogenated alkyl, Ci-6 deuterated haloalkyl, C1-6 hydroxyalkyl, C1-630316435300Docket No. 43658-02205 (EXAV-024 / 001WO)deuterated hydroxyalkyl, Ci-e sulfanyl, Ci-6 deuterated sulfanyl, Ci-6 alkoxy, Ci-6 deuterated alkoxy, Ci-6 halogenated alkoxy, Ci-6 deuterated haloalkoxy, C2-6 alkenyl, C2- 6 alkynyl, C3- s Cycloalkyl, 3-8 membered heterocyclyl, C6-10aryl, 5-10 membered heteroaryl, -(CH2)mGA2ORGAc2, -(CH2)mGA3C(O)NRGAa1RGAb1, or -(CH2)mGA4C(O)ORGAa2is optionally further substituted with deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, thio, C1-6 alkyl, C1-6 deuterated alkyl, C1-6 halogenated alkyl, C1-6 deuterated haloalkyl, C1-6 hydroxyalkyl, Ci-6 deuterated hydroxyalkyl, C1-6 sulfanyl, C1-6 deuterated sulfanyl, C1-6 alkoxy, C1-6 deuterated alkoxy, C1-6 halogenated alkoxy, Ci-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-8 Cycloalkyl, 3-8 membered heterocyclyl, Ce-io aryl, or 5-10 membered heteroaryl substituted by one or more substituents;RGAal, RGAa2, RGAbl, and RGAc2are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, thio, C1-6 alkyl, Ci-6 deuterated alkyl, C1-6 halogenated alkyl, C1-6 deuterated haloalkyl, C1-6 hydroxyalkyl, C1-6 deuterated hydroxyalkyl, Ci- 6 sulfanyl, C1-6 deuterated sulfanyl, C1-6 alkoxy, C1-6 deuterated alkoxy, C1-6 halogenated alkoxy, C1-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-8 Cycloalkyl, 3-8 membered heterocyclyl, C6-10aryl or 5-10 membered heteroaryl, wherein the amino, C1-6 alkyl, C1-6 deuterated alkyl, C1-6 halogenated alkyl, C1-6 deuterated haloalkyl, C1-6 hydroxyalkyl, C1-6 deuterated hydroxyalkyl, C1-6 sulfanyl, C1-6 deuterated sulfanyl, C1-6 alkoxy, C1-6 deuterated alkoxy, C1-6 halogenated alkoxy, C1-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, 3-8 membered heterocyclyl, Ce-io aryl, or 5-10 membered heteroaryl is optionally further substituted by deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C1-6 alkyl, Ci-e deuterated alkyl, C1-6 halogenated alkyl, Ci-6 deuterated haloalkyl, C1-6 hydroxyalkyl, C1-6 deuterated hydroxyalkyl, C1-6 sulfanyl, C1-6 deuterated sulfanyl, C1-6 alkoxy, C1-6 deuterated alkoxy, C1-6 halogenated alkoxy, C1-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, 3-8 membered heterocyclyl, Ce-io aryl, or 5-10 membered heteroaryl substituted by one or more substituents;or, RGA9and RGA16together with the atoms connected to them form C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-12 aryl or 5-12 membered heteroaryl;or, when nGA is not 1,RGA1and RGA1', RGA2and RGA2', RGA4and RGA5, RGA5and RGA6, RGA7and RGA8, together with the atoms connected to them, form C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-12 aryl,31316435300Docket No. 43658-02205 (EXAV-024 / 001WO)or 5-12 membered heteroaryl, optionally further substituted by deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, thio, Ci-6 alkyl, Ci-6 deuterated alkyl, Ci-6 halogenated alkyl, Ci-6 deuterated haloalkyl, Ci- 6-hydroxyalkyl, Ci-6 deuterated hydroxyalkyl, Ci-6 sulfanyl, Ci-6 deuterated sulfanyl, Ci-6 alkoxy, Ci-6 deuterated alkoxy, Ci- 6-halogenated alkoxy, Ci-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C’3-8 Cycloalkyl, 3-8 membered heterocyclyl, Ce-io aryl, or 5-10 membered heteroaryl substituted by one or more substituents; andnGA, nGAl, nGAl, mGA2, mGA3, and mGA4 are each independently selected from 0, 1, 2, 3, 4 or 5; orwherein:Ring AGBis selected from C3-15 carbocyclyl, 3-12 membered heterocyclyl, C6-14aryl, and 5-12 membered heteroaryl;Ring BGBis selected from 3-12 membered heterocyclyl, C6-14 aryl, and 5-12 membered heteroaryl;Ring CGBis 9-membered bicyclic heteroaryl;Ring DGBis selected from C3-15 carbocyclyl, 3-12 membered heterocyclyl, C6-14 aryl, and 5-12 membered heteroaryl;Ring EGBis selected from C3-15 carbocyclyl, 3-12 membered heterocyclyl, C6-14aryl, and 5-12 membered heteroaryl;each RGBais independently selected from hydrogen, deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -ORGBal, -S(O)RGBal, -SO2(RGBal),-C(O)RGBal, -C(O)ORGBal, - OC(O)RGBal, -N(RGBal)(RGBa2), -C(O)N(RGBal)(RGBa2), -N(RGBal)C(O)RGBa2, - 32316435300Docket No. 43658-02205 (EXAV-024 / 001WO)S(O)N(RGBal)(RGBa2), -SO2N(RGBa1)(RGBa2), -N(RGBal)S(O)RGBa2, -N(RGBal)S(O)2RGBa2, and optionally replaced by one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) RGBa3substituted with the following groups: Ci-6 alkyl, Ci-6 alkoxy, Ci-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, or 5-12 membered heteroaryl;or two RGBa, together with the atoms to which they are attached, form a 3-10 membered heterocyclyl or 5-12 membered heteroaryl, wherein the 3-10 membered heterocyclyl or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, Ci-6 alkyl, C1-6 alkoxy, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14 aryl, or 5-12 membered heteroaryl;RGBa1and RGBa2are each independently selected from hydrogen, deuterium, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14 aryl, and 5-12 membered heteroaryl, wherein the C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14 aryl, or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, a 3-6 membered heterocyclyl, phenyl, or 5-6 membered heteroaryl; each RGBa3is independently selected from hydrogen, deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -RGBa4, -ORGBa4, -SRGBa4, -S(O)RGBa4, -S(O)2RGBa4, - C(O)RGBa4, -C(O)ORGBa4, -OC(O)RGBa4, -N(RGBa4)(RGBa5), -C(O)N(RGBa4)(RGBa5), - N(RGBa4)C(O)RGBa5, -S(O)N(RGBa4)(RGBa5), -S(O)2N(RGBa4)(RGBa5), -N(RGBa4)S(O)RGBa5, - N(RGBa4)S(O)2RGBa5;RGBa4and RGBa5are each independently selected from hydrogen, deuterium, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, and 5-12 membered heteroaryl, wherein the C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3- 10 cycloalkyl, 3-10 membered heterocyclyl, C6-14 aryl, or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, 3-7 membered heterocyclyl, phenyl, and 5-6 membered heteroaryl;RGBbis each independently selected from hydrogen, deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 alkylamino, C2-6 alkenyl, C2-633316435300Docket No. 43658-02205 (EXAV-024 / 001WO)alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, and 5-12 membered heteroaryl, wherein the C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C8-14 aryl, or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) RGBbl;or two RGBb, together with the atoms to which they are attached, form 3-10 membered heterocyclyl or 5-12 membered heteroaryl, wherein the 3-10 membered heterocyclyl or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) groups independently selected from deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, C1-6 alkoxy, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, and 5-12 membered heteroaryl;RGBblis each independently selected from deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -RGBb2, -ORGBb2, -SRGBb2, -S(O)RGBb2, -S(O)2RGBb2, -C(O)RGBb2, -C(O)ORGBb2, -OC(O)RGBb2, -N(RGBb2)(RGBb3), -C(O)N(RGBb2)(RGBb3), -N(RGBb2)C(O)RGBb3, -S(O)N(RGBb2)(RGBb3), -S(O)2N(RGBb2)(RGBb3), -N(RGBb2)S(O)RGBb3, and -N(RGBb2)S(O)2RGBb3;RGBb2and RGBb3are each independently selected from hydrogen, deuterium, Ci-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C’6-14 aryl, and 5-12 membered heteroaryl, wherein the Ci-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14 aryl, or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10cycloalkyl, 3-10 membered heterocyclyl, C6-14 aryl, and 5-12 membered heteroaryl;RGBcis each independently selected from hydrogen, deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, C1-6 alkoxy, Ci-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C’3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, and 5-12 membered heteroaryl, wherein the Ci-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) RGBcl;or two RGBe, together with the atoms to which they are attached, form 3-10 membered heterocyclyl or 5-12 membered heteroaryl, wherein the 3-10 membered heterocyclyl or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) groups34316435300Docket No. 43658-02205 (EXAV-024 / 001WO)independently selected from deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, Ci-6 alkyl, Ci-6 alkoxy, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, and 5-12 membered heteroaryl;RGBc1is each independently selected from deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -RGBc2, -ORGBc2, -SRGBc2, -S(O)RGBc2, -S(O)2RGBc2, -C(O)RGBc2, - C(O)ORGBc2, -OC(O)RGBC2, -N(RGBC2)(RGBC3), -C(O)N(RGBC2)(RGBC3), -N(RGBC2)C(O)RGBC3, -S(O)N(RGBC2)(RGBC3), -S(O)2N(RGBC2)(RGBC3), -N(RGBC2)S(O)RGBC3, -N(RGBC2)S(O)2RGBC3;RGBC2and RGBC3are each independently selected from hydrogen, deuterium, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14 aryl, and 5-12 membered heteroaryl, wherein the C1-6alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3- 10 cycloalkyl, 3-10 membered heterocyclyl, C6-14 aryl, or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14 aryl, and 5-12 membered heteroaryl;RGBdis each independently selected from hydrogen, deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -ORGBdl, -S(O)RGBdl, -S(O)2RGBdl, -C(O)RGBdl, - C(O)ORGBdl, -OC(O)RGBdl, -N(RGBdl)(RGBd2), -C(O)N(RGBdl)(RGBd2), -N(RGBdl)C(O)RGBd2, - S(O)N(RGBdl)(RGBd2), -S(O)2N(RGBdl)(RGBd2), -N(RGBdl)S(O)RGBd2, -N(RGBdl)S(O)2RGBd2, and optionally replaced by one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) RGBd3substituted with the following groups: Ci-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, or 5-12 membered heteroaryl;or two RGBd, together with the atoms to which they are attached, form 3-10 membered heterocyclyl, 3-7 membered cycloalkyl, or 5-12 membered heteroaryl, wherein the 3-10 membered heterocyclyl, 3-7 membered cycloalkyl, or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7, or 8) groups independently selected from deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, C1-6 alkoxy, C3- io cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, and 5-12 membered heteroaryl;RGBdland RGBd2are each independently selected from hydrogen, deuterium, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, and 5-12 membered heteroaryl, wherein the Ci-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-35316435300Docket No. 43658-02205 (EXAV-024 / 001WO)io cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, Ci-6 alkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, 3-6 membered heterocyclyl, phenyl, and 5-6 membered heteroaryl;RGBd3is each independently selected from hydrogen, deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -RGBd4, -ORGBd4, -SRGBd4, -S(O)RGBd4, -S(O)2RGBd4, - C(O)RGBd4, -C(O)ORGBd4, -OC(O)RGBd4, -N(RGBd4)(RGBd5), -C(O)N(RGBd4)(RGBd5), - N(RGBd4)C(O)RGBd5, -S(O)N(RGBd4)(RGBd5), -S(O)2N(RGBd4)(RGBd5), -N(RGBd4)S(O)RGBd5, and - N(RGBd4)S(O)2RGBd5;RGBd4and RGBd5are each independently selected from hydrogen, deuterium, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14 aryl, and 5-12 membered heteroaryl, wherein the C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3- 10 cycloalkyl, 3-10 membered heterocyclyl, C6-14 aryl, or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C’3-7 cycloalkyl, 3-7 membered heterocyclyl, phenyl, or 5-6 membered heteroaryl;RGBeis each independently selected from hydrogen, deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -ORGBel, -SRGBel, -S(O)RGBel, -S(O)2RGBel, -C(O)RGBel, -C(O)ORGBel, -OC(O)RGBel, -N(RGBel)(RGBe2), -C(O)N(RGBel)(RGBe2), -N(RGBel)C(O)RGBe2, - S(O)N(RGBel)(RGBe2), -S(O)2N(RGBel)(RGBe2), -N(RGBel)S(O)RGBe2, -N(RGBel)S(O)2RGBe2, - C(O)N(RGBel)S(O)2N(RGBel)(RGBe2), -C(O)N(RGBel)S(O)2RGBe2, -P(O)(RGBel)RGBe2, and optionally replaced by one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) RGBe3substituted with the following groups: C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, or 5-12 membered heteroaryl;or two RGBe, together with the atoms to which they are attached, form 3-10 membered heterocyclyl or 5-12 membered heteroaryl, wherein the 3-10 membered heterocyclyl or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) groups independently selected from deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, C1-6 alkoxy, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14 aryl, and 5-12 membered heteroaryl;36316435300Docket No. 43658-02205 (EXAV-024 / 001WO)RGBeland RGBe2are each independently selected from hydrogen, deuterium, Ci-6 alkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, and 5-12 membered heteroaryl, wherein the C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3- 10 cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from hydrogen, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, 3-6 membered heterocyclyl, phenyl, and 5-6 membered heteroaryl;RGBe3is each independently selected from hydrogen, deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -RGBe4, -ORGBe4, -SRGBe4, -S(O)RGBe4, -S(O)2RGBe4, - C(O)RGBe4, -C(O)ORGBe4, -OC(O)RGBe4, -N(RGBe4)(RGBe5), -C(O)N(RGBe4)(RGBe5), - N(RGBe4)C(O)RGBe5, -S(O)N(RGBe4)(RGBe5), -S(O)2N(RGBe4)(RGBe5), -N(RGBe4)S(O)RGBe5, - N(RGBe4)S(O)2RGBe5, -C(O)N(RGBe4)S(O)2N(RGBe4)(RGBe5), -C(O)N(RGBe4)S(O)2RGBe5, and - (O)(RGBe4)RGBe5;RGBe4and RGBe5are each independently selected from hydrogen, deuterium, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C’6-14 aryl, and 5-12 membered heteroaryl, wherein the C1-6 alkyl, Cue alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3- 10 cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, or 5-12 membered heteroaryl are optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, 3-7 membered heterocyclyl, phenyl, and 5-6 membered heteroaryl;RGB1and RGB2together with the atoms to which they are attached, form C3-15 carbocyclyl optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7, or 8) RGB3;RGB3is each independently selected from hydrogen, deuterium, halogen, hydroxyl, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C3-10 cycloalkyl, and 3-10 membered heterocyclyl, wherein the C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C3-10 cycloalkyl, or 3-10 membered heterocyclyl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from deuterium, halogen, hydroxyl, amino, cyano, oxo, C3-10 cycloalkyl, and 3-10 membered heterocyclyl;37316435300Docket No. 43658-02205 (EXAV-024 / 001WO)LGB1is selected from a bond, -C(RGBL1)2-, -O-, -C(RGBL1)2O-, -S-, -C(O)-, -C(O)O-, -OC(O)-, -N(RGBL1)C(O)-, -C(O)N(RGBL1)-, and -N(RGBL1)-;RGBL1is each independently selected from hydrogen, deuterium, Ci-6 alkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl, wherein the C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, or 3-10 membered heterocyclyl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from deuterium, halogen, hydroxyl, amino, nitro, mercapto, cyano, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl;LGB2 is selected from a bond, -C(RGBL2)2-, -O-, -C(RGBL2)2O-, -S-, -C(O)-, -C(O)O-, - OC(O)-, -N(RGBL2)C(O)-, -C(O)N(RGBL2)-, and -N(RGBL2)-;RGBL2are each independently selected from hydrogen, deuterium, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl, wherein the Ci-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, or 3-10 membered heterocyclyl are optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from deuterium, halogen, hydroxyl, amino, nitro, mercapto, cyano, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl;LGB3is selected from a bond, -C(RGBL3)2-, -O-, -S-, -C(O)-, -C(O)O-, -OC(O)-, - N(RGBL3)C(O)-, -C(O)N(RGBL3)-, and -N(RGBL3)-;RGBL3is each independently selected from hydrogen, deuterium, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl, wherein the Ci-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, or 3-10 membered heterocyclyl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from deuterium, halogen, hydroxyl, amino, nitro, mercapto, cyano, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl;LGB4is a bond, -LGB4x-C(RGBL4a)(RGBL4b)-LGB4y-, -LGB4x-O-LGB4y-, -LGB4x-S-LGB4y-, -LGB4x-C(O)-LGB4y-, -LGB4x-C(O)O-LGB4y-, -LGB4x-OC(O)-LGB4y-, -LGB4x-N(RGBL4a)C(O)-LGB4y-, -LGB4x-C(O)N(RGBL4a)-LGB4y-, -LGB4x-N(RGBL4a)-LGB4y-, -LGB4X -38316435300Docket No. 43658-02205 (EXAV-024 / 001WO)N(RGBL4a)C(O)N(RGBL4b)iGB4y„N(RGBL4a)C(S)N(RGBL4b)-LGB4y -, Of(RGBL4z)rGBLGB4X and LGB4y are each independently a bond or Ci-io alkylene, wherein the Ci-io alkylene is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from deuterium, halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl;RGBL4aand RGBL4bare each independently selected from hydrogen, deuterium, C1-6 alkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl, wherein the C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, or 3-10 membered heterocyclyl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from deuterium, halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, Ci-e alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 substituted by a cycloalkyl group or a 3-10 membered heterocyclyl;Ring LGB4Z is C3-15 carbocyclyl, 3-12 membered heterocyclyl, C6-14 aryl, or 5-12 membered heteroaryl;RGB4Zis each independently selected from hydrogen, deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl, wherein the C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, or 3-10 membered heterocyclyl are optionally substituted with one or more substituents independently selected from deuterium, halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, Ci-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl;LGBSX and LGBSV are each independently a bond or Ci-io alkylene, wherein the Ci-10 alkylene is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from deuterium, halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C.3-io cycloalkyl, and 3-10 membered heterocyclyl;mGB, nGB, oGB, pGB, qGB, and rGB are each independently 0, 1, 2, or 3;39316435300Docket No. 43658-02205 (EXAV-024 / 001WO)unless otherwise specified, the heteroatoms in the above heterocyclyl and heteroaryl are independently selected from O, N or S, and the number of heteroatoms is 1, 2, 3 or 4; and wherein the definitions of the above variables are combined to form a stable chemical structure;A' is or a tautomer thereof;RAis selected from the group consisting of hydrogen, Ci-6 alkyl and (Ci-6 alkyl) carbonyl, wherein C1-6 alkyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen and C1-6 alkoxy;the counterion comprises an amine-containing polymer, a diamine or a conjugate thereof, a poly amine or a conjugate thereof, or M+;RN1and RN2are each independently hydrogen or C1-C30 alkyl;Yi, Y2, Yf, and Y2’ are each independently a bond, -O-, or -NH-;Li, L2, L3, Li’, and L2’ are each independently a bond, C1-C25 alkylene, or Ce-Cio arylene, wherein the alkylene and arylene are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryL Ci-Ce alkoxy, or Ci-Ce haloalkyl;40316435300Docket No. 43658-02205 (EXAV-024 / 001WO)Ri is C1-C30 alkyl, C2-C30 alkenyl, C6-C10 aryl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl, wherein the alkyl, alkenyl, aryl, heterocyclyl, and heteroaryl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6 alkyl, Ce-Cio aryl, C1-C6 alkoxy, Ci-Ce haloalkyl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl; andm is 0 or 1.

[0005] In some aspects, the present disclosure provides a salt comprising anion G-A-and a counterion, wherein:a stereoisomer thereof, or a tautomer thereof;XG is — N= or — CRaG=; RaGis selected from a hydrogen atom, a halogen atom, and Ci- 6 alkyl,YG is selected from — C(=O) —, — CHRG—, and — S(=O)2 —; RGis a hydrogen atom or Ci -6 alkyl,QGiis Ce-io aryl or 5 to 10 membered heteroaryl, wherein the Ce-io aryl and 5 to 10 membered heteroaryl are optionally substituted with one to five substituents independently selected from a halogen atom, C1-6 alkyl (wherein C1-6 alkyl is optionally substituted with one or more halogen atoms), C3-6 cycloalkyl, and C1-6 alkoxy;QG2is 3 to 12 membered heterocyclyl or 5 to 10 membered heteroaryl, wherein the 3 to 12 membered heterocyclyl and 5 to 10 membered heteroaryl are optionally substituted with one41316435300Docket No. 43658-02205 (EXAV-024 / 001WO)to three substituents independently selected from a halogen atom, Ci-6 alkyl (wherein Ci-6 alkyl is optionally substituted with one or more halogen atoms), Ci-6 alkoxy, and — NRGQaRGQb, and two Ci-6 alkyl groups together with a carbon atom to which they are attached may form C3- 8 carbocyclic ring; and RQaand RQbare independently selected from a hydrogen atom, Ci- 6 alkyl, and (C1-6 alkyl)carbonyl;Z3, Z4, Zs, Ze, Z”, Zs, Z9, Z10, Zu, Zi? and Zi< are each independently selected from the group consisting of N and C;RG1, RG, RG3, RGI, RG2’, and RG3are each independently selected from a hydrogen atom, halogen atom, C1-6 alkyl, C1-6 alkoxy, C 1-6 haloalkoxy, cycloalkyl, and heterocycloalkyl, wherein the Ci-6 alkyl, cycloalkyl, or heterocycloalkyl is optionally substituted by one or more substituents independently selected from a halogen atom, C1-6 alkoxy, and hydroxy; or RG2and RG3together with the carbon atom to which they are attached form 4- to 8-membered heterocycloalkyl;RG4, RG’ and RG6are independently selected from a hydrogen atom, a halogen atom, and CJ-6 alkyl;RG7and RG8are independently a hydrogen atom or C1-6 alkyl, wherein the C1-6 alkyl is optionally substituted with one or more substituents independently selected from a halogen atom and C3-15 cycloalkyl, or RG7and RG8together with a carbon atom to which they are attached may¬ form C3-15 cycloalkane ring, wherein the C3-15 cycloalkane ring formed by RG7and RG8together is optionally substituted with one to three C1-6 alkyl, wherein the C1-6 alkyl is optionally substituted with one or more substituents independently selected from a halogen atom, hydroxy, — NRG7aRG7b, C1-6 alkoxy, and 3 to 12 membered heterocyclyl, and RG7aand RG7bare independently selected from a hydrogen atom, C1-6 alkyl, and (C1-6 alkyl)carbonyl; and any two C1-6 alkyl optionally together with the carbon atom to which they are attached form C3-15 carbocyclic ring;nGl is an integer of 0 to 3; nG2 is an integer of 0 to 5; nG3 is 0 or 1;ZGlis selected from the group consisting of42316435300Docket No. 43658-02205 (EXAV-024 / 001WO)wherein Rzais selected from a hydrogen atom, Ci-6 alkyl, and (Ci-6 alkyl)carbonyl; Rzband Rzcare each independently a hydrogen atom or Ci-6 alkyl; n4 is an integer of 1 to 3; n5 and n6 are independently an integer of 0 to 10 (* represents a binding position with a pyrazolopyridine structure, and ** represents a binding position with ZG2);ZG2is selected from the group consisting of Ci-6 alkyl, C3-15 cycloalkyl, 3 to 12 membered heterocyclyl, C6-14 aryl, and 5 to 10 membered heteroaryl, wherein the C3-15 cycloalkyl, 3 to 12 membered heterocyclyl, C6-10 aryl, and 5 to 10 membered heteroaryl are optionally substituted with one to five substituents independently selected from Group A:Group A: a) oxo,b) a halogen atom,c) cyano,d) - NRzdRze; wherein Rzdand Rzeare independently selected from a hydrogen atom, Ci-6 alkyl and (Ci-6 alkyl)carbonyl, wherein Ci-6 alkyl is optionally- substituted with one or more substituents independently selected from hydroxy, a halogen atom and Ci-6 alkoxy,e) — C(=O) — NRzfRzg; wherein Rzfand Rzgare independently selected from a hydrogen atom, C1-6 alkyl and (C1-6 alkyl)carbonyl, wherein C1-6 alkyl is optionally substituted with one or more substituents independently selected from hydroxy, a halogen atom and C1-6 alkoxy,f) — S(=O)n7 — Rzh; wherein n7 is an integer of 0 to 2; and Rzhis a hydrogen atom or Ci-6 alkyl,g) C1-6 alkyl optionally substituted with one or more substituent independently selected from a halogen atom, hydroxy, — NRziRzj, C1-6 alkoxy, and 3 to 12 membered heterocyclyl, wherein Rziand Rzjare independently a hydrogen atom or43316435300Docket No. 43658-02205 (EXAV-024 / 001WO)Ci-6 alkyl, and wherein 3 to 12 membered heterocyclyl is optionally substituted with one or more substituents independently selected from hydroxy, Ci-6 alkyl and 3 to 12 membered heterocyclyl,h) Ci-6 alkoxy optionally substituted with one or more substituent independently selected from hydroxy, a halogen atom, and Ci-6 alkoxy,i) 3 to 12 membered heterocyclyl optionally substituted with one or more substituents independently selected from Ci-6 alkyl and (Ci-6alkyl)carbonyl, j) C6-10 aryl optionally substituted with one or more (C1-6 alkyl)carbonyl, k) 5 to 10 membered heteroaryl optionally substituted with one or more substituents independently selected from C1-6 alkyl, Ci-6 alkoxy, — NRzkRzl, and 3 to 12 membered heterocyclyl, wherein Rzkand Rzlare independently selected from a hydrogen atom, Ci-6 alkyl and (Ci-6 alkyl)carbonyl, and wherein 3 to 12 membered heterocyclyl is optionally substituted with one or more substituents independently selected from Ci-6 alkyl and (Ci-6 alkyl)carbonyl,1) — P(=O)(Rzm)(Rzn), wherein Rzmand Rznare each independently a hydrogen atom or C1-6alkyl;m) C3-C15 cycloalkyl optionally substituted with one or more substituents independently selected from the group consisting of halogen, oxo, C1-6 alkyl, C1-6 alkoxy and (C1-6 alkyl) carbonyl, wherein each of alkyl and alkoxy is optionally substituted with halogen; andn) C1-C6 alkyl-C3-C15 cycloalkyl wherein the cycloalkyl or alkyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, oxo, Ci-6 alkyl, Ci-6 alkoxy and (Ci-6 alkyl) carbonyl, wherein each of alkyl and alkoxy is optionally substituted with halogen;A" isNN O, R, or O, or a tautomer thereof;RAis selected from the group consisting of hydrogen, Ci-6 alkyl and (Ci-6 alkyl) carbonyl, wherein Ci-6 alkyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen and Ci-6 alkoxy;44316435300Docket No. 43658-02205 (EXAV-024 / 001WO)the counterion comprises an amine-containing polymer, a diamine or a conjugate thereof, a polyamine or a conjugate thereof, or Mh;RN1and RN2are each independently hydrogen or C1-C30 alkyl;Yi, Y?, Yi’, and Y ’ are each independently a bond, -O-, or -NH-;Li, L2, L3, Li’, and L2’ are each independently a bond, C1-C25 alkylene, or Ce-Cio arylene, wherein the alkylene and arylene are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl;Ri is C1-C30 alkyl, C2-C30 alkenyl, C6-C10 aryl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl, wherein the alkyl, alkenyl, aryl, heterocyclyl, and heteroaryl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, Ci-Ce haloalkyl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl; andm is 0 or 1.

[0006] In some aspects, the present disclosure provides a salt comprising anion G-A-and a counterion, wherein:45316435300Docket No. 43658-02205 (EXAV-024 / 001WO)XG is — N= or — CRaG=; RaGis selected from a hydrogen atom, a halogen atom, and Ci- 6 alkyl;YG is selected from — C(=O) -, CHRG—, and - -S(=O)2 - RGis a hydrogen atom or Ci-6 alkyl;QG1is C6-10 aryl or 5 to 10 membered heteroaryl, wherein the Ce-io aryl and 5 to 10 membered heteroaryl are optionally substituted with one to five substituents independently selected from a halogen atom, Ci-6 alkyl (wherein Ci-6 alkyl is optionally substituted with one or more halogen atoms), C3-6 cycloalkyl, and C1-6 alkoxy;QG2is 3 to 12 membered heterocyclyl or 5 to 10 membered heteroaryl, wherein the 3 to 12 membered heterocyclyl and 5 to 10 membered heteroaryl are optionally substituted with one to three substituents independently selected from a halogen atom, C1-6 alkyl (wherein C1-6 alkyl is optionally substituted with one or more halogen atoms), C1-6 alkoxy, and — NRGQaRGQb, and two Ci-6 alkyl groups together with a carbon atom to which they are attached may form C3- 8 carbocyclic ring; and RQaand RQbare independently selected from a hydrogen atom, Ci-6 alkyl, and (Ci-6 alkyl)carbonyl;Z3, Z4, Z5, Ze, Z7, Zs, Z9, Z10, Z11, Z12 and Z13 are each independently selected from the group consisting of N and C;46316435300Docket No. 43658-02205 (EXAV-024 / 001WO)RG1, RG2, RG3, RG1', RG2', and RG3'are each independently selected from a hydrogen atom, halogen atom, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 haloalkoxy, cycloalkyl, and heterocycloalkyl, wherein the Ci-6 alkyl, cycloalkyl, or heterocycloalkyl is optionally substituted by one or more substituents independently selected from a halogen atom, Ci-6 alkoxy, and hydroxy; or RG2and RG3together with the carbon atom to which they are attached form 4- to 8-membered heterocy cl oalky 1;RG4, RG5and RG6are independently selected from a hydrogen atom, a halogen atom, and Ci-6 alkyl;RG7and RG8are independently a hydrogen atom or Ci-6 alkyl, wherein the Ci-6 alkyl is optionally substituted with one or more substituents independently selected from a halogen atom and C3-15 cycloalkyl, or RG7and RG8together with a carbon atom to which they are attached may form C3-15 cycloalkane ring, wherein the C3-15 cycloalkane ring formed by RG7and RG8together is optionally substituted with one to three Ci-6 alkyl, wherein the Ci-6 alkyl is optionally substituted with one or more substituents independently selected from a halogen atom, hydroxy, ---NRG7aRG7b, Ci-6 alkoxy, and 3 to 12 membered heterocyclyl, and RG7aand RG7bare independently selected from a hydrogen atom, C1-6 alkyl, and (C1-6 alkyl)carbonyl; and any two C1-6 alkyl optionally together with the carbon atom to which they are attached form C3-15 carbocyclic ring;nGl is an integer of 0 to 3; nG2 is an integer of 0 to 5; nG3 is 0 or 1;ZG1is selected from the group consisting ofwherein Rzais selected from a hydrogen atom, C1-6 alkyl, and (C1-6 alkyl)carbonyl; Rzband Rzcare each independently a hydrogen atom or C1-6 alkyl; n4 is an integer of 1 to 3; n5 and n6 are independently an integer of 0 to 10 (* represents a binding position with a pyrazolopyridine structure, and ** represents a binding position with ZG2);47316435300Docket No. 43658-02205 (EXAV-024 / 001WO)ZG2is selected from the group consisting of Ci-6 alkyl, C3-15 cycloalkyl, 3 to 12 membered heterocyclyl, Ce-io aryl, and 5 to 10 membered heteroaryl, wherein the C3-15 cycloalkyl, 3 to 12 membered heterocyclyl, C6-10 aryl, and 5 to 10 membered heteroaryl are optionally substituted with one to five substituents independently selected from Group A:Group A a) oxo,b) a halogen atom,c) cyano,d) — NRzdRze; wherein Rzdand Rzeare independently selected from a hydrogen atom, C1-6 alkyl and (C1-6 alkyl)carbonyl, wherein C1-6 alkyl is optionally substituted with one or more substituents independently selected from hydroxy, a halogen atom and C1-6 alkoxy,e) — C(=O) — NRzfRzg; wherein Rzfand Rzgare independently selected from a hydrogen atom, Ci-6 alkyl and (Ci-6alkyl)carbonyl, wherein C1-6 alkyl is optionally substituted with one or more substituents independently selected from hydroxy, a halogen atom and Ci-6 alkoxy,f) - -S(=O)n7 - Rzh; wherein n7 is an integer of 0 to 2; and Rzhis a hydrogen atom or C i-6 alkyl,g) C1-6 alkyl optionally substituted with one or more substituent independently selected from a halogen atom, hydroxy, — NRziRzj, C1-6 alkoxy, and 3 to 12 membered heterocyclyl, wherein Rziand Rzjare independently a hydrogen atom or C1-6 alkyl, and wherein 3 to 12 membered heterocyclyl is optionally substituted with one or more substituents independently selected from hydroxy, Ci-6 alkyl and 3 to 12 membered heterocyclyl,h) C1-6 alkoxy optionally substituted with one or more substituent independently selected from hydroxy, a halogen atom, and C1-6 alkoxy,i) 3 to 12 membered heterocyclyl optionally substituted with one or more substituents independently selected from C1-6 alkyl and (C1-6 alkyl)carbonyl, j) C6-10 aryl optionally substituted with one or more (C1-6 alkyl)carbonyl, k) 5 to 10 membered heteroaryl optionally substituted with one or more substituents independently selected from C1-6 alkyl, C1-6 alkoxy, - -NRzkRzl, and 3 to 12 membered heterocyclyl, wherein Rzkand Rzlare independently selected from48316435300Docket No. 43658-02205 (EXAV-024 / 001WO)a hydrogen atom, Ci-6 alkyl and (Ci-6 alkyl)carbonyl, and wherein 3 to 12 membered heterocyclyl is optionally substituted with one or more substituents independently selected from Ci-6 alkyl and (Ci-6 alkyl)carbonyl,l) — P(=O)(Rzm)(Rzn), wherein Rzmand Rznare each independently a hydrogen atom or C1-6 alkyl;m) C3-C15 cycloalkyl optionally substituted with one or more substituents independently selected from the group consisting of halogen, oxo, C1-6 alkyl, Ci- 6 alkoxy and (C1-6 alkyl) carbonyl, wherein each of alkyl and alkoxy is optionally substituted with halogen; andn) C1-C6 alkyl-C3-C15 cycloalkyl wherein the cycloalkyl or alkyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, oxo, Ci-6 alkyl, Ci-6 alkoxy and (Ci-6 alkyl) carbonyl, wherein each of alkyl and alkoxy is optionally substituted with halogen;A' is or a tautomer thereof;RAis selected from the group consisting of hydrogen, Ci-6 alkyl and (Ci-6 alkyl) carbonyl, wherein C1-6 alkyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen and Ci-6 alkoxy;the counterion comprises an amine-containing polymer, a diamine or a conjugate thereof, a poly amine or a conjugate thereof, or M+;49316435300Docket No. 43658-02205 (EXAV-024 / 001WO)RN1and RN2are each independently hydrogen or C1-C30 alkyl;Yi, Y2, Yi’, and Y2’ are each independently a bond, -O-, or -NH-;Li, L2, L3, Li’, and L2’ are each independently a bond, C1-C25 alkylene, or Ce-Cio arylene, wherein the alkylene and arylene are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl; andRi is C1-C30 alkyl, C2-C30 alkenyl, Ce-Cio aryl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl, wherein the alkyl, alkenyl, aryl, heterocyclyl, and heteroaryl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, C6-C10 aryl, Ci-Ce alkoxy, Ci-Ce haloalkyl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl; andm is 0 or 1.

[0007] In some embodiments, A' is O or a tautomer thereof.

[0008] In some aspects, the present disclosure provides a salt comprising anion G-A‘ and a counterion, wherein:50316435300Docket No. 43658-02205 (EXAV-024 / 001WO)51316435300Docket No. 43658-02205 (EXAV-024 / 001WO), a stereoisomer thereof, or a tautomer thereof;N^N®A' is °~4 O or a tautomer thereof;the counterion is M+;52316435300Docket No. 43658-02205 (EXAV-024 / 001WO)RN1and RN2are each independently hydrogen or C1-C30 alkyl;Yi, Y2, Yf, and Y?’ are each independently a bond, -O-, or -NH-;Li, L2, L, Li’, and L2’ are each independently a bond, C1-C25 alkylene, or Ce-Cio arylene, wherein the alkylene and arylene are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6 alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl;Ri is C1-C30 alkyl, C2-C30 alkenyl, C6-C10 aryl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl, wherein the alkyl, alkenyl, aryl, heterocyclyl, and heteroaryl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6 alkyl, Ce-Cio aryl, C1-C6 alkoxy, Ci-Ce haloalkyl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl; andm is 0 or 1.

[0009] In some aspects, the present disclosure provides a salt comprising anion G-A" and a53316435300Docket No. 43658-02205 (EXAV-024 / 001WO)or a tautomer thereof;N^N®A“ i ■s O or a tautomer thereof;the counterion is M+;54316435300Docket No. 43658-02205 (EXAV-024 / 001WO)RN1and RN2are each independently hydrogen or C1-C30 alkyl;Yi, Y2, Yi’, and Y2’ are each independently a bond, -O-, or -NH-;Li, L2, L3, Li’, and L2’ are each independently a bond, C1-C25 alkylene, or Ce-Cio arylene, wherein the alkylene and arylene are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl;Ri is C1-C30 alkyl, C2-C30 alkenyl, Ce-Cio aryl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl, wherein the alkyl, alkenyl, aryl, heterocyclyl, and heteroaryl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, C6-C10 aryl, Ci-Ce alkoxy, Ci-Ce haloalkyl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl; andm is 0 or 1.

[0010] In some aspects, the present disclosure provides a salt comprising anion G-A' and a counterion, wherein:55316435300Docket No. 43658-02205 (EXAV-024 / 001WO)°~4A' is O or a tautomer thereof;the counterion is M⁺;1 1^HN' -R1M+is RN2RN1and RN2are each independently hydrogen or C1-C25 alkyl;¥1, ¥2, Yi’, and Y2’ are each independently a bond, -O-, or -NH-;56316435300Docket No. 43658-02205 (EXAV-024 / 001WO)Li, L2, L3, Li’, and L2’ are each independently a bond, C1-C25 alkylene, or Ce-Cio arylene, wherein the alkylene and arylene are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, C6-C10 aryl, C1-C6 alkoxy, or Ci-Ce haloalkyl; andRi is C1-C30 alkyl, C2-C30 alkenyl, Ce-Cio aryl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl, wherein the alkyl, alkenyl, aryl, heterocyclyl, and heteroaryl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, C6-C10 aryl, Ci-Ce alkoxy, Ci-Ce haloalkyl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl.

[0011] In some aspects, the present disclosure provides a salt comprising anion G-A‘ and a counterion, wherein:G is \, a stereoisomer thereof, or a tautomer thereof;A“ is O or a tautomer thereof; the counterion is M+;57316435300Docket No. 43658-02205 (EXAV-024 / 001WO)RN1and RN2are each independently hydrogen or C1-C30 alkyl;Yi, Y2, Yi’, and Y2’ are each independently a bond, -O-, or -NH-;Li, L2, L3, Li’, and L2’ are each independently a bond, C1-C25 alkylene, or Ce-Cio arylene, wherein the alkylene and arylene are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl;Ri is C1-C30 alkyl, C2-C30 alkenyl, Ce-Cio aryl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl, wherein the alkyl, alkenyl, aryl, heterocyclyl, and heteroaryl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, C6-C10 aryl, Ci-Ce alkoxy, Ci-Ce haloalkyl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl; andm is 0 or 1.

[0012] In some aspects, the present disclosure provides a salt comprising anion G-A' and a counterion, wherein:G is \, a stereoisomer thereof, or a tautomer thereof;A" is O or a tautomer thereof; the counterion is M+;58316435300Docket No. 43658-02205 (EXAV-024 / 001WO)RN1and RN2are each independently hydrogen or C1-C25 alkyl;Yi, Y2, Yf, and Y2’ are each independently a bond, -O-, or -NH-;Li, L2, L3, Li’, and L2’ are each independently a bond, C1-C25 alkylene, or C6-C10 arylene, wherein the alkylene and arylene are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6 alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or C1-C6 haloalkyl; andRi is C1-C30 alkyl, C2-C30 alkenyl, Ce-Cio aryl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl, wherein the alkyl, alkenyl, aryl, heterocyclyl, and heteroaryl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6 alkyl, Ce-Cio aryl, C1-C6 alkoxy, Ci-Ce haloalkyl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl.

[0013] In some aspects, the present disclosure provides a salt comprising anion G-A-and a counterion, wherein the salt is selected from the compounds described in Table 1, stereoisomers thereof, and tautomers thereof.

[0014] In some aspects, the present disclosure provides a pharmaceutical composition comprising a salt of the present disclosure, a stereoisomer thereof, or a tautomer thereof, and a pharmaceutically acceptable diluent or carrier.

[0015] In some aspects, the present disclosure provides a method of treating or preventing a disease or disorder disclosed herein in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the salt or pharmaceutical composition of the present disclosure.

[0016] In some aspects, the present disclosure provides a salt or pharmaceutical composition of the present disclosure for use in treating or preventing a disease or disorder disclosed herein.

[0017] In some aspects, the present disclosure provides the use of a salt or pharmaceutical composition of the present disclosure in the manufacture of a medicament for treating or preventing a disease or disorder disclosed herein.59316435300Docket No. 43658-02205 (EXAV-024 / 001WO)

[0018] In some aspects, the present disclosure provides a method of preparing a salt of the present disclosure.

[0019] In some aspects, the present disclosure provides a method of preparing a salt, comprising one or more steps described herein.

[0020] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. In the specification, the singular forms also include the plural unless the context clearly dictates otherwise. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present disclosure, suitable methods and materials are described below. All publications, patent applications, patents and other references mentioned herein are incorporated by reference. The references cited herein are not admitted to be prior art to the claimed invention. In the case of conflict, the present specification, including definitions, will control. In addition, the materials, methods and examples are illustrative only and are not intended to be limiting. In the case of conflict between the chemical structures and names of the compounds disclosed herein, the chemical structures will control.

[0021] Other features and advantages of the disclosure will be apparent from the following detailed description and claims.BRIEF DESCRIPTION OF THE DRAWINGS

[0022] The accompanying drawings, which are incorporated into and form a part of the specification, illustrate several embodiments of the present disclosure and, together with the description, serve to explain the principles of the present disclosure. The drawings are only for the purpose of illustrating an embodiment of the disclosure and are not to be construed as limiting the invention. Further objects, features and advantages of the invention will become apparent from the following detailed description taken in conjunction with the accompanying figures showing illustrative embodiments of the disclosure.

[0023] FIG. 1 depicts the1H NMR spectra of Compound 1-17, obtained in deuterated DMSO.

[0024] FIG. 2 depicts thel3C NMR spectra of Compound 1-17, obtained in deuterated DMSO.

[0025] FIG. 3 depicts the1H NMR spectra of Compound 1-17, obtained in CDCl3.

[0026] FIG. 4 depicts the13C NMR spectra of Compound 1-17, obtained in CDCl3.60316435300Docket No. 43658-02205 (EXAV-024 / 001WO)

[0027] FIG. 5 depicts the Fourier transform infrared (FT-IR) spectra overlay of orforglipron and Compound 1-17.

[0028] FIG. 6 depicts the pharmacokinetic (PK) profile of Compound 1-17.

[0029] FIG. 7 depicts the pharmacokinetic (PK) profile of Compound 1-17 over 56 days.

[0030] FIG. 8 depicts the pharmacokinetic (PK) profile of Compound 1-17 over 154 days.DETAILED DESCRIPTION

[0031] The present disclosure relates to salts of heterocyclic GLP1 receptor agonists like orforglipron. The present disclosure also relates to processes for the preparation of salts, to pharmaceutical compositions (e.g. nanoparticle compositions) comprising these salts and the use of the salts to treat and / or prevent diseases or disorders including, but not limited to obesity, type 2 diabetes, sleep apnea, cardiovascular disease, polycystic ovary syndrome, depression, substance use disorder, heart failure, and metabolic dysfunction-associated steatohepatitis.Without wishing to be bound by theory, the salts of heterocyclic GLP1 receptor agonists disclosed herein allow for sustained release of said heterocyclic GLP1 receptor agonists over an extended time period.Definitions

[0032] Unless otherwise stated, the following terms used in the specification and claims have the following meanings set out below.

[0033] Without wishing to be limited by this statement, it is understood that, while various options for variables are described herein, the disclosure intends to encompass operable embodiments having combinations of the options. The disclosure may be interpreted as excluding the non-operable embodiments caused by certain combinati ons of the options.

[0034] As used herein, “alkyl”, “Ci, Cb, C3, C4, Cs or Ce alkyl” or “Ci-C 6 alkyl” is intended to include Ci, C2, C3, C4, Cs or Cs straight chain (linear) saturated aliphatic hydrocarbon groups and C3, C4, Cs or Ce branched saturated aliphatic hydrocarbon groups. For example, C1-C6alkyl is intends to include C1, C2, C3, C4, C5and C6alkyl groups. Examples of alkyl include, moi eties having from one to six carbon atoms, such as, but not limited to, methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl, t-butyl, n-pentyl, i-pentyl, or n-hexyl. In some embodiments, a straight chain or branched alkyl has six or fewer carbon atoms (e.g., Ci-Ce for straight chain, C3-C6 for61316435300Docket No. 43658-02205 (EXAV-024 / 001WO)branched chain), and in another embodiment, a straight chain or branched alkyl has four or fewer carbon atoms. A divalent alkyl group is referred to herein as “alkylene,”

[0035] As used herein, the term “optionally substituted alkyl” refers to unsubstituted alkyl or alkyl having designated substituents replacing one or more hydrogen atoms on one or more carbons of the hydrocarbon backbone. Such substituents can include, for example, alkyl, alkenyl, alkynyl, halogen, hydroxyl, alkylcarbonyloxy, arylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, carboxylate, alkyl carbonyl, arylcarbonyl, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkylthiocarbonyl, alkoxyl, phosphate, phosphonato, phosphinato, amino (including alkylamino, dialkylamino, arylamino, diarylamino and alkylarylamino), acylamino (including alkylcarbonylamino, arylcarbonylamino, carbamoyl and ureido), amidino, imino, sulfhydryl, alkylthio, arylthio, thiocarboxylate, sulfates, alkylsulfinyl, sulfonato, sulfamoyl, sulfonamido, nitro, trifluoromethyl, cyano, azido, heterocyclyl, alkylaryl, or an aromatic or heteroaromatic moiety.

[0036] As used herein, the term “alkenyl” includes unsaturated aliphatic groups analogous in length and possible substitution to the alkyls described above, but that contain at least one double bond. For example, the term “alkenyl” includes straight chain alkenyl groups (e.g., ethenyl, propenyl, butenyl, pentenyl, hexenyl, heptenyl, octenyl, nonenyl, decenyl), and branched alkenyl groups. In certain embodiments, a straight chain or branched alkenyl group has six or fewer carbon atoms in its backbone (e.g, C2-C6 for straight chain, C3-C6 for branched chain). The term “C2-C6” includes alkenyl groups containing two to six carbon atoms. The term “C3-C6” includes alkenyl groups containing three to six carbon atoms. A divalent alkenyl group is referred to herein as “alkenylene.”

[0037] As used herein, the term “optionally substituted alkenyl” refers to unsubstituted alkenyl or alkenyl having designated substituents replacing one or more hydrogen atoms on one or more hydrocarbon backbone carbon atoms. Such substituents can include, for example, alkyl, alkenyl, alkynyl, halogen, hydroxyl, alkylcarbonyloxy, arylcarbonyloxy, alkoxycarbonyloxy,aryl oxy carbonyl oxy, carboxylate, alkylcarbonyl, arylcarbonyl, alkoxy carbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkylthiocarbonyl, alkoxyl, phosphate, phosphonato, phosphinato, amino (including alkylamino, dialkylamino, arylamino, diarylamino and alkylarylamino), acylamino (including alkylcarbonylamino, arylcarbonylamino, carbamoyl and ureido), amidino, imino, sulfhydryl, alkylthio, arylthio, thiocarboxylate, sulfates, alkylsulfinyl,62316435300Docket No. 43658-02205 (EXAV-024 / 001WO)sulfonato, sulfamoyl, sulfonamido, nitro, trifluoromethyl, cyano, heterocyclyl, alkylaryl, or an aromatic or heteroaromatic moiety.

[0038] As used herein, the term “alkynyl” includes unsaturated aliphatic groups analogous in length and possible substitution to the alkyls described above, but which contain at least one triple bond. For example, “alkynyl” includes straight chain alkynyl groups (e.g, ethynyl, propynyl, butynyl, pentynyl, hexynyl, heptynyl, octynyl, nonynyl, decynyl), and branched alkynyl groups. In certain embodiments, a straight chain or branched alkynyl group has six or fewer carbon atoms in its backbone e.g., C2-C6 for straight chain, C3-C6 for branched chain). The term “C2-C6” includes alkynyl groups containing two to six carbon atoms. The term “Cs-Ce” includes alkynyl groups containing three to six carbon atoms. As used herein, “C2-C6 alkenylene linker” or “C2-C6 alkynylene linker” is intended to include C2, C3, C4, Cs or Ce chain (linear or branched) divalent unsaturated aliphatic hydrocarbon groups. For example, C2-C6alkenylene linker is intended to include C2, C3, C4, C5and C6alkenylene linker groups. A divalent alkynyl group is referred to herein as “alkynylene.”

[0039] As used herein, the term “optionally substituted alkynyl” refers to unsubstituted alkynyl or alkynyl having designated substituents replacing one or more hydrogen atoms on one or more hydrocarbon backbone carbon atoms. Such substituents can include, for example, alkyl, alkenyl, alkynyl, halogen, hydroxyl, alkylcarbonyloxy, aryl carbonyl oxy, alkoxycarbonyloxy, aryloxycarbonyloxy, carboxylate, alkylcarbonyl, aryl carbonyl, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkylthiocarbonyl, alkoxyl, phosphate, phosphonato, phosphinate, amino (including alkylamino, dialkylamino, arylamino, diarylamino and alkylarylamino), acylamino (including alkylcarbonylamino, arylcarbonylamino, carbamoyl and ureido), amidino, imino, sulfhydryl, alkylthio, arylthio, thiocarboxylate, sulfates, alkyl sulfinyl, sulfonato, sulfamoyl, sulfonamido, nitro, trifluoromethyl, cyano, azido, heterocyclyl, alkylaryl, or an aromatic or heteroaromatic moiety.

[0040] Other optionally substituted moieties (such as optionally substituted cycloalkyl, heterocyclyl, aryl, or heteroaryl) include both the unsubstituted moieties and the moieties having one or more of the designated substituents. For example, substituted heterocyclyl includes those substituted with one or more alkyl groups, such as 2,2,6,6-tetramethyl-piperidinyl and 2, 2,6,6-tetram ethyl - 1,2,3,6-tetrahydropyridinyl.63316435300Docket No. 43658-02205 (EXAV-024 / 001WO)

[0041] As used herein, the term “cycloalkyl” refers to a saturated or partially unsaturated hydrocarbon monocyclic or polycyclic (e.g., fused, bridged, or spiro rings) system having 3 to 30 carbon atoms (e.g., C3-C12, C3-C10, or Cs-Cs). Examples of cycloalkyl include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, 1,2,3,4-tetrahydronaphthalenyl, and adamantyl. In the case of polycyclic cycloalkyl, only one of the rings in the cycloalkyl needs to be non-aromatic. A divalent cycloalkyl group is referred to herein as “cycloalkylene.”

[0042] As used herein, the term “heterocyclyl” refers to a saturated or partially unsaturated 3-8 membered monocyclic, 7-12 membered bicyclic (fused, bridged, or spiro rings), or 11-14 membered tricyclic ring system (fused, bridged, or spiro rings) having one or more heteroatonis (such as O, N, S, P, or Se), e.g., 1 or 1-2 or 1-3 or 1-4 or 1-5 or 1-6 heteroatoms, or e.g., 1, 2, 3, 4, 5, or 6 heteroatoms, independently selected from the group consisting of nitrogen, oxygen and sulfur, unless specified otherwise. Examples of heterocyclyl groups include, but are not limited to, piperidinyl, piperazinyl, pyrrolidinyl, dioxanyl, tetrahydrofuranyl, isoindolinyl, indolinyl, imidazolidinyl, pyrazolidinyl, oxazolidinyl, isoxazolidinyl, triazolidinyl, oxiranyl, azetidinyl, oxetanyl, thietanyl, 1,2,3,6-tetrahydropyridinyl, tetrahydropyranyl, dihydropyranyl, pyranyl, morpholinyl, tetrahydrothiopyranyl, 1,4-diazepanyl, 1,4-oxazepanyl, 2-oxa-5-azabicyclo[2.2. I]heptanyl, 2,5-diazabicyclo[2.2, l]heptanyl, 2-oxa-6-azaspiro[3.3]heptanyl, 2,6-diazaspiro[3.3]heptanyl, l,4-dioxa-8-azaspiro[4.5]decanyl, l,4-dioxaspiro[4.5]decanyl, 1-oxaspiro[4.5]decanyl, l-azaspiro[4.5]decanyl, 3'H-spiro[cyclohexane-l,r-isobenzofuran]-yl, 7'H-spiro[cyclohexane-l,5'-furo[3,4-b]pyridin]-yl, 3'H-spiro[cyclohexane-l,r-furo[3,4-c]pyridin]-yl, 3-azabicyclo[3.1.0]hexanyl, 3-azabicyclo[3.1.0]hexan-3-yl, 1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazolyl, 3,4,5,6,7,8-hexahydropyrido[4,3-d]pyrimidinyl, 4, 5,6,7-tetrahydro-lH-pyrazolo[3,4-c]pyridinyl, 5,6,7,8-tetrahydropyrido[4,3-d]pyrimidinyl, 2-azaspiro[3.3]heptanyl, 2-methyl-2-azaspiro[3.3]heptanyl, 2-azaspiro[3.5]nonanyl, 2-methyl-2-azaspiro[3.5]nonanyl, 2-azaspiro[4.5]decanyl, 2-methyl-2-azaspiro[4.5]decanyl, 2-oxa-azaspiro[3,4]octanyl, 2-oxa-azaspiro[3,4]octan-6-yl, 5,6-dihydro-4H-cyclopenta[b]thiophenyl, and the like. In the case of multicyclic heterocyclyl, only one of the rings in the heterocyclyl needs to be non-aromatic (e.g., 4,5,6,7-tetrahydrobenzo[c]isoxazolyl, benzo[d][ 1,3] di oxole, 2,3-dihydrobenzo[b][l,4]dioxine, and the like). A divalent heterocyclyl group is referred to herein as “heterocyclylene.”64316435300Docket No. 43658-02205 (EXAV-024 / 001WO)

[0043] It is understood that when a variable has two attachments to the rest of the formula of the compound, the two attachments could be at the same atom or different atoms of the variable, as allowed by valency. For example, when a variable (e.g., variable X) is cycloalkyl or heterocyclyl, and has two attachments to the rest of the formula of the compound, the two attachments could be at the same atom or different atoms of the cycloalkyl or heterocyclyl.

[0044] As used herein, the term “aryl” refers to groups monocyclic or multicyclic systems with one or more aromatic rings that do not contain any heteroatom in the ring structure(s). The term aryl includes both monovalent species and divalent species. Examples of aryl groups include, but are not limited to, phenyl, biphenyl, naphthyl and the like. For example, an aryl is phenyl, A divalent aryl group is referred to herein as “arylene.”

[0045] As used herein, the term “heteroaryl” refers to a stable 5-, 6-, or 7-membered monocyclic or 7-, 8-, 9-, 10-, 11- or 12-membered bicyclic aromatic heterocyclic ring which consists of carbon atoms and one or more heteroatoms, e.g., 1 or 1-2 or 1-3 or 1-4 or 1-5 or 1-6 heteroatoms, or e.g., 1, 2, 3, 4, 5, or 6 heteroatoms, independently selected from the group consisting of nitrogen, oxygen and sulfur. The nitrogen atom may be substituted or unsubstituted (z.e., N or NR wherein R is H or other substituents, as defined). The nitrogen and sulfur heteroatoms may optionally be oxidized (i.e., N- O and S(O)P, where p = 1 or 2). It is to be noted that total number of S and O atoms in the aromatic heterocycle is not more than 1. Examples of heteroaryl groups include pyrrole, furan, thiophene, thiazole, isothiazole, imidazole, triazole, tetrazole, pyrazole, oxazole, isoxazole, pyridine, pyrazine, purine, pyridazine, pyrimidine, and the like. Heteroaryl groups can also be fused or bridged with alicyclic or heterocyclic rings, which are not aromatic so as to form a multicyclic system e.g., 4,5,6,7-tetrahydrobenzo[c]isoxazolyl, 2,3- dihydro-77 / -pyrrolopyridine, 1,2,3,4-tetrahydronaphthyridine, 2,3-dihydro-pyridooxazine, 2,3- dihydro-777-pyrrolopyridine, 2,3-dihydrooxazolopyridine, and the like). A divalent heteroaryl group is referred to herein as “heteroarylene.”

[0046] Furthermore, the terms “aryl” and “heteroaryl” include multicyclic aryl and heteroaryl groups, respectively, e.g., tricyclic, bicyclic, e.g., naphthalene, benzoxazole, benzodi oxazole, benzothiazole, benzoimidazole, benzothiophene, quinoline, isoquinoline, naphthrydine, indole, benzofuran, purine, benzofuran, deazapurine, indolizine.

[0047] The cycloalkyl, heterocyclyl, aryl, or heteroaryl ring can be substituted at one or more ring positions (e.g., the ring-forming carbon or heteroatom such as N) with such substituents as65316435300Docket No. 43658-02205 (EXAV-024 / 001WO)described above, for example, alkyl, alkenyl, alkynyl, halogen, hydroxyl, alkoxy, alkylcarbonyloxy, aryl carbonyl oxy, alkoxy carbonyloxy, aryloxycarbonyloxy, carboxylate, alkylcarbonyl, alkylaminocarbonyl, aralkylaminocarbonyl, alkenylaminocarbonyl, alkylcarbonyl, arylcarbonyl, aralkyl carbonyl, alkenylcarbonyl, alkoxy carbonyl, aminocarbonyl, alkylthiocarbonyl, phosphate, phosphonato, phosphinato, amino (including alkylamino, dialkylamino, arylamino, diarylamino and alkylarylamino), acylamino (includingalkyl carbonyl amino, arylcarbonylamino, carbamoyl and ureido), amidino, imino, sulfhydryl, alkylthio, arylthio, thiocarboxylate, sulfates, alkylsulfinyl, sulfonato, sulfamoyl, sulfonamido, nitro, trifluoromethyl, cyano, azido, heterocyclyl, alkylaryl, or an aromatic or heteroaromatic moiety. Aryl and heteroaryl groups can also be fused or bridged with alicyclic or heterocyclic rings, which are not aromatic so as to form a multicyclic system (e.g., tetralin, methylenedioxyphenyl such as benzo[d][l,3]dioxole-5-yl).

[0048] As used herein, the term “substituted,” means that any one or more hydrogen atoms on the designated atom is replaced with a selection from the indicated groups, provided that the designated atom’s normal valency is not exceeded, and that the substitution results in a stable compound. When a substituent is oxo or keto (z.e., =0), then 2 hydrogen atoms on the atom are replaced. Keto substituents are not present on aromatic moieties. Ring double bonds, as used herein, are double bonds that are formed between two adjacent ring atoms (e.g., C=C, C=N or N=N).

[0049] “Stable compound” and “stable structure” are meant to indicate a compound that is sufficiently robust to survive isolation to a useful degree of purity from a reaction mixture, and formulation into an efficacious therapeutic agent.

[0050] When a bond to a substituent is shown to cross a bond connecting two atoms in a ring, then such substituent may be bonded to any atom in the ring. When a substituent is listed without indicating the atom via which such substituent is bonded to the rest of the compound of a given formula, then such substituent may be bonded via any atom in such formula. Combinations of substituents and / or variables are permissible, but only if such combinations result in stable compounds.

[0051] When any variable (e.g., R) occurs more than one time in any constituent or formula for a compound, its definition at each occurrence is independent of its definition at every other occurrence. Thus, for example, if a group is shown to be substituted with 0-2 R moieties, then66316435300Docket No. 43658-02205 (EXAV-024 / 001WO)the group may optionally be substituted with up to two R moieties and R at each occurrence is selected independently from the definition of R. Also, combinations of substituents and / or variables are permissible, but only if such combinations result in stable compounds.

[0052] As used herein, the term “hydroxy” or “hydroxyl” includes groups with an -OH or -O'.

[0053] As used herein, the term “halo” or “halogen” refers to fluoro, chloro, bromo and iodo.

[0054] The term “haloalkyl” or “haloalkoxyl” refers to an alkyl or alkoxyl substituted with one or more halogen atoms.

[0055] The term “heteroalkyl” refers to an alkyl group, as defined herein, wherein at least one carbon atom has been replaced by a heteroatom selected from the group consisting of oxygen, nitrogen, or sulfur. The nitrogen atom may be substituted or unsubstituted (e.g., NR wherein R is H or other substituents, as defined). The nitrogen and sulfur heteroatoms may optionally be oxidized (i.e., N→O and S(O)p, where p = 1 or 2). A divalent heteroalkyl is referred to herein as “heteroalkylene.”

[0056] As used herein, the term “optionally substituted haloalkyl” refers to unsubstituted haloalkyl having designated substituents replacing one or more hydrogen atoms on one or more hydrocarbon backbone carbon atoms. Such substituents can include, for example, alkyl, alkenyl, alkynyl, halogen, hydroxyl, alkyl carbonyl oxy, arylcarbonyl oxy, alkoxycarbonyloxy, aryloxycarbonyloxy, carboxylate, alkylcarbonyl, aryl carbonyl, alkoxycarbonyl, aminocarbonyl, alkyl aminocarbonyl, dialkyl aminocarbonyl, alkyl thiocarbonyl, alkoxyl, phosphate, phosphonato, phosphinate, amino (including alkylamino, dialkylamino, arylamino, diarylamino and alkylarylamino), acylamino (including alkylcarbonylamino, aryl carbonyl ami no, carbamoyl and ureido), amidino, imino, sulfhydryl, alkylthio, arylthio, thiocarboxylate, sulfates, alkylsulfinyl, sulfonate, sulfamoyl, sulfonamide, nitro, trifluoromethyl, cyano, azido, heterocyclyl, alkylaryl, or an aromatic or heteroaromatic moiety.

[0057] As used herein, the term “alkoxy” or “alkoxyl” includes substituted and unsubstituted alkyl, alkenyl and alkynyl groups covalently linked to an oxygen atom. Examples of alkoxy groups or alkoxyl radicals include, but are not limited to, methoxy, ethoxy, isopropyloxy, propoxy, butoxy and pentoxy groups. Examples of substituted alkoxy groups include halogenated alkoxy groups. The alkoxy groups can be substituted with groups such as alkenyl, alkynyl, halogen, hydroxyl, alkylcarbonyloxy, aryl carbonyl oxy, alkoxy carbonyloxy, aryloxycarbonyloxy, carboxylate, alkyl carbonyl, arylcarbonyl, alkoxy carbonyl, aminocarbonyl,67316435300Docket No. 43658-02205 (EXAV-024 / 001WO)alkylaminocarbonyl, dialkylaminocarbonyl, alkylthiocarbonyl, alkoxyl, phosphate, phosphonato, phosphinato, amino (including alkylamino, dialkylamino, arylamino, diarylamino, and alkylarylamino), acylamino (including alkylcarbonylamino, arylcarbonylamino, carbamoyl and ureido), amidino, imino, sulfhydryl, alkylthio, arylthio, thiocarboxylate, sulfates, alkyl sulfinyl, sulfonato, sulfamoyl, sulfonamido, nitro, trifluoromethyl, cyano, azido, heterocyclyl, alkylaryl, or an aromatic or heteroaromatic moi eties. Examples of halogen substituted alkoxy groups include, but are not limited to, fluoromethoxy, difluoromethoxy, trifluoromethoxy, chloromethoxy, di chloromethoxy and trichloromethoxy.

[0058] As used herein, the term “heteroalkoxy” or “heteroalkoxyl” includes substituted and unsubstituted heteroalkyl, heteroalkenyl and heteroalkynyl groups covalently linked to an oxygen atom.

[0059] “Cation” or “counterion” refers to a charged species (i.e. positive charge in the case of cation) which may form a salt with the anions of the present disclosure (e.g., G-A ). Examples of suitable counterions include cationic counterions, including monovalent and divalent cations. As understood by those of ordinary skill in the art, when the counterion is divalent it is present in a 1:2 stoichiometry with the anion of the present disclosure. It will also be understood that multiple cations or counterions may be present in a pharmaceutical composition or in a crystalline form. The representation of a single counterion should not be limiting to only having a single counterion present. Those of ordinary' skill in the art will appreciate that counterions are readily substituted and where a single counterion species is depicted, all available counterions are considered.

[0060] As would be understood by a skilled artisan, amines (e.g., primary, secondary, or tertiary amines) that are drawn herein may be protonated to serve as counterions. For example, when theL2\L< ^RN1'N RN2‘structureis drawn,68316435300Docket No. 43658-02205 (EXAV-024 / 001WO)L2\ Y2' ©7 RN2RN2'all contemplated.

[0061] As used herein, the expressions “one or more of A, B, or C,” “one or more A, B, or C,” “one or more of A, B, and C,” “one or more A, B, and C,” “selected from the group consisting of A, B, and C”, “selected from A, B, and C”, and the like are used interchangeably and all refer to a selection from a group consisting of A, B, and / or C, i.e., one or more As, one or more Bs, one or more Cs, or any combination thereof, unless indicated otherwise.

[0062] It is to be understood that the present disclosure provides methods for the synthesis of the salts of the present disclosure. The present disclosure also provides detailed methods for the synthesis of various disclosed compounds of the present disclosure according to the following schemes as well as those shown in the Examples.

[0063] It is to be understood that, throughout the description, where compositions are described as having, including, or comprising specific components, it is contemplated that compositions also consist essentially of, or consist of, the recited components. Similarly, where methods or processes are described as having, including, or comprising specific process steps, the processes also consist essentially of, or consist of, the recited processing steps. Further, it should be understood that the order of steps order for performing certain actions is immaterial so long as the invention remains operable. Moreover, two or more steps or actions can be conducted simultaneously.

[0064] It is to be understood that the synthetic processes of the disclosure can tolerate a wide variety of functional groups, therefore various substituted starting materials can be used.

[0065] It is to be understood that compounds of the present disclosure can be prepared in a variety of ways using commercially available starting materials, compounds known in the literature, or from readily prepared intermediates, by employing standard synthetic methods and procedures either known to those skilled in the art, or which will be apparent to the skilled artisan in light of the teachings herein. Standard synthetic methods and procedures for the preparation of organic molecules and functional group transformations and manipulations can be69316435300Docket No. 43658-02205 (EXAV-024 / 001WO)obtained from the relevant scientific literature or from standard textbooks in the field. Although not limited to any one or several sources, classic texts such as Smith, M. B., March, J., March 's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 5thedition, John Wiley & Sons: New York, 2001; Greene, T. W., Wuts, P. G. M., Protective Groups in Organic Synthesis, 3rdedition, John Wiley & Sons: New York, 1999; R. Larock, Comprehensive Organic Transformations, VCH Publishers (1989); L. Fieser and M. Fieser, Fieser and Fieser ’s Reagents for organic Synthesis, John Wiley and Sons (1994); and L. Paquette, ed.. Encyclopedia of Reagents for organic Synthesis, John Wiley and Sons (1995), incorporated by reference herein, are useful and recognized reference textbooks of organic synthesis known to those in the art

[0066] One of ordinary skill in the art will note that, during the reaction sequences and synthetic schemes described herein, the order of certain steps may be changed, such as the introduction and removal of protecting groups. One of ordinary skill in the art will recognize that certain groups may require protection from the reaction conditions via the use of protecting groups. Protecting groups may also be used to differentiate similar functional groups in molecules. A list of protecting groups and how to introduce and remove these groups can be found in Greene, T. W., Wuts, P. G. M., Protective Groups in Organic Synthesis, 3rdedition, John Wiley & Sons: New York, 1999.

[0067] It is to be understood that, unless otherwise stated, any description of a method of treatment or prevention includes use of the compounds to provide such treatment or prevention as is described herein. It is to be further understood, unless otherwise stated, any description of a method of treatment or prevention includes use of the compounds to prepare a medicament to treat or prevent such condition. The treatment or prevention includes treatment or prevention of human or non-human animals including rodents and other disease models.

[0068] It is to be understood that, unless otherwise stated, any description of a method of treatment includes use of the compounds to provide such treatment as is described herein. It is to be further understood, unless otherwise stated, any description of a method of treatment includes use of the compounds to prepare a medicament to treat such condition. The treatment includes treatment of human or non-human animals including rodents and other disease models.

[0069] As used herein, the term “subject” includes human and non-human animals, as well as cell lines, cell cultures, tissues, and organs. In some embodiments, the subject is a mammal. The mammal can be e.g., a human or appropriate non-human mammal, such as primate, mouse, rat,70316435300Docket No. 43658-02205 (EXAV-024 / 001WO)dog, cat, cow, horse, goat, camel, sheep or a pig. The subject can also be a bird or fowl. In some embodiments, the subject is a human.

[0070] As used herein, the term “subject in need thereof’ refers to a subject having a disease or having an increased risk of developing the disease. A subject in need thereof can be one who has been previously diagnosed or identified as having a disease or disorder disclosed herein. A subject in need thereof can also be one who is suffering from a disease or disorder disclosed herein. Alternatively, a subject in need thereof can be one who has an increased risk of developing such disease or disorder relative to the population at large (i.e., a subject who is predisposed to developing such disorder relative to the population at large). A subject in need thereof can have a refractory or resistant a disease or disorder disclosed herein (i.e., a disease or disorder disclosed herein that does not respond or has not yet responded to treatment). The subject may be resistant at start of treatment or may become resistant during treatment. In some embodiments, the subject in need thereof received and failed all known effective therapies for a disease or disorder disclosed herein. In some embodiments, the subject in need thereof received at least one prior therapy.

[0071] As used herein, the term “treating” or “treat” describes the management and care of a patient for the purpose of combating a disease, condition, or disorder and includes the administration of a salt of the present disclosure, polymorph or solvate thereof, to alleviate the symptoms or complications of a disease, condition or disorder, or to eliminate the disease, condition or disorder. The term “treat” can also include treatment of a cell in vitro or an animal model. It is to be appreciated that references to “treating” or “treatment” include the alleviation of established symptoms of a condition. “Treating” or “treatment” of a state, disorder or condition therefore includes: (1) preventing or delaying the appearance of clinical symptoms of the state, disorder or condition developing in a human that may be afflicted with or predisposed to the state, disorder or condition but does not yet experience or display clinical or subclinical symptoms of the state, disorder or condition, (2) inhibiting the state, disorder or condition, i.e., arresting, reducing or delaying the development of the disease or a relapse thereof (in case of maintenance treatment) or at least one clinical or subclinical symptom thereof, or (3) relieving or attenuating the disease, i.e., causing regression of the state, disorder or condition or at least one of its clinical or subclinical symptoms.71316435300Docket No. 43658-02205 (EXAV-024 / 001WO)

[0072] It is to be understood that a salt of the present disclosure, or a polymorph or solvate thereof, can or may also be used to prevent a relevant disease, condition or disorder, or used to identify suitable candidates for such purposes.

[0073] As used herein, the term “preventing,” “prevent,” or “protecting against” describes reducing or eliminating the onset of the symptoms or complications of such disease, condition or disorder.

[0074] It is to be understood that one skilled in the art may refer to general reference texts for detailed descriptions of known techniques discussed herein or equivalent techniques. These texts include Ausubel et al., Current Protocols in Molecular Biology, John Wiley and Sons, Inc. (2005); Sambrook et al., Molecular Cloning, A Laboratory Manual (3rdedition), Cold Spring Harbor Press, Cold Spring Harbor, New York (2000); Coligan etal., Current Protocols in Immunology, John Wiley & Sons, N. Y.; Enna et al., Current Protocols in Pharmacology, John Wiley & Sons, N. Y.; Fingi et al., The Pharmacological Basis of Therapeutics (1975), Remington's Pharmaceutical Sciences, Mack Publishing Co., Easton, P / X, 18thedition (1990). These texts can, of course, also be referred to in making or using an aspect of the disclosure.

[0075] It is to be understood that the present disclosure also provides phar aceutical compositions comprising any compound described herein in combination with at least one pharmaceutically acceptable excipient or carrier.

[0076] As used herein, the term “pharmaceutical composition” is a formulation containing the compounds of the present disclosure in a form suitable for administration to a subject. In one embodiment, the pharmaceutical composition is in bulk or in unit dosage form. The unit dosage form is any of a variety of forms, including, for example, a capsule, an IV bag, a tablet, a single pump on an aerosol inhaler or a vial. The quantity of active ingredient e.g., a formulation of the disclosed compound or hydrate, solvate or isomer thereof) in a unit dose of composition is an effective amount and is varied according to the particular treatment involved. One skilled in the art will appreciate that it is sometimes necessary to make variations to the dosage depending on the age and condition of the patient. The dosage will also depend on the route of administration. A variety of routes are contemplated, including oral, pulmonary, rectal, parenteral, transdernial, subcutaneous, intravenous, intramuscular, intraperitoneal, inhalational, buccal, sublingual, intrapleural, intrathecal, intranasal, and the like. Dosage forms for the topical or transdernial administration of a salt of this disclosure include powders, sprays, ointments, pastes, creams,72316435300Docket No. 43658-02205 (EXAV-024 / 001WO)lotions, gels, solutions, patches and inhalants. In one embodiment, the active compound is mixed under sterile conditions with a pharmaceutically acceptable carrier, and with any preservatives, buffers, or propellants that are required.

[0077] As used herein, the term “pharmaceutically acceptable'’ refers to those compounds, anions, cations, materials, compositions, carriers, and / or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit / risk ratio.

[0078] As used herein, the term “pharmaceutically acceptable excipient” means an excipient that is useful in preparing a pharmaceutical composition that is generally safe, non-toxic and neither biologically nor otherwise undesirable, and includes excipient that is acceptable for veterinary use as well as human pharmaceutical use. A “pharmaceutically acceptable excipient” as used in the specification and claims includes both one and more than one such excipient.

[0079] It is to be understood that a pharmaceutical composition of the disclosure is formulated to be compatible with its intended route of administration. Examples of routes of administration include parenteral, e.g., intravenous, intradermal, subcutaneous, oral (e.g, ingestion), inhalation, transdermal (topical), and transmucosal administration. Solutions or suspensions used for parenteral, intradermal, or subcutaneous application can include the following components: a sterile diluent such as water for injection, saline solution, fixed oils, polyethylene glycols, glycerine, propylene glycol or other synthetic solvents; antibacterial agents such as benzyl alcohol or methyl parabens; antioxidants such as ascorbic acid or sodium bisulfite; chelating agents such as ethylenediaminetetraacetic acid; buffers such as acetates, citrates or phosphates, and agents for the adjustment of tonicity such as sodium chloride or dextrose. The pH can be adjusted with acids or bases, such as hydrochloric acid or sodium hydroxide. The parenteral preparation can be enclosed in ampoules, disposable syringes or multiple dose vials made of glass or plastic.

[0080] It is to be understood that a compound or pharmaceutical composition of the disclosure can be administered to a subject in many of the well-known methods currently used for chemotherapeutic treatment. For example, a salt of the disclosure may be injected into the blood stream or body cavities or taken orally or applied through the skin with patches. The dose chosen should be sufficient to constitute effective treatment but not so high as to cause unacceptable side73316435300Docket No. 43658-02205 (EXAV-024 / 001WO)effects. The state of the disease condition (e.g., a disease or disorder disclosed herein) and the health of the patient should preferably be closely monitored during and for a reasonable period after treatment.

[0081] As used herein, the term “therapeutically effective amount”, refers to an amount of a pharmaceutical agent to treat, ameliorate, or prevent an identified disease or condition, or to exhibit a detectable therapeutic or inhibitory effect. The effect can be detected by any assay method known in the art. The precise effective amount for a subject will depend upon the subject’s body weight, size, and health; the nature and extent of the condition; and the therapeutic or combination of therapeutics selected for administration. Therapeutically effective amounts for a given situation can be determined by experimentation that is within the skill and judgment of the clinician.

[0082] It is to be understood that, for any compound, the therapeutically effective amount can be estimated initially either in cell culture assays, e.g, of neoplastic cells, or in animal models, usually rats, mice, rabbits, dogs, or pigs. The animal model may also be used to determine the appropriate concentration range and route of administration. Such information can then be used to determine useful doses and routes for administration in humans. Therapeutic / prophylactic efficacy and toxicity may be determined by standard pharmaceutical procedures in cell cultures or experimental animals, e.g., ED50 (the dose therapeutically effective in 50 % of the population) and LD50 (the dose lethal to 50 % of the population). The dose ratio between toxic and therapeutic effects is the therapeutic index, and it can be expressed as the ratio, LD50 / ED50. Pharmaceutical compositions that exhibit large therapeutic indices are preferred. The dosage may vary within this range depending upon the dosage form employed, sensitivity of the patient, and the route of administration.

[0083] Dosage and administration are adjusted to provide sufficient levels of the active agent(s) or to maintain the desired effect. Factors which may be taken into account include the severity of the disease state, general health of the subject, age, weight, and gender of the subject, diet, time and frequency of administration, drug combination(s), reaction sensitivities, and tolerance / response to therapy. Long-acting pharmaceutical compositions may be administered every 3 to 4 days, every week, or once every two weeks depending on half-life and clearance rate of the particular formulation.74316435300Docket No. 43658-02205 (EXAV-024 / 001WO)

[0084] For the avoidance of doubt, as used herein, terms such as “mg / kg ORF-eq.,” “mg / kg ORF equiv.,” or “mg orforglipron eq. / kg,” refer to [the amount in mg of the parent molecule (e.g., orforglipron or corresponding non-prodrug active GLP-1R agonist) in the formulation being administered] / [the mass in kg of the animal receiving administration],

[0085] As used herein, the term “orforglipron” or “ORF” refers to the compound “3-[(1S,2S)-1-[5-[(4S)-2,2-dimethyloxan-4-yl]-2-[(4S)-2-(4-fluoro-3,5-dimethylphenyl)-3-[3-(4-fluoro-l-methylindazol-5-yl)-2-oxoimidazol-l-yl]-4-methyl-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-5-carbonyl]indol- 1 -yl]-2-methylcyclopropyl]-4H- 1,2,4-oxadiazol-5-one,” having the structure shown below:

[0086] The pharmaceutical compositions containing active compounds of the present disclosure may be manufactured in a manner that is generally known, e.g., by means of conventional mixing, dissolving, granulating, dragee-making, levigating, emulsifying, encapsulating, entrapping, or lyophilizing processes. Pharmaceutical compositions may be formulated in a conventional manner using one or more pharmaceutically acceptable carriers comprising excipients and / or auxiliaries that facilitate processing of the active compounds into preparations that can be used pharmaceutically. Of course, the appropriate formulation is dependent upon the route of administration chosen.

[0087] Pharmaceutical compositions suitable for injectable use include sterile aqueous solutions (where water soluble) or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersion. For intravenous administration, suitable carriers include physiological saline, bacteriostatic water, Cremophor EL™ (BASF, Parsippany, N. J.) or phosphate buffered saline (PBS). In all cases, the composition must be sterile and should be fluid75316435300Docket No. 43658-02205 (EXAV-024 / 001WO)to the extent that easy syringeability exists. It must be stable under the conditions of manufacture and storage and must be preserved against the contaminating action of microorganisms such as bacteria and fungi. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (for example, glycerol, propylene glycol, and liquid polyethylene glycol, and the like), cyclodextrins and suitable mixtures thereof. The proper fluidity can be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersion and by the use of surfactants. Prevention of the action of microorganisms can be achieved by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, ascorbic acid, thimerosal, and the like. In many cases, it will be preferable to include isotonic agents, for example, sugars, polyalcohols such as mannitol and sorbitol, and sodium chloride in the composition. Prolonged absorption of the injectable compositions can be brought about by including in the composition an agent which delays absorption, for example, aluminum monostearate and gelatin.

[0088] Sterile injectable solutions can be prepared by incorporating the active compound in the required amount in an appropriate solvent with one or a combination of ingredients enumerated above, as required, followed by filtered sterilization. Generally, dispersions are prepared by incorporating the active compound into a sterile vehicle that contains a basic dispersion medium and the required other ingredients from those enumerated above. In the case of sterile powders for the preparation of sterile injectable solutions, methods of preparation are vacuum drying and freeze-drying that yields a powder of the active ingredient plus any additional desired ingredient from a previously sterile-filtered solution thereof.

[0089] Oral compositions generally include an inert diluent or an edible pharmaceutically acceptable carrier. They can be enclosed in gelatin capsules or compressed into tablets. For the purpose of oral therapeutic administration, the active compound can be incorporated with excipients and used in the form of tablets, troches, capsules or sachets. Oral compositions can also be prepared using a fluid carrier for use as a mouthwash, wherein the compound in the fluid carrier is applied orally and swished and expectorated or swallowed. Pharmaceutically compatible binding agents, and / or adjuvant materials can be included as part of the composition. The tabl ets, pills, capsul es, troches and the like can contain any of the following ingredients, or compounds of a similar nature: a binder such as microcrystalline cellulose, gum tragacanth or gelatin; an excipient such as starch or lactose, a disintegrating agent such as alginic acid,76316435300Docket No. 43658-02205 (EXAV-024 / 001WO)Primogel, or corn starch; a lubricant such as magnesium stearate or Sterotes; a glidant such as colloidal silicon dioxide; a sweetening agent such as sucrose or saccharin; or a flavoring agent such as peppermint, methyl salicylate, orange flavoring.

[0090] For administration by inhalation, the compounds are delivered in the form of an aerosol spray from pressured container or dispenser, which contains a suitable propellant, e.g., a gas such as carbon dioxide, or a nebuliser.

[0091] Systemic administration can also be by transmucosal or transdermal means. For transmucosal or transdermal administration, penetrants appropriate to the barrier to be permeated are used in the formulation. Such penetrants are generally known in the art, and include, for example, for transmucosal administration, detergents, bile salts, and fusidic acid derivatives. Transmucosal administration can be accomplished through the use of nasal sprays, powders or suppositories. For transdermal administration, the active compounds are formulated into ointments, salves, gels, or creams as generally known in the art.

[0092] The active compounds can be prepared with pharmaceutically acceptable carriers that will protect the compound against rapid elimination from the body, such as a controlled release formulation, including implants and microencapsulated delivery systems. Biodegradable, biocompatible polymers can be used, such as ethylene vinyl acetate, polyanhydrides, polyglycolic acid, collagen, polyorthoesters, and polylactic acid. Methods for preparation of such formulations will be apparent to those skilled in the art. The materials can also be obtained commercially from Alza Corporation and Nova Pharmaceuticals, Inc. Liposomal suspensions (including liposomes targeted to infected cells with monoclonal antibodies to viral antigens) can also be used as pharmaceutically acceptable carriers. These can be prepared according to methods known to those skilled in the art, for example, as described in U. S. Pat. No. 4,522,811.

[0093] It may be advantageous to formulate oral or parenteral compositions in dosage unit form for ease of administration and uniformity of dosage. Dosage unit form as used herein refers to physically discrete units suited as unitary dosages for the subject to be treated; each unit containing a predetermined quantity of active compound calculated to produce the desired therapeutic effect in association with the required pharmaceutical carrier. The specification for the dosage unit forms of the disclosure is dictated by and directly dependent on the unique characteristics of the active compound and the particular therapeutic effect to be achieved.77316435300Docket No. 43658-02205 (EXAV-024 / 001WO)

[0094] In therapeutic applications, the dosages of the pharmaceutical compositions used in accordance with the disclosure vary depending on the agent, the age, weight, and clinical condition of the recipient patient, and the experience and judgment of the clinician or practitioner administering the therapy, among other factors affecting the selected dosage. Generally, the dose should be sufficient to result in slowing, and preferably regressing, the symptoms of the disease or disorder disclosed herein and also preferably causing complete regression of the disease or disorder. An effective amount of a pharmaceutical agent is that which provides an objectively identifiable improvement as noted by the clinician or other qualified observer. Improvement in survival and growth indicates regression. As used herein, the term “dosage effective manner” refers to amount of an active compound to produce the desired biological effect in a subject or cell.

[0095] It is to be understood that the pharmaceutical compositions can be included in a container, pack, or dispenser together with instructions for administration.

[0096] It is to be understood that, for the compounds of the present disclosure being capable of further forming salts, all of these forms are also contemplated within the scope of the claimed disclosure.

[0097] In the salt form, it is understood that the ratio of the compound to the cation or anion of the salt can be 1.1, or any ratio other than 1:1, e.g., 3:1, 2:1, 1:2, or 1:3,

[0098] It is to be understood that all references to pharmaceutically acceptable salts include solvent addition forms (solvates) or crystal forms (polymorphs) as defined herein, of the same salt.

[0099] The compounds are administered orally, nasally, transdermally, pulmonary, inhalationally, buccally, sublingually, intraperitoneally, subcutaneously, intramuscularly, intravenously, rectally, intrapleurally, intrathecally and parenterally. In one embodiment, the compound is administered orally. One skilled in the art will recognize the advantages of certain routes of administration.

[0100] The dosage regimen utilizing the compounds is selected in accordance with a variety of factors including type, species, age, weight, sex and medical condition of the patient; the severity of the condition to be treated; the route of administration; the renal and hepatic function of the patient; and the particular compound employed.78316435300Docket No. 43658-02205 (EXAV-024 / 001WO)

[0101] Techniques for formulation and administration of the disclosed compounds of the disclosure can be found in Remington: the Science and Practice of Pharmacy, 19thedition, Mack Publishing Co., Easton, PA (1995). In an embodiment, the compounds described herein are used in pharmaceutical preparations in combination with a pharmaceutically acceptable carrier or diluent. Suitable pharmaceutically acceptable carriers include inert solid fillers or diluents and sterile aqueous organic solutions. The compounds will be present in such pharmaceutical compositions in amounts sufficient to provide the desired dosage amount in the range described herein.

[0102] All percentages and ratios used herein, unless otherwise indicated, are by weight. Other features and advantages of the present disclosure are apparent from the different examples. The provided examples illustrate different components and methodology useful in practicing the present disclosure. The examples do not limit the claimed disclosure. Based on the present disclosure the skilled artisan can identify and employ other components and methodology useful for practicing the present disclosure.

[0103] In the synthetic schemes described herein, compounds may be drawn with one particular configuration for simplicity. Such particular configurations are not to be constmed as limiting the disclosure to one or another isomer, tautomer, regioisomer or stereoisomer, nor does it exclude mixtures of isomers, tautomers, regioisomers or stereoisomers; however, it will be understood that a given isomer, tautomer, regioisomer or stereoisomer may have a higher level of activity than another isomer, tautomer, regioisomer or stereoisomer,

[0104] All publications and patent documents cited herein are incorporated herein by reference as if each such publication or document was specifically and individually indicated to be incorporated herein by reference. Citation of publications and patent documents is not intended as an admission that any is pertinent prior art, nor does it constitute any admission as to the contents or date of the same. The invention having now been described by way of written description, those of skill in the art will recognize that the invention can be practiced in a variety of embodiments and that the foregoing description and examples below are for purposes of illustration and not limitation of the claims that follow.

[0105] As use herein, the phrase “compound of the disclosure” or “salt of the disclosure” refers to those salts and compounds which are disclosed herein, both generically and specifically.79316435300Docket No. 43658-02205 (EXAV-024 / 001WO)

[0106] Salts of the Present Disclosure

[0107] In some aspects, the present disclosure provides a salt comprising anion G-A-and a counterion, wherein:G is:, a stereoisomer thereof, or a tautomer thereof;XG is - -N= or CRaG=; RaGis selected from a hydrogen atom, a halogen atom, and Ci- 6 alkyl;YG is selected from — ('(—()) —, — CHRG—, and — S(=O)2 —; RGis a hydrogen atom or C1-6 alkyl;QG1is Ce-io aryl or 5 to 10 membered heteroaryl, wherein the Ce-io aryl and 5 to 10 membered heteroaryl are optionally substituted with one to five substituents independently selected from a halogen atom, Ci-6 alkyl (wherein Ci-6 alkyl is optionally substituted with one or more halogen atoms), C’3-6 cycloalkyl, and C1-6 alkoxy;QG2is 3 to 12 membered heterocyclyl or 5 to 10 membered heteroaryl, wherein the 3 to 12 membered heterocyclyl and 5 to 10 membered heteroaryl are optionally substituted with one to three substituents independently selected from a halogen atom, C1-6 alkyl (wherein Ci-6 alkyl is optionally substituted with one or more halogen atoms), C1-6 alkoxy, and — NRGQaRGQb, and two C1-6 alkyl groups together with a carbon atom to which they are attached may form C3-80316435300Docket No. 43658-02205 (EXAV-024 / 001WO)8 carbocyclic ring; and RGQaand RGQbare independently selected from a hydrogen atom, Ci- 6 alkyl, and (Ci-6 alkyl)carbonyl;Z3, Z4, Z5, Z6, Z7, Z8, Z9, Z10, Z11, Z12 and Z13 are each independently selected from the group consisting of N and C;RCH, RG3 J^GI RG2,an(| pG3’afejnc[epenc[entiy selected from a hydrogen atom, halogen atom, C1-6 alkyl, CJ -6 alkoxy, Ci -6 haloalkoxy, cycloalkyl, and heterocycloalkyl, wherein the C1-6 alkyl, cycloalkyl, or heterocycloalkyl is optionally substituted by one or more substituents independently selected from a halogen atom, C1-6 alkoxy, and hydroxy; or RG2and RG3together with the carbon atom to which they are attached form 4- to 8-membered heterocycloalkyl;RG4, RG5and RG6are independently selected from a hydrogen atom, a halogen atom, and C1-6 alkyl;RG7and RG8are independently a hydrogen atom or C1-6 alkyl, wherein the C1-6 alkyl is optionally substituted with one or more substituents independently selected from a halogen atom and C3-15 cycloalkyl, or RG7and RG8together with a carbon atom to which they are attached may form C3-15 cycloalkane ring, wherein the C3-15 cycloalkane ring formed by RG7and RG8together is optionally substituted with one to three Ci-6 alkyl, wherein the C1-6 alkyl is optionally substituted with one or more substituents independently selected from a halogen atom, hydroxy, — NRG7aRG7b, C1-6alkoxy, and 3 to 12 membered heterocyclyl, and RG7aand RG7bare independently selected from a hydrogen atom, C1-6 alkyl, and (C1-6 alkyl)carbonyl; and any two C1-6 alkyl optionally together with the carbon atom to which they are attached form C3-15 carbocyclic ring;nGl is an integer of 0 to 3; nG2 is an integer of 0 to 5; nG3 is 0 or 1;ZG1is selected from the group consisting of81316435300Docket No. 43658-02205 (EXAV-024 / 001WO)wherein Rzais selected from a hydrogen atom, Ci-6 alkyl, and (Ci-6 alkyl)carbonyl; Rzband Rzcare each independently a hydrogen atom or Ci-6 alkyl; n4 is an integer of 1 to 3; n5 and n6 are independently an integer of 0 to 10 (* represents a binding position with a pyrazolopyridine structure, and ** represents a binding position with ZG2);ZG2is selected from the group consisting of Ci-6 alkyl, C3-15 cycloalkyl, 3 to 12 membered heterocyclyl, Ce-io aryl, and 5 to 10 membered heteroaryl, wherein the C3-15 cycloalkyl, 3 to 12 membered heterocyclyl, C6-10aryl, and 5 to 10 membered heteroaryl are optionally substituted with one to five substituents independently selected from Group A:Group A: a) oxo,b) a halogen atom,c) cyano,d) — NRzdRze; wherein Rzdand Rzeare independently selected from a hydrogen atom, C1-6 alkyl and (C1-6 alkyl)carbonyl, wherein C1-6 alkyl is optionally substituted with one or more substituents independently selected from hydroxy, a halogen atom and Ci-6 alkoxy,e) C(=O) NRzfRzg; wherein Rzfand Rzgare independently selected from a hydrogen atom, Ci-6 alkyl and (Ci-6alkyl)carbonyl, wherein C1-6 alkyl is optionally substituted with one or more substituents independently selected from hydroxy, a halogen atom and C1-6 alkoxy,f) — S(=O)n7 — Rzh; wherein n7 is an integer of 0 to 2; and Rzhis a hydrogen atom or C i-6 alkyl,g) Ci-6 alkyl optionally substituted with one or more substituent independently selected from a halogen atom, hydroxy, —NRziRzj, C1-6 alkoxy, and 3 to 12 membered heterocyclyl, wherein Rziand Rzjare independently a hydrogen atom or C1-6 alkyl, and wherein 3 to 12 membered heterocyclyl is optionally substituted with one or more substituents independently selected from hydroxy, Ci-6 alkyl and 3 to 12 membered heterocyclyl,h) C1-6 alkoxy optionally substituted with one or more substituent independently selected from hydroxy, a halogen atom, and C1-6 alkoxy,i) 3 to 12 membered heterocyclyl optionally substituted with one or more substituents independently selected from Ci-6 alkyl and (Ci-6alkyl)carbonyl,82316435300Docket No. 43658-02205 (EXAV-024 / 001WO)j) C6-10 aryl optionally substituted with one or more (Ci-6 alkyl)carbonyl, k) 5 to 10 membered heteroaryl optionally substituted with one or more substituents independently selected from Ci-6 alkyl, Ci-6 alkoxy, — NRzkRzl, and 3 to 12 membered heterocyclyl, wherein Rzkand RzIare independently selected from a hydrogen atom, Ci-6 alkyl and (Ci-6 alkyl)carbonyl, and wherein 3 to 12 membered heterocyclyl is optionally substituted with one or more substituents independently selected from Ci-6 alkyl and (Ci-6 alkyl)carbonyl,l) — P(=O)(Rzm)(Rzn), wherein Rzmand Rznare each independently a hydrogen atom or Ci-6 alkyl;m) C3-C15 cycloalkyl optionally substituted with one or more substituents independently selected from the group consisting of halogen, oxo, C1-6 alkyl, Ci- 6 alkoxy and (C1-6 alkyl) carbonyl, wherein each of alkyl and alkoxy is optionally substituted with halogen; andn) Ci-Ce alkyl-C'3-Ci5 cycloalkyl wherein the cycloalkyl or alkyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, oxo, C1-6 alkyl, C1-6 alkoxy and (C1-6 alkyl) carbonyl, wherein each of alkyl and alkoxy is optionally substituted with halogen; orwherein:RWWis selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, thio, C1-6 alkyl, C1-6 deuterated alkyl, C1-6 halogenated alkyl, Ci-6 deuterated haloalkyl, Cn83316435300Docket No. 43658-02205 (EXAV-024 / 001WO)6 hydroxyalkyl, Ci-6 deuterated hydroxyalkyl, Ci-6 sulfanyl, Ci-e deuterated sulfanyl, Ci-6 alkoxy, Ci-6 deuterated alkoxy, Ci-6 halogenated alkoxy, Ci-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-8 Cycloalkyl, 3-8 membered heterocyclyl, Ce-io aryl, and 5-10 membered heteroaryl, wherein the amino, C1-6 alkyl, C1-6 deuterated alkyl, C1-6 halogenated alkyl, C1-6 deuterated haloalkyl, C1-6 hydroxyalkyl, C1-6 deuterated hydroxyalkyl, C1-6 sulfanyl, C1-6 deuterated sulfanyl, C1-6 alkoxy, C1-6 deuterated alkoxy, C1-6 halogenated alkoxy, Ci-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C’3-8 Cycloalkyl, 3-8 membered heterocyclyl, Ce-io aryl, or 5-10 membered heteroaryl is optionally further substituted by deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, thio, C1-6 alkyl, C1-6 deuterated alkyl, C1-6 halogenated alkyl, C1-6 deuterated haloalkyl, Ci-e hydroxyalkyl, C1-6 deuterated hydroxyalkyl, C1-6 sulfanyl, Cue deuterated sulfanyl, C1-6 alkoxy, C1-6 deuterated alkoxy, C1-6 halogenated alkoxy, C1-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, 3-8 membered heterocyclyl, Ce-io aryl, or 5-10 membered heteroaryl substituted by one or more substituents;LGA1, LGA2, and LGA3are each independently selected from a bond, C2-4 alkenylene, C2-4 alkynylene and -(CH2)nGA1Ring AGAis selected from C3-14 cycloalkyl, 3-14 membered heterocyclyl, C6-14aryl, and 5-14 membered heteroaryl;Ring BGAis selected from C3-12 cycloalkyl, 3-12 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl, wherein the C3-12 cycloalkyl, 3-12 membered heterocyclyl, C6-14aryl, or 5-14 membered heteroaryl is optionally further substituted by deuterium, halogen, amino, nitro, hydroxyl, cyano, oxo, thiol, thio, C1-6 alkyl, Ci-e deuterated alkyl, C1-6 halogenated alkyl, Ci-6 deuterated haloalkyl, Ci-6 hydroxyalkyl, C1-6 deuterated hydroxyalkyl, Ci-6 sulfanyl, C1-6 deuterated sulfanyl, C1-6 alkoxy, C1-6 deuterated alkoxy, C1-6 haloalkoxy or C1-6 deuterated haloalkoxy substituted by one or more substituents;Ring DGAis selected from C3-12 cycloalkyl, 3-12 membered heterocyclyl, C6-14aryl, and 5-14 membered heteroaryl;Ring EGAis selected from C3-14 cycloalkyl, 3-14 membered heterocyclyl, C6-14aryl, and 5-14 membered heteroaryl, wherein the C3-14 cycloalkyl, 3-14 membered heterocyclyl, C6-14aryl, or 5-14 membered heteroaryl is optionally further substituted by deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, thio, C1-6 alkyl, C1-6 deuterated alkyl, C1-6 halogenated alkyl, C1-6 deuterated haloalkyl, Ci-6 hydroxyalkyl, C1-6 deuterated hydroxyalkyl, C1-6 sulfanyl, C1-684316435300Docket No. 43658-02205 (EXAV-024 / 001WO)deuterated sulfanyl, Ci-6 alkoxy, Ci-6 deuterated alkoxy, Ci-6 halogenated alkoxy, Ci-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, 3-8 membered heterocyclyl, Ce-io aryl, or 5-10 membered heteroaryl substituted by one or more substituents;oftalternatively, ringEGAis ‘ ’ optionally substituted with one or more substituents selected from the group consisting of methyl, ethyl, methoxy, and ethoxy;RGA1, RGA2, RGA3, RGA4, RGA5, RGA6, RGA7, RGAS, RGA9, RGA14, RGA15, and RGAI6are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, thio, C1-6 alkyl, C1-6 deuterated alkyl, C1-6 halogenated alkyl, C1-6 deuterated haloalkyl, C1-6 hydroxyalkyl, C1-6 deuterated hydroxyalkyl, C1-6 sulfanyl, Ci-6 deuterated sulfanyl, C1-6 alkoxy, C1-6 deuterated alkoxy, C1-6 halogenated alkoxy, C1-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, 3-8 membered heterocyclyl, Ce-io aryl, 5-10 membered heteroaryl, -(CH2)mGAiORGAcl, and (=C)RGAc3RGAc4, wherein the amino, C1-6 alkyl, C1-6 deuterated alkyl, Ci-6 halogenated alkyl, C1-6 deuterated haloalkyl, Ci-6 hydroxyalkyl, C1-6 deuterated hydroxyalkyl, C1-6 sulfanyl, C1-6 deuterated sulfanyl, C1-6 alkoxy, C1-6 deuterated alkoxy, C1-6 halogenated alkoxy, C1-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-8 Cycloalkyl, 3-8 membered heterocyclyl, Ce-io aryl, 5-10 membered heteroaryl, -(CH2)mGAiORGAcl, or (=C)RGAc3RGAc4is optionally further substituted with deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, thio, Ci-6 alkyl, C1-6 deuterated alkyl, C1-6 halogenated alkyl, C1-6 deuterated haloalkyl, Ci-6 hydroxyalkyl, C1-6 deuterated hydroxyalkyl, C1-6 sulfanyl, C1-6 deuterated sulfanyl, C1-6 alkoxy, CJ-6 deuterated alkoxy, C1-6 halogenated alkoxy, C1-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C’3-8 Cycloalkyl, 3-8 membered heterocyclyl, C6-10 aryl, or 5-10 membered heteroaryl substituted by one or more substituents;RGAC1, RGAC3, and RGAc4are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, thio, C1-6 alkyl, Ci-6 deuterated alkyl, C1-6 halogenated alkyl, C1-6 deuterated haloalkyl, C1-6 hydroxyalkyl, C1-6 deuterated hydroxyalkyl, Ci- 6 sulfanyl, C1-6 deuterated sulfanyl, C1-6 alkoxy, C1-6 deuterated alkoxy, C1-6 halogenated alkoxy, Ci-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-8 Cycloalkyl, 3-8 membered85316435300Docket No. 43658-02205 (EXAV-024 / 001WO)heterocyclyl, C6-10 aryl, 5-10 membered heteroaryl,, -(CH2)mGA2ORGAc2, - (CH2)mGA3C(O)NRGAalRGAbl, and -(CH2)mGA4C(O)ORGAa2, wherein the amino, C1-6 alkyl, C1-6 deuterated alkyl, C1-6 halogenated alkyl, Ci-6 deuterated haloalkyl, C1-6 hydroxyalkyl, C1-6 deuterated hydroxyalkyl, C1-6 sulfanyl, C1-6 deuterated sulfanyl, C1-6 alkoxy, C1-6 deuterated alkoxy, C1-6 halogenated alkoxy, C1-6 deuterated haloalkoxy, C2-6 alkenyl, C2- 6 alkynyl, C3- 8 Cycloalkyl, 3-8 membered heterocyclyl, Ce-io aryl, 5-10 membered heteroaryl, -(CH2)mGA2ORGAc2, -(CH2)mGA3C(O)NRGAalRGAbl, or -(CH2)mGA4C(O)ORGAa2is optionally further substituted with deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, thio, C1-6 alkyl, C1-6 deuterated alkyl, C1-6 halogenated alkyl, C1-6 deuterated haloalkyl, C1-6 hydroxyalkyl, C1-6 deuterated hydroxyalkyl, Ci-e sulfanyl, C1-6 deuterated sulfanyl, C1-6 alkoxy, C1-6 deuterated alkoxy, C1-6 halogenated alkoxy, C1-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-s Cycloalkyl, 3-8 membered heterocyclyl, Ce-io aryl, or 5-10 membered heteroaryl substituted by one or more substituents;RGAa1, RGAa2, RGAb1, and RGAc2are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, thio, C1-6 alkyl, C1-6 deuterated alkyl, Ci-6 halogenated alkyl, C1-6 deuterated haloalkyl, C1-6 hydroxyalkyl, C1-6 deuterated hydroxyalkyl, Ci- 6 sulfanyl, C1-6 deuterated sulfanyl, C1-6 alkoxy, Ci-e deuterated alkoxy, Ci-e halogenated alkoxy, C1-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-8 Cycloalkyl, 3-8 membered heterocyclyl, C6-10 aryl or 5-10 membered heteroaryl, wherein the amino, C1-6 alkyl, C1-6 deuterated alkyl, C1-6 halogenated alkyl, C1-6 deuterated haloalkyl, C1-6 hydroxyalkyl, C1-6 deuterated hydroxyalkyl, C1-6 sulfanyl, C1-6 deuterated sulfanyl, C1-6 alkoxy, C1-6 deuterated alkoxy, C1-6 halogenated alkoxy, Ci-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, 3-8 membered heterocyclyl, Ce-io aryl, or 5-10 membered heteroaryl is optionally further substituted by deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C1-6 alkyl, Ci-6 deuterated alkyl, C1-6 halogenated alkyl, C1-6 deuterated haloalkyl, C1-6 hydroxyalkyl, C1-6 deuterated hydroxyalkyl, C1-6 sulfanyl, C1-6 deuterated sulfanyl, C1-6 alkoxy, C1-6 deuterated alkoxy, C1-6 halogenated alkoxy, C1-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, 3-8 membered heterocyclyl, Ce-io aryl, or 5-10 membered heteroaryl substituted by one or more substituents;or, RGA9and RGA16together with the atoms connected to them form C’3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-12 aryl or 5-12 membered heteroaryl;86316435300Docket No. 43658-02205 (EXAV-024 / 001WO)or, when nGA is not 1,RGA1and RGA1', RGA2and RGA2', RGA4and RGA5, RGA5and RGA6, RGA7and RGA8, together with the atoms connected to them, form C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-12 aryl, or 5-12 membered heteroaryl, optionally further substituted by deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, thio, C1-6 alkyl, C1-6 deuterated alkyl, C1-6 halogenated alkyl, C1-6 deuterated haloalkyl, Cn 6-hydroxyalkyl, Ci-6 deuterated hydroxyalkyl, C1-6 sulfanyl, C1-6 deuterated sulfanyl, C1-6 alkoxy, C1-6 deuterated alkoxy, Ci- 6-halogenated alkoxy, C1-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-8 Cycloalkyl, 3-8 membered heterocyclyl, Ce-io aryl, or 5-10 membered heteroaryl substituted by one or more substituents; and11GA, nGAl, mGAl, mGA2, mGA3, and mGA4 are each independently selected from 0, 1, 2, 3, 4 or 5;(RGBe)qGB wherein:Ring AGBis selected from C3-15 carbocyclyl, 3-12 membered heterocyclyl, C6-14aryl, and 5-12 membered heteroaryl;Ring BGBis selected from 3-12 membered heterocyclyl, C6-14 aryl, and 5-12 membered heteroaryl;Ring CGBis 9-membered bicyclic heteroaryl;Ring DGBis selected from C3-15 carbocyclyl, 3-12 membered heterocyclyl, C6-14 aryl, and 5-12 embered heteroaryl;Ring EGBis selected from C3-15 carbocyclyl, 3-12 membered heterocyclyl, C6-14 aryl, and 5-12 membered heteroaryl;87316435300Docket No. 43658-02205 (EXAV-024 / 001WO)each RGBais independently selected from hydrogen, deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -ORGBal, -S(O)RGBal, -SO2(RGBal),-C(O)RGBai, -C(O)ORGBal, - OC(O)RGBal, -N(RGBal)(RGBa2), -C(O)N(RGBal)(RGBa2), -N(RGBal)C(O)RGBa2, - S(O)N(RGBal)(RGBa2), -SO2N(RGBal)(RGBa2), -N(RGBal)S(O)RGBa2, -N(RGBal)S(O)2RGBa2, and optionally replaced by one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) RGBa3substituted with the following groups: Ci-6 alkyl, Ci-6 alkoxy, Ci-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C’6-14 aryl, or 5-12 membered heteroaryl;or two RGBa, together with the atoms to which they are attached, form a 3-10 membered heterocyclyl or 5-12 membered heteroaryl, wherein the 3-10 membered heterocyclyl or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, Ci-e alkoxy, C3-J0 cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, or 5-12 membered heteroaryl;RGBa1and RGBa2are each independently selected from hydrogen, deuterium, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14 aryl, and 5-12 membered heteroaryl, wherein the C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3- 10 cycloalkyl, 3-10 membered heterocyclyl, C8-14 aryl, or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, a 3-6 membered heterocyclyl, phenyl, or 5-6 membered heteroaryl; each RGBa3is independently selected from hydrogen, deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -RGBa4, -ORGBa4, -SRGBa4, -S(O)RGBa4, -S(O)2RGBa4, - C(O)RGBa4, -C(O)ORGBa4, -OC(O)RGBa4, -N(RGBa4)(RGBa5), -C(O)N(RGBa4)(RGBa5), - N(RGBa4)C(O)RGBa5, -S(O)N(RGBa4)(RGBa5), -S(O)2N(RGBa4)(RGBa5), -N(RGBa4)S(O)RGBa5, - N(RGBa4)S(O)2RGBa5;RGBa4and RGBa5are each independently selected from hydrogen, deuterium, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, and 5-12 membered heteroaryl, wherein the C1-6 alkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3- 10 cycloalkyl, 3-10 membered heterocyclyl, C6-14 aryl, or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from88316435300Docket No. 43658-02205 (EXAV-024 / 001WO)halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, Ci-6 alkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, 3-7 membered heterocyclyl, phenyl, and 5-6 membered heteroaryl;RGBbis each independently selected from hydrogen, deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C’6-14 aryl, and 5-12 membered heteroaryl, wherein the C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C’6-14 aryl, or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) RGBbl;or two RGBb, together with the atoms to which they are attached, form 3-10 membered heterocyclyl or 5-12 membered heteroaryl, wherein the 3-10 membered heterocyclyl or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) groups independently selected from deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, Ci-6 alkyl, Ct-6 alkoxy, C3-10 cycloalkyl, 3-10 membered heterocyclyl, Ce-M aryl, and 5-12 membered heteroaryl;RGBblis each independently selected from deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -RGBb2, -ORGBb2, -SRGBb2, -S(O)RGBb2, -S(O)2RGBb2, -C(O)RGBb2, - C(O)ORGBb2, -OC(O)RGBb2, -N(RGBb2)(RGBb3), -C(O)N(RGBb2)(RGBb3), -N(RGBb2)C(O)RGBb3, - S(O)N(RGBb2)(RGBb3), -S(O)2N(RGBb2)(RGBb3), -N(RGBb2)S(O)RGBb3, and -N(RGBb2)S(O)2RGBb3;RGBb2and RGBb3are each independently selected from hydrogen, deuterium, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, and 5-12 membered heteroaryl, wherein the C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3- 10 cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C’3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, and 5-12 membered heteroaryl;RGBcis each independently selected from hydrogen, deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, and 5-12 membered heteroaryl, wherein the C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-89316435300Docket No. 43658-02205 (EXAV-024 / 001WO)io cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) RGBcl;or two RGBC, together with the atoms to which they are attached, form 3-10 membered heterocyclyl or 5-12 membered heteroaryl, wherein the 3-10 membered heterocyclyl or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) groups independently selected from deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, C1-6 alkoxy, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C’6-14 and, and 5-12 membered heteroaryl;RGBclis each independently selected from deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -RGBc2, -ORGBc2, -SRGBc2, -S(O)RGBc2, -S(O)2RGBc2, -C(O)RGBc2, - C(O)ORGBC2, -OC(O)RGBC2, -N(RGBC2)(GBC3), -C(O)N(RGBC2)(RGBC3), -N(RGBC2)C(O)RGBC3, - S(O)N(RGBc2)(RGBc3), -S(O)2N(RGBC2)(RGBC3), -N(RGBC2)S(O)RGBC3, -N(RGBC2)S(O)2RGBC3;RGBC2and RGBC3are each independently selected from hydrogen, deuterium, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C’3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, and 5-12 membered heteroaryl, wherein the C1-6 alkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3- 10 cycloalkyl, 3-10 membered heterocyclyl, C’6-14 aryl, or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, Ci-6 alkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, and 5-12 membered heteroaryl;RGBdis each independently selected from hydrogen, deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -ORGBdl, -S(O)RGBdl, -S(O)2RGBdl, -C(O)RGBdl, - C(O)ORGBd!, -OC(O)RGBdl, -N(RGBdl)(RGBd2), -C(O)N(RGBdl)(RGBd2), -N(RGBdl)C(O)RGBd2, - S(O)N(RGBdl)(RGBd2), -S(O)2N(RGBdl)(RGBd2), -N(RGBdl)S(O)RGBd2, -N(RGBdl)S(O)2RGBd2, and optionally replaced by one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) RGBd3substituted with the following groups: Ci-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, or 5-12 membered heteroaryl;or two RGBd, together with the atoms to which they are attached, form 3-10 membered heterocyclyl, 3-7 membered cycloalkyl, or 5-12 membered heteroaryl, wherein the 3-10 membered heterocyclyl, 3-7 membered cycloalkyl, or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7, or 8) groups independently selected from90316435300Docket No. 43658-02205 (EXAV-024 / 001WO)deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, Ci-6 alkoxy, C3- 10 cycloalkyl, 3-10 membered heterocyclyl, C6-14 aryl, and 5-12 membered heteroaryl;RGBdland RGBd2are each independently selected from hydrogen, deuterium, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, and 5-12 membered heteroaryl, wherein the C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3- io cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, 3-6 membered heterocyclyl, phenyl, and 5-6 membered heteroaryl;RGBd3is each independently selected from hydrogen, deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -RGBd4, -ORGBd4, -SRGBd4, -S(O)RGBd4, -S(O)2RGBd4, -C(O)RGBd4, -C(O)ORGBd4, -OC(O)RGBd4, -N(RGBd4)(RGBd5), -C(O)N(RGBd4)(RGBd5), - N(RGBd4)C(O)RGBd5, -S(O)N(RGBd4)(RGBd5), -S(O)2N(RGBd4)(RGBd5), -N(RGBd4)S(O)RGBd5, and - N(RGBd4)S(O)2RGBd5;RGBd4and RGBd5are each independently selected from hydrogen, deuterium, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C’6-14 aryl, and 5-12 membered heteroaryl, wherein the C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3- 10 cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, 3-7 membered heterocyclyl, phenyl, or 5-6 membered heteroaryl;RGBeis each independently selected from hydrogen, deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -ORGBe1, -SRGBel, -S(O)RGBel, -S(O)2RGBel, -C(O)RGBel, - C(O)ORGBel, -OC(O)RGBel, -N(RGBe1)(RGBe2), -C(O)N(RGBel)(RGBe2), -N(RGBel)C(O)RGBe2, -S(O)N(RGBel)(RGBe2), -S(O)2N(RGBel)(RGBe2), -N(RGBel)S(O)RGBe2, -N(RGBel)S(O)2RGBe2, - C(O)N(RGBel)S(O)2N(RGBel)(RGBe2), -C(O)N(RGBel)S(O)2RGBe2, -P(O)(RGBel)RGBe2, and optionally replaced by one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) RGBe3substituted with the following groups: C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14 aryl, or 5-12 membered heteroaryl;or two RGBe, together with the atoms to which they are attached, form 3-10 membered heterocyclyl or 5-12 membered heteroaryl, wherein the 3-10 membered heterocyclyl or 5-1291316435300Docket No. 43658-02205 (EXAV-024 / 001WO)membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) groups independently selected from deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, Ci-6 alkyl, Ci-6 alkoxy, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14 aryl, and 5-12 membered heteroaryl;RGBe1and RGBe2are each independently selected from hydrogen, deuterium, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14 aryl, and 5-12 membered heteroaryl, wherein the C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3- 10 cycloalkyl, 3-10 membered heterocyclyl, C6-14 aryl, or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from hydrogen, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, 3-6 membered heterocyclyl, phenyl, and 5-6 membered heteroaryl;RGBe3is each independently selected from hydrogen, deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -RGBe4, -ORGBe4, -SRGBe4, -S(O)RGBe4, -S(O)2RGBe4, -C(O)RGBe4, -C(O)ORGBe4, -OC(O)RGBe4, -N(RGBe4)(RGBe5), -C(O)N(RGBe4)(RGBe5), - N(RGBe4)C(O)RGBe5, -S(O)N(RGBe4)(RGBe5), -S(O)2N(RGBe4)(RGBe5), -N(RGBe4)S(O)RGBe5, - N(RGBe4)S(O)2RGBe5, -C(O)N(RGBe4)S(O)2N(RGBe4)(RGBe5), -C(O)N(RGBe4)S(O)2RGBe5, and - P(O)(RGBe4)RGBe5;RGBe4and RGBe5are each independently selected from hydrogen, deuterium, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14 aryl, and 5-12 membered heteroaryl, wherein the Ci-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3- 10 cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, or 5-12 membered heteroaryl are optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, 3-7 membered heterocyclyl, phenyl, and 5-6 membered heteroaryl;RGB1and RGB2together with the atoms to which they are attached, form Cais carbocyclyl optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7, or 8) RGB3;RGB3is each independently selected from hydrogen, deuterium, halogen, hydroxyl, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C3-10 cycloalkyl, and 3-10 membered heterocyclyl, wherein the C1-6 alkyl, C1-6 alkoxy, Ci-6 alkylamino, C3-10 cycloalkyl, or 3-10 membered heterocyclyl is92316435300Docket No. 43658-02205 (EXAV-024 / 001WO)optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from deuterium, halogen, hydroxyl, amino, cyano, oxo, C3-10 cycloalkyl, and 3-10 membered heterocyclyl;LGB1is selected from a bond, -C(RGBL1)2-, -O-, -C(RGBL1)2O-, -S-, -C(O)-, -C(O)O-, -OC(O)-, -N(RGBL1)C(O)-, -C(O)N(RGBL1)-, and -N(RGBL1)-;RGBL1is each independently selected from hydrogen, deuterium, C1-6 alkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl, wherein the C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, or 3-10 membered heterocyclyl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from deuterium, halogen, hydroxyl, amino, nitro, mercapto, cyano, C1-6 alkyl, Ci-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl;LGB2 is selected from a bond, -C(RGBL2)2-, -O-, -C(RGBL2)2O-, -S-, -C(O)-, -C(O)O-, -OC(O)-, -N(RGBL2)C(O)-, -C(O)N(RGBL2)-, and -N(RGBL2)-;RGBL2are each independently selected from hydrogen, deuterium, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl, wherein the C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, or 3-10 membered heterocyclyl are optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from deuterium, halogen, hydroxyl, amino, nitro, mercapto, cyano, C1-6 alkyl, Ci-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl;LGB3 is selected from a bond, -C(RGBL3)2-, -O-, -S-, -C(O)-, -C(O)O-, -OC(O)-, - N(RGBL3)C(O)-, -C(O)N(RGBL3)-, and -N(RGBL3)-;RGBL3is independently selected from hydrogen, deuterium, C1-6 alkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl, wherein the C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, or 3-10 membered heterocyclyl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from deuterium, halogen, hydroxyl, amino, nitro, mercapto, cyano, C1-6 alkyl, Ci-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl;93316435300Docket No. 43658-02205 (EXAV-024 / 001WO)LGB4 is a bond, -LGB4X -C(RGBL'4a)(RGBL4b)-LGB4y -LGB4X -0LGB4y -LGB4X -SLGB4V -LGB4X -C(O)-lx3B4y -, -LGB4X -C(0)0LGB4V -, -LGB4X -0C(0)-LGB4y -, -LGB4X -N(RGBL4a)C(O)-LGB4V -LGB4X -C(O)N(RGBL4a)-LGB4y -LGB4X -N(RGBL4a)-LGB4y -, -LGB4X -N(RGBL4a)C(O)N(RGBL4b)-LGB4y -, -LGB4X -N(RGBL4a)C(S)N(RGBL4b)-I., GB4y or (RGBL4z)rGBLGB4; GB4yLGB4X and LGB4Yare each independently a bond or Ci-io alkylene, wherein the Ci-io alkylene is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from deuterium, halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl;RGBL4aand RGBL4bare each independently selected from hydrogen, deuterium, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C’3-10 cycloalkyl, and 3-10 membered heterocyclyl, wherein the Ci-6 alkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, or 3-10 membered heterocyclyl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from deuterium, halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 substituted by a cycloalkyl group or a 3-10 membered heterocyclyl;Ring LGB Z is C3-15 carbocyclyl, 3-12 membered heterocyclyl, C6-14aryl, or 5-12 membered heteroaryl;RLGB4Zare each independently selected from hydrogen, deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl, wherein the Ci-6 alkyl, Ci-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, or 3-10 membered heterocyclyl are optionally substituted with one or more substituents independently selected from deuterium, halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl;LGBSX and LGBSY are each independently a bond or C1-10 alkylene, wherein the C1-10 alkylene is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents94316435300Docket No. 43658-02205 (EXAV-024 / 001WO)independently selected from deuterium, halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl;mGB, nGB, oGB, pGB, qGB, and rGB are each independently 0, 1, 2, or 3;unless otherwise specified, the heteroatoms in the above heterocyclyl and heteroaryl are independently selected from O, N or S, and the number of heteroatoms is 1, 2, 3 or 4; and wherein the definitions of the above variables are combined to form a stable chemical structure;(iv)(RGC3)pGCwherein:XGC1, XGC2, and XGC3are independently selected from the group consisting of N and C; rings AGC, BGC, and CGCare independently selected from the group consisting of C3- 10 cycloalkyl, heterocyclyl, aryl, and heteroaryl;each RGC1is independently selected from the group consisting of hydrogen, halogen, Ci- io alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-10 cycloalkyl, C3-10 cycloalkyl-Ci-4 alkyl, heterocyclyl, heterocyclyl-Ci-4 alkyl, aryl, aryl-Ci-4 alkyl, heteroaryl, heteroaryl-Ci-4 alkyl, — CN, — NO2, — NRGCA1RGCBi, __ _QRGCAI, ___(2(0)RGCAI, ___c(O)ORGCAi, OC(O)RGCA1, — C(O)NRGCA1RGCBI, NRGCA1C(O)RGCB1, — OC(O)NRGCA1RGCB1, — S(O)rGCRGCA1, —S(O)2ORGCA1, —95316435300Docket No. 43658-02205 (EXAV-024 / 001WO)OS(O)2RGCA1, — NRGCA1S(O)rGCRGCB1, — S(O)rGcNRGCA1RGCB1, — P(O)RGCA1RGCB1, and — P(O)(ORGCA1)(ORGCBi), wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is unsubstituted or substituted independently with at least one RGCXl;each RGC2is independently selected from the group consisting of hydrogen, halogen, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-10 cycloalkyl, C3-10 cycloalkyl-Ci-4 alkyl, heterocyclyl, heterocyclyl-Ci-4 alkyl, aryl, aryl-C1-4 alkyl, heteroaryl, heteroaryl-Ci-4 alkyl, — (CH2)sGCCF3, — CN, — NO2, -- NRGCA2RGCB2, --ORGCA2, -- C(O)RGCA2, - - -C(O)ORGCA2, -- OC(O)RGCA2, --- C(O)NRGCA2RGCB2, — NRGCA2C(O)RGCB2, — OC(O)NRGCA2RGCB2, — NRGCA2C(O)ORGCB2, — S(O)rGcRGCA2, — P(O)RGCA2RGCB2, — S(O)rGcNRGCA2RGCB2, and — P(O)(ORGCA2)(ORGCB2), wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is unsubstituted or substituted independently with at least one RGCX2;each RGC3is independently selected from the group consisting of hydrogen, halogen, Ci- 10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-10 cycloalkyl, C3-10 cycloalkyl-Ci-4 alkyl, heterocyclyl, heterocyclyl-Ci-4 alkyl, aryl, aryl-C 1-4 alkyl, heteroaryl, heteroaryl-Ci-4 alkyl, ----- CN, - -NO2, — NRGCA3RGCB3, — ORGCA3, and — C(O)RGCA3, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is unsubstituted or substituted independently with at least one RGCX3; ortwo RGC3, together with the atom(s) to which they are attached, form a C3-10 cycloalkyl or 4- to 12-membered heterocyclyl containing 1, 2, or 3 heteroatoms, wherein the heteroatoms are independently selected from the group consisting of oxygen, sulfur, nitrogen, and phosphorus, and the ring thereof is unsubstituted or substituted independently with 1, 2, or 3 RGCX3;RGC4is selected from the group consisting of — C(O)OH, heterocyclyl, and heteroaryl; RGC5is selected from the group consisting of hydrogen and C1-6 alkyl;RGC6is selected from the group consisting of hydrogen, halogen, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-10 cycloalkyl, C3-10 cycloalkyl-Ci-4 alkyl, heterocyclyl, heterocyclyl-Ci-4 alkyl, aryl, aryl-C 1-4 alkyl, heteroaryl, heteroaryl-C 1-4 alkyl, — CN, — NO2, — NRGCA4RGCB4, — ORGCA4, and — C(O)RGCA4, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is unsubstituted or substituted independently with at least one RGCX4;96316435300Docket No. 43658-02205 (EXAV-024 / 001WO)RGC7and RGC8, together with the atom to which they are attached, form a fragment WjGC, and RGC9and RGC10are independently selected from the group consisting of hydrogen, halogen, and C1-3 alkyl; orRGC9and RGC10, together with the atom to which they are attached, form a fragmentand RGC7and RGC8are independently selected from the group consisting of hydrogen, halogen, and C1-3 alkyl; orRGC8and RGC9, together with the carbon atoms to which they are attached, form awGCfragment, and RGC7and RGC10are independently selected from the group consisting of hydrogen, halogen, and C1-3 alkyl;rings TGC, T'GC, and WGCare independently selected from the group consisting of C3-10 cycloalkyl, C3-8 cycloalkenyl, 3- to 12-membered heterocyclyl, and 5- to 6-membered heteroaryl, and the rings are unsubstituted or substituted independently with 1, 2, or 3 RGCX;is a single bond or a double bond; orRGC8and RGC6, together with the atoms to which they are attached, form a C3-10 cycloalkyl or 4- to 12-membered heterocyclyl containing 1, 2, or 3 heteroatoms, wherein the heteroatoms are independently selected from the group consisting of oxygen, sulfur, nitrogen, and phosphorus, and the ring thereof is un substituted or substituted with 1, 2, or 3 RGCX; and RGC7, RGC9, and RGC10are each independently selected from the group consisting of hydrogen, halogen, and C1-3 alkyl; orRGC9and RGC6, together with the atoms to which they are attached, form a C3-10 cycloalkyl or 4- to 12-membered heterocyclyl containing 1, 2, or 3 heteroatoms, wherein the heteroatoms97316435300Docket No. 43658-02205 (EXAV-024 / 001WO)are independently selected from the group consisting of oxygen, sulfur, nitrogen, and phosphorus, and the ring thereof is unsubstituted or substituted independently with 1, 2, or 3 RGCX; and RGC7, RGC8, and RGC10are each independently selected from the group consisting of hydrogen, halogen, and C1-3 alkyl;each of RGCA1, RGCA2, RGCA3, RGCA4, RGCB1, RGCB2, RGCB3, and RGCB4independently selected from the group consisting of hydrogen, Ci-io alkyl, C2-10 alkenyl, C2-10 alkynyl, C3- 10 cycloalkyl, C3-10 cycloalkyl-Ci-4 alkyl, heterocyclyl, heterocyclyl-Ci-4 alkyl, aryl, aryl-Ci- 4 alkyl, heteroaryl, and heteroaryl-C 1-4 alkyl, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is unsubstituted or substituted with at least one substituent independently selected from the group consisting of hydroxyl, oxo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, cyano, alkoxy, alkylamino, di(alkyl)amino, haloalkyl, acyl, sulfonyl, sulfonamido, and halogen; or“RGCA1and RGCB1” or -RGi- - and RGCB2” or “RGCA3and RGCB3”, together with single or multiple atom(s) to which they are attached, form a 4- to 12-membered heterocyclic ring containing 0, 1, or 2 additional heteroatoms independently selected from the group consisting of oxygen, sulfur, nitrogen, and phosphorus, and the ring is unsubstituted or substituted with 1, 2, or 3 substituents selected from the group consisting of hydroxyl, oxo, Ci -6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, cyano, alkoxy, alkylamino, di(alkyl)amino, haloalkyl, acyl, sulfonyl, sulfonamido, and halogen;each of RGCX, RGCX1, RGCX2, RGCX3, and RGCX4is independently selected from the group consisting of hydroxyl, oxo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, cyano, alkoxy, alkylamino, di(alkyl)amino, haloalkyl, acyl, sulfonyl, sulfonamido, and halogen;mGC, nGC, and pGC are independently selected from the group consisting of 0, 1, 2, and 3; andrGC and sGC are independently selected from the group consisting of 0, 1, and 2; or(v)98316435300Docket No. 43658-02205 (EXAV-024 / 001WO)wherein:LGD1is selected from -CO-, -SO-, -SO2-, -NRcroa -and-CRGDaRGDb -;LGD2is selected from, QGD, -RGDL-NRGDa -*, -RGDL-CO- N GDa-*, -RGDL -NRGDa-CO-NRGDa-*, -RGDL-C(S)-NRGDa-*, -RGDL -NRGDa-C(S)-NRGDa-*, where the asterisk indicates a connection to the N atom in the central ring;Ring A is C3-10 cycloalkyl, C3-10 cycloalkenyl, 3-10 membered heterocyclic alkyl, 3-10 membered heterocyclic alkenyl, Ce-io aryl, or 5-10 membered heteroaryl each optionally substituted with one or more RGD3 groups, each RGD3 group being independently selected from halogen, cyano, hydroxyl, NRoDaRoDb Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, Ci- 6 alkylthio, Ci-6 haloalkyl, C1-6 cyanoalkyl, Ci-e hydroxyalkyl, and (optionally selected independently by one or more halogens and C1-6 alkyl-substituted C3-10 cycloalkyl)-RGDL-, or two of the RGD3S, together with the atoms they are attached to, form a 4- to 6-membered ring optionally containing one or more heteroatoms independently selected from N, O, or S, wherein the 4- to 6-membered ring is optionally substituted with one or more substituents independently selected from halogen, cyano, hydroxyl, oxo, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 cyanoalkyl and C1-6 hydroxyalkyl;Ring B is a naphthylene or an 8-10 membered bicyclic heteroarylene, each optionally substituted by one or more RGD4 groups, each RGD4 group independently selected from halogen, cyano, hydroxyl, NRGDaRGDb, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 alkylthio, Ci-6 haloalkyl, C1-6 cyanoalkyl, C1-6 hydroxyalkyl, (C3-10 cycloalkyl)-RGDL-, (5-10 membered heterocyclic alkyl)-RGDL-, (Ce-io aryl)-RGDL, and (5-10 membered heteroaryl)-RGDL-, wherein the cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents each independently selected from halogen, C1-6 alkyl, or C1-6 alkoxy;99316435300Docket No. 43658-02205 (EXAV-024 / 001WO)Ring C is C3-10 cycloalkyl, C3-10 cycloalkenyl, 3-10 membered heterocyclic alkyl, 3-10 membered heterocyclic alkenyl, Ce-io aryl, or 5-10 membered heteroaryl optionally substituted by one or more substituents, wherein each substituent is independently selected from H, halogen, cyano, hydroxyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, (C1-6 alkoxy)-RGDL-, (C1-6 alkylthio)-RGDL-, C1-6 alkoxy-Ci-6 alkoxy-, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 cyanoalkyl, Ci-6 hydroxyalkyl, Ci-6 alkyl, Ci-6 halogenated alkyl, COOH, -CONH2, -CONH(Ci-6 alkyl), - O-^-O-P-ORcDa C(=S)NH2, -C(=S)NH(CI-6alkyl), -P(RGDa)(RGDb), -PH(CI-6alkyl)(Ci-6 alkyl),ORGDb, C1-6 alkyl-CO-, (C1-6 haloalkoxy)-RGDL-(C3-10 cycloalkyl optionally substituted with halogen or hydroxyl groups)-RGDi-, (C3-10cycloalkyl)-C2-4 alkenyl-, (C3-10 cycloalkyl)-C2-4 a-ethynyl-, (C3- 10 cycloalkyloxy)-RGDL-, (3-10 membered heterocyclic alkyl)-RGDL-, (3-10 membered heterocyclic alkyloxy)-RGDL-, (Ce-io aryl)-RGDL-, (Ce-io aryloxy)-RGDL-, (Ce-io aryl-Ci- 6 (alkyleneoxy)-RGDL-, (5-10 membered heteroaryl)-RGDi-, (5-10-membered heteroaryloxy)- RGDL-, NRGDsRGDt -(CRGDaRGDb)mGD-, NRGDaGDb-CO- and RGD6, or two of these substituents together with the atoms they are attached to, form a 3- to 7-membered ring optionally containing one or more heteroatoms selected from N, O, or S, said ring optionally being substituted with one or more substituents each independently selected from oxo, halogen, cyano, C1-6 alkyl, Ci- 6 haloalkyl, C3-10 cycloalkyl, 3-10 membered heterocyclic alkyl, Ce-io aryl, and 5-7 membered heteroaryl;Ring D is C3-10 cycloalkyl, C3-10 cycloalkenyl, 3-10 membered heterocyclic alkyl, 3-10 membered heterocyclic alkenyl, Ce-io aryl, or 5-10 membered heteroaryl;RGDI is each independently H, halogen, cyano, hydroxyl, mercapto, NGDaRGDb, Ci-6 alkyl, C2-6 alkenyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C1-6 cyanoalkyl, C1-6 hydroxyalkyl, Ci-6 alkoxy, Ci-6 alkylthio, C1-6 halogenated alkoxy, or C3-8 cycloalkyl, or two RGDI atoms together with the carbon atoms they are atached to form C3-4 cycloalkyl;RGD2 is each independently selected from H, halogen, cyano, OH, NRGDaRGDb, Ci-6 alkyl, C2-6 alkenyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkyl, C1-6 halogenated alkoxy, optionally substituted with one or more substituents selected from C1-6 alkyl-substituted 5-10-membered heteroaryl, -P(O)(Ci-6 alkyl)(Ci-6 alkyl), -C(O)(Ci-6 alkyl), -S(O)(Ci-6 alkyl), -S(O)2(Ci-6 alkyl), -NRGDa-S(O)2-(Ci-6 alkyl), -C(0)-(C3-10 cycloalkyl), -S(0)-(C3-10 cycloalkyl), -S(0)2-(C3-10 cycloalkyl), -S(=0)(=NRGDa)-(C3-10 cycloalkyl), or -C(=O)-N(RGDa)-(C3- 100316435300Docket No. 43658-02205 (EXAV-024 / 001WO)io cycloalkyl), or two of the RGD2 groups together with the atoms they are attached form a 6-membered aromatic ring or a 5-6 membered saturated, partially unsaturated, or aromatic heterocycle, wherein the ring is optionally substituted with a substituent selected from the following: halogen, oxo, NRGDaRGDb)-RGDL-, Ci-6 alkyl, Ci-6 deuterated alkyl, Ci-6 haloalkyl, Ci-6 cyanoalkyl, Ci-6 hydroxyalkyl, (Ci-6 alkoxy)-RGDL-, (Ci-6 alkylthio)-RGDL-, (C3-10 cycloalkyl optionally substituted with one or more halogens, C1-6 alkyl or Ci-6 alkoxy)-RGDL- (3-10 membered heterocyclic alkyl optionally substituted with one or more halogen, C1-6 alkyl, or Ci- 6 haloalkyl)-RGDL-, and (Ce-io aryl)-RGDL -, where C3-10 cycloalkyl groups can be monocyclic, bicyclic, spirocyclic, or bridged rings;RGD6 is a 5- or 6-membered partially unsaturated or aromatic heterocycle containing one or more heteroatoms independently selected from N, O, or S;RGDp is each independently halogen, cyano, hydroxyl, NH2, C1-6 alkyl, or absent;RGDa and RGDb is each independently H or Ci-6 alkyl;RGDS and RGDI are each independently H, C1-6 alkyl, C1-6 haloalkyl, Ce-io aryl, or 5-10 membered heteroaryl;RGDL is each independently a bond; C1-10 alkylene optionally substituted with halogen, cyano, or hydroxyl; or Ci-4 deuterated alkylene;TGD is Ci-4 alkylene, C2-4 imidene, C2-4 acetylene, or C3-6 cycloalkylene group bonded to the rest of the molecule through two different ring carbon atoms;QGD is O or S;mGD is 0, 1, 2, 3, 4, or 5;nGD is 0, 1, or 2; andqGD is 0, 1, 2, or 3;»AAA / s / VWNxN® N^N0N®}=N S-^A" is O, R, or O, or a tautomer thereof;RAis selected from the group consisting of hydrogen, C1-6 alkyl and (C1-6 alkyl) carbonyl, wherein C1-6 alkyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen and C1-6 alkoxy;101316435300Docket No. 43658-02205 (EXAV-024 / 001WO)the counterion comprises an amine-containing polymer, a diamine or a conjugate thereof, a polyamine or a conjugate thereof, or Mh;RN1and RN2are each independently hydrogen or C1-C30 alkyl;Yi, Y2, Yd, and Y?’ are each independently a bond, -O-, or -NH-;Li, L2, L3, Li’, and L2’ are each independently a bond, C1-C25 alkylene, or Ce-Cio arylene, wherein the alkylene and arylene are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl;Ri is C1-C30 alkyl, C2-C30 alkenyl, C6-C10 aryl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl, wherein the alkyl, alkenyl, aryl, heterocyclyl, and heteroaryl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6 alkyl, Ce-Cio aryl, C1-C6 alkoxy, Ci-Ce haloalkyl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl; andm is 0 or 1.

[0108] In some aspects, the present disclosure provides a salt comprising anion G-A-and a counterion, wherein:Gis:316435300Docket No. 43658-02205 (EXAV-024 / 001WO)\, a stereoisomer thereof, or a tautomer thereof;XG is — N= or — CRaG=; RaGis selected from a hydrogen atom, a halogen atom, and Ci- 6 alkyl;YG is selected from — C(=O) -, CHRG, and - -S(=O)2 - -; RGis a hydrogen atom or Ci-6 alkyl;QG1is C6-10 aryl or 5 to 10 membered heteroaryl, wherein the Ce-io aryl and 5 to 10 membered heteroaryl are optionally substituted with one to five substituents independently selected from a halogen atom, Ci-6 alkyl (wherein Ci-6 alkyl is optionally substituted with one or more halogen atoms), C3-6 cycloalkyl, and C1-6 alkoxy;QG2is 3 to 12 membered heterocyclyl or 5 to 10 membered heteroaryl, wherein the 3 to 12 membered heterocyclyl and 5 to 10 membered heteroaryl are optionally substituted with one to three substituents independently selected from a halogen atom, C1-6 alkyl (wherein C1-6 alkyl is optionally substituted with one or more halogen atoms), C1-6 alkoxy, and — NRGQaRGQb, and two Ci-6 alkyl groups together with a carbon atom to which they are attached may form C3- 8 carbocyclic ring; and RQaand RQbare independently selected from a hydrogen atom, Ci-6 alkyl, and (Ci-6 alkyl)carbonyl;Z3, Z4, Z5, Ze, Z7, Zs, Z9, Z10, Z11, Z12 and Z13 are each independently selected from the group consisting of N and C;103316435300Docket No. 43658-02205 (EXAV-024 / 001WO)RG1, RG2, RG3, RG1', RG2', and RG3'are each independently selected from a hydrogen atom, halogen atom, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 haloalkoxy, cycloalkyl, and heterocycloalkyl, wherein the Ci-6 alkyl, cycloalkyl, or heterocycloalkyl is optionally substituted by one or more substituents independently selected from a halogen atom, Ci-6 alkoxy, and hydroxy; or RG2and RG3together with the carbon atom to which they are attached form 4- to 8-membered heterocy cl oalky 1;RG4, RG5and RG6are independently selected from a hydrogen atom, a halogen atom, and Ci-6 alkyl;RG7and RG8are independently a hydrogen atom or Ci-6 alkyl, wherein the Ci-6 alkyl is optionally substituted with one or more substituents independently selected from a halogen atom and C3-15 cycloalkyl, or RG7and RG8together with a carbon atom to which they are attached may form C3-15 cycloalkane ring, wherein the C3-15 cycloalkane ring formed by RG7and RG8together is optionally substituted with one to three Ci-6 alkyl, wherein the Ci-6 alkyl is optionally substituted with one or more substituents independently selected from a halogen atom, hydroxy, ---NRG7aRG7b, Ci-6 alkoxy, and 3 to 12 membered heterocyclyl, and RG7aand RG7bare independently selected from a hydrogen atom, C1-6 alkyl, and (C1-6 alkyl)carbonyl; and any two C1-6 alkyl optionally together with the carbon atom to which they are attached form C3-15 carbocyclic ring;nGl is an integer of 0 to 3; nG2 is an integer of 0 to 5; nG3 is 0 or 1;ZG1is selected from the group consisting ofwherein Rzais selected from a hydrogen atom, C1-6 alkyl, and (C1-6 alkyl)carbonyl; Rzband Rzcare each independently a hydrogen atom or C1-6 alkyl; n4 is an integer of 1 to 3; n5 and n6 are independently an integer of 0 to 10 (* represents a binding position with a pyrazolopyridine structure, and ** represents a binding position with ZG2);104316435300Docket No. 43658-02205 (EXAV-024 / 001WO)ZG2is selected from the group consisting of Ci-6 alkyl, C3-15 cycloalkyl, 3 to 12 membered heterocyclyl, Ce-io aryl, and 5 to 10 membered heteroaryl, wherein the C3-15 cycloalkyl, 3 to 12 membered heterocyclyl, C6-10 aryl, and 5 to 10 membered heteroaryl are optionally substituted with one to five substituents independently selected from Group A:Group A a) oxo,b) a halogen atom,c) cyano,d) — NRzdRze; wherein Rzdand Rzeare independently selected from a hydrogen atom, C1-6 alkyl and (C1-6 alkyl)carbonyl, wherein C1-6 alkyl is optionally substituted with one or more substituents independently selected from hydroxy, a halogen atom and C1-6 alkoxy,e) — C(=O) — NRzfRzg; wherein Rzfand Rzgare independently selected from a hydrogen atom, Ci-6 alkyl and (Ci-6alkyl)carbonyl, wherein C1-6 alkyl is optionally substituted with one or more substituents independently selected from hydroxy, a halogen atom and Ci-6 alkoxy,f) - -S(=O)n7 - Rzh; wherein n7 is an integer of 0 to 2; and Rzhis a hydrogen atom or C i-6 alkyl,g) C1-6 alkyl optionally substituted with one or more substituent independently selected from a halogen atom, hydroxy, — NRziRzj, C1-6 alkoxy, and 3 to 12 membered heterocyclyl, wherein Rziand Rzjare independently a hydrogen atom or C1-6 alkyl, and wherein 3 to 12 membered heterocyclyl is optionally substituted with one or more substituents independently selected from hydroxy, Ci-6 alkyl and 3 to 12 membered heterocyclyl,h) C1-6 alkoxy optionally substituted with one or more substituent independently selected from hydroxy, a halogen atom, and C1-6 alkoxy,i) 3 to 12 membered heterocyclyl optionally substituted with one or more substituents independently selected from C1-6 alkyl and (C1-6 alkyl)carbonyl, j) C6-10 aryl optionally substituted with one or more (C1-6 alkyl)carbonyl, k) 5 to 10 membered heteroaryl optionally substituted with one or more substituents independently selected from C1-6 alkyl, C1-6 alkoxy, - -NRzkRzl, and 3 to 12 membered heterocyclyl, wherein Rzkand Rzlare independently selected from105316435300Docket No. 43658-02205 (EXAV-024 / 001WO)a hydrogen atom, Ci-6 alkyl and (Ci-6 alkyl)carbonyl, and wherein 3 to 12 membered heterocyclyl is optionally substituted with one or more substituents independently selected from Ci-6 alkyl and (Ci-6 alkyl)carbonyl,l) — P(==O)(Rzm)(Rzn), wherein Rzmand Rznare each independently a hydrogen atom or Ci-6 alkyl;m) C3-C15 cycloalkyl optionally substituted with one or more substituents independently selected from the group consisting of halogen, oxo, C1-6 alkyl, Ci- 6 alkoxy and (C1-6 alkyl) carbonyl, wherein each of alkyl and alkoxy is optionally substituted with halogen; andn) C1-C6 alkyl-C3-C15 cycloalkyl wherein the cycloalkyl or alkyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, oxo, C1-6 alkyl, C1-6 alkoxy and (C1-6 alkyl) carbonyl, wherein each of alkyl and alkoxy is optionally substituted with halogen; orwherein:RGA13isselected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, thio, Ci-6 alkyl, Ci-6 deuterated alkyl, C1-6 halogenated alkyl, C1-6 deuterated haloalkyl, Ci-6 hydroxyalkyl, C1-6 deuterated hydroxyalkyl, C1-6 sulfanyl, C1-6 deuterated sulfanyl, C1-6 alkoxy, Ci-6 deuterated alkoxy, Ci-6 halogenated alkoxy, C1-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-8 Cycloalkyl, 3-8 membered heterocyclyl, Ce-io aryl, and 5-10 membered heteroaryl, wherein the amino, C1-6 alkyl, C1-6 deuterated alkyl, C1-6 halogenated alkyl, C1-6 deuterated106316435300Docket No. 43658-02205 (EXAV-024 / 001WO)haloalkyl, Ci-6 hydroxyalkyl, Ci-6 deuterated hydroxyalkyl, Ci-6 sulfanyl, Ci-e deuterated sulfanyl, Ci-6 alkoxy, Ci-6 deuterated alkoxy, Ci-6 halogenated alkoxy, C1-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-8 Cycloalkyl, 3-8 membered heterocyclyl, C6-10 aryl, or 5-10 membered heteroaryl is optionally further substituted by deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, thio, C1-6 alkyl, C1-6 deuterated alkyl, C1-6 halogenated alkyl, C1-6 deuterated haloalkyl, C1-6 hydroxyalkyl, C1-6 deuterated hydroxyalkyl, Ci-6 sulfanyl, C1-6 deuterated sulfanyl, C1-6 alkoxy, C1-6 deuterated alkoxy, C1-6 halogenated alkoxy, C1-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, 3-8 membered heterocyclyl, Ce-io aryl, or 5-10 membered heteroaryl substituted by one or more substituents;LGA1, LGA2, and LGA3are each independently selected from a bond, C2-4 alkenylene, C2-4 alkynylidene and -(CH2)nGAi -;Ring AGAis selected from C3-14 cycloalkyl, 3-14 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl;Ring BGAis selected from C’3-12 cycloalkyl, 3-12 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl, wherein the C3-12 cycloalkyl, 3-12 membered heterocyclyl, C6-14 aryl, or 5-14 membered heteroaryl is optionally further substituted by deuterium, halogen, amino, nitro, hydroxyl, cyano, oxo, thiol, thio, C1-6 alkyl, C1-6 deuterated alkyl, C1-6 halogenated alkyl, C1-6 deuterated haloalkyl, C1-6 hydroxyalkyl, C1-6 deuterated hydroxyalkyl, C1-6 sulfanyl, C1-6 deuterated sulfanyl, Ci-6 alkoxy, C1-6 deuterated alkoxy, C1-6 haloalkoxy or C1-6 deuterated haloalkoxy substituted by one or more substituents;Ring DGAis selected from C3-12 cycloalkyl, 3-12 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl;Ring EGAis selected from C3-14 cycloalkyl, 3-14 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl, wherein the C3-14 cycloalkyl, 3-14 membered heterocyclyl, C6-14 aryl, or 5-14 membered heteroaryl is optionally further substituted by deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, thio, Ci-6 alkyl, C1-6 deuterated alkyl, C1-6 halogenated alkyl, Ci-6 deuterated haloalkyl, C1-6 hydroxyalkyl, C1-6 deuterated hydroxyalkyl, C1-6 sulfanyl, C1-6 deuterated sulfanyl, Ci-6 alkoxy, C1-6 deuterated alkoxy, C1-6 halogenated alkoxy, C1-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, 3-8 membered heterocyclyl, Ce-io aryl, or 5-10 membered heteroaryl substituted by one or more substituents;107316435300Docket No. 43658-02205 (EXAV-024 / 001WO) o..alternatively, ringEGA- is ’ optionally substituted with one or more substituents selected from the group consisting of methyl, ethyl, methoxy, and ethoxy;RGA1, RGA3, RGA4, RGA5, RGA6, RGA7, RGA8, RGA9, RGA14, RGA15, and RGA16eachindependently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, thio, Ci-6 alkyl, Ci-6 deuterated alkyl, Ci-6 halogenated alkyl, Ci-6 deuterated haloalkyl, Ci-6 hydroxyalkyl, Ci-6 deuterated hydroxyalkyl, Ci-6 sulfanyl, Ci-6 deuterated sulfanyl, Ci-6 alkoxy, Ci-6 deuterated alkoxy, Ci-6 halogenated alkoxy, Ci-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, 3-8 membered heterocyclyl, Ce-io aryl, 5-10 membered heteroaryl, - (CH2)mGAiORGAci, and (=C)RGAc3RGAc4, wherein the amino, Ci-6 alkyl, C1-6 deuterated alkyl, Ci-6 halogenated alkyl, C1-6 deuterated haloalkyl, C1-6 hydroxyalkyl, C1-6 deuterated hydroxyalkyl, C1-6 sulfanyl, C1-6 deuterated sulfanyl, C1-6 alkoxy, Ci-6 deuterated alkoxy, Ci-6 halogenated alkoxy, C1-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C’3-8 Cycloalkyl, 3-8 membered heterocyclyl, Ce-io aryl, 5-10 membered heteroaryl, -(CH2)mGAiORGAcl, or (=C)RGAc3RGAc4is optionally further substituted with deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, thio, C1-6 alkyl, C1-6 deuterated alkyl, Ci-6 halogenated alkyl, Ci-6 deuterated haloalkyl, C1-6 hydroxyalkyl, C1-6 deuterated hydroxyalkyl, C1-6 sulfanyl, C1-6 deuterated sulfanyl, C1-6 alkoxy, Ci-6 deuterated alkoxy, Ci-6 halogenated alkoxy, C1-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-8 Cycloalkyl, 3-8 membered heterocyclyl, C6-10 aryl, or 5-10 membered heteroaryl substituted by one or more substituents;RGAc1, RGAc3, and RGAc4are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, thio, C1-6 alkyl, C1-6 deuterated alkyl, C1-6 halogenated alkyl, C1-6 deuterated haloalkyl, C1-6 hydroxyalkyl, C1-6 deuterated hydroxyalkyl, Ci- 6 sulfanyl, C1-6 deuterated sulfanyl, C1-6 alkoxy, C1-6 deuterated alkoxy, C1-6 halogenated alkoxy, C1-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-8 Cycloalkyl, 3-8 membered heterocyclyl, Ce-io aryl, 5-10 membered heteroaryl,, -(CH2)mGA2ORGAc2, -(CH2)mGA3C(O)NRGAa1RGAb1, and -(CH2)mGA4C(O)ORGAa2, wherein the amino, C1-6 alkyl, C1-6 deuterated alkyl, C1-6 halogenated alkyl, Ci-6 deuterated haloalkyl, C1-6 hydroxyalkyl, C1-6108316435300Docket No. 43658-02205 (EXAV-024 / 001WO)deuterated hydroxyalkyl, Ci-e sulfanyl, Ci-6 deuterated sulfanyl, Ci-6 alkoxy, Ci-6 deuterated alkoxy, Ci-6 halogenated alkoxy, Ci-6 deuterated haloalkoxy, C2-6 alkenyl, C2- 6 alkynyl, C3- s Cycloalkyl, 3-8 membered heterocyclyl, C6-10aryl, 5-10 membered heteroaryl, -(CH2)mGA2ORGAc2, -(CH2)mGA3C(O)NRGAa1RGAb1, or -(CH2)mGA4C(O)ORGAa2is optionally further substituted with deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, thio, C1-6 alkyl, C1-6 deuterated alkyl, C1-6 halogenated alkyl, C1-6 deuterated haloalkyl, C1-6 hydroxyalkyl, Ci-6 deuterated hydroxyalkyl, C1-6 sulfanyl, C1-6 deuterated sulfanyl, C1-6 alkoxy, C1-6 deuterated alkoxy, C1-6 halogenated alkoxy, Ci-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-8 Cycloalkyl, 3-8 membered heterocyclyl, Ce-io aryl, or 5-10 membered heteroaryl substituted by one or more substituents;RGAal, RGAa2, RGAbl, and RGAc2are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, thio, C1-6 alkyl, Ci-6 deuterated alkyl, C1-6 halogenated alkyl, C1-6 deuterated haloalkyl, C1-6 hydroxyalkyl, C1-6 deuterated hydroxyalkyl, Ci- 6 sulfanyl, C1-6 deuterated sulfanyl, C1-6 alkoxy, C1-6 deuterated alkoxy, C1-6 halogenated alkoxy, C1-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-8 Cycloalkyl, 3-8 membered heterocyclyl, C6-10aryl or 5-10 membered heteroaryl, wherein the amino, C1-6 alkyl, C1-6 deuterated alkyl, C1-6 halogenated alkyl, C1-6 deuterated haloalkyl, C1-6 hydroxyalkyl, C1-6 deuterated hydroxyalkyl, C1-6 sulfanyl, C1-6 deuterated sulfanyl, C1-6 alkoxy, C1-6 deuterated alkoxy, C1-6 halogenated alkoxy, C1-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, 3-8 membered heterocyclyl, Ce-io aryl, or 5-10 membered heteroaryl is optionally further substituted by deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, C1-6 alkyl, Ci-e deuterated alkyl, C1-6 halogenated alkyl, Ci-6 deuterated haloalkyl, C1-6 hydroxyalkyl, C1-6 deuterated hydroxyalkyl, C1-6 sulfanyl, C1-6 deuterated sulfanyl, C1-6 alkoxy, C1-6 deuterated alkoxy, C1-6 halogenated alkoxy, C1-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, 3-8 membered heterocyclyl, Ce-io aryl, or 5-10 membered heteroaryl substituted by one or more substituents;or, RGA9and RGA16together with the atoms connected to them form C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-12 aryl or 5-12 membered heteroaryl;or, when nGA is not 1,RGA1and RGA1', RGA2and RGA2', RGA4and RGA5, RGA5and RGA6, RGA7and RGA8, together with the atoms connected to them, form C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-12 aryl,109316435300Docket No. 43658-02205 (EXAV-024 / 001WO)or 5-12 membered heteroaryl, optionally further substituted by deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, thio, Ci-6 alkyl, Ci-6 deuterated alkyl, Ci-6 halogenated alkyl, Ci-6 deuterated haloalkyl, Ci- 6-hydroxyalkyl, Ci-6 deuterated hydroxyalkyl, Ci-6 sulfanyl, Ci-6 deuterated sulfanyl, Ci-6 alkoxy, Ci-6 deuterated alkoxy, Ci- 6-halogenated alkoxy, Ci-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C’3-8 Cycloalkyl, 3-8 membered heterocyclyl, Ce-io aryl, or 5-10 membered heteroaryl substituted by one or more substituents; andnGA, nGAl, nGAl, mGA2, mGA3, and mGA4 are each independently selected from 0, 1, 2, 3, 4 or 5; orwherein:Ring AGBis selected from C3-15 carbocyclyl, 3-12 membered heterocyclyl, C6-14aryl, and 5-12 membered heteroaryl;Ring BGBis selected from 3-12 membered heterocyclyl, C6-14 aryl, and 5-12 membered heteroaryl;Ring CGBis 9-membered bicyclic heteroaryl;Ring DGBis selected from C3-15 carbocyclyl, 3-12 membered heterocyclyl, C6-14 aryl, and 5-12 membered heteroaryl;Ring EGBis selected from C3-15 carbocyclyl, 3-12 membered heterocyclyl, C6-14aryl, and 5-12 membered heteroaryl;each RGBais independently selected from hydrogen, deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -ORGBal, -S(O)RGBal, -SO2(RGBal),-C(O)RGBal, -C(O)ORGBal, - OC(O)RGBal, -N(RGBal)(RGBa2), -C(O)N(RGBal)(RGBa2), -N(RGBal)C(O)RGBa2, - no316435300Docket No. 43658-02205 (EXAV-024 / 001WO)S(O)N(RGBal)(RGBa2), -SO2N(RGBa1)(RGBa2), -N(RGBal)S(O)RGBa2, -N(RGBal)S(O)2RGBa2, and optionally replaced by one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) RGBa3substituted with the following groups: Ci-6 alkyl, Ci-6 alkoxy, Ci-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, or 5-12 membered heteroaryl;or two RGBa, together with the atoms to which they are attached, form a 3-10 membered heterocyclyl or 5-12 membered heteroaryl, wherein the 3-10 membered heterocyclyl or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, Ci-6 alkyl, C1-6 alkoxy, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14 aryl, or 5-12 membered heteroaryl;RGBa1and RGBa2are each independently selected from hydrogen, deuterium, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14 aryl, and 5-12 membered heteroaryl, wherein the C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14 aryl, or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, a 3-6 membered heterocyclyl, phenyl, or 5-6 membered heteroaryl; each RGBa3is independently selected from hydrogen, deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -RGBa4, -ORGBa4, -SRGBa4, -S(O)RGBa4, -S(O)2RGBa4, - C(O)RGBa4, -C(O)ORGBa4, -OC(O)RGBa4, -N(RGBa4)(RGBa5), -C(O)N(RGBa4)(RGBa5), - N(RGBa4)C(O)RGBa5, -S(O)N(RGBa4)(RGBa5), -S(O)2N(RGBa4)(RGBa5), -N(RGBa4)S(O)RGBa5, - N(RGBa4)S(O)2RGBa5;RGBa4and RGBa5are each independently selected from hydrogen, deuterium, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, and 5-12 membered heteroaryl, wherein the C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3- 10 cycloalkyl, 3-10 membered heterocyclyl, C6-14 aryl, or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, 3-7 membered heterocyclyl, phenyl, and 5-6 membered heteroaryl;RGBbis each independently selected from hydrogen, deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 alkylamino, C2-6 alkenyl, C2-6111316435300Docket No. 43658-02205 (EXAV-024 / 001WO)alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, and 5-12 membered heteroaryl, wherein the C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C8-14 aryl, or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) RGBbl;or two RGBb, together with the atoms to which they are attached, form 3-10 membered heterocyclyl or 5-12 membered heteroaryl, wherein the 3-10 membered heterocyclyl or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) groups independently selected from deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, C1-6 alkoxy, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, and 5-12 membered heteroaryl;RGBblis each independently selected from deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -RGBb2, -ORGBb2, -SRGBb2, -S(O)RGBb2, -S(O)2RGBb2, -C(O)RGBb2, -C(O)ORGBb2, -OC(O)RGBb2, -N(RGBb2)(RGBb3), -C(O)N(RGBb2)(RGBb3), -N(RGBb2)C(O)RGBb3, -S(O)N(RGBb2)(RGBb3), -S(O)2N(RGBb2)(RGBb3), -N(RGBb2)S(O)RGBb3, and -N(RGBb2)S(O)2RGBb3;RGBb2and RGBb3are each independently selected from hydrogen, deuterium, Ci-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C’6-14 aryl, and 5-12 membered heteroaryl, wherein the Ci-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14 aryl, or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10cycloalkyl, 3-10 membered heterocyclyl, C6-14 aryl, and 5-12 membered heteroaryl;RGBcis each independently selected from hydrogen, deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, C1-6 alkoxy, Ci-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C’3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, and 5-12 membered heteroaryl, wherein the Ci-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) RGBcl;or two RGBe, together with the atoms to which they are attached, form 3-10 membered heterocyclyl or 5-12 membered heteroaryl, wherein the 3-10 membered heterocyclyl or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) groups112316435300Docket No. 43658-02205 (EXAV-024 / 001WO)independently selected from deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, Ci-6 alkyl, Ci-6 alkoxy, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, and 5-12 membered heteroaryl;RGBc1is each independently selected from deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -RGBc2, -ORGBc2, -SRGBc2, -S(O)RGBc2, -S(O)2RGBc2, -C(O)RGBc2, - C(O)ORGBc2, -OC(O)RGBC2, -N(RGBC2)(RGBC3), -C(O)N(RGBC2)(RGBC3), -N(RGBC2)C(O)RGBC3, -S(O)N(RGBC2)(RGBC3), -S(O)2N(RGBC2)(RGBC3), -N(RGBC2)S(O)RGBC3, -N(RGBC2)S(O)2RGBC3;RGBC2and RGBC3are each independently selected from hydrogen, deuterium, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14 aryl, and 5-12 membered heteroaryl, wherein the C1-6alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3- 10 cycloalkyl, 3-10 membered heterocyclyl, C6-14 aryl, or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14 aryl, and 5-12 membered heteroaryl;RGBdis each independently selected from hydrogen, deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -ORGBdl, -S(O)RGBdl, -S(O)2RGBdl, -C(O)RGBdl, - C(O)ORGBdl, -OC(O)RGBdl, -N(RGBdl)(RGBd2), -C(O)N(RGBdl)(RGBd2), -N(RGBdl)C(O)RGBd2, - S(O)N(RGBdl)(RGBd2), -S(O)2N(RGBdl)(RGBd2), -N(RGBdl)S(O)RGBd2, -N(RGBdl)S(O)2RGBd2, and optionally replaced by one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) RGBd3substituted with the following groups: Ci-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, or 5-12 membered heteroaryl;or two RGBd, together with the atoms to which they are attached, form 3-10 membered heterocyclyl, 3-7 membered cycloalkyl, or 5-12 membered heteroaryl, wherein the 3-10 membered heterocyclyl, 3-7 membered cycloalkyl, or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7, or 8) groups independently selected from deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, C1-6 alkoxy, C3- io cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, and 5-12 membered heteroaryl;RGBdland RGBd2are each independently selected from hydrogen, deuterium, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, and 5-12 membered heteroaryl, wherein the Ci-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-113316435300Docket No. 43658-02205 (EXAV-024 / 001WO)io cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, Ci-6 alkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, 3-6 membered heterocyclyl, phenyl, and 5-6 membered heteroaryl;RGBd3is each independently selected from hydrogen, deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -RGBd4, -ORGBd4, -SRGBd4, -S(O)RGBd4, -S(O)2RGBd4, - C(O)RGBd4, -C(O)ORGBd4, -OC(O)RGBd4, -N(RGBd4)(RGBd5), -C(O)N(RGBd4)(RGBd5), - N(RGBd4)C(O)RGBd5, -S(O)N(RGBd4)(RGBd5), -S(O)2N(RGBd4)(RGBd5), -N(RGBd4)S(O)RGBd5, and - N(RGBd4)S(O)2RGBd5;RGBd4and RGBd5are each independently selected from hydrogen, deuterium, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14 aryl, and 5-12 membered heteroaryl, wherein the C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3- 10 cycloalkyl, 3-10 membered heterocyclyl, C6-14 aryl, or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C’3-7 cycloalkyl, 3-7 membered heterocyclyl, phenyl, or 5-6 membered heteroaryl;RGBeis each independently selected from hydrogen, deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -ORGBel, -SRGBel, -S(O)RGBel, -S(O)2RGBel, -C(O)RGBel, -C(O)ORGBel, -OC(O)RGBel, -N(RGBel)(RGBe2), -C(O)N(RGBel)(RGBe2), -N(RGBel)C(O)RGBe2, - S(O)N(RGBel)(RGBe2), -S(O)2N(RGBel)(RGBe2), -N(RGBel)S(O)RGBe2, -N(RGBel)S(O)2RGBe2, - C(O)N(RGBel)S(O)2N(RGBel)(RGBe2), -C(O)N(RGBel)S(O)2RGBe2, -P(O)(RGBel)RGBe2, and optionally replaced by one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) RGBe3substituted with the following groups: C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, or 5-12 membered heteroaryl;or two RGBe, together with the atoms to which they are attached, form 3-10 membered heterocyclyl or 5-12 membered heteroaryl, wherein the 3-10 membered heterocyclyl or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) groups independently selected from deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, C1-6 alkoxy, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14 aryl, and 5-12 membered heteroaryl;114316435300Docket No. 43658-02205 (EXAV-024 / 001WO)RGBeland RGBe2are each independently selected from hydrogen, deuterium, Ci-6 alkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, and 5-12 membered heteroaryl, wherein the C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3- 10 cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from hydrogen, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, 3-6 membered heterocyclyl, phenyl, and 5-6 membered heteroaryl;RGBe3is each independently selected from hydrogen, deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -RGBe4, -ORGBe4, -SRGBe4, -S(O)RGBe4, -S(O)2RGBe4, - C(O)RGBe4, -C(O)ORGBe4, -OC(O)RGBe4, -N(RGBe4)(RGBe5), -C(O)N(RGBe4)(RGBe5), - N(RGBe4)C(O)RGBe5, -S(O)N(RGBe4)(RGBe5), -S(O)2N(RGBe4)(RGBe5), -N(RGBe4)S(O)RGBe5, - N(RGBe4)S(O)2RGBe5, -C(O)N(RGBe4)S(O)2N(RGBe4)(RGBe5), -C(O)N(RGBe4)S(O)2RGBe5, and - (O)(RGBe4)RGBe5;RGBe4and RGBe5are each independently selected from hydrogen, deuterium, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C’6-14 aryl, and 5-12 membered heteroaryl, wherein the C1-6 alkyl, Cue alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3- 10 cycloalkyl, 3-10 membered heterocyclyl, C6-14aryl, or 5-12 membered heteroaryl are optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, 3-7 membered heterocyclyl, phenyl, and 5-6 membered heteroaryl;RGB1and RGB2together with the atoms to which they are attached, form C3-15 carbocyclyl optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7, or 8) RGB3;RGB3is each independently selected from hydrogen, deuterium, halogen, hydroxyl, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C3-10 cycloalkyl, and 3-10 membered heterocyclyl, wherein the C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C3-10 cycloalkyl, or 3-10 membered heterocyclyl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from deuterium, halogen, hydroxyl, amino, cyano, oxo, C3-10 cycloalkyl, and 3-10 membered heterocyclyl;115316435300Docket No. 43658-02205 (EXAV-024 / 001WO)LGB1is selected from a bond, -C(RGBL1)2-, -O-, -C(RGBL1)2O-, -S-, -C(O)-, -C(O)O-, -OC(O)-, -N(RGBL1)C(O)-, -C(O)N(RGBL1)-, and -N(RGBL1)-;RGBL1is each independently selected from hydrogen, deuterium, Ci-6 alkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl, wherein the C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, or 3-10 membered heterocyclyl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from deuterium, halogen, hydroxyl, amino, nitro, mercapto, cyano, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl;LGB2 is selected from a bond, -C(RGBL2)2-, -O-, -C(RGBL2)2O-, -S-, -C(O)-, -C(O)O-, - OC(O)-, -N(RGBL2)C(O)-, -C(O)N(RGBL2)-, and -N(RGBL2)-;RGBL2are each independently selected from hydrogen, deuterium, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl, wherein the Ci-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, or 3-10 membered heterocyclyl are optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from deuterium, halogen, hydroxyl, amino, nitro, mercapto, cyano, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl;LGB3is selected from a bond, -C(RGBL3)2-, -O-, -S-, -C(O)-, -C(O)O-, -OC(O)-, - N(RGBL3)C(O)-, -C(O)N(RGBL3)-, and -N(RGBL3)-;RGBL3is each independently selected from hydrogen, deuterium, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl, wherein the Ci-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, or 3-10 membered heterocyclyl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from deuterium, halogen, hydroxyl, amino, nitro, mercapto, cyano, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl;LGB4is a bond, -LGB4x-C(RGBL4a)(RGBL4b)-LGB4y-, -LGB4x-O-LGB4y-, -LGB4x-S-LGB4y-, -LGB4x-C(O)-LGB4y-, -LGB4x-C(O)O-LGB4y-, -LGB4x-OC(O)-LGB4y-, -LGB4x-N(RGBL4a)C(O)-LGB4y-, -LGB4x-C(O)N(RGBL4a)-LGB4y-, -LGB4x-N(RGBL4a)-LGB4y-, -LGB4X -116316435300Docket No. 43658-02205 (EXAV-024 / 001WO)N(RGBL4a)C(O)N(RGBL4b)iGB4y„N(RGBL4a)C(S)N(RGBL4b)-LGB4y -, Of(RGBL4z)rGBLGB4X and LGB4y are each independently a bond or Ci-io alkylene, wherein the Ci-io alkylene is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from deuterium, halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl;RGBL4aand RGBL4bare each independently selected from hydrogen, deuterium, C1-6 alkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl, wherein the C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, or 3-10 membered heterocyclyl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from deuterium, halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, Ci-e alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 substituted by a cycloalkyl group or a 3-10 membered heterocyclyl;Ring LGB4Z is C3-15 carbocyclyl, 3-12 membered heterocyclyl, C6-14 aryl, or 5-12 membered heteroaryl;RGB4Zis each independently selected from hydrogen, deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl, wherein the C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, or 3-10 membered heterocyclyl are optionally substituted with one or more substituents independently selected from deuterium, halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, C1-6 alkyl, Ci-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl;LGBSX and LGBSV are each independently a bond or Ci-io alkylene, wherein the Ci-10 alkylene is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents independently selected from deuterium, halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C.3-io cycloalkyl, and 3-10 membered heterocyclyl;mGB, nGB, oGB, pGB, qGB, and rGB are each independently 0, 1, 2, or 3;117316435300Docket No. 43658-02205 (EXAV-024 / 001WO)unless otherwise specified, the heteroatoms in the above heterocyclyl and heteroaryl are independently selected from O, N or S, and the number of heteroatoms is 1, 2, 3 or 4; and wherein the definitions of the above variables are combined to form a stable chemical structure;A' is or a tautomer thereof;RAis selected from the group consisting of hydrogen, Ci-6 alkyl and (Ci-6 alkyl) carbonyl, wherein Ci-6 alkyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen and Ci-6 alkoxy;the counterion comprises an amine-containing polymer, a diamine or a conjugate thereof, a poly amine or a conjugate thereof, or M+;R"1i U L, i I wL-YAYrL2-RlWLI>^RIM+is RN2, RN2RN1and RN2are each independently hydrogen or C1-C30 alkyl;Yi, Y2, Yf, and Y2’ are each independently a bond, -O-, or -NH-;Li, L2, L3, Lj ’, and L2’ are each independently a bond, C1-C25 alkylene, or Ce-Cio arylene, wherein the alkylene and arylene are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6 alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or C1-C6 haloalkyl;118316435300Docket No. 43658-02205 (EXAV-024 / 001WO)Ri is C1-C30 alkyl, C2-C30 alkenyl, C6-C10 aryl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl, wherein the alkyl, alkenyl, aryl, heterocyclyl, and heteroaryl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6 alkyl, Ce-Cio aryl, C1-C6 alkoxy, Ci-Ce haloalkyl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl; andm is 0 or 1.

[0109] In some aspects, the present disclosure provides a salt comprising anion G-A-and a counterion, wherein:a stereoisomer thereof, or a tautomer thereof;XG is — N= or — CRaG=; RaGis selected from a hydrogen atom, a halogen atom, and Ci- 6 alkyl,YG is selected from — C(=O) —, — CHRG—, and — S(=O)2 —; RGis a hydrogen atom or Ci -6 alkyl,QGiis Ce-io aryl or 5 to 10 membered heteroaryl, wherein the Ce-io aryl and 5 to 10 membered heteroaryl are optionally substituted with one to five substituents independently selected from a halogen atom, C1-6 alkyl (wherein C1-6 alkyl is optionally substituted with one or more halogen atoms), C3-6 cycloalkyl, and C1-6 alkoxy;QG2is 3 to 12 membered heterocyclyl or 5 to 10 membered heteroaryl, wherein the 3 to 12 membered heterocyclyl and 5 to 10 membered heteroaryl are optionally substituted with one119316435300Docket No. 43658-02205 (EXAV-024 / 001WO)to three substituents independently selected from a halogen atom, Ci-6 alkyl (wherein Ci-6 alkyl is optionally substituted with one or more halogen atoms), Ci-6 alkoxy, and — NRGQaRGQb, and two Ci-6 alkyl groups together with a carbon atom to which they are attached may form C3- 8 carbocyclic ring; and RQaand RQbare independently selected from a hydrogen atom, Ci- 6 alkyl, and (C1-6 alkyl)carbonyl;Z3, Z4, Zs, Ze, Z”, Zs, Z9, Z10, Zu, Zi? and Zi< are each independently selected from the group consisting of N and C;RG1, RG, RG3, RGI, RG2’, and RG3are each independently selected from a hydrogen atom, halogen atom, C1-6 alkyl, C1-6 alkoxy, C 1-6 haloalkoxy, cycloalkyl, and heterocycloalkyl, wherein the Ci-6 alkyl, cycloalkyl, or heterocycloalkyl is optionally substituted by one or more substituents independently selected from a halogen atom, C1-6 alkoxy, and hydroxy; or RG2and RG3together with the carbon atom to which they are attached form 4- to 8-membered heterocycloalkyl;RG4, RG’ and RG6are independently selected from a hydrogen atom, a halogen atom, and CJ-6 alkyl;RG7and RG8are independently a hydrogen atom or C1-6 alkyl, wherein the C1-6 alkyl is optionally substituted with one or more substituents independently selected from a halogen atom and C3-15 cycloalkyl, or RG7and RG8together with a carbon atom to which they are attached may¬ form C3-15 cycloalkane ring, wherein the C3-15 cycloalkane ring formed by RG7and RG8together is optionally substituted with one to three C1-6 alkyl, wherein the C1-6 alkyl is optionally substituted with one or more substituents independently selected from a halogen atom, hydroxy, — NRG7aRG7b, C1-6 alkoxy, and 3 to 12 membered heterocyclyl, and RG7aand RG7bare independently selected from a hydrogen atom, C1-6 alkyl, and (C1-6 alkyl)carbonyl; and any two C1-6 alkyl optionally together with the carbon atom to which they are attached form C3-15 carbocyclic ring;nGl is an integer of 0 to 3; nG2 is an integer of 0 to 5; nG3 is 0 or 1;ZGlis selected from the group consisting of120316435300Docket No. 43658-02205 (EXAV-024 / 001WO)wherein Rzais selected from a hydrogen atom, Ci-6 alkyl, and (Ci-6 alkyl)carbonyl; Rzband Rzcare each independently a hydrogen atom or Ci-6 alkyl; n4 is an integer of 1 to 3; n5 and n6 are independently an integer of 0 to 10 (* represents a binding position with a pyrazolopyridine structure, and ** represents a binding position with ZG2);ZG2is selected from the group consisting of Ci-6 alkyl, C3-15 cycloalkyl, 3 to 12 membered heterocyclyl, C6-14 aryl, and 5 to 10 membered heteroaryl, wherein the C3-15 cycloalkyl, 3 to 12 membered heterocyclyl, C6-10 aryl, and 5 to 10 membered heteroaryl are optionally substituted with one to five substituents independently selected from Group A:Group A: a) oxo,b) a halogen atom,c) cyano,d) - NRzdRze; wherein Rzdand Rzeare independently selected from a hydrogen atom, Ci-6 alkyl and (Ci-6 alkyl)carbonyl, wherein Ci-6 alkyl is optionally- substituted with one or more substituents independently selected from hydroxy, a halogen atom and Ci-6 alkoxy,e) — C(=O) — NRzfRzg; wherein Rzfand Rzgare independently selected from a hydrogen atom, C1-6 alkyl and (C1-6 alkyl)carbonyl, wherein C1-6 alkyl is optionally substituted with one or more substituents independently selected from hydroxy, a halogen atom and C1-6 alkoxy,f) — S(=O)n7 — Rzh; wherein n7 is an integer of 0 to 2; and Rzhis a hydrogen atom or Ci-6 alkyl,g) C1-6 alkyl optionally substituted with one or more substituent independently selected from a halogen atom, hydroxy, — NRziRzj, C1-6 alkoxy, and 3 to 12 membered heterocyclyl, wherein Rziand Rzjare independently a hydrogen atom or121316435300Docket No. 43658-02205 (EXAV-024 / 001WO)Ci-6 alkyl, and wherein 3 to 12 membered heterocyclyl is optionally substituted with one or more substituents independently selected from hydroxy, Ci-6 alkyl and 3 to 12 membered heterocyclyl,h) Ci-6 alkoxy optionally substituted with one or more substituent independently selected from hydroxy, a halogen atom, and Ci-6 alkoxy,i) 3 to 12 membered heterocyclyl optionally substituted with one or more substituents independently selected from Ci-6 alkyl and (Ci-6alkyl)carbonyl, j) C6-io aryl optionally substituted with one or more (Ci-6 alkyl)carbonyl, k) 5 to 10 membered heteroaryl optionally substituted with one or more substituents independently selected from C1-6 alkyl, Ci-6 alkoxy, — NRzkRzl, and 3 to 12 membered heterocyclyl, wherein Rzkand Rzlare independently selected from a hydrogen atom, Ci-6 alkyl and (Ci-6 alkyl)carbonyl, and wherein 3 to 12 membered heterocyclyl is optionally substituted with one or more substituents independently selected from Ci-6 alkyl and (Ci-6 alkyl)carbonyl,l) — P(=O)(Rzm)(Rzn), wherein Rzmand Rznare each independently a hydrogen atom or C1-6alkyl;m) C3-C15 cycloalkyl optionally substituted with one or more substituents independently selected from the group consisting of halogen, oxo, C1-6 alkyl, C1-6 alkoxy and (C1-6 alkyl) carbonyl, wherein each of alkyl and alkoxy is optionally substituted with halogen; andn) C1-C6 alkyl-C3-C15 cycloalkyl wherein the cycloalkyl or alkyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, oxo, Ci-6 alkyl, Ci-6 alkoxy and (Ci-6 alkyl) carbonyl, wherein each of alkyl and alkoxy is optionally substituted with halogen;A" isNN O, R, or O, or a tautomer thereof;RAis selected from the group consisting of hydrogen, Ci-6 alkyl and (Ci-6 alkyl) carbonyl, wherein Ci-6 alkyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen and Ci-6 alkoxy;122316435300Docket No. 43658-02205 (EXAV-024 / 001WO)the counterion comprises an amine-containing polymer, a diamine or a conjugate thereof, a polyamine or a conjugate thereof, or Mh;RN1and RN2are each independently hydrogen or C1-C30 alkyl;Yi, Y?, Yi’, and Y ’ are each independently a bond, -O-, or -NH-;Li, L2, L3, Li’, and L2’ are each independently a bond, C1-C25 alkylene, or Ce-Cio arylene, wherein the alkylene and arylene are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl;Ri is C1-C30 alkyl, C2-C30 alkenyl, C6-C10 aryl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl, wherein the alkyl, alkenyl, aryl, heterocyclyl, and heteroaryl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, Ci-Ce haloalkyl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl; andm is 0 or 1.

[0110] In some aspects, the present disclosure provides a salt comprising anion G-A-and a counterion, wherein:316435300Docket No. 43658-02205 (EXAV-024 / 001WO)X is CH or N;each RP1is independently selected from H and Ci-Ce alkyl;RP2is H, Ci-Ce alkyl, C2-C6 alkenyl or C2-C6 alkynyl;each RP3is H; or the two RP3are taken together with the carbon atom to which they are connected to form a C3-C6 cycloalkyl optionally substituted with one or more halogen;RP4is Ce-Cio aryl or 5-15 membered heteroaryl, wherein the Ce-Cio aryl is optionally substituted with one or more substituents independently selected from halogen, Ci-Ce alkyl, - NH(Ci-Ce alkyl), and -P(=O)(Ci-Ce al kyl)2, and wherein the 5-15 membered heteroaryl is optionally substituted with one or more substituents independently selected from halogen, Ci-Ce alkyl, Ci-Cb deuteroalkyl, and C3-C6 cycloalkyl;each RP5is independently selected from H, Ci-Ce alkyl, and C3-C6 cycloalkyl;1A' is O or a tautomer thereof;the counterion is M+;124316435300Docket No. 43658-02205 (EXAV-024 / 001WO)RN1and RN2are each independently hydrogen or C1-C30 alkyl;Yi, Y2, Yi’, and Y2’ are each independently a bond, -O-, or -NH-;Li, L?, L3, Lj ’, and L2’ are each independently a bond, C1-C25 alkylene, or Ce-Cio arylene, wherein the alkylene and arylene are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6 alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl;Ri is C1-C30 alkyl, C2-C30 alkenyl, Ce-Cio aryl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl, wherein the alkyl, alkenyl, aryl, heterocyclyl, and heteroaryl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, Ci-Ce haloalkyl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl; andm is 0 or 1.

[0111] In some aspects, the present disclosure provides a salt comprising anion G-A' and a counterion, wherein:125316435300Docket No. 43658-02205 (EXAV-024 / 001WO)X is CH;RP2is H, C1-C6 alkyl, C2-C6 alkenyl or C2-C6 alkynyl;each RP3is independently selected from H, Ci-Ce alkyl, and C3-C6 cycloalkyl;A' isO or a tautomer thereof;the counterion is M+;126316435300Docket No. 43658-02205 (EXAV-024 / 001WO)RN1and RN2are each independently hydrogen or C1-C30 alkyl;Yi, Y2, Yi’, and Y2’ are each independently a bond, -O-, or -NH-;Li, L2, L3, Lf, and L2’ are each independently a bond, C1-C25 alkylene, or Ce-Cio arylene, wherein the alkylene and arylene are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl;Ri is C1-C30 alkyl, C2-C30 alkenyl, Ce-Cio aryl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl, wherein the alkyl, alkenyl, aryl, heterocyclyl, and heteroaryl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, C1-C6 haloalkyl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl; andm is 0 or 1,

[0112] In some aspects, the present disclosure provides a salt comprising anion G-A‘ and a counterion, wherein:127316435300Docket No. 43658-02205 (EXAV-024 / 001WO)X is CH;RP2is H, C1-C6alkyl, C2-C6alkenyl or C2-C6alkynyl;each RP3is independently selected from H, Ci-Ce alkyl, and C3-C6 cycloalkyl;A' isO or a tautomer thereof;the counterion is Mlr“ 1 J.. L, RN; 1 1’'vlYf 'R,eHN'1'Y'2'RiDN2 QN2MisKorK;RN1and RN2are each independently hydrogen or C1-C30 alkyl;Y1and Y2are each independently a bond, -O-, or -NH-; L1and L2are each independently a bond, C1-C25alkylene, or Ce-Cio arylene, wherein the alkylene and arylene are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6 alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl; andR1is C1-C30alkyl, C2-C30alkenyl, Ce-Cio aryl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl, wherein the alkyl, alkenyl, aryl, heterocyclyl, and heteroaryl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, Ci-Ce haloalkyl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl.

[0113] In some aspects, the present disclosure provides a salt comprising anion G-A‘ and a counterion, wherein:G is \ or a stereoisomer thereof;128316435300Docket No. 43658-02205 (EXAV-024 / 001WO)Nx|\|OA' is O or a tautomer thereof;the counterion is M+;r“ i?. L, Rt;;..™' ’'YAYZ 'R,eHN'1'Y'2'RiMisKorK;RN1and RN2are each independently hydrogen or C1-C30 alkyl;Y1and Y2are each independently a bond, -O-, or -NH-;Li and L2 are each independently a bond, C1-C25 alkylene, or Ce-Cio arylene, wherein the alkylene and arylene are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6 alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl; andRi is C1-C30 alkyl, C2-C30 alkenyl, Ce-Cio aryl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl, wherein the alkyl, alkenyl, aryl, heterocyclyl, and heteroaryl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, Ci-Ce haloalkyl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl.

[0114] In some aspects, the present disclosure provides a salt comprising anion G-A‘ and a129316435300Docket No. 43658-02205 (EXAV-024 / 001WO)130316435300Docket No. 43658-02205 (EXAV-024 / 001WO)JW I V N Al ®A' is O or a tautomer thereof;the counterion is M+;RN1and RN2are each independently hydrogen or C 1-C30 alkyl;Yi, Y2, Yi’, and Y2’ are each independent!}' a bond, -O-, or -NH-;Li, L2, L3, Li’, and L2’ are each independently a bond, C1-C25 alkylene, or Ce-Cio arylene, wherein the alkylene and arylene are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl;Ri is Ci-C30 alkyl, C2-C30 alkenyl, Ce-Cio aryl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl, wherein the alkyl, alkenyl, aryl, heterocyclyl, and heteroaryl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, C6-C10 aryl, Ci-Ce alkoxy, Ci-Ce haloalkyl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl; andm is 0 or 1.

[0115] In some aspects, the present disclosure provides a salt comprising anion G-A‘ and a counterion, wherein:131316435300Docket No. 43658-02205 (EXAV-024 / 001WO)316435300Docket No. 43658-02205 (EXAV-024 / 001WO)N^N®4A' is O or a tautomer thereof;the counterion is M+;RN1and RN2are each independently hydrogen or C1-C30 alkyl;Yi, Y2, Yf, and Y2’ are each independently a bond, -O-, or -NH-;Li, L2, L3, Li’, and L2’ are each independently a bond, C1-C25 alkylene, or Ce-Cio arylene, wherein the alkylene and arylene are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl;Ri is C1-C30 alkyl, C2-C30 alkenyl, Ce-Cio aryl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl, wherein the alkyl, alkenyl, aryl, heterocyclyl, and heteroaryl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, Ci-Ce haloalkyl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl; andm is 0 or 1.

[0116] In some aspects, the present disclosure provides a salt comprising anion G-A‘ and a counterion, wherein:133316435300Docket No. 43658-02205 (EXAV-024 / 001WO), a stereoisomer thereof, or a tautomer thereof;A’ is O or a tautomer thereof;the counterion is M⁺;134316435300Docket No. 43658-02205 (EXAV-024 / 001WO)RN1and RN2are each independently hydrogen or C1-C30 alkyl;Yi, Y2, Yi’, and Y2’ are each independently a bond, -O-, or -NH-;Li, L2, L3, Li’, and L2’ are each independently a bond, C1-C25 alkylene, or Ce-Cio arylene, wherein the alkylene and arylene are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl;Ri is C1-C30 alkyl, C2-C30 alkenyl, Ce-Cio aryl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl, wherein the alkyl, alkenyl, aryl, heterocyclyl, and heteroaryl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, C6-C10 aryl, Ci-Ce alkoxy, Ci-Ce haloalkyl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl; andm is 0 or 1.

[0117] In some aspects, the present disclosure provides a salt comprising anion G-A' and a counterion, wherein:G is \, a stereoisomer thereof, or a tautomer thereof;A" is O or a tautomer thereof; the counterion is M+;135316435300Docket No. 43658-02205 (EXAV-024 / 001WO)RN1and RN2are each independently hydrogen or C1-C30 alkyl;Yi, Y2, Yf, and Y2’ are each independently a bond, -O-, or -NH-;Li, L2, L3, Li’, and L2’ are each independently a bond, C1-C25 alkylene, or Ce-Cio arylene, wherein the alkylene and arylene are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl;Ri is C1-C30 alkyl, C2-C30 alkenyl, Ce-Cio aryl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl, wherein the alkyl, alkenyl, aryl, heterocyclyl, and heteroaryl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, C6-C10 aryl, Ci-Ce alkoxy, Ci-Ce haloalkyl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl; andm is 0 or 1.

[0118] In some aspects, the present disclosure provides a salt comprising anion G-A' and a counterion, wherein:136316435300Docket No. 43658-02205 (EXAV-024 / 001WO)XG is — N= or — CRaG=; RaGis selected from a hydrogen atom, a halogen atom, and Ci- 6 alkyl;YG is selected from — C(=O) -, CHRG—, and - -S(=O)2 - RGis a hydrogen atom or Ci-6 alkyl;QG1is C6-10 aryl or 5 to 10 membered heteroaryl, wherein the Ce-io aryl and 5 to 10 membered heteroaryl are optionally substituted with one to five substituents independently selected from a halogen atom, Ci-6 alkyl (wherein Ci-6 alkyl is optionally substituted with one or more halogen atoms), C3-6 cycloalkyl, and C1-6 alkoxy;QG2is 3 to 12 membered heterocyclyl or 5 to 10 membered heteroaryl, wherein the 3 to 12 membered heterocyclyl and 5 to 10 membered heteroaryl are optionally substituted with one to three substituents independently selected from a halogen atom, C1-6 alkyl (wherein C1-6 alkyl is optionally substituted with one or more halogen atoms), C1-6 alkoxy, and — NRGQaRGQb, and two Ci-6 alkyl groups together with a carbon atom to which they are attached may form C3- 8 carbocyclic ring; and RQaand RQbare independently selected from a hydrogen atom, Ci-6 alkyl, and (Ci-6 alkyl)carbonyl;Z3, Z4, Z5, Ze, Z7, Zs, Z9, Z10, Z11, Z12 and Z13 are each independently selected from the group consisting of N and C;137316435300Docket No. 43658-02205 (EXAV-024 / 001WO)RG1, RG2, RG3, RG1', RG2', and RG3'are each independently selected from a hydrogen atom, halogen atom, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 haloalkoxy, cycloalkyl, and heterocycloalkyl, wherein the Ci-6 alkyl, cycloalkyl, or heterocycloalkyl is optionally substituted by one or more substituents independently selected from a halogen atom, Ci-6 alkoxy, and hydroxy; or RG2and RG3together with the carbon atom to which they are attached form 4- to 8-membered heterocy cl oalky 1;RG4, RG5and RG6are independently selected from a hydrogen atom, a halogen atom, and Ci-6 alkyl;RG7and RG8are independently a hydrogen atom or Ci-6 alkyl, wherein the Ci-6 alkyl is optionally substituted with one or more substituents independently selected from a halogen atom and C3-15 cycloalkyl, or RG7and RG8together with a carbon atom to which they are attached may form C3-15 cycloalkane ring, wherein the C3-15 cycloalkane ring formed by RG7and RG8together is optionally substituted with one to three Ci-6 alkyl, wherein the Ci-6 alkyl is optionally substituted with one or more substituents independently selected from a halogen atom, hydroxy, ---NRG7aRG7b, Ci-6 alkoxy, and 3 to 12 membered heterocyclyl, and RG7aand RG7bare independently selected from a hydrogen atom, C1-6 alkyl, and (C1-6 alkyl)carbonyl; and any two C1-6 alkyl optionally together with the carbon atom to which they are attached form C3-15 carbocyclic ring;nGl is an integer of 0 to 3; nG2 is an integer of 0 to 5; nG3 is 0 or 1;ZG1is selected from the group consisting ofwherein Rzais selected from a hydrogen atom, C1-6 alkyl, and (C1-6 alkyl)carbonyl; Rzband Rzcare each independently a hydrogen atom or C1-6 alkyl; n4 is an integer of 1 to 3; n5 and n6 are independently an integer of 0 to 10 (* represents a binding position with a pyrazolopyridine structure, and ** represents a binding position with ZG2);138316435300Docket No. 43658-02205 (EXAV-024 / 001WO)ZG2is selected from the group consisting of Ci-6 alkyl, C3-15 cycloalkyl, 3 to 12 membered heterocyclyl, Ce-io aryl, and 5 to 10 membered heteroaryl, wherein the C3-15 cycloalkyl, 3 to 12 membered heterocyclyl, C6-10 aryl, and 5 to 10 membered heteroaryl are optionally substituted with one to five substituents independently selected from Group A:Group A a) oxo,b) a halogen atom,c) cyano,d) — NRzdRze; wherein Rzdand Rzeare independently selected from a hydrogen atom, C1-6 alkyl and (C1-6 alkyl)carbonyl, wherein C1-6 alkyl is optionally substituted with one or more substituents independently selected from hydroxy, a halogen atom and C1-6 alkoxy,e) — C(=O) — NRzfRzg; wherein Rzfand Rzgare independently selected from a hydrogen atom, Ci-6 alkyl and (Ci-6alkyl)carbonyl, wherein C1-6 alkyl is optionally substituted with one or more substituents independently selected from hydroxy, a halogen atom and Ci-6 alkoxy,f) - -S(=O)n7 - Rzh; wherein n7 is an integer of 0 to 2; and Rzhis a hydrogen atom or C i-6 alkyl,g) C1-6 alkyl optionally substituted with one or more substituent independently selected from a halogen atom, hydroxy, — NRziRzj, C1-6 alkoxy, and 3 to 12 membered heterocyclyl, wherein Rziand Rzjare independently a hydrogen atom or C1-6 alkyl, and wherein 3 to 12 membered heterocyclyl is optionally substituted with one or more substituents independently selected from hydroxy, Ci-6 alkyl and 3 to 12 membered heterocyclyl,h) C1-6 alkoxy optionally substituted with one or more substituent independently selected from hydroxy, a halogen atom, and C1-6 alkoxy,i) 3 to 12 membered heterocyclyl optionally substituted with one or more substituents independently selected from C1-6 alkyl and (C1-6 alkyl)carbonyl, j) C6-10 aryl optionally substituted with one or more (C1-6 alkyl)carbonyl, k) 5 to 10 membered heteroaryl optionally substituted with one or more substituents independently selected from C1-6 alkyl, C1-6 alkoxy, - -NRzkRzl, and 3 to 12 membered heterocyclyl, wherein Rzkand Rzlare independently selected from139316435300Docket No. 43658-02205 (EXAV-024 / 001WO)a hydrogen atom, Ci-6 alkyl and (Ci-6 alkyl)carbonyl, and wherein 3 to 12 membered heterocyclyl is optionally substituted with one or more substituents independently selected from Ci-6 alkyl and (Ci-6 alkyl)carbonyl,l) — P(=O)(Rzm)(Rzn), wherein Rzmand Rznare each independently a hydrogen atom or C1-6 alkyl;m) C3-C15 cycloalkyl optionally substituted with one or more substituents independently selected from the group consisting of halogen, oxo, C1-6 alkyl, Ci- 6 alkoxy and (C1-6 alkyl) carbonyl, wherein each of alkyl and alkoxy is optionally substituted with halogen; andn) C1-C6 alkyl-C3-C15 cycloalkyl wherein the cycloalkyl or alkyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, oxo, Ci-6 alkyl, Ci-6 alkoxy and (Ci-6 alkyl) carbonyl, wherein each of alkyl and alkoxy is optionally substituted with halogen;A' is or a tautomer thereof;RAis selected from the group consisting of hydrogen, Ci-6 alkyl and (Ci-6 alkyl) carbonyl, wherein C1-6 alkyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen and C1-6 alkoxy;the counterion comprises an amine-containing polymer, a diamine or a conjugate thereof, a poly amine or a conjugate thereof, or M+;Rx L< S R"1.Ri HNXLIRi© I1+RNM is RN22. orOR- A / L2^|XL2;L<N, R- (HNKY^Y2L3I RN2'RN2RN1and RN2are each independently hydrogen or C1-C30 alkyl;Yi, Y2, YI’, and Y2’ are each independently a bond, -O-, or -NH-;140316435300Docket No. 43658-02205 (EXAV-024 / 001WO)Li, L2, L3, Li’, and L2’ are each independently a bond, C1-C25 alkylene, or Ce-Cio arylene, wherein the alkylene and arylene are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, C6-C10 aryl, C1-C6 alkoxy, or Ci-Ce haloalkyl; andRi is C1-C30 alkyl, C2-C30 alkenyl, Ce-Cio aryl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl, wherein the alkyl, alkenyl, aryl, heterocyclyl, and heteroaryl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, C6-C10 aryl, Ci-Ce alkoxy, Ci-Ce haloalkyl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl.

[0119] In some aspects, the present disclosure provides a salt comprising anion G-A‘ and a counterion, wherein:141316435300Docket No. 43658-02205 (EXAV-024 / 001WO)stereoisomer thereof, or a tautomer thereof;the counterion is M⁺;142316435300Docket No. 43658-02205 (EXAV-024 / 001WO)I 1 Lo R1^ I IWL^YlAYf2-RiWL^L2-RIM+is RN2, RN2RN1and RN2are each independently hydrogen or C1-C25 alkyl;Yi, Y2, Yi’, and Y2’ are each independent!}' a bond, -O-, or -NH-;Li, L2, L3, Li’, and L2’ are each independently a bond, C1-C25 alkylene, or Ce-Cio arylene, wherein the alkylene and arylene are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl; andRi is Ci-C30 alkyl, C2-C30 alkenyl, Ce-Cio aryl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl, wherein the alkyl, alkenyl, aryl, heterocyclyl, and heteroaryl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, C6-C10 aryl, Ci-Ce alkoxy, Ci-Ce haloalkyl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl.

[0120] In some aspects, the present disclosure provides a salt comprising anion G-A‘ and a counterion, wherein:143316435300Docket No. 43658-02205 (EXAV-024 / 001WO)or a tautomer thereof;JW IVN^N®A' is O or a tautomer thereof;the counterion is M+;RN1and RN2are each independently hydrogen or C1-C25 alkyl;Yi, Y2, Yf, and Y2’ are each independently a bond, -O-, or -NH-;Li, L2, L3, Li’, and L2’ are each independently a bond, C1-C25 alkylene, or Ce-Cio arylene, wherein the alkylene and arylene are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl; and144316435300Docket No. 43658-02205 (EXAV-024 / 001WO)Ri is C1-C30 alkyl, C2-C30 alkenyl, C6-C10 aryl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl, wherein the alkyl, alkenyl, aryl, heterocyclyl, and heteroaryl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6 alkyl, Ce-Cio aryl, C1-C6 alkoxy, Ci-Ce haloalkyl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl.

[0121] In some aspects, the present disclosure provides a salt comprising anion G-A' and a counterion, wherein:, a stereoisomer thereof, or a tautomer thereof;N°A“ is O or a tautomer thereof;the counterion is M+;145316435300Docket No. 43658-02205 (EXAV-024 / 001WO)- IIL, Rx L L-R1WL-Y;L2-R1M+isrN2,rN2RN1and RN2are each independently hydrogen or C1-C25 alkyl;Yi, Y2, Yf, and Y2’ are each independently a bond, -O-, or -NH-;Li, L2, L3, Li’, and L2’ are each independently a bond, C1-C25 alkylene, or C6-C10 arylene, wherein the alkylene and arylene are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6 alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or C1-C6 haloalkyl; andRi is C1-C30 alkyl, C2-C30 alkenyl, Ce-Cio aryl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl, wherein the alkyl, alkenyl, aryl, heterocyclyl, and heteroaryl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6 alkyl, Ce-Cio aryl, C1-C6 alkoxy, Ci-Ce haloalkyl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl.

[0122] In some aspects, the present disclosure provides a salt comprising anion G-A-and a counterion, wherein:G is \, a stereoisomer thereof, or a tautomer thereof;A' is O or a tautomer thereof; the counterion is M+;146316435300Docket No. 43658-02205 (EXAV-024 / 001WO)R™ 1 1 L?R»1.HNAI^YI Y2RI HNAI© I1© I RiRN2M+is RN2OpN1A ^RN1’HN YI' N© IRN2RN2'RN1and RN2are each independently hydrogen or C1-C25 alkyl;YI, Y2, Yf, and Y2’ are each independently a bond, -O-, or -NH-;Li, L2, L3, Li’, and L2’ are each independently a bond, C1-C25 alkylene, or C6-C10 arylene, wherein the alkylene and arylene are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6 alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or C1-C6 haloalkyl; andRi is C1-C30 alkyl, C2-C30 alkenyl, Ce-Cio aryl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl, wherein the alkyl, alkenyl, aryl, heterocyclyl, and heteroaryl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6 alkyl, Ce-Cio aryl, C1-C6 alkoxy, Ci-Ce haloalkyl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl.

[0123] In some embodiments, the ratio of the anion to the counterion is 1:1. In some embodiments, the ratio of the anion to the counterion is 2:1.

[0124] In some embodiments. In some embodiments,147316435300Docket No. 43658-02205 (EXAV-024 / 001WO)

[0125] In some embodiments,. In some embodiments,

[0126] In some embodiments, each RP1is Ci-Ce alkyl. In some embodiments, each RP1is methyl.

[0127] In some embodiments, each RP2is Ci-Co alkyl. In some embodiments, each RP2is methyl.

[0128] In some embodiments, each RP3is hydrogen.

[0129] In some embodiments, RP4is 5-15 membered heteroaryl optionally substituted with one or more substituents independently selected from halogen, Ci-Ce alkyl, Ci-Ce deuteroalkyl, andC3-C6 cycloalkyl. In some embodiments,RP4is

[0130] In some embodiments, each RP5is Ci-Ce alkyl. In some embodiments, each RP5is methyl.

[0131] In some embodiments,G is \. In some embodiments, G is148316435300Docket No. 43658-02205 (EXAV-024 / 001WO)

[0132] In some embodiments, G is. In some embodiments, G

[0133] In some embodiments, G is149316435300Docket No. 43658-02205 (EXAV-024 / 001WO)

[0134] In some embodiments,G is. In some embodiments, G

[0135] In some embodiments, A’ isNN in some embodiments, A" is O. In some IN^N®embodiments, A’ isrAIn some embodiments,A' is O150316435300Docket No. 43658-02205 (EXAV-024 / 001WO)hr N®°~4

[0136] In some embodiments,A' is O or a tautomer thereof.

[0137] In some embodiments, the counterion comprises an amine-containing polymer, a diamine or a conjugate thereof, or a poly amine or a conjugate thereof. In some embodiments, the amine-containing polymer is polylysine. In some embodiments, the diamine or conjugate thereof is putrescine, cadaverine, agmatine, or 1,3 diaminopropane. In some embodiments, the polyamine or conjugate thereof is spermidine, spermine, thermospermine, caldine, sym-homospermidine, or thermine.

[0138] In some embodiments, the counterion comprises M+. In some embodiments, the counterion is Mrl JL L7HN'LI^YI Y2R1© In2

[0139] In some embodiments,AT isR. In some embodiments, M+is151316435300Docket No. 43658-02205 (EXAV-024 / 001WO)

[0141] In some embodiments, M+isA0, wherein n is 1 -27 and Rxis C1-30 alkyl.

[0143] In some embodiments, Yi is a bond. In some embodiments, Yi is -O-. In some embodiments, Yi is -NH-. In some embodiments, Yi is a bond or -O-. In some embodiments, Yi is a bond or -NH-. In some embodiments, Yi is -O- or -NH-.

[0144] In some embodiments, Yz is a bond. In some embodiments, Yz is -O-. In some embodiments, Yz is -NH-. In some embodiments, Yz is a bond or -O-. In some embodiments, Yz is a bond or -NH- In some embodiments, Yz is -O- or -NH-.152316435300Docket No. 43658-02205 (EXAV-024 / 001WO)

[0145] In some embodiments, Yi is a bond. In some embodiments, Yi is -O-. In some embodiments, Yi is -NH-. In some embodiments, Yi is a bond or -O-. In some embodiments, Yi is a bond or -NH-. In some embodiments, Yi is -O- or -NH-.

[0146] In some embodiments, Y2 is a bond. In some embodiments, Y2 is -O- In some embodiments, Y2 is -NH-. In some embodiments, Y2 is a bond or -O-. In some embodiments, Y2 is a bond or -NH- In some embodiments, Y2 is -O- or -NH-.

[0147] In some embodiments, Li is a bond.

[0148] In some embodiments, Li is C1-C25 alkylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl. In some embodiments, Li is C1-C25 alkylene optionally substituted with one or more halo, cyano, Ce-Cio aryl, or Ci-Ce alkoxy. In some embodiments, Li is linear C1-C25 alkylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6 alkyl, Ce-Cio aryl, C1-C6 alkoxy, or Ci-Ce haloalkyl. In some embodiments, Li is branched C1-C25 alkylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or C1-C6 haloalkyl. In some embodiments, Li is C1-C25 alkylene.

[0149] In some embodiments, Li is C1-C25 alkylene substituted with one Ce-Cio aryl. In some embodiments, Li is C1-C25 alkylene substituted with one phenyl.

[0150]

[0151] In some embodiments, Li is C15-C25 alkylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl. In some embodiments, Li is C15-C25 alkylene optionally substituted with one or more halo, cyano, C -C10 aryl, or Ci-Ce alkoxy. In some embodiments, Li is linear C15-C25 alkylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl. In some embodiments, Li is branched C15-C25 alkylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl.. In some embodiments, Li is C15-C25 alkylene.

[0152] In some embodiments, Li is C15-C25 alkylene substituted with one Ce-Cio aryl. In some embodiments, Li is C15-C25 alkylene substituted with one phenyl.

[0153] In some embodiments, Li is Ci-Ce alkylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl. In some embodiments, Li is C1-C6 alkylene optionally substituted with one or more halo, cyano,153316435300Docket No. 43658-02205 (EXAV-024 / 001WO)C6-Cio aryl, or C1-C6 alkoxy. In some embodiments, Li is linear Ci-Ce alkylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl. In some embodiments, Li is branched C1-C6 alkylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl.. In some embodiments, Li is Ci-C6 alkylene.

[0154] In some embodiments, Li is C1-C6 alkylene substituted with one C6-C10 aryl. In some embodiments, Li is Ci-Ce alkylene substituted with one phenyl.

[0155] In some embodiments, Li is Ce-Cio arylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl. In some embodiments, Li is Ce-Cio arylene optionally substituted with one or more halo, cyano, Ci-Ce alkyl, or Ci-Ce alkoxy. In some embodiments, Li is phenylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl. In some embodiments, Li is 1,2-phenylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl. In some embodiments, Li is 1,3 -phenylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl. In some embodiments, Li is 1,4-phenylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl. In some embodiments, Li is Ce-Cio arylene. In some embodiments, Li is phenylene.

[0156] In some embodiments, L2 is a bond.

[0157] In some embodiments, L2 is C1-C25 alkylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl. In some embodiments, L2 is C1-C25 alkylene optionally substituted with one or more halo, cyano, Ce-Cio aryl, or Ci-Ce alkoxy. In some embodiments, L2 is linear C1-C25 alkylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl. In some embodiments, L2 is branched C1-C25 alkylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl. In some embodiments, L2 is C1-C25 alkylene.

[0158] In some embodiments, L2 is C15-C25 alkylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl. In some embodiments, L2 is C15-C25 alkylene optionally substituted with one or more halo,154316435300Docket No. 43658-02205 (EXAV-024 / 001WO)cyano, C6-C10 aryl, or C1-C6 alkoxy. In some embodiments, L2 is linear C15-C25 alkylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl. In some embodiments, L2 is branched C15-C25 alkylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl.. In some embodiments, L2 is C15-C25 alkylene.

[0159] In some embodiments, L2 is C1-C6 alkylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl. In some embodiments, L2 is C1-C6 alkylene optionally substituted with one or more halo, cyano, C6-C10 aryl, or Ci-Ce alkoxy. In some embodiments, L2 is linear Ci-Ce alkylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, C6-C10 aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl. In some embodiments, L2 is branched Ci-Ce alkylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6 alkyl, Ce-Cio aryl, C1-C6 alkoxy, or Ci-Ce haloalkyl. In some embodiments, L2 is C1-C6 alkylene.

[0160] In some embodiments, L2 is Ce-Cio arylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, C6-C10 aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl. In some embodiments, L2 is Ce-Cio arylene optionally substituted with one or more halo, cyano, Ci-Ce alkyl, or C1-C6 alkoxy. In some embodiments, L2 is phenylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl. In some embodiments, L2 is 1,2-phenylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl. In some embodiments, L2 is 1,3 -phenylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or C1-C6 haloalkyl. In some embodiments, L2 is 1,4-phenylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6 alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl. In some embodiments, L2 is Ce-Cio arylene. In some embodiments, L2 is phenylene.

[0161] In some embodiments, L3 is a bond.

[0162] In some embodiments, L3 is C1-C25 alkylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, C6-C10 aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl. In some embodiments, L3 is C1-C25 alkylene optionally substituted with one or more halo, cyano, C6-Cio aryl, or Ci-Ce alkoxy. In some embodiments, L3 is linear C1-C25 alkylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6 alkyl, Ce-Cio aryl, C1-C6155316435300Docket No. 43658-02205 (EXAV-024 / 001WO)alkoxy, or C1-C6 haloalkyl. In some embodiments, L3 is branched C1-C25 alkylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl. In some embodiments, L3 is C1-C25 alkylene.

[0163] In some embodiments, L3 is C15-C25 alkylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, C6-C10 aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl. In some embodiments, L3 is C15-C25 alkylene optionally substituted with one or more halo, cyano, Ce-Cio aryl, or Ci-Ce alkoxy. In some embodiments, L3 is linear C15-C25 alkylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl. In some embodiments, L3 is branched C15-C25 alkylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, C6-C10 aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl,. In some embodiments, L3 is C15-C25 alkylene.

[0164] In some embodiments, L3 is C1-C6 alkylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or C1-C6 haloalkyl. In some embodiments, L3 is Ci-Ce alkylene optionally substituted with one or more halo, cyano, Ce-Cio aryl, or Ci-Ce alkoxy. In some embodiments, L3 is linear Ci-Ce alkylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl. In some embodiments, L3 is branched C1-C6 alkylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or C1-C6 haloalkyl. In some embodiments, L3 is C1-C6 alkylene.

[0165] In some embodiments, L3 is Ce-Cio arylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6 alkyl, Ce-Cio aryl, C1-C6 alkoxy, or C1-C6 haloalkyl. In some embodiments, L3 is C6-C10 arylene optionally substituted with one or more halo, cyano, Ci- Ce alkyl, or Ci-Ce alkoxy. In some embodiments, L3 is phenylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl. In some embodiments, L3 is 1,2-phenylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl. In some embodiments, L3 is 1,3-phenylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl. In some embodiments, L3 is 1,4-phenylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl. In some embodiments, L3 is C6-Cio arylene. In some embodiments, L3 is phenylene.156316435300Docket No. 43658-02205 (EXAV-024 / 001WO)

[0166] In some embodiments, Ri is C1-C30 alkyl optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Cs alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl. In some embodiments, Ri is C1-C30 alkyl optionally substituted with one or more halo, hydroxyl, cyano, amino, halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl. In some embodiments, Ri is C1-C30 alkyl optionally substituted with one or more halo or Ce-Cio aryl. In some embodiments, Ri is C10-C30 alkyl optionally substituted with one or more halo, hydroxyl, cyano, amino, halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl. In some embodiments, Ri is C10-C30 alkyl optionally- substituted with one or more halo, hydroxyl, cyano, amino, halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl. In some embodiments, Ri is C10-C30 alkyl optionally substituted with one or more halo or Ce-Cio aryl. In some embodiments, Ri is C1-C30 alkyl. In some embodiments, Ri is C10-C30 alkyl.

[0167] In some embodiments, Ri is C1-C20 alkyl optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl. In some embodiments, Ri is C1-C20 alkyl optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl. In some embodiments, Ri is C1-C20 alkyl optionally substituted with one or more halo or C6-C10 aryl. In some embodiments, Ri is C10-C20 alkyl optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6 alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or C1-C6 haloalkyl. In some embodiments, Ri is C10-C20 alkyl optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, C6-C10 aryl, C1-C6 alkoxy, or Ci-Ce haloalkyl. In some embodiments, Ri is C10-C20 alkyl optionally substituted with one or more halo or C6-C10 aryl. In some embodiments, Ri is C1-C20 alkyl. In some embodiments, Ri is C10-C20 alkyl.

[0168] In some embodiments, Ri is C15-C25 alkyl. In some embodiments, Ri is Cis alkyl.

[0169] In some embodiments, Ri is C2-C30 alkenyl optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6 alkyl, Ce-Cio aryl, C1-C6 alkoxy, or C1-C6 haloalkyl.

[0170] In some embodiments, Ri is C2-C20 alkenyl optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, C6-C10 aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl.

[0171] In some embodiments, Ri is C10-C30 alkenyl optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl.157316435300Docket No. 43658-02205 (EXAV-024 / 001WO)

[0172] In some embodiments, Ri is Ce-Cio aryl optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Cs alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl. In some embodiments, Ri is Ce-Cio aryl optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ci-Ce alkoxy, or Ci-Ce haloalkyl. In some embodiments, Ri is Ce-Cio aryl optionally substituted with one or more Ci-Ce alkyl, Ci-Ce alkoxy, or Ci-Ce haloalkyl. In some embodiments, Ri is phenyl optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl. In some embodiments, Ri is phenyl optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ci-Ce alkoxy, or Ci-Ce haloalkyl. In some embodiments, Ri is phenyl optionally substituted with one or more Ci-Ce alkyl, Ci-Ce alkoxy, or Ci-Ce haloalkyl.

[0173] In some embodiments, the salt is selected from the salts described in Tables 1-11, tautomers thereof, and stereoisomers thereof.

[0174] In some embodiments, the salt is selected from the salts described in Tables 1-11 and stereoisomers thereof.

[0175] In some embodiments, the salt is selected from the salts described in Tables 1-11.

[0176] In some embodiments, the salt is selected from the salts described in Tables 1-8, tautomers thereof, and stereoisomers thereof.

[0177] In some embodiments, the salt is selected from the salts described in Tables 1-8 and stereoisomers thereof.

[0178] In some embodiments, the salt is selected from the salts described in Tables 1-8.

[0179] In some embodiments, the salt is selected from the salts described in Table 1, tautomers thereof, and stereoisomers thereof.

[0180] In some embodiments, the salt is selected from the salts described in Table 1 and stereoisomers thereof.

[0181] In some embodiments, the salt is selected from the salts described in Table 1.

[0182] In some embodiments, the salt is selected from the salts described in Table 2, tautomers thereof, and stereoisomers thereof.

[0183] In some embodiments, the salt is selected from the salts described in Table 2 and stereoisomers thereof.

[0184] In some embodiments, the salt is selected from the salts described in Table 2.158316435300Docket No. 43658-02205 (EXAV-024 / 001WO)

[0185] In some embodiments, the salt is selected from the salts described in Table 3, tautomers thereof, and stereoisomers thereof.

[0186] In some embodiments, the salt is selected from the salts described in Table 3 and stereoisomers thereof.

[0187] In some embodiments, the salt is selected from the salts described in Table 3.

[0188] In some embodiments, the salt is selected from the salts described in Table 4, tautomers thereof, and stereoisomers thereof.

[0189] In some embodiments, the salt is selected from the salts described in Table 4 and stereoisomers thereof.

[0190] In some embodiments, the salt is selected from the salts described in Table 4.

[0191] In some embodiments, the salt is selected from the salts described in Table 5, tautomers thereof, and stereoisomers thereof.

[0192] In some embodiments, the salt is selected from the salts described in Table 5 and stereoisomers thereof.

[0193] In some embodiments, the salt is selected from the salts described in Table 5.

[0194] In some embodiments, the salt is selected from the salts described in Table 6, tautomers thereof, and stereoisomers thereof.

[0195] In some embodiments, the salt is selected from the salts described in Table 6 and stereoisomers thereof.

[0196] In some embodiments, the salt is selected from the salts described in Table 6.

[0197] In some embodiments, the salt is selected from the salts described in Table 7, tautomers thereof, and stereoisomers thereof.

[0198] In some embodiments, the salt is selected from the salts described in Table 7 and stereoisomers thereof.

[0199] In some embodiments, the salt is selected from the salts described in Table 7.

[0200] In some embodiments, the salt is selected from the salts described in Table 8, tautomers thereof, and stereoisomers thereof.

[0201] In some embodiments, the salt is selected from the salts described in Table 8 and stereoisomers thereof.

[0202] In some embodiments, the salt is selected from the salts described in Table 8.159316435300Docket No. 43658-02205 (EXAV-024 / 001WO)

[0203] In some embodiments, the salt is selected from the salts described in Table 9, tautomers thereof, and stereoisomers thereof.

[0204] In some embodiments, the salt is selected from the salts described in Table 9 and stereoisomers thereof.

[0205] In some embodiments, the salt is selected from the salts described in Table 9.

[0206] In some embodiments, the salt is selected from the salts described in Table 10, tautomers thereof, and stereoisomers thereof.

[0207] In some embodiments, the salt is selected from the salts described in Table 10 and stereoisomers thereof.

[0208] In some embodiments, the salt is selected from the salts described in Table 10.

[0209] In some embodiments, the salt is selected from the salts described in Table 11, tautomers thereof, and stereoisomers thereof.

[0210] In some embodiments, the salt is selected from the salts described in Table 11 and stereoisomers thereof.

[0211] In some embodiments, the salt is selected from the salts described in Table 11.160316435300Docket No. 43658-02205 (EXAV-024 / 001WO)Table 1CompoundNo. StructureCompounds I-1 through I-29 have the structurewherein Rxis defined as follows.RX=1-11-2RX=?£XX1-3 Rx= Yx / x1-4 Rx=1-5 Rx=1-6RX=1-7 Rx=1-8RX=1-9RX=1-10RX=,\^xX\XX^X^XX1-11RX=1-12 RX= ^\zX / ZVN / XNZ1-13RX=1-14RX=1-15RX=1-16RX=?i^^^x / X^^^X / X^^^X / 1-17RX= Y^^X^X^^XX^X^^^W^XR1-18X=161316435300Docket No. 43658-02205 (EXAV-024 / 001WO)1-19 Rx=1-20 Rx=1-211-22RX=1-23 Rx=1-24 Rx= ^X / X^ / N^ / XZNXZNXZNXZ1-25 RX=1-26 Rx=1-27 RX= ^X^ / X / XN / X / XXXXN / X^ / NX 1-28 Rx=1-29 Rx= \^^^^X^X^X^^^^^^X^X^X^^^^^^X Compounds I-30 through I-58 have the structure0—4-X^X^N z— / M lhK xCQVV° ' <NY° F^■N>^ / xo-NI\H=N-AC. Rx5wherein Rxis defined as follows.Rx= yx1-301-31 Rx=1-32 Rx= Y^^x1-33 Rx=1-34 RX= yx / ^ / x1-35RX= ^yXXZ1-36 Rx=1-37 Rx= ^X / \^ / \ / RX= ^\ / \^X1-38 / \162316435300Docket No. 43658-02205 (EXAV-024 / 001WO)1-39 RX= Yx^x^x^x^xx1-40 Rx=1-41RX=1-42 Rx= ^x / x / x / x / x^X1-43RX=1-44 Rx=1-45 Rx=1-46RX=1-47 Rx=1-48 RX=1-49RX=1-50RX=1-51RX=1-52RX=1-53RX=,\^^X^^^^X^X^X^X^X^^X^X / 1-54RX=1-55RX=1-56rx= ^j^^xx^x / ^^^x^x^x^x^x^x^^^x / x / ^ 1-571-58Compounds 1-59 through 1-87 have the structureo— Z- Z z^x^NM 1 iF0 L o i N^° 'N^X\7 4 1 fo=^ H Y FN 1°^N £n k IrI \ N©1 fi 'H2NXJ<. Rxwherein Rxis defined as follows.163316435300Docket No. 43658-02205 (EXAV-024 / 001WO)Rx= Yx1-591-60RX=?£X^1-61 Rx= ^X / X1-62 Rx=1-63 Rx=1-64RX=1-65 Rx=1-66 Rx=1-67RX=1-68RX= \^^X^\^X^XX1-69 Rx=1-70RX=1-71RX=1-72RX= ^X / N^X / N / X / X / XZ1-73RX=1-74 RX= yx^x / ^ / x^x / ^ / x^x / 1-75RX= )^xz\Z\ZX / X / NZXZ\Z\1-76RX= >!^X^^^X^X^^^X^^^X^X / 1-77 Rx=1-78RX=1-79RX=,\X^^X^X^\^^X^X^X1-80RX=1-81RX=1-82 Rx=1-83rx=1-84RX= ^j^^x / X / ^^X / X^^^X^X^X^X^X^X / 1-85 Rx= ^X^ / X / XN / S / X / NZ^X / X^ / N^ 1-86RX=1-87RX= \^^^^X^X^X^^^^^^^X^X^X^^^^^^^XCompounds 1-88 through 1-116 have the structure164316435300Docket No. 43658-02205 (EXAV-024 / 001WO)3 OS' o II rAII \® 3 ()±OZ / .X 3 \ / / 'T / w i / 10Z— < \ / \- ^ ' 'f^ " T'T— ✓ r •J \ O a=-.x\^N / r~LI ZNY FX. JC^\. R:<efined as follows.Rx=1-881-89 Rx=1-90 Rx=1-91 RX=1-92 RX=1-93RX=1-94 Rx= X^^X / ^ / X1-95 Rx=1-96RX=1-97 Rx=1-98 Rx=1-99RX=I-100RX=1-101RX=1-102RX=1-103RX=1-104RX=1-105RX=1-106RX=1-107165316435300Docket No. 43658-02205 (EXAV-024 / 001WO)1-108RX=1-109 Rx=1-110 Rx= X^^XX / ^XX / ^XX / ^XX / ^XX / ^XX1-111 Rx=1-112 Rx=1-113 RX= ^XX / X / XN / X / S / XNX / XZ'XX 1-114 Rx= \^^^XX^XXX^X\XXX^^X 1-115 Rx= \^^X^X^X^XX^^X / X^X^X^XX^ / X^XX 1-116 Rx=Compounds I-117 through I-145 have the structure0—\X\X / rV1 | N— f V- FX / N^^^X \ — / N''S i,NY° FX^N'X^Xb-N=Xx AT^N\ / \ZCxRxwherein Rxis defined as follows.Rx=1-1171-118 Rx=1-119 Rx= ^^Xx^\1-120 RX=1-121 RX=1-122RX=1-123 Rx= X^^X / ^ / X1-124 Rx=1-125RX=1-126RX=1-127RX=1-128RX=1-129RX=166316435300Docket No. 43658-02205 (EXAV-024 / 001WO) 1-130 RX=1-131 Rx=1-132 RX=1-133 Rx=1-134 Rx= \^X^X^^^^^X^X1-135 Rx=1-136 Rx=1-137 Rx=1-138 Rx=1-139 Rx=1-140 Rx= ^^^XX^XX^XX^X^XX^XX^XX^XX1-141 Rx=1-142 Rx=: T^ / X / \XXXXX^\^^^^^^X / 1-143 Rx= yx^^^^ / X^^ / x / ^ / ^ / X / ^ / ^ / X / ^ / X 1-144 Rx=1-145 Rx= \^^^^X^Xz^X^^^^^X^X^Xz^X^^^^^^X Compounds I-146 through I-174 have the structure0Z / XJN zrVl\K CNCQ^Q^0 / NY FkX^NH3N ©^ 2 \C zRxwherein Rxis defined as follows.Rx= ^x.1-1461-147 Rx= \^x / 1-148 Rx= Y^^X1-149 Rx=Rx= )1-150 ^x / \167316435300Docket No. 43658-02205 (EXAV-024 / 001WO)1-151RX=1-152 Rx=1-153 Rx=1-154RX=1-155 Rx=1-156 Rx=1-157RX= ^XX / ZV / X / ZW1-158RX=1-159RX=1-160RX=1-161RX=1-162RX=1-163RX=1-164RX=1-165 Rx=1-166 Rx=1-167RX=1-168RX=1-169RX=1-170rx=1-1711-172RX=1-1731-174RX= \^^^^X^X^X^^^^^^^X^X^X^^^^^^^XCompounds 1-175 through 1-203 have the structure168316435300Docket No. 43658-02205 (EXAV-024 / 001WO)M l 1 | N— f Y— FNS = / NY ° <o-( Y YVN=NH2II \xRxwherein Rxis defined as follows.Rx=1-1751-176 Rx=1-177 Rx=1-178 Rx=1-179 Rx=1-180RX=1-181 Rx=1-182 Rx=1-183RX=1-184 RX=1-185 Rx=1-186RX=1-187RX=1-188RX= )ifX^X^X^X^^^^^^^1-189RX=1-190RX=1-191RX=1-192RX=1-193RX=1-194RX= ^^z-^x / x^^zx / XXXz^^x / 1-195RX=1-196169316435300Docket No. 43658-02205 (EXAV-024 / 001WO)170316435300Docket No. 43658-02205 (EXAV-024 / 001WO)I-218 Rx=I-219 Rx=I-220 Rx=I-221 Rx=I-222 Rx=I-223 Rx=I-224 Rx=I-225 Rx=I-226I-227 Rx=I-228I-229 Rx=I-230 Rx= I-231 Rx=I-232 Rx=o — e- / \x X^X-N / r~L MX M^'N<>FJx(z0 a< 'f fo^ il Y ^N\^xUPN10'I-233171316435300Docket No. 43658-02205 (EXAV-024 / 001WO)316435300Docket No. 43658-02205 (EXAV-024 / 001WO)173316435300Docket No. 43658-02205 (EXAV-024 / 001WO)174316435300Docket No. 43658-02205 (EXAV-024 / 001WO)1-321through I- 3471-348through I- 3741-375through I- 401175316435300Docket No. 43658-02205 (EXAV-024 / 001WO)1-402°— 4- through I- 430Z / F~CM 1 J X / NNHN V" ■,° -? Y° FXo=< il Y VN. JcrN £M k ITI \ Ni” L o° wherein Rxis a linear C2-C30alkyl, respectively1-431through I- ° \- 459Z / F~CI J, L W / F°N A0‘ 1 N° Fo=< il Y°"N £T k I / ITA N.\’’ L Q0wherein Rxis a linear C2-C30alkyl, respectively176316435300Docket No. 43658-02205 (EXAV-024 / 001WO)177316435300Docket No. 43658-02205 (EXAV-024 / 001WO)178316435300Docket No. 43658-02205 (EXAV-024 / 001WO)1-576°— e- through I- 604V0 1X fo=< H Y MNMXR * N N X*n0 wherein Rxis a linear C2-C30alkyl, respectively1-605through I- °— (—633C / “ AX X < CFo=< 1 YO? Nr^N \RXHN u HJNi-^ZY0 wherein Rxis a linear C2-C30alkyl, respectively179316435300Docket No. 43658-02205 (EXAV-024 / 001WO)1-634through I- 6621-663through I- 691RV0^^n © i0 wherein Rxis a linear C2-C30alkyl, respectively180316435300Docket No. 43658-02205 (EXAV-024 / 001WO)1-692through I- 720wherein Rxis a linear C2-C30Table 2CompoundNo. StructureCompounds II- 1 through 11-29 have the...

Claims

Docket No. 43658-02205 (EXAV-024 / 001WO)CLAIMSWhat is claimed is:

1. A salt comprising anion G-A' and a counterion, wherein:X is CH orN;each RP1is independently selected from H and Ci-Ce alkyl;RP2is H, C1-C6 alkyl, C2-C6 alkenyl or C2-C6 alkynyl;each RP3is H; or the two RP3are taken together with the carbon atom to which they are connected to form a C3-C6 cycloalkyl optionally substituted with one or more halogen;RP4is Ce-Cio aryl or 5-15 membered heteroaryl, wherein the Ce-Cio aryl is optionally substituted with one or more substituents independently selected from halogen, Ci-Ce alkyl, - NH(Ci-Ce alkyl), and -P(=O)(Ci-C6 alkyl)2, and wherein the 5-15 membered heteroaryl is optionally substituted with one or more substituents independently selected from halogen, Ci-Ce alkyl, C1-C6 deuteroalkyl, and C3-C6 cycloalkyl;each RP5is independently selected from H, Ci-Ce alkyl, and C3-C6 cycloalkyl;Docket No. 43658-02205 (EXAV-024 / 001WO)A' isO or a tautomer thereof;the counterion is M+;RN1and RN2are each independently hydrogen or C1-C30 alkyl;Yi, Y2, Yi’, and Y2’ are each independently a bond, -O-, or -NH-;Li, L2, L3, Li’, and L2’ are each independently a bond, C1-C25 alkylene, or Ce-Cio arylene, wherein the alkylene and arylene are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6 alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl;Ri is C1-C30 alkyl, C2-C30 alkenyl, Ce-Cio aryl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl, wherein the alkyl, alkenyl, aryl, heterocyclyl, and heteroaryl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, Ci-Ce haloalkyl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl; andm is 0 or 1.The salt of claim 1, wherein:Docket No. 43658-02205 (EXAV-024 / 001WO)Docket No. 43658-02205 (EXAV-024 / 001WO)I\r N®A' is 0 or a tautomer thereof; the counterion is M+;Docket No. 43658-02205 (EXAV-024 / 001WO)RN1and RN2are each independently hydrogen or C1-C30 alkyl;Yi, Y2, Yf, and Y2’ are each independently a bond, -O-, or -NH-;Li, L2, L3, Li’, and L2’ are each independently a bond, C1-C25 alkylene, or Ce-Cio arylene, wherein the alkylene and arylene are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl;Ri is C1-C30 alkyl, C2-C30 alkenyl, Ce-Cio aryl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl, wherein the alkyl, alkenyl, aryl, heterocyclyl, and heteroaryl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, Ci-Ce haloalkyl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl; andm is 0 or 1.Docket No. 43658-02205 (EXAV-024 / 001WO)4. The salt of any one of claims 1-3, wherein Gis stereoisomer thereof, or a tautomer thereof.RN1. HNAI© I The salt of any one of claims 1-4, wherein M isRN2or I I@HN'1'Y,'2-R,RN2Li 1 RI © I RN216. The salt of any one of claims 1-5, whereinisDocket No. 43658-02205 (EXAV-024 / 001WO)7. The salt of any one of claims 1-6, wherein Yi is a bond.

8. The salt of any one of claims 1-7, wherein Y is O.

9. The salt of any one of claims 1-8, wherein Ri is C1-C30 alkyl.

10. The salt of any one of claims 1-9, wherein RN1and RN2are both hydrogen.

11. The salt of any one of claims 1-10, wherein Li is C1-C25 alkylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6 alkyl, Ce-Cio aryl, C1-C6 alkoxy, or Ci-Ce haloalkyl.

12. The salt of any one of claims 1-11, wherein Li is C1-C25 alkylene optionally substituted with one Cs-Cio aryl.

13. The salt of any one of claims 1-12, wherein the salt is selected from the salts described in Table 1, stereoisomers thereof, and tautomers thereof.

14. The salt of any one of claims 1-13, wherein the salt is selected from a salt described in Table 1 and stereoisomers thereof.

15. The salt of any one of claims 1-14, wherein the salt is selected from a salt described in Table 1.

16. A pharmaceutical composition comprising the salt of any one of claims 1-15, a stereoisomer thereof, or a tautomer thereof, and a pharmaceutically acceptable diluent or carrier.

17. The pharmaceutical composition of claim 16, wherein the salt is selected from a salt described in Table 1.Docket No. 43658-02205 (EXAV-024 / 001WO)18. A method of treating or preventing a disease or disorder in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the salt or pharmaceutical composition of any one of claims 1-17.

19. A salt or pharmaceutical composition of any one of claims 1-17 for use in treating or preventing a disease or disorder.

20. Use of a compound or pharmaceutical composition of any one of claims 1-17 in the manufacture of a medicament for treating or preventing a disease or disorder.

21. The method, salt, pharmaceutical composition, or use of any one of claims 18-20, wherein the disease or disorder is selected from:i) obesity;ii) type 2 diabetes;iii) sleep apnea;i v) cardiovascular disease;v) polycystic ovary syndrome;vi) depression;vii) substance use disorder;viii) heart failure; andix) metabolic dysfunction-associated steatohepatitis (MASH).

Images