Compositions comprising a werner syndrome helicase inhibitor and methods of use thereof

Abstract

The presently disclosed subject matter relates to compositions comprising Werner Syndrome helicase (WRN) inhibitors and methods of using the same.

Claims

1. A compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof: (I) (II) in K and J are independently selected from C, N, O, or S; R, R0, and R5 are independently selected from H, halogen, -OH, =O, -C(O)-C1-C6 alkyl, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkyl-halo-halo-halo-halo-C6 hydroxyalkyl, alkyl-halo-C1-C6 alkoxy, or C3-C6 cycloalkyl; R6 and R7 are independently selected from H or halogens; R6 or R7 can optionally be connected to R5 to form C3-C8 cycloalkyl, 4- to 8-membered heterocyclic rings, or C6-C... 10 Aryl or 5- to 10-membered heteroaryl rings; and in (A) R1 is NR 30 R 31 aryl, C3-C7 cycloalkyl ring, 5- to 10-membered heteroaryl or 4-, 5- or 6-membered heterocyclic ring; Where R1 is NR 30 R 31 At that time, R 30 and R 31 Independently selected from optionally substituted C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl or H; When R1 is an aryl group, the aryl group is reacted with one or more -O-(C1-C6)alkyl-COOH, three C1-C6 alkoxy groups, or -C(O)-R. 33 -C(O)-NH-R 33 -S(O)R 33 -S(O2)R 33 -NH-S(O2)R 33 -NH-C(O)-NH-R 33 Substitution, or fusion of the aryl group with a 5- to 10-membered heteroaryl group, a C3-C8 cycloalkyl ring, a C3-C8 cycloalkenyl ring, a 5- or 6-membered heterocyclic ring, wherein the 5- or 6-membered heterocyclic ring comprises a carbon atom and at least one oxygen and / or at least one nitrogen atom, wherein R 33 Selected from C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, haloC1-C6 alkoxy, C3-C8 cycloalkyl, 4- to 8-membered heterocyclic rings, C6-C 10 Aryl or 5- to 10-membered heteroaryl groups, and The aryl, 5- to 10-membered heteroaryl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl ring and 5- or 6-membered heterocyclic ring are optionally surrounded by one or more C1-C3 alkyl, halogen, -OH, =O, -C(O)-C1-C6 alkyl, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkoxy, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, haloC1-C6 alkoxy, C3-C8 cycloalkyl; C3-C8 cycloalkenyl, second C6-C 10 Aryl, second 5- to 10-membered heteroaryl, or 3- to 8-membered heterocyclic group substitution; When R1 is a C3-C7 cycloalkyl ring, the C3-C7 cycloalkyl ring is a fully saturated ring, wherein the C3-C7 cycloalkyl ring is optionally combined with a second C3-C8 cycloalkyl ring, a 3- to 8-membered heterocyclic group, or a C6-C8 cycloalkyl ring. 10 Aryl or 5- to 10-membered heteroaryl groups are linked to form a spirocycle, or The C3-C7 cycloalkyl ring is optionally associated with a second C3-C8 cycloalkyl ring, a 3- to 8-membered heterocyclic group, or a C6-C... 10 Aryl or 5- to 10-membered heteroaryl groups are linked to form a fused ring, unless R4 is a substituted phenyl group; When R1 is a 5- to 10-membered heteroaryl ring, the 5- to 10-membered heteroaryl ring is replaced by -OH, -C(O)-C1-C6 alkyl, or -O-(C1-C6)alkyl-COOH, or the 5- to 10-membered heteroaryl ring is combined with a second 5- to 10-membered heteroaryl ring, C6-C 10 Fusing of aryl rings, C3-C8 cycloalkyl rings, C3-C8 cycloalkenyl rings, or 4- to 8-membered heterocyclic rings; When R1 is a 4-membered heterocyclic base ring The 4-membered heterocyclic base ring comprises at least one of a carbon atom and a nitrogen or oxygen atom, or The 4-membered heterocyclic base ring is optionally connected to a second substituted or unsubstituted 4-, 5-, or 6-membered heterocyclic base ring, wherein the second 4-, 5-, or 6-membered heterocyclic base ring comprises at least one of a carbon atom and a nitrogen or oxygen atom, wherein the 4- or 7-membered heterocyclic base ring is connected to the second 4-, 5-, or 6-membered heterocyclic base ring by one carbon atom to form a spirocyclic ring or by two carbon atoms to form a fused ring; When R1 is a 5-membered or 6-membered heterocyclic base ring The 5- or 6-membered heterocyclic base ring is a fully saturated ring comprising at least one of a carbon atom and a nitrogen atom or an oxygen atom, wherein the 5- or 6-membered heterocyclic base ring is substituted with one or more C2-C6 alkenyl or C2-C6 haloalkenyl groups, or is connected to a second substituted or unsubstituted 4-, 5-, or 6-membered heterocyclic base ring to form a spirocyclic ring, or the 5- or 6-membered heterocyclic base ring is connected to a second substituted or unsubstituted 4-, 5-, or 6-membered heterocyclic base ring to form a fused ring, wherein the second 4-, 5-, or 6-membered heterocyclic base ring comprises at least one of a carbon atom and a nitrogen atom or an oxygen atom. Wherein, when the 5-membered or 6-membered heterocyclic base ring is connected to the second 5-membered heterocyclic base ring by a carbon atom to form a spirocyclic ring, and the second 5-membered heterocyclic base ring is fully saturated, one or more heteroatoms in the second 5-membered heterocyclic base ring are selected from N or S; Wherein, when the 5- or 6-membered heterocyclic base ring is connected to the second 4-, 5-, or 6-membered heterocyclic base ring through two carbon atoms to form a fused ring, the second 4-, 5-, or 6-membered heterocyclic base ring is partially or completely unsaturated; or The 5- or 6-membered heterocyclic base ring comprises a carbon atom and at least one silicon atom; or The 5-membered heterocyclic base ring is a pyrazole ring, wherein the pyrazole ring is connected to a second substituted or unsubstituted 4-, 5-, or 6-membered heterocyclic base ring to form a fused ring, wherein the second 4-, 5-, or 6-membered heterocyclic base ring is a saturated ring containing at least one of a carbon atom and a nitrogen atom or an oxygen atom, or The 6-membered heterocyclic base ring is a pyridyl ring, wherein the pyridyl ring is connected to a second substituted or unsubstituted 4-, 5-, or 6-membered heterocyclic base ring to form a fused ring. Where n is 0, 1, 2 or 3; This refers to a single or double bond; B, D, E, X, and Y are independently selected from C or N; R a R b R1 and R3 are independently selected from H, -OH, =O, substituted or unsubstituted alkyl groups, or linked together to form a fused cycloalkyl ring, cycloalkenyl ring, aryl ring, heterocyclic ring, or heteroaryl ring; R2 and R3 are independently selected from H, -OH, =O, substituted or unsubstituted alkyl groups, substituted or unsubstituted alkenyl groups, substituted or unsubstituted heterocyclic rings, or linked together to form an unsubstituted or substituted fused heterocyclic ring, and Wherein R4 is H, -OH, =O, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl; substituted or unsubstituted aryl ring, substituted or unsubstituted heterocyclic ring, substituted or unsubstituted heteroaryl ring; (B) n is 0, 1, 2 or 3; This refers to a single or double bond; B, D, E, X, and Y are independently selected from C or N; R a and R b R1 and R2 are independently selected from H, -OH, =O, C1-C6 alkyl; R3 are independently selected from H, -OH, =O, C1-C6 alkyl, -NR8R9, -C(O)R. 10 -S(O2)R 10 substituted or unsubstituted C2-C3 alkenyl groups or substituted or unsubstituted 5- or 6-membered heterocyclic rings, or R a It is linked with R2 to form a fused C3-C8 cycloalkyl ring, C3-C8 cycloalkenyl ring, C6-C 10 An aryl ring, a 3- to 8-membered heterocyclic ring, or a 5- to 10-membered heteroaryl ring; or R2 and R3 linked together to form an unsubstituted or substituted fused 4-, 5-, or 6-membered heterocyclic ring, wherein when the 4-, 5-, or 6-membered heterocyclic ring is substituted, the substituent is optionally selected from -OH, =O, C1-C6 alkyl, 5- or 6-membered heterocyclic ring, or -C(O)R. 11 , where R 11 It is a C1-C3 alkyl group or a substituted 5- or 6-membered heterocyclic ring; Where R a It is linked with R2 to form a fused C3-C8 cycloalkyl ring, C3-C8 cycloalkenyl ring, C6-C 10 When aryl rings, 3- to 8-membered heterocyclic rings, or 5- to 10-membered heteroaryl rings are used, the fused C3-C8 cycloalkyl rings, C3-C8 cycloalkenyl rings, and C6-C... 10 Aryl rings, 3- to 8-membered heterocyclic rings, or 5- to 10-membered heteroaryl rings are coated with -C(O)R 34 or -S(O2)R 34 Replace, where R 34 It is a C1-C6 alkyl ring, a C3-C8 cycloalkyl ring, a C4-C8 cycloalkenyl ring, or a C6-C6 cycloalkyl ring. 10 Aryl rings, 4- to 8-membered heterocyclic rings, or 5- to 10-membered heteroaryl rings; When n is 0, X is N, Y is C, R2 is NR8R9 and R3 is H; When n is 1, X and Y are C, R2 is NR8R9 and R3 is H, or R2 and R3 are connected together to form a substituted fused 4-membered heterocyclic base ring, wherein the substituted 4-membered heterocyclic base ring is -C(O)R 11 Replace, and where R 11 It is a substituted 5- or 6-membered heterocyclic base ring; When R2 is NR8R9, R8 and R9 are independently selected from H, C1-C4 alkyl groups, and -C(O)R. 11 , where R 11 It is a substituted or unsubstituted 5- or 6-membered heterocyclic ring; When n is 2, X is C, Y is N, and R2 and R3 are connected together to form an unsubstituted or substituted fused 4- or 5-membered heterocyclic base ring, wherein when the 5-membered heterocyclic base ring is substituted, the substituent is selected from a 5- or 6-membered heterocyclic base ring or -C(O)R 11 , where R 11 It is a C1-C3 alkyl or a substituted 5- or 6-membered heterocyclic ring, or X is C, Y is N, R2 is H, and R3 is -C(O)R. 10 or -S(O2)R 10 And R 10 It is C2-C6 alkenyl, C3-C7 cycloalkyl, or C1-C6 hydroxyalkyl, wherein R 10 Optionally substituted with -OH, C1-C6 alkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C3 alkoxy, optionally substituted C3-C5 cycloalkyl ring, halogen, optionally substituted 3- to 8-membered heterocyclic group, -S(O2)CH3 or -C(O)N(CH3)2, or or X is C, Y is N, R2 is H, and R3 is -C(O)R. 10 or -S(O2)R 10 And R 10 for W, U, V, and Z are independently selected from H, C, N, S, or O, and This refers to a single bond or a double bond; Where R 10 for hour, Where U is N + At that time, R 15 For O - R 16 and R 17 For H, and U V is a double bond; When U is C, R 15 For -NR 19 R 20 U V is a double bond and R 16 R 17 R 18 Independently selected from H, -CH3, R 19 and R 20 Independently selected from -C(O)R 21 -S(O2)R 21 and -S(O)R 21 R 22 , where R 21 and R 22 Independently selected from C1-C3 alkyl, C3-C5 cycloalkyl ring, or 5- or 6-membered heterocyclic ring, or R 21 and R 22 They are linked together to form substituted or unsubstituted C3-C5 cycloalkyl rings; Wherein R1 is H, -OH, =O, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl; substituted or unsubstituted aryl ring, substituted or unsubstituted heterocyclic ring, substituted or unsubstituted heteroaryl ring, and Wherein R4 is H, -OH, =O, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl; substituted or unsubstituted aryl ring, substituted or unsubstituted heterocyclic ring, substituted or unsubstituted heteroaryl ring; or (C) R4 is selected from , , and Where L and G are independently selected from C, N or O, n is 0, 1 or 2, and x is 0, 1 or 2; Where R4 is When L is C or O, n is 0 or 1, and R 23 It is a C1-C4 alkyl group, wherein the C1-C4 alkyl group is optionally substituted with a halogen selected from F or Cl, or R 23 It is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkoxy, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, haloC1-C6 alkoxy, C3-C8 cycloalkyl, bridged C3-C8 cycloalkyl, 3- to 8-membered heterocyclic ring, C6-C 10 Aryl or 5- to 10-membered heteroaryl groups; Where R4 is When L is C or O, n is 0, 1 or 2, x is 0, 1 or 2, and R is... 24 It is a C1-C4 alkyl group, wherein the C1-C4 alkyl group is optionally substituted with a halogen selected from F or Cl, or R 24 It is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, haloC1-C6 alkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocyclic ring, C6-C 10 Aryl or 5- to 10-membered heteroaryl, or the R 24 It is a spirocyclic or fused ring, wherein L is optionally substituted with -OH, halogen, or C1-C6 alkyl; Where R4 is When n is 0, 1, or 2, R 24 It is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, haloC1-C6 alkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocyclic ring, C6-C 10 Aryl or 5- to 10-membered heteroaryl, or the R 24 It is a spiral ring or a fused ring; Where R4 is At that time, L G is a single or double bond; where L is a single or double bond. When G is a double bond, G and L are independently selected from C or N, and R 25 and R 29 Independently selected from H, halogens, or -C(O), R 26 and R 27 It can be independently selected from H, -OCF2Cl, or -S(O). m R 28 Where m is between 0 and 2, R 28 It is a methyl or trihalomethyl group, or R 25 Or R 27 With R 26 Linked to form a 5- or 6-membered heterocyclic ring optionally substituted with -OH, alkyl, haloalkyl, or halogen; Wherein R1 is H, -OH, =O, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl; substituted or unsubstituted aryl ring, substituted or unsubstituted heterocyclic ring, substituted or unsubstituted heteroaryl ring; and Where n is 0, 1, 2 or 3; This refers to a single or double bond; B, D, E, X, and Y are independently selected from C or N; R a R b R1 and R3 are independently selected from H, -OH, =O, substituted or unsubstituted alkyl groups, or linked together to form a fused cycloalkyl ring, cycloalkenyl ring, aryl ring, heterocyclic ring, or heteroaryl ring; R2 and R3 are independently selected from H, -OH, =O, substituted or unsubstituted alkyl groups, substituted or unsubstituted alkenyl groups, substituted or unsubstituted heterocyclic rings, or linked together to form an unsubstituted or substituted fused heterocyclic ring.

2. A compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof: (I) (II) in K and J are independently selected from C, N, O, or S; R, R0, and R5 are independently selected from H, halogen, -OH, =O, -C(O)-C1-C6 alkyl, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkyl-halo-halo-halo-halo-C6 hydroxyalkyl, alkyl-halo-C1-C6 alkoxy, or C3-C6 cycloalkyl; R6 and R7 are independently selected from H or halogens; R6 or R7 can optionally be connected to R5 to form C3-C8 cycloalkyl, 4- to 8-membered heterocyclic rings, or C6-C... 10 Aryl or 5- to 10-membered heteroaryl rings; and in (A) R1 is NR 30 R 31 aryl, C3-C7 cycloalkyl, 5- to 10-membered heteroaryl or 3- to 8-membered heterocyclic; Where R1 is NR 30 R 31 At that time, R 30 and R 31 Independently selected from optionally substituted C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl or H; Wherein, when R1 is an aryl, C3-C7 cycloalkyl, 5- to 10-membered heteroaryl, or 3- to 8-membered heterocyclic group, the aryl, C3-C7 cycloalkyl, 5- to 10-membered heteroaryl, or 3- to 8-membered heterocyclic group is optionally surrounded by one or more R 36 Substitution, or the aryl, C3-C7 cycloalkyl, 5- to 10-membered heteroaryl or 3- to 8-membered heterocyclic group with a second C3- to C8 cycloalkyl ring, 3- to 8-membered heterocyclic group, C6-C 10 The aryl group or a 5- to 10-membered heteroaryl group is linked to form a spirocyclic ring, or the aryl group, C3-C7 cycloalkyl group, 5- to 10-membered heteroaryl group or 3- to 8-membered heterocyclic group is fused with a second 5- to 10-membered heteroaryl group, C3-C8 cycloalkyl ring, 3- to 8-membered heterocyclic ring or C3-C8 cycloalkenyl ring. Where R 36 Independently selected from -OH, -COOH, -NH2, -CN, oxo, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 hydroxyalkyl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, C3-C8 cycloalkyl, 3- to 8-membered heterocyclic, -O-(C1-C6)alkyl-COOH, -C(O)-R 33 -C(O)-NH-R 33 -S(O)R 33 -S(O2)R 33 -NH-S(O2)R 33 -NH-C(O)-NH-R 33 , Where R 33 Selected from C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, haloC1-C6 alkoxy, C3-C8 cycloalkyl, 4- to 8-membered heterocyclic rings, C6-C 10 Aryl or 5- to 10-membered heteroaryl groups; and (B) n is 0, 1, 2 or 3; This refers to a single or double bond; B, D, E, X, and Y are independently selected from C or N; R a R b R1 and R2 are independently selected from H, -OH, =O, C1-C6 alkyl; R3 are independently selected from H, -OH, =O, C1-C6 alkyl, -NR8R9, -C(O)R. 10 -S(O2)R 10 substituted or unsubstituted C2-C3 alkenyl groups or substituted or unsubstituted 5- or 6-membered heterocyclic rings, or R a It is linked with R2 to form a fused C3-C8 cycloalkyl ring, C3-C8 cycloalkenyl ring, C6-C 10 An aryl ring, a 3- to 8-membered heterocyclic ring, or a 5- to 10-membered heteroaryl ring; or R2 and R3 linked together to form an unsubstituted or substituted fused 4-, 5-, or 6-membered heterocyclic ring, wherein when the 4-, 5-, or 6-membered heterocyclic ring is substituted, the substituent is optionally selected from -OH, =O, C1-C6 alkyl, 5- or 6-membered heterocyclic ring, or -C(O)R. 11 , where R 11 It is a C1-C3 alkyl group or a substituted 5- or 6-membered heterocyclic ring; Where R a It is linked with R2 to form a fused C3-C8 cycloalkyl ring, C3-C8 cycloalkenyl ring, C6-C 10 When aryl rings, 3- to 8-membered heterocyclic rings, or 5- to 10-membered heteroaryl rings are used, the fused C3-C8 cycloalkyl rings, C3-C8 cycloalkenyl rings, and C6-C... 10 Aryl rings, 3- to 8-membered heterocyclic rings, or 5- to 10-membered heteroaryl rings are coated with -C(O)R 34 or -S(O2)R 34 Replace, where R 34 It is a C1-C6 alkyl ring, a C3-C8 cycloalkyl ring, a C4-C8 cycloalkenyl ring, or a C6-C6 cycloalkyl ring. 10 Aryl rings, 4- to 8-membered heterocyclic rings, or 5- to 10-membered heteroaryl rings; When n is 0, X is N, Y is C, R2 is NR8R9 and R3 is H; When n is 1, X and Y are C, R2 is NR8R9 and R3 is H, or R2 and R3 are connected together to form a substituted fused 4-membered heterocyclic base ring, wherein the substituted 4-membered heterocyclic base ring is -C(O)R 11 Replace, and where R 11 It is a substituted 5- or 6-membered heterocyclic base ring; When R2 is NR8R9, R8 and R9 are independently selected from H, C1-C4 alkyl groups, and -C(O)R. 11 , where R 11 It is a substituted or unsubstituted 5- or 6-membered heterocyclic ring; When n is 2, X is C, Y is N, and R2 and R3 are connected together to form an unsubstituted or substituted fused 4- or 5-membered heterocyclic base ring, wherein when the 5-membered heterocyclic base ring is substituted, the substituent is selected from a 5- or 6-membered heterocyclic base ring or -C(O)R 11 , where R 11 It is a C1-C3 alkyl or a substituted 5- or 6-membered heterocyclic ring, or X is C, Y is N, R2 is H, and R3 is -C(O)R. 10 or -S(O2)R 10 And R 10 It is a C1-C6 hydroxyalkyl, C2-C6 alkenyl, or C3-C7 cycloalkyl ring, wherein R 10 Optionally substituted with -OH, C1-C6 alkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C3 alkoxy, optionally substituted C3-C5 cycloalkyl ring, halogen, optionally substituted 3- to 8-membered heterocyclic group, -S(O2)CH3 or -C(O)N(CH3)2, or X is C, Y is N, R2 is H, and R3 is -C(O)R. 10 or -S(O2)R 10 And R 10 for ， Where W, U, V, and Z are independently selected from H, C, N, S, or O, and where This refers to a single bond or a double bond; Where R 10 for hour, Where U is N + At that time, R 15 For O - R 16 and R 17 For H, and U V is a double bond; When U is C, R 15 For -NR 19 R 20 U V is a double bond, and R 16 R 17 and R 18 Independently selected from H, -CH3, -C(O)R 21 -S(O2)R 21 and -S(O)R 21 R 22 R 19 and R 20 Independently selected from -C(O)R 21 -S(O2)R 21 and -S(O)R 21 R 22 , where R 21 and R 22 Independently selected from C1-C3 alkyl, C3-C5 cycloalkyl ring, or 5- or 6-membered heterocyclic ring, or R 21 and R 22 They are linked together to form substituted or unsubstituted C3-C5 cycloalkyl rings; and Wherein R4 is H, -OH, =O, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl; substituted or unsubstituted aryl ring, substituted or unsubstituted heterocyclic ring, substituted or unsubstituted heteroaryl ring; or (C) R4 is selected from , , and , where L and G are independently selected from C, N or O, n is 0, 1 or 2, and x is 1 or 2; Where R4 is When L is C or O, n is 0 or 1, and R 23 It is a C1-C4 alkyl group, wherein the C1-C4 alkyl group is optionally substituted with a halogen selected from F or Cl, or R 23 It is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkoxy, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, haloC1-C6 alkoxy, C3-C8 cycloalkyl, bridged C3-C8 cycloalkyl, 3- to 8-membered heterocyclic ring, C6-C 10 Aryl or 5- to 10-membered heteroaryl groups; Where R4 is When L is C or O, n is 0, 1 or 2, x is 0, 1 or 2, and R is... 24 It is a C1-C4 alkyl group, wherein the C1-C4 alkyl group is optionally substituted with a halogen selected from F or Cl, or R 24 It is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, haloC1-C6 alkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocyclic ring, C6-C 10 Aryl or 5- to 10-membered heteroaryl, or the R 24 It is a spirocyclic or fused ring, wherein L is optionally substituted with -OH, halogen, or C1-C6 alkyl; Where R4 is When n is 0, 1, or 2, R 24 It is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, haloC1-C6 alkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocyclic ring, C6-C 10 Aryl or 5- to 10-membered heteroaryl, or the R 24 It is a spiral ring or a fused ring; Where R4 is At that time, L G is a single or double bond; where L is a single or double bond. When G is a double bond, G and L are independently selected from C or N, and R 25 and R 29 Independently selected from H, halogens, =O or -C(O), R 26 and R 27 It is independently selected from H, -C(F2)-C(F2Cl), -OC(F2Cl), -OC(HF2), or -S(O). m R 28 Where m is between 0 and 2, R 28 It is a methyl or trihalomethyl group, or R 25 Or R 27 With R 26 Linked to form a 5- or 6-membered heterocyclic ring optionally substituted with -OH, alkyl, haloalkyl, or halogen; and Where n is 0, 1, 2 or 3; This refers to a single or double bond; B, D, E, X, and Y are independently selected from C or N; R a R b R1 and R3 are independently selected from H, -OH, =O, substituted or unsubstituted alkyl groups, or linked together to form a fused cycloalkyl ring, cycloalkenyl ring, aryl ring, heterocyclic ring, or heteroaryl ring; R2 and R3 are independently selected from H, -OH, =O, substituted or unsubstituted alkyl groups, substituted or unsubstituted alkenyl groups, substituted or unsubstituted heterocyclic rings, or linked together to form an unsubstituted or substituted fused heterocyclic ring.

3. A compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof: (I) (II) in K and J are independently selected from C, N, O, or S; R, R0, and R5 are independently selected from H, halogen, -OH, =O, -C(O)-C1-C6 alkyl, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkyl-halo-halo-halo-halo-C6 hydroxyalkyl, alkyl-halo-C1-C6 alkoxy, or C3-C6 cycloalkyl; R6 and R7 are independently selected from H or halogens; R6 or R7 can optionally be connected to R5 to form C3-C8 cycloalkyl, 4- to 8-membered heterocyclic rings, or C6-C... 10 Aryl or 5- to 10-membered heteroaryl rings; and in (A) n is 0, 1, 2 or 3; This refers to a single or double bond; B, D, E, X, and Y are independently selected from C or N; R a R b R1 and R2 are independently selected from H, -OH, =O, C1-C6 alkyl; R3 are independently selected from H, -OH, =O, C1-C6 alkyl, -NR8R9, -C(O)R. 10 -S(O2)R 10 substituted or unsubstituted C2-C3 alkenyl groups or substituted or unsubstituted 5- or 6-membered heterocyclic rings, or R a It is linked with R2 to form a fused C3-C8 cycloalkyl ring, C3-C8 cycloalkenyl ring, C6-C 10 Aryl rings, 3- to 8-membered heterocyclic rings, or 5- to 10-membered heteroaryl rings; Where R a It is linked with R2 to form a fused C3-C8 cycloalkyl ring, C3-C8 cycloalkenyl ring, C6-C 10 When aryl rings, 3- to 8-membered heterocyclic rings, or 5- to 10-membered heteroaryl rings are used, the fused C3-C8 cycloalkyl rings, C3-C8 cycloalkenyl rings, and C6-C... 10 Aryl rings, 3- to 8-membered heterocyclic rings, or 5- to 10-membered heteroaryl rings are coated with -C(O)R 34 or -S(O2)R 34 Replace, where R 34 It is a C1-C6 alkyl ring, a C3-C8 cycloalkyl ring, a C4-C8 cycloalkenyl ring, or a C6-C6 cycloalkyl ring. 10 Aryl rings, 4- to 8-membered heterocyclic rings, or 5- to 10-membered heteroaryl rings; or R2 and R3 are linked together to form an unsubstituted or substituted fused 3- to 8-membered heterocyclic ring, wherein when the 3- to 8-membered heterocyclic ring is substituted, the substituent is optionally selected from -OH, =O, C1-C6 alkyl, 5- or 6-membered heterocyclic ring or -C(O)R 11 , where R 11 It is a C1-C3 alkyl group or a substituted 5- or 6-membered heterocyclic ring; R8 and R9 are independently selected from H, C1-C6 alkyl groups and -C(O)R 11 , where R 11 It is a substituted or unsubstituted 5- or 6-membered heterocyclic ring; Where R 10 Selected from C1-C6 alkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, C6-C 10 Aryl rings, 3- to 8-membered heterocyclic rings, or 5- to 10-membered heteroaryl rings, wherein R 10 Optionally substituted with -OH, C1-C6 alkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 alkoxy, C3-C8 cycloalkyl, halogen, 3- to 8-membered heterocyclic group, -S(O2)CH3 or -C(O)N(CH3)2, or R 10 With second C3-C8 cycloalkyl, C3-C8 cycloalkenyl, C6-C 10 Aryl, 3- to 8-membered heterocyclic or 5- to 10-membered heteroaryl fusion; and (B) R1 is NR 30 R 31 aryl, C3-C7 cycloalkyl ring, 5- to 10-membered heteroaryl or 4-, 5- or 6-membered heterocyclic ring; Where R1 is NR 30 R 31 At that time, R 30 and R 31 Independently selected from optionally substituted C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl or H; When R1 is an aryl group, the aryl group is reacted with one or more -O-(C1-C6)alkyl-COOH, three C1-C6 alkoxy groups, or -C(O)-R. 33 -C(O)-NH-R 33 -S(O)R 33 -S(O2)R 33 -NH-S(O2)R 33 -NH-C(O)-NH-R 33 Substitution, or fusion of the aryl group with a 5- to 10-membered heteroaryl group, a C3-C8 cycloalkyl ring, a C3-C8 cycloalkenyl ring, a 5- or 6-membered heterocyclic ring, wherein the 5- or 6-membered heterocyclic ring comprises a carbon atom and at least one oxygen and / or at least one nitrogen atom, wherein R 33 Selected from C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, haloC1-C6 alkoxy, C3-C8 cycloalkyl, 4- to 8-membered heterocyclic rings, C6-C 10 Aryl or 5- to 10-membered heteroaryl groups, and The aryl, 5- to 10-membered heteroaryl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl ring and 5- or 6-membered heterocyclic ring are optionally surrounded by one or more C1-C3 alkyl, halogen, -OH, =O, -C(O)-C1-C6 alkyl, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkoxy, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, haloC1-C6 alkoxy, C3-C8 cycloalkyl; C3-C8 cycloalkenyl, second C6-C 10 Aryl, second 5- to 10-membered heteroaryl, or 3- to 8-membered heterocyclic group substitution; When R1 is a C3-C7 cycloalkyl ring, the C3-C7 cycloalkyl ring is a fully saturated ring, wherein the C3-C7 cycloalkyl ring is optionally combined with a second C3-C8 cycloalkyl ring, a 3- to 8-membered heterocyclic group, or a C6-C8 cycloalkyl ring. 10 Aryl or 5- to 10-membered heteroaryl groups are linked to form a spirocycle, or The C3-C7 cycloalkyl ring is optionally associated with a second C3-C8 cycloalkyl ring, a 3- to 8-membered heterocyclic group, or a C6-C... 10 Aryl or 5- to 10-membered heteroaryl groups are linked to form a fused ring, unless R4 is a substituted phenyl group; When R1 is a 5- to 10-membered heteroaryl ring, the 5- to 10-membered heteroaryl ring is replaced by -OH, -C(O)-C1-C6 alkyl, or -O-(C1-C6)alkyl-COOH, or the 5- to 10-membered heteroaryl ring is combined with a second 5- to 10-membered heteroaryl ring, C6-C 10 Fusing of aryl rings, C3-C8 cycloalkyl rings, C3-C8 cycloalkenyl rings, or 4- to 8-membered heterocyclic rings; When R1 is a 4-membered heterocyclic base ring The 4-membered heterocyclic base ring comprises at least one of a carbon atom and a nitrogen or oxygen atom, or The 4-membered heterocyclic base ring is optionally connected to a second substituted or unsubstituted 4-, 5-, or 6-membered heterocyclic base ring, wherein the second 4-, 5-, or 6-membered heterocyclic base ring comprises at least one of a carbon atom and a nitrogen or oxygen atom, wherein the 4- or 7-membered heterocyclic base ring is connected to the second 4-, 5-, or 6-membered heterocyclic base ring by one carbon atom to form a spirocyclic ring or by two carbon atoms to form a fused ring; When R1 is a 5-membered or 6-membered heterocyclic base ring The 5- or 6-membered heterocyclic base ring is a fully saturated ring comprising at least one of a carbon atom and a nitrogen atom or an oxygen atom, wherein the 5- or 6-membered heterocyclic base ring is substituted with one or more C2-C6 alkenyl or C2-C6 haloalkenyl groups, or is connected to a second substituted or unsubstituted 4-, 5-, or 6-membered heterocyclic base ring to form a spirocyclic ring, or the 5- or 6-membered heterocyclic base ring is connected to a second substituted or unsubstituted 4-, 5-, or 6-membered heterocyclic base ring to form a fused ring, wherein the second 4-, 5-, or 6-membered heterocyclic base ring comprises at least one of a carbon atom and a nitrogen atom or an oxygen atom. Wherein, when the 5-membered or 6-membered heterocyclic base ring is connected to the second 5-membered heterocyclic base ring by a carbon atom to form a spirocyclic ring, and the second 5-membered heterocyclic base ring is fully saturated, one or more heteroatoms in the second 5-membered heterocyclic base ring are selected from N or S; Wherein, when the 5- or 6-membered heterocyclic base ring is connected to the second 4-, 5-, or 6-membered heterocyclic base ring through two carbon atoms to form a fused ring, the second 4-, 5-, or 6-membered heterocyclic base ring is partially or completely unsaturated; or The 5- or 6-membered heterocyclic base ring comprises a carbon atom and at least one silicon atom; or The 5-membered heterocyclic base ring is a pyrazole ring, wherein the pyrazole ring is connected to a second substituted or unsubstituted 4-, 5-, or 6-membered heterocyclic base ring to form a fused ring, wherein the second 4-, 5-, or 6-membered heterocyclic base ring is a saturated ring containing at least one of a carbon atom and a nitrogen atom or an oxygen atom, or The 6-membered heterocyclic base ring is a pyridyl ring, wherein the pyridyl ring is connected to a second substituted or unsubstituted 4-, 5-, or 6-membered heterocyclic base ring to form a fused ring; and Wherein R4 is H, -OH, =O, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl; substituted or unsubstituted aryl ring, substituted or unsubstituted heterocyclic ring, substituted or unsubstituted heteroaryl ring. or (C) R4 is selected from , , and , where L and G are independently selected from C, N or O, n is 0, 1 or 2, and x is 1 or 2; Where R4 is When L is C or O, n is 0 or 1, and R 23 It is a C1-C4 alkyl group, wherein the C1-C4 alkyl group is optionally substituted with a halogen selected from F or Cl, or R 23 It is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkoxy, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, haloC1-C6 alkoxy, C3-C8 cycloalkyl, bridged C3-C8 cycloalkyl, 3- to 8-membered heterocyclic ring, C6-C 10 Aryl or 5- to 10-membered heteroaryl groups; Where R4 is When L is C or O, n is 0, 1 or 2, x is 0, 1 or 2, and R is... 24 It is a C1-C4 alkyl group, wherein the C1-C4 alkyl group is optionally substituted with a halogen selected from F or Cl, or R 24 It is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, haloC1-C6 alkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocyclic ring, C6-C 10 Aryl or 5- to 10-membered heteroaryl, or the R 24 It is a spirocyclic or fused ring, wherein L is optionally substituted with -OH, halogen, or C1-C6 alkyl; Where R4 is When n is 0, 1, or 2, R 24 It is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, haloC1-C6 alkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocyclic ring, C6-C 10 Aryl or 5- to 10-membered heteroaryl, or the R 24 It is a spiral ring or a fused ring; Where R4 is At that time, L G is a single or double bond; where L is a single or double bond. When G is a double bond, G and L are independently selected from C or N, and R 25 and R 29 Independently selected from H, halogens, =O or -C(O), R 26 and R 27 It is independently selected from H, -C(F2)-C(F2Cl), -OC(F2Cl), -OC(HF2), or -S(O). m R 28 Where m is between 0 and 2, R 28 It is a methyl or trihalomethyl group, or R 25 Or R 27 With R 26 Linked to form a 5- or 6-membered heterocyclic ring optionally substituted with -OH, alkyl, haloalkyl, or halogen; and Wherein R1 is H, -OH, =O, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl; substituted or unsubstituted aryl ring, substituted or unsubstituted heterocyclic ring, substituted or unsubstituted heteroaryl ring.

4. A compound of formula (I) or formula (II), or a pharmaceutically acceptable salt thereof: (I) (II) in K and J are independently selected from C, N, O, or S; R, R0, and R5 are independently selected from H, halogen, -OH, =O, -C(O)-C1-C6 alkyl, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkyl-halo-halo-halo-halo-C6 hydroxyalkyl, alkyl-halo-C1-C6 alkoxy, or C3-C6 cycloalkyl; R6 and R7 are independently selected from H or halogens; R6 or R7 can optionally be connected to R5 to form C3-C8 cycloalkyl, 4- to 8-membered heterocyclic rings, or C6-C... 10 Aryl or 5- to 10-membered heteroaryl rings; and in (A) R4 is selected from , , and Where L and G are independently selected from C, N or O, n is 0, 1 or 2, and x is 0, 1 or 2; Where R 23 and R 24 Independently selected from -OH, -COOH, -NH2, -CN, oxo, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 hydroxyalkyl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, bridged or unbridged C3-C8 cycloalkyl, 3- to 8-membered heterocyclic, 3- to 8-membered heterocyclic ring, C6-C 10 Aryl or 5- to 10-membered heteroaryl groups; Where R4 is At that time, L G is a single or double bond; R 25 R 29 and R 35 Independently selected from H, halogen, -OH, =O, -C(O); C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, alkoxy, haloalkoxy, or C3-C8 cycloalkyl; R 26 and R 27 Independently selected from H, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 haloalkenyl, C1-C6 hydroxyalkyl, alkoxy, haloalkoxy, or C3-C8 cycloalkyl, -OR 28 or -S(O) m R 28 Where m is between 0 and 2, R 28 It is a C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, alkoxy, haloalkoxy, or C3-C8 cycloalkyl; wherein R 25 Or R 27 With R 26 Connected to form C3-C8 cycloalkyl rings, 3- to 8-membered heterocyclic rings, or 5- to 10-membered heteroaryl rings; and (B) R1 is NR 30 R 31 aryl, C3-C7 cycloalkyl ring, 5- to 10-membered heteroaryl or 4-, 5- or 6-membered heterocyclic ring; Where R1 is NR 30 R 31 At that time, R 30 and R 31 Independently selected from optionally substituted C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl or H; When R1 is an aryl group, the aryl group is reacted with one or more -O-(C1-C6)alkyl-COOH, three C1-C6 alkoxy groups, or -C(O)-R. 33 -C(O)-NH-R 33 -S(O)R 33 -S(O2)R 33 -NH-S(O2)R 33 -NH-C(O)-NH-R 33 Substitution, or fusion of the aryl group with a 5- to 10-membered heteroaryl group, a C3-C8 cycloalkyl ring, a C3-C8 cycloalkenyl ring, a 5- or 6-membered heterocyclic ring, wherein the 5- or 6-membered heterocyclic ring comprises a carbon atom and at least one oxygen and / or at least one nitrogen atom, wherein R 33 Selected from C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, haloC1-C6 alkoxy, C3-C8 cycloalkyl, 4- to 8-membered heterocyclic rings, C6-C 10 Aryl or 5- to 10-membered heteroaryl groups, and The aryl, 5- to 10-membered heteroaryl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl ring and 5- or 6-membered heterocyclic ring are optionally surrounded by one or more C1-C3 alkyl, halogen, -OH, =O, -C(O)-C1-C6 alkyl, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkoxy, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, haloC1-C6 alkoxy, C3-C8 cycloalkyl; C3-C8 cycloalkenyl, second C6-C 10 Aryl, second 5- to 10-membered heteroaryl, or 3- to 8-membered heterocyclic group substitution; When R1 is a C3-C7 cycloalkyl ring, the C3-C7 cycloalkyl ring is a fully saturated ring, wherein the C3-C7 cycloalkyl ring is optionally combined with a second C3-C8 cycloalkyl ring, a 3- to 8-membered heterocyclic group, or a C6-C8 cycloalkyl ring. 10 Aryl or 5- to 10-membered heteroaryl groups are linked to form a spirocycle, or The C3-C7 cycloalkyl ring is optionally associated with a second C3-C8 cycloalkyl ring, a 3- to 8-membered heterocyclic group, or a C6-C... 10 Aryl or 5- to 10-membered heteroaryl groups are linked to form a fused ring, unless R4 is a substituted phenyl group; When R1 is a 5- to 10-membered heteroaryl ring, the 5- to 10-membered heteroaryl ring is replaced by -OH, -C(O)-C1-C6 alkyl, or -O-(C1-C6)alkyl-COOH, or the 5- to 10-membered heteroaryl ring is combined with a second 5- to 10-membered heteroaryl ring, C6-C 10 Fusing of aryl rings, C3-C8 cycloalkyl rings, C3-C8 cycloalkenyl rings, or 4- to 8-membered heterocyclic rings; When R1 is a 4-membered heterocyclic base ring The 4-membered heterocyclic base ring comprises at least one of a carbon atom and a nitrogen or oxygen atom, or The 4-membered heterocyclic base ring is optionally connected to a second substituted or unsubstituted 4-, 5-, or 6-membered heterocyclic base ring, wherein the second 4-, 5-, or 6-membered heterocyclic base ring comprises at least one of a carbon atom and a nitrogen or oxygen atom, wherein the 4- or 7-membered heterocyclic base ring is connected to the second 4-, 5-, or 6-membered heterocyclic base ring by one carbon atom to form a spirocyclic ring or by two carbon atoms to form a fused ring; When R1 is a 5-membered or 6-membered heterocyclic base ring The 5- or 6-membered heterocyclic base ring is a fully saturated ring comprising at least one of a carbon atom and a nitrogen atom or an oxygen atom, wherein the 5- or 6-membered heterocyclic base ring is substituted with one or more C2-C6 alkenyl or C2-C6 haloalkenyl groups, or is connected to a second substituted or unsubstituted 4-, 5-, or 6-membered heterocyclic base ring to form a spirocyclic ring, or the 5- or 6-membered heterocyclic base ring is connected to a second substituted or unsubstituted 4-, 5-, or 6-membered heterocyclic base ring to form a fused ring, wherein the second 4-, 5-, or 6-membered heterocyclic base ring comprises at least one of a carbon atom and a nitrogen atom or an oxygen atom. Wherein, when the 5-membered or 6-membered heterocyclic base ring is connected to the second 5-membered heterocyclic base ring by a carbon atom to form a spirocyclic ring, and the second 5-membered heterocyclic base ring is fully saturated, one or more heteroatoms in the second 5-membered heterocyclic base ring are selected from N or S; Wherein, when the 5- or 6-membered heterocyclic base ring is connected to the second 4-, 5-, or 6-membered heterocyclic base ring through two carbon atoms to form a fused ring, the second 4-, 5-, or 6-membered heterocyclic base ring is partially or completely unsaturated; or The 5- or 6-membered heterocyclic base ring comprises a carbon atom and at least one silicon atom; or The 5-membered heterocyclic base ring is a pyrazole ring, wherein the pyrazole ring is connected to a second substituted or unsubstituted 4-, 5-, or 6-membered heterocyclic base ring to form a fused ring, wherein the second 4-, 5-, or 6-membered heterocyclic base ring is a saturated ring containing at least one of a carbon atom and a nitrogen atom or an oxygen atom, or The 6-membered heterocyclic base ring is a pyridyl ring, wherein the pyridyl ring is connected to a second substituted or unsubstituted 4-, 5-, or 6-membered heterocyclic base ring to form a fused ring; and Where n is 0, 1, 2 or 3; This refers to a single or double bond; B, D, E, X, and Y are independently selected from C or N; R a R b R1 and R3 are independently selected from H, -OH, =O, substituted or unsubstituted alkyl groups, or linked together to form a fused cycloalkyl ring, cycloalkenyl ring, aryl ring, heterocyclic ring, or heteroaryl ring; R2 and R3 are independently selected from H, -OH, =O, substituted or unsubstituted alkyl groups, substituted or unsubstituted alkenyl groups, substituted or unsubstituted heterocyclic rings, or linked together to form an unsubstituted or substituted fused heterocyclic ring. or (C) n is 0, 1, 2 or 3; This refers to a single or double bond; B, D, E, X, and Y are independently selected from C or N; R a R b R1 and R2 are independently selected from H, -OH, =O, C1-C6 alkyl; R3 are independently selected from H, -OH, =O, C1-C6 alkyl, -NR8R9, -C(O)R. 10 -S(O2)R 10 substituted or unsubstituted C2-C3 alkenyl groups or substituted or unsubstituted 5- or 6-membered heterocyclic rings, or R a It is linked with R2 to form a fused C3-C8 cycloalkyl ring, C3-C8 cycloalkenyl ring, C6-C 10 An aryl ring, a 3- to 8-membered heterocyclic ring, or a 5- to 10-membered heteroaryl ring; or R2 and R3 linked together to form an unsubstituted or substituted fused 4-, 5-, or 6-membered heterocyclic ring, wherein when the 4-, 5-, or 6-membered heterocyclic ring is substituted, the substituent is optionally selected from -OH, =O, C1-C6 alkyl, 5- or 6-membered heterocyclic ring, or -C(O)R. 11 , where R 11 It is a C1-C3 alkyl group or a substituted 5- or 6-membered heterocyclic ring; Where R a It is linked with R2 to form a fused C3-C8 cycloalkyl ring, C3-C8 cycloalkenyl ring, C6-C 10 When aryl rings, 3- to 8-membered heterocyclic rings, or 5- to 10-membered heteroaryl rings are used, the fused C3-C8 cycloalkyl rings, C3-C8 cycloalkenyl rings, and C6-C... 10 Aryl rings, 3- to 8-membered heterocyclic rings, or 5- to 10-membered heteroaryl rings are coated with -C(O)R 34 or -S(O2)R 34 Replace, where R 34 It is a C1-C6 alkyl ring, a C3-C8 cycloalkyl ring, a C4-C8 cycloalkenyl ring, or a C6-C6 cycloalkyl ring. 10 Aryl rings, 4- to 8-membered heterocyclic rings, or 5- to 10-membered heteroaryl rings; When n is 0, X is N, Y is C, R2 is NR8R9 and R3 is H; When n is 1, X and Y are C, R2 is NR8R9 and R3 is H, or R2 and R3 are connected together to form a substituted fused 4-membered heterocyclic base ring, wherein the substituted 4-membered heterocyclic base ring is -C(O)R 11 Replace, and where R 11 It is a substituted 5- or 6-membered heterocyclic base ring; When R2 is NR8R9, R8 and R9 are independently selected from H, C1-C4 alkyl groups, and -C(O)R. 11 , where R 11 It is a substituted or unsubstituted 5- or 6-membered heterocyclic ring; When n is 2, X is C, Y is N, and R2 and R3 are connected together to form an unsubstituted or substituted fused 4- or 5-membered heterocyclic base ring, wherein when the 5-membered heterocyclic base ring is substituted, the substituent is selected from a 5- or 6-membered heterocyclic base ring or -C(O)R 11 , where R 11 It is a C1-C3 alkyl or a substituted 5- or 6-membered heterocyclic ring, or X is C, Y is N, R2 is H, and R3 is -C(O)R. 10 or -S(O2)R 10 And R 10 It is a C1-C6 hydroxyalkyl, C2-C6 alkenyl, or C3-C7 cycloalkyl ring, wherein R 10 Optionally substituted with -OH, C1-C6 alkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C3 alkoxy, optionally substituted C3-C5 cycloalkyl ring, halogen, optionally substituted 3- to 8-membered heterocyclic group, -S(O2)CH3 or -C(O)N(CH3)2, or X is C, Y is N, R2 is H, and R3 is -C(O)R. 10 or -S(O2)R 10 And R 10 for ， Where W, U, V, and Z are independently selected from H, C, N, S, or O, and where This refers to a single bond or a double bond; Where U is N + At that time, R 15 For O - R 16 and R 17 For H, and U V is a double bond; When U is C, R 15 For -NR 19 R 20 U V is a double bond, and R 16 R 17 and R 18 Independently selected from H, -CH3, -C(O)R 21 -S(O2)R 21 and -S(O)R 21 R 22 R 19 and R 20 Independently selected from -C(O)R 21 -S(O2)R 21 and -S(O)R 21 R 22 , where R 21 and R 22 Independently selected from C1-C3 alkyl, C3-C5 cycloalkyl ring, or 5- or 6-membered heterocyclic ring, or R 21 and R 22 They are linked together to form substituted or unsubstituted C3-C5 cycloalkyl rings; and Wherein R1 is H, -OH, =O, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl; substituted or unsubstituted aryl ring, substituted or unsubstituted heterocyclic ring, substituted or unsubstituted heteroaryl ring.

5. The compound according to claims 1 to 4, wherein R1 is an aryl group fused with a 5- or 6-membered heterocyclic ring, wherein the 5- or 6-membered heterocyclic ring comprises a carbon atom and at least one oxygen atom, and wherein the 5- or 6-membered heterocyclic ring is optionally substituted with a C1-C3 alkyl group.

6. The compound according to claims 1 to 4, wherein n is 2; B, D, E and X are C; Y is N; R a and R b R1 is H; R2 is H; and R3 is -C(O)R 10 , where R 10 It consists of 5- to 10-membered heteroaryl rings, and R... 10 Optionally substituted with -OH or C1-C6 alkyl groups.

7. The compound according to claims 1 to 4, wherein R4 is Where R4 is At that time, L G is a double bond; where L is a double bond. When G is a double bond, R 25 and R 33 For H and R 29 It is a halogen; and R 26 For H and R 27 It is a C1-C6 haloalkyl group.

8. The compound according to claims 1 to 4, wherein K and J are N; R0 is H, R is =O, and R5 is C1-C6 alkyl; and R6 and R7 are H.

9. The compound according to claim 5, wherein R1 is an aryl group fused with a 5- or 6-membered heterocyclic ring, wherein the 5- or 6-membered heterocyclic ring comprises a carbon atom and at least one oxygen atom, and wherein the 5- or 6-membered heterocyclic ring is optionally substituted with a C1-C3 alkyl group; and Where n is 2; B, D, E, and X are C; Y is N; R a and R b R1 is H; R2 is H; and R3 is -C(O)R 10 , where R 10 It is a 5- to 10-membered heteroaryl ring, wherein R10 is optionally substituted with -OH or C1-C6 alkyl groups.

10. The compound according to claim 5, wherein R1 is an aryl group fused with a 5- or 6-membered heterocyclic ring, wherein the 5- or 6-membered heterocyclic ring comprises a carbon atom and at least one oxygen atom, and wherein the 5- or 6-membered heterocyclic ring is optionally substituted with a C1-C3 alkyl group; and Where R4 is Where R4 is At that time, L G is a double bond; where L is a double bond. When G is a double bond, R 25 and R 33 For H and R 29 It is a halogen; and R 26 For H and R 27 It is a C1-C6 haloalkyl group.

11. The compound according to claim 5, wherein R1 is an aryl group fused with a 5- or 6-membered heterocyclic ring, wherein the 5- or 6-membered heterocyclic ring comprises a carbon atom and at least one oxygen atom, and wherein the 5- or 6-membered heterocyclic ring is optionally substituted with a C1-C3 alkyl group; and Where K and J are N; R0 is H, R is =O, and R5 is a C1-C6 alkyl group; and R6 and R7 are H.

12. The compound according to claim 6, wherein n is 2; B, D, E and X are C; Y is N; R a and R b R1 is H; R2 is H; and R3 is -C(O)R 10 , where R 10 It is a 5- to 10-membered heteroaryl ring, wherein R10 is optionally substituted with -OH or C1-C6 alkyl groups; and Where R4 is Where R4 is At that time, L G is a double bond; where L is a double bond. When G is a double bond, R 25 and R 33 For H and R 29 It is a halogen; R26 is H and R27 is a C1-C6 haloalkyl group.

13. The compound according to claim 6, wherein n is 2; B, D, E and X are C; Y is N; R a and R b R1 is H; R2 is H; and R3 is -C(O)R 10 , where R 10 It is a 5- to 10-membered heteroaryl ring, wherein R10 is optionally substituted with -OH or C1-C6 alkyl groups; and Where K and J are N; R0 is H, R is =O, and R5 is a C1-C6 alkyl group; and R6 and R7 are H.

14. The compound according to claim 7, wherein R4 is Where R4 is At that time, L G is a double bond; where L is a double bond. When G is a double bond, R 25 and R 33 For H and R 29 It is a halogen; R26 is H and R27 is a C1-C6 haloalkyl group; and Where K and J are N; R0 is H, R is =O, and R5 is a C1-C6 alkyl group; and R6 and R7 are H.

15. The compound according to claim 5, wherein R1 is an aryl group fused with a 5- or 6-membered heterocyclic ring, wherein the 5- or 6-membered heterocyclic ring comprises a carbon atom and at least one oxygen atom, wherein the 5- or 6-membered heterocyclic ring is optionally substituted with a C1-C3 alkyl group. Where n is 2; B, D, E, and X are C; Y is N; R a and R b R1 is H; R2 is H; and R3 is -C(O)R 10 , where R 10 It is a 5- to 10-membered heteroaryl ring, wherein R10 is optionally substituted with -OH or C1-C6 alkyl groups; and Where R4 is Where R4 is At that time, L G is a double bond; where L is a double bond. When G is a double bond, R 25 and R 33 For H and R 29 It is a halogen; R26 is H and R27 is a C1-C6 haloalkyl group.

16. The compound according to claim 5, wherein R1 is an aryl group fused with a 5- or 6-membered heterocyclic ring, wherein the 5- or 6-membered heterocyclic ring comprises a carbon atom and at least one oxygen atom, wherein the 5- or 6-membered heterocyclic ring is optionally substituted with a C1-C3 alkyl group. Where n is 2; B, D, E, and X are C; Y is N; R a and R b R1 is H; R2 is H; and R3 is -C(O)R 10 , where R 10 It is a 5- to 10-membered heteroaryl ring, wherein R10 is optionally substituted with -OH or C1-C6 alkyl groups; and Where K and J are N; R0 is H, R is =O, and R5 is a C1-C6 alkyl group; and R6 and R7 are H.

17. The compound according to claim 5, wherein R1 is an aryl group fused with a 5- or 6-membered heterocyclic ring, wherein the 5- or 6-membered heterocyclic ring comprises a carbon atom and at least one oxygen atom, wherein the 5- or 6-membered heterocyclic ring is optionally substituted with a C1-C3 alkyl group. Where R4 is Where R4 is At that time, L G is a double bond; where L is a double bond. When G is a double bond, R 25 and R 33 For H and R 29 It is a halogen; and R 26 For H and R 27 It is a C1-C6 haloalkyl group. Where K and J are N; R0 is H, R is =O, and R5 is a C1-C6 alkyl group; and R6 and R7 are H.

18. The compound according to claim 6, wherein n is 2; B, D, E and X are C; Y is N; R a and R b R1 is H; R2 is H; and R3 is -C(O)R 10 , where R 10 It is a 5- to 10-membered heteroaryl ring, wherein R10 is optionally substituted with -OH or C1-C6 alkyl groups; Where R4 is Where R4 is At that time, L G is a double bond; where L is a double bond. When G is a double bond, R 25 and R 33 For H and R 29 It is a halogen; and R 26 For H and R 27 It is a C1-C6 haloalkyl group; and Where K and J are N; R0 is H, R is =O, and R5 is a C1-C6 alkyl group; and R6 and R7 are H.

19. The compound according to claim 5, wherein R1 is an aryl group fused with a 5- or 6-membered heterocyclic ring, wherein the 5- or 6-membered heterocyclic ring comprises a carbon atom and at least one oxygen atom, and wherein the 5- or 6-membered heterocyclic ring is optionally substituted with a C1-C3 alkyl group. Where n is 2; B, D, E, and X are C; Y is N; R a and R b R1 is H; R2 is H; and R3 is -C(O)R 10 , where R 10 It is a 5- to 10-membered heteroaryl ring, wherein R10 is optionally substituted with -OH or C1-C6 alkyl groups; Where R4 is Where R4 is At that time, L G is a double bond; where L is a double bond. When G is a double bond, R 25 and R 33 For H and R 29 It is a halogen; and R 26 For H and R 27 It is a C1-C6 haloalkyl group; and Where K and J are N; R0 is H, R is =O, and R5 is a C1-C6 alkyl group; and R6 and R7 are H.

20. The compound of claim 5, wherein R1 is an aryl group fused with a 5- or 6-membered heterocyclic ring, wherein the 5- or 6-membered heterocyclic ring comprises a carbon atom and at least one oxygen atom.

21. The compound of claim 5, wherein R1 is an aryl group fused with a 5- or 6-membered heterocyclic ring, wherein the 5- or 6-membered heterocyclic ring comprises a carbon atom and at least one oxygen atom, and wherein the 5- or 6-membered heterocyclic ring is substituted with a C1-C3 alkyl group.

22. The compound according to any one of the preceding claims, wherein when R1 is an aryl group fused with a 5- or 6-membered heterocyclic base ring, the 5- or 6-membered heterocyclic base ring is a 5-membered heterocyclic base ring.

23. The compound according to any one of the preceding claims, wherein when R 10 When the heteroaryl ring is 5- to 10-membered, the 5- to 10-membered heteroaryl ring is a 6-membered heteroaryl ring.

24. The compound according to any one of the preceding claims, wherein when R 10 When optionally substituted with a C1-C6 alkyl group, the C1-C6 alkyl group is a C1 alkyl group.

25. The compound according to any one of the preceding claims, wherein when R 29 When the halogen is halogen, the halogen is Cl.

26. The compound according to any one of the preceding claims, wherein when R 27 When it is a C1-C6 haloalkyl group, the C1-C6 haloalkyl group is trifluoromethyl.

27. The compound according to any one of the preceding claims, wherein when R5 is a C1-C6 alkyl group, the C1-C6 alkyl group is a C2 alkyl group.

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