Analogs of heterocyclic GLP1 receptor agonists and uses thereof

Abstract

The present application provides compounds, and pharmaceutically acceptable salts thereof, that may be used as GLP1 receptor agonists. Also provided are pharmaceutical compositions containing such compounds, or pharmaceutically acceptable salts thereof. Methods of preparing these compounds and compositions, and methods of using these compounds and compositions to treat or prevent a disease or a condition mediated by GLP1, are also provided.

Description

43658-02201 AVO (EX AV-023 / 001 WO)ANALOGS OF HETEROCYCLIC GLP1 RECEPTOR AGONISTS AND USES THEREOFRELATED APPLICATIONS

[0001] This application is a PCT International Patent Application claiming the benefit of and priority to U. S. Provisional Application Nos. 63 / 761,402 filed February 21, 2025, 63 / 779,519 filed March 28, 2025, 63 / 811,121 filed May 23, 2025, 63 / 910,390 filed November 3, 2025, and 63 / 955,579 filed January 7, 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 analogs and / or prodrugs 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 analogs and / or prodrugs of heterocyclic GLP1 receptor agonists like orforglipron, as well as pharmaceutical compositions comprising these analogs and / or prodrugs. Without wishing to be bound by theory, the compounds and pharmaceutical compositions provided herein allow for sustained-release of heterocyclic GLP1 receptor agonists like orforglipron over extended time periods. Accordingly, the compounds 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 compound of Formula (I):G-A (I),a stereoisomer thereof, a tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein:Gis:43658-02201 AVO (EX AV-023 / 001 WO)|G2RG7"^ I ^(CH2)nG2R^8\, a stereoisomer thereof, or a tautomer thereof;XG IS - -N= or CR:—. RaGis selected from a hydrogen atom, a halogen atom, and Cj- 6 alkyl;YG is selected from — C(=O) —, — CHRG—, and — S(=O)2 —; RGis a hydrogen atom or Ci-6 alkyl;QG1IS C6-IO aryl or 5 to 10 membered heteroaryl, wherein the Cg-io aryl and 5 to 10 membered heteroaryl are optionally substituted with one to five substituents independently selected from a halogen atom, Ci^ alkyl (wherein Ci-6 alkyl is optionally substituted with one or more halogen atoms), C -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 C1-6 alkyl groups together with a carbon atom to which they are attached may form C3- s carbocyclic ring; and RGQaand RGQbare independently selected from a hydrogen atom, Cn 6 alkyl, and (C1-6 alkyl) carbonyl;Z3, Z4, Z5, Z6, Z7, Z5, Z9, Z10, Zj 1, Zi2 and Z13 are each independently selected from the group consisting of N and C;43658-02201 / WO (EXAV-023 / 001 WO)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 heterocycloalkyl;RG4, RG5and RG6are independently selected from a hydrogen atom, a halogen atom, and Ci-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 C3-15cycloalkane 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, Ci-6 alkoxy, and 3 to 12 membered heterocyclyl, and RG7aand RG7bare independently selected from a hydrogen atom, C1-6 alkyl, and (Ci-6alkyl)carbonyl; and any two Ci -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);43658-02201 AVO (EX AV-023 / 001 WO)ZG2is selected from the group consisting of Ci-6 alkyl, C3-15 cycloalkyl, 3 to 12 membered heterocyclyl, Cg-io aryl, and 5 to 10 membered heteroaryl, wherein the C3-15 cycloalkyl, 3 to 12 membered heterocyclyl, Ce-ioaryl, 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 (Cj-6alkyl)carbonyl, wherein Ci -6 alkyl is optionally substituted with one or more substituents independently selected from hydroxy, a halogen atom and Cj-6 alkoxy,e) —C(=O)—NRzfRzg; wherein Rzfand Rzgare independently selected from a hydrogen atom, C1-6 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 Cj-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) Ci-6alkyl optionally substituted with one or more substituent independently selected from a halogen atom, hydroxy, —NRziRzj, Ci-6alkoxy, and 3 to 12 membered heterocyclyl, wherein Rziand Rzjare independently a hydrogen atom or 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-6 alkyl)carbonyl, j) C6-10aryl optionally substituted with one or more (C1-6alkyl)carbonyl, k) 5 to 10 membered heteroaryl optionally substituted with one or more substituents independently selected from C1-6alkyl, C1-6alkoxy, —NRzkRzl, and 3 to 12 membered heterocyclyl, wherein Rzkand Rzlare independently selected from43658-02201 / WO (EXAV-023 / 001 WO)a hydrogen atom, Ci-6 alkyl and (C 1-6 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, Ci-6 alkyl, Ci- 6 alkoxy and (C1-6 alkyl) carbonyl, wherein each of alkyl and alkoxy is optionally substituted with halogen; andn) C1-C6alkyl-C3-C15cycloalkyl wherein the cycloalkyl or alkyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, oxo, C1-6alkyl, Ci-6 alkoxy and (Ci-6 alkyl) carbonyl, wherein each of alkyl and alkoxy is optionally substituted with halogen;(11)RGA13wherein:RA131S se|eC ecj 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, and 5-10 membered heteroaryl, wherein the amino, Ci-6 alkyl, Ci-6 deuterated alkyl, Ci-6 halogenated alkyl, Ci-6 deuterated43658-02201 / WO (EXAV-023 / 001 WO)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, Co-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, Ci-6 hydroxyalkyl, Ci-e deuterated hydroxyalkyl, C1-6 sulfanyl, C1-6 deuterated sulfanyl, Ci-6 alkoxy, C1-6 deuterated alkoxy, Ci-e halogenated alkoxy, Ct-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-U cycloalkyl, 3-14 membered heterocyclyl, Ce-14 aryl, 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, Ce-14 aryl, or 5-14 membered heteroaryl is optionally further substituted by deuterium, halogen, amino, nitro, hydroxyl, cyano, oxo, thiol, thio, Ci-6 alkyl, Cue deuterated alkyl, Cue halogenated alkyl, Ci-6 deuterated haloalkyl, C 1-6 hydroxyalkyl, Ci-6 deuterated hydroxyalkyl, Ci-6 sulfanyl, Ci-6 deuterated sulfanyl, Ci-6 alkoxy, Ci-6 deuterated alkoxy, Ci-6 haloalkoxy or Ci-6 deuterated haloalkoxy substituted by one or more substituents;Ring DAIS selected from C3-12 cycloalkyl, 3-12 membered heterocyclyl, Ce-14 aryl, and 5-14 membered heteroaryl;Ring EGAis selected from C3-14 cycloalkyl, 3-14 membered heterocyclyl, Ce-14 aryl, and 5-14 membered heteroaryl, wherein the C3-14 cycloalkyl, 3-14 membered heterocyclyl, Ce-14 aryl, or 5-14 membered heteroaryl is 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, C3-8 cycloalkyl, 3-8 membered heterocyclyl, Ce-io aryl, or 5-10 membered heteroaryl substituted by one or more substituents;43658-02201 / WO (EXAV-023 / 001 WO)alternatively, rmgEGAoptionally substituted with one or more substituents selected from the group consisting of methyl, ethyl, methoxy, and ethoxy;RGA1, RGA3, RGA4, RGA5, RGA6, RGA7, RGA8, RO, RGA14, RGA15, and RGA16are each independently 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, Cj-6 sulfanyl, Ct-6 deuterated sulfanyl, Cj-6 alkoxy, Ci -6 deuterated alkoxy, Cue 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)MGAIORGAC1, and (=C)RGAc3RGAc4, wherein the amino, C1-6 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, Cj-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, Cue alkyl, Ci-6 deuterated alkyl, Ci-6 halogenated alkyl, Ci-6 deuterated haloalkyl, Ci-6 hydroxyalkyl, Ci-6 deuterated hydroxyalkyl, Cj-6 sulfanyl, Ci-6 deuterated sulfanyl, Cj-6 alkoxy, Cue deuterated alkoxy, Ci-6 halogenated alkoxy, Ci-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-8 Cycloalkyl, 3-8 membered heterocyclyl, Cg-ioaryl, or 5-10 membered heteroaryl substituted by one or more substituents;RGAcl, ]^OAe3,an(j gGAc4areinc[epenc|entiy 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, Cn 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, CAio aryl, 5-10 membered heteroaryl, -(CH2)mGA2ORGAc2, -(CH2)mGA3C(O)NRGAalRGAbl, and -(CH2)mGA4C(O)ORGAa2, wherein the amino, Ci-6alkyl, Ci-6deuterated alkyl, Ci-6 halogenated alkyl, Ci-6 deuterated haloalkyl, Ci-6 hydroxyalkyl, Ci-643658-02201 / WO (EXAV-023 / 001 WO)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- s 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, Ci-6 halogenated alkyl, Ci-6 deuterated haloalkyl, Ci-6 hydroxyalkyl, C1-6 deuterated hydroxyalkyl, Ci-6 sulfanyl, Ci-6 deuterated sulfanyl, C1-6 alkoxy, Ci-6 deuterated alkoxy, Ci-6 halogenated alkoxy, Ci-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, ('3.8 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, Ci-6 alkyl, Ci-6 deuterated alkyl, Ci-6 halogenated alkyl, Cj-6 deuterated haloalkyl, Ci-6 hydroxyalkyl, Ci-6 deuterated hydroxyalkyl, Cj-6 sulfanyl, Ci-6 deuterated sulfanyl, Cj-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, wherein the amino, Ci-6 alkyl, Cj-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, or 5-10 membered heteroaryl is optionally further substituted by deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, 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, 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 RGA1', RGA4and RGA5, RGA5and RGA6, RGA7and RGA8, together with the atoms connected to them, form C3-10 cycloalkyl, 3-10 membered heterocyclyl, Ce-12 aryl,43658-02201 AVO (EX AV-023 / 001 WO)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-e 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; andnGA, nGAl, mGAl, mGA2, mGA3, and mGA4 are each independently selected from 0, 1, 2, 3, 4 or 5;(iii)(RGBa)mGB (RGBb)nGB (RGBC)OGB (RGBd)pGB( AGBj LGB1(RGBe)qGB wherein:Ring AGBis selected from C3-15 carbocyclyl, 3-12 membered heterocyclyl, Ce-14 aryl, 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, C -14 aryl, and 5-12 membered heteroaryl;Ring EGBIS selected from C3-15 carbocyclyl, 3-12 membered heterocyclyl, Cg-w aryl, and 5-12 membered heteroaryl;each RBais independently selected from hydrogen, deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -ORGBal, -S(O)RGBal, -SO2(RGBa!),-C(O)RGBal, -C(O)ORGBa!, - ()C(O)RGBai-N(RGBai)(RGBa2-C(O)N(R GBa 1 ^> GBa2, -N(RGBal)C(())RGBa2, -43658-02201 / WO (EXAV-023 / 001 WO)S(O)N(RGBa,)(RGBa2), -SO2N(RGBal)(RGBa2), -N(RGBa,)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) RGBajsubstituted 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, Co-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, Ci-6 alkyl, Ci-6 alkoxy, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C - 14 aryl, or 5-12 membered heteroaryl;RGBaland RGBaare 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, Ce-14 aryl, and 5-12 membered heteroaryl, wherein the Ci-6 alkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3- 10 cycloalkyl, 3-10 membered heterocyclyl, CVu aryl, or 5-12 membered heteroaiyl 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, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, a 3-6 membered heterocyclyl, phenyl, or 5-6 membered heteroaryl; each RBa3is independently selected from hydrogen, deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -RGBa4, -ORGBa4, -SRGBa4, -S(())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, Ci-6 alkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, Ce-14 aryl, and 5-12 membered heteroaryl, wherein the Ci-6 alkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, Ce-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, C3-7 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, C2-643658-02201 / WO (EXAV-023 / 001 WO)alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, Ce-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, Ce-14 aryl, or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) RGBb1;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, Ce-14 aryl, and 5-12 membered heteroaryl;RGBb1is 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(())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, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, Ce-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, Cg-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, Ce-14 aryl, and 5-12 membered heteroaryl;RBcis 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,alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, Ce-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, Ce-14 aryl, or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) RGBc1;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) groups43658-02201 / WO (EXAV-023 / 001 WO)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;RGBC1is each independently selected from deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -RGBe2, -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, Ce-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, Ce-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, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, Ce-14 aryl, and 5-12 membered heteroaryl;RGBdis each independently selected from hydrogen, deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -ORGBdl, -S(O)RGBd1, -S(O)2RGBd1, -C(O)RGBdl, -C(O)ORGBd1, -OC(O)RGBdl, -N(RGBdl)(RGBd2), -C(O)N(RGBd1)(RGBd2), -N(RGBdl)C(O)RGBd2S(O)N(RGBdl)(RGBd2), -S(O)2N(RGBd1)(RGBd2), -N(RGBd1)S(O)RGBd2, -N(RGBd1)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: C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, Ce-14 aryl, 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- 10 cycloalkyl, 3-10 membered heterocyclyl, Ce-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, Ce-14 aryl, and 5-12 membered heteroaryl, wherein the C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-43658-02201 / WO (EXAV-023 / 001 WO)io cycloalkyl, 3-10 membered heterocyclyl, Ce-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, C3-6 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, Ce-14 aryl, and 5-12 membered heteroaryl, wherein the Ci-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 from 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, or 5-6 membered heteroaryl;RBeis each independently selected from hydrogen, deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -ORGBei, -SRGBe1, -S(O)RGBe1, -S(O)2RGBe1, -C(O)RGBel, -C(O)ORGBel, -OC(O)RGBe1, -N(RGBel)(RGBe2), -C(O)N(RGBel)(RGBe2), -N(RGBel)C(O)RGBe2, -S(O)N(RGBel)(RGBe2), -S(O)2N(RGBe1)(RGBe2), -N(RGBe1)S(O)RGBe2, -N(RGBe1)S(O)2RGBe2, -C(O)N(RGBei)S(O)2N(RGBel)(RGBe2), -C(O)N(RGBe!)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: Ci-6 alkyl, Ci-6 alkoxy, Ci-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, Ce-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 5-12 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, Ci-6 alkoxy, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14 aryl, and 5-12 membered heteroaryl;43658-02201 / WO (EXAV-023 / 001 WO)RGBe1and RGBe2are 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, C6-14 aryl, and 5-12 membered heteroaryl, wherein the Ci-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 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, Ci-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, C6-14 aryl, 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, Ci-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, 3-7 membered heterocyclyl, phenyl, and 5-6 membered heteroaryl;RRGB1and 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, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 alkylamino, C3-10 cycloalkyl, and 3-10 membered heterocyclyl, wherein the Ci-6 alkyl, Ci-6 alkoxy, Ci-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;43658-02201 / WO (EXAV-023 / 001 WO)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 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;LGB2is 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 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 Ci-6 alkyl, Ci-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, Ci-6 alkyl, C1-6 alkoxy, Ci-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)-;RGBL3isindependently 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 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, Ci-6 alkyl, Ci-6 alkoxy, Ci-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-OLGB4y-, -LGB4x-SLGB4y-, -LGB4x-C(O)-LGB4y-, -LGB4x-C(O)OLGB4y-, -LGB4x-OC(O)-LGB4y-, -LGB4x-N(RGBL4a)C(O)-LGB4y-, -LGB4x-C(O)N(RGBL4a)-LGB4y-, -LGB4x-N(RGBL4a)-LGB4y-,43658-02201 / WO (EXAV-023 / 001 WO)-N(RGBL4a)C(O)N(RGBL4b)-LGB4y-, -LGB4x-(RGBL4z)rGB- L, Qg4"j ^-GB4z? ®~GB4yLGB4xand LGB4yare each independently a bond or C1-10 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, 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, 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, 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 LGB4Z is C3-15 carbocyclyl, 3-12 membered heterocyclyl, Ce-14 aryl, 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, Ci-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl;LGB5xand LGB5yare 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) substituents independently selected from deuterium, halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, Ci-6 alkyl, Ci-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl;43658-02201 / WO (EXAV-023 / 001 WO)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)wherein: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- 10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-10 cycloalkyl, C3-iocycloalkyl-Ci-4 alkyl, heterocyclyl, heterocyclyl-Ci-4 alkyl, aryl, aryl-Ci-4 alkyl, heteroaryl, heteroaryl-C 1-4 alkyl, — CN, — NO2, — NRGCA1RGCB1, — ORGCA1, — C(O)RGCA1, — C(O)ORGCA1, — OC(O)RGCA1, — C(O)NRGCA1RGCB1, — NRGCA1C(O)RGCB1, — OC(O)NRGCA1RGCB1, — S(O)RGCA1, — S(O)2ORGCA1, —OS(O)2RGCA1, -NR^’SCOW'R^1, — S(O)rGcNRGCA1RGCB1, — P(O)RGCA1RGCB1, and — P(O)(ORGCA1)(ORGCB1), w'herein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is unsubstituted or substituted independently with at least one RGCX1;43658-02201 / WO (EXAV-023 / 001 WO)each RGC2is independently selected from the group consisting of hydrogen, halogen, Ci- 10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-10 cycloalkyl, C3-iocycloalkyl-Ci-4 alkyl, heterocyclyl, heterocyclyl-Ci-4 alkyl, aryl, aryl-Ci-4 alkyl, heteroaryl, heteroaryl-C 1-4 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(0WRGCA2, — P(O)RGCA2RGCB2, — SiOjrGcNR^R^132, 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-C1-4 alkyl, heterocyclyl, heterocyclyl-C1-4 alkyl, aryl, aryl-Ci-4 alkyl, heteroaryl, heteroaryl-C 1-4 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 RGC' ‘’; ortwo RGC3, together with the atom(s) to which they are attached, form a C3-] 0 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 Ci-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-Ci-4 alkyl, heteroaryl, heteroaryl-C 1-4 alkyl, — CN, — NO2, —— 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;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 Cj-3 alkyl; or43658-02201 / WO (EXAV-023 / 001 WO)RGC9and 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 afragment, 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;” js asingle bond or a double bond; orRGC8and 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 Cj-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 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, Ci-io alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-10 cycloalkyl, C3-iocycloalkyl-Ci-4 alkyl, heterocyclyl, heterocyclyl-C 1-4 alkyl, aryl, aryl-Ci-43658-02201 / WO (EXAV-023 / 001 WO)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 “R00-42and RGCB2„OR«RGCA3AND RGCB3^TOGETHER WLTH SINGLE ORmultiple 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, Ci-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)wherein:LGD1is selected from -CO-, -SO-, -SO2-, -NRGDa- and -CRGDaRGDb-43658-02201 / WO (EXAV-023 / 001 WO)§ ^GDL^^ TGDLGD2is selected from,®GD, -RGDL-NRGDa -RGDL-CO- NRGDa-*, -RGDL -NRGDa-CO-NRGDa-*, -RGDL" C(S)-NRGDa-*, -RGDL -NRGDa-C(S)-N GDa"*, 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, NRoDaRoDb C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, Ci-6 alkylthio, Ci-6 haloalkyl, Ci-e cyanoalkyl, C1-6 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 attach ed 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, Ci-6 alkoxy, Ci-6 alkylthio, Ci-6 deuterated alkyl, Ci-6 haloalkyl, Ci-6 cyanoalkyl and Cj-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, NRoDaRoDb, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 alkoxy, Ci-6 alkylthio, Ci- 6 haloalkyl, Ci-6 cyanoalkyl, Ci-6 hydroxyalkyl, (C3-10 cycloalkyl)-RGDL-, (5-10 membered heterocyclic alkyl)-RGDL-, (Ce-io aryl)-RGDL, and (5-10 membered heteroaiyl)-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 Ci-6 alkoxy;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, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, (Ci-6 alkoxy)-RGDL-, (Ci-6 alkylthio)-RGDL-, Ci-6 alkoxy-Ci-6 alkoxy-, Ci-6 deuterated alkyl, Ci-6 haloalkyl, Ci-6 cyanoalkyl, Ci-6 hydroxyalkyl, Ci-6 alkyl, Ci-6 halogenated alkyl, COOH, -CONH2, -CONH(CI-6 alkyl), -43658-02201 / WO (EXAV-023 / 001 WO)o fO-^-ORGDaC(=S)NH2, -C(=S)NH(CI-6 alkyl), -P(RGDa)( GDb), -PH(Ci-6 alkyl)(Ci-6alkyl), ^ReDb, Ci-6 alkyl-CO-, (Ci-6 haloalkoxy)-RGDL-(C3-io 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)-RcDL-, (Ce-io aryl)-RGDL-> (Ce-io aryloxy)-RGDL-, (Ce-io aryl-Cn6 (alkyleneoxy)-RGDL-, (5-10 membered heteroaryl)-RGDL-, (5-10-membered heteroaryloxy)- GDL-, N GDS GDI -(CRGDaRGDb)mGD-, N oDa cDb-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 haloalky 1, 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, NRoDaRcDb, Cn 6 alkyl, C2-6 alkenyl, Cue deuterated alkyl, Cue haloalkyl, Ci-6 cyanoalkyl, C1-6 hydroxyalkyl, Cn 6 alkoxy, Cue alkylthio, Ci-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, NRoDaRoDb, Ci-6 alkyl, C2-6 alkenyl, Ci-6 alkoxy, Ci-6 alkylthio, Ci-6 haloalkyl, Ci-6 halogenated alkoxy, optionally substituted with one or more substituents selected from Ci-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-io cycloalkyl), -S(0)-(C3-io cycloalkyl), - S(0)2-(C3-io cycloalkyl), -S(=0)(=NRGDa)-(C3-io 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 rmg is optionally substituted with a substituent selected from the following: halogen, oxo, N oDaRGDb)-RGDL-, Ci-6 alkyl, Ci-6 deuterated alkyl, Ci-6 haloalkyl, Cj.6 cyanoalkyl, Ci-6 hydroxyalkyl, (Ci-6 alkoxy)-RGDL-, (Ci-6 alkylthio)-RGDL-, (C3-10 cycloalkyl optionally substituted with one or more halogens, Ci-6 alkyl or Ci-6 alkoxy)-RGDL- (3-1043658-02201 / WO (EXAV-023 / 001 WO)membered heterocyclic alkyl optionally substituted with one or more halogen, Ci-6 alkyl, or Ci-6 haloalkyl)-RoDL-, and (Ce-io aryl)-RoDL 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;RGDPIS each independently halogen, cyano, hydroxyl, NH2, C1-6 alkyl, or absent;RoDa and RoDb is each independently H or C1-6 alkyl;RGDS and RG» are each independently H, C1-6 alkyl, C1-6 haloalkyl, C6-10 aryl, or 5-10 membered heteroaryl;RGDL is each independently a bond; Ci-to alkylene optionally substituted with halogen, cyano, or hydroxyl; or C1-4 deuterated alkylene;TGD is C1-4 alkylene, C2-4 alkylidene, 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;Yi, Y2, Y3, Y4, Ys, Y6, and Y7 are each independently a bond, -O-, or -NH-;Li, L2, and L3 are each independently a bond, -O-, C1-C25 alkylene, 3-12 membered heterocyclylene, or Ce-Cio arylene, wherein the alkylene, heterocyclylene, and arylene are43658-02201 / WO (EXAV-023 / 001 WO)optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Cg alkyl, Cg-Cio aryl, Ci-Cg alkoxy, or Ci-Ce haloalkyl;Ri, R2, R3, and R4 are each independently Ci-Ceo alkyl, C2-C30 alkenyl, Cg-Cio aryl, or 3-15 membered heterocyclyl, wherein the alkyl, alkenyl, aryl, and heterocyclyl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Cg-Cio aryl, Ci-C30 alkoxy, -O-(Cj-C6 alkylene)-(C6-Cio aryl), -N(RN), or Ci-Cg haloalkyl;RN is each independently H, C1-C30 alkyl or C6-C10 aryl; andRp is C1-C20 alkyl or Cg-Cio aryl, wherein the alkyl and aryl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Cg alkyl, Ci-Ce alkoxy, or Ci-Ce haloalkyl.

[0004] In some aspects, the present disclosure provides a compound of Formula (I):G-A (I),a stereoisomer thereof, a tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein:G is:RG5R®2R1RG2RG4 R®5X „. Q®2\. / y,,x. Q62N- N-YG-{.NQ- (CH2UZG2 ’ ■ J XKH, RG7" / 'X(CH2U2RGR- 1(i) orRRG2 RG4 RG5G1 RGrQG212'Z^ XZ5Z7-2Z8 N--YG--Z11H iL Z. W -R® X"13xf XROSZ10 RG3QG1(CH2)nG1ZG1RG7I '"(CH2')nG2ZG2Rd8 \\, a stereoisomer thereof, or a tautomer thereof;XGis —N= or —CRaG=; RaGis selected from a hydrogen atom, a halogen atom, and Cj.6 alkyl;43658-02201 / WO (EXAV-023 / 001 WO)YG is selected from — C(=O) —, — CHR° —, and — S(=O)2 —; RGis a hydrogen atom or Ci-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), 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), Cj-6 alkoxy, and — NR^R*3^, and two C1-6 alkyl groups together with a carbon atom to which they are attached may form C3- 8 carbocyclic ring; and RGQand RGQbare independently selected from a hydrogen atom, Cn 6 alkyl, and (Ci-6 alkyl)carbonyl;Z3, Z4, Z5, Zg, Z7, Z5, Z9, Z10, Zu, Z12 and Z13 are each independently selected from the group consisting of N and C;1, R2, R ’, R1, RG2, and R3are each independently selected from a hydrogen atom, halogen atom, Cj -6 alkyl, C1-6 alkoxy, C1-6 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 RGtogether with the carbon atom to which they are attached form 4- to 8-membered heterocycloalkyl;RG4, RG5and R°6are independently selected from a hydrogen atom, a halogen atom, and C1-6 alkyl;RG7and R°8are 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, w’herein 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, — NRG / aRG7b, C1-6 alkoxy, and 3 to 12 membered heterocyclyl, and RG / aand RG / bare independently43658-02201 AVO (EX AV-023 / 001 WO)selected from a hydrogen atom, Ci-6 alkyl, and (Ci-6alkyl)carbonyl; and any two Ci-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 pyrazolopyndine structure, and ** represents a binding position with ZG2);ZG2is selected from the group consisting of C1-6 alkyl, C3-15 cycloalkyl, 3 to 12 membered heterocyclyl, Cg-io aryl, and 5 to 10 membered heteroaryl, wherein the C3-15 cycloalkyl, 3 to 12 membered heterocyclyl, Ce-ioaryl, 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 (Ci-6 alky l)car bony 1, wherein Ci^ 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, C1-6 alkyl and (Ci-ealkyl)carbonyl, wherein C1-6 alkyl is optionally substituted with one or more substituents independently selected from hydroxy, a halogen atom and C1-6 alkoxy,43658-02201 / WO (EXAV-023 / 001 WO)f) — S(=0)n7 — Rzh; wherein n7 is an integer of 0 to 2; and Rzhis a hydrogen atom or Ci-6 alkyl,g) Ci-6 alkyl optionally substituted with one or more substituent independently selected from a halogen atom, hydroxy, — NRZ1RZ', Ci-e alkoxy, and 3 to 12 membered heterocyclyl, w’herein RZ1and RZJare independently a hydrogen atom or 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 Cj-6 alkoxy,i) 3 to 12 membered heterocyclyl optionally substituted with one or more substituents independently selected from Ci-6 alkyl and (Ci-6 alkyl)carbonyl, j) Ce-ioaryl 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, - -NRzkRzi, and 3 to 12 membered heterocyclyl, wherein Rzkand Rzlare independently selected from a hydrogen atom, Cj.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-6alkyl)carbonyl,l) — P(=O)(Rzm)(Rz”), 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, Ci-6 alkyl, Ci- 6 alkoxy and (Ci-6 alkyl) carbonyl, wherein each of alkyl and alkoxy is optionally substituted with halogen; andn) Ci-Ce lkyl-Cs-Cis 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;(11)43658-02201 / WO (EXAV-023 / 001 WO)wherein:RA13is 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, 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, C1-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-8 Cycloalkyl, 3-8 membered heterocyclyl, Co-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, Ci-6 hydroxyalkyl, Ci-e deuterated hydroxyalkyl, C1-6 sulfanyl, C1-6 deuterated sulfanyl, Ci-6 alkoxy, Ci-6 deuterated alkoxy, Ci-e 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;LGA1, LGA2, and LGA3are each independently selected from a bond, C2-4 alkenylene, C2-4 alkynylidene and -(CH2)nGAi -;Ring AGAis selected from C3-U cycloalkyl, 3-14 membered heterocyclyl, Ce-14 aryl, 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, Ce-14 aryl,43658-02201 / WO (EXAV-023 / 001 WO)or 5-14 membered heteroaryl is optionally further substituted by deuterium, halogen, amino, nitro, hydroxyl, cyano, oxo, thiol, 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 haloalkoxy or Ci-6 deuterated haloalkoxy substituted by one or more substituents;Ring DGAis selected from C3-12 cycloalkyl, 3-12 membered heterocyclyl, Ce-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, Ce-14 aryl, 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, Cj-6 halogenated alkyl, Cj-6 deuterated haloalkyl, C1-6 hydroxyalkyl, Ci-6 deuterated hydroxy alkyl, Ci-6 sulfanyl, C1-6 deuterated sulfanyl, Ci-6 alkoxy, C 1 -6 deuterated alkoxy, Ci-6 halogenated alkoxy, Ci-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;alternatively, ringEGAis ‘ ’ 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 RGA16are each independently 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)mGAiORGAc!, and (=C)RGAc3RGAc4, wherein the amino, Ci-6 alkyl, Ci-6 deuterated alkyl, Cn 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 membered43658-02201 / WO (EXAV-023 / 001 WO)heterocyclyl, Ce-io aryl, 5-10 membered heteroaryl, ~(CH2)mGAiORGAcl, or (=C)RGACJRGAC4is optionally further substituted with 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-ioaryl, or 5-10 membered heteroaryl substituted by one or more substituents;RGAci, RGAC3, and RGAc4are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, thio, C1-6 alkyl, Ct-6 deuterated alkyl, Ct-6 halogenated alkyl, Ci-6 deuterated haloalkyl, Ci-6 hydroxyalkyl, Cue deuterated hydroxyalkyl, Ci- 6 sulfanyl, C1-6 deuterated sulfanyl, C1-6 alkoxy, C1-6 deuterated alkoxy. Cue 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)mGA2ORGAc2, - (CH2)mGA3C(O)NRGAalRGAbl, and -(CH2)mGA4C(O)ORGAa2, wherein the amino, Ci-6alkyl, Ci-6deuterated 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)mGA2ORGAc2, -(CH2)mGA3C(O)NRGAalRGAbl, or -(CH2)mGA4C(O)ORGAa2is optionally further substituted with 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, 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, 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, Co-10 aryl or 5-10 membered heteroaryl, wherein the amino, Ci-6 alkyl, Ci-643658-02201 / WO (EXAV-023 / 001 WO)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, C6-10 aryl, or 5-10 membered heteroaryl is optionally further substituted by deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, Ci-6 alkyl, Ci-6 deuterated alkyl, Ci-6 halogenated alkyl, Ci-6 deuterated haloalkyl, Ci-6 hydroxyalkyl, Ci-6 deuterated hydroxyalkyl, Ci-e sulfanyl, Ci-6 deuterated sulfanyl, C1-6 alkoxy, Ci-6 deuterated alkoxy, Ci-6 halogenated alkoxy, Ci-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C.i.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, Co-12 aryl or 5-12 membered heteroaryl;or, when nGA is not 1,RGA1and RGA1', RGA2and RGA1', 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, Ci-6 alkyl, Ci-6 deuterated alkyl, Ci-6 halogenated alkyl, Ci-6 deuterated haloalkyl, Ci- 6-hy dr oxy alkyl, 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, C’6-10 aryl, or 5-10 membered heteroaryl substituted by one or more substituents; andnGA, nGAl, mGAl, mGA2, mGA3, and mGA4 are each independently selected from 0, 1, 2, 3, 4 or 5; or(iii)43658-02201 / WO (EXAV-023 / 001 WO)(RGBa)mGB (RGB|)nGB (RGBC)OGB (RGBd)pGB•-GB4(RGBe)qGB wherein:Ring AGBis selected from C3-15 carbocyclyl, 3-12 membered heterocyclyl, Cg-14 aryl, 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, Cg-14 aryl, and 5-12 membered heteroaryl;Ring EGBis selected from C3-15 carbocyclyl, 3-12 membered heterocyclyl, Cg-14 aryl, 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)RGBa1, -N(RGBa1)(RGBa2), -C(O)N(RGBal)(RGBa2), -N(RGBal)C(O)RGBa2-S(O)N(RGBa1)(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: C1-6 alkyl, Ci-6 alkoxy, Ci-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, Cg-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, C4-6 alkyl, Ci-6 alkoxy, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14 aryl, or 5-12 membered heteroaryl;43658-02201 / WO (EXAV-023 / 001 WO)RGBaland RGBa2are 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, C6-14 aryl, and 5-12 membered heteroaryl, wherein the Ci-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 from halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, Ci-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, Ci-6 alkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, Ce-14 aryl, and 5-12 membered heteroaryl, wherein the Ci-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 heteroaiyl 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, C3-7 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, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14 aryl, and 5-12 membered heteroaryl, wherein the Ci-6 alkyl, Ci-6 alkoxy, Ci-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, Cg-i4 aryl, or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) RGBb1;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, Ci-6 alkoxy, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14 aryl, and 5-12 membered heteroaryl;43658-02201 / WO (EXAV-023 / 001 WO)RGBb1is 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, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, Ce-14 aryl, 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 from halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, Ci-6 alkyl, Cj-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, Ce-14 aryl, and 5-12 membered heteroaryl;RGBcis 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, 3-10 membered heterocyclyl, C6-14 aryl, and 5-12 membered heteroaryl, wherein the C1-6 alkyl, Ci-6 alkoxy, Ci-6 alkylamino, 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) RGBc1;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, Ci-6 alkyl, Ci-6 alkoxy, C3-10 cycloalkyl, 3-10 membered heterocyclyl, Ce-14 aryl, 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, Ci-6 alkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, Ce-14 aryl, and 5-12 membered heteroaryl, wherein the Ci-6 alkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-43658-02201 / WO (EXAV-023 / 001 WO)io cycloalkyl, 3-10 membered heterocyclyl, Ce-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)2RGBd1, -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(RGBd1)(RGBd2), -N(RGBd1)S(O)RGBd2, -N(RGBd1)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: C1-6 alkyl, C1-6 alkoxy, Ci-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 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- 10 cycloalkyl, 3-10 membered heterocyclyl, C6-14 aryl, and 5-12 membered heteroaryl;RGBd1and RGBd2are each independently selected from hydrogen, deuterium, C1-6 alkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, Ce-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, 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;43658-02201 / WO (EXAV-023 / 001 WO)RGBd4and RGBd5are 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, C6-14 aryl, and 5-12 membered heteroaryl, wherein the Ci-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 from halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, Ci-6 alkyl, Cj-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, -SRGBe1, -S(O)RGBe1, -S(O)2RGBe1, -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(RGBe1)(RGBe2), -N(RGBe1)S(O)RGBe2, -N(RGBe1)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: Ci-6 alkyl, Ci-6 alkoxy, Ci-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 5-12 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, 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, Ci-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, Ce-14 aryl, and 5-12 membered heteroaryl, wherein the Ci-6 alkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, Ce-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, 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;RGBe3is independently selected from hydrogen, deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -RGBe4, -ORGBe4, -SRGBe4, -S(O)RGBe4, -S(O)2RGBe4, -43658-02201 / WO (EXAV-023 / 001 WO)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, Ci-6 alkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, Ce-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 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;RRGB1and 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, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 alkylamino, C3-10 cycloalkyl, and 3-10 membered heterocyclyl, wherein the Ci-6 alkyl, Ci-6 alkoxy, Ci-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;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 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, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl;LGB2is 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)-;43658-02201 / WO (EXAV-023 / 001 WO)RGBL2are 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 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 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, 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, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl;LGB4 IS a bond, -LGB4X -C(RGB!'4a)(RGBMb)-LGB4y -LGB4X -OLGB4y ", -LGB4 -SLGB4y - LGB4X -C(O)-LGB4y -, -LGB4X -C(())OLGB4y -, -LGB4X -OC(O)-LGB4y -LGB4X -N(RGBL4a)C(())- LGB4V ", -LGB4X -C(O)N(RGBL4a)-LGB4y ", -LGB4X -N(RGBL4a)-LGB4y ~, -LGB4X - N(RGBL4a)C(O)N(RGBL4b)-LGB4y -N(RGBIA'l)C(S)N(RGBMb)-LGB4y ”, Or (RGBL4z)rGB-LGB47~LGB4yLGB4xand LGB4yare 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) substituents independently selected from deuterium, halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, Ci-6 alkyl, Ci-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl;RGBL4aand RGBL4bare 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,43658-02201 / WO (EXAV-023 / 001 WO)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, Ci-6 alkyl, Ci-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 LGB4Z is C3-15 carbocyclyl, 3-12 membered heterocyclyl, Ce-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, 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, Ci-6 alkyl, C1-6 alkoxy, Ci-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl;LGB5xand LGB5yare 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) 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;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;O-N43658-02201 / WO (EXAV-023 / 001 WO)Y1, Y2, Y3, Y4, Y5, Y6, and Y7 are each independently a bond, -O-, or -NH-;L1, L2, and L3 are each independently a bond, -O-, C1-C25 alkylene, 3-12 membered heterocyclylene, or Ce-Cio arylene, wherein the alkylene, heterocyclylene, 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 haloalky 1;R1, R2, R3, and R4 are each independently C1-C60 alkyl, C2-C30 alkenyl, C6-C10 aryl, or 3-15 membered heterocyclyl, wherein the alkyl, alkenyl, aryl, and heterocyclyl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-C30 alkoxy, -O-(Ci-Ce alkylene)-(C6-Cw aryl), -N(RN)2, or Ci-Ce haloalkyl;RN is each independently H, C1-C30 alkyl or C6-C10 aryl; andRp is C1-C20 alkyl or Cg-Cio aryl, wherein the alkyl and aiyl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ci-Ce alkoxy, or Ci-Cg haloalkyl.

[0005] In some aspects, the present disclosure provides a compound of Formula (I):G-A (I),a stereoisomer thereof, a tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein:43658-02201 / WO (EXAV-023 / 001 WO)XGis —N= or —CRaG=; RaGis selected from a hydrogen atom, a halogen atom, and Cn 6 alkyl;YGis selected from —C(=O)—, —CHRG—, and —S(=O)2—; RGis a hydrogen atom or Ci-6 alkyl;QG1is C6-10aryl 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 Cue alkyl is optionally substituted with one or more halogen atoms), C3-6 cycloalkyl, and Ci- 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 RGQaand RGQbare independently selected from a hydrogen atom, Ci- 6 alkyl, and (C1-6 alkyl)carbonyl;Z3, Z4, Z5, Z6, Z7, Z8, Z9, Z10, Z11, Z12and Z13are each independently selected from the group consisting of N and C;43658-02201 / WO (EXAV-023 / 001 WO)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 heterocycloalkyl;RG4, RG5and RG6are independently selected from a hydrogen atom, a halogen atom, and Ci-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 C3-15cycloalkane 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, Ci-6 alkoxy, and 3 to 12 membered heterocyclyl, and RG7aand RG7bare independently selected from a hydrogen atom, C1-6 alkyl, and (Ci-6alkyl)carbonyl; and any two Ci -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, C1-6alkyl, and (C1-6alkyl)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);43658-02201 AVO (EX AV-023 / 001 WO)ZG2is selected from the group consisting of Ci-6 alkyl, C3-15 cycloalkyl, 3 to 12 membered heterocyclyl, Cg-io aryl, and 5 to 10 membered heteroaryl, wherein the C3-15 cycloalkyl, 3 to 12 membered heterocyclyl, Ce-ioaryl, 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 (Cj-6alkyl)carbonyl, wherein Ci -6 alkyl is optionally substituted with one or more substituents independently selected from hydroxy, a halogen atom and Cj-6 alkoxy,e) —C(=O)—NRzfRzg; wherein Rzfand Rzgare independently selected from a hydrogen atom, C1-6 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 Cj-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) Ci-6alkyl optionally substituted with one or more substituent independently selected from a halogen atom, hydroxy, —NRziRzj, Ci-6alkoxy, and 3 to 12 membered heterocyclyl, wherein Rziand Rzjare independently a hydrogen atom or 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-6 alkyl)carbonyl, j) C6-10aryl optionally substituted with one or more (C1-6alkyl)carbonyl, k) 5 to 10 membered heteroaryl optionally substituted with one or more substituents independently selected from C1-6alkyl, C1-6alkoxy, —NRzkRzl, and 3 to 12 membered heterocyclyl, wherein Rzkand Rzlare independently selected from43658-02201 / WO (EXAV-023 / 001 WO)a hydrogen atom, Ci-6 alkyl and (C 1-6 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, Ci-6 alkyl, Ci- 6 alkoxy and (C1-6 alkyl) carbonyl, wherein each of alkyl and alkoxy is optionally substituted with halogen; andn) C1-C6alkyl-C3-C15cycloalkyl wherein the cycloalkyl or alkyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, oxo, C1-6alkyl, Ci-6 alkoxy and (Ci-6 alkyl) carbonyl, wherein each of alkyl and alkoxy is optionally substituted with halogen;O O OYi, Y2, Y3, Y4, Y5, Ye, and Y7 are each independently a bond, -O-, or -NH-;Li, L2, and L3 are each independently a bond, -O-, C1-C25 alkylene, 3-12 membered heterocyclylene, or Ce-Cio arylene, wherein the alkylene, heterocyclylene, and arylene are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Co alkyl, Ce-Cio aryl, Ci-Cs alkoxy, or Ci-Ce haloalkyl;Rt, Rz, R3, and R4 are each independently Ci-Cso alkyl, C2-C30 alkenyl, Ce-Cio aryl, or 3- 15 membered heterocyclyl, wherein the alkyl, alkenyl, aryl, and heterocyclyl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci- C30 alkoxy, -O-(Ci-Ce alkyl ene)-(C6-Cio aryl), -N(RN)2, or Ci-Ce haloalkyl;43658-02201 / WO (EXAV-023 / 001 WO)RN is each independently H, C1-C30 alkyl or C6-C10 aryl; andRpis C1-C20alkyl or C6-C10aryl, wherein the alkyl and aryl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6alkyl, C1-C6alkoxy, or C1-C6haloalkyl.

[0006] In some aspects, the present disclosure provides a compound of Formula (I) wherein:43658-02201 / WO (EXAV-023 / 001 WO)o43658-02201 / WO (EXAV-023 / 001 WO)0 0 °Yi, Y2, Y3, Y4, Y5, Ye, and Y7 are each independently a bond, -0-, or -NH-;Li, L2, and L3 are each independently a bond, -0-, 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;R1, R2, R3, and R4 are each independently C1-C60 alkyl, C2-C30 alkenyl, C6-C10 aryl, or 3-15 membered heterocyclyl, wherein the alkyl, alkenyl, aryl, and heterocyclyl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-C30 alkoxy, -0-(Ci-C6 alkylene)-(Ce-Cio aryl), -N(RN)2, or Ci-Ce haloalkyl; andRN is each independently H, C1-C30 alkyl or C6-C10 aryl; andRp is C1-C20 alkyl or C6-C10 aryl, wherein the alkyl and aryl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Cs alkyl, Ci-Ce alkoxy, or Ci-Ce haloalkyl.

[0007] In some embodiments,A isKR O~No— -4 H

[0008] In some embodiments,A is

[0009] In some aspects, the present disclosure provides a compound of Formula (I) wherein:43658-02201 / WO (EXAV-023 / 001 WO), a stereoisomer thereof, or a tautomer thereof;°-N R,°-N O=A 'll5"0—4 £sN" ZA IS or43658-02201 AVO (EX AV-023 / 001 WO)oY1, Y2, Y3, Y4, Y5, Y6, and Y7 are each independently a bond, -O-, or -NH-;Li, L2, and L are each independently a bond, -O-, 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;R1, R2, R3, and R4are each independently C1-C60alkyl, C2-C30alkenyl, C6-C10aryl, or 3-15 membered heterocyclyl, wherein the alkyl, alkenyl, aryl, and heterocyclyl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6alkyl, C6-C10aryl, C1-C30alkoxy, -O-(C1-C6alkylene)-(C6-C10aryl), -N(RN)2, or C1-C6haloalkyl; andRN is each independently H, C1-C30 alkyl or C6-C10 aryl; andRp is C1-C20 alkyl or Ce-Cio aryl, wherein the alkyl and aryl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ci-Ce alkoxy, or Ci-Ce haloalkyl.

[0010] In some embodiments,A is

[0011] In some embodiments,A is

[0012]

[0013] In some aspects, the present disclosure provides a compound of Formula (I) wherein:43658-02201 / WO (EXAV-023 / 001 WO)Y1, Y2, Y3, Y4, Y5, Y6, and Y7 are each independently a bond, -O-, or -NH-;Li, L2, and L3 are each independently a bond, -O-, 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, C6-C10 aryl, C1-C6 alkoxy, or C1-C6 haloalkyl;R1, R2, R3, and R4 are each independently C1-C60 alkyl, C2-C30 alkenyl, C6-C10 aryl, or 3-15 membered heterocyclyl, wherein the alkyl, alkenyl, aryl, and heterocyclyl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-C30 alkoxy, -O-(Ci-Ce alkylene)-(C6-Cw aryl), -N(RN)2, or Ci-Ce haloalkyl; andRN is each independently H, C1-C30 alkyl or C6-C10 aryl; and43658-02201 AVO (EX AV-023 / 001 WO)Rp is C1-C20 alkyl or Ce-Cio aryl, wherein the alkyl and aryl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-C6 alkyl, Ci-C6 alkoxy, or Ci-C6 haloalkyl.

[0014] In some aspects, the compound is of Formula (I), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein:Yi, Y2, and Y3 are each independently a bond, -O-, or -NH-;Li and L2 are each independently a bond, -O-, 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 and R2 are each independently Ci-Ceo alkyl, C2-C30 alkenyl, Ce-Cio aryl, or 3-15 membered heterocyclyl, wherein the alkyl, alkenyl, aryl, and heterocyclyl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-C30 alkoxy, -O-(Ci-Ce alkylene)-(Ce-Cio aryl), -N(RN)2, or Ci-Ce haloalkyl; andRN is each independently H, C1-C30 alkyl or C6-C10 aryl.

[0015] In some aspects, the present disclosure provides a compound of Formula (I) wherein:43658-02201 / WO (EXAV-023 / 001 WO)Y4, Y., Ye, and Y7 are each independently a bond, -O-, or -NH-;L3 is 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, Ci-Ce alkoxy, or Ci-Ce haloalkyl; andR3 and R 4 are each independently C1-C30 alkyl, C2-C30 alkenyl, or Ce-Cio aryl, wherein the alkyl, alkenyl, and aryl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, C6-C10 aryl, Ci-Ce alkoxy, or C1-C6 haloalkyl.

[0016] In some aspects, the compound is of Formula (I), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein:G is43658-02201 / WO (EXAV-023 / 001 WO)Yi, Y2, and Y3 are each independently a bond, -O-, or -NH-;Li and L2 are each independently a bond, -O-, 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, Ci-Ce alkoxy, or Ci-Ce haloalkyl;R1 and R2 are each independently C1-C60 alkyl, C2-C30 alkenyl, Ce-Cio aryl, or 3-15 membered heterocyclyl, wherein the alkyl, alkenyl, aryl, and heterocyclyl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci- C30 alkoxy, -O-(C1-C6 alkylene)-(C6-C10 aryl), -N(RN)2, or Ci-Ce haloalkyl; andRN is each independently H, C1-C30 alkyl or C6-C10 aryl.

[0017] In some aspects, the present disclosure provides a compound of Formula (I) wherein:Y4, Y5, Ye, and Y7 are each independently a bond, -O-, or -NH-;L3 is 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; and43658-02201 / WO (EXAV-023 / 001 WO)R3 and R4 are each independently C1-C30 alkyl, C2-C30 alkenyl, or Cg-Cio aryl, wherein the alkyl, alkenyl, and aryl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6 alkyl, C6-C10 aryl, C1-C6 alkoxy, or C1-C6 haloalkyl.

[0018] In some aspects, the present disclosure provides a compound of Formula (I) wherein the compound is selected from the compounds described in Table 1, stereoisomers thereof, and pharmaceutically acceptable salts thereof,

[0019] In some aspects, the present disclosure provides a compound of Formula (I) wherein the compound is selected from the compounds described in Table 2, stereoisomers thereof, and pharmaceutically acceptable salts thereof.

[0020] In some aspects, the present disclosure provides a compound of Formula (I) wherein the compound is selected from the compounds described in Tables 3-6, stereoisomers thereof, and pharmaceutically acceptable salts thereof.

[0021] In some aspects, the present disclosure provides a compound of Formula (I) wherein the compound is selected from the compounds described in Table 7, stereoisomers thereof, and pharmaceutically acceptable salts thereof.

[0022] In some aspects, the present disclosure provides a compound of Formula (I) wherein the compound is selected from the compounds described in Tables 8-11, stereoisomers thereof, and pharmaceutically acceptable salts thereof.

[0023] In some aspects, the present disclosure provides a compound of Formula (I) wherein the compound is selected from the compounds described in Tables 12-17, stereoisomers thereof, and pharmaceutically acceptable salts thereof.

[0024] In some aspects, the present disclosure provides a compound of Formula (I) wherein the compound is selected from the compounds described in Tables 18-23, stereoisomers thereof, and pharmaceutically acceptable salts thereof.

[0025] In some aspects, the present disclosure provides a pharmaceutical composition comprising a compound of the present disclosure, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable diluent or carrier.

[0026] 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 compound or pharmaceutical composition of the present disclosure.43658-02201 / WO (EXAV-023 / 001 WO)

[0027] In some aspects, the present disclosure provides a compound or pharmaceutical composition of the present disclosure for use in treating or preventing a disease or disorder disclosed herein.

[0028] In some aspects, the present disclosure provides the use of a compound or pharmaceutical composition of the present disclosure in the manufacture of a medicament for treating or preventing a disease or disorder disclosed herein,

[0029] In some aspects, the present disclosure provides a method of preparing a compound of the present disclosure.

[0030] In some aspects, the present disclosure provides a method of preparing a compound, comprising one or more steps described herein.

[0031] 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.

[0032] Other features and advantages of the disclosure will be apparent from the following detailed description and claims.BRIEF DESCRIPTION OF THE DRAWINGS

[0033] 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.43658-02201 AVO (EX AV-023 / 001 WO)

[0034] FIG. 1 depicts the13C NMR spectra of Compound 1, obtained at 125 MHz in CDCh.

[0035] FIG. 2 depicts the1H NMR spectra of Compound 2, obtained at 500 MHz in CDCh.

[0036] FIG. 3 depicts the13C NMR spectra of Compound 2, obtained at 125 MHz in CDCh.

[0037] FIG. 4 depicts the1H NMR spectra of Compound 5, obtained at 500 MHz in CDCh

[0038] FIG. 5 depicts the1H NMR spectra of Compound 11, obtained in CDCh.

[0039] FIG.6 depicts the1H NMR spectra of Compound 12, obtained in CDCh

[0040] FIG. 7 depicts the1H NMR spectra of Compound 13, obtained in CDCI3.

[0041] FIG. 8 depicts the1H NMR spectra of Compound 14, obtained in CDCh

[0042] FIG.9 depicts the1H NMR spectra of Compound 15, obtained in CDCI3.

[0043] FIG. 10 depicts the 'H NMR spectra of a palmitoylated orforglipron imide prodrug, obtained in CDCh.

[0044] FIG. 11 depicts the13C NMR spectra of a palmitoylated orforglipron imide prodrug, obtained in CDCh.

[0045] FIG. 12 depicts a comparison of the Fourier transform infrared (FT-IR) spectra of orforglipron and a palmitoylated orforglipron prodrug.

[0046] FIG. 13 depicts a comparison of the Fourier transform infrared (FT-IR) spectra of orforglipron and a stearoylated orforglipron prodrug.

[0047] FIG. 14 depicts the pharmacokinetic (PK) profile of a palmitoylated orforglipron prodrug (Formulation Fl) and a stearoylated orforglipron prodrug (Formulation 1).

[0048] FIG. 15 depicts the1H NMR spectra of Compound VI-35, obtained in CDCh.

[0049] FIG. 16 depicts the1H NMR spectra of Compound VI-170, obtained in CDCh.

[0050] FIG. 17 depicts the13C NMR spectra of Compound VI-170, obtained in CDCh.

[0051] FIG. 18 depicts the pharmacokinetic (PK) profile of a palmitoylated orforglipron prodrug (Formulation Fl), a stearoylated orforglipron prodrug (Formulation 1), a para-(dodecyloxy)benzoylated orforglipron prodrug (Formulation 1), and a 1,1-dimethyl-myristoylated orforglipron prodrug (Formulation 1). ORF = orforglipron; IM = intramuscular administration.

[0052] FIG. 19 depicts the pharmacokinetic (PK) profile of a palmitoylated orforglipron prodrug (Formulation Fl) over 230 days. ORF = orforglipron; IM = intramuscular administration. Data expressed as mean + / - SEM.43658-02201 / WO (EXAV-023 / 001 WO)

[0053] FIG.20 depicts the pharmacokinetic (PK) profile of a stearoylated orforglipron prodrug (Formulation 1) and a 1, 1 -dimethyl-myristoylated orforglipron prodrug (Formulation 1) over 119 days. ORF = orforglipron; IM = intramuscular administration.

[0054] FIG.21 depicts the pharmacokinetic (PK) profile of Formulation F3, comparing intramuscular administration (75 mg / kg ORF equiv.) and subcutaneous administration (75 mg / kg ORF equiv. and 150 mg / kg ORF equiv.). ORF = orforglipron; IM = intramuscular administration; SC = subcutaneous administration. Data expressed as mean + / - SEM,

[0055] FIG.22 depicts the pharmacokinetic (PK) profile of Formulation 1 of a para-(pentyloxy)benzoylated orforglipron prodrug, administered subcutaneously at 75 mg / kg ORF equiv. ORF = orforglipron; SC = subcutaneous administration,

[0056] FIG. 23 depicts the PK profile of Formulation F2A, comparing intramuscular administration (75 mg / kg ORF equiv.) and subcutaneous administration (75 mg / kg ORF equiv. and 150 mg / kg ORF equiv.). ORF = orforglipron; IM = intramuscular administration; SC = subcutaneous administration.

[0057] FIGs. 24-34 depict results from a four-week humanized GLP-1R DIO mouse study comparing the effects of Group 1 (vehicle administered Days 1-15), Group 2 (vehicle administered Day 1, orforglipron administered Days 1-15), Group 3 (single subcutaneous injection of 65 mg / kg ORF equiv. Formulation F2B administered Day 1, vehicle administered Days 1-15), and Group 4 (single subcutaneous injection of 217 mg / kg ORF equiv. Formulation F2B administered Day 1, vehicle administered Days 1-15).

[0058] FIG.24 depicts the % body weight relative to baseline for Groups 1-4 over the course of the study. Data expressed as mean + / - SEM.

[0059] FIG.25 depicts the % change in placebo-adjusted weight loss relative to baseline for Groups 2-4 over the course of the study. Data expressed as mean + / - SEM.

[0060] FIG.26 depicts the % change in placebo-adjusted weight loss relative to baseline for Groups 2-4 at Day 15 (left) and Day 31 (right). Data expressed as mean + / - SEM.

[0061] FIG.27 depicts the 3 -hour fasted blood glucose levels for Groups 1-4 as measured on Week -1 (baseline), Week 1, Week 2, and Week 3.

[0062] FIG.28 depicts the % change in blood glucose relative to baseline for Groups 1-4 at Day 22. Data expressed as mean + / - SEM.43658-02201 AVO (EX AV-023 / 001 WO)

[0063] FIG. 29 depicts the oral glucose tolerance test (OGTT) measurements conducted for Groups 1-4 on Day 15 (DI 5) and Day 29 (D29), showing change in blood glucose levels over time. Data expressed as mean + / - SEM.

[0064] FIG. 30 depicts the oral glucose tolerance test (OGTT) measurements conducted for Groups 1-4 on Day 15 (DI 5, left) and Day 29 (D29, right), showing the difference in blood glucose AUG. Data expressed as mean + / - SEM, *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001 vs Group 1 (vehicle); #p<0.05, ##p<0.01, ###p<0,001, ####p<0.0001 vs Group 2 (orforglipron).

[0065] FIG. 31 depicts the % change in total fat mass against % change in total lean mass for Groups 2-4 at Day 13.

[0066] FIG. 32 depicts the % change in body weight relative to baseline for Groups 1-4 at Day 13. Data expressed as mean + / - SEM.

[0067] FIG. 33 depicts the change in % body fat relative to baseline for Groups 1-4 at Week 2 (left) and Week 4 (right). Data expressed as mean + / - SEM. Fat mass change at each timepoint was analyzed by one-way ANOVA and Fisher’s LSD test. * p < 0.05, ** p < 0.01, *** p < 0.001, ****p<0.0001 vs Group 1 (vehicle); # p < 0.05, ## p < 0.01, ### p < 0.001, #### p< 0.0001 vs Group 2 (orforglipron).

[0068] FIG. 34 depicts the cumulative food intake for Groups 1-4 over the course of the study. Data expressed as mean + / - SEM

[0069] FIG. 35 depicts the1H NMR spectra of a palmitoylated AZD5004 prodrug, obtained in CDCh.

[0070] FIG. 36 depicts the1H NMR spectra of a para-(pentyloxy)benzoylated AZD5004 prodrug, obtained in CDCI3.

[0071] FIG. 37 depicts the pharmacokinetic (PK) profile of Formulation F4, comparing subcutaneous administration at 75 mg / kg ORF equiv. and at 150 mg / kg ORF equiv. ORF = orforglipron; SC = subcutaneous administration. Data expressed as mean + / - SEM.

[0072] FIG. 38 depicts the pharmacokinetic (PK) profile of Formulation F2A, comparing subcutaneous administration at 75 mg / kg ORF equiv. and at 150 mg / kg ORF equiv. ORF = orforglipron; SC = subcutaneous administration. Data expressed as mean + / - SEM.

[0073] FIG. 39 depicts the pharmacokinetic (PK) profile of a palmitoylated AZD5004 prodrug (Formulation 1) administered subcutaneously at 150 mg / kg ORF equiv. Data expressed as mean + / - SEM.43658-02201 AVO (EX AV-023 / 001 WO)

[0074] FIG. 40 depicts the pharmacokinetic (PK) profile of a para-(pentyloxy)benzoylated AZD5004 prodrug (Formulation 1) administered subcutaneously at 150 mg / kg ORF equiv. Data expressed as mean + / - SEM.

[0075] FIG. 41 depicts the pharmacokinetic (PK) profile of a palmitoylated AZD5004 prodrug (Formulation 1) administered subcutaneously at 150 mg / kg ORF equiv. Data expressed as mean + / - SEM.

[0076] FIG. 42 depicts the pharmacokinetic (PK) profile of a para-(pentyloxy)benzoylated AZD5004 prodrug (Formulation 1) administered subcutaneously at 150 mg / kg ORF equiv. Data expressed as mean + / - SEM.DETAILED DESCRIPTION

[0077] The present disclosure relates to analogs and / or prodrugs of heterocyclic GLP1 receptor agonists like orforglipron and pharmaceutically acceptable salts thereof. The present disclosure also relates to processes for the preparation of these compounds, to pharmaceutical compositions (e.g. nanoparticle compositions) comprising these compounds and the use of the compounds 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 analogs and / or prodrugs of heterocyclic GLP1 receptor agonists disclosed herein allow for sustained release of said heterocyclic GLP1 receptor agonists over an extended time period.Definitions

[0078] Unless otherwise stated, the following terms used in the specification and claims have the following meanings set out below.

[0079] 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 combinations of the options.

[0080] As used herein, “alkyl”, “Ci, C2, C3, C4, C5 or C alkyl” or “Ci-C 6 alkyl” is intended to include Ci, C2, C3, C4, C5 or Ce straight chain (linear) saturated aliphatic hydrocarbon groups and43658-02201 AVO (EX AV-023 / 001 WO)C3, C4, C5 or C6 branched saturated aliphatic hydrocarbon groups. For example, C1-C6 alkyl is intended to include C1, C2, C3, C4, C5and C6alkyl groups. Examples of alkyl include, moieties 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., C1-C6 for straight chain, C3-C6 for 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.”

[0081] 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, alkyl carbonyloxy, arylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, carboxylate, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkyl aminocarbonyl, 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, alkylsulfinyl, sulfonato, sulfamoyl, sulfonamide, nitro, trifluoromethyl, cyano, azido, heterocyclyl, alkylaryl, or an aromatic or heteroaromatic moiety.

[0082] “Deuteroalkyl” refers to an alkyl, as defined above, that is substituted by one or more deuteriums. In some embodiments, the alkyl is substituted with one deuterium. In some embodiments, the alkyl is substituted with one, two, or three deuteriums. In some embodiments, the alkyl is substituted with one, two, three, four, five, or six deuteriums. Deuteroalkyl include, for example, CD3, CH2D, CHD2, CH2CD3, CD2CD3, CHDCD3, CH2CH2D, or CH2CHD2. In some embodiments, the deuteroalkyl is CD3.

[0083] 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-C6for straight chain, C3-C6for branched chain). The term “C2-C6” includes alkenyl groups containing two to six carbon atoms. The term “C3-C6” includes43658-02201 AVO (EX AV-023 / 001 WO)alkenyl groups containing three to six carbon atoms. A divalent alkenyl group is referred to herein as “alkenylene.”

[0084] 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, aryloxycarbonyloxy, carboxylate, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aminocarbonyl, alkyl aminocarbonyl, 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, alkylsulfinyl, sulfonato, sulfamoyl, sulfonamide, nitro, trifluoromethyl, cyano, heterocyclyl, alkylaryl, or an aromatic or heteroaromatic moiety.

[0085] 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, C5 and C6 alkenylene linker groups. A divalent alkynyl group is referred to herein as “alkynylene.”

[0086] 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, arylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, carboxylate, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkylthiocarbonyl, alkoxyl, phosphate, phosphonato,43658-02201 / WO (EX AV-023 / 001 WO)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.

[0087] 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-tetramethyl-1,2,3,6-tetrahydropyridinyl.

[0088] 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 C3-C8). 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.”

[0089] As used herein, the term “heterocyclyl” or “heterocycloalkyl” 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 heteroatoms (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[2.2.1 ]heptanyl, 2,5-diazabicyclo[2.2.1 ]heptanyl, 2-oxa-6-azaspiro[3.3]heptanyl, 2,6-diazaspiro[3.3]heptanyl, l,4-dioxa-8-azaspiro[4.5]decanyl, 1,4-dioxaspiro[4.5]decanyl, 1 -oxaspiro[4.5]decanyl, 1 -azaspiro[4.5]decanyl, 3'H-spiro[cyclohexane-1,1'-isobenzofuran]-yl, 7'H-spiro[cyclohexane-l,5'-furo[3,4-b]pyridin]-yl, 3'H-43658-02201 AVO (EX AV-023 / 001 WO)spiro[cyclohexane-l,r-furo[3,4-c]pyridin]-yl, 3-azabicyclo[3.1.0]hexanyl, 3-azabicyclo[3.1.0]hexan-3-yl, l,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]isoxazoly1, benzo[d][l,3]dioxole, 2,3-dihydrobenzo[b][l,4]dioxine, and the like). A divalent heterocyclyl group is referred to herein as “heterocyclylene.”

[0090] 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.

[0091] 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 aiyl group is referred to herein as “arylene.”

[0092] 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 (i.e., N or NR wherein R is H or other substituents, as defined). The nitrogen and sulfur heteroatoms may optionally be oxidized (z.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 or43658-02201 AVO (EX AV-023 / 001 WO)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-7H-pyrrolopyridine, 1,2,3,4-tetrahydronaphthyridine, 2,3-dihydro-pyridooxazine, 2,3-dihydro-1H-pyrrolopyridine, 2,3-dihydrooxazolopyridine, and the like). A divalent heteroaryl group is referred to herein as “heteroarylene.”

[0093] Furthermore, the terms “aryl” and “heteroaryl” include multicyclic aryl and heteroaryl groups, respectively, e.g, tricyclic, bicyclic, e.g., naphthalene, benzoxazole, benzodioxazole, benzothiazole, benzoimidazole, benzothiophene, quinoline, isoquinoline, naphthrydine, indole, benzofuran, purine, benzofuran, deazapurine, indolizine,

[0094] 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 as described above, for example, alkyl, alkenyl, alkynyl, halogen, hydroxyl, alkoxy, alkylcarbonyloxy, arylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, carboxylate, alkylcarbonyl, alkylaminocarbonyl, aralkylaminocarbonyl, alkenylaminocarbonyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, alkenylcarbonyl, alkoxy carbonyl, aminocarbonyl, alkylthiocarbonyl, 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. 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).

[0095] 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 (i.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).43658-02201 AVO (EX AV-023 / 001 WO)

[0096] “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.

[0097] 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.

[0098] 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, then 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.

[0099] As used herein, the term “hydroxy” or “hydroxyl” includes groups with an -OH or -O’.

[0100] As used herein, the term “halo” or “halogen” refers to fluoro, chloro, bromo and iodo.

[0101] The term “haloalkyl” or “haloalkoxyl” refers to an alkyl or alkoxyl substituted with one or more halogen atoms.

[0102] 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.”

[0103] 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, alkylcarbonyloxy, arylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, carboxylate, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkylthiocarbonyl, alkoxyl, phosphate, phosphonato,43658-02201 AVO (EX AV-023 / 001 WO)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.

[0104] As used herein, the term “alkoxy” or “alkoxy!” 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, arylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, carboxylate, alkylcarbonyl, 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 moieties. Examples of halogen substituted alkoxy groups include, but are not limited to, fluoromethoxy, difluoromethoxy, trifluoromethoxy, chloromethoxy, dichloromethoxy and trichloromethoxy.

[0105] As used herein, the term “heteroalkoxy” or “heteroalkoxyl” includes substituted and unsubstituted heteroalkyl, heteroalkenyl and heteroalkynyl groups covalently linked to an oxygen atom.

[0106] 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.

[0107] It is to be understood that the present disclosure provides methods for the synthesis of the compounds of any of the Formulae described herein. The present disclosure also provides43658-02201 / WO (EXAV-023 / 001 WO)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.

[0108] 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,

[0109] 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. The processes generally provide the desired final compound at or near the end of the overall process, although it may be desirable in certain instances to further convert the compound to a pharmaceutically acceptable salt thereof.

[0110] 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 be 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 art43658-02201 AVO (EX AV-023 / 001 WO)

[0111] 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.

[0112] 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.

[0113] 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.

[0114] 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, 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.

[0115] As used herein, the term “subject m 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 need43658-02201 / WO (EXAV-023 / 001 WO)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.

[0116] 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 compound of the present disclosure, or a pharmaceutically acceptable salt, 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.

[0117] It is to be understood that a compound of the present disclosure, or a pharmaceutically acceptable salt, 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.

[0118] 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.

[0119] 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 Spring43658-02201 AVO (EX AV-023 / 001 WO)Harbor Press, Cold Spring Harbor, New York (2000); Coligan et al., Current Protocols in Immunology, John Wiley & Sons, N. Y.; Enna et al., Current Protocols in Pharmacology, John Wiley & Sons, N. Y.; Fingl et al., The Pharmacological Basis of Therapeutics (1975), Remington's Pharmaceutical Sciences, Mack Publishing Co., Easton, PA, 18thedition (1990). These texts can, of course, also be referred to in making or using an aspect of the disclosure.

[0120] It is to be understood that the present disclosure also provides pharmaceutical compositions comprising any compound described herein in combination with at least one pharmaceutically acceptable excipient or carrier.

[0121] 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 salt, 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, transdermal, subcutaneous, intravenous, intramuscular, intraperitoneal, inhalational, buccal, sublingual, intrapleural, intrathecal, intranasal, and the like. Dosage forms for the topical or transdermal administration of a compound of this disclosure include powders, sprays, ointments, pastes, creams, 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.

[0122] 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.

[0123] 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 and43658-02201 / WO (EXAV-023 / 001 WO)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.

[0124] As used herein, the term “about” and the like, as used herein, in association with numeric values or ranges, reflects the fact that there is a certain level of variation that is recognized and tolerated in the art due to practical and / or theoretical limitations. For example, minor variation is tolerated due to inherent variances in the manner in which certain devices operate and / or measurements are taken. In accordance with the above, the phrase “about” is normally used to encompass values within the standard deviation or standard error. In some embodiments, the phrase “about” indicates a range of ±10%, ±9%, ±8%, ±7%, ±6%, ±5%, ±4%, ±3%, ±2%, ±1%, ±0.5%, or ±0.1% from the associated numeric value,

[0125] 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.

[0126] 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 compound 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 side effects. The state of the disease condition (e.g., a disease or disorder disclosed43658-02201 / WO (EXAV-023 / 001 WO)herein) and the health of the patient should preferably be closely monitored during and for a reasonable period after treatment.

[0127] 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.

[0128] 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., EDso (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.

[0129] 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, andtolerance / 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.

[0130] 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 molecule7943658-02201 AVO (EX AV-023 / 001 WO)(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],

[0131] As used herein, the term “orforglipron” or “ORF” refers to the compound “3-[(l S,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-l,2,4-oxadiazol-5-one,” having the structure shown below:P"

[0132] As used herein, the term “AZD5004” or “ECC5004” refers to the compound “3-(l-(2-((S)-2-(3-cyclopropyl-4-fluorophenyl)-3-(3-(4-fluoro-l-methyl-lH-indazol-5-yl)-2-oxo- 2,3-dihydro-lH-imidazol-l-yl)-4-methyl-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridine-5-carbonyl)-7-((R)-2,2-dimethyltetrahydro-2H-pyran-4-yl)indolizm-3-yl)cyclopropyl)-l,2,4-oxadiazol-5(4H)-one,” having the structure shown below:

[0133] 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 a43658-02201 / WO (EXAV-023 / 001 WO)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.

[0134] 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 fluid to the extent that easy syring eability 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 m the composition an agent which delays absorption, for example, aluminum monostearate and gelatin.

[0135] 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.43658-02201 / WO (EXAV-023 / 001 WO)

[0136] 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 tablets, pills, capsules, 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 algimc acid, 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.

[0137] 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.

[0138] 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.

[0139] 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) can43658-02201 AVO (EX AV-023 / 001 WO)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.

[0140] 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.

[0141] 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.

[0142] It is to be understood that the pharmaceutical compositions can be included in a container, pack, or dispenser together with instructions for administration.

[0143] 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.

[0144] As used herein, the term “pharmaceutically acceptable salts” refer to derivatives of the compounds of the present disclosure wherein the parent compound is modified by making acid or base salts thereof. Examples of pharmaceutically acceptable salts include, but are not limited to, mineral organic acid salts of basic residues such as amines, alkali organic salts of acidic residues such as carboxylic acids, and the like. The pharmaceutically acceptable salts include the conventional non-toxic salts or the quaternary' ammonium salts of the parent compound formed,43658-02201 / WO (EXAV-023 / 001 WO)for example, from non-toxic inorganic organic acids. For example, such conventional non-toxic salts include, but are not limited to, those derived from inorganic and organic acids selected from 2-acetoxybenzoic, 2-hydroxyethane sulfonic, acetic, ascorbic, benzene sulfonic, benzoic, bicarbonic, carbonic, citric, edetic, ethane disulfonic, 1,2-etliane sulfonic, fumaric, glucoheptonic, gluconic, glutamic, glycolic, glycollyarsanilic, hexylresorcinic, hydrabamic, hydrobromic, hydrochloric, hydroiodic, hydroxymaleic, hydroxynaphthoic, isethionic, lactic, lactobionic, lauryl sulfonic, maleic, malic, mandelic, methane sulfonic, napsylic, nitric, oxalic, pamoic, pantothenic, phenylacetic, phosphoric, polygalacturonic, propionic, salicylic, stearic, subacetic, succinic, sulfamic, sulfanilic, sulfuric, tannic, tartaric, toluene sulfonic, and the commonly occurring amine acids, e.g., glycine, alanine, phenylalanine, arginine, etc.

[0145] In some embodiments, the pharmaceutically acceptable salt is a sodium salt, a potassium salt, a calcium salt, a magnesium salt, a diethylamine salt, a choline salt, a meglumine salt, a benzathine salt, a tromethamine salt, an ammonia salt, an arginine salt, or a lysine salt.

[0146] Other examples of pharmaceutically acceptable salts include hexanoic acid, cyclopentane propionic acid, pyruvic acid, malonic acid, 3-(4-hydroxybenzoyl)benzoic acid, cinnamic acid, 4-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, 4-toluenesulfomc acid, camphorsulfonic acid, 4-methylbicyclo-[2.2.2]-oct-2-ene-l -carboxylic acid, 3-phenylpropionic acid, trimethylacetic acid, tertiary butylacetic acid, muconic acid, and the like. The present disclosure also encompasses salts formed when an acidic proton present in the parent compound either is replaced by a metal ion, e.g., an alkali metal ion, an alkaline earth ion, or an aluminum ion; or coordinates with an organic base such as ethanolamme, diethanolamine, triethanolamine, tromethamine, N-methylglucamine, and the like. 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.

[0147] 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.

[0148] The compounds, or pharmaceutically acceptable salts thereof, are administered orally, nasally, transdermally, pulmonary, inhalationally, buccally, sublingually, intraperitoneally, subcutaneously, intramuscularly, intravenously, rectally, intrapleurally, intrathecally and43658-02201 / WO (EXAV-023 / 001 WO)parenterally. In one embodiment, the compound is administered orally. One skilled in the art will recognize the advantages of certain routes of administration.

[0149] The dosage regimen utilizing the compounds is selected m 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 or salt thereof employed.

[0150] 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, and the pharmaceutically acceptable salts thereof, 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.

[0151] 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.

[0152] In the synthetic schemes described herein, compounds may be drawn with one particular configuration for simplicity. Such particular configurations are not to be construed 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.

[0153] 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 written43658-02201 / WO (EXAV-023 / 001 WO)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.

[0154] As use herein, the phrase “compound of the disclosure” refers to those compounds which are disclosed herein, both generically and specifically.

[0155] Compounds of the Present Disclosure

[0156] In some aspects, the present disclosure provides a compound of Formula (I):G-A (I),a stereoisomer thereof, a tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein:RGI RG1' RG2R'f 7U ' / 'n-SG3\\'RG2 / 7 / -Z Z3-^ - Z z_s-Q<32Z-c:~a hl — YG— ZnI,£ y ■»31 ^1° RG3 (CH2)nG12<51LRG7^ f^(CH2)nG2-I \RG8\h, 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-JO 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 independently43658-02201 / WO (EXAV-023 / 001 WO)selected from a halogen atom, Ci^ 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), Cj-6 alkoxy, and — NRGQaRGQb, and two C1-6 alkyl groups together with a carbon atom to which they are attached may form C3- 8 carbocyclic rmg; and RGQaand RGQbare independently selected from a hydrogen atom, Ci- 6 alkyl, and (C1-6 alkyl)carbonyl;Z3, Z4, Z5, Z6, Z7, Z8, Z9, Z10, Z11, Z12and Z13are each independently selected from the group consisting of N and C;RG1, RG2, RG3, RG1', RG2', and RG3'are each independently selected from a hydrogen atom, halogen atom, Cj -6 alkyl, C1-6 alkoxy, C1-6 haloalkoxy, cycloalkyl, and heterocycloalkyl, wherein the C1- 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, RG5anj j^G6are indepencient]y selected from a hydrogen atom, a halogen atom, and C1-6 alkyl;R7and 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, — NRG / aRG7b, C1-6 alkoxy, and 3 to 12 membered heterocyclyl, and RG'aand RG7bare independently selected from a hydrogen atom, C 1-6 alkyl, and (C 1-6 alkyl)carbonyl; and any two C1-6 alkyl optionally together with the carbon atom to which they are attached form C3-15 carbocyclic ring;11GI 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 of43658-02201 AVO (EX AV-023 / 001 WO)wherein Rzais selected from a hydrogen atom, C1-6alkyl, and (C1-6alkyl)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-ioaryl, and 5 to 10 membered heteroaryl, wherein the C3-15 cycloalkyl, 3 to 12 membered heterocyclyl, Ce-ioaryl, 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, Cj -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, C1-6alkyl and (C1-6alkyl)carbonyl, wherein C1-6alkyl 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 Ci-6 alkyl,g) Ci-6 alkyl optionally substituted with one or more substituent independently selected from a halogen atom, hydroxy, — NRZ1RA Ci-6 alkoxy, and 3 to 12 membered heterocyclyl, wherein RZ1and Rzj are independently a hydrogen atom or43658-02201 / WO (EXAV-023 / 001 WO)C 1-6 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-6 alkyl)carbonyl, j) C6-ioaryl optionally substituted with one or more (Ci^>alkyl)carbonyl, k) 5 to 10 membered heteroaryl optionally substituted with one or more substituents independently selected from Ci-6 alkyl, Ci-6 alkoxy, — NRzkRz!, and 3 to 12 membered heterocyclyl, wherein Rzkand Rzlare independently selected from a hydrogen atom, Ci-6 alkyl and ( -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, Ci- 6 alkoxy and (C1-6 alkyl) carbonyl, wherein each of alkyl and alkoxy is optionally- substituted with halogen; andn) Ci-Cealkyl-Cs-Cis cycloalkyl wherein the cycloalkyl or alkyl is optionally- substituted with one or more substituents independently selected from the group consisting of halogen, oxo, Ci^ alkyl, C1-6 alkoxy and (C1-6 alkyl) carbonyl, wherein each of alkyl and alkoxy is optionally substituted with halogen; or(11)43658-02201 / WO (EXAV-023 / 001 WO)RGA13wherein:RGA13is selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, thio, Ci-6 alkyl, Cj-6 deuterated alkyl, Cj-6 halogenated alkyl, Cj-6 deuterated haloalkyl, Ci- 6 hydroxyalkyl, Ci-6 deuterated hydroxyalkyl, Ci-6 sulfanyl, Ct-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, and 5-10 membered heteroaryl, wherein the amino, C1-6 alkyl, C1-6 deuterated alkyl, C1-6 halogenated alkyl, Ci-6 deuterated haloalkyl, C1-6 hydroxyalkyl, Ci-6 deuterated hydroxyalkyl, Ci-6 sulfanyl, C1-6 deuterated sulfanyl, Cj-6 alkoxy, Ci-6 deuterated alkoxy, C1-6 halogenated alkoxy, Ci-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-8 Cycloalkyl, 3-8 membered heterocyclyl, C6-14 aryl, or 5-10 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, C1-6 deuterated haloalkyl, Ci-6 hydroxyalkyl, Cue 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, or 5-10 membered heteroaryl substituted by one or more substituents;LGA1, LGA2, and LGA3are each independently selected from a bond, C2-4alkenylene, C2-4alkynylene and -(CH2)nGA1-;Ring AGAis selected from C3-14 cycloalkyl, 3-14 membered heterocyclyl, C’6-14 aryl, 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, C6-14 aryl,43658-02201 / WO (EXAV-023 / 001 WO)or 5-14 membered heteroaryl is optionally further substituted by deuterium, halogen, amino, nitro, hydroxyl, cyano, oxo, thiol, 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 haloalkoxy or Ci-6 deuterated haloalkoxy substituted by one or more substituents;Ring DGAis selected from C3-12 cycloalkyl, 3-12 membered heterocyclyl, Ce-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, Ce-14 aryl, 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, Cj-6 halogenated alkyl, Cj-6 deuterated haloalkyl, C1-6 hydroxyalkyl, Ci-6 deuterated hydroxy alkyl, Ci-6 sulfanyl, C1-6 deuterated sulfanyl, Ci-6 alkoxy, C 1 -6 deuterated alkoxy, Ci-6 halogenated alkoxy, Ci-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;alternatively, ringEGAis ‘ ’ 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 RGA16are each independently 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)mGAiORGAc!, and (=C)RGAc3RGAc4, wherein the amino, Ci-6 alkyl, Ci-6 deuterated alkyl, Cn 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 membered43658-02201 / WO (EXAV-023 / 001 WO)heterocyclyl, Ce-io aryl, 5-10 membered heteroaryl, ~(CH2)mGAiORGAcl, or (=C)RGACJRGAC4is optionally further substituted with 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-ioaryl, or 5-10 membered heteroaryl substituted by one or more substituents;RGAci, RGAC3, and RGAc4are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, thio, C1-6 alkyl, Ct-6 deuterated alkyl, Ct-6 halogenated alkyl, Ci-6 deuterated haloalkyl, Ci-6 hydroxyalkyl, Cue deuterated hydroxyalkyl, Ci- 6 sulfanyl, C1-6 deuterated sulfanyl, C1-6 alkoxy, C1-6 deuterated alkoxy. Cue 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)mGA2ORGAc2, - (CH2)mGA3C(O)NRGAalRGAbl, and -(CH2)mGA4C(O)ORGAa2, wherein the amino, Ci-6alkyl, Ci-6deuterated 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)mGA2ORGAc2, -(CH2)mGA3C(O)NRGAalRGAbl, or -(CH2)mGA4C(O)ORGAa2is optionally further substituted with 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, 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, 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, Co-10 aryl or 5-10 membered heteroaryl, wherein the amino, Ci-6 alkyl, Ci-643658-02201 / WO (EXAV-023 / 001 WO)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, C6-10 aryl, or 5-10 membered heteroaryl is optionally further substituted by deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, Ci-6 alkyl, Ci-6 deuterated alkyl, Ci-6 halogenated alkyl, Ci-6 deuterated haloalkyl, Ci-6 hydroxyalkyl, Ci-6 deuterated hydroxyalkyl, Ci-e sulfanyl, Ci-6 deuterated sulfanyl, C1-6 alkoxy, Ci-6 deuterated alkoxy, Ci-6 halogenated alkoxy, Ci-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C.i.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, Co-12 aryl or 5-12 membered heteroaryl;or, when nGA is not 1,RGA1and RGA1', RGA2and RGA1', 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, Ci-6 alkyl, Ci-6 deuterated alkyl, Ci-6 halogenated alkyl, Ci-6 deuterated haloalkyl, Ci- 6-hy dr oxy alkyl, 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, C’6-10 aryl, or 5-10 membered heteroaryl substituted by one or more substituents; andnGA, nGAl, mGAl, mGA2, mGA3, and mGA4 are each independently selected from 0, 1, 2, 3, 4 or 5;(iii)43658-02201 / WO (EXAV-023 / 001 WO)(RG^)mGB (RGB|)nGB (RGBC)OGB (RGBd)pGB (AGJ) — LGB1*-GB5xI-GB4 ^RGB1i-GBSy^ " RGB2UX / W(RGBe)qGB wherein:Ring AGBis selected from C3-15 carbocyclyl, 3-12 membered heterocyclyl, Cg-14 aryl, and 5-12 membered heteroaryl;Ring BGBis selected from 3-12 membered heterocyclyl, Cg-14 aryl, and 5-12 membered heteroaryl;Ring CGBis 9-membered bicyclic heteroaryl;Ring DGBis selected from C3-15 carbocyclyl, 3-12 membered heterocyclyl, Cg-14 aryl, and 5-12 membered heteroaryl;Ring EGBis selected from C3-15 carbocyclyl, 3-12 membered heterocyclyl, Cg-14 aryl, 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(RGBai)(RGBa2), -C(O)N(RGBal)(RGBa2), -N(RGBal)C(O)RGBa2, --S(O)N(RGBa1)(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: C1-6 alkyl, Ci- alkoxy, Ci- alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, Cg-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-6 alkoxy, C3-10 cycloalkyl, 3-10 membered heterocyclyl, Cg- 14 aryl, or 5-12 membered heteroaryl;43658-02201 / WO (EXAV-023 / 001 WO)RGBaland RGBa2are 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, C6-14 aryl, and 5-12 membered heteroaryl, wherein the Ci-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 from halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, Ci-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, Ci-6 alkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, Ce-14 aryl, and 5-12 membered heteroaryl, wherein the Ci-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 heteroaiyl 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, C3-7 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, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C6-14 aryl, and 5-12 membered heteroaryl, wherein the Ci-6 alkyl, Ci-6 alkoxy, Ci-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, Cg-i4 aryl, or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) RGBb1;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, Ci-6 alkoxy, C3-10 cycloalkyl, 3-10 membered heterocyclyl, Ce-14 aryl, and 5-12 membered heteroaryl;43658-02201 / WO (EXAV-023 / 001 WO)RGBb1is 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, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, Ce-14 aryl, 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 from halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, Ci-6 alkyl, Cj-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, Ce-14 aryl, and 5-12 membered heteroaryl;RGBcis 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, 3-10 membered heterocyclyl, C6-14 aryl, and 5-12 membered heteroaryl, wherein the C1-6 alkyl, Ci-6 alkoxy, Ci-6 alkylamino, 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) RGBc1;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, Ci-6 alkyl, Ci-6 alkoxy, C3-10 cycloalkyl, 3-10 membered heterocyclyl, Ce-14 aryl, 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, Ci-6 alkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, Ce-14 aryl, and 5-12 membered heteroaryl, wherein the Ci-6 alkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-43658-02201 / WO (EXAV-023 / 001 WO)io cycloalkyl, 3-10 membered heterocyclyl, Ce-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)2RGBd1, -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(RGBd1)(RGBd2), -N(RGBd1)S(O)RGBd2, -N(RGBd1)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: C1-6 alkyl, C1-6 alkoxy, Ci-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 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- 10 cycloalkyl, 3-10 membered heterocyclyl, C6-14 aryl, and 5-12 membered heteroaryl;RGBd1and RGBd2are each independently selected from hydrogen, deuterium, C1-6 alkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, Ce-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, 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;43658-02201 / WO (EXAV-023 / 001 WO)RGBd4and RGBd5are 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, C6-14 aryl, and 5-12 membered heteroaryl, wherein the Ci-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 from halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, Ci-6 alkyl, Cj-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, -SRGBe1, -S(O)RGBe1, -S(O)2RGBe1, -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(RGBe1)(RGBe2), -N(RGBe1)S(O)RGBe2, -N(RGBe1)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: Ci-6 alkyl, Ci-6 alkoxy, Ci-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 5-12 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, 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, Ci-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, Ce-14 aryl, and 5-12 membered heteroaryl, wherein the Ci-6 alkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, Ce-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, 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;RGBe3is independently selected from hydrogen, deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -RGBe4, -ORGBe4, -SRGBe4, -S(O)RGBe4, -S(O)2RGBe4, -43658-02201 / WO (EXAV-023 / 001WO)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, Ci-6 alkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, Ce-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 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;RRGB1and 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, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 alkylamino, C3-10 cycloalkyl, and 3-10 membered heterocyclyl, wherein the Ci-6 alkyl, Ci-6 alkoxy, Ci-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;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 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, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl;LGB2is 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)-;43658-02201 / WO (EXAV-023 / 001 WO)RGBL2are 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 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 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, 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, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl;LGB4 IS a bond, -LGB4X -C(RGBMa)(RGBMb)-LGB4y -LGB4X -OLGB4y ", -LGB4 -SLGB4y - LGB4X -C(O)-LGB4y -, -LGB4X -C(())OLGB4y -, -LGB4X -OC(O)-LGB4y -LGB4X -N(RGBL4a)C(())- LGB4V ", -LGB4X -C(O)N(RGBL4a)-LGB4y ", -LGB4X -N(RGBL4a)-LGB4y ~, -LGB4X - N(RGBL4a)C(O)N(RGBL4b)-LGB4y -N(RGBIA'l)C(S)N(RGBMb)-LGB4y ”, Or (R )rGB■GB4yLGB4xand LGB4yare 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) substituents independently selected from deuterium, halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, Ci-6 alkyl, Ci-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl;RGBL4aand RGBL4bare 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,43658-02201 / WO (EXAV-023 / 001 WO)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, Ci-6 alkyl, Ci-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 LGB4Z is C3-15 carbocyclyl, 3-12 membered heterocyclyl, Ce-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, 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, Ci-6 alkyl, C1-6 alkoxy, Ci-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl;LGB5xand LGB5yare 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) 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;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)43658-02201 / WO (EXAV-023 / 001 WO)(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, C1-10alkyl, C2-10alkenyl, C2-10alkynyl, C3-10cycloalkyl, C3-10cycloalkyl-C1-4alkyl, heterocyclyl, heterocyclyl-C1-4alkyl, aryl, aryl-C1-4alkyl, heteroaryl, heteroaryl-C1-4alkyl, — CN, — NO2, — NRGCA1RGCB1, — ORGCA1, — C(O)RGCA1, — C(O)ORGCA1, — OC(O)RGCA1, — C(O)NRGCA1RGCB1, — NRGCA1C(O)RGCB1, — OC(O)NRGCA1RGCB1, — S(O)2RGCA1, — S(O)2ORGCA1, — OS(O)2RGCA1, — NRGCA1S(O)2RGCB1, — S(O)2NRGCA1RGCB1, — P(O)RGCA1RGCB1, 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;each RGC2is independently selected from the group consisting of hydrogen, halogen, C1-10alkyl, C2-10alkenyl, C2-10alkynyl, C3-10cycloalkyl, C3-10cycloalkyl-C1-4alkyl, heterocyclyl, heterocyclyl-C1-4alkyl, aryl, aryl-C1-4alkyl, heteroaryl, heteroaryl-C1-4alkyl, — (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)2RGCA2, — S(O)2ORGCA2, — OS(O)2RGCA2, — NRGCA2S(O)2RGCB2, — S(O)2NRGCA2RGCB2, — P(O)RGCA2RGCB2, and — P(O)(ORGCA2)(ORGCB2),43658-02201 / WO (EXAV-023 / 001 WO)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- loalkyl, C2-ioalkenyl, C2-10 alkynyl, C3-10 cycloalkyl, C3-10 cycloalkyl-Ci-4 alkyl, heterocyclyl, heterocyclyl-Ci-4 alkyl, aryl, aryl-Ci-4 alkyl, heteroaryl, heteroaryl-C 1-4 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 RGC'"’; 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 C1-6alkyl;RGC6is selected from the group consisting of hydrogen, halogen, C1-10alkyl, C2-10alkenyl, C2-10alkynyl, C3-10cycloalkyl, C3-10cycloalkyl-C1-4alkyl, heterocyclyl, heterocyclyl-C1-4alkyl, aryl, aryl-C1-4alkyl, heteroaryl, heteroaryl-C1-4alkyl, — 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;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; orRGC9and RGC10, together with the atom to which they are attached, form a fragment / vw*and RGC7and RGC8are independently selected from the group consisting of hydrogen, halogen, and C1-3 alkyl; or43658-02201 / WO (EXAV-023 / 001 WO)RGC8and RGC9, together with the carbon atoms to which they are attached, form afragment, 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 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 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 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, C3-10 cycloalkyl, C3-10 cycloalkyl-Ci-4 alkyl, heterocyclyl, heterocyclyl-C 1-4 alkyl, aryl, aryl-Ci-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, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, cyano, alkoxy, alkylamino, di(alkyl)amino, haloalkyl, acyl, sulfonyl, sulfonamido, and halogen; or43658-02201 / WO (EXAV-023 / 001 WO)“RGCA1and RG, CBl” 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, Ci-6 alkyl, C2-6 alkenyl, C2- ealkynyl, C3-6 cycloalkyl, cyano, alkoxy, alkylamino, di(alkyl)amino, haloalkyl, acyl, sulfonyl, sulfonamido, and halogen;each of RGCX, R^1, RG<RCiCX3, and RGCX4is independently selected from the group consisting of hydroxyl, oxo, Ci-6 alkyl, C2-6 alkenyl, C2-6alkynyl, 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; orwherein:LGD1is selected from -CO-, -SO-, -SO2-, -NRGDa- and -CRGDaRGDb-;-RGDL>. ~>GDI *QGD^ / 'LGD2is selected from QGD, -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, Ce-io aryl, or 5-10 membered heteroaryl each optionally substituted with one or more RGD3 groups, each RGD3 group being independently selected from43658-02201 / WO (EXAV-023 / 001 WO)halogen, cyano, hydroxyl, NRGDaRGDb, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, C1-6alkylthio, C1-6haloalkyl, C1-6cyanoalkyl, C1-6hydroxyalkyl, and (optionally selected independently by one or more halogens and C1-6alkyl-substituted C3-10cycloalkyl)-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, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 alkylthio, Cj-6 deuterated alkyl, Cj-6 haloalkyl, Ct-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 RGD4groups, each RGD4group independently selected from halogen, cyano, hydroxyl, NRGDaRGDb, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, C1-6alkylthio, C1-6haloalkyl, C1-6cyanoalkyl, C1-6hydroxyalkyl, (C3-10cycloalkyl)-RGDL-, (5-10 membered heterocyclic alkyl)-RGDL-, (C6-10aryl)-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 Cj-6 alkoxy;Ring C is C3-10 cycloalkyl, C3-10 cycloalkenyl, 3-10 membered heterocyclic alkyl, 3-10 membered heterocyclic alkenyl, C6-10aryl, or 5-10 membered heteroaryl optionally substituted by one or more substituents, wherein each substituent is independently selected from H, halogen, cyano, hydroxyl, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, (Ci-6 alkoxy)-RGDL-, (Ci-6 alkylthio)-RoDL-, Ci-6 alkoxy-Ci-6 alkoxy-, Ci-6 deuterated alkyl, Ci-6 haloalkyl, Ci-6 cyanoalkyl, Ci-6 hydroxyalkyl, Ci-6 alkyl, Ci-6 halogenated alkyl, COOH, -CONH2, -CONH(CI-6 alkyl), - O-^-O— j^-ORGDaC(=S)NH2, -C(=S)NH(CI-6 alkyl), -P(RGDa)(RGDb), -PH(CI-6alkyl)(Ci-6alkyl), ^RcDb, Ci-6 alkyl-CO-, (Ci-6 haloalkoxy)-RGDL-(C3-io cycloalkyl optionally substituted with halogen or hydroxyl groups)-RGDL-, (C3-10 cycloalkyl)-C2-4 alkenyl-, (C3-10 cycloalkyl )-C2-4 alkynyl-, (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)-RoDL-, (5- 10-membered heteroaryloxy)-RGDL-, NRGDSRGDI -(CRGDaRGDb)mGD-, NRoDaRoDb-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 with43658-02201 / WO (EXAV-023 / 001 WO)one or more substituents each independently selected from oxo, halogen, cyano, Ci-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;RGD1is each independently H, halogen, cyano, hydroxyl, mercapto, NRGDaRGDb, C1-6alkyl, C2-6alkenyl, C1-6deuterated alkyl, C1-6haloalkyl, C1-6cyanoalkyl, C1-6hydroxyalkyl, C1-6alkoxy, C1-6alkylthio, C1-6halogenated alkoxy, or C3-8cycloalkyl, or two RGD1atoms together with the carbon atoms they are attached to form C3-4 cycloalkyl;RGD2is each independently selected from H, halogen, cyano, OH, NRGDaRGDb, C1-6alkyl, C2-6alkenyl, C1-6alkoxy, C1-6alkylthio, C1-6haloalkyl, C1-6halogenated alkoxy, optionally substituted with one or more substituents selected from C1-6alkyl-substituted 5-10-membered heteroaryl, -P(O)(C1-6alkyl)(C1-6alkyl), -C(O)(C1-6alkyl), -S(O)(C1-6alkyl), -S(O)2(C1-6alkyl), -NRGDa-S(O)2-(C1-6alkyl), -C(O)-(C3-10cycloalkyl), -S(O)-(C3-10cycloalkyl), -S(O)2-(C3-10cycloalkyl), -S(O)(NRGDa)-(C3-10cycloalkyl), or -C(O)-N(RGDa)-(C3-10cycloalkyl), or two of the RGD2groups 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-, C1-6alkyl, C1-6deuterated alkyl, C1-6haloalkyl, C1-6cyanoalkyl, C1-6hydroxyalkyl, (C1-6alkoxy)-RGDL-, (C1-6alkylthio)-RGDL-, (C3-10cycloalkyl optionally substituted with one or more halogens, C1-6alkyl or C1-6alkoxy)-RGDL-, (3-10 membered heterocyclic alkyl optionally substituted with one or more halogen, C1-6alkyl, or C1-6haloalkyl)-RGDL-, and (C6-10aryl)-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;RGDpis each independently halogen, cyano, hydroxyl, NH2, C1-6alkyl, or absent;RGDaand RGDbis each independently H or C1-6alkyl;RGD5and RGDIare each independently H, C1-6alkyl, C1-6haloalkyl, C6-10aryl, or 5-10 membered heteroaryl;43658-02201 / WO (EXAV-023 / 001 WO)RGDL is each independently a bond; Ci-io alkylene optionally substituted with halogen, cyano, or hydroxyl; or C1-4 deuterated alkylene;TGD is C1-4 alkylene, C2-4 alkylidene, 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;O -NOo o oYi, Y2, Y3, Y4, Y5, Ye, and Y7 are each independently a bond, -O-, or -NH-;Li, L2, and L3 are each independently a bond, -O-, C1-C25 alkylene, 3-12 membered heterocyclylene, or Ce-Cio arylene, wherein the alkylene, heterocyclylene, and arylene are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Co alkyl, Ce-Cio aryl, Ci-Cg alkoxy, or Ci-Ce haloalkyl;Ri, R2, R3, and R are each independently Ci-Coo alkyl, C2-C30 alkenyl, Ce-Cio aryl, or 3- 15 membered heterocyclyl, wherein the alkyl, alkenyl, aryl, and heterocyclyl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-C30 alkoxy, -O-(Ci-Ce alkyl ene)-(C6-Cio aryl), -N(RN)2, or Ci-Ce haloalkyl;RN is each independently H, C1-C30 alkyl or C6-C10 aryl; andRp is C1-C20 alkyl or C6-C10 aryl, wherein the alkyl and aryl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Cs alkyl, Ci-Ce alkoxy, or Ci-Ce haloalkyl.43658-02201 / WO (EXAV-023 / 001 WO)

[0157] In some aspects, the present disclosure provides a compound of Formula (I):G-A (I),a stereoisomer thereof, a tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein:RG5> RG2RG4 RGS>■■■■■■( )N > • y^^Rt3gG’-':tRt*--— Hi-.. 1 R03< CHQ"’ gG'i2}.,G1(CH2U2Z':(’) orG2RGRG5G1 RGRR 4R> L_RG2' QG2' / 'nG3\ > / / X-z A-j ■v"^-4 "^11 ii> / -6■^RG3'^11 / / Zs" RG6Z10QG1RG3(CH2)nG17G1£G2RG7"^ I ^(CH2)nG2RGS\\, a stereoisomer thereof, or a tautomer thereof;XG is — N== or — CRaG==; RaGis selected from a hydrogen atom, a halogen atom, and Cn 6 alkyl;YGis selected from —C(=O)—, —CHRG—, and —S(=O)2—; RGis a hydrogen atom or C1-6 alkyl;QG1is C6-10aryl or 5 to 10 membered heteroaryl, wherein the CA-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 C1-6 alkyl is optionally substituted with one or more halogen atoms), C3-6 cycloalkyl, and C1-6 alkoxy;QGis 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, Ci^ alkyl (wherein C1-6 alkyl is optionally substituted with one or more halogen atoms), C1-6 alkoxy, and > - -NRtlQaRGQb, and two C1-6 alkyl groups together with a carbon atom to which they are attached may form C3-43658-02201 / WO (EXAV-023 / 001 WO)s carbocyclic ring; and RGQaand RGQbare independently selected from a hydrogen atom, C1-6alkyl, and (C1-6alkyl)carbonyl;Z3, Z4, Z5, Z6, Z7, Z8, Z9, Z10, Z11, Z12and Z13are each independently selected from the group consisting of N and C;RG1, RG2, RG3, RG1', RG2', and RG3'are each independently selected from a hydrogen atom, halogen atom, C1-6 alkyl, Ci-e alkoxy, Ci-e 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- alkoxy, and hydroxy; or RGand 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 Ci -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 C3-15cycloalkane 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, Ci-6 alkoxy, and 3 to 12 membered heterocyclyl, and RG7aand RG7bare independently selected from a hydrogen atom, C1-6 alkyl, and (C 1-6 alky l)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 of43658-02201 AVO (EX AV-023 / 001 WO)wherein Rzais selected from a hydrogen atom, C1-6alkyl, and (C1-6alkyl)carbonyl; Rzband Rzcare each independently a hydrogen atom or Ci-6 alkyl; n4 is an integer of 1 to 3; n5 and 116 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 C1-6 alkyl, C3-15 cycloalkyl, 3 to 12 membered heterocyclyl, C6-10aryl, and 5 to 10 membered heteroaryl, wherein the C3-15 cycloalkyl, 3 to 12 membered heterocyclyl, Ce-ioaryl, 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 (Cj-6alkyl)carbonyl, wherein Cj -6 alkyl is optionally substituted with one or more substituents independently selected from hydroxy, a halogen atom and Cj-6 alkoxy,e) —C(=O)—NRzfRzg; wherein Rzfand Rzgare independently selected from a hydrogen atom, C1-6 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 Cj-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) Ci-6 alkyl optionally substituted with one or more substituent independently selected from a halogen atom, hydroxy, — NRziRzj, Ci-6 alkoxy, and 3 to 12 membered heterocyclyl, wherein Rziand Rzjare independently a hydrogen atom or 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-6 alkyl)carbonyl,43658-02201 / WO (EXAV-023 / 001WO)j) C6-10aryl optionally substituted with one or more (C1-6alkyl)carbonyl, k) 5 to 10 membered heteroaryl optionally substituted with one or more substituents independently selected from C1-6alkyl, C1-6alkoxy, —NRzkRzl, and 3 to 12 membered heterocyclyl, wherein Rzkand Rzlare independently selected from a hydrogen atom, Ci-6 alkyl and (C i-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 (Ch -6 alkyl) carbonyl, wherein each of alkyl and alkoxy is optionally substituted with halogen; andn) C1-C6alkyl-C3-C15cycloalkyl 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 (C1-6 alkyl) carbonyl, wherein each of alkyl and alkoxy is optionally substituted with halogen; or(11)^GA13wherein:RGA13isfrom hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, thio, C1-6 alkyl, C1-6 deuterated alkyl, C1-6 halogenated alkyl, C1-6 deuterated haloalkyl, C1-43658-02201 / WO (EXAV-023 / 001 WO)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, 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, Cj-6 alkoxy, Ct-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, thio, C1-6 alkyl, Ct-6 deuterated alkyl, C1-6 halogenated alkyl, Ct-6 deuterated haloalkyl, Ci-6 hydroxyalkyl, Cue deuterated hydroxyalkyl, C1-6 sulfanyl, C1-6 deuterated sulfanyl, Ci-6 alkoxy, C1-6 deuterated alkoxy, Ci-e halogenated alkoxy, Ct-6 deuterated haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, 3-8 membered heterocyclyl, C&.10 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 C3-14cycloalkyl, 3-14 membered heterocyclyl, Ce-14 aryl, and 5-14 membered heteroaryl;Ring BGAis selected from C3-12 cycloalkyl, 3-12 membered heterocyclyl, Ce-14 aryl, and 5-14 membered heteroaryl, wherein the C3-12 cycloalkyl, 3-12 membered heterocyclyl, Ce-14 aryl, or 5-14 membered heteroaryl is optionally further substituted by deuterium, halogen, amino, nitro, hydroxyl, cyano, oxo, thiol, 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 haloalkoxy or Ci-6 deuterated haloalkoxy substituted by one or more substituents;Ring DGAis selected from C3-12cycloalkyl, 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, Co-14 aryl, or 5-14 membered heteroaryl is optionally further substituted by deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, thio, Ci-6 alkyl, C1-0 deuterated alkyl, Ci-6 halogenated alkyl, C1-0 deuterated haloalkyl, Ci-6 hydroxyalkyl, C1-0 deuterated hydroxyalkyl, Ci-6 sulfanyl, C1-043658-02201 / WO (EXAV-023 / 001 WO)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;alternatively, ringEGAis optionally substituted with one or more substituents selected from the group consisting of methyl, ethyl, methoxy, and ethoxy;RGA1 T? GA3 T? GA4 T? GA5 pGA6 pGA7 pGA8 pGA9 r? GA14 r? GA15 J T? GA16 Eindependently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, thio, C1-6 alkyl, Cj-6 deuterated alkyl, Cj-6 halogenated alkyl, Cj-6 deuterated haloalkyl, C1-6 hydroxyalkyl, Cue 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)mGA1ORGAc1, and —C(=O)RGAc3RGAc4, wherein the amino, Ci-6 alkyl, Ci-6 deuterated alkyl, Cn 6 halogenated alkyl, Ci-6 deuterated haloalkyl, Ci-6 hydroxyalkyl, Ci-6 deuterated hydroxyalkyl, Ci-6 sulfanyl, Cj-6 deuterated sulfanyl, Ci-6 alkoxy, Cj-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)mGAiORGAcl, or —C(=O)RGAc3RGAc4is optionally further substituted with 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-ioaryl, 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, 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 membered43658-02201 / WO (EXAV-023 / 001 WO)heterocyclyl, Ce-io aryl, 5-10 membered heteroaryl, -(CH2)mGA2ORGAc2, - (CH2)mGA3C(O)NRGAalRGAbl, and -(CH2)mGA4C(O)ORGAa2, wherein the amino, 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-e deuterated sulfanyl, Ci-6 alkoxy, Ci-e deuterated alkoxy, Ci-6 halogenated alkoxy, Ci-6 deuterated haloalkoxy, C2-6 alkenyl, C2- 6 alkynyl, C3- 8 Cycloalkyl, 3-8 membered heterocyclyl, Cs-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, Ci-6 alkyl, Cj-6 deuterated alkyl, Ci-6 halogenated alkyl, Ci-6 deuterated haloalkyl, Ci-6 hydroxyalkyl, Ci-6 deuterated hydroxyalkyl, C1-6 sulfanyl, Ci-e deuterated sulfanyl, Ct-6 alkoxy, Ci-e 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;RGAai, RGAa2, RGAbl, and RGAc2are each independently selected from hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, thio, Ci-6 alkyl, Ci-6 deuterated alkyl, C1-6 halogenated alkyl, Ci-6 deuterated haloalkyl, Ci-6 hydroxyalkyl, Ci-6 deuterated hydroxyalkyl, Ci- 6 sulfanyl, Ci-6 deuterated sulfanyl, Ci-6 alkoxy, Cj-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, wherein the amino, 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, or 5-10 membered heteroaryl is optionally further substituted by deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, 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, Co-10 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, Co-12 aryl or 5-12 membered heteroaryl;43658-02201 AVO (EX AV-023 / 001 WO)or, when nGA is not 1,RGA1and RGAi, RGA2and RGA1, RGA4and RGA5, RGA5and RGA6, RGA7and RGA8, together with the atoms connected to them, form C3-10cycloalkyl, 3-10 membered heterocyclyl, C6-12aryl, 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, Ci- 6-hydroxy lkyl, Ci-6 deuterated hydroxyalkyl, C1-6 sulfanyl, C1-6 deuterated sulfanyl, Ci-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; andnGA, nGA l, mGAl, mGA2, mGA3, and mGA4 are each independently selected from 0, 1, 2, 3, 4 or 5; or(lii)(RGBa)mGB (RGB,)nGB (RGBc)oGB (RGBd)pGB1-GB4(RGBe)qGB wherein:Ring AGBis selected from C3-15 carbocyclyl, 3-12 membered heterocyclyl, C6-14 aryl, and 5-12 membered heteroaryl;Ring BGBis selected from 3-12 membered heterocyclyl, C6-14aryl, and 5-12 membered heteroaryl;Ring CGBis 9-membered bicyclic heteroaryl;Ring DGBis selected from C3-15carbocyclyl, 3-12 membered heterocyclyl, C6-14aryl, and 5-12 membered heteroaryl;Ring EGBis selected from C3-15 carbocyclyl, 3-12 membered heterocyclyl, Ce-M aryl, and 5-12 membered heteroaryl;43658-02201 / WO (EXAV-023 / 001 WO)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, - -S(O)N(RGBa1)(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-e alkoxy, Ci-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 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-6 alkoxy, C3-10 cycloalkyl, 3-10 membered heterocyclyl, Ce- 14 aryl, or 5-12 membered heteroaryl;RGBaland RGBa2are 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, Ce-14 aryl, and 5-12 membered heteroaryl, wherein the Ci-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 from halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, Ci-6 alkyl, Ci-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, Ci-6 alkyl, Ci-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, 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 from43658-02201 / WO (EXAV-023 / 001 WO)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, Ct-6 alkoxy, C1-6 alkylamino, 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, Ci-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3- 10 cycloalkyl, 3-10 membered heterocyclyl, C<5-14 aryl, or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) RGBb1;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, Ce-14 aryl, and 5-12 membered heteroaryl;RGBb1is 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(())N(RGBb2)(RGBb3), -S(O)2N(RGBb2)(RGBb3), -N(RGBb2)S(O)RGBb3, and -N(RGBb2)S(())2RGBb3;RGBb2and RGBb3are each independently selected from hydrogen, deuterium, C1-6 alkyl, Ci-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, C3-10 cycloalkyl, 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, C1-6 alkylamino, 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, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-43658-02201 / WO (EXAV-023 / 001 WO)io cycloalkyl, 3-10 membered heterocyclyl, Ce-14 aryl, or 5-12 membered heteroaryl is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) RGBel;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, Ce-14 aryl, and 5-12 membered heteroaryl;GBC1is 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)OGBC2, -OC(O)RGBC2, -N(RGBC2)(RGBC3), -C(O)N(RGBC2)(RGBC3), -N(GBC2)C(O)RGBC3, -S(())N(RGBC2)(RGBC3), -S(O)2N(RGBC2)(GBC3), -N(GBC2)S(O)RGBC3, -N(RGBC2)S(())2RGBC3;GBC2and RGBC3are 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, C6-14 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 heteroaiyl 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)2RGBd1, -C(O)RGBdl, - C(O)ORGBdl, -OC(O)RGBdl, -N(RGBdl)(RGBd2), -C(O)N(RGBd!)(RGBd2), -N(RGBd!)C(O)RGBd2, - S(O)N(RGBdl)(RGBd2), -S(O)2N(RGBdl)(RGBd2), -N(RGBdl)S(O)RGBd2, -N(RGBd,)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: C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, Co-14 aryl, 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 heteroaiyl, 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 from43658-02201 / WO (EXAV-023 / 001 WO)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;RGBdland RGBd2are 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, 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, Ci-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 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(())ORGBd4, -OC(())RGBd4, -N(RGBd4)(RGBd5), -C(O)N(RGBd4)(RGBd5), - N(RGBd4)C(O)RGBd5, -S(())N(RGBd4)(RGBd5), -S(())2N(RGBd4)(RGBd5), -N(RGBd4)S(())RGBd5, and - N(RGBd4)S(())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, Ce-14 aryl, and 5-12 membered heteroaryl, wherein the Ci-6 alkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3- 10 cycloalkyl, 3-10 membered heterocyclyl, Cg-14 aryl, or 5-12 membered heteroaiyl 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, C3-7 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)RGBei, -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(RGBe!)(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: Ci-6 alkyl, Ci-6 alkoxy, Ci-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, Co-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 5-1243658-02201 / WO (EXAV-023 / 001 WO)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, Ce-14 aryl, and 5-12 membered heteroaryl;RGBe1and 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, C6-14 aryl, and 5-12 membered heteroaryl, wherein the Ci-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 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(())2RGBe5, and -P(O)(RGBe4)RGBe5;RGBe4and RGBe5are 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, C6-14 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 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, Ci-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, 3-7 membered heterocyclyl, phenyl, and 5-6 membered heteroaryl;RRGB1and RGB2together with the atoms to which they are attached, form C3-15carbocyclyl 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, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 alkylamino, C3-10 cycloalkyl, and 3-10 membered heterocyclyl, wherein the Ci-6 alkyl, Ci-6 alkoxy, Ci-6 alkylamino, C3-10 cycloalkyl, or 3-10 membered heterocyclyl is43658-02201 / WO (EXAV-023 / 001 WO)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;LGBI is 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)-;RGBL1|s 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 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, 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, Cj-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, Ci-6 alkyl, C1-6 alkoxy, C4-6 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, Ci-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, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl;43658-02201 / WO (EXAV-023 / 001 WO)LGB4 is a bond, -LGB4X -C(RGBI a)(RGBI b)-LGB4y -LGB X -0LGB4y -LGB4X -SLGB4V - LGB4X -C(O)-LGB4y ", -LGB4X -C(0)0LGB4V ", -LGB4X -0C(0)-LGB4V -LGB4X -N(RGBL4a)C(O)-LGB4V -LGB4 -C(O)N(RGBL4d)-LGB4y ", -LGB4X -N(RGBD*d)-LGB4y ", ~LGB X " N(RGBL4a)C(O)N(RGBL4b)-LGB4y -LGB4X -N(RGBL4a)C(S)N(RGBL4b)-LGB4y or(RGBL4z)rGBLGB4xand 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 alkylannno, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl;RGBL4aand RGBL4bare 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, 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 LGB4Z is C3-15 carbocyclyl, 3-12 membered heterocyclyl, C6-14 aryl, 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 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, C1-6 alkoxy, C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, and 3-10 membered heterocyclyl;LGB5Xand LGB5Yare each independently a bond or C1-10alkylene, wherein the Ci-10 alkylene is optionally substituted with one or more (e.g., 2, 3, 4, 5, 6, 7 or 8) substituents43658-02201 / WO (EXAV-023 / 001 WO)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 m 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 variabl es are combined to form a stable chemicalYi, Y2, Y3, Y4, Y5, Ye, and Y7 are each independently a bond, -O-, or -NH-;Li, L2, and L3 are each independently a bond, -O-, C1-C25 alkylene, 3-12 membered heterocyclylene, or C’e-Cio arylene, wherein the alkylene, heterocyclylene, and arylene are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Cg alkyl, Cg-Cio aryl, Ci-Cg alkoxy, or Ci-Ce haloalkyl;Ri, R2, R3, and R4 are each independently Ci-Ceo alkyl, C2-C30 alkenyl, Cg-Cio aryl, or 3- 15 membered heterocyclyl, wherein the alkyl, alkenyl, aryl, and heterocyclyl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Cg-Cio aryl, Ci-C30 alkoxy, -O-(Ci-C6 alkylene)-(C6-Cio aryl), -N(RN), or Ci-Cg haloalkyl;RN is each independently H, C1-C30 alkyl or C6-C10 aryl; andRp is C1-C20 alkyl or Ce-Cio aryl, wherein the alkyl and aryl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Cg alkyl, Ci-Ce alkoxy, or Ci-Ce haloalkyl.

[0158] In an aspect, the present disclosure provides a compound of Formula (I):43658-02201 AVO (EX AV-023 / 001 WO)G-A (I),a stereoisomer thereof, a tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein:XG is — N= or — CRaG==; RaGis selected from a hydrogen atom, a halogen atom, and Cu 6 alkyl;YG is selected from — C(=O) —, — CHRG—, and — S(=O)2 —; RGis a hydrogen atom or Ci -6 alkyl;QG1IS C6-JO 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, Cj -6 alkyl (wherein Ci-6 alkyl is optionally substituted with one or more halogen atoms), C3-6 cycloalky 1, 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, Cj -e, alkyl (wherein Ci-6 alkyl is optionally substituted with one or more halogen atoms), C 1-6 alkoxy, and — NRGQaRfiQb, and two Ci-6 alkyl groups together with a carbon atom to which they are attached may form C3-43658-02201 / WO (EXAV-023 / 001 WO)s carbocyclic ring; and RGQaand RGQbare independently selected from a hydrogen atom, C1-6alkyl, and (C1-6alkyl)carbonyl;Z3, Z4, Z5, Z6, Z7, Z8, Z9, Z10, Z11, Z12and Z13are each independently selected from the group consisting of N and C;RG1, RG2, RG3, RG1', RG2', and RG3'are each independently selected from a hydrogen atom, halogen atom, C1-6 alkyl, Ci-e alkoxy, Ci-e 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- alkoxy, and hydroxy; or RGand 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 Ci -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 C3-15cycloalkane 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, Ci-6 alkoxy, and 3 to 12 membered heterocyclyl, and RG7aand RG7bare independently selected from a hydrogen atom, C1-6 alkyl, and (C 1-6 alky l)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 of43658-02201 AVO (EX AV-023 / 001 WO)wherein Rzais selected from a hydrogen atom, C1-6alkyl, and (C1-6alkyl)carbonyl; Rzband Rzcare each independently a hydrogen atom or Ci-6 alkyl; n4 is an integer of 1 to 3; n5 and 116 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 C1-6 alkyl, C3-15 cycloalkyl, 3 to 12 membered heterocyclyl, C6-10aryl, and 5 to 10 membered heteroaryl, wherein the C3-15 cycloalkyl, 3 to 12 membered heterocyclyl, Ce-ioaryl, 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 (Cj-6alkyl)carbonyl, wherein Cj -6 alkyl is optionally substituted with one or more substituents independently selected from hydroxy, a halogen atom and Cj-6 alkoxy,e) —C(=O)—NRzfRzg; wherein Rzfand Rzgare independently selected from a hydrogen atom, C1-6 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 Cj-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) Ci-6 alkyl optionally substituted with one or more substituent independently selected from a halogen atom, hydroxy, — NRziRzj, Ci-6 alkoxy, and 3 to 12 membered heterocyclyl, wherein Rziand Rzjare independently a hydrogen atom or 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-6 alkyl)carbonyl,43658-02201 / WO (EXAV-023 / 001 WO)j) C6-10aryl optionally substituted with one or more (C1-6alkyl)carbonyl, k) 5 to 10 membered heteroaryl optionally substituted with one or more substituents independently selected from C1-6alkyl, C1-6alkoxy, —NRzkRzl, and 3 to 12 membered heterocyclyl, wherein Rzkand Rzlare independently selected from a hydrogen atom, Ci-6 alkyl and (C i-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 (Ch -6 alkyl) carbonyl, wherein each of alkyl and alkoxy is optionally substituted with halogen; andn) C1-CAalkyl-C1-Cis cycloalkyl wherein the cycloalkyl or alkyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, oxo, Ch -6 alkyl, Ci-6 alkoxy and (C1-6 alkyl) carbonyl, wherein each of alkyl and alkoxy is optionally substituted with halogen;Y1, Y2, Y3, Y4, Y5, Y6, and Y7 are each independently a bond, -O-, or -NH-;Li, L2, and L3 are each independently a bond, -O-, C1-C25 alkylene, 3-12 membered heterocyclylene, or C1-Ch 0 arylene, wherein the alkylene, heterocyclylene, and arylene are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Cs alkyl, C6-C10 aryl, Ci-Cs alkoxy, or C1-Ch haloalkyl;43658-02201 / WO (EXAV-023 / 001 WO)R1, R2, R3, and R4 are each independently C1-C60 alkyl, C2-C30 alkenyl, C6-C10 aryl, or 3-15 membered heterocyclyl, wherein the alkyl, alkenyl, aryl, and heterocyclyl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-C30 alkoxy, -O-(Ci-C6 alkylene)-(C6-Cio aryl), -N(RN), or C1-C6 haloalkyl;RN is each independently H, C1-C30 alkyl or C6-C10 aryl; andRp is C1-C20 alkyl or Ce-Cio aryl, wherein the alkyl and aryl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ci-Ce alkoxy, or Ci-Ce haloalkyl.

[0159] In an aspect, the present disclosure provides compounds of Formula (I):G-A (I),a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein: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 C1-6 alkyl;QG1is C6-10aryl or 5 to 10 membered heteroaryl, wherein the C6-10aryl and 5 to 10 membered heteroaryl are optionally substituted with one to five substituents independently selected from a halogen atom, C1-6 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 C1-6 alkyl groups together with a carbon atom to which they are attached may form C3-43658-02201 / WO (EXAV-023 / 001 WO)s carbocyclic ring; and RGQaand RGQbare independently selected from a hydrogen atom, Cn 6 alkyl, and (Ci-6alkyl)carbonyl;RG1, RG2and RG3are each independently selected from a hydrogen atom and Ci-6 alkyl (wherein, Ci -6 alkyl is optionally substituted with one or more substituents independently selected from a halogen atom, Ci-6 alkoxy, and hydroxy);RG4, RG5and RG6are independently selected from a hydrogen atom, a halogen atom, and C1-6 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 Cue alkyl, wherein the C1-6 alkyl is optionally substituted with one or more substituents independently selected from a halogen atom, hydroxy, - -NRG / aRG7b, C1-6 alkoxy, and 3 to 12 membered heterocyclyl, and RG / aand RG7bare independently selected from a hydrogen atom, Ci-6 alkyl, and (Ci-6 alkyl)carbonyl;nGl is an integer of 0 to 3; nG2 is an integer of 0 to 5;ZG1is selected from the group consisting ofwherein Rzais selected from a hydrogen atom, C1-6 alkyl, and (C1-6 alkyl)carbonyl; Rzband Rzcare 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);ZG2is selected from the group consisting of C1-6 alkyl, C3-15 cycloalkyl, 3 to 12 membered heterocyclyl, Ce-ioaryl, and 5 to 10 membered heteroaryl, wherein the C3-15 cycloalkyl, 3 to 1243658-02201 AVO (EX AV-023 / 001 WO)membered heterocyclyl, Ce-ioaryl, 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 (Cj-6alkyl)carbonyl, wherein Ci -6 alkyl is optionally substituted with one or more substituents independently selected from hydroxy, a halogen atom and Cj-6 alkoxy,e) — C(=O) — NRzfRzg; wherein Rzfand Rzgare independently selected from a hydrogen atom, C1-6 alkyl and (C1-6alkyl)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 Ci -6 alkyl,g) Ci-6 alkyl optionally substituted with one or more substituent independently selected from a halogen atom, hydroxy, - -NRz'Rzj, Ci-6 alkoxy, and 3 to 12 membered heterocyclyl, wherein Rziand Rzjare independently a hydrogen atom or 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 C1-6 alkyl and (C1-6alkyl)carbonyl, j) Co-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 Ci-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 (C i-6 alkyl)carbonyl, and wherein 3 to 1243658-02201 / WO (EXAV-023 / 001 WO)membered heterocyclyl is optionally substituted with one or more substituents independently selected from Ci-6 alkyl and (C 1-6 alkyl)carbonyl, and l) — P(=O)(Rzm)(Rzn), wherein Rzmand Rznare each independently a hydrogen atom or C1-6 alkyl;b Rf / , orYi, Y2, Y3, Y4, Y5, Ye, and Y7 are each independently a bond, -O-, or -NH-;Li, L2, and L3 are each independently a bond, -O-, 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-C’e alkoxy, or Ci-Ce haloalkyl;R1, R2, R3, and R4 are each independently C1-C60 alkyl, C2-C30 alkenyl, C6-C10 aryl, or 3- 15 membered heterocyclyl, wherein the alkyl, alkenyl, aryl, and heterocyclyl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-C’e alkyl, Ce-Cio aryl, C’i-C30 alkoxy, -O-(Ci-Ce alkylene)-(Ce-Cio aryl), -N(RN)2, or Ci-Ce haloalkyl;RN is each independently H, C1-C30 alkyl or C6-C10 aryl; andRp is C1-C20 alkyl or Ce-Cio aryl, wherein the alkyl and aryl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ci-Ce alkoxy, or Ci-Ce haloalkyl.

[0160] In an aspect, the compound is of Formula (I), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein:43658-02201 / WO (EXAV-023 / 001 WO)43658-02201 / WO (EXAV-023 / 001 WO)Y1, Y2, Y3, Y4, Y5, Y6, and Y7 are each independently a bond, -O-, or -NH-;L1, L2, and L3 are each independently a bond, -O-, C1-C25 alkylene, or C6-C10 arylene, wherein the alkylene and arylene are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ct-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl;R1, R2, R3, and R4 are each independently C1-C60 alkyl, C2-C30 alkenyl, Ce-Cio aryl, or 3- 15 membered heterocyclyl, wherein the alkyl, alkenyl, aryl, and heterocyclyl are optionally43658-02201 / WO (EXAV-023 / 001 WO)substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Cg-Cio aryl, Ci- C30 alkoxy, -O-(Ci-C6 alkylene)-(C6-Cio aryl), -N(RN)2, or Ci-Cg haloalkyl;RN is each independently H, C1-C30 alkyl or C6-C10 aryl; andRp is C1-C20 alkyl or Ce-Cio aryl, wherein the alkyl and aryl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Cg alkyl, Ci-Ce alkoxy, or Ci-Cg haloalkyl.

[0161] In an aspect, the compound is of Formula (I), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein:43658-02201 / WO (EXAV-023 / 001 WO)Yi, Y2, Y3, Y4, Y5, Ye, and Y7 are each independently a bond, -O-, or -NH-;L1, L2, and L3 are each independently a bond, -O-, 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, C6-C10 aryl, C1-C6 alkoxy, or C1-C6 haloalkyl;Ri, R2, R3, and R4 are each independently Ci-Cso alkyl, C2-C30 alkenyl, Ce-Cio aryl, or 3- 15 membered heterocyclyl, wherein the alkyl, alkenyl, aryl, and heterocyclyl are optionally43658-02201 / WO (EXAV-023 / 001 WO)substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Cg-Cio aryl, Ci-C30 alkoxy, -O-(Ci-Ce alkylene)-(Ce-Cio aryl), -N(RN)2, or Ci-Cg haloalkyl;RN is each independently H, C1-C30 alkyl or C6-C10 aryl; andRp is C1-C20 alkyl or Ce-Cio aryl, wherein the alkyl and aryl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Cg alkyl, Ci-Ce alkoxy, or Ci-Cg haloalkyl.

[0162] In an aspect, the compound is of Formula (I), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein:43658-02201 / WO (EXAV-023 / 001 WO)Y1, Y2, Y3, Y4, Y5, Y6, and Y7 are each independently a bond, -O-, or -NH-;L1, L2, and L3 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, Ct-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl;R1, R2, R3, and R4 are each independently C1-C60 alkyl, C2-C30 alkenyl, Ce-Cio aryl, or 3- 15 membered heterocyclyl, wherein the alkyl, alkenyl, aryl, and heterocyclyl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-C’e alkyl, Ce-Cio aryl, Ci-C30 alkoxy, -O-(C'i-Ce alkylene)-(Ce-Cio aryl), -N(RN)2, or Ci-Ce haloalkyl;RN is each independently H, C1-C30 alkyl or C6-C10 aryl; andRp is C1-C20 alkyl or Ce-Cio aryl, wherein the alkyl and aryl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-C’ alkyl, Ci-C’e alkoxy, or Ci-Ce haloalkyl.43658-02201 / WO (EXAV-023 / 001 WO)

[0163] In an aspect, the compound is of Formula (I), a stereoisomer thereof, or aY1, Y2, Y3, Y4, Y5, Y6, and Y7 are each independently a bond, -O-, or -NH-;Li, L2, and L3 are each independently a bond, -O-, 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, C6-C10 aryl, C1-C6 alkoxy, or C1-C6 haloalkyl;R1, R2, R3, and R4 are each independently C1-C60 alkyl, C2-C30 alkenyl, C6-C10 aryl, or 3- 15 membered heterocyclyl, wherein the alkyl, alkenyl, aryl, and heterocyclyl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-C30 alkoxy, -O-(Ci-Ce alkylene)-(C6-Cw aryl), -N(RN)2, or Ci-Ce haloalkyl;43658-02201 / WO (EXAV-023 / 001 WO)RN is each independently H, C1-C30 alkyl or C6-C10 aryl; andRpis C1-C20alkyl or C6-C10aryl, wherein the alkyl and aryl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6alkyl, C1-C6alkoxy, or C1-C6haloalkyl.

[0164] In an aspect, the compound is of Formula (I), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein:43658-02201 / WO (EXAV-023 / 001 WO)Y1, Y2, Y3, Y4, Y5, Y6, and Y7 are each independently a bond, -O-, or -NH-;L1, L2, and L3 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, Cj-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Cj-Ce haloalkyl;R1, R2, R3, and R4 are each independently C1-C30 alkyl, C2-C30 alkenyl, or C6-C10 aryl, wherein the alkyl, alkenyl, and aryl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6 alkyl, C6-C10 aryl, C1-C6 alkoxy, or C1-C6 haloalkyl; andRp is C1-C20 alkyl or Ce-Cio aryl, wherein the alkyl and aryl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Cg alkyl, Ci-C’e alkoxy, or Ci-Ce haloalkyl.

[0165] In an aspect, the compound is of Formula (I), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein:43658-02201 / WO (EXAV-023 / 001 WO)Y1, Y2, Y3, Y4, Y5, Y6, and Y7 are each independently a bond, -O-, or -NH-;L1, L2, and L3 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, C6-C10 aryl, C1-C6 alkoxy, or C1-C6 haloalkyl;R1, R2, R3, and R4 are each independently C1-C30 alkyl, C2-C30 alkenyl, or C6-C10 aryl, wherein the alkyl, alkenyl, and aryl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6 alkyl, C6-C10 aryl, C1-C6 alkoxy, or C1-C6 haloalkyl; andRp is C1-C20 alkyl or Ce-Cio aryl, wherein the alkyl and aryl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Cg alkyl, Ci-Ce alkoxy, or Ci-Cg haloalkyl.43658-02201 / WO (EXAV-023 / 001 WO)

[0166] In an aspect, the compound is of Formula (I), a tautomer thereof, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein:G isX is CH or N;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 C6-C10 aryl or 5-15 membered heteroaryl, wherein the C6-C10 aryl is optionally substituted with one or more substituents independently selected from halogen, C1-C6 alkyl, -NH(C1-C6 alkyl), and -P(=O)(C1-C6 alkyl)2, and wherein the 5-15 membered heteroaryl is optionally substituted with one or more substituents independently selected from halogen, C1-C6 alkyl, C1-C6 deuteroalkyl, and C3-C6 cycloalkyl;each RP5is independently selected from H, C1-C6 alkyl, and C3-C6 cycloalkyl;43658-02201 / WO (EXAV-023 / 001 WO)Y1, Y2, Y3, Y4, Y5, Y6, and Y7 are each independently a bond, -O-, or -NH-;L1, L2, and L3 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, C6-C10 aryl, C1-C6 alkoxy, or C1-C6 haloalkyl;R1, R2, R3, and R4 are each independently C1-C60 alkyl, C2-C30 alkenyl, C6-C10 aryl, or 3-15 membered heterocyclyl, wherein the alkyl, alkenyl, aryl, and heterocyclyl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6 alkyl, C6-C10 aryl, C1-C30 alkoxy, -O-(C1-C6 alkylene)-(C6-C10 aryl), -N(RN)2, or C1-C6 haloalkyl; andRN is each independently H, C1-C30 alkyl or C6-C10 aryl,

[0167] In an aspect, the compound is of Formula (I), a tautomer thereof, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein:RPIG is43658-02201 / WO (EXAV-023 / 001 WO)X is CH or N;each RP1is independently selected from H and C1-C6 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 C6 aryl or 9-13 membered heteroaryl, wherein the C6 aryl is optionally substituted with one or more substituents independently selected from halogen, C1-C6 alkyl, -NH(C1-C6 alkyl), and -P(=O)(C1-C6 alkyl)2, and wherein the 9-13 membered heteroaryl is optionally substituted with one or more substituents independently selected from halogen, C1-C6 alkyl, C1-C6 deuteroalkyl, and C3-C6 cycloalkyl;each RP5is independently selected from H, C1-C6 alkyl, and C3-C6 cycloalkyl;Y1, Y2, Y3, Y4, Y5, Y6, and Y7 are each independently a bond, -O-, or -NH-;L1, L2, and L3 are each independently a bond, C1-C25 alkylene, or Cg-Cio arylene; and Ri, R2, R3. and R4 are each independently Ci-Cgo alkyl.

[0168] In an aspect, the compound is of Formula (I), a tautomer thereof, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein:43658-02201 / WO (EXAV-023 / 001 WO)X is CH;RP2is H, Ci-Ce alkyl, C2-C6 alkenyl or C2-C6 alkynyl;each RP5is independently selected from H, Ci-Ce alkyl, and C3-C6 cycloalkyl;Y1, Y2, Y3, Y4, Y5, Y6, and Y7 are each independently a bond, -O-, or -NH-;Li, L2, and L3 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;R1, R2, R3, and R4 are each independently C1-C60 alkyl, C2-C30 alkenyl, C6-C10 aryl, or 3-15 membered heterocyclyl, wherein the alkyl, alkenyl, aryl, and heterocyclyl are optionally43658-02201 / WO (EXAV-023 / 001 WO)substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6 alkyl, C6-C10 aryl, C1-C30 alkoxy, -O-(C1-C6 alkylene)-(C6-C10 aryl), -N(RN)2, or C1-C6 haloalkyl; andRN is each independently H, C1-C30 alkyl or C6-C10 aryl.

[0169] In an aspect, the compound is of Formula (I), a tautomer thereof, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein:G isX is CH;RP2is H, Ci-Ce alkyl, C2-C6 alkenyl or C2-C6 alkynyl;each RP5is independently selected from H, Ci-Ce alkyl, and C3-C6 cycloalkyl;O o0JIY / L3XYAY, R3XY1, Y2, Y3, Y4, Y5, Y6, and Y7 are each independently a bond, -O-, or -NH-;43658-02201 / WO (EXAV-023 / 001 WO)Li, L2, and L3 are each independently a bond, C1-C25 alkylene, or Ce-Cio arylene; and Ri, R2, R3, and R4 are each independently C1-C60 alkyl.

[0170] In an aspect, the compound is of Formula (I), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein:Yi, Y2, and Y3 are each independently a bond, -O-, or -NH-;Li and L2 are each independently a bond, -O-, C1-C25 alkylene, or Cg-Cio arylene, wherein the alkylene and arylene are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Cg alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Cg haloalkyl;Ri and R2 are each independently Ci-Ceo alkyl, C2-C30 alkenyl, Ce-Cio aryl, or 3-15 membered heterocyclyl, wherein the alkyl, alkenyl, aryl, and heterocyclyl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-C30 alkoxy, -O-(Ci-Ce alkylene)-(Ce-Cio aryl), -N(RN)2, or Ci-Ce haloalkyl; andRN is each independently H, C1-C30 alkyl or C6-C10 aryl.

[0171] In an aspect, the compound is of Formula (I), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein:43658-02201 / WO (EXAV-023 / 001WO)A is orRY1, Y2, and Y3are each independently a bond,or -NH-;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, Ci-Cg alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Cg haloalkyl;Ri and R2 are each independently Ci-Ceo alkyl, C2-C30 alkenyl, Cg-Cio aryl, or 3-15 membered heterocyclyl, wherein the alkyl, alkenyl, aryl, and heterocyclyl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-C30 alkoxy, -O-(Ci-Ce alkylene)-(C6-Cio aryl), -N(RN)2, or Ci-Ce haloalkyl; andRN is each independently H, C1-C30 alkyl or C6-C10 aryl.

[0172] In an aspect, the compound is of Formula (I), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein:°— 4-43658-02201 / WO (EXAV-023 / 001 WO)Yi, Y2, and Y3 are each independently a bond, -O-, or -NH-;Li and L-_> 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, C6-C10 aryl, C1-C6 alkoxy, or C1-C6 haloalkyl;R1 and R2 are each independently C1-C30 alkyl, C2-C30 alkenyl, or C6-C10 aryl, wherein the alkyl, alkenyl, and aryl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6 alkyl, C6-C10 aryl, C1-C6 alkoxy, or C1-C6 haloalkyl.

[0173] In an aspect, the compound is of Formula (I), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein:Yi, Y2, and Y3 are each independently a bond, -O-, or -NH-;Li and L2 are each independently a bond, -O-, 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, C6-C10 aryl, C1-C6 alkoxy, or C1-C6 haloalkyl;R1 and R2 are each independently C1-C60 alkyl, C2-C30 alkenyl, Ce-Cio aryl, or 3-15 membered heterocyclyl, wherein the alkyl, alkenyl, aryl, and heterocyclyl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cw aryl, Ci- C30 alkoxy, -O-(Ci-Ce alkylene)-(Ce-Cw aryl), -N(RN)2, or Ci-Ce haloalkyl; and43658-02201 / WO (EXAV-023 / 001 WO)RN is each independently H, C1-C30 alkyl or C6-C10 aryl.

[0174] In an aspect, the compound is of Formula (I), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein:Y1, Y2, and Y3are each independently a bond,or -NH-;Li and L2 are each independently a bond, -O-, C1-C25 alkylene, or Cg-Cio arylene, wherein the alkylene and arylene are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Cg alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Cg haloalkyl;Ri and R2 are each independently Ci-Ceo alkyl, C2-C30 alkenyl, Cg-Cio aryl, or 3-15 membered heterocyclyl, wherein the alkyl, alkenyl, aryl, and heterocyclyl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-C30 alkoxy, -O-(Ci-Ce alkylene)-(Ce-Cio aryl), -N(RN)2, or Ci-Ce haloalkyl; andRN is each independently H, C1-C30 alkyl or C6-C10 aryl.

[0175] In an aspect, the compound is of Formula (I), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein:Gis43658-02201 / WO (EXAV-023 / 001 WO)R P~NA is orYi, Y2, and Y3 are each independently a bond, -O-, or -NH-;Li and L2 are each independently a bond, C1-C25 alkylene, or Cg-Cio arylene, wherein the alkylene and arylene are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Cg alkyl, Cg-Cio aryl, Ci-Cg alkoxy, or Ci-Cg haloalkyl;Ri and R2 are each independently C1-C30 alkyl, C2-C30 alkenyl, or Cg-Cio aryl, wherein the alkyl, alkenyl, and aryl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6 alkyl, C6-C10 aryl, C1-C6 alkoxy, or C1-C6 haloalkyl.

[0176] In some embodiments,G is /

[0177] In some embodiments,1is. In some embodiments,

[0178] In some embodiments, X is CH. In some embodiments, X is N.43658-02201 / WO (EXAV-023 / 001 WO)

[0180] In some embodiments, ^P3 p*P3

[0181] In some embodiments, each RP3is H.

[0182] In some embodiments, 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.

[0183] In some embodiments, 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 fluoro.

[0184] In some embodiments, the two RP3are taken together with the carbon atom to which they are connected to form a C3-C4 cycloalkyl optionally substituted with one or more halogen.

[0185] In some embodiments, the two RP3are taken together with the carbon atom to which they are connected to form a C3-C4 cycloalkyl optionally substituted with one or more fluoro.

[0186] In some embodiments, the two RP3are taken together with the carbon atom to which they are connected to form a C3 cycloalkyl optionally substituted with one or more halogen.43658-02201 / WO (EXAV-023 / 001 WO)RP3RP3RP3RP3\ / VVx / »;: j™ - I II '' _.5.. N. tA

[0187] In some embodiments, is and each RP3is H.

[0188] In some embodiments, the two RP3are taken together with the carbon atom to which they are connected to form a C3 cycloalkyl optionally substituted with one or more fluoro.

[0189] In some embodiments, each RP1is H. In some embodiments, each RP1is independently Ci-Ce alkyl. In some embodiments, each RP1is independently Ci alkyl.

[0190] In some embodiments, RP2is H, Ci-Ce alkyl, or C2-C6 alkynyl. In some embodiments, RP2is H or Ci-Ce alkyl. In some embodiments, RP2is C1-C6 alkyl or C2-C6 alkynyl.

[0191] In some embodiments, RP2is H, Ci alkyl, or C2 alkynyl. In some embodiments, RP2is H or Ci alkyl. In some embodiments, RP2is Ci alkyl or C2 alkynyl.

[0192] In some embodiments, RP4is C6-C10 aryl optionally substituted with one or more substituents independently selected from halogen, C1-C6 alkyl, -NH(C1-C6 alkyl), and -P(=O)(C1-C6 alkyl)2. In some embodiments, RP4is C6-C10 aryl optionally substituted with one or more substituents independently selected from -NH(C1-C6 alkyl) and -P(=O)(C1-C6 alkyl)2. In some embodiments, RP4is C6 aryl optionally substituted with one or more substituents independently selected from halogen, C1-C6 alkyl, -NH(C1-C6 alkyl), and -P(=O)(C1-C6 alkyl)2. In some embodiments, RP4is C6 aryl optionally substituted with one or more substituents independently selected from -NH(C1-C6 alkyl) and -P(=O)(C1-C6 alkyl)2. In some embodiments,

[0193] In some embodiments, RP4is 5-15 membered heteroaryl optionally substituted with one or more substituents independently selected from halogen, Ci-Cg alkyl, Ci-Cg deuteroalkyl, and C3-C6 cycloalkyl. In some embodiments, RP4is 9-13 membered heteroaryl optionally substituted with one or more substituents independently selected from halogen, Ci-Cg alkyl, Ci-Cg deuteroalkyl, and C3-C6 cycloalkyl.

[0194] In some embodiments, RP4is indazole optionally substituted with one or more substituents independently selected from halogen, Ci-Cg alkyl, Ci-Cg deuteroalkyl, and C3-C6 cycloalkyl. In some embodiments, RP4is indazole optionally substituted with one or more43658-02201 / WO (EXAV-023 / 001 WO)substituents independently selected from halogen, Ci-Ce alkyl, and C3-C6 cycloalkyl. In some

[0195] In some embodiments, each RP5is independently selected from H, C1 alkyl, and C3 cycloalkyl. In some embodiments, at least one RP5is Ci-Cs alkyl or C3-C6 cycloalkyl.

[0196] In some embodiments, each RP5is independently Ci-CA alkyl. In some embodiments, each RP5is independently Ci alkyl. In some embodiments, one RP5is H and the other RP5is C3-C6 cycloalkyl.

[0197] In some embodiments, G is ' or43658-02201 / WO (EXAV-023 / 001WO)

[0198] In some embodiments, Gis \. In some embodiments, G is

[0199] In some embodiments, G isIn some embodiments, G is43658-02201 / WO (EXAV-023 / 001 WO)In some embodiments, G is43658-02201 / WO (EXAV-023 / 001WO)

[0200] In some embodiments, G is. In some embodiments, GP-N P~N N

[0201] In some embodiments, A is. In some embodiments, A isOLi AG RI ° O ’'■L< Y a R2Ji Y L

[0202] In some embodiments, 322' R R is2or43658-02201 AVO (EX AV-023 / 001 WO)oR1O>zx2^YI J / LI'-'Ll~^'£ e ll R ■.2

[0203] In some embodiments, Ris, orO o% 1 A-;R' P2"2. In some embodiments, R is i~2 R2'OR. oR2

[0204] In some embodiments, R isor 3. In someOR. O11 R2embodiments, R is. In some embodiments, R is Y3". In some Oembodiments,R is. In some embodiments, R iso R P-N R O

[0205] In some embodiments,A is ' and R is or P-N OR. OR2In some embodiments,A is and R is or P~NN A

[0206] In some embodiments,A is R and R isO oLKYAY, R3

[0207] In some embodiments, X is5 6. In some embodiments, X is O43658-02201 VO (EX AV-023 / 001 WO)o oAY / AYAY, R3

[0208] In some embodiments, X is45 6anc| y6js_Q_ jn someembodiments, O oAYA3XYAY. R3X is45 6ancjiSCi-Cgg alkyl. In some embodiments, X isO oAY. R34 5 6, Ye is -O-, and Rs is Ci-Ceo alkyl.o oL „A3X-y-zJAI yA R3

[0209] In some embodiments, X is45 6anj Ye is -O-. In some embodiments, O oJIY / AYAY. R3X is45 6and p3 1SC1-C30 alkyl. In some embodiments, X isO oJ.Y / \ A R34 Y5 Y6, Y6IS -O-, and R3IS C1-C30 alkyl.O O AY / AYAY, R3

[0210] In some embodiments, X is45 6an(ja]eastone of Y4 and Y5 is a O obond. In some embodiments, X isAY4A5 6'R3, Y4 is a bond, and Y5 is a bond. In O oJkYA\YAY, R3some embodiments, X is45 6anj j3 1SC1-C25 alkylene. In someO oYA3YAY, R3embodiments, X is45 6, L3 is C1-C25 alkylene, and at least one of Y4 and Ys o oAYA3YAY, R3is a bond. In some embodiments, X IS4 5 6, L3is C1-C25 alkylene, Y4 is a bond, and Y5 is a bond.O

[0211] In some embodiments, X is7and Y7 is a bond. In some embodiments, X is O O, WY, R XAY, R7and Y7 is -O-. In some embodiments, X is7and R is Ci-Ceo alkyl. In43658-02201 / WO (EXAV-023 / 001 WO)osome embodiments, X is7Y7 is a bond, and R4 is Ci-Coo alkyl. In some embodiments, OXis7Y7 is -O-, and R4 is Ci-Ceo alkyl.OX*Y^R«

[0212] In some embodiments, X is ' and Y7 is a bond. In some embodiments, X is O OX'yR41and Y7 is -O-. In some embodiments, X isY! Rand R4is C1-C30 alkyl. In O>YrR4some embodiments, X is7, Y? is a bond, and R4 is Ci-C / jo alkyl. In some embodiments, OXis7, Y7 is -O-, and R4is C1-C30 alkyl.

[0213] In some embodiments, Yi is a bond. In some embodiments, Yi is -O-. In some embodiments, Yj is -NH-. In some embodiments, Yj is a bond or -O-, In some embodiments, Yi is a bond or -NH-. In some embodiments, Yi is -O- or -NH-.

[0214] In some embodiments, Y2 is a bond. In some embodiments, Y2 is -()-. In some embodiments, Y2 is -NH-. In some embodiments, Y2 is a bond or -O-. In some embodiments, Y2 is a bond or -Nil-. In some embodiments, Y2 is -O- or -Nil-.

[0215] In some embodiments, Y3 is a bond. In some embodiments, Y3 is -O-. In some embodiments, Y3 is -NH-. In some embodiments, Y3 is a bond or -()-. In some embodiments, Y3 is a bond or -Nil-. In some embodiments, Y3 is -O- or -NTI-.

[0216] In some embodiments, Y4is a bond. In some embodiments, Y4is -()-. In some embodiments, Y4is -Ni l-. In some embodiments, Y4is a bond or -O-. In some embodiments, Y4is a bond or -NH-. In some embodiments, Y4is -O- or -NH-.

[0217] In some embodiments, Ys is a bond. In some embodiments, Y5 is -O-. In some embodiments, Y5 is -NH-. In some embodiments, Y5 is a bond or -O-. In some embodiments, Y5 is a bond or -NH-. In some embodiments, Ys is -O- or -NH-.43658-02201 / WO (EXAV-023 / 001 WO)

[0218] In some embodiments, Ye is a bond. In some embodiments, Ye is -O-. In some embodiments, Ye is -NH-. In some embodiments, Ye is a bond or -O-. In some embodiments, Ye is a bond or -NH-. In some embodiments, Ye is -O- or -NH-.

[0219] In some embodiments, Y? is a bond. In some embodiments, Y7 is -O-. In some embodiments, Y7 is -NH-. In some embodiments, Y7 is a bond or -O-. In some embodiments, Y7 is a bond or -NH-. In some embodiments, Y7 is -O- or -NH-.

[0220] In some embodiments, Li is a bond.

[0221] In some embodiments, Li is -O-,

[0222] In some embodiments, Li is C1-C25 alkylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Cg alkyl, Ce-Cio aryl, Ci-Cg alkoxy, or Ci-Cg 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 C 1-C25 alkylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Cg 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-Cg alkoxy, or Ci-Ce haloalkyl.. In some embodiments, Li is C1-C25 alkylene.

[0223] In some embodiments, Li is C15-C25 alkylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Cg-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, Ce-Cio 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-Cg alkyl, Ce-Cio aryl, Ci-Cg 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-Cg alkyl, Ce-Cio aryl, Ci-Cg alkoxy, or Ci-Ce haloalkyl.. In some embodiments, Li is C15-C25 alkylene.

[0224] In some embodiments, Li is Ci-Cg alkylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Cg alkyl, Ce-Cio aryl, Ci-Cg alkoxy, or Ci-Cg haloalkyl. In some embodiments, Li is Ci-Cg alkylene optionally substituted with one or more halo, cyano, Ce-Cio aryl, or Ci-Cg alkoxy. In some embodiments, Li is linear Ci-Cg alkylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6 alkyl, C6-C10 aryl, C1-C6 alkoxy, or C1-C6 haloalkyl. In some embodiments, Li is branched Ci-Ce alkylene optionally43658-02201 / WO (EXAV-023 / 001 WO)substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6 alkyl, C6-C10 aryl, C1-C6 alkoxy, or C1-C6 haloalkyl.. In some embodiments, Li is Ci-Cg alkylene.

[0225] In some embodiments, Li is Cg-Cio arylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6 alkyl, C6-C10 aryl, C1-C6 alkoxy, or C1-C6 haloalkyl. In some embodiments, Li is Cg-Cio arylene optionally substituted with one or more halo, cyano, Ci-Cg alkyl, or Ci-Cg alkoxy. In some embodiments, Li is phenylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6 alkyl, C6-C10 aryl, C1-C6 alkoxy, or C1-C6 haloalkyl. In some embodiments, Li is 1,2-phenylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6 alkyl, C6-C10 aryl, C1-C6 alkoxy, or C1-C6 haloalkyl. In some embodiments, Li is 1,3-phenylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6 alkyl, C6-C10 aryl, C1-C6 alkoxy, or C1-C6 haloalkyl. In some embodiments, Lj is 1,4-phenylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Cj-Cg alkyl, Cg-Cjo aryl, Ci-Cg alkoxy, or Ci-Cg haloalkyl. In some embodiments, Li is Cg-Cjo arylene. In some embodiments, Lj is phenylene.

[0226] In some embodiments, Li is a bond, C1-C25 alkylene, or Ce-Cio arylene. In some embodiments, Li is a bond, C1-C25 alkylene, or Cg arylene.

[0227] In some embodiments, L2 is a bond.

[0228] In some embodiments, L2 is -O-.

[0229] In some embodiments, L2 is C1-C25 alkylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6 alkyl, C6-C10 aryl, C1-C6 alkoxy, or C1-C6 haloalkyl. In some embodiments, L2 is C1-C25 alkylene optionally substituted with one or more halo, cyano, Cg-Cio aryl, or Ci-Cg alkoxy. In some embodiments, L2 is linear C1-C25 alkylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6 alkyl, C6-C10 aryl, C1-C6 alkoxy, or C1-C6 haloalkyl. In some embodiments, L2 is branched C1-C25 alkylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6 alkyl, C6-C10 aryl, C1-C6 alkoxy, or C1-C6 haloalkyl.. In some embodiments, L2 is C1-C25 alkylene.

[0230] In some embodiments, L2 is C15-C25 alkylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6 alkyl, C6-C10 aryl, C1-C6 alkoxy, or C1-C6 haloalkyl. In some embodiments, L2 is C15-C25 alkylene optionally substituted with one or more halo, cyano, Cg-Cio aryl, or Ci-Cg alkoxy. In some embodiments, L? is linear C15-C25 alkylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Cg alkyl, Cg-Cio43658-02201 / WO (EXAV-023 / 001 WO)aryl, Ci-Co 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-Co alkyl, Ce-Cio aryl, Ci-Co alkoxy, or Ci-Ce haloalkyl.. In some embodiments, L2 is C15-C25 alkylene.

[0231] In some embodiments, L2 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, L2 is Ci-Ce alkylene optionally substituted with one or more halo, cyano, Ce-Cio 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, Ce-Cio aryl, Ci-Ce alkoxy, or Cj-Cc, haloalkyl. In some embodiments, L2 is branched Ci-Ce alkylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Cj-Cr, haloalkyl,, In some embodiments, L2 is Ci-Ce alkylene.

[0232] In some embodiments, L2 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, L? is C6-C10 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, L? 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, L2 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, L2 is Ce-Cio arylene. In some embodiments, L2 is phenylene.

[0233] In some embodiments, L2 is a bond, C1-C25 alkylene, or Cg-Cio arylene. In some embodiments, L2 is a bond, C1-C25 alkylene, or Ce arylene.

[0234] In some embodiments, L3 is a bond.

[0235] In some embodiments, L3 is -O-.

[0236] In some embodiments, L3 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, L3 is C1-C25 alkylene optionally substituted with one or more halo, cyano, Ce-Cio aryl, or Ci-Ce alkoxy. In some embodiments, L3 is linear C1-C25 alkylene optionally43658-02201 / WO (EXAV-023 / 001 WO)substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Ce alkyl, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Co 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.

[0237] In some embodiments, L3 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, 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-Cr, 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, Ce-Cio aryl, Ci-Ce alkoxy, or Ci-Ce haloalkyl.. In some embodiments, L3 is C15-C25 alkylene.

[0238] In some embodiments, L3 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, 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 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 Ci-Ce alkylene.

[0239] In some embodiments, L3 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, L3 is Ce-Cio 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,43658-02201 / WO (EXAV-023 / 001 WO)cyano, amino, nitro, C1-C6 alkyl, C6-C10 aryl, C1-C6 alkoxy, or C1-C6 haloalkyl. In some embodiments, L3 is Cg-Cio arylene. In some embodiments, L3 is phenylene.

[0240] In some embodiments, L3 is a bond, C1-C25 alkylene, or Cg-Cio arylene. In some embodiments, L3 is a bond, C1-C25 alkylene, or Cg arylene.

[0241] In some embodiments, Li, L2, and L3 are each independently a bond, C1-C25 alkylene, or Cg-Cio arylene. In some embodiments, Li, L2, and L3 are each independently a bond, C1-C25 alkylene, or Cg arylene.O

[0242] In some embodiments, R is° and at least one of Lj and L2 is a> AYfLl'^L<Y2'yRlbond. In some embodiments, R is®, Li is Ci-Cg alkylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-C alkyl, Cg-Cio aryl, Ci-Cg alkoxy, or Ci-Cg haloalkyl, and L2 is Cg-Cio arylene optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6 alkyl, C6-C10 aryl, C1-C6 alkoxy, or C1-C6 haloalkyl.5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25.

[0244] In some embodiments, Rj is Ci-Cgo alkyl optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Cg alkyl, C -Cio aryl, C1-C30 alkoxy, -O-(Cj-Cg alkylene)-(Cg- C10 aryl), -N(RN)2, or Cj-Cg haloalkyl. In some embodiments, Ri is Ci-Cgo alkyl optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6 alkyl, C6-C10 aryl, C1-C6 alkoxy, or C1-C6 haloalkyl. In some embodiments, Ri is Ci-C30 alkyl optionally substituted with one or more halo or Cg-Cio aryl. In some embodiments, Ri is Cio-Cgo alkyl optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6 alkyl, C6-C10 aryl, C1-C6 alkoxy, or C1-C6 haloalkyl. In some embodiments, Ri is Cio-Cgo alkyl optionally substituted with one or43658-02201 / WO (EXAV-023 / 001 WO)more halo, hydroxyl, cyano, amino, nitro, C1-C6 alkyl, C6-C10 aryl, C1-C6 alkoxy, or C1-C6 haloalkyl. In some embodiments, Ri is Cio-Cgo alkyl optionally substituted with one or more halo or Cg-Cio aryl. In some embodiments, Ri is Ci-Cgo alkyl. In some embodiments, Ri is Cio-Cgo alkyl. In some embodiments, Ri is C2o-Cgo alkyl. In some embodiments, Ri is Cso-Cgo alkyl.

[0245] In some embodiments, Ri is C1-C30 alkyl optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Cg alkyl, Cg-Cio aryl, C1-C30 alkoxy, -O-(Ci-Cg alkylene)-(Cg-C10 aryl), -N(RN)2, or Ci-Cg haloalkyl. In some embodiments, Ri is C1-C30 alkyl optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6 alkyl, C6-C10 aryl, C1-C6 alkoxy, or C1-C6 haloalkyl. In some embodiments, Ri is C1-C30 alkyl optionally substituted with one or more halo or Cg-Cio aryl. In some embodiments, Ri is Cio-C30 alkyl optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Cg alkyl, Cg-Cio aryl, Ci-C30 alkoxy, -O-(Ci-Cg alkylene)-(Cg-Cio aryl), -N(RN)2, or Ci-Cg haloalkyl. In some embodiments, Rj is CIO- CGO alkyl optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6 alkyl, C6-C10 aryl, C1-C6 alkoxy, or C1-C6 haloalkyl. In some embodiments, Ri is C10-C30 alkyl optionally substituted with one or more halo or Cg-Cio aryl. In some embodiments, Ri is C1-C30 alkyl. In some embodiments, Ri is C10-C30 alkyl.

[0246] In some embodiments, Ri is C1-C20 alkyl optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Cg alkyl, Cg-Cio aryl, C1-C30 alkoxy, -O-(Ci-Cg alkylene)-(Cg-C10 aryl), -N(RN)2, or Ci-Cg haloalkyl. In some embodiments, Ri is C1-C20 alkyl optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6 alkyl, C6-C10 aryl, C1-C6 alkoxy, or C1-C6 haloalkyl. In some embodiments, Ri is C1-C20 alkyl optionally substituted with one or more halo or Cg-Cio aryl. In some embodiments, Ri is C10-C20 alkyl optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, Ci-Cg alkyl, Cg-Cio aryl, C1-C30 alkoxy, - O-(Ci-Cg alkylene)-(Cg-Cio aryl), -N(RN)2, or Ci-Cg haloalkyl. In some embodiments, Ri is CIO-CGO alkyl optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6 alkyl, C6-C10 aryl, C1-C6 alkoxy, or C1-C6 haloalkyl. In some embodiments, Ri is C10-C20 alkyl optionally substituted with one or more halo or Cg-Cio aryl. In some embodiments, Ri is C1-C20 alkyl. In some embodiments, Ri is C10-C20 alkyl.

[0247] In some embodiments, Ri is C11-C19 alkyl. In some embodiments, Ri is C12-C18 alkyl. In some embodiments, Ri is C13-C17 alkyl.43658-02201 / WO (EXAV-023 / 001 WO)

[0248] In some embodiments, Ri is C2-C30 alkenyl optionally substituted with one or more halo, hydroxyl, cyano, am...

Claims

1. 43658-02201 / WO (EXAV-023 / 001WO)CLAIMSWhat is claimed is:

1. A compound of F ormula (I):G-A (I),a tautomer thereof, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein:RP1X is CH or N;each RP1is independently selected from H and Ci-C alkyl;RP2is H, Ci-C6alkyl, 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 C6-C10 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 alkyl)2, and wherein the 5-15 membered heteroaryl is optionally substituted with one or more substituents independently selected from halogen, Cj-Ce alkyl, Ct-Ce deuteroalkyl, and C3-C6 cycloalkyl;43658-02201 / WO (EXAV-023 / 001WO)each RP5is independently selected from H, Ci-Ce alkyl, and C3-C6 cycloalkyl;P~NR P" N b-4 JGA is R or N A ■O, Rf RisYo L2AR 32, orQ O 0L3. A RorYi, Y2, Y3, Y4, Y5, Ye, and Y? are each independently a bond, -O-, or -NH-;Li, L2, and L3 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, R2, Ri and R4 are each independently Ci-Cso alkyl, C2-C30 alkenyl, Ce-Cio aryl, or 3-15 membered heterocyclyl, wherein the alkyl, alkenyl, aryl, and heterocyclyl are optionally substituted with one or more halo, hydroxyl, cyano, amino, nitro, C1-C6 alkyl, C6-C10 aryl, C1-C30 alkoxy, -O-(C1-C6 alkylene)-(C6-C10 aryl), -N(RN)2, or C1-C6 haloalkyl; andRN is each independently H, C1-C30 alkyl or C6-C10 aryl.

2. The compound of claim 1, wherein RP4is Ce aryl or 9-13 membered heteroaryl, wherein the ( 6 aryl is optionally substituted with one or more substituents independently selected from halogen, Ci-CY alkyl, -NH(CI-C6 alkyl), and -P(:::O)(Ci-C6 alkyl)2, and wherein the 9-13 membered heteroaryl is optionally substituted with one or more substituents independently selected from halogen, Ci-Ce alkyl, Cj-Ce deuteroalkyl, and C3-C6 cycloalkyl.

3. The compound of claim 1, wherein43658-02201 / WO (EXAV-023 / 001WO)X is CH;RP2is H, Ci-Ce alkyl, C2-C6 alkenyl or C2-C6 alkynyl; andeach RP5is independently selected from H, Ci-Ce alkyl, and C3-C6 cycloalkyl.

4. The compound of any one of claims 1-3, wherein43658-02201 / WO (EXAV-023 / 001WO)43658-02201 / WO (EXAV-023 / 001WO)5. The compound of any one of claims 1-4, wherein:G is > orThe compound of any one of claims 1-5, whereinG is7. The compound of any one of claims 1-5, whereinG isO-NN y- 8. The compound of any one of claims 1-7, wherein A is RR P~- <9. The compound of any one of claims 1-7, wherein A is N43658-02201 / WO (EXAV-023 / 001WO)10. The compound of any one of claims 1-9, wherein R isor A - cJOX^Y-R. Th com oun411 e p d of any one of claims 1-10, wherein X is12. The compound of any one of claims 1-11, wherein Yj is a bond.

13. The compound of any one of claims 1-12, wherein Yj is -O- or -Nil-.

14. The compound of any one of claims 1-13, wherein Y3 is a bond.

15. The compound of any one of claims 1-14, wherein Y4 is a bond.

16. The compound of any one of claims 1-15, wherein Y5 is a bond.

17. The compound of any one of claims 1-16, wherein Ye is -O-.

18. The compound of any one of claims 1-17, wherein Y7IS a bond or -O-.

19. The compound of any one of claims 1-18, whereinLi, L2, and L3 are each independently a bond, C1-C25 alkylene, or Ce-Cio arylene; and Ri, R2, Ry and R4 are each independently Ci-Ceo alkyl.

20. The compound of any one of claims 1-19, wherein Li is a bond or C1-C25 alkylene.

21. The compound of any one of claims 1-20, wherein L2 is a bond or Ce-Cio arylene.22, The compound of any one of claims 1-21, wherein L3 is Cj-C? alkylene43658-02201 / WO (EXAV-023 / 001WO)23. The compound of any one of claims 1-22, wherein Ri, R2, R3, and R4 are each independently C1-C20 alkyl.

24. The compound of any one of claims 1-23, wherein Ri, Rz, Ry and R4 are each independently C10-C20 alkyl.

25. The compound of any one of claims 1 -24, wherein Ri, R2, R3, and R4 are each independently C12-C18 alkyl.

26. The compound of any one of claims 1-25, wherein RisThe compound of any one of claims 1-25, wherein R is, w'herein ms 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25.

28. The compound of any one of claims 1-27, wherein the compound is selected from the compounds described in Tables 1, 2, or 7, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

29. The compound of any one of claims 1-28, wherein the compound is selected from a compound described in Tables 1, 2, or 7, or a pharmaceutically acceptable salt thereof.

30. The compound of any one of claims 1-29, wherein the compound is selected from a compound described in Tables 1, 2, or 7.

31. A pharmaceutical composition comprising the compound of any one of claims 1-30, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable diluent or carrier.43658-02201 / WO (EXAV-023 / 001WO)32. The pharmaceutical composition of claim 31, wherein the compound is selected from a compound described in Tables 1, 2, or 7.

33. 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 compound or pharmaceutical composition of any one of claims 1-32.

34. The compound or pharmaceutical composition of any one of claims 1-32 for use in treating or preventing a disease or disorder.

35. Use of the compound or pharmaceutical composition of any one of claims 1-32 in the manufacture of a medicament for treating or preventing a disease or disorder.

36. The method, compound, pharmaceutical composition, or use of any one of claims 33-35, wherein the disease or disorder is selected from:i) obesity;ii) type 2 diabetes;iii) sleep apnea;iv) cardiovascular disease;v) polycystic ovary syndrome;vi) depression;vii) substance use disorder;viii) heart failure; andix) metabolic dysfunction-associated steatohepatitis (MASH).

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