Small molecule inhibitors of ubiquitin-specific protease 1 (USP1) and uses thereof

Abstract

Provided herein are small molecule inhibitor compounds of ubiquitin-specific protease 1 (USP1) and compositions comprising same. Also provided herein are methods for targeting ubiquitin-specific protease 1 (USP1) and methods for treating diseases or disorders associated with USP1, such as cancer.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This patent application claims the benefit of International Application No. PCT / CN2021 / 130284, filed November 12, 2021, and International Application No. PCT / CN2022 / 123821, filed October 8, 2022, each of which is incorporated by reference in its entirety herein. [Background technology]

[0002] Ubiquitin-specific protease 1 (USP1) is a gene that plays a role in DNA damage repair.The compounds and pharmaceutical compositions that target USP1, as well as the methods of treating USP1-related diseases and disorders, such as certain cancers, have not been widely developed.Therefore, there remains a need to address the methods of treating USP1-related diseases. Summary of the Invention

[0003] The present disclosure addresses the above needs and provides additional advantages as well.

[0004] In one aspect, described herein is a compound having the structure of formula (I), or a salt or solvate thereof: [ka] During the ceremony, X 1 is N or CR 1 and X 3 is N or CR 3 and X 7 is N or CR 7 and R 1 , R 3 , and R 7 each independently represents hydrogen, halo, -CN, -OR 11 , -SR 11 , -N(R 12 ) 2 , optionally substituted C1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 alkynyl, R 8 and R 9 Each of is independently hydrogen, halo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 alkynyl or R 8 and R 9 are taken together to form oxo or R 8 and R 9 together with the carbons to which they are attached form an optionally substituted 3- to 6-membered cycloalkyl or heterocycloalkyl; Ring A is phenyl, naphthyl, monocyclic heteroaryl, or bicyclic heteroaryl; R A Each of the groups is independently a halogen, -NO 2 , oxo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 ) 2 S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , and -S(O) 2 N(R 12 )(R 11 ), R 11 is hydrogen, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted -C 1~4 Alkylene-C 3~8 Cycloalkyl, optionally substituted -C 1~4 Alkylene-C 2~7 Heterocycloalkyl, optionally substituted -C 1~4 Alkylene-phenyl, or optionally substituted -C 1~4 alkylene-heteroaryl, R 12 Each of the groups is independently hydrogen, -NO 2 , -CN,C 1~6 Alkyl, C 1~6 Aminoalkyl, C 1~6 Hydroxyalkyl, C 1~6 Haloalkyl, C 1~6 Heteroalkyl, C 3~6 Carbocyclic rings and 3- to 6-membered heterocyclic rings; 3~6The carbocycle and the 3- to 6-membered heterocycle are independently selected from halogen, -OH, oxo, amino, -NO 2 , -CN,C 1~6 Alkyl, C 1~6 Alkoxy and C 1~6 optionally substituted with one or more substituents selected from haloalkyl; B is a 6-membered heteroaryl, phenyl, or phenylisostere; R B1 , halo, -CN, -NO 2 , optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 )S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , -S(O) 2 N(R 12 )(R 11 ), optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~9heterocycloalkyl, optionally substituted naphthyl, optionally substituted phenyl, optionally substituted monocyclic heteroaryl, or optionally substituted bicyclic heteroaryl; Each R B are independently halo, -CN, -NO 2 , optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 )S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , -S(O) 2 N(R 12 )(R 11 ), optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~9 heterocycloalkyl, optionally substituted naphthyl, optionally substituted phenyl, optionally substituted monocyclic heteroaryl, or optionally substituted bicyclic heteroaryl, or R on adjacent atoms B1 and R Band one of, taken together with the atom to which they are attached, is optionally substituted phenyl, optionally substituted naphthyl, optionally substituted monocyclic heteroaryl, optionally substituted bicyclic heteroaryl, optionally substituted C 3~8 Cycloalkyl or optionally substituted C 2~9 forming a heterocycloalkyl, or R on the same atom B1 and R B one of which, together with the atom to which they are attached, is an optionally substituted C 3~8 Cycloalkyl or optionally substituted C 2~9 forming a heterocycloalkyl, or R on the same atom B Two of them, together with the atoms to which they are attached, are optionally substituted C 3~8 Cycloalkyl or optionally substituted C 2~9 forming a heterocycloalkyl, m is 1, 2, 3, or 4; n is 0, 1, 2, 3, or 4; p is 0 or 1.

[0005] In one aspect, provided herein is a compound having the structure of formula (I), or a salt thereof: [ka] During the ceremony, X 1 is N or CR 1 and X 3 is N or CR 3 and X 7 is N or CR 7 and R 1 , R 3 , and R 7 each independently represents hydrogen, halo, -CN, -OR 11 , -SR 11 , -N(R 12) 2 , optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 alkynyl, R 8 and R 9 Each of is independently hydrogen, halo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 alkynyl or R 8 and R 9 are taken together to form oxo or R 8 and R 9 together with the carbons to which they are attached form an optionally substituted 3- to 6-membered cycloalkyl or heterocycloalkyl; Ring A is phenyl, naphthyl, monocyclic heteroaryl, or bicyclic heteroaryl; R A Each of the groups is independently a halogen, -NO 2 , oxo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12)(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 ) 2 S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , and -S(O) 2 N(R 12 )(R 11 ), R 11 is hydrogen, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted -C 1~4 Alkylene-C 3~8 Cycloalkyl, optionally substituted -C 1~4 Alkylene-C 2~7 Heterocycloalkyl, optionally substituted -C 1~4 Alkylene-phenyl, or optionally substituted -C 1~4 alkylene-heteroaryl, R 12 Each of the groups is independently hydrogen, -NO 2 , -CN,C 1~6 Alkyl, C 1~6 Aminoalkyl, C 1~6 Hydroxyalkyl, C 1~6 Haloalkyl, C 1~6 Heteroalkyl, C 3~6 Carbocyclic rings and 3- to 6-membered heterocyclic rings; 3~6The carbocycle and the 3- to 6-membered heterocycle are independently selected from halogen, -OH, oxo, amino, -NO 2 , -CN,C 1~6 Alkyl, C 1~6 Alkoxy and C 1~6 optionally substituted with one or more substituents selected from haloalkyl; B is a 6-membered heteroaryl, phenyl, or phenylisostere; R B1 is an optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~9 heterocycloalkyl, optionally substituted naphthyl, optionally substituted phenyl, optionally substituted monocyclic heteroaryl, or optionally substituted bicyclic heteroaryl; Each R B are independently halo, -CN, -NO 2 , optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 )S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12, -S(O) 2 N(R 12 )(R 11 ), optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~9 heterocycloalkyl, optionally substituted naphthyl, optionally substituted phenyl, optionally substituted monocyclic heteroaryl, or optionally substituted bicyclic heteroaryl; or R on the same atom B Two of them, together with the atoms to which they are attached, are optionally substituted C 3~8 Cycloalkyl or optionally substituted C 2~9 forming a heterocycloalkyl, m is 1, 2, 3, or 4; n is 0, 1, 2, 3, or 4; p is 0 or 1.

[0006] In some embodiments, the compound has the structure of Formula (Ia): [ka] During the ceremony, X 1 is N or CR 1 and X 3 is N or CR 3 and X 7 is N or CR 7 and R 1 , R 3 , and R 7 each independently represents hydrogen, halo, -CN, -OR 11 , -SR 11 , -N(R 12 ) 2 , optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6alkynyl, Y 1 is N or CR Y1 and Y 2 is N or CR Y2 and Y 3 is N or CR Y3 and Y 4 is N or CR Y4 and R Y1 , R Y2 , R Y3 , and R Y4 each independently represents hydrogen, halo, -CN, -OR 11 , -SR 11 , -N(R 12 ) 2 , optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 alkynyl, R 8 and R 9 Each of is independently hydrogen, halo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 alkynyl or R 8 and R 9 are taken together to form oxo or R 8 and R 9 together with the carbons to which they are attached form an optionally substituted 3- to 6-membered cycloalkyl or heterocycloalkyl; Ring A is phenyl, naphthyl, monocyclic heteroaryl, or bicyclic heteroaryl; R A Each of the groups is independently a halogen, -NO 2 , oxo, -CN, optionally substituted C1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 ) 2 S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , and -S(O) 2 N(R 12 )(R 11 ), R 11 is hydrogen, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted -C 1~4 Alkylene-C3~8 Cycloalkyl, optionally substituted -C 1~4 Alkylene-C 2~7 Heterocycloalkyl, optionally substituted -C 1~4 Alkylene-phenyl, or optionally substituted -C 1~4 alkylene-heteroaryl, R 12 Each of the groups is independently hydrogen, -NO 2 , -CN,C 1~6 Alkyl, C 1~6 Aminoalkyl, C 1~6 Hydroxyalkyl, C 1~6 Haloalkyl, C 1~6 Heteroalkyl, C 3~6 Carbocyclic rings and 3- to 6-membered heterocyclic rings; 3~6 The carbocycle and the 3- to 6-membered heterocycle are independently selected from halogen, -OH, oxo, amino, -NO 2 , -CN,C 1~6 Alkyl, C 1~6 Alkoxy and C 1~6 optionally substituted with one or more substituents selected from haloalkyl; R B1 is an optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~9 heterocycloalkyl, optionally substituted naphthyl, optionally substituted phenyl, optionally substituted monocyclic heteroaryl, or optionally substituted bicyclic heteroaryl; m is 1, 2, 3, or 4; p is 0 or 1.

[0007] In some embodiments, the compound has the structure of formula (Ib): [ka]

[0008] In one aspect, the structure of formula (II'), or a salt or solvate thereof, is described herein: [ka] During the ceremony, X 1 is N or CR 1 and X 2 is N or CR 2 and X 3 is N or CR 3 and X 5 is N, X 6 , N, NR 6 , C.R. 6 , C(R 6 ) 2 , S(=O) 2 , C(=O), or C(=S); X 7 , N, NR 7 ,O.S.,C.R. 7 , S(=O) 2 , C(=O), or C(=S); (i)X 2 , X 3 , and X 5 is N and X 6 If C(=O), then X 7 But O, S, CR 7 , C(=O), or C(=S); and (ii) X 2 , X 3 , and X 5 If N, then X 6 and X 7 At least one of is O, S, or S(=O) 2 , C(=O), or C(=S); [ka] is a single or double bond, R 1 , R 2 , R 3 , R 6 , and R 7 each independently represents hydrogen, halo, -CN, -OR 11 , -SR 11 , -N(R12 ) 2 , optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 alkynyl, R 8 and R 9 Each of is independently hydrogen, halo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 alkynyl or R 8 and R 9 are taken together to form oxo or R 8 and R 9 together with the carbons to which they are attached form an optionally substituted 3- to 6-membered cycloalkyl or heterocycloalkyl; Ring A is phenyl, naphthyl, monocyclic heteroaryl, or bicyclic heteroaryl; R A Each of the groups is independently a halogen, -NO 2 , oxo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 ) 2 S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , and -S(O) 2 N(R 12 )(R 11 ), R 11 is hydrogen, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted -C 1~4 Alkylene-C 3~8 Cycloalkyl, optionally substituted -C 1~4 Alkylene-C 2~7 Heterocycloalkyl, optionally substituted -C 1~4 Alkylene-phenyl, or optionally substituted -C 1~4 alkylene-heteroaryl, R 12 Each of the groups is independently hydrogen, -NO 2 , -CN,C 1~6 Alkyl, C 1~6 Aminoalkyl, C 1~6 Hydroxyalkyl, C 1~6 Haloalkyl and C 3~6 Carbocyclic ring, 3- to 6-membered heterocyclic ring, 3~6The carbocycle and the 3- to 6-membered heterocycle are independently selected from halogen, -OH, oxo, amino, -NO 2 , -CN,C 1~6 Alkyl, C 1~6 Alkoxy and C 1~6 optionally substituted with one or more substituents selected from haloalkyl; B is a 6-membered heteroaryl, phenyl, or phenylisostere; R B1 , halo, -CN, -NO 2 , optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 )S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , -S(O) 2 N(R 12 )(R 11 ), optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~9heterocycloalkyl, optionally substituted naphthyl, optionally substituted phenyl, optionally substituted monocyclic heteroaryl, or optionally substituted bicyclic heteroaryl; Each R B are independently halo, -CN, -NO 2 , optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 )S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , -S(O) 2 N(R 12 )(R 11 ), optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~9 heterocycloalkyl, optionally substituted naphthyl, optionally substituted phenyl, optionally substituted monocyclic heteroaryl, or optionally substituted bicyclic heteroaryl; or R on adjacent atoms B1 and R Band one of, taken together with the atom to which they are attached, is optionally substituted phenyl, optionally substituted naphthyl, optionally substituted monocyclic heteroaryl, optionally substituted bicyclic heteroaryl, optionally substituted C 3~8 Cycloalkyl or optionally substituted C 2~9 forming a heterocycloalkyl, or R on the same atom B1 and R B one of which, together with the atom to which they are attached, is an optionally substituted C 3~8 Cycloalkyl or optionally substituted C 2~9 forming a heterocycloalkyl, or R on the same atom B Two of them, together with the atoms to which they are attached, are optionally substituted C 3~8 Cycloalkyl or optionally substituted C 2~9 forming a heterocycloalkyl, m is 1, 2, 3, or 4; n is 0, 1, 2, 3, or 4; p is 0 or 1.

[0009] In some embodiments, X 2 is N.

[0010] In some embodiments, R B1 is an optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~9 heterocycloalkyl, optionally substituted naphthyl, optionally substituted phenyl, optionally substituted monocyclic heteroaryl, or optionally substituted bicyclic heteroaryl; Each R B are independently halo, -CN, -NO 2 , optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6Alkynyl, optionally substituted C 1~6 Heteroalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 )S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , -S(O) 2 N(R 12 )(R 11 ), optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~9 heterocycloalkyl, optionally substituted naphthyl, optionally substituted phenyl, optionally substituted monocyclic heteroaryl, or optionally substituted bicyclic heteroaryl, or R B Two of them, together with the atoms to which they are attached, are optionally substituted C 3~8 Cycloalkyl or optionally substituted C 2~9 Forms a heterocycloalkyl.

[0011] In some embodiments, the compound has the structure of formula (IIa): [ka]

[0012] In some embodiments, the compound has the structure of formula (IIa-1): [ka] During the ceremony, X 1 is N or CR 1 and X 2 is N or CR 2 and X 3 is N or CR 3 and X 7 is NR 7 , O, S, S(=O) 2 , C(=O), or C(=S); R 1 , R 2 , R 3 , and R 7 each independently represents hydrogen, halo, -CN, -OR 11 , -SR 11 , -N(R 12 ) 2 , optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 alkynyl, Y 1 is N or CR Y1 and Y 2 is N or CR Y2 and Y 3 is N or CR Y3 and Y 4 is N or CR Y4 and R Y1 , R Y2 , R Y3 , and R Y4 each independently represents hydrogen, halo, -CN, -OR 11 , -SR 11 , -N(R 12 )2 , optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 alkynyl, R 8 and R 9 Each of is independently hydrogen, halo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 alkynyl or R 8 and R 9 are taken together to form oxo or R 8 and R 9 together with the carbons to which they are attached form an optionally substituted 3- to 6-membered cycloalkyl or heterocycloalkyl; Ring A is phenyl, naphthyl, monocyclic heteroaryl, or bicyclic heteroaryl; R A Each of the groups is independently a halogen, -NO 2 , oxo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 ) 2 S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , and -S(O) 2 N(R 12 )(R 11 ), R 11 is hydrogen, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted -C 1~4 Alkylene-C 3~8 Cycloalkyl, optionally substituted -C 1~4 Alkylene-C 2~7 Heterocycloalkyl, optionally substituted -C 1~4 Alkylene-phenyl, or optionally substituted -C 1~4 alkylene-heteroaryl, R 12 Each of the groups is independently hydrogen, -NO 2 , -CN,C 1~6 Alkyl, C 1~6 Aminoalkyl, C 1~6 Hydroxyalkyl, C 1~6 Haloalkyl and C 3~6 Carbocyclic ring, 3- to 6-membered heterocyclic ring, 3~6The carbocycle and the 3- to 6-membered heterocycle are independently selected from halogen, -OH, oxo, amino, -NO 2 , -CN,C 1~6 Alkyl, C 1~6 Alkoxy and C 1~6 optionally substituted with one or more substituents selected from haloalkyl; R B1 is an optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~9 heterocycloalkyl, optionally substituted naphthyl, optionally substituted phenyl, optionally substituted monocyclic heteroaryl, or optionally substituted bicyclic heteroaryl; m is 1, 2, 3, or 4; p is 0 or 1.

[0013] In some embodiments, the compound of formula (IIa-1) has the structure of formula (IIa-1a): [ka]

[0014] In some embodiments, the compound has the structure of formula (IIb): [ka]

[0015] In some embodiments, the compound has the structure of formula (IIb-1): [ka] During the ceremony, X 1 is N or CR 1 and X 2 is N or CR 2 and X 3 is N or CR 3 and X 1 , X2 , and X 3 is N; R 1 , R 2 , and R 3 each independently represents hydrogen, halo, -CN, -OR 11 , -SR 11 , -N(R 12 ) 2 , optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 alkynyl, Y 1 is N or CR Y1 and Y 2 is N or CR Y2 and Y 3 is N or CR Y3 and Y 4 is N or CR Y4 and R Y1 , R Y2 , R Y3 , and R Y4 each independently represents hydrogen, halo, -CN, -OR 11 , -SR 11 , -N(R 12 ) 2 , optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 alkynyl, R 8 and R 9 Each of is independently hydrogen, halo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6Alkenyl, and optionally substituted C 2~6 alkynyl or R 8 and R 9 are taken together to form oxo or R 8 and R 9 together with the carbons to which they are attached form an optionally substituted 3- to 6-membered cycloalkyl or heterocycloalkyl; Ring A is phenyl, naphthyl, monocyclic heteroaryl, or bicyclic heteroaryl; R A Each of the groups is independently a halogen, -NO 2 , oxo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 ) 2 S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , and -S(O) 2 N(R12 )(R 11 ), R 11 is hydrogen, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted -C 1~4 Alkylene-C 3~8 Cycloalkyl, optionally substituted -C 1~4 Alkylene-C 2~7 Heterocycloalkyl, optionally substituted -C 1~4 Alkylene-phenyl, or optionally substituted -C 1~4 alkylene-heteroaryl, R 12 Each of the groups is independently hydrogen, -NO 2 , -CN,C 1~6 Alkyl, C 1~6 Aminoalkyl, C 1~6 Hydroxyalkyl, C 1~6 Haloalkyl and C 3~6 Carbocyclic ring, 3- to 6-membered heterocyclic ring, 3~6 The carbocycle and the 3- to 6-membered heterocycle are independently selected from halogen, -OH, oxo, amino, -NO 2 , -CN,C 1~6 Alkyl, C 1~6 Alkoxy and C 1~6 optionally substituted with one or more substituents selected from haloalkyl; R B1 , halo, -CN, -NO 2 , optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6Heteroalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 )S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , -S(O) 2 N(R 12 )(R 11 ), optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~9 heterocycloalkyl, optionally substituted naphthyl, optionally substituted phenyl, optionally substituted monocyclic heteroaryl, or optionally substituted bicyclic heteroaryl; m is 1, 2, 3, or 4; p is 0 or 1.

[0016] In some embodiments, the compound of formula (IIb-1) has the structure of formula (IIb-1a): [ka]

[0017] In some embodiments, the compound has the structure of formula (IIc): [ka]

[0018] In some embodiments, the compound has the structure of formula (IIc-1): [ka] During the ceremony, R 1 , R 3 , and R 7 each independently represents hydrogen, halo, -CN, -OR 11 , -SR 11 , -N(R 12 ) 2 , optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 alkynyl, Y 1 is N or CR Y1 and Y 2 is N or CR Y2 and Y 3 is N or CR Y3 and Y 4 is N or CR Y4 and R Y1 , R Y2 , R Y3 , and R Y4 each independently represents hydrogen, halo, -CN, -OR 11 , -SR 11 , -N(R 12 ) 2 , optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 alkynyl, R 8 and R 9 Each of is independently hydrogen, halo, -CN, optionally substituted C1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 alkynyl or R 8 and R 9 are taken together to form oxo or R 8 and R 9 together with the carbons to which they are attached form an optionally substituted 3- to 6-membered cycloalkyl or heterocycloalkyl; Ring A is phenyl, naphthyl, monocyclic heteroaryl, or bicyclic heteroaryl; R A Each of the groups is independently a halogen, -NO 2 , oxo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 ) 2 S(O) 2 (R 12 ), -S(O)R12 , -S(O) 2 R 12 , and -S(O) 2 N(R 12 )(R 11 ), R 11 is hydrogen, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted -C 1~4 Alkylene-C 3~8 Cycloalkyl, optionally substituted -C 1~4 Alkylene-C 2~7 Heterocycloalkyl, optionally substituted -C 1~4 Alkylene-phenyl, or optionally substituted -C 1~4 alkylene-heteroaryl, R 12 Each of the groups is independently hydrogen, -NO 2 , -CN,C 1~6 Alkyl, C 1~6 Aminoalkyl, C 1~6 Hydroxyalkyl, C 1~6 Haloalkyl and C 3~6 Carbocyclic ring, 3- to 6-membered heterocyclic ring, 3~6 The carbocycle and the 3- to 6-membered heterocycle are independently selected from halogen, -OH, oxo, amino, -NO 2 , -CN,C 1~6 Alkyl, C 1~6 Alkoxy and C 1~6 optionally substituted with one or more substituents selected from haloalkyl; R B1 is an optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~9heterocycloalkyl, optionally substituted naphthyl, optionally substituted phenyl, optionally substituted monocyclic heteroaryl, or optionally substituted bicyclic heteroaryl; m is 1, 2, 3, or 4; p is 0 or 1.

[0019] In some embodiments, the compound has the structure of formula (IId): [ka]

[0020] In some embodiments, the compound has the structure of formula (IId-1): [ka]

[0021] In some embodiments, the compound has the structure of formula (IIe): [ka]

[0022] In some embodiments, the compound has the structure of formula (IIg): [ka]

[0023] In one aspect, described herein is a compound having the structure of formula (VI), or a salt or solvate thereof: [ka] During the ceremony, Ring C is phenyl or 6-membered heteroaryl, each of which is optionally substituted; Ring D is an aromatic saturated or partially saturated 5-membered carbocyclic or heterocyclic ring, each of which is optionally substituted; R 8 and R 9 Each of is independently hydrogen, halo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 alkynyl or R 8 and R 9 are taken together to form oxo or R 8 and R 9 together with the carbons to which they are attached form an optionally substituted 3- to 6-membered cycloalkyl or heterocycloalkyl; Ring A is phenyl, naphthyl, monocyclic heteroaryl, or bicyclic heteroaryl; R A Each of the groups is independently a halogen, -NO 2 , oxo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11), -N(R 12 ) 2 S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , and -S(O) 2 N(R 12 )(R 11 ), R 11 is hydrogen, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted -C 1~4 Alkylene-C 3~8 Cycloalkyl, optionally substituted -C 1~4 Alkylene-C 2~7 Heterocycloalkyl, optionally substituted -C 1~4 Alkylene-phenyl, or optionally substituted -C 1~4 alkylene-heteroaryl, R 12 Each of the groups is independently hydrogen, -NO 2 , -CN,C 1~6 Alkyl, C 1~6 Aminoalkyl, C 1~6 Hydroxyalkyl, C 1~6 Haloalkyl and C 3~6 Carbocyclic ring, 3- to 6-membered heterocyclic ring, 3~6 The carbocycle and the 3- to 6-membered heterocycle are independently selected from halogen, -OH, oxo, amino, -NO 2 , -CN,C 1~6 Alkyl, C 1~6 Alkoxy and C 1~6 optionally substituted with one or more substituents selected from haloalkyl; R Bis hydrogen, halo, -CN, -NO 2 , optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 )S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , -S(O) 2 N(R 12 )(R 11 ), optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~9 heterocycloalkyl, optionally substituted naphthyl, optionally substituted phenyl, optionally substituted monocyclic heteroaryl, or optionally substituted bicyclic heteroaryl; m is 1, 2, 3, or 4; p is 0 or 1.

[0024] In one aspect, described herein is a pharmaceutical composition comprising a compound described herein, or a pharma- ceutically acceptable salt or solvate thereof, and a pharma- ceutically acceptable carrier or excipient.

[0025] In one aspect, described herein is a method of modulating ubiquitin-specific protease 1 (USP1) in a subject, the method comprising administering to the subject a compound described herein, a pharma- ceutically acceptable salt or solvate thereof, or a pharmaceutical composition of a compound described herein.

[0026] In one aspect, described herein is a method of inhibiting ubiquitin-specific protease 1 (USP1) in a subject, the method comprising administering to the subject a compound described herein, a pharma- ceutically acceptable salt or solvate thereof, or a pharmaceutical composition of a compound described herein.

[0027] In one aspect, described herein is a method of inhibiting or reducing DNA repair activity regulated by ubiquitin-specific protease 1 (USP1) in a subject, comprising administering to a subject in need thereof an effective amount of a compound described herein, a pharma- ceutically acceptable salt or solvate thereof, or a pharmaceutical composition of a compound described herein.

[0028] In one aspect, described herein is a method of treating a disease or disorder associated with ubiquitin-specific protease 1 (USP1) in a subject, comprising administering to the subject a compound described herein, a pharma- ceutically acceptable salt or solvate thereof, or a pharmaceutical composition of a compound described herein.

[0029] In one aspect, described herein is a method of treating a disease or disorder associated with the regulation of ubiquitin-specific protease 1 (USP1) in a subject, comprising administering to the subject a compound described herein, a pharma- ceutically acceptable salt or solvate thereof, or a pharmaceutical composition of a compound described herein. In some embodiments, the disease or disorder is cancer.

[0030] In one aspect, described herein is a method of treating cancer in a subject, comprising administering to a subject in need thereof an effective amount of a compound described herein, or a pharma- ceutically acceptable salt or solvate thereof, or a pharmaceutical composition of a compound described herein. In some embodiments, the cancer is selected from the group consisting of lung cancer, non-small cell lung cancer (NSCLC), colon cancer, bladder cancer, osteosarcoma, ovarian cancer, skin cancer, and breast cancer. In some embodiments, the cancer is ovarian cancer. In some embodiments, the cancer is breast cancer. In some embodiments, the cancer is ovarian cancer or breast cancer.

[0031] In some embodiments, the cancer comprises cancer cells with elevated levels of RAD 18. In some embodiments, the cancer is a DNA damage repair pathway deficient cancer. In some embodiments, the cancer is a PARP inhibitor resistant or refractory cancer. In some embodiments, the cancer is a BRCA1 mutated cancer and / or a BRCA2 mutated cancer. In some embodiments, the cancer is a BRAC1 deficient cancer.

[0032] Incorporation by Reference All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. To the extent that the publications and patents or patent applications incorporated by reference conflict with the disclosure contained herein, the present specification is intended to supersede and / or take precedence over any such conflicting material. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0033] While various embodiments of the present disclosure have been shown and described herein, it will be apparent to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions may occur to those skilled in the art without departing from the present disclosure. It is understood that various alternatives to the embodiments of the present disclosure described herein may be employed.

[0034] A.Definition Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. All patents and publications referenced herein are incorporated by reference.

[0035] "Alkyl" refers to an optionally substituted straight chain or an optionally substituted branched chain saturated hydrocarbon monoradical, preferably having 1 to 15 carbon atoms (i.e., C 1 ~C 15 In certain embodiments, alkyl has 1 to 13 carbon atoms (i.e., C 1 ~C 13 In certain embodiments, alkyl includes 1 to 8 carbon atoms (i.e., C 1 ~C 8 In other embodiments, alkyl includes 1 to 5 carbon atoms (i.e., C 1 ~C 5 In other embodiments, alkyl includes 1 to 4 carbon atoms (i.e., C 1 ~C 4 In other embodiments, alkyl includes 1 to 3 carbon atoms (i.e., C 1 ~C 3 In other embodiments, alkyl includes 1 to 2 carbon atoms (i.e., C 1 ~C 2 Each time it appears in this specification, the term "C 1 ~C 3 Numeric ranges such as "alkyl" mean that the alkyl group consists of 1 carbon atom, 2 carbon atoms, or 3 carbon atoms. In other embodiments, the alkyl group consists of 1 carbon atom (i.e., C 1 In other embodiments, alkyl includes 5 to 15 carbon atoms (i.e., C 5 ~C 15 In other embodiments, alkyl includes 5 to 8 carbon atoms (i.e., C 5 ~C 8In other embodiments, alkyl includes 2 to 5 carbon atoms (i.e., C 2 ~C 5 In other embodiments, alkyl includes 3 to 5 carbon atoms (i.e., C 3 ~C 5 In certain embodiments, the alkyl group is selected from methyl, ethyl, 1-propyl (n-propyl), 1-methylethyl (iso-propyl), 1-butyl (n-butyl), 1-methylpropyl (sec-butyl), 2-methylpropyl (iso-butyl), 1,1-dimethylethyl (tert-butyl), 1-pentyl (n-pentyl). In other embodiments, examples include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, 2-methyl-1-propyl, 2-methyl-2-propyl, 2-methyl-1-butyl, 3-methyl-1-butyl, 2-methyl-3-butyl, 2,2-dimethyl-1-propyl, 2-methyl-1-pentyl, 3-methyl-1-pentyl, 4-methyl-1-pentyl, 2-methyl-2-pentyl, 3-methyl-2-pentyl, 4-methyl-2-pentyl, 2,2-dimethyl-1-butyl, 3,3-dimethyl-1-butyl, 2-ethyl-1-butyl, n-butyl, isobutyl, sec-butyl, t-butyl, n-pentyl, isopentyl, neopentyl, tert-amyl, and hexyl, as well as longer alkyl groups such as heptyl, octyl, and the like. The alkyl is attached to the remainder of the molecule by a single bond. Unless otherwise stated in the specification, alkyl groups are optionally substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, and the like. In some embodiments, alkyl is substituted with oxo, halogen, -CN, -CF 3 , -OH, -OMe, -NH 2 , -NO 2 or -C≡CH. In some embodiments, alkyl is optionally substituted with oxo, halogen, -CN, -CF 3, -OH, or -OMe. In some embodiments, the alkyl is optionally substituted with a halogen, such as F.

[0036] As used herein, C 1 ~C x (or C 1~x ) is C 1 ~C 2 , C 1 ~C 3 ...C 1 ~C x As just one example, "C 1 ~C 4 " indicates that the moiety contains from 1 to 4 carbon atoms, i.e., 1 carbon atom, 2 carbon atoms, 3 carbon atoms, or 4 carbon atoms. Thus, by way of example only, "C 1 ~C 4 "Alkyl" indicates that there are 1 to 4 carbon atoms in the alkyl group, i.e., the alkyl group is selected from among methyl, ethyl, propyl, isopropyl, n-butyl, iso-butyl, sec-butyl, and t-butyl. 0 ~C 2 Alkylene is a direct bond, -CH 2 - and -CH 2 CH 2 - Includes bonds.

[0037] "Alkoxy" refers to a radical attached through an oxygen atom of the formula -O-alkyl, where alkyl is an alkyl chain as defined above. Unless otherwise stated in the specification, an alkoxy group can be optionally substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, and the like. In some embodiments, an alkoxy is an oxo, halogen, -CN, -CF 3 , -OH, -OMe, -NH 2 , or -NO 2 In some embodiments, alkoxy is optionally substituted with oxo, halogen, -CN, -CF3 , -OH, or -OMe. In some embodiments, the alkoxy is optionally substituted with halogen.

[0038] "Alkenyl" refers to an alkyl group containing at least one carbon-carbon double bond and preferably having 2 to 12 carbon atoms (i.e., C 2 ~C 12 alkenyl) refers to an optionally substituted straight or branched chain hydrocarbon radical group having 2 to 8 carbon atoms (i.e., C 2 ~C 8 In certain embodiments, alkenyl includes 2 to 6 carbon atoms (i.e., C 2 ~C 6 In other embodiments, alkenyl includes 2 to 4 carbon atoms (i.e., C 2 ~C 4 alkenyl). The group may be in either the cis or trans configuration about the double bond(s) and should be understood to include both isomers. Examples include ethenyl (-CH=CH 2 ), 1-propenyl (-CH 2 CH=CH 2 ), isopropenyl [-C(CH 3 )=CH 2 ], butenyl, 1,3-butadienyl, and the like. 2 ~C 6 Numerical ranges such as "alkenyl" mean that the alkenyl group can be composed of 2 carbon atoms, 3 carbon atoms, 4 carbon atoms, 5 carbon atoms, or 6 carbon atoms. Unless stated otherwise in the specification, alkenyl groups are optionally substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, and the like. In some embodiments, alkenyl is substituted with oxo, halogen, -CN, -CF 3 , -OH, -OMe, -NH 2 , or -NO 2In some embodiments, alkenyl is optionally substituted with oxo, halogen, -CN, -CF 3 , -OH, or -OMe. In some embodiments, the alkenyl is optionally substituted with a halogen. The alkenyl is attached to the remainder of the molecule by a single bond, e.g., ethenyl (i.e., vinyl), prop-1-enyl (i.e., allyl), but-1-enyl, pent-1-enyl, penta-1,4-dienyl, and the like. Unless otherwise stated herein, the alkenyl group is optionally substituted with, e.g., oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, and the like. In some embodiments, the alkenyl is optionally substituted with, e.g., oxo, halogen, -CN, -CF 3 , -OH, -OMe, -NH 2 , or -NO 2 In some embodiments, alkenyl is optionally substituted with oxo, halogen, -CN, -CF 3 , -OH, or -OMe. In some embodiments, alkenyl is optionally substituted with halogen.

[0039] "Alkynyl" refers to an alkynyl group containing at least one carbon-carbon triple bond and preferably containing 2 to 12 carbon atoms (i.e., C 2 ~C 12 alkynyl) refers to an optionally substituted straight or branched chain hydrocarbon radical group having 2 to 8 carbon atoms (i.e., C 2 ~C 8 In other embodiments, alkynyl includes 2 to 6 carbon atoms (i.e., C 2 ~C 6 In other embodiments, alkynyl includes 2 to 4 carbon atoms (i.e., C 2 ~C 4 Each occurrence of "C" in this specification includes "C 2 ~C 6Numerical ranges such as "alkynyl" mean that the alkynyl group can be composed of 2 carbon atoms, 3 carbon atoms, 4 carbon atoms, 5 carbon atoms, or 6 carbon atoms. The alkynyl is attached to the remainder of the molecule by a single bond, e.g., ethynyl, propynyl, butynyl, pentynyl, hexynyl, 2-propynyl, 2-butynyl, 1,3-butadinyl, and the like. Unless stated otherwise in the specification, the alkynyl group is optionally substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, and the like. In some embodiments, the alkynyl is substituted with, for example, oxo, halogen, -CN, -CF 3 , -OH, -OMe, -NH 2 , or -NO 2 In some embodiments, alkynyl is optionally substituted with oxo, halogen, -CN, -CF 3 , -OH, or -OMe. In some embodiments, alkynyl is optionally substituted with halogen.

[0040] "Alkylene" or "alkylene chain" refers to an optionally substituted straight or branched divalent hydrocarbon chain that contains no unsaturation and preferably has 1 to 12 carbon atoms, linking the rest of the molecule to a radical group, e.g., methylene, ethylene, propylene, n-butylene, and the like. The alkylene chain is attached to the rest of the molecule through a single bond and to the radical group through a single bond. The points of attachment of the alkylene chain to the rest of the molecule and to the radical group can be through any two carbons within the chain. In certain embodiments, alkylene is an alkylene having 1 to 10 carbon atoms (i.e., C 1 ~C 8 In certain embodiments, the alkylene includes an alkylene having 1 to 8 carbon atoms (i.e., C 1 ~C 8 In other embodiments, the alkylene includes 1 to 5 carbon atoms (i.e., C 1 ~C 5In other embodiments, the alkylene includes 1 to 4 carbon atoms (i.e., C 1 ~C 4 In other embodiments, the alkylene includes 1 to 3 carbon atoms (i.e., C 1 ~C 3 In other embodiments, the alkylene includes 1 to 2 carbon atoms (i.e., C 1 ~C 2 In other embodiments, the alkylene includes one carbon atom (i.e., C 1 In other embodiments, the alkylene includes 5 to 8 carbon atoms (i.e., C 5 ~C 8 In other embodiments, the alkylene includes 2 to 5 carbon atoms (i.e., C 2 ~C 5 In other embodiments, the alkylene includes 3 to 5 carbon atoms (i.e., C 3 ~C 5 Unless stated otherwise in the specification, alkylene groups can be optionally substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, and the like. In some embodiments, alkylene is substituted with oxo, halogen, -CN, -CF 3 , -OH, -OMe, -NH 2 , or -NO 2 In some embodiments, alkylene is optionally substituted with oxo, halogen, -CN, -CF 3 , -OH, or -OMe. In some embodiments, alkylene is optionally substituted with halogen. In some embodiments, alkylene is optionally substituted with -CH 2 -, -CH 2 CH 2 -, or -CH 2 CH 2 CH 2 In some embodiments, alkylene is -CH 2In some embodiments, alkylene is -CH 2 CH 2 In some embodiments, alkylene is -CH 2 CH 2 CH 2 -It is.

[0041] "Aryl" refers to a radical derived from a hydrocarbon ring system containing at least one aromatic ring. In some embodiments, aryl includes hydrogen and 6 to 30 carbon atoms. The aryl radical can be a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, which can include fused (when fused with a cycloalkyl or heterocycloalkyl ring, the aryl is bonded through an aromatic ring atom) or bridged ring systems. In some embodiments, the aryl is a 6- to 10-membered aryl. In some embodiments, the aryl is a 6-membered aryl. Aryl radicals include, but are not limited to, aryl radicals derived from anthrylene, naphthylene, phenanthrylene, anthracene, azulene, benzene, chrysene, fluoranthene, fluorene, indane, indene, naphthalene, phenalene, phenanthrene, pleiadene, pyrene, and triphenylene hydrocarbon ring systems. In some embodiments, the aryl is phenyl. Unless otherwise specified in the specification, aryl includes, for example, halogen, amino, alkylamino, aminoalkyl, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, heteroalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, -S(O) 2 NH-C 1 ~C 6 In some embodiments, aryl can be optionally substituted with halogen, methyl, ethyl, -CN, -CF 3 , -OH, -OMe, -NH 2 , -NO 2 , -S(O) 2 NH 2 , -S(O) 2 NHCH 3 , -S(O) 2 NHCH2 CH 3 , -S(O) 2 NHCH ( CH 3 ) 2 , -S(O) 2 N(CH 3 ) 2 , or -S(O) 2 NHC(CH 3 ) 3 In some embodiments, aryl is optionally substituted with halogen, methyl, ethyl, -CN, -CF 3 , -OH, or -OMe. In some embodiments, aryl is optionally substituted with halogen. In some embodiments, aryl is substituted with alkyl, alkenyl, alkynyl, haloalkyl, or heteroalkyl, each alkyl, alkenyl, alkynyl, haloalkyl, heteroalkyl being independently unsubstituted or halogen, methyl, ethyl, -CN, -CF 3 , -OH, -OMe, -NH 2 , or -NO 2 is replaced by.

[0042] "Aralkyl" is a group of the formula -R c- aryl radical, where R c is an alkylene chain as defined above, e.g., methylene, ethylene, and the like.

[0043] "Aralkenyl" is a group of the formula -R d- aryl radical, where R d is an alkenylene chain as defined above. "Aralkynyl" refers to a group of the formula -R e- aryl radical, where R e is an alkynylene chain as defined above.

[0044] "Carbocycle" refers to a saturated, unsaturated, or aromatic ring in which each atom of the ring is carbon. Carbocycles can include 3-10 membered monocyclic rings and 6-12 membered bicyclic rings (such as spiro, fused, or bridged rings). Each ring of a bicyclic carbocycle can be selected from saturated, unsaturated, and aromatic rings. An aromatic ring, e.g., phenyl, can be fused to a saturated or unsaturated ring, e.g., cyclohexane, cyclopentane, or cyclohexene. Any combination of saturated, unsaturated, and aromatic bicyclic rings is included in the definition of carbocycle, as valence permits. In an exemplary embodiment, an aromatic ring, e.g., phenyl, can be fused to a saturated or unsaturated ring, e.g., cyclohexane, cyclopentane, or cyclohexene. Bicyclic carbocycles include any combination of saturated, unsaturated, and aromatic bicyclic rings, as valence permits. Bicyclic carbocycles include any combination of ring sizes, such as 4-5 fused ring systems, 5-5 fused ring systems, 5-6 fused ring systems, 6-6 fused ring systems, 5-7 fused ring systems, 6-5 fused ring systems, 6-7 fused ring systems, 5-8 fused ring systems, and 6-8 fused ring systems. Exemplary carbocycles include cyclopentyl, cyclohexyl, cyclohexenyl, adamantyl, phenyl, indanyl, and naphthyl. The term "unsaturated carbocycle" refers to a carbocycle having at least one degree of unsaturation, excluding aromatic carbocycles. Examples of unsaturated carbocycles include cyclohexadiene, cyclohexene, and cyclopentene. The term "saturated cycloalkyl" as used herein refers to a saturated carbocycle. Exemplary carbocycles include cyclopropyl, cyclopentyl, cyclohexyl, cyclohexenyl, adamantyl, phenyl, indanyl, norborane, and naphthyl. Carbocycles can be optionally substituted with one or more substituents such as those described herein.

[0045] "Cycloalkyl" may be a stable partially or fully saturated monocyclic or polycyclic carbocyclic ring system, which may include fused (when fused with an aryl or heteroaryl ring, the cycloalkyl is attached through a non-aromatic ring atom), bridged, or spiro ring systems. Representative cycloalkyls include those having 3 to 15 carbon atoms (C 3 ~C 15Cycloalkyl), 3 to 10 carbon atoms (C 3 -C 10 cycloalkyl), 3 to 8 carbon atoms (C 3 ~C 8 Cycloalkyl), 3 to 6 carbon atoms (C 3 ~C 6 Cycloalkyl), 3 to 5 carbon atoms (C 3 ~C 5 cycloalkyl), or 3-4 carbon atoms (C 3 ~C 4 In some embodiments, the cycloalkyl is a 3- to 6-membered cycloalkyl. In some embodiments, the cycloalkyl is a 5- to 6-membered cycloalkyl. Monocyclic cycloalkyls include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Polycyclic cycloalkyls or carbocycles include, for example, adamantyl, norbornyl, decalinyl, bicyclo[3.3.0]octane, bicyclo[4.3.0]nonane, cisdecalin, transdecalin, bicyclo[2.1.1]hexane, bicyclo[2.2.1]heptane, bicyclo[2.2.2]octane, bicyclo[3.2.2]nonane, and bicyclo[3.3.2]decane, and 7,7-dimethyl-bicyclo[2.2.1]heptanyl. Partially saturated cycloalkyls include, for example, cyclopentenyl, cyclohexenyl, cycloheptenyl, and cyclooctenyl. Unless otherwise stated in the specification, cycloalkyls are optionally substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, and the like. In some embodiments, cycloalkyls are optionally substituted with, for example, oxo, halogen, methyl, ethyl, -CN, -CF 3 , -OH, -OMe, -NH 2 , or -NO 2 In some embodiments, cycloalkyl is optionally substituted with oxo, halogen, methyl, ethyl, -CN, -CF3 , -OH, or -OMe. In some embodiments, cycloalkyl is optionally substituted with halogen.

[0046] "Cycloalkylalkyl" refers to a group of the formula -R c- refers to a cycloalkyl radical, where R c is an alkylene chain as defined above.

[0047] "Cycloalkylalkoxy" refers to a group of the formula -OR c- refers to a radical bonded through the oxygen atom of a cycloalkyl, where R c is an alkylene chain as defined above.

[0048] "Halo" or "halogen" refers to halogen substituents such as bromo, chloro, fluoro and iodo substituents.

[0049] As used herein, the term "haloalkyl" or "haloalkane" refers to an alkyl radical, as defined above, substituted with one or more halogen radicals, such as trifluoromethyl, dichloromethyl, bromomethyl, 2,2,2-trifluoroethyl, 1-fluoromethyl-2-fluoroethyl, and the like. In some embodiments, the alkyl portion of the fluoroalkyl radical is optionally further substituted. Examples of halogen-substituted alkanes ("haloalkanes") include halomethanes (e.g., chloromethane, bromomethane, fluoromethane, iodomethane), di- and trihalomethanes (e.g., trichloromethane, tribromomethane, trifluoromethane, triiodomethane), 1-haloethane, 2-haloethane, 1,2-dihaloethane, 1-halopropane, 2-halopropane, 3-halopropane, 1,2-dihalopropane, 1,3-dihalopropane, 2,3-dihalopropane, 1,2,3-trihalopropane, and any other suitable combination of an alkane (or substituted alkane) and a halogen (e.g., Cl, Br, F, I, etc.). When an alkyl group is substituted with more than one halogen radical, each halogen is independently selected and can be, for example, 1-chloro, 2-fluoroethane.

[0050] "Fluoroalkyl" refers to an alkyl radical as defined above that is substituted by one or more fluoro radicals, such as trifluoromethyl, difluoromethyl, fluoromethyl, 2,2,2-trifluoroethyl, 1-fluoromethyl-2-fluoroethyl, and the like.

[0051] "Hydroxyalkyl" refers to an alkyl radical, as defined above, substituted with one or more hydroxyls. In some embodiments, the alkyl is substituted with one hydroxyl. In some embodiments, the alkyl is substituted with one, two, or three hydroxyls. Hydroxyalkyl includes, for example, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, or hydroxypentyl. In some embodiments, the hydroxyalkyl is hydroxymethyl.

[0052] "Aminoalkyl" refers to an alkyl radical, as defined above, substituted with one or more amines. In some embodiments, the alkyl is substituted with one amine. In some embodiments, the alkyl is substituted with one, two, or three amines. Aminoalkyl includes, for example, aminomethyl, aminoethyl, aminopropyl, aminobutyl, or aminopentyl. In some embodiments, the aminoalkyl is aminomethyl.

[0053] The term "heteroalkyl" refers to an alkyl group in which one or more skeletal atoms of the alkyl are selected from atoms other than carbon, such as oxygen, nitrogen (e.g., -NH-, -N(alkyl)-), sulfur, or combinations thereof. The heteroalkyl is attached to the remainder of the molecule at a carbon atom of the heteroalkyl. In one aspect, a heteroalkyl is a C 1 ~C 6 Heteroalkyl, which consists of 1-6 carbon atoms and one or more atoms other than carbon, such as oxygen, nitrogen (e.g., -NH-, -N(alkyl)-), sulfur, or combinations thereof, and which is attached to the remainder of the molecule at a carbon atom of the heteroalkyl. Examples of such heteroalkyls include, for example, -CH 2 OCH 3 , -CH 2 CH 2 OCH 3 , -CH 2 CH 2 OCH 2 CH2 OCH 3 , or -CH(CH 3 )OCH 3 Unless otherwise stated in the specification, heteroalkyl is optionally substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, and the like. In some embodiments, heteroalkyl is oxo, halogen, methyl, ethyl, -CN, -CF 3 , -OH, -OMe, -NH 2 , or -NO 2 In some embodiments, heteroalkyl is optionally substituted with oxo, halogen, methyl, ethyl, -CN, -CF 3 , -OH, or -OMe. In some embodiments, heteroalkyl is optionally substituted with halogen.

[0054] "Heterocycloalkyl" refers to a stable 3- to 24-membered partially or fully saturated ring radical containing 2 to 23 carbon atoms and at least one ring heteroatom. In some embodiments, a heterocycloalkyl contains 1 to 8 heteroatoms selected from the group consisting of nitrogen, oxygen, phosphorus, and sulfur. Unless otherwise stated in the specification, a heterocycloalkyl radical can be a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, which can include fused (when fused with an aryl or heteroaryl ring, the heterocycloalkyl is attached through a non-aromatic ring atom) or bridged ring systems, and the nitrogen, carbon, or sulfur atoms in the heterocycloalkyl radical can be optionally oxidized and the nitrogen atom can be optionally quaternized.

[0055] Representative heterocycloalkyls include those having 2 to 15 carbon atoms (C 2 ~C 15 Heterocycloalkyl), 2 to 10 carbon atoms (C 2 ~C 10 Heterocycloalkyl), 2 to 8 carbon atoms (C 2~C 8 Heterocycloalkyl), 2 to 6 carbon atoms (C 2 ~C 6 Heterocycloalkyl), 2 to 5 carbon atoms (C 2 ~C 5 heterocycloalkyl), or 2 to 4 carbon atoms (C 2 ~C 4Examples of heterocycloalkyl radicals include, but are not limited to, heterocycloalkyls having a heterocycloalkyl group (heterocycloalkyl). In some embodiments, the heterocycloalkyl is a 3- to 6-membered heterocycloalkyl. In some embodiments, the heterocycloalkyl is a 5- to 6-membered heterocycloalkyl. Examples of such heterocycloalkyl radicals include aziridinyl, azetidinyl, dioxolanyl, thienyl[1,3]dithianyl, decahydroisoquinolyl, imidazolinyl, imidazolidinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, piperidinyl, piperazinyl, 4-piperidonyl, pyrrolidinyl, Examples of heterocycloalkyl include, but are not limited to, pyrazolidinyl, quinuclidinyl, thiazolidinyl, tetrahydrofuryl, trithianyl, tetrahydropyranyl, thiomorpholinyl, thiamorpholinyl, 1-oxo-thiomorpholinyl, 1,1-dioxo-thiomorpholinyl, 1,3-dihydroisobenzofuran-1-yl, 3-oxo-1,3-dihydroisobenzofuran-1-yl, methyl-2,3-oxo-1-dioxol-4-yl, and 2-oxo-1,3-dioxol-4-yl. The term heterocycloalkyl also includes all ring forms of carbohydrates, including, but not limited to, monosaccharides, disaccharides, and oligosaccharides. When referring to the number of carbon atoms in a heterocycloalkyl, it is understood that the number of carbon atoms in the heterocycloalkyl is not the same as the total number of atoms (including heteroatoms) that make up the heterocycloalkyl (i.e., the skeletal atoms of the heterocycloalkyl ring). Unless otherwise stated in the specification, heterocycloalkyl is optionally substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, and the like. In some embodiments, heterocycloalkyl is optionally substituted with, for example, oxo, halogen, methyl, ethyl, -CN, -CF 3 , -OH, -OMe, -NH 2 , or -NO 2In some embodiments, heterocycloalkyl is optionally substituted with oxo, halogen, methyl, ethyl, -CN, -CF 3 , -OH, or -OMe. In some embodiments, heterocycloalkyl is optionally substituted with halogen.

[0056] "Heterocycle" or "heterocyclyl" refers to a saturated, unsaturated, or aromatic ring containing one or more ring heteroatoms. Exemplary heteroatoms include N, O, Si, P, B, and S atoms. Heterocycles can include, for example, 3- to 10-membered monocyclic rings and 6- to 12-membered bicyclic rings, including spiro, fused, or bridged rings. Unless otherwise stated in the specification, a heterocyclyl radical is a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, optionally including a fused, bridged, or spiro ring system. The heteroatoms in a heterocyclyl radical are optionally oxidized. One or more nitrogen atoms, if present, are optionally quaternized. The heterocyclyl radical can be partially or fully saturated. The heterocyclyl is attached to the remainder of the molecule through any atom of the ring(s). Examples of such heterocyclyl radicals include, but are not limited to, dioxolanyl, thienyl[1,3]dithianyl, decahydroisoquinolyl, imidazolinyl, imidazolidinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, piperidinyl, piperazinyl, 4-piperidonyl, pyrrolidinyl, pyrazolidinyl, quinuclidinyl, thiazolidinyl, tetrahydrofuryl, trithianyl, tetrahydropyranyl, thiomorpholinyl, thiamorpholinyl, 1-oxo-thiomorpholinyl, and 1,1-dioxo-thiomorpholinyl. Unless stated otherwise in the specification, the term "heterocyclyl" is intended to include heterocyclyl radicals as defined above, optionally substituted by one or more substituents.For example, heterocyclyl is alkyl, alkenyl, alkynyl, halo, fluoroalkyl, oxo, thioxo, cyano, nitro, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted aralkynyl, optionally substituted carbocyclyl, optionally substituted carbocyclylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R. b -OR a , -R b -OC(O)-R a , -R b -OC(O)-OR a , -R b -OC(O)-N(R a ) 2 , -R b -N(R a ) 2 , -R b -C(O)R a , -R b -C(O)OR a , -R b -C(O)N(R a ) 2 , -R b -CN, -R b -OR e -C(O)N(R a ) 2 , -R b -N(R a )C(O)OR a , -R b -N(R a )C(O)R a , -R b -N(R a )S(O) t R a (wherein t is 1 or 2), -R b -S(O) t R a (wherein t is 1 or 2), -R b -S(O) t OR a (wherein t is 1 or 2), and -R b-S(O) t N(R a ) 2 where t is 1 or 2, and each R a are independently hydrogen, alkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), fluoroalkyl, cycloalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), cycloalkylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aralkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heteroaryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), or heteroarylalkyl (optionally substituted with halogen); and each R b are independently a direct bond or a straight or branched alkylene or alkenylene chain; R e is a straight or branched alkylene or alkenylene chain and each of the above substituents is unsubstituted unless otherwise indicated.

[0057] "Heteroaryl" or "aromatic heterocycle" refers to a ring system radical that contains carbon atom(s) and one or more ring heteroatoms (e.g., selected from the group consisting of nitrogen, oxygen, phosphorus, silicon, and sulfur), and at least one aromatic ring. In some embodiments, the heteroaryl is a 5- to 14-membered ring system radical that contains 1-13 carbon atoms and 1-6 heteroatoms selected from the group consisting of nitrogen, oxygen, phosphorus, and sulfur. The heteroaryl radical can be a monocyclic, bicyclic, tricyclic, or tetracyclic ring system that can include fused (when fused with a cycloalkyl or heterocycloalkyl ring, the heteroaryl is bonded through an aromatic ring atom) or bridged ring systems, and the nitrogen, carbon, or sulfur atoms in the heteroaryl radical can be optionally oxidized and the nitrogen atom can be optionally quaternized. In some embodiments, the heteroaryl is a 5- to 10-membered heteroaryl. In some embodiments, the heteroaryl is a 5- to 6-membered heteroaryl.Examples include azepinyl, acridinyl, benzimidazolyl, benzothiazolyl, benzindolyl, benzodioxolyl, benzofuranyl, benzoxazolyl, benzothiazolyl, benzothiadiazolyl, benzo[b][1,4]dioxepinyl, 1,4-benzodioxanyl, benzonaphthofuranyl, benzoxazolyl, benzodioxolyl, benzodioxinyl, benzopyranyl, benzopyranonyl, benzofuranyl, benzofuranonyl, benzothienyl (benzothiophenyl), benzotriazolyl, benzo[4,6]imidazo[1,2-a]pyridinyl, carbazolyl, cinnolinyl, dibenzofuranyl, dibenzothiophenyl, furanyl, furanonyl, isothiazolyl, imidazolyl group, indazolyl, indolyl, indazolyl, isoindolyl, indophenyl, iso ... Examples include, but are not limited to, dolinyl, isoindolinyl, isoquinolyl, indolizinyl, isoxazolyl, naphthyridinyl, oxadiazolyl, 2-oxoazepinyl, oxazolyl, oxiranyl, 1-oxidopyridinyl, 1-oxidopyrimidinyl, 1-oxidopyrazinyl, 1-oxidopyridazinyl, 1-phenyl-1H-pyrrolyl, phenazinyl, phenothiazinyl, phenoxazinyl, phthalazinyl, pteridinyl, purinyl, pyrrolyl, pyrazolyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, quinazolinyl, quinoxalinyl, quinolinyl, quinuclidinyl, isoquinolinyl, tetrahydroquinolinyl, thiazolyl, thiadiazolyl, triazolyl, tetrazolyl, triazinyl, and thiophenyl (i.e., thienyl). Unless otherwise stated in the specification, heteroaryl is optionally substituted with, for example, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, and the like. In some embodiments, heteroaryl is halogen, methyl, ethyl, -CN, -CF. 3 , -OH, -OMe, -NH 2 , or -NO 2 In some embodiments, heteroaryl is optionally substituted with halogen, methyl, ethyl, -CN, -CF 3, -OH, or -OMe. In some embodiments, heteroaryl is optionally substituted with halogen.

[0058] The term "substituted" refers to a moiety having a substituent replacing a hydrogen on one or more carbon or substitutable heteroatoms, e.g., NH, of the structure. It will be understood that "substituted" or "substituted with" includes the implicit proviso that such substitution is in accordance with the allowed valences of the replacing atoms and substituents, as well as the implicit proviso that the substitution results in a stable compound, i.e., a compound that does not spontaneously undergo transformation by rearrangement, cyclization, elimination, and the like. In certain embodiments, substituted refers to a moiety having a substituent replacing two hydrogen atoms on the same carbon atom, such as replacing two hydrogen atoms on a single carbon with an oxo, imino, or thioxo group. As used herein, the term "substituted" is intended to include all permissible substituents of organic compounds. In a broad aspect, the permissible substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and nonaromatic substituents of organic compounds. The permissible substituents can be one or more, the same, or different for appropriate organic compounds. For purposes of this disclosure, the heteroatoms such as nitrogen can have hydrogen substituents and / or any permissible substituents of organic compounds described herein which satisfy the valences of the heteroatoms.

[0059] In some embodiments, a substituent may be any of the substituents described herein, for example, halogen, hydroxy, oxo (=O), thioxo (=S), cyano (-CN), nitro (-NO 2 ), imino (=NH), oximo (=N-OH), hydrazino (=N-NH 2 ), -R b -OR a , -R b -OC(O)-R a , -R b -OC(O)-OR a , -R b -OC(O)-N(R a )2 , -R b -N(R a ) 2 , -R b -C(O)R a , -R b -C(O)OR a , -R b -C(O)N(R a ) 2 , -R b -OR c -C(O)N(R a ) 2 , -R b -N(R a )C(O)OR a , -R b -N(R a )C(O)R a , -R b -N(R a )S(O) t R a (wherein t is 1 or 2), -R b -S(O) t R a (wherein t is 1 or 2), -R b -S(O) t OR a (wherein t is 1 or 2), and -R b -S(O) t N(R a ) 2 where t is 1 or 2, as well as alkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, aralkynyl, cycloalkyl, cycloalkylalkyl, and heterocycle, any of which may be alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo (=O), thioxo (=S), cyano (-CN), nitro (-NO 2 ), imino (=NH), oximo (=N-OH), hydrazine (=N-NH 2 ),SCIENCE FICTION 5 , -R b -OR a , -R b -OC(O)-R a , -R b -OC(O)-OR a , -R b -OC(O)-N(R a ) 2 , -R b -N(R a ) 2 , -R b -C(O)R a , -R b -C(O)OR a , -R b -C(O)N(R a ) 2 , -R b -OR c -C(O)N(R a ) 2 , -R b -N(R a )C(O)OR a , -R b -N(R a )C(O)R a , -R b -N(R a )S(O) t R a (wherein t is 1 or 2), -R b -S(O) t R a (wherein t is 1 or 2), -R b- S(O) t OR a (wherein t is 1 or 2), and -R b -S(O) t N(R a ) 2 where t is 1 or 2, and each R a is independently selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, and heterocycle; a is, as far as valence permits, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, oxo (=O), thioxo (=S), cyano (-CN), nitro (-NO 2 ), imino (=NH), oximo (=N-OH), hydrazine (=N-NH 2 ), -R b -OR a , -R b-OC(O)-R a , -R b -OC(O)-OR a , -R b -OC(O)-N(R a ) 2 , -R b -N(R a ) 2 , -R b -C(O)R a , -R b -C(O)OR a , -R b -C(O)N(R a ) 2 , -R b -OR c -C(O)N(R a ) 2 , -R b -N(R a )C(O)OR a , -R b -N(R a )C(O)R a , -R b- N(R a )S(O) t R a (wherein t is 1 or 2), -R b- S(O) t R a (wherein t is 1 or 2), -R b- S(O) t OR a (wherein t is 1 or 2), and -R b- S(O) t N(R a ) 2 where t is 1 or 2, and each R b is independently a direct bond, or a straight or branched alkylene, alkenylene, or alkynylene chain; each R c is a straight or branched alkylene, alkenylene, or alkynylene chain.

[0060] As used in this specification and claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.

[0061] The term "salt" or "pharmaceutically acceptable salt" refers to salts derived from a variety of organic and inorganic counterions well known in the art. Pharmaceutically acceptable acid addition salts can be formed with inorganic and organic acids. Inorganic acids from which salts can be derived include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like. Organic acids from which salts can be derived include, for example, acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, and the like. Pharmaceutically acceptable base addition salts can be formed with inorganic and organic bases. Inorganic bases include, for example, sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum, and the like. Organic bases from which salts can be derived include, for example, primary, secondary, and tertiary amines, substituted amines, including naturally occurring substituted amines, cyclic amines, basic ion exchange resins, and reactants, specifically, for example, isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, and ethanolamine. In some embodiments, the pharma-ceutically acceptable base addition salts are selected from ammonium, potassium, sodium, calcium, and magnesium salts.

[0062] The phrases "parenteral administration" or "administered orally" as used herein mean modes of administration other than enteral and topical administration, usually by injection, and include, but are not limited to, intravenous, intramuscular, intraarterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, subcuticular, intraarticular, subcapsular, subarachnoid, intraspinal, and intrasternal injection and inhalation.

[0063] The phrase "pharmacologically acceptable" is employed to refer to compounds, materials, compositions, and / or dosage forms that are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without undue toxicity, irritation, allergic response, or other problem or complication, and are commensurate with a reasonable benefit / risk ratio.

[0064] The phrases "pharmacologically acceptable excipient" or "pharmacologically acceptable carrier" as used herein refer to pharma- ceutically acceptable materials, compositions, or vehicles, such as liquid or solid fillers, diluents, excipients, solvents, or encapsulating materials. Each carrier must be "acceptable" in the sense of being compatible with the other ingredients of the formulation and not harmful to the patient. Some examples of materials that can function as pharma-ceutically acceptable carriers include: (1) sugars, such as lactose, glucose, and sucrose; (2) starches, such as corn starch and potato starch; (3) cellulose and its derivatives, such as sodium carboxymethylcellulose, ethylcellulose, and cellulose acetate; (4) powdered tragacanth; (5) malt; (6) gelatin; (7) talc; (8) excipients, such as cocoa butter and suppository wax; (9) peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil, and oats; (10) oils such as soybean oil, (11) polyols such as glycerin, sorbitol, mannitol, and polyethylene glycols, (12) esters such as ethyl oleate and ethyl laurate, (13) agar, (14) buffers such as magnesium hydroxide and aluminum hydroxide, (15) alginic acid, (16) pyrogen-free water, (17) isotonic saline, (18) Ringer's solution, (19) ethyl alcohol, (20) phosphate buffer solutions, and (21) other non-toxic compatible substances employed in pharmaceutical formulations.

[0065] In certain embodiments, the term "prevent" or "preventing" in relation to a disease or disorder may refer to a compound that reduces the occurrence of a disorder or condition in a treated sample relative to an untreated control sample, or delays the onset of or reduces the severity of one or more symptoms of a disorder or condition relative to an untreated control sample in a statistical sample.

[0066] The terms "treat", "treating" or "treatment" as used herein can include alleviating, attenuating or ameliorating the symptoms of a disease or condition, preventing additional symptoms, ameliorating or preventing the underlying cause of the symptoms, inhibiting the disease or condition, e.g., arresting the onset of the disease or condition, relieving the disease or condition, causing regression of the disease or condition, alleviating conditions caused by the disease or condition, or halting the symptoms of the disease or condition, either prophylactically and / or therapeutically.

[0067] The term "effective amount" or "therapeutically effective amount" as used herein refers to a sufficient amount of a compound disclosed herein being administered that relieves to some extent one or more of the symptoms of the disease or condition being treated, e.g., cancer or inflammatory disease. In some embodiments, the result is a reduction and / or alleviation of the signs, symptoms, or causes of a disease, or any other desired change in a biological system. For example, an "effective amount" for therapeutic use is the amount of a composition comprising a compound disclosed herein that is required to provide a clinically significant reduction in a symptom of the disease. In some embodiments, the appropriate "effective" amount in any individual case is determined using techniques such as a dose escalation study.

[0068] The term "optionally" or "optionally" means that the subsequently described event or circumstance can occur, and that the description includes instances when the event or circumstance occurs and instances when it does not occur. For example, "optionally substituted alkyl" means either "alkyl" or "substituted alkyl" as defined above. Additionally, an optionally substituted group can be an unsubstituted (e.g., -CH 2 CH 3 ), full substitutions (e.g., -CF 2 CF 3 ), monosubstituted (e.g., -CH 2 CH 2 F) or can be substituted at any level between fully and monosubstituted (e.g., -CH 2 CHF 2 , -CH 2 CF 3 , -CF 2 CH 3 , -CFHCHF 2 etc.).

[0069] As used herein, the term "subject" may be a vertebrate, such as a mammal, fish, bird, reptile, or amphibian. Thus, the subject of the methods disclosed herein may be a human, a non-human primate, a horse, a pig, a rabbit, a dog, a sheep, a goat, a cow, a cat, a guinea pig, or a rodent. The term does not denote a particular age or sex. Thus, adult and newborn subjects, whether female or male, as well as fetuses, are intended to be encompassed. In one aspect, the subject is a mammal.

[0070] It is understood that the ranges provided herein are shorthand notations of all values ​​within the range. For example, the range of 1 to 50 is understood to include any number, combination of numbers, or subranges from the group consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50, as well as all intervening decimal values ​​between the aforementioned integers, such as, for example, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, and 1.9. With respect to subranges, "nested subranges" extending from either end of the range are specifically contemplated. For example, nested subranges of the exemplary range of 1 to 50 could include 1 to 10, 1 to 20, 1 to 30, and 1 to 40 in one direction, or 50 to 40, 50 to 30, 50 to 20, and 50 to 10 in the other direction.

[0071] B. Compounds of the Present Disclosure In one aspect, the disclosure provides a compound represented by formula (I), or a pharma- ceutically acceptable salt or solvate thereof: [ka] During the ceremony, X 1 is N or CR 1 and X 3 is N or CR 3 and X 7 is N or CR 7 and R 1 , R 3 , and R 7 each independently represents hydrogen, halo, -CN, -OR 11 , -SR 11 , -N(R 12 ) 2 , optionally substituted C 1~6 Alkyl, optionally substituted C 1~6Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 alkynyl, R 8 and R 9 Each of is independently hydrogen, halo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 alkynyl or R 8 and R 9 are taken together to form oxo or R 8 and R 9 together with the carbons to which they are attached form an optionally substituted 3- to 6-membered cycloalkyl or heterocycloalkyl; Ring A is phenyl, naphthyl, monocyclic heteroaryl, or bicyclic heteroaryl; R A Each of the groups is independently a halogen, -NO 2 , oxo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12)C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 ) 2 S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , and -S(O) 2 N(R 12 )(R 11 ), R 11 is hydrogen, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted -C 1~4 Alkylene-C 3~8 Cycloalkyl, optionally substituted -C 1~4 Alkylene-C 2~7 Heterocycloalkyl, optionally substituted -C 1~4 Alkylene-phenyl, or optionally substituted -C 1~4 alkylene-heteroaryl, R 12 each independently represents hydrogen, halogen, -OH, -NO 2 , -CN,C 1~6 Alkyl, C 1~6 Aminoalkyl, C 1~6 Hydroxyalkyl, C 1~6 Haloalkyl, C 1~6 Heteroalkyl, C 3~6 Carbocyclic rings and 3- to 6-membered heterocyclic rings; 3~6 The carbocycle and the 3- to 6-membered heterocycle are independently selected from halogen, -OH, oxo, amino, -NO 2 , C.N., C.1~6 Alkyl, C 1~6 Alkoxy and C 1~6 optionally substituted with one or more substituents selected from haloalkyl; B is a 6-membered heteroaryl, phenyl, or phenylisostere; R B1 , halo, -CN, -NO 2 , optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 )S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , -S(O) 2 N(R 12 )(R 11 ), optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~9 heterocycloalkyl, optionally substituted naphthyl, optionally substituted phenyl, optionally substituted monocyclic heteroaryl, or optionally substituted bicyclic heteroaryl; Each R Bare independently halo, -CN, -NO 2 , optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 )S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , -S(O) 2 N(R 12 )(R 11 ), optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~9 heterocycloalkyl, optionally substituted naphthyl, optionally substituted phenyl, optionally substituted monocyclic heteroaryl, or optionally substituted bicyclic heteroaryl; or R on adjacent atoms B1 and R B and one of, taken together with the atom to which they are attached, is optionally substituted phenyl, optionally substituted naphthyl, optionally substituted monocyclic heteroaryl, optionally substituted bicyclic heteroaryl, optionally substituted C 3~8Cycloalkyl or optionally substituted C 2~9 forming a heterocycloalkyl, or R on the same atom B1 and R B one of which, together with the atom to which they are attached, is an optionally substituted C 3~8 Cycloalkyl or optionally substituted C 2~9 forming a heterocycloalkyl, or R on the same atom B Two of them, together with the atoms to which they are attached, are optionally substituted C 3~8 Cycloalkyl or optionally substituted C 2~9 forming a heterocycloalkyl, m is 0, 1, 2, 3, or 4; n is 0, 1, 2, 3, or 4; p is 0 or 1.

[0072] In some embodiments, the compound of formula (I) is X 1 is N or CR 1 and X 3 is N or CR 3 and X 7 is N or CR 7 and R 1 , R 3 , and R 7 each independently represents hydrogen, halo, -CN, -OR 11 , -SR 11 , -N(R 12 ) 2 , optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 alkynyl, Alkyl, heteroalkyl, alkenyl, or alkynyl are independently selected from halogen, amino, oxo, -OH, -NO 2 , -CN, and C 1~3 Optionally substituted with one or more substituents selected from alkoxyl, R 8 and R 9 Each of is independently hydrogen, halo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 alkynyl or R 8 and R 9 are taken together to form oxo or R 8 and R 9 together with the carbons to which they are attached form an optionally substituted 3- to 6-membered cycloalkyl or heterocycloalkyl; Alkyl, alkenyl, alkynyl, cycloalkyl, or heterocycloalkyl are independently selected from halogen, amino, -OH, -NO 2 , oxo, -CN, C 1~3 Alkoxyl, C 1~3 Alkyl, and C 1~3 optionally substituted with one or more substituents selected from haloalkyl; Ring A is phenyl, naphthyl, monocyclic heteroaryl, or bicyclic heteroaryl; R A Each of the groups is independently a halogen, -NO 2 , oxo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, -OR 11 , -SR 11, -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 ) 2 S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , and -S(O) 2 N(R 12 )(R 11 ), Alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, or heterocycloalkyl are independently selected from halogen, -OH, -NO 2 , oxo, amino, -CN, C 1~6 Alkoxyl, C 1~6 Alkyl, C 1~6 Haloalkyl, C 3~6 Optionally substituted with one or more substituents selected from a carbocycle and a 3- to 6-membered heterocycle, 3~6 The carbocycle and the 3- to 6-membered heterocycle are independently selected from halogen, -OH, amino, -NO 2 , oxo, -CN, C 1~6 Alkyl, C 1~6 Alkoxy and C 1~6 optionally substituted with one or more substituents selected from haloalkyl; R 11 is hydrogen, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted -C 1~4 Alkylene-C 3~8 Cycloalkyl, optionally substituted -C 1~4 Alkylene-C 2~7 Heterocycloalkyl, optionally substituted -C 1~4 Alkylene-phenyl, or optionally substituted -C 1~4 alkylene-heteroaryl, Alkyl, alkenyl, alkynyl, heteroalkyl, alkylene, cycloalkyl, heterocycloalkyl, phenyl, or heteroaryl are independently selected from halogen, -OH, amino, -NO 2 , Oxo, C 1~6 Alkoxy, -CN, C 1~6 Alkyl, and C 1~6 optionally substituted with one or more substituents selected from haloalkyl; R 12 each independently represents hydrogen, halogen, -OH, -NO 2 , -CN,C 1~6 Alkyl, C 1~6 Aminoalkyl, C 1~6 Hydroxyalkyl, C 1~6 Haloalkyl, C 1~6 Heteroalkyl, C 3~6 Carbocyclic rings and 3- to 6-membered heterocyclic rings; 3~6 The carbocycle and the 3- to 6-membered heterocycle are independently selected from halogen, -OH, oxo, amino, -NO 2 , C.N., C. 1~6 Alkyl, C 1~6 Alkoxy and C 1~6 optionally substituted with one or more substituents selected from haloalkyl; B is a 6-membered heteroaryl, phenyl, or phenylisostere; R B1 , halo, -CN, -NO 2, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 )S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , -S(O) 2 N(R 12 )(R 11 ), optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~9 heterocycloalkyl, optionally substituted naphthyl, optionally substituted phenyl, optionally substituted monocyclic heteroaryl, or optionally substituted bicyclic heteroaryl; Each of alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, naphthyl, phenyl, or heteroaryl is independently selected from halogen, -NO 2 , oxo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 )S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , and -S(O) 2 N(R 12 )(R 11 ), wherein alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, or heterocycloalkyl is independently selected from halogen, -OH, -NO 2 , amino, -NH(C 1~6 alkyl), -N(C 1~6 Alkyl) 2 , oxo, -CN, C 1~3 Alkoxyl, C 1~3 Alkyl, and C 1~3 optionally substituted with one or more substituents selected from haloalkyl; Each R B are independently halo, -CN, -NO 2 , optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6Alkynyl, optionally substituted C 1~6 Heteroalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 )S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , -S(O) 2 N(R 12 )(R 11 ), optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~9 heterocycloalkyl, optionally substituted naphthyl, optionally substituted phenyl, optionally substituted monocyclic heteroaryl, or optionally substituted bicyclic heteroaryl; Each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, naphthyl, phenyl, or heteroaryl is independently selected from halogen, -OH, -NO 2 , amino, oxo, -CN, C 1~3 Alkoxyl, C 1~3 Alkyl, and C 1~3 optionally substituted with one or more substituents selected from haloalkyl, R on adjacent atoms B1 and R Band one of, taken together with the atom to which they are attached, is optionally substituted phenyl, optionally substituted naphthyl, optionally substituted monocyclic heteroaryl, optionally substituted bicyclic heteroaryl, optionally substituted C 3~8 Cycloalkyl or optionally substituted C 2~9 forming a heterocycloalkyl, Phenyl, naphthyl, heteroaryl, cycloalkyl, or heterocycloalkyl are independently selected from halogen, -OH, amino, -NO 2 , Oxo, C 1~6 Alkoxy, -CN, C 1~6 Alkyl, C 1~6 optionally substituted with one or more substituents selected from haloalkyl, R on the same atom B1 and R B one of which, together with the atom to which they are attached, is an optionally substituted C 3~8 Cycloalkyl or optionally substituted C 2~9 forming a heterocycloalkyl, Cycloalkyl or heterocycloalkyl are independently selected from halogen, -OH, amino, -NO 2 , Oxo, C 1~6 Alkoxy, -CN, C 1~6 Alkyl, C 1~6 optionally substituted with one or more substituents selected from haloalkyl, R on the same atom B Two of them, together with the atoms to which they are attached, are optionally substituted C 3~8 Cycloalkyl or optionally substituted C 2~9 forming a heterocycloalkyl, Cycloalkyl or heterocycloalkyl are independently selected from halogen, -OH, amino, -NO 2 , Oxo, C 1~6 Alkoxy, -CN, C 1~6 Alkyl, C 1~6 optionally substituted with one or more substituents selected from haloalkyl; m is 0, 1, 2, 3, or 4; n is 0, 1, 2, 3, or 4; p is 0 or 1.

[0073] In some embodiments of the compounds of formula (I), X 1 is N or CR 1 and X 3 is N or CR 3 and X 7 is N or CR 7 and R 1 , R 3 , and R 7 each independently represents hydrogen, halo, -CN, -OR 11 , -SR 11 , -N(R 12 ) 2 , optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 alkynyl, Alkyl, heteroalkyl, alkenyl, or alkynyl are independently selected from halogen, amino, oxo, -OH, -NO 2 , -CN, and C 1~3 Optionally substituted with one or more substituents selected from alkoxyl, R 8 and R 9 Each of is independently hydrogen, halo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 alkynyl or R 8 and R 9 are taken together to form oxo or R 8 and R 9together with the carbons to which they are attached form an optionally substituted 3- to 6-membered cycloalkyl or heterocycloalkyl; Alkyl, alkenyl, alkynyl, cycloalkyl, or heterocycloalkyl are independently selected from halogen, amino, -OH, -NO 2 , oxo, -CN, C 1~3 Alkoxyl, C 1~3 Alkyl, and C 1~3 optionally substituted with one or more substituents selected from haloalkyl; Ring A is phenyl, naphthyl, monocyclic heteroaryl, or bicyclic heteroaryl; R A Each of the groups is independently a halogen, -NO 2 , oxo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 ) 2 S(O) 2 (R 12 ), -S(O)R 12 , -S(O)2 R 12 , and -S(O) 2 N(R 12 )(R 11 ), Alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, or heterocycloalkyl are independently selected from halogen, -OH, -NO 2 , oxo, amino, -CN, C 1~6 Alkoxyl, C 1~6 Alkyl, C 1~6 Haloalkyl, C 3~6 Optionally substituted with one or more substituents selected from a carbocycle and a 3- to 6-membered heterocycle, 3~6 The carbocycle and the 3- to 6-membered heterocycle are independently selected from halogen, -OH, amino, -NO 2 , oxo, -CN, C 1~6 Alkyl, C 1~6 Alkoxy and C 1~6 optionally substituted with one or more substituents selected from haloalkyl; R 11 is hydrogen, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted -C 1~4 Alkylene-C 3~8 Cycloalkyl, optionally substituted -C 1~4 Alkylene-C 2~7 Heterocycloalkyl, optionally substituted -C 1~4 Alkylene-phenyl, or optionally substituted -C 1~4 alkylene-heteroaryl, Alkyl, alkenyl, alkynyl, heteroalkyl, alkylene, cycloalkyl, heterocycloalkyl, phenyl, or heteroaryl are independently selected from halogen, -OH, amino, -NO 2 , Oxo, C 1~6 Alkoxy, -CN, C 1~6 Alkyl, and C 1~6 optionally substituted with one or more substituents selected from haloalkyl; R 12 Each of the groups is independently hydrogen, -NO 2 , -CN,C 1~6 Alkyl, C 1~6 Aminoalkyl, C 1~6 Hydroxyalkyl, C 1~6 Haloalkyl, C 1~6 Heteroalkyl, C 3~6 Carbocyclic rings and 3- to 6-membered heterocyclic rings; 3~6 The carbocycle and the 3- to 6-membered heterocycle are independently selected from halogen, -OH, oxo, amino, -NO 2 , -CN,C 1~6 Alkyl, C 1~6 Alkoxy and C 1~6 optionally substituted with one or more substituents selected from haloalkyl; B is a 6-membered heteroaryl, phenyl, or phenylisostere; R B1 is an optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~9 heterocycloalkyl, optionally substituted naphthyl, optionally substituted phenyl, optionally substituted monocyclic heteroaryl, or optionally substituted bicyclic heteroaryl; Each of cycloalkyl, heterocycloalkyl, naphthyl, phenyl, or heteroaryl is independently selected from halogen, -NO 2 , oxo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 )S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , and -S(O) 2 N(R 12 )(R 11 ), wherein alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, or heterocycloalkyl is independently selected from halogen, -OH, -NO 2 , amino, -NH(C 1~6 alkyl), -N(C 1~6 Alkyl) 2 , oxo, -CN, C 1~3 Alkoxyl, C 1~3 Alkyl, and C 1~3 optionally substituted with one or more substituents selected from haloalkyl; Each R B are independently halo, -CN, -NO 2 , optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6Alkynyl, optionally substituted C 1~6 Heteroalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 )S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , -S(O) 2 N(R 12 )(R 11 ), optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~9 heterocycloalkyl, optionally substituted naphthyl, optionally substituted phenyl, optionally substituted monocyclic heteroaryl, or optionally substituted bicyclic heteroaryl; Each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, naphthyl, phenyl, or heteroaryl is independently selected from halogen, -OH, -NO 2 , amino, oxo, -CN, C 1~3 Alkoxyl, C 1~3 Alkyl, and C 1~3 optionally substituted with one or more substituents selected from haloalkyl, R on the same atom B Two of them, together with the atoms to which they are attached, are optionally substituted C 3~8Cycloalkyl or optionally substituted C 2~9 forming a heterocycloalkyl, Cycloalkyl or heterocycloalkyl are independently selected from halogen, -OH, amino, -NO 2 , Oxo, C 1~6 Alkoxy, -CN, C 1~6 Alkyl, C 1~6 optionally substituted with one or more substituents selected from haloalkyl; m is 1, 2, 3, or 4; n is 0, 1, 2, 3, or 4; p is 0 or 1.

[0074] In some embodiments, the compound of formula (I) is represented by formula (Ia): [ka] During the ceremony, X 1 is N or CR 1 and X 3 is N or CR 3 and X 7 is N or CR 7 and R 1 , R 3 , and R 7 each independently represents hydrogen, halo, -CN, -OR 11 , -SR 11 , -N(R 12 ) 2 , optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 alkynyl, Y 1 is N or CR Y1 and Y 2 is N or CR Y2 and Y3 is N or CR Y3 and Y 4 is N or CR Y4 and R Y1 , R Y2 , R Y3 , and R Y4 each independently represents hydrogen, halo, -CN, -OR 11 , -SR 11 , -N(R 12 ) 2 , optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 alkynyl, R 8 and R 9 Each of is independently hydrogen, halo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 alkynyl or R 8 and R 9 are taken together to form oxo or R 8 and R 9 together with the carbons to which they are attached form an optionally substituted 3- to 6-membered cycloalkyl or heterocycloalkyl; Ring A is phenyl, naphthyl, monocyclic heteroaryl, or bicyclic heteroaryl; R A Each of the groups is independently a halogen, -NO 2 , oxo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 ) 2 S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , and -S(O) 2 N(R 12 )(R 11 ), R 11 is hydrogen, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted -C 1~4 Alkylene-C 3~8 Cycloalkyl, optionally substituted -C 1~4 Alkylene-C 2~7 Heterocycloalkyl, optionally substituted -C 1~4 Alkylene-phenyl, or optionally substituted -C 1~4alkylene-heteroaryl, R 12 each independently represents hydrogen, halogen, -OH, -NO 2 , -CN,C 1~6 Alkyl, C 1~6 Aminoalkyl, C 1~6 Hydroxyalkyl, C 1~6 Haloalkyl, C 1~6 Heteroalkyl, C 3~6 Carbocyclic rings and 3- to 6-membered heterocyclic rings; 3~6 The carbocycle and the 3- to 6-membered heterocycle are independently selected from halogen, -OH, oxo, amino, -NO 2 , C.N., C. 1~6 Alkyl, C 1~6 Alkoxy and C 1~6 optionally substituted with one or more substituents selected from haloalkyl; R B1 is an optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~9 heterocycloalkyl, optionally substituted naphthyl, optionally substituted phenyl, optionally substituted monocyclic heteroaryl, or optionally substituted bicyclic heteroaryl; m is 1, 2, 3, or 4; p is 0 or 1.

[0075] In some embodiments, the compound of formula (I) is represented by formula (Ib): or a pharma- ceutically acceptable salt or solvate thereof. [ka]

[0076] In some embodiments of the compounds of Formula (I), (Ia), and (Ib), R 12 Each of the groups is independently hydrogen, -NO 2 , C.N., C. 1~6 Alkyl, C 1~6 Aminoalkyl, C 1~6 Hydroxyalkyl, C 1~6 Haloalkyl, C1~6 Heteroalkyl, C 3~6 Carbocyclic rings and 3- to 6-membered heterocyclic rings; 3~6 The carbocycle and the 3- to 6-membered heterocycle are independently selected from halogen, -OH, oxo, amino, -NO 2 , C.N., C. 1~6 Alkyl, C 1~6 Alkoxy and C 1~6 In some embodiments of the compounds of Formula (I), (Ia), and (Ib), R 12 each independently represents hydrogen, halogen, -OH, -NO 2 , C.N., C. 1~6 Alkyl, C 1~6 Aminoalkyl, C 1~6 Hydroxyalkyl, C 1~6 Haloalkyl, C 1~6 Heteroalkyl, C 3~6 Carbocyclic rings and 3- to 6-membered heterocyclic rings; 3~6 The carbocycle and the 3- to 6-membered heterocycle are independently selected from halogen, -OH, oxo, amino, -NO 2 , C.N., C. 1~6 Alkyl, C 1~6 Alkoxy and C 1~6 Optionally substituted with one or more substituents selected from haloalkyl.

[0077] In some embodiments of the compounds of Formula (I), (Ia), and (Ib), R 8 and R 9 Each of is independently hydrogen, —CN, optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 alkynyl or R 8 and R 9 are taken together to form oxo or R 8 and R 9together with the carbon to which they are attached form an optionally substituted 3- to 6-membered cycloalkyl or heterocycloalkyl.

[0078] In some embodiments of the compounds of Formula (I), (Ia), and (Ib), X 1 is N. In some embodiments, X 1 CR 1 In some embodiments, X 3 is N. In some embodiments, X 3 CR 3 In some embodiments, X 7 is N. In some embodiments, X 7 CR 7 It is.

[0079] In some embodiments of the compounds of Formula (I), (Ia), and (Ib), R 1 , R 3 , and R 7 Each of is independently hydrogen, —CN, optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 In some embodiments of the compounds of Formula (I), (Ia), and (Ib), R 1 , R 3 , and R 7 each independently represents hydrogen and C 1 ~C 6 is selected from alkyl. In one aspect, the disclosure provides a compound represented by formula (II), or a pharma- ceutically acceptable salt or solvate thereof: [ka] During the ceremony, X 1 is N or CR 1 and X 2 is N or CR2 and X 3 is N or CR 3 and X 5 is N or C, X 6 , N, NR 6 , C.R. 6 , C(R 6 ) 2 , S(=O) 2 , C(=O), or C(=S); X 7 , N, NR 7 ,O.S.,C.R. 7 , S(=O) 2 , C(=O), or C(=S); (i)X 2 , X 3 , and X 5 is N and X 6 If C(=O), then X 7 But O, S, CR 7 , C(=O), or C(=S); and (ii) X 2 , X 3 , and X 5 If N, then X 6 and X 7 At least one of is O, S, or S(=O) 2 , C(=O), or C(=S); [ka] is a single or double bond, R 1 , R 2 , R 3 , R 6 , and R 7 each independently represents hydrogen, halo, -CN, -OR 11 , -SR 11 , -N(R 12 ) 2 , optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6Alkenyl, and optionally substituted C 2~6 alkynyl, R 8 and R 9 Each of is independently hydrogen, —CN, optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 alkynyl or R 8 and R 9 are taken together to form oxo or R 8 and R 9 together with the carbons to which they are attached form an optionally substituted 3- to 6-membered cycloalkyl or heterocycloalkyl; Ring A is phenyl, naphthyl, monocyclic heteroaryl, or bicyclic heteroaryl; R A Each of the groups is independently a halogen, -NO 2 , oxo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R12 )C(O)N(R 12 )(R 11 ), -N(R 12 ) 2 S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , and -S(O) 2 N(R 12 )(R 11 ), R 11 is hydrogen, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted -C 1~4 Alkylene-C 3~8 Cycloalkyl, optionally substituted -C 1~4 Alkylene-C 2~7 Heterocycloalkyl, optionally substituted -C 1~4 Alkylene-phenyl, or optionally substituted -C 1~4 alkylene-heteroaryl, R 12 Each of the groups is independently hydrogen, -NO 2 , -CN,C 1~6 Alkyl, C 1~6 Aminoalkyl, C 1~6 Hydroxyalkyl, C 1~6 Haloalkyl and C 3~6 Carbocyclic ring, 3- to 6-membered heterocyclic ring, 3~6 The carbocycle and the 3- to 6-membered heterocycle are independently selected from halogen, -OH, oxo, amino, -NO 2 , -CN,C 1~6 Alkyl, C 1~6 Alkoxy and C 1~6optionally substituted with one or more substituents selected from haloalkyl; B is a 6-membered heteroaryl, phenyl, or phenylisostere; R B1 , halo, -CN, -NO 2 , optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 )S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , -S(O) 2 N(R 12 )(R 11 ), optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~9 heterocycloalkyl, optionally substituted naphthyl, optionally substituted phenyl, optionally substituted monocyclic heteroaryl, or optionally substituted bicyclic heteroaryl; Each R B are independently halo, -CN, -NO 2 , optionally substituted C 1~6Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 )S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , -S(O) 2 N(R 12 )(R 11 ), optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~9 heterocycloalkyl, optionally substituted naphthyl, optionally substituted phenyl, optionally substituted monocyclic heteroaryl, or optionally substituted bicyclic heteroaryl, or R on adjacent atoms B1 and R B and one of, taken together with the atom to which they are attached, is optionally substituted phenyl, optionally substituted naphthyl, optionally substituted monocyclic heteroaryl, optionally substituted bicyclic heteroaryl, optionally substituted C 3~8 Cycloalkyl or optionally substituted C 2~9 forming a heterocycloalkyl, or R on the same atom B1 and R B one of which, together with the atom to which they are attached, is an optionally substituted C 3~8 Cycloalkyl or optionally substituted C 2~9 forming a heterocycloalkyl, or R on the same atom B Two of them, together with the atoms to which they are attached, are optionally substituted C 3~8 Cycloalkyl or optionally substituted C 2~9 forming a heterocycloalkyl, m is 0, 1, 2, 3, or 4; n is 0, 1, 2, 3, or 4; p is 0 or 1.

[0080] In some embodiments of formula (II) or (II′), R 1 , R 2 , R 3 , R 6 , and R 7 Each of is independently hydrogen, —CN, optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 In some embodiments of formula (II) or (II'), R 1 , R 3 , R 6 , and R 7 each independently represents hydrogen and C 1~6 In some embodiments of formula (II) or (II'), R 1 , R 3 , R 6 , and R 7 is hydrogen. In some embodiments of formula (II) or (II'), (NR 6 R 6 is hydrogen, -CN, optionally substituted C 1~6Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 alkenyl, or optionally substituted C 2~6 In some embodiments of formula (II) or (II'), X is alkynyl. 6 , N, NR N6 , C.R. 6 , C(R 6 ) 2 , S(=O) 2 , C(=O), or C(=S), and R N6 is hydrogen, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 alkenyl, or optionally substituted C 2~6 In some embodiments of formula (II) or (II'), X is alkynyl. 6 is NR N6 and R N6 is hydrogen, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 alkenyl, or optionally substituted C 2~6 It is alkynyl.

[0081] In some embodiments of formula (II) or (II′), (NR 7 R 7 is hydrogen, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 alkenyl, or optionally substituted C 2~6 In some embodiments of formula (II) or (II'), X is alkynyl. 7 , N, NR N7 ,O.S.,C.R. 7 , S(=O) 2 , C(=O), or C(=S), and R N7is hydrogen, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 alkenyl, or optionally substituted C 2~6 In some embodiments of formula (II) or (II'), X is alkynyl. 7 is NR N7 and R N7 is hydrogen, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 alkenyl, or optionally substituted C 2~6 It is alkynyl.

[0082] In some embodiments of formula (II) or (II′), R 12 Each of the groups is independently hydrogen, -NO 2 , C.N., C. 1~6 Alkyl, C 1~6 Aminoalkyl, C 1~6 Hydroxyalkyl, C 1~6 Haloalkyl, C 1~6 Heteroalkyl, C 3~6 Carbocyclic rings and 3- to 6-membered heterocyclic rings; 3~6 The carbocycle and the 3- to 6-membered heterocycle are independently selected from halogen, -OH, oxo, amino, -NO 2 , C.N., C. 1~6 Alkyl, C 1~6 Alkoxy and C 1~6 In some embodiments of formula (II) or (II'), R 12 each independently represents hydrogen, halogen, -OH, -NO 2 , C.N., C. 1~6 Alkyl, C 1~6 Aminoalkyl, C 1~6 Hydroxyalkyl, C 1~6 Haloalkyl, C 1~6 Heteroalkyl, C 3~6 Carbocyclic rings and 3- to 6-membered heterocyclic rings;3~6 The carbocycle and the 3- to 6-membered heterocycle are independently selected from halogen, -OH, oxo, amino, -NO 2 , C.N., C. 1~6 Alkyl, C 1~6 Alkoxy and C 1~6 Optionally substituted with one or more substituents selected from haloalkyl.

[0083] In some embodiments of the compound of Formula (II) or (II′), R 8 and R 9 Each of is independently hydrogen, —CN, optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 alkynyl or R 8 and R 9 are taken together to form oxo or R 8 and R 9 together with the carbon to which they are attached form an optionally substituted 3- to 6-membered cycloalkyl or heterocycloalkyl.

[0084] In some embodiments of the compound of formula (II) or (II′), X 2 is N.

[0085] In some embodiments, the compound of formula (II) has the structure of formula (II'). [ka]

[0086] In some embodiments of formula (II′), X 5 is N.

[0087] In one aspect, the disclosure provides a compound represented by formula (II') or a pharma- ceutically acceptable salt or solvate thereof: [ka] During the ceremony, X 1 is N or CR 1 and X 2 is N or CR 2 and X 3 is N or CR 3 and X 5 is N, X 6 , N, NR N6 , C.R. 6 , C(R 6 ) 2 , S(=O) 2 , C(=O), or C(=S); X 7 , N, NR N7 ,O.S.,C.R. 7 , S(=O) 2 , C(=O), or C(=S); (i)X 2 , X 3 , and X 5 is N and X 6 If C(=O), then X 7 But O, S, CR 7 , C(=O), or C(=S); and (ii) X 2 , X 3 , and X 5 If N, then X 6 and X 7 At least one of is O, S, or S(=O) 2 , C(=O), or C(=S); [ka] is a single or double bond, R 1 , R 2 , R 3 , R 6 , and R 7 each independently represents hydrogen, halo, -CN, -OR 11 , -SR 11 , -N(R12 ) 2 , optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 alkynyl, R N6 and R N7 Each of is independently hydrogen, —CN, optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 alkynyl, R 8 and R 9 Each of is independently hydrogen, —CN, optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 alkynyl or R 8 and R 9 are taken together to form oxo or R 8 and R 9 together with the carbons to which they are attached form an optionally substituted 3- to 6-membered cycloalkyl or heterocycloalkyl; Ring A is phenyl, naphthyl, monocyclic heteroaryl, or bicyclic heteroaryl; R A Each of the groups is independently a halogen, -NO 2 , oxo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7Heterocycloalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 ) 2 S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , and -S(O) 2 N(R 12 )(R 11 ), R 11 is hydrogen, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted -C 1~4 Alkylene-C 3~8 Cycloalkyl, optionally substituted -C 1~4 Alkylene-C 2~7 Heterocycloalkyl, optionally substituted -C 1~4 Alkylene-phenyl, or optionally substituted -C 1~4 alkylene-heteroaryl, R12 Each of the groups independently represents -NO 2 , -CN,C 1~6 Alkyl, C 1~6 Aminoalkyl, C 1~6 Hydroxyalkyl, C 1~6 Haloalkyl and C 3~6 Carbocyclic ring, 3- to 6-membered heterocyclic ring, 3~6 The carbocycle and the 3- to 6-membered heterocycle are independently selected from halogen, -OH, oxo, amino, -NO 2 , -CN,C 1~6 Alkyl, C 1~6 Alkoxy and C 1~6 optionally substituted with one or more substituents selected from haloalkyl; B is a 6-membered heteroaryl, phenyl, or phenylisostere; R B1 , halo, -CN, -NO 2 , optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 )S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , -S(O)2 N(R 12 )(R 11 ), optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~9 heterocycloalkyl, optionally substituted naphthyl, optionally substituted phenyl, optionally substituted monocyclic heteroaryl, or optionally substituted bicyclic heteroaryl; Each R B are independently halo, -CN, -NO 2 , optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 )S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , -S(O) 2 N(R 12 )(R 11 ), optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~9heterocycloalkyl, optionally substituted naphthyl, optionally substituted phenyl, optionally substituted monocyclic heteroaryl, or optionally substituted bicyclic heteroaryl; or R on adjacent atoms B1 and R B and one of, taken together with the atom to which they are attached, is optionally substituted phenyl, optionally substituted naphthyl, optionally substituted monocyclic heteroaryl, optionally substituted bicyclic heteroaryl, optionally substituted C 3~8 Cycloalkyl or optionally substituted C 2~9 forming a heterocycloalkyl, or R on the same atom B1 and R B one of which, together with the atom to which they are attached, is an optionally substituted C 3~8 Cycloalkyl or optionally substituted C 2~9 forming a heterocycloalkyl, or R on the same atom B Two of them, together with the atoms to which they are attached, are optionally substituted C 3~8 Cycloalkyl or optionally substituted C 2~9 forming a heterocycloalkyl, m is 1, 2, 3, or 4; n is 0, 1, 2, 3, or 4; p is 0 or 1.

[0088] In some embodiments of Formula (II) and Formula (II'), X 1 is N or CR 1 and X 2 is N or CR 2 and X 3 is N or CR 3 and X 5 is N, X 6, N, NR 6 , C.R. 6 , S(=O) 2 , C(=O), or C(=S); X 7 , N, NR 7 ,O.S.,C.R. 7 , S(=O) 2 , C(=O), or C(=S); (i)X 2 , X 3 , and X 5 is N and X 6 If C(=O), then X 7 But O, S, CR 7 , C(=O), or C(=S); and (ii) X 2 , X 3 , and X 5 If N, then X 6 and X 7 At least one of is O, S, or S(=O) 2 , C(=O), or C(=S); [ka] is a single or double bond, R 1 , R 2 , R 3 , R 6 , and R 7 each independently represents hydrogen, halo, -CN, -OR 11 , -SR 11 , -N(R 12 ) 2 , optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 alkynyl, Alkyl, heteroalkyl, alkenyl, or alkynyl are independently selected from halogen, amino, oxo, -OH, -NO 2 , -CN, and C 1~3 Optionally substituted with one or more substituents selected from alkoxyl, R 8 and R 9 Each of is independently hydrogen, halo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 alkynyl or R 8 and R 9 are taken together to form oxo or R 8 and R 9 together with the carbons to which they are attached form an optionally substituted 3- to 6-membered cycloalkyl or heterocycloalkyl; Alkyl, alkenyl, alkynyl, cycloalkyl, or heterocycloalkyl are independently selected from halogen, amino, -OH, -NO 2 , oxo, -CN, C 1~3 Alkoxyl, C 1~3 Alkyl, and C 1~3 optionally substituted with one or more substituents selected from haloalkyl; Ring A is phenyl, naphthyl, monocyclic heteroaryl, or bicyclic heteroaryl; R A Each of the groups is independently a halogen, -NO 2 , oxo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 ) 2 S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , and -S(O) 2 N(R 12 )(R 11 ), Alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, or heterocycloalkyl are independently selected from halogen, -OH, -NO 2 , oxo, amino, -CN, C 1~6 Alkoxyl, C 1~6 Alkyl, C 1~6 Haloalkyl, C 3~6 Optionally substituted with one or more substituents selected from a carbocycle and a 3- to 6-membered heterocycle, 3~6 The carbocycle and the 3- to 6-membered heterocycle are independently selected from halogen, -OH, amino, -NO 2 , oxo, -CN, C 1~6 Alkyl, C 1~6 Alkoxy and C 1~6 optionally substituted with one or more substituents selected from haloalkyl; R 11 is hydrogen, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7Heterocycloalkyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted -C 1~4 Alkylene-C 3~8 Cycloalkyl, optionally substituted -C 1~4 Alkylene-C 2~7 Heterocycloalkyl, optionally substituted -C 1~4 Alkylene-phenyl, or optionally substituted -C 1~4 alkylene-heteroaryl, Alkyl, alkenyl, alkynyl, heteroalkyl, alkylene, cycloalkyl, heterocycloalkyl, phenyl, or 5- or 6-membered heteroaryl are independently selected from halogen, -OH, amino, -NO 2 , Oxo, C 1~6 Alkoxy, -CN, C 1~6 Alkyl, C 1~6 optionally substituted with one or more substituents selected from haloalkyl; R 12 Each of the groups is independently hydrogen, -NO 2 , -CN,C 1~6 Alkyl, C 1~6 Aminoalkyl, C 1~6 Hydroxyalkyl, C 1~6 Haloalkyl and C 3~6 Carbocyclic ring, 3- to 6-membered heterocyclic ring, 3~6 The carbocycle and the 3- to 6-membered heterocycle are independently selected from halogen, -OH, oxo, amino, -NO 2 , -CN,C 1~6 Alkyl, C 1~6 Alkoxy and C 1~6 optionally substituted with one or more substituents selected from haloalkyl; B is a 6-membered heteroaryl, phenyl, or phenylisostere; R B1 , halo, -CN, -NO 2 , optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C1~6 Heteroalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 )S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , -S(O) 2 N(R 12 )(R 11 ), optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~9 heterocycloalkyl, optionally substituted naphthyl, optionally substituted phenyl, optionally substituted monocyclic heteroaryl, or optionally substituted bicyclic heteroaryl; Each of alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, naphthyl, phenyl, or heteroaryl is independently selected from halogen, -NO 2 , oxo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, -OR 11 , -SR11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 )S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , and -S(O) 2 N(R 12 )(R 11 ), wherein alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, or heterocycloalkyl is independently selected from halogen, -OH, -NO 2 , amino, oxo, -CN, C 1~3 Alkoxyl, C 1~3 Alkyl, and C 1~3 optionally substituted with one or more substituents selected from haloalkyl; Each R B are independently halo, -CN, -NO 2 , optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12, -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 )S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , -S(O) 2 N(R 12 )(R 11 ), optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~9 heterocycloalkyl, optionally substituted naphthyl, optionally substituted phenyl, optionally substituted monocyclic heteroaryl, or optionally substituted bicyclic heteroaryl; Each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, naphthyl, phenyl, or heteroaryl is independently selected from halogen, -OH, -NO 2 , amino, oxo, -CN, C 1~3 Alkoxyl, C 1~3 Alkyl, and C 1~3 optionally substituted with one or more substituents selected from haloalkyl, R on adjacent atoms B1 and R B and one of, taken together with the atom to which they are attached, is optionally substituted phenyl, optionally substituted naphthyl, optionally substituted monocyclic heteroaryl, optionally substituted bicyclic heteroaryl, optionally substituted C 3~8 Cycloalkyl or optionally substituted C 2~9 forming a heterocycloalkyl, Phenyl, naphthyl, heteroaryl, cycloalkyl, or heterocycloalkyl are independently selected from halogen, -OH, amino, -NO 2 , Oxo, C 1~6 Alkoxy, -CN, C 1~6 Alkyl, C 1~6 optionally substituted with one or more substituents selected from haloalkyl, R on the same atom B1 and R B one of which, together with the atom to which they are attached, is an optionally substituted C 3~8 Cycloalkyl or optionally substituted C 2~9 forming a heterocycloalkyl, Cycloalkyl or heterocycloalkyl are independently selected from halogen, -OH, amino, -NO 2 , Oxo, C 1~6 Alkoxy, -CN, C 1~6 Alkyl, C 1~6 optionally substituted with one or more substituents selected from haloalkyl, R on the same atom B Two of them, together with the atoms to which they are attached, are optionally substituted C 3~8 Cycloalkyl or optionally substituted C 2~9 forming a heterocycloalkyl, Cycloalkyl or heterocycloalkyl are independently selected from halogen, -OH, amino, -NO 2 , Oxo, C 1~6 Alkoxy, -CN, C 1~6 Alkyl, C 1~6 optionally substituted with one or more substituents selected from haloalkyl; m is 0, 1, 2, 3, or 4; n is 0, 1, 2, 3, or 4; p is 0 or 1.

[0089] In some embodiments of formula (II) and (II′), X 6 is NR N6 and R N6is hydrogen, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 alkenyl, or optionally substituted C 2~6 In some embodiments of formula (II) and (II′), X is alkynyl. 7 is NR N7 and R N7 is hydrogen, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 alkenyl, or optionally substituted C 2~6 It is alkynyl.

[0090] In some embodiments of formula (II) and (II′), R 12 each independently represents hydrogen, halogen, -OH, -NO 2 , -CN,C 1~6 Alkyl, C 1~6 Aminoalkyl, C 1~6 Hydroxyalkyl, C 1~6 Haloalkyl and C 3~6 Carbocyclic ring, 3- to 6-membered heterocyclic ring, 3~6 The carbocycle and the 3- to 6-membered heterocycle are independently selected from halogen, -OH, oxo, amino, -NO 2 , -CN,C 1~6 Alkyl, C 1~6 Alkoxy and C 1~6 Optionally substituted with one or more substituents selected from haloalkyl.

[0091] In some embodiments, X 1 , X 2 , X 3 At least two of X are N. 6 or X 7 At least one of is N.

[0092] In some embodiments, X 2 is N and X5 If N, then R 1 , R 3 , R 6 , and R 7 Each of 1 ~C 6 It is an alkyl.

[0093] In some embodiments of formula (I), (Ia), (Ib), (II), or (II'), [ka] teeth, [ka] and Y 1 is N or CR Y1 and Y 2 is N or CR Y2 and Y 3 is N or CR Y3 and Y 4 is N or CR Y4 and R Y1 , R Y2 , R Y3 , and R Y4 each independently represents hydrogen, halo, -CN, -OR 11 , -SR 11 , -N(R 12 ) 2 , optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 alkynyl.

[0094] In some embodiments of formula (I), (Ia), (Ib), (II), or (II′), X 1 is N. In some embodiments, X 2is N. In some embodiments, X 3 is N. In some embodiments, X 5 is N. In some embodiments, X 6 is N. In some embodiments, X 7 is N.

[0095] In some embodiments, the compound of formula (II) or (II') has the structure of formula (IIa): [ka]

[0096] In some embodiments, the compound of Formula (II) or (II') has the structure of Formula (IIa-1): [ka] During the ceremony, X 1 is N or CR 1 and X 2 is N or CR 2 and X 3 is N or CR 3 and X 7 is NR 7 , O, S, S(=O) 2 , C(=O), or C(=S); R 1 , R 2 , R 3 , and R 7 each independently represents hydrogen, halo, -CN, -OR 11 , -SR 11 , -N(R 12 ) 2 , optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 alkynyl, Y1 is N or CR Y1 and Y 2 is N or CR Y2 and Y 3 is N or CR Y3 and Y 4 is N or CR Y4 and R Y1 , R Y2 , R Y3 , and R Y4 each independently represents hydrogen, halo, -CN, -OR 11 , -SR 11 , -N(R 12 ) 2 , optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 alkynyl, R 8 and R 9 Each of is independently hydrogen, halo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 alkynyl or R 8 and R 9 are taken together to form oxo or R 8 and R 9 together with the carbons to which they are attached form an optionally substituted 3- to 6-membered cycloalkyl or heterocycloalkyl; Ring A is phenyl, naphthyl, monocyclic heteroaryl, or bicyclic heteroaryl; R A Each of the groups is independently a halogen, -NO 2 , oxo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 ) 2 S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , and -S(O) 2 N(R 12 )(R 11 ), R 11 is hydrogen, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted -C 1~4 Alkylene-C 3~8 Cycloalkyl, optionally substituted -C1~4 Alkylene-C 2~7 Heterocycloalkyl, optionally substituted -C 1~4 Alkylene-phenyl, or optionally substituted -C 1~4 alkylene-heteroaryl, R 12 Each of the groups is independently hydrogen, -NO 2 , -CN,C 1~6 Alkyl, C 1~6 Aminoalkyl, C 1~6 Hydroxyalkyl, C 1~6 Haloalkyl and C 3~6 Carbocyclic ring, 3- to 6-membered heterocyclic ring, 3~6 The carbocycle and the 3- to 6-membered heterocycle are independently selected from halogen, -OH, oxo, amino, -NO 2 , -CN,C 1~6 Alkyl, C 1~6 Alkoxy and C 1~6 optionally substituted with one or more substituents selected from haloalkyl; R B1 is an optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~9 heterocycloalkyl, optionally substituted naphthyl, optionally substituted phenyl, optionally substituted monocyclic heteroaryl, or optionally substituted bicyclic heteroaryl; m is 1, 2, 3, or 4; p is 0 or 1.

[0097] In some embodiments of formulas (IIa-1) and (II′), X 7 is NR N7 and R N7 is hydrogen, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 alkenyl, or optionally substituted C 2~6 It is alkynyl.

[0098] In some embodiments, the compound of formula (II) or (II') has the structure of formula (IIa-1a): [ka]

[0099] In some embodiments, the compound of formula (II) or (II') has the structure of formula (IIb): [ka]

[0100] In some embodiments, the compound of Formula (II) or (II') has the structure of Formula (IIb-1): [ka] During the ceremony, X 1 is N or CR 1 and X 2 is N or CR 2 and X 3 is N or CR 3 and X 1 , X 2 , and X 3 is N; R 1 , R 2 , and R 3 each independently represents hydrogen, halo, -CN, -OR 11 , -SR 11 , -N(R 12 ) 2 , optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 alkynyl, Y 1 is N or CR Y1 and Y 2 is N or CR Y2 and Y 3 is N or CR Y3 and Y 4 is N or CR Y4 and R Y1 , R Y2 , R Y3 , and R Y4 each independently represents hydrogen, halo, -CN, -OR 11 , -SR 11 , -N(R 12 ) 2 , optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 alkynyl, R 8 and R 9 Each of is independently hydrogen, halo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 alkynyl or R 8 and R 9 are taken together to form oxo or R 8 and R 9 together with the carbons to which they are attached form an optionally substituted 3- to 6-membered cycloalkyl or heterocycloalkyl; Ring A is phenyl, naphthyl, monocyclic heteroaryl, or bicyclic heteroaryl; R A Each of the groups is independently a halogen, -NO 2 , oxo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6Alkynyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 ) 2 S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , and -S(O) 2 N(R 12 )(R 11 ), R 11 is hydrogen, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted -C 1~4 Alkylene-C 3~8 Cycloalkyl, optionally substituted -C 1~4 Alkylene-C 2~7Heterocycloalkyl, optionally substituted -C 1~4 Alkylene-phenyl, or optionally substituted -C 1~4 alkylene-heteroaryl, R 12 Each of the groups is independently hydrogen, -NO 2 , -CN,C 1~6 Alkyl, C 1~6 Aminoalkyl, C 1~6 Hydroxyalkyl, C 1~6 Haloalkyl and C 3~6 Carbocyclic ring, 3- to 6-membered heterocyclic ring, 3~6 The carbocycle and the 3- to 6-membered heterocycle are independently selected from halogen, -OH, oxo, amino, -NO 2 , -CN,C 1~6 Alkyl, C 1~6 Alkoxy and C 1~6 optionally substituted with one or more substituents selected from haloalkyl; R B1 , halo, -CN, -NO 2 , optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 )S(O) 2 (R 12), -S(O)R 12 , -S(O) 2 R 12 , -S(O) 2 N(R 12 )(R 11 ), optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~9 heterocycloalkyl, optionally substituted naphthyl, optionally substituted phenyl, optionally substituted monocyclic heteroaryl, or optionally substituted bicyclic heteroaryl; m is 1, 2, 3, or 4; p is 0 or 1.

[0101] In some embodiments, the compound of formula (II) or (II') has the structure of formula (IIb-1a): [ka]

[0102] In some embodiments, the compound of Formula (II) has the structure of Formula (IIc): [ka]

[0103] In some embodiments, the compound of formula (II) or (II') has the structure of formula (IIc'). [ka]

[0104] In some embodiments, the compound of Formula (II) or (II') has the structure of Formula (IIc-1): [ka] During the ceremony, R 1 , R 3 , and R 7each independently represents hydrogen, halo, -CN, -OR 11 , -SR 11 , -N(R 12 ) 2 , optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 alkynyl, Y 1 is N or CR Y1 and Y 2 is N or CR Y2 and Y 3 is N or CR Y3 and Y 4 is N or CR Y4 and R Y1 , R Y2 , R Y3 , and R Y4 each independently represents hydrogen, halo, -CN, -OR 11 , -SR 11 , -N(R 12 ) 2 , optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 alkynyl, R 8 and R 9 Each of is independently hydrogen, —CN, optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 alkynyl or R 8 and R 9 are taken together to form oxo or R 8 and R 9together with the carbons to which they are attached form an optionally substituted 3- to 6-membered cycloalkyl or heterocycloalkyl; Ring A is phenyl, naphthyl, monocyclic heteroaryl, or bicyclic heteroaryl; R A Each of the groups is independently a halogen, -NO 2 , oxo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 ) 2 S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , and -S(O) 2 N(R 12 )(R 11 ), R 11 is hydrogen, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted -C 1~4 Alkylene-C 3~8 Cycloalkyl, optionally substituted -C 1~4 Alkylene-C 2~7 Heterocycloalkyl, optionally substituted -C 1~4 Alkylene-phenyl, or optionally substituted -C 1~4 alkylene-heteroaryl, R 12 Each of the groups is independently hydrogen, -NO 2 , -CN,C 1~6 Alkyl, C 1~6 Aminoalkyl, C 1~6 Hydroxyalkyl, C 1~6 Haloalkyl and C 3~6 Carbocyclic ring, 3- to 6-membered heterocyclic ring, 3~6 The carbocycle and the 3- to 6-membered heterocycle are independently selected from halogen, -OH, oxo, amino, -NO 2 , -CN,C 1~6 Alkyl, C 1~6 Alkoxy and C 1~6 optionally substituted with one or more substituents selected from haloalkyl; R B1 is an optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~9 heterocycloalkyl, optionally substituted naphthyl, optionally substituted phenyl, optionally substituted monocyclic heteroaryl, or optionally substituted bicyclic heteroaryl; m is 1, 2, 3, or 4; p is 0 or 1.

[0105] In some embodiments, the compound of formula (II) has the structure of formula (IId): [ka]

[0106] In some embodiments, the compound of formula (II) or (II') has the structure of formula (IId'). [ka]

[0107] In some embodiments, the compound of formula (II) or (II') has the structure of formula (IId-1): [ka]

[0108] In some embodiments, the compound of formula (II) or (II') has the structure of formula (IIe): [ka]

[0109] In some embodiments, the compound of formula (II) has the structure of formula (IIf): [ka]

[0110] In some embodiments, the compound of formula (II) or (II') has the structure of formula (IIg): [ka] =

[0111] In some embodiments of Formula (I), (Ia), (Ib), (II), (II'), (IIc'), (IId'), (IIa), (IIa-1), (IIa-1a), (IIb), (IIb-1), (IIb-1a), (IIc), (IIc-1), (IId), (IId-1), (IIe), (IIf), or (IIg), ring A is phenyl. In some embodiments, [ka] teeth, [ka] In some embodiments, ring A is naphthyl. In some embodiments, ring A is a 5- or 6-membered monocyclic heteroaryl. In some embodiments, ring A is pyridine, pyrimidine, pyrazine, pyridazine, triazine, imidazole, pyrazole, triazole, oxazole, isoxazole, or thiophene. In some embodiments, ring A is a 6-membered monocyclic heteroaryl containing 1-3 heteroatoms. In some embodiments, ring A is pyridine. In some embodiments, ring A is pyrimidine. In some embodiments, [ka] teeth, [ka] In some embodiments, ring A is a bicyclic heteroaryl. In some embodiments, ring A is a fused 5-6, 6-6, or 6-5 bicyclic heteroaryl.

[0112] In some embodiments of formula (I), (Ia), (Ib), (II), (II′), (IIa), (IIa-1), (IIa-1a), (IIb), (IIb-1), (IIb-1a), (IIc), (IIc-1), (IId), (IIc′), (IId′), (IId-1), (IIe), (IIf), or (IIg), R Aare independently halogen, -NO 2 , oxo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 ) 2 S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , and -S(O) 2 N(R 12 )(R 11 In some embodiments, R A independently, -NO 2 , oxo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, -OR 11 , -SR 11 , -N(R 12 )(R11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 ) 2 S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , and -S(O) 2 N(R 12 )(R 11 ) is selected.

[0113] In some embodiments of formula (I), (Ia), (Ib), (II), (II′), (IIa), (IIa-1), (IIa-1a), (IIb), (IIb-1), (IIb-1a), (IIc), (IIc-1), (IId), (IIc′), (IId′), (IId-1), (IIe), (IIf), or (IIg), R A are independently halogen, -OH, -NO 2 , amino, -CN, C 1~6 Alkoxyl, C 1~6 Alkyl, C 1~6 Haloalkyl, C 3~6 is independently substituted with one or more substituents selected from a carbocycle and a 3- to 6-membered heterocycle; 3~6 The carbocycle and the 3- to 6-membered heterocycle are independently selected from halogen, -OH, amino, -NO 2 , oxo, -CN, C 1~6 Alkyl, C 1~6 Alkoxy and C 1~6 In some embodiments, R is optionally substituted with one or more substituents selected from haloalkyl.A independently, -NO 2 , oxo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 ) 2 S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , and -S(O) 2 N(R 12 )(R 11 ) is selected.

[0114] In some embodiments of formula (I), (Ia), (Ib), (II), (II'), (IIc'), (IId'), (IIa), (IIa-1), (IIa-1a), (IIb), (IIb-1), (IIb-1a), (IIc), (IIc-1), (IId), (IId-1), (IIe), (IIf), or (IIg), [ka] teeth, [ka] [ka] In some embodiments, [ka] teeth, [ka] In some embodiments, [ka] teeth, [ka] In some embodiments, [ka] teeth, [ka] In some embodiments, [ka] teeth, [ka] In some embodiments, [ka] teeth, [ka] In some embodiments, [ka] teeth, [ka] In some embodiments, [ka] teeth, [ka] In some embodiments, [ka] teeth, [ka] In some embodiments, [ka] teeth, [ka] It is.

[0115] In some embodiments of formula (I), (Ia), (Ib), (II), (II'), (IIc'), (IId'), (IIa), (IIa-1), (IIa-1a), (IIb), (IIb-1), (IIb-1a), (IIc), (IIc-1), (IId), (IId-1), (IIe), (IIf), or (IIg), p is 1. In some embodiments, p is 0.

[0116] In some embodiments of formula (I), (Ia), (Ib), (II), (II′), (IIc′), (IId′), (IIa), (IIa-1), (IIa-1a), (IIb), (IIb-1), (IIb-1a), (IIc), (IIc-1), (IId), (IId-1), (IIe), (IIf), or (IIg), R 8 and R 9 Each of is independently hydrogen, halo, -CN, optionally substituted C1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 In some embodiments, R is selected from alkynyl. 8 and R 9 taken together form oxo. In some embodiments, R 8 and R 9 taken together with the carbons to which they are attached form an optionally substituted 3- to 6-membered cycloalkyl or heterocycloalkyl. In some embodiments, R 8 and R 9 Each of is independently hydrogen, —CN, optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 alkynyl or R 8 and R 9 are taken together to form oxo or R 8 and R 9 together with the carbon to which they are attached form an optionally substituted 3- to 6-membered cycloalkyl or heterocycloalkyl.

[0117] In some embodiments of Formula (I), (Ia), (Ib), (II), (II'), (IIc'), (IId'), (IIa), (IIa-1), (IIa-1a), (IIb), (IIb-1), (IIb-1a), (IIc), (IIc-1), (IId), (IId-1), (IIe), (IIf), or (IIg), B is a ring. In some embodiments of formula (I), (Ia), (Ib), (II), (II'), (IIc'), (IId'), (IIa), (IIa-1), (IIa-1a), (IIb), (IIb-1), (IIb-1a), (IIc), (IIc-1), (IId), (IId-1), (IIe), (IIf), or (IIg), ring B is phenyl or 6-membered heteroaryl. In some embodiments, ring B is phenyl, pyridine, pyrimidine, pyrazine, pyridazine, or triazine.

[0118] In some embodiments of formula (I), (Ia), (Ib), (II), (II'), (IIc'), (IId'), (IIa), (IIa-1), (IIa-1a), (IIb), (IIb-1), (IIb-1a), (IIc), (IIc-1), (IId), (IId-1), (IIe), (IIf), or (IIg), B is a phenyl isostere. In some embodiments, B is cubane. In some embodiments, B is [ka] and n is 0. In some embodiments, [ka] teeth, [ka] It is.

[0119] In some embodiments of formula (I), (Ia), (Ib), (II), (II′), (IIc′), (IId′), (IIa), (IIa-1), (IIa-1a), (IIb), (IIb-1), (IIb-1a), (IIc), (IIc-1), (IId), (IId-1), (IIe), (IIf), or (IIg), R B1 , halo, -CN, -NO 2 , optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 )S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , -S(O) 2 N(R 12 )(R 11 ), optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~9 In some embodiments, R is a heterocycloalkyl, an optionally substituted phenyl, an optionally substituted monocyclic heteroaryl, or an optionally substituted bicyclic heteroaryl. B1 -CN, -NO 2, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 )S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , -S(O) 2 N(R 12 )(R 11 ), optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~9 In some embodiments, R is a heterocycloalkyl, an optionally substituted phenyl, an optionally substituted monocyclic heteroaryl, or an optionally substituted bicyclic heteroaryl. B1 is an optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~9 In some embodiments, R is a heterocycloalkyl, an optionally substituted phenyl, an optionally substituted monocyclic heteroaryl, or an optionally substituted bicyclic heteroaryl. B1is an optionally substituted monocyclic 5-6 membered heterocycloalkyl or heteroaryl. In some embodiments, R B1 is an optionally substituted C 3~8 In some embodiments, R B1 is C 3 In some embodiments, R B1 is C 5 In some embodiments, R B1 is C 6 In some embodiments, R B1 is optionally substituted phenyl. In some embodiments, R B1 is an optionally substituted C 2~9 In some embodiments, R B1 is C 3 In some embodiments, R B1 is C 5 In some embodiments, R B1 is C 6 In some embodiments, R B1 is an optionally substituted monocyclic heteroaryl. In some embodiments, R B1 is an optionally substituted bicyclic heteroaryl.

[0120] In some embodiments of formula (I), (Ia), (Ib), (II), (II′), (IIc′), (IId′), (IIa), (IIa-1), (IIa-1a), (IIb), (IIb-1), (IIb-1a), (IIc), (IIc-1), (IId), (IId-1), (IIe), (IIf), or (IIg), R B1 is an optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~9In some embodiments, R is an optionally substituted heterocycloalkyl, an optionally substituted naphthyl, an optionally substituted phenyl, an optionally substituted monocyclic heteroaryl, or an optionally substituted bicyclic heteroaryl. B1 is an optionally substituted 5-membered monocyclic heteroaryl having 1-4 heteroatoms selected from N, O, S, and P. In some embodiments, R B1 is imidazole, pyrazole, triazole, or tetrazole, each of which is optionally substituted. In some embodiments, R B1 is an optionally substituted fused 5-6, 6-6, or 6-5 heteroaryl. In some embodiments, R B1 are independently halogen, -NO 2 , oxo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 )S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , and -S(O) 2 N(R 12)(R 11 ), wherein alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, or heterocycloalkyl is independently selected from halogen, -OH, -NO 2 , amino, oxo, -CN, C 1~3 Alkoxyl, C 1~3 Alkyl, and C 1~3 In some embodiments, R is optionally substituted with one or more substituents selected from haloalkyl. B1 are independently halogen, -OR 11 , -NO 2 , oxo, -CN, optionally substituted C 1~6 Haloalkyl, optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Aminoalkyl, optionally substituted C 1~6 Hydroxyalkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl and optionally substituted C 2~7 In some embodiments, R is optionally substituted with one or more substituents selected from heterocycloalkyl. B1 are independently halogen, -OR 11 , -NO 2 , oxo, -CN, C 1~3 Haloalkyl, C 1~3 Alkyl, C 1~3 Aminoalkyl, C 1~3 Hydroxyalkyl, optionally substituted C 1~4 Heteroalkyl (e.g., -CH 2 C(=O)N(CH 3 ) 2 ), optionally substituted C 3~6 Cycloalkyl and optionally substituted C 2~5 In some embodiments, R is optionally substituted with one or more substituents selected from heterocycloalkyl. B1 are independently halogen, oxo, -CN, C 1~3 Haloalkyl, C 1~3Alkyl, C 1~3 Aminoalkyl, C 1~3 Hydroxyalkyl, C 3~6 Cycloalkyl and C 2~5 In some embodiments, R is optionally substituted with one or more substituents selected from heterocycloalkyl. B1 is independently 1~3 Haloalkyl and C 1~3 In some embodiments, R is optionally substituted with one or more substituents (e.g., 1, 2, or 3) selected from alkyl. B1 is substituted with halogen. In some embodiments, R B1 -OR 11 In some embodiments, R B1 -NO 2 In some embodiments, R B1 is substituted with oxo. In some embodiments, R B1 is substituted with -CN. In some embodiments, R B1 is an optionally substituted C 1~6 In some embodiments, R B1 is an optionally substituted C 1~6 In some embodiments, R B1 is an optionally substituted C 1~6 Substituted with aminoalkyl.

[0121] In some embodiments of formula (I), (Ia), (Ib), (II), (II′), (IIc′), (IId′), (IIa), (IIa-1), (IIa-1a), (IIb), (IIb-1), (IIb-1a), (IIc), (IIc-1), (IId), (IId-1), (IIe), (IIf), or (IIg), R B1 teeth, [ka] In some embodiments, R B1 teeth, [ka] In some embodiments, R B1 teeth, [ka] In some embodiments, R B1 teeth, [ka] In some embodiments, R B1 teeth, [ka] In some embodiments, R B1 teeth, [ka] In some embodiments, R B1 teeth, [ka] It is.

[0122] In some embodiments of formula (I), (Ia), (Ib), (II), (II′), (IIc′), (IId′), (IIa), (IIa-1), (IIa-1a), (IIb), (IIb-1), (IIb-1a), (IIc), (IIc-1), (IId), (IId-1), (IIe), (IIf), or (IIg), R B1 teeth, [ka] In some embodiments of formula (I), (Ia), (Ib), (II), (II'), (IIc'), (IId'), (IIa), (IIa-1), (IIa-1a), (IIb), (IIb-1), (IIb-1a), (IIc), (IIc-1), (IId), (IId-1), (IIe), (IIf), or (IIg), R B1 and R Bone of which, together with the atom to which they are attached, is an optionally substituted C 3~8 Cycloalkyl or optionally substituted C 2~9 In some embodiments, R on adjacent atoms forms a heterocycloalkyl. B1 and R B and one of, taken together with the atom to which they are attached, is optionally substituted phenyl, optionally substituted naphthyl, optionally substituted monocyclic heteroaryl, optionally substituted bicyclic heteroaryl, optionally substituted C 3~8 Cycloalkyl, or optionally substituted C 2~9 In some embodiments, R on adjacent atoms forms a heterocycloalkyl. B1 and R B together with the atom to which they are attached form an optionally substituted 5- or 6-membered monocyclic heterocycloalkyl.

[0123] In some embodiments of formula (I), (Ia), (Ib), (II), (II′), (IIc′), (IId′), (IIa), (IIb), (IIc), (IId), (IId-1), (IIe), (IIf), or (IIg), R B , halo, -CN, -NO 2 , optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~9 In some embodiments, R 1 and R 2 are independently substituted or unsubstituted heterocycloalkyl, optionally substituted phenyl, optionally substituted monocyclic heteroaryl, or optionally substituted bicyclic heteroaryl. B Two of them, together with the atoms to which they are attached, are optionally substituted C 3~6 Cycloalkyl or optionally substituted C 2~5 Forms a heterocycloalkyl.

[0124] In some embodiments of formula (I), (Ia), (Ib), (II), (II'), (IIc'), (IId'), (IIa), (IIa-1), (IIa-1a), (IIb), (IIb-1), (IIb-1a), (IIc), (IIc-1), (IId), (IId-1), (IIe), (IIf), or (IIg), n is 0.

[0125] In some embodiments of the compounds of Formula (I), (Ia), (Ib), (II), (II′), (IIa), (IIa-1), (IIa-1a), (IIb), (IIb-1), X 1 is N or CR 1 In some embodiments, X 1 is N. In some embodiments, X 1 CR 1 It is.

[0126] In some embodiments of the compounds of Formula (I), (Ia), (Ib), (II), (II′), (IIa), (IIa-1), (IIa-1a), (IIb), (IIb-1), (IIb-1a), X 3 is N or CR 3 In some embodiments, X 3 is N. In some embodiments, X 3 CR 3 It is.

[0127] In some embodiments of a compound of Formula (I), (Ia), (Ib), (II), (II′), (IIc′), (IId′), (IIa), (IIa-1), (IIa-1a), (IIc), (IIc-1), (IId), (IId-1), or (IIg), X 7 is N or CR 7 In some embodiments, X 7 is N. In some embodiments, X 7 CR 7 It is.

[0128] In some embodiments of a compound of Formula (II), (II'), (IIc'), (IId'), (IIa), (IIa-1), (IIa-1a), (IIb), (IIb-1), (IIb-1a), (IIc), (IIc-1), (IId), (IId-1), (IIe), (IIf), or (IIg), [ka] is a single bond or a double bond. In some embodiments, [ka] is a single bond. In some embodiments, [ka] is a double bond.

[0129] In some embodiments of a compound of Formula (I), (Ia), (Ib), (II), (II′), (IIc′), (IId′), (IIa), (IIa-1), (IIa-1a), (IIb), (IIb-1), (IIb-1a), (IIc), (IIc-1), (IId), (IId-1), (IIe), (IIf), or (IIg), R 1 , R 2 , and R 7 each independently represents hydrogen, halo, -CN, -OR 11 , -SR 11 , -N(R 12 ) 2 , optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 In some embodiments, R is selected from alkynyl. 1 is hydrogen. In some embodiments, R 1 is halo. In some embodiments, R 1 is -CN. In some embodiments, R 1 -OR 11In some embodiments, R 1 -SR 11 In some embodiments, R 1 is -N(R 12 ) 2 In some embodiments, R 1 is an optionally substituted C 1~6 In some embodiments, R 1 is an optionally substituted C 1~6 In some embodiments, R 1 is an optionally substituted C 2~6 In some embodiments, R is alkenyl. 1 is an optionally substituted C 2~6 In some embodiments, R is alkynyl. 2 is hydrogen. In some embodiments, R 2 is halo. In some embodiments, R 2 In some embodiments, R 2 -OR 11 In some embodiments, R 2 -SR 11 In some embodiments, R 2 is -N(R 12 ) 2 In some embodiments, R 2 is an optionally substituted C 1~6 In some embodiments, R 2 is an optionally substituted C 1~6 In some embodiments, R 2 is an optionally substituted C 2~6 In some embodiments, R is alkenyl. 2 is an optionally substituted C 2~6 In some embodiments, R is alkynyl. 7 is hydrogen. In some embodiments, R 7 is halo. In some embodiments, R 7 In some embodiments, R7 -OR 11 In some embodiments, R 7 -SR 11 In some embodiments, R 7 is -N(R 12 ) 2 In some embodiments, R 7 is an optionally substituted C 1~6 In some embodiments, R 7 is an optionally substituted C 1~6 In some embodiments, R 7 is an optionally substituted C 2~6 In some embodiments, R is alkenyl. 7 is an optionally substituted C 2~6 It is alkynyl.

[0130] In some embodiments of a compound of Formula (I), (Ia), (Ib), (II), (II′), (IIc′), (IId′), (IIa), (IIa-1), (IIa-1a), (IIb), (IIb-1), (IIb-1a), (IIc), (IIc-1), (IId), (IId-1), (IIe), (IIf), or (IIg), R 8 and R 9 Each of is independently hydrogen, halo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 In some embodiments, R is selected from alkynyl. 8 and R 9 Each of is independently hydrogen, —CN, optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 alkynyl or R 8 and R 9are taken together to form oxo or R 8 and R 9 taken together with the carbons to which they are attached form an optionally substituted 3-6 membered cycloalkyl or heterocycloalkyl. In some embodiments, R 8 is hydrogen. In some embodiments, R 8 is halo. In some embodiments, R 8 is -CN. In some embodiments, R 8 is an optionally substituted C 1~6 In some embodiments, R 8 is an optionally substituted C 1~6 In some embodiments, R 8 is an optionally substituted C 2~6 In some embodiments, R is alkenyl. 8 is an optionally substituted C 2~6 In some embodiments, R is alkynyl. 9 is hydrogen. In some embodiments, R 9 is halo. In some embodiments, R 9 is -CN. In some embodiments, R 9 is an optionally substituted C 1~6 In some embodiments, R 9 is an optionally substituted C 1~6 In some embodiments, R 9 is an optionally substituted C 2~6 In some embodiments, R is alkenyl. 9 is an optionally substituted C 2~6 In some embodiments, R is alkynyl. 8 and R 9 taken together form oxo. In some embodiments, R 8 and R 9 together with the carbon to which they are attached form an optionally substituted 3- to 6-membered cycloalkyl or heterocycloalkyl.

[0131] In some embodiments of the compound of formula (I), (Ia), (Ib), (II), (II'), (IIc'), (IId'), (IIa), (IIa-1), (IIa-1a), (IIb), (IIb-1), (IIb-1a), (IIc), (IIc-1), (IId), (IId-1), (IIe), (IIf), or (IIg), ring A is phenyl, naphthyl, monocyclic heteroaryl, or bicyclic heteroaryl. In some embodiments, ring A is phenyl. In some embodiments, ring A is naphthyl. In some embodiments, ring A is monocyclic heteroaryl. In some embodiments, ring A is bicyclic heteroaryl.

[0132] In some embodiments of a compound of Formula (I), (Ia), (Ib), (II), (II′), (IIc′), (IId′), (IIa), (IIa-1), (IIa-1a), (IIb), (IIb-1), (IIb-1a), (IIc), (IIc-1), (IId), (IId-1), (IIe), (IIf), or (IIg), R A Each of the groups is independently a halogen, -NO 2 , oxo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 ) 2 S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , and -S(O) 2 N(R 12 )(R 11 In some embodiments, R A independently, -NO 2 , oxo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 ) 2 S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12, and -S(O) 2 N(R 12 )(R 11 In some embodiments, each R A are independently halogen, OH, -NO 2 , oxo, -CN, C 1~6 Alkyl, C 1~6 Alkoxyl, C 1~6 Haloalkyl, C 1~6 Heteroalkyl, and C 3~6 In some embodiments, each R A are independently halogen, C 1~6 Alkyl, C 1~6 Alkoxyl, C 1~6 Haloalkyl and C 3~6 In some embodiments, each R A is independently 1~6 Alkyl, C 1~6 Alkoxyl, C 1~6 Haloalkoxyl, C 1~6 Haloalkyl and C 3~6 In some embodiments, each R A are independently halogen, C 1~6 Alkyl, C 1~6 Alkoxyl and C 3~6 In some embodiments, each R is selected from the group consisting of alkyl, alkoxy, and cycloalkyl, where alkyl, alkoxy, and cycloalkyl are optionally substituted with one or more halogens (e.g., 1 to 3 fluorines). A are independently methyl, ethyl, propyl, butyl, -O-methyl, -O-ethyl, -O-propyl, -O-butyl, cyclopropyl, CN, OH, -O-CHF 2 , -O-CH 2 F, CHF 2 , C.H. 2 F, and CF 3 In some embodiments, R A is halogen. In some embodiments, R A -NO 2 In some embodiments, R Ais oxo. In some embodiments, R A In some embodiments, R A is an optionally substituted C 1~6 In some embodiments, R A is an optionally substituted C 1~3 In some embodiments, R A is methyl, ethyl, propyl, isopropyl, n-butyl, iso-butyl, sec-butyl, t-butyl, -CF 3 , -CH 2 CF 3 , or -CH 2 CH 2 F. In some embodiments, R A is an optionally substituted C 2~6 In some embodiments, R is alkenyl. A is an optionally substituted C 2~6 In some embodiments, R is alkynyl. A is an optionally substituted C 1~6 In some embodiments, R A is an optionally substituted C 3~8 In some embodiments, R A is an optionally substituted C 3~6 cycloalkyl, e.g., cyclopropyl. In some embodiments, R A teeth, [ka] In some embodiments, R A is an optionally substituted C 2~7 In some embodiments, R A is an optionally substituted C 2~5 In some embodiments, R A -OR 11 In some embodiments, R A -OC 1~3In some embodiments, R A -OCH 3 , -OCH 2 CH 3 , -OCH 2 OMe, -OCH 2 CH 2 OH, -OC(CH 3 ) 3 , or -OCH 2 CH 2 OCH 3 In some embodiments, R A -OCH 3 In some embodiments, R A teeth, [ka] In some embodiments, R A -SR 11 In some embodiments, R A is -N(R 12 )(R 11 In some embodiments, R A is -C(O)R 12 In some embodiments, R A is C(O)OR 12 In some embodiments, R A is -OC(O)R 12 In some embodiments, R A is -OC(O)N(R 12 )(R 11 In some embodiments, R A is -C(O)N(R 12 )(R 11 In some embodiments, R A is -N(R 12 )C(O)R 12 In some embodiments, R A is -N(R 12 )C(O)OR 12 In some embodiments, R A is -N(R 12 )C(O)N(R 12 )(R11 In some embodiments, R A is -N(R 12 ) 2 S(O) 2 (R 12 In some embodiments, R A is -S(O)R 12 In some embodiments, R A -S(O) 2 R 12 In some embodiments, R A -S(O) 2 N(R 12 )(R 11 ).

[0133] In some embodiments of a compound of Formula (I), (Ia), (Ib), (II), (II′), (IIc′), (IId′), (IIa), (IIa-1), (IIa-1a), (IIb), (IIb-1), (IIb-1a), (IIc), (IIc-1), (IId), (IId-1), (IIe), (IIf), or (IIg), R 11 is hydrogen, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted -C 1~4 Alkylene-C 3~8 Cycloalkyl, optionally substituted -C 1~4 Alkylene-C 2~7 Heterocycloalkyl, optionally substituted -C 1~4 Alkylene-phenyl, or optionally substituted -C 1~4 In some embodiments, R is an alkylene-heteroaryl. 11 is hydrogen. In some embodiments, R 11is an optionally substituted C 1~6 In some embodiments, R 11 is an optionally substituted C 1~3 In some embodiments, R 11 is methyl, ethyl, propyl, isopropyl, n-butyl, iso-butyl, sec-butyl, t-butyl, -CF 3 , -CH 2 CF 3 , or -CH 2 CH 2 F. In some embodiments, R 11 is an optionally substituted C 2~6 In some embodiments, R is alkenyl. 11 is an optionally substituted C 2~6 In some embodiments, R is alkynyl. 11 is an optionally substituted C 1~6 In some embodiments, R 11 is an optionally substituted C 3~8 In some embodiments, R 11 is an optionally substituted C 2~7 In some embodiments, R 11 is optionally substituted phenyl. In some embodiments, R 11 is optionally substituted heteroaryl. In some embodiments, R 11 is an optionally substituted -C 1~4 Alkylene-C 3~8 In some embodiments, R 11 is an optionally substituted -C 1~4 Alkylene-C 2~7 In some embodiments, R 11 is an optionally substituted -C 1~4 In some embodiments, R is alkylene-phenyl. 11 is an optionally substituted -C 1~4 It is an alkylene-heteroaryl.

[0134] In some embodiments of a compound of Formula (I), (Ia), (Ib), (II), (II′), (IIc′), (IId′), (IIa), (IIa-1), (IIa-1a), (IIb), (IIb-1), (IIb-1a), (IIc), (IIc-1), (IId), (IId-1), (IIe), (IIf), or (IIg), R 12 each independently represents hydrogen, halogen, -OH, -NO 2 , C.N., C. 1~6 Alkyl, C 1~6 Aminoalkyl, C 1~6 Hydroxyalkyl, C 1~6 Haloalkyl, C 1~6 Heteroalkyl, C 3~6 Carbocyclic rings and 3- to 6-membered heterocyclic rings; 3~6 The carbocycle and the 3- to 6-membered heterocycle are independently selected from halogen, -OH, oxo, amino, -NO 2 , C.N., C. 1~6 Alkyl, C 1~6 Alkoxy and C 1~6 In some embodiments of a compound of Formula (I), (Ia), (Ib), (II), (II'), (IIc'), (IId'), (IIa), (IIa-1), (IIa-1a), (IIb), (IIb-1), (IIb-1a), (IIc), (IIc-1), (IId), (IId-1), (IIe), (IIf), or (IIg), R 12 Each of the groups is independently hydrogen, -NO 2 , C.N., C. 1~6 Alkyl, C 1~6 Aminoalkyl, C 1~6 Hydroxyalkyl, C 1~6 Haloalkyl, C 1~6 Heteroalkyl, C 3~6 Carbocyclic rings and 3- to 6-membered heterocyclic rings; 3~6 The carbocycle and the 3- to 6-membered heterocycle are independently selected from halogen, -OH, oxo, amino, -NO 2 , C.N., C. 1~6 Alkyl, C 1~6 Alkoxy and C 1~6In some embodiments, R is optionally substituted with one or more substituents selected from haloalkyl. 12 is hydrogen. In some embodiments, R 12 is halogen. In some embodiments, R 12 is -OH. In some embodiments, R 12 -NO 2 In some embodiments, R 12 is CN. In some embodiments, R 12 is C 1~6 In some embodiments, R 12 is C 1~6 In some embodiments, R 12 is C 1~6 In some embodiments, R 12 is C 1~6 In some embodiments, R 12 is C 1~6 In some embodiments, R 12 is C 3~6 In some embodiments, R 12 and 3-6 membered heterocycle, C 3~6 The carbocycle and the 3- to 6-membered heterocycle are independently selected from halogen, -OH, oxo, amino, -NO 2 , C.N., C. 1~6 Alkyl, C 1~6 Alkoxy and C 1~6 In some embodiments, one or more of the substituents is optionally substituted with one or more substituents selected from haloalkyl. In some embodiments, one or more of the substituents is halogen. In some embodiments, one or more of the substituents is -OH. In some embodiments, one or more of the substituents is oxo. In some embodiments, one or more of the substituents is amino. In some embodiments, one or more of the substituents is -NO 2 In some embodiments, one or more of the substituents is CN. In some embodiments, one or more of the substituents is C 1~6 In some embodiments, one or more of the substituents is C 1~6In some embodiments, one or more of the substituents is C 1~6 It is haloalkyl.

[0135] In some embodiments of a compound of Formula (I), (Ia), (Ib), (II), (II'), (IIc'), (IId'), (IIa), (IIa-1), (IIa-1a), (IIb), (IIb-1), (IIb-1a), (IIc), (IIc-1), (IId), (IId-1), (IIe), (IIf), or (IIg), B is a 6-membered heteroaryl, phenyl, or phenyl isostere. In some embodiments, the ring is a 6-membered heteroaryl. In some embodiments, ring B is phenyl. In some embodiments, ring B is a phenyl isostere. In some embodiments, B is cubane. In some embodiments, B is [ka] and n is 0. In some embodiments, [ka] teeth, [ka] It is.

[0136] In some embodiments of a compound of Formula (I), (Ia), (Ib), (II), (II′), (IIc′), (IId′), (IIa), (IIa-1), (IIa-1a), (IIb), (IIb-1), (IIb-1a), (IIc), (IIc-1), (IId), (IId-1), (IIe), (IIf), or (IIg), R B1 , halo, -CN, -NO 2 , optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, -OR11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 )S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , -S(O) 2 N(R 12 )(R 11 ), optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~9 In some embodiments, R is an optionally substituted heterocycloalkyl, an optionally substituted naphthyl, an optionally substituted phenyl, an optionally substituted monocyclic heteroaryl, or an optionally substituted bicyclic heteroaryl. B1 -CN, -NO 2 , optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 )S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , -S(O) 2 N(R 12 )(R 11 ), optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~9 In some embodiments, R is a heterocycloalkyl, an optionally substituted phenyl, an optionally substituted monocyclic heteroaryl, or an optionally substituted bicyclic heteroaryl. B1 is an optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~9 In some embodiments, R is a heterocycloalkyl, an optionally substituted phenyl, an optionally substituted monocyclic heteroaryl, or an optionally substituted bicyclic heteroaryl. B1 is halo. In some embodiments, R B1 In some embodiments, R B1 -NO 2 In some embodiments, R B1 is an optionally substituted C 1~6 In some embodiments, R B1 is an optionally substituted C 1~3 In some embodiments, R B1 is methyl, ethyl, propyl, isopropyl, n-butyl, iso-butyl, sec-butyl, t-butyl, -CF 3 , -CH 2 CF 3 , or -CH 2 CH2 F. In some embodiments, R B1 is an optionally substituted C 2~6 In some embodiments, R is alkenyl. B1 is an optionally substituted C 2~6 In some embodiments, R is alkynyl. B1 is an optionally substituted C 1~6 In some embodiments, R B1 -OR 11 In some embodiments, R B1 -SR 11 In some embodiments, R B1 is -N(R 12 )(R 11 In some embodiments, R B1 is -C(O)R 12 In some embodiments, R B1 is C(O)OR 12 In some embodiments, R B1 is -OC(O)R 12 In some embodiments, R B1 is -OC(O)N(R 12 )(R 11 In some embodiments, R B1 is -C(O)N(R 12 )(R 11 In some embodiments, R B1 is -N(R 12 )C(O)R 12 In some embodiments, R B1 is -N(R 12 )C(O)OR 12 In some embodiments, R B1 is -N(R 12 )C(O)N(R 12 )(R 11 In some embodiments, R B1 is -N(R 12 )S(O) 2 (R 12 In some embodiments, R B1is -S(O)R 12 In some embodiments, R B1 -S(O) 2 R 12 In some embodiments, R B1 -S(O) 2 N(R 12 )(R 11 In some embodiments, R B1 is an optionally substituted C 3~8 In some embodiments, R B1 is an optionally substituted C 2~9 In some embodiments, R B1 is optionally substituted naphthyl. In some embodiments, R B1 is optionally substituted phenyl. In some embodiments, R B1 is an optionally substituted monocyclic heteroaryl. In some embodiments, the optionally substituted monocyclic heteroaryl is -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, or -OR 11 In some embodiments, R B1 is an optionally substituted bicyclic heteroaryl. In some embodiments, the optionally substituted bicyclic heteroaryl is -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, or -OR 11 is replaced by.

[0137] In some embodiments of a compound of Formula (I), (Ia), (Ib), (II), (II′), (IIc′), (IId′), (IIa), (IIb), (IIc), (IId), (IId-1), (IIe), (IIf), or (IIg), R B is hydrogen, halo, -CN, -NO 2 , optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 )S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , -S(O) 2 N(R 12 )(R 11 ), optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~9 In some embodiments, R is an optionally substituted heterocycloalkyl, an optionally substituted naphthyl, an optionally substituted phenyl, an optionally substituted monocyclic heteroaryl, or an optionally substituted bicyclic heteroaryl. B is halo. In some embodiments, R BIn some embodiments, R B -NO 2 In some embodiments, R B is an optionally substituted C 1~6 In some embodiments, R B is an optionally substituted C 2~6 In some embodiments, R is alkenyl. B is an optionally substituted C 2~6 In some embodiments, R is alkynyl. B is an optionally substituted C 1~6 In some embodiments, R B -OR 11 In some embodiments, R B -SR 11 In some embodiments, R B is -N(R 12 )(R 11 In some embodiments, R B is -C(O)R 12 In some embodiments, R B is C(O)OR 12 In some embodiments, R B is -OC(O)R 12 In some embodiments, R B is -OC(O)N(R 12 )(R 11 In some embodiments, R B is -C(O)N(R 12 )(R 11 In some embodiments, R B is -N(R 12 )C(O)R 12 In some embodiments, R B is -N(R 12 )C(O)OR 12 In some embodiments, R B is -N(R 12 )C(O)N(R 12 )(R 11 In some embodiments, RB is -N(R 12 )S(O) 2 (R 12 In some embodiments, R B is -S(O)R 12 In some embodiments, R B -S(O) 2 R 12 In some embodiments, R B -S(O) 2 N(R 12 )(R 11 In some embodiments, R B is an optionally substituted C 3~8 In some embodiments, R B is an optionally substituted C 2~9 In some embodiments, R B is optionally substituted naphthyl. In some embodiments, R B is optionally substituted phenyl. In some embodiments, R B is an optionally substituted monocyclic heteroaryl. In some embodiments, R B is an optionally substituted bicyclic heteroaryl. In some embodiments, the substituted bicyclic heteroaryl is selected from the group consisting of halogen, -OH, -NO 2 , amino, oxo, -CN, C 1~3 Alkoxyl, C 1~3 Alkyl, or C 1~3 In some embodiments, the substituted bicyclic heteroaryl is substituted with haloalkyl. In some embodiments, the substituted bicyclic heteroaryl is substituted with halogen. In some embodiments, the substituted bicyclic heteroaryl is substituted with -OH. In some embodiments, the substituted bicyclic heteroaryl is substituted with -NO 2 In some embodiments, the substituted bicyclic heteroaryl is substituted with -C. In some embodiments, the substituted bicyclic heteroaryl is substituted with amino. In some embodiments, the substituted bicyclic heteroaryl is substituted with oxo. In some embodiments, the substituted bicyclic heteroaryl is substituted with -CN. In some embodiments, the substituted bicyclic heteroaryl is substituted with -C. 1~3In some embodiments, the substituted bicyclic heteroaryl is C 1~3 In some embodiments, the substituted bicyclic heteroaryl is selected from the group consisting of, or C 1~3 Substituted with haloalkyl.

[0138] In some embodiments of a compound of Formula (I), (Ia), (Ib), (II), (II′), (IIc′), (IId′), (IIa), (IIa-1), (IIa-1a), (IIb), (IIb-1), (IIb-1a), (IIc), (IIc-1), (IId), (IId-1), (IIe), (IIf), or (IIg), R on adjacent atoms may be B1 and R B and one of, taken together with the atom to which they are attached, is optionally substituted phenyl, optionally substituted naphthyl, optionally substituted monocyclic heteroaryl, optionally substituted bicyclic heteroaryl, optionally substituted C 3~8 Cycloalkyl, or optionally substituted C 2~9 In some embodiments, R on adjacent atoms forms a heterocycloalkyl. B1 and R B together with the atom to which they are attached form an optionally substituted phenyl. In some embodiments, the R B1 and R B together with the atom to which they are attached form an optionally substituted naphthyl. In some embodiments, the R B1 and R B In some embodiments, one of R on the adjacent atom is taken together with the atom to which they are attached to form an optionally substituted monocyclic heteroaryl. B1 and R B and one of R on adjacent atoms together with the atom to which they are attached form an optionally substituted bicyclic heteroaryl. B1 and R Bone of which, together with the atom to which they are attached, is an optionally substituted C 3~8 In some embodiments, R on adjacent atoms forms a cycloalkyl. B1 and R B one of which, together with the atom to which they are attached, is an optionally substituted C 2~9 Forms a heterocycloalkyl.

[0139] In some embodiments of a compound of Formula (I), (Ia), (Ib), (II), (II′), (IIc′), (IId′), (IIa), (IIa-1), (IIa-1a), (IIb), (IIb-1), (IIb-1a), (IIc), (IIc-1), (IId), (IId-1), (IIe), (IIf), or (IIg), R B1 and R B one of which, together with the atom to which they are attached, is an optionally substituted C 3~8 Cycloalkyl, or optionally substituted C 2~9 In some embodiments, R on the same atom form a heterocycloalkyl. B1 and R B one of which, together with the atom to which they are attached, is an optionally substituted C 3~8 In some embodiments, R on the same atom form a cycloalkyl. B1 and R B one of which, together with the atom to which they are attached, is an optionally substituted C 2~9 Forms a heterocycloalkyl.

[0140] In some embodiments of a compound of Formula (I), (Ia), (Ib), (II), (II′), (IIc′), (IId′), (IIa), (IIb), (IIc), (IId), (IId-1), (IIe), (IIf), or (IIg), R B Two of them, together with the atoms to which they are attached, are optionally substituted C 3~8 Cycloalkyl, or optionally substituted C 2~9In some embodiments, R on the same atom form a heterocycloalkyl. B Two of them, together with the atoms to which they are attached, are optionally substituted C 3~8 In some embodiments, R on the same atom form a cycloalkyl. B Two of them, together with the atoms to which they are attached, are optionally substituted C 2~9 Forms a heterocycloalkyl.

[0141] In some embodiments of a compound of Formula (I), (Ia), (Ib), (II), (II'), (IIc'), (IId'), (IIa), (IIa-1), (IIa-1a), (IIb), (IIb-1), (IIb-1a), (IIc), (IIc-1), (IId), (IId-1), (IIe), (IIf), or (IIg), m is 1, 2, 3, or 4. In some embodiments, m is 1. In some embodiments, m is 2. In some embodiments, m is 3. In some embodiments, m is 4.

[0142] In some embodiments of a compound of Formula (I), (Ia), (Ib), (II), (II'), (IIc'), (IId'), (IIa), (IIa-1), (IIa-1a), (IIb), (IIc), (IIc-1), (IId), (IId-1), (IIe), (IIf), or (IIg), n is 0, 1, 2, 3, or 4. In some embodiments, n is 0. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 3. In some embodiments, n is 4.

[0143] In some embodiments of a compound of Formula (I), (Ia), (Ib), (II), (II'), (IIc'), (IId'), (IIa), (IIa-1), (IIa-1a), (IIb), (IIb-1), (IIb-1a), (IIc), (IIc-1), (IId), (IId-1), (IIe), (IIf), or (IIg), p is 0 or 1. In some embodiments, p is 0. In some embodiments, p is 1.

[0144] In an embodiment of the compound of formula (Ib), X 1 CR 1 and X 3 is N or CR 3 and X 7 CR 7 and R 1 and R 3 is hydrogen, and each R 8 and R 9 each is hydrogen; [ka] teeth, [ka] And each R A is independently 1 ~C 6 Alkyl, C 1 ~C 6 Alkoxyl, C 1 ~C 6 Haloalkyl and C 3~ C 6 cycloalkyl; R B1 is C 1~3 Haloalkyl and C 1~3 Alkyl (e.g. [ka] ), and p is 1. In some embodiments, each R A are independently OH, C 1~3Alkyl, -OCH 3 , C 1~3 Haloalkyl, or C 3 ~C 6 In some embodiments, each R A are independently OH, -OCH 3 , C 1~3 Alkyl, C 1~3 haloalkyl, or cyclopropyl. In some embodiments, each R A is independently 1~3 Alkyl, C 1~3 haloalkyl, or cyclopropyl. In some embodiments, -OCH 3 -OCD 3 In some embodiments, R B1 is C 1~3 Haloalkyl and C 1~3 Optionally substituted with 1 or 2 substituents selected from alkyl.

[0145] In one aspect, described herein is a compound having the structure of formula (VI), or a salt or solvate thereof: [ka] During the ceremony, Ring C is phenyl or 6-membered heteroaryl, each of which is optionally substituted; Ring D is an aromatic saturated or partially saturated 5-membered carbocyclic or heterocyclic ring, each of which is optionally substituted; R 8 and R 9 Each of is independently hydrogen, halo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 alkynyl or R 8 and R 9 are taken together to form oxo or R8 and R 9 together with the carbons to which they are attached form an optionally substituted 3- to 6-membered cycloalkyl or heterocycloalkyl; Ring A is phenyl, naphthyl, monocyclic heteroaryl, or bicyclic heteroaryl; R A Each of the groups is independently a halogen, -NO 2 , oxo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 ) 2 S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , and -S(O) 2 N(R 12 )(R 11 ), R 11 is hydrogen, optionally substituted C 1~6 Alkyl, optionally substituted C2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted -C 1~4 Alkylene-C 3~8 Cycloalkyl, optionally substituted -C 1~4 Alkylene-C 2~7 Heterocycloalkyl, optionally substituted -C 1~4 Alkylene-phenyl, or optionally substituted -C 1~4 alkylene-heteroaryl, R 12 each independently represents hydrogen, halogen, -OH, -NO 2 , -CN,C 1~6 Alkyl, C 1~6 Aminoalkyl, C 1~6 Hydroxyalkyl, C 1~6 Haloalkyl and C 3~6 Carbocyclic ring, 3- to 6-membered heterocyclic ring, 3~6 The carbocycle and the 3- to 6-membered heterocycle are independently selected from halogen, -OH, oxo, amino, -NO 2 , -CN,C 1~6 Alkyl, C 1~6 Alkoxy and C 1~6 optionally substituted with one or more substituents selected from haloalkyl; R B is hydrogen, halo, -CN, -NO 2 , optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12, -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 )S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , -S(O) 2 N(R 12 )(R 11 ), optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~9 heterocycloalkyl, optionally substituted naphthyl, optionally substituted phenyl, optionally substituted monocyclic heteroaryl, or optionally substituted bicyclic heteroaryl; or m is 0, 1, 2, 3, or 4; p is 0 or 1.

[0146] In some embodiments of Formula (VI), Ring C is phenyl or 6-membered heteroaryl; Each of the phenyl or heteroaryl may have one, two, three, or four R 1C and each R 1C are independently halogen, -CN, -NO 2 , -OH, -OR a , -OC(=O)R a , -OC(=O)OR b , -OC(=O)NR c R d , -SH, -SR a , -S(=O)R a , -S(=O) 2 R a, -S(=O) 2 NR c R d , -NR c R d , -NR b C(=O)NR c R d , -NR b C(=O)R a , -NR b C(=O)OR b , -NR b S(=O) 2 R a , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 1~6 Heteroalkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~8 Cycloalkyl, C 2~7 heterocycloalkyl, aryl, or heteroaryl, wherein alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are optionally and independently selected from one or more R 1Ca is replaced by Ring D is an aromatic saturated or partially saturated 5-membered carbocyclic or heterocyclic ring, each of which may contain 1, 2, 3, 4, or 5 or 6 R 1D and optionally substituted with Each R 1D are independently halogen, -CN, -NO 2 , -OH, -OR a , -OC(=O)R a , -OC(=O)OR b , -OC(=O)NR c R d , -SH, -SR a , -S(=O)R a , -S(=O) 2 R a , -S(=O)2 NR c R d , -NR c R d , -NR b C(=O)NR c R d , -NR b C(=O)R a , -NR b C(=O)OR b , -NR b S(=O) 2 R a , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 1~6 Heteroalkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~8 Cycloalkyl, C 2~7 heterocycloalkyl, aryl, or heteroaryl, wherein alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are optionally and independently selected from one or more R 1Da is replaced by R 8 and R 9 Each of is independently hydrogen, halo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 alkynyl or R 8 and R 9 are taken together to form oxo or R 8 and R 9taken together with the carbons to which they are attached form an optionally substituted 3- to 6-membered cycloalkyl or heterocycloalkyl, where the alkyl, alkenyl, alkynyl, cycloalkyl, or heterocycloalkyl are independently selected from halogen, amino, -OH, -NO 2 , oxo, -CN, C 1~3 Alkoxyl, C 1~3 Alkyl, and C 1~3 optionally substituted with one or more substituents selected from haloalkyl; R A Each of the groups is independently a halogen, -NO 2 , oxo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 ) 2 S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , and -S(O) 2 N(R 12 )(R11 ), wherein alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, or heterocycloalkyl is independently selected from halogen, -OH, -NO 2 , oxo, amino, -CN, C 1~6 Alkoxyl, C 1~6 Alkyl, C 1~6 Haloalkyl, C 3~6 Optionally substituted with one or more substituents selected from a carbocycle and a 3- to 6-membered heterocycle, 3~6 The carbocycle and the 3- to 6-membered heterocycle are independently selected from halogen, -OH, amino, -NO 2 , oxo, -CN, C 1~6 Alkyl, C 1~6 Alkoxy and C 1~6 optionally substituted with one or more substituents selected from haloalkyl; Ring A is phenyl, naphthyl, monocyclic heteroaryl, or bicyclic heteroaryl; R A Each of the groups is independently a halogen, -NO 2 , oxo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12)C(O)N(R 12 )(R 11 ), -N(R 12 ) 2 S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , and -S(O) 2 N(R 12 )(R 11 ), Alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, or heterocycloalkyl are independently selected from halogen, -OH, -NO 2 , oxo, amino, -CN, C 1~6 Alkoxyl, C 1~6 Alkyl, C 1~6 Haloalkyl, C 3~6 Optionally substituted with one or more substituents selected from a carbocycle and a 3- to 6-membered heterocycle, 3~6 The carbocycle and the 3- to 6-membered heterocycle are independently selected from halogen, -OH, amino, -NO 2 , oxo, -CN, C 1~6 Alkyl, C 1~6 Alkoxy and C 1~6 optionally substituted with one or more substituents selected from haloalkyl; R 11 is hydrogen, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted -C 1~4 Alkylene-C 3~8 Cycloalkyl, optionally substituted -C 1~4 Alkylene-C 2~7 Heterocycloalkyl, optionally substituted -C 1~4Alkylene-phenyl, or optionally substituted -C 1~4 alkylene-heteroaryl, where the alkyl, alkenyl, alkynyl, heteroalkyl, alkylene, cycloalkyl, heterocycloalkyl, phenyl, or heteroaryl are independently selected from halogen, -OH, amino, -NO 2 , Oxo, C 1~6 Alkoxy, -CN, C 1~6 Alkyl, C 1~6 optionally substituted with one or more substituents selected from haloalkyl; R 12 Each of the groups is independently hydrogen, -NO 2 , -CN,C 1~6 Alkyl, C 1~6 Aminoalkyl, C 1~6 Hydroxyalkyl, C 1~6 Haloalkyl and C 3~6 Carbocyclic ring, 3- to 6-membered heterocyclic ring, 3~6 The carbocycle and the 3- to 6-membered heterocycle are independently selected from halogen, -OH, oxo, amino, -NO 2 , -CN,C 1~6 Alkyl, C 1~6 Alkoxy and C 1~6 optionally substituted with one or more substituents selected from haloalkyl; R B is hydrogen, halo, -CN, -NO 2 , optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12)C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 )S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , -S(O) 2 N(R 12 )(R 11 ), optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~9 heterocycloalkyl, optionally substituted naphthyl, optionally substituted phenyl, optionally substituted monocyclic heteroaryl, or optionally substituted bicyclic heteroaryl, wherein each of alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, naphthyl, phenyl, or heteroaryl is independently selected from halogen, -NO 2 , oxo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 )S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , and -S(O) 2 N(R 12 )(R 11 ), wherein alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, or heterocycloalkyl is independently selected from halogen, -OH, -NO 2 , amino, -NH(C 1~6 alkyl), -N(C 1~6 Alkyl) 2 , oxo, -CN, C 1~3 Alkoxyl, C 1~3 Alkyl, and C 1~3 optionally substituted with one or more substituents selected from haloalkyl; Each R a is independently 1 ~C 6 Alkyl, C 1 ~C 6 Haloalkyl, C 1 ~C 6 Hydroxyalkyl, C 1 ~C 6 Aminoalkyl, C 1 ~C 6 Heteroalkyl, C 2 ~C 6 Alkenyl, C 2 ~C 6 Alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, -C 1 ~C 6 Alkylene-cycloalkyl, -C 1 ~C 6 Alkylene-heterocycloalkyl, -C 1 ~C 6 Alkylene-aryl, or -C 1 ~C 6alkylene-heteroaryl, wherein each alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl independently represents one or more of oxo, halogen, -CN, -OH, -OC 1 ~C 6 Alkyl, -S(=O)C 1 ~C 6 Alkyl, -S(=O) 2 C 1 ~C 6 Alkyl, -S(=O) 2 NH 2 , -S(=O) 2 NHC 1 ~C 6 Alkyl, -S(=O) 2 N(C 1 ~C 6 Alkyl) 2 , -NH 2 , -NHC 1 ~C 6 Alkyl, -N(C 1 ~C 6 Alkyl) 2 , -NHC(=O)OC 1 ~C 6 Alkyl, -C(=O)C 1 ~C 6 Alkyl, -C(=O)OH, -C(=O)OC 1 ~C 6 Alkyl, -C(=O)NH 2 , -C(=O)N(C 1 ~C 6 Alkyl) 2 , -C(=O)NHC 1 ~C 6 Alkyl, C 1 ~C 6 Alkyl, C 1 ~C 6 Haloalkyl, C 1 ~C 6 Hydroxyalkyl, C 1 ~C 6 Aminoalkyl, or C 1 ~C 6 optionally substituted with heteroalkyl; Each R b are independently hydrogen, C 1 ~C6 Alkyl, C 1 ~C 6 Haloalkyl, C 1 ~C 6 Hydroxyalkyl, C 1 ~C 6 Aminoalkyl, C 1 ~C 6 Heteroalkyl, C 2 ~C 6 Alkenyl, C 2 ~C 6 Alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, -C 1 ~C 6 Alkylene-cycloalkyl, -C 1 ~C 6 Alkylene-heterocycloalkyl, -C 1 ~C 6 Alkylene-aryl, or -C 1 ~C 6 alkylene-heteroaryl, wherein each alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl independently represents one or more of oxo, halogen, -CN, -OH, -OC 1 ~C 6 Alkyl, -S(=O)C 1 ~C 6 Alkyl, -S(=O) 2 C 1 ~C 6 Alkyl, -S(=O) 2 NH 2 , -S(=O) 2 N.H.C. 1 ~C 6 Alkyl, -S(=O) 2 N(C 1 ~C 6 Alkyl) 2 , -NH 2 , -NHC 1 ~C 6 Alkyl, -N(C 1 ~C 6 Alkyl) 2 , -NHC(=O)OC 1 ~C 6 Alkyl, -C(=O)C 1 ~C6 Alkyl, -C(=O)OH, -C(=O)OC 1 ~C 6 Alkyl, -C(=O)NH 2 , -C(=O)N(C 1 ~C 6 Alkyl) 2 , -C(=O)NHC 1 ~C 6 Alkyl, C 1 ~C 6 Alkyl, C 1 ~C 6 Haloalkyl, C 1 ~C 6 Hydroxyalkyl, C 1 ~C 6 Aminoalkyl, or C 1 ~C 6 optionally substituted with heteroalkyl; Each R c and R d are independently hydrogen, C 1 ~C 6 Alkyl, C 1 ~C 6 Haloalkyl, C 1 ~C 6 Hydroxyalkyl, C 1 ~C 6 Aminoalkyl, C 1 ~C 6 Heteroalkyl, C 2 ~C 6 Alkenyl, C 2 ~C 6 Alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, -C 1 ~C 6 Alkylene-cycloalkyl, -C 1 ~C 6 Alkylene-heterocycloalkyl, -C 1 ~C 6 Alkylene-aryl or -C 1 ~C 6 alkylene-heteroaryl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl independently represents one or more of oxo, halogen, -CN, -OH, -OC 1~C 6 Alkyl, -S(=O)C 1 ~C 6 Alkyl, -S(=O) 2 C 1 ~C 6 Alkyl, -S(=O) 2 NH 2 , -S(=O) 2 NHC 1 ~C 6 Alkyl, -S(=O) 2 N(C 1 ~C 6 Alkyl) 2 , -NH 2 , -NHC 1 ~C 6 Alkyl, -N(C 1 ~C 6 Alkyl) 2 , -NHC(=O)OC 1 ~C 6 Alkyl, -C(=O)C 1 ~C 6 Alkyl, -C(=O)OH, -C(=O)OC 1 ~C 6 Alkyl, -C(=O)NH 2 , -C(=O)N(C 1 ~C 6 Alkyl) 2 , -C(=O)NHC 1 ~C 6 Alkyl, C 1 ~C 6 Alkyl, C 1 ~C 6 Haloalkyl, C 1 ~C 6 Hydroxyalkyl, C 1 ~C 6 Aminoalkyl, or C 1 ~C 6 optionally substituted with heteroalkyl; or R c and R d together with the atoms to which they are attached, can be one or more of oxo, halogen, -CN, -OH, -OC 1 ~C 6 Alkyl, -S(=O)C 1 ~C 6Alkyl, -S(=O) 2 C 1 ~C 6 Alkyl, -S(=O) 2 NH 2 , -S(=O) 2 NHC 1 ~C 6 Alkyl, -S(=O) 2 N(C 1 ~C 6 Alkyl) 2 , -NH 2 , -NHC 1 ~C 6 Alkyl, -N(C 1 ~C 6 Alkyl) 2 , -NHC(=O)OC 1 ~C 6 Alkyl, -C(=O)C 1 ~C 6 Alkyl, -C(=O)OH, -C(=O)OC 1 ~C 6 Alkyl, -C(=O)NH 2 , -C(=O)N(C 1 ~C 6 Alkyl) 2 , -C(=O)NHC 1 ~C 6 Alkyl, C 1 ~C 6 Alkyl, C 1 ~C 6 Haloalkyl, C 1 ~C 6 Hydroxyalkyl, C 1 ~C 6 Aminoalkyl, or C 1 ~C 6 forming a heterocycloalkyl optionally substituted with a heteroalkyl; Each R 1Ca and R 1Da are independently halogen, -CN, -NO 2 , -OH, -OR a , -OC(=O)R a , -OC(=O)OR b , -OC(=O)NR c R d , -SH, -SR a , -S(=O)Ra , -S(=O) 2 R a , -S(=O) 2 NR c R d , -NR c R d , -NR b C(=O)NR c R d , -NR b C(=O)R a , -NR b C(=O)OR b , -NR b S(=O) 2 R a , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C 1 ~C 6 Alkyl, C 1 ~C 6 Haloalkyl, C 1 ~C 6 Hydroxyalkyl, C 1 ~C 6 Aminoalkyl, C 1 ~C 6 Heteroalkyl, C 2 ~C 6 Alkenyl, C 2 ~C 6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; m is 1, 2, 3, or 4; p is 0 or 1.

[0147] In some embodiments of Formula (VI), ring C is a 6-membered heteroaryl and ring D is a 5-membered heteroaryl. In some embodiments, ring C is a 5-membered heteroaryl and ring D is a 6-membered heterocycloalkyl.

[0148] In some embodiments of formula (VI), R 12 Each of the groups is independently hydrogen, -NO 2 , -CN,C 1~6 Alkyl, C 1~6Aminoalkyl, C 1~6 Hydroxyalkyl, C 1~6 Haloalkyl and C 3~6 Carbocyclic ring, 3- to 6-membered heterocyclic ring, 3~6 The carbocycle and the 3- to 6-membered heterocycle are independently selected from halogen, -OH, oxo, amino, -NO 2 , -CN,C 1~6 Alkyl, C 1~6 Alkoxy and C 1~6 Optionally substituted with one or more substituents selected from haloalkyl.

[0149] In some embodiments of Formula (VI), each of rings C and D is independently halo, -CN, -OR a , -SH, -SR a , -NR c R d , optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 Optionally substituted with one or more substituents selected from alkyl, heteroalkyl, alkenyl, or alkynyl, independently selected from halogen, amino, oxo, -OH, -NO 2 , -CN, and C 1~3 Optionally substituted with one or more substituents selected from alkoxyl.

[0150] In some embodiments of Formula (VI), [ka] teeth, [ka] In some embodiments, [ka] teeth, [ka] In some embodiments, [ka] teeth, [ka] In some embodiments, [ka] teeth, [ka] In some embodiments, [ka] teeth, [ka] In some embodiments, [ka] teeth, [ka] In some embodiments, [ka] teeth, [ka] In some embodiments, [ka] teeth, [ka] In some embodiments, [ka] teeth, [ka] In some embodiments, [ka] teeth, [ka] In some embodiments, [ka] teeth, [ka] In some embodiments, [ka] teeth, [ka] In some embodiments, [ka] teeth, [ka] It is.

[0151] In some embodiments of formula (VI), ring A is phenyl. In some embodiments, ring A is naphthyl. In some embodiments, ring A is a 5- or 6-membered monocyclic heteroaryl. In some embodiments, ring A is a 6-membered monocyclic heteroaryl containing 1-3 heteroatoms.

[0152] In some embodiments of Formula (VI), [ka] teeth, [ka] It is.

[0153] In some embodiments of formula (VI), ring A is pyridine, pyrimidine, pyrazine, pyridazine, triazine, imidazole, pyrazole, triazole, oxazole, isoxazole, or thiophene. [ka] teeth, [ka] In some embodiments, [ka] teeth, [ka] In some embodiments, [ka] teeth, [ka] In some embodiments, [ka] teeth, [ka] In some embodiments, [ka] teeth, [ka] In some embodiments, [ka] teeth, [ka] In some embodiments, [ka] teeth, [ka] In some embodiments, [ka] teeth, [ka] In some embodiments, [ka] teeth, [ka] In some embodiments, [ka] teeth, [ka] In some embodiments, [ka] teeth, [ka] In some embodiments, [ka] teeth, [ka] In some embodiments, [ka] teeth, [ka] In some embodiments, [ka] teeth, [ka] It is.

[0154] In some embodiments of formula (VI), ring A is a bicyclic heteroaryl. In some embodiments, ring A is a fused 5-6, 6-6, or 6-5 bicyclic heteroaryl.

[0155] In some embodiments of formula (VI), R A Each of the groups is independently a halogen, -NO 2 , oxo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12, -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 ) 2 S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , and -S(O) 2 N(R 12 )(R 11 In some embodiments, each R A are independently halogen, -OH, -NO 2 , amino, -CN, C 1~6 Alkoxyl, C 1~6 Alkyl, C 1~6 Haloalkyl, C 3~6 is independently substituted with one or more substituents selected from a carbocycle and a 3- to 6-membered heterocycle; 3~6 The carbocycle and the 3- to 6-membered heterocycle are independently selected from halogen, -OH, amino, -NO 2 , oxo, -CN, C 1~6 Alkyl, C 1~6 Alkoxy and C 1~6 In some embodiments, R is optionally substituted with one or more substituents selected from haloalkyl. A independently, -NO 2 , oxo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12, -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 ) 2 S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , and -S(O) 2 N(R 12 )(R 11 ) is selected.

[0156] In some embodiments of Formula (VI), [ka] teeth, [ka] [ka] In some embodiments, [ka] teeth, [ka] In some embodiments, [ka] teeth, [ka] In some embodiments, [ka] teeth, [ka] In some embodiments, [ka] teeth, [ka] In some embodiments, [ka] teeth, [ka] In some embodiments, [ka] teeth, [ka] In some embodiments, [ka] teeth, [ka] In some embodiments, [ka] teeth, [ka] In some embodiments, [ka] teeth, [ka] It is.

[0157] In some embodiments of Formula (VI), p is 0. In some embodiments, p is 1.

[0158] In some embodiments of formula (VI), R 8 and R 9 Each of is independently hydrogen, halo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 In some embodiments, R is selected from alkynyl. 8 and R 9 Each of is independently hydrogen, —CN, optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 alkynyl or R 8 and R 9 are taken together to form oxo or R 8 and R 9 together with the carbon to which they are attached form an optionally substituted 3- to 6-membered cycloalkyl or heterocycloalkyl.

[0159] In some embodiments of formula (VI), R 8 and R 9 together form oxo.

[0160] In some embodiments of formula (VI), R 8 and R 9 together with the carbon to which they are attached form an optionally substituted 3- to 6-membered cycloalkyl or heterocycloalkyl.

[0161] In some embodiments of formula (VI), R B , halo, -CN, -NO 2 , optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 )S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , -S(O) 2 N(R 12 )(R 11 ), optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~9 In some embodiments, R is a heterocycloalkyl, an optionally substituted phenyl, an optionally substituted monocyclic heteroaryl, or an optionally substituted bicyclic heteroaryl. B is an optionally substituted 5-membered monocyclic heteroaryl having 1-4 heteroatoms selected from N, O, S, and P. In some embodiments, R B is imidazole, pyrazole, triazole, or tetrazole, each of which is optionally substituted. In some embodiments, RB is an optionally substituted fused 5-6, 6-6, or 6-5 heteroaryl.

[0162] In some embodiments of formula (VI), R B are independently halogen, -NO 2 , oxo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 )S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , and -S(O) 2 N(R 12 )(R 11 ), wherein alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, or heterocycloalkyl is independently selected from halogen, -OH, -NO 2 , amino, oxo, -CN, C 1~3 Alkoxyl, C 1~3 Alkyl, and C 1~3In some embodiments, R is optionally substituted with one or more substituents selected from haloalkyl. B are independently halogen, -OR 11 , -NO 2 , oxo, -CN, optionally substituted C 1~6 Haloalkyl, optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Aminoalkyl, optionally substituted C 1~6 Hydroxyalkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl and optionally substituted C 2~7 In some embodiments, R is optionally substituted with one or more substituents selected from heterocycloalkyl. B are independently halogen, -OR 11 , -NO 2 , oxo, -CN, C 1~3 Haloalkyl, C 1~3 Alkyl, C 1~3 Aminoalkyl, C 1~3 Hydroxyalkyl, optionally substituted C 1~4 Heteroalkyl (e.g., -CH 2 C(=O)N(CH 3 ) 2 ), optionally substituted C 3~6 Cycloalkyl and optionally substituted C 2~5 In some embodiments, R is optionally substituted with one or more substituents selected from heterocycloalkyl. B is an optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~9 In some embodiments, R is a heterocycloalkyl, an optionally substituted phenyl, an optionally substituted monocyclic heteroaryl, or an optionally substituted bicyclic heteroaryl. B is an optionally substituted monocyclic 5-6 membered heterocycloalkyl or heteroaryl. In some embodiments, R Bis an optionally substituted C 3~8 In some embodiments, R B is C 3 In some embodiments, R B is C 5 In some embodiments, R B is C 6 In some embodiments, R B is optionally substituted phenyl. In some embodiments, R B is an optionally substituted C 2~9 In some embodiments, R B is C 3 In some embodiments, R B is C 5 In some embodiments, R B is C 6 In some embodiments, R B is an optionally substituted monocyclic heteroaryl. In some embodiments, R B is an optionally substituted bicyclic heteroaryl. In some embodiments, R B is imidazole, pyrazole, triazole, or tetrazole, each of which is optionally substituted. In some embodiments, R B is imidazole. In some embodiments, R B is pyrazole. In some embodiments, R B is triazole. In some embodiments, R B is tetrazole.

[0163] In some embodiments of formula (VI), R B teeth, [ka] is selected from.

[0164] In some embodiments of formula (VI), R B teeth, [ka] In some embodiments, R B teeth, [ka] In some embodiments, R B teeth, [ka] In some embodiments, R B teeth, [ka] In some embodiments, R B teeth, [ka] In some embodiments, R B teeth, [ka] In some embodiments, R B teeth, [ka] It is.

[0165] In some embodiments of formula (VI), ring C is phenyl or 6-membered heteroaryl, each of which is optionally substituted. In some embodiments, ring C is an optionally substituted phenyl. In some embodiments, ring C is an optionally substituted 6-membered heteroaryl.

[0166] In some embodiments of formula (VI), ring D is an aromatic saturated or partially saturated 5-membered carbocyclic or heterocyclic ring, each of which is optionally substituted. In some embodiments, ring D is an optionally substituted aromatic 5-membered carbocyclic ring. In some embodiments, ring D is an optionally substituted aromatic 5-membered heterocyclic ring. In some embodiments, ring D is an optionally substituted saturated 5-membered carbocyclic ring. In some embodiments, ring D is an optionally substituted saturated 5-membered heterocyclic ring. In some embodiments, ring D is an optionally substituted partially saturated 5-membered carbocyclic ring. In some embodiments, ring D is an optionally substituted partially saturated 5-membered heterocyclic ring.

[0167] In some embodiments of formula (VI), R 8 and R 9 Each of is independently hydrogen, halo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 In some embodiments, R is selected from alkynyl. 8 and R 9 Each of is independently hydrogen, —CN, optionally substituted C 1~6 Alkyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 2~6 Alkenyl, and optionally substituted C 2~6 alkynyl or R 8 and R 9 are taken together to form oxo or R 8 and R 9 taken together with the carbons to which they are attached form an optionally substituted 3-6 membered cycloalkyl or heterocycloalkyl. In some embodiments, R 8 is hydrogen. In some embodiments, R 8 is halo. In some embodiments, R 8In some embodiments, R 8 is an optionally substituted C 1~6 In some embodiments, R 8 is an optionally substituted C 1~6 In some embodiments, R 8 is an optionally substituted C 2~6 In some embodiments, R is alkenyl. 8 is an optionally substituted C 2~6 In some embodiments, R is alkynyl. 9 is hydrogen. In some embodiments, R 9 is halo. In some embodiments, R 9 In some embodiments, R 9 is an optionally substituted C 1~6 In some embodiments, R 9 is an optionally substituted C 1~6 In some embodiments, R 9 is an optionally substituted C 2~6 In some embodiments, R is alkenyl. 9 is an optionally substituted C 2~6 In some embodiments, R is alkynyl. 8 and R 9 taken together form oxo. In some embodiments, R 8 and R 9 together with the carbon to which they are attached form an optionally substituted 3- to 6-membered cycloalkyl or heterocycloalkyl.

[0168] In some embodiments of formula (VI), ring A is phenyl, naphthyl, monocyclic heteroaryl, or bicyclic heteroaryl. In some embodiments, ring A is phenyl. In some embodiments, ring A is a 6-membered monocyclic heteroaryl containing 1-3 heteroatoms. In some embodiments, ring A is pyridine. In some embodiments, ring A is pyrimidine. In some embodiments, ring A is naphthyl. In some embodiments, ring A is a monocyclic heteroaryl. In some embodiments, ring A is or a bicyclic heteroaryl.

[0169] In some embodiments of formula (VI), R A are independently halogen, -NO 2 , oxo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 ) 2 S(O) 2 (R 12 ), -S(O)R 12 , -S(O)2 R 12 , and -S(O) 2 N(R 12 )(R 11 In some embodiments, R A independently, -NO 2 , oxo, -CN, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12 , -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 ) 2 S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , and -S(O) 2 N(R 12 )(R 11 In some embodiments, R A is halogen. In some embodiments, R A -NO 2 In some embodiments, R A is oxo. In some embodiments, RA In some embodiments, R A is an optionally substituted C 1~6 In some embodiments, R A is an optionally substituted C 1~3 In some embodiments, R A is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, t-butyl, -CF 3 , -CH 2 CF 3 , or -CH 2 CH 2 F. In some embodiments, R A is an optionally substituted C 2~6 In some embodiments, R is alkenyl. A is an optionally substituted C 2~6 In some embodiments, R is alkynyl. A is an optionally substituted C 1~6 In some embodiments, R A is an optionally substituted C 3~8 In some embodiments, R A is an optionally substituted C 3~6 cycloalkyl, e.g., cyclopropyl. In some embodiments, R A teeth, [ka] In some embodiments, R A is an optionally substituted C 2~7 In some embodiments, R A is an optionally substituted C 2~5 In some embodiments, R A -OR 11 In some embodiments, R A -OC 1~3 In some embodiments, R A -OCH3 , -OCH 2 CH 3 , -OCH 2 OMe, -OCH 2 CH 2 OH, -OC(CH 3 ) 3 , or -OCH 2 CH 2 OCH 3 In some embodiments, R A -OCH 3 In some embodiments, R A teeth, [ka] In some embodiments, R A -SR 11 In some embodiments, R A is -N(R 12 )(R 11 In some embodiments, R A is -C(O)R 12 In some embodiments, R A is -C(O)OR 12 In some embodiments, R A is -OC(O)R 12 In some embodiments, R A is -OC(O)N(R 12 )(R 11 In some embodiments, R A is -C(O)N(R 12 )(R 11 In some embodiments, R A is -N(R 12 )C(O)R 12 In some embodiments, R A is -N(R 12 )C(O)OR 12 In some embodiments, R A is -N(R 12 )C(O)N(R 12 )(R 11 In some embodiments, R Ais -N(R 12 ) 2 S(O) 2 (R 12 In some embodiments, R A is -S(O)R 12 In some embodiments, R A -S(O) 2 R 12 In some embodiments, R A -S(O) 2 N(R 12 )(R 11 ).

[0170] In some embodiments of formula (VI), R 11 is hydrogen, optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~7 Heterocycloalkyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted -C 1~4 Alkylene-C 3~8 Cycloalkyl, optionally substituted -C 1~4 Alkylene-C 2~7 Heterocycloalkyl, optionally substituted -C 1~4 Alkylene-phenyl, or optionally substituted -C 1~4 In some embodiments, R is an alkylene-heteroaryl. 11 is hydrogen. In some embodiments, R 11 is an optionally substituted C 1~6 In some embodiments, R 11 is an optionally substituted C 1~3 In some embodiments, R A is methyl, ethyl, propyl, isopropyl, n-butyl, iso-butyl, sec-butyl, t-butyl, -CF3 , -CH 2 CF 3 , or -CH 2 CH 2 F. In some embodiments, R 11 is an optionally substituted C 2~6 In some embodiments, R is alkenyl. 11 is an optionally substituted C 2~6 In some embodiments, R is alkynyl. 11 is an optionally substituted C 1~6 In some embodiments, R 11 is an optionally substituted C 3~8 In some embodiments, R 11 is an optionally substituted C 2~7 In some embodiments, R 11 is optionally substituted phenyl. In some embodiments, R 11 is optionally substituted heteroaryl. In some embodiments, R 11 is an optionally substituted -C 1~4 Alkylene-C 3~8 In some embodiments, R 11 is an optionally substituted -C 1~4 Alkylene-C 2~7 In some embodiments, R 11 is an optionally substituted -C 1~4 In some embodiments, R is alkylene-phenyl. 11 is an optionally substituted -C 1~4 It is an alkylene-heteroaryl.

[0171] In some embodiments of formula (VI), R 12 each independently represents hydrogen, halogen, -OH, -NO 2 , -CN,C 1~6 Alkyl, C 1~6 Aminoalkyl, C 1~6 Hydroxyalkyl, C1~6 Haloalkyl and C 3~6 Carbocyclic ring, 3- to 6-membered heterocyclic ring, 3~6 The carbocycle and the 3- to 6-membered heterocycle are independently selected from halogen, -OH, oxo, amino, -NO 2 , -CN,C 1~6 Alkyl, C 1~6 Alkoxy and C 1~6 In some embodiments of formula (VI), R 12 Each of the groups is independently hydrogen, -NO 2 , -CN,C 1~6 Alkyl, C 1~6 Aminoalkyl, C 1~6 Hydroxyalkyl, C 1~6 Haloalkyl and C 3~6 Carbocyclic ring, 3- to 6-membered heterocyclic ring, 3~6 The carbocycle and the 3- to 6-membered heterocycle are independently selected from halogen, -OH, oxo, amino, -NO 2 , -CN,C 1~6 Alkyl, C 1~6 Alkoxy and C 1~6 In some embodiments, R is optionally substituted with one or more substituents selected from haloalkyl. 12 is hydrogen. In some embodiments, R 12 is halogen. In some embodiments, R 12 is -OH. In some embodiments, R 12 -NO 2 In some embodiments, R 12 is -CN. In some embodiments, R 12 is C 1~6 In some embodiments, R 12 is C 1~6 In some embodiments, R 12 is C 1~6 In some embodiments, R 12 is C 1~6 In some embodiments, R 12 and C 3~6In some embodiments, R 12 is a 3- to 6-membered heterocycle, C 3~6 The carbocycle and the 3- to 6-membered heterocycle are independently selected from halogen, -OH, oxo, amino, -NO 2 , C.N., C. 1~6 Alkyl, C 1~6 Alkoxy and C 1~6 In some embodiments, one or more of the substituents is optionally substituted with one or more substituents selected from haloalkyl. In some embodiments, one or more of the substituents is halogen. In some embodiments, one or more of the substituents is -OH. In some embodiments, one or more of the substituents is oxo. In some embodiments, one or more of the substituents is amino. In some embodiments, one or more of the substituents is -NO 2 In some embodiments, one or more of the substituents is -CN. In some embodiments, one or more of the substituents is -C 1~6 In some embodiments, one or more of the substituents is C 1~6 In some embodiments, one or more of the substituents is C 1~6 It is haloalkyl.

[0172] In some embodiments of formula (VI), R B is hydrogen, halo, -CN, -NO 2 , optionally substituted C 1~6 Alkyl, optionally substituted C 2~6 Alkenyl, optionally substituted C 2~6 Alkynyl, optionally substituted C 1~6 Heteroalkyl, -OR 11 , -SR 11 , -N(R 12 )(R 11 ), -C(O)R 12 , -C(O)OR 12 , -OC(O)R 12 , -OC(O)N(R 12 )(R 11 ), -C(O)N(R 12 )(R 11 ), -N(R 12 )C(O)R 12, -N(R 12 )C(O)OR 12 , -N(R 12 )C(O)N(R 12 )(R 11 ), -N(R 12 )S(O) 2 (R 12 ), -S(O)R 12 , -S(O) 2 R 12 , -S(O) 2 N(R 12 )(R 11 ), optionally substituted C 3~8 Cycloalkyl, optionally substituted C 2~9 In some embodiments, R is an optionally substituted heterocycloalkyl, an optionally substituted naphthyl, an optionally substituted phenyl, an optionally substituted monocyclic heteroaryl, or an optionally substituted bicyclic heteroaryl. B is hydrogen. In some embodiments, R B is halo. In some embodiments, R B In some embodiments, R B -NO 2 In some embodiments, R B is an optionally substituted C 1~6 In some embodiments, R B is an optionally substituted C 2~6 In some embodiments, R is alkenyl. B is an optionally substituted C 2~6 In some embodiments, R is alkynyl. B is an optionally substituted C 1~6 In some embodiments, R B -OR 11 In some embodiments, R B -SR 11 In some embodiments, R B is -N(R 12 )(R 11 In some embodiments, R B is -C(O)R12 In some embodiments, R B is C(O)OR 12 In some embodiments, R B is -OC(O)R 12 In some embodiments, R B is -OC(O)N(R 12 )(R 11 In some embodiments, R B is -C(O)N(R 12 )(R 11 In some embodiments, R B is -N(R 12 )C(O)R 12 In some embodiments, R B is -N(R 12 )C(O)OR 12 In some embodiments, R B is -N(R 12 )C(O)N(R 12 )(R 11 In some embodiments, R B is -N(R 12 )S(O) 2 (R 12 In some embodiments, R B is -S(O)R 12 In some embodiments, R B -S(O) 2 R 12 In some embodiments, R B -S(O) 2 N(R 12 )(R 11 In some embodiments, R B is an optionally substituted C 3~8 In some embodiments, R B is an optionally substituted C 2~9 In some embodiments, R B is optionally substituted naphthyl. In some embodiments, R Bis optionally substituted phenyl. In some embodiments, R B is an optionally substituted monocyclic heteroaryl. In some embodiments, R B is an optionally substituted bicyclic heteroaryl.

[0173] In some embodiments of Formula (VI), m is 1, 2, 3, or 4. In some embodiments, m is 1. In some embodiments, m is 2. In some embodiments, m is 3. In some embodiments, m is 4.

[0174] In some embodiments of Formula (VI), p is 0 or 1. In some embodiments, p is 0. In some embodiments, p is 1.

[0175] Non-limiting examples of compounds described herein are those presented in Table 1, and pharma- ceutically acceptable salts or solvates thereof. [Table 1-1] [Table 1-2]

[0176] Table 2 shows the USP1 IC50 (nM) and MDA-MB-436 IC50 (nM) of the compounds listed in Table 1. 50 The corresponding biological data are presented in (nM). [Table 2]

[0177] IC50(nM):0 <A≦50、50<B≦1,000、1,000<C≦10,000、10,000<D

[0178] The present disclosure includes the salts of the compounds described herein, particularly pharma-ceutically acceptable salts.Compounds of the present disclosure that possess sufficiently acidic, sufficiently basic, or both functional groups can react with any of several inorganic bases, and inorganic and organic acids to form salts.Alternatively, compounds that are inherently charged, such as compounds that have quaternary nitrogen, can form salts with suitable counterions, for example halides such as bromide, chloride, or fluoride, particularly bromide.

[0179] Chemical substances having carbon-carbon or carbon-nitrogen double bonds can exist in Z or E forms (or cis or trans forms). Additionally, some chemical substances can exist in various tautomeric forms. Unless otherwise specified, the compounds described herein are intended to include all Z, E, and tautomeric forms.

[0180] As used herein, "phenyl isostere" refers to a moiety or functional group that exhibits similar physical, biological, and / or chemical properties to a phenyl group. Exemplary phenyl isosteres include, but are not limited to, cubane, bicyclo[1.1.1]pentane (BCP), bicyclo[2.2.1]heptane, bicyclo[2.1.1]hexane, bicyclo[2.2.2]octane, adamantane, norbornene, closo-1,2-carborane, closo-1,7-carborane, closo-1,12-carborane, and ethynyl groups. In some embodiments, the phenyl isostere is cubane. In some embodiments, the phenyl isostere is an ethynyl group.

[0181] "Tautomer" refers to a molecule in which a proton shift from one atom of the molecule to another atom of the same molecule is possible. The compounds presented herein exist in certain embodiments as tautomers. In situations where tautomerization is possible, a chemical equilibrium of tautomers will exist. The exact ratio of tautomers depends on several factors, including physical conditions, temperature, solvent, and pH. Some examples of tautomeric equilibrium include: [ka] Includes:

[0182] The compounds disclosed herein are, in some embodiments, used in different isotopically enriched forms, e.g. 2 H, 3 H, 11 C. 13 C, and / or 14 The C content is enriched. In one particular embodiment, the compound is deuterated at at least one position. Such deuterated forms can be made by the procedures described in U.S. Patent Nos. 5,846,514 and 6,334,997. As described in U.S. Patent Nos. 5,846,514 and 6,334,997, deuteration can improve metabolic stability and / or efficacy, thus increasing the duration of action of the drug.

[0183] Unless otherwise stated, the compounds described herein may exhibit their natural isotopic abundance, or one or more of the atoms may be artificially enriched in a particular isotope having the same atomic number but an atomic mass or mass number different from that found predominantly in nature. All isotopic variations of the compounds of the present disclosure, whether radioactive or not, are encompassed within the scope of the present disclosure. For example, the compounds described herein may be artificially enriched in one or more particular isotopes. In some embodiments, the compounds described herein may be artificially enriched in one or more isotopes not found predominantly in nature. In some embodiments, the compounds described herein may be artificially enriched in deuterium ( 2 H), tritium ( 3 H), iodine-125( 125 I), or carbon-14 ( 14 C) may be artificially enriched with one or more isotopes selected from: 2 H, 11 C. 13 C. 14 C. 15 C.12 N, 13 N, 15 N, 16 N, 16 O. 17 O. 14 F, 15 F, 16 F, 17 F, 18 F, 33 S, 34 S, 35 S, 36 S, 35 Cl, 37 Cl, 79 Br, 81 Br, 131 I, and 125 The isotopes are artificially enriched in one or more isotopes selected from I. In some embodiments, the abundance of the enriched isotopes is independently at least 1%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100% by molar.

[0184] In some embodiments of the compounds disclosed herein, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 11 , R 12 , R Y1 , R Y2 , R Y3 , R Y4 , R A , R B , R B1 , R 1Ca , R 1Da , R a , R b , R c , and / or R d One or more of the groups contains deuterium at a percentage greater than the natural abundance of deuterium.

[0185] In some embodiments of the compounds disclosed herein, one or more 1 H is the following group R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 11 , R 12 , R Y1 , R Y2 , R Y3 , R Y4 , R A , R B , R B1 , R 1Ca , R 1Da , R a , R b , R c , and / or R d is replaced with one or more deuterium atoms.

[0186] In some embodiments of the compounds disclosed herein, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 11 , R 12 , R Y1 , R Y2 , R Y3 , R Y4 , R A , R B , R B1 , R 1Ca , R 1Da , R a , R b , R c , and / or R d The abundance of deuterium in each of is independently at least 1%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100% by molar.

[0187] In some embodiments of the compounds disclosed herein, one or more of ring A, ring B, ring C, and / or ring D may be 1 H is replaced by one or more deuterium atoms.

[0188] In certain embodiments, the compounds disclosed herein are 2 Replaced by H atom 1 H atoms. Methods for the synthesis of deuterium-containing compounds are known in the art and include, by way of non-limiting example only, the following synthesis methods: Deuterium-substituted compounds can be synthesized using a variety of methods, such as those described in Dean, Dennis C.; Editor. Recent Advances in the Synthesis and Applications of Radiolabeled Compounds for Drug Discovery and Development. [In: Curr., Pharm. Des., 2000; 6(10)] 2000, 110 pp; George W.; Varma, Rajender S. The Synthesis of Radiolabeled Compounds via Organometallic Intermediates, Tetrahedron, 1989, 45(21), 6601-21, and Evans, E. Anthony. Synthesis of radiolabeled compounds, J. Radioanal. Chem., 1981, 64(1-2), 9-32.

[0189] Deuterated starting materials are readily available and amenable to the synthetic methods described herein to provide for the synthesis of deuterium-containing compounds. Many deuterium-containing reagents and building blocks are commercially available from chemical vendors such as Aldrich Chemical Co.

[0190] The compounds of the present disclosure also include crystalline and amorphous forms of these compounds, including, for example, polymorphs, pseudopolymorphs, solvates, hydrates, nonsolvated polymorphs (including anhydrates), conformational polymorphs, and amorphous forms of the compounds, and mixtures thereof, pharma- ceutically acceptable salts, and active metabolites of these compounds having the same type of activity.

[0191] The compounds described herein may exist as diastereomers, enantiomers, or other stereoisomeric forms in some cases. When absolute stereochemistry is not specified, the compounds presented herein include all diastereomeric, enantiomeric, and epimeric forms, and the appropriate mixtures thereof. Separation of stereoisomers can be carried out by chromatography, or by forming diastereomers and separating them by recrystallization or chromatography, or any combination thereof. (Jean Jacques, Andre Collet, Samuel H. Wilen, "Enantiomers, Racemates and Resolutions", John Wiley And Sons, Inc., 1981, which is incorporated herein by reference for the present disclosure). Stereoisomers can also be obtained by stereoselective synthesis.

[0192] The methods and compositions described herein include the use of amorphous and crystalline forms (also known as polymorphs). The compounds described herein may be in the form of pharmaceutically acceptable salts. Similarly, in some embodiments, the active metabolites of these compounds with the same type of activity are included within the scope of the present disclosure. In addition, the compounds described herein can exist in unsolvated and solvated forms with pharmaceutically acceptable solvents such as water, ethanol, and the like. The solvated forms of the compounds presented herein are also considered to be disclosed herein.

[0193] In some embodiments, the compound or salt of the compound may be a prodrug, for example, where hydroxyl in the parent compound is presented as an ester or carbonate, or carboxylic acid present in the parent compound is presented as an ester. The term "prodrug" is intended to encompass compounds that are converted to the pharmaceutical agent of the present disclosure under physiological conditions. One method for making a prodrug is to include one or more selected moieties that are hydrolyzed under physiological conditions to reveal the desired molecule. In other embodiments, the prodrug is converted by the enzyme activity of the host animal, such as specific target cells in the host animal. For example, esters or carbonates (e.g., esters or carbonates of alcohols or carboxylic acids, and esters of phosphonic acids) are preferred prodrugs of the present disclosure.

[0194] Prodrug forms of the compounds described herein, where the prodrug is metabolized in vivo to produce a compound described herein, are included within the scope of the claims. In some cases, some of the compounds described herein may be prodrugs of another derivative or active compound.

[0195] Prodrugs are often useful because in some situations they may be easier to administer than the parent drug. They may be, for example, bioavailable by oral administration, whereas the parent is not. Prodrugs may help to enhance the cell permeability of the compound relative to the parent drug. Prodrugs may also have improved solubility in pharmaceutical compositions compared to the parent drug. Prodrugs can be designed as reversible drug derivatives to enhance drug transport to site-specific tissues or to be used as modifiers to increase drug retention inside cells.

[0196] In some embodiments, the prodrug design increases the lipophilicity of the pharmaceutical agent, hi some embodiments, the prodrug design increases the effective water solubility. For example, Fedorak et al., Am.J.Physiol.,269:G210-218(1995), McLoed et al.,Gastroenterol,106:405-413(1994), Hochhaus et al.,Biomed.Chrom.,6:283-286 (1992), J.Larsen and H.Bundgaard, Int.J.Pharmaceutics,37,87(1987), J.Larsen et al.,Int.J.Pharmaceutics,47,103(1988), Sinkula et al.,J.Pharm.Sci.,64:181-210(1975), T.Higuchi and V.Stella,Pro-drugs as Novel Delivery Systems,Vol.14 of the ACSSymposium Series, and Edward (See B. Roche, Bioreversible Carriers in Drug Design, American Pharmaceutical Association and Pergamon Press, 1987). According to another embodiment, the present disclosure provides a method for producing the compounds defined above. The compounds can be synthesized using conventional techniques. Advantageously, these compounds are conveniently synthesized from readily available starting materials.

[0197] Synthetic chemistry transformations and methodologies useful for synthesizing the compounds described herein are known in the art and include, for example, those described in R. Larock, Comprehensive Organic Transformations (1989), T. W. Greene and P. G. Muts, Protective Groups in Organic Synthesis, 2d Ed. (1991), L. Fieser and M. Fieser, Fieser and Fieser's Reagents for Organic Synthesis (1994), and L. Paquette, ed., Encyclopedia of Reagents for Organic Synthesis (1995).

[0198] C. Pharmaceutical Compositions In certain embodiments, provided herein are compositions comprising a therapeutically effective amount of any compound or salt of any one of Formulae (I), (Ia), (Ib), (II), (IIa), (IIa-1), (IIa-1a), (IIb), (IIb-1), (IIb-1a), (IIc), (IIc-1), (IId), (IId-1), (IIe), (IIf), (II'), and (VI) (also referred to herein as a "pharmaceutical agent").

[0199] Pharmaceutical compositions can be formulated using one or more physiologically acceptable carriers, including excipients and auxiliary agents that facilitate the processing of pharmaceutical agents into pharmaceutical preparations. Appropriate formulations depend on the route of administration selected. Overviews of pharmaceutical compositions can be found, for example, in Remington: The Science and Practice of Pharmacy, Nineteenth Ed (Easton, Pa., Mack Publishing Company, 1995); Hoover, John E., Remington's Pharmaceutical Sciences, Mack Publishing Co., Easton, Pennsylvania 1975; Liberman, HA and Lachman, L., Eds., Pharmaceutical Dosage Forms, Marcel Decker, New York, NY, 1980, and Pharmaceutical Dosage Forms and Drug Delivery Systems, Seventh Ed. (Lippincott Williams & Wilkins, 1999).

[0200] The compositions and methods of the present disclosure can be utilized to treat an individual in need thereof. In some embodiments, the individual is a mammal, such as a human, or a non-human mammal. When administered to an animal, such as a human, the composition or pharmaceutical agent is preferably administered as a pharmaceutical composition, for example, comprising a pharmaceutical agent and a pharmaceutically acceptable carrier or excipient. Pharmaceutically acceptable carriers are well known in the art and include, for example, aqueous solutions, such as water or physiologically buffered saline, or other solvents or vehicles, such as glycols, glycerol, oils, such as olive oil, or injectable organic esters. In a preferred embodiment, when such pharmaceutical compositions are for human administration, particularly for invasive routes of administration, such as injection or implantation, which avoid transport or diffusion through epithelial barriers, the aqueous solution is pyrogen-free or substantially pyrogen-free. The excipient can be selected, for example, to provide delayed release of the agent or to selectively target one or more cells, tissues, or organs. The pharmaceutical composition may be in unit dosage form, such as tablets, capsules, granules, lyophilized forms for reconstitution, powders, solutions, syrups, suppositories, injections, and the like. The composition may also be present in a transdermal delivery system, such as a skin patch. The composition may also be present in a solution suitable for topical administration, such as eye drops.

[0201] A pharma- ceutically acceptable excipient can contain a physiologically acceptable agent that acts, for example, to stabilize, increase solubility, or increase absorption of a compound, such as a pharmaceutical agent. Such physiologically acceptable agents include, for example, carbohydrates, such as glucose, sucrose, or dextran, antioxidants, such as ascorbic acid or glutathione, chelating agents, low molecular weight proteins, or other stabilizers or excipients. The choice of a pharma- ceutical acceptable excipient that includes a physiologically acceptable agent depends, for example, on the route of administration of the composition. The preparation or pharmaceutical composition can be a self-emulsifying drug delivery system or a self-microemulsifying drug delivery system. The pharmaceutical composition (preparation) can also be, for example, a liposome or other polymer matrix into which the compound of the present disclosure can be incorporated. For example, liposomes containing phospholipids or other lipids are non-toxic, physiologically acceptable, metabolizable carriers that are relatively easy to prepare and administer.

[0202] The pharmaceutical composition (preparation) can be administered to a subject by any of several routes of administration, including orally, e.g., as a drench, such as an aqueous or non-aqueous solution or suspension, as a tablet, as a capsule, including a sprinkle capsule and a gelatin capsule, as a bolus, as a powder, as a granule, as a paste for application to the tongue, as absorbed through the oral mucosa, e.g., sublingually, as anally, rectally, or vaginally, e.g., as a pessary, cream, or foam, as intramuscularly, intravenously, subcutaneously, or intrathecally, e.g., as a sterile solution or suspension, as a parenteral, nasally, intraperitoneally, subcutaneously, transdermally, e.g., as a patch applied to the skin, and topically, e.g., as a cream, ointment, or spray applied to the skin, or as eye drops. The compound can also be formulated for inhalation. In some embodiments, the compound can simply be dissolved or suspended in sterile water.

[0203] Pharmaceutical compositions can be sterile aqueous or non-aqueous solutions, suspensions, or emulsions, such as microemulsions.The excipients described herein are examples and are in no way limiting.Effective amount or therapeutically effective amount refers to the amount of one or more pharmaceutical agents administered to a subject, either as a single dose or as part of a series of doses, that is effective to produce the desired therapeutic effect.

[0204] The subject can generally be monitored for therapeutic effectiveness using assays and methods suitable for the condition being treated, which assays will be known to those skilled in the art and are described herein.The pharmacokinetics of the pharmaceutical agent or one or more metabolites thereof administered to the subject can be monitored by determining the level of the pharmaceutical agent or metabolite in a biological fluid, such as blood, blood fractions, such as serum, and / or urine, and / or other biological samples or biological tissues from the subject.Any method practiced in the art for detecting pharmaceutical agents and described herein can be used to measure the level of the pharmaceutical agent or metabolite during the course of treatment.

[0205] The dose of the pharmaceutical agent described herein for treating a disease or disorder may depend on the condition of the subject, i.e., the stage of the disease, the severity of the symptoms caused by the disease, the general health condition, as well as the age, sex, and weight, and other factors that are evident to those skilled in the art. The pharmaceutical composition can be administered in a manner appropriate to the disease being treated, as determined by those skilled in the art. In addition to the factors described herein and above related to the use of the pharmaceutical agent for treating a disease or disorder, the suitable duration and frequency of administration of the pharmaceutical agent can also be determined or adjusted depending on factors such as the condition of the patient, the type and severity of the patient's disease, the specific form of the active ingredient, and the method of administration. The optimal dose of the drug can generally be determined using experimental models and / or clinical trials. The optimal dose may depend on the subject's body mass, body weight, or blood volume. The use of the minimum dose that is sufficient to provide effective treatment is usually preferred. The design and execution of preclinical and clinical trials of the pharmaceutical agents described herein, including those administered for prophylactic benefit, is well within the skill of those skilled in the relevant art. When two or more pharmaceutical agents are administered to treat a disease or disorder, the optimal dose of each pharmaceutical agent may be different, such as less than when either agent is administered alone as a monotherapy. In certain embodiments, two pharmaceutical agents may act synergistically or additively in combination, and either agent may be used in a lower amount than when administered alone. The amount of pharmaceutical agent that can be administered per day may be, for example, about 0.01 mg / kg to 100 mg / kg, such as about 0.1 to 1 mg / kg, about 1 to 10 mg / kg, about 10 to 50 mg / kg, or about 50 to 100 mg / kg body weight. In other embodiments, the amount of pharmaceutical agent that can be administered per day is about 0.01 mg / kg to 1000 mg / kg, about 100 to 500 mg / kg, or about 500 to 1000 mg / kg body weight. The optimal dose per day or per course of treatment may differ for the disease or disorder being treated and may also vary with the route of administration and treatment regimen.

[0206] The pharmaceutical composition containing the pharmaceutical agent can be formulated in a manner suitable for the delivery method by using techniques routinely practiced in the art.The composition can be in the form of a solid, such as a tablet, a capsule, a semi-solid, such as a gel, a liquid, or a gas, such as an aerosol.In other embodiments, the pharmaceutical composition is administered as a bolus injection.

[0207] Pharmaceutically acceptable excipients are well known in the pharmaceutical art and are described, for example, in Rowe et al., Handbook of Pharmaceutical Excipients: A Comprehensive Guide to Uses, Properties, and Safety, 5 th Ed., 2006, and Remington: The Science and Practice of Pharmacy (Gennaro, 21 st Ed. Mack Pub. Co., Easton, PA (2005). Exemplary pharma- ceutical acceptable excipients include sterile saline and phosphate buffered saline at physiological pH. Preservatives, stabilizers, dyes, buffers, and the like can be provided in the pharmaceutical composition. In addition, antioxidants and suspending agents can also be used. In general, the type of excipient is selected based on the mode of administration and the chemical composition of the active ingredient(s). Alternatively, the compositions described herein can be formulated as lyophilizates. The compositions described herein can be lyophilized or otherwise formulated as lyophilized products using one or more appropriate excipient solutions to solubilize and / or dilute the pharmaceutical agent(s) of the composition upon administration. In other embodiments, the pharmaceutical agent can be encapsulated in liposomes using techniques known and practiced in the art. In certain embodiments, the pharmaceutical agent is not formulated in liposomes for application to stents used to treat highly, but not completely, blocked arteries. The pharmaceutical composition can be formulated for any suitable mode of administration as described herein and in the art.

[0208] For example, pharmaceutical compositions for oral administration or for injection, infusion, subcutaneous delivery, intramuscular delivery, intraperitoneal delivery, or other methods may be in the form of a liquid. Liquid pharmaceutical compositions may, for example, contain one or more of the following: water, saline, preferably saline, Ringer's solution, isotonic sodium chloride, sterile diluents such as fixed oils, polyethylene glycol, glycerin, propylene glycol, or other solvents that can function as solvents or suspending media, antibacterial agents, antioxidants, chelating agents, buffers and agents for adjusting isotonicity such as sodium chloride or dextrose. Parenteral compositions may be enclosed in ampoules, disposable syringes, or multi-dose vials made of glass or plastic. The use of saline is preferred, and injectable pharmaceutical compositions are preferably sterile. In another embodiment, liquid pharmaceutical compositions may be applied to the eye in the form of eye drops for the treatment of ophthalmic conditions or diseases. Liquid pharmaceutical compositions may be delivered orally.

[0209] For oral formulations, at least one of the pharmaceutical agents described herein can be used alone or in combination with suitable additives for making tablets, powders, granules, or capsules, and if desired, in combination with diluents, buffers, wetting agents, preservatives, coloring agents, and flavoring agents.The pharmaceutical agent can be formulated with a buffer to provide protection of the compound from the low pH of the stomach environment and / or enteric coating.The pharmaceutical agent included in the pharmaceutical composition can be formulated with flavoring agents, for example, in liquid, solid, or semi-solid formulations, and / or with enteric coating for oral delivery.

[0210] Pharmaceutical compositions containing any one of the pharmaceutical agents described herein can be formulated for sustained or extended release, also referred to as timed or controlled release. Such compositions can generally be prepared using well-known techniques and administered, for example, by oral, rectal, intradermal, or subcutaneous implantation, or by implantation at a desired target site. Sustained release formulations can contain the compound dispersed in a carrier matrix and / or contained within a reservoir surrounded by a rate-controlling membrane. The excipients for use within such formulations can be biocompatible and biodegradable, and preferably the formulation provides a relatively constant level of active ingredient release. The amount of pharmaceutical agent contained within a sustained release formulation depends on the site of implantation, the rate and expected duration of release, and the nature of the condition, disease, or disorder being treated or prevented.

[0211] In some embodiments, the pharmaceutical composition containing the medicinal agent is formulated for transdermal, intradermal, or topical administration. The composition can be administered as a powder / talc or other solid, liquid, spray, aerosol, ointment, foam, cream, gel, paste, using a syringe, bandage, transdermal patch, insert, or applicator such as a syringe. It is preferably in the form of a controlled or sustained release formulation that is administered topically or injected directly into the skin adjacent to or within the area to be treated, for example, injected intradermally or subcutaneously. The active composition can also be delivered via iontophoresis. Preservatives can be used to prevent the growth of fungi and other microorganisms. Suitable preservatives include, but are not limited to, benzoic acid, butylparaben, ethylparaben, methylparaben, propylparaben, sodium benzoate, sodium propionate, benzalkonium chloride, benzethonium chloride, benzyl alcohol, cetylpyridinium chloride, chlorobutanol, phenol, phenylethyl alcohol, thimerosal, and combinations thereof.

[0212] Pharmaceutical compositions containing medicinal agents can be formulated as emulsions for topical application. Emulsions contain one liquid distributed within a second liquid. Emulsions can be oil-in-water emulsions or oil-in-water emulsions. Either or both of the oil and water phases can contain one or more surfactants, emulsifiers, emulsion stabilizers, buffers, and other excipients. The oil phase can contain other oil-based pharma- ceutical approved excipients. Suitable surfactants include, but are not limited to, anionic surfactants, nonionic surfactants, cationic surfactants, and amphoteric surfactants. Compositions for topical application can also contain at least one suitable suspending agent, antioxidant, chelating agent, emollient, or moisturizing agent.

[0213] Ointments and creams can be formulated with an aqueous or oily base, for example, with the addition of suitable thickening and / or gelling agents.Lotions can be formulated with an aqueous or oily base, and generally also contain one or more emulsifiers, stabilizers, dispersants, suspending agents, thickening agents, or colorants.Liquid sprays can be delivered from pressurized packs, for example, through specially shaped closures.Oil-in-water emulsions can also be used in compositions, patches, dressings, and articles.These systems are semisolid emulsions, microemulsions, or foam emulsion systems.

[0214] In some embodiments, the pharmaceutical agents described herein can be formulated as inhalants. Inhalation can deliver the agent directly to the airways. The pharmaceutical agents can be formulated as aerosols, microspheres, liposomes, or nanoparticles. The pharmaceutical agents can be formulated with solvents, gases, nitrates, or any combination thereof. The compositions described herein are optionally formulated for delivery as liquid aerosols or inhalable dry powders. Liquid aerosol formulations are optionally nebulized into particle sizes that can be delivered primarily to the terminal and respiratory bronchioles. Liquid aerosol and inhalable dry powder formulations are preferably delivered throughout the endobronchial tree to the terminal bronchioles and ultimately to parenchymal tissues.

[0215] The aerosolized formulations described herein are optionally delivered using an aerosol-forming device, such as a jet, a vibrating porous plate, or an ultrasonic nebulizer, which is preferably selected to allow the formation of aerosol particles having a mass median mean diameter of mainly 1-5μ. Furthermore, the formulations preferably have a balanced osmotic ionic strength and chloride concentration, as well as a minimum aerosolizable volume capable of delivering an effective amount of pharmaceutical agent. In addition, the aerosolized formulations preferably do not adversely affect the function of the airways and do not cause undesirable side effects.

[0216] Aerosolization devices suitable for administration of the aerosol formulations described herein include, for example, jet, vibrating porous plate, ultrasonic nebulizers, and electrochemical dry powder inhalers that can nebulize the formulation into aerosol particle sizes primarily within the 1-5μ size range. In this application, "primarily" means that at least 70% but preferably more than 90% of all generated aerosol particles are within the 1-5μ range. Jet nebulizers break up solutions into aerosol droplets by air pressure. Vibrating porous plate nebulizers work by pushing solvent droplets through a porous plate using a sonic vacuum generated by a rapidly vibrating porous plate. Ultrasonic nebulizers work by piezoelectric crystals that shear the liquid into small aerosol droplets. A variety of suitable devices are available, including, for example, AeroNeb™ and AeroDose™ vibrating porous plate nebulizers (AeroGen, Inc., Sunnyvale, California), Sidestream® nebulizers (Medic-Aid Ltd., West Sussex, England), Pari LC® and Pari LC Star® jet nebulizers (Pari Respiratory Equipment, Inc., Richmond, Virginia), as well as Aerosonic™ (DeVilbiss Medizinische Produkte (Deutschland) GmbH, Heiden, Germany) and UltraAire® (Omron Healthcare, Inc., Vernon Hills, Illinois) ultrasonic nebulizers.

[0217] In some embodiments, the pharmaceutical agent(s) can be formulated with an oleaginous base or ointment to form a semi-solid composition with a desired shape. In addition to the pharmaceutical agent, these semi-solid compositions can contain a dissolving and / or suspending bactericide, a preservative, and / or a buffer system. The petrolatum component that can be included can be any paraffin ranging in viscosity from mineral oil to paraffin wax incorporating isobutylene, colloidal silica, or stearates. Absorption bases can be used with oleaginous systems. Additives include cholesterol, lanolin (lanolin derivatives, beeswax, fatty alcohols, wool fat alcohol, low HLB (hydrophobic lipophobic balance) emulsifiers, and a wide variety of ionic and non-ionic surfactants, alone or in combination.

[0218] Controlled or sustained release transdermal or topical formulations can be achieved by adding time-release additives such as polymeric structures, matrices, etc., available in the art.For example, the composition can be administered through the use of hot-melt extrusion articles, such as bioadhesive hot-melt extrusion films.The formulation can include cross-linked polycarboxylic acid polymer formulations.The cross-linking agent can be present in an amount that provides sufficient adhesive strength to allow the system to remain attached to the target epithelial or endothelial cell surface for a sufficient period of time to allow the desired release of the compound.

[0219] The insert, transdermal patch, bandage, or article can include a polymer mixture or coating that provides a constant rate of release of the pharmaceutical agent over an extended period of time. In some embodiments, the article, transdermal patch, or insert includes a water-soluble pore former, such as polyethylene glycol (PEG), that can be mixed with the water-insoluble polymer to increase the durability of the insert and extend the release of the active ingredient.

[0220] Transdermal devices (inserts, patches, bandages) can also contain water-insoluble polymers. Rate-controlling polymers can be useful for administration to sites where pH changes can be used to effect release. These rate-controlling polymers can be applied using a continuous coating film during the process of spraying with the active compound and drying. In one embodiment, the coating formulation is used to coat pellets containing the active ingredient that are compressed to form a solid biodegradable insert.

[0221] Polymer formulations can also be utilized to provide controlled or sustained release. Bioadhesive polymers described in the art can be used. As an example, sustained release gels and compounds can be incorporated into polymer matrices, such as hydrophobic polymer matrices. Examples of polymer matrices include microparticles. The microparticles can be microspheres, and the core can be a different material than the polymer shell. Alternatively, the polymer can be cast as a thin slab or film, a powder produced by grinding or other standard techniques, or a gel, such as a hydrogel. The polymer can also be in the form of a coating or part of a bandage, stent, catheter, vascular graft, or other device to facilitate delivery of the pharmaceutical agent. Matrices can be formed by solvent evaporation, spray drying, solvent extraction, and other methods known to those skilled in the art.

[0222] Usually, a kit is provided with one or more unit doses of the drugs described herein in oral or injectable doses.Such a kit can include a container containing the unit dose, an information package insert that describes the use of the drug in the treatment of disease and the associated benefits, and optionally an instrument or device for delivery of the composition.

[0223] D. Treatment Methods Ubiquitin-specific protease 1 (USP1) is a member of the ubiquitin-specific processing family of proteases. USP1 is a deubiquitinating enzyme ("DUB") that deubiquitinates and regulates the function of its substrates involved in major oncogenic pathways. Among its roles, USP1 exhibits DNA-mediated activation at replication forks, and can protect the forks and promote survival in BRCA1-deficient cells. Because loss of both USP1 and BRCA1 leads to replication fork degradation, inhibition of USP1 can selectively reduce the viability or kill tumor cells with BRCA deficiency without affecting the survival of cells with normal BRCA function.

[0224] In the United States (US), it is estimated that inherited BRCA1 and BRCA2 mutations are present in 5-10% of breast cancers and 10-15% of ovarian cancers. Breast cancer is the most common cancer worldwide and the most common malignancy in women. BRCA1 and BRCA2 can be detected in at least 5% of unselected breast cancer patients and in approximately 30% of patients with a family history of developing breast or ovarian cancer. Currently, treatment options including chemotherapy and immune checkpoint inhibitors are limited to breast cancer patients with germline BRCA mutations, more aggressive progression, and higher risk of recurrence. PARP inhibitors have been approved by the US Food and Drug Administration (FDA) as monotherapy for harmful / suspected harmful germline BRCA-mutated HER2-negative breast cancer, but in some cases, resistance to PARP inhibitors can be observed to rapidly develop in breast cancer patients. Ovarian cancer represents a heterogeneous group of solid tumors. On average, one in five ovarian cancers can be associated with germline mutations. Of those ovarian cancers with germline mutations, 65-85% may be associated with germline BRCA mutations. Similar to the breast cancer setting, PARP inhibitors may be first-line maintenance therapy for patients with BRCA-mutated ovarian cancer, but these patients may develop resistance to PARP inhibitors.

[0225] The compounds described herein can be used as inhibitors of USP1. Such compounds can exhibit BRCA1 and / or BRCA2 mutant selective anti-proliferative activity. The compounds described herein can be used to treat BRCA1 and / or BRCA2 mutations or homologous recombination (HRD) positive cancers. The compounds described herein can exhibit anti-proliferative activity in cancer cells with BRCA1 and / or BRCA2 mutations, particularly MDA-MB-436 cells. The compounds described herein may not exhibit similar anti-proliferative activity in cancer cells with wild-type BRCA, particularly SNG-M cells. In some embodiments, the compounds described herein can exhibit selectivity for mutant BRCA1 and / or BRCA2 at least 50-fold, 100-fold, 150-fold, 200-fold, 250-fold, 300-fold, 350-fold, 400-fold, 450-fold, 500-fold, 550-fold, 600-fold, or more, compared to wild-type BRCA.

[0226] The compounds described herein can be used for the preparation of medicaments for the prevention or treatment of disease or condition. In some embodiments, the compounds described herein are used in a method for modulating USP1 in a subject. In some embodiments, the compounds described herein are used in a method for inhibiting USP1 in a subject. In some embodiments, the compounds described herein are used in a method for inhibiting or reducing the DNA repair activity regulated by USP1 in a subject. In some embodiments, the compounds described herein are used in a method for treating a disease or disorder associated with USP1 in a subject. In some embodiments, the compounds described herein are used in a method for treating a disease or disorder associated with the regulation of USP in a subject. In addition, a method for the treatment of any of the diseases or conditions described herein in a subject in need of such treatment involves the administration of a pharmaceutical composition containing at least one compound described herein in a therapeutically effective amount, or a pharma-ceutically acceptable salt, pharma-ceutically acceptable prodrug, or pharma-ceutically acceptable solvate thereof, to the subject.

[0227] The compositions containing the compound(s) described herein can be administered for prophylactic and / or therapeutic treatment. In therapeutic applications, the compositions are administered to a patient already suffering from a disease or condition in an amount sufficient to cure or at least partially arrest the symptoms of the disease or condition. Amounts effective for this use will depend on the severity and course of the disease or condition, previous treatments, the patient's health status, weight, response to drugs, and the judgment of the treating physician.

[0228] In prophylactic applications, compositions containing the compounds described herein are administered to patients susceptible to or otherwise at risk of a particular disease, disorder, or condition. Such an amount is defined as a "prophylactically effective amount or dose." In this use, the exact amount also depends on the patient's health, weight, and the like. When used in patients, the effective amount for this use depends on the severity, course of the disease, disorder, or condition, previous treatments, the patient's health and response to the drug, and the judgment of the treating physician.

[0229] If the patient's condition does not improve, at the physician's discretion, administration of the compound can be administered chronically, i.e., for an extended period of time, including throughout the patient's lifespan, to ameliorate or otherwise control or limit the symptoms of the patient's disease or condition.

[0230] When the improvement of the patient's condition occurs, a maintenance dose is administered if necessary.Then, the dosage or frequency of administration, or both, can be reduced as a function of symptoms to a level at which the improved disease, disorder or condition is maintained.However, the patient may require intermittent treatment on a long-term basis upon the recurrence of any symptoms.

[0231] The amount of a given agent that corresponds to such an amount will vary depending on factors such as the particular compound, the disease or condition and its severity, the identity (e.g., body weight) of the subject or host requiring treatment, but can nevertheless be determined in a field-recognized manner according to the particular circumstances surrounding the case, including, for example, the specific agent being administered, the route of administration, the condition being treated, and the subject or host being treated. In general, however, doses employed for adult treatment will typically range from about 0.02 to about 5000 mg per day, and in some embodiments, from about 1 to about 1500 mg per day. The desired dose can conveniently be presented as a single dose or as divided doses administered simultaneously (or over a short period of time) or at appropriate intervals, for example, as two, three, four or more subdoses per day.

[0232] The pharmaceutical compositions described herein may be in unit dosage form suitable for single administration of precise dosage. In unit dosage form, the formulation is divided into unit doses containing appropriate amounts of one or more compounds. The unit dose may be in the form of a package containing a discrete amount of the formulation. Non-limiting examples are packaged tablets or capsules, and powders in vials or ampoules. Aqueous suspension compositions may be packaged in single-dose non-reclosable containers. Alternatively, multi-dose reclosable containers may be used, in which case it is typical to include a preservative in the composition. By way of example only, parenteral injection formulations may be presented in unit dosage form, including but not limited to ampoules, or in multi-dose containers with added preservative.

[0233] The toxicity and therapeutic efficacy of such treatment regimens are evaluated using the LD 50 (the dose lethal to 50% of the population) and ED 50 The LD (the dose therapeutically effective in 50% of the population) can be determined by standard pharmaceutical procedures in cell cultures or experimental animals. The dose ratio between toxic and therapeutic effects is the therapeutic index, and is known as the LD 50 and ED 50The therapeutic index can be expressed as a ratio between ED and ED. Compounds that exhibit high therapeutic indices are preferred. The data obtained from cell culture assays and animal studies can be used in formulating a range of dosages for use in humans. The dosage of such compounds is preferably administered at a therapeutically acceptable dose that results in an ED with minimal toxicity. 50 The dosage may vary within this range depending upon the dosage form employed and the route of administration utilized.

[0234] In one aspect, the disclosure provides a method of modulating USP1 in a subject, comprising administering to the subject a compound described herein, or a pharma- ceutically acceptable salt or solvate thereof.

[0235] In one aspect, the disclosure provides a method of inhibiting USP1 in a subject, comprising administering to the subject a compound described herein, or a pharma- ceutically acceptable salt or solvate thereof.

[0236] In one aspect, the disclosure provides a method of inhibiting or reducing DNA repair activity regulated by USP1 in a patient in need thereof, comprising administering a therapeutically effective amount of a compound described herein, or a pharma- ceutically acceptable salt or solvate thereof, or a pharmaceutical composition described herein.

[0237] In one aspect, the present disclosure provides a method of treating a disease or disorder associated with USP1 in a subject in need of such treatment, comprising administering a therapeutically effective amount of a compound described herein, or a pharma- ceutically acceptable salt or solvate thereof, or a pharmaceutical composition described herein. In some embodiments, the disease or disorder is cancer.

[0238] In one aspect, the present disclosure provides a method for treating a disease or disorder associated with the regulation of USP1 in a subject, comprising administering a therapeutically effective amount of a compound as described herein, or a pharma- ceutically acceptable salt or solvate thereof, or a pharmaceutical composition as described herein. In some embodiments, the disease or disorder is cancer.

[0239] In one aspect, the disclosure provides a method of treating cancer in a subject, comprising administering to a subject in need thereof an effective amount of a compound described herein, or a pharma- ceutically acceptable salt or solvate thereof, or a pharmaceutical composition described herein.

[0240] In some embodiments, administration of the compounds described herein, or pharma- ceutically acceptable salts or solvates thereof, can further include combination with other biologically active ingredients (e.g., a second therapeutic agent). The other biologically active ingredients can include a second different anti-tumor agent or a second agent that targets a USP1-independent mechanism of DNA repair. In some embodiments, administration of the compounds described herein, or pharma- ceutically acceptable salts or solvates thereof, can further include combination with non-pharma- ceutical therapy. Non-pharma- ceutical therapy can include surgery, radiation therapy, or any other type of therapy that does not include administering a drug. Such combination of the compounds described herein, or pharma- ceutical acceptable salts or solvates thereof, with other biologically active ingredients or non-pharma- ceutical therapy can enhance the effect of the compounds described herein, or pharma- ceutical acceptable salts or solvates thereof. The compounds described herein can be administered simultaneously with or sequentially with the other biologically active ingredients, although at least two or more compounds or biologically active ingredients can be administered during a single cycle or course of treatment. In some embodiments, the second therapeutic agent is a poly ADP-ribose polymerase (PARP) inhibitor. In some embodiments, the USP1 inhibitor described herein is administered with two PARP inhibitors. In some embodiments, the PARP inhibitor is olaparib, niraparib, talazoparib, or rucaparib.

[0241] In one aspect, the present disclosure provides a method for treating cancer in a subject, comprising administering to a subject in need thereof an amount of a compound as described herein, or a pharma- ceutically acceptable salt or solvate thereof, or an amount of a pharmaceutical composition as described herein.In some embodiments, the cancer is leukemia, acute myeloid leukemia (AML), chronic myeloid leukemia, acute lymphoblastic leukemia (ALL), non-Hodgkin's lymphoma (NHL), Hodgkin's lymphoma (HL), or multiple myeloma (MM).

[0242] In some embodiments, the cancer is carcinoma, squamous cell carcinoma, adenocarcinoma, sarcoma, endometrial cancer, breast cancer, ovarian cancer, cervical cancer, fallopian tube cancer, primary peritoneal cancer, colon cancer, colorectal cancer, squamous cell carcinoma of the anogenital tract, melanoma, renal cell carcinoma, lung cancer, non-small cell lung cancer, squamous cell carcinoma of the lung, gastric cancer, bladder cancer, gallbladder cancer, liver cancer, thyroid cancer, laryngeal cancer, salivary gland cancer, esophageal cancer, head and neck cancer, glioblastoma, glioma, squamous cell carcinoma of the head and neck, prostate cancer, pancreatic cancer, mesothelioma, sarcoma, blood cancer, leukemia, lymphoma, neuroma, and combinations thereof. In some embodiments, the cancers treated by the methods of the present disclosure include, for example, carcinomas, squamous cell carcinomas (e.g., cervix, eyelid, conjunctiva, vagina, lung, oral cavity, skin, bladder, tongue, larynx, and esophagus), and adenocarcinomas (e.g., prostate, small intestine, endometrium, cervix, colon, lung, pancreas, esophagus, rectum, uterus, stomach, breast, and ovary). In some embodiments, the cancers treated by the methods of the present disclosure further include sarcomas (e.g., myogenic sarcomas), leukemias, neuromas, melanomas, and lymphomas. In some embodiments, the cancers treated by the methods of the present disclosure are breast cancers. In some embodiments, the cancers treated by the therapeutic methods of the present disclosure are triple-negative breast cancers (TNBC). In some embodiments, the cancers treated by the therapeutic methods of the present disclosure are ovarian cancers. In some embodiments, the cancers treated by the therapeutic methods of the present disclosure are colon cancers. In some embodiments, the cancers are homologous recombination deficient cancers. In some embodiments, the cancer comprises cancer cells that have a mutation in the gene encoding p53.

[0243] In some embodiments, the patient or patient population treated with the pharmaceutical composition of the present disclosure has a solid tumor. In some embodiments, the solid tumor is melanoma, renal cell carcinoma, lung cancer, bladder cancer, breast cancer, cervical cancer, colon cancer, gallbladder cancer, laryngeal cancer, liver cancer, thyroid cancer, gastric cancer, salivary gland cancer, prostate cancer, pancreatic cancer, or Merkel cell carcinoma. In some embodiments, the patient or patient population treated with the pharmaceutical composition of the present disclosure has a hematological cancer. In some embodiments, the patient has a hematological cancer, such as diffuse large B-cell lymphoma ("DLBCL"), Hodgkin's lymphoma ("HL"), non-Hodgkin's lymphoma ("NHL"), follicular lymphoma ("FL"), acute myeloid leukemia ("AML"), or multiple myeloma ("MM"). In some embodiments, the patient or patient population treated has a cancer selected from the group consisting of ovarian cancer, lung cancer, and melanoma.

[0244] Specific examples of cancers that can be prevented and / or treated in accordance with the present disclosure include, but are not limited to, renal carcinoma, kidney cancer, glioblastoma multiforme, metastatic breast cancer, breast cancer, breast sarcoma, neurofibroma, neurofibromatosis, pediatric tumors, neuroblastoma, malignant melanoma, epidermoid carcinoma, acute leukemia, acute lymphocytic leukemia, acute myeloid leukemia such as myeloblastic, promyelocytic, myelomonocytic, monocytic, erythroid leukemia, and myodysplastic syndrome, chronic myeloid (granulocytic) leukemia, chronic lymphocytic leukemia, hairy cell leukemia, and the like. Multiple myeloma including, but not limited to, leukemia, polycythemia vera, lymphomas such as Hodgkin's disease, non-Hodgkin's disease, smoldering multiple myeloma, non-secretory myeloma, osteosclerotic myeloma, plasma cell leukemia, solitary plasmacytoma, and extramedullary plasmacytoma, Waldenstrom's macroglobulinemia, monoclonal gammopathy of undetermined significance, benign monoclonal gammopathy, heavy chain disease, osteosarcoma, myeloma bone disease, multiple myeloma, cholesteatoma-induced osteosarcoma, Paget's disease of bone, osteosarcoma, chondrosarcoma, Ewing's sarcoma, malignant Bone and connective tissue sarcomas, such as, but not limited to, giant cell tumor, fibrosarcoma of bone, spinal tumor, periosteal sarcoma, soft tissue sarcoma, angiosarcoma (hemangiosarcoma), fibrosarcoma, Kaposi's sarcoma, leiomyosarcoma, liposarcoma, lymphangiosarcoma, schwannoma, rhabdomyosarcoma, and synovial sarcoma; brain tumors, including, but not limited to, glioma, astrocytoma, brain stem glioma, ependymoma, oligodendroglioma, non-glioma, acoustic neuroma, craniopharyngioma, medulloblastoma, meningioma, pineoblastoma, and primary brain lymphoma; adenocarcinoma, lobular (small cell) carcinoma, intraductal carcinoma, medullary carcinoma, breast cancer, including but not limited to, mucinous breast cancer, tubular breast cancer, papillary breast cancer, Paget's disease (including juvenile Paget's disease) and inflammatory breast cancer; adrenal gland cancer, such as pheochromocytoma and adrenocortical carcinoma; thyroid cancer, such as but not limited to, papillary or follicular thyroid cancer, medullary thyroid cancer, and anaplastic thyroid cancer; pancreatic cancer, such as insulinoma, gastrinoma, glucagonoma, vipoma, somatostatin-secreting tumors, and carcinoid or islet cell tumors; pituitary cancer, such as but not limited to, Cushing's disease, prolactin-secreting tumors, acromegaly, and diabetes mellitus;ocular melanomas such as iris melanoma, choroidal melanoma, and ciliary body melanoma, and eye cancers such as, but not limited to, retinoblastoma; vaginal cancers such as squamous cell carcinoma, adenocarcinoma, and melanoma; vulvar cancers such as squamous cell carcinoma, melanoma, adenocarcinoma, basal cell carcinoma, sarcoma, and Paget's disease; cervical cancers such as squamous cell carcinoma and adenocarcinoma; uterine cancers such as endometrial carcinoma and uterine sarcoma; ovarian cancers such as ovarian epithelial carcinoma, borderline tumors, germ cell tumors, and stromal tumors; cervical cancers, squamous cell carcinoma, adenocarcinoma, adenoid cystic carcinoma, mucoepidermoid carcinoma, adenosquamous carcinoma, esophageal cancer, such as, but not limited to, carcinoma, sarcoma, melanoma, plasmacytoma, verrucous carcinoma, and oat cell (small cell) carcinoma; gastric cancer, such as, but not limited to, adenocarcinoma, fungal (polypoid), ulcerative, superficial spreading, diffuse spreading, malignant lymphoma, liposarcoma, fibrosarcoma, and carcinosarcoma; colon cancer, colorectal cancer, KRAS mutant colorectal cancer, colon cancer, rectal cancer; liver cancer, such as hepatocellular carcinoma and hepatoblastoma; gallbladder cancer, such as adenocarcinoma; bile duct cancer, such as papillary, nodular, and diffuse; KRAS mutant non-small cell lung cancer, non-small cell lung cancer , lung cancer, such as squamous cell carcinoma (epidermoid carcinoma), adenocarcinoma, large cell carcinoma, and small cell carcinoma; testicular cancer, such as, but not limited to, lung cancer, embryonal tumor, seminoma, undifferentiated, classical (classical), spermatocytic, non-seminoma, embryonal carcinoma, teratocarcinoma, choriomas (yolk sac tumors); prostate cancer, such as, but not limited to, androgen-independent prostate cancer, androgen-dependent prostate cancer, adenocarcinoma, leiomyosarcoma, and rhabdomyosarcoma; penile cancer; oral cancer, such as squamous cell carcinoma, basal carcinoma, adenocarcinoma, mucoepidermoid carcinoma, and adenoid cyst carcinoma; Salivary gland cancer, such as but not limited to vesicular carcinoma, pharyngeal cancer, such as squamous cell carcinoma and verrucous carcinoma, skin cancer, such as but not limited to basal cell carcinoma, squamous cell carcinoma and melanoma, superficial spreading melanoma, nodular melanoma, lentigo maligna melanoma, acral lentigo melanoma, kidney cancer, such as but not limited to renal cell carcinoma, adenocarcinoma, adrenal gland tumor, fibrosarcoma, transitional cell carcinoma (renal pelvis and / or ureter), bladder cancer, such as but not limited to renal cell carcinoma, renal cell carcinoma, Wilms' tumor, transitional cell carcinoma, squamous cell carcinoma, adenocarcinoma, carcinosarcoma. In addition, cancers include myxosarcoma, osteogenic sarcoma, endothelioma, lymphangioendothelioma, mesothelioma, synovium, hemangioblastoma, epithelial carcinoma, cystadenocarcinoma, bronchogenic carcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma, and papillary adenocarcinoma.

[0245] In one aspect, the disclosure provides a method of treating cancer in a subject, comprising administering to a subject in need thereof an effective amount of a compound described herein, or a pharma- ceutically acceptable salt or solvate thereof, or a pharmaceutical composition described herein. In some embodiments, the cancer can include cancer cells with elevated levels of RAD 18 mRNA expression. In some embodiments, the elevated levels of RAD 18 are elevated levels of RAD 18 protein. In some embodiments, the RAD 18 levels can be detected using quantitative methods such as microarray, RNA-Seq, or reverse transcriptase polymerase chain reaction (RT-PCR). In some embodiments, the levels of RAD 18 in cancer cells can be detected prior to administration of a compound described herein. In some embodiments, the RAD 18 levels can be detected in a cancer sample obtained from the subject. In some embodiments, when the subject has elevated levels of RAD 18, the subject can be treated with a compound described herein. In some embodiments, elevated levels of RAD 18 in cancer cells indicate that a subject administered a compound or pharmaceutical composition described herein will respond to treatment using a compound or pharmaceutical composition described herein. In some embodiments, a compound described herein is not administered to a subject with elevated levels of RAD 18.

[0246] In some embodiments, the cancer is a DNA damage repair pathway defective cancer. In some embodiments, the cancer is a PARP inhibitor resistant or refractory BRCA1 or BRCA2 mutant cancer. In some embodiments, the cancer comprises cells with elevated levels of RAD 18, the elevated levels of RAD 18 being at least as high as RAD 18 mRNA and / or protein levels in ES2 cells or HEP3B217 cells.

[0247] In some embodiments, the cancer is a BRCA1 mutated cancer and / or a BRCA2 mutated cancer. In some embodiments, the cancer is a BRCA1 or BRCA2 wild type cancer. In some embodiments, the cancer is a BRCA1 deficient cancer. In some embodiments, the cancer is a BRCA2 deficient cancer. In some embodiments, the cancer comprises cancer cells with mutations in genes encoding BRCA1 and / or BRCA2. In some embodiments, the cancer is a BRCA1 mutated cancer and a BRCA2 deficient cancer. In some embodiments, the cancer is a BRCA1 deficient cancer and a BRCA2 mutated cancer. In some embodiments, the cancer comprises cells with elevated levels of RAD 18, the elevated levels of RAD 18 being at least as high as RAD 18 mRNA and / or protein levels in ES2 cells or HEP3B217 cells. EXAMPLES

[0248] The following examples are provided to illustrate, but not to limit, the claimed disclosure. The following examples further illustrate the present disclosure but, of course, should not be construed as in any way limiting its scope.

[0249] The following synthetic schemes are provided for illustration and not limitation. The following examples illustrate various methods of making the compounds described herein. It is understood that those skilled in the art may be able to make these compounds by similar methods or by combining other methods known to those skilled in the art. It is also understood that those skilled in the art can make in a similar manner to those described below by using appropriate starting materials and modifying the synthetic route as necessary. In general, starting materials and reagents can be obtained from commercial vendors or synthesized according to sources known to those skilled in the art, or prepared as described herein.

[0250] The compounds and salts of formula (I), (Ia), (Ib), (II), (II'), (IIa), (IIa-1), (IIa-1a), (IIb), (IIb-1), (IIb-1a), (IIc), (IIc'), (IIc-1), (IId), (IId'), (IId-1), (IIe), (IIf), (IIg), and (VI) can be synthesized according to one or more of the illustrative schemes herein and / or techniques known in the art. The materials used herein are either commercially available or prepared by synthetic methods generally known in the art. These schemes are not limited to the compounds listed in the examples or by any particular substituents employed for illustrative purposes. Although various steps are described and depicted in the following synthetic schemes, the steps can, in some cases, be performed in a different order than that shown below. The numbering or R groups in each scheme do not necessarily correspond to that in the claims or other schemes or tables herein.

[0251] Example A - Biological Assays

[0252] Example A1: Enzyme Assay Human recombinant USP1 / UAF1 expressed in baculovirus-infected Sf21 cells was used (R&D, E-568-050). Test compounds and / or vehicle were incubated with 2 nM USP1 / UAF1 in modified HEPES buffer at pH 8.0 for 15 min at room temperature. The reaction was started by adding 500 nM ubiquitin rhodamine 110 (R&D, U-555-050) for kinetic readings. The slope change of fluorescence intensity was read by spectrofluorimetry at 485 nm / 535 nm. The dose response of the test compounds or the reference compound ML-323 was analyzed by nonlinear regression in GraphPad Prism software. The results of the assay are illustrated in Table 2.

[0253] Example A2: MDA-MB-436 breast cancer cell culture

[0254] MDA-MB-436 cells were grown in Leibovitz's L-15 medium containing 10ug / ml insulin, 16ug / ml glutathione, and 10% FBS. Cells were subcultured at subconfluence after trypsinization and incubated at 37 °C for 24 h in an incubator with 5% CO 2 The plates were maintained at 37°C in a humidified atmosphere containing

[0255] Example A3: MDA-MB-436 breast cancer cell proliferation assay

[0256] Cell proliferation was determined using the CellTiter-Glo® Luminescent Cell Viability Assay (Promega, #G7573). MDA-MB-436 cells were seeded in 384-well plates and allowed to attach for 24 hours. Compounds were added to the 384-well plates by ECHO and incubated at 37 °C for 24 h at 5% CO 2 The plates were incubated at 37° C. in a humidified atmosphere containing 0.1% ethanol. After 7 days, CellTiter-Glo was added into the 384-well plate and the contents were mixed for 2 minutes on an orbital shaker at 400 g before the plate was centrifuged at 1000 rpm for 2 minutes. After 30 minutes of incubation at room temperature, luminescence was read on an envision. The results of the assay are illustrated in Table 2.

[0257] Example B - Chemical Synthesis

[0258] Example B1: LCMS Method The LCMS methods used in the following synthetic procedures are provided in Table 3. [Table 3]

[0259] Example B2: Synthesis of intermediate A: [ka]

[0260] 4-Cyclopropyl-6-methoxypyrimidine

[0261] Dioxane (1500 mL) and H 2 To a solution of 4-chloro-6-methoxypyrimidine (150.00 g, 1.04 mol) in 20O (300 mL), cyclopropylboronic acid (178.27 g, 2.08 mol), K 2 CO 3 (286.82 g, 2.08 mol), and Pd(dppf)Cl 2 (75.92 g, 0.10 mol) was added. The mixture was stirred at 100° C. under Ar atmosphere for 16 h. The mixture was then diluted with water (500 mL) and extracted with EtOAc (400 mL×3). The combined organic layers were washed with brine (500 mL) and diluted with Na 2 SO 4 It was dried over, filtered and concentrated. The residue was purified by column chromatography on silica gel eluted with PE / EtOAc=20 / 1 to give the desired product (82.10 g, 0.55 mol, 53%) as a yellow oil. LCMS: Retention time: 1.157 min, (M+H) + =151.1, Method A.

[0262] 5-Bromo-4-cyclopropyl-6-methoxypyrimidine

[0263] A solution of 4-cyclopropyl-6-methoxypyrimidine (82.00 g, 546.01 mmol) in EtOH (900 mL) was treated with Br 2 (30.85 mL, 600.61 mmol) was added at 0° C. The reaction mixture was stirred at room temperature for 16 h. The suspension was filtered and washed with MeOH (200 mL). The solid was dried to give the desired product (99.70 g, 435.22 mmol, 80%) as a white solid. LCMS: Retention time: 1.707 min, (M+H) + =229.1, Method A.

[0264] 4-Cyclopropyl-6-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine

[0265] To a solution of 5-bromo-4-cyclopropyl-6-methoxypyrimidine (50.00 g, 218.26 mmol) in DMSO (500 mL) was added 4,4,5,5-tetramethyl-2-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3,2-dioxaborolane (110.88 g, 436.53 mmol), KOAc (64.26 g, 654.79 mmol), and Pd(dppf)Cl 2 (15.97 g, 21.83 mmol) was added. The mixture was stirred at 100° C. under Ar atmosphere for 16 h. The mixture was then diluted with 600 mL of water and extracted with EtOAc (500 mL×3). The combined organic layers were washed with brine (200 mL×3) and diluted with Na 2 SO 4 It was dried over, filtered and concentrated in vacuo. The residue was purified by column chromatography on silica gel eluted with PE / EtOAc=10:1 to give the desired product (28.00 g, 101.40 mmol, 46%) as a white solid. LCMS: Retention time: 1.627 min, (M+H) + =277.2, Method A. 1 H NMR (400 MHz, DMSO-d 6 ) : δ = 8.59 (s, 1 H), 3.86 (s, 3 H), 2.05- 2.02 (m, 1H), 1.32 (s, 12 H), 1.04 - 1.00 (m, 4 H).

[0266] Example B3: Synthesis of intermediate B: [ka]

[0267] Methyl 4-hydrazinylbenzoate hydrochloride

[0268] To a suspension of methyl 4-aminobenzoate (3.00 g, 19.85 mmol) in water (65 mL) and concentrated HCl (25 mL) was added dropwise a solution of sodium nitrite (1.51 g, 21.83 mmol) in water (15 mL) at 0 °C. The mixture was kept at 0 °C for 45 min and then dissolved in SnCl in concentrated HCl (10 mL). 2 A solution of (3.76 g, 19.85 mmol) was added. Upon completion of the addition, the temperature was allowed to rise slowly until room temperature was achieved. The suspension was filtered and the solid was washed with saturated brine (50 mL) and diethyl ether (50 mL). The solid was dried to yield the desired product (3.02 g, 18.19 mmol, 92%) as a yellow solid. LCMS: Retention time: 0.827 min, (M+H) + =167.1, Method A.

[0269] Methyl 4-(5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzoate

[0270] To a solution of methyl 4-hydrazinylbenzoate hydrochloride (1.98 g, 11.92 mmol) and 1,1,1-trifluoropentane-2,4-dione (1.84 g, 11.92 mmol) in HFIP (20 mL) was added TEA (2.41 g, 23.84 mmol) slowly at 0° C. The mixture was warmed to room temperature and stirred for 1 h. The reaction mixture was then quenched with water (40 mL) and extracted with DCM (20 mL×3). The combined organic layers were washed with brine (50 mL) and diluted with Na 2 SO 4 It was dried over, filtered and concentrated to give the crude product, which was purified by silica gel chromatography (eluting with 15% ethyl acetate in petroleum ether) to give the desired product (2.2 g, 7.75 mmol, 65% yield) as a white solid. LCMS: Retention time: 1.887 min, (M+H) + =285.0, Method A.

[0271] (4-(5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)phenyl)methanol To a solution of methyl 4-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzoate (1.70 g, 5.99 mmol) in dry THF (20 mL) was added LiAlH 4 (0.45 g, 11.98 mmol) was added at 0° C. The mixture was then warmed to room temperature and stirred for 2 h. The resulting mixture was diluted with THF (20 mL) and quenched with water (0.5 mL) at 0° C. After 0.5 h, Na 2 SO 4 was added. The suspension was then stirred for about 15 minutes and filtered. The filtrate was concentrated to give a residue. The residue was purified by column chromatography on silica gel (eluting with 30% ethyl acetate in petroleum ether) to give the desired product (0.75 g, 2.93 mmol, 49%) as a yellow oil. LCMS: Retention time: 1.677 min, (M+H) + =257.0, Method A. 1-(4-(chloromethyl)phenyl)-5-methyl-3-(trifluoromethyl)-1H-pyrazole A solution of (4-(5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)phenyl)methanol (0.75 g, 2.93 mmol) in DCE (15 mL) was diluted with SOCl 2 (1.04 g, 8.78 mmol) was added in one portion. The reaction was stirred at 50° C. for 0.5 h, after which the mixture was cooled to 0° C. and quenched with water (10 mL). The resulting solution was diluted with saturated NaHCO 3 The solution was neutralized with ethyl acetate and extracted with DCM (50 mL x 3). The combined organic layers were washed with anhydrous Na 2 SO 4 Drying over, filtration and concentration afforded the desired product (0.5 g, 1.82 mmol, 62%) as a brown oil which was used directly in the next step. LCMS: Retention time: 1.917 min, (M+H) + =275.0, Method A.

[0272] Example B4: Synthesis of intermediate C: [ka]

[0273] 2-(4-Hydrazinylphenyl)acetic acid

[0274] H 2 NaNO in O (10 mL) 2 A solution of (2.28 g, 33.08 mmol) was diluted with N 2 At 0 °C, concentrated HCl (25 mL) and H 2 A solution of 2-(4-aminophenyl)acetic acid (5.00 g, 33.08 mmol) in 2H2O (65 mL) was added dropwise. The mixture was stirred at 0° C. for 30 min. Then, SnCl in concentrated HCl (10 mL) was added dropwise. 2 (18.75 g, 99.23 mmol) was added dropwise at 0° C. After stirring for 1.5 h, the mixture was filtered and washed with MeCN (15 mL×2) to give the desired product (5.00 g, 30.09 mmol, 91% yield) as a white solid. LCMS: Retention time: 0.324 min, (M+H) + =167.1, Method A.

[0275] 2-(4-(5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)phenyl)acetic acid

[0276] To a solution of 2-(4-hydrazinylphenyl)acetic acid (5.00 g, 30.09 mmol) in HFIP (15 mL), 1,1,1-trifluoropentane-2,4-dione (4.64 g, 30.09 mmol) and TEA (6.09 g, 60.17 mmol) were added with N 2 The mixture was stirred at 0° C. for 1 h. Then HCl (1 mol / L, 15 mL) was added to adjust the pH to 5-6. The mixture was extracted with EtOAc (15 mL×3). The combined organic phase was washed with brine (15 mL) and diluted with Na 2 SO 4 It was dried over, filtered and concentrated under reduced pressure to give the desired product (5.00 g, 17.6 mmol, 59% yield) as a yellow solid. LCMS: Retention time: 1.683 min, (M+H) + =285.0, Method A.

[0277] Example B5: Synthesis of intermediate D: [ka]

[0278] 4-Hydrazinylbenzonitrile hydrochloride

[0279] To a cooled (-5 to 0°C) and stirred suspension of 4-aminobenzonitrile (10.00 g, 84.65 mmol) in concentrated HCl (100 mL) was added dropwise an aqueous solution of sodium nitrite (6.42 g, 93.11 mmol). To this cooled (0°C) solution was added tin chloride dihydrate (42.086 g, 186.22 mmol) in concentrated hydrochloric acid while stirring and maintaining the temperature below 0°C. The resulting solution was stirred for an additional 30 min. The white precipitate so formed was collected by filtration and diluted with Et 2 O (50 mL) to give the desired product (10.00 g, 58.96 mmol, 70%) as a pale yellow solid. 1 H NMR: (400 MHz, DMSO-d 6 ) δ = 10.55 (s, 2 H), 9.12 (s, 1 H), 7.73 (d, J = 8.8 Hz, 2 H), 7.04 (d, J = 8.8 Hz, 2 H)

[0280] 4-(5-Methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzonitrile A mixture of 4-hydrazinylbenzonitrile hydrochloride (10.00 g, 58.96 mmol), 1,1,1-trifluoropentane-2,4-dione (15.035 g, 97.63 mmol), sodium acetate (12.32 g, 150.21 mmol) and acetic acid (100 mL) was stirred for 1 h at 120° C. After cooling to ambient temperature, the reaction mixture was concentrated in vacuo and purified by silica gel chromatography (PE / EtOAc from 50 / 1 to 10 / 1) to give the desired product (6.90 g, 27.5 mmol, 47%) as a pale yellow solid. 1 H NMR: (400 MHz, DMSO-d 6 ) δ = 8.08 - 8.06 (m, 2 H), 7.86 - 7.84 (m, 2 H), 6.84 (s, 1 H), 2.44 (s, 3 H) (4-(5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)phenyl)methanamine To a mixture of 4-(5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzonitrile (500 mg, 1.99 mmol) in MeOH (15 mL) and THF (5 mL) was added ammonium hydroxide (1 mL) followed by an excess of wet Raney Ni. The mixture was stirred at room temperature under hydrogen pressure (0.5 Mpa) for 2 h. The mixture was then filtered and concentrated to give the crude product as a yellow oil, which was used directly in the next step. LCMS: Retention time: 0.813 min, (M+H) + =256.0, Method A.

[0281] Example B6: Synthesis of intermediate E: [ka]

[0282] 6-Chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidine

[0283] A mixture of 6-chloro-1H-pyrazolo[3,4-d]pyrimidine (500 mg, 3.23 mmol), 4-methylbenzene-1-sulfonate pyridin-1-ium (81 mg, 0.32 mmol), and 3,4-dihydro-2H-pyran (544 mg, 6.47 mmol) in DCM (10 mL) was stirred at 40° C. for 6 h. The mixture was then concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (eluting with PE / EtOAc 10 / 1 to 3 / 1) to give the desired product (720 mg, 3.02 mmol, 93%) as a yellow solid. LCMS: Retention time: 1.635 minutes (M+H) + =239.0, Method A.

[0284] 6-(4-Cyclopropyl-6-methoxypyrimidin-5-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidine

[0285] 6-Chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidine (200 mg, 0.84 mmol), 4-cyclopropyl-6-methoxy-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine (347 mg, 1.26 mmol), Pd(dppf)Cl in dioxane (8 mL) / water (1 mL). 2 (123 mg, 0.17 mmol), and K 2 CO 3 (290 mg, 2.09 mmol) was stirred at 100° C. for 16 h. The mixture was then cooled to room temperature, diluted with water (30 mL), and extracted with EtOAc (20 mL×3). The combined organic fractions were washed with brine (20 mL) and diluted with Na 2 SO 4 It was dried over, filtered and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (eluting with PE / EtOAc 10 / 1 to 1 / 1) to give the desired product (252 mg, 0.72 mmol, 86%) as a yellow solid. LCMS: Retention time: 1.407 min (M+H) + =353.2, Method A.

[0286] 6-(4-Cyclopropyl-6-methoxypyrimidin-5-yl)-1H-pyrazolo[3,4-d]pyrimidine

[0287] A solution of 6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidine (215 mg, 0.61 mmol) in TFA (10 mL) was stirred at room temperature for 16 h. The mixture was then concentrated under reduced pressure and dissolved in DCM (20 mL). The solution was diluted with saturated NaHCO 3 solution (20 mL), washed with brine (20 mL), and then with Na 2 SO 4 It was dried over, filtered and concentrated under reduced pressure to give the crude product (200 mg) as a brown oil which was used directly in the next step. LCMS: Retention time: 0.958 min (M+H) + =269.1, Method A. ...

Claims

1. A compound having the structure of formula (I), or a pharmaceutically acceptable salt thereof: 【Chemical Engineering 201】 During the ceremony, X １ But N or CR １ and X ３ But N or CR ３ and X ７ But N or CR ７ and R １ , R ３ , and R ７ each independently represents hydrogen, halo, —CN, —OR １１ , -SR １１ , -N(R １２ ) ２ , optionally substituted C １～６ Alkyl, optionally substituted C １～６ Heteroalkyl, optionally substituted C ２～６ Alkenyl, and optionally substituted C ２～６ alkynyl, R ８ and R ９ each independently represents hydrogen, halo, —CN, optionally substituted C １～６ Alkyl, optionally substituted C １～６ Heteroalkyl, optionally substituted C ２～６ Alkenyl, and optionally substituted C ２～６ alkynyl, or R ８ and R ９ together form an oxo, or R ８ and R ９ taken together with the carbons to which they are attached form an optionally substituted 3- to 6-membered cycloalkyl or heterocycloalkyl; Ring A is phenyl, naphthyl, monocyclic heteroaryl, or bicyclic heteroaryl; R Ａ each independently represents a halogen, —NO ２ , oxo, —CN, optionally substituted C １～６ Alkyl, optionally substituted C ２～６ Alkenyl, optionally substituted C ２～６ Alkynyl, optionally substituted C １～６ Heteroalkyl, optionally substituted C ３～８ Cycloalkyl, optionally substituted C ２～７ heterocycloalkyl, —OR １１ , -SR １１ , -N(R １２ ) (R １１ ), -C(O)R １２ , -C(O)OR １２ , -OC(O)R １２ , -OC(O)N(R １２ ) (R １１ ), -C(O)N(R １２ ) (R １１ ), -N(R １２ ) C(O)R １２ , -N(R １２ )C(O)OR １２ , -N(R １２ )C(O)N(R １２ ) (R １１ ), -N(R １２ ) ２ S (O) ２ (R １２ ), -S(O)R １２ , -S(O) ２ R １２ , and -S(O) ２ N (R １２ ) (R １１ ) are selected from R １１ is hydrogen, optionally substituted C １～６ Alkyl, optionally substituted C ２～６ Alkenyl, optionally substituted C ２～６ Alkynyl, optionally substituted C １～６ Heteroalkyl, optionally substituted C ３～８ Cycloalkyl, optionally substituted C ２～７ Heterocycloalkyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted —C １～４ Alkylene-C ３～８ Cycloalkyl, optionally substituted -C １～４ Alkylene-C ２～７ Heterocycloalkyl, optionally substituted -C １～４ alkylene-phenyl, or optionally substituted -C １～４ alkylene-heteroaryl; R １２ each independently represents hydrogen, —NO ２ , -CN,C １～６ Alkyl, C １～６ Aminoalkyl, C １～６ Hydroxyalkyl, C １～６ Haloalkyl, C １～６ Heteroalkyl, C ３～６ a carbocyclic ring and a 3- to 6-membered heterocyclic ring, ３～６ The carbocycle and the 3- to 6-membered heterocycle are independently selected from halogen, —OH, oxo, amino, —NO ２ , -CN,C １～６ Alkyl, C １～６ Alkoxy, and C １～６ optionally substituted with one or more substituents selected from haloalkyl; B is a 6-membered heteroaryl, phenyl, or phenylisostere; R Ｂ１ is optionally substituted C ３～８ Cycloalkyl, optionally substituted C ２～９ heterocycloalkyl, optionally substituted naphthyl, optionally substituted phenyl, optionally substituted monocyclic heteroaryl, or optionally substituted bicyclic heteroaryl; Each R Ｂ are independently halo, -CN, -NO ２ , optionally substituted C １～６ Alkyl, optionally substituted C ２～６ Alkenyl, optionally substituted C ２～６ Alkynyl, optionally substituted C １～６ Heteroalkyl, —OR １１ , -SR １１ , -N(R １２ ) (R １１ ), -C(O)R １２ , -C(O)OR １２ , -OC(O)R １２ , -OC(O)N(R １２ ) (R １１ ), -C(O)N(R １２ ) (R １１ ), -N(R １２ ) C(O)R １２ , -N(R １２ )C(O)OR １２ , -N(R １２ )C(O)N(R １２ ) (R １１ ), -N(R １２ ) S (O) ２ (R １２ ), -S(O)R １２ , -S(O) ２ R １２ , -S(O) ２ N (R １２ ) (R １１ ), optionally substituted C ３～８ Cycloalkyl, optionally substituted C ２～９ heterocycloalkyl, optionally substituted naphthyl, optionally substituted phenyl, optionally substituted monocyclic heteroaryl, or optionally substituted bicyclic heteroaryl; or R on the same atom Ｂ two of which, together with the atoms to which they are attached, are optionally substituted C ３～８ Cycloalkyl or optionally substituted C ２～９ forming a heterocycloalkyl, m is 1, 2, 3, or 4; n is 0, 1, 2, 3, or 4; The compound or a pharmaceutically acceptable salt thereof, wherein p is 0 or 1.

2. X １ But N or CR １ and X ３ But N or CR ３ and X ７ But N or CR ７ and R １ , R ３ , and R ７ each independently represents hydrogen, halo, —CN, —OR １１ , -SR １１ , -N(R １２ ) ２ , optionally substituted C １～６ Alkyl, optionally substituted C １～６ Heteroalkyl, optionally substituted C ２～６ Alkenyl, and optionally substituted C ２～６ alkynyl, The alkyl, heteroalkyl, alkenyl, or alkynyl is independently halogen, amino, oxo, —OH, —NO ２ , -CN, and C １～３ optionally substituted with one or more substituents selected from alkoxy; R ８ and R ９ each independently represents hydrogen, halo, —CN, optionally substituted C １～６ Alkyl, optionally substituted C １～６ Heteroalkyl, optionally substituted C ２～６ Alkenyl, and optionally substituted C ２～６ alkynyl, or R ８ and R ９ together form an oxo, or R ８ and R ９ taken together with the carbons to which they are attached form an optionally substituted 3- to 6-membered cycloalkyl or heterocycloalkyl; The alkyl, alkenyl, alkynyl, cycloalkyl, or heterocycloalkyl are independently selected from the group consisting of halogen, amino, —OH, —NO ２ , oxo, -CN, C １～３ Alkoxy, C １～３ Alkyl, and C １～３ optionally substituted with one or more substituents selected from haloalkyl; Ring A is phenyl, naphthyl, monocyclic heteroaryl, or bicyclic heteroaryl; R Ａ each independently represents a halogen, —NO ２ , oxo, —CN, optionally substituted C １～６ Alkyl, optionally substituted C ２～６ Alkenyl, optionally substituted C ２～６ Alkynyl, optionally substituted C １～６ Heteroalkyl, optionally substituted C ３～８ Cycloalkyl, optionally substituted C ２～７ heterocycloalkyl, —OR １１ , -SR １１ , -N(R １２ ) (R １１ ), -C(O)R １２ , -C(O)OR １２ , -OC(O)R １２ , -OC(O)N(R １２ ) (R １１ ), -C(O)N(R １２ ) (R １１ ), -N(R １２ ) C(O)R １２ , -N(R １２ )C(O)OR １２ , -N(R １２ )C(O)N(R １２ ) (R １１ ), -N(R １２ ) ２ S (O) ２ (R １２ ), -S(O)R １２ , -S(O) ２ R １２ , and -S(O) ２ N (R １２ ) (R １１ ) are selected from The alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, or heterocycloalkyl is independently selected from halogen, —OH, —NO ２ , oxo, amino, -CN, C １～６ Alkoxy, C １～６ Alkyl, C １～６ Haloalkyl, C ３～６ optionally substituted with one or more substituents selected from a carbocycle and a 3- to 6-membered heterocycle, ３～６ The carbocycle and the 3- to 6-membered heterocycle are independently selected from halogen, —OH, amino, —NO ２ , oxo, -CN, C １～６ Alkyl, C １～６ Alkoxy, and C １～６ optionally substituted with one or more substituents selected from haloalkyl; R １１ is hydrogen, optionally substituted C １～６ Alkyl, optionally substituted C ２～６ Alkenyl, optionally substituted C ２～６ Alkynyl, optionally substituted C １～６ Heteroalkyl, optionally substituted C ３～８ Cycloalkyl, optionally substituted C ２～７ Heterocycloalkyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted —C １～４ Alkylene-C ３～８ Cycloalkyl, optionally substituted -C １～４ Alkylene-C ２～７ Heterocycloalkyl, optionally substituted -C １～４ alkylene-phenyl, or optionally substituted -C １～４ alkylene-heteroaryl; The alkyl, alkenyl, alkynyl, heteroalkyl, alkylene, cycloalkyl, heterocycloalkyl, phenyl, or heteroaryl may independently be halogen, —OH, amino, —NO ２ , oxo, C １～６ Alkoxy, -CN, C １～６ Alkyl, and C １～６ optionally substituted with one or more substituents selected from haloalkyl; R １２ each independently represents hydrogen, —NO ２ , -CN,C １～６ Alkyl, C １～６ Aminoalkyl, C １～６ Hydroxyalkyl, C １～６ Haloalkyl, C １～６ Heteroalkyl, C ３～６ a carbocyclic ring and a 3- to 6-membered heterocyclic ring, ３～６ The carbocycle and the 3- to 6-membered heterocycle are independently selected from halogen, —OH, oxo, amino, —NO ２ , -CN,C １～６ Alkyl, C １～６ Alkoxy, and C １～６ optionally substituted with one or more substituents selected from haloalkyl; B is a 6-membered heteroaryl, phenyl, or phenylisostere; R Ｂ１ is optionally substituted C ３～８ Cycloalkyl, optionally substituted C ２～９ heterocycloalkyl, optionally substituted naphthyl, optionally substituted phenyl, optionally substituted monocyclic heteroaryl, or optionally substituted bicyclic heteroaryl; The cycloalkyl, heterocycloalkyl, naphthyl, phenyl, or heteroaryl are independently selected from halogen, —NO ２ , oxo, —CN, optionally substituted C １～６ Alkyl, optionally substituted C ２～６ Alkenyl, optionally substituted C ２～６ Alkynyl, optionally substituted C １～６ Heteroalkyl, optionally substituted C ３～８ Cycloalkyl, optionally substituted C ２～７ heterocycloalkyl, —OR １１ , -SR １１ , -N(R １２ ) (R １１ ), -C(O)R １２ , -C(O)OR １２ , -OC(O)R １２ , -OC(O)N(R １２ ) (R １１ ), -C(O)N(R １２ ) (R １１ ), -N(R １２ ) C(O)R １２ , -N(R １２ )C(O)OR １２ , -N(R １２ )C(O)N(R １２ ) (R １１ ), -N(R １２ ) S (O) ２ (R １２ ), -S(O)R １２ , -S(O) ２ R １２ , and -S(O) ２ N (R １２ ) (R １１ ), wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, or heterocycloalkyl is independently selected from halogen, —OH, —NO ２ , amino, -NH(C １～６ alkyl), -N(C １～６ alkyl) ２ , oxo, -CN, C １～３ Alkoxy, C １～３ Alkyl, and C １～３ optionally substituted with one or more substituents selected from haloalkyl; Each R Ｂ are independently halo, -CN, -NO ２ , optionally substituted C １～６ Alkyl, optionally substituted C ２～６ Alkenyl, optionally substituted C ２～６ Alkynyl, optionally substituted C １～６ Heteroalkyl, —OR １１ , -SR １１ , -N(R １２ ) (R １１ ), -C(O)R １２ , -C(O)OR １２ , -OC(O)R １２ , -OC(O)N(R １２ ) (R １１ ), -C(O)N(R １２ ) (R １１ ), -N(R １２ ) C(O)R １２ , -N(R １２ )C(O)OR １２ , -N(R １２ )C(O)N(R １２ ) (R １１ ), -N(R １２ ) S (O) ２ (R １２ ), -S(O)R １２ , -S(O) ２ R １２ , -S(O) ２ N (R １２ ) (R １１ ), optionally substituted C ３～８ Cycloalkyl, optionally substituted C ２～９ heterocycloalkyl, optionally substituted naphthyl, optionally substituted phenyl, optionally substituted monocyclic heteroaryl, or optionally substituted bicyclic heteroaryl; The alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, naphthyl, phenyl, or heteroaryl are independently selected from the group consisting of halogen, —OH, —NO ２ , amino, oxo, -CN, C １～３ Alkoxy, C １～３ Alkyl, and C １～３ optionally substituted with one or more substituents selected from haloalkyl, or R on the same atom Ｂ two of which, together with the atoms to which they are attached, are optionally substituted C ３～８ Cycloalkyl or optionally substituted C ２～９ forming a heterocycloalkyl, The cycloalkyl or heterocycloalkyl is independently selected from halogen, —OH, amino, —NO ２ , oxo, C １～６ Alkoxy, -CN, C １～６ Alkyl, C １～６ optionally substituted with one or more substituents selected from haloalkyl; m is 1, 2, 3, or 4; n is 0, 1, 2, 3, or 4; 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein p is 0 or 1.

3. The compound has the structure of formula (Ia): 【Chemical Engineering 202】 During the ceremony, X １ But N or CR １ and X ３ But N or CR ３ and X ７ But N or CR ７ and R １ , R ３ , and R ７ each independently represents hydrogen, halo, —CN, —OR １１ , -SR １１ , -N(R １２ ) ２ , optionally substituted C １～６ Alkyl, optionally substituted C １～６ Heteroalkyl, optionally substituted C ２～６ Alkenyl, and optionally substituted C ２～６ alkynyl, Y １ But N or CR Ｙ１ and Y ２ But N or CR Ｙ２ and Y ３ But N or CR Ｙ３ and Y ４ But N or CR Ｙ４ and R Ｙ１ , R Ｙ２ , R Ｙ３ , and R Ｙ４ each independently represents hydrogen, halo, —CN, —OR １１ , -SR １１ , -N(R １２ ) ２ , optionally substituted C １～６ Alkyl, optionally substituted C １～６ Heteroalkyl, optionally substituted C ２～６ Alkenyl, and optionally substituted C ２～６ alkynyl, R ８ and R ９ each independently represents hydrogen, halo, —CN, optionally substituted C １～６ Alkyl, optionally substituted C １～６ Heteroalkyl, optionally substituted C ２～６ Alkenyl, and optionally substituted C ２～６ alkynyl, or R ８ and R ９ together form an oxo, or R ８ and R ９ taken together with the carbons to which they are attached form an optionally substituted 3- to 6-membered cycloalkyl or heterocycloalkyl; Ring A is phenyl, naphthyl, monocyclic heteroaryl, or bicyclic heteroaryl; R Ａ each independently represents a halogen, —NO ２ , oxo, —CN, optionally substituted C １～６ Alkyl, optionally substituted C ２～６ Alkenyl, optionally substituted C ２～６ Alkynyl, optionally substituted C １～６ Heteroalkyl, optionally substituted C ３～８ Cycloalkyl, optionally substituted C ２～７ heterocycloalkyl, —OR １１ , -SR １１ , -N(R １２ ) (R １１ ), -C(O)R １２ , -C(O)OR １２ , -OC(O)R １２ , -OC(O)N(R １２ ) (R １１ ), -C(O)N(R １２ ) (R １１ ), -N(R １２ ) C(O)R １２ , -N(R １２ )C(O)OR １２ , -N(R １２ )C(O)N(R １２ ) (R １１ ), -N(R １２ ) ２ S (O) ２ (R １２ ), -S(O)R １２ , -S(O) ２ R １２ , and -S(O) ２ N (R １２ ) (R １１ ) are selected from R １１ is hydrogen, optionally substituted C １～６ Alkyl, optionally substituted C ２～６ Alkenyl, optionally substituted C ２～６ Alkynyl, optionally substituted C １～６ Heteroalkyl, optionally substituted C ３～８ Cycloalkyl, optionally substituted C ２～７ Heterocycloalkyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted —C １～４ Alkylene-C ３～８ Cycloalkyl, optionally substituted -C １～４ Alkylene-C ２～７ Heterocycloalkyl, optionally substituted -C １～４ alkylene-phenyl, or optionally substituted -C １～４ alkylene-heteroaryl; R １２ each independently represents hydrogen, —NO ２ , -CN,C １～６ Alkyl, C １～６ Aminoalkyl, C １～６ Hydroxyalkyl, C １～６ Haloalkyl, C １～６ Heteroalkyl, C ３～６ a carbocyclic ring and a 3- to 6-membered heterocyclic ring, ３～６ The carbocycle and the 3- to 6-membered heterocycle are independently selected from halogen, —OH, oxo, amino, —NO ２ , -CN,C １～６ Alkyl, C １～６ Alkoxy, and C １～６ optionally substituted with one or more substituents selected from haloalkyl; R Ｂ１ is optionally substituted C ３～８ Cycloalkyl, optionally substituted C ２～９ heterocycloalkyl, optionally substituted naphthyl, optionally substituted phenyl, optionally substituted monocyclic heteroaryl, or optionally substituted bicyclic heteroaryl; m is 1, 2, 3, or 4; 3. The compound of claim 1 or 2, or a pharmaceutically acceptable salt thereof, wherein p is 0 or 1.

4. 10. The compound of claim 1, wherein the compound has the structure of Formula (Ib): 【Chemical 203】

5. A compound having the structure of formula (II'), or a pharmaceutically acceptable salt thereof: 【Chemical 204】 During the ceremony, X １ But N or CR １ and X ２ is N, X ３ But N or CR ３ and X ５ is N, X ６ But N, NR ６ , C.R. ６ , C(R ６ ) ２ , S(=O) ２ , C(=O), or C(=S); X ７ But N, NR ７ ,O.S.,CR. ７ , S(=O) ２ , C(=O), or C(=S); (i) X ２ , X ３ , and X ５ is N and X ６ When is C(=O), X ７ But O, S, CR ７ , C(═O), or C(═S), and (ii) X ２ , X ３ , and X ５ If N, then X ６ and X ７ At least one of is O, S, S(=O) ２ , C(=O), or C(=S); 【Chemical 205】 is a single bond or a double bond, R １ , R ３ , R ６ , and R ７ each independently represents hydrogen, halo, —CN, —OR １１ , -SR １１ , -N(R １２ ) ２ , optionally substituted C １～６ Alkyl, optionally substituted C １～６ Heteroalkyl, optionally substituted C ２～６ Alkenyl, and optionally substituted C ２～６ alkynyl, R ８ and R ９ each independently represents hydrogen, halo, —CN, optionally substituted C １～６ Alkyl, optionally substituted C １～６ Heteroalkyl, optionally substituted C ２～６ Alkenyl, and optionally substituted C ２～６ alkynyl, or R ８ and R ９ together form an oxo, or R ８ and R ９ taken together with the carbons to which they are attached form an optionally substituted 3- to 6-membered cycloalkyl or heterocycloalkyl; Ring A is phenyl, naphthyl, monocyclic heteroaryl, or bicyclic heteroaryl; R Ａ each independently represents a halogen, —NO ２ , oxo, —CN, optionally substituted C １～６ Alkyl, optionally substituted C ２～６ Alkenyl, optionally substituted C ２～６ Alkynyl, optionally substituted C １～６ Heteroalkyl, optionally substituted C ３～８ Cycloalkyl, optionally substituted C ２～７ heterocycloalkyl, —OR １１ , -SR １１ , -N(R １２ ) (R １１ ), -C(O)R １２ , -C(O)OR １２ , -OC(O)R １２ , -OC(O)N(R １２ ) (R １１ ), -C(O)N(R １２ ) (R １１ ), -N(R １２ ) C(O)R １２ , -N(R １２ )C(O)OR １２ , -N(R １２ )C(O)N(R １２ ) (R １１ ), -N(R １２ ) ２ S (O) ２ (R １２ ), -S(O)R １２ , -S(O) ２ R １２ , and -S(O) ２ N (R １２ ) (R １１ ) are selected from R １１ is hydrogen, optionally substituted C １～６ Alkyl, optionally substituted C ２～６ Alkenyl, optionally substituted C ２～６ Alkynyl, optionally substituted C １～６ Heteroalkyl, optionally substituted C ３～８ Cycloalkyl, optionally substituted C ２～７ Heterocycloalkyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted —C １～４ Alkylene-C ３～８ Cycloalkyl, optionally substituted -C １～４ Alkylene-C ２～７ Heterocycloalkyl, optionally substituted -C １～４ alkylene-phenyl, or optionally substituted -C １～４ alkylene-heteroaryl; R １２ each independently represents hydrogen, —NO ２ , -CN,C １～６ Alkyl, C １～６ Aminoalkyl, C １～６ Hydroxyalkyl, C １～６ Haloalkyl, and C ３～６ a carbocyclic ring, a 3- to 6-membered heterocyclic ring, ３～６ The carbocycle and the 3- to 6-membered heterocycle are independently selected from halogen, —OH, oxo, amino, —NO ２ , -CN,C １～６ Alkyl, C １～６ Alkoxy, and C １～６ optionally substituted with one or more substituents selected from haloalkyl; B is a 6-membered heteroaryl, phenyl, or phenylisostere; R Ｂ１ is optionally substituted C ３～８ Cycloalkyl, optionally substituted C ２～９ heterocycloalkyl, optionally substituted naphthyl, optionally substituted phenyl, optionally substituted monocyclic heteroaryl, or optionally substituted bicyclic heteroaryl; Each R Ｂ are independently halo, -CN, -NO ２ , optionally substituted C １～６ Alkyl, optionally substituted C ２～６ Alkenyl, optionally substituted C ２～６ Alkynyl, optionally substituted C １～６ Heteroalkyl, —OR １１ , -SR １１ , -N(R １２ ) (R １１ ), -C(O)R １２ , -C(O)OR １２ , -OC(O)R １２ , -OC(O)N(R １２ ) (R １１ ), -C(O)N(R １２ ) (R １１ ), -N(R １２ ) C(O)R １２ , -N(R １２ )C(O)OR １２ , -N(R １２ )C(O)N(R １２ ) (R １１ ), -N(R １２ ) S (O) ２ (R １２ ), -S(O)R １２ , -S(O) ２ R １２ , -S(O) ２ N (R １２ ) (R １１ ), optionally substituted C ３～８ Cycloalkyl, optionally substituted C ２～９ heterocycloalkyl, optionally substituted naphthyl, optionally substituted phenyl, optionally substituted monocyclic heteroaryl, or optionally substituted bicyclic heteroaryl; or R on the same atom Ｂ two of which, together with the atoms to which they are attached, are optionally substituted C ３～８ Cycloalkyl or optionally substituted C ２～９ forming a heterocycloalkyl, m is 1, 2, 3, or 4; n is 0, 1, 2, 3, or 4; The compound or a pharmaceutically acceptable salt thereof, wherein p is 0 or 1.

6. During the ceremony, X １ But N or CR １ and X ２ is N, X ３ But N or CR ３ and X ５ is N, X ６ But N, NR ６ , C.R. ６ , S(=O) ２ , C(=O), or C(=S); X ７ But N, NR ７ ,O.S.,CR. ７ , S(=O) ２ , C(=O), or C(=S); (i) X ２ , X ３ , and X ５ is N and X ６ When is C(=O), X ７ But O, S, CR ７ , C(═O), or C(═S), and (ii) X ２ , X ３ , and X ５ If N, then X ６ and X ７ At least one of is O, S, S(=O) ２ , C(=O), or C(=S); 【Chemical 206】 is a single bond or a double bond, R １ , R ３ , R ６ , and R ７ each independently represents hydrogen, halo, —CN, —OR １１ , -SR １１ , -N(R １２ ) ２ , optionally substituted C １～６ Alkyl, optionally substituted C １～６ Heteroalkyl, optionally substituted C ２～６ Alkenyl, and optionally substituted C ２～６ alkynyl, The alkyl, heteroalkyl, alkenyl, or alkynyl is independently halogen, amino, oxo, —OH, —NO ２ , -CN, and C １～３ optionally substituted with one or more substituents selected from alkoxy; R ８ and R ９ each independently represents hydrogen, halo, —CN, optionally substituted C １～６ Alkyl, optionally substituted C １～６ Heteroalkyl, optionally substituted C ２～６ Alkenyl, and optionally substituted C ２～６ alkynyl, or R ８ and R ９ together form an oxo, or R ８ and R ９ taken together with the carbons to which they are attached form an optionally substituted 3- to 6-membered cycloalkyl or heterocycloalkyl; The alkyl, alkenyl, alkynyl, cycloalkyl, or heterocycloalkyl are independently selected from the group consisting of halogen, amino, —OH, —NO ２ , oxo, -CN, C １～３ Alkoxy, C １～３ Alkyl, and C １～３ optionally substituted with one or more substituents selected from haloalkyl; Ring A is phenyl, naphthyl, monocyclic heteroaryl, or bicyclic heteroaryl; R Ａ each independently represents a halogen, —NO ２ , oxo, —CN, optionally substituted C １～６ Alkyl, optionally substituted C ２～６ Alkenyl, optionally substituted C ２～６ Alkynyl, optionally substituted C １～６ Heteroalkyl, optionally substituted C ３～８ Cycloalkyl, optionally substituted C ２～７ heterocycloalkyl, —OR １１ , -SR １１ , -N(R １２ ) (R １１ ), -C(O)R １２ , -C(O)OR １２ , -OC(O)R １２ , -OC(O)N(R １２ ) (R １１ ), -C(O)N(R １２ ) (R １１ ), -N(R １２ ) C(O)R １２ , -N(R １２ )C(O)OR １２ , -N(R １２ )C(O)N(R １２ ) (R １１ ), -N(R １２ ) ２ S (O) ２ (R １２ ), -S(O)R １２ , -S(O) ２ R １２ , and -S(O) ２ N (R １２ ) (R １１ ) are selected from The alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, or heterocycloalkyl is independently selected from halogen, —OH, —NO ２ , oxo, amino, -CN, C １～６ Alkoxy, C １～６ Alkyl, C １～６ Haloalkyl, C ３～６ optionally substituted with one or more substituents selected from a carbocycle and a 3- to 6-membered heterocycle, ３～６ The carbocycle and the 3- to 6-membered heterocycle are independently selected from halogen, —OH, amino, —NO ２ , oxo, -CN, C １～６ Alkyl, C １～６ Alkoxy, and C １～６ optionally substituted with one or more substituents selected from haloalkyl; R １１ is hydrogen, optionally substituted C １～６ Alkyl, optionally substituted C ２～６ Alkenyl, optionally substituted C ２～６ Alkynyl, optionally substituted C １～６ Heteroalkyl, optionally substituted C ３～８ Cycloalkyl, optionally substituted C ２～７ Heterocycloalkyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted —C １～４ Alkylene-C ３～８ Cycloalkyl, optionally substituted -C １～４ Alkylene-C ２～７ Heterocycloalkyl, optionally substituted -C １～４ alkylene-phenyl, or optionally substituted -C １～４ alkylene-heteroaryl; The alkyl, alkenyl, alkynyl, heteroalkyl, alkylene, cycloalkyl, heterocycloalkyl, phenyl, or 5- or 6-membered heteroaryl are independently selected from the group consisting of halogen, —OH, amino, —NO ２ , oxo, C １～６ Alkoxy, -CN, C １～６ Alkyl, C １～６ optionally substituted with one or more substituents selected from haloalkyl; R １２ each independently represents hydrogen, —NO ２ , -CN,C １～６ Alkyl, C １～６ Aminoalkyl, C １～６ Hydroxyalkyl, C １～６ Haloalkyl, and C ３～６ a carbocyclic ring, a 3- to 6-membered heterocyclic ring, ３～６ The carbocycle and the 3- to 6-membered heterocycle are independently selected from halogen, —OH, oxo, amino, —NO ２ , -CN,C １～６ Alkyl, C １～６ Alkoxy, and C １～６ optionally substituted with one or more substituents selected from haloalkyl; B is a 6-membered heteroaryl, phenyl, or phenylisostere; R Ｂ１ is optionally substituted C ３～８ Cycloalkyl, optionally substituted C ２～９ heterocycloalkyl, optionally substituted naphthyl, optionally substituted phenyl, optionally substituted monocyclic heteroaryl, or optionally substituted bicyclic heteroaryl; The cycloalkyl, heterocycloalkyl, naphthyl, phenyl, or heteroaryl are independently selected from halogen, —NO ２ , oxo, —CN, optionally substituted C １～６ Alkyl, optionally substituted C ２～６ Alkenyl, optionally substituted C ２～６ Alkynyl, optionally substituted C １～６ Heteroalkyl, optionally substituted C ３～８ Cycloalkyl, optionally substituted C ２～７ heterocycloalkyl, —OR １１ , -SR １１ , -N(R １２ ) (R １１ ), -C(O)R １２ , -C(O)OR １２ , -OC(O)R １２ , -OC(O)N(R １２ ) (R １１ ), -C(O)N(R １２ ) (R １１ ), -N(R １２ ) C(O)R １２ , -N(R １２ )C(O)OR １２ , -N(R １２ )C(O)N(R １２ ) (R １１ ), -N(R １２ ) S (O) ２ (R １２ ), -S(O)R １２ , -S(O) ２ R １２ , and -S(O) ２ N (R １２ ) (R １１ ), wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, or heterocycloalkyl is independently selected from halogen, —OH, —NO ２ , amino, oxo, -CN, C １～３ Alkoxy, C １～３ Alkyl, and C １～３ optionally substituted with one or more substituents selected from haloalkyl; Each R Ｂ are independently halo, -CN, -NO ２ , optionally substituted C １～６ Alkyl, optionally substituted C ２～６ Alkenyl, optionally substituted C ２～６ Alkynyl, optionally substituted C １～６ Heteroalkyl, —OR １１ , -SR １１ , -N(R １２ ) (R １１ ), -C(O)R １２ , -C(O)OR １２ , -OC(O)R １２ , -OC(O)N(R １２ ) (R １１ ), -C(O)N(R １２ ) (R １１ ), -N(R １２ ) C(O)R １２ , -N(R １２ )C(O)OR １２ , -N(R １２ )C(O)N(R １２ ) (R １１ ), -N(R １２ ) S (O) ２ (R １２ ), -S(O)R １２ , -S(O) ２ R １２ , -S(O) ２ N (R １２ ) (R １１ ), optionally substituted C ３～８ Cycloalkyl, optionally substituted C ２～９ heterocycloalkyl, optionally substituted naphthyl, optionally substituted phenyl, optionally substituted monocyclic heteroaryl, or optionally substituted bicyclic heteroaryl; The alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, naphthyl, phenyl, or heteroaryl are independently selected from the group consisting of halogen, —OH, —NO ２ , amino, oxo, -CN, C １～３ Alkoxy, C １～３ Alkyl, and C １～３ optionally substituted with one or more substituents selected from haloalkyl, or R on the same atom Ｂ two of which, together with the atoms to which they are attached, are optionally substituted C ３～８ Cycloalkyl or optionally substituted C ２～９ forming a heterocycloalkyl, The cycloalkyl or heterocycloalkyl is independently selected from halogen, —OH, amino, —NO ２ , oxo, C １～６ Alkoxy, -CN, C １～６ Alkyl, C １～６ optionally substituted with one or more substituents selected from haloalkyl; m is 1, 2, 3, or 4; n is 0, 1, 2, 3, or 4; 6. The compound of claim 5, or a pharmaceutically acceptable salt thereof, wherein p is 0 or 1. 【Request Item 7】 【Chemistry 207】 but, 【Chemical 208】 and Y １ But N or CR Ｙ１ and Y ２ But N or CR Ｙ２ and Y ３ But N or CR Ｙ３ and Y ４ But N or CR Ｙ４ and R Ｙ１ , R Ｙ２ , R Ｙ３ , and R Ｙ４ each independently represents hydrogen, halo, —CN, —OR １１ , -SR １１ , -N(R １２ ) ２ , optionally substituted C １～６ Alkyl, optionally substituted C １～６ Heteroalkyl, optionally substituted C ２～６ Alkenyl, and optionally substituted C ２～６ 7. The compound of claim 5 or 6, or a pharmaceutically acceptable salt thereof, wherein:

8. X １ , X ２ , X ３ 6. The compound of claim 5, wherein at least two of are N, or a pharmaceutically acceptable salt thereof.

9. X ６ or X ７ or a pharmaceutically acceptable salt thereof.

6. The compound of claim 5, wherein at least one of:

10. 6. The compound of claim 5, wherein the compound has the structure of Formula (IIa), or a pharmaceutically acceptable salt thereof. 【Chemical Engineering 209】

11. 6. The compound of claim 5, wherein the compound has the structure of formula (IIb), or a pharmaceutically acceptable salt thereof. 【Chemical Engineering 212】

12. 6. The compound of claim 5, wherein the compound has the structure of formula (IIc'), or a pharmaceutically acceptable salt thereof. 【Chemical 215】

13. 6. The compound of claim 5, wherein the compound has the structure of formula (IId'), or a pharmaceutically acceptable salt thereof. 【Chemical 217】

14. 6. The compound of claim 5, wherein the compound has the structure of formula (IIe), or a pharmaceutically acceptable salt thereof. 【Chemical 219】

15. 6. The compound of claim 5, wherein the compound has the structure of formula (IIg), or a pharmaceutically acceptable salt thereof. 【Chemical 220】

16. 6. The compound of claim 1 or 5, or a pharmaceutically acceptable salt thereof, wherein ring A is phenyl. 【Request Item 17】 【Chemistry 221】 but, 【Chemistry 222】 6. The compound of claim 1 or 5, wherein:

18. 6. The compound of claim 1 or 5, or a pharmaceutically acceptable salt thereof, wherein ring A is naphthyl.

19. 6. The compound of claim 1 or 5, or a pharmaceutically acceptable salt thereof, wherein ring A is a 5- or 6-membered monocyclic heteroaryl.

20. 6. The compound of claim 1 or 5, or a pharmaceutically acceptable salt thereof, wherein Ring A is a bicyclic heteroaryl.

21. R Ａ each independently represents a halogen, —NO ２ , oxo, —CN, optionally substituted C １～６ Alkyl, optionally substituted C １～６ Heteroalkyl, optionally substituted C ３～８ Cycloalkyl, optionally substituted C ２～７ heterocycloalkyl, —OR １１ , -SR １１ , -N(R １２ ) (R １１ ), -C(O)R １２ , -C(O)OR １２ , -OC(O)R １２ , -OC(O)N(R １２ ) (R １１ ), -C(O)N(R １２ ) (R １１ ), -N(R １２ ) C(O)R １２ , -N(R １２ )C(O)OR １２ , -N(R １２ )C(O)N(R １２ ) (R １１ ), -N(R １２ ) ２ S (O) ２ (R １２ ), -S(O)R １２ , -S(O) ２ R １２ , and -S(O) ２ N (R １２ ) (R １１ 6. The compound of claim 1 or 5, or a pharmaceutically acceptable salt thereof, selected from: 【Request Item 22】 【Chemistry 225】 but, 【Chemistry 226-1】 【Chemistry 226-2】 6. The compound of claim 1 or 5, or a pharmaceutically acceptable salt thereof, selected from:

23. 6. The compound of claim 1 or 5, or a pharmaceutically acceptable salt thereof, wherein p is 1.

24. R ８ and R ９ 6. The compound of claim 1 or 5, or a pharmaceutically acceptable salt thereof, wherein each of is hydrogen.

25. R ８ and R ９ 10. The compound of claim 1 or 5, or a pharmaceutically acceptable salt thereof, wherein: are taken together to form oxo.

26. R ８ and R ９ taken together with the carbon to which they are attached form an optionally substituted 3- to 6-membered cycloalkyl or heterocycloalkyl, or a pharmaceutically acceptable salt thereof.

27. 6. The compound of claim 1 or 5, or a pharmaceutically acceptable salt thereof, wherein p is 0.

28. 6. The compound of claim 1 or 5, or a pharmaceutically acceptable salt thereof, wherein Ring B is phenyl or 6-membered heteroaryl.

29. R Ｂ１ 6. The compound of claim 1 or 5, or a pharmaceutically acceptable salt thereof, wherein is an optionally substituted monocyclic 5- to 6-membered heterocycloalkyl or heteroaryl.

30. R Ｂ１ are independently halogen, -NO ２ , oxo, -CN, C １～６ Haloalkyl, C １～６ Alkyl, C １～６ Aminoalkyl, C １～６ Hydroxyalkyl, C １～６ Heteroalkyl, optionally substituted C ３～８ Cycloalkyl and optionally substituted C ２～７ 30. The compound of claim 29, or a pharmaceutically acceptable salt thereof, optionally substituted with one or more substituents selected from heterocycloalkyl.

31. R Ｂ１ but, 【Chemistry 227】 30. The compound of claim 29, selected from: or a pharmaceutically acceptable salt thereof.

32. Each R Ｂ are independently halo, -CN, -NO ２ , optionally substituted C １～６ Alkyl, optionally substituted C １～６ Heteroalkyl, optionally substituted C ３～８ Cycloalkyl, optionally substituted C ２～９ 10. The compound of claim 1 or 5, which is heterocycloalkyl, optionally substituted phenyl, optionally substituted monocyclic heteroaryl, or optionally substituted bicyclic heteroaryl, or a pharmaceutically acceptable salt thereof.

33. R on the same atom Ｂ two of which, together with the atoms to which they are attached, are optionally substituted C ３～６ cycloalkyl or optionally substituted C ２～５ 10. The compound of claim 1 or 5, or a pharmaceutically acceptable salt thereof, which forms a heterocycloalkyl.

34. 6. The compound of claim 1 or 5, wherein n is 0, or a pharmaceutically acceptable salt thereof.

35. R １ , R ３ , R ６ , and R ７ each independently represents hydrogen or C １ ~C ６ 10. The compound of claim 1 or 5, or a pharmaceutically acceptable salt thereof, wherein R is alkyl.

36. A compound having the structure of formula (VI), or a pharmaceutically acceptable salt thereof: 【Chemistry 232】 During the ceremony, Ring C is phenyl or 6-membered heteroaryl, each of said phenyl or said heteroaryl being optionally substituted; Ring D is an aromatic saturated or partially saturated 5-membered carbocyclic or heterocyclic ring, each of which is optionally substituted; R ８ and R ９ each independently represents hydrogen, halo, —CN, optionally substituted C １～６ Alkyl, optionally substituted C １～６ Heteroalkyl, optionally substituted C ２～６ Alkenyl, and optionally substituted C ２～６ alkynyl, or R ８ and R ９ together form an oxo, or R ８ and R ９ taken together with the carbons to which they are attached form an optionally substituted 3- to 6-membered cycloalkyl or heterocycloalkyl; Ring A is phenyl, naphthyl, monocyclic heteroaryl, or bicyclic heteroaryl; R Ａ each independently represents a halogen, —NO ２ , oxo, —CN, optionally substituted C １～６ Alkyl, optionally substituted C ２～６ Alkenyl, optionally substituted C ２～６ Alkynyl, optionally substituted C １～６ Heteroalkyl, optionally substituted C ３～８ Cycloalkyl, optionally substituted C ２～７ heterocycloalkyl, —OR １１ , -SR １１ , -N(R １２ ) (R １１ ), -C(O)R １２ , -C(O)OR １２ , -OC(O)R １２ , -OC(O)N(R １２ ) (R １１ ), -C(O)N(R １２ ) (R １１ ), -N(R １２ ) C(O)R １２ , -N(R １２ )C(O)OR １２ , -N(R １２ )C(O)N(R １２ ) (R １１ ), -N(R １２ ) ２ S (O) ２ (R １２ ), -S(O)R １２ , -S(O) ２ R １２ , and -S(O) ２ N (R １２ ) (R １１ ) are selected from R １１ is hydrogen, optionally substituted C １～６ Alkyl, optionally substituted C ２～６ Alkenyl, optionally substituted C ２～６ Alkynyl, optionally substituted C １～６ Heteroalkyl, optionally substituted C ３～８ Cycloalkyl, optionally substituted C ２～７ Heterocycloalkyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted —C １～４ Alkylene-C ３～８ Cycloalkyl, optionally substituted -C １～４ Alkylene-C ２～７ Heterocycloalkyl, optionally substituted -C １～４ alkylene-phenyl, or optionally substituted -C １～４ alkylene-heteroaryl; R １２ each independently represents hydrogen, —NO ２ , -CN,C １～６ Alkyl, C １～６ Aminoalkyl, C １～６ Hydroxyalkyl, C １～６ Haloalkyl, and C ３～６ a carbocyclic ring, a 3- to 6-membered heterocyclic ring, ３～６ The carbocycle and the 3- to 6-membered heterocycle are independently selected from halogen, —OH, oxo, amino, —NO ２ , -CN,C １～６ Alkyl, C １～６ Alkoxy, and C １～６ optionally substituted with one or more substituents selected from haloalkyl; R Ｂ is hydrogen, halo, -CN, -NO ２ , optionally substituted C １～６ Alkyl, optionally substituted C ２～６ Alkenyl, optionally substituted C ２～６ Alkynyl, optionally substituted C １～６ Heteroalkyl, —OR １１ , -SR １１ , -N(R １２ ) (R １１ ), -C(O)R １２ , -C(O)OR １２ , -OC(O)R １２ , -OC(O)N(R １２ ) (R １１ ), -C(O)N(R １２ ) (R １１ ), -N(R １２ ) C(O)R １２ , -N(R １２ )C(O)OR １２ , -N(R １２ )C(O)N(R １２ ) (R １１ ), -N(R １２ ) S (O) ２ (R １２ ), -S(O)R １２ , -S(O) ２ R １２ , -S(O) ２ N (R １２ ) (R １１ ), optionally substituted C ３～８ Cycloalkyl, optionally substituted C ２～９ heterocycloalkyl, optionally substituted naphthyl, optionally substituted phenyl, optionally substituted monocyclic heteroaryl, or optionally substituted bicyclic heteroaryl; m is 1, 2, 3, or 4; The compound or a pharmaceutically acceptable salt thereof, wherein p is 0 or 1.

37. Ring C is phenyl or 6-membered heteroaryl, and each of said phenyl or said heteroaryl is selected from the group consisting of 1, 2, 3, or 4 R １Ｃ optionally substituted with Each R １Ｃ are independently halogen, —CN, —NO ２ , —OH, —OR ａ , —OC(═O)R ａ , -OC(=O)OR ｂ , -OC(=O)NR ｃ R ｄ , -SH, -SR ａ , -S(=O)R ａ , -S(=O) ２ R ａ , -S(=O) ２ NR ｃ R ｄ , -NR ｃ R ｄ , -NR ｂ C(=O)NR ｃ R ｄ , -NR ｂ C(=O)R ａ , -NR ｂ C(=O)OR ｂ , -NR ｂ S (= O) ２ R ａ , -C(=O)R ａ , -C(=O)OR ｂ , —C(═O)NR ｃ R ｄ , C １～６ Alkyl, C １～６ Haloalkyl, C １～６ Hydroxyalkyl, C １～６ Aminoalkyl, C １～６ Heteroalkyl, C ２～６ Alkenyl, C ２～ C ６ Alkynyl, C ３～８ Cycloalkyl, C ２～７ heterocycloalkyl, aryl, or heteroaryl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are optionally and independently selected from one or more R １Ｃａ is replaced by Ring D is an aromatic saturated or partially saturated 5-membered carbocyclic or heterocyclic ring, each of which may contain 1, 2, 3, 4, 5, or 6 R １Ｄ optionally substituted with Each R １Ｄ are independently halogen, —CN, —NO ２ , —OH, —OR ａ , —OC(═O)R ａ , -OC(=O)OR ｂ , -OC(=O)NR ｃ R ｄ , -SH, -SR ａ , -S(=O)R ａ , -S(=O) ２ R ａ , -S(=O) ２ NR ｃ R ｄ , -NR ｃ R ｄ , -NR ｂ C(=O)NR ｃ R ｄ , -NR ｂ C(=O)R ａ , -NR ｂ C(=O)OR ｂ , -NR ｂ S (= O) ２ R ａ , -C(=O)R ａ , -C(=O)OR ｂ , —C(═O)NR ｃ R ｄ , C １～６ Alkyl, C １～６ Haloalkyl, C １～６ Hydroxyalkyl, C １～６ Aminoalkyl, C １～６ Heteroalkyl, C ２～６ Alkenyl, C ２～ C ６ Alkynyl, C ３～８ Cycloalkyl, C ２～７ heterocycloalkyl, aryl, or heteroaryl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are optionally and independently selected from one or more R １Ｄａ is replaced by R ８ and R ９ each independently represents hydrogen, halo, —CN, optionally substituted C １～６ Alkyl, optionally substituted C １～６ Heteroalkyl, optionally substituted C ２～６ Alkenyl, and optionally substituted C ２～６ alkynyl, or R ８ and R ９ together form an oxo, or R ８ and R ９ taken together with the carbons to which they are attached form an optionally substituted 3- to 6-membered cycloalkyl or heterocycloalkyl; The alkyl, alkenyl, alkynyl, cycloalkyl, or heterocycloalkyl are independently selected from the group consisting of halogen, amino, —OH, —NO ２ , oxo, -CN, C １～３ Alkoxy, C １～３ Alkyl, and C １～３ optionally substituted with one or more substituents selected from haloalkyl; Ring A is phenyl, naphthyl, monocyclic heteroaryl, or bicyclic heteroaryl; R Ａ each independently represents a halogen, —NO ２ , oxo, —CN, optionally substituted C １～６ Alkyl, optionally substituted C ２～６ Alkenyl, optionally substituted C ２～６ Alkynyl, optionally substituted C １～６ Heteroalkyl, optionally substituted C ３～８ Cycloalkyl, optionally substituted C ２～７ heterocycloalkyl, —OR １１ , -SR １１ , -N(R １２ ) (R １１ ), -C(O)R １２ , -C(O)OR １２ , -OC(O)R １２ , -OC(O)N(R １２ ) (R １１ ), -C(O)N(R １２ ) (R １１ ), -N(R １２ ) C(O)R １２ , -N(R １２ )C(O)OR １２ , -N(R １２ )C(O)N(R １２ ) (R １１ ), -N(R １２ ) ２ S (O) ２ (R １２ ), -S(O)R １２ , -S(O) ２ R １２ , and -S(O) ２ N (R １２ ) (R １１ ) are selected from The alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, or heterocycloalkyl is independently selected from halogen, —OH, —NO ２ , oxo, amino, -CN, C １～６ Alkoxy, C １～６ Alkyl, C １～６ Haloalkyl, C ３～６ optionally substituted with one or more substituents selected from a carbocycle and a 3- to 6-membered heterocycle, ３～６ The carbocycle and the 3- to 6-membered heterocycle are independently selected from halogen, —OH, amino, —NO ２ , oxo, -CN, C １～６ Alkyl, C １～６ Alkoxy, and C １～６ optionally substituted with one or more substituents selected from haloalkyl; R １１ is hydrogen, optionally substituted C １～６ Alkyl, optionally substituted C ２～６ Alkenyl, optionally substituted C ２～６ Alkynyl, optionally substituted C １～６ Heteroalkyl, optionally substituted C ３～８ Cycloalkyl, optionally substituted C ２～７ Heterocycloalkyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted —C １～４ Alkylene-C ３～８ Cycloalkyl, optionally substituted -C １～４ Alkylene-C ２～７ Heterocycloalkyl, optionally substituted -C １～４ alkylene-phenyl, or optionally substituted -C １～４ alkylene-heteroaryl; The alkyl, alkenyl, alkynyl, heteroalkyl, alkylene, cycloalkyl, heterocycloalkyl, phenyl, or heteroaryl may independently be halogen, —OH, amino, —NO ２ , oxo, C １～６ Alkoxy, -CN, C １～６ Alkyl, C １～６ optionally substituted with one or more substituents selected from haloalkyl; R １２ each independently represents hydrogen, —NO ２ , -CN,C １～６ Alkyl, C １～６ Aminoalkyl, C １～６ Hydroxyalkyl, C １～６ Haloalkyl, and C ３～６ a carbocyclic ring, a 3- to 6-membered heterocyclic ring, ３～６ The carbocycle and the 3- to 6-membered heterocycle are independently selected from halogen, —OH, oxo, amino, —NO ２ , -CN,C １～６ Alkyl, C １～６ Alkoxy, and C １～６ optionally substituted with one or more substituents selected from haloalkyl; R Ｂ is hydrogen, halo, -CN, -NO ２ , optionally substituted C １～６ Alkyl, optionally substituted C ２～６ Alkenyl, optionally substituted C ２～６ Alkynyl, optionally substituted C １～６ Heteroalkyl, —OR １１ , -SR １１ , -N(R １２ ) (R １１ ), -C(O)R １２ , -C(O)OR １２ , -OC(O)R １２ , -OC(O)N(R １２ ) (R １１ ), -C(O)N(R １２ ) (R １１ ), -N(R １２ ) C(O)R １２ , -N(R １２ )C(O)OR １２ , -N(R １２ )C(O)N(R １２ ) (R １１ ), -N(R １２ ) S (O) ２ (R １２ ), -S(O)R １２ , -S(O) ２ R １２ , -S(O) ２ N (R １２ ) (R １１ ), optionally substituted C ３～８ Cycloalkyl, optionally substituted C ２～９ heterocycloalkyl, optionally substituted naphthyl, optionally substituted phenyl, optionally substituted monocyclic heteroaryl, or optionally substituted bicyclic heteroaryl; The alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, naphthyl, phenyl, or heteroaryl are independently selected from halogen, —NO ２ , oxo, —CN, optionally substituted C １～６ Alkyl, optionally substituted C ２～６ Alkenyl, optionally substituted C ２～６ Alkynyl, optionally substituted C １～６ Heteroalkyl, optionally substituted C ３～８ Cycloalkyl, optionally substituted C ２～７ heterocycloalkyl, —OR １１ , -SR １１ , -N(R １２ ) (R １１ ), -C(O)R １２ , -C(O)OR １２ , -OC(O)R １２ , -OC(O)N(R １２ ) (R １１ ), -C(O)N(R １２ ) (R １１ ), -N(R １２ ) C(O)R １２ , -N(R １２ )C(O)OR １２ , -N(R １２ )C(O)N(R １２ ) (R １１ ), -N(R １２ ) S (O) ２ (R １２ ), -S(O)R １２ , -S(O) ２ R １２ , and -S(O) ２ N (R １２ ) (R １１ ), wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, or heterocycloalkyl is independently selected from halogen, —OH, —NO ２ , amino, -NH(C １～６ alkyl), -N(C １～６ alkyl) ２ , oxo, -CN, C １～３ Alkoxy, C １～３ Alkyl, and C １～３ optionally substituted with one or more substituents selected from haloalkyl; Each R ａ But independently, C １ ~C ６ Alkyl, C １ ~C ６ Haloalkyl, C １ ~C ６ Hydroxyalkyl, C １ ~C ６ Aminoalkyl, C １ ~C ６ Heteroalkyl, C ２ ~C ６ Alkenyl, C ２ ~C ６ Alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, -C １ ~C ６ Alkylene-cycloalkyl, -C １ ~C ６ alkylene-heterocycloalkyl, -C １ ~C ６ alkylene-aryl, or -C １ ~C ６ alkylene-heteroaryl, wherein each alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl independently is selected from the group consisting of one or more of oxo, halogen, —CN, —OH, —OC １ ~C ６ Alkyl, —S(═O)C １ ~C ６ Alkyl, —S(═O) ２ C １ ~C ６ Alkyl, —S(═O) ２ NH ２ , -S(=O) ２ NHC １ ~C ６ Alkyl, —S(═O) ２ N (C １ ~C ６ alkyl) ２ , -NH ２ , -NHC １ ~C ６ Alkyl, —N(C １ ~C ６ alkyl) ２ , -NHC(=O)OC １ ~C ６ Alkyl, —C(═O)C １ ~C ６ Alkyl, —C(═O)OH, —C(═O)OC １ ~C ６ Alkyl, —C(═O)NH ２ , -C(=O)N(C １ ~C ６ alkyl) ２ , -C(=O)NHC １ ~C ６ Alkyl, C １ ~C ６ Alkyl, C １ ~C ６ Haloalkyl, C １ ~C ６ Hydroxyalkyl, C １ ~C ６ aminoalkyl, or C １ ~C ６ optionally substituted with heteroalkyl; Each R ｂ are independently hydrogen, C １ ~C ６ Alkyl, C １ ~C ６ Haloalkyl, C １ ~C ６ Hydroxyalkyl, C １ ~C ６ Aminoalkyl, C １ ~C ６ Heteroalkyl, C ２ ~C ６ Alkenyl, C ２ ~C ６ Alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, -C １ ~C ６ Alkylene-cycloalkyl, -C １ ~C ６ alkylene-heterocycloalkyl, -C １ ~C ６ alkylene-aryl, or -C １ ~C ６ alkylene-heteroaryl, wherein each alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl independently is selected from the group consisting of one or more of oxo, halogen, —CN, —OH, —OC １ ~C ６ Alkyl, —S(═O)C １ ~C ６ Alkyl, —S(═O) ２ C １ ~C ６ Alkyl, —S(═O) ２ NH ２ , -S(=O) ２ N.H.C. １ ~C ６ Alkyl, —S(═O) ２ N (C １ ~C ６ alkyl) ２ , -NH ２ , -NHC １ ~C ６ Alkyl, —N(C １ ~C ６ alkyl) ２ , -NHC(=O)OC １ ~C ６ Alkyl, —C(═O)C １ ~C ６ Alkyl, —C(═O)OH, —C(═O)OC １ ~C ６ Alkyl, —C(═O)NH ２ , -C(=O)N(C １ ~C ６ alkyl) ２ , -C(=O)NHC １ ~C ６ Alkyl, C １ ~C ６ Alkyl, C １ ~C ６ Haloalkyl, C １ ~C ６ Hydroxyalkyl, C １ ~C ６ aminoalkyl, or C １ ~C ６ optionally substituted with heteroalkyl; Each R ｃ and R ｄ are independently hydrogen, C １ ~C ６ Alkyl, C １ ~C ６ Haloalkyl, C １ ~C ６ Hydroxyalkyl, C １ ~C ６ Aminoalkyl, C １ ~C ６ Heteroalkyl, C ２ ~C ６ Alkenyl, C ２ ~C ６ Alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, -C １ ~C ６ Alkylene-cycloalkyl, -C １ ~C ６ alkylene-heterocycloalkyl, -C １ ~C ６ Alkylene-aryl, or -C １ ~C ６ alkylene-heteroaryl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl independently is selected from one or more of oxo, halogen, —CN, —OH, —OC １ ~C ６ Alkyl, —S(═O)C １ ~C ６ Alkyl, —S(═O) ２ C １ ~C ６ Alkyl, —S(═O) ２ NH ２ , -S(=O) ２ NHC １ ~C ６ Alkyl, —S(═O) ２ N (C １ ~C ６ alkyl) ２ , -NH ２ , -NHC １ ~C ６ Alkyl, —N(C １ ~C ６ alkyl) ２ , -NHC(=O)OC １ ~C ６ Alkyl, —C(═O)C １ ~C ６ Alkyl, —C(═O)OH, —C(═O)OC １ ~C ６ Alkyl, —C(═O)NH ２ , -C(=O)N(C １ ~C ６ alkyl) ２ , -C(=O)NHC １ ~C ６ Alkyl, C １ ~C ６ Alkyl, C １ ~C ６ Haloalkyl, C １ ~C ６ Hydroxyalkyl, C １ ~C ６ aminoalkyl, or C １ ~C ６ optionally substituted with heteroalkyl; or R ｃ and R ｄ together with the atoms to which they are attached, may be one or more of oxo, halogen, —CN, —OH, —OC １ ~C ６ Alkyl, —S(═O)C １ ~C ６ Alkyl, —S(═O) ２ C １ ~C ６ Alkyl, —S(═O) ２ NH ２ , -S(=O) ２ NHC １ ~C ６ Alkyl, —S(═O) ２ N (C １ ~C ６ alkyl) ２ , -NH ２ , -NHC １ ~C ６ Alkyl, —N(C １ ~C ６ alkyl) ２ , -NHC(=O)OC １ ~C ６ Alkyl, —C(═O)C １ ~C ６ Alkyl, —C(═O)OH, —C(═O)OC １ ~C ６ Alkyl, —C(═O)NH ２ , -C(=O)N(C １ ~C ６ alkyl) ２ , -C(=O)NHC １ ~C ６ Alkyl, C １ ~C ６ Alkyl, C １ ~C ６ Haloalkyl, C １ ~C ６ Hydroxyalkyl, C １ ~C ６ aminoalkyl, or C １ ~C ６ forming a heterocycloalkyl optionally substituted with a heteroalkyl; Each R １Ｃａ and R １Ｄａ are independently halogen, —CN, —NO ２ , —OH, —OR ａ , —OC(═O)R ａ , -OC(=O)OR ｂ , -OC(=O)NR ｃ R ｄ , -SH, -SR ａ , -S(=O)R ａ , -S(=O) ２ R ａ , -S(=O) ２ NR ｃ R ｄ , -NR ｃ R ｄ , -NR ｂ C(=O)NR ｃ R ｄ , -NR ｂ C(=O)R ａ , -NR ｂ C(=O)OR ｂ , -NR ｂ S (= O) ２ R ａ , -C(=O)R ａ , -C(=O)OR ｂ , —C(═O)NR ｃ R ｄ , C １ ~C ６ Alkyl, C １ ~C ６ Haloalkyl, C １ ~C ６ Hydroxyalkyl, C １ ~C ６ Aminoalkyl, C １ ~C ６ Heteroalkyl, C ２ ~C ６ Alkenyl, C ２ ~C ６ alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; m is 1, 2, 3, or 4; 37. The compound of claim 36, or a pharmaceutically acceptable salt thereof, wherein p is 0 or 1.

38. 37. The compound of any one of claims 1, 5, or 36, wherein the compound is a compound of Table 1, or a pharmaceutically acceptable salt thereof.

39. 1. A compound, or a pharmaceutically acceptable salt thereof, comprising: 【Chemistry 243】 or a pharmaceutically acceptable salt thereof.

40. 40. A pharmaceutical composition comprising a compound of any one of claims 1, 5, 36, and 39, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient.

41. A composition comprising a compound of any one of claims 1, 5, 36, and 39, or a pharmaceutically acceptable salt thereof, for use in a method for treating a disease or disorder associated with ubiquitin-specific protease 1 (USP1) or associated with modulation of USP1 in a subject, or a pharmaceutical composition comprising a compound of any one of claims 1, 5, 36, and 39, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient, wherein the method comprises administering the composition to the subject.

42. 42. The composition for use according to claim 41, wherein the disease or disorder is cancer.

43. 43. The composition for use of claim 42, wherein the cancer is selected from the group consisting of lung cancer, non-small cell lung cancer (NSCLC), colon cancer, bladder cancer, osteosarcoma, ovarian cancer, skin cancer, and breast cancer.

44. 43. The composition for use of claim 42, wherein the cancer comprises cancer cells with elevated levels of RAD18.

45. 43. The composition for use of claim 42, wherein the cancer is selected from the group consisting of DNA damage repair pathway deficient cancer, PARP inhibitor resistant or refractory cancer, BRCA1 mutant cancer, BRCA2 mutant cancer, and BRCA1 deficient cancer.

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