Selective JAK2 inhibitors and uses thereof

Abstract

Described herein are compounds that are JAK2 inhibitors, methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds, and methods of using such compounds in the treatment of conditions, diseases, or disorders that would benefit from modulation of JAK2 activity.

Description

SELECTIVE JAK2 INHIBITORS AND USES THEREOF CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of US Provisional Application No. 63 / 570,043, filedon March 26, 2024; and US Provisional Application No.63 / 704,926, filed on October 8, 2024, each of which is hereby incorporated by reference in its entirety. BACKGROUND OF THE INVENTION

[0002] The present disclosure relates to compounds that bind to the pseudokinase domain(JH2) of the non-receptor tyrosine kinase Janus kinase 2 (JAK2). Compounds of the present disclosure may selectively bind the JH2 domain of JAK2 over the JH1 domain of JAK2. Compounds of the present disclosure may selectively bind the V617F mutant of JAK2 over wild-type JAK2. Additional aspects of the disclosure include pharmaceutical compositions comprising the compounds described herein, methods of using the compounds to treat certain diseases, and intermediates and processes useful in the synthesis of the compounds.

[0003] JAK2 is a non-receptor tyrosine kinase member of the Janus kinase (JAKs) family ofprotein kinases. The mammalian JAK family consists of four members, TYK2, JAK1, JAK2, and JAK3. JAK proteins, including JAK2, are integral to cytokine signaling through the JAK- STAT pathway. Small molecule inhibitors of JAK family kinases have proven effective for the treatment of numerous diseases, including cancer.

[0004] All FDA-approved JAK2 inhibitors are type 1 inhibitors targeting the JH1 domain.However, JAK2 inhibitors that selectively bind the pseudokinase (JH2) domain may present several advantages.

[0005] Mutant JAK2 V617F is widespread in the myeloproliferative neoplasms (MPNs),presenting over half of all cases of essential thrombocythemia and myelofibrosis and presenting in 95% of all cases of polycythemia vera. The V617F mutation rigidifies the α-helix C in the N lobe of the JH2 domain. Inhibitors of JAK2 JH2 with selectivity for the JAK2 V617F mutant over wild-type JAK2 may be useful for treating various pathologies, such as MPNs, while minimizing effects to the off-target function of wild-type JAK2. SUMMARY OF THE INVENTION

[0006] Compounds described herein are modulators of the JAK family of kinases. Morespecifically, the compounds of the present disclosure are inhibitors of JAK2. In some embodiments, compounds are selective for JAK2 over other JAKs. In some embodiments, compounds are selective for the pseudokinase domain (JH2) of JAK2 over the kinase domain (JH1). In some embodiments, compounds are selective for the V617F mutant of JAK2 over - 1 -wild-type JAK2. In some embodiments, a compound of the present disclosure may be an allosteric modulator or noncompetitive inhibitor of JAK2. In additional embodiments, a compound described herein may be useful in the treatment of JAK2 mediated diseases or disorders. In some embodiments, the compounds of the present disclosure are useful for the treatment of cancer. In some embodiments, the compounds of the present disclosure are useful for the treatment of myeloproliferative neoplasms (MPNs). In some embodiments, the compounds of the present invention are useful for the treatment of a disease selected from myelofibrosis, polycythemia vera, and essential thrombocythemia.

[0007] In one aspect, described herein is a compound of Formula (I):Formula (I), or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: R1is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)-heterocyclyl, -C(O)R18, -(C1-C6alkylene)-C(O)R18, - C(O)OR18, -(C1-C6alkylene)-C(O)OR18, -C(O)N(R18)2, -(C1-C6alkylene)-C(O)N(R18)2, - S(O)R19, -(C1-C6alkylene)-S(O)R19, -S(O)2R19, -(C1-C6alkylene)-S(O)2R19, - S(O)2N(R18)2, or -(C1-C6alkylene)-S(O)2N(R18)2; or R1is -RA-L-RB; RAis unsubstituted or substituted carbocyclylene or unsubstituted or substituted heterocyclylene; L is absent, -(C(R5)2)n-, -C(O)-, -O-, -N(R6)-, -NR6-(C(R5)2)n-, -(C(R5)2)n-NR6-, -O- (C(R5)2)n-, -(C(R5)2)n-O-, -C(O)N(R6)-, -N(R6)C(O), -S(O)-, -S(O)2-, or -S(O)2N(R6)- ; - 2 -each R5is independently hydrogen, deuterium, -OH, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; or two R5on the same carbon atom or on adjacent carbon atoms are taken together with the intervening carbon atom to which they are attached to form a C3-C6cycloalkyl, or a 3- to 6-membered heterocycloalkyl; R6is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; n is 1 or 2; RBis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; wherein if RBis substituted then it is substituted by v Rxgroups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -ORb, - C(O)Ra, -C(O)ORa, -C(O)N(Ra)2, -N(Ra)2, -NRaC(O)Rb, -NRaC(O)ORa, -SRa, - S(O)Rb, -P(O)(Rb)2, -S(O)2Rb, -S(O)N(Ra)2, -S(O)2N(Ra)2, or -N=S(Rb)2=O; each Rais independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6deuteroalkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Raon the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each Rbis independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6deuteroalkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Rbon the same P atom are taken together with the P atom to which they are attached to form a substituted or unsubstituted P-containing heterocyclyl; v is an integer selected from 1, 2, 3, and 4; R2is hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, - 3 -unsubstituted or substituted C2-C6alkenyl, unsubstitutedy or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, - C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; R3is hydrogen, deuterium, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted monocyclic heterocycloalkyl, unsubstituted or substituted -(C1-C3alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C3alkylene)- heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, - NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; R4is hydrogen, deuterium, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted monocyclic heterocycloalkyl, unsubstituted or substituted -(C1-C3alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C3alkylene)- heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, - NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; or R3and R4are taken together with the carbon atom to which they are attached to form - C(O)-, an unsubstituted or substituted C3-C6cycloalkylene, or an unsubstituted or substituted 3- to 6-membered heterocycloalkylene; Y is -N(R7)-, -O-, -S-, -S(O)-, or -S(O)2-, wherein: R7is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; X1is CR8or N; X2is CR9or N; X3is CR10or N; R8, R9, and R10are each independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, - N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; Ring A is a carbocyclic ring or a heterocyclic ring; RCis -N(R11)(R12); - 4 -R11is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; R12is -C(O)R13, -C(O)NR13R14, or -C(O)OR13; R13is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted monocyclic carbocyclyl, unsubstituted or substituted bicyclic carbocyclyl, unsubstituted orsubstituted monocyclic heterocyclyl, or unsubstituted or substituted bicyclic heterocyclyl; R14is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; or R13and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted heterocyclyl; or R11and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted 5- or 6-membered monocyclic heterocyclyl; or R12is an unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1- C6heteroalkyl, unsubstituted or substituted heterocyclyl, or unsubstituted or substituted carbocyclyl, wherein if R12is substituted then it is substituted with 1 or more groups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)-heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, - C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; RDis -C(=O)-W-R15; W is -NR16-, -C(R17)2- or -O-; R16is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; each R17is independently hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; R15is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1- C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted - 5 -or substituted C1-C6alkoxy, unsubstituted or substituted C3-C6cycloalkyl, or unsubstituted or substituted monocyclic heterocycloalkyl; or R15and R16are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocycloalkyl; or RDis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; each REis independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, - C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or - S(O)2N(R18)2; wherein if REis attached to a N atom, then it is selected from the group consisting of unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -S(O)R19, - S(O)2R19, and -S(O)2N(R18)2; or two REattached to the same aliphatic carbon atom are taken together with the carbon atom to which they are attached to form -C(O)-; each R18is independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two R18on the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each R19is independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; p is 0 or 1; q is 0 or 1; and m is 0-4; - 6 -with the proviso that the compound of Formula (I) is not.

[0008] In some embodiments, the compound is a compound of Formula (I-1):Formula (I-1), or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: R1is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1- C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)-heterocyclyl, - C(O)R18, -(C1-C6alkylene)-C(O)R18, -C(O)OR18, -(C1-C6alkylene)-C(O)OR18, - C(O)N(R18)2, -(C1-C6alkylene)-C(O)N(R18)2, -S(O)R19, -(C1-C6alkylene)-S(O)R19, - S(O)2R19, -(C1-C6alkylene)-S(O)2R19, -S(O)2N(R18)2, or -(C1-C6alkylene)- S(O)2N(R18)2; or R1is -RA-L-RB; RAis unsubstituted or substituted carbocyclylene or unsubstituted or substituted heterocyclylene; L is absent, -(C(R5)2)n-, -C(O)-, -O-, -N(R6)-, -NR6-(C(R5)2)n-, -(C(R5)2)n-NR6-, -O- (C(R5)2)n-, -(C(R5)2)n-O-, -C(O)N(R6)-, -N(R6)C(O), -S(O)-, -S(O)2-, or - S(O)2N(R6)-; - 7 -each R5is independently hydrogen, deuterium, -OH, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; or two R5on the same carbon atom or on adjacent carbon atoms are taken together with the intervening carbon atom to which they are attached to form a C3-C6cycloalkyl, or a 3- to 6-membered heterocycloalkyl; R6is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; n is 1 or 2; RBis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; wherein if RBis substituted then it is substituted by v Rxgroups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1- C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -ORb, -C(O)Ra, -C(O)ORa, -C(O)N(Ra)2, -N(Ra)2, - NRaC(O)Rb, -NRaC(O)ORa, -SRa, -S(O)Rb, -P(O)(Rb)2, -S(O)2Rb, -S(O)N(Ra)2, - S(O)2N(Ra)2, or -N=S(Rb)2=O; each Rais independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6deuteroalkyl, substituted or unsubstituted C1- C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8- membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Raon the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each Rbis independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6deuteroalkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Rbon the same P atom are taken together with the P atom to which they are attached to form a substituted or unsubstituted P-containing heterocyclyl; v is an integer selected from 1, 2, 3, and 4; - 8 -R2is hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, - C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or - S(O)2N(R18)2; R3is hydrogen, deuterium, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted monocyclic heterocycloalkyl, unsubstituted or substituted -(C1-C3alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C3alkylene)-heterocyclyl, -CN, -OH, -OR19, - C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, - S(O)2R19, or -S(O)2N(R18)2; R4is hydrogen, deuterium, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted monocyclic heterocycloalkyl, unsubstituted or substituted -(C1-C3alkylene)-carbocyclyl, unsubstituted or substituted -( C1-C3alkylene)-heterocyclyl, -CN, -OH, -OR19, - C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, - S(O)2R19, or -S(O)2N(R18)2; or R3and R4are taken together with the carbon atom to which they are attached to form - C(O)-, an unsubstituted or substituted C3-C6cycloalkylene, or an unsubstituted or substituted 3- to 6-membered heterocycloalkylene; R7is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; X1is CR8or N; X2is CR9or N; X3is CR10or N; R8, R9, and R10are each independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted - 9 -carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, - C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, - S(O)2R19, or -S(O)2N(R18)2; Ring A is a carbocyclic ring or a heterocyclic ring; RCis -N(R11)(R12); R11is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; R12is -C(O)R13, -C(O)NR13R14, or -C(O)OR13; R13is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted monocyclic carbocyclyl, unsubstituted or substituted bicyclic carbocyclyl, unsubstituted or substituted monocyclic heterocyclyl, or unsubstituted or substituted bicyclic heterocyclyl; R14is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; or R13and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted heterocyclyl; or R11and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted 5- or 6-membered monocyclic heterocyclyl; or R12is an unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2- C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted heterocyclyl, or unsubstituted or substituted carbocyclyl, wherein if R12is substituted then it is substituted with 1 or more groups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)-heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, - N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; RDis -C(=O)-W-R15; W is -NR16-, -C(R17)2- or -O-; - 10 -R16is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; each R17is independently hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; R15is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6alkoxy, unsubstituted or substituted C3-C6cycloalkyl, or unsubstituted or substituted monocyclic heterocycloalkyl; or R15and R16are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocycloalkyl; or RDis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; each REis independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, - C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, - S(O)2R19, or -S(O)2N(R18)2; wherein if REis attached to a N atom, then it is selected from the group consisting of unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, - C(O)OR18, -C(O)N(R18)2, -S(O)R19, -S(O)2R19, and -S(O)2N(R18)2; or two REattached to the same aliphatic carbon atom are taken together with the carbon atom to which they are attached to form -C(O)-; each R18is independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two R18on the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; - 11 -each R19is independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; p is 0 or 1; q is 0 or 1; and m is 0-4.- 12 -C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C2-C6alkynyl, unsubstituted or substituted C3- C6cycloalkyl, unsubstituted or substituted 3- to 6-membered heterocycloalkyl, -CN, -OH, - OR19, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, or -S(O)2N(R18)2; wherein if REis attached to a N atom, then it is selected from the group consisting of C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted 3- to 6-membered heterocycloalkyl, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -S(O)R19, - S(O)2R19, and -S(O)2N(R18)2; or two REattached to the same aliphatic carbon atom are taken together with the carbon atom to which they are attached to form -C(O)-.REis independently hydrogen, halogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C2- C6alkynyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted 3- to 6- membered heterocycloalkyl, -CN, -OH, -OR19, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, - NR18C(O)R19, or -S(O)2N(R18)2; wherein if REis attached to a N atom, then it is selected from the group consisting of C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted 3- to 6-membered heterocycloalkyl, - C(O)R18, -C(O)OR18, -C(O)N(R18)2, -S(O)R19, -S(O)2R19, and -S(O)2N(R18)2. - 13 -

[0012] In some embodiments,wherein Z is N or CH; and REis hydrogen, halogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C2-C6alkynyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted 3- to 6-membered heterocycloalkyl, -CN, -OH, -OR19, -C(O)OR18, - C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, or -S(O)2N(R18)2; wherein if REis attached to a N atom, then it is selected from the group consisting of C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted 3- to 6- membered heterocycloalkyl, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -S(O)R19, -S(O)2R19, and - S(O)2N(R18)2.

[0013] In some embodiments, the compound is a compound of Formula (IIa-1):or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: Z is N, CH, or C-RE; REis hydrogen, halogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C2-C6alkynyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted 3- to 6-membered heterocycloalkyl, -CN, -OH, -OR19, -C(O)OR18, -C(O)N(R18)2, - N(R18)2, -NR18C(O)R19, or -S(O)2N(R18)2.

[0014] In some embodiments, the compound is a compound of Formula (IIIa-1), or apharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof: - 14 -

[0015] In some embodiments, the compound is a compound of Formula (IVa-1), or apharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof:

[0016] In some embodiments, the compound is a compound of Formula (A1):, or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: R1is -RA-L-RB;- 15 -L is -CH2-, -CHD-, -CD2-, or -C(O)-; RBis unsubstituted or substituted 2-pyridyl, phenyl, or pyrazol-3-yl ring; wherein if RBis substituted then it is substituted by v Rxgroups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1- C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -ORb, -C(O)Ra, -C(O)ORa, -C(O)N(Ra)2, -N(Ra)2, -NRaC(O)Rb, -SRa, -S(O)Rb, -P(O)(Rb)2, - S(O)2Rb, -S(O)N(Ra)2, or -S(O)2N(Ra)2; each Rais independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6deuteroalkyl, substituted or unsubstituted C1- C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8- membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Raon the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each Rbis independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6deuteroalkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; v is an integer selected from 1, 2, 3, and 4; R2is hydrogen, halogen, C1-C3alkyl, or -CN; R3is hydrogen, deuterium, C1-C4alkyl, C1-C4deuteroalkyl, C1-C4heteroalkyl, or C3-C4cycloalkyl; R4is hydrogen, deuterium, C1-C4alkyl, C1-C4deuteroalkyl, C1-C4heteroalkyl, or C3-C4cycloalkyl; R7is hydrogen, cyclopropyl, or -CH3; X1is CR8or N; X2is CR9or N; X3is CR10or N; - 16 -R8, R9, and R10are each independently hydrogen, halogen, C1-C3alkyl, C1-C3fluoroalkyl, or -CN; R13is cyclopropyl substituted with 1, 2, or 3 fluorines; R15is hydrogen, C1-C4alkyl, C1-C4deuteroalkyl, C1-C4fluoroalkyl, or unsubstituted or substituted C3-C6cycloalkyl; and Z is N or CH.

[0017] In some embodiments, RB is unsubstituted or substituted 2-pyridyl; wherein if RB issubstituted then it is substituted by v Rxgroups. In some embodiments, RBis unsubstituted or substituted phenyl; wherein if RBis substituted then it is substituted by v Rxgroups.

[0018] In some embodiments, the compound is a compound of Formula (A2), Formula (A4),Formula (A6), Formula (A8), Formula (A10), or Formula (A12):Formula (A2), Formula (A4), - 17 -Formula (A10), Formula (A12), or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: each Rxis independently selected from halogen, unsubstituted or substituted C1-C4alkyl, unsubstituted or substituted C1-C4deuteroalkyl, unsubstituted or substituted C1-C4fluoroalkyl, unsubstituted or substituted C1-C4heteroalkyl, unsubstituted or substituted C3-C5 cycloalkyl, unsubstituted or substituted 4- to 5-membered heterocyclyl, -CN, -OH, -ORb, -C(O)Ra, -C(O)ORa, -C(O)N(Ra)2, -N(Ra)2, - NRaC(O)Rb, -SRa, -S(O)Rb, -P(O)(Rb)2, -S(O)2Rb, -S(O)N(Ra)2, or -S(O)2N(Ra)2; and - 18 -w is an integer selected from 0, 1, and 2.

[0019] In some embodiments, the compound is a compound of Formula (B1):Formula (B1), or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: REis independently hydrogen, -F, -Cl, -CH3, difluoromethyl, -CD3, ethynyl, propynyl, cyano, -C(O)NHCH3, cyclopropyl, or cyclobutyl.

[0020] Any combination of the groups described above for the various variables iscontemplated herein. Throughout the specification, groups and substituents thereof are chosen by one skilled in the field to provide stable moieties and compounds.

[0021] Also described herein are pharmaceutical compositions comprising a compounddescribed herein, or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, and a pharmaceutically acceptable excipient. In some embodiments, the pharmaceutical composition is formulated for administration to a mammal by intravenous administration, subcutaneous administration, oral administration, inhalation, nasal administration, dermal administration, or ophthalmic administration. In some embodiments, the pharmaceutical composition is formulated for administration to a mammal by oral administration. In some embodiments, the pharmaceutical composition is in the form of a tablet, a pill, a capsule, a liquid, a suspension, a gel, a dispersion, a solution, an emulsion, an ointment, or a lotion. In some embodiments, the pharmaceutical composition is in the form of a tablet, a pill, or a capsule.

[0022] Described herein are compounds and pharmaceutically acceptable salts, tautomers, orsolvates thereof useful in the treatment of JAK2-mediated disorders. Described herein is a - 19 -compound of Formula (I), or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, useful in the treatment of a JAK2-mediated disorder.

[0023] In some embodiments, the compound described herein, or a pharmaceuticallyacceptable salt, N-oxide, tautomer, or solvate thereof, are useful in the treatment of a JAK2- V617F-mediated disorder.

[0024] In some embodiments, the compound described herein, or a pharmaceuticallyacceptable salt, N-oxide, tautomer, or solvate thereof, are useful in the treatment of a myeloproliferative diseases (MPDs).

[0025] In any of the aforementioned aspects are further embodiments in which the effectiveamount of the compound described herein, or a pharmaceutically acceptable salt, or solvate thereof, is: (a) systemically administered to the mammal; and / or (b) administered orally to the mammal; and / or (c) intravenously administered to the mammal; and / or (d) administered by inhalation; and / or (e) administered by nasal administration; or and / or (f) administered by injection to the mammal; and / or (g) administered topically to the mammal; and / or (h) administered by ophthalmic administration; and / or (i) administered rectally to the mammal; and / or (j) administered non-systemically or locally to the mammal.

[0026] In any of the aforementioned aspects are further embodiments comprising singleadministrations of the effective amount of the compound, including further embodiments in which the compound is administered once a day to the mammal or the compound is administered to the mammal multiple times over the span of one day. In some embodiments, the compound is administered on a continuous dosing schedule. In some embodiments, the compound is administered on a continuous daily dosing schedule.

[0027] In any of the embodiments disclosed herein, the mammal is a human.

[0028] In some embodiments, compounds provided herein are orally administered to a human.

[0029] Articles of manufacture, which include packaging material, a compound describedherein, or a pharmaceutically acceptable salt thereof, within the packaging material, and a label that indicates that the compound or composition, or pharmaceutically acceptable salt, tautomers, pharmaceutically acceptable N-oxide, pharmaceutically active metabolite, pharmaceutically acceptable prodrug, or pharmaceutically acceptable solvate thereof, is used for modulating JAK2, or for the treatment, prevention or amelioration of one or more symptoms of a disease or condition that would benefit from modulating JAK2, are provided.

[0030] Other objects, features and advantages of the compounds, methods and compositionsdescribed herein will become apparent from the following detailed description. It should be understood, however, that the detailed description and the specific examples, while indicating specific embodiments, are given by way of illustration only, since various changes and - 20 -modifications within the spirit and scope of the instant disclosure will become apparent to those skilled in the art from this detailed description. DETAILED DESCRIPTION OF THE INVENTION

[0031] JAK activity has been linked to numerous diseases, including inflammatory diseasesand disorders, autoimmune diseases and disorders, respiratory diseases and disorders, and cancer.

[0032] Mutations to JAK2 are associated with myeloproliferative neoplasms (MPNs). Forexample, the JAK2-V617F mutation occurs in 95% of patients with polycythemia vera (PV), 60% of patients with essential thrombocythemia (ET), and 55% of patients with myelofibrosis (MF). Additionally, gain-of-function mutations to JAK2 exon 12 and in the thrombopoietin receptor are often present in JAK2-V617F-negative MPNs.

[0033] There is a continuing need to provide novel inhibitors of Janus kinases having moreeffective or advantageous pharmaceutically relevant properties. For example, compounds with increased selectivity for JAK2 over other JAK kinases, and / or selectivity for particular mutant JAKs. There is a need for novel inhibitors that selectively bind the pseudokinase domain (JH2) over the kinase domain (JH1), as this may introduce unique selectivity and limit off-target effects. There is also a need for inhibitors that selectively bind to mutant JAK2-V617F over wild-type JAK2. JAK2 inhibitors that selectively bind mutant JAK2-V617F over wild-type JAK2 may limit off-target effects and / or facilitate mutant allele burden reduction.

[0034] In some embodiments, the JAK2 inhibitors described herein have selectivity for JAK2over JAK1, JAK3, and / or TYK2. In some embodiments, the JAK2 inhibitors described herein have selectivity for JH2 binding over JH1 binding. In some embodiments, the JAK2 inhibitors described herein have selectivity for mutant JAK2-V617F binding over wild-type JAK2 binding.

[0035] In some embodiments, compounds with selectivity for JH2 binding deliver apharmacological response that favorably treats one or more of the diseases or conditions described herein without the side-effects associated with the inhibition of wild-type JAK2. The present disclosure relates to compounds that bind to the pseudokinase domain (JH2) of Janus Kinase 2 (JAK2), to pharmaceutical compositions comprising the compounds, to methods of using the compounds to treat certain cancers, and to intermediates and processes useful in the synthesis of the compounds.

[0036] In some embodiments, the JAK2 inhibitors described herein are used in the treatmentof a disease or condition in a mammal. - 21 -Compounds of the Present Disclosure

[0037] Compounds described herein, including pharmaceutically acceptable salts, tautomers,and solvates thereof, are inhibitors of JAK2. In some embodiments, compounds described herein are selective for JAK2 over other JAKs. In some embodiments, compounds described herein bind selectively / specifically to the pseudokinase domain (JH2) of JAK2. In some embodiments, compounds described herein bind selectively / specifically to the V617F mutant of JAK2. In some embodiments, a compound described herein binds to an allosteric site of JAK2. In additional embodiments, a compound described herein may be useful in the treatment of JAK2-mediated diseases or disorders. In some embodiments, a compound described herein may be useful in the treatment of JAK2-V617F-mediated diseases or disorders.

[0038] In one aspect, the present disclosure provides compounds of Formula (I):Formula (I), or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: R1is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)-heterocyclyl, -C(O)R18, -(C1-C6alkylene)-C(O)R18, - C(O)OR18, -(C1-C6alkylene)-C(O)OR18, -C(O)N(R18)2, -(C1-C6alkylene)-C(O)N(R18)2, - S(O)R19, -(C1-C6alkylene)-S(O)R19, -S(O)2R19, -(C1-C6alkylene)-S(O)2R19, - S(O)2N(R18)2, or -(C1-C6alkylene)-S(O)2N(R18)2; or R1is -RA-L-RB; RAis unsubstituted or substituted carbocyclylene or unsubstituted or substituted heterocyclylene; - 22 -L is absent, -(C(R5)2)n-, -C(O)-, -O-, -N(R6)-, -NR6-(C(R5)2)n-, -(C(R5)2)n-NR6-, -O- (C(R5)2)n-, -(C(R5)2)n-O-, -C(O)N(R6)-, -N(R6)C(O), -S(O)-, -S(O)2-, or -S(O)2N(R6)- ; each R5is independently hydrogen, deuterium, -OH, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; or two R5on the same carbon atom or on adjacent carbon atoms are taken together with the intervening carbon atom to which they are attached to form a C3-C6cycloalkyl, or a 3- to 6-membered heterocycloalkyl; R6is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; n is 1 or 2; RBis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; wherein if RBis substituted then it is substituted by v Rxgroups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -ORb, - C(O)Ra, -C(O)ORa, -C(O)N(Ra)2, -N(Ra)2, -NRaC(O)Rb, -NRaC(O)ORa, -SRa, - S(O)Rb, -P(O)(Rb)2, -S(O)2Rb, -S(O)N(Ra)2, -S(O)2N(Ra)2, or -N=S(Rb)2=O; each Rais independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6deuteroalkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Raon the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each Rbis independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6deuteroalkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Rbon the same P atom are taken together with the P atom to which they are attached to form a substituted or unsubstituted P-containing heterocyclyl; - 23 -v is an integer selected from 1, 2, 3, and 4; R2is hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, - C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; R3is hydrogen, deuterium, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted monocyclic heterocycloalkyl, unsubstituted or substituted -(C1-C3alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C3alkylene)- heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, - NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; R4is hydrogen, deuterium, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted monocyclic heterocycloalkyl, unsubstituted or substituted -(C1-C3alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C3alkylene)- heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, - NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; or R3and R4are taken together with the carbon atom to which they are attached to form - C(O)-, an unsubstituted or substituted C3-C6cycloalkylene, or an unsubstituted or substituted 3- to 6-membered heterocycloalkylene; Y is -N(R7)-, -O-, -S-, -S(O)-, or -S(O)2-, wherein: R7is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; X1is CR8or N; X2is CR9or N; X3is CR10or N; R8, R9, and R10are each independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted - 24 -or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, - N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; Ring A is a carbocyclic ring or a heterocyclic ring; RCis -N(R11)(R12); R11is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; R12is -C(O)R13, -C(O)NR13R14, or -C(O)OR13; R13is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted monocyclic carbocyclyl, unsubstituted or substituted bicyclic carbocyclyl, unsubstituted orsubstituted monocyclic heterocyclyl, or unsubstituted or substituted bicyclic heterocyclyl; R14is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; or R13and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted heterocyclyl; or R11and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted 5- or 6-membered monocyclic heterocyclyl; or R12is an unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1- C6heteroalkyl, unsubstituted or substituted heterocyclyl, or unsubstituted or substituted carbocyclyl, wherein if R12is substituted then it is substituted with 1 or more groups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)-heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, - C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; RDis -C(=O)-W-R15; W is -NR16-, -C(R17)2-, or -O-; R16is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; - 25 -each R17is independently hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; R15is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1- C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6alkoxy, unsubstituted or substituted C3-C6cycloalkyl, or unsubstituted or substituted monocyclic heterocycloalkyl; or R15and R16are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocycloalkyl; or RDis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; each REis independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, - C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or - S(O)2N(R18)2; wherein if REis attached to a N atom, then it is selected from the group consisting of unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -S(O)R19, - S(O)2R19, and -S(O)2N(R18)2; or two REattached to the same aliphatic carbon atom are taken together with the carbon atom to which they are attached to form -C(O)-; each R18is independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two R18on the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each R19is independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- - 26 -to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; p is 0 or 1; q is 0 or 1; and m is 0-4.

[0039] In some embodiments, the present disclosure provides compounds of Formula (I):Formula (I), or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: R1is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)-heterocyclyl, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, - S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; or R1is -RA-L-RB; RAis unsubstituted or substituted carbocyclylene or unsubstituted or substituted heterocyclylene; L is absent, -(C(R5)2)n-, -C(O)-, -O-, -N(R6)-, -C(O)N(R6)-, -N(R6)C(O), -S(O)-, -S(O)2-, or -S(O)2N(R6)-; each R5is independently hydrogen, deuterium, -OH, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; or two R5on the same carbon atom or on adjacent carbon atoms are taken together with the intervening carbon atom to which they are attached to form a C3-C6cycloalkyl, or a 3- to 6-membered heterocycloalkyl; R6is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; n is 1 or 2; - 27 -RBis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; wherein if RBis substituted then it is substituted by 1 or more groups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -ORb, - C(O)Ra, -C(O)ORa, -C(O)N(Ra)2, -N(Ra)2, -NRaC(O)Rb, -SRa, -S(O)Rb, -P(O)(Rb)2, - S(O)2Rb, -S(O)N(Ra)2, or -S(O)2N(Ra)2; each Rais independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6deuteroalkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Raon the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each Rbis independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6deuteroalkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Rbon the same P atom are taken together with the P atom to which they are attached to form a substituted or unsubstituted P-containing heterocyclyl; R2is hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, - C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; R3is hydrogen, deuterium, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted monocyclic heterocycloalkyl, unsubstituted or - 28 -substituted -(C1-C3alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C3alkylene)- heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, - NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; R4is hydrogen, deuterium, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted monocyclic heterocycloalkyl, unsubstituted or substituted -(C1-C3alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C3alkylene)- heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, - NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; or R3and R4are taken together with the carbon atom to which they are attached to form - C(O)-, an unsubstituted or substituted C3-C6cycloalkylene, or an unsubstituted or substituted 3- to 6-membered heterocycloalkylene; Y is -N(R7)-, -O-, -S-, -S(O)-, or -S(O)2-, wherein: R7is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; X1is CR8or N; X2is CR9or N; X3is CR10or N; R8, R9, and R10are each independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, - N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; Ring A is a carbocyclic ring or a heterocyclic ring; RCis -N(R11)(R12); R11is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; R12is -C(O)R13, -C(O)NR13R14, or -C(O)OR13; R13is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted monocyclic carbocyclyl, unsubstituted or substituted bicyclic carbocyclyl, unsubstituted orsubstituted monocyclic heterocyclyl, or unsubstituted or substituted bicyclic heterocyclyl; - 29 -R14is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; or R13and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted heterocyclyl; or R11and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted 5- or 6-membered monocyclic heterocyclyl; or R12is an unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1- C6heteroalkyl, unsubstituted or substituted heterocyclyl, or unsubstituted or substituted carbocyclyl, wherein if R12is substituted then it is substituted with 1 or more groups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)-heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, - C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; RDis -C(=O)-W-R15; W is -NR16-, -C(R17)2-, or -O-; R16is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; each R17is independently hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; R15is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1- C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6alkoxy, unsubstituted or substituted C3-C6cycloalkyl, or unsubstituted or substituted monocyclic heterocycloalkyl; or R15and R16are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocycloalkyl; or RDis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; each REis independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6- 30 -alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, - C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or - S(O)2N(R18)2; wherein if REis attached to a N atom, then it is selected from the group consisting of unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -S(O)R19, - S(O)2R19, and -S(O)2N(R18)2; or two REattached to the same aliphatic carbon atom are taken together with the carbon atom to which they are attached to form -C(O)-; each R18is independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two R18on the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each R19is independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; p is 0 or 1; q is 0 or 1; and m is 0-4.

[0040] In some embodiments, the present disclosure provides compounds of Formula (I):- 31 -, or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: R1is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)-heterocyclyl, -C(O)R18, -(C1-C6alkylene)-C(O)R18, - C(O)OR18, -(C1-C6alkylene)-C(O)OR18, -C(O)N(R18)2, -(C1-C6alkylene)-C(O)N(R18)2, - S(O)R19, -(C1-C6alkylene)-S(O)R19, -S(O)2R19, -(C1-C6alkylene)-S(O)2R19, - S(O)2N(R18)2, or -(C1-C6alkylene)-S(O)2N(R18)2; or R1is -RA-L-RB; RAis unsubstituted or substituted carbocyclylene or unsubstituted or substituted heterocyclylene; L is absent, -(C(R5)2)n-, -C(O)-, -O-, -N(R6)-, -NR6-(C(R5)2)n-, -(C(R5)2)n-NR6-, -O- (C(R5)2)n-, -(C(R5)2)n-O-, -C(O)N(R6)-, -N(R6)C(O), -S(O)-, -S(O)2-, or -S(O)2N(R6)- ; each R5is independently hydrogen, deuterium, -OH, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; or two R5on the same carbon atom or on adjacent carbon atoms are taken together with the intervening carbon atom to which they are attached to form a C3-C6cycloalkyl, or a 3- to 6-membered heterocycloalkyl; R6is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; n is 1 or 2; RBis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; wherein if RBis substituted then it is substituted by v Rxgroups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, - 32 -unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -ORb, - C(O)Ra, -C(O)ORa, -C(O)N(Ra)2, -N(Ra)2, -NRaC(O)Rb, -NRaC(O)ORa, -SRa, - S(O)Rb, -P(O)(Rb)2, -S(O)2Rb, -S(O)N(Ra)2, -S(O)2N(Ra)2, or -N=S(Rb)2=O; each Rais independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6deuteroalkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Raon the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each Rbis independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6deuteroalkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Rbon the same P atom are taken together with the P atom to which they are attached to form a substituted or unsubstituted P-containing heterocyclyl; v is an integer selected from 1, 2, 3, and 4; R2is hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, - C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; R3is hydrogen, deuterium, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted monocyclic heterocycloalkyl, unsubstituted or substituted -(C1-C3alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C3alkylene)- - 33 -heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, - NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; R4is hydrogen, deuterium, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted monocyclic heterocycloalkyl, unsubstituted or substituted -(C1-C3alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C3alkylene)- heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, - NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; or R3and R4are taken together with the carbon atom to which they are attached to form - C(O)-, an unsubstituted or substituted C3-C6cycloalkylene, or an unsubstituted or substituted 3- to 6-membered heterocycloalkylene; Y is -N(R7)-, -O-, -S-, -S(O)-, or -S(O)2-, wherein: R7is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; X1is CR8or N; X2is CR9or N; X3is CR10or N; R8, R9, and R10are each independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, - N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; Ring A is a carbocyclic ring or a heterocyclic ring; RCis -N(R11)(R12); R11is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; R12is -C(O)R13, -C(O)NR13R14, or -C(O)OR13; R13is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted monocyclic carbocyclyl, unsubstituted or substituted bicyclic carbocyclyl, unsubstituted orsubstituted monocyclic heterocyclyl, or unsubstituted or substituted bicyclic heterocyclyl; R14is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; - 34 -or R13and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted heterocyclyl; or R11and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted 5- or 6-membered monocyclic heterocyclyl; or R12is an unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1- C6heteroalkyl, unsubstituted or substituted heterocyclyl, or unsubstituted or substituted carbocyclyl, wherein if R12is substituted then it is substituted with 1 or more groups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)-heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, - C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; RDis -C(=O)-W-R15; W is -NR16-, -C(R17)2- or -O-; R16is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; each R17is independently hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; R15is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1- C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6alkoxy, unsubstituted or substituted C3-C6cycloalkyl, or unsubstituted or substituted monocyclic heterocycloalkyl; or R15and R16are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocycloalkyl; or RDis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; each REis independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted - 35 -carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, - C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or - S(O)2N(R18)2; wherein if REis attached to a N atom, then it is selected from the group consisting of unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -S(O)R19, - S(O)2R19, and -S(O)2N(R18)2; or two REattached to the same aliphatic carbon atom are taken together with the carbon atom to which they are attached to form -C(O)-; each R18is independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two R18on the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each R19is independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; p is 0 or 1; q is 0 or 1; and m is 0-4; with the proviso that the compound of Formula (I) is not.

[0041] In some embodiments, the present disclosure provides compounds of Formula (I):- 36 -Formula (I), or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: R1is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)-heterocyclyl, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, - S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; or R1is -RA-L-RB; RAis unsubstituted or substituted carbocyclylene or unsubstituted or substituted heterocyclylene; L is absent, -(C(R5)2)n-, -C(O)-, -O-, -N(R6)-, -C(O)N(R6)-, -N(R6)C(O), -S(O)-, -S(O)2-, or -S(O)2N(R6)-; each R5is independently hydrogen, deuterium, -OH, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; or two R5on the same carbon atom or on adjacent carbon atoms are taken together with the intervening carbon atom to which they are attached to form a C3-C6cycloalkyl, or a 3- to 6-membered heterocycloalkyl; R6is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; n is 1 or 2; RBis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; wherein if RBis substituted then it is substituted by 1 or more groups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or - 37 -substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -ORb, - C(O)Ra, -C(O)ORa, -C(O)N(Ra)2, -N(Ra)2, -NRaC(O)Rb, -SRa, -S(O)Rb, -P(O)(Rb)2, - S(O)2Rb, -S(O)N(Ra)2, or -S(O)2N(Ra)2; each Rais independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6deuteroalkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Raon the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each Rbis independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6deuteroalkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Rbon the same P atom are taken together with the P atom to which they are attached to form a substituted or unsubstituted P-containing heterocyclyl; R2is hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, - C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; R3is hydrogen, deuterium, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted monocyclic heterocycloalkyl, unsubstituted or substituted -(C1-C3alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C3alkylene)- heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, - NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; R4is hydrogen, deuterium, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted C3-C6- 38 -cycloalkyl, unsubstituted or substituted monocyclic heterocycloalkyl, unsubstituted or substituted -(C1-C3alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C3alkylene)- heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, - NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; or R3and R4are taken together with the carbon atom to which they are attached to form - C(O)-, an unsubstituted or substituted C3-C6cycloalkylene, or an unsubstituted or substituted 3- to 6-membered heterocycloalkylene; Y is -N(R7)-, -O-, -S-, -S(O)-, or -S(O)2-, wherein: R7is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; X1is CR8or N; X2is CR9or N; X3is CR10or N; R8, R9, and R10are each independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, - N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; Ring A is a carbocyclic ring or a heterocyclic ring; RCis -N(R11)(R12); R11is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; R12is -C(O)R13, -C(O)NR13R14, or -C(O)OR13; R13is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted monocyclic carbocyclyl, unsubstituted or substituted bicyclic carbocyclyl, unsubstituted orsubstituted monocyclic heterocyclyl, or unsubstituted or substituted bicyclic heterocyclyl; R14is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; or R13and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted heterocyclyl; or R11and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted 5- or 6-membered monocyclic heterocyclyl; - 39 -or R12is an unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1- C6heteroalkyl, unsubstituted or substituted heterocyclyl, or unsubstituted or substituted carbocyclyl, wherein if R12is substituted then it is substituted with 1 or more groups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)-heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, - C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; RDis -C(=O)-W-R15; W is -NR16-, -C(R17)2- or -O-; R16is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; each R17is independently hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; R15is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1- C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6alkoxy, unsubstituted or substituted C3-C6cycloalkyl, or unsubstituted or substituted monocyclic heterocycloalkyl; or R15and R16are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocycloalkyl; or RDis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; each REis independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, - C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or - S(O)2N(R18)2; wherein if REis attached to a N atom, then it is selected from the group consisting of unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted - 40 -C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -S(O)R19, - S(O)2R19, and -S(O)2N(R18)2; or two REattached to the same aliphatic carbon atom are taken together with the carbon atom to which they are attached to form -C(O)-; each R18is independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two R18on the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each R19is independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; p is 0 or 1; q is 0 or 1; and m is 0-4; with the proviso that the compound of Formula (I) is not. - 41 -

[0042] In some embodiments, the present disclosure provides compounds of Formula (I):Formula (I), or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: R1is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)-heterocyclyl, -C(O)R18, -(C1-C6alkylene)-C(O)R18, - C(O)OR18, -(C1-C6alkylene)-C(O)OR18, -C(O)N(R18)2, -(C1-C6alkylene)-C(O)N(R18)2, - S(O)R19, -(C1-C6alkylene)-S(O)R19, -S(O)2R19, -(C1-C6alkylene)-S(O)2R19, - S(O)2N(R18)2, or -(C1-C6alkylene)-S(O)2N(R18)2; or R1is -RA-L-RB; RAis unsubstituted or substituted carbocyclylene or unsubstituted or substituted heterocyclylene; L is absent, -(C(R5)2)n-, -C(O)-, -O-, -N(R6)-, -NR6-(C(R5)2)n-, -(C(R5)2)n-NR6-, -O- (C(R5)2)n-, -(C(R5)2)n-O-, -C(O)N(R6)-, -N(R6)C(O), -S(O)-, -S(O)2-, or -S(O)2N(R6)- ; each R5is independently hydrogen, deuterium, -OH, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; or two R5on the same carbon atom or on adjacent carbon atoms are taken together with the intervening carbon atom to which they are attached to form a C3-C6cycloalkyl, or a 3- to 6-membered heterocycloalkyl; R6is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; n is 1 or 2; RBis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; wherein if RBis substituted then it is substituted by v Rxgroups - 42 -independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -ORb, - C(O)Ra, -C(O)ORa, -C(O)N(Ra)2, -N(Ra)2, -NRaC(O)Rb, -NRaC(O)ORa, -SRa, - S(O)Rb, -P(O)(Rb)2, -S(O)2Rb, -S(O)N(Ra)2, -S(O)2N(Ra)2, or -N=S(Rb)2=O; each Rais independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6deuteroalkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Raon the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each Rbis independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6deuteroalkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Rbon the same P atom are taken together with the P atom to which they are attached to form a substituted or unsubstituted P-containing heterocyclyl; v is an integer selected from 1, 2, 3, and 4; R2is hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, - C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; R3is hydrogen, deuterium, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted monocyclic heterocycloalkyl, unsubstituted or substituted -(C1-C3alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C3alkylene)- - 43 -heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, - NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; R4is hydrogen, deuterium, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted monocyclic heterocycloalkyl, unsubstituted or substituted -(C1-C3alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C3alkylene)- heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, - NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; or R3and R4are taken together with the carbon atom to which they are attached to form - C(O)-, an unsubstituted or substituted C3-C6cycloalkylene, or an unsubstituted or substituted 3- to 6-membered heterocycloalkylene; Y is -N(R7)-, -O-, -S-, -S(O)-, or -S(O)2-, wherein: R7is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; X1is CR8or N; X2is CR9or N; X3is CR10or N; R8, R9, and R10are each independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, - N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; Ring A is a carbocyclic ring or a heterocyclic ring; RCis -N(R11)(R12); R11is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; R12is -C(O)R13, -C(O)NR13R14, or -C(O)OR13; R13is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted monocyclic carbocyclyl, unsubstituted or substituted bicyclic carbocyclyl, unsubstituted orsubstituted monocyclic heterocyclyl, or unsubstituted or substituted bicyclic heterocyclyl; R14is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; - 44 -or R13and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted heterocyclyl; or R11and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted 5- or 6-membered monocyclic heterocyclyl; or R12is an unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1- C6heteroalkyl, unsubstituted or substituted heterocyclyl, or unsubstituted or substituted carbocyclyl, wherein if R12is substituted then it is substituted with 1 or more groups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)-heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, - C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; RDis -C(=O)-W-R15; W is -NR16-, -C(R17)2- or -O-; R16is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; each R17is independently hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; R15is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1- C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6alkoxy, unsubstituted or substituted C3-C6cycloalkyl, or unsubstituted or substituted monocyclic heterocycloalkyl; or R15and R16are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocycloalkyl; or RDis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; each REis independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted - 45 -carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, - C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or - S(O)2N(R18)2; wherein if REis attached to a N atom, then it is selected from the group consisting of unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -S(O)R19, - S(O)2R19, and -S(O)2N(R18)2; or two REattached to the same aliphatic carbon atom are taken together with the carbon atom to which they are attached to form -C(O)-; each R18is independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two R18on the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each R19is independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; p is 0 or 1; q is 0 or 1; and m is 0-4; wherein when ring A is pyrimidinyl, Y is -N(R7)-. - 46 -

[0043] In some embodiments, the present disclosure provides compounds of Formula (I):Formula (I), or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: R1is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)-heterocyclyl, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, - S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; or R1is -RA-L-RB; RAis unsubstituted or substituted carbocyclylene or unsubstituted or substituted heterocyclylene; L is absent, -(C(R5)2)n-, -C(O)-, -O-, -N(R6)-, -C(O)N(R6)-, -N(R6)C(O), -S(O)-, -S(O)2-, or -S(O)2N(R6)-; each R5is independently hydrogen, deuterium, -OH, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; or two R5on the same carbon atom or on adjacent carbon atoms are taken together with the intervening carbon atom to which they are attached to form a C3-C6cycloalkyl, or a 3- to 6-membered heterocycloalkyl; R6is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; n is 1 or 2; RBis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; wherein if RBis substituted then it is substituted by 1 or more groups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted - 47 -C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -ORb, - C(O)Ra, -C(O)ORa, -C(O)N(Ra)2, -N(Ra)2, -NRaC(O)Rb, -SRa, -S(O)Rb, -P(O)(Rb)2, - S(O)2Rb, -S(O)N(Ra)2, or -S(O)2N(Ra)2; each Rais independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6deuteroalkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Raon the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each Rbis independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6deuteroalkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Rbon the same P atom are taken together with the P atom to which they are attached to form a substituted or unsubstituted P-containing heterocyclyl; R2is hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, - C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; R3is hydrogen, deuterium, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted monocyclic heterocycloalkyl, unsubstituted or substituted -(C1-C3alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C3alkylene)- heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, - NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; R4is hydrogen, deuterium, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, - 48 -unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted monocyclic heterocycloalkyl, unsubstituted or substituted -(C1-C3alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C3alkylene)- heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, - NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; or R3and R4are taken together with the carbon atom to which they are attached to form - C(O)-, an unsubstituted or substituted C3-C6cycloalkylene, or an unsubstituted or substituted 3- to 6-membered heterocycloalkylene; Y is -N(R7)-, -O-, -S-, -S(O)-, or -S(O)2-, wherein: R7is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; X1is CR8or N; X2is CR9or N; X3is CR10or N; R8, R9, and R10are each independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, - N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; Ring A is a carbocyclic ring or a heterocyclic ring; RCis -N(R11)(R12); R11is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; R12is -C(O)R13, -C(O)NR13R14, or -C(O)OR13; R13is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted monocyclic carbocyclyl, unsubstituted or substituted bicyclic carbocyclyl, unsubstituted orsubstituted monocyclic heterocyclyl, or unsubstituted or substituted bicyclic heterocyclyl; R14is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; or R13and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted heterocyclyl; - 49 -or R11and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted 5- or 6-membered monocyclic heterocyclyl; or R12is an unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1- C6heteroalkyl, unsubstituted or substituted heterocyclyl, or unsubstituted or substituted carbocyclyl, wherein if R12is substituted then it is substituted with 1 or more groups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)-heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, - C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; RDis -C(=O)-W-R15; W is -NR16-, -C(R17)2- or -O-; R16is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; each R17is independently hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; R15is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1- C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6alkoxy, unsubstituted or substituted C3-C6cycloalkyl, or unsubstituted or substituted monocyclic heterocycloalkyl; or R15and R16are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocycloalkyl; or RDis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; each REis independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, - C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or - - 50 -S(O)2N(R18)2; wherein if REis attached to a N atom, then it is selected from the group consisting of unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -S(O)R19, - S(O)2R19, and -S(O)2N(R18)2; or two REattached to the same aliphatic carbon atom are taken together with the carbon atom to which they are attached to form -C(O)-; each R18is independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two R18on the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each R19is independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; p is 0 or 1; q is 0 or 1; and m is 0-4; wherein when ring A is pyrimidinyl, Y is -N(R7)-.

[0044] In some embodiments, the present disclosure provides compounds of Formula (I):Formula (I), - 51 -or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: R1is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)-heterocyclyl, -C(O)R18, -(C1-C6alkylene)-C(O)R18, - C(O)OR18, -(C1-C6alkylene)-C(O)OR18, -C(O)N(R18)2, -(C1-C6alkylene)-C(O)N(R18)2, - S(O)R19, -(C1-C6alkylene)-S(O)R19, -S(O)2R19, -(C1-C6alkylene)-S(O)2R19, - S(O)2N(R18)2, or -(C1-C6alkylene)-S(O)2N(R18)2; or R1is -RA-L-RB; RAis unsubstituted or substituted carbocyclylene or unsubstituted or substituted heterocyclylene; L is absent, -(C(R5)2)n-, -C(O)-, -O-, -N(R6)-, -C(O)N(R6)-, -N(R6)C(O), -S(O)-, -S(O)2-, or -S(O)2N(R6)-; each R5is independently hydrogen, deuterium, -OH, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; or two R5on the same carbon atom or on adjacent carbon atoms are taken together with the intervening carbon atom to which they are attached to form a C3-C6cycloalkyl, or a 3- to 6-membered heterocycloalkyl; R6is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; n is 1 or 2; RBis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; wherein if RBis substituted then it is substituted by v Rxgroups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -ORb, - C(O)Ra, -C(O)ORa, -C(O)N(Ra)2, -N(Ra)2, -NRaC(O)Rb, -NRaC(O)ORa, -SRa, - S(O)Rb, -P(O)(Rb)2, -S(O)2Rb, -S(O)N(Ra)2, -S(O)2N(Ra)2, or -N=S(Rb)2=O; each Rais independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6deuteroalkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered - 52 -heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Raon the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each Rbis independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6deuteroalkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Rbon the same P atom are taken together with the P atom to which they are attached to form a substituted or unsubstituted P-containing heterocyclyl; v is an integer selected from 1, 2, 3, and 4; R2is hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, - C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; R3is hydrogen, deuterium, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted monocyclic heterocycloalkyl, unsubstituted or substituted -(C1-C3alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C3alkylene)- heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, - NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; R4is hydrogen, deuterium, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted monocyclic heterocycloalkyl, unsubstituted or substituted -(C1-C3alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C3alkylene)- heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, - NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; - 53 -or R3and R4are taken together with the carbon atom to which they are attached to form - C(O)-, an unsubstituted or substituted C3-C6cycloalkylene, or an unsubstituted or substituted 3- to 6-membered heterocycloalkylene; Y is -N(R7)-, -O-, -S-, -S(O)-, or -S(O)2-, wherein: R7is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; X1is CR8or N; X2is CR9or N; X3is CR10or N; R8, R9, and R10are each independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, - N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; Ring A is a carbocyclic ring or a heterocyclic ring; RCis -N(R11)(R12); R11is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; R12is -C(O)R13, -C(O)NR13R14, or -C(O)OR13; R13is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted monocyclic carbocyclyl, unsubstituted or substituted bicyclic carbocyclyl, unsubstituted orsubstituted monocyclic heterocyclyl, or unsubstituted or substituted bicyclic heterocyclyl; R14is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; or R13and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted heterocyclyl; or R11and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted 5- or 6-membered monocyclic heterocyclyl; or R12is an unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1- C6heteroalkyl, unsubstituted or substituted heterocyclyl, or unsubstituted or substituted carbocyclyl, wherein if R12is substituted then it is substituted with 1 or - 54 -more groups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)-heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, - C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; RDis -C(=O)-W-R15; W is -NR16-, -C(R17)2- or -O-; R16is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; each R17is independently hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; R15is unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6alkoxy, unsubstituted or substituted C3-C6cycloalkyl, or unsubstituted or substituted monocyclic heterocycloalkyl; or R15and R16are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocycloalkyl; or RDis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; each REis independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, - C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or - S(O)2N(R18)2; wherein if REis attached to a N atom, then it is selected from the group consisting of unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -S(O)R19, - S(O)2R19, and -S(O)2N(R18)2; - 55 -or two REattached to the same aliphatic carbon atom are taken together with the carbon atom to which they are attached to form -C(O)-; each R18is independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two R18on the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each R19is independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; p is 0 or 1; q is 0 or 1; and m is 0-4.

[0045] In some embodiments, the present disclosure provides compounds of Formula (I):, or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: R1is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)-heterocyclyl, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, - S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; - 56 -or R1is -RA-L-RB; RAis unsubstituted or substituted carbocyclylene or unsubstituted or substituted heterocyclylene; L is absent, -(C(R5)2)n-, -C(O)-, -O-, -N(R6)-, -C(O)N(R6)-, -N(R6)C(O), -S(O)-, -S(O)2-, or -S(O)2N(R6)-; each R5is independently hydrogen, deuterium, -OH, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; or two R5on the same carbon atom or on adjacent carbon atoms are taken together with the intervening carbon atom to which they are attached to form a C3-C6cycloalkyl, or a 3- to 6-membered heterocycloalkyl; R6is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; n is 1 or 2; RBis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; wherein if RBis substituted then it is substituted by 1 or more groups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -ORb, - C(O)Ra, -C(O)ORa, -C(O)N(Ra)2, -N(Ra)2, -NRaC(O)Rb, -SRa, -S(O)Rb, -P(O)(Rb)2, - S(O)2Rb, -S(O)N(Ra)2, or -S(O)2N(Ra)2; each Rais independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6deuteroalkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Raon the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each Rbis independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6deuteroalkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; - 57 -or two Rbon the same P atom are taken together with the P atom to which they are attached to form a substituted or unsubstituted P-containing heterocyclyl; R2is hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, - C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; R3is hydrogen, deuterium, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted monocyclic heterocycloalkyl, unsubstituted or substituted -(C1-C3alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C3alkylene)- heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, - NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; R4is hydrogen, deuterium, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted monocyclic heterocycloalkyl, unsubstituted or substituted -(C1-C3alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C3alkylene)- heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, - NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; or R3and R4are taken together with the carbon atom to which they are attached to form - C(O)-, an unsubstituted or substituted C3-C6cycloalkylene, or an unsubstituted or substituted 3- to 6-membered heterocycloalkylene; Y is -N(R7)-, -O-, -S-, -S(O)-, or -S(O)2-, wherein: R7is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; X1is CR8or N; X2is CR9or N; X3is CR10or N; R8, R9, and R10are each independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted - 58 -or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, - N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; Ring A is a carbocyclic ring or a heterocyclic ring; RCis -N(R11)(R12); R11is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; R12is -C(O)R13, -C(O)NR13R14, or -C(O)OR13; R13is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted monocyclic carbocyclyl, unsubstituted or substituted bicyclic carbocyclyl, unsubstituted orsubstituted monocyclic heterocyclyl, or unsubstituted or substituted bicyclic heterocyclyl; R14is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; or R13and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted heterocyclyl; or R11and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted 5- or 6-membered monocyclic heterocyclyl; or R12is an unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1- C6heteroalkyl, unsubstituted or substituted heterocyclyl, or unsubstituted or substituted carbocyclyl, wherein if R12is substituted then it is substituted with 1 or more groups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)-heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, - C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; RDis -C(=O)-W-R15; W is -NR16-, -C(R17)2- or -O-; R16is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; - 59 -each R17is independently hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; R15is unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6alkoxy, unsubstituted or substituted C3-C6cycloalkyl, or unsubstituted or substituted monocyclic heterocycloalkyl; or R15and R16are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocycloalkyl; or RDis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; each REis independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, - C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or - S(O)2N(R18)2; wherein if REis attached to a N atom, then it is selected from the group consisting of unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -S(O)R19, - S(O)2R19, and -S(O)2N(R18)2; or two REattached to the same aliphatic carbon atom are taken together with the carbon atom to which they are attached to form -C(O)-; each R18is independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two R18on the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each R19is independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- - 60 -to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; p is 0 or 1; q is 0 or 1; and m is 0-4.

[0046] In some embodiments, the present disclosure provides compounds of Formula (I):Formula (I), or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: R1is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)-heterocyclyl, -C(O)R18, -(C1-C6alkylene)-C(O)R18, - C(O)OR18, -(C1-C6alkylene)-C(O)OR18, -C(O)N(R18)2, -(C1-C6alkylene)-C(O)N(R18)2, - S(O)R19, -(C1-C6alkylene)-S(O)R19, -S(O)2R19, -(C1-C6alkylene)-S(O)2R19, - S(O)2N(R18)2, or -(C1-C6alkylene)-S(O)2N(R18)2; or R1is -RA-L-RB; RAis unsubstituted or substituted carbocyclylene or unsubstituted or substituted heterocyclylene; L is absent, -(C(R5)2)n-, -C(O)-, -O-, -N(R6)-, -NR6-(C(R5)2)n-, -(C(R5)2)n-NR6-, -O- (C(R5)2)n-, -(C(R5)2)n-O-, -C(O)N(R6)-, -N(R6)C(O), -S(O)-, -S(O)2-, or -S(O)2N(R6)- ; each R5is independently hydrogen, deuterium, -OH, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; - 61 -or two R5on the same carbon atom or on adjacent carbon atoms are taken together with the intervening carbon atom to which they are attached to form a C3-C6cycloalkyl, or a 3- to 6-membered heterocycloalkyl; R6is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; n is 1 or 2; RBis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; wherein if RBis substituted then it is substituted by v Rxgroups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -ORb, - C(O)Ra, -C(O)ORa, -C(O)N(Ra)2, -N(Ra)2, -NRaC(O)Rb, -NRaC(O)ORa, -SRa, - S(O)Rb, -P(O)(Rb)2, -S(O)2Rb, -S(O)N(Ra)2, -S(O)2N(Ra)2, or -N=S(Rb)2=O; each Rais independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6deuteroalkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Raon the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each Rbis independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6deuteroalkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Rbon the same P atom are taken together with the P atom to which they are attached to form a substituted or unsubstituted P-containing heterocyclyl; v is an integer selected from 1, 2, 3, and 4; R2is hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, - 62 -unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, - C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; R3is hydrogen, deuterium, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted monocyclic heterocycloalkyl, unsubstituted or substituted -(C1-C3alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C3alkylene)- heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, - NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; R4is hydrogen, deuterium, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted monocyclic heterocycloalkyl, unsubstituted or substituted -(C1-C3alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C3alkylene)- heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, - NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; or R3and R4are taken together with the carbon atom to which they are attached to form - C(O)-, an unsubstituted or substituted C3-C6cycloalkylene, or an unsubstituted or substituted 3- to 6-membered heterocycloalkylene; Y is -N(R7)-, -S-, -S(O)-, or -S(O)2-, wherein: R7is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; X1is CR8or N; X2is CR9or N; X3is CR10or N; R8, R9, and R10are each independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, - N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; Ring A is a carbocyclic ring or a heterocyclic ring; RCis -N(R11)(R12); R11is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; R12is -C(O)R13, -C(O)NR13R14, or -C(O)OR13; - 63 -R13is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted monocyclic carbocyclyl, unsubstituted or substituted bicyclic carbocyclyl, unsubstituted orsubstituted monocyclic heterocyclyl, or unsubstituted or substituted bicyclic heterocyclyl; R14is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; or R13and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted heterocyclyl; or R11and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted 5- or 6-membered monocyclic heterocyclyl; or R12is an unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1- C6heteroalkyl, unsubstituted or substituted heterocyclyl, or unsubstituted or substituted carbocyclyl, wherein if R12is substituted then it is substituted with 1 or more groups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)-heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, - C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; RDis -C(=O)-W-R15; W is -NR16-, -C(R17)2- or -O-; R16is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; each R17is independently hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; R15is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1- C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6alkoxy, unsubstituted or substituted C3-C6cycloalkyl, or unsubstituted or substituted monocyclic heterocycloalkyl; - 64 -or R15and R16are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocycloalkyl; or RDis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; each REis independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, - C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or - S(O)2N(R18)2; wherein if REis attached to a N atom, then it is selected from the group consisting of unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -S(O)R19, - S(O)2R19, and -S(O)2N(R18)2; or two REattached to the same aliphatic carbon atom are taken together with the carbon atom to which they are attached to form -C(O)-; each R18is independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two R18on the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each R19is independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; p is 0 or 1; q is 0 or 1; and m is 0-4.

[0047] In some embodiments, the present disclosure provides compounds of Formula (I):- 65 -Formula (I), or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: R1is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)-heterocyclyl, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, - S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; or R1is -RA-L-RB; RAis unsubstituted or substituted carbocyclylene or unsubstituted or substituted heterocyclylene; L is absent, -(C(R5)2)n-, -C(O)-, -O-, -N(R6)-, -C(O)N(R6)-, -N(R6)C(O), -S(O)-, -S(O)2-, or -S(O)2N(R6)-; each R5is independently hydrogen, deuterium, -OH, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; or two R5on the same carbon atom or on adjacent carbon atoms are taken together with the intervening carbon atom to which they are attached to form a C3-C6cycloalkyl, or a 3- to 6-membered heterocycloalkyl; R6is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; n is 1 or 2; RBis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; wherein if RBis substituted then it is substituted by 1 or more groups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or - 66 -substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -ORb, - C(O)Ra, -C(O)ORa, -C(O)N(Ra)2, -N(Ra)2, -NRaC(O)Rb, -SRa, -S(O)Rb, -P(O)(Rb)2, - S(O)2Rb, -S(O)N(Ra)2, or -S(O)2N(Ra)2; each Rais independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6deuteroalkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Raon the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each Rbis independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6deuteroalkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Rbon the same P atom are taken together with the P atom to which they are attached to form a substituted or unsubstituted P-containing heterocyclyl; R2is hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, - C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; R3is hydrogen, deuterium, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted monocyclic heterocycloalkyl, unsubstituted or substituted -(C1-C3alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C3alkylene)- heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, - NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; R4is hydrogen, deuterium, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted C3-C6- 67 -cycloalkyl, unsubstituted or substituted monocyclic heterocycloalkyl, unsubstituted or substituted -(C1-C3alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C3alkylene)- heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, - NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; or R3and R4are taken together with the carbon atom to which they are attached to form - C(O)-, an unsubstituted or substituted C3-C6cycloalkylene, or an unsubstituted or substituted 3- to 6-membered heterocycloalkylene; Y is -N(R7)-, -S-, -S(O)-, or -S(O)2-, wherein: R7is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; X1is CR8or N; X2is CR9or N; X3is CR10or N; R8, R9, and R10are each independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, - N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; Ring A is a carbocyclic ring or a heterocyclic ring; RCis -N(R11)(R12); R11is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; R12is -C(O)R13, -C(O)NR13R14, or -C(O)OR13; R13is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted monocyclic carbocyclyl, unsubstituted or substituted bicyclic carbocyclyl, unsubstituted orsubstituted monocyclic heterocyclyl, or unsubstituted or substituted bicyclic heterocyclyl; R14is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; or R13and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted heterocyclyl; or R11and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted 5- or 6-membered monocyclic heterocyclyl; - 68 -or R12is an unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1- C6heteroalkyl, unsubstituted or substituted heterocyclyl, or unsubstituted or substituted carbocyclyl, wherein if R12is substituted then it is substituted with 1 or more groups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)-heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, - C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; RDis -C(=O)-W-R15; W is -NR16-, -C(R17)2- or -O-; R16is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; each R17is independently hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; R15is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1- C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6alkoxy, unsubstituted or substituted C3-C6cycloalkyl, or unsubstituted or substituted monocyclic heterocycloalkyl; or R15and R16are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocycloalkyl; or RDis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; each REis independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, - C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or - S(O)2N(R18)2; wherein if REis attached to a N atom, then it is selected from the group consisting of unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted - 69 -C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -S(O)R19, - S(O)2R19, and -S(O)2N(R18)2; or two REattached to the same aliphatic carbon atom are taken together with the carbon atom to which they are attached to form -C(O)-; each R18is independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two R18on the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each R19is independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; p is 0 or 1; q is 0 or 1; and m is 0-4.

[0048] In some embodiments, the present disclosure provides compounds of Formula (I-st-1):Formula (I-st-1). - 70 -

[0049] In some embodiments, the present disclosure provides compounds of Formula (I-st-2):Formula (I-st-2).

[0050] In some embodiments, the present disclosure provides compounds of Formula (I-st-3):Formula (I-st-3); wherein R3is hydrogen, deuterium, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted monocyclic heterocycloalkyl, unsubstituted or substituted -(C1-C3alkylene)-carbocyclyl, unsubstituted or substituted - (C1-C3alkylene)-heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, - N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2.

[0051] In some embodiments, the present disclosure provides compounds of Formula (I-st-4):Formula (I-st-4); - 71 -wherein R3is hydrogen, deuterium, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted monocyclic heterocycloalkyl, unsubstituted or substituted -(C1-C3alkylene)-carbocyclyl, unsubstituted or substituted - (C1-C3alkylene)-heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, - N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2.

[0052] In some embodiments, the present disclosure provides compounds of Formula (I-st-5):Formula (I-st-5); wherein R3is hydrogen, deuterium, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted monocyclic heterocycloalkyl, unsubstituted or substituted -(C1-C3alkylene)-carbocyclyl, unsubstituted or substituted - (C1-C3alkylene)-heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, - N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2.

[0053] In some embodiments, the present disclosure provides compounds of Formula (I-1):or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: - 72 -R1is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1- C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)-heterocyclyl, - C(O)R18, -(C1-C6alkylene)-C(O)R18, -C(O)OR18, -(C1-C6alkylene)-C(O)OR18, - C(O)N(R18)2, -(C1-C6alkylene)-C(O)N(R18)2, -S(O)R19, -(C1-C6alkylene)-S(O)R19, - S(O)2R19, -(C1-C6alkylene)-S(O)2R19, -S(O)2N(R18)2, or -(C1-C6alkylene)- S(O)2N(R18)2; or R1is -RA-L-RB; RAis unsubstituted or substituted carbocyclylene or unsubstituted or substituted heterocyclylene; L is absent, -(C(R5)2)n-, -C(O)-, -O-, -N(R6)-, -NR6-(C(R5)2)n-, -(C(R5)2)n-NR6-, -O- (C(R5)2)n-, -(C(R5)2)n-O-, -C(O)N(R6)-, -N(R6)C(O), -S(O)-, -S(O)2-, or - S(O)2N(R6)-; each R5is independently hydrogen, deuterium, -OH, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; or two R5on the same carbon atom or on adjacent carbon atoms are taken together with the intervening carbon atom to which they are attached to form a C3-C6cycloalkyl, or a 3- to 6-membered heterocycloalkyl; R6is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; n is 1 or 2; RBis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; wherein if RBis substituted then it is substituted by v Rxgroups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1- C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -ORb, -C(O)Ra, -C(O)ORa, -C(O)N(Ra)2, -N(Ra)2, - NRaC(O)Rb, -NRaC(O)ORa, -SRa, -S(O)Rb, -P(O)(Rb)2, -S(O)2Rb, -S(O)N(Ra)2, - S(O)2N(Ra)2, or -N=S(Rb)2=O; each Rais independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6deuteroalkyl, substituted or unsubstituted C1- - 73 -C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8- membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Raon the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each Rbis independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6deuteroalkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Rbon the same P atom are taken together with the P atom to which they are attached to form a substituted or unsubstituted P-containing heterocyclyl; v is an integer selected from 1, 2, 3, and 4; R2is hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, - C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or - S(O)2N(R18)2; R3is hydrogen, deuterium, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted monocyclic heterocycloalkyl, unsubstituted or substituted -(C1-C3alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C3alkylene)-heterocyclyl, -CN, -OH, -OR19, - C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, - S(O)2R19, or -S(O)2N(R18)2; R4is hydrogen, deuterium, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted monocyclic heterocycloalkyl, unsubstituted or substituted -(C1-C3alkylene)-carbocyclyl, - 74 -unsubstituted or substituted -(C1-C3alkylene)-heterocyclyl, -CN, -OH, -OR19, - C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, - S(O)2R19, or -S(O)2N(R18)2; or R3and R4are taken together with the carbon atom to which they are attached to form - C(O)-, an unsubstituted or substituted C3-C6cycloalkylene, or an unsubstituted or substituted 3- to 6-membered heterocycloalkylene; R7is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; X1is CR8or N; X2is CR9or N; X3is CR10or N; R8, R9, and R10are each independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, - C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, - S(O)2R19, or -S(O)2N(R18)2; Ring A is a carbocyclic ring or a heterocyclic ring; RCis -N(R11)(R12); R11is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; R12is -C(O)R13, -C(O)NR13R14, or -C(O)OR13; R13is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted monocyclic carbocyclyl, unsubstituted or substituted bicyclic carbocyclyl, unsubstituted or substituted monocyclic heterocyclyl, or unsubstituted or substituted bicyclic heterocyclyl; R14is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; or R13and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted heterocyclyl; or R11and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted 5- or 6-membered monocyclic heterocyclyl; - 75 -or R12is an unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2- C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted heterocyclyl, or unsubstituted or substituted carbocyclyl, wherein if R12is substituted then it is substituted with 1 or more groups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)-heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, - N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; RDis -C(=O)-W-R15; W is -NR16-, -C(R17)2- or -O-; R16is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; each R17is independently hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; R15is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6alkoxy, unsubstituted or substituted C3-C6cycloalkyl, or unsubstituted or substituted monocyclic heterocycloalkyl; or R15and R16are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocycloalkyl; or RDis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; each REis independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, - C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, - S(O)2R19, or -S(O)2N(R18)2; wherein if REis attached to a N atom, then it is selected - 76 -from the group consisting of unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, - C(O)OR18, -C(O)N(R18)2, -S(O)R19, -S(O)2R19, and -S(O)2N(R18)2; or two REattached to the same aliphatic carbon atom are taken together with the carbon atom to which they are attached to form -C(O)-; each R18is independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two R18on the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each R19is independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; p is 0 or 1; q is 0 or 1; and m is 0-4.

[0054] In some embodiments, the present disclosure provides compounds of Formula (I-1):or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: - 77 -R1is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1- C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)-heterocyclyl, - C(O)R18, -C(O)OR18, -C(O)N(R18)2, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; or R1is -RA-L-RB; RAis unsubstituted or substituted carbocyclylene or unsubstituted or substituted heterocyclylene; L is absent, -(C(R5)2)n-, -C(O)-, -O-, -N(R6)-, -C(O)N(R6)-, -N(R6)C(O), -S(O)-, - S(O)2-, or -S(O)2N(R6)-; each R5is independently hydrogen, deuterium, -OH, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; or two R5on the same carbon atom or on adjacent carbon atoms are taken together with the intervening carbon atom to which they are attached to form a C3-C6cycloalkyl, or a 3- to 6-membered heterocycloalkyl; R6is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; n is 1 or 2; RBis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; wherein if RBis substituted then it is substituted by 1 or more groups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -ORb, -C(O)Ra, -C(O)ORa, -C(O)N(Ra)2, -N(Ra)2, - NRaC(O)Rb, -SRa, -S(O)Rb, -P(O)(Rb)2, -S(O)2Rb, -S(O)N(Ra)2, or -S(O)2N(Ra)2; each Rais independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6deuteroalkyl, substituted or unsubstituted C1- C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8- membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; - 78 -or two Raon the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each Rbis independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6deuteroalkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Rbon the same P atom are taken together with the P atom to which they are attached to form a substituted or unsubstituted P-containing heterocyclyl; R2is hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, - C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or - S(O)2N(R18)2; R3is hydrogen, deuterium, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted monocyclic heterocycloalkyl, unsubstituted or substituted -(C1-C3alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C3alkylene)-heterocyclyl, -CN, -OH, -OR19, - C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, - S(O)2R19, or -S(O)2N(R18)2; R4is hydrogen, deuterium, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted monocyclic heterocycloalkyl, unsubstituted or substituted -(C1-C3alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C3alkylene)-heterocyclyl, -CN, -OH, -OR19, - C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, - S(O)2R19, or -S(O)2N(R18)2; - 79 -or R3and R4are taken together with the carbon atom to which they are attached to form - C(O)-, an unsubstituted or substituted C3-C6cycloalkylene, or an unsubstituted or substituted 3- to 6-membered heterocycloalkylene; R7is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; X1is CR8or N; X2is CR9or N; X3is CR10or N; R8, R9, and R10are each independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, - C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, - S(O)2R19, or -S(O)2N(R18)2; Ring A is a carbocyclic ring or a heterocyclic ring; RCis -N(R11)(R12); R11is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; R12is -C(O)R13, -C(O)NR13R14, or -C(O)OR13; R13is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted monocyclic carbocyclyl, unsubstituted or substituted bicyclic carbocyclyl, unsubstituted or substituted monocyclic heterocyclyl, or unsubstituted or substituted bicyclic heterocyclyl; R14is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; or R13and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted heterocyclyl; or R11and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted 5- or 6-membered monocyclic heterocyclyl; or R12is an unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2- C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted heterocyclyl, or unsubstituted or substituted carbocyclyl, wherein if R12is substituted then it is - 80 -substituted with 1 or more groups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)-heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, - N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; RDis -C(=O)-W-R15; W is -NR16-, -C(R17)2- or -O-; R16is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; each R17is independently hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; R15is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6alkoxy, unsubstituted or substituted C3-C6cycloalkyl, or unsubstituted or substituted monocyclic heterocycloalkyl; or R15and R16are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocycloalkyl; or RDis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; each REis independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, - C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, - S(O)2R19, or -S(O)2N(R18)2; wherein if REis attached to a N atom, then it is selected from the group consisting of unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted - 81 -carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, - C(O)OR18, -C(O)N(R18)2, -S(O)R19, -S(O)2R19, and -S(O)2N(R18)2; or two REattached to the same aliphatic carbon atom are taken together with the carbon atom to which they are attached to form -C(O)-; each R18is independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two R18on the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each R19is independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; p is 0 or 1; q is 0 or 1; and m is 0-4.

[0055] In some embodiments, the present disclosure provides compounds of Formula (I-1-st-Formula (I-1-st-1).

[0056] In some embodiments, the present disclosure provides compounds of Formula (I-1-st-- 82 -Formula (I-1-st-2).

[0057] In some embodiments, the present disclosure provides compounds of Formula (I-1-st-3):Formula (I-1-st-3); wherein R3is hydrogen, deuterium, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted monocyclic heterocycloalkyl, unsubstituted or substituted -(C1-C3alkylene)-carbocyclyl, unsubstituted or substituted - (C1-C3alkylene)-heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, - N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2.

[0058] In some embodiments, the present disclosure provides compounds of Formula (I-1-st-4):Formula (I-1-st-4); wherein R3is hydrogen, deuterium, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6- 83 -fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted monocyclic heterocycloalkyl, unsubstituted or substituted -(C1-C3alkylene)-carbocyclyl, unsubstituted or substituted - (C1-C3alkylene)-heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, - N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2.

[0059] In some embodiments, the present disclosure provides compounds of Formula (I-1-st-5):Formula (I-1-st-5); wherein R3is hydrogen, deuterium, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted monocyclic heterocycloalkyl, unsubstituted or substituted -(C1-C3alkylene)-carbocyclyl, unsubstituted or substituted - (C1-C3alkylene)-heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, - N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2.

[0060] In some embodiments, the present disclosure provides a compound of Formula (I-st-1),Formula (I-st-2), Formula (I-st-3), Formula (I-st-4), or Formula (I-st-5):Formula (I-st-2), - 84 -- - .

[0061] In one aspect, the present disclosure provides compounds of Formula (I):Formula (I), or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: R1is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)-heterocyclyl, -C(O)R18, -(C1-C6alkylene)-C(O)R18, - C(O)OR18, -(C1-C6alkylene)-C(O)OR18, -C(O)N(R18)2, -(C1-C6alkylene)-C(O)N(R18)2, - - 85 -S(O)R19, -(C1-C6alkylene)-S(O)R19, -S(O)2R19, -(C1-C6alkylene)-S(O)2R19, - S(O)2N(R18)2, or -(C1-C6alkylene)-S(O)2N(R18)2; or R1is -RA-L-RB; RAis unsubstituted or substituted carbocyclylene or unsubstituted or substituted heterocyclylene; L is absent, -(C(R5)2)n-, -C(O)-, -O-, -N(R6)-, -NR6-(C(R5)2)n-, -(C(R5)2)n-NR6-, -O- (C(R5)2)n-, -(C(R5)2)n-O-, -C(O)N(R6)-, -N(R6)C(O), -S(O)-, -S(O)2-, or -S(O)2N(R6)- ; each R5is independently hydrogen, deuterium, -OH, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; or two R5on the same carbon atom or on adjacent carbon atoms are taken together with the intervening carbon atom to which they are attached to form a C3-C6cycloalkyl, or a 3- to 6-membered heterocycloalkyl; R6is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; n is 1 or 2; RBis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; wherein if RBis substituted then it is substituted by v Rxgroups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -ORb, - C(O)Ra, -C(O)ORa, -C(O)N(Ra)2, -N(Ra)2, -NRaC(O)Rb, -NRaC(O)ORa, -SRa, - S(O)Rb, -P(O)(Rb)2, -S(O)2Rb, -S(O)N(Ra)2, -S(O)2N(Ra)2, or -N=S(Rb)2=O; each Rais independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Raon the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each Rbis independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted - 86 -monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Rbon the same P atom are taken together with the P atom to which they are attached to form a substituted or unsubstituted P-containing heterocyclyl; v is an integer selected from 1, 2, 3, and 4; R2is hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, - C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; R3and R4are each independently hydrogen, deuterium, halogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, - S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; or R3and R4are taken together with the carbon atom to which they are attached to form - C(O)-, an unsubstituted or substituted C3-C6cycloalkylene, or an unsubstituted or substituted 3- to 6-membered heterocycloalkylene; Y is -N(R7)-, -O-, -S-, -S(O)-, or -S(O)2-, wherein: R7is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; X1is CR8or N; X2is CR9or N; X3is CR10or N; R8, R9, and R10are each independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, - N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; Ring A is a carbocyclic ring or a heterocyclic ring; RCis -N(R11)(R12); R11is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; R12is -C(O)R13, -C(O)NR13R14, or -C(O)OR13; - 87 -R13is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted monocyclic carbocyclyl, unsubstituted or substituted bicyclic carbocyclyl, unsubstituted orsubstituted monocyclic heterocyclyl, or unsubstituted or substituted bicyclic heterocyclyl; R14is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; or R13and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted heterocyclyl; or R11and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted 5- or 6-membered monocyclic heterocyclyl; or R12is an unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1- C6heteroalkyl, unsubstituted or substituted heterocyclyl, or unsubstituted or substituted carbocyclyl, wherein if R12is substituted then it is substituted with 1 or more groups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)-heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, - C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; RDis -C(=O)-W-R15; W is -NR16-, -C(R17)2-, or -O-; R16is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; each R17is independently hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; R15is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1- C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6alkoxy, unsubstituted or substituted C3-C6cycloalkyl, or unsubstituted or substituted monocyclic heterocycloalkyl; - 88 -or R15and R16are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocycloalkyl; or RDis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; each REis independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, - C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or - S(O)2N(R18)2; wherein if REis attached to a N atom, then it is selected from the group consisting of unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -S(O)R19, - S(O)2R19, and -S(O)2N(R18)2; or two REattached to the same aliphatic carbon atom are taken together with the carbon atom to which they are attached to form -C(O)-; each R18is independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two R18on the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each R19is independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; p is 0 or 1; q is 0 or 1; and m is 0-4.

[0062] In one aspect, the present disclosure provides compounds of Formula (I):- 89 -Formula (I), or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: R1is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)-heterocyclyl, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, - S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; or R1is -RA-L-RB; RAis unsubstituted or substituted carbocyclylene or unsubstituted or substituted heterocyclylene; L is absent, -(C(R5)2)n-, -C(O)-, -O-, -N(R6)-, -C(O)N(R6)-, -N(R6)C(O), -S(O)-, -S(O)2-, or -S(O)2N(R6)-; each R5is independently hydrogen, deuterium, -OH, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; or two R5on the same carbon atom or on adjacent carbon atoms are taken together with the intervening carbon atom to which they are attached to form a C3-C6cycloalkyl, or a 3- to 6-membered heterocycloalkyl; R6is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; n is 1 or 2; RBis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; wherein if RBis substituted then it is substituted by 1 or more groups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or - 90 -substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -ORb, - C(O)Ra, -C(O)ORa, -C(O)N(Ra)2, -N(Ra)2, -NRaC(O)Rb, -SRa, -S(O)Rb, -P(O)(Rb)2, - S(O)2Rb, -S(O)N(Ra)2, or -S(O)2N(Ra)2; each Rais independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Raon the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each Rbis independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Rbon the same P atom are taken together with the P atom to which they are attached to form a substituted or unsubstituted P-containing heterocyclyl; R2is hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, - C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; R3and R4are each independently hydrogen, deuterium, halogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, - S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; or R3and R4are taken together with the carbon atom to which they are attached to form - C(O)-, an unsubstituted or substituted C3-C6cycloalkylene, or an unsubstituted or substituted 3- to 6-membered heterocycloalkylene; Y is -N(R7)-, -O-, -S-, -S(O)-, or -S(O)2-, wherein: R7is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; X1is CR8or N; X2is CR9or N; - 91 -X3is CR10or N; R8, R9, and R10are each independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, - N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; Ring A is a carbocyclic ring or a heterocyclic ring; RCis -N(R11)(R12); R11is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; R12is -C(O)R13, -C(O)NR13R14, or -C(O)OR13; R13is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted monocyclic carbocyclyl, unsubstituted or substituted bicyclic carbocyclyl, unsubstituted orsubstituted monocyclic heterocyclyl, or unsubstituted or substituted bicyclic heterocyclyl; R14is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; or R13and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted heterocyclyl; or R11and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted 5- or 6-membered monocyclic heterocyclyl; or R12is an unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1- C6heteroalkyl, unsubstituted or substituted heterocyclyl, or unsubstituted or substituted carbocyclyl, wherein if R12is substituted then it is substituted with 1 or more groups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)-heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, - C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; - 92 -RDis -C(=O)-W-R15; W is -NR16-, -C(R17)2-, or -O-; R16is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; each R17is independently hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; R15is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1- C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6alkoxy, unsubstituted or substituted C3-C6cycloalkyl, or unsubstituted or substituted monocyclic heterocycloalkyl; or R15and R16are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocycloalkyl; or RDis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; each REis independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, - C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or - S(O)2N(R18)2; wherein if REis attached to a N atom, then it is selected from the group consisting of unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -S(O)R19, - S(O)2R19, and -S(O)2N(R18)2; or two REattached to the same aliphatic carbon atom are taken together with the carbon atom to which they are attached to form -C(O)-; each R18is independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; - 93 -or two R18on the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each R19is independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; p is 0 or 1; q is 0 or 1; and m is 0-4.

[0063] In some embodiments, the present disclosure provides compounds of Formula (I):Formula (I), or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: R1is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)-heterocyclyl, -C(O)R18, -(C1-C6alkylene)-C(O)R18, - C(O)OR18, -(C1-C6alkylene)-C(O)OR18, -C(O)N(R18)2, -(C1-C6alkylene)-C(O)N(R18)2, - S(O)R19, -(C1-C6alkylene)-S(O)R19, -S(O)2R19, -(C1-C6alkylene)-S(O)2R19, - S(O)2N(R18)2, or -(C1-C6alkylene)-S(O)2N(R18)2; or R1is -RA-L-RB; RAis unsubstituted or substituted carbocyclylene or unsubstituted or substituted heterocyclylene; L is absent, -(C(R5)2)n-, -C(O)-, -O-, -N(R6)-, -C(O)N(R6)-, -N(R6)C(O), -S(O)-, -S(O)2-, or -S(O)2N(R6)-; - 94 -each R5is independently hydrogen, deuterium, -OH, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; or two R5on the same carbon atom or on adjacent carbon atoms are taken together with the intervening carbon atom to which they are attached to form a C3-C6cycloalkyl, or a 3- to 6-membered heterocycloalkyl; R6is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; n is 1 or 2; RBis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; wherein if RBis substituted then it is substituted by v Rxgroups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -ORb, - C(O)Ra, -C(O)ORa, -C(O)N(Ra)2, -N(Ra)2, -NRaC(O)Rb, -SRa, -S(O)Rb, -P(O)(Rb)2, - S(O)2Rb, -S(O)N(Ra)2, or -S(O)2N(Ra)2; each Rais independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Raon the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each Rbis independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Rbon the same P atom are taken together with the P atom to which they are attached to form a substituted or unsubstituted P-containing heterocyclyl; v is an integer selected from 1, 2, 3, and 4; R2is hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, - 95 -unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, - C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; R3and R4are each independently hydrogen, deuterium, halogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, - S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; or R3and R4are taken together with the carbon atom to which they are attached to form - C(O)-, an unsubstituted or substituted C3-C6cycloalkylene, or an unsubstituted or substituted 3- to 6-membered heterocycloalkylene; Y is -N(R7)-, -O-, -S-, -S(O)-, or -S(O)2-, wherein: R7is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; X1is CR8or N; X2is CR9or N; X3is CR10or N; R8, R9, and R10are each independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, - N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; Ring A is a carbocyclic ring or a heterocyclic ring; RCis -N(R11)(R12); R11is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; R12is -C(O)R13, -C(O)NR13R14, or -C(O)OR13; R13is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted monocyclic carbocyclyl, unsubstituted or substituted bicyclic carbocyclyl, unsubstituted orsubstituted monocyclic heterocyclyl, or unsubstituted or substituted bicyclic heterocyclyl; R14is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; or R13and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted heterocyclyl; - 96 -or R11and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted 5- or 6-membered monocyclic heterocyclyl; or R12is an unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1- C6heteroalkyl, unsubstituted or substituted heterocyclyl, or unsubstituted or substituted carbocyclyl, wherein if R12is substituted then it is substituted with 1 or more groups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)-heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, - C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; RDis -C(=O)-W-R15; W is -NR16-, -C(R17)2- or -O-; R16is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; each R17is independently hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; R15is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1- C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6alkoxy, unsubstituted or substituted C3-C6cycloalkyl, or unsubstituted or substituted monocyclic heterocycloalkyl; or R15and R16are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocycloalkyl; or RDis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; each REis independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, - C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or - - 97 -S(O)2N(R18)2; wherein if REis attached to a N atom, then it is selected from the group consisting of unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -S(O)R19, - S(O)2R19, and -S(O)2N(R18)2; or two REattached to the same aliphatic carbon atom are taken together with the carbon atom to which they are attached to form -C(O)-; each R18is independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two R18on the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each R19is independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; p is 0 or 1; q is 0 or 1; and m is 0-4; with the proviso that the compound of Formula (I) is not.

[0064] In some embodiments, the present disclosure provides compounds of Formula (I):- 98 -Formula (I), or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: R1is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)-heterocyclyl, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, - S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; or R1is -RA-L-RB; RAis unsubstituted or substituted carbocyclylene or unsubstituted or substituted heterocyclylene; L is absent, -(C(R5)2)n-, -C(O)-, -O-, -N(R6)-, -C(O)N(R6)-, -N(R6)C(O), -S(O)-, -S(O)2-, or -S(O)2N(R6)-; each R5is independently hydrogen, deuterium, -OH, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; or two R5on the same carbon atom or on adjacent carbon atoms are taken together with the intervening carbon atom to which they are attached to form a C3-C6cycloalkyl, or a 3- to 6-membered heterocycloalkyl; R6is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; n is 1 or 2; RBis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; wherein if RBis substituted then it is substituted by 1 or more groups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or - 99 -substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -ORb, - C(O)Ra, -C(O)ORa, -C(O)N(Ra)2, -N(Ra)2, -NRaC(O)Rb, -SRa, -S(O)Rb, -P(O)(Rb)2, - S(O)2Rb, -S(O)N(Ra)2, or -S(O)2N(Ra)2; each Rais independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Raon the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each Rbis independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Rbon the same P atom are taken together with the P atom to which they are attached to form a substituted or unsubstituted P-containing heterocyclyl; R2is hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, - C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; R3and R4are each independently hydrogen, deuterium, halogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, - S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; or R3and R4are taken together with the carbon atom to which they are attached to form - C(O)-, an unsubstituted or substituted C3-C6cycloalkylene, or an unsubstituted or substituted 3- to 6-membered heterocycloalkylene; Y is -N(R7)-, -O-, -S-, -S(O)-, or -S(O)2-, wherein: R7is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; X1is CR8or N; X2is CR9or N; - 100 -X3is CR10or N; R8, R9, and R10are each independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, - N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; Ring A is a carbocyclic ring or a heterocyclic ring; RCis -N(R11)(R12); R11is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; R12is -C(O)R13, -C(O)NR13R14, or -C(O)OR13; R13is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted monocyclic carbocyclyl, unsubstituted or substituted bicyclic carbocyclyl, unsubstituted orsubstituted monocyclic heterocyclyl, or unsubstituted or substituted bicyclic heterocyclyl; R14is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; or R13and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted heterocyclyl; or R11and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted 5- or 6-membered monocyclic heterocyclyl; or R12is an unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1- C6heteroalkyl, unsubstituted or substituted heterocyclyl, or unsubstituted or substituted carbocyclyl, wherein if R12is substituted then it is substituted with 1 or more groups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)-heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, - C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; - 101 -RDis -C(=O)-W-R15; W is -NR16-, -C(R17)2- or -O-; R16is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; each R17is independently hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; R15is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1- C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6alkoxy, unsubstituted or substituted C3-C6cycloalkyl, or unsubstituted or substituted monocyclic heterocycloalkyl; or R15and R16are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocycloalkyl; or RDis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; each REis independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, - C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or - S(O)2N(R18)2; wherein if REis attached to a N atom, then it is selected from the group consisting of unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -S(O)R19, - S(O)2R19, and -S(O)2N(R18)2; or two REattached to the same aliphatic carbon atom are taken together with the carbon atom to which they are attached to form -C(O)-; each R18is independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; - 102 -or two R18on the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each R19is independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; p is 0 or 1; q is 0 or 1; and m is 0-4; with the proviso that the compound of Formula (I) is not.

[0065] In some embodiments, the present disclosure provides compounds of Formula (I):Formula (I), or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: R1is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)-heterocyclyl, -C(O)R18, -(C1-C6alkylene)-C(O)R18, - - 103 -C(O)OR18, -(C1-C6alkylene)-C(O)OR18, -C(O)N(R18)2, -(C1-C6alkylene)-C(O)N(R18)2, - S(O)R19, -(C1-C6alkylene)-S(O)R19, -S(O)2R19, -(C1-C6alkylene)-S(O)2R19, - S(O)2N(R18)2, or -(C1-C6alkylene)-S(O)2N(R18)2; or R1is -RA-L-RB; RAis unsubstituted or substituted carbocyclylene or unsubstituted or substituted heterocyclylene; L is absent, -(C(R5)2)n-, -C(O)-, -O-, -N(R6)-, -NR6-(C(R5)2)n-, -(C(R5)2)n-NR6-, -O- (C(R5)2)n-, -(C(R5)2)n-O-, -C(O)N(R6)-, -N(R6)C(O), -S(O)-, -S(O)2-, or -S(O)2N(R6)- ; each R5is independently hydrogen, deuterium, -OH, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; or two R5on the same carbon atom or on adjacent carbon atoms are taken together with the intervening carbon atom to which they are attached to form a C3-C6cycloalkyl, or a 3- to 6-membered heterocycloalkyl; R6is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; n is 1 or 2; RBis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; wherein if RBis substituted then it is substituted by v Rxgroups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -ORb, - C(O)Ra, -C(O)ORa, -C(O)N(Ra)2, -N(Ra)2, -NRaC(O)Rb, -NRaC(O)ORa, -SRa, - S(O)Rb, -P(O)(Rb)2, -S(O)2Rb, -S(O)N(Ra)2, -S(O)2N(Ra)2, or -N=S(Rb)2=O; each Rais independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Raon the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each Rbis independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted - 104 -monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Rbon the same P atom are taken together with the P atom to which they are attached to form a substituted or unsubstituted P-containing heterocyclyl; v is an integer selected from 1, 2, 3, and 4; R2is hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, - C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; R3and R4are each independently hydrogen, deuterium, halogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, - S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; or R3and R4are taken together with the carbon atom to which they are attached to form - C(O)-, an unsubstituted or substituted C3-C6cycloalkylene, or an unsubstituted or substituted 3- to 6-membered heterocycloalkylene; Y is -N(R7)-, -O-, -S-, -S(O)-, or -S(O)2-, wherein: R7is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; X1is CR8or N; X2is CR9or N; X3is CR10or N; R8, R9, and R10are each independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, - N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; Ring A is a carbocyclic ring or a heterocyclic ring; RCis -N(R11)(R12); R11is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; R12is -C(O)R13, -C(O)NR13R14, or -C(O)OR13; - 105 -R13is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted monocyclic carbocyclyl, unsubstituted or substituted bicyclic carbocyclyl, unsubstituted orsubstituted monocyclic heterocyclyl, or unsubstituted or substituted bicyclic heterocyclyl; R14is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; or R13and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted heterocyclyl; or R11and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted 5- or 6-membered monocyclic heterocyclyl; or R12is an unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1- C6heteroalkyl, unsubstituted or substituted heterocyclyl, or unsubstituted or substituted carbocyclyl, wherein if R12is substituted then it is substituted with 1 or more groups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)-heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, - C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; RDis -C(=O)-W-R15; W is -NR16-, -C(R17)2- or -O-; R16is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; each R17is independently hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; R15is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1- C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6alkoxy, unsubstituted or substituted C3-C6cycloalkyl, or unsubstituted or substituted monocyclic heterocycloalkyl; - 106 -or R15and R16are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocycloalkyl; or RDis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; each REis independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, - C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or - S(O)2N(R18)2; wherein if REis attached to a N atom, then it is selected from the group consisting of unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -S(O)R19, - S(O)2R19, and -S(O)2N(R18)2; or two REattached to the same aliphatic carbon atom are taken together with the carbon atom to which they are attached to form -C(O)-; each R18is independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two R18on the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each R19is independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; p is 0 or 1; q is 0 or 1; and m is 0-4; wherein when ring A is pyrimidinyl, Y is -N(R7)-. - 107 -

[0066] In some embodiments, the present disclosure provides compounds of Formula (I):Formula (I), or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: R1is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)-heterocyclyl, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, - S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; or R1is -RA-L-RB; RAis unsubstituted or substituted carbocyclylene or unsubstituted or substituted heterocyclylene; L is absent, -(C(R5)2)n-, -C(O)-, -O-, -N(R6)-, -C(O)N(R6)-, -N(R6)C(O), -S(O)-, -S(O)2-, or -S(O)2N(R6)-; each R5is independently hydrogen, deuterium, -OH, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; or two R5on the same carbon atom or on adjacent carbon atoms are taken together with the intervening carbon atom to which they are attached to form a C3-C6cycloalkyl, or a 3- to 6-membered heterocycloalkyl; R6is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; n is 1 or 2; RBis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; wherein if RBis substituted then it is substituted by 1 or more groups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted - 108 -C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -ORb, - C(O)Ra, -C(O)ORa, -C(O)N(Ra)2, -N(Ra)2, -NRaC(O)Rb, -SRa, -S(O)Rb, -P(O)(Rb)2, - S(O)2Rb, -S(O)N(Ra)2, or -S(O)2N(Ra)2; each Rais independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Raon the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each Rbis independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Rbon the same P atom are taken together with the P atom to which they are attached to form a substituted or unsubstituted P-containing heterocyclyl; R2is hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, - C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; R3and R4are each independently hydrogen, deuterium, halogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, - S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; or R3and R4are taken together with the carbon atom to which they are attached to form - C(O)-, an unsubstituted or substituted C3-C6cycloalkylene, or an unsubstituted or substituted 3- to 6-membered heterocycloalkylene; Y is -N(R7)-, -O-, -S-, -S(O)-, or -S(O)2-, wherein: R7is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; X1is CR8or N; - 109 -X2is CR9or N; X3is CR10or N; R8, R9, and R10are each independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, - N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; Ring A is a carbocyclic ring or a heterocyclic ring; RCis -N(R11)(R12); R11is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; R12is -C(O)R13, -C(O)NR13R14, or -C(O)OR13; R13is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted monocyclic carbocyclyl, unsubstituted or substituted bicyclic carbocyclyl, unsubstituted orsubstituted monocyclic heterocyclyl, or unsubstituted or substituted bicyclic heterocyclyl; R14is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; or R13and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted heterocyclyl; or R11and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted 5- or 6-membered monocyclic heterocyclyl; or R12is an unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1- C6heteroalkyl, unsubstituted or substituted heterocyclyl, or unsubstituted or substituted carbocyclyl, wherein if R12is substituted then it is substituted with 1 or more groups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or - 110 -substituted -(C1-C6alkylene)-heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, - C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; RDis -C(=O)-W-R15; W is -NR16-, -C(R17)2- or -O-; R16is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; each R17is independently hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; R15is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1- C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6alkoxy, unsubstituted or substituted C3-C6cycloalkyl, or unsubstituted or substituted monocyclic heterocycloalkyl; or R15and R16are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocycloalkyl; or RDis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; each REis independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, - C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or - S(O)2N(R18)2; wherein if REis attached to a N atom, then it is selected from the group consisting of unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -S(O)R19, - S(O)2R19, and -S(O)2N(R18)2; or two REattached to the same aliphatic carbon atom are taken together with the carbon atom to which they are attached to form -C(O)-; each R18is independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- - 111 -to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two R18on the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each R19is independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; p is 0 or 1; q is 0 or 1; and m is 0-4; wherein when ring A is pyrimidinyl, Y is -N(R7)-.

[0067] In some embodiments, the present disclosure provides compounds of Formula (I):Formula (I), or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: R1is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)-heterocyclyl, -C(O)R18, -(C1-C6alkylene)-C(O)R18, - C(O)OR18, -(C1-C6alkylene)-C(O)OR18, -C(O)N(R18)2, -(C1-C6alkylene)-C(O)N(R18)2, - S(O)R19, -(C1-C6alkylene)-S(O)R19, -S(O)2R19, -(C1-C6alkylene)-S(O)2R19, - S(O)2N(R18)2, or -(C1-C6alkylene)-S(O)2N(R18)2; or R1is -RA-L-RB; - 112 -RAis unsubstituted or substituted carbocyclylene or unsubstituted or substituted heterocyclylene; L is absent, -(C(R5)2)n-, -C(O)-, -O-, -N(R6)-, -NR6-(C(R5)2)n-, -(C(R5)2)n-NR6-, -O- (C(R5)2)n-, -(C(R5)2)n-O-, -C(O)N(R6)-, -N(R6)C(O), -S(O)-, -S(O)2-, or -S(O)2N(R6)- ; each R5is independently hydrogen, deuterium, -OH, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; or two R5on the same carbon atom or on adjacent carbon atoms are taken together with the intervening carbon atom to which they are attached to form a C3-C6cycloalkyl, or a 3- to 6-membered heterocycloalkyl; R6is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; n is 1 or 2; RBis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; wherein if RBis substituted then it is substituted by v Rxgroups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -ORb, - C(O)Ra, -C(O)ORa, -C(O)N(Ra)2, -N(Ra)2, -NRaC(O)Rb, -NRaC(O)ORa, -SRa, - S(O)Rb, -P(O)(Rb)2, -S(O)2Rb, -S(O)N(Ra)2, -S(O)2N(Ra)2, or -N=S(Rb)2=O; each Rais independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Raon the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each Rbis independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Rbon the same P atom are taken together with the P atom to which they are attached to form a substituted or unsubstituted P-containing heterocyclyl; - 113 -v is an integer selected from 1, 2, 3, and 4; R2is hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, - C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; R3and R4are each independently hydrogen, deuterium, halogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, - S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; or R3and R4are taken together with the carbon atom to which they are attached to form - C(O)-, an unsubstituted or substituted C3-C6cycloalkylene, or an unsubstituted or substituted 3- to 6-membered heterocycloalkylene; Y is -N(R7)-, -O-, -S-, -S(O)-, or -S(O)2-, wherein: R7is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; X1is CR8or N; X2is CR9or N; X3is CR10or N; R8, R9, and R10are each independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, - N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; Ring A is a carbocyclic ring or a heterocyclic ring; RCis -N(R11)(R12); R11is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; R12is -C(O)R13, -C(O)NR13R14, or -C(O)OR13; R13is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted monocyclic carbocyclyl, unsubstituted or substituted bicyclic carbocyclyl, unsubstituted or- 114 -substituted monocyclic heterocyclyl, or unsubstituted or substituted bicyclic heterocyclyl; R14is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; or R13and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted heterocyclyl; or R11and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted 5- or 6-membered monocyclic heterocyclyl; or R12is an unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1- C6heteroalkyl, unsubstituted or substituted heterocyclyl, or unsubstituted or substituted carbocyclyl, wherein if R12is substituted then it is substituted with 1 or more groups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)-heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, - C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; RDis -C(=O)-W-R15; W is -NR16-, -C(R17)2- or -O-; R16is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; each R17is independently hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; R15is unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6alkoxy, unsubstituted or substituted C3-C6cycloalkyl, or unsubstituted or substituted monocyclic heterocycloalkyl; or R15and R16are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocycloalkyl; or RDis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; - 115 -each REis independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, - C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or - S(O)2N(R18)2; wherein if REis attached to a N atom, then it is selected from the group consisting of unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -S(O)R19, - S(O)2R19, and -S(O)2N(R18)2; or two REattached to the same aliphatic carbon atom are taken together with the carbon atom to which they are attached to form -C(O)-; each R18is independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two R18on the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each R19is independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; p is 0 or 1; q is 0 or 1; and m is 0-4.

[0068] In some embodiments, the present disclosure provides compounds of Formula (I):- 116 -Formula (I), or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: R1is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)-heterocyclyl, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, - S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; or R1is -RA-L-RB; RAis unsubstituted or substituted carbocyclylene or unsubstituted or substituted heterocyclylene; L is absent, -(C(R5)2)n-, -C(O)-, -O-, -N(R6)-, -C(O)N(R6)-, -N(R6)C(O), -S(O)-, -S(O)2-, or -S(O)2N(R6)-; each R5is independently hydrogen, deuterium, -OH, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; or two R5on the same carbon atom or on adjacent carbon atoms are taken together with the intervening carbon atom to which they are attached to form a C3-C6cycloalkyl, or a 3- to 6-membered heterocycloalkyl; R6is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; n is 1 or 2; RBis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; wherein if RBis substituted then it is substituted by 1 or more groups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or - 117 -substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -ORb, - C(O)Ra, -C(O)ORa, -C(O)N(Ra)2, -N(Ra)2, -NRaC(O)Rb, -SRa, -S(O)Rb, -P(O)(Rb)2, - S(O)2Rb, -S(O)N(Ra)2, or -S(O)2N(Ra)2; each Rais independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Raon the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each Rbis independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Rbon the same P atom are taken together with the P atom to which they are attached to form a substituted or unsubstituted P-containing heterocyclyl; R2is hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, - C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; R3and R4are each independently hydrogen, deuterium, halogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, - S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; or R3and R4are taken together with the carbon atom to which they are attached to form - C(O)-, an unsubstituted or substituted C3-C6cycloalkylene, or an unsubstituted or substituted 3- to 6-membered heterocycloalkylene; Y is -N(R7)-, -O-, -S-, -S(O)-, or -S(O)2-, wherein: R7is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; X1is CR8or N; X2is CR9or N; - 118 -X3is CR10or N; R8, R9, and R10are each independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, - N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; Ring A is a carbocyclic ring or a heterocyclic ring; RCis -N(R11)(R12); R11is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; R12is -C(O)R13, -C(O)NR13R14, or -C(O)OR13; R13is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted monocyclic carbocyclyl, unsubstituted or substituted bicyclic carbocyclyl, unsubstituted orsubstituted monocyclic heterocyclyl, or unsubstituted or substituted bicyclic heterocyclyl; R14is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; or R13and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted heterocyclyl; or R11and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted 5- or 6-membered monocyclic heterocyclyl; or R12is an unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1- C6heteroalkyl, unsubstituted or substituted heterocyclyl, or unsubstituted or substituted carbocyclyl, wherein if R12is substituted then it is substituted with 1 or more groups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)-heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, - C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; - 119 -RDis -C(=O)-W-R15; W is -NR16-, -C(R17)2- or -O-; R16is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; each R17is independently hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; R15is unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6alkoxy, unsubstituted or substituted C3-C6cycloalkyl, or unsubstituted or substituted monocyclic heterocycloalkyl; or R15and R16are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocycloalkyl; or RDis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; each REis independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, - C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or - S(O)2N(R18)2; wherein if REis attached to a N atom, then it is selected from the group consisting of unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -S(O)R19, - S(O)2R19, and -S(O)2N(R18)2; or two REattached to the same aliphatic carbon atom are taken together with the carbon atom to which they are attached to form -C(O)-; each R18is independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; - 120 -or two R18on the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each R19is independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; p is 0 or 1; q is 0 or 1; and m is 0-4.

[0069] In some embodiments, the present disclosure provides compounds of Formula (I):Formula (I), or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: R1is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)-heterocyclyl, -C(O)R18, -(C1-C6alkylene)-C(O)R18, - C(O)OR18, -(C1-C6alkylene)-C(O)OR18, -C(O)N(R18)2, -(C1-C6alkylene)-C(O)N(R18)2, - S(O)R19, -(C1-C6alkylene)-S(O)R19, -S(O)2R19, -(C1-C6alkylene)-S(O)2R19, - S(O)2N(R18)2, or -(C1-C6alkylene)-S(O)2N(R18)2; or R1is -RA-L-RB; RAis unsubstituted or substituted carbocyclylene or unsubstituted or substituted heterocyclylene; - 121 -L is absent, -(C(R5)2)n-, -C(O)-, -O-, -N(R6)-, -NR6-(C(R5)2)n-, -(C(R5)2)n-NR6-, -O- (C(R5)2)n-, -(C(R5)2)n-O-, -C(O)N(R6)-, -N(R6)C(O), -S(O)-, -S(O)2-, or -S(O)2N(R6)- ; each R5is independently hydrogen, deuterium, -OH, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; or two R5on the same carbon atom or on adjacent carbon atoms are taken together with the intervening carbon atom to which they are attached to form a C3-C6cycloalkyl, or a 3- to 6-membered heterocycloalkyl; R6is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; n is 1 or 2; RBis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; wherein if RBis substituted then it is substituted by v Rxgroups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -ORb, - C(O)Ra, -C(O)ORa, -C(O)N(Ra)2, -N(Ra)2, -NRaC(O)Rb, -NRaC(O)ORa, -SRa, - S(O)Rb, -P(O)(Rb)2, -S(O)2Rb, -S(O)N(Ra)2, -S(O)2N(Ra)2, or -N=S(Rb)2=O; each Rais independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Raon the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each Rbis independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Rbon the same P atom are taken together with the P atom to which they are attached to form a substituted or unsubstituted P-containing heterocyclyl; v is an integer selected from 1, 2, 3, and 4; - 122 -R2is hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, - C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; R3and R4are each independently hydrogen, deuterium, halogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, - S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; or R3and R4are taken together with the carbon atom to which they are attached to form - C(O)-, an unsubstituted or substituted C3-C6cycloalkylene, or an unsubstituted or substituted 3- to 6-membered heterocycloalkylene; Y is -N(R7)-, -S-, -S(O)-, or -S(O)2-, wherein: R7is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; X1is CR8or N; X2is CR9or N; X3is CR10or N; R8, R9, and R10are each independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, - N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; Ring A is a carbocyclic ring or a heterocyclic ring; RCis -N(R11)(R12); R11is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; R12is -C(O)R13, -C(O)NR13R14, or -C(O)OR13; R13is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted monocyclic carbocyclyl, unsubstituted or substituted bicyclic carbocyclyl, unsubstituted orsubstituted monocyclic heterocyclyl, or unsubstituted or substituted bicyclic heterocyclyl; - 123 -R14is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; or R13and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted heterocyclyl; or R11and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted 5- or 6-membered monocyclic heterocyclyl; or R12is an unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1- C6heteroalkyl, unsubstituted or substituted heterocyclyl, or unsubstituted or substituted carbocyclyl, wherein if R12is substituted then it is substituted with 1 or more groups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)-heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, - C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; RDis -C(=O)-W-R15; W is -NR16-, -C(R17)2- or -O-; R16is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; each R17is independently hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; R15is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1- C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6alkoxy, unsubstituted or substituted C3-C6cycloalkyl, or unsubstituted or substituted monocyclic heterocycloalkyl; or R15and R16are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocycloalkyl; or RDis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; each REis independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6- 124 -alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, - C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or - S(O)2N(R18)2; wherein if REis attached to a N atom, then it is selected from the group consisting of unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -S(O)R19, - S(O)2R19, and -S(O)2N(R18)2; or two REattached to the same aliphatic carbon atom are taken together with the carbon atom to which they are attached to form -C(O)-; each R18is independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two R18on the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each R19is independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; p is 0 or 1; q is 0 or 1; and m is 0-4.

[0070] In some embodiments, the present disclosure provides compounds of Formula (I):- 125 -Formula (I), or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: R1is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)-heterocyclyl, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, - S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; or R1is -RA-L-RB; RAis unsubstituted or substituted carbocyclylene or unsubstituted or substituted heterocyclylene; L is absent, -(C(R5)2)n-, -C(O)-, -O-, -N(R6)-, -C(O)N(R6)-, -N(R6)C(O), -S(O)-, -S(O)2-, or -S(O)2N(R6)-; each R5is independently hydrogen, deuterium, -OH, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; or two R5on the same carbon atom or on adjacent carbon atoms are taken together with the intervening carbon atom to which they are attached to form a C3-C6cycloalkyl, or a 3- to 6-membered heterocycloalkyl; R6is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; n is 1 or 2; RBis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; wherein if RBis substituted then it is substituted by 1 or more groups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or - 126 -substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -ORb, - C(O)Ra, -C(O)ORa, -C(O)N(Ra)2, -N(Ra)2, -NRaC(O)Rb, -SRa, -S(O)Rb, -P(O)(Rb)2, - S(O)2Rb, -S(O)N(Ra)2, or -S(O)2N(Ra)2; each Rais independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Raon the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each Rbis independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Rbon the same P atom are taken together with the P atom to which they are attached to form a substituted or unsubstituted P-containing heterocyclyl; R2is hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, - C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; R3and R4are each independently hydrogen, deuterium, halogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, - S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; or R3and R4are taken together with the carbon atom to which they are attached to form - C(O)-, an unsubstituted or substituted C3-C6cycloalkylene, or an unsubstituted or substituted 3- to 6-membered heterocycloalkylene; Y is -N(R7)-, -S-, -S(O)-, or -S(O)2-, wherein: R7is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; X1is CR8or N; X2is CR9or N; - 127 -X3is CR10or N; R8, R9, and R10are each independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, - N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; Ring A is a carbocyclic ring or a heterocyclic ring; RCis -N(R11)(R12); R11is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; R12is -C(O)R13, -C(O)NR13R14, or -C(O)OR13; R13is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted monocyclic carbocyclyl, unsubstituted or substituted bicyclic carbocyclyl, unsubstituted orsubstituted monocyclic heterocyclyl, or unsubstituted or substituted bicyclic heterocyclyl; R14is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; or R13and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted heterocyclyl; or R11and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted 5- or 6-membered monocyclic heterocyclyl; or R12is an unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1- C6heteroalkyl, unsubstituted or substituted heterocyclyl, or unsubstituted or substituted carbocyclyl, wherein if R12is substituted then it is substituted with 1 or more groups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)-heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, - C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; - 128 -RDis -C(=O)-W-R15; W is -NR16-, -C(R17)2- or -O-; R16is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; each R17is independently hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; R15is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1- C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6alkoxy, unsubstituted or substituted C3-C6cycloalkyl, or unsubstituted or substituted monocyclic heterocycloalkyl; or R15and R16are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocycloalkyl; or RDis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; each REis independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, - C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or - S(O)2N(R18)2; wherein if REis attached to a N atom, then it is selected from the group consisting of unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -S(O)R19, - S(O)2R19, and -S(O)2N(R18)2; or two REattached to the same aliphatic carbon atom are taken together with the carbon atom to which they are attached to form -C(O)-; each R18is independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; - 129 -or two R18on the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each R19is independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; p is 0 or 1; q is 0 or 1; and m is 0-4.

[0071] In some embodiments, the present disclosure provides compounds of Formula (I-1):or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: R1is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1- C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)-heterocyclyl, - C(O)R18, -(C1-C6alkylene)-C(O)R18, -C(O)OR18, -(C1-C6alkylene)-C(O)OR18, - C(O)N(R18)2, -(C1-C6alkylene)-C(O)N(R18)2, -S(O)R19, -(C1-C6alkylene)-S(O)R19, - S(O)2R19, -(C1-C6alkylene)-S(O)2R19, -S(O)2N(R18)2, or -(C1-C6alkylene)- S(O)2N(R18)2; or R1is -RA-L-RB; RAis unsubstituted or substituted carbocyclylene or unsubstituted or substituted heterocyclylene; - 130 -L is absent, -(C(R5)2)n-, -C(O)-, -O-, -N(R6)-, -NR6-(C(R5)2)n-, -(C(R5)2)n-NR6-, -O- (C(R5)2)n-, -(C(R5)2)n-O-, -C(O)N(R6)-, -N(R6)C(O), -S(O)-, -S(O)2-, or - S(O)2N(R6)-; each R5is independently hydrogen, deuterium, -OH, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; or two R5on the same carbon atom or on adjacent carbon atoms are taken together with the intervening carbon atom to which they are attached to form a C3-C6cycloalkyl, or a 3- to 6-membered heterocycloalkyl; R6is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; n is 1 or 2; RBis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; wherein if RBis substituted then it is substituted by v Rxgroups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1- C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -ORb, -C(O)Ra, -C(O)ORa, -C(O)N(Ra)2, -N(Ra)2, - NRaC(O)Rb, -NRaC(O)ORa, -SRa, -S(O)Rb, -P(O)(Rb)2, -S(O)2Rb, -S(O)N(Ra)2, - S(O)2N(Ra)2, or -N=S(Rb)2=O; each Rais independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Raon the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each Rbis independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Rbon the same P atom are taken together with the P atom to which they are attached to form a substituted or unsubstituted P-containing heterocyclyl; v is an integer selected from 1, 2, 3, and 4; - 131 -R2is hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, - C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or - S(O)2N(R18)2; R3and R4are each independently hydrogen, deuterium, halogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl, - CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, - SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; or R3and R4are taken together with the carbon atom to which they are attached to form - C(O)-, an unsubstituted or substituted C3-C6cycloalkylene, or an unsubstituted or substituted 3- to 6-membered heterocycloalkylene; R7is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; X1is CR8or N; X2is CR9or N; X3is CR10or N; R8, R9, and R10are each independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, - C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, - S(O)2R19, or -S(O)2N(R18)2; Ring A is a carbocyclic ring or a heterocyclic ring; RCis -N(R11)(R12); R11is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; R12is -C(O)R13, -C(O)NR13R14, or -C(O)OR13; R13is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted monocyclic carbocyclyl, unsubstituted or substituted bicyclic carbocyclyl, - 132 -unsubstituted or substituted monocyclic heterocyclyl, or unsubstituted or substituted bicyclic heterocyclyl; R14is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; or R13and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted heterocyclyl; or R11and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted 5- or 6-membered monocyclic heterocyclyl; or R12is an unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2- C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted heterocyclyl, or unsubstituted or substituted carbocyclyl, wherein if R12is substituted then it is substituted with 1 or more groups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)-heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, - N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; RDis -C(=O)-W-R15; W is -NR16-, -C(R17)2- or -O-; R16is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; each R17is independently hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; R15is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6alkoxy, unsubstituted or substituted C3-C6cycloalkyl, or unsubstituted or substituted monocyclic heterocycloalkyl; or R15and R16are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocycloalkyl; - 133 -or RDis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; each REis independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, - C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, - S(O)2R19, or -S(O)2N(R18)2; wherein if REis attached to a N atom, then it is selected from the group consisting of unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, - C(O)OR18, -C(O)N(R18)2, -S(O)R19, -S(O)2R19, and -S(O)2N(R18)2; or two REattached to the same aliphatic carbon atom are taken together with the carbon atom to which they are attached to form -C(O)-; each R18is independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two R18on the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each R19is independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; p is 0 or 1; q is 0 or 1; and m is 0-4.

[0072] For any and all of the embodiments, substituents are selected from among a subset ofthe listed alternatives. For example, in some embodiments, Y is -N(R7)-. In other embodiments, - 134 -Y is -CH2-. In other embodiments, Y is -O-. In other embodiments, Y is -S-. In other embodiments, Y is -S(O)-. In other embodiments, Y is -S(O)2-.

[0073] In some embodiments, Ring A is a heterocyclic ring. In some embodiments, Ring A isa monocyclic heterocyclic ring. In some embodiments, Ring A is a bicyclic heterocyclic ring.

[0074] In some embodiments, Ring A is a heteroaryl. In some embodiments, Ring A is amonocyclic heteroaryl or a bicyclic heteroaryl. In some embodiments, Ring A is a monocyclic heteroaryl. In some embodiments, Ring A is a bicyclic heteroaryl.

[0075] In some embodiments, Ring A is selected from the group consisting of pyrrolyl,pyrazolyl, imidazolyl, triazolyl, tetrazolyl, furyl, oxazolyl, isoxazolyl, oxadiazolyl, furazanyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, benzofuranyl, benzoxazole, benzisoxazole, furopyridine, furopyrimidine, furopyridazine, furopyrazine, isoxazolopyridine, isoxazolopyridazine, isoxazolopyrimidine, isoxazolopyrazine, oxazolopyridine, oxazolopyridazine, oxazolopyrimidine, oxazolopyrazine, oxazolotriazine, indolyl, azaindolyl, diazaindolyl, indazolyl, azaindazolyl, diazaindazolyl, benzimidazolyl, imidazopyridine, benzotriazolyl, triazolopyridine, benzothiophenyl, thienopyridine, thienopyridazine, thienopyrimidine, thienopyrazine, benzothiazole, thiazolopyridine, thiazolopyridazine, thiazolopyrimidine, thiazolopyrazine, benzisothiazole, isothiazolopyridine, isothiazolopyridazine, isothiazolopyrimidine, isothiazolopyrazine, purinyl, indolizinyl, imidazolopyridinyl, pyrrolopyridazinyl, pyrrolopyrimidinyl, pyrrolopyrazinyl, pyrazolopyridinyl, pyrazolopyridazinyl, pyrazolopyrimidinyl, pyrazolopyrazinyl, imidazopyridinyl, imidazopyridazinyl, imidazopyrimidinyl, imidazopyrazinyl, triazolopyridinyl, triazolopyridazinyl, triazolopyrimidinyl, triazolopyrazinyl, imidazopyrimidinonyl, quinolizinyl, quinolizinonyl, quinolinyl, isoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, naphthyridinyl, pyridopyridazine, pyridopyrimidine, pyridopyrazine, pteridinyl, and naphthyridinonyl.

[0076] In some embodiments, Ring A is selected from the group consisting of pyrrolyl,pyrazolyl, imidazolyl, triazolyl, tetrazolyl, furyl, oxazolyl, isoxazolyl, oxadiazolyl, furazanyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrazinyl, triazinyl, benzofuranyl, benzoxazole, benzisoxazole, furopyridine, furopyrimidine, furopyridazine, furopyrazine, isoxazolopyridine, isoxazolopyridazine, isoxazolopyrimidine, isoxazolopyrazine, oxazolopyridine, oxazolopyridazine, oxazolopyrimidine, oxazolopyrazine, oxazolotriazine, indolyl, azaindolyl, diazaindolyl, indazolyl, azaindazolyl, diazaindazolyl, benzimidazolyl, imidazopyridine, benzotriazolyl, triazolopyridine, benzothiophenyl, thienopyridine, thienopyridazine, thienopyrimidine, thienopyrazine, benzothiazole, thiazolopyridine, thiazolopyridazine, thiazolopyrimidine, thiazolopyrazine, benzisothiazole, isothiazolopyridine, - 135 -isothiazolopyridazine, isothiazolopyrimidine, isothiazolopyrazine, purinyl, indolizinyl, imidazolopyridinyl, pyrrolopyridazinyl, pyrrolopyrimidinyl, pyrrolopyrazinyl, pyrazolopyridinyl, pyrazolopyridazinyl, pyrazolopyrimidinyl, pyrazolopyrazinyl, imidazopyridinyl, imidazopyridazinyl, imidazopyrimidinyl, imidazopyrazinyl, triazolopyridinyl, triazolopyridazinyl, triazolopyrimidinyl, triazolopyrazinyl, imidazopyrimidinonyl, quinolizinyl, quinolizinonyl, quinolinyl, isoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, naphthyridinyl, pyridopyridazine, pyridopyrimidine, pyridopyrazine, pteridinyl, and naphthyridinonyl.

[0077] In some embodiments, Ring A is selected from the group consisting of benzofuranyl,benzoxazole, benzisoxazole, furopyridine, furopyrimidine, furopyridazine, furopyrazine, isoxazolopyridine, isoxazolopyridazine, isoxazolopyrimidine, isoxazolopyrazine, oxazolopyridine, oxazolopyridazine, oxazolopyrimidine, oxazolopyrazine, oxazolotriazine, indolyl, azaindolyl, diazaindolyl, indazolyl, azaindazolyl, diazaindazolyl, benzimidazolyl, imidazopyridine, benzotriazolyl, triazolopyridine, benzothiophenyl, thienopyridine, thienopyridazine, thienopyrimidine, thienopyrazine, benzothiazole, thiazolopyridine, thiazolopyridazine, thiazolopyrimidine, thiazolopyrazine, benzisothiazole, isothiazolopyridine, isothiazolopyridazine, isothiazolopyrimidine, isothiazolopyrazine, purinyl, indolizinyl, imidazolopyridinyl, pyrrolopyridazinyl, pyrrolopyrimidinyl, pyrrolopyrazinyl, pyrazolopyridinyl, pyrazolopyridazinyl, pyrazolopyrimidinyl, pyrazolopyrazinyl, imidazopyridinyl, imidazopyridazinyl, imidazopyrimidinyl, imidazopyrazinyl, triazolopyridinyl, triazolopyridazinyl, triazolopyrimidinyl, triazolopyrazinyl, imidazopyrimidinonyl, quinolizinyl, quinolizinonyl, quinolinyl, isoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, naphthyridinyl, pyridopyridazine, pyridopyrimidine, pyridopyrazine, pteridinyl, and naphthyridinonyl.

[0078] In some embodiments, Ring A is selected from the group consisting of pyridinyl,imidazolyl, pyrimidinyl, pyrazolyl, triazolyl, pyrazinyl, tetrazolyl, furyl, thienyl, isoxazolyl, thiazolyl, oxazolyl, isothiazolyl, pyrrolyl, pyridazinyl, triazinyl, oxadiazolyl, thiadiazolyl, furazanyl, indolizinyl, indolyl, benzofuranyl, benzothiophenyl, indazolyl, benzimidazolyl, purinyl, quinolizinyl, quinolinyl, isoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 1,8-naphthyridinyl, pteridinyl, pyrazolopyrimidinyl, imidazopyridazinyl, triazolopyrimidinyl, naphthyridinonyl, and imidazopyrimidinonyl.

[0079] In some embodiments, Ring A is selected from the group consisting of pyridinyl,imidazolyl, pyrazolyl, triazolyl, pyrazinyl, tetrazolyl, furyl, thienyl, isoxazolyl, thiazolyl, oxazolyl, isothiazolyl, pyrrolyl, pyridazinyl, triazinyl, oxadiazolyl, thiadiazolyl, furazanyl, indolizinyl, indolyl, benzofuranyl, benzothiophenyl, indazolyl, benzimidazolyl, purinyl, - 136 -quinolizinyl, quinolinyl, isoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 1,8- naphthyridinyl, pteridinyl, pyrazolopyrimidinyl, imidazopyridazinyl, triazolopyrimidinyl, naphthyridinonyl, and imidazopyrimidinonyl.

[0080] In some embodiments, Ring A is selected from the group consisting of pyridinyl,pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, indolizinyl, indazolyl, benzimidazolyl, purinyl, quinolizinyl, quinolinyl, isoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, naphthyridinyl, pteridinyl, pyrazolopyrimidinyl, imidazopyridazinyl, triazolopyrimidinyl, naphthyridinonyl, and imidazopyrimidinonyl.

[0081] In some embodiments, Ring A is selected from the group consisting of pyridinyl,pyrazinyl, pyridazinyl, triazinyl, indolizinyl, indazolyl, benzimidazolyl, purinyl, quinolizinyl, quinolinyl, isoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, naphthyridinyl, pteridinyl, pyrazolopyrimidinyl, imidazopyridazinyl, triazolopyrimidinyl, naphthyridinonyl, and imidazopyrimidinonyl.

[0082] In some embodiments, Ring A is a monocyclic heterocyclic ring. In someembodiments, Ring A is a monocyclic heteroaryl. In some embodiments, Ring A is a 6- membered monocyclic heteroaryl or a 5-membered monocyclic heteroaryl.

[0083] In some embodiments, Ring A is a pyridine, pyrimidine, pyridazine, pyrazine ortriazine ring. In some embodiments, Ring A is a pyridine ring. In some embodiments, Ring A is a pyrimidine ring. In some embodiments, Ring A is a pyridazine ring. In some embodiments, Ring A is a pyrazine ring. In some embodiments, Ring A is a triazine ring.- 137 -.

[0085] In some embodiments, Ring A is a bicyclic heterocyclic ring.- 138 -.

[0088] In some embodiments,wherein: - 139 -each REis independently hydrogen, halogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C2-C6alkynyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted 3- to 6-membered heterocycloalkyl, -CN, -OH, -OR19, -C(O)OR18, - C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, or -S(O)2N(R18)2; wherein if REis attached to a N atom, then it is selected from the group consisting of C1-C6alkyl, C1-C6deuteroalkyl, C1- C6fluoroalkyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted 3- to 6-membered heterocycloalkyl, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -S(O)R19, - S(O)2R19, and -S(O)2N(R18)2; or two REattached to the same aliphatic carbon atom are taken together with the carbon atom to which they are attached to form -C(O)-.

[0089] In some embodiments,wherein: each REis independently hydrogen, halogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C2-C6alkynyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted 3- to 6-membered heterocycloalkyl, -CN, -OH, -OR19, -C(O)OR18, - C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, or -S(O)2N(R18)2; wherein if REis attached to a N atom, then it is selected from the group consisting of C1-C6alkyl, C1-C6deuteroalkyl, C1- C6fluoroalkyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted 3- to 6-membered heterocycloalkyl, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -S(O)R19, - S(O)2R19, and -S(O)2N(R18)2; or two REattached to the same aliphatic carbon atom are taken together with the carbon atom to which they are attached to form -C(O)-. - 140 -

[0090] In some embodiments,wherein: Z is N or CH; and each REis independently hydrogen, halogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C2-C6alkynyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted 3- to 6-membered heterocycloalkyl, -CN, -OH, -OR19, -C(O)OR18, - C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, or -S(O)2N(R18)2; wherein if REis attached to a N atom, then it is selected from the group consisting of C1-C6alkyl, C1-C6deuteroalkyl, C1- C6fluoroalkyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted 3- to 6-membered heterocycloalkyl, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -S(O)R19, - S(O)2R19, and -S(O)2N(R18)2.

[0091] In some embodiments,wherein: Z is N or CH; and REis hydrogen, halogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C2-C6alkynyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted 3- to 6- membered heterocycloalkyl, -CN, -OH, -OR19, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, - NR18C(O)R19, or -S(O)2N(R18)2; wherein if REis attached to a N atom, then it is selected from the group consisting of C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted 3- to 6- membered heterocycloalkyl, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -S(O)R19, -S(O)2R19, and -S(O)2N(R18)2. - 141 -

[0092] In some embodiments,N or CH; R13is cyclopropyl substituted with 1, 2, or 3 fluorines; and R15is hydrogen, C1-C4alkyl, C1-C4deuteroalkyl, C1-C4fluoroalkyl, or unsubstituted or substituted C3-C6cycloalkyl.

[0093] In some embodiments, Ring A is a carbocyclic ring. In some embodiments, Ring A is amonocyclic or bicyclic carbocyclic ring. In some embodiments, Ring A is a cycloalkyl ring or an aryl ring. In some embodiments, Ring A is a cycloalkyl ring. In some embodiments, Ring A is a monocyclic cycloalkyl ring. In some embodiments, Ring A is a C3-C6cycloalkyl ring. In some embodiments, Ring A is a bicyclic cycloalkyl ring. In some embodiments, Ring A is an aryl ring. In some embodiments, Ring A is phenyl. In some embodiments, Ring A is naphthyl.

[0094] In some embodiments, the compound is a compound of Formula (II):or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: Z is N, CH, or C-RE; and REis hydrogen, halogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C2-C6alkynyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted 3- to 6- membered heterocycloalkyl, -CN, -OH, -OR19, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, - NR18C(O)R19, or -S(O)2N(R18)2. - 142 -

[0095] In some embodiments, the present disclosure provides compounds of Formula (II-st-1):

[0096] In some embodiments, the present disclosure provides compounds of Formula (II-st-2):

[0097] In some embodiments, the present disclosure provides compounds of Formula (II-st-3):wherein R3is hydrogen, deuterium, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted monocyclic heterocycloalkyl, unsubstituted or substituted -(C1-C3alkylene)-carbocyclyl, unsubstituted or substituted - (C1-C3alkylene)-heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, - N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2. - 143 -

[0098] In some embodiments, the present disclosure provides compounds of Formula (II-st-4):Formula (II-st-4); wherein R3is hydrogen, deuterium, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted monocyclic heterocycloalkyl, unsubstituted or substituted -(C1-C3alkylene)-carbocyclyl, unsubstituted or substituted - (C1-C3alkylene)-heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, - N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2.

[0099] In some embodiments, the present disclosure provides compounds of Formula (II-st-5):Formula (II-st-5); wherein R3is hydrogen, deuterium, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or subst...

Claims

1. CLAIMS What is claimed is:

1. A compound of Formula (I): , or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: R1is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)-heterocyclyl, -C(O)R18, -(C1-C6alkylene)-C(O)R18, - C(O)OR18, -(C1-C6alkylene)-C(O)OR18, -C(O)N(R18)2, -(C1-C6alkylene)-C(O)N(R18)2, - S(O)R19, -(C1-C6alkylene)-S(O)R19, -S(O)2R19, -(C1-C6alkylene)-S(O)2R19, - S(O)2N(R18)2, or -(C1-C6alkylene)-S(O)2N(R18)2; or R1is -RA-L-RB; RAis unsubstituted or substituted carbocyclylene or unsubstituted or substituted heterocyclylene; L is absent, -(C(R5)2)n-, -C(O)-, -O-, -N(R6)-, -NR6-(C(R5)2)n-, -(C(R5)2)n-NR6-, -O- (C(R5)2)n-, -(C(R5)2)n-O-, -C(O)N(R6)-, -N(R6)C(O), -S(O)-, -S(O)2-, or -S(O)2N(R6)- ; each R5is independently hydrogen, deuterium, -OH, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; or two R5on the same carbon atom or on adjacent carbon atoms are taken together with the intervening carbon atom to which they are attached to form a C3-C6cycloalkyl, or a 3- to 6-membered heterocycloalkyl; R6is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; n is 1 or 2; - 931 -RBis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; wherein if RBis substituted then it is substituted by v Rxgroups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -ORb, - C(O)Ra, -C(O)ORa, -C(O)N(Ra)2, -N(Ra)2, -NRaC(O)Rb, -NRaC(O)ORa, -SRa, - S(O)Rb, -P(O)(Rb)2, -S(O)2Rb, -S(O)N(Ra)2, -S(O)2N(Ra)2, or -N=S(Rb)2=O; each Rais independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6deuteroalkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Raon the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each Rbis independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6deuteroalkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Rbon the same P atom are taken together with the P atom to which they are attached to form a substituted or unsubstituted P-containing heterocyclyl; v is an integer selected from 1, 2, 3, and 4; R2is hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, - C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; R3is hydrogen, deuterium, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted C3-C6- 932 -cycloalkyl, unsubstituted or substituted monocyclic heterocycloalkyl, unsubstituted or substituted -(C1-C3alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C3alkylene)- heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, - NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; R4is hydrogen, deuterium, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted monocyclic heterocycloalkyl, unsubstituted or substituted -(C1-C3alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C3alkylene)- heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, - NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; or R3and R4are taken together with the carbon atom to which they are attached to form - C(O)-, an unsubstituted or substituted C3-C6cycloalkylene, or an unsubstituted or substituted 3- to 6-membered heterocycloalkylene; Y is -N(R7)-, -O-, -S-, -S(O)-, or -S(O)2-, wherein: R7is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; X1is CR8or N; X2is CR9or N; X3is CR10or N; R8, R9, and R10are each independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, - N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; Ring A is a carbocyclic ring or a heterocyclic ring; RCis -N(R11)(R12); R11is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; R12is -C(O)R13, -C(O)NR13R14, or -C(O)OR13; R13is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted monocyclic carbocyclyl, unsubstituted or substituted bicyclic carbocyclyl, unsubstituted or- 933 -substituted monocyclic heterocyclyl, or unsubstituted or substituted bicyclic heterocyclyl; R14is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; or R13and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted heterocyclyl; or R11and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted 5- or 6-membered monocyclic heterocyclyl; or R12is an unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1- C6heteroalkyl, unsubstituted or substituted heterocyclyl, or unsubstituted or substituted carbocyclyl, wherein if R12is substituted then it is substituted with 1 or more groups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)-heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, - C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; RDis -C(=O)-W-R15; W is -NR16-, -C(R17)2- or -O-; R16is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; each R17is independently hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; R15is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1- C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6alkoxy, unsubstituted or substituted C3-C6cycloalkyl, or unsubstituted or substituted monocyclic heterocycloalkyl; or R15and R16are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocycloalkyl; or RDis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; - 934 -each REis independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, - C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or - S(O)2N(R18)2; wherein if REis attached to a N atom, then it is selected from the group consisting of unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -S(O)R19, - S(O)2R19, and -S(O)2N(R18)2; or two REattached to the same aliphatic carbon atom are taken together with the carbon atom to which they are attached to form -C(O)-; each R18is independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two R18on the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each R19is independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; p is 0 or 1; q is 0 or 1; and m is 0-4; - 935 -with the proviso that the compound of Formula (I) is not.

2. The compound of claim 1, or a pharmaceutically acceptable salt, N-oxide, tautomer, orsolvate thereof, wherein Y is -N(R7)- or -O-.

3. The compound of claim 1 or claim 2, or a pharmaceutically acceptable salt, N-oxide,tautomer, or solvate thereof, wherein Y is -N(R7)-.

4. A compound of Formula (I-1):or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: R1is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1- C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)-heterocyclyl, - C(O)R18, -(C1-C6alkylene)-C(O)R18, -C(O)OR18, -(C1-C6alkylene)-C(O)OR18, - C(O)N(R18)2, -(C1-C6alkylene)-C(O)N(R18)2, -S(O)R19, -(C1-C6alkylene)-S(O)R19, - S(O)2R19, -(C1-C6alkylene)-S(O)2R19, -S(O)2N(R18)2, or -(C1-C6alkylene)- S(O)2N(R18)2; or R1is -RA-L-RB; - 936 -RAis unsubstituted or substituted carbocyclylene or unsubstituted or substituted heterocyclylene; L is absent, -(C(R5)2)n-, -C(O)-, -O-, -N(R6)-, -NR6-(C(R5)2)n-, -(C(R5)2)n-NR6-, -O- (C(R5)2)n-, -(C(R5)2)n-O-, -C(O)N(R6)-, -N(R6)C(O), -S(O)-, -S(O)2-, or - S(O)2N(R6)-; each R5is independently hydrogen, deuterium, -OH, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; or two R5on the same carbon atom or on adjacent carbon atoms are taken together with the intervening carbon atom to which they are attached to form a C3-C6cycloalkyl, or a 3- to 6-membered heterocycloalkyl; R6is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; n is 1 or 2; RBis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; wherein if RBis substituted then it is substituted by v Rxgroups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1- C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -ORb, -C(O)Ra, -C(O)ORa, -C(O)N(Ra)2, -N(Ra)2, - NRaC(O)Rb, -NRaC(O)ORa, -SRa, -S(O)Rb, -P(O)(Rb)2, -S(O)2Rb, -S(O)N(Ra)2, - S(O)2N(Ra)2, or -N=S(Rb)2=O; each Rais independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6deuteroalkyl, substituted or unsubstituted C1- C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8- membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Raon the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each Rbis independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6deuteroalkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered - 937 -heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Rbon the same P atom are taken together with the P atom to which they are attached to form a substituted or unsubstituted P-containing heterocyclyl; v is an integer selected from 1, 2, 3, and 4; R2is hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, - C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or - S(O)2N(R18)2; R3is hydrogen, deuterium, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted monocyclic heterocycloalkyl, unsubstituted or substituted -(C1-C3alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C3alkylene)-heterocyclyl, -CN, -OH, -OR19, - C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, - S(O)2R19, or -S(O)2N(R18)2; R4is hydrogen, deuterium, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted monocyclic heterocycloalkyl, unsubstituted or substituted -(C1-C3alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C3alkylene)-heterocyclyl, -CN, -OH, -OR19, - C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, - S(O)2R19, or -S(O)2N(R18)2; or R3and R4are taken together with the carbon atom to which they are attached to form - C(O)-, an unsubstituted or substituted C3-C6cycloalkylene, or an unsubstituted or substituted 3- to 6-membered heterocycloalkylene; R7is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; X1is CR8or N; X2is CR9or N; - 938 -X3is CR10or N; R8, R9, and R10are each independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, - C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, - S(O)2R19, or -S(O)2N(R18)2; Ring A is a carbocyclic ring or a heterocyclic ring; RCis -N(R11)(R12); R11is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; R12is -C(O)R13, -C(O)NR13R14, or -C(O)OR13; R13is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted monocyclic carbocyclyl, unsubstituted or substituted bicyclic carbocyclyl, unsubstituted or substituted monocyclic heterocyclyl, or unsubstituted or substituted bicyclic heterocyclyl; R14is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; or R13and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted heterocyclyl; or R11and R14are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted 5- or 6-membered monocyclic heterocyclyl; or R12is an unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C2- C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted heterocyclyl, or unsubstituted or substituted carbocyclyl, wherein if R12is substituted then it is substituted with 1 or more groups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6- 939 -alkylene)-heterocyclyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, - N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2; RDis -C(=O)-W-R15; W is -NR16-, -C(R17)2- or -O-; R16is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; each R17is independently hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; R15is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6alkoxy, unsubstituted or substituted C3-C6cycloalkyl, or unsubstituted or substituted monocyclic heterocycloalkyl; or R15and R16are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocycloalkyl; or RDis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; each REis independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, - C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, - S(O)2R19, or -S(O)2N(R18)2; wherein if REis attached to a N atom, then it is selected from the group consisting of unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, -C(O)R18, - C(O)OR18, -C(O)N(R18)2, -S(O)R19, -S(O)2R19, and -S(O)2N(R18)2; or two REattached to the same aliphatic carbon atom are taken together with the carbon atom to which they are attached to form -C(O)-; each R18is independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted - 940 -monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two R18on the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each R19is independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; p is 0 or 1; q is 0 or 1; and m is 0-4.

5. The compound of any one of claims 1-4, or a pharmaceutically acceptable salt, N-oxide,tautomer, or solvate thereof, wherein Ring A is a monocyclic heterocyclic ring.

6. The compound of claim 5, or a pharmaceutically acceptable salt, N-oxide, tautomer, orsolvate thereof, wherein:.

7. The compound of any one of claims 1-4, or a pharmaceutically acceptable salt, N-oxide,tautomer, or solvate thereof, wherein Ring A is a bicyclic heterocyclic ring.

8. The compound of claim 7, or a pharmaceutically acceptable salt, N-oxide, tautomer, orsolvate thereof, wherein:, - 941 -each REis independently hydrogen, halogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C2-C6alkynyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted 3- to 6-membered heterocycloalkyl, -CN, -OH, -OR19, - C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, or -S(O)2N(R18)2; wherein if REis attached to a N atom, then it is selected from the group consisting of C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted 3- to 6-membered heterocycloalkyl, -C(O)R18, - C(O)OR18, -C(O)N(R18)2, -S(O)R19, -S(O)2R19, and -S(O)2N(R18)2; or two REattached to the same aliphatic carbon atom are taken together with the carbon atom to which they are attached to form -C(O)-.

9. The compound of any one of claims 1-4, or a pharmaceutically acceptable salt, N-oxide,tautomer, or solvate thereof, wherein: - 942 -wherein: Z is N or CH; and each REis independently hydrogen, halogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C2-C6alkynyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted 3- to 6-membered heterocycloalkyl, -CN, -OH, -OR19, - C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, or -S(O)2N(R18)2; wherein if REis attached to a N atom, then it is selected from the group consisting of C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted 3- to 6-membered heterocycloalkyl, -C(O)R18, - C(O)OR18, -C(O)N(R18)2, -S(O)R19, -S(O)2R19, and -S(O)2N(R18)2.

10. The compound of any one of claims 1-4, or a pharmaceutically acceptable salt, N-oxide,tautomer, or solvate thereof, wherein:wherein: Z is N or CH; and REis hydrogen, halogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C2-C6alkynyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted 3- to 6-membered heterocycloalkyl, -CN, -OH, -OR19, -C(O)OR18, -C(O)N(R18)2, - N(R18)2, -NR18C(O)R19, or -S(O)2N(R18)2; wherein if REis attached to a N atom, then it is selected from the group consisting of C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted 3- to 6-membered heterocycloalkyl, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -S(O)R19, -S(O)2R19, and -S(O)2N(R18)2. - 943 -11. The compound of any one of claims 1-4, wherein the compound is a compound ofFormula (IIa-1):Formula (IIa-1), or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: Z is N, CH, or C-RE; REis hydrogen, halogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C2-C6alkynyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted 3- to 6-membered heterocycloalkyl, -CN, -OH, -OR19, -C(O)OR18, -C(O)N(R18)2, - N(R18)2, -NR18C(O)R19, or -S(O)2N(R18)2.

12. The compound of any one of claims 1-11, or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: W is -NH-, -N(CH3)-, -O-, or -CH2-; and R15is C1-C4alkyl or C1-C4deuteroalkyl.

13. The compound of any one of claims 1-12, or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: W is -NH- or -CH2-; and R15is -CH3or -CD3.

14. The compound of any one of claims 1-4, wherein the compound is a compound ofFormula (IIIa-1), or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof: - 944 -Formula (IIIa-1).

15. The compound of claim 1, wherein the compound is a compound of Formula (IVa-1), ora pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof:Formula (IVa-1).

16. The compound of any one of claims 1-15, or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: each REis independently hydrogen, halogen, C1-C6alkyl, C2-C6alkynyl, C3-C6cycloalkyl, 3- to 6-membered heterocycloalkyl, -CN, -N(R18)2; wherein if REis attached to a N atom, then it is selected from the group consisting of C1-C6alkyl, C1- C6deuteroalkyl, C3-C6cycloalkyl, and 3- to 6-membered; or two REattached to the same aliphatic carbon atom are taken together with the carbon atom to which they are attached to form -C(O)-.

17. The compound of claim 16, or a pharmaceutically acceptable salt, N-oxide, tautomer, orsolvate thereof, wherein: each REis independently hydrogen, fluoro, chloro, C1-C4alkyl, C2-C4alkynyl, or -CN; wherein if REis attached to a N atom, then it is selected from the group consisting of C1-C4alkyl and C1-C4deuteroalkyl; or two REattached to the same aliphatic carbon atom are taken together with the carbon atom to which they are attached to form -C(O)-. - 945 -18. The compound of any one of claims 1-17, wherein:p is 1.

19. The compound of claim 18, or a pharmaceutically acceptable salt, N-oxide, tautomer, orsolvate thereof, wherein R11is hydrogen or C1-C4alkyl.

20. The compound of claim 18 or claim 19, or a pharmaceutically acceptable salt, N-oxide,tautomer, or solvate thereof, wherein R12is -C(=O)R13, -C(=O)NR13R14, or -C(=O)OR13.

21. The compound of any one of claims 18-20, or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein R12is -C(=O)R13.

22. The compound of any one of claims 18-21, or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein R13is unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C3-C6 monocyclic cycloalkyl, or unsubstituted orsubstituted 4- to 6-membered monocyclic heterocycloalkyl.

23. The compound of any one of claims 18-22, or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein R13is unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C3-C4 cycloalkyl, or unsubstituted or substituted 4-membered heterocycloalkyl; wherein the substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, or substituted heterocycloalkyl is substituted with 1 or more groups independently selected from the group consisting of deuterium, halogen, -CN, - NH2, -OH, -NH(CH3), -N(CH3)2, -CH3, -CH2CH3, -CHF2, -CF3, -OCH3, -OCHF2, and - OCF3.

24. The compound of any one of claims 18-23, or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein R13is unsubstituted or substituted C3-C4cycloalkyl.

25. The compound of claim 18 or claim 19, or a pharmaceutically acceptable salt, N-oxide,tautomer, or solvate thereof, wherein R12is an unsubstituted or substituted heterocyclyl or unsubstituted or substituted carbocyclyl, wherein if R12is substituted then it is substituted with 1 or more groups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -OR19, - C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, - S(O)2R19, or -S(O)2N(R18)2.

26. The compound of claim 25, or a pharmaceutically acceptable salt, N-oxide, tautomer, orsolvate thereof, wherein R12is an unsubstituted or substituted pyridinyl or unsubstituted - 946 -or substituted pyrimidinyl, wherein if R12is substituted then it is substituted with 1 or more groups independently selected from halogen, C1-C6alkyl, C1-C6deuteroalkyl, C1- C6fluoroalkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6heteroalkyl, unsubstituted or substituted C3-C6 monocyclic cycloalkyl, or unsubstituted or substituted 4- to 6-membered monocyclic heterocycloalkyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, - C(O)N(R18)2, -N(R18)2, -NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2.

27. The compound of claim 25 or claim 26, or a pharmaceutically acceptable salt, N-oxide,tautomer, or solvate thereof, wherein R12is an unsubstituted or substituted pyrimidinyl, wherein if R12is substituted then it is substituted with 1 to 3 groups independently selected from halogen, C1-C6alkyl, and -CN.

28. The compound of any one of claims 1-27, wherein:p is 0.

29. The compound of any one of claims 1-4, or a pharmaceutically acceptable salt, N-oxide,tautomer, or solvate thereof, wherein:- 947 -- 948 -- 949 -- 950 -30. The compound of any one of claims 1-29, or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: X1is CR8, X2is CR9, and X3is CR10; or X1is CR8, X2is CR9, and X3is N; and - 951 -R8, R9, and R10are each independently hydrogen, halogen, C1-C6alkyl, C1-C6fluoroalkyl, -CN, -OH, -OR19, or -N(R18)2.

31. The compound of any one of claims 1-30, or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: X1is CH, X2is CH, and X3is CH; or X1is CH, X2is CH, and X3is N.

32. The compound of any one of claims 1-31, or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: R7is hydrogen or C1-C6alkyl; R3is hydrogen, deuterium, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted C3-C6cycloalkyl, or unsubstituted or substituted monocyclic heterocycloalkyl, unsubstituted or substituted -(C1-C3alkylene)-carbocyclyl, or unsubstituted or substituted -(C1-C3alkylene)-heterocyclyl; and R4is hydrogen, deuterium, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted C3-C6cycloalkyl, or unsubstituted or substituted monocyclic heterocycloalkyl, unsubstituted or substituted -(C1-C3alkylene)-carbocyclyl, or unsubstituted or substituted -(C1-C3alkylene)-heterocyclyl; or R3and R4are taken together with the carbon atom to which they are attached to form an unsubstituted or substituted C3-C6cycloalkylene or an unsubstituted or substituted 3- to 6-membered heterocycloalkylene.

33. The compound of any one of claims 1-32, or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: R7is C1-C6alkyl; R3is hydrogen, deuterium, halogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C1-C6heteroalkyl, or C3-C6cycloalkyl; and R4is hydrogen, deuterium, halogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C1-C6heteroalkyl, or C3-C6cycloalkyl; or R3and R4are taken together with the carbon atom to which they are attached to form an unsubstituted or substituted C3-C6cycloalkylene or an unsubstituted or substituted 3- to 6-membered heterocycloalkylene. - 952 -34. The compound of any one of claims 1-33, or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: R7is C1-C6alkyl; R3is hydrogen, deuterium, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl, sec-butyl, n-pentyl, 2- methylbutan-2-yl, 2,2-dimethylpropyl, 3-methylbutyl, pentan-2-yl, pentan-3-yl, 3- methylbutan-2-yl, 2-methylbutyl, -CH2OCH3,, ; and R4is hydrogen, deuterium, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl, sec-butyl, n-pentyl, 2- methylbutan-2-yl, 2,2-dimethylpropyl, 3-methylbutyl, pentan-2-yl, pentan-3-yl, 3- methylbutan-2-yl, 2-methylbutyl, -CH2OCH3,, .

35. The compound of any one of claims 1-34, or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: R7is -CH3; R3is hydrogen, -CH3, -CH2CH3, cyclopentyl, cyclopropyl, or 3-methylbut-2-yl; and R4is hydrogen, deuterium, -CH3, -CH2CH3, or cyclopropyl.

36. The compound of any one of claims 1-34, or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: R3is hydrogen or deuterium; and R4is hydrogen or deuterium.

37. The compound of any one of claims 1-36, or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein R2is hydrogen, halogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, unsubstituted or substituted C3-C6monocyclic cycloalkyl, or unsubstituted or substituted 4- to 6-membered monocyclicheterocycloalkyl, -CN, -OH, -OR19, -C(O)R18, -C(O)OR18, -C(O)N(R18)2, -N(R18)2, - NR18C(O)R19, -SR18, -S(O)R19, -S(O)2R19, or -S(O)2N(R18)2.

38. The compound of any one of claims 1-37, or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein R2is hydrogen, halogen, C1-C6alkyl, -CN, - OH, -OR19, or -N(R18)2.

39. The compound of any one of claims 1-38, or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein R1is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or - 953 -substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted -(C1-C6alkylene)-carbocyclyl, unsubstituted or substituted -(C1-C6alkylene)- heterocyclyl, -C(O)R18, -(C1-C6alkylene)-C(O)R18, -C(O)OR18, -(C1-C6alkylene)- C(O)OR18, -C(O)N(R18)2, -(C1-C6alkylene)-C(O)N(R18)2, -S(O)R19, -(C1-C6alkylene)- S(O)R19, -S(O)2R19, -(C1-C6alkylene)-S(O)2R19, -S(O)2N(R18)2, or -(C1-C6alkylene)- S(O)2N(R18)2.

40. The compound of any one of claims 1-38, or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein R1is -RA-L-RB.

41. The compound of claim 40, or a pharmaceutically acceptable salt, N-oxide, tautomer, orsolvate thereof, wherein: RAis unsubstituted or substituted cycloalkylene or unsubstituted or substituted heterocycloalkylene; L is absent, -(C(R5)2)n-, -C(O)-, -O-, -N(R6)-, -NR6-(C(R5)2)n-, -(C(R5)2)n-NR6-, -O- (C(R5)2)n-, -(C(R5)2)n-O-, -C(O)N(R6)-, or -N(R6)C(O)-; each R5is independently hydrogen, deuterium, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; or two R5on the same carbon atom or on adjacent carbon atoms are taken together with the intervening carbon atom to which they are attached to form a C3-C6cycloalkyl, or a 3- to 6-membered heterocycloalkyl; R6is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6fluoroalkyl; n is 1 or 2; and RBis unsubstituted or substituted carbocyclyl or unsubstituted or substituted heterocyclyl; wherein if RBis substituted then it is substituted by v Rxgroups independently selected from halogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6heteroalkyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted 3- to 6-membered heterocycloalkyl, -CN, -OH, -ORb, -C(O)Ra, -C(O)ORa, -C(O)N(Ra)2, -N(Ra)2, - NRaC(O)Rb, -NRaC(O)ORa, -SRa, -S(O)Rb, -S(O)2Rb, -S(O)2N(Ra)2, or - N=S(Rb)2=O; and v is an integer selected from 1, 2, and 3.

42. The compound of claim 40 or claim 41, or a pharmaceutically acceptable salt, N-oxide,tautomer, or solvate thereof, wherein: RAis C3-C6monocyclic cycloalkylene, bicyclic cycloalkylene, 4- to 6-membered monocyclic heterocycloalkylene, or bicyclic heterocycloalkylene; L is absent, -(C(R5)2)n-, -C(O)-, -O-, -N(R6)-, -NR6-(C(R5)2)n-, or -C(O)N(R6)-; each R5is independently hydrogen, deuterium, or C1-C6alkyl; - 954 -or two R5on the same carbon atom or on adjacent carbon atoms are taken together with the intervening carbon atom to which they are attached to form a cyclopropyl or cyclobutyl; R6is hydrogen or C1-C6alkyl; and n is 1 or 2.

43. The compound of any one of claims 40-42, or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: RAis C3-C6monocyclic cycloalkylene or 4- to 6-membered monocyclic heterocycloalkylene; L is absent, or -(C(R5)2)n-; each R5is independently hydrogen, deuterium, or C1-C6alkyl; and n is 1.

44. The compound of any one of claims 40-43, or a pharmaceutically acceptable salt, N-,, , , , - 955 -45. The compound of any one of claims 40-44, or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein RBis unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted 4- to 6-membered heterocyloalkyl, unsubstituted or substituted phenyl, unsubstituted or substituted 5-membered heteroaryl, or unsubstituted or substituted 6-membered heteroaryl; wherein if RBis substituted then it is substituted by v Rxgroups independently selected from halogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6heteroalkyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted 3- to 6- membered heterocycloalkyl, -CN, -OH, -ORb, -C(O)Ra, -C(O)ORa, -C(O)N(Ra)2, - N(Ra)2, -NRaC(O)Rb, -SRa, -S(O)Rb, -S(O)2Rb, or -S(O)2N(Ra)2; and v is an integer selected from 1, 2, and 3.

46. The compound of any one of claims 40-45, or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein RBunsubstituted or substituted phenyl or unsubstituted or substituted 6-membered heteroaryl; wherein if RBis substituted then it is substituted by v Rxgroups independently selected from halogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, 3- to 6-membered heterocycloalkyl, - CN, -OH, -ORb, -C(O)ORa, -C(O)N(Ra)2, -N(Ra)2, -NRaC(O)Rb, -S(O)2Rb, or - S(O)2N(Ra)2; and v is an integer selected from 1, 2, and 3.

47. The compound of any one of claims 40-46, or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein RBunsubstituted or substituted phenyl or unsubstituted or substituted pyridinyl; wherein if RBis substituted then it is substituted by v Rxgroups independently selected from halogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, 3- to 6-membered heterocycloalkyl, -CN, -OH, - ORb, -C(O)ORa, -C(O)N(Ra)2, -N(Ra)2, -NRaC(O)Rb, -S(O)2Rb, or -S(O)2N(Ra)2; and v is an integer selected from 1, 2, and 3. - 956 -48. The compound of any one of claims 40-47, or a pharmaceutically acceptable salt, N-- 957 -. The compound of any one of claims 40-48, or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: each Rais independently hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C7cycloalkyl, monocyclic 3- to 8-membered heterocycloalkyl, phenyl, or monocyclic heteroaryl; or two Raon the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each Rbis independently C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C7cycloalkyl, monocyclic 3- to 8-membered heterocycloalkyl, phenyl, or monocyclic heteroaryl. - 958 -50. The compound of any one of claims 40-47, or a pharmaceutically acceptable salt, N-oxid- 960 -, - 961 -- 962 -, - 963 -- 964 -- 965 -- 966 -- 967 -- 968 -- 969 -- 970 -- 971 -- 972 -52. The compound of any one of claims 1-10, or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: - 973 -q is 1.

53. The compound of claim 52, or a pharmaceutically acceptable salt, N-oxide, tautomer, orsolvate thereof, wherein: RDis -C(=O)-W-R15; W is -NR16-, -C(R17)2- or -O-; R16is hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; each R17is independently hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, or monocyclic heterocycloalkyl; R15is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6alkoxy, unsubstituted or substituted C3-C6cycloalkyl, or unsubstituted or substituted monocyclic heterocycloalkyl; or R15and R16are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocycloalkyl.

54. The compound of claim 52 or claim 53, or a pharmaceutically acceptable salt, N-oxide,tautomer, or solvate thereof, wherein:

55. The compound of any one of claims 1-5, wherein the compound is a compound ofFormula (A1):Formula (A1), - 974 -or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: R1is -RA-L-RB;L is -CH2-, -CHD-, -CD2-, or -C(O)-; RBis unsubstituted or substituted 2-pyridyl, phenyl, or pyrazol-3-yl ring; wherein if RBis substituted then it is substituted by v Rxgroups independently selected from halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1- C6deuteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C2-C6alkenyl, unsubstituted or substituted C2-C6alkynyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, -CN, -OH, -ORb, -C(O)Ra, -C(O)ORa, -C(O)N(Ra)2, -N(Ra)2, -NRaC(O)Rb, -SRa, -S(O)Rb, -P(O)(Rb)2, - S(O)2Rb, -S(O)N(Ra)2, or -S(O)2N(Ra)2; each Rais independently hydrogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6deuteroalkyl, substituted or unsubstituted C1- C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8- membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two Raon the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each Rbis independently substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6deuteroalkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C7cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; v is an integer selected from 1, 2, 3, and 4; R2is hydrogen, halogen, C1-C3alkyl, or -CN; R3is hydrogen, deuterium, C1-C4alkyl, C1-C4deuteroalkyl, C1-C4heteroalkyl, or C3-C4cycloalkyl; R4is hydrogen, deuterium, C1-C4alkyl, C1-C4deuteroalkyl, C1-C4heteroalkyl, or C3-C4cycloalkyl; - 975 -R7is hydrogen, cyclopropyl, or -CH3; X1is CR8or N; X2is CR9or N; X3is CR10or N; R8, R9, and R10are each independently hydrogen, halogen, C1-C3alkyl, C1-C3fluoroalkyl, or -CN; R13is cyclopropyl substituted with 1, 2, or 3 fluorines; R15is hydrogen, C1-C4alkyl, C1-C4deuteroalkyl, C1-C4fluoroalkyl, or unsubstituted or substituted C3-C6cycloalkyl; and Z is N or CH.

56. The compound claim 55, or a pharmaceutically acceptable salt, N-oxide, tautomer, orsolvate thereof, wherein RBis unsubstituted or substituted 2-pyridyl; wherein if RBis substituted then it is substituted by v Rxgroups.

57. The compound of claim 55, or a pharmaceutically acceptable salt, N-oxide, tautomer, orsolvate thereof, wherein RBis unsubstituted or substituted phenyl; wherein if RBis substituted then it is substituted by v Rxgroups.

58. The compound of claim 55, wherein the compound is a compound of Formula (A2),Formula (A4), Formula (A6), Formula (A8), Formula (A10), or Formula (A12):Formula (A2), Formula (A4), - 976 -Formula (A10), Formula (A12), or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: each Rxis independently selected from halogen, unsubstituted or substituted C1-C4alkyl, unsubstituted or substituted C1-C4deuteroalkyl, unsubstituted or substituted C1-C4fluoroalkyl, unsubstituted or substituted C1-C4heteroalkyl, unsubstituted or substituted C3-C5 cycloalkyl, unsubstituted or substituted 4- to 5-membered heterocyclyl, -CN, -OH, -ORb, -C(O)Ra, -C(O)ORa, -C(O)N(Ra)2, -N(Ra)2, - NRaC(O)Rb, -SRa, -S(O)Rb, -P(O)(Rb)2, -S(O)2Rb, -S(O)N(Ra)2, or -S(O)2N(Ra)2; and - 977 -w is an integer selected from 0, 1, and 2.

59. The compound of any one of claims 55-58, or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: R15is C1-C4alkyl, C1-C4deuteroalkyl, C1-C4fluoroalkyl, or unsubstituted or substituted C3-C6cycloalkyl.

60. The compound of any one of claims 55-59, or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: R15is C1-C4alkyl or C1-C4deuteroalkyl.

61. The compound of any one of claims 55-60, or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: R15is -CH3or -CD3.

62. The compound of any one of claims 1-4 or 7, wherein the compound is a compound ofFormula (B1):Formula (B1), or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: REis independently hydrogen, -F, -Cl, -CH3, difluoromethyl, -CD3, ethynyl, propynyl, cyano, -C(O)NHCH3, cyclopropyl, or cyclobutyl.

63. The compound of any one of claims 55-62, or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: Z is N.

64. The compound of any one of claims 55-62, or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: - 978 -Z is CH.

65. The compound of any one of claims 55-64, or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: R2is hydrogen or -CH3; R3is hydrogen, deuterium, -CH3, -CH2CH3, or cyclopropyl; R4is hydrogen, deuterium, -CH3, -CH2CH3, or cyclopropyl; and R7is hydrogen or -CH3.

66. The compound of any one of claims 55-64, or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: R2is hydrogen; R3is hydrogen, deuterium, -CH3, or -CH2CH3; R4is hydrogen, deuterium, -CH3, or -CH2CH3; and R7is -CH3.

67. The compound of any one of claims 55-66, or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: X1is CR8; X2is CR9; X3is CR10; and R8, R9, and R10are each independently hydrogen, halogen, C1-C3alkyl, C1-C3fluoroalkyl, or -CN.

68. The compound of any one of claims 55-67, or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: X1is CH; X2is CH; and X3is CH.

69. The compound of any one of claims 55-68, or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: w is 0.

70. The compound of any one of claims 55-69, or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: w is 0. R13is cyclopropyl.

71. The compound of any one of claims 55-70, or a pharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, wherein: - 979 -each Rais independently hydrogen, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C7cycloalkyl, monocyclic 3- to 8-membered heterocycloalkyl, phenyl, or monocyclic heteroaryl; or two Raon the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocyclyl; each Rbis independently C1-C6alkyl, C1-C6deuteroalkyl, C1-C6fluoroalkyl, C3-C7cycloalkyl, monocyclic 3- to 8-membered heterocycloalkyl, phenyl, or monocyclic heteroaryl.

72. A compound selected from the compounds in Table 1, or a pharmaceutically acceptablesalt, N-oxide, tautomer, or solvate thereof.

73. A pharmaceutical composition comprising the compound of any one of claims 1-72, or apharmaceutically acceptable salt, N-oxide, tautomer, or solvate thereof, and a pharmaceutically acceptable excipient.

74. A method of inhibiting an activity of the V617F variant of JAK2 kinase, comprisingcontacting the kinase with a compound of any one of claims 1-72, or a pharmaceutically acceptable salt or solvate thereof.

75. A method of treating a JAK2-mediated disorder in a patient in need thereof, comprisingadministering to a patient a compound of any one of claims 1-72, or a pharmaceutically acceptable salt or solvate thereof.

76. A method of treating a JAK2-V617F-mediated disorder in a patient in need thereof,comprising administering to a patient a compound of any one of claims 1-72, or a pharmaceutically acceptable salt or solvate thereof.

77. A method of treating cancer in a patient in need thereof, the method comprisingadministering to the patient a therapeutically effective amount of a compound of any one of claims 1-72, or a pharmaceutically acceptable salt or solvate thereof.

78. The method of claim 77, wherein the cancer is selected from bladder cancer, breastcancer, cervical cancer, colorectal cancer, cancer of the small intestine, colon cancer, rectal cancer, cancer of the anus, endometrial cancer, gastric cancer, head and neck cancer, kidney cancer, liver cancer, lung cancer, ovarian cancer, prostate cancer, testicular cancer, uterine cancer, vulvar cancer, esophageal cancer, gall bladder cancer, pancreatic cancer, stomach cancer, thyroid cancer, parathyroid cancer, neuroendocrine cancer, skin cancer, and brain cancer.

79. The method of claim 77, wherein the cancer is a hematological cancer.

80. The method of claim 77, wherein the cancer is selected from leukemia, lymphoma,multiple myeloma, chronic lymphocytic lymphoma, adult T cell leukemia, acute myeloid - 980 -leukemia, B-cell lymphoma, cutaneous T-cell lymphoma, acute myelogenous leukemia, Hodgkin's or non-Hodgkin's lymphoma, a myeloproliferative neoplasm), myelodysplastic syndrome, chronic eosinophilic leukemia, Waldenstrom's Macroglubulinemia, hairy cell lymphoma, chronic myelogenic lymphoma, acute lymphoblastic lymphoma, AIDS-related lymphoma, and Burkitt's lymphoma.

81. A method of treating a myeloproliferative disorder in a patient in need thereof, themethod comprising administering to the patient a therapeutically effective amount of a compound of any one of claims 1-72, or a pharmaceutically acceptable salt or solvate thereof.

82. The method of claim 81, wherein the myeloproliferative disorder is selected frompolycythemia vera, essential thrombocythemia, myelofibrosis with myeloid metaplasia, primary myelofibrosis, post-essential thrombocythemia myelofibrosis, post polycythemia vera myelofibrosis, chronic myelogenous leukemia, chronic myelomonocytic leukemia, hypereosinophilic syndrome, and systemic mast cell disease.

83. A method of treating myelodysplastic syndrome in a patient in need thereof, the methodcomprising administering to the patient a therapeutically effective amount of a compound of any one of claims 1-72, or a pharmaceutically acceptable salt or solvate thereof.

84. A method of treating skeletal and chondrocyte disorders in a patient in need thereof, themethod comprising administering to the patient a therapeutically effective amount of a compound of any one of claims 1-72, or a pharmaceutically acceptable salt or solvate thereof.

85. The method of claim 84, wherein the skeletal and chondrocyte disorder isachrondroplasia, hypochondroplasia, dwarfism, thanatophoric dysplasia, Apert syndrome, Crouzon syndrome, Jackson-Weiss syndrome, Beare-Stevenson cutis gyrate syndrome, Pfeiffer syndrome, or craniosynostosis syndrome.

86. A method of treating fibrotic diseases in a patient in need thereof, the method comprisingadministering to the patient a therapeutically effective amount of a compound of any one of claims 1-72, or a pharmaceutically acceptable salt or solvate thereof.

87. The method of claim 86, wherein the fibrotic disease is liver cirrhosis,glomerulonephritis, pulmonary fibrosis, systemic fibrosis, rheumatoid arthritis, or wound healing.

88. A method of treating a hypophosphatemia disorder in a patient in need thereof, themethod comprising administering to the patient a therapeutically effective amount of a - 981 -compound of any one of claims 1-82, or a pharmaceutically acceptable salt or solvate thereof.

89. The method of claim 88, wherein the hypophosphatemia disorder is X-linkedhypophosphatemic rickets, autosomal recessive hypophosphatemic rickets, and autosomal dominant hypophosphatemic rickets, or tumor-induced osteromalacia.

90. The method of any one of claims 74-89, further comprising administration of at least onecompound selected from ruxolitinib, pacritinib, momelotinib, and fedratinib.

91. The method of any one of claims 74-89, wherein the patient undergoing treatment haspreviously undergone treatment with at least one compound selected from ruxolitinib, pacritinib, momelotinib, and fedratinib.

92. A method of treating a JAK2-mediated disorder in a patient in need thereof, comprisingadministering a selective small molecule antagonist of JAK2 to a patient in need thereof.

93. A method of inhibiting an activity of JAK2 kinase in a patient in need thereof,comprising contacting the JAK2 kinase with a selective small molecule antagonist of JAK2.

94. The method of claim 92 or claim 93, wherein the selective small molecule JAK2antagonist binds to or interacts with JAK2 and does not substantially bind to or interact with any other JAK family member.

95. The method of claim 94, wherein the selective small molecule JAK2 antagonist is at least5-fold, 10-fold, 15-fold, 20-fold, 30-fold, 40-fold, 50-fold, or more selective for JAK2 than for any other JAK family member.

96. The method of claim 94 or claim 95, wherein the other JAK family members compriseJAK1, JAK3, TYK2, or a combination thereof.

97. The method of any one of claims 92-96, wherein the selective small molecule JAK2antagonist binds to or interacts with the JAK2-JH2 domain of JAK2 and does not substantially bind to or interact with the JAK2-JH1 domain of JAK2.

98. The method of claim 97, wherein the selective small molecule JAK2 antagonist is at least2-fold, 3-fold, 4-fold, 5-fold, 10-fold, 15-fold, 20-fold or more selective for the JAK2- JH2 domain of JAK2 than for the JAK2-JH1 domain of JAK2.

99. The method of any one of claims 92-98, wherein the selective small molecule JAK2antagonist is a compound of any one of claims 1-72. - 982 -

Images