Calcitonin and / or amylin receptor agonist and use

Abstract

The present invention provides a compound that can be used as a modulator of calcitonin and / or amylin receptor activity, and methods for preparing and using a medicament comprising the compound for treating calcitonin receptor- and amylin receptor-mediated diseases (such as bone and metabolic diseases). Specifically disclosed are a compound represented by formula (I) or a pharmaceutically acceptable salt, stereoisomer, and mixture of stereoisomers thereof.

Description

A calcitonin and / or amyloid receptor agonist and its application Technical Field

[0001] This invention belongs to the field of biomedicine, specifically relating to a compound that can be used as a modulator of calcitonin and / or amyloid receptor activity, and the preparation and use of the compound in the treatment of calcitonin and amyloid receptor-mediated diseases (such as bone and metabolic diseases). Background Technology

[0002] Calcitonin and amylin play important physiological roles in the human body. Calcitonin is mainly secreted by parafollicular cells of the thyroid gland and plays a crucial role in maintaining bone metabolic homeostasis; while amylin is co-secreted with insulin and participates in regulating postprandial blood glucose levels. Early calcitonin receptor modulators were mainly peptide compounds based on calcitonin itself or its analogues. These peptide compounds exert pharmacological effects such as inhibiting bone resorption and increasing bone mineral density by binding to calcitonin receptors. However, peptide compounds have disadvantages such as poor stability, poor oral absorption, and the need for injection, leading to low patient compliance and high production costs. To overcome the disadvantages of peptide modulators, scientists have focused on developing non-peptide calcitonin receptor modulators in recent years. These compounds typically have lower molecular weights, good oral absorption, and stability. The amylin receptor (also known as the amyloid receptor) and the calcitonin receptor share some structural similarities, and their signal transduction pathways overlap.

[0003] Due to the physiological effects of hormones such as calcitonin and amyloid, modulators of the activity of calcitonin and amyloid receptors have potential application value in the treatment of metabolic diseases such as osteoporosis and diabetes.

[0004] In addition, in literature such as US7396936B, WO2025015269, and WO2025015268, compounds involving calcitonin and / or amyloid receptor activity modulators have been studied to varying degrees.

[0005] In summary, compounds containing calcitonin and / or amyloid receptor activity modulators show broad application prospects in the treatment of metabolic diseases such as osteoporosis and diabetes. With the increasing aging population and rising incidence of metabolic diseases, the clinical demand for calcitonin and amyloid receptor modulators is constantly growing. The development of novel modulators can not only meet the current treatment needs of patients but also provide solutions for potential new clinical challenges in the future. Summary of the Invention

[0006] This invention provides a compound of formula (I) or a pharmaceutically acceptable salt, stereoisomer, or mixture of stereoisomers thereof, having the following structure:

[0007] in:

[0008] The structural unit represents a nitrogen-containing heterocycle, selected from...

[0009] or The structural unit represents a nitrogen-containing heterocycle, selected from...

[0010] Cy1 is selected from: C3-C12 cyclic hydrocarbon groups, aryl groups, heterocyclic groups comprising one, two, or three 5- or 6-membered rings and 1-3 heteroatoms selected from N, O, and S, or heteroaryl groups comprising one, two, or three 5- or 6-membered rings and 1-3 heteroatoms selected from N, O, and S; said cyclic hydrocarbon group, aryl group, heterocyclic group, or heteroaryl group is a spirocyclic, bridged ring, fused ring, or monocyclic ring; said cyclic hydrocarbon group, heterocyclic group, aryl group, or heteroaryl group is optionally substituted by one or more substituents independently selected from: deuterium, OH, carboxyl, halogen, NH2, CN, NO2. Oxylated, thiolated, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cyclic hydrocarbon, 3-8 membered heterocyclic, aryl or heteroaryl, wherein the C3-C8 cyclic hydrocarbon, 3-8 membered heterocyclic, aryl or heteroaryl is optionally substituted by one or more substituents independently selected from: deuterium, OH, carboxyl, halogen, NH2, CN, NO2, C1-C8 alkyl, C3-C8 cyclic hydrocarbon, C1-C6 haloalkyl, C1-C6 hydroxylated alkyl, C1-C8 alkoxy or The cyclic hydrocarbon group, aryl group, heterocyclic group, or heteroaryl group is a spirocyclic, bridged ring, fused ring, or monocyclic ring;

[0011] A is selected from: C3-C12 cyclic hydrocarbon groups, aryl groups, heterocyclic groups comprising one, two, or three 5- or 6-membered rings and 1-3 heteroatoms selected from N, O, and S, or heteroaryl groups comprising one, two, or three 5- or 6-membered rings and 1-3 heteroatoms selected from N, O, and S; wherein the cyclic hydrocarbon group, aryl group, heterocyclic group, or heteroaryl group is a spirocyclic, bridged ring, fused ring, or monocyclic ring; wherein the cyclic hydrocarbon group, heterocyclic group, aryl group, or heteroaryl group is optionally composed of one or more independently selected from R 1A Substituents of the substituents;

[0012] R 1ASelected from: hydrogen, deuterium, OH, carboxyl, halogen, NH2, CN, NO2, oxo, thio, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C2-C8 alkenyl, haloC2-C8 alkenyl, C2-C8 alkynyl, haloC2-C8 alkynyl, C3-C8 cyclic hydrocarbon, 3-8 membered heterocyclic group, aryl or heteroaryl;

[0013] Or, R 1A The connection between A and L2 causes A and L2 to form a heterocyclic group together; or R 1A The connection between R4 and A, L2, and R4 forms a heterocyclic group; in this case, R 1A The structural part is independently selected from: C1-C8 alkylene, C1-C8 haloalkylene, C1-C8 alkoxide, C1-C8 haloalkoxide, C2-C8 alkenyl, haloC2-C8 alkenyl, C2-C8 alkyne, haloC2-C8 alkyne, -NH-alkylene-, -NHC(O)-, -C(O)NH-, -alkylene-NHC(O)-, -alkylene-C(O)NH-, -NHC(O)-alkylene-, -C(O)NH-alkylene-, -C(O)-;

[0014] R1 is selected from: None C3-C12 alkyl, C3-C12 cycloalkyl, The alkyl, cycloalkyl, aryl, heterocyclic, or heteroaryl group comprises one, two, or three 5- or 6-membered rings and one to four heteroatoms selected from N, O, and S, wherein the alkyl, cycloalkyl, aryl, heterocyclic, or heteroaryl group is optionally substituted by one or more substituents independently selected from: deuterium, halogen, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cycloalkyl, OH, NH2, oxo, thio, -NH-(C1-C6 alkyl), -N(C1-C6 alkyl)2, CN, NO2, carboxyl, 3-8 membered heterocyclic groups, aryl groups, or heteroaryl groups;

[0015] X is selected from: Where W is selected from O, CH2, CF2, CHF, S, SO, SO2 or SO(NH);

[0016] R2 is selected from: none, NH2, C1-C10 alkyl, -(CH2). 0-6 -C3-C10 cyclic hydrocarbon groups, -(CH2) 0-6-3-10 membered epoxy group, wherein the alkyl, cycloalkyl, and epoxy group are optionally substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocyclic, aryl or heteroaryl;

[0017] R3 and R4 are each independently selected from: C1-C10 alkyl, C3-C10 cycloalkyl, aryl, heterocyclic groups comprising one, two, or three 3-, 4-, 5-, 6-, or 7-membered rings and one to three heteroatoms selected from N, O, and S, or heteroaryl groups comprising one, two, or three 3-, 4-, 5-, 6-, or 7-membered rings and one to three heteroatoms selected from N, O, and S, wherein the cycloalkyl, aryl, heterocyclic, or heteroaryl group is a spirocyclic, bridged ring, fused ring, or monocyclic ring, and the alkyl, cycloalkyl, aryl, heterocyclic, or heteroaryl group is optionally composed of one or more independent The substituents are selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cyclic hydrocarbon, -O-C3-C8 cyclic hydrocarbon, 3-8 membered heterocyclic group, aryl, heteroaryl, deuterated C1-C8 alkyl, deuterated C1-C8 haloalkyl, deuterated C1-C8 alkoxy, deuterated C1-C8 haloalkoxy, deuterated C3-C8 cyclic hydrocarbon, deuterated -O-C3-C8 cyclic hydrocarbon;

[0018] L1 and L2 are each independently selected from: none, C1-C6 alkylene, halo-C1-C6 alkylene, C2-C6 alkenyl, halo-C2-C6 alkenyl, C2-C6 alkyne, halo-C2-C6 alkyne, -O-alkylene-, -NH-alkylene-, -NHC(O)-, -C(O)NH-, -alkylene-NHC(O)-, -alkylene-C(O)NH-, -NHC(O)-alkylene-, -C(O)NH-alkylene-, -C(O)-, -NH-aryl, -NH-, C3-C10 cyclic hydrocarbon, aryl, containing one or two or three 3-membered, 4-membered, 5-membered or 6-membered rings and 1-3 selected from Heterocyclic groups containing N, O, and S heteroatoms, or heteroaryl groups comprising one or two or three 3-, 4-, 5-, or 6-membered rings and one to three heteroatoms selected from N, O, and S, wherein the alkylene, cycloalkyl, aryl, heterocyclic, or heteroaryl group is optionally substituted by one or more substituents independently selected from: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cycloalkyl, 3-8-membered heterocyclic, aryl, or heteroaryl group, wherein the cycloalkyl, aryl, heterocyclic, or heteroaryl group is a spirocyclic, bridged ring, fused ring, or monocyclic.

[0019] R 1e R 1h and R 1g Independently selected from: hydrogen, OH, carboxyl, NH2, C1-C10 alkyl, C1-C10 haloalkyl, C1-C10 alkoxy, C1-C10 haloalkoxy, C1-C10 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, -O-C3-C10 cycloalkyl or aryl;

[0020] R 1a and R 1b Independently selected from: hydrogen, C3-C10 cyclic hydrocarbon group, C1-C10 alkyl group, Or R1a and R 1b Together with the nitrogen atom to which they are attached, they form a C3-C10 heterocyclic group, wherein the heterocyclic group, cycloalkyl group and alkyl group are optionally substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocyclic group, aryl or heteroaryl;

[0021] R 1c and R 1d Independently selected from: hydrogen, C3-C10 cyclic hydrocarbon group, C1-C10 alkyl group, Or R1c and R 1d Together with the carbon atoms to which they are attached, they form a C3-C10 cyclic hydrocarbon group, wherein the cyclic hydrocarbon group and the alkyl group are optionally substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cyclic hydrocarbon group, 3-8 membered heterocyclic group, aryl or heteroaryl;

[0022] R6 is selected from: hydrogen, halogen, C1-C10 alkyl, -(CH2). 0-6 -C3-C10 cyclic hydrocarbon groups, -(CH2) 0-6 -3-10 membered epoxy group, wherein the alkyl, cycloalkyl, and epoxy group are optionally substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocyclic, aryl or heteroaryl;

[0023] R5 is selected from:

[0024] 1) Hydrogen, C1-C10 alkyl group, -(CH2) 0-6 -C3-C10 cyclic hydrocarbon groups, -(CH2) 0-6 -C3-C10 epoxy group, aryl group, heterocyclic group comprising one, two or three 5-membered or 6-membered rings and 1-4 heteroatoms selected from N, O and S, or heteroaryl group comprising one, two or three 5-membered or 6-membered rings and 1-4 heteroatoms selected from N, O and S, wherein the alkyl, cycloalkyl, epoxy, aryl, heterocyclic and heteroaryl groups are optionally substituted by one or more substituents independently selected from: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cycloalkyl, 3-8-membered heterocyclic, aryl or heteroaryl;

[0025] 2) R5 and L1 and Atoms bonded together on a structural unit form a structure optionally composed of one or more independently selected atoms from R. 1f The substituents of the heterocycles;

[0026] 3) R5 and R2 and Atoms bonded together on a structural unit form a structure optionally composed of one or more independently selected atoms from R. 1f The substituents of the heterocycles;

[0027] R 1fIndependently selected from: hydrogen, deuterium, halogen, OH, carboxyl, NH2, CN, NO2, C1-C10 alkyl, -(CH2) 0-6 -C3-C10 cyclic hydrocarbon groups, -(CH2) 0-6 -3-10 membered epoxy group, aryl group, heterocyclic group comprising one, two or three 5- or 6-membered rings and 1-4 heteroatoms selected from N, O and S, or heteroaryl group comprising one, two or three 5- or 6-membered rings and 1-4 heteroatoms selected from N, O and S, wherein the alkyl, cycloalkyl, epoxy, aryl, heterocyclic and heteroaryl groups are optionally substituted by one or more substituents independently selected from: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocyclic group, aryl or heteroaryl;

[0028] Among them, X1, X2 and X3 contain at least one heteroatom selected from N, O and S;

[0029] Or when Structural units are selected from When, X1 is selected X2 and X3 are selected from CH or N, and X2 and X3 together with the atoms attached to them form a C3-C15 cyclic hydrocarbon group or a C3-C15 heterocyclic group, which is optionally substituted by one or more substituents independently selected from the following: C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, OH or halogen, wherein the cyclic hydrocarbon group or heterocyclic group is a spirocyclic, bridged ring, fused ring or monocyclic;

[0030] Among them, when Structural units are selected from When X1 is independently selected from: -CR7-, -N-; X2 is independently selected from: -O-, -S-, -S(O)2-, -NR8-, -C(R8)2-, -NR8-C(R8)2-; X3 is independently selected from: -N-, -CR9-;

[0031] when Structural units are selected from When X1 is independently selected from: -CR7-, -N-; X2 is independently selected from: -N-, -CR8-, -CR8-NR8-, -NC(R8)2-; X3 is independently selected from: -O-, -S-, -S(O)2- 、 -NR9-, -C(R9)2-, -NR9-C(R9)2-;

[0032] when Structural units are selected from When X1, X2, and X3 are independently selected from: -O-, -S-, -S(O)2-, -C(R7)2-, -C(R7)2-C(R7)2-, -NR8-, -CO-;

[0033] R7, R8, and R9 are each independently selected from: H, C1-C10 alkane groups, -(CH2) 0-6 -C3-C10 cyclic hydrocarbon groups, -(CH2) 0-6 -3-10-membered epoxy group, aryl group, heterocyclic group comprising one, two or three 5-membered or 6-membered rings and 1-4 heteroatoms selected from N, O and S, or heteroaryl group comprising one, two or three 5-membered or 6-membered rings and 1-4 heteroatoms selected from N, O and S; wherein the alkane group, cycloalkyl group, epoxy group, aryl group, heterocyclic group, or heteroaryl group is optionally substituted by one or more substituents independently selected from: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cycloalkyl, 3-8-membered heterocyclic group, aryl or heteroaryl group;

[0034] In R7, R8, and R9, two groups attached to the same carbon atom can form a heterocycle; any two groups attached to different atoms can be further linked to form a heterocycle, which is optionally substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cyclic hydrocarbon, 3-8 membered heterocyclic group, aryl or heteroaryl.

[0035] In some embodiments of the present invention, the Cy1 is selected from: C3-C12 cyclic hydrocarbon groups, aryl groups, or heterocyclic groups comprising one, two, or three 5- or 6-membered rings and 1-3 heteroatoms selected from N, O, and S, wherein the cyclic hydrocarbon group, aryl group, or heterocyclic group is a spirocyclic, bridged ring, fused ring, or monocyclic; the cyclic hydrocarbon group, aryl group, or heterocyclic group is optionally substituted by one or more substituents independently selected from: deuterium, OH, carboxyl, halogen, NH2, CN, NO2, oxo, thio, C1-C8 alkyl, C1- C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocyclic, aryl or heteroaryl, wherein the C3-C8 cycloalkyl, 3-8 membered heterocyclic, aryl or heteroaryl is optionally substituted by one or more substituents independently selected from: deuterium, OH, carboxyl, halogen, NH2, CN, NO2, C1-C8 alkyl, C3-C8 cycloalkyl, C1-C6 haloalkyl, C1-C6 hydroxysubstituted alkyl, C1-C8 alkoxy or The cyclic hydrocarbon group, aryl group, heterocyclic group, or heteroaryl group is a spirocyclic, bridged ring, fused ring, or monocyclic ring.

[0036] In some embodiments of the present invention, the Cy1 mentioned above is selected from: a heteroaryl group comprising one, two, or three 5- or 6-membered rings and 1 to 3 heteroatoms selected from N, O, and S, wherein the heteroaryl group is a fused ring or a monocyclic ring; the heteroaryl group is optionally substituted by one or more substituents independently selected from: C3-C8 cyclic hydrocarbon group, 3-8-membered heterocyclic group, aryl group, or heteroaryl group, wherein the C3-C8 cyclic hydrocarbon group, 3-8-membered heterocyclic group, aryl group, or heteroaryl group is optionally substituted by one or more substituents independently selected from: deuterium, OH, carboxyl, halogen, NH2, CN, NO2, C1-C8 alkyl, C3-C8 cyclic hydrocarbon group, C1-C6 haloalkyl, C1-C6 hydroxysubstituted alkyl, C1-C8 alkoxy, or The cyclic hydrocarbon group, aryl group, heterocyclic group, or heteroaryl group is a spirocyclic, bridged ring, fused ring, or monocyclic ring.

[0037] In some embodiments of the present invention, the Cy1 is selected from: a heterocyclic group comprising one, two, or three 5- or 6-membered rings and 1 to 3 heteroatoms selected from N, O, and S; or a heteroaryl group comprising one, two, or three 5- or 6-membered rings and 1 to 3 heteroatoms selected from N, O, and S; the heterocyclic group or heteroaryl group is a spirocyclic, bridged ring, fused ring, or monocyclic; the heterocyclic group or heteroaryl group is optionally substituted by one or more substituents independently selected from: deuterium, OH, carboxyl, halogen, NH2, CN, NO2, oxo, thio, C 1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocyclic, aryl or heteroaryl, wherein the C3-C8 cycloalkyl, 3-8 membered heterocyclic, aryl or heteroaryl is optionally substituted by one or more substituents independently selected from: deuterium, OH, carboxyl, halogen, NH2, CN, NO2, C1-C8 alkyl, C3-C8 cycloalkyl, C1-C6 haloalkyl, C1-C6 hydroxysubstituted alkyl, C1-C8 alkoxy or

[0038] In some embodiments of the present invention, the Cy1 mentioned above is selected from: heterocyclic groups comprising one, two, or three 5- or 6-membered rings and 1 to 3 heteroatoms selected from N, O, and S; said heterocyclic group is optionally substituted by one or more substituents independently selected from: C1-C5 alkyl, oxo, C1-C5 haloalkyl, C1-C5 alkoxy, C1-C5 haloalkoxy, C3-C5 cyclic hydrocarbon, 3-5-membered heterocyclic, aryl, or heteroaryl, wherein said C3-C5 cyclic hydrocarbon, 3-5-membered heterocyclic, aryl, or heteroaryl is optionally substituted by one or more substituents independently selected from: deuterium, OH, carboxyl, halogen, NH2, CN, NO2, C1-C5 alkyl, C3-C5 cyclic hydrocarbon, C1-C4 haloalkyl, C1-C4 hydroxylated alkyl, C1-C3 alkoxy,

[0039] In some embodiments of the present invention, A is selected from: a heterocyclic group comprising one, two, or three 5- or 6-membered rings and 1 to 3 heteroatoms selected from N, O, and S; or a heteroaryl group comprising one, two, or three 5- or 6-membered rings and 1 to 3 heteroatoms selected from N, O, and S; the heterocyclic group or heteroaryl group is a spirocyclic, bridged ring, fused ring, or monocyclic ring; the heterocyclic group or heteroaryl group is optionally substituted by one or more substituents independently selected from: deuterium, OH, carboxyl, halogen, NH2, CN, NO2, oxo, thio, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C2-C8 alkenyl, haloC2-C8 alkenyl, C2-C8 alkynyl, haloC2-C8 alkynyl, C3-C8 cyclic hydrocarbon, 3-8-membered heterocyclic group, aryl, or heteroaryl; or, R1A The connection between A and L2 causes A and L2 to form a heterocyclic group together, or R 1A The connection between R4 and A, L2, and R4 forms a heterocyclic group, R 1A The structural components are independently selected from -NH-alkylene-, -NHC(O)-, -C(O)NH-, -alkylene-NHC(O)-, -alkylene-C(O)NH-, -NHC(O)-alkylene-, -C(O)NH-alkylene-, -C(O)-.

[0040] In some embodiments of the present invention, A is selected from: a heterocyclic group comprising one, two, or three 5- or 6-membered rings and 1 to 3 heteroatoms selected from N, O, and S; or a heteroaryl group comprising one, two, or three 5- or 6-membered rings and 1 to 3 heteroatoms selected from N, O, and S; the heterocyclic group or heteroaryl group is a spirocyclic, bridged ring, fused ring, or monocyclic; the heterocyclic group or heteroaryl group is optionally composed of one or more independently selected from R. 1A Substituents of R; 1A The connection between A and L2 causes A and L2 to form a heterocyclic group together. In this case, the R 1A The structural part is selected from: C1-C8 alkylene, C1-C8 haloalkylene, C1-C8 alkoxide, C1-C8 haloalkoxide, C2-C8 alkenyl, haloC2-C8 alkenyl, C2-C8 alkyne, haloC2-C8 alkyne, -NH-alkylene-, -NHC(O)-, -C(O)NH-, -alkylene-NHC(O)-, -alkylene-C(O)NH-, -NHC(O)-alkylene-, -C(O)NH-alkylene-, -C(O)-.

[0041] In some embodiments of the present invention, A is selected from: a heterocyclic group comprising one, two, or three 5- or 6-membered rings and 1 to 3 heteroatoms selected from N, O, and S; or a heteroaryl group comprising one, two, or three 5- or 6-membered rings and 1 to 3 heteroatoms selected from N, O, and S; the heterocyclic group or heteroaryl group is a spirocyclic, bridged ring, fused ring, or monocyclic; the heterocyclic group or heteroaryl group is optionally composed of one or more independently selected from R. 1A Substituents of R; 1A The connection between R4 and A, L2, and R4 forms a heterocyclic group, in which case the R 1AThe structural part is selected from: C1-C8 alkylene, C1-C8 haloalkylene, C1-C8 alkoxide, C1-C8 haloalkoxide, C2-C8 alkenyl, haloC2-C8 alkenyl, C2-C8 alkyne, haloC2-C8 alkyne, -NH-alkylene-, -NHC(O)-, -C(O)NH-, -alkylene-NHC(O)-, -alkylene-C(O)NH-, -NHC(O)-alkylene-, -C(O)NH-alkylene-, -C(O)-.

[0042] In some embodiments of the present invention, R1 is selected from:

[0043] In some embodiments of the present invention, R1 is selected from:

[0044] In some embodiments of the present invention, R1 is selected from: none, C3-C8 alkyl, C3-C8 cycloalkyl, heterocyclic group comprising one or two 5- or 6-membered rings and 1-4 heteroatoms selected from N, O, and S, or heteroaryl group comprising one 5- or 6-membered ring and 1-4 heteroatoms selected from N, O, and S, wherein the alkyl, cycloalkyl, heterocyclic, or heteroaryl group is optionally substituted by one or more substituents independently selected from: deuterium, halogen, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cycloalkyl, OH, NH2, oxo, thio, -NH-(C1-C6 alkyl), -N(C1-C6 alkyl)2, CN, NO2, carboxyl, 3-8 membered heterocyclic, aryl, or heteroaryl.

[0045] In some embodiments of the present invention, R1 is selected from:

[0046] In some embodiments of the present invention, R1 is selected from: C3-C10 alkyl, C3-C10 cycloalkyl, wherein the alkyl and cycloalkyl are optionally substituted by one or more substituents independently selected from: deuterium, halogen, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cycloalkyl, OH, NH2, oxo, thio, -NH-(C1-C6 alkyl), -N(C1-C6 alkyl)2, CN, NO2, carboxyl, 3-8 membered heterocyclic, aryl, or heteroaryl.

[0047] In some embodiments of the present invention, R1 is selected from: C3-C8 alkyl, C3-C8 cycloalkyl, wherein the alkyl and cycloalkyl are optionally substituted by one or more substituents independently selected from: deuterium, halogen, C1-C8 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C3-C6 cycloalkyl, OH, NH2, oxo, thio, -NH-(C1-C6 alkyl), -N(C1-C6 alkyl)2, CN, NO2, carboxyl, 3-8 membered heterocyclic, aryl, or heteroaryl.

[0048] In some embodiments of the present invention, R1 is selected from: heterocyclic groups containing one, two, or three 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S; or heteroaryl groups containing one, two, or three 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, wherein the heterocyclic group or heteroaryl group is optionally substituted by one or more substituents independently selected from: deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C3-C8 cyclic hydrocarbon, OH, NH2, oxo, thio, -NH-(C1-C6 alkyl), -N(C1-C6 alkyl)2, CN, NO2, carboxyl,

[0049] In some embodiments of the present invention, X is selected from: W is selected from O and CH2.

[0050] In some embodiments of the present invention, R2 is selected from: none, C1-C8 alkyl, -(CH2). 0-3 -C3-C10 cyclic hydrocarbon groups, -(CH2) 0-3 -C3-C10 epoxy group, wherein the alkyl, cyclic hydrocarbon, or epoxy group is optionally substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cyclic hydrocarbon, 3-8 membered heterocyclic group, aryl or heteroaryl.

[0051] In some embodiments of the present invention, R2 is selected from: none, C1-C8 alkyl, -(CH2). 0-3 -C3-C8 cyclic hydrocarbon groups, -(CH2) 0-3-3-8 membered epoxy group, wherein the alkyl, cycloalkyl, and epoxy group are optionally substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocyclic group, aryl or heteroaryl.

[0052] In some embodiments of the present invention, R2 is selected from: none, C1-C5 alkyl, -(CH2). 0-3 -C3-C5 cyclic hydrocarbon groups, -(CH2) 0-3 -3-5 membered epoxy group, wherein the alkyl, cycloalkyl, and epoxy group are optionally substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C5 alkyl, C1-C5 haloalkyl, C1-C5 alkoxy, C1-C5 haloalkoxy, C3-C5 cycloalkyl, 3-5 membered heterocyclic group, aryl or heteroaryl.

[0053] In some embodiments of the present invention, R1 and R2 are both selected as none.

[0054] In some embodiments of the present invention, R3 and R4 are each independently selected from: C3-C8 cyclic hydrocarbon groups, aryl groups, heterocyclic groups comprising one, two, or three 3-membered, 4-membered, 5-membered, 6-membered, or 7-membered rings and one to three heteroatoms selected from N, O, and S, or heteroaryl groups comprising one, two, or three 3-membered, 4-membered, 5-membered, 6-membered, or 7-membered rings and one to three heteroatoms selected from N, O, and S, wherein the cyclic hydrocarbon group, aryl group, heterocyclic group, or heteroaryl group is a spirocyclic, bridged ring, fused ring, or monocyclic ring, and the cyclic hydrocarbon group, aryl group, heterocyclic group, or heteroaryl group is optionally composed of one or more independent The substituents are selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cyclic hydrocarbon, -O-C3-C8 cyclic hydrocarbon, 3-8 membered heterocyclic group, aryl, heteroaryl, deuterated C1-C8 alkyl, deuterated C1-C8 haloalkyl, deuterated C1-C8 alkoxy, deuterated C1-C8 haloalkoxy, deuterated C3-C8 cyclic hydrocarbon, deuterated -O-C3-C8 cyclic hydrocarbon.

[0055] In some embodiments of the present invention, R3 is selected from: C3-C8 cyclic hydrocarbon group, aryl group, heterocyclic group comprising one, two, or three 3-membered, 4-membered, 5-membered, 6-membered, or 7-membered rings and one to three heteroatoms selected from N, O, and S, wherein the cyclic hydrocarbon group, aryl group, or heterocyclic group is a spirocyclic, bridged ring, fused ring, or monocyclic ring, and the cyclic hydrocarbon group, aryl group, or heterocyclic group is optionally substituted by one or more substituents independently selected from: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cyclic hydrocarbon group, -O-C3-C8 cyclic hydrocarbon group, 3-8 membered heterocyclic group, aryl, or heteroaryl.

[0056] In some embodiments of the present invention, R3 is selected from: C3-C5 cyclic hydrocarbon group, aryl group, heterocyclic group comprising one, two, or three 3-membered, 4-membered, 5-membered, 6-membered, or 7-membered rings and one to three heteroatoms selected from N, O, and S, wherein the cyclic hydrocarbon group, aryl group, or heterocyclic group is a spirocyclic, bridged ring, fused ring, or monocyclic ring, and the cyclic hydrocarbon group, aryl group, or heterocyclic group is optionally substituted by one or more substituents independently selected from: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C5 alkyl, C1-C5 haloalkyl, C1-C5 alkoxy, C1-C5 haloalkoxy, C3-C5 cyclic hydrocarbon group, -O-C3-C5 cyclic hydrocarbon group, 3-5 membered heterocyclic group, aryl, or heteroaryl.

[0057] In some embodiments of the present invention, R4 is selected from: C3-C9 cyclic hydrocarbon groups, wherein the cyclic hydrocarbon group is a spirocyclic, bridged ring, fused ring, or monocyclic ring, and the cyclic hydrocarbon group is optionally substituted by one or more substituents independently selected from: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cyclic hydrocarbon group, -O-C3-C8 cyclic hydrocarbon group, 3-8 membered heterocyclic group, aryl, heteroaryl, deuterated C1-C8 alkyl, deuterated C1-C8 haloalkyl, deuterated C1-C8 alkoxy, deuterated C1-C8 haloalkoxy, deuterated C3-C8 cyclic hydrocarbon group, deuterated -O-C3-C8 cyclic hydrocarbon group.

[0058] In some embodiments of the present invention, R4 is selected from: aryl, heterocyclic groups comprising one, two, or three 3-, 4-, 5-, 6-, or 7-membered rings and one to three heteroatoms selected from N, O, and S, or heteroaryl groups comprising one, two, or three 3-, 4-, 5-, 6-, or 7-membered rings and one to three heteroatoms selected from N, O, and S, wherein the heterocyclic group or heteroaryl group is a spirocyclic, bridged ring, fused ring, or monocyclic, and the heterocyclic group or heteroaryl group is optionally substituted by one or more substituents independently selected from: deuterium, halogen... Element, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cyclic hydrocarbon, -O-C3-C8 cyclic hydrocarbon, 3-8 membered heterocyclic group, aryl, heteroaryl, deuterated C1-C8 alkyl, deuterated C1-C8 haloalkyl, deuterated C1-C8 alkoxy, deuterated C1-C8 haloalkoxy, deuterated C3-C8 cyclic hydrocarbon, deuterated -O-C3-C8 cyclic hydrocarbon.

[0059] In some embodiments of the present invention, R4 is selected from: aryl, heterocyclic groups comprising one, two, or three 3-, 4-, 5-, 6-, or 7-membered rings and one to three heteroatoms selected from N, O, and S, or heteroaryl groups comprising one, two, or three 3-, 4-, 5-, 6-, or 7-membered rings and one to three heteroatoms selected from N, O, and S, wherein the heterocyclic group or heteroaryl is a spirocyclic, bridged ring, fused ring, or monocyclic, and the aryl, heterocyclic, or heteroaryl group is optionally substituted by one or more substituents independently selected from: deuterium, Halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C5 alkyl, C1-C5 haloalkyl, C1-C5 alkoxy, C1-C5 haloalkoxy, C3-C5 cyclic hydrocarbon, -O-C3-C5 cyclic hydrocarbon, 3-5 membered heterocyclic group, aryl, heteroaryl, deuterated C1-C5 alkyl, deuterated C1-C5 haloalkyl, deuterated C1-C5 alkoxy, deuterated C1-C5 haloalkoxy, deuterated C3-C5 cyclic hydrocarbon, deuterated -O-C3-C5 cyclic hydrocarbon.

[0060] In some embodiments of the present invention, R4 is selected from: aryl, wherein the aryl is a spirocyclic, bridged ring, fused ring, or monocyclic ring, and the aryl is optionally substituted by one or more substituents independently selected from: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cyclic hydrocarbon, -O-C3-C8 cyclic hydrocarbon, 3-8 membered heterocyclic group, aryl, heteroaryl, deuterated C1-C8 alkyl, deuterated C1-C8 haloalkyl, deuterated C1-C8 alkoxy, deuterated C1-C8 haloalkoxy, deuterated C3-C8 cyclic hydrocarbon, deuterated -O-C3-C8 cyclic hydrocarbon.

[0061] In some embodiments of the present invention, R4 is selected from: aryl, wherein the aryl is a spirocyclic, bridged ring, fused ring, or monocyclic ring, and the aryl is optionally substituted by one or more substituents independently selected from: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C5 alkyl, C1-C5 haloalkyl, C1-C5 alkoxy, C1-C5 haloalkoxy, C3-C5 cyclic hydrocarbon, -O-C3-C5 cyclic hydrocarbon, 3-5 membered heterocyclic group, aryl or heteroaryl, deuterated C1-C5 alkyl, deuterated C1-C5 haloalkyl, deuterated C1-C5 alkoxy, deuterated C1-C5 haloalkoxy, deuterated C3-C5 cyclic hydrocarbon, deuterated -O-C3-C5 cyclic hydrocarbon.

[0062] In some embodiments of the present invention, L1 and L2 are each independently selected from: none, C1-C3 alkylene, halo-C1-C3 alkylene, C2-C3 alkenyl, halo-C2-C3 alkenyl, C2-C3 alkyneyl, halo-C2-C3 alkyneyl, -O-alkylene-, -NH-alkylene-, -NHC(O)-, -C(O)NH-, -alkylene-NHC(O)-, -alkylene-C(O)NH-, -NHC(O)-alkylene-, -C(O)NH-alkylene-, -C(O)-, -NH-, C3-C8 cyclic hydrocarbon, aryl, comprising one, two or three ternary or A heterocyclic group comprising a 4-, 5-, or 6-membered ring and 1 to 3 heteroatoms selected from N, O, and S, or a heteroaryl group comprising one, two, or three 3-, 4-, 5-, or 6-membered rings and 1 to 3 heteroatoms selected from N, O, and S, wherein the alkylene, cycloalkyl, aryl, heterocyclic, or heteroaryl group is optionally substituted by one or more substituents independently selected from: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cycloalkyl, 3-8-membered heterocyclic, aryl, or heteroaryl.

[0063] In some embodiments of the present invention, L1 is selected from: none, C1-C3 alkylene, C2-C3 alkynylene, aryl, heterocyclic group comprising one, two or three 3-membered, 4-membered, 5-membered or 6-membered rings and 1-3 heteroatoms selected from N, O and S, or heteroaryl group comprising one, two or three 3-membered, 4-membered, 5-membered or 6-membered rings and 1-3 heteroatoms selected from N, O and S; the aryl, heterocyclic or heteroaryl group is a spirocyclic, bridged ring, fused ring or monocyclic; the aryl, heterocyclic or heteroaryl group is optionally substituted by one or more substituents independently selected from: deuterium, OH, carboxyl, halogen, NH2, CN, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cyclic hydrocarbon, 3-8 membered heterocyclic, aryl or heteroaryl.

[0064] In some embodiments of the present invention, L1 is selected from: none, C1-C3 alkylene, C2-C3 alkynylene, aryl, heterocyclic group comprising one, two or three 3-membered, 4-membered, 5-membered or 6-membered rings and 1-3 heteroatoms selected from N, O and S, or heteroaryl group comprising one, two or three 3-membered, 4-membered, 5-membered or 6-membered rings and 1-3 heteroatoms selected from N, O and S; the aryl, heterocyclic or heteroaryl group is a spirocyclic, bridged ring, fused ring or monocyclic; the aryl, heterocyclic or heteroaryl group is optionally substituted by one or more substituents independently selected from: deuterium, OH, carboxyl, halogen, NH2, CN, NO2, C1-C5 alkyl, C1-C5 haloalkyl, C1-C5 alkoxy, C1-C5 haloalkoxy, C3-C5 cyclic hydrocarbon, 3-5 membered heterocyclic group, aryl or heteroaryl.

[0065] In some embodiments of the present invention, the L2 is selected from: -C(O)NH-, -alkylene-C(O)NH-, -C(O)-, -NH-aryl, heterocyclic groups comprising one, two, or three 5- or 6-membered rings and one to three heteroatoms selected from N, O, and S, or heteroaryl groups comprising one, two, or three 5- or 6-membered rings and one to three heteroatoms selected from N, O, and S, wherein the aryl, heterocyclic, or heteroaryl group is Spirocyclic, bridged ring, fused ring, or monocyclic, wherein the alkylene, aryl, heterocyclic, or heteroaryl group is optionally substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cyclic hydrocarbon, 3-8 membered heterocyclic, aryl, or heteroaryl.

[0066] In some embodiments of the present invention, the L2 is selected from: -C(O)NH-, -alkylene-C(O)NH-, -C(O)-, -NH-aryl, heterocyclic groups comprising one, two, or three 5- or 6-membered rings and one to three heteroatoms selected from N, O, and S, or heteroaryl groups comprising one, two, or three 5- or 6-membered rings and one to three heteroatoms selected from N, O, and S, wherein the aryl, heterocyclic, or heteroaryl group is Spirocyclic, bridged ring, fused ring, or monocyclic, wherein the alkylene, aryl, heterocyclic, or heteroaryl group is optionally substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C5 alkyl, C1-C5 haloalkyl, C1-C5 alkoxy, C1-C5 haloalkoxy, C3-C5 cyclic hydrocarbon, 3-5 membered heterocyclic, aryl, or heteroaryl.

[0067] In some embodiments of the present invention, the above-mentioned R 1e R 1g and R 1h It is independently selected from: hydrogen, OH, carboxyl, NH2, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C8 cyclic hydrocarbon, -O-C3-C8 cyclic hydrocarbon, or aryl.

[0068] In some embodiments of the present invention, the above-mentioned R 1e Selected from: hydrogen, NH2, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 hydroxyalkyl, C2-C3 alkenyl, C2-C3 alkynyl, C3-C5 cyclic hydrocarbon or aryl.

[0069] In some embodiments of the present invention, the above-mentioned R 1e Selected from: hydrogen, NH2, methyl, vinyl, ethynyl, C3-C5 cyclic hydrocarbon groups.

[0070] In some embodiments of the present invention, the above-mentioned R 1g It is independently selected from: hydrogen, OH, carboxyl, NH2, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 hydroxyalkyl, C2-C3 alkenyl, C2-C3 alkynyl, C3-C5 cyclic hydrocarbon, -O-C3-C5 cyclic hydrocarbon, or aryl.

[0071] In some embodiments of the present invention, the above-mentioned R 1h It is independently selected from: hydrogen, OH, carboxyl, NH2, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 hydroxyalkyl, C2-C3 alkenyl, C2-C3 alkynyl, C3-C5 cyclic hydrocarbon, -O-C3-C5 cyclic hydrocarbon, or aryl.

[0072] In some embodiments of the present invention, the above-mentioned R 1a and R 1b Independently selected from: hydrogen, C3-C8 cyclic hydrocarbon groups, C1-C8 alkyl groups, Or R 1a and R 1b Together with the nitrogen atom to which they are attached, they form a C3-C8 heterocyclic group, wherein the heterocyclic group, cyclic hydrocarbon group, and alkyl group are optionally substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cyclic hydrocarbon group, 3-8 membered heterocyclic group, aryl or heteroaryl.

[0073] In some embodiments of the present invention, R1a and R... 1b Independently selected from: hydrogen, C3-C5 cyclic hydrocarbon group, C1-C5 alkyl group, Or R 1a and R 1b Together with the nitrogen atom to which they are attached, they form a C3-C8 heterocyclic group, wherein the heterocyclic group, cyclic hydrocarbon group, and alkyl group are optionally substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cyclic hydrocarbon group, 3-8 membered heterocyclic group, aryl or heteroaryl.

[0074] In some embodiments of the present invention, the above-mentioned R 1a and R 1b Independently selected from: hydrogen, C3-C5 cyclic hydrocarbon group, C1-C5 alkyl group, or R 1a and R 1b Together with the nitrogen atom to which they are attached, they form a C3-C5 heterocyclic group, wherein the heterocyclic group, cyclic hydrocarbon group, and alkyl group are optionally substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C5 alkyl, C1-C5 haloalkyl, C1-C5 alkoxy, C1-C5 haloalkoxy, C3-C5 cyclic hydrocarbon group, 3-5 membered heterocyclic group, aryl or heteroaryl.

[0075] In some embodiments of the present invention, the above-mentioned R 1c and R 1d Independently selected from: hydrogen, C3-C8 cyclic hydrocarbon group, C1-C8 alkyl group, or R 1c and R 1dTogether with the carbon atoms to which they are attached, they form a C3-C8 cyclic hydrocarbon group, wherein the cyclic hydrocarbon group and the alkyl group are optionally substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cyclic hydrocarbon group, 3-8 membered heterocyclic group, aryl or heteroaryl.

[0076] In some embodiments of the present invention, the above-mentioned R 1c and R 1d Independently selected from: hydrogen, C3-C5 cyclic hydrocarbon group, C1-C5 alkyl group, or R 1c and R 1d Together with the carbon atoms to which they are attached, they form a C3-C5 cyclic hydrocarbon group, wherein the cyclic hydrocarbon group and the alkyl group are optionally substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cyclic hydrocarbon group, 3-8 membered heterocyclic group, aryl or heteroaryl.

[0077] In some embodiments of the present invention, the above-mentioned R 1c and R 1d Independently selected from: hydrogen, C3-C5 cyclic hydrocarbon group, C1-C5 alkyl group, or R 1c and R 1d Together with the carbon atoms to which they are attached, they form a C3-C5 cyclic hydrocarbon group, wherein the cyclic hydrocarbon group and the alkyl group are optionally substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C5 haloalkyl, C1-C5 alkoxy, C1-C5 haloalkoxy, C3-C5 cyclic hydrocarbon group, 3-5 membered heterocyclic group, aryl or heteroaryl.

[0078] In some embodiments of the present invention, R6 is independently selected from: hydrogen, C1-C8 alkyl, -(CH2). 0-3 -C3-C8 cyclic hydrocarbon groups, -(CH2) 0-3 -3-8 membered epoxy group, wherein the alkyl, cycloalkyl, and epoxy group are optionally substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocyclic group, aryl or heteroaryl.

[0079] In some embodiments of the present invention, R6 is independently selected from: hydrogen, C1-C5 alkyl, -(CH2). 0-3-C3-C5 cyclic hydrocarbon groups, -(CH2) 0-3 -3-5 membered epoxy group, wherein the alkyl, cycloalkyl, and epoxy group are optionally substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocyclic group, aryl or heteroaryl.

[0080] In some embodiments of the present invention, R5 is independently selected from: hydrogen, C1-C8 alkyl, -(CH2). 0-3 -C3-C8 cyclic hydrocarbon groups, -(CH2) 0-3 -3-8 membered epoxy group, wherein the alkyl, cycloalkyl, and epoxy group are optionally substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thioNO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocyclic group, aryl or heteroaryl.

[0081] In some embodiments of the present invention, R5 is independently selected from: hydrogen, C1-C5 alkyl, -(CH2). 0-3 -C3-C5 cyclic hydrocarbon groups, -(CH2) 0-3 -3-5 membered epoxy group, wherein the alkyl, cycloalkyl, and epoxy group are optionally substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocyclic group, aryl or heteroaryl.

[0082] In some embodiments of the present invention, the above-mentioned R 1f Independently selected from: hydrogen, deuterium, halogen, OH, carboxyl group, NH2, CN, NO2, C1-C8 alkane group, -(CH2) 0-3 -C3-C8 cyclic hydrocarbon groups, -(CH2) 0-3 -3-8 membered epoxy group, wherein the alkane group, cycloalkyl group and epoxy group are optionally substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocyclic group, aryl or heteroaryl.

[0083] In some embodiments of the present invention, the above-mentioned R 1f Independently selected from: hydrogen, deuterium, C1-C5 alkane groups, -(CH2) 0-3-C3-C5 cyclic hydrocarbon groups, -(CH2) 0-3 -3-5 membered epoxy group, wherein the alkane group, cycloalkyl group, epoxy group is optionally substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocyclic group, aryl or heteroaryl.

[0084] In some embodiments of the present invention, R7, R8, and R9 are each independently selected from: C1-C8 alkane groups, -(CH2) 0-3 -C3-C8 cyclic hydrocarbon groups, -(CH2) 0-3 -3-8 membered epoxy group, aryl group; the alkane group, epoxy group and aryl group are optionally substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cyclic hydrocarbon group, 3-8 membered heterocyclic group, aryl or heteroaryl.

[0085] In some embodiments of the present invention, R7, R8, and R9 are each independently selected from: C1-C5 alkane groups, -(CH2) 0-3 -C3-C5 cyclic hydrocarbon groups, -(CH2) 0-3 -3-5 membered epoxy group, aryl group; the alkane group, epoxy group and aryl group are optionally substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cyclic hydrocarbon group, 3-8 membered heterocyclic group, aryl or heteroaryl.

[0086] In some embodiments of the present invention, R7, R8, and R9 are each independently selected from: C1-C5 alkane groups, -(CH2) 0-3 -C3-C5 cyclic hydrocarbon groups, -(CH2) 0-3 -3-5 membered epoxy group, aryl group; the alkane group, epoxy group and aryl group are optionally substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C5 alkyl, C1-C5 haloalkyl, C1-C5 alkoxy, C1-C5 haloalkoxy, C3-C5 cyclic hydrocarbon group, 3-5 membered heterocyclic group, aryl or heteroaryl.

[0087] In some embodiments of the present invention, the above-mentioned R 1e Independently selected from: hydrogen, OH, NH2, methyl, vinyl, ethynyl, In some embodiments of the present invention, the above-mentioned R 1g Independently selected from: hydrogen, methyl, OH, NH2,

[0088] In some embodiments of the present invention, the above-mentioned R 1h Independently selected from: hydrogen, methyl, OH, NH2,

[0089] In some embodiments of the present invention, the above-mentioned R 1a R 1b Independently selected from: hydrogen,

[0090] In some embodiments of the present invention, the above-mentioned R 1c R 1d Independently selected from: hydrogen, -CF3.

[0091] In some embodiments of the present invention, the above-mentioned Independent selection from: In some embodiments of the present invention, the above-mentioned Independent selection from: In some embodiments of the present invention, the above-mentioned Selected from:

[0092] In some embodiments of the present invention, the above-mentioned Selected from:

[0093] In some embodiments of the present invention, the compounds shown in formula (I) are selected from:

[0094] In some embodiments of the present invention, the compounds shown in formula (I) are selected from:

[0095] In some embodiments of the present invention, the compounds shown in formula (I) are selected from:

[0096] In some embodiments of the present invention, the compounds shown in formula (I) are selected from:

[0097] In some embodiments of the present invention, the above-mentioned Structural units are selected from:

[0098] In some embodiments of the present invention, the compounds shown in formula (I) are selected from:

[0099] In some embodiments of the present invention, R6 is selected from hydrogen and methyl.

[0100] In some embodiments of the present invention, R5 is selected from: hydrogen,

[0101] In some embodiments of the present invention, R5 and L1 are... The atoms bonded together on the structural unit form a heterocycle, and the compound shown in formula (I) is selected from the following groups:

[0102] In some embodiments of the present invention, R5 and R2 together with the atoms attached to the nitrogen ring form a heterocycle, and the compound shown in formula (I) is selected from the following groups:

[0103] In some embodiments of the present invention, the above-mentioned R 1f Independently selected from: hydrogen,

[0104] In some embodiments of the present invention, the above-mentioned Structural units are selected from:

[0105] In some embodiments of the present invention, the above-mentioned Structural units are selected from:

[0106] In some embodiments of the present invention, the above-mentioned Structural units are selected from:

[0107] In some embodiments of the present invention, the above-mentioned Structural units are selected from:

[0108] In some embodiments of the present invention, the above-mentioned Structural units are selected from:

[0109] In some embodiments of the present invention, R7 is selected from: hydrogen,

[0110] In some embodiments of the present invention, R8 is selected from:

[0111] In some embodiments of the present invention, R9 is selected from:

[0112] In some embodiments of the present invention, the Cy1 mentioned above is selected from:

[0113] In some embodiments of the present invention, the Cy1 mentioned above is selected from:

[0114] In some embodiments of the present invention, A is selected from: * indicates the direction of connection with L2.

[0115] In some embodiments of the present invention, A is selected from: * indicates the direction of connection with L2.

[0116] In some embodiments of the present invention, the above-mentioned R 1A Selected from: hydrogen, methyl, ethyl.

[0117] In some embodiments of the present invention, the above-mentioned R 1A The connection between A and L2 causes A and L2 to form a heterocyclic group, wherein the heterocyclic group is selected from:

[0118] In some embodiments of the present invention, the above-mentioned R 1A The connection between A, L2, and R4 forms a heterocyclic group, wherein the heterocyclic group is selected from:

[0119] In some embodiments of the present invention, in In structural units, R 1A It is an alkylene group, selected from -CH2- or -CH2CH2-.

[0120] In some embodiments of the present invention, A is selected from: * indicates the direction of connection with L2.

[0121] In some embodiments of the present invention, the above-mentioned Selected from:

[0122] In some embodiments of the present invention, the above-mentioned Selected from:

[0123] In some embodiments of the present invention, the above-mentioned Selected from: NH2.

[0124] In some embodiments of the present invention, the above-mentioned Selected from:

[0125] In some embodiments of the present invention, the above-mentioned Selected from:

[0126] In some embodiments of the present invention, the above-mentioned Selected from:

[0127] In some embodiments of the present invention, the above-mentioned Selected from:

[0128] In some embodiments of the present invention, the above-mentioned Selected from:

[0129] In some embodiments of the present invention, R1 is selected from: none, NH2,

[0130] In some embodiments of the present invention, R1 is selected from NH2.

[0131] In some embodiments of the present invention, R1 is selected from:

[0132] In some embodiments of the present invention, R1 is selected from:

[0133] In some embodiments of the present invention, R2 is selected from: none,

[0134] In some embodiments of the present invention, R3 is selected from:

[0135] In some embodiments of the present invention, R3 is selected from:

[0136] In some embodiments of the present invention, R4 is selected from:

[0137] In some embodiments of the present invention, R4 is selected from:

[0138] In some embodiments of the present invention, R4 is selected from:

[0139] In some embodiments of the present invention, L1 is selected from: none, -CH2CH2-, acetylene group,

[0140] In some embodiments of the present invention, L1 is selected from: -CH2-.

[0141] In some embodiments of the present invention, L1 is selected from:

[0142] In some embodiments of the present invention, L2 is selected from: none,

[0143] In some embodiments of the present invention, L2 is selected from:

[0144] In some embodiments of the present invention, the above-mentioned The structure is selected from:

[0145] In some embodiments of the present invention, the above-mentioned compounds have the following formulas (I-1), (I-2), (I-3), (I-4), (I-5), (I-6), (I-7), (I-8), or (I-9):

[0146] Among them, A, Cy1, R1, R2, R3, R4, R5, R6, L1, L2, R 1A The variables are as defined in this invention.

[0147] This invention provides a compound of formula (I-1) or a pharmaceutically acceptable salt, stereoisomer, or mixture of stereoisomers thereof, having the following structure:

[0148] The variables A, Cy1, R1, R2, R3, R4, L1, and L2 are as defined in this invention.

[0149] This invention provides a compound of formula (I-5) or a pharmaceutically acceptable salt, stereoisomer, or mixture of stereoisomers thereof, having the following structure:

[0150] Wherein: X1, X2, and X3 contain at least one heteroatom selected from N, O, and S; X1 is independently selected from: -CR7-, -N-; X2 is selected from: -O-, -S-, -S(O)2-, -NR8-, -C(R8)2-, -NR8-C(R8)2-, or -CO-; X3 is selected from: -N-, -CR9-; wherein: X1, X2, and X3 contain at least one heteroatom selected from N, O, and S;

[0151] R7, R8, and R9 are each independently selected from: C1-C10 alkane groups, -(CH2) 0-6 -C3-C10 cyclic hydrocarbon groups, -(CH2) 0-6 -3-10-membered epoxy group, aryl group, heterocyclic group comprising one, two or three 5-membered or 6-membered rings and 1-4 heteroatoms selected from N, O and S, or heteroaryl group comprising one, two or three 5-membered or 6-membered rings and 1-4 heteroatoms selected from N, O and S; wherein the alkane group, cycloalkyl group, epoxy group, aryl group, heterocyclic group, or heteroaryl group is optionally substituted by one or more substituents independently selected from: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cycloalkyl, 3-8-membered heterocyclic group, aryl or heteroaryl group;

[0152] In R7, R8, and R9, two groups attached to the same carbon atom may be further linked to form a heterocycle; any two groups attached to different atoms may be further linked to form a heterocycle, wherein the heterocycle may optionally be substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cyclic hydrocarbon, 3-8 membered heterocyclic group, aryl or heteroaryl;

[0153] Other variables A, Cy1, R3, R4, L1, and L2 are as defined in this invention.

[0154] This invention provides a compound of formula (I-6) or a pharmaceutically acceptable salt, stereoisomer, or mixture of stereoisomers thereof, having the following structure:

[0155] Wherein: X1, X2, and X3 contain at least one heteroatom selected from N, O, and S; X1 is independently selected from: -CR7-, -N-; X2 is independently selected from: -N-, -CR8-, -CR8-NR8-, -NC(R8)2-; X3 is independently selected from: -O-, -S-, -S(O).2、 -NR9-, -C(R9)2-, -NR9-C(R9)2- or -CO-;

[0156] R7, R8, and R9 are each independently selected from: C1-C10 alkane groups, -(CH2) 0-6 -C3-C10 cyclic hydrocarbon groups, -(CH2) 0-6 -3-10-membered epoxy group, aryl group, heterocyclic group comprising one, two or three 5-membered or 6-membered rings and 1-4 heteroatoms selected from N, O and S, or heteroaryl group comprising one, two or three 5-membered or 6-membered rings and 1-4 heteroatoms selected from N, O and S; wherein the alkane group, cycloalkyl group, epoxy group, aryl group, heterocyclic group, or heteroaryl group is optionally substituted by one or more substituents independently selected from: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cycloalkyl, 3-8-membered heterocyclic group, aryl or heteroaryl group;

[0157] In R7, R8, and R9, two substituents attached to the same carbon atom can form a heterocycle; any two substituents attached to different atoms can form a heterocycle, which is optionally substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocyclic, aryl, or heteroaryl.

[0158] Other variables A, Cy1, R3, R4, L1, and L2 are as defined in this invention.

[0159] This invention provides a compound of formula (I-7) or a pharmaceutically acceptable salt, stereoisomer, or mixture of stereoisomers thereof, having the following structure:

[0160] Wherein: X1, X2, and X3 contain at least one heteroatom selected from N, O, and S; X1, X2, and X3 are independently selected from: -O-, -S-, -S(O)2, -C(R7)2-, -C(R7)2-C(R7)2-, -NR8-, or -CO-; wherein: X1, X2, and X3 contain at least one heteroatom selected from N, O, and S;

[0161] Or X1 is selected from X2 and X3 are selected from CH or N, and X2 and X3 together with the atoms attached to them form a C3-C15 cyclic hydrocarbon group or a C3-C15 heterocyclic group, which is optionally substituted by one or more substituents independently selected from the following: C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, OH or halogen, wherein the cyclic hydrocarbon group or heterocyclic group is a spirocyclic, bridged ring, fused ring or monocyclic;

[0162] R7 and R8 are each selected independently from: C1-C10 alkane groups, -(CH2) 0-6 -C3-C10 cyclic hydrocarbon groups, -(CH2) 0-6 -3-10-membered epoxy group, aryl group, heterocyclic group comprising one, two or three 5-membered or 6-membered rings and 1-4 heteroatoms selected from N, O and S, or heteroaryl group comprising one, two or three 5-membered or 6-membered rings and 1-4 heteroatoms selected from N, O and S; wherein the alkane group, cycloalkyl group, epoxy group, aryl group, heterocyclic group, or heteroaryl group is optionally substituted by one or more substituents independently selected from: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cycloalkyl, 3-8-membered heterocyclic group, aryl or heteroaryl group;

[0163] In R7 and R8, two groups attached to the same carbon atom can be further linked to form a heterocycle; any two groups attached to different atoms can be further linked to form a heterocycle, wherein the heterocycle is optionally substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cyclic hydrocarbon, 3-8 membered heterocyclic group, aryl or heteroaryl;

[0164] Other variables A, Cy1, R3, R4, L1, and L2 are as defined in this invention.

[0165] This invention provides a compound of formula (I-8) or a pharmaceutically acceptable salt, stereoisomer, or mixture of stereoisomers thereof, having the following structure:

[0166] in:

[0167] R 1ASelected from: C1-C8 alkylene, C1-C8 haloalkylene, C1-C8 alkoxy, C1-C8 haloalkoxy, C2-C8 alkenyl, haloC2-C8 alkenyl, C2-C8 alkyne, haloC2-C8 alkyne, -NH-alkylene-, -NHC(O)-, -C(O)NH-, -alkylene-NHC(O)-, -alkylene-C(O)NH-, -NHC(O)-alkylene-, -C(O)NH-alkylene-, -C(O)-;

[0168] L2 is independently selected from: none, C1-C6 alkylene, halo-C1-C6 alkylene, C2-C6 alkenyl, halo-C2-C6 alkenyl, C2-C6 alkyne, halo-C2-C6 alkyne, -O-alkylene-, -NH-alkylene-, -NHC(O)-, -C(O)NH-, -alkylene-NHC(O)-, -alkylene-C(O)NH-, -NHC(O)-alkylene-, -C(O)NH-alkylene-, -C(O)-, -NH-, C3-C10 cycloalkyl, aryl, containing one, two, or three 5- or 6-membered groups. A heterocyclic group comprising a membered ring and one to three heteroatoms selected from N, O, and S, or a heteroaryl group comprising one or two or three 5- or 6-membered rings and one to three heteroatoms selected from N, O, and S, wherein the alkylene, cycloalkyl, aryl, heterocyclic, or heteroaryl group is optionally substituted by one or more substituents independently selected from: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cycloalkyl, 3-8-membered heterocyclic, aryl, or heteroaryl;

[0169] R4 is independently selected from: C1-C10 alkyl, C3-C10 cycloalkyl, aryl, heterocyclic group comprising one, two, or three 4-, 5-, 6-, or 7-membered rings and one to three heteroatoms selected from N, O, and S, or heteroaryl group comprising one, two, or three 4-, 5-, 6-, or 7-membered rings and one to three heteroatoms selected from N, O, and S, wherein the cycloalkyl, aryl, heterocyclic, or heteroaryl group is a spirocyclic, bridged ring, fused ring, or monocyclic ring, and the alkyl, cycloalkyl, aryl, heterocyclic, or heteroaryl group is optionally selected by one or more independently from the following Substituents: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cyclic hydrocarbon, -O-C3-C8 cyclic hydrocarbon, 3-8 membered heterocyclic group, aryl, heteroaryl, deuterated C1-C8 alkyl, deuterated C1-C8 haloalkyl, deuterated C1-C8 alkoxy, deuterated C1-C8 haloalkoxy, deuterated C3-C8 cyclic hydrocarbon, deuterated -O-C3-C8 cyclic hydrocarbon;

[0170] other The structural units, Cy1, R1, R2, R3, and L2 variables are as defined in this invention.

[0171] This invention provides a compound of formula (I-9) or a pharmaceutically acceptable salt, stereoisomer, or mixture of stereoisomers thereof, having the following structure:

[0172] Among them, the variables Cy1, R3, R4, L1, L2, and A are as defined in this invention.

[0173] Some solutions in this invention are derived from arbitrary combinations of the above variables.

[0174] This invention also provides the following compounds or their pharmaceutically acceptable salts, stereoisomers, or mixtures of stereoisomers:

[0175] This invention also provides the following compounds or pharmaceutically acceptable salts thereof:

[0176] The present invention provides a pharmaceutical composition comprising the above-described compound or its pharmaceutically acceptable salt, stereoisomer, or mixture of stereoisomers, and a pharmaceutically acceptable carrier.

[0177] This invention provides the use of the above-mentioned compounds or pharmaceutically acceptable salts, stereoisomers, or mixtures of stereoisomers thereof in the preparation of medicaments for treating diseases or disorders related to calcitonin receptors and / or amyloid receptors.

[0178] In some embodiments of the present invention, the diseases or disorders related to the calcitonin receptor and / or amyloid receptor mentioned above are bone disorders, metabolic disorders, pain, neurodegenerative diseases or disorders, and cardiovascular diseases.

[0179] In some embodiments of the present invention, the diseases or disorders related to the calcitonin receptor and / or amyloid receptor mentioned above are type 1 diabetes, type 2 diabetes, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), insulin-dependent diabetes mellitus, non-insulin-dependent diabetes mellitus, impaired glucose tolerance, obesity, and diabetic complications.

[0180] Technical effect

[0181] Some of the compounds provided by this invention have in vitro amyloid and calcitonin receptor activity, and have potential as dual amyloid and calcitonin receptor agonists.

[0182] Definitions and Explanations

[0183] Unless otherwise stated, the following terms and phrases as used herein are intended to have the following meanings. A particular term or phrase should not be considered uncertain or unclear unless specifically defined, but should be understood in its ordinary sense. When a trade name appears herein, it is intended to refer to the corresponding product or its active ingredient.

[0184] The term "halogen" is used individually to refer to fluorine (F), chlorine (Cl), bromine (Br), or iodine (I). Fluorine (F) and chlorine (Cl) are particularly noteworthy.

[0185] The term “pharmaceutically acceptable” as used herein refers to compounds, materials, compositions, and / or dosage forms that, within the bounds of reliable medical judgment, are suitable for use in contact with human and animal tissues without excessive toxicity, irritation, allergic reactions, or other problems or complications, in proportion to a reasonable benefit / risk ratio.

[0186] The term "pharmaceutically acceptable salt" refers to a salt of the compounds of this invention, prepared by reacting a compound having specific substituents discovered in this invention with a relatively non-toxic acid or base. When the compounds of this invention contain relatively acidic functional groups, base addition salts can be obtained by contacting a neutral form of such compound with a sufficient amount of base in a pure solution or a suitable inert solvent. Pharmaceutically acceptable base addition salts include sodium, potassium, calcium, ammonium, organic amine, or magnesium salts or similar salts. When the compounds of this invention contain relatively basic functional groups, acid addition salts can be obtained by contacting a neutral form of such compound with a sufficient amount of acid in a pure solution or a suitable inert solvent.

[0187] The pharmaceutically acceptable salts of the present invention can be synthesized from parent compounds containing acid radicals or bases by conventional chemical methods. Generally, such salts are prepared by reacting these compounds in free acid or base form with a stoichiometric amount of a suitable base or acid in water or an organic solvent or a mixture thereof.

[0188] The compounds, their isomers, or pharmaceutically acceptable salts described in this application refer to both solvent-added and crystalline forms, particularly solvates or polymorphs. Solvates contain stoichiometric or non-stoichiometric solvents and are selectively formed during crystallization with pharmaceutically acceptable solvents such as water, ethanol, etc. For example, hydrates are formed when the solvent is water, or alcohols are formed when the solvent is ethanol. Solvates of general formula compounds are readily prepared or formed according to the methods described herein. For example, hydrates of general formula compounds are readily prepared by recrystallization from a mixture of water and an organic solvent, including but not limited to tetrahydrofuran, acetone, ethanol, or methanol. Furthermore, the compounds mentioned herein can exist in both solvated and non-solvated forms. Therefore, the compounds of the present invention (including their salts) include both solvated and non-solvated forms. In summary, for the purposes of the compounds and methods provided herein, the solvated form is considered equivalent to the non-solvated form.

[0189] "Pharmaceutical composition" means containing one or more of the compounds described in this application, their isomers or pharmaceutically acceptable salts thereof, and other components such as physiologically / pharmaceuticalally acceptable carriers and excipients. The purpose of a pharmaceutical composition is to facilitate administration to a living organism, thereby promoting the absorption of the active ingredient and the exertion of its biological activity.

[0190] The term "therapeutic effective amount" refers to an amount of a compound, when administered, sufficient to stop or slow the progression of one or more symptoms or conditions of a disease to a certain extent. The term "therapeutic effective amount" also refers to an amount of a compound sufficient to detect a biological or pharmaceutical response (e.g., protein, enzyme, RNA, or DNA) in a biomolecule, cell, tissue, system, animal, or human. This response is desired by researchers, veterinarians, physicians, or clinicians.

[0191] Unless otherwise stated, the term "isomer" is intended to include geometric isomers, cis-trans isomers, stereo isomers, enantiomers, optical isomers, diastereomers and tautomers.

[0192] The compounds of this invention can exist in specific geometric or stereoisomeric forms. This invention contemplates all such compounds, including cis and trans isomers, (-)- and (+)- enantiomers, (R)- and (S)- enantiomers, diastereomers, (D)- isomers, (L)- isomers, and racemic mixtures thereof, as well as other mixtures, such as mixtures enriched with enantiomers or diastereomers, all of which are within the scope of this invention. Additional asymmetric carbon atoms may be present in substituents such as alkyl groups. All such isomers and mixtures thereof are included within the scope of this invention.

[0193] Unless otherwise stated, the terms "enantiomer" or "optical isomer" refer to stereoisomers that are mirror images of each other.

[0194] Unless otherwise stated, the terms "cis-trans isomers" or "geometric isomers" arise because the single bonds of double bonds or cyclic carbon atoms cannot rotate freely.

[0195] Unless otherwise stated, the term "diastereomer" refers to a stereoisomer of a molecule having two or more chiral centers and being in a non-mirror relationship with each other.

[0196] Unless otherwise stated, "(+)" indicates right-handed rotation, "(-)" indicates left-handed rotation, and "(±)" indicates racemic rotation.

[0197] Unless otherwise specified, use wedge-shaped solid line keys. and wedge-shaped dashed key The absolute configuration of the center of a solid is represented by a straight solid line key. and straight dashed key The relative configuration of the center of a solid is indicated by a wavy line. Indicates wedge-shaped solid line key or wedge-shaped dashed key Or use wavy lines Indicates a straight solid line key Or straight dashed key

[0198] Unless otherwise stated, the terms "rich in one isomer," "isomer enrichment," "rich in one enantiomer," or "enantiomer enrichment" mean that the content of one isomer or enantiomer is less than 100%, and the content of the isomer or enantiomer is greater than or equal to 60%, or greater than or equal to 70%, or greater than or equal to 80%, or greater than or equal to 90%, or greater than or equal to 95%, or greater than or equal to 96%, or greater than or equal to 97%, or greater than or equal to 98%, or greater than or equal to 99%, or greater than or equal to 99.5%, or greater than or equal to 99.6%, or greater than or equal to 99.7%, or greater than or equal to 99.8%, or greater than or equal to 99.9%.

[0199] Unless otherwise stated, the terms "isomer excess" or "enantiomer excess" refer to the difference between the relative percentages of two isomers or two enantiomers. For example, if one isomer or enantiomer is 90% and the other isomer or enantiomer is 10%, then the isomer or enantiomer excess (ee value) is 80%.

[0200] Optically active (R)- and (S)- isomers, as well as D- and L- isomers, can be prepared by chiral synthesis, chiral reagents, or other conventional techniques. To obtain an enantiomer of a compound of the present invention, it can be prepared by asymmetric synthesis or derivatization with a chiral auxiliary, wherein the resulting diastereomeric mixture is separated, and the auxiliary group is cleaved to provide the desired enantiomer in pure form. Alternatively, when the molecule contains a basic functional group (such as an amino group) or an acidic functional group (such as a carboxyl group), a salt of the diastereomeric isomer is formed with a suitable optically active acid or base, followed by diastereomeric resolution using conventional methods known in the art, and then the pure enantiomer is recovered. Furthermore, the separation of enantiomers and diastereomeric isomers is typically accomplished by using chromatography employing a chiral stationary phase, optionally combined with chemical derivatization (e.g., from amines to carbamates).

[0201] The compounds of this invention may contain atomic isotopes in non-natural proportions on one or more atoms constituting the compound. For example, the compounds may be labeled with radioactive isotopes, such as tritium. 3 H), Iodine-125 125 I) or C-14 14C). For example, deuterium can be used to replace hydrogen to form deuterated drugs. The bond between deuterium and carbon is stronger than that between ordinary hydrogen and carbon. Compared with undeuterated drugs, deuterated drugs have advantages such as reduced toxicity, increased drug stability, enhanced efficacy, and prolonged drug biological half-life. All isotopic variations of the compounds of the present invention, regardless of radioactivity, are included within the scope of the present invention. Any structural formulas given herein are also intended to represent the unlabeled and isotopically labeled forms of the compounds. Isotopically labeled compounds have the structures depicted in the structural formulas given herein, except that one or more atoms are replaced by atoms having a selected atomic mass or mass number. Examples of isotopes that can be incorporated into the compounds of the present invention include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine, and chlorine, such as 2H, 3H, 11C, 13C, 14C, 15N, 18F, 31P, 32P, 35S, 36Cl, and 125I, respectively. This invention includes compounds as defined herein labeled with various isotopes, such as those containing radioactive isotopes such as 3H, 13C, and 14C.

[0202] The terms “optional” or “optionally” refer to events or conditions that may occur but are not required to occur as described below, and the description includes both cases where said events or conditions occur and cases where said events or conditions do not occur.

[0203] The terms "substituted" or "substituted" refer to the substitution of one or more hydrogen atoms on a particular atom by a substituent, which can include deuterium and hydrogen variants, provided the valence state of the particular atom is normal and the resulting compound is stable. When the substituent is oxygen (i.e., =O), it means that two hydrogen atoms are substituted. Oxygen substitution does not occur on aromatic groups. The term "optionally substituted" means that it may or may not be substituted, unless otherwise specified, and the type and number of substituents can be arbitrary on a chemically feasible basis.

[0204] When any variable (e.g., R) appears more than once in the composition or structure of a compound, its definition is independent in each case. Therefore, for example, if a group is substituted by 0-2 Rs, the group can optionally be substituted by at most two Rs, and the Rs in each case have independent options. Furthermore, combinations of substituents and / or their variants are only permitted if such combinations produce stable compounds. In some embodiments of the invention, the number of substitutions can each independently be 1, 2, 3, or 4.

[0205] When the number of a linking group is 0, such as -(CRR)0-, it indicates that the linking group is a single bond.

[0206] When the number of a substituent is 0, it means that the substituent does not exist. For example, -A-(R)0 means that the structure is actually -A.

[0207] When a substituent is vacant, it means that the substituent does not exist. For example, if X is vacant in AX, it means that the structure is actually A.

[0208] When one of the variables is selected as a single bond, it means that the two groups it connects to are directly connected. For example, when L in ALZ represents a single bond, it means that the structure is actually AZ.

[0209] When a substituent can be cross-bonded to two or more atoms on a ring, this substituent can bond with any atom on that ring, for example, structural units. This indicates that the substituent R can be substituted at any position on the cyclohexyl or cyclohexadiene. When the listed substituents do not specify which atom they are attached to the substituted group, such substituents can be bonded to any of their atoms. For example, a pyridyl group as a substituent can be attached to the substituted group through any carbon atom on the pyridine ring.

[0210] When the listed linking groups do not specify their linking direction, the linking direction is arbitrary, for example, The linker group L is -MW-. In this case, -MW- can connect ring A and ring B in the same direction as the reading order from left to right to form a ring. Alternatively, rings A and B can be connected in the opposite direction to the left-to-right reading order to form a ring. The combination of linking groups, substituents, and / or their variants is permitted only if such a combination produces a stable compound.

[0211] Unless otherwise specified, when a group has one or more connectable sites, any one or more sites of that group can be connected to other groups by chemical bonds. When the chemical bond connection is non-directional and the connectable site contains H atoms, the number of H atoms at that site will decrease accordingly with the number of chemical bonds connected, resulting in a group with a corresponding valence. The chemical bonds connecting the site to other groups can be straight solid line bonds. Straight dashed key or wavy line For example, a straight solid line bond in -OCH3 indicates that the oxygen atom in that group is connected to other groups; The straight dashed bond in the diagram indicates that the group is connected to other groups through both ends of the nitrogen atom in the group; The wavy lines in the diagram indicate that the phenyl group is connected to other groups through the carbon atoms at positions 1 and 2.

[0212] Unless otherwise specified, the number of atoms in a ring is usually defined as the elemental number of the ring. For example, a “5-7 elemental ring” refers to a “ring” with 5-7 atoms arranged around it.

[0213] Unless otherwise specified, C n-n+m Or C n -C n+m This includes any specific case with n to n+m carbons, such as C 1-12 Including C1, C2, C3, C4, C5, C6, C7, C8, C9, C 10 C 11 and C 12 It also includes any range from n to n+m, such as C 1-12 Including C 1-3 C 1-6 C 1-9 C 3-6 C 3-9 C 3-12 C 6-9 C 6-12 and C 9-12 Similarly, n-membered to n+m-membered rings represent the number of atoms in the ring from n to n+m. For example, 3-12-membered rings include 3-membered, 4-membered, 5-membered, 6-membered, 7-membered, 8-membered, 9-membered, 10-membered, 11-membered, and 12-membered rings, and also any range from n to n+m. For example, 3-12-membered rings include 3-6-membered, 3-9-membered, 5-6-membered, 5-7-membered, 6-7-membered, 6-8-membered, and 6-10-membered rings, etc.

[0214] Unless otherwise specified, the term "C1-C6 alkyl" is used to denote a straight-chain or branched saturated hydrocarbon group consisting of 1 to 6 carbon atoms. The C1-C6 alkyl group includes C... 1-6 C 1-5 C 1-4 C 1-3 C 1-2 C 2-6 C 2-4 C6, C5, C4, and C3 alkyl groups, etc.; they can be monovalent (e.g., methyl), divalent (e.g., methylene), or polyvalent (e.g., methine). 1-8 Examples of alkyl groups include, but are not limited to, methyl (Me), ethyl (Et), propyl (including n-propyl and isopropyl), butyl (including n-butyl, isobutyl, s-butyl and t-butyl), pentyl (including n-pentyl, isopentyl and neopentyl), hexyl, heptyl, octyl, etc.

[0215] Unless otherwise specified, the term "C" 1-4 "alkyl" is used to denote a straight-chain or branched saturated hydrocarbon group consisting of 1 to 4 carbon atoms. The C1-4 Alkyl groups include C 1-2 C 1-3 and C 2-3 Alkyl groups, etc.; they can be monovalent (e.g., methyl), divalent (e.g., methylene), or polyvalent (e.g., methine). C 1-4 Examples of alkyl groups include, but are not limited to, methyl (Me), ethyl (Et), propyl (including n-propyl and isopropyl), butyl (including n-butyl, isobutyl, s-butyl and t-butyl), etc.

[0216] Unless otherwise specified, the term "C" 1-3 "alkyl" is used to denote a straight-chain or branched saturated hydrocarbon group consisting of 1 to 3 carbon atoms. The C 1-3 Alkyl groups include C 1-2 and C 2-3 Alkyl groups, etc.; they can be monovalent (e.g., methyl), divalent (e.g., methylene), or polyvalent (e.g., methine). C 1-3 Examples of alkyl groups include, but are not limited to, methyl (Me), ethyl (Et), propyl (including n-propyl and isopropyl), etc.

[0217] Unless otherwise specified, "C3-C 10 "Cyclic hydrocarbon group" refers to a saturated or unsaturated cyclic hydrocarbon group consisting of 3 to 10 carbon atoms, including monocyclic, bicyclic, and tricyclic systems, wherein bicyclic and tricyclic systems include spirocyclic, fused, and bridged rings. The C3-C 10 Cyclic hydrocarbon groups include C 3-8 C 3-6 C 3-5 C 4-10 C 4-8 C 4-6 C 4-5 C 5-8 Or C 5-6 etc.; it can be monovalent, divalent, or polyvalent. C 3-10 Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, norbornelalkyl, [2.2.2]bicyclooctane, [4.4.0]bicyclodecane, spiro[2.4]cyclohexane, etc.

[0218] Unless otherwise specified, "C3-C6 cyclic hydrocarbon group" refers to a saturated or unsaturated cyclic hydrocarbon group consisting of 3 to 6 carbon atoms, including monocyclic, bicyclic, and tricyclic systems, wherein bicyclic and tricyclic systems include spirocyclic, fused, and bridged rings. The C3-C6 cyclic hydrocarbon group includes C 3-6 C 3-5 C 4-6 C 4-5 or C 5-6 etc.; it can be monovalent, divalent, or polyvalent. C 3-6Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc.

[0219] Unless otherwise specified, the term "3-10 membered heterocyclic alkyl" on its own or in combination with other terms refers to a saturated cyclic group consisting of 3 to 10 ring atoms, wherein 1, 2, 3, or 4 of the ring atoms are heteroatoms independently selected from O, S, N, P, and Se, and the remainder are carbon atoms, wherein the nitrogen atom is optionally quaternized, and the nitrogen, sulfur, and phosphorus heteroatoms may optionally be oxidized (i.e., NO, S(O)). p and P(O) p (where p is 1 or 2). It includes monocyclic, bicyclic, and tricyclic systems, with bicyclic and tricyclic systems including spirocyclic, fused, and bridged rings. Furthermore, regarding the "3-10 membered heterocyclic alkyl," the heteroatom can occupy the connection position between the heterocyclic alkyl group and the rest of the molecule. The 3-10 membered heterocyclic alkyl groups include 3-9, 3-8, 3-6, 5-9, 5, 6, 7, 8, and 9 membered heterocyclic alkyl groups, etc. Examples of 3-10 membered heterocyclic alkyl groups include, but are not limited to, azirrobutyl, oxacyclobutyl, thiocyclobutyl, pyrrolidinyl, pyrazolyl, imidazoalkyl, tetrahydrothiopheneyl (including tetrahydrothiophene-2-yl and tetrahydrothiophene-3-yl, etc.), tetrahydrofuranyl (including tetrahydrofuran-2-yl, etc.), tetrahydropyranyl, piperidinyl (including 1-piperidinyl, 2-piperidinyl and 3-piperidinyl, etc.), piperazinyl (including 1-piperidinyl and 2-piperidinyl, etc.), morpholinyl (including 3-morpholinyl and 4-morpholinyl, etc.), dioxane, dithiaalkyl, isoxazolyl, isothiazolyl, 1,2-oxazinyl, 1,2-thiaazinyl, hexahydropyridazinyl, homopiperidinyl, homopiperidinyl, or dioxaneheptyl, etc.

[0220] Unless otherwise specified, the term "5-membered heterocyclic alkyl" on its own or in combination with other terms refers to a saturated cyclic group consisting of 5 ring atoms, wherein 1, 2, or 3 of the ring atoms are heteroatoms independently selected from O, S, N, P, and Se, and the remainder are carbon atoms, wherein the nitrogen atom is optionally quaternized, and the nitrogen, sulfur, and phosphorus heteroatoms may optionally be oxidized (i.e., NO, S(O)). p and P(O) p (where p is 1 or 2). Examples of 5-membered heterocyclic alkyl groups include, but are not limited to, pyrrolidinyl, pyrazolyl, imidazoalkyl, tetrahydrothiophenyl (including tetrahydrothiophen-2-yl and tetrahydrothiophen-3-yl, etc.), tetrahydrofuranyl (including tetrahydrofuran-2-yl, etc.), tetrahydropyranyl, etc.

[0221] Unless otherwise specified, the term "aryl" refers to an aromatic hydrocarbon group, which may be monosubstituted or polysubstituted, monovalent, divalent, or polyvalent, and may be monocyclic or polycyclic (e.g., 1 to 3 rings; at least one of which is aromatic), fused together or covalently linked. "Aryl" can also be understood as a carbon-ring monocyclic or polycyclic aromatic ring system having a fully delocalized π-electron system throughout the ring; or a ring system in which an aromatic hydrocarbon group is fused with one or more non-aromatic ring groups, such as indenyl. The number of carbon atoms in "aryl" can vary, for example, 6, 7, 8, 9, 10, 11, or 12 carbon atoms. For example, the term "6-12-membered aryl" refers to a monocyclic or polycyclic aromatic ring system having 6 to 12 carbon atoms. Similarly, the term "6-membered aryl" can be understood as a monocyclic or polycyclic aromatic ring system having 6 carbon atoms. In this invention, aryl includes, but is not limited to, phenyl, biphenyl, naphthyl, etc.

[0222] Unless otherwise specified, the term "heteroaryl" refers to a fused or non-fused group or ring system having at least one aromatic ring and having five to fourteen ring atoms (one of which is selected from S, O, and N; zero, one, or two of which are other heteroatoms independently selected from S, O, and N; and the remaining ring atoms are carbon) of either a monocyclic or polycyclic (e.g., bicyclic, tricyclic, or more rings). The number of atoms in the ring of a heteroaryl can vary, for example, 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14 atoms. A "heteroaryl" can contain 5 to 12 atoms in the ring, 5 to 8 atoms in the ring, or 5 to 6 atoms in the ring. Specifically, the term "5-12-membered heteroaryl" is understood to refer to a monocyclic or polycyclic compound having 5 to 12 ring atoms (including 5, 6, 7, 8, 9, 10, 11, and 12) and at least one ring atom selected from heteroatoms of S, O, and N, including fused-ring and non-fused-ring systems. In this invention, heteroaryl includes, but is not limited to, triazolyl, tetrazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyrroleyl, pyrazolyl, imidazoleyl, thiazolyl, oxazolyl, isoxazolyl, thiadiazolyl, oxadiazolyl, thiophenyl, furanyl, quinolinyl, isoquinolinyl, benzimidazolyl, benzoxazolyl, quinoxalinyl, and similar groups.

[0223] Unless otherwise specified, the terms “heterocyclic group” or “heterocyclic hydrocarbon group” or “non-aromatic heterocycle” are synonymous and refer to saturated or unsaturated non-aromatic 3-, 4-, 5-, 6-, 7-, or 8-membered monocyclic ring systems, 7-, 8-, 9-, 10-, 11-, or 12-membered bicyclic ring systems (fused ring, bridged ring, or spirocycle), or 11-, 12-, 13-, or 14-membered tricyclic ring systems (fused ring, bridged ring, or spirocycle), wherein (i) each ring contains one to three heteroatoms independently selected from oxygen, sulfur, and nitrogen, (ii) each 5-membered ring has 0 to 1 double bonds, and each 6-membered ring has 0 to 2 double bonds, (iii) nitrogen heteroatoms and sulfur heteroatoms may optionally be oxidized, and (iv) nitrogen heteroatoms may optionally be quaternized. Representative heterocyclic hydrocarbon groups include, but are not limited to, [1,3]dioxacyclopentyl, pyrrolidinyl, pyrazolyl, pyrazolinyl, imidazolinyl, imidazolinyl, piperidinyl, piperazinyl, 2-pyridinone, oxazolyl, isoxazolyl, morpholinyl, tetrahydropyranyl, thiazolinyl, isothiazolyl, tetrahydrofuranyl, dioxacyclohexyl, oxetanyl, azetidinyl, thietanyl, oxiranyl, aziridinyl, thiiranyl, 2-oxa-5-azabicyclo[2.2.1]heptyl, 2,5-diazabicyclo[2.2.1]heptyl, 2-oxa-6-azaspiro[3.3]heptyl, 2,6-diazaspiro[ 3.3] Heptyl, 1,4-dioxa-8-azaspiro[4.5] Decyl, 2-azaspiro[3.3] Hept-5-amine, 1-azaspiro[3.3] Hept-5-amine, 1-oxa-6-azaspiro[3.3] Hept-3-amine, 2-azaspiro[3.3] Hept-6-amine, 1-azaspiro[3.3] Hept-6-amine, 6-azaspiro[3.4] Oct-2-amine, 5-azaspiro[3.4] Oct-2 -amine, 6-azaspiro[3.4]oct-1-amine, 5-azaspiro[3.4]oct-1-amine, 5-oxa-2-azaspiro[3.4]oct-7-amine, 7-amino-5-thia-2-azaspiro[3.4]octane 5,5-dioxide, 5-oxa-2-azaspiro[3.4]oct-8-amine, 8-amino-5-thia-2-azaspiro[3.4]octane 5,5-dioxide and similar groups.

[0224] Furthermore, the term "heterocyclic group" also includes groups that form spirocyclic or bridged rings from "heterocyclic groups" and "cyclic hydrocarbon groups," such as the following groups:

[0225] According to this application, any one of the aryl, substituted aryl, heteroaryl, and substituted heteroaryl groups described herein can be any aromatic group. The aromatic group can be substituted or unsubstituted.

[0226] In various parts of this invention, linking substituents are described. When the structure clearly requires a linking group, the Markush variables listed for that group should be understood as linking groups. For example, if the structure requires a linking group and the Markush group definition for that variable lists "alkyl," "aryl," or "cycloalkyl," it should be understood that "alkyl" or "aryl" represents a linked alkylene group, an arylene group, or a cycloalkylene group, respectively.

[0227] The compounds of the present invention can be prepared by a variety of synthetic methods known to those skilled in the art, including the specific embodiments listed below, embodiments formed by combining them with other chemical synthetic methods, and equivalent substitutions known to those skilled in the art. Preferred embodiments include, but are not limited to, the embodiments of the present invention.

[0228] The structures of the compounds of this invention can be confirmed by conventional methods well known to those skilled in the art. If this invention relates to the absolute configuration of a compound, that absolute configuration can be confirmed by conventional techniques in the art. For example, single-crystal X-ray diffraction (SXRD) is used, where the cultured single crystal is used to collect diffraction intensity data using a Bruker D8 venture diffractometer with CuKα radiation as the light source. The scanning method is as follows: After scanning and collecting relevant data, the crystal structure can be further analyzed using the direct method (Shelxs97) to confirm the absolute configuration.

[0229] The solvent used in this invention is commercially available.

[0230] This invention uses the following abbreviations: ACN represents acetonitrile; Boc represents tert-butyloxycarbonyl; Bn represents benzyl; DCM represents dichloromethane; DMSO represents dimethyl sulfoxide; ℃ represents degrees Celsius; hr represents hours; NaBH4 represents sodium borohydride; THF represents tetrahydrofuran; Ts represents p-toluenesulfonyl; Ac represents acetyl; Me represents methyl; Et represents ethyl; N2 represents nitrogen; PE represents petroleum ether; EA represents ethyl acetate; DIEA or DIPEA represents N,N-diisopropylethylamine; K2CO3 represents potassium carbonate; CuI represents cuprous iodide; TBAF represents tetrabutylammonium fluoride; CuBr represents... The table shows cuprous bromide; DMF represents N,N-dimethylformamide; HCl represents hydrogen chloride; MeOH represents methanol; TEA represents triethylamine; DMAP represents 4-dimethylaminopyridine; DIBAL-H represents diisobutylaluminum hydride; Dioxane represents dioxane; HATU represents 2-(7-azabenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate; EtOH represents ethanol; TsOH.H2O represents p-toluenesulfonic acid monohydrate; TosCl represents p-benzenesulfonyl chloride; DMA represents dimethylacetamide; IBX represents 2-iodobenzoic acid.

[0231] Compounds are named according to conventional naming principles in the field or using Software naming conventions are used; commercially available compounds use supplier catalog names. Detailed Implementation

[0232] The present invention will be described in detail below with reference to embodiments, but this does not imply any adverse limitation on the invention. The present invention has been described in detail, and specific embodiments thereof have been disclosed. It will be apparent to those skilled in the art that various changes and modifications can be made to the specific embodiments of the present invention without departing from the spirit and scope thereof. The compounds synthesized in this application can be referenced in documents such as WO2025015269 and WO2025015268. For some intermediates or starting materials, those skilled in the art can synthesize them by referring to the same or similar routes disclosed in the prior art, or they can be obtained commercially.

[0233] Example 1

[0234] Synthesis of Compound 1

[0235] Synthesis route:

[0236] Synthesis steps:

[0237] Step 1: Synthesis of compounds 1-3

[0238] In a clean single-necked flask, compound 1-1 (0.74 mL, 6 mmol) and compound 1-2 (0.87 g, 6 mmol) dissolved in 10 mL of dichloromethane were added at 0 °C. DMAP (1.51 g, 12.4 mmol) was added, and the reaction was continued for 2 h. 10 mL of water was added, and the aqueous phase was extracted with DCM (10 mL x 2). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated to give 1.36 g of the title compound 1-3 (yield: 99.3%).

[0239] Step 2: Synthesis of compounds 1-4

[0240] In a clean single-necked flask, compound 1-3 (1.0 g, 4.38 mmol) was added, dissolved in 10 mL of ethanol, and refluxed for 12 h. The solvent was concentrated to give the title compound 1-4, 0.75 g, yield: 99.4%.

[0241] Step 3: Synthesis of compounds 1-5

[0242] Compound 1-4 (3.0 g, 17.42 mmol) was added to a clean single-necked flask, dissolved in 30 mL of ethanol, and ammonia (8.0 mL, 142 mmol, wt = 30%) was added. The mixture was reacted for 12 h, the solvent was concentrated, and the mixture was purified by column chromatography (DCM / MeOH (v / v) = 20 / 1) to give 0.5 g of the title compound 1-5, yield: 20.2%.

[0243] Step 4: Synthesis of compounds 1-8

[0244] In a clean single-necked flask, compounds 1-6 (2.0 g, 12.33 mmol), 1-7 (1.49 g, 12.33 mmol), and tetraisopropyl titanate (7.0 g, 24.66 mmol) dissolved in THF (20 mL) were added and refluxed for 12 h. The solvent was concentrated, and the mixture was purified by column chromatography (PE / EA(v / v) = 10 / 1) to give the title compound 1-8, 3.0 g, yield: 91.7%.

[0245] Step 5: Synthesis of compounds 1-9

[0246] In a clean double-necked flask, compound 1-8 (3.0 g, 11.30 mmol) dissolved in THF (20 mL) was added at 0 °C, followed by the addition of DIBAL-H (22.6 mL, 22.60 mmol) and reaction for 2 h. Water and ethyl acetate were added, the mixture was separated, the organic phase was concentrated, and HCl / Dioxane (10 mL, 4 M) was added and stirred for 4 h. The solvent was then concentrated to give the title compound 1-9, 0.7 g, yield: 37.9%.

[0247] Step 6: Synthesis of compounds 1-11

[0248] In a clean single-necked flask, compounds 1-9 (0.7 g, 4.29 mmol) and 1-10 (0.67 g, 4.29 mmol) dissolved in DCM (2 mL) were added at 0 °C. HATU (2.45 g, 6.44 mmol) and DIEA (1.58 g, 12.26 mmol) were added, and the reaction was continued for 2 h. 10 mL of water was added, and the aqueous phase was extracted with ethyl acetate (20 mL * 2). The organic phases were combined, washed three times with saturated brine, dried over anhydrous sodium sulfate, filtered, and purified by concentrated solvent column chromatography (PE / EA (v / v) = 5 / 1) to give title compound 1-11, 1.00 g, yield: 77.37%.

[0249] Step 7: Synthesis of compounds 1-13

[0250] In a clean single-necked flask, compound 1-12 (2.0 g, 11.89 mmol) and compound 1-2 (2.57 g, 17.84 mmol) dissolved in DCM (20 mL) were added. DCC (4.90 g, 23.78 mmol) and DMAP (0.145 g, 1.19 mmol) were added, and the reaction was continued for 4 h. The solvent was concentrated, and the mixture was purified by column chromatography (PE / EA(v / v) = 5 / 1) to give title compound 1-13, 3.00 g, yield: 85.72%.

[0251] Step 8: Synthesis of compounds 1-14

[0252] Compound 1-13 (3.0 g, 10.19 mmol) was added to a clean single-necked flask and dissolved in EtOH (30 mL). The mixture was refluxed for 12 h, the solvent was concentrated, and the mixture was purified by column chromatography (PE / EA (v / v) = 5 / 1) to give the title compound 1-14, 2.00 g, yield: 82.4%.

[0253] Step 9: Synthesis of compounds 1-15

[0254] In a clean single-necked flask, compound 1-14 (1.4 g, 5.88 mmol), ethylene glycol (3.28 mL, 58.8 mmol), and TsOH·H₂O (8 mg, 0.042 mmol) dissolved in toluene (15 mL) were added. The mixture was refluxed for 12 h. The solvent was concentrated, and the mixture was purified by column chromatography (PE / EA (v / v) = 10 / 1) to give title compound 1-15, 0.37 g, yield: 22.0%.

[0255] Step 10: Synthesis of compounds 1-16

[0256] In a clean single-necked flask, compound 1-15 (0.37 g, 1.31 mmol), MeOH (3 mL), and H₂O (1 mL) were added. NaOH (210 mg, 5.24 mol) was then added, and the reaction proceeded for 3 h. The solvent was concentrated, and the pH was adjusted to approximately 4 with 1 N dilute hydrochloric acid. Ethyl acetate was added, and the mixture was separated. The aqueous phase was extracted twice with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and the solvent was concentrated to obtain compound 1-16 (0.30 g, yield: 90.0%). Step 11: Synthesis of compound 1-17

[0257] In a clean single-necked flask, compound 1-16 (0.30 g, 1.18 mmol), acetylhydrazine (0.175 g, 2.36 mmol), DMF (3 mL), HATU (538 mg, 1.42 mol), and DIEA (457 mg, 3.54 mol) were added, and the mixture was reacted at 50 °C for 3 h. Water and ethyl acetate were added, and the mixture was separated. The aqueous phase was extracted twice with ethyl acetate, and the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the solvent was concentrated. The mixture was purified by column chromatography (PE / EA (v / v) = 1 / 1) to give compound 1-17, 0.28 g, yield: 76.5%.

[0258] Step 12: Synthesis of compounds 1-18

[0259] In a clean single-necked flask, compound 1-17 (0.25 g, 0.81 mmol), DCM (3 mL), triethylamine (0.106 g, 1.05 mmol), and TosCl (184 mg, 0.97 mol) were added, and the mixture was reacted at 30 °C for 12 h. The solvent was concentrated, and the mixture was purified by column chromatography (DCM / MeOH (v / v) = 20 / 1) to give the title compound 1-18, 0.18 g, yield: 76.4%.

[0260] Step 13: Synthesis of compounds 1-19

[0261] In a clean single-necked flask, compound 1-18 (0.18 g, 6.16 mmol), formic acid (1 mL), and two drops of concentrated sulfuric acid were added. The mixture was reacted at 45 °C for 2 h. Water and ethyl acetate were added, and the mixture was separated. The aqueous phase was extracted twice with ethyl acetate, and the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the solvent was concentrated. The mixture was purified by column chromatography (PE / EA(v / v) = 3 / 1) to give compound 1-19, 0.12 g, yield: 78.5%.

[0262] Step 14: Synthesis of compounds 1-20

[0263] In a clean single-necked flask, compounds 1-19 (0.18 g, 0.725 mmol), 1-11 (0.218 g, 0.725 mmol), and 1-5 (0.113 g, 0.798 mmol) were added, along with 5 mL of ethanol. The mixture was reacted at 110 °C for 12 h. The solvent was concentrated, and the mixture was purified by column chromatography (PE / EA(v / v) = 3 / 1) to give the title compound 1-20, 0.4 g, yield: 84.13%.

[0264] Step 15: Synthesis of compounds 1-21

[0265] In a clean single-necked flask, compound 1-20 (0.40 g, 0.61 mmol), ethanol (2 mL), and cerium ammonium nitrate (548 mg, 0.999 mmol) were added, and the mixture was reacted at room temperature for 2 h. Water and ethyl acetate were added, and the mixture was separated. The aqueous phase was extracted twice with ethyl acetate, and the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the solvent was concentrated. The mixture was purified by column chromatography (PE / EA(v / v) = 1 / 1) to give compound 1-21, 0.300 g, yield: 75.23%.

[0266] Step 16: Synthesis of compounds 1-22

[0267] In a clean single-necked flask, compound 1-21 (0.300 g, 0.458 mmol), MeOH (3 mL), and H₂O (1 mL) were added. NaOH (55 mg, 1.374 mol) was then added, and the reaction was carried out at 50 °C for 3 h. The solvent was concentrated, and the pH was adjusted to approximately 4 with 1 N dilute hydrochloric acid. Ethyl acetate was added, and the mixture was separated. The aqueous phase was extracted twice with ethyl acetate. The combined organic phases were dried over anhydrous sodium sulfate, filtered, and the solvent was concentrated to give compound 1-22 (0.30 g), yield: 99.85%.

[0268] Step 17: Synthesis of Compound 1

[0269] In a clean single-necked flask, compounds 1-12 (0.30 g, 0.458 mmol), cyclopropanesulfonamide (0.055 g, 0.458 mmol), DMF (3 mL), HATU (261 mg, 0.687 mol), and DIEA (296 mg, 2.29 mol) were added, and the mixture was reacted for 12 h. Water and ethyl acetate were added, and the mixture was separated. The aqueous phase was extracted twice with ethyl acetate, and the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the solvent was concentrated. The mixture was purified by column chromatography (PE / EA (v / v) = 1 / 1) to give title compound 1, 0.167 g, yield: 48.09%, MS: (ESI, pos.ion) m / z: 758.2401 [M+H] + .

[0270] Example 2

[0271] Synthesis of Compound 2

[0272] Synthesis route:

[0273] Synthesis steps: Intermediates 2-5 and 2-8 are synthesized according to the method in Example 1.

[0274] Step 1: Synthesis of Compound 2

[0275] In a clean single-necked flask, compounds 2-8 (0.200 g, 0.732 mmol), 1-11 (0.220 g, 0.732 mmol), 2-5 (0.123 g, 0.878 mmol), and ethanol (5 mL) were added, and the mixture was reacted at 110 °C for 12 h. After cooling to room temperature, cerium ammonium nitrate (602 mg, 1.1 mmol) was added, and the mixture was reacted at room temperature for 2 h. Water and ethyl acetate were added, and the mixture was separated. The aqueous phase was extracted twice with ethyl acetate, and the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the solvent was concentrated. The mixture was purified by column chromatography (PE / EA(v / v) = 1 / 1) to give title compound 2, 0.315 g, yield: 63.5%. LCMS: (ESI, pos.ion) m / z: 678.7481 [M+H] + .

[0276] Example 3

[0277] Synthesis of Compound 3

[0278] Synthesis route:

[0279] Synthesis steps: Intermediates 1-5, 1-11, and 2-8 are synthesized according to the method in Example 1.

[0280] Step 1: Synthesis of Compound 3

[0281] In a clean single-necked flask, compounds 2-8 (0.200 g, 0.732 mmol), 1-11 (0.220 g, 0.732 mmol), 1-5 (0.125 g, 0.878 mmol), and ethanol (5 mL) were added, and the mixture was reacted at 110 °C for 12 h. After cooling to room temperature, cerium ammonium nitrate (602 mg, 1.1 mmol) was added, and the mixture was reacted at room temperature for 2 h. Water and ethyl acetate were added, and the mixture was separated. The aqueous phase was extracted twice with ethyl acetate, and the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and purified by solvent column chromatography (PE / EA (v / v) = 1 / 1) to obtain the title compound 3, 0.30 g, yield 60.3%. LCMS: (ESI, pos.ion) m / z: 680.2639 [M+H]+ .

[0282] Example 4

[0283] Synthesis of Compound 4

[0284] Synthesis route:

[0285] Step 1: Synthesis of compound 4-4

[0286] In a clean flask, compound 4-1 (232 mg, 802.06 μmol), compound 2-8 (220 mg, 802.06 μmol), compound 4-2 (162.87 mg, 962.47 μmol), and EtOH (10 mL) were added. The mixture was refluxed at 110 °C overnight, then cooled to room temperature before proceeding to the next step. Cerium ammonium nitrate (659.55 mg, 1.2 mmol) was added, and the mixture was reacted at room temperature for 4 h. Post-treatment: EA (50 mL) was added, the mixture was washed twice with water, dried, and purified by column chromatography (PE / EA (v / v) = 2 / 3) to give 155 mg of a brown solid, yield 27.8%, which was compound 4-4. LCMS: (ESI, pos.ion) m / z: 695.2569 [M+H] + .

[0287] Step 2: Synthesis of compounds 4-5

[0288] In a clean single-necked flask, compound 4-4 (155 mg, 223.09 μmol), lithium chloride (325.38 mg, 7.67 mmol), and DMA (5 mL) were added, and the mixture was refluxed at 150 °C for 12 h. Post-treatment: After cooling to room temperature, EA and water were added, the mixture was separated, and the organic phase was washed twice with NaCl solution, dried, and ready for the next step.

[0289] Step 3: Synthesis of Compound 4

[0290] In a clean single-necked flask, compounds 4-5 (145 mg, 217.47 μmol), ammonium chloride (58.16 mg, 1.09 mmol), HATU (2.25 g, 5.91 mmol), and DMF (10 mL) were added. The mixture was cooled to 0 °C, and DIPEA (2.55 g, 19.69 mmol) was added. The reaction was allowed to proceed for 12 h. Post-treatment: EA (50 mL) and water (20 mL) were added. The mixture was separated, and the organic phase was washed twice with NaCl solution, dried, and purified by column chromatography (PE / EA (v / v) = 1 / 2) to give 52 mg of a yellow solid, yield: 35.9%, which was compound 4. LCMS: (ESI, pos.ion) m / z: 666.2382 [M+H] + .

[0291] Referring to the synthetic routes of the compounds in Examples 1-4, and combining with existing technologies to disclose similar structural synthetic methods, the compounds described in this application form were synthesized.

[0292] Example 5

[0293] Synthesis of Compound 5

[0294] Synthesis route:

[0295] Synthesis steps:

[0296] Step 1: Synthesis of compound 5-5-3

[0297] In a clean two-necked flask, compound 5-5-1 (0.500 g, 1.84 mmol), compound 5-5-2 (0.414 g, 2.20 mmol), Pd2(dba)3 (0.168 g, 0.184 mmol), BINAP (0.229 g, 0.368 mmol), cesium carbonate (2.5 g, 7.36 mmol), and dioxane (10 mL) were added. The mixture was purged with nitrogen three times and reacted at 100 °C for 10 h. The solvent was concentrated, and the mixture was purified by column chromatography (PE / EA(v / v) = 3 / 1) to give the title compound 5-5-3, 0.550 g, yield: 87.4%. LCMS: (ESI, pos.ion) m / z: 343.0965 [M+H] + .

[0298] Step 2: Synthesis of compound 5-5-4

[0299] Compound 5-5-3 (0.500 g, 1.46 mmol) was added to a clean two-necked flask. The mixture was purged three times with nitrogen (10 mL THF) and reacted at 0 °C. Sodium borohydride (0.110 g, 2.92 mmol) and anhydrous calcium chloride (0.324 g, 2.92 mmol) were added, and the reaction was allowed to proceed for 2 h. 20 mL of water and ethyl acetate were added, and the mixture was separated. The organic phase was washed once with saturated brine, dried over anhydrous sodium sulfate, filtered, and the solvent was concentrated. The mixture was purified by column chromatography (PE / EA (v / v) = 3 / 1) to give the title compound 5-5-4, 0.345 g, yield: 75.15%. LCMS: (ESI, pos.ion) m / z: 315.0913 [M+H] + .

[0300] Step 3: Synthesis of compound 5-5-5

[0301] In a clean single-necked flask, compound 5-5-4 (0.345 g, 1.10 mmol) was added, along with ethyl acetate (10 mL) and IBX (0.616 g, 2.20 mmol). The mixture was reacted at 80 °C for 12 h. After filtration, the solvent was concentrated, and the mixture was purified by column chromatography (PE / EA (v / v) = 5 / 1) to give the title compound 5-5-5, 0.287 g, yield: 83.73%. LCMS: (ESI, pos.ion) m / z: 313.0837 [M+H] + .

[0302] Step 4: Synthesis of compound 5-6-2

[0303] In a clean single-necked flask, compound 5-6-1 (0.576 g, 3.79 mmol), ethoxyformylmethylenetriphenylphosphine (1.58 g, 4.54 mmol), and xylene (6 mL) were added, and the mixture was reacted at 150 °C for 12 h. The solution was concentrated with silica gel, and the mixture was purified by column chromatography (PE / EA(v / v) = 10 / 1) to give the title compound 5-6-2, 0.600 g, yield: 71.2%.

[0304] Step 5: Synthesis of compound 5-6-3

[0305] In a clean double-necked flask, compound 5-6-2 (0.600 g, 2.70 mmol), methanol (6 mL), and 10% Pd / C (0.3 g) were added. The mixture was purged three times with hydrogen and reacted at room temperature for 12 h. The mixture was filtered through diatomaceous earth, and the solvent was concentrated to obtain the title compound 5-6-3. The yield was assumed to be 100%, and the mixture was directly used in the next step.

[0306] Step 6: Synthesis of compound 5-6-4

[0307] In a clean single-necked flask, compound 5-6-3 (0.605 g, 2.70 mmol), methanol (6 mL), and sodium hydroxide (0.324 g, 8.09 mmol) were added, and the mixture was reacted at room temperature for 2 h. The solvent was concentrated, and the pH was adjusted to 4 with 1 N dilute hydrochloric acid. 20 mL of water and 20 mL of ethyl acetate were added, and the mixture was separated. The solution was washed once with saturated brine, dried over anhydrous sodium sulfate, and the solvent was concentrated to give the title compound 5-6-4, 500 mg, yield: 94.46%.

[0308] Step 7: Synthesis of compounds 5-6

[0309] In a clean single-necked flask, compound 5-6-4 (0.500 g, 2.55 mmol), THF (5 mL), and CDI (0.496 g, 3.06 mmol) were added to form component A. Compound 5-6-5 (0.630 g, 3.06 mmol), THF (5 mL), and magnesium chloride (0.243 g, 2.55 mmol) were added to form component B. The mixture was stirred at room temperature for 20 min. Component A was then added dropwise to component B, and the reaction was carried out at 50 °C for 12 h. The mixture was filtered through diatomaceous earth, the solvent was concentrated, and purified by column chromatography (PE / EA (v / v) = 2 / 1) to obtain the title compound 5-6, 500 mg, yield: 64.89%. LCMS: (ESI, pos.ion) m / z: 303.1141 [M+H] + .

[0310] Step 8: Synthesis of Compound 5-2

[0311] In a clean single-necked flask, compound 5-1 (4.7 g, 21.64 mmol), DCM (50 mL), DCC (4.51 g, 21.84 mmol), and DMAP (2.69 g, 22.03 mmol) were added. McFarland acid (3.78 g, 26.20 mmol) was added under ice bath conditions, and the reaction was carried out at room temperature for 12 h. The mixture was filtered through diatomaceous earth, and the filtrate was washed with 1 N citric acid solution. The first wash was with saturated sodium bicarbonate solution. The organic phase was dried over anhydrous sodium sulfate. The solvent was concentrated to obtain the title compound 5-2, which was then directly proceeded to the next step.

[0312] Step 9: Synthesis of Compound 5-3

[0313] In a clean single-necked flask, compound 5-2 (7.0 g, 20.51 mmol) and EtOH (70 mL) were added, and the reaction was carried out at 80 °C for 2 h. The solvent was concentrated to obtain the title compound 5-3, which was directly used in the next step based on a 100% yield.

[0314] Step 10: Synthesis of Compound 5-4

[0315] In a clean single-necked flask, compound 5-3 (6.0 g, 21.03 mmol), EtOH (60 mL), and ammonia (6 mL, wt = 30%) were added, and the reaction was carried out at room temperature for 12 h. The solvent was concentrated, and the mixture was purified by column chromatography (PE / EA (v / v) = 5 / 1) to give the title compound 5-4, 3.2 g, yield: 53.52%. LCMS: (ESI, pos.ion) m / z: 285.1842 [M+H] + .

[0316] Step 11: Synthesis of compounds 5-7

[0317] In a clean single-necked flask, compounds 5-5 (0.200 g, 0.64 mmol), 5-6 (0.193 g, 0.64 mmol), and 5-4 (0.218 g, 0.77 mmol) were dissolved in EtOH (3 mL) and reacted at 120 °C for 12 h. The solvent was concentrated, and the mixture was purified by column chromatography (PE / EA (v / v) = 1 / 1) to give the title compound 5-7, 200 mg, yield: 36.20%. LCMS: (ESI, pos.ion) m / z: 863.3434 [M+H] + .

[0318] Step 12: Synthesis of compounds 5-8

[0319] Compound 5-7 (0.200 g, 0.231 mmol) was added to a clean single-necked flask and dissolved in 2 mL of EtOH. Cerium ammonium nitrate (0.183 g, 0.346 mmol) was then added, and the mixture was reacted at room temperature for 2 h. The solvent was concentrated, and the mixture was purified by column chromatography (PE / EA (v / v) = 2 / 1) to give the title compound 5-8, 145 mg, yield: 72.67%. LCMS: (ESI, pos.ion) m / z: 860.3271 [M+H] + .

[0320] Step 13: Synthesis of compounds 5-9

[0321] In a clean single-necked flask, compound 5-8 (0.145 g, 0.168 mmol) was added and dissolved in DCM (1 mL) and TFA (1 mL). The reaction was carried out at room temperature for 1 h. The solvent was concentrated to give the title compound 5-9. The yield was assumed to be 100%, and the reaction proceeded directly to the next step.

[0322] Step 14: Synthesis of Compound 5

[0323] Compound 5-9 (0.120 g, 0.158 mmol) was added to a clean single-necked flask, dissolved in DCM (2 mL) and TEA (80 mg, 0.79 mmol), and reacted at 50 °C for 2 h. Purification by column chromatography (PE / EA (v / v) = 1 / 2) yielded the title compound 5, 78 mg, in 69.2% yield. LCMS: (ESI, pos.ion) m / z: 715.2331 [M+H] + .

[0324] Example 6

[0325] Synthesis of Compound 6

[0326] Synthesis route:

[0327] Synthesis steps:

[0328] Step 1: Synthesis of Compound 6

[0329] Following the synthesis method described in Example 5, a yellow solid compound 6 was obtained, with LCMS (ESI, pos.ion) m / z: 695.2651 [M+H]. + .

[0330] Example 7

[0331] Synthesis of Compound 7

[0332] Synthesis route:

[0333] Synthesis steps:

[0334] Step 1: Synthesis of Compound 7

[0335] Following the synthesis method described in Example 5, a yellow solid compound 7 was obtained, with LCMS (ESI, pos.ion) m / z: 695.2530 [M+H]. + .

[0336] Example 8

[0337] Synthesis of Compound 8

[0338] Synthesis route:

[0339] Synthesis steps:

[0340] Step 1: Synthesis of Compound 8

[0341] Following the synthesis method described in Example 5, a yellow solid compound 8 was obtained, with LCMS (ESI, pos.ion) m / z: 695.2647 [M+H]. + . 1H NMR(600MHz, CDCl3)δ8.07(d,J=5.6Hz,1H),7.35–7.26(m,5H),7.22–7.17(m,2H),7.07–7.01(m,2H),6.92(t,J=8.6 Hz,1H),5.89(q,J=7.8Hz,1H),4.82(ddd,J=31.6,10.3,6.3Hz,1H),4.51(d,J=6.8Hz,1H),3.85–3.71(m,2H),3.51–3 .37(m,2H),3.02–2.95(m,1H),2.91–2.84(m,1H),2.76(ddd,J=11.1,7.7,3.8Hz,1H),2.67–2.47(m,5H),2.38(ddd,J =18.2,9.7,4.9Hz,2H),2.06–2.00(m,2H),1.95(dtd,J=16.9,8.4,4.2Hz,1H),1.01–0.93(m,2H),0.80–0.62(m,2H).

[0342] Example 9

[0343] Synthesis of Compound 9

[0344] Synthesis route:

[0345] Synthesis steps:

[0346] Step 1: Synthesis of Compound 9

[0347] Following the synthesis method described in Example 5, a yellow solid compound 9 was obtained, with LCMS (ESI, pos.ion) m / z: 707.2652 [M+H]. + .

[0348] Example 10

[0349] Synthesis of Compound 10

[0350] Synthesis route:

[0351] Synthesis steps:

[0352] Step 1: Synthesis of compound 10-1-3

[0353] Compound 10⁻¹⁻¹ (2.0 g, 11.43 mmol) and THF (50 mL) were added to a 250 mL double-necked flask. The mixture was purged with nitrogen three times, cooled to -78 °C, and then 24.10 mL of n-butyllithium (1.6 M in THF) was added. The mixture was stirred for 1 h, followed by the addition of 20 mL of THF solution containing compound 10⁻¹⁻² (2.0 g, 17.53 mmol). The mixture was then cooled to -25 °C and reacted for 1 h. Post-treatment: The reaction was quenched with ammonium chloride solution, diluted with 100 mL of water, and the aqueous phase was washed twice with 20 mL of n-hexane. The pH of the aqueous phase was adjusted to approximately 2-3 with 1 N HCl. The aqueous phase was extracted with 100 mL of MTBE. The organic phase was washed twice with sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give 2.6 g of white solid compound 10⁻¹⁻³, yield 70.56%.

[0354] Step 2: Synthesis of compound 10-1-4

[0355] Compound 10⁻¹⁻³ (500 mg, 2.38 mmol), K₂CO₃ (394.5 mg, 2.85 mmol), DMF (5 mL), and CH₃I (405.1 mg, 2.85 mmol) were added to a clean single-necked flask, and the mixture was heated to 50 °C and reacted for 3 h. Post-treatment: Water (10 mL) and EA (20 mL) were added, the mixture separated into layers, the organic phase was washed once with water, twice with sodium chloride solution, dried over anhydrous sodium sulfate, and directly concentrated to give a colorless oily compound 10⁻¹⁻⁴, with a yield of 100%.

[0356] Step 3: Synthesis of compound 10-1-5

[0357] Compound 10⁻¹⁻⁴ (530 mg, 2.36 mmol) and DCM (5 mL) were added to a clean single-necked flask. The mixture was cooled to 0 °C, and then triethylsilane (1.65 g, 14.18 mmol) and TFA (3.5 mL) were added. The reaction was maintained at this temperature for 14 h. Post-treatment: The mixture was concentrated under reduced pressure until almost no fraction remained. DCM (20 mL) was added, and the pH was adjusted to approximately 8 with sodium bicarbonate solution. The mixture was allowed to separate into layers. The organic phase was washed twice with water and dried. The solution was concentrated to obtain a colorless oily compound 10⁻¹⁻⁵. The yield was calculated as 100%.

[0358] Step 4: Synthesis of Compound 10-1

[0359] Compound 10⁻¹⁻⁵ (490 mg, 2.35 mmol) and THF (5 mL) were added to a clean single-necked flask, followed by lithium hydroxide (281.7 mg, 11.77 mmol) dissolved in water (2 mL). After the addition was complete, the mixture was allowed to react at room temperature for 3 h. Post-treatment: The mixture was diluted with 20 mL of water, and the pH was adjusted to approximately 2-3 with 1 N HCl. The mixture was extracted twice with EA, and the organic phases were combined, washed twice with water, and once with sodium chloride solution. The mixture was dried and directly concentrated to obtain a colorless oily compound 10⁻¹, with a yield of 100%.

[0360] Step 5: Synthesis of Compound 10

[0361] Following the synthesis method described in Example 5, a yellow solid compound 10 was obtained, with LCMS (ESI, pos.ion) m / z: 713.2563 [M+H]. + .

[0362] Example 11

[0363] Synthesis of Compound 11

[0364] Synthesis route:

[0365] Synthesis steps:

[0366] Note: Intermediates 11-4 are synthesized using the same method as 1-9 in Example 1.

[0367] Step 1: Synthesis of compound 11-8-2

[0368] Compound 11-8-1 (15 g, 90.57 mmol) dissolved in water (150 mL) was added to a clean single-necked flask. Acetic anhydride (11.10 g, 108.68 mmol) and NaHCO3 (23 g, 273.38 mmol) were added, and the mixture was stirred at room temperature for 16 h. 100 mL of ethyl acetate was added, and the mixture was separated. The aqueous phase was extracted with ethyl acetate (2 x 100 mL). The organic phases were combined, washed once with saturated brine, dried over anhydrous sodium sulfate, filtered, and the solvent was concentrated to give 14.8 g of the title compound 11-8-2, yield: 95.45%.

[0369] Step 2: Synthesis of Compounds 11-8

[0370] Compound 11-8-2 (14.5 g, 84.70 mmol) dissolved in 290 mL of THF was added to a clean single-necked flask. Potassium tert-butoxide (19.01 g, 169.40 mmol) was added under ice bath conditions. After the addition was complete, the mixture was stirred at 80 °C for 3 h. The pH was adjusted to approximately 7 with dilute hydrochloric acid. The mixture was separated, and the aqueous phase was extracted with ethyl acetate (2 x 100 mL). The combined organic phases were washed once with saturated brine, dried over anhydrous sodium sulfate, filtered, and the solvent was concentrated to give 3.0 g of the title compound 11-8, yield: 25.4%.

[0371] Step 3: Synthesis of Compound 11-6

[0372] Compound 11-5 (0.25 g, 1.47 mmol), compound 11-4 (363.68 mg, 1.78 mmol), Pd(OAc)₂ (33 mg, 0.147 mmol), BINAP (183 mg, 0.294 mmol), and cesium carbonate (1.92 g, 5.88 mmol) dissolved in Dioxane (5 mL) were added to a clean two-necked flask. The mixture was purged three times with nitrogen and reacted at 100 °C for 12 h. The solvent was concentrated, and the mixture was purified by column chromatography (PE / EA(v / v) = 10 / 1) to give a yellow solid, compound 11-6, 353 mg, yield: 79.21%.

[0373] Step 4: Synthesis of Compounds 11-7

[0374] Compound 11-6 (350 mg, 1.16 mmol) was dissolved in THF (7 mL) and purged with nitrogen three times in a clean two-necked flask. The flask was then incubated at -78 °C. LDA (2 M, 3 mL) was added and stirring continued for 30 min. DMF (0.72 mL) was added and stirring continued for 1 h. The reaction was quenched with saturated ammonium chloride solution. The mixture was separated by adding 20 mL of ethyl acetate, and the aqueous phase was extracted with ethyl acetate (2 x 20 mL). The organic phases were combined, washed once with saturated brine, dried over anhydrous sodium sulfate, filtered, and the solvent was concentrated to give the title compound 11-7, 220 mg, in 57.5% yield.

[0375] Step 5: Compounds 11-9

[0376] In a clean single-necked flask, compound 11-7 (0.100 g, 0.303 mmol), compound 9-2 (89.1 mg, 0.303 mmol), compound 11-8 (50 mg, 0.359 mmol), and ammonium acetate (47 mg, 0.605 mmol) dissolved in AcOH (1 mL) were added. The mixture was purged three times with nitrogen and reacted at 120 °C for 2 h. Saturated sodium bicarbonate solution was added to adjust the pH to approximately 7. Ethyl acetate was added and the mixture was separated. The aqueous phase was extracted with ethyl acetate (2 x 20 mL). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, concentrated, and purified by solvent column chromatography (PE / EA (v / v) = 1 / 1) to give the title compound 11-9, 138 mg, yield: 62.71%. LCMS: (ESI, pos.ion) m / z: 727.2924 [M+H] + .

[0377] Step 6: Compound 11

[0378] In a clean single-necked flask, compound 11-9 (0.138 g, 0.190 mmol) was dissolved in EtOH (2 mL), followed by cerium ammonium nitrate (156 mg, 0.285 mmol). The reaction was carried out at room temperature for 1 h. 10 mL of water and ethyl acetate were added, and the mixture was separated. The aqueous phase was extracted with ethyl acetate (2 x 20 mL). The combined organic phases were dried over anhydrous sodium sulfate, filtered, and the solvent was concentrated. The mixture was purified by column chromatography (PE / EA (v / v) = 2 / 1) to give the title compound 11, 78 mg, yield: 56.67%. LCMS: (ESI, pos.ion) m / z: 725.2836 [M+H] + .

[0379] Example 12

[0380] Synthesis of Compound 12

[0381] Synthesis route:

[0382] Synthesis steps:

[0383] Step 1: Synthesis of Compound 12

[0384] Following the synthesis method of Example 11, a yellow solid compound 12 was obtained, with LCMS (ESI, pos.ion) m / z: 729.2189 [M+H]. + .

[0385] Example 13

[0386] Synthesis of Compound 13

[0387] Synthesis route:

[0388] Synthesis steps:

[0389] Note: Intermediates 13-6 are synthesized using the same methods as 1-9 in Example 1, and intermediates 13-8 are synthesized using the same methods as 11-7 in Example 11.

[0390] Step 1: Synthesis of Compound 13-2

[0391] In a clean double-necked flask, compound 13-1 (0.500 g, 2.18 mmol), copper acetylacetonate (0.370 g, 1.41 mmol), N,N'-bis(4-hydroxy-2,6-dimethylphenyl)oxalamide (0.430 g, 1.31 mmol), and DMSO (4 mL) were added. Potassium hydroxide (0.367 g, 6.55 mmol) was dissolved in H₂O (1 mL) and added to the reaction system. The mixture was purged with nitrogen three times and reacted at 80 °C for 3 h. The pH was adjusted to 4 with dilute hydrochloric acid, filtered through diatomaceous earth, and 20 mL of water and 20 mL of ethyl acetate were added. The mixture was separated, and the aqueous phase was extracted with ethyl acetate (2 x 20 mL). The organic phases were combined, washed three times with saturated brine, dried over anhydrous sodium sulfate, filtered, the solvent was concentrated, and purified by column chromatography (PE / EA (v / v) = 3 / 1) to give the title compound 13-2, 258 mg, yield: 71.2%. 1 H NMR (600MHz, CDCl3) δ7.05–7.00(m,1H),6.79(dd,J=9.6,2.1Hz,1H),3.04–2.98(m,2H),2.75(dd,J=6.6,4.8Hz,2H).

[0392] Step 2: Synthesis of Compound 13-3

[0393] In a clean single-necked flask, compound 13-2 (1.06 g, 6.38 mmol), potassium carbonate (2.65 g, 19.14 mmol), DMF (10 mL), and methyl iodoform (1.81 g, 12.76 mmol) were added. The mixture was reacted at room temperature for 2.5 h. 50 mL of water and 50 mL of ethyl acetate were added and the mixture was separated. The aqueous phase was extracted with ethyl acetate (2 x 50 mL), washed three times with saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated, and purified by column chromatography (PE / EA (v / v) = 4 / 1) to give the title compound 13-3, 657 mg, yield: 57.13%. 1H NMR (600MHz, CDCl3) δ6.99 (dd, J=7.2, 1.9Hz, 1H), 6.77 (dd, J=10.5, 1.9Hz, 1H), 3.89 (s, 3H), 3.02–2.96 (m, 2H), 2.72–2.66 (m, 2H).

[0394] Step 3: Synthesis of Compound 13

[0395] Following the synthesis method of Example 11, a yellow solid compound 13 was obtained, with LCMS (ESI, pos.ion) m / z: 725.2811 [M+H]. + . 1 H NMR(600MHz, CDCl3)δ8.06(d,J=5.6Hz,1H),7.34–7.26(m,5H),7.21(dd,J=15.9,8.8Hz,2H),7.04(d d,J=5.6,1.7Hz,1H),6.66(t,J=7.2Hz,1H),5.87(d,J=7.7Hz,1H),4.85–4.76(m,1H),4.49(s,1H),3 .85–3.74(m,5H),3.51–3.38(m,2H),2.95(dd,J=17.7,9.0Hz,1H),2.79–2.72(m,2H),2.68–2.50(m, 5H),2.42–2.34(m,2H),2.08–1.98(m,2H),1.97–1.87(m,1H),1.02–0.91(m,2H),0.79–0.60(m,2H).

[0396] Example 14

[0397] Synthesis of Compound 14

[0398] Synthesis route:

[0399] Synthesis steps:

[0400] Note: Intermediates 14-6 are synthesized using the same methods as 1-9 in Example 1, and intermediates 14-8 are synthesized using the same methods as 11-7 in Example 11.

[0401] Step 1: Synthesis of Compound 14-2

[0402] Formic acid (59.72 g, 1.3 mol) was weighed into a clean single-necked flask. Triethylamine (45.95 g, 454.13 mmol) was slowly added dropwise at 0 °C, followed by compound 14-1 (10 g, 64.88 mmol) and McFarland acid (9.35 g, 64.88 mmol). The mixture was stirred at 100 °C for 3 h. Post-treatment: The mixture was quenched with water, the pH was adjusted to 3-4 with concentrated hydrochloric acid, and 50 mL of ethyl acetate was added. The mixture was separated, and the aqueous phase was extracted with ethyl acetate (2 x 50 mL). The organic phases were combined, washed three times with saturated brine, dried over anhydrous sodium sulfate, filtered, the solvent was concentrated, and purified by column chromatography (PE / EA(v / v) = 3 / 1) to give the title compound 14-2, 10.9 g, yield: 84.77%. 1 H NMR (600MHz, CDCl3) δ7.00–6.88(m,3H),3.94(d,J=2.0Hz,3H),2.97(t,J=7.8Hz,2H),2.66(t,J=7.8Hz,2H).

[0403] Step 2: Synthesis of Compound 14-3

[0404] 10.9 g (55.00 mmol) of 14-2 was weighed into a clean single-necked flask, dissolved in 120 mL of DCE, and trifluoromethanesulfonic acid (41.27 g, 274.98 mmol) was added dropwise at 0 °C. After the addition was complete, the mixture was stirred at 120 °C for 1 h. 50 mL of water and 50 mL of ethyl acetate were added, and the mixture was separated. The aqueous phase was extracted with ethyl acetate (2 x 50 mL), washed three times with saturated brine, dried over anhydrous sodium sulfate, filtered, and the solvent was concentrated. The mixture was purified by column chromatography (PE / EA (v / v) = 4 / 1) to give the title compound 14-3, 7.23 g, yield: 72.96%.

[0405] Step 3: Synthesis of Compound 14

[0406] Following the synthesis method of Example 11, a yellow solid compound 14 was obtained, with LCMS (ESI, pos.ion) m / z: 725.2710 [M+H]. + .

[0407] Example 15

[0408] Synthesis of Compound 15

[0409] Synthesis steps:

[0410] Step 1: Synthesis of Compound 15

[0411] Following the synthesis method of Example 11, a yellow solid compound 15 was obtained, with LCMS (ESI, pos.ion) m / z: 713.2531 [M+H].+ . 1 H NMR (600MHz, CDCl3) δ8.07(d,J=5.6Hz,1H),7.35–7.27(m,5H),7.20(t,J=7.2Hz,1H),7.06(dd,J=5.6,1.3Hz,1H),6.87(t, J=7.0Hz,1H),6.68(t,J=9.0Hz,1H),5.93(q,J=7.9Hz,1H),4.82(ddd,J=31.7,10.4,6.3Hz,1H),4.49(d,J=8.4Hz,1H),3.85 –3.74(m,2H),3.51–3.39(m,2H),3.06(dd,J=15.0,7.8Hz,1H),2.86(dd,J=15.9,8.1Hz,1H),2.79(dtd,J=10.9,7.7,2.9Hz, 1H),2.70–2.51(m,5H),2.43–2.34(m,2H),2.00(dddd,J=21.0,16.7,8.5,3.8Hz,3H),1.01–0.93(m,2H),0.79–0.63(m,2H).

[0412] Example 16

[0413] Synthesis of Compound 16

[0414] Synthesis steps:

[0415] Step 1: Synthesis of Compound 16

[0416] Following the synthesis method of Example 11, a yellow solid compound 16 was obtained, with LCMS (ESI, pos.ion) m / z: 713.2532 [M+H]. + . 1H NMR(600MHz, CDCl3)δ8.06(d,J=5.6Hz,1H),7.35–7.26(m,5H),7.20(t,J=7.2Hz,1H),7.14(dd,J=16.0,6.8H z,1H),7.08–7.01(m,2H),5.86(q,J=7.7Hz,1H),4.82(ddd,J=31.7,10.3,6.4Hz,1H),4.48(s,1H),3.85–3.73 (m,2H),3.51–3.39(m,2H),2.97(dd,J=14.8,8.9Hz,1H),2.87(dt,J=15.4,7.7Hz,1H),2.79–2.71(m,1H),2. 69–2.50(m,5H),2.38(ddd,J=18.0,9.8,6.4Hz,2H),2.08–1.92(m,3H),1.02–0.92(m,2H),0.79–0.62(m,2H).

[0417] Example 17

[0418] Synthesis of Compound 17

[0419] Synthesis route:

[0420] Synthesis steps:

[0421] Note: Intermediate 17-6 is synthesized according to the method described in Example 6-2.

[0422] Step 1: Synthesis of Compound 17-2

[0423] Compound 17-1 (2.0 g, 13.32 mmol) was added to a clean 100 mL single-necked flask, dissolved in 20 mL of ethanol, and then 5.34 g of hydrazine hydrate (wt = 50%) was added. The mixture was stirred at 80 °C for 2 h. The solvent was concentrated to obtain the product, which was directly used in the next step with a yield of 100%.

[0424] Step 2: Synthesis of Compound 17-4

[0425] Compound 17-2 (2.0 g, 13.32 mmol) was added to a clean 100 mL single-necked flask and dissolved in 20 mL of ethanol. Compound 17-3 (2.29 g, 14.65 mmol) and sodium carbonate (1.55 g, 14.65 mmol) were then added, and the mixture was stirred at 80 °C for 2 h. The solvent was concentrated, and the mixture was purified by column chromatography (PE / EA = 2 / 1) to give compound 17-4, 887 mg, yield: 27.0%. LCMS (ESI, pos.ion) m / z: 247.0901 [M+H]+ Step 3: Synthesis of compound 17-5

[0426] Compound 17-4 (0.887 g, 3.60 mmol) was added to a clean 25 mL single-necked flask, dissolved in 9 mL of ethanol, and then potassium hydroxide (0.243 g, 4.32 mmol) was added. The mixture was stirred for 2 h. The solvent was concentrated to obtain a yellow solid product, which was then directly used in the next step.

[0427] Step 4: Synthesis of Compound 17

[0428] Following the synthesis method of Example 11, a yellow solid compound 17 was obtained, with LCMS (ESI, pos.ion) m / z: 745.2595 [M+H]. + . 1 H NMR(600MHz, CDCl3)δ8.07(d,J=5.6Hz,1H),7.36–7.26(m,5H),7.22–7.17(m,2H),7.02(t,J=5.8Hz,2 H),6.93(t,J=8.6Hz,1H),5.87(q,J=7.0Hz,1H),4.84(ddd,J=31.4,10.3,6.4Hz,1H),4.49(d,J=7.6Hz ,1H),3.82(ddt,J=29.0,12.2,8.4Hz,2H),3.46(ddd,J=23.2,16.1,6.5Hz,3H),3.00–2.95(m,1H),2. 91–2.72(m,5H),2.68–2.47(m,7H),2.38(dd,J=20.4,11.3Hz,2H),1.94(ddd,J=12.2,8.1,4.0Hz,1H).

[0429] Example 18

[0430] Synthesis of Compound 18

[0431] Synthesis steps:

[0432] Step 1: Synthesis of Compound 18

[0433] Following the synthesis method of Example 17, a yellow solid compound 18 was obtained, with LCMS (ESI, pos.ion) m / z: 725.2733 [M+H]. + . 1H NMR(600MHz, DMSO_d6)δ12.01(d,J=25.8Hz,1H),7.97(d,J=5.5Hz,1H),7.38–7.34(m,1H),7.29(dt,J=29.7,7.1Hz,6H),7.19(t,J=7.2Hz ,1H),7.06(dd,J=5.4,2.3Hz,1H),7.04–6.98(m,1H),6.94(d,J=9.0Hz,1H),6.72(d,J=32.2Hz,1H),5.89–5.81(m,1H),5.18(ddd,J=11.4, 6.6,2.2Hz,1H),4.15–4.06(m,1H),3.84–3.76(m,1H),3.71(dd,J=26.3,8.1Hz,1H),3.51(ddt,J=25.6,16.1,8.1Hz,3H),2.95(dd,J=13. 6,9.2Hz,1H),2.85–2.75(m,1H),2.60–2.51(m,3H),2.48–2.43(m,1H),2.29–2.08(m,6H),2.07–2.00(m,1H),0.85(dd,J=9.1,4.9Hz,2H).

[0434] Example 19

[0435] Synthesis of Compound 19

[0436] Synthesis steps:

[0437] Step 1: Synthesis of Compound 19

[0438] Following the synthesis method of Example 17, a yellow solid compound 19 was obtained, with LCMS (ESI, pos.ion) m / z: 713.2531 [M+H]. + . 1H NMR(600MHz, CDCl3)δ8.07(d,J=5.5Hz,1H),7.31(ddd,J=21.3,12.1,4.6Hz,5H),7.22–7.17(m,2H),7.06–7.00(m,2H),6 .93(t,J=8.6Hz,1H),5.88(dd,J=15.4,7.7Hz,1H),4.84(ddd,J=31.9,10.3,6.3Hz,1H),4.50(s,1H),3.83–3.73(m,2H), 3.46(ddd,J=20.8,14.9,9.1Hz,2H),3.01–2.95(m,1H),2.91–2.85(m,1H),2.80–2.72(m,1H),2.72–2.51(m,5H),2.38(d d,J=20.7,11.3Hz,2H),1.99–1.91(m,1H),1.57–1.48(m,2H),1.47(d,J=1.8Hz,1H),1.08(ddd,J=23.2,15.4,7.6Hz,2H).

[0439] Example 20

[0440] Synthesis of Compound 20

[0441] Synthesis steps:

[0442] Step 1: Synthesis of Compound 20-2

[0443] Compound 20-1 (1.0 g, 7.74 mmol) was added to a clean 50 mL single-necked flask and dissolved in 10 mL of dichloromethane. Triethylamine (0.94 g, 9.29 mmol) and methanesulfonyl chloride (1.06 g, 9.29 mmol) were added under ice bath conditions. The mixture was stirred at room temperature for 1 h. After washing once with 10 mL of saturated ammonium chloride, the product was dried over anhydrous sodium sulfate and filtered to concentrate the solvent. The product was then directly used in the next step with a yield of 100%.

[0444] Step 2: Synthesis of Compound 20

[0445] Following the synthesis method of Example 17, a yellow solid compound 20 was obtained, with LCMS (ESI, pos.ion) m / z: 802.2576.

[0446] Compounds 21-25 were synthesized according to the synthesis method of Example 17.

[0447] Example 27

[0448] Synthesis of Compound 27

[0449] Synthesis steps:

[0450] Step 1: Synthesis of Compound 27-2

[0451] Compound 27-1 (0.42 g, 2.91 mmol) was dissolved in 5 mL of DCM in a clean 25 mL single-necked flask. Two drops of DMF and thionyl chloride (0.518 g, 4.36 mmol) were added, and the mixture was stirred at room temperature under nitrogen protection for 2 h. The solvent was then concentrated to obtain the title compound 27-2, which was reserved for the next step.

[0452] Step 2: Synthesis of compound 27-4

[0453] Compound 27-3 (1.0 g, 4.83 mmol) was dissolved in 50 mL THF in a clean 250 mL two-necked flask, purged three times with nitrogen, and placed at -78 °C. DIBAL-H (14 mL, 1.5 M) was then added, and the mixture was stirred at room temperature for 4 h. The reaction was quenched by adding saturated ammonium chloride in an ice bath. The mixture was separated by ethyl acetate, washed once with saturated brine, dried over anhydrous sodium sulfate, filtered, the solvent was concentrated, and purified by column chromatography to give the title compound 27-4, 0.83 g, yield: 96.0%.

[0454] Step 3: Synthesis of compound 27-5

[0455] 27-4 (0.83 g, 4.63 mmol) was added to a clean 25 mL two-necked flask and dissolved in 9 mL of ethyl acetate. IBX (2.59 g, 9.26 mmol) was then added, and the mixture was stirred at 80 °C for 2 h. The mixture was filtered, the solvent was concentrated, and the solution was purified by column chromatography to give the title compound 27-5, 0.64 g, yield: 78.0%.

[0456] Step 4: Synthesis of compound 27-6

[0457] Compound 27-5 (0.48 g, 2.71 mmol) was added to a clean 25 mL two-necked flask and dissolved in 5 mL of DMF. Potassium carbonate (1.12 g, 8.13 mmol) and compound 27-2 (0.442 g, 2.71 mmol) were added, followed by a catalytic amount of KI. The mixture was stirred at 60 °C for 2 h. 20 mL of water and 20 mL of ethyl acetate were added, and the mixture was separated. The aqueous phase was washed three times with saturated brine, dried over anhydrous sodium sulfate, filtered, and purified by column chromatography to give the title compound 27-6, 0.343 g, yield: 41.7%.

[0458] Step 5: Synthesis of Compound 27

[0459] Following the synthesis method of Example 17, a yellow solid compound 27 was obtained, with LCMS (ESI, pos.ion) m / z: 736.2272.

[0460] Example 28

[0461] Synthesis of Compound 28

[0462] Synthesis steps:

[0463] Step 1: Synthesis of Compound 28

[0464] Following the synthesis method of Example 27, a yellow solid compound 28 was obtained, with LCMS (ESI, pos.ion) m / z: 720.2568.

[0465] Example 29

[0466] Synthesis of Compound 29

[0467] Synthesis steps:

[0468] Step 1: Synthesis of Compound 29-3

[0469] Compound 29-1 (4.0 g, 21.27 mmol) was added to a clean 250 mL two-necked flask and dissolved in 50 mL of ethyl acetate. Triethylamine (3.26 mL, 23.40 mmol) and compound 29-2 (3.8 mL, 29.78 mmol) were added. The mixture was purged three times with nitrogen and stirred at 85 °C for 2 h. The solvent was concentrated, and the mixture was purified by column chromatography to give the title compound 29-3, 5.21 g, yield: 71.7%.

[0470] Step 2: Synthesis of compound 29-4

[0471] Compound 29-3 (3.86 g, 11.19 mmol) was added to a clean 250 mL single-necked flask, dissolved in 40 mL of DMF, and potassium carbonate (3.09 g, 22.38 mmol) was added. The mixture was placed at 60 °C and stirred for 2 h. 50 mL of water and 50 mL of ethyl acetate were added, the mixture was separated, washed three times with saturated brine, dried over anhydrous sodium sulfate, filtered, the solvent was concentrated, and purified by column chromatography to give 1.7 g of the title compound 29-4 (yield: 57.6%).

[0472] Step 3: Synthesis of Compound 29-5

[0473] Compound 29-4 (1.70 g, 6.44 mmol) was added to a clean 250 mL two-necked flask and dissolved in 17 mL of THF. The mixture was placed at -10 °C, and isopropylmagnesium bromide (7 mL, 7 mmol) was added. The mixture was stirred for 30 min, cooled to -30 °C, and n-butyllithium (16 mL, 25.6 mmol) was added. The mixture was stirred for 30 min, and DMF (2 mL, 25.76 mmol) was added. After the addition was complete, the mixture was allowed to react at room temperature for 1 h. 50 mL of saturated ammonium chloride solution and 50 mL of ethyl acetate were added. The mixture was separated, washed once with saturated brine, dried over anhydrous sodium sulfate, filtered, and the solvent was concentrated. The solution was purified by column chromatography to give the title compound 29-5, 0.77 g, yield: 56.1%.

[0474] Step 4: Synthesis of Compound 29

[0475] Following the synthesis method of Example 27, a yellow solid compound 29 was obtained, with LCMS (ESI, pos.ion) m / z: 772.2084.

[0476] Example 30

[0477] Experiment 1: In vitro hCTR and hAMYR3 (CTR & RAMP3) target agonist activity assay

[0478] In vitro efficacy evaluation: Stable expression of CTR & RAMP3 COS7 (purchased from Nanjing Kebai Biotechnology Co., Ltd., catalog number CBP71505) and CTR COS7 cell lines (purchased from Nanjing Kebai Biotechnology Co., Ltd., catalog number CBP71484) were used. Stable cells were stimulated with different concentrations of agonists. The time-resolved fluorescence resonance energy (TRRF) signal of the cells after stimulation with each dose was measured using HTRF technology, and the bioactivity of the agonists was calculated. EC50 was obtained through statistical calculations. 50 Value, using EC 50 The values ​​are used to characterize the in vitro activity of the compounds.

[0479] Reagents: Prepare the Assay buffer (DMEM + 10% FBS + 500 μM IBMX) according to the table below, aliquot it, and store it at -20℃ for later use.

[0480] Testing process:

[0481] 1) CTR&RAMP3 COS7 cells or CTR COS7 cells were cultured in a CO2 incubator at 37°C using complete culture medium until the cell density reached 70-80% confluence, at which point the cell suspension was collected. Experimental wells and blank control wells were also provided.

[0482] 2) Compound Preparation: The natural peptide Amylin or Calcitonin (salmon calcitonin) or the analyte compound should first be prepared to a 400X working solution concentration using DMSO. Both the natural peptide and the compound should be diluted 5-fold, with 10 spots, replicates, or single wells. Then, the compound should be diluted 100-fold using Assy buffer to prepare a 2X working solution concentration (the working concentration should be twice the final concentration). The final DMSO concentration should be 0.5%.

[0483] 3) Seed CTR&RAMP3 COS7 cells or CTR COS7 cells at a density of approximately 5000 cells / well in 5 μL of serum-containing complete medium into 384-well microplates with an opaque white bottom. Add an equal volume of complete medium to each blank control well.

[0484] 4) Add 5 μL of serially diluted test compound or quality control STD (cAMP) to each well of a 384 microplate, centrifuge at 200g for 30s, and incubate at 37℃ for 30min. Add an equal volume of Assay buffer to each blank control well.

[0485] 5) Remove the 384-well plate after incubation. Add 5 μL of Eu-anti-cAMP (1 / 5 times) to each well, then add 5 μL of Eu-Camp tracer (1 / 5 times) to each well. Cover the plate, centrifuge at 200g for 30s, and incubate at 25℃ for 60min.

[0486] 6) Data were read using an Enhance 2014 multi-functional microplate reader. Detection conditions were: excitation light: 340 nM, emission light: 665 nM and 620 nM. Data reading: Ratio = 665 nM / 620 nM * 1000.

[0487] 7) Data Analysis: Use the "log(agonist) vs. response -- variable slope" model in GraphPad Prism 8.0 to fit and process the data, and calculate EC. 50 %Activity = (VC - Detection Data) / (VC - PC) * 100%;

[0488] CTR & RAMP3 Assay: PC is the average value of well data corresponding to 20nMAmylin; VC is the average value of well data corresponding to 0.5% DMSO.

[0489] CTR Assay: PC is the average value of well data corresponding to 20 nM Calcitonin (salmon); VC is the average value of well data corresponding to 0.5% DMSO.

[0490] The experimental results are as follows:

[0491] Experiment 2: In vitro hCTR and hAMYR3 (CTR & RAMP3) target agonist activity assay

[0492] Testing process:

[0493] (1) Prepare the Assay buffer (HBSS, 20mM HEPES, 0.1% Casein, 500uM IBMX) in advance for later use.

[0494] (2) Compound preparation: Natural peptide Amylin or Calcitonin (salmon, frog calcitonin), or the test compound or cAMP (quality control) were first prepared into a 200X working solution concentration using DMSO. Both the natural peptide and the compound were diluted 4-fold, resulting in 10 concentration points. Using an Echo device, the diluted test compound or cAMP was added to a 384-well microplate at a rate of 50 nL per well, with a final DMSO concentration of 0.5%.

[0495] (3) Thaw either AMP3 HEK293 (constructed by WuXi AppTec) or CTR HEK293 (constructed by WuXi AppTec). Then wash twice with HBSS, resuspend in assay buffer for cell counting, and adjust the cell density to 1.0 × 10⁻⁶. 6 Cells / mL. Prepared AMP3 HEK293 (10000 cells / 10 μL) or CTRHEK293 (5000 cells / 10 μL) cell suspensions were seeded into 384-well microplates containing the compound. An equal volume of buffer was added to each well for the blank control. The plates were then vortexed for 20 seconds, centrifuged at 1000 rpm for 10 seconds, and incubated at 23°C for 1 hour.

[0496] (4) Add 10 μL of Eu-labeled antibody + cAMP tracer solution (50 μL Eu-labeled antibody + 50 μL tracer solution, placed in 5 mL of detection buffer) to a 384 microplate, vortex for 20 seconds, centrifuge at 1000 rpm for 10 seconds, and then incubate at 23 degrees Celsius for 1 hour.

[0497] (5) Data were read using the Envsion multi-mode microplate reader. The detection conditions were: excitation light: 340 nM, emission light: 665 nM and 615 nM. The experimental data were processed using GraphPad Prism 8.0.

[0498] The experimental results are as follows: Note: ＊The control compound 122 is WO2025015268A1 compound 122; ＊＊ The reference compound 199 is WO2025015269A1.

[0499] The results show that the compounds provided by this invention have good in vitro activity in regulating amyloid and / or calcitonin receptors, and have potential for use as dual amyloid and calcitonin receptor agonists.

[0500] Example 31 Liver microsomal stability experiment

[0501] Experimental objective: To test the stability of the compounds of this invention in the liver microsomes of CD-1 mice, SD rats, beagle dogs, cynomolgus monkeys and humans.

[0502] Experimental procedure:

[0503] 1. Prepare the microparticle working solution according to the table below.

[0504] 2. Add microsomal working solution to the incubation plate. In this study, diclofenac was used as a positive control. The final concentration of both the test sample and diclofenac was 1 μM. The working solution was preheated at 37°C for 5 minutes.

[0505] 3. Add NADPH regeneration solution to the incubation plate to start the reaction. Samples without NADPH (named NCF60 and NCF0, respectively) are used as negative controls. Incubate the solution at 37°C.

[0506] 4. At 0, 5, 15, 30, and 60 minutes, the reaction was stopped by adding 300 μL of a 1:1 solution of cold methanol:acetonitrile containing internal standards (100 ng / mL labetalol, 100 ng / mL toluenebutyramide). The sample was centrifuged at 4000 rpm for 10 minutes. 100 μL of the supernatant was mixed with 100 μL of H2O and then used for LC-MS / MS analysis.

[0507] 5. Data Analysis

[0508] All calculations were performed using Microsoft Excel.

[0509] Peak areas were determined based on the extracted ion chromatograms. The slope value k was determined by linear regression of the natural logarithm of the remaining percentage of parent drug against the incubation time curve.

[0510] Determine the in vitro half-life (in vitro t) based on the slope value. 1 / 2 )

[0511] in vitro t 1 / 2 =-(0.693 / k)

[0512] The following equation (average of repeated measurements) was used to calculate the in vitro t 1 / 2 (min) is converted to in vitro intrinsic clearance rate (in vitro CLint, in μL / min / mg protein).

[0513] 【1】CL int (mL / min / kg)=(0.693 / T 1 / 2 )×(1 / (microsomal protein concentration (0.5 mg / mL)))×conversion factor

[0514] [1] Conversion factor = (amount of microsomal protein per gram of liver) × (weight of liver per kilogram of body weight)

[0515] The results for representative compounds are shown in the table below: Note: ＊ The control compound 122 is WO2025015268A1 compound 122; ＊＊ The reference compound 199 is WO2025015269A1.

[0516] The results showed that the compound in this patent significantly improved the stability of liver microsomes compared to the control compound.

[0517] Example 32: Pharmacokinetic Experiment of SD Rats

[0518] laboratory animals

[0519] Adaptation: SD rats (SPF grade, male, over 6 weeks old, weighing >180g) were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. Upon arrival at the facility, veterinarians or other authorized personnel will assess the overall health of the animals. Animals must acclimatize for at least 3 days before being used in experiments.

[0520] Environmental conditions: Environmental controls will be set to maintain a temperature between 20 and 26 degrees Celsius, a relative humidity between 30% and 70%, an air exchange rate of at least 15 times per hour, and a 12-hour light / 12-hour dark cycle. The light / dark cycle may be interrupted due to research-related activities. Any deviations from these ranges will be assessed according to relevant standard operating procedures.

[0521] Husbandry: During the acclimatization and research periods, animals will be housed in groups (maximum four same-sex animals per cage) in polysulfone cages lined with certified willow shavings or corn cob bedding. Animals may also be housed individually after surgery, as required by the experimental protocol, for behavioral or health reasons, or due to the death of other animals in the same cage. Animals will have free access to certified rodent breeding and growth feed daily, except for fasting for research purposes. Each batch of feed will be analyzed for nutritional composition, chemical contaminants, and microorganisms; the results will be reviewed and evaluated by a veterinarian before being provided to the animals. Analysis reports will be maintained and archived. Animals will be fed their daily diet. Autoclaved reverse osmosis water will be provided free of charge to all animals. Toys will be provided during the acclimatization period.

[0522] Feed and water composition analysis: Autoclaved reverse osmosis water is provided to the animals freely through water bottles. Water samples are periodically tested by a certified laboratory to determine the presence of specific microorganisms and environmental contaminants. The diet is also routinely tested by the manufacturer to determine the presence of specific microorganisms, nutrients, and environmental contaminants. Test results are reviewed and evaluated by veterinarians and archived.

[0523] Main reagents

[0524] Experimental procedure:

[0525] The pharmacokinetic characteristics of the compounds in rats after a single intravenous injection or a single oral administration were tested using a standard protocol. In the experiment, all candidate compounds were prepared into a clear solution using a solvent system of 5% DMSO + 10% Solutol + 85% Saline. A single intravenous injection (iv, n=3) of 1 mg / kg and a single oral administration (po, n=3) of 5 mg / kg were administered. Whole blood was collected from the animals at 5 min, 15 min, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h, and 24 h after administration. Plasma was separated, and pharmacokinetic parameters were calculated using Phoenix WinNonlin 8.2.0 based on the blood drug concentration data at different time points.

[0526] Rat pharmacokinetic parameters table Note: ＊ The control compound 122 is WO2025015268A1 compound 122; ＊＊ The reference compound 199 is WO2025015269A1.

[0527] The results showed that the patented compound had significant advantages in pharmacokinetic parameters and a significant improvement in exposure levels compared to the control compound.

[0528] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention shall be considered equivalent substitutions and shall be included within the protection scope of the present invention.

Claims

1. A compound of formula (I) or a pharmaceutically acceptable salt, stereoisomer, or mixture of stereoisomers thereof, having the following structure: in: The structural unit represents a nitrogen-containing heterocycle, selected from... or, The structural unit represents a nitrogen-containing heterocycle, selected from... Cy1 is selected from: C3-C12 cyclic hydrocarbon groups, aryl groups, heterocyclic groups comprising one, two, or three 5- or 6-membered rings and 1-3 heteroatoms selected from N, O, and S, or heteroaryl groups comprising one, two, or three 5- or 6-membered rings and 1-3 heteroatoms selected from N, O, and S; said cyclic hydrocarbon group, aryl group, heterocyclic group, or heteroaryl group is a spirocyclic, bridged ring, fused ring, or monocyclic ring; said cyclic hydrocarbon group, heterocyclic group, aryl group, or heteroaryl group is optionally substituted by one or more substituents independently selected from: deuterium, OH, carboxyl, halogen, NH2, CN, NO2. Oxylated, thiolated, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cyclic hydrocarbon, 3-8 membered heterocyclic, aryl or heteroaryl, wherein the C3-C8 cyclic hydrocarbon, 3-8 membered heterocyclic, aryl or heteroaryl is optionally substituted by one or more substituents independently selected from: deuterium, OH, carboxyl, halogen, NH2, CN, NO2, C1-C8 alkyl, C3-C8 cyclic hydrocarbon, C1-C6 haloalkyl, C1-C6 hydroxylated alkyl, C1-C8 alkoxy or The cyclic hydrocarbon group, aryl group, heterocyclic group, or heteroaryl group is a spirocyclic, bridged ring, fused ring, or monocyclic ring; A is selected from: C3-C12cycloalkyl, aryl, heterocyclyl comprising one, two or three 5- or 6-membered rings and 1-3 heteroatoms selected from N, O and S, or heteroaryl comprising one, two or three 5- or 6-membered rings and 1-3 heteroatoms selected from N, O and S; said cycloalkyl, aryl, heterocyclyl or heteroaryl is spirocyclic, bridged cyclic, fused cyclic or monocyclic; said cycloalkyl, heterocyclyl, aryl or heteroaryl is optionally substituted with one or more substituents independently selected from R 1A ; R 1A Selected from: hydrogen, deuterium, OH, carboxyl, halogen, NH2, CN, NO2, oxo, thio, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C2-C8 alkenyl, haloC2-C8 alkenyl, C2-C8 alkynyl, haloC2-C8 alkynyl, C3-C8 cyclic hydrocarbon, 3-8 membered heterocyclic group, aryl or heteroaryl; Or, R 1A The connection between A and L2 causes A and L2 to form a heterocyclic group together; or R 1A The connection between R4 and A, L2, and R4 forms a heterocyclic group; in this case, R 1A The structural part is independently selected from: C1-C8 alkylene, C1-C8 haloalkylene, C1-C8 alkoxide, C1-C8 haloalkoxide, C2-C8 alkenyl, haloC2-C8 alkenyl, C2-C8 alkyne, haloC2-C8 alkyne, -NH-alkylene-, -NHC(O)-, -C(O)NH-, -alkylene-NHC(O)-, -alkylene-C(O)NH-, -NHC(O)-alkylene-, -C(O)NH-alkylene-, -C(O)-; R1 is selected from: None C3-C12 alkyl, C3-C12 cycloalkyl, The alkyl, cycloalkyl, aryl, heterocyclic, or heteroaryl group comprises one, two, or three 5- or 6-membered rings and one to four heteroatoms selected from N, O, and S, wherein the alkyl, cycloalkyl, aryl, heterocyclic, or heteroaryl group is optionally substituted by one or more substituents independently selected from: deuterium, halogen, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cycloalkyl, OH, NH2, oxo, thio, -NH-(C1-C6 alkyl), -N(C1-C6 alkyl)2, CN, NO2, carboxyl, 3-8 membered heterocyclic groups, aryl groups, or heteroaryl groups; X is selected from: Wherein, W is selected from O, CH2, CF2, CHF, S, SO, SO2 or SO(NH); R2 is selected from: none, NH2, C1-C10 alkyl, -(CH2). 0-6 -C3-C10 cyclic hydrocarbon groups, -(CH2) 0-6 -3-10 membered epoxy group, wherein the alkyl, cycloalkyl, and epoxy group are optionally substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocyclic, aryl or heteroaryl; R3 and R4 are each independently selected from: C1-C10 alkyl, C3-C10 cycloalkyl, aryl, heterocyclic groups comprising one, two, or three 3-, 4-, 5-, 6-, or 7-membered rings and one to three heteroatoms selected from N, O, and S, or heteroaryl groups comprising one, two, or three 3-, 4-, 5-, 6-, or 7-membered rings and one to three heteroatoms selected from N, O, and S, wherein the cycloalkyl, aryl, heterocyclic, or heteroaryl group is a spirocyclic, bridged ring, fused ring, or monocyclic ring, and the alkyl, cycloalkyl, aryl, heterocyclic, or heteroaryl group is optionally composed of one or more independent The substituents are selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cyclic hydrocarbon, -O-C3-C8 cyclic hydrocarbon, 3-8 membered heterocyclic group, aryl, heteroaryl, deuterated C1-C8 alkyl, deuterated C1-C8 haloalkyl, deuterated C1-C8 alkoxy, deuterated C1-C8 haloalkoxy, deuterated C3-C8 cyclic hydrocarbon, deuterated -O-C3-C8 cyclic hydrocarbon; L1 and L2 are each independently selected from: none, C1-C6 alkylene, halo-C1-C6 alkylene, C2-C6 alkenyl, halo-C2-C6 alkenyl, C2-C6 alkyne, halo-C2-C6 alkyne, -O-alkylene-, -NH-alkylene-, -NHC(O)-, -C(O)NH-, -alkylene-NHC(O)-, -alkylene-C(O)NH-, -NHC(O)-alkylene-, -C(O)NH-alkylene-, -C(O)-, -NH-aryl, -NH-, C3-C10 cyclic hydrocarbon, aryl, containing one or two or three 3-membered, 4-membered, 5-membered or 6-membered rings and 1-3 selected from Heterocyclic groups containing N, O, and S heteroatoms, or heteroaryl groups comprising one or two or three 3-, 4-, 5-, or 6-membered rings and one to three heteroatoms selected from N, O, and S, wherein the alkylene, cycloalkyl, aryl, heterocyclic, or heteroaryl group is optionally substituted by one or more substituents independently selected from: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cycloalkyl, 3-8-membered heterocyclic, aryl, or heteroaryl group, wherein the cycloalkyl, aryl, heterocyclic, or heteroaryl group is a spirocyclic, bridged ring, fused ring, or monocyclic. R 1e R 1h and R 1g Independently selected from: hydrogen, OH, carboxyl, NH2, C1-C10 alkyl, C1-C10 haloalkyl, C1-C10 alkoxy, C1-C10 haloalkoxy, C1-C10 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, -O-C3-C10 cycloalkyl or aryl; R 1a and R 1b Independently selected from: hydrogen, C3-C10 cyclic hydrocarbon group, C1-C10 alkyl group, Or R 1a and R 1b Together with the nitrogen atom to which they are attached, they form a C3-C10 heterocyclic group, wherein the heterocyclic group, cycloalkyl group and alkyl group are optionally substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocyclic group, aryl or heteroaryl; R 1c and R 1d Independently selected from: hydrogen, C3-C10 cyclic hydrocarbon group, C1-C10 alkyl group, Or R 1c and R 1d Together with the carbon atoms to which they are attached, they form a C3-C10 cyclic hydrocarbon group, wherein the cyclic hydrocarbon group and the alkyl group are optionally substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cyclic hydrocarbon group, 3-8 membered heterocyclic group, aryl or heteroaryl; R6 is selected from: hydrogen, halogen, C1-C10 alkyl, -(CH2). 0-6 -C3-C10 cyclic hydrocarbon groups, -(CH2) 0-6 -3-10 membered epoxy group, wherein the alkyl, cycloalkyl, and epoxy group are optionally substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocyclic, aryl or heteroaryl; R5 is selected from: 1) Hydrogen, C1-C10 alkyl group, -(CH2) 0-6 -C3-C10 cyclic hydrocarbon groups, -(CH2) 0-6 -C3-C10 epoxy group, aryl group, heterocyclic group comprising one, two or three 5-membered or 6-membered rings and 1-4 heteroatoms selected from N, O and S, or heteroaryl group comprising one, two or three 5-membered or 6-membered rings and 1-4 heteroatoms selected from N, O and S, wherein the alkyl, cycloalkyl, epoxy, aryl, heterocyclic and heteroaryl groups are optionally substituted by one or more substituents independently selected from: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cycloalkyl, 3-8-membered heterocyclic, aryl or heteroaryl; 2) R5 and L1 and Atoms bonded together on a structural unit form a structure optionally composed of one or more independently selected atoms from R. 1f The substituents of the heterocycles; 3) R5 and R2 and Atoms bonded together on a structural unit form a structure optionally composed of one or more independently selected atoms from R. 1f The substituents of the heterocycles; R 1f Independently selected from: hydrogen, deuterium, halogen, OH, carboxyl, NH2, CN, NO2, C1-C10 alkyl, -(CH2) 0-6 -C3-C10 cyclic hydrocarbon groups, -(CH2) 0-6 -3-10 membered epoxy group, aryl group, heterocyclic group comprising one, two or three 5- or 6-membered rings and 1-4 heteroatoms selected from N, O and S, or heteroaryl group comprising one, two or three 5- or 6-membered rings and 1-4 heteroatoms selected from N, O and S, wherein the alkyl, cycloalkyl, epoxy, aryl, heterocyclic and heteroaryl groups are optionally substituted by one or more substituents independently selected from: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocyclic group, aryl or heteroaryl; X1, X2 and X3 contain at least one heteroatom selected from N, O and S; Among them, when Structural units are selected from When, X1 is selected X2 and X3 are selected from CH or N, and X2 and X3 together with the atoms attached to them form a C3-C15 cyclic hydrocarbon group or a C3-C15 heterocyclic group, which is optionally substituted by one or more substituents independently selected from the following: C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, OH or halogen, wherein the cyclic hydrocarbon group or heterocyclic group is a spirocyclic, bridged ring, fused ring or monocyclic; when Structural units are selected from When X1 is independently selected from: -CR7-, -N-; X2 is independently selected from: -O-, -S-, -S(O)2-, -NR8-, -C(R8)2-, -NR8-C(R8)2-; X3 is independently selected from: -N-, -CR9-; when Structural units are selected from When X1 is independently selected from: -CR7-, -N-; X2 is independently selected from: -N-, -CR8-, -CR8-NR8-, -NC(R8)2-; X3 is independently selected from: -O-, -S-, -S(O)2-, -NR9-, -C(R9)2-, -NR9-C(R9)2-; when Structural units are selected from When X1, X2, and X3 are independently selected from: -O-, -S-, -S(O)2-, -C(R7)2-, -C(R7)2-C(R7)2-, -NR8-, -CO-; R7, R8, and R9 are each independently selected from: H, C1-C10 alkane groups, -(CH2) 0-6 -C3-C10 cyclic hydrocarbon groups, -(CH2) 0-6 -3-10-membered epoxy group, aryl group, heterocyclic group comprising one, two or three 5-membered or 6-membered rings and 1-4 heteroatoms selected from N, O and S, or heteroaryl group comprising one, two or three 5-membered or 6-membered rings and 1-4 heteroatoms selected from N, O and S; wherein the alkane group, cycloalkyl group, epoxy group, aryl group, heterocyclic group, or heteroaryl group is optionally substituted by one or more substituents independently selected from: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cycloalkyl, 3-8-membered heterocyclic group, aryl or heteroaryl group; In R7, R8, and R9, two groups attached to the same carbon atom may be further linked to form a heterocycle; any two groups attached to different atoms may be further linked to form a heterocycle, wherein the heterocycle is optionally substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cyclic hydrocarbon, 3-8 membered heterocyclic group, aryl or heteroaryl.

2. The compound according to claim 1, wherein, Cy1 is selected from: C3-C12 cyclic hydrocarbon groups, aryl groups, or heterocyclic groups comprising one, two, or three 5- or 6-membered rings and 1-3 heteroatoms selected from N, O, and S, wherein the cyclic hydrocarbon group, aryl group, or heterocyclic group is a spirocyclic, bridged ring, fused ring, or monocyclic ring; wherein the cyclic hydrocarbon group, aryl group, or heterocyclic group is optionally substituted by one or more substituents independently selected from: deuterium, OH, carboxyl, halogen, NH2, CN, NO2, oxo, thio, C1-C8 alkyl, C1-C8 haloalkyl. C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cyclic hydrocarbon, 3-8 membered heterocyclic, aryl or heteroaryl, wherein the C3-C8 cyclic hydrocarbon, 3-8 membered heterocyclic, aryl or heteroaryl is optionally substituted by one or more substituents independently selected from: deuterium, OH, carboxyl, halogen, NH2, CN, NO2, C1-C8 alkyl, C3-C8 cyclic hydrocarbon, C1-C6 haloalkyl, C1-C6 hydroxysubstituted alkyl, C1-C8 alkoxy or The cyclic hydrocarbon group, aryl group, heterocyclic group, or heteroaryl group is a spirocyclic, bridged ring, fused ring, or monocyclic ring.

3. The compound according to claim 1, wherein Cy1 is selected from: a heteroaryl group comprising one, two, or three 5- or 6-membered rings and 1 to 3 heteroatoms selected from N, O, and S, said heteroaryl group being a fused ring or a monocyclic ring; said heteroaryl group is optionally substituted by one or more substituents independently selected from: C3-C8 cyclic hydrocarbon group, 3-8-membered heterocyclic group, aryl group, or heteroaryl group, wherein said C3-C8 cyclic hydrocarbon group, 3-8-membered heterocyclic group, aryl group, or heteroaryl group is optionally substituted by one or more substituents independently selected from: deuterium, OH, carboxyl, halogen, NH2, CN, NO2, C1-C8 alkyl, C3-C8 cyclic hydrocarbon group, C1-C6 haloalkyl, C1-C6 hydroxysubstituted alkyl, C1-C8 alkoxy, or The cyclic hydrocarbon group, aryl group, heterocyclic group, or heteroaryl group is a spirocyclic, bridged ring, fused ring, or monocyclic ring.

4. The compound according to claim 1, wherein, Cy1 is selected from: a heterocyclic group comprising one, two, or three 5- or 6-membered rings and 1 to 3 heteroatoms selected from N, O, and S; or a heteroaryl group comprising one, two, or three 5- or 6-membered rings and 1 to 3 heteroatoms selected from N, O, and S; said heterocyclic group or heteroaryl group is a spirocyclic, bridged ring, fused ring, or monocyclic ring; said heterocyclic group or heteroaryl group is optionally substituted by one or more substituents independently selected from: deuterium, OH, carboxyl, halogen, NH2, CN, NO2, oxo, thio, C1-C8 alkyl. C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cyclic hydrocarbon, 3-8 membered heterocyclic, aryl or heteroaryl, wherein the C3-C8 cyclic hydrocarbon, 3-8 membered heterocyclic, aryl or heteroaryl is optionally substituted by one or more substituents independently selected from: deuterium, OH, carboxyl, halogen, NH2, CN, NO2, C1-C8 alkyl, C3-C8 cyclic hydrocarbon, C1-C6 haloalkyl, C1-C6 hydroxysubstituted alkyl, C1-C8 alkoxy or 5. The compound according to claim 1, wherein, Cy1 is selected from: heterocyclic groups comprising one, two, or three 5- or 6-membered rings and 1 to 3 heteroatoms selected from N, O, and S; said heterocyclic group is optionally substituted by one or more substituents independently selected from the following: C1-C5 alkyl, oxo, C1-C5 haloalkyl, C1-C5 alkoxy, C1-C5 haloalkoxy, C3-C5 cyclic hydrocarbon, 3-5-membered heterocyclic, aryl, or heteroaryl, wherein said C3-C5 cyclic hydrocarbon, 3-5-membered heterocyclic, aryl, or heteroaryl is optionally substituted by one or more substituents independently selected from the following: deuterium, OH, carboxyl, halogen, NH2, CN, NO2, C1-C5 alkyl, C3-C5 cyclic hydrocarbon, C1-C4 haloalkyl, C1-C4 hydroxylated alkyl, C1-C3 alkoxy, 6. The compound according to claim 1, wherein, A is selected from: a heterocyclic group comprising one, two, or three 5- or 6-membered rings and 1 to 3 heteroatoms selected from N, O, and S; or a heteroaryl group comprising one, two, or three 5- or 6-membered rings and 1 to 3 heteroatoms selected from N, O, and S; said heterocyclic group or heteroaryl group is a spirocyclic, bridged ring, fused ring, or monocyclic ring; said heterocyclic group or heteroaryl group is optionally substituted by one or more substituents independently selected from: deuterium, OH, carboxyl, halogen, NH2, CN, NO2, oxo, thio, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C2-C8 alkenyl, haloC2-C8 alkenyl, C2-C8 alkynyl, haloC2-C8 alkynyl, C3-C8 cyclic hydrocarbon, 3-8 membered heterocyclic group, aryl, or heteroaryl; or, R 1A The connection between A and L2 causes A and L2 to form a heterocyclic group together, or R 1A The connection between R4 and A, L2, and R4 forms a heterocyclic group, R 1A The structural components are independently selected from -NH-alkylene-, -NHC(O)-, -C(O)NH-, -alkylene-NHC(O)-, -alkylene-C(O)NH-, -NHC(O)-alkylene-, -C(O)NH-alkylene-, -C(O)-.

7. The compound according to claim 1, wherein, A is selected from: a heterocyclic group comprising one, two, or three 5- or 6-membered rings and 1 to 3 heteroatoms selected from N, O, and S; or a heteroaryl group comprising one, two, or three 5- or 6-membered rings and 1 to 3 heteroatoms selected from N, O, and S; said heterocyclic group or heteroaryl group is a spirocyclic, bridged ring, fused ring, or monocyclic ring; said heterocyclic group or heteroaryl group is optionally composed of one or more independently selected from R 1A Substituents of R; 1A The connection between A and L2 causes A and L2 to form a heterocyclic group together. In this case, the R 1A The structural part is selected from: C1-C8 alkylene, C1-C8 haloalkylene, C1-C8 alkoxide, C1-C8 haloalkoxide, C2-C8 alkenyl, haloC2-C8 alkenyl, C2-C8 alkyne, haloC2-C8 alkyne, -NH-alkylene-, -NHC(O)-, -C(O)NH-, -alkylene-NHC(O)-, -alkylene-C(O)NH-, -NHC(O)-alkylene-, -C(O)NH-alkylene-, -C(O)-.

8. The compound according to claim 1, wherein, A is selected from: a heterocyclic group comprising one, two, or three 5- or 6-membered rings and 1 to 3 heteroatoms selected from N, O, and S; or a heteroaryl group comprising one, two, or three 5- or 6-membered rings and 1 to 3 heteroatoms selected from N, O, and S; said heterocyclic group or heteroaryl group is a spirocyclic, bridged ring, fused ring, or monocyclic ring; said heterocyclic group or heteroaryl group is optionally composed of one or more independently selected from R 1A Substituents of R; 1A The connection between R4 and A, L2, and R4 forms a heterocyclic group together. In this case, the R 1A The structural part is selected from: C1-C8 alkylene, C1-C8 haloalkylene, C1-C8 alkoxide, C1-C8 haloalkoxide, C2-C8 alkenyl, haloC2-C8 alkenyl, C2-C8 alkyne, haloC2-C8 alkyne, -NH-alkylene-, -NHC(O)-, -C(O)NH-, -alkylene-NHC(O)-, -alkylene-C(O)NH-, -NHC(O)-alkylene-, -C(O)NH-alkylene-, -C(O)-.

9. The compound according to claim 1, wherein, R1 is selected from:

10. The compound according to claim 1, wherein, R1 is selected from:

11. The compound according to claim 1, wherein, R1 is selected from: none, C3-C8 alkyl, C3-C8 cycloalkyl, heterocyclic group comprising one or two 5- or 6-membered rings and 1-4 heteroatoms selected from N, O, and S, or heteroaryl group comprising one 5- or 6-membered ring and 1-4 heteroatoms selected from N, O, and S, wherein the alkyl, cycloalkyl, heterocyclic, or heteroaryl group is optionally substituted by one or more substituents independently selected from: deuterium, halogen, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cycloalkyl, OH, NH2, oxo, thio, -NH-(C1-C6 alkyl), -N(C1-C6 alkyl)2, CN, NO2, carboxyl, 3-8 membered heterocyclic, aryl, or heteroaryl.

12. The compound according to claim 1, wherein, X is selected from: Among them, W is selected from O and CH2.

13. The compound according to claim 1, wherein, R1 is selected from:

14. The compound according to claim 1, wherein, R1 is selected from: C3-C10 alkyl, C3-C10 cycloalkyl, wherein the alkyl and cycloalkyl are optionally substituted by one or more substituents independently selected from: deuterium, halogen, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cycloalkyl, OH, NH2, oxo, thio, -NH-(C1-C6 alkyl), -N(C1-C6 alkyl)2, CN, NO2, carboxyl, 3-8 membered heterocyclic, aryl, or heteroaryl.

15. The compound of claim 1, wherein, R1 is selected from: C3-C8 alkyl, C3-C8 cycloalkyl, wherein the alkyl and cycloalkyl are optionally substituted by one or more substituents independently selected from: deuterium, halogen, C1-C8 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C3-C6 cycloalkyl, OH, NH2, oxo, thio, -NH-(C1-C6 alkyl), -N(C1-C6 alkyl)2, CN, NO2, carboxyl, 3-8 membered heterocyclic, aryl, or heteroaryl.

16. The compound of claim 1, wherein, R1 is selected from: heterocyclic groups containing one, two, or three 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S; or heteroaryl groups containing one, two, or three 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, wherein the heterocyclic group or heteroaryl group is optionally substituted by one or more substituents independently selected from: deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C3-C8 cyclic hydrocarbon, OH, NH2, oxo, thio, -NH-(C1-C6 alkyl), -N(C1-C6 alkyl)2, CN, NO2, carboxyl, 17. The compound according to claim 1, wherein, R2 is selected from: none, C1-C8 alkyl, -(CH2) 0-3 -C3-C10 cyclic hydrocarbon groups, -(CH2) 0-3 -3-10 membered epoxy groups, wherein the alkyl, cycloalkyl, and epoxy groups are optionally substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocyclic, aryl, or heteroaryl.

18. The compound according to claim 1, wherein, R2 is selected from: none, C1-C8 alkyl, -(CH2) 0-3 -C3-C8 cyclic hydrocarbon groups, -(CH2) 0-3 -3-8 membered epoxy group, wherein the alkyl, cycloalkyl, and epoxy group are optionally substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocyclic group, aryl or heteroaryl.

19. The compound according to claim 1, wherein, R2 is selected from: none, C1-C5 alkyl, -(CH2) 0-3 -C3-C5 cyclic hydrocarbon groups, -(CH2) 0-3 -3-5 membered epoxy group, wherein the alkyl, cycloalkyl, and epoxy group are optionally substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C5 alkyl, C1-C5 haloalkyl, C1-C5 alkoxy, C1-C5 haloalkoxy, C3-C5 cycloalkyl, 3-5 membered heterocyclic group, aryl or heteroaryl.

20. The compound according to claim 1, wherein, Both R1 and R2 are selected from none.

21. The compound according to claim 1, wherein, R3 and R4 are each independently selected from: C3-C8 cyclic hydrocarbon groups, aryl groups, heterocyclic groups comprising one, two, or three 3-, 4-, 5-, 6-, or 7-membered rings and one to three heteroatoms selected from N, O, and S, or heteroaryl groups comprising one, two, or three 3-, 4-, 5-, 6-, or 7-membered rings and one to three heteroatoms selected from N, O, and S, wherein the cyclic hydrocarbon group, aryl group, heterocyclic group, or heteroaryl group is a spirocyclic, bridged ring, fused ring, or monocyclic ring, and wherein the cyclic hydrocarbon group, aryl group, heterocyclic group, or heteroaryl group is optionally selected by one or more independently from the following: Substituents: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cyclic hydrocarbon, -O-C3-C8 cyclic hydrocarbon, 3-8 membered heterocyclic group, aryl, heteroaryl, deuterated C1-C8 alkyl, deuterated C1-C8 haloalkyl, deuterated C1-C8 alkoxy, deuterated C1-C8 haloalkoxy, deuterated C3-C8 cyclic hydrocarbon, deuterated -O-C3-C8 cyclic hydrocarbon.

22. The compound according to claim 1, wherein, R3 is selected from: C3-C8 cyclic hydrocarbon group, aryl group, heterocyclic group comprising one, two, or three 3-, 4-, 5-, 6-, or 7-membered rings and 1-3 heteroatoms selected from N, O, and S, wherein the cyclic hydrocarbon group, aryl group, or heterocyclic group is a spirocyclic, bridged ring, fused ring, or monocyclic ring, and wherein the cyclic hydrocarbon group, aryl group, or heterocyclic group is optionally substituted by one or more substituents independently selected from: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cyclic hydrocarbon group, -O-C3-C8 cyclic hydrocarbon group, 3-8 membered heterocyclic group, aryl, or heteroaryl.

23. The compound according to claim 1, wherein, R3 is selected from: C3-C5 cyclic hydrocarbon group, aryl group, heterocyclic group comprising one, two, or three 3-, 4-, 5-, 6-, or 7-membered rings and 1-3 heteroatoms selected from N, O, and S, wherein the cyclic hydrocarbon group, aryl group, or heterocyclic group is a spirocyclic, bridged ring, fused ring, or monocyclic ring, and wherein the cyclic hydrocarbon group, aryl group, or heterocyclic group is optionally substituted by one or more substituents independently selected from: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C5 alkyl, C1-C5 haloalkyl, C1-C5 alkoxy, C1-C5 haloalkoxy, C3-C5 cyclic hydrocarbon group, -O-C3-C5 cyclic hydrocarbon group, 3-5 membered heterocyclic group, aryl, or heteroaryl.

24. The compound according to claim 1, wherein, R4 is independently selected from: C3-C9 cyclic hydrocarbon groups, wherein the cyclic hydrocarbon group is a spirocyclic, bridged ring, fused ring, or monocyclic ring, and the cyclic hydrocarbon group is optionally substituted by one or more substituents independently selected from: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cyclic hydrocarbon group, -O-C3-C8 cyclic hydrocarbon group, 3-8 membered heterocyclic group, aryl, heteroaryl, deuterated C1-C8 alkyl, deuterated C1-C8 haloalkyl, deuterated C1-C8 alkoxy, deuterated C1-C8 haloalkoxy, deuterated C3-C8 cyclic hydrocarbon group, deuterated -O-C3-C8 cyclic hydrocarbon group.

25. The compound according to claim 1, wherein, R4 is selected from: aryl, heterocyclic groups comprising one, two, or three 3-, 4-, 5-, 6-, or 7-membered rings and one to three heteroatoms selected from N, O, and S, or heteroaryl groups comprising one, two, or three 3-, 4-, 5-, 6-, or 7-membered rings and one to three heteroatoms selected from N, O, and S, wherein the heterocyclic group or heteroaryl group is a spirocyclic, bridged ring, fused ring, or monocyclic ring, and the heterocyclic group or heteroaryl group is optionally substituted by one or more substituents independently selected from: deuterium, halogen, OH, carboxyl. alkyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cyclic hydrocarbon, -O-C3-C8 cyclic hydrocarbon, 3-8 membered heterocyclic group, aryl, heteroaryl, deuterated C1-C8 alkyl, deuterated C1-C8 haloalkyl, deuterated C1-C8 alkoxy, deuterated C1-C8 haloalkoxy, deuterated C3-C8 cyclic hydrocarbon, deuterated -O-C3-C8 cyclic hydrocarbon.

26. The compound according to claim 1, wherein, R4 is selected from: aryl, heterocyclic groups comprising one, two, or three 3-, 4-, 5-, 6-, or 7-membered rings and one to three heteroatoms selected from N, O, and S, or heteroaryl groups comprising one, two, or three 3-, 4-, 5-, 6-, or 7-membered rings and one to three heteroatoms selected from N, O, and S, wherein the heterocyclic group or heteroaryl group is a spirocyclic, bridged ring, fused ring, or monocyclic ring, and the aryl, heterocyclic, or heteroaryl group is optionally substituted by one or more substituents independently selected from: deuterium, halogen, OH, Carboxyl, NH2, CN, oxo, thio, NO2, C1-C5 alkyl, C1-C5 haloalkyl, C1-C5 alkoxy, C1-C5 haloalkoxy, C3-C5 cyclic hydrocarbon, -O-C3-C5 cyclic hydrocarbon, 3-5 membered heterocyclic group, aryl or heteroaryl, deuterated C1-C5 alkyl, deuterated C1-C5 haloalkyl, deuterated C1-C5 alkoxy, deuterated C1-C5 haloalkoxy, deuterated C3-C5 cyclic hydrocarbon, deuterated -O-C3-C5 cyclic hydrocarbon.

27. The compound according to claim 1, wherein, R4 is selected from aryl, which is a spirocyclic, bridged ring, fused ring, or monocyclic ring, and is optionally substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cyclic hydrocarbon, -O-C3-C8 cyclic hydrocarbon, 3-8 membered heterocyclic group, aryl, heteroaryl, deuterated C1-C8 alkyl, deuterated C1-C8 haloalkyl, deuterated C1-C8 alkoxy, deuterated C1-C8 haloalkoxy, deuterated C3-C8 cyclic hydrocarbon, deuterated -O-C3-C8 cyclic hydrocarbon.

28. The compound of claim 1, wherein, R4 is selected from aryl, which is a spirocyclic, bridged ring, fused ring, or monocyclic ring, and is optionally substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C5 alkyl, C1-C5 haloalkyl, C1-C5 alkoxy, C1-C5 haloalkoxy, C3-C5 cyclic hydrocarbon, -O-C3-C5 cyclic hydrocarbon, 3-5 membered heterocyclic group, aryl or heteroaryl, deuterated C1-C5 alkyl, deuterated C1-C5 haloalkyl, deuterated C1-C5 alkoxy, deuterated C1-C5 haloalkoxy, deuterated C3-C5 cyclic hydrocarbon, deuterated -O-C3-C5 cyclic hydrocarbon.

29. The compound according to claim 1, wherein, L1 and L2 are each independently selected from: none, C1-C3 alkylene, halo-C1-C3 alkylene, C2-C3 alkenyl, halo-C2-C3 alkenyl, C2-C3 alkyne, halo-C2-C3 alkyne, -O-alkylene-, -NH-alkylene-, -NHC(O)-, -C(O)NH-, -alkylene-NHC(O)-, -alkylene-C(O)NH-, -NHC(O)-alkylene-, -C(O)NH-alkylene-, -C(O)-, -NH-, C3-C8 cyclic hydrocarbon, aryl, containing one, two, or three 3-membered, 4-membered, or 5-membered groups. A heterocyclic group comprising a 6-membered ring and 1 to 3 heteroatoms selected from N, O, and S, or a heteroaryl group comprising one, two, or three 3-, 4-, 5-, or 6-membered rings and 1 to 3 heteroatoms selected from N, O, and S, wherein the alkylene, cycloalkyl, aryl, heterocyclic, or heteroaryl group is optionally substituted by one or more substituents independently selected from: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cycloalkyl, 3-8-membered heterocyclic, aryl, or heteroaryl.

30. The compound according to claim 1, wherein, L1 is selected from: none, C1-C3 alkylene, C2-C3 alkynyl, aryl, heterocyclic group comprising one, two or three 3-membered, 4-membered, 5-membered or 6-membered rings and 1-3 heteroatoms selected from N, O and S, or heteroaryl group comprising one, two or three 3-membered, 4-membered, 5-membered or 6-membered rings and 1-3 heteroatoms selected from N, O and S; the aryl, heterocyclic or heteroaryl group is a spirocyclic, bridged ring, fused ring or monocyclic; the aryl, heterocyclic or heteroaryl group is optionally substituted by one or more substituents independently selected from: deuterium, OH, carboxyl, halogen, NH2, CN, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cyclic hydrocarbon, 3-8 membered heterocyclic, aryl or heteroaryl.

31. The compound according to claim 1, wherein, L1 is selected from: none, C1-C3 alkylene, C2-C3 alkynyl, aryl, heterocyclic group comprising one, two or three 3-membered, 4-membered, 5-membered or 6-membered rings and 1-3 heteroatoms selected from N, O and S, or heteroaryl group comprising one, two or three 3-membered, 4-membered, 5-membered or 6-membered rings and 1-3 heteroatoms selected from N, O and S; the aryl, heterocyclic or heteroaryl group is a spirocyclic, bridged ring, fused ring or monocyclic; the aryl, heterocyclic or heteroaryl group is optionally substituted by one or more substituents independently selected from: deuterium, OH, carboxyl, halogen, NH2, CN, NO2, C1-C5 alkyl, C1-C5 haloalkyl, C1-C5 alkoxy, C1-C5 haloalkoxy, C3-C5 cyclic hydrocarbon, 3-5 membered heterocyclic group, aryl or heteroaryl.

32. The compound according to claim 1, wherein, L2 is selected from: -C(O)NH-, -alkylene-C(O)NH-, -C(O)-, -NH-aryl, heterocyclic group comprising one, two or three 5- or 6-membered rings and 1 to 3 heteroatoms selected from N, O and S, or heteroaryl group comprising one, two or three 5- or 6-membered rings and 1 to 3 heteroatoms selected from N, O and S, wherein the aryl, heterocyclic or heteroaryl group is a spirocyclic, bridged ring, fused ring or monocyclic, and the alkylene, aryl, heterocyclic or heteroaryl group is optionally substituted by one or more substituents independently selected from: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cyclic hydrocarbon, 3-8 membered heterocyclic group, aryl or heteroaryl.

33. The compound according to claim 1, wherein, L2 is selected from: -C(O)NH-, -alkylene-C(O)NH-, -C(O)-, -NH-, aryl, heterocyclic group comprising one, two or three 5- or 6-membered rings and 1 to 3 heteroatoms selected from N, O and S, or heteroaryl group comprising one, two or three 5- or 6-membered rings and 1 to 3 heteroatoms selected from N, O and S, wherein the aryl, heterocyclic or heteroaryl group is a spirocyclic, bridged ring, fused ring or monocyclic, and the alkylene, aryl, heterocyclic or heteroaryl group is optionally substituted by one or more substituents independently selected from: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C5 alkyl, C1-C5 haloalkyl, C1-C5 alkoxy, C1-C5 haloalkoxy, C3-C5 cyclic hydrocarbon, 3-5-membered heterocyclic group, aryl or heteroaryl.

34. The compound according to claim 1, wherein, R 1e R 1g and R 1h It is independently selected from: hydrogen, OH, carboxyl, NH2, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C8 cyclic hydrocarbon, -O-C3-C8 cyclic hydrocarbon, or aryl.

35. The compound according to claim 1, wherein, R 1e Selected from: hydrogen, NH2, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 hydroxyalkyl, C2-C3 alkenyl, C2-C3 alkynyl, C3-C5 cyclic hydrocarbon or aryl.

36. The compound according to claim 1, wherein, R 1e Selected from: hydrogen, NH2, methyl, vinyl, ethynyl, C3-C5 cyclic hydrocarbon groups.

37. The compound according to claim 1, wherein, R 1g It is independently selected from: hydrogen, OH, carboxyl, NH2, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 hydroxyalkyl, C2-C3 alkenyl, C2-C3 alkynyl, C3-C5 cyclic hydrocarbon, -O-C3-C5 cyclic hydrocarbon, or aryl.

38. The compound according to claim 1, wherein, R 1h It is independently selected from: hydrogen, OH, carboxyl, NH2, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 hydroxyalkyl, C2-C3 alkenyl, C2-C3 alkynyl, C3-C5 cyclic hydrocarbon, -O-C3-C5 cyclic hydrocarbon, or aryl.

39. The compound according to claim 1, wherein, R 1a and R 1b Independently selected from: hydrogen, C3-C8 cyclic hydrocarbon groups, C1-C8 alkyl groups, Or R 1a and R 1b Together with the nitrogen atom to which they are attached, they form a C3-C8 heterocyclic group, wherein the heterocyclic group, cyclic hydrocarbon group, and alkyl group are optionally substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cyclic hydrocarbon group, 3-8 membered heterocyclic group, aryl or heteroaryl.

40. The compound according to claim 1, wherein, R 1a and R 1b Independently selected from: hydrogen, C3-C5 cyclic hydrocarbon group, C1-C5 alkyl group, Or, R 1a and R 1b Together with the nitrogen atom to which they are attached, they form a C3-C8 heterocyclic group, wherein the heterocyclic group, cyclic hydrocarbon group, and alkyl group are optionally substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C5 haloalkyl, C1-C5 alkoxy, C1-C5 haloalkoxy, C3-C5 cyclic hydrocarbon, 3-5 membered heterocyclic group, aryl or heteroaryl.

41. The compound according to claim 1, wherein, R 1a and R 1b Independently selected from: hydrogen, C3-C5 cyclic hydrocarbon group, C1-C5 alkyl group; or, R 1a and R 1b Together with the nitrogen atom to which they are attached, they form a C3-C5 heterocyclic group, wherein the heterocyclic group, cyclic hydrocarbon group, and alkyl group are optionally substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C5 alkyl, C1-C5 haloalkyl, C1-C5 alkoxy, C1-C5 haloalkoxy, C3-C5 cyclic hydrocarbon group, 3-5 membered heterocyclic group, aryl or heteroaryl.

42. The compound according to claim 1, wherein, R 1c and R 1d Independently selected from: hydrogen, C3-C8 cyclic hydrocarbon group, C1-C8 alkyl group; or, R 1c and R 1d Together with the carbon atoms to which they are attached, they form a C3-C8 cyclic hydrocarbon group, wherein the cyclic hydrocarbon group and the alkyl group are optionally substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cyclic hydrocarbon group, 3-8 membered heterocyclic group, aryl or heteroaryl.

43. The compound according to claim 1, wherein, R 1c and R 1d The group is independently selected from: hydrogen, C3-C5 cyclic hydrocarbon, C1-C5 alkyl; or, R1c and R1d together with the carbon atoms to which they are attached form a C3-C5 cyclic hydrocarbon, wherein the cyclic hydrocarbon and alkyl are optionally substituted by one or more substituents independently selected from: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cyclic hydrocarbon, 3-8 membered heterocyclic group, aryl or heteroaryl.

44. The compound according to claim 1, wherein, R 1c and R 1d Independently selected from: hydrogen, C3-C5 cyclic hydrocarbon group, C1-C5 alkyl group, or, R 1c and R 1d Together with the carbon atoms to which they are attached, they form a C3-C5 cyclic hydrocarbon group, wherein the cyclic hydrocarbon group and the alkyl group are optionally substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C5 haloalkyl, C1-C5 alkoxy, C1-C5 haloalkoxy, C3-C5 cyclic hydrocarbon group, 3-5 membered heterocyclic group, aryl or heteroaryl.

45. The compound according to claim 1, wherein, R6 is independently selected from: hydrogen, C1-C8 alkyl groups, and -(CH2). 0-3 -C3-C8 cyclic hydrocarbon groups, -(CH2) 0-3 -3-8 membered epoxy group, wherein the alkyl, cycloalkyl, and epoxy group are optionally substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocyclic group, aryl or heteroaryl.

46. ​​The compound according to claim 1, wherein, R6 is independently selected from: hydrogen, C1-C5 alkyl groups, and -(CH2). 0-3 -C3-C5 cyclic hydrocarbon groups, -(CH2) 0-3 -3-5 membered epoxy group; the alkyl, cycloalkyl, and epoxy group may optionally be substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocyclic, aryl or heteroaryl.

47. The compound according to claim 1, wherein, R5 is independently selected from: hydrogen, C1-C8 alkyl groups, and -(CH2). 0-3 -C3-C8 cyclic hydrocarbon groups, -(CH2) 0-3 -3-8 membered epoxy group; the alkyl, cyclic hydrocarbon, and epoxy group are optionally substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cyclic hydrocarbon.

48. The compound according to claim 1, wherein, R5 is independently selected from: hydrogen, C1-C5 alkyl, -(CH2). 0-3 -C3-C5 cyclic hydrocarbon groups, -(CH2) 0-3 -3-5 membered epoxy group; the alkyl, cycloalkyl, and epoxy group may optionally be substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocyclic, aryl or heteroaryl.

49. The compound according to claim 1, wherein, R 1f Independently selected from: hydrogen, deuterium, halogen, OH, carboxyl group, NH2, CN, NO2, C1-C8 alkane group, -(CH2) 0-3 -C3-C8 cyclic hydrocarbon groups, -(CH2) 0-3 -3-8 membered epoxy group; the alkane group, cycloalkyl group and epoxy group are optionally substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocyclic group, aryl or heteroaryl.

50. The compound according to claim 1, wherein, R 1f Independently selected from: hydrogen, deuterium, C1-C5 alkane groups, -(CH2) 0-3 -C3-C5 cyclic hydrocarbon groups, -(CH2) 0-3 -3-5 membered epoxy group; the alkane group, cycloalkyl group, epoxy group are optionally substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cycloalkyl, 3-8 membered heterocyclic group, aryl or heteroaryl.

51. The compound according to claim 1, wherein, R7, R8, and R9 are each independently selected from: C1-C8 alkane groups, -(CH2) 0-3 -C3-C8 cyclic hydrocarbon groups, -(CH2) 0-3 -3-8 membered epoxy group, aryl group; the alkane group, epoxy group and aryl group are optionally substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cyclic hydrocarbon group, 3-8 membered heterocyclic group, aryl or heteroaryl.

52. The compound according to claim 1, wherein, R7, R8, and R9 are each independently selected from: C1-C5 alkane groups, -(CH2) 0-3 -C3-C5 cyclic hydrocarbon groups, -(CH2) 0-3 -3-5 membered epoxy group, aryl group; the alkane group, epoxy group and aryl group are optionally substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cyclic hydrocarbon group, 3-8 membered heterocyclic group, aryl or heteroaryl.

53. The compound according to claim 1, wherein, R7, R8, and R9 are each independently selected from: C1-C5 alkane groups, -(CH2) 0-3 -C3-C5 cyclic hydrocarbon groups, -(CH2) 0-3 -3-5 membered epoxy group, aryl group; the alkane group, epoxy group and aryl group are optionally substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C5 alkyl, C1-C5 haloalkyl, C1-C5 alkoxy, C1-C5 haloalkoxy, C3-C5 cyclic hydrocarbon group, 3-5 membered heterocyclic group, aryl or heteroaryl.

54. The compound according to claim 1, wherein, R 1e Independently selected from: hydrogen, OH, NH2, methyl, vinyl, ethynyl, 55. The compound according to claim 1, wherein, R 1g Independently selected from: hydrogen, methyl, OH, NH2, 56. The compound according to claim 1, wherein, R 1h Independently selected from: hydrogen, methyl, OH, NH2, 57. The compound according to claim 1, wherein, R 1a R 1b Independently selected from: hydrogen, 58. The compound according to claim 1, wherein, R 1c R 1d Independently selected from: hydrogen, -CF3.

59. The compound according to claim 1, wherein, Independent selection from:

60. The compound according to claim 1, wherein, Independent selection from:

61. The compound according to claim 1, wherein, Selected from:

62. The compound according to claim 1, wherein, Selected from:

63. The compound according to claim 1, wherein, Structural units are selected from:

64. The compound according to claim 1, wherein, The compounds shown in formula (I) are selected from:

65. The compound according to claim 1, wherein, The compounds shown in formula (I) are selected from:

66. The compound according to claim 1, wherein, The compounds shown in formula (I) are selected from:

67. The compound according to claim 1, wherein, Structural units are selected from:

68. The compound according to claim 1, wherein, The compounds shown in formula (I) are selected from:

69. The compound according to claim 1, wherein, R6 is selected from: hydrogen, methyl.

70. The compound according to claim 1, wherein, R5 is selected from: hydrogen, 71. The compound according to claim 1, wherein, R5 and L1 and The atoms bonded together on the structural unit form a heterocycle; and the compound shown in formula (I) is selected from:

72. The compound according to claim 1, wherein, R5 and R2 and The atoms bonded together on the structural unit form a heterocycle; and the compound shown in formula (I) is selected from:

73. The compound according to claim 1, wherein, R 1f Independently selected from: hydrogen, 74. The compound according to claim 1, wherein, Structural units are selected from:

75. The compound according to claim 1, wherein, Structural units are selected from:

76. The compound according to claim 1, wherein, Structural units are selected from:

77. The compound according to claim 1, wherein, The compound shown in formula (I) is selected from:

78. The compound according to claim 1, wherein, Structural units are selected from:

79. The compound according to claim 1, wherein, R7 is selected from: hydrogen, 80. The compound according to claim 1, wherein, R8 is selected from:

81. The compound according to claim 1, wherein, R9 is selected from:

82. The compound according to claim 1, wherein, Cy1 is selected from:

83. The compound according to claim 1, wherein, A is selected from one or more R's. 1A Replaced by: * indicates the direction of connection with L2.

84. The compound according to claim 1, wherein, A is selected from: * indicates the direction of connection with L2.

85. The compound according to claim 1, wherein R 1A Selected from: hydrogen, methyl, ethyl.

86. The compound according to claim 1, wherein R 1A The connection between A and L2 causes A and L2 to form a heterocyclic group together, wherein the heterocyclic group is selected from:

87. The compound according to claim 1, wherein, R 1A The connection between A, L2, and R4 forms a heterocyclic group, wherein the heterocyclic group is selected from:

88. The compound according to claim 84 or 85, wherein, exist In structural units, R 1A It is an alkylene group, selected from -CH2- or -CH2CH2-.

89. The compound according to claim 1, wherein, A is selected from: * indicates the direction of connection with L2.

90. The compound according to claim 1, wherein, Selected independently from:

91. The compound according to claim 1, wherein, Selected independently from:

92. The compound according to claim 1, wherein, Selected from: NH2.

93. The compound according to claim 1, wherein, Selected from:

94. The compound according to claim 1, wherein, Selected from:

95. The compound according to claim 1, wherein, Selected from:

96. The compound according to claim 1, wherein, Selected from:

97. The compound according to claim 1, wherein, Selected from:

98. The compound according to claim 1, wherein, R1 is selected from: None, NH2, 99. The compound according to claim 1, wherein, R2 is selected from: None 100. The compound according to claim 1, wherein, R3 is selected from:

101. The compound according to claim 1, wherein, R4 is selected from:

102. The compound according to claim 1, wherein, L1 is selected from: none, -CH2-, -CH2CH2-, ethynyl group, 103. The compound according to claim 1, wherein, L2 is selected from: None 104. The compound according to claim 1 or 86, wherein, The structure is selected from:

105. The compound according to claim 1, having the following formulas (I-1), (I-2), (I-3), (I-4), (I-5), (I-6), (I-7), (I-8), or (I-9): in, A, Cy1, R1, R2, R3, R4, R5, R6, L1, L2, R 1A As defined in claim 1.

106. A compound according to claim 1, or a pharmaceutically acceptable salt, stereoisomer, or mixture of stereoisomers thereof, having a structure as shown in formula (I-1): in, The variables A, Cy1, R1, R2, R3, R4, L1, and L2 are defined as described in claim 1.

107. A compound according to claim 1, or a pharmaceutically acceptable salt, stereoisomer, or mixture of stereoisomers thereof, having a structure as shown in formula (I-5): X1 is selected from: -CR7-, -N-; X2 is selected from: -O-, -S-, -S(O)2-, -NR8-, -C(R8)2-, -NR8-C(R8)2- or -CO-; X3 is selected from: -N-, -CR9-; in: X1, X2 and X3 contain at least one heteroatom selected from N, O and S; R7, R8, and R9 are each independently selected from: H, C1-C10 alkane groups, -(CH2) 0-6 -C3-C10 cyclic hydrocarbon groups, -(CH2) 0-6 -3-10-membered epoxy group, aryl group, heterocyclic group comprising one, two or three 5-membered or 6-membered rings and 1-4 heteroatoms selected from N, O and S, or heteroaryl group comprising one, two or three 5-membered or 6-membered rings and 1-4 heteroatoms selected from N, O and S; wherein the alkane group, cycloalkyl group, epoxy group, aryl group, heterocyclic group, or heteroaryl group is optionally substituted by one or more substituents independently selected from: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cycloalkyl, 3-8-membered heterocyclic group, aryl or heteroaryl group; In R7, R8, and R9, two groups attached to the same carbon atom may be further linked to form a heterocycle; any two groups attached to different atoms may be further linked to form a heterocycle, wherein the heterocycle may optionally be substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cyclic hydrocarbon, 3-8 membered heterocyclic group, aryl or heteroaryl; The other variables A, Cy1, R3, R4, L1, and L2 are defined as described in claim 1.

108. A compound according to claim 1, or a pharmaceutically acceptable salt, stereoisomer, or mixture of stereoisomers thereof, having a structure as shown in formula (I-6): X1 is independently selected from: -CR7-, -N-; X2 is independently selected from: -N-, -CR8-, -CR8-NR8-, -NC(R8)2-; X3 is independently selected from: -O-, -S-, -S(O) 2、 -NR9-, -C(R9)2-, -NR9-C(R9)2- or -CO-; in: X1, X2 and X3 contain at least one heteroatom selected from N, O and S; R7, R8, and R9 are each independently selected from: H, C1-C10 alkane groups, -(CH2) 0-6 -C3-C10 cyclic hydrocarbon groups, -(CH2) 0-6 -3-10-membered epoxy group, aryl group, heterocyclic group comprising one, two or three 5-membered or 6-membered rings and 1-4 heteroatoms selected from N, O and S, or heteroaryl group comprising one, two or three 5-membered or 6-membered rings and 1-4 heteroatoms selected from N, O and S; wherein the alkane group, cycloalkyl group, epoxy group, aryl group, heterocyclic group, or heteroaryl group is optionally substituted by one or more substituents independently selected from: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cycloalkyl, 3-8-membered heterocyclic group, aryl or heteroaryl group; In R7, R8, and R9, two groups attached to the same carbon atom may be further linked to form a heterocycle; any two groups attached to different atoms may be further linked to form a heterocycle, wherein the heterocycle may optionally be substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cyclic hydrocarbon, 3-8 membered heterocyclic group, aryl or heteroaryl; Other variables A, Cy1, R3, R4, L1, and L2 are as defined in requirement 1.

109. A compound according to claim 1, or a pharmaceutically acceptable salt, stereoisomer, or mixture of stereoisomers thereof, having a structure as shown in formula (I-7): X1, X2, and X3 are independently selected from: -O-, -S-, -S(O)2, -C(R7)2-, -C(R7)2-C(R7)2-, -NR8-, or -CO-; where: X1 X1, X2, and X3 contain at least one heteroatom selected from N, O, and S; Or X1 is selected from X2 and X3 are selected from CH or N, and X2, X3 and the atoms attached to them together form a C3-C15 cyclic hydrocarbon group or a C3-C15 heterocyclic group, which is optionally substituted by one or more substituents independently selected from the following: C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, OH or halogen, wherein the cyclic hydrocarbon group or heterocyclic group is a spirocyclic, bridged ring, fused ring or monocyclic; R7 and R8 are each independently selected from: H, C1-C10 alkane groups, -(CH2) 0-6 -C3-C10 cyclic hydrocarbon groups, -(CH2) 0-6 -3-10-membered epoxy group, aryl group, heterocyclic group comprising one, two or three 5-membered or 6-membered rings and 1-4 heteroatoms selected from N, O and S, or heteroaryl group comprising one, two or three 5-membered or 6-membered rings and 1-4 heteroatoms selected from N, O and S; wherein the alkane group, cycloalkyl group, epoxy group, aryl group, heterocyclic group, or heteroaryl group is optionally substituted by one or more substituents independently selected from: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cycloalkyl, 3-8-membered heterocyclic group, aryl or heteroaryl group; In R7 and R8, two groups attached to the same carbon atom can be further linked to form a heterocycle; any two groups attached to different atoms can be further linked to form a heterocycle, wherein the heterocycle is optionally substituted by one or more substituents independently selected from the following: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cyclic hydrocarbon, 3-8 membered heterocyclic group, aryl or heteroaryl; The other variables A, Cy1, R3, R4, L1, and L2 are defined as described in claim 1.

110. A compound according to claim 1, or a pharmaceutically acceptable salt, stereoisomer, or mixture of stereoisomers thereof, specifically having the structure shown in formula (I-8): in: R 1A Selected from: C1-C8 alkylene, C1-C8 haloalkylene, C1-C8 alkoxy, C1-C8 haloalkoxy, C2-C8 alkenyl, haloC2-C8 alkenyl, C2-C8 alkyne, haloC2-C8 alkyne, -NH-alkylene-, -NHC(O)-, -C(O)NH-, -alkylene-NHC(O)-, -alkylene-C(O)NH-, -NHC(O)-alkylene-, -C(O)NH-alkylene-, -C(O)-; L2 is selected from: none, C1-C6 alkylene, halo-C1-C6 alkylene, C2-C6 alkenyl, halo-C2-C6 alkenyl, C2-C6 alkyne, halo-C2-C6 alkyne, -O-alkylene-, -NH-alkylene-, -NHC(O)-, -C(O)NH-, -alkylene-NHC(O)-, -alkylene-C(O)NH-, -NHC(O)-alkylene-, -C(O)NH-alkylene-, -C(O)-, -NH-, C3-C10 cyclic hydrocarbon, aryl, containing one, two, or three 5- or 6-membered rings. And a heterocyclic group with 1 to 3 heteroatoms selected from N, O and S, or a heteroaryl group comprising one or two or three 5- or 6-membered rings and 1 to 3 heteroatoms selected from N, O and S, wherein the alkylene, cycloalkyl, aryl, heterocyclic or heteroaryl group is optionally substituted by one or more substituents independently selected from: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cycloalkyl, 3-8-membered heterocyclic, aryl or heteroaryl; R4 is independently selected from: C1-C10 alkyl, C3-C10 cycloalkyl, aryl, heterocyclic group comprising one, two, or three 4-, 5-, 6-, or 7-membered rings and one to three heteroatoms selected from N, O, and S, or heteroaryl group comprising one, two, or three 4-, 5-, 6-, or 7-membered rings and one to three heteroatoms selected from N, O, and S, wherein the cycloalkyl, aryl, heterocyclic, or heteroaryl group is a spirocyclic, bridged ring, fused ring, or monocyclic ring, and the alkyl, cycloalkyl, aryl, heterocyclic, or heteroaryl group is optionally selected by one or more independently from the following Substituents: deuterium, halogen, OH, carboxyl, NH2, CN, oxo, thio, NO2, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C3-C8 cyclic hydrocarbon, -O-C3-C8 cyclic hydrocarbon, 3-8 membered heterocyclic group, aryl, heteroaryl, deuterated C1-C8 alkyl, deuterated C1-C8 haloalkyl, deuterated C1-C8 alkoxy, deuterated C1-C8 haloalkoxy, deuterated C3-C8 cyclic hydrocarbon, deuterated -O-C3-C8 cyclic hydrocarbon; other The structural unit, Cy1, R1, R2, R3, and L2 variables are defined as in claim 1.

111. A compound according to claim 1, or a pharmaceutically acceptable salt, stereoisomer, or mixture of stereoisomers thereof, specifically having the structure shown in formula (I-9): in, The variables Cy1, R3, R4, L1, L2, and A are defined as in claim 1.

112. The following compounds or their pharmaceutically acceptable salts, stereoisomers, or mixtures of stereoisomers:

113. The following compounds or their pharmaceutically acceptable salts:

114. A pharmaceutical composition comprising the compound of any one of claims 1-112 or a pharmaceutically acceptable salt, stereoisomer, or mixture of stereoisomers thereof, and a pharmaceutically acceptable carrier.

115. Use of the compound of any one of claims 1-112 or a pharmaceutically acceptable salt, stereoisomer, or mixture of stereoisomers thereof in the preparation of a medicament for treating diseases or disorders related to calcitonin receptors and / or amyloid receptors.

116. The use according to claim 114, wherein the disease or disorder associated with the calcitonin receptor and / or amyloid receptor is a bone disorder, metabolic disorder, pain, neurodegenerative disease or disorder, or cardiovascular disease.

117. The use according to claim 114, wherein the calcitonin receptor and / or amyloid receptor-related diseases or disorders are type 1 diabetes, type 2 diabetes, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), insulin-dependent diabetes mellitus, non-insulin-dependent diabetes mellitus, impaired glucose tolerance, obesity, or diabetic complications.

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