Substituted derivative of 2-(pyrrolidine-3-yl)acetic acid, method of preparation thereof and use thereof

Abstract

The present invention provides a compound as shown in Formula (I), and a pharmaceutically acceptable salt of the compound. The compound in the present invention exhibits a strong inhibitory effect on the Lp(a) complex and can be used to treat cardiovascular diseases (CVD).

Description

A substituted 2-(pyrrolidin-3-yl)acetic acid derivative and its preparation method and use

[0001] Citation of Related Applications

[0002] The present invention claims priority to invention patent application No. 202311536343.5 filed in China on November 17, 2023, invention patent application No. 202410174573.X filed in China on February 7, 2024, invention patent application No. 202410811526.1 filed in China on June 21, 2024, and invention patent application No. 202411250214.4 filed in China on September 6, 2024, the entire contents of which are incorporated herein by reference. Technical Field

[0003] The present invention relates to the field of medical technology, and in particular to compounds serving as Lp(a) inhibitors, particularly substituted 2-(pyrrolidin-3-yl)acetic acid derivatives, and preparation methods and uses thereof. Background Art

[0004] Lipoprotein(a) (Lp(a)) is a lipoprotein particle synthesized in the liver. It consists of cholesterol-rich low-density lipoprotein (LDL-C)-like particles attached to apolipoprotein(a). Lp(a) levels are primarily determined by genetics, vary significantly among different populations, and are rarely affected by lifestyle interventions.

[0005] Lipoprotein (Lp(a)) is associated with an increased risk of coronary artery disease, ischemic stroke, aortic valve stenosis, heart failure, atrial fibrillation, and peripheral arterial disease. Approximately 20% of the population has elevated plasma Lp(a) levels (≥30 mg / dL). The increased risk of cardiovascular disease (CVD) associated with Lp(a) is primarily attributed to the dual procoagulant effects of apo(a) (its structure is similar to plasminogen) and the atherogenic (AS) and proinflammatory effects of apo B (apolipoprotein B) containing oxidized phospholipids (OxPL). Lp(a) is a causative factor not only for atherosclerotic cardiovascular disease (ASCVD) but also for calcific aortic valve disease. Elevated plasma Lp(a) levels are an independent risk factor for CVD.

[0006] There are few approved treatment options for patients with elevated Lp(a) concentrations. Plasmapheresis (apheresis) can be used to filter the blood to remove LDL and Lp(a); however, the effect is temporary and typically needs to be repeated every two weeks, and patient compliance is not very good. Currently, there are no approved pharmacological therapies for lowering Lp(a) levels. Therefore, there is a significant need for pharmaceutical compounds and treatment options to lower plasma Lp(a) levels in patients with CVD. Summary of the Invention

[0007] The present invention aims to provide a novel compound for reducing plasma Lp(a) levels, a method for preparing the compound, and its use in treating diseases mediated by Lp(a). The novel compound is biochemically effective and physiologically active.

[0008] The first aspect of the present invention provides a compound represented by the following formula (I), or a pharmaceutically acceptable salt of the compound:

[0009] in, is a single bond or a double bond;

[0010] A is CR X 、P、P(O)、N、C 6-12 Aryl, 5-14 membered heteroaryl, C 3-8 Carbocyclic group, 5-18 membered heterocyclic group; the aryl, heteroaryl, carbocyclic group, heterocyclic group are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 Alkyl, C 1-3 substituted by an alkoxy substituent;

[0011] when When it is a single bond; R X H, -OH, C 1-3 alkoxy;

[0012] when When it is a double bond; R X does not exist;

[0013] L1 is selected from -C 1-3 Alkylene-C 6-10 Aryl-C 6-10 Aryl-C 1-3 Alkylene-, -C 1-3 Alkylene-C 6-10 Aryl-5-12 membered heteroaryl-C 1-3 Alkylene-, -C 1-3 Alkylene-5-12 membered heteroaryl-5-12 membered heteroaryl-C 1-3 Alkylene-, The C 1-3 The alkylene group is optionally substituted by one or more groups independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The aryl and heteroaryl groups are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 Alkoxy is substituted by a substituent; * is the connection end between L1 and A;

[0014] L2 is selected from -C 1-3 Alkylene-C 6-10 Aryl-C 6-10 Aryl-C 1-3 Alkylene-, -C 1-3 Alkylene-C 6-10 Aryl-5-12 membered heteroaryl-C 1-3 Alkylene-, -C 1-3 Alkylene-5-12 membered heteroaryl-5-12 membered heteroaryl-C 1-3 Alkylene-, The C 1-3 The alkylene group is optionally substituted by one or more groups independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The aryl and heteroaryl groups are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 is substituted by an alkoxy substituent; * is the connecting end between L2 and A;

[0015] R is selected from H, -C 1-3 Alkylene-C 6-10 Aryl, -C 1-3 Alkylene-5-12 membered heteroaryl, C 1-6 alkyl, The C 1-3 The alkylene group is optionally substituted by one or more groups independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The aryl and heteroaryl groups are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 Alkoxy, C 1-3 Substituted by an aminoalkyl substituent; the C 1-6 The alkyl group is optionally substituted with one or more groups independently selected from deuterium, halogen, oxo, carboxyl, -CN, -OH, -NH2, C 1-3 Alkyl, C 1-3 is substituted by an alkoxy substituent; * is the connecting end between R and A;

[0016] L3 is selected from -C 1-6 Alkylene-, -C 2-6Alkenylene-, -C 2-6 Alkynylidene-, -C 1-3 Alkylene-C 6-10 Aryl-C 6-10 Aryl-C 1-3 Alkylene-, -C 1-3 Alkylene-C 6-10 Aryl-5-12 membered heteroaryl-C 1-3 Alkylene-, -C 1-3 Alkylene-5-12 membered heteroaryl-C 6-10 Aryl-C 1-3 Alkylene-, -C1-3 alkylene-5-12 membered heteroaryl-5-12 membered heteroaryl-C 1-3 Alkylene-, The alkylene, alkenylene and alkynylene groups are optionally substituted by one or more groups independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The aryl and heteroaryl groups are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 Alkyl, C 1-3 is substituted by an alkoxy substituent; * is the connecting end between L3 and A;

[0017] Rings W1, W2, and W3 are independently selected from C 6-12 Aryl, 5-12 membered heteroaryl, C 6-14 Cycloalkyl, 5-12 membered heterocyclic group; the aryl, heteroaryl, cycloalkyl, heterocyclic group are optionally substituted by one or more independently selected from deuterium, halogen, -CN, -OH, -NH2, -CHO, C 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkyl, C 1-3 Haloalkoxy, -N(C 1-3 Alkyl)2, -NH(C 1-3 alkyl), -C(O)C 1-3 substituted by an alkyl substituent;

[0018] Z 11 、Z 12 、Z 21 、Z 22 、Z 31 、Z 32 are independently selected from a bond, -O-, -S-, -NH-, -Se-, -C 1-4 Alkylene-, -C 1-8 Oxyalkylene-, -C 1-4 Thiaalkylene-, -C 1-4 Azaalkylene-, -C 1-4Selenylheteroalkylene-; the alkylene, oxaalkylene, thiaalkylene, azaalkylene, selenylheteroalkylene are optionally substituted by one or more selected from Z 41 Substituted by a substituent; Z 41 independently selected from deuterium, halogen, oxo, thio, -CN, -OH, -NH2, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 haloalkoxy; or any two Z 41 Together with the atoms they are attached to form C 3-6 Cycloalkyl, 3-6 membered heterocyclyl, phenyl, 5-6 membered heteroaryl;

[0019] R 31 、R 32 、R 33 are independently selected from hydrogen, deuterium, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Deuterated alkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 1-6 deuterated alkoxy;

[0020] h1, h2, h3, h4, h5, and h6 are independently 0, 1, and 2;

[0021] R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 、R 11 、R 12 、R 41 、R 42 、R 43 、R 44 、R 45 、R 46 、R 47 、R 48 、R 49 are independently selected from H, deuterium, -CN, -OH, -NH2, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -N(C 1-3 Alkyl)2, -NH(C 1-3 alkyl);

[0022] R 50 、R 51 、R 52 are independently selected from H, deuterium, C 1-6 Alkyl, C 2-6Alkenyl, C 1-6 Alkoxy, -C 1-3 Alkylene OC 1-6 Alkyl, -C 1-3 Alkylene-OC(O)-C 1-6 Alkyl, the alkyl, alkenyl, alkoxy, alkylene are optionally substituted by one or more independently selected from deuterium, halogen, -OH, -NH2, -CN, oxo, C 1-3 Alkyl, C 1-3 substituted by an alkoxy substituent;

[0023] The condition is that when A is N, R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 、R 11 、R 12 、R 41 、R 42 、R 43 、R 44 、R 45 、R 46 、R 47 、R 48 、R 49 When they are H at the same time, L1, L2, and L3 are not H at the same time.

[0024] The condition is that when A is N and R is R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 、R 11 、R 12 、R 41 、R 42 When both are H, L1 and L2 are not at the same time * is the connection terminal between R and A;

[0025] The condition is that it is not

[0026] The heteroatoms in the heterocyclic group and heteroaryl group are independently selected from O, N or S, and the number of heteroatoms is 1, 2, 3 or 4.

[0027] In one embodiment of the compound represented by the above formula (I), R is a group including L3, L1, L2 and L3 are respectively Z 11 、Z 21 and Z 31 The group, and Z 11 、Z 21 and Z 31There is only one group containing a double bond; the double bond is, for example, a double bond between C and O in -C(O)-, or a double bond between C and S in -C(S)-; further preferably, Z 11 、Z 21 and Z 31 Different from each other, or Z 11 、Z 21 and Z 31 The two groups not containing a double bond in Z are identical, and the two identical groups contain -O-, -NH-, -S-, or -Se-, preferably, -O-; Still more preferably, Z 11 、Z 21 and Z 31 The molecular weight of Z is independently 14.0-107.1, preferably 14.0-60; preferably about 14, about 16, about 28, about 30, about 42, about 43, about 44, about 46, about 58, or about 60; still more preferably, Z 11 、Z 21 and Z 31 Selected from -CH2-, -CD2-, -CH2CH2-, -CD2CH2-, -C(O)-, -CH2C(O)-, -NHC(O)-, -OC(O)-, -CH2CH2O-, -OCH2C(O)-, -CH2OC(O)-, -CH2CH2CH2O-, -SC(O)-.

[0028] In some embodiments, a compound represented by the following formula (I-1-P1), or a pharmaceutically acceptable salt thereof is provided:

[0029] in, is a single bond or a double bond;

[0030] A is CR X , P, P(O) or N;

[0031] when When it is a single bond; R X H, -OH, C 1-3 alkoxy;

[0032] when When it is a double bond; R X does not exist;

[0033] L1 is selected from -C 1-3 Alkylene-C 6-10 Aryl-C 6-10 Aryl-C 1-3 Alkylene-, -C 1-3 Alkylene-C6-10 Aryl-5-12 membered heteroaryl-C 1-3 Alkylene-, -C 1-3 Alkylene-5-12 membered heteroaryl-5-12 membered heteroaryl-C 1-3 Alkylene-, The C 1-3 The alkylene group is optionally substituted by one or more groups independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The aryl and heteroaryl groups are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 Alkoxy is substituted by a substituent; * is the connection end between L1 and A;

[0034] L2 is selected from -C 1-3 Alkylene-C 6-10 Aryl-C 6-10 Aryl-C 1-3 Alkylene-, -C 1-3 Alkylene-C 6-10 Aryl-5-12 membered heteroaryl-C 1-3 Alkylene-, -C 1-3 Alkylene-5-12 membered heteroaryl-5-12 membered heteroaryl-C 1-3 Alkylene-, The C 1-3 The alkylene group is optionally substituted by one or more groups independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The aryl and heteroaryl groups are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 is substituted by an alkoxy substituent; * is the connecting end between L2 and A;

[0035] R is selected from H, -C 1-3 Alkylene-C 6-10 Aryl, -C 1-3 Alkylene-5-12 membered heteroaryl, C 1-6 alkyl, The C1-3 alkylene group is optionally replaced by one or more independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The aryl and heteroaryl groups are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 Alkoxy, C 1-3 Substituted by an aminoalkyl substituent; the C 1-6 The alkyl group is optionally substituted with one or more groups independently selected from deuterium, halogen, oxo, carboxyl, -CN, -OH, -NH2, C 1-3Alkyl, C 1-3 is substituted by an alkoxy substituent; * is the connecting end between R and A;

[0036] L3 is selected from -C 1-6 Alkylene-, -C 2-6 Alkenylene-, -C 2-6 Alkynylidene-, -C 1-3 Alkylene-C 6-10 Aryl-C 6-10 Aryl-C 1-3 Alkylene-, -C 1-3 Alkylene-C 6-10 Aryl-5-12 membered heteroaryl-C 1-3 Alkylene-, -C 1-3 Alkylene-5-12 membered heteroaryl-C 6-10 Aryl-C 1-3 Alkylene-, -C1-3 alkylene-5-12 membered heteroaryl-5-12 membered heteroaryl-C 1-3 Alkylene-, The alkylene, alkenylene and alkynylene groups are optionally substituted by one or more groups independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The aryl and heteroaryl groups are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 Alkyl, C 1-3 is substituted by an alkoxy substituent; * is the connecting end between L3 and A;

[0037] Rings W1, W2, and W3 are independently selected from C 6-12 Aryl, 5-12 membered heteroaryl, C 6-14 Cycloalkyl, 5-12 membered heterocyclic group; the aryl, heteroaryl, cycloalkyl, heterocyclic group are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 Alkyl, C 1-3 substituted by an alkoxy substituent;

[0038] Z 11 、Z 12 、Z 21 、Z 22 、Z 31 、Z 32 are independently selected from a bond, -C 1-4 Alkylene-, -C 1-4 Oxyalkylene-; the alkylene and oxyalkylene groups are optionally substituted by one or more groups independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 Alkyl, C 1-3 substituted by an alkoxy substituent;

[0039] R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 、R 11 、R 12 are independently selected from H, deuterium;

[0040] The condition is that when A is N, L1, L2, and L3 are not simultaneously

[0041] The condition is that when A is N and R is When L1 and L2 are not at the same time * is the connection terminal between R and A;

[0042] The heteroatoms in the heterocyclic group and heteroaryl group are independently selected from O, N or S, and the number of heteroatoms is 1, 2 or 3.

[0043] In one embodiment of the compound represented by the above formula (I-1-P1), R is a group including L3, L1, L2 and L3 are respectively 11 、Z 21 and Z 31 The group, and Z 11 、Z 21 and Z 31 There is only one group containing a double bond; the double bond is, for example, a double bond between C and O in -C(O)-, or a double bond between C and S in -C(S)-; further preferably, Z 11 、Z 21 and Z 31 Different from each other, or Z 11 、Z 21 and Z 31 The two groups not containing a double bond in Z are identical, and the two identical groups contain -O-, -NH-, -S-, or -Se-, preferably, -O-; Still more preferably, Z 11 、Z 21 and Z 31 The molecular weight of Z is independently 14.0-107.1, preferably 14.0-60; preferably about 14, about 16, about 28, about 30, about 42, about 43, about 44, about 46, about 58, or about 60; still more preferably, Z 11 、Z 21 and Z 31 Selected from -CH2-, -CD2-, -CH2CH2-, -CD2CH2-, -C(O)-, -CH2C(O)-, -NHC(O)-, -OC(O)-, -CH2CH2O-, -OCH2C(O)-, -CH2OC(O)-, -CH2CH2CH2O-, -SC(O)-.

[0044] In some embodiments, a compound represented by the following formula (I-1-P2), or a pharmaceutically acceptable salt thereof is provided:

[0045] in, is a single bond or a double bond;

[0046] A is CR X , P, P(O) or N;

[0047] when When it is a single bond; R X H, -OH, C 1-3 alkoxy;

[0048] when When it is a double bond; R X does not exist;

[0049] L1 is selected from -C 1-3 Alkylene-C 6-10 Aryl-C 6-10 Aryl-C 1-3 Alkylene-, -C 1-3 Alkylene-C 6-10 Aryl-5-12 membered heteroaryl-C 1-3 Alkylene-, -C 1-3 Alkylene-5-12 membered heteroaryl-5-12 membered heteroaryl-C 1-3 Alkylene-, The C 1-3 Alkylene is optionally substituted by one or more independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The aryl and heteroaryl groups are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 Alkoxy is substituted by a substituent; * is the connection end between L1 and A;

[0050] L2 is selected from -C 1-3 Alkylene-C 6-10 Aryl-C 6-10 Aryl-C 1-3 Alkylene-, -C 1-3 Alkylene-C 6-10 Aryl-5-12 membered heteroaryl-C 1-3 Alkylene-, -C 1-3 Alkylene-5-12 membered heteroaryl-5-12 membered heteroaryl-C 1-3 Alkylene-, The C 1-3Alkylene is optionally substituted by one or more independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The aryl and heteroaryl groups are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 is substituted by an alkoxy substituent; * is the connecting end between L2 and A;

[0051] R is selected from H, -C 1-3 Alkylene-C 6-10 Aryl, -C 1-3 Alkylene-5-12 membered heteroaryl, C 1-6 alkyl, The C1-3 alkylene group is optionally substituted by one or more independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The aryl and heteroaryl groups are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 Alkoxy, C 1-3 Substituted by an aminoalkyl substituent; the C 1-6 The alkyl group is optionally substituted by one or more groups independently selected from deuterium, halogen, oxo, carboxyl, -CN, -OH, -NH2, C 1-3 Alkyl, C 1-3 is substituted by an alkoxy substituent; * is the connecting end between R and A;

[0052] L3 is selected from -C 1-6 Alkylene-, -C 2-6 Alkenylene-, -C 2-6 Alkynylidene-, -C 1-3 Alkylene-C 6-10 Aryl-C 6-10 Aryl-C 1-3 Alkylene-, -C 1-3 Alkylene-C 6-10 Aryl-5-12 membered heteroaryl-C 1-3 Alkylene-, -C 1-3 Alkylene-5-12 membered heteroaryl-C 6-10 Aryl-C 1-3 Alkylene-, -C1-3 alkylene-5-12 membered heteroaryl-5-12 membered heteroaryl-C 1-3 Alkylene-, The alkylene, alkenylene and alkynylene groups are optionally substituted by one or more groups independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The aryl and heteroaryl groups are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 Alkyl, C1-3 is substituted by an alkoxy substituent; * is the connecting end between L3 and A;

[0053] Rings W1, W2, and W3 are independently selected from C 6-12 Aryl, 5-12 membered heteroaryl, C 6-14 Cycloalkyl, 5-12 membered heterocyclic group; the aryl, heteroaryl, cycloalkyl, heterocyclic group are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 Alkyl, C 1-3 substituted by an alkoxy substituent;

[0054] Z 11 、Z 12 、Z 21 、Z 22 、Z 31 、Z 32 are independently selected from a bond, -C 1-4 Alkylene-, -C 1-4 Oxyalkylene-, -C 1-4 Thiaalkylene-, -C 1-4 Azaalkylene-; the alkylene, oxaalkylene, thiaalkylene, azaalkylene are optionally substituted by one or more independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 Alkyl, C 1-3 substituted by an alkoxy substituent;

[0055] R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 、R 11 、R 12 are independently selected from H, deuterium;

[0056] The condition is that when A is N, L1, L2, and L3 are not simultaneously

[0057] The condition is that when A is N and R is When L1 and L2 are not at the same time * is the connection terminal between R and A;

[0058] The heteroatoms in the heterocyclic group and heteroaryl group are independently selected from O, N or S, and the number of heteroatoms is 1, 2 or 3.

[0059] In one embodiment of the compound represented by the above formula (I-1-P2), R is a group including L3, L1, L2 and L3 are respectively 11 、Z 21 and Z 31 The group, and Z 11 、Z 21 and Z31 There is only one group containing a double bond; the double bond is, for example, a double bond between C and O in -C(O)-, or a double bond between C and S in -C(S)-; further preferably, Z 11 、Z 21 and Z 31 Different from each other, or Z 11 、Z 21 and Z 31 The two groups not containing a double bond in Z are identical, and the two identical groups contain -O-, -NH-, -S-, or -Se-, preferably, -O-; Still more preferably, Z 11 、Z 21 and Z 31 The molecular weight of Z is independently 14.0-107.1, preferably 14.0-60; preferably about 14, about 16, about 28, about 30, about 42, about 43, about 44, about 46, about 58, or about 60; still more preferably, Z 11 、Z 21 and Z 31 Selected from -CH2-, -CD2-, -CH2CH2-, -CD2CH2-, -C(O)-, -CH2C(O)-, -NHC(O)-, -OC(O)-, -CH2CH2O-, -OCH2C(O)-, -CH2OC(O)-, -CH2CH2CH2O-, -SC(O)-.

[0060] In some embodiments, a compound represented by the following formula (I-1-P3), or a pharmaceutically acceptable salt thereof is provided:

[0061] in, is a single bond or a double bond;

[0062] A is CR X 、P、P(O)、N、C 6-12 Aryl, 5-14 membered heteroaryl, 5-18 membered heterocyclic group; the aryl, heteroaryl, heterocyclic group are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 Alkyl, C 1-3 substituted by an alkoxy substituent;

[0063] when When it is a single bond; R X H, -OH, C 1-3 alkoxy;

[0064] when When it is a double bond; R X does not exist;

[0065] L1 is selected from -C 1-3 Alkylene-C 6-10 Aryl-C 6-10 Aryl-C 1-3 Alkylene-, -C 1-3 Alkylene-C 6-10 Aryl-5-12 membered heteroaryl-C 1-3 Alkylene-, -C 1-3 Alkylene-5-12 membered heteroaryl-5-12 membered heteroaryl-C 1-3 Alkylene-, The C 1-3 The alkylene group is optionally substituted by one or more groups independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The aryl and heteroaryl groups are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 Alkoxy is substituted by a substituent; * is the connection end between L1 and A;

[0066] L2 is selected from -C 1-3 Alkylene-C 6-10 Aryl-C 6-10 Aryl-C 1-3 Alkylene-, -C 1-3 Alkylene-C 6-10 Aryl-5-12 membered heteroaryl-C 1-3 Alkylene-, -C 1-3 Alkylene-5-12 membered heteroaryl-5-12 membered heteroaryl-C 1-3 Alkylene-, The C 1-3 The alkylene group is optionally substituted by one or more groups independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The aryl and heteroaryl groups are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 is substituted by an alkoxy substituent; * is the connecting end between L2 and A;

[0067] R is selected from H, -C 1-3 Alkylene-C 6-10 Aryl, -C 1-3 Alkylene-5-12 membered heteroaryl, C 1-6 alkyl, The C1-3 alkylene group is optionally replaced by one or more independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The aryl and heteroaryl groups are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C1-3 Alkoxy, C 1-3 Substituted by an aminoalkyl substituent; the C 1-6 The alkyl group is optionally substituted with one or more groups independently selected from deuterium, halogen, oxo, carboxyl, -CN, -OH, -NH2, C 1-3 Alkyl, C 1-3 is substituted by an alkoxy substituent; * is the connecting end between R and A;

[0068] L3 is selected from -C 1-6 Alkylene-, -C 2-6 Alkenylene-, -C 2-6 Alkynylidene-, -C 1-3 Alkylene-C 6-10 Aryl-C 6-10 Aryl-C 1-3 Alkylene-, -C 1-3 Alkylene-C 6-10 Aryl-5-12 membered heteroaryl-C 1-3 Alkylene-, -C 1-3 Alkylene-5-12 membered heteroaryl-C 6-10 Aryl-C 1-3 Alkylene-, -C1-3 alkylene-5-12 membered heteroaryl-5-12 membered heteroaryl-C 1-3 Alkylene-, The alkylene, alkenylene and alkynylene groups are optionally substituted by one or more groups independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The aryl and heteroaryl groups are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 Alkyl, C 1-3 is substituted by an alkoxy substituent; * is the connecting end between L3 and A;

[0069] Rings W1, W2, and W3 are independently selected from C 6-12 Aryl, 5-12 membered heteroaryl, C 6-14 Cycloalkyl, 5-12 membered heterocyclic group; the aryl, heteroaryl, cycloalkyl, heterocyclic group are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 Alkyl, C 1-3 substituted by an alkoxy substituent;

[0070] Z 11 、Z 12 、Z 21 、Z 22 、Z 31 、Z 32 are independently selected from a bond, -C 1-4 Alkylene-, -C 1-4Oxyalkylene-, -C 1-4 Thiaalkylene-, -C 1-4 Azaalkylene-; the alkylene, oxaalkylene, thiaalkylene, azaalkylene are optionally substituted by one or more independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 substituted by a haloalkoxy substituent;

[0071] R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 、R 11 、R 12 are independently selected from H, deuterium;

[0072] The condition is that when A is N, R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 、R 11 、R 12 When they are H at the same time, L1, L2, and L3 are not H at the same time.

[0073] The condition is that when A is N and R is R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 、R 11 、R 12 When both are H, L1 and L2 are not at the same time * is the connection terminal between R and A;

[0074] The condition is that it is not

[0075] The heteroatoms in the heterocyclic group and heteroaryl group are independently selected from O, N or S, and the number of heteroatoms is 1, 2, 3 or 4.

[0076] In one embodiment of the compound represented by the above formula (I-1-P3), R is a group including L3, L1, L2 and L3 are respectively 11 、Z 21 and Z 31 The group, and Z 11 、Z 21 and Z 31 There is only one group containing a double bond; the double bond is, for example, a double bond between C and O in -C(O)-, or a double bond between C and S in -C(S)-; further preferably, Z 11 、Z 21 and Z 31Different from each other, or Z 11 、Z 21 and Z 31 The two groups not containing a double bond in Z are identical, and the two identical groups contain -O-, -NH-, -S-, or -Se-, preferably, -O-; Still more preferably, Z 11 、Z 21 and Z 31 The molecular weight of Z is independently 14.0-107.1, preferably 14.0-60; preferably about 14, about 16, about 28, about 30, about 42, about 43, about 44, about 46, about 58, or about 60; still more preferably, Z 11 、Z 21 and Z 31 Selected from -CH2-, -CD2-, -CH2CH2-, -CD2CH2-, -C(O)-, -CH2C(O)-, -NHC(O)-, -OC(O)-, -CH2CH2O-, -OCH2C(O)-, -CH2OC(O)-, -CH2CH2CH2O-, -SC(O)-.

[0077] In some embodiments, a compound represented by the following formula (I-1-P4), or a pharmaceutically acceptable salt of the compound is provided:

[0078] in, is a single bond or a double bond;

[0079] A is CR X 、P、P(O)、N、C 6-12 Aryl, 5-14 membered heteroaryl, 5-18 membered heterocyclic group; the aryl, heteroaryl, heterocyclic group are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 Alkyl, C 1-3 substituted by an alkoxy substituent;

[0080] when When it is a single bond; R X H, -OH, C 1-3 alkoxy;

[0081] when When it is a double bond; R X does not exist;

[0082] L1 is selected from -C 1-3 Alkylene-C 6-10 Aryl-C 6-10 Aryl-C 1-3 Alkylene-, -C 1-3 Alkylene-C 6-10Aryl-5-12 membered heteroaryl-C 1-3 Alkylene-, -C 1-3 Alkylene-5-12 membered heteroaryl-5-12 membered heteroaryl-C 1-3 Alkylene-, The C 1-3 The alkylene group is optionally substituted by one or more groups independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The aryl and heteroaryl groups are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 Alkoxy is substituted by a substituent; * is the connection end between L1 and A;

[0083] L2 is selected from -C 1-3 Alkylene-C 6-10 Aryl-C 6-10 Aryl-C 1-3 Alkylene-, -C 1-3 Alkylene-C 6-10 Aryl-5-12 membered heteroaryl-C 1-3 Alkylene-, -C 1-3 Alkylene-5-12 membered heteroaryl-5-12 membered heteroaryl-C 1-3 Alkylene-, The C 1-3 The alkylene group is optionally substituted by one or more groups independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The aryl and heteroaryl groups are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 is substituted by an alkoxy substituent; * is the connecting end between L2 and A;

[0084] R is selected from H, -C 1-3 Alkylene-C 6-10 Aryl, -C 1-3 Alkylene-5-12 membered heteroaryl, C 1-6 alkyl, The C1-3 alkylene group is optionally replaced by one or more independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The aryl and heteroaryl groups are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 Alkoxy, C 1-3 Substituted by an aminoalkyl substituent; the C 1-6 The alkyl group is optionally substituted with one or more groups independently selected from deuterium, halogen, oxo, carboxyl, -CN, -OH, -NH2, C 1-3 Alkyl, C1-3 is substituted by an alkoxy substituent; * is the connecting end between R and A;

[0085] L3 is selected from -C 1-6 Alkylene-, -C 2-6 Alkenylene-, -C 2-6 Alkynylidene-, -C 1-3 Alkylene-C 6-10 Aryl-C 6-10 Aryl-C 1-3 Alkylene-, -C 1-3 Alkylene-C 6-10 Aryl-5-12 membered heteroaryl-C 1-3 Alkylene-, -C 1-3 Alkylene-5-12 membered heteroaryl-C 6-10 Aryl-C 1-3 Alkylene-, -C1-3 alkylene-5-12 membered heteroaryl-5-12 membered heteroaryl-C 1-3 Alkylene-, The alkylene, alkenylene and alkynylene groups are optionally substituted by one or more groups independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The aryl and heteroaryl groups are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 Alkyl, C 1-3 is substituted by an alkoxy substituent; * is the connecting end between L3 and A;

[0086] Rings W1, W2, and W3 are independently selected from C 6-12 Aryl, 5-12 membered heteroaryl, C 6-14 Cycloalkyl, 5-12 membered heterocyclic group; the aryl, heteroaryl, cycloalkyl, heterocyclic group are optionally substituted by one or more independently selected from deuterium, halogen, -CN, -OH, -NH2, -CHO, C 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkyl, C 1-3 Haloalkoxy, -N(C 1-3 Alkyl)2, -NH(C 1-3 alkyl), -C(O)C 1-3 substituted by an alkyl substituent;

[0087] Z 11 、Z 12 、Z 21 、Z 22 、Z 31 、Z 32 are independently selected from a bond, -O-, -S-, -NH-, -Se-, -C 1-4Alkylene-, -C 1-8 Oxyalkylene-, -C 1-4 Thiaalkylene-, -C 1-4 Azaalkylene-, -C 1-4 Selenylheteroalkylene-; the alkylene, oxaalkylene, thiaalkylene, azaalkylene, selenylheteroalkylene are optionally substituted by one or more selected from Z 41 Substituted by a substituent; Z 41 independently selected from deuterium, halogen, oxo, thio, -CN, -OH, -NH2, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 haloalkoxy; or any two Z 41 Together with the atoms they are attached to form C 3-6 Cycloalkyl, 3-6 membered heterocyclyl, phenyl, 5-6 membered heteroaryl;

[0088] R 31 、R 32 、R 33 are independently selected from hydrogen, deuterium, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Deuterated alkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 1-6 deuterated alkoxy;

[0089] h1, h2, h3, h4, h5, and h6 are independently 0, 1, and 2;

[0090] R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 、R 11 、R 12 are independently selected from H, deuterium;

[0091] The condition is that when A is N, R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 、R 11 、R 12 When they are H at the same time, L1, L2, and L3 are not H at the same time.

[0092] The condition is that when A is N and R is R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 、R 11 、R 12 When both are H, L1 and L2 are not at the same time * is the connection terminal between R and A;

[0093] The condition is that it is not

[0094] The heteroatoms in the heterocyclic group and heteroaryl group are independently selected from O, N or S, and the number of heteroatoms is 1, 2, 3 or 4.

[0095] In one embodiment of the compound represented by the above formula (I-1-P4), R is a group including L3, L1, L2 and L3 are respectively 11 、Z 21 and Z 31 The group, and Z 11 、Z 21 and Z 31 There is only one group containing a double bond; the double bond is, for example, a double bond between C and O in -C(O)-, or a double bond between C and S in -C(S)-; further preferably, Z 11 、Z 21 and Z 31 Different from each other, or Z 11 、Z 21 and Z 31 The two groups not containing a double bond in Z are identical, and the two identical groups contain -O-, -NH-, -S-, or -Se-, preferably, -O-; Still more preferably, Z 11 、Z 21 and Z 31 The molecular weight of Z is independently 14.0-107.1, preferably 14.0-60; preferably about 14, about 16, about 28, about 30, about 42, about 43, about 44, about 46, about 58, or about 60; still more preferably, Z 11 、Z 21 and Z 31 Selected from -CH2-, -CD2-, -CH2CH2-, -CD2CH2-, -C(O)-, -CH2C(O)-, -NHC(O)-, -OC(O)-, -CH2CH2O-, -OCH2C(O)-, -CH2OC(O)-, -CH2CH2CH2O-, -SC(O)-.

[0096] In some embodiments, a compound represented by the following formula (I-2), or a pharmaceutically acceptable salt thereof is provided:

[0097] Among them, A, L1, L2, R, R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 、R11 、R 12 、R 31 、R 32 As described in the compounds of formula (I), formula (I-1-P1), formula (I-1-P2), formula (I-1-P3), and formula (I-1-P4).

[0098] In one embodiment of the compound represented by the above formula (I-2), R is a group including L3, L1, L2 and L3 are respectively Z 11 、Z 21 and Z 31 The group, and Z 11 、Z 21 and Z 31 There is only one group containing a double bond; the double bond is, for example, a double bond between C and O in -C(O)-, or a double bond between C and S in -C(S)-; further preferably, Z 11 、Z 21 and Z 31 Different from each other, or Z 11 、Z 21 and Z 31 The two groups not containing a double bond in Z are identical, and the two identical groups contain -O-, -NH-, -S-, or -Se-, preferably, -O-; Still more preferably, Z 11 、Z 21 and Z 31 The molecular weight of Z is independently 14.0-107.1, preferably 14.0-60; preferably about 14, about 16, about 28, about 30, about 42, about 43, about 44, about 46, about 58, or about 60; still more preferably, Z 11 、Z 21 and Z 31 Selected from -CH2-, -CD2-, -CH2CH2-, -CD2CH2-, -C(O)-, -CH2C(O)-, -NHC(O)-, -OC(O)-, -CH2CH2O-, -OCH2C(O)-, -CH2OC(O)-, -CH2CH2CH2O-, -SC(O)-.

[0099] In some embodiments, a compound represented by the following formula (I-3), or a pharmaceutically acceptable salt thereof is provided:

[0100] Among them, A, L1, L2, R, R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 、R 11 、R12 As described in the compounds of formula (I), formula (I-1-P1), formula (I-1-P2), formula (I-1-P3), and formula (I-1-P4).

[0101] In one embodiment of the compound represented by the above formula (I-3), R is a group including L3, L1, L2 and L3 are respectively 11 、Z 21 and Z 31 The group, and Z 11 、Z 21 and Z 31 There is only one group containing a double bond; the double bond is, for example, a double bond between C and O in -C(O)-, or a double bond between C and S in -C(S)-; further preferably, Z 11 、Z 21 and Z 31 Different from each other, or Z 11 、Z 21 and Z 31 The two groups not containing a double bond in Z are identical, and the two identical groups contain -O-, -NH-, -S-, or -Se-, preferably, -O-; Still more preferably, Z 11 、Z 21 and Z 31 The molecular weight of Z is independently 14.0-107.1, preferably 14.0-60; preferably about 14, about 16, about 28, about 30, about 42, about 43, about 44, about 46, about 58, or about 60; still more preferably, Z 11 、Z 21 and Z 31 Selected from -CH2-, -CD2-, -CH2CH2-, -CD2CH2-, -C(O)-, -CH2C(O)-, -NHC(O)-, -OC(O)-, -CH2CH2O-, -OCH2C(O)-, -CH2OC(O)-, -CH2CH2CH2O-, -SC(O)-.

[0102] In one embodiment of the present invention, A is CR X , P, P(O), N, phenyl, 5-6 membered heterocyclic group, 12 membered heterocyclic group; the heteroatom in the heterocyclic group is N, and the number of heteroatoms is 1, 2, 3 or 4.

[0103] In one embodiment of the present invention, A is CR X 、P、P(O)、N、phenyl、piperazinyl、 In one embodiment of the present invention, A is CR X 、P、P(O)、N、 Preferably, A is N,

[0104] In one embodiment of the present invention, A is CR X ,P,P(O),N.

[0105] In one embodiment of the present invention, A is N.

[0106] In one embodiment of the present invention, A is P(O);

[0107] In one embodiment of the present invention, A is selected from CR X ; R X It is H, -OH, and methoxy.

[0108] In one embodiment of the present invention, A is selected from C-OH, C-OCH3.

[0109] In one embodiment of the present invention, A is a 6-12 membered heterocyclyl.

[0110] In one embodiment of the present invention, A is a 6-membered heterocyclic group; preferably, A is a piperazinyl group; preferably

[0111] In one embodiment of the present invention, A is

[0112] In one embodiment of the present invention, A is phenyl; preferably

[0113] In one embodiment of the present invention, R X It is H, -OH, and methoxy.

[0114] In one embodiment of the present invention, L1 is selected from -methylene-C 6-10 Aryl-C 6-10 Aryl-methylene-, -methylene-5-12 membered heteroaryl-5-12 membered heteroaryl-methylene-, The methylene group is optionally replaced by one or more independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The aryl and heteroaryl groups are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 The substituent of the alkoxy group is substituted; * is the connecting end between L1 and A.

[0115] In one embodiment of the present invention, L1 is selected from -C 1-3 Alkylene-phenyl-phenyl-C 1-3Alkylene-, -C 1-3 Alkylene-5-6 membered heteroaryl-5-6 membered heteroaryl-C 1-3 Alkylene-, The C 1-3 The alkylene group is optionally substituted by one or more groups independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The phenyl and heteroaryl groups are optionally substituted by one or more groups independently selected from halogen, -CN, C 1-3 The substituent of the alkoxy group is substituted; * is the connecting end between L1 and N.

[0116] In one embodiment of the present invention, L1 is selected from -methylene-phenyl-phenyl-methylene-, -ethylene-phenyl-phenyl-ethylidene-, -methylene-5-6 membered heteroaryl-5-6 membered heteroaryl-methylene-, -ethylidene-5-6 membered heteroaryl-5-6 membered heteroaryl-ethylidene-, The methylene and ethylene groups are optionally replaced by one or more groups independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The phenyl and heteroaryl groups are optionally substituted by one or more groups independently selected from halogen, -CN, C 1-3 The substituent of the alkoxy group is substituted; * is the connecting end between L1 and A.

[0117] In one embodiment of the present invention, L1 is selected from -methylene-phenyl-phenyl-methylene-, -methylene-6-membered heteroaryl-6-membered heteroaryl-methylene-, The methylene group is optionally replaced by one or more independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The phenyl and heteroaryl groups are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 The substituent of the alkoxy group is substituted; * is the connecting end between L1 and A.

[0118] In one embodiment of the present invention, L1 is selected from -methylene-phenyl-phenyl-methylene-, -methylene-pyridyl-pyridyl-methylene-, * is the L1 and A connection terminal.

[0119] In one embodiment of the present invention, L1 is selected from * is the L1 and A connection terminal.

[0120] In one embodiment of the present invention, L1 is * is the L1 and A connection terminal.

[0121] In one embodiment of the present invention, L2 is selected from -methylene-C 6-10 Aryl-C 6-10 Aryl-methylene-, -methylene-5-12 membered heteroaryl-5-12 membered heteroaryl-methylene-, The methylene group is optionally replaced by one or more independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The aryl and heteroaryl groups are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 The substituent of the alkoxy group is substituted; * is the connecting end between L2 and A.

[0122] In one embodiment of the present invention, L2 is selected from -C 1-3 Alkylene-phenyl-phenyl-C 1-3 Alkylene-, -C 1-3 Alkylene-5-6 membered heteroaryl-5-6 membered heteroaryl-C 1-3 Alkylene-, The C 1-3 The alkylene group is optionally substituted by one or more groups independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The phenyl and heteroaryl groups are optionally substituted by one or more groups independently selected from halogen, -CN, C 1-3 The substituent of the alkoxy group is substituted; * is the connecting terminal of L2 and N.

[0123] In one embodiment of the present invention, L2 is selected from -methylene-phenyl-phenyl-methylene-, -ethylene-phenyl-phenyl-ethylidene-, -methylene-5-6 membered heteroaryl-5-6 membered heteroaryl-methylene-, -ethylidene-5-6 membered heteroaryl-5-6 membered heteroaryl-ethylidene-, The methylene and ethylene groups are optionally replaced by one or more groups independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The phenyl and heteroaryl groups are optionally substituted by one or more groups independently selected from halogen, -CN, C 1-3 The substituent of the alkoxy group is substituted; * is the connecting end between L2 and A.

[0124] In one embodiment of the present invention, L2 is selected from -methylene-phenyl-phenyl-methylene-, -methylene-6-membered heteroaryl-6-membered heteroaryl-methylene-, The methylene group is optionally replaced by one or more independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3The phenyl and heteroaryl groups are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 The substituent of the alkoxy group is substituted; * is the connecting end between L2 and A.

[0125] In one embodiment of the present invention, L2 is selected from -methylene-phenyl-phenyl-methylene-, -methylene-pyridyl-pyridyl-methylene-, * is the L2 and A connection terminal.

[0126] In one embodiment of the present invention, L2 is selected from * is the L2 and A connection terminal.

[0127] In one embodiment of the present invention, L2 is selected from * is the L2 and A connection terminal.

[0128] In one embodiment of the present invention, R is selected from H, -C 1-3 Alkylene-C 6-10 Aryl, -C 1-3 Alkylene-5-12 membered heteroaryl, C 1-6 alkyl, The C 1-3 The alkylene group is optionally substituted by one or more groups independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The aryl and heteroaryl groups are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 Alkoxy, C 1-3 Substituted by an aminoalkyl substituent; the C 1-6 The alkyl group is optionally substituted with one or more groups independently selected from deuterium, halogen, oxo, carboxyl, -CN, -OH, -NH2, C 1-3 Alkyl, C 1-3 The substituent of the alkoxy group is substituted; * is the connecting end between R and A.

[0129] In one embodiment of the present invention, R is selected from H, -C 1-3 Alkylene-C 6-10 Aryl, -C 1-3 Alkylene-5-10 membered heteroaryl, C 1-6 alkyl, The C 1-3 The alkylene group is optionally substituted by one or more substituents independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2; the aryl and heteroaryl groups are optionally substituted by one or more substituents independently selected from deuterium, halogen, -CN, methoxy, C 1-3 Substituted by an aminoalkyl substituent; the C1-6 The alkyl group is optionally substituted with one or more groups independently selected from deuterium, halogen, oxo, carboxyl, -CN, -OH, -NH2, C 1-3 Alkyl, C 1-3 The substituent of the alkoxy group is substituted; * is the connecting end between R and A.

[0130] In one embodiment of the present invention, R is selected from H, -methylene-phenyl, -ethylene-phenyl, -methylene-5-6 membered heteroaryl, -ethylene-5-6 membered heteroaryl, C 1-6 alkyl, The methylene and ethylene groups are optionally substituted by one or more substituents independently selected from halogen, oxo, -CN, -OH, and -NH2; the phenyl and heteroaryl groups are optionally substituted by one or more substituents independently selected from halogen, -CN, methoxy, Substituted by a substituent; the C 1-6 The alkyl group is optionally substituted by one or more substituents independently selected from halogen, oxo, carboxyl, -CN, -OH, and -NH2; * is the connecting terminal of R and A.

[0131] In one embodiment of the present invention, R is selected from H, -methylene-phenyl, -ethylene-phenyl, -methylene-pyridyl, -ethylene-pyridyl, methyl, ethyl, n-propyl, isopropyl, n-butyl, n-pentyl, n-hexyl, The phenyl and pyridyl groups are optionally substituted by one or more groups independently selected from halogen, methoxy, The methyl, ethyl, n-propyl, isopropyl, n-butyl, n-pentyl and n-hexyl groups are optionally substituted by one or more substituents independently selected from carboxyl and -NH2; * is the connecting terminal of R and A.

[0132] In one embodiment of the present invention, R is selected from H, -C 1-3 Alkylene-phenyl, -C 1-3 Alkylene-5-6 membered heteroaryl, C 1-6 Alkyl; the C 1-3 The alkylene group is optionally substituted by one or more groups independently selected from halogen, oxo, -CN, -OH, -NH2, C 1-3 The phenyl and heteroaryl groups are optionally substituted by one or more groups independently selected from halogen, -CN, C 1-3 Alkoxy, C 1-3 Substituted by an aminoalkyl substituent; the C 1-6 The alkyl group is optionally substituted with one or more substituents each independently selected from halogen, carboxyl, -NH2, methyl, methoxy.

[0133] In one embodiment of the present invention, R is selected from H, * is the R and A connection terminal.

[0134] In one embodiment of the present invention, R is selected from H, Preferred Preferred Preferred Preferred Preferred Among them, * is the connection end with A.

[0135] In one embodiment of the present invention, L3 is selected from -C 1-6 Alkylene-, -C 2-6 Alkynylidene-, -methylene-C 6-10 Aryl-C 6-10 Aryl-methylene-, -methylene-5-12 membered heteroaryl-5-12 membered heteroaryl-methylene-, The alkylene, methylene and alkynylene groups are optionally substituted by one or more groups independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The aryl and heteroaryl groups are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 Alkyl, C 1-3 The substituent of the alkoxy group is substituted; * is the connecting end between L3 and A.

[0136] In one embodiment of the present invention, L3 is selected from -C 1-6 Alkylene-, -C 2-6 Alkyne-, -methylene-phenyl-phenyl-methylene-, -ethylene-phenyl-phenyl-ethylidene-, -methylene-5-6 membered heteroaryl-5-6 membered heteroaryl-methylene-, -ethylidene-5-6 membered heteroaryl-5-6 membered heteroaryl-ethylidene-, The alkylene-, methylene, ethylene, and alkynylene groups are optionally substituted with one or more substituents independently selected from halogen, oxo, -CN, -OH, -NH2, methyl, and ethyl; the phenyl and heteroaryl groups are optionally substituted with one or more substituents independently selected from halogen, -CN, methyl, ethyl, methoxy, and ethoxy; * is the connecting terminal of L3 and A.

[0137] In one embodiment of the present invention, L3 is selected from -C 1-6 Alkylene-, -C 2-6 Alkyne-, -methylene-phenyl-phenyl-methylene-, -methylene-6-membered heteroaryl-6-membered heteroaryl-methylene-, The alkylene group and methylene group are optionally substituted by one or more substituents independently selected from fluorine, chlorine, bromine, oxo, -CN, -OH, and -NH2; the phenyl group and heteroaryl group are optionally substituted by one or more substituents independently selected from fluorine, chlorine, bromine, -CN, methyl, ethyl, methoxy, and ethoxy; * is the connecting terminal of L3 and A.

[0138] In one embodiment of the present invention, L3 is selected from methylene, ethylene, n-propylene, isopropylene, n-butylene, n-pentylene, n-hexylene, n-propynylene, n-butynylene, n-pentynylene, n-hexynylene, -methylene-phenyl-phenyl-methylene-, -methylene-pyridyl-pyridyl-methylene-, * is the L3 and A connection terminal.

[0139] In one embodiment of the present invention, L3 is selected from * is the L3 and A connection terminal.

[0140] In one embodiment of the present invention, L3 is selected from * is the L3 and A connection terminal.

[0141] In one embodiment of the present invention, rings W1, W2, and W3 are independently selected from C 6-12 Aryl, 5-12 membered heteroaryl, C 6-14 Cycloalkyl; the aryl, heteroaryl, cycloalkyl are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 Alkyl, C 1-3 substituted by an alkoxy substituent.

[0142] In one embodiment of the present invention, rings W1, W2, and W3 are independently selected from C 6-10 Aryl, 5-10 membered heteroaryl, C 6-10 Cycloalkyl; the aryl, heteroaryl, cycloalkyl are optionally substituted by one or more substituents independently selected from fluorine, chlorine, bromine, -CN, methyl, ethyl, methoxy, ethoxy.

[0143] In one embodiment of the present invention, rings W1, W2, and W3 are independently selected from phenyl, naphthyl, 8-10 membered bicyclic heteroaryl, C 8- 10 Bicyclic cycloalkyl, 5-6 membered monocyclic heteroaryl; the phenyl, naphthyl, heteroaryl, cycloalkyl are optionally substituted by one or more independently selected from halogen, -CN, C 1-3 Alkyl, C 1-3 substituted by an alkoxy substituent.

[0144] In one embodiment of the present invention, rings W1, W2, and W3 are independently selected from phenyl, naphthyl, 5-membered / 5-membered fused heteroaryl, 5-membered / 6-membered fused heteroaryl, 6-membered / 5-membered fused heteroaryl, 6-membered / 6-membered fused heteroaryl, 4-membered / 6-membered spirocycloalkyl, 6-membered / 4-membered spirocycloalkyl, 5-membered / 5-membered spirocycloalkyl, 5-membered / 6-membered spirocycloalkyl, 6-membered / 5-membered spirocycloalkyl, 6-membered / 6-membered spirocycloalkyl, and 5-6-membered monocyclic heteroaryl; and the phenyl, naphthyl, fused heteroaryl, spirocycloalkyl, and monocyclic heteroaryl are optionally substituted by one or more substituents independently selected from fluorine, chlorine, bromine, -CN, methyl, ethyl, methoxy, and ethoxy.

[0145] In one embodiment of the present invention, rings W1, W2, and W3 are independently selected from phenyl, naphthyl, 5-membered / 5-membered fused heteroaryl, 5-membered / 6-membered fused heteroaryl, 6-membered / 5-membered fused heteroaryl, 6-membered / 6-membered fused heteroaryl, 4-membered / 6-membered spiroalkyl, 6-membered / 4-membered spiroalkyl, and 5-6-membered monocyclic heteroaryl; and the phenyl, naphthyl, fused heteroaryl, spiroalkyl, and monocyclic heteroaryl are optionally substituted with one or more substituents independently selected from fluorine, chlorine, bromine, methyl, ethyl, methoxy, and ethoxy.

[0146] In one embodiment of the present invention, ring W1, W2, and W3 are independently selected from phenyl and 5-6 membered monocyclic heteroaryl; the phenyl and heteroaryl are optionally substituted by one or more independently selected from deuterium, halogen, -CN, -OH, -NH2, -CHO, C 1-3 Alkyl, C 1-3 Alkoxy, -N(C 1-3 Alkyl)2, -NH(C 1-3 alkyl), -C(O)C 1-3 The heteroatom in the heteroaryl group is O, N or S, and the number of heteroatoms is 1 or 2.

[0147] In one embodiment of the present invention, rings W1, W2, and W3 are each independently selected from the following optionally substituted groups: The optional substitution refers to being unsubstituted or being substituted by one or more independently selected from deuterium, halogen, -CN, -OH, -NH2, -CHO, C 1-3 Alkyl, C 1-3 Alkoxy, -N(C 1-3 Alkyl)2, -NH(C 1-3 alkyl), -C(O)C 1-3 substituted by an alkyl substituent.

[0148] In one embodiment of the present invention, rings W1, W2, and W3 are each independently selected from the following optionally substituted groups: The optional substitution means unsubstituted or substituted by one or more substituents independently selected from deuterium, fluorine, chlorine, bromine, -CN, -OH, -NH2, -CHO, methyl, ethyl, methoxy, ethoxy, -N(CH3)2, -NH(CH3), -C(O)CH3.

[0149] In one embodiment of the present invention, rings W1, W2, and W3 are independently selected from phenyl and thienyl; the phenyl and thienyl are optionally substituted by one or more substituents independently selected from deuterium, fluorine, chlorine, bromine, -CN, -OH, -NH2, -CHO, methyl, ethyl, methoxy, ethoxy, -N(CH3)2, -NH(CH3), and -C(O)CH3.

[0150] In one embodiment of the present invention, rings W1, W2, and W3 are each independently selected from the following optionally substituted groups: The optional substitution means unsubstituted or substituted by one or more substituents independently selected from deuterium, fluorine, chlorine, bromine, -CN, -OH, -NH2, -CHO, methyl, ethyl, methoxy, ethoxy, -N(CH3)2, -NH(CH3), -C(O)CH3.

[0151] In one embodiment of the present invention, rings W1, W2, and W3 are independently selected from phenyl; the phenyl is optionally substituted by one or more substituents independently selected from fluorine, chlorine, bromine, methyl, ethyl, methoxy, and ethoxy.

[0152] In one embodiment of the present invention, W1, W2, and W3 are independently selected from

[0153] In one embodiment of the present invention, Z 11 、Z 12 、Z 21 、Z 22 、Z 31 、Z 32 are independently selected from a bond, -O-, -S-, -NH-, -Se-, -C 1-4 Alkylene-, -C 1-6 Oxyalkylene-, -C 1-4 Thiaalkylene-, -C 1-4 Azaalkylene-, -C 1-4 Selenylheteroalkylene-; the alkylene, oxaalkylene, thiaalkylene, azaalkylene, selenylheteroalkylene are optionally substituted by one or more selected from Z 41 Substituted by a substituent; Z 41are independently selected from deuterium, halogen (e.g., fluorine, chlorine), oxo, thio, -CN, -OH, -NH2, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 haloalkoxy; or any two Z 41 Together with the atoms they are attached to form C 3-6 Cycloalkyl, 3-6 membered heterocyclic group (such as oxetane); the heteroatom in the heterocyclic group is O, N or S, and the number of heteroatoms is 1 or 2.

[0154] In one embodiment of the present invention, Z 11 、Z 12 、Z 21 、Z 22 、Z 31 、Z 32 are independently selected from a bond, -C 1-3 Alkylene-, -C 1-3 Oxyalkylene-, -C 1-3 Thiaalkylene-, -C 1-3 Azaalkylene-; the alkylene, oxaalkylene, thiaalkylene, and azaalkylene are optionally substituted with one or more substituents each independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, methyl, and methoxy; preferably, the alkylene, oxaalkylene, thiaalkylene, and azaalkylene are optionally substituted with one or more substituents each independently selected from deuterium and oxo.

[0155] In one embodiment of the present invention, Z 11 、Z 12 、Z 21 、Z 22 、Z 31 、Z 32 are independently selected from -C 1-2 Alkylene-, -C 1-2 Oxyalkylene-, -C 1-2 Thiaalkylene-, -C 1-2 Azaalkylene-; the alkylene, oxaalkylene, thiaalkylene, and azaalkylene are optionally substituted with one or more substituents independently selected from deuterium and oxo.

[0156] In one embodiment of the present invention, Z 11 、Z 12 、Z 21 、Z 22 、Z 31 、Z 32 are independently selected from a bond, -C 1-3 Alkylene-, -C1-3 Oxoalkylene-; the alkylene and oxoalkylene groups are optionally substituted with one or more substituents each independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, methyl, and methoxy; preferably, the alkylene and oxoalkylene groups are optionally substituted with one or more substituents each independently selected from deuterium and oxo.

[0157] In one embodiment of the present invention, Z 11 、Z 12 、Z 21 、Z 22 、Z 31 、Z 32 are independently selected from -C 1-2 Alkylene-, -C 1-3 Oxyalkylene-, -C 1-3 Azaalkylene-; the alkylene, oxaalkylene, and azaalkylene groups are optionally substituted with one or more substituents each independently selected from oxo.

[0158] In one embodiment of the present invention, when Z 11 、Z 21 and Z 31 When Z 11 、Z 21 and Z 31 The combination defined in the following comprises at least one heteroatom or heteroatom group selected from -O-, -S-, -Se-, -NH-, -CO-, and -C(S)-.

[0159] In one embodiment of the present invention, when Z 11 、Z 21 and Z 31 When Z 11 、Z 21 and Z 31 The combination defined in the following comprises at least one heteroatom or heteroatom group selected from -CO- or -C(S)-.

[0160] In one embodiment of the present invention, when Z 11 、Z 21 and Z 31 When Z 11 、Z 21 and Z 31 The combination of the definitions of One of *Indicates the connection terminal to A.

[0161] In one embodiment of the present invention, when Z 11 、Z 21 and Z 31 When Z 11 、Z 21 and Z 31 The combination defined in the following comprises at least one heteroatom or heteroatom group selected from -O-, -NH-, and -CO-.

[0162] In one embodiment of the present invention, when Z 11 、Z 21 and Z 31 When Z 11 、Z 21 and Z 31 The combination defined in the present invention comprises 1-4 heteroatoms or heteroatom groups, wherein the heteroatoms or heteroatom groups are selected from -O-, -S-, -Se-, -NH-, -CO-, -C(S)-, specifically 1, 2, 3, or 4; preferably 1-3 heteroatoms or heteroatom groups, specifically 1, 2, or 3; more preferably 2-4 heteroatoms or heteroatom groups, specifically 2, 3, or 4; more preferably 2 or 3 heteroatoms or heteroatom groups; the heteroatoms or heteroatom groups are preferably -O-, -S-, -NH-, or -CO-; the heteroatoms or heteroatom groups are more preferably -O- or -CO-; preferably, the heteroatoms or heteroatom groups contain at least -CO- or -C(S)-.

[0163] In one embodiment of the present invention, Z 21 Contains a heteroatom or heteroatom group selected from -O-, -S-, -Se-, -NH-; and Z 31 Contains a heteroatom or heteroatom group selected from -CO-, -C(S)-; and Z 21 and Z 31 In the constituted combination, the total number of the heteroatoms or heteroatom groups is 1-4.

[0164] In one embodiment of the present invention, when Z 11 、Z 21 and Z 31 When Z 11 、Z 21 and Z 31 The combination defined in the following comprises 1-4 heteroatoms or heteroatom groups, wherein the heteroatoms or heteroatom groups are selected from -O-, -NH-, and -CO-; preferably 1-3; more preferably 2-3; preferably, the heteroatoms or heteroatom groups contain at least -CO-.

[0165] In one embodiment of the present invention, Z 11 、Z 21 and Z 31 It contains 1 to 4 heteroatoms or heteroatom groups in total, and the heteroatoms or heteroatom groups are selected from -O-, -NH-, and -CO-, specifically 1, 2, 3, or 4 heteroatoms or heteroatom groups.

[0166] In one embodiment of the present invention, Z 11 、Z 21 and Z 31 It contains 1-3 heteroatoms or heteroatom groups in total, and the heteroatoms or heteroatom groups are selected from -O-, -NH-, and -CO-, specifically 1, 2, or 3 heteroatoms.

[0167] In one embodiment of the present invention, Z 11 、Z 21 and Z 31 Contains 2-3 heteroatoms or heteroatom groups in total, wherein the heteroatoms or heteroatom groups are selected from -O-, -NH-, and -CO-, specifically 2 or 3; preferably, the heteroatoms or heteroatom groups contain at least -CO-.

[0168] In one embodiment of the present invention, Z 11 、Z 12 、Z 21 、Z 22 、Z 31 、Z 32 are independently selected from -CD2-, -C 1-4 Alkylene-, -OC 1-3 Alkylene-, -C(O)-, -C 1-3 Alkylene-C(O)-, -OC 1-3 Alkylene-C(O)-, -NH-C 1-3 Alkylene-C(O)-, -SC 1-3 Alkylene-C(O)-, -OC 1-2 Alkylene-C(O)-C 1-3 Alkylene-, -C 1-2 Alkyl-OC 1-3 Alkylene-, -NH-C 1-3 Alkylene-, -SC 1-3 Alkylene-, -C 1-3 Alkylene-NH-C(O)-, -C 1-3 Alkylene-OC(O)-, -NH-C(O)-, -OC(O)-, -SC(O)-, -C 1-3 Alkylene-C(S)-, -Se-C 1- 3 alkylene-, The alkylene, methylene and ethylene groups are optionally substituted by one or more substituents independently selected from deuterium, fluorine and chlorine.

[0169] In one embodiment of the present invention, Z 11 、Z 12 、Z 21 、Z 22 、Z 31 、Z 32 are independently selected from -CD2-, -C 1-3 Alkylene-, -OC 1-3 Alkylene-, -C(O)-, -C 1-3 Alkylene-C(O)-, -OC 1-3 Alkylene-C(O)-, -NH-C 1-3 Alkylene-C(O)-, -SC 1-3 Alkylene-C(O)-, -OC 1-3 Alkylene-C(O)-C 1-3 Alkylene-, -C 1-3 Alkylene-OC 1-3 Alkylene-, -NH-C 1-3 Alkylene-, -SC 1-3 Alkylene-, -C 1-3 Alkylene-NH-C(O)-, -C 1-3 Alkylene-OC(O)-, -NH-C(O)-, -OC(O)-, -SC(O)-.

[0170] In one embodiment of the present invention, Z 11 、Z 12 、Z 21 、Z 22 、Z 31 、Z 32 are independently selected from a bond, -CD2-, -C 1-3 Alkylene-, -OC 1-3 Alkylene-, -C(O)-, -C 1-3 Alkylene-C(O)-, -OC 1-3 Alkylene-C(O)-, -NH-C 1-3 Alkylene-C(O)-, -SC 1-3 Alkylene-C(O)-, -OC 1-3 Alkylene-C(O)-C 1-3 Alkylene-.

[0171] In a preferred embodiment of the present invention, Z 11 、Z 12 、Z 21 、Z 22 、Z31 、Z 32 are independently selected from -C 1-3 Alkylene-, -OC 1- 3 alkylene-, -C 1-3 Alkylene-C(O)-, -OC 1-3 Alkylene-C(O)-, -NH-C(O)-, -OC(O)-.

[0172] In one embodiment of the present invention, Z 11 、Z 12 、Z 21 、Z 22 、Z 31 、Z 32 are independently selected from -CD2-, -C 1-2 Alkylene-, -OC 1-3 Alkylene-, -C(O)-, -C 1-2 Alkylene-C(O)-, -OC 1-2 Alkylene-C(O)-, -NH-C 1-2 Alkylene-C(O)-, -SC 1-2 Alkylene-C(O)-, -OC 1-2 Alkylene-C(O)-C 1-2 Alkylene-, -C 1-2 Alkylene-OC 1-2 Alkylene-, -NH-C 1-2 Alkylene-, -SC 1-2 Alkylene-, -C 1-2 Alkylene-NH-C(O)-, -C 1-2 Alkylene-OC(O)-, -NH-C(O)-, -OC(O)-, -SC(O)-.

[0173] In one embodiment of the present invention, Z 11 、Z 12 、Z 21 、Z 22 、Z 31 、Z 32 are independently selected from a bond, -CD2-, -C 1-2 Alkylene-, -OC 1-2 Alkylene-, -C(O)-, -C 1-2 Alkylene-C(O)-, -OC 1-2 Alkylene-C(O)-, -NH-C 1-2 Alkylene-C(O)-, -SC 1-2 Alkylene-C(O)-, -OC 1-2 Alkylene-C(O)-C 1-2 Alkylene-.

[0174] In one embodiment of the present invention, Z 11 、Z 12 、Z 21 、Z 22 、Z 31 、Z 32 Each independently selected from a bond, methylene, ethylene, -CD2-, -O-, -S-, -NH-,

[0175] In one embodiment of the present invention, Z 11 、Z 12 、Z 21 、Z 22 、Z 31 、Z 32 are independently selected from methylene, ethylene,

[0176] In one embodiment of the present invention, Z 11 、Z 12 、Z 21 、Z 22 、Z 31 、Z 32 are independently selected from methylene, ethylene, *Indicates the connection terminal to A.

[0177] In one embodiment of the present invention, Z 11 、Z 12 、Z 21 、Z 22 、Z 31 、Z 32 are independently selected from methylene, ethylene, -CD2, *Indicates the connection terminal to A.

[0178] In one embodiment of the present invention, Z 12 、Z 22 、Z 32 are independently selected from methylene, -CD2, and Z 11 Selected from methylene, ethylene, -CD2, And Z 21 Selected from methylene, ethylene, -CD2, And Z 31 Selected from More preferably, Z 31 Selected from *Indicates the connection terminal to A.

[0179] In one embodiment of the present invention, Z 12 、Z 22 、Z 32 are independently selected from methylene, -CD2, and Z 11 Selected from methylene, ethylene, -CD2, And Z 21 Selected from methylene, ethylene, -CD2, And Z 31 Selected from *Indicates the connection terminal to A.

[0180] In one embodiment of the present invention, Z 11 、Z 12 、Z 21 、Z 22 、Z 31 、Z 32 are independently selected from methylene, ethylene,

[0181] In one embodiment of the present invention, Z 11 、Z 12 、Z 21 、Z 22 Each is independently selected from -CD2, methylene; preferably methylene.

[0182] In one embodiment of the present invention, Z 12 、Z 22 、Z 32 Each is independently selected from -CD2, methylene, and ethylene.

[0183] In one embodiment of the present invention, Z 12 、Z 22 、Z 32 All are -CD2, methylene; preferably methylene.

[0184] In one embodiment of the present invention, Z 11 Selected from -CD2, -C 1-3 Alkylene-, -OC 1-3 Alkylene-; preferably -C 1-3 Alkylene-; preferably -CD2, methylene, ethylene, methyleneoxy, ethyleneoxy; more preferably methylene.

[0185] In one embodiment of the present invention, Z 21 Selected from -OC 1-3 Alkylene-, -NH-C 1-3 Alkylene-, -SC 1-3Alkylene-, -Se-C 1-3 Alkylene-, -C 1-2 Alkylene-OC 1-3 Alkylene-; preferably -OC 1-3 Alkylene-, -NH-C 1-2 Alkylene-, -SC 1-2 Alkylene-, -C 1-2 Alkylene-OC 1-3 Alkylene-.

[0186] In one embodiment of the present invention, Z 31 Selected from -C(O)-, -C 1-3 Alkylene-C(O)-, -OC 1-3 Alkylene-C(O)-, -NH-C 1-3 Alkylene-C(O)-, -SC 1-3 Alkylene-C(O)-, -OC 1-2 Alkylene-C(O)-C 1-3 Alkylene-, -C 1-3 Alkylene-NH-C(O)-, -C 1-3 Alkylene-OC(O)-, -NH-C(O)-, -OC(O)-, -SC(O)-, -C 1-3 Alkylene -C(S)-; preferably -C(O)-, -C 1-2 Alkylene-C(O)-, -OC 1- 2 alkylene-C(O)-, -NH-C(O)-, -OC(O)-, -SC(O)-; preferably -C 1-2 Alkylene-C(O)-, -OC 1-2 Alkylene -C(O)-, -NH-C(O)-, -OC(O)-, -SC(O)-; preferably -CH2C(O)-.

[0187] In one embodiment of the present invention, Z 11 Independently selected from -OC 1-3 Alkyl-, -NH-C 1-3 Alkyl-, -SC 1-3 Alkyl-, -Se-C 1-3 Alkyl-, -C 1-3 Alkyl-OC 1-3 Alkyl-; and Z 21 are independently selected from -OC 1-3 Alkyl-, -NH-C 1-3 Alkyl-, -SC 1-3 Alkyl-, -Se-C 1-3 Alkyl-, -C 1-3 Alkyl-OC 1-3alkyl-.

[0188] In one embodiment of the present invention, Z 21 Selected from -OC 1-3 Alkylene-, -NH-C 1-3 Alkylene-, -SC 1-3 Alkylene-, -Se-C 1-3 Alkylene-, -C 1-2 Alkylene-OC 1-3 Alkylene-; and Z 31 Selected from -C(O)-, -C 1-3 Alkylene-C(O)-, -OC 1-3 Alkylene-C(O)-, -NH-C 1- 3 alkylene-C(O)-, -SC 1-3 Alkylene-C(O)-, -OC 1-2 Alkylene-C(O)-C 1-3 Alkyl-, -C 1-3 Alkylene-NH-C(O)-, -C 1-3 Alkylene-OC(O)-, -NH-C(O)-, -OC(O)-, -SC(O)-, -C 1-3 Alkylene-C(S)-.

[0189] In one embodiment of the present invention, Z 11 -CD2, -C 1-3 Alkylene-, -OC 1-3 Alkylene-; and Z 21 Selected from -OC 1-3 Alkylene-, -NH-C 1-3 Alkylene-, -SC 1-3 Alkylene-, -Se-C 1-3 Alkylene-, -C 1-2 Alkylene-OC 1-3 Alkylene-; and Z 31 Selected from -C(O)-, -C 1-3 Alkylene-C(O)-, -OC 1-3 Alkylene-C(O)-, -NH-C 1-3 Alkylene-C(O)-, -SC 1-3 Alkylene-C(O)-, -OC 1-2 Alkylene-C(O)-C 1- 3 alkylene-, -C 1-3 Alkylene-NH-C(O)-, -C 1-3 Alkylene-OC(O)-, -NH-C(O)-, -OC(O)-, -SC(O)-, -C 1-3Alkylene-C(S)-. In one embodiment of the present invention, Z 11 Selected from -CD2, -C 1-3 Alkylene-, -OC 1-3 Alkylene-; and Z 21 Selected from -OC 1-3 Alkylene-, -NH-C 1-3 Alkylene-, -SC 1-3 Alkylene-, -Se-C 1-3 Alkylene-, -C 1-2 Alkylene-OC 1-3 Alkylene-; and Z 31 Selected from -C(O)-, -C 1-3 Alkylene-C(O)-, -OC 1-3 Alkylene-C(O)-, -NH-C 1-3 Alkylene-C(O)-, -SC 1-3 Alkylene-C(O)-, -OC 1-2 Alkylene-C(O)-C 1-3 Alkylene-, -C 1-3 Alkylene-NH-C(O)-, -C 1-3 Alkylene-OC(O)-, -NH-C(O)-, -OC(O)-, -SC(O)-, -C 1-3 Alkylene-C(S)-.

[0190] In one embodiment of the present invention, Z 11 -C 1-3 Alkylene-, -OC 1-3 Alkylene-; and Z 21 Selected from -OC 1-3 Alkylene-, -NH-C 1-3 Alkylene-, -SC 1-3 Alkylene-, -Se-C 1-3 Alkylene-, -C 1-2 Alkylene-OC 1-3 Alkylene-; and Z 31 Selected from -C(O)-, -C 1-3 Alkylene-C(O)-, -OC 1-3 Alkylene-C(O)-, -NH-C 1-3 Alkylene-C(O)-, -SC 1-3 Alkylene-C(O)-, -OC 1-2 Alkylene-C(O)-C 1-3 Alkylene-, -C 1-3 Alkylene-NH-C(O)-, -C 1-3Alkylene-OC(O)-, -NH-C(O)-, -OC(O)-, -SC(O)-, -C 1-3 Alkylene-C(S)-. In one embodiment of the present invention, Z 11 -CD2, -C 1-3 Alkylene-, -OC 1-3 Alkylene-*; and Z 21 Selected from -OC 1-3 Alkylene-*, -NH-C 1-3 Alkylene-*, -SC 1-3 Alkylene-*, -Se-C 1-3 Alkylene-*, -C 1-2 Alkylene-OC 1-3 Alkylene-*; and Z 31 Selected from -C(O)-, -C 1-3 Alkylene-C(O)-*, -OC 1-3 Alkylene-C(O)-*, -NH-C 1-3 Alkylene-C(O)-*, -SC 1-3 Alkylene-C(O)-*, -OC 1-2 Alkylene-C(O)-C 1-3 Alkylene-*, -C 1-3 Alkylene-NH-C(O)-*, -C 1-3 Alkylene-OC(O)-*, -NH-C(O)-*, -OC(O)-*, -SC(O)-*, -C 1- 3-alkylene-C(S)-*; * indicates the end connected to A.

[0191] In one embodiment of the present invention, Z 11 -C 1-3 Alkylene-, -OC 1-3 Alkylene-*; and Z 21 Selected from -OC 1-3 Alkylene-*, -NH-C 1-3 Alkylene-*, -SC 1-3 Alkylene-*, -Se-C 1-3 Alkylene-*, -C 1-2 Alkylene-OC 1-3 Alkylene-*; and Z 31 Selected from -C(O)-, -C 1-3 Alkylene-C(O)-*, -OC 1-3 Alkylene-C(O)-*, -NH-C 1-3 Alkylene-C(O)-*, -SC 1-3 Alkylene-C(O)-*, -OC 1-2Alkylene-C(O)-C 1-3 Alkylene-*, -C 1-3 Alkylene-NH-C(O)-*, -C 1-3 Alkylene-OC(O)-*, -NH-C(O)-*, -OC(O)-*, -SC(O)-*, -C 1- 3-alkylene-C(S)-*; * indicates the end connected to A.

[0192] In one embodiment of the present invention, Z 11 -CD2-, -C 1-2 Alkylene-, -OC 1-2 Alkylene-*; and Z 21 Selected from -OC 1-2 Alkylene-*, -NH-C 1-2 Alkylene-*, -SC 1-2 Alkylene-*, -Se-C 1-2 Alkylene-*, -CH2-OC 1-2 Alkylene-*; and Z 31 Selected from -C(O)-, -C 1- 2-alkylene-C(O)-*, -OC 1-2 Alkylene-C(O)-*, -NH-C 1-2 Alkylene-C(O)-*, -SC 1-2 Alkylene-C(O)-*, -C 1-2 Alkylene-NH-C(O)-*, -C 1-2 Alkylene-OC(O)-*, -NH-C(O)-*, -OC(O)-*, -SC(O)-*, -C 1-2 Alkylene-C(S)-*; further preferably, Z 31 Selected from -C 1-2 Alkylene-C(O)-*, -OC 1-2 Alkylene-C(O)-*, -NH-C 1-2 Alkylene-C(O)-*, -SC 1-2 Alkylene-C(O)-*, -C 1-2 Alkylene-NH-C(O)-*, -C 1-2 Alkylene-OC(O)-*, -CH2NH-C(O)-*, -NH-C(O)-*, -OC(O)-*, -SC(O)-*, -C 1-2 Alkylene-C(S)-*; further preferably, Z 31 Selected from -C 1-2Alkylene-C(O)-*, -OCH2-C(O)-*, -CH2-OC(O)-*, -NH-C(O)-*, -OC(O)-*, -SC(O)-*; further preferably, Z 31 Selected from -CH2C(O)-*; * represents the terminal connected to A.

[0193] In one embodiment of the present invention, L1 and L2 are independently selected from *Indicates the connection terminal to A.

[0194] In one embodiment of the present invention, L1 and L2 are independently selected from *Indicates the terminal connected to N (i.e. A).

[0195] In one embodiment of the present invention, L3 is selected from *Indicates the connection terminal to A.

[0196] In one embodiment of the present invention, L1, L2, and L3 are independently selected from *Indicates the end connected to N (i.e. A).

[0197] In one embodiment of the present invention, R is selected from H, *Indicates the connection terminal to A.

[0198] In one embodiment of the present invention, R is selected from H, *Indicates the connection terminal to A.

[0199] The first aspect of the present invention provides a compound represented by the following formula (I'-1), formula (I'-2), or formula (I'-3), or a pharmaceutically acceptable salt thereof:

[0200] Among them, A, L1, L2, R, R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 、R 11 、R 12 、R31 、R 32 、R 41 、R 42 、R 50 、R 51 , h1, h2, h3, and h4 are as described in the compounds of formula (I), formula (I-1-P1), formula (I-1-P2), formula (I-1-P3), and formula (I-1-P4).

[0201] In one embodiment of the compound represented by the above formula (I'-1), (I'-2), (I'-3), R is a group including L3, and Z 11 、Z 21 and Z 31 There is only one group containing a double bond; the double bond is, for example, a double bond between C and O in -C(O)-, or a double bond between C and S in -C(S)-; further preferably, Z 11 、Z 21 and Z 31 Different from each other, or Z 11 、Z 21 and Z 31 The two groups not containing a double bond in Z are identical, and the two identical groups contain -O-, -NH-, -S-, or -Se-, preferably, -O-; Still more preferably, Z 11 、Z 21 and Z 31 The molecular weight of Z is independently 14.0-107.1, preferably 14.0-60; preferably about 14, about 16, about 28, about 30, about 42, about 43, about 44, about 46, about 58, or about 60; still more preferably, Z 11 、Z 21 and Z 31 Selected from -CH2-, -CD2-, -CH2CH2-, -CD2CH2-, -C(O)-, -CH2C(O)-, -NHC(O)-, -OC(O)-, -CH2CH2O-, -OCH2C(O)-, -CH2OC(O)-, -CH2CH2CH2O-, -SC(O)-.

[0202] The present invention also provides a compound represented by the following formula (II), or a pharmaceutically acceptable salt thereof:

[0203] Wherein, L1 and L2 are as described in the compounds of formula (I), formula (I-1-P1), formula (I-1-P2), formula (I-1-P3), and formula (I-1-P4);

[0204] R' is selected from H, -C 1-3Alkylene-C 6-10 Aryl, -C 1-3 Alkylene-5-12 membered heteroaryl, C 1-6 Alkyl; the C 1-3 The alkylene group is optionally substituted by one or more groups independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The aryl and heteroaryl groups are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 Alkoxy, C 1-3 Substituted by an aminoalkyl substituent; the C 1-6 The alkyl group is optionally substituted with one or more groups independently selected from deuterium, halogen, oxo, carboxyl, -CN, -OH, -NH2, C1-3 alkyl, C 1-3 substituted by an alkoxy substituent.

[0205] In one embodiment of the present invention, R' is selected from H, -C 1-3 Alkylene-C 6-10 Aryl, -C 1-3 Alkylene-5-10 membered heteroaryl, C 1-6 Alkyl; the C 1-3 The alkylene group is optionally substituted by one or more substituents independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2; the aryl and heteroaryl groups are optionally substituted by one or more substituents independently selected from deuterium, halogen, -CN, methoxy, C 1-3 Substituted by an aminoalkyl substituent; the C 1-6 The alkyl group is optionally substituted with one or more groups independently selected from deuterium, halogen, oxo, carboxyl, -CN, -OH, -NH2, C 1-3 Alkyl, C 1-3 substituted by an alkoxy substituent;

[0206] L1 is * indicates the N-connection terminal;

[0207] L2 is * indicates the N-connection terminal;

[0208] Rings W1 and W2 are independently selected from C 6-12 Aryl, 5-12 membered heteroaryl; the aryl and heteroaryl are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 Alkyl, C 1-3 substituted by an alkoxy substituent;

[0209] Z 11 、Z 12 、Z 21 、Z22 are independently selected from -C 1-3 Alkylene-, -C 1-3 Oxoalkylene-; the alkylene and oxoalkylene groups are optionally substituted with one or more substituents independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, methyl, and methoxy.

[0210] In one embodiment of the present invention, R' is selected from H, -C 1-3 Alkylene-phenyl, -methylene-5-6 membered heteroaryl, C 1-6 Alkyl; the methylene, C 1-3 The alkylene group is optionally substituted by one or more groups independently selected from halogen, oxo, -CN, -OH, -NH2, C 1-3 The phenyl and heteroaryl groups are optionally substituted by one or more groups independently selected from halogen, -CN, C 1-3 Alkoxy, C 1-3 Substituted by an aminoalkyl substituent; the C 1-6 The alkyl group is optionally substituted by one or more groups independently selected from halogen, oxo, carboxyl, -CN, -OH, -NH2, C 1-3 Alkyl, C 1-3 substituted by an alkoxy substituent.

[0211] In one embodiment of the present invention, R' is selected from H, -methylene-phenyl, -ethylene-phenyl, -methylene-pyridyl, C 1-6 Alkyl; the phenyl and pyridyl groups are optionally substituted by one or more groups independently selected from halogen, -CN, methoxy, Substituted by a substituent; the C 1-6 The alkyl group is optionally substituted with one or more substituents each independently selected from carboxy, -NH2.

[0212] In one embodiment of the present invention, R' is selected from H,

[0213] In one embodiment of the present invention, rings W1 and W2 are independently selected from phenyl and 5-12 membered heteroaryl; the phenyl and heteroaryl are optionally substituted with one or more substituents independently selected from halogen and -CN.

[0214] In one embodiment of the present invention, rings W1 and W2 are independently selected from phenyl and 8-10 membered bicyclic heteroaryl; the phenyl and bicyclic heteroaryl are optionally substituted by one or more substituents independently selected from halogen and -CN; the heteroatoms in the bicyclic heteroaryl are independently selected from O, N or S, and the number of heteroatoms is 1 or 2.

[0215] In one embodiment of the present invention, rings W1 and W2 are independently selected from

[0216] In one embodiment of the present invention, Z 11 、Z 12 、Z 21 、Z 22 are independently selected from -C 1-3 Alkylene-, -C 1-3 Oxoalkylene-; the alkylene and oxoalkylene groups are optionally substituted with one or more substituents independently selected from deuterium and oxo.

[0217] In one embodiment of the present invention, Z 11 、Z 12 、Z 21 、Z 22 are independently selected from methylene, ethylene,

[0218] In one embodiment of the present invention, L1 and L2 are independently selected from *Indicates the N-connection terminal.

[0219] The present invention also provides a compound represented by the following formula (II-A), (II-B), (II-C), (II-A'), (II-B'), (II-C'), or a pharmaceutically acceptable salt thereof:

[0220] Wherein, W1, W2, and R' are as described in the compound of formula (I), formula (I-1-P1), formula (I-1-P2), formula (I-1-P3), formula (I-1-P4) or (II).

[0221] The present invention also provides a compound represented by the following formula (III), or a pharmaceutically acceptable salt thereof:

[0222] Among them, A, L1, L2, and L3 are as described in the compounds of formula (I), formula (I-1-P1), formula (I-1-P2), formula (I-1-P3), and formula (I-1-P4).

[0223] In one embodiment of the compound represented by formula (III), L1, L2 and L3 are respectively Z 11 、Z 21 and Z 31 The group, and Z 11 、Z 21 and Z31 There is only one group containing a double bond; the double bond is, for example, a double bond between C and O in -C(O)-, or a double bond between C and S in -C(S)-; further preferably, Z 11 、Z 21 and Z 31 Different from each other, or Z 11 、Z 21 and Z 31 The two groups not containing a double bond in Z are identical, and the two identical groups contain -O-, -NH-, -S-, or -Se-, preferably, -O-; Still more preferably, Z 11 、Z 21 and Z 31 The molecular weight of Z is independently 14.0-107.1, preferably 14.0-60; preferably about 14, about 16, about 28, about 30, about 42, about 43, about 44, about 46, about 58, or about 60; still more preferably, Z 11 、Z 21 and Z 31 Selected from -CH2-, -CD2-, -CH2CH2-, -CD2CH2-, -C(O)-, -CH2C(O)-, -NHC(O)-, -OC(O)-, -CH2CH2O-, -OCH2C(O)-, -CH2OC(O)-, -CH2CH2CH2O-, -SC(O)-.

[0224] The present invention also provides a compound represented by the following formula (III-1), or a pharmaceutically acceptable salt thereof:

[0225] Among them, W1, W2, W3, Z 11 、Z 12 、Z 21 、Z 22 、Z 31 、Z 32 As described by the compound of formula (I), formula (I-1-P1), formula (I-1-P2), formula (I-1-P3), formula (I-1-P4) or formula (III).

[0226] In one embodiment of the present invention, Z 12 、Z 22 、Z 32 are independently selected from methylene and ethylene;

[0227] Z 11 、Z 21 、Z 31 are independently selected from a bond, -C 1-4 Alkylene-, -C1-6 Oxaalkylene-(e.g. -C 1-4 Oxaalkylene-), -C 1-4 Thiaalkylene-, -C 1-4 Azaalkylene-, -C 1-4 Selenylheteroalkylene-; the alkylene, oxaalkylene, thiaalkylene, azaalkylene, selenylheteroalkylene are optionally substituted by one or more selected from Z 41 Substituted by a substituent; Z 41 are independently selected from deuterium, halogen (e.g., fluorine, chlorine), oxo, thio, -CN, -OH, -NH2, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 haloalkoxy; or any two Z 41 Together with the atoms they are attached to form C 3-6 Cycloalkyl, 3-6 membered heterocyclic group (e.g., oxetane); the heteroatom in the heterocyclic group is O, N or S, and the number of heteroatoms is 1;

[0228] Ring W1, W2, W3 are independently selected from phenyl, 5-6 membered monocyclic heteroaryl; the phenyl and heteroaryl are optionally substituted by one or more independently selected from deuterium, halogen, -CN, -OH, -NH2, -CHO, C 1-3 Alkyl, C 1-3 Alkoxy, -N(C 1-3 alkyl)2, -NH(C1-3 alkyl), -C(O)C 1-3 The heteroatom in the heteroaryl group is O, N or S, and the number of heteroatoms is 1 or 2.

[0229] In one embodiment of the present invention, Z 12 、Z 22 、Z 32 All are methylene.

[0230] In one embodiment of the present invention, when Z 11 、Z 21 and Z 31 When Z 11 、Z 21 and Z 31 In the combination defined as , 2 or 3 heteroatoms or heteroatom groups are included, and the heteroatoms or heteroatom groups are selected from -O-, -S-, -NH-, and -CO-. In one embodiment of the present invention, ring W1, W2, and W3 are independently selected from phenyl and thienyl; the phenyl and thienyl groups are optionally replaced by one or more independently selected from deuterium, halogen, -CN, -OH, -NH2, -CHO, C1-3 Alkyl, C 1-3 Alkoxy, -N(C 1-3 Alkyl)2, -NH(C 1-3 alkyl), -C(O)C 1-3 substituted by an alkyl substituent.

[0231] In one embodiment of the present invention, rings W1, W2, and W3 are independently selected from The above groups are optionally substituted by one or more substituents independently selected from deuterium, fluorine, chlorine, bromine, methyl, ethyl, methoxy, and ethoxy.

[0232] In one embodiment of the compound represented by the above formula (III-1), Z 11 、Z 21 and Z 31 There is only one group containing a double bond; the double bond is, for example, a double bond between C and O in -C(O)-, or a double bond between C and S in -C(S)-; further preferably, Z 11 、Z 21 and Z 31 Different from each other, or Z 11 、Z 21 and Z 31 The two groups not containing a double bond in Z are identical, and the two identical groups contain -O-, -NH-, -S-, or -Se-, preferably, -O-; Still more preferably, Z 11 、Z 21 and Z 31 The molecular weight of Z is independently 14.0-107.1, preferably 14.0-60; preferably about 14, about 16, about 28, about 30, about 42, about 43, about 44, about 46, about 58, or about 60; still more preferably, Z 11 、Z 21 and Z 31 Selected from -CH2-, -CD2-, -CH2CH2-, -CD2CH2-, -C(O)-, -CH2C(O)-, -NHC(O)-, -OC(O)-, -CH2CH2O-, -OCH2C(O)-, -CH2OC(O)-, -CH2CH2CH2O-, -SC(O)-.

[0233] The present invention also provides a compound represented by the following formula (III-2), or a pharmaceutically acceptable salt thereof:

[0234] Among them, W1, W2, W3, Z 11 、Z 12 、Z21 、Z 22 、Z 31 、Z 32 , R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 、R 11 、R 12 、R 44 、R 45 、R 46 、R 47 、R 48 、R 49 、R 31 、R 32 、R 33 As described by the compound of formula (I), formula (I-1-P1), formula (I-1-P2), formula (I-1-P3), formula (I-1-P4), formula (III) or formula (III-1).

[0235] In one embodiment of the present invention, Z 31 The heteroatom or heteroatom group contains -CO- or -C(S)-.

[0236] In one embodiment of the present invention, R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 、R 11 、R 12 、R 44 、R 45 、R 46 、R 47 、R 48 、R 49 、R 31 、R 32 、R 33 Selected from hydrogen or deuterium.

[0237] In one embodiment of the compound represented by the above formula (III-2), Z 11 、Z 21 and Z 31 There is only one group containing a double bond; the double bond is, for example, a double bond between C and O in -C(O)-, or a double bond between C and S in -C(S)-; further preferably, Z 11 、Z 21 and Z 31 Different from each other, or Z 11 、Z 21 and Z 31 The two groups not containing a double bond in Z are identical, and the two identical groups contain -O-, -NH-, -S-, or -Se-, preferably, -O-; Still more preferably, Z 11 、Z21 and Z 31 The molecular weight of Z is independently 14.0-107.1, preferably 14.0-60; preferably about 14, about 16, about 28, about 30, about 42, about 43, about 44, about 46, about 58, or about 60; still more preferably, Z 11 、Z 21 and Z 31 Selected from -CH2-, -CD2-, -CH2CH2-, -CD2CH2-, -C(O)-, -CH2C(O)-, -NHC(O)-, -OC(O)-, -CH2CH2O-, -OCH2C(O)-, -CH2OC(O)-, -CH2CH2CH2O-, -SC(O)-.

[0238] The present invention also provides a compound represented by the following formula (III-1-1) or formula (III-2-1), or a pharmaceutically acceptable salt thereof:

[0239] Among them, W1, W2, W3, Z 11 、Z 12 、Z 21 、Z 22 、Z 31 、Z 32 , R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 、R 11 、R 12 、R 44 、R 45 、R 46 、R 47 、R 48 、R 49 、R 31 、R 32 、R 33 As described by the compound of formula (I), formula (I-1-P1), formula (I-1-P2), formula (I-1-P3), formula (I-1-P4), formula (III), formula (III-1) or formula (III-2).

[0240] The present invention also provides a compound represented by the following formula (III-A), or a pharmaceutically acceptable salt thereof:

[0241] Wherein, L3 is as described in the compound of formula (I), formula (I-1-P1), formula (I-1-P2), formula (I-1-P3), formula (I-1-P4), formula (III) or formula (III-1).

[0242] In one embodiment of the present invention, L3 is selected from -C 1-6 Alkylene-, -C 2-6 Alkyne-, -methylene-phenyl-phenyl-methylene-, -methylene-6-membered heteroaryl-6-membered heteroaryl-methylene- (e.g. -methylene-pyridyl-pyridyl-methylene-), The alkylene, methylene and alkynyl groups are optionally substituted by one or more substituents independently selected from halogen, oxo, -CN, -OH and -NH2; the aryl and heteroaryl groups are optionally substituted by one or more substituents independently selected from halogen, -CN, C 1-3 Alkyl, C 1-3 The alkoxy group is substituted by a substituent; * indicates the N-terminal connection.

[0243] In one embodiment of the present invention, ring W3 is selected from phenyl, naphthyl, 8-10 membered bicyclic heteroaryl, C 8-10 Bicyclic cycloalkyl; the phenyl, naphthyl, heteroaryl, cycloalkyl are optionally substituted by one or more independently selected from halogen, -CN, C 1-3 Alkyl, C 1-3 substituted by an alkoxy substituent.

[0244] In one embodiment of the present invention, ring W3 is selected from phenyl, naphthyl, 5-membered / 5-membered fused heteroaryl, 5-membered / 6-membered fused heteroaryl, 6-membered / 5-membered fused heteroaryl, 6-membered / 6-membered fused heteroaryl, 4-membered / 6-membered spiroalkyl, 6-membered / 4-membered spiroalkyl; and the phenyl, naphthyl, fused heteroaryl, and spiroalkyl are optionally substituted with one or more substituents independently selected from fluorine, chlorine, bromine, methyl, ethyl, methoxy, and ethoxy.

[0245] In one embodiment of the present invention, W3 is selected from

[0246] In one embodiment of the present invention, Z 31 、Z 32 are independently selected from -C 1-3 Alkylene-, -C 1-3 Oxyalkylene-, -C 1-3 Thiaalkylene-, -C 1-3 Azaalkylene-; preferably, Z 31 、Z 32 are independently selected from -C 1-2 Alkylene-, -C 1-2 Oxyalkylene-, -C 1-2 Thiaalkylene-, -C 1-2Azaalkylene-; wherein the alkylene, oxaalkylene, thiaalkylene, and azaalkylene are optionally substituted with one or more substituents independently selected from deuterium and oxo.

[0247] In one embodiment of the present invention, Z 31 、Z 32 are independently selected from -CD2-, -C 1-2 Alkylene-, -OC 1-2 Alkylene-, -C(O)-, -C 1-2 Alkylene-C(O)-, -OC 1-2 Alkylene-C(O)-, -NH-C 1-2 Alkylene-C(O)-, -SC 1-2 Alkylene-C(O)-, -OC 1-2 Alkylene-C(O)-C 1-2 Alkylene-.

[0248] In one embodiment of the present invention, Z 31 、Z 32 are independently selected from -C 1-3 Alkylene-, -C 1-3 Oxoalkylene-; the alkylene and oxoalkylene groups are optionally substituted with one or more substituents independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, methyl, and methoxy.

[0249] In one embodiment of the present invention, Z 31 、Z 32 are independently selected from -C 1-3 Alkylene-; the alkylene is optionally substituted by one or more substituents independently selected from deuterium and oxo.

[0250] In one embodiment of the present invention, Z 31 、Z 32 are independently selected from methylene, ethylene, -CD2-,

[0251] In one embodiment of the present invention, L3 is selected from *Indicates the N-connection terminal.

[0252] The present invention also provides a compound represented by the following formula (III-A'), or a pharmaceutically acceptable salt thereof:

[0253] Wherein, L3 is as described by the compound of formula (I), formula (I-1-P1), formula (I-1-P2), formula (I-1-P3), formula (I-1-P4), formula (III), formula (III-1) or formula (III-A).

[0254] The present invention also provides a compound represented by the following formula (III-B), or a pharmaceutically acceptable salt thereof:

[0255] Wherein, L1 and L2 are as described in the compound of formula (I), formula (I-1-P1), formula (I-1-P2), formula (I-1-P3), formula (I-1-P4), formula (III) or formula (III-1).

[0256] In one embodiment of the present invention, L1 is *Indicates the N-connection terminal.

[0257] In one embodiment of the present invention, L2 is *Indicates the N-connection terminal.

[0258] In one embodiment of the present invention, rings W1 and W2 are independently selected from C 6-12 Aryl, 5-12 membered heteroaryl; the aryl and heteroaryl are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 Alkyl, C 1-3 substituted by an alkoxy substituent.

[0259] In one embodiment of the present invention, rings W1 and W2 are independently selected from phenyl, C 8-12 Aryl, 7-12 membered heteroaryl; the phenyl, aryl and heteroaryl are optionally substituted by one or more substituents independently selected from halogen, -CN, methyl and methoxy.

[0260] In one embodiment of the present invention, ring W1 and W2 are independently selected from phenyl, naphthyl, 8-10 membered bicyclic heteroaryl; the phenyl, naphthyl, heteroaryl are optionally substituted by one or more independently selected from halogen, -CN, C 1-3 Alkyl, C 1-3 substituted by an alkoxy substituent.

[0261] In one embodiment of the present invention, rings W1 and W2 are independently selected from phenyl, naphthyl, 5-membered / 5-membered fused heteroaryl, 5-membered / 6-membered fused heteroaryl, 6-membered / 5-membered fused heteroaryl, and 6-membered / 6-membered fused heteroaryl; and the phenyl, naphthyl, and fused heteroaryl are optionally substituted with one or more substituents independently selected from fluorine, chlorine, bromine, -CN, methyl, ethyl, methoxy, and ethoxy.

[0262] In one embodiment of the present invention, rings W1 and W2 are independently selected from

[0263] In one embodiment of the present invention, Z 11 、Z 12 、Z 21 、Z 22 are independently selected from -C 1-3 Alkylene-, -C 1-3 Oxyalkylene-, -C 1-3 Thiaalkylene-, -C 1-3 Azaalkylene-; the alkylene, oxaalkylene, thiaalkylene, azaalkylene are optionally substituted with one or more substituents each independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, methyl, methoxy.

[0264] In one embodiment of the present invention, Z 11 、Z 12 、Z 21 、Z 22 are independently selected from -C 1-3 Alkylene-, -C 1-3 Oxoalkylene-; the alkylene and oxoalkylene groups are optionally substituted with one or more substituents independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, methyl, and methoxy.

[0265] In one embodiment of the present invention, Z 11 、Z 12 、Z 21 、Z 22 are independently selected from -C 1-2 Alkylene-, -C 1-2 Oxyalkylene-, -C 1-2 Thiaalkylene-, -C 1-2 Azaalkylene-; the alkylene, oxaalkylene, thiaalkylene, azaalkylene are optionally substituted with one or more substituents each independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, methyl, methoxy.

[0266] In one embodiment of the present invention, Z 11 、Z 12 、Z 21 、Z 22 are each independently selected from methylene.

[0267] In a preferred embodiment of the present invention, Z 11 、Z 12 、Z21 、Z 22 are independently selected from methylene,

[0268] In particular, L1 and L2 are the 11 and Z 21 The group, and Z 11 and Z 21 There is only one group containing a double bond; the double bond is, for example, a double bond between C and O in -C(O)-, or a double bond between C and S in -C(S)-; preferably, the double bond is, for example, a double bond between C and O in -C(O)-; further preferably, Z 11 and Z 21 Neither methylene nor Z 11 and Z 21 The group not containing a double bond in Z contains -O-, -NH-, -S-, or -Se-, preferably, -O-; Still more preferably, 11 and Z 21 The molecular weight of Z is independently 14.0-107.1, preferably 14.0-60; preferably about 14, about 16, about 28, about 30, about 42, about 43, about 44, about 46, about 58, or about 60; still more preferably, Z 11 、Z 21 and Z 31 Selected from -CH2-, -CD2-, -CH2CH2-, -CD2CH2-, -C(O)-, -CH2C(O)-, -NHC(O)-, -OC(O)-, -CH2CH2O-, -OCH2C(O)-, -CH2OC(O)-, -CH2CH2CH2O-, -SC(O)-.

[0269] In one embodiment of the present invention, L1 and L2 are independently selected from *Indicates the N-connection terminal.

[0270] The present invention also provides a compound represented by the following formula (III-B'), formula (III-B'-1), or a pharmaceutically acceptable salt thereof:

[0271] Wherein, L1 and L2 are as described in the compound of formula (I), formula (I-1-P1), formula (I-1-P2), formula (I-1-P3), formula (I-1-P4), formula (III), formula (III-1) or formula (III-B).

[0272] In particular, L1 and L2 are the 11 and Z 21 The group, and Z 11 and Z 21 There is only one group containing a double bond; the double bond is, for example, a double bond between C and O in -C(O)-, or a double bond between C and S in -C(S)-; further preferably, Z 11 and Z 21 Neither methylene nor Z 11 and Z 21 The group not containing a double bond in Z contains -O-, -NH-, -S-, or -Se-, preferably, -O-; Still more preferably, 11 and Z 21 The molecular weight of Z is independently 14.0-107.1, preferably 14.0-60; preferably about 14, about 16, about 28, about 30, about 42, about 43, about 44, about 46, about 58, or about 60; still more preferably, Z 11 、Z 21 and Z 31 Selected from -CH2-, -CD2-, -CH2CH2-, -CD2CH2-, -C(O)-, -CH2C(O)-, -NHC(O)-, -OC(O)-, -CH2CH2O-, -OCH2C(O)-, -CH2OC(O)-, -CH2CH2CH2O-, -SC(O)-.

[0273] The present invention also provides a compound represented by the following formula (III-C), or a pharmaceutically acceptable salt thereof:

[0274] Wherein, W1, W2, and W3 are as described in the compound of formula (I), formula (I-1-P1), formula (I-1-P2), formula (I-1-P3), formula (I-1-P4), formula (III) or formula (III-1).

[0275] In one embodiment of the present invention, ring W1, W2, and W3 are independently selected from phenyl, naphthyl, 8-10 membered bicyclic heteroaryl, and 5-6 membered monocyclic heteroaryl; the phenyl, naphthyl, and heteroaryl are optionally substituted by one or more independently selected from halogen, C 1-3 Alkyl, C 1-3 substituted by an alkoxy substituent.

[0276] In one embodiment of the present invention, rings W1, W2, and W3 are independently selected from

[0277] The present invention also provides a compound represented by the following formula (III-C'), or a pharmaceutically acceptable salt thereof:

[0278] Wherein, W1, W2, and W3 are as described in the compound of formula (I), formula (I-1-P1), formula (I-1-P2), formula (I-1-P3), formula (I-1-P4), formula (III), formula (III-1) or formula (III-C).

[0279] The present invention also provides a compound represented by the following formula (III-D), or a pharmaceutically acceptable salt thereof:

[0280] Wherein, W1, W2, and W3 are as described in the compound of formula (I), formula (I-1-P1), formula (I-1-P2), formula (I-1-P3), formula (I-1-P4), formula (III) or formula (III-1).

[0281] In one embodiment of the present invention, ring W1, W2, and W3 are independently selected from phenyl, naphthyl, and 8-10 membered bicyclic heteroaryl; the phenyl, naphthyl, and heteroaryl are optionally substituted by one or more independently selected from halogen, C 1-3 Alkyl, C 1-3 substituted by an alkoxy substituent.

[0282] In one embodiment of the present invention, rings W1, W2, and W3 are independently selected from phenyl and 9-10 membered bicyclic heteroaryl; the heteroatoms in the heteroaryl are independently selected from O or N, and the number of heteroatoms is 1 or 2; the phenyl and heteroaryl are optionally substituted with one or more substituents independently selected from fluorine, chlorine, methyl, and methoxy.

[0283] In one embodiment of the present invention, rings W1, W2, and W3 are independently selected from

[0284] The present invention also provides a compound represented by the following formula (III-D'), or a pharmaceutically acceptable salt thereof:

[0285] Wherein, W1, W2, and W3 are as described in the compound of formula (I), formula (I-1-P1), formula (I-1-P2), formula (I-1-P3), formula (I-1-P4), formula (III), formula (III-1) or formula (III-D).

[0286] The present invention also provides a compound represented by the following formula (III-E), or a pharmaceutically acceptable salt thereof:

[0287] Wherein, W1, W2, and W3 are as described in the compound of formula (I), formula (I-1-P1), formula (I-1-P2), formula (I-1-P3), formula (I-1-P4), formula (III) or formula (III-1).

[0288] In one embodiment of the present invention, ring W1, W2, and W3 are independently selected from phenyl, naphthyl, and 8-10 membered bicyclic heteroaryl; the phenyl, naphthyl, and heteroaryl are optionally substituted by one or more independently selected from halogen, C 1-3 Alkyl, C 1-3 substituted by an alkoxy substituent.

[0289] In one embodiment of the present invention, rings W1, W2, and W3 are independently selected from 9-membered bicyclic heteroaryl groups; the heteroatoms in the heteroaryl groups are independently selected from O or N, and the number of heteroatoms is 1 or 2.

[0290] In one embodiment of the present invention, rings W1, W2, and W3 are independently selected from

[0291] The present invention also provides a compound represented by the following formula (III-E'), or a pharmaceutically acceptable salt thereof:

[0292] Wherein, W1, W2, and W3 are as described in the compound of formula (I), formula (I-1-P1), formula (I-1-P2), formula (I-1-P3), formula (I-1-P4), formula (III), formula (III-1) or formula (III-E).

[0293] The present invention also provides a compound represented by the following formula (IV), or a pharmaceutically acceptable salt thereof:

[0294] Among them, R3, R4, R9, R 10 、R 13 、R 14 、R 15 、R 16 、R 17 、R 18 、R 19 、R 20 、R 21 、R 22 、R 23 、R 24 、R 25 、R 26 are independently selected from H, deuterium, and R3, R4, R9, R 10 、R 13 -R26 At least one of them is deuterium.

[0295] The present invention also provides a compound represented by the following formula (A), or a pharmaceutically acceptable salt thereof:

[0296] Among them, R3, R4, R9, R 10 、R 13 、R 14 、R 15 、R 16 、R 17 、R 18 、R 19 、R 20 、R 21 、R 22 、R 23 、R 24 、R 25 、R 26 are independently selected from H, deuterium, and R3, R4, R9, R 10 、R 13 -R 26 At least one is deuterium;

[0297] R A 、R B 、R C are independently selected from hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 1-6 Alkoxy, -C 1-3 Alkylene OC 1-6 Alkyl, -C 1-3 Alkylene-OC(O)-C 1-6 Alkyl, the alkyl, alkenyl, alkoxy, alkylene are optionally substituted by one or more independently selected from deuterium, halogen, -OH, -NH2, -CN, oxo, C 1-3 Alkyl, C 1-3 substituted by an alkoxy substituent.

[0298] In one embodiment of the present invention, R A 、R B 、R C Each independently selected from C 1-6 Alkyl, C 1-6 Alkoxy, -C 1-2 Alkylene OC 1- 4-alkyl, -C 1-2 Alkylene OC(O)-C 1-4 Alkyl, the alkyl, C 1-6Alkoxy and alkylene are optionally substituted by one or more substituents each independently selected from deuterium, fluorine, chlorine, bromine, -OH, -NH2, -CN, oxo, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, and isopropoxy.

[0299] In one embodiment of the present invention, R A 、R B 、R C Each independently selected from C 1-3 Alkyl, -methylene-OC 1-4 Alkyl, -methylene-OC(O)-C 1-3 The alkyl group, the methylene group, and the alkyl group are optionally substituted by one or more substituents independently selected from methyl, ethyl, n-propyl, and isopropyl.

[0300] In one embodiment of the present invention, R A 、R B 、R C Each independently selected from methyl, ethyl, -CH2-OC(O)-CH(CH3)2.

[0301] The present invention also provides a compound represented by the following formula (B), formula (B-1), formula (C), formula (C-1), formula (D), formula (D-1), or a pharmaceutically acceptable salt thereof:

[0302] Among them, Z 11 、Z 21 、Z 31 、R 31 、R 32 、R 33 , h1, h2, h3, h4, h5, h6 are as described in the compound of formula (I), formula (I-1-P1), formula (I-1-P2), formula (I-1-P3), formula (I-1-P4), formula (III), formula (III-1) or formula (III-B), respectively; X, X2 are independently selected from O, CH2, NH, S, Se, X1 is independently selected from O, S, n, n1, n3 are independently 0 or 1, n2 is independently 0, 1, 2 or 3; Z 12 、Z 22 、Z 32 Each of them is independently selected from methylene, ethylene, -CD2- or selected from methylene, ethylene;

[0303] Ring W1, W2, W3 are independently selected from phenyl, 5-6 membered monocyclic heteroaryl; the phenyl and heteroaryl are optionally substituted by one or more independently selected from deuterium, halogen, -CN, -OH, -NH2, -CHO, C 1-3 Alkyl, C1-3 Alkoxy, -N(C 1-3 Alkyl)2, -NH(C 1-3 alkyl), -C(O)C 1-3 The heteroatom in the heteroaryl group is O, N or S, and the number of heteroatoms is 1 or 2.

[0304] In one embodiment of the present invention, Z 12 、Z 22 、Z 32 Each is independently selected from methylene, -CD2-.

[0305] In one embodiment of the present invention, Z 11 It is -CD2-.

[0306] In one embodiment of the present invention, Z 11 Independently selected from -C 1-3 Alkylene-, -OC 1-3 Alkylene-, -NH-C 1-3 Alkylene-, -SC 1- 3-alkylene-, -Se-C 1-3 Alkylene-, -C 1-2 Alkylene-OC 1-3 Alkylene-; preferably, Z 11 Independently selected from -C 1-3 Alkylene-, -OC 1-3 Alkylene-; preferably, Z 11 are independently selected from methylene, ethylene, methyleneoxy, ethyleneoxy; preferably, Z 11 is independently selected from methylene, -CD2-; preferably, Z 11 are independently selected from methylene.

[0307] In one embodiment of the present invention, Z 21 It is -CD2-.

[0308] In one embodiment of the present invention, Z 21 Independently selected from -C 1-3 Alkylene-, -OC 1-3 Alkylene-, -NH-C 1-3 Alkylene-, -S-C1-3 alkylene-, -Se-C 1-3 Alkylene-, -C 1-2 Alkylene-OC 1-3 Alkylene-; preferably -OC 1-3 Alkylene-, -NH-C 1-2 Alkylene-, -SC 1-2 Alkylene-, -C 1-2 Alkylene-OC1-3 Alkylene-.

[0309] In one embodiment of the present invention, Z 31 Independently selected from -C(O)-, -C 1-3 Alkylene-C(O)-, -OC 1-3 Alkylene-C(O)-, -NH-C 1-3 Alkylene-C(O)-, -SC 1-3 Alkylene-C(O)-, -OC 1-2 Alkylene-C(O)-C 1-3 Alkylene-, -C 1-3 Alkylene-NH-C(O)-, -C 1-3 Alkylene-OC(O)-, -NH-C(O)-, -OC(O)-, -SC(O)-, -C 1-3 Alkylene -C(S)-; preferably -C(O)-, -C 1-2 Alkylene-C(O)-, -OC 1-2 Alkylene-C(O)-, -NH-C(O)-, -OC(O)-, -SC(O)-.

[0310] In one embodiment of the present invention, Z 12 、Z 22 、Z 32 All are methylene.

[0311] In one embodiment of the present invention, X2 is selected from O, NH, S; preferably X2 is O.

[0312] In one embodiment of the present invention, n2 is 0 or 1, n3 is 0, and X2 is CH2.

[0313] In one embodiment of the present invention, n2 is 2 or 3, n3 is 0, X2 is O, NH, S; or n2 is 1 or 2, n3 is 1, X2 is O, NH, S; further preferably, n2 is 2 or 3, n3 is 0, X2 is O; or n2 is 2, n3 is 1, X2 is O.

[0314] In one embodiment of the present invention, n2 is 2, n3 is 0, and X2 is O, NH, or S; preferably, n2 is 2, n3 is 0, and X2 is O.

[0315] In one embodiment of the present invention, the sum of n2 and n3 is not greater than 3 (specifically 0, 1, 2, 3); preferably, the sum of n2 and n3 is not greater than 2 (specifically 0, 1, 2); preferably, the sum of n2 and n3 is 1 or 2 (i.e., n2 is 2, n3 is 0; or n2 is 1, n3 is 1; or n2 is 0, n3 is 2).

[0316] In one embodiment of the present invention, X1 is O.

[0317] In one embodiment of the present invention, X is CH2.

[0318] In one embodiment of the present invention, X is selected from O, CH2, NH, S, n is 1, and n1 is 0; or X is O or CH2, n is 1, and n1 is 1.

[0319] In one embodiment of the present invention, X1 is O, X is selected from O, CH2, NH, S, n is 1, and n1 is 0; or X1 is O, X is O or CH2, n is 1, and n1 is 1; further preferably, X1 is O, X is selected from O, CH2, n is 1, and n1 is 0; or X1 is O, X is O or CH2, n is 1, and n1 is 1; further preferably, X1 is O, X is selected from CH2, n is 1, and n1 is 0.

[0320] In one embodiment of the present invention, the sum of n and n1 is 0, 1, or 2; preferably, the sum of n and n1 is 1 or 2 (i.e., n is 1, n1 is 0; or n is 0, n1 is 1; or n is 1, n1 is 1; or n is 0, n1 is 2; or n is 2, n1 is 0); preferably, the sum of n and n1 is 1 (i.e., n is 1, n1 is 0; or n is 0, n1 is 1).

[0321] In particular, in the above-mentioned formula (B) and formula (B-1), Z 11 and Z 21 are groups without double bonds; the double bond is, for example, a double bond between C and O in -C(O)-, or a double bond between C and S in -C(S)-; further preferably, Z 11 With Z 21 Same or different, and Z 11 With Z 21 At least one of them is a group containing -O-, -NH-, -S-, or -Se-, preferably, a group containing -O-, such as *-CH2O-, *-CH2CH2O-, * is the terminal connected to N; Still further preferably, Z 11 、Z 21 and *-C(X1)-(CH2) n1 -(X) n - has a molecular weight independently of one another of 14.0-107.1, preferably 14.0-60; preferably about 14, about 16, about 28, about 30, about 42, about 43, about 44, about 46, about 58, or about 60; still more preferably, Z 11 、Z 21 and Z 31Selected from -CH2-, -CD2-, -CH2CH2-, -CD2CH2-, -C(O)-, -CH2C(O)-, -NHC(O)-, -OC(O)-, -CH2CH2O-, -OCH2C(O)-, -CH2OC(O)-, -CH2CH2CH2O-, -SC(O)-.

[0322] In particular, in the above-mentioned formula (B) and formula (B-1), Z 12 、Z 22 、Z 32 are independently selected from methylene, -CD2-;

[0323] Z 11 、Z 21 are independently selected from -CD2-, -C 1-3 Alkylene-(preferably -C 1-2 Alkylene-), -OC 1-3 Alkylene-*(preferably -OC 1-2 Alkylene-*), -SC 1-3 Alkylene-*, -NHC 1-3 Alkylene-*, -Se-C 1-3 Alkylene-*, -CH2-OC 1-2 Alkylene-* is the end connected to N;

[0324] X1 is O or S, X is selected from O, CH2, NH, S, n is 1, and n1 is 0; or X1 is O or S, X is O or CH2, n is 1, and n1 is 1; or X1 is O or S, n is 0, and n1 is 0.

[0325] In particular, in the above-mentioned formula (B) and formula (B-1), Z 12 、Z 22 、Z 32 are independently selected from methylene, -CD2-;

[0326] Z 11 Independently selected from -CD2-, -CH2-, -CH2CH2-, -OCH2-*, -OCH2CH2-*, and the like;

[0327] Z 21 Independently selected from -OCH2CH2-*, -CH2OCH2CH2-*, -OCH2CH2CH2-*, * is connected to N;

[0328] X1 is O, X is selected from O, CH2, NH, S, n is 1, and n1 is 0; or X1 is O, X is O or CH2, n is 1, and n1 is 1.

[0329] In particular, in the above-mentioned formula (B) and formula (B-1), Z 12 、Z 22 、Z 32 are independently selected from methylene, -CD2-; Z 11 、Z 21 are independently selected from -CD2-, -C 1-3 Alkylene-(preferably -C 1-2 Alkylene-), -OC 1-3 Alkylene-*(preferably -OC 1-2 Alkylene-*), -SC 1-3 Alkylene-*, -NHC 1-3 Alkylene-*, -Se-C 1-3 Alkylene-*, -CH2-OC 1-2 Alkylene-, * is connected to N, X1 is O or S, X is selected from O, CH2, NH, S, and the sum of n and n1 is 0, 1, or 2; further preferably, Z 21 Independently selected from -OCH2CH2-*, -CH2OCH2CH2-*, -OCH2CH2CH2-*, *, is the end connected to N; further preferably, X1 is O, X is selected from O, CH2, NH, S, and the sum of n and n1 is 1 or 2.

[0330] In particular, in the above-mentioned formula (C) and formula (C-1), Z 11 and Z 31 There is only one group containing a double bond; the double bond is, for example, a double bond between C and O in -C(O)-, or a double bond between C and S in -C(S)-; further preferably, Z 11 and Z 31 The group without double bond and *-(CH2) n2 -X2-(CH2) n3 - (* is the end connected to N) are the same or different; Still more preferably, Z 11 、-(CH2) n2 -X2-(CH2) n3 - and Z 31 The molecular weight of Z is independently 14.0-107.1, preferably 14.0-60; preferably about 14, about 16, about 28, about 30, about 42, about 43, about 44, about 46, about 58, or about 60; still more preferably, Z 11 、Z 21 and Z 31Selected from -CH2-, -CD2-, -CH2CH2-, -CD2CH2-, -C(O)-, -CH2C(O)-, -NHC(O)-, -OC(O)-, -CH2CH2O-, -OCH2C(O)-, -CH2OC(O)-, -CH2CH2CH2O-, -SC(O)-.

[0331] In particular, in the above-mentioned formula (C) and formula (C-1), Z 12 、Z 22 、Z 32 are independently selected from methylene, -CD2-;

[0332] Z 11 Independently selected from -CD2-, -C 1-3 Alkylene-(preferably -C 1-2 Alkylene-), -OC 1-3 Alkylene-*(preferably -OC 1-2 Alkylene-*), -SC 1-2 Alkylene-*, -NHC 1-2 Alkylene-*, -Se-C 1-2 Alkylene-*, -CH2-OC 1-2 Alkylene-* is the end connected to N;

[0333] Z 31 Independently selected from -C(O)-, -C 1-3 Alkylene-C(O)-*, -OC 1-2 Alkylene-C(O)-*, -NHCH2-C(O)-*, -SCH2-C(O)-*, -CH2-NHC(O)-*, -C 1-2 Alkylene-OC(O)-*, -NH-C(O)-*, -OC(O)-*, -SC(O)-*, -C 1-2 Alkylene-C(S)-* is the end connected to N;

[0334] n2 is 2 or 3, n3 is 0, X2 is O, NH, S; or n2 is 1 or 2, n3 is 1, X2 is O, NH, S; or n2 is 0 or 1, n3 is 0, X2 is CH2.

[0335] In particular, in the above-mentioned formula (C) and formula (C-1), Z 12 、Z 22 、Z 32 are independently selected from methylene, -CD2-;

[0336] Z 11Independently selected from -CD2-, -CH2-, -CH2CH2-, -OCH2-*, -OCH2CH2-*, and the like;

[0337] Z 31 Independently selected from -C(O)-, -CH2CH2C(O)-*, -CH2C(O)-*, -OCH2C(O)-*, -NHC(O)-*, -OC(O)-*, -SC(O)-*, * is the end connected to N;

[0338] n2 is 2 or 3, n3 is 0, and X2 is O; or n2 is 1 or 2, n3 is 1, and X2 is O; or n2 is 0 or 1, n3 is 0, and X2 is CH2.

[0339] In particular, in the above-mentioned formula (C) and formula (C-1), Z 12 、Z 22 、Z 32 are independently selected from methylene, -CD2-; Z 11 Independently selected from -CD2-, -C 1-3 Alkylene-(preferably -C 1-2 Alkylene-), -OC 1-3 Alkylene-*(preferably -OC 1-2 Alkylene-*), -SC 1-2 Alkylene-*, -NHC 1-2 Alkylene-*, -Se-C 1-2 Alkylene-*, -CH2-OC 1-2 Alkylene-*, Z 31 Independently selected from -C(O)-, -C 1-3 Alkylene-C(O)-*, -OC 1-2 Alkylene-C(O)-*, -NHCH2-C(O)-*, -SCH2-C(O)-*, -CH2-NHC(O)-*, -C 1-2 Alkylene-OC(O)-*, -NH-C(O)-*, -OC(O)-*, -SC(O)-*, -C 1-2 Alkylene-C(S)-* is connected to N; further preferably, Z 11 Independently selected from -CD2-, -CH2-, -CH2CH2-, -OCH2CH2-, *, and N-connected terminal; further preferably, Z 31Independently selected from -CH2CH2C(O)-*, -CH2C(O)-*, -OCH2C(O)-*, -NHC(O)-*, -OC(O)-*, -SC(O)-*, *, is the end connected to N; further preferably, X2 is O, NH, S, Se, and the sum of n2 and n3 is 1, 2, or 3; further preferably, X2 is O, and the sum of n2 and n3 is 2 or 3.

[0340] In particular, in the above formula (D) and formula (D-1), Z 11 is a group not containing a double bond; the double bond is, for example, a double bond between C and O in -C(O)-, or a double bond between C and S in -C(S)-; further preferably, Z 11 With *-(CH2) n2 -X2-(CH2) n3 - (* is the end connected to N) are the same or different; Still more preferably, Z 11 、-C(X1)-(CH2) n1 -(X) n - and -(CH2) n2 -X2-(CH2) n3 - has a molecular weight independently of one another of 14.0-107.1, preferably 14.0-60; preferably about 14, about 16, about 28, about 30, about 42, about 43, about 44, about 46, about 58, or about 60; still more preferably, Z 11 、Z 21 and Z 31 Selected from -CH2-, -CD2-, -CH2CH2-, -CD2CH2-, -C(O)-, -CH2C(O)-, -NHC(O)-, -OC(O)-, -CH2CH2O-, -OCH2C(O)-, -CH2OC(O)-, -CH2CH2CH2O-, -SC(O)-.

[0341] In particular, in the above formula (D) and formula (D-1), Z 12 、Z 22 、Z 32 are independently selected from methylene, -CD2-;

[0342] Z 11 Independently selected from -CD2-, -C 1-2 Alkylene-, -OC 1-2 Alkylene-*, -SC 1-2 Alkylene-*, -NHC 1-2 Alkylene-*, -Se-C 1-2 Alkylene-*, -CH2-OC 1-2 Alkylene-* is the end connected to N;

[0343] n2 is 2 or 3, n3 is 0, X2 is O, NH, S; or n2 is 1 or 2, n3 is 1, X2 is O, NH, S; or n2 is 0 or 1, n3 is 0, X2 is CH2;

[0344] X1 is O or S, X is selected from O, CH2, NH, S, n is 1, and n1 is 0; or X1 is O or S, X is O or CH2, n is 1, and n1 is 1.

[0345] In particular, in the above formula (D) and formula (D-1), Z 12 、Z 22 、Z 32 are independently selected from methylene, -CD2-;

[0346] Z 11 Independently selected from -CD2-, -CH2-, -CH2CH2-, -OCH2-*, -OCH2CH2-*, and the like;

[0347] n2 is 2 or 3, n3 is 0, and X2 is O; or n2 is 1 or 2, n3 is 1, and X2 is O; or n2 is 0 or 1, n3 is 0, and X2 is CH2;

[0348] X1 is O, X is selected from O, CH2, NH, S, n is 1, and n1 is 0; or X1 is O, X is O or CH2, n is 1, and n1 is 1.

[0349] In particular, in the above formula (D) and formula (D-1), Z 12 、Z 22 、Z 32 are independently selected from methylene, -CD2-;

[0350] Z 11 Independently selected from -CD2-, -CH2-, -CH2CH2-, -OCH2CH2-, * is connected to N;

[0351] n2 is 2 or 3, n3 is 0, and X2 is 0; or n2 is 2, n3 is 1, and X2 is 0;

[0352] X1 is O, X is selected from O, CH2, NH, S, n is 1, and n1 is 0.

[0353] In particular, in the above formula (D) and formula (D-1), Z 12 、Z 22 、Z 32 are independently selected from methylene, -CD2-; Z 11 Independently selected from -CD2-, -C 1-2 Alkylene-, -OC1-2 Alkylene-*, -SC 1-2 Alkylene-*, -NHC 1-2 Alkylene-*, -Se-C 1-2 Alkylene-*, -CH2-OC 1-2 Alkylene-, * is connected to N; X2 is O, NH, S, Se, the sum of n2 and n3 is 1, 2, 3; X1 is O or S, X is selected from O, CH2, NH, S, the sum of n and n1 is 0, 1, 2; further preferably, Z 11 Independently selected from -CD2-, -CH2-, -CH2CH2-, -OCH2CH2-, *, and is connected to N; further preferably, X2 is O, and the sum of n2 and n3 is 2 or 3; X1 is O, and X is selected from O, CH2, NH, S, and the sum of n and n1 is 1 or 2.

[0354] In one embodiment of the present invention, rings W1, W2, and W3 are each independently selected from the following optionally substituted groups: The optional substitution refers to being unsubstituted or being substituted by one or more independently selected from deuterium, halogen, -CN, -OH, -NH2, -CHO, C 1-3 Alkyl, C 1-3 Alkoxy, -N(C 1-3 Alkyl)2, -NH(C 1-3 alkyl), -C(O)C 1-3 substituted by an alkyl substituent.

[0355] In one embodiment of the present invention, rings W1, W2, and W3 are each independently selected from the following optionally substituted groups: The optionally substituted group refers to being unsubstituted or substituted by one or more substituents independently selected from deuterium, fluorine, chlorine, bromine, methyl, ethyl, methoxy, and ethoxy.

[0356] The present invention also provides a compound represented by the following formula (B-2), formula (B-3), formula (C-2), formula (C-3), formula (D-2), formula (D-3), or a pharmaceutically acceptable salt thereof:

[0357] Among them, Z in formula (B-2) and formula (B-3) 11 、Z 21 、Z 12 、Z 22 、Z 32 , X, X1, n, n1, ring W1, W2, W3 are as described for the compound of formula (B); Z in formula (C-2) and formula (C-3)11 、Z 31 、Z 12 、Z 22 、Z 32 , X2, n2, n3, ring W1, W2, W3 are as described for the compound of formula (C); Z in formula (D-2) and formula (D-3) 11 、Z 12 、Z 22 、Z 32 , X, X1, X2, n, n1, n2, n3, ring W1, W2, W3 are as described for the compound of formula (D).

[0358] In particular, in the above formula (B-2) and formula (B-3), Z 11 and Z 21 are groups without double bonds; the double bond is, for example, a double bond between C and O in -C(O)-, or a double bond between C and S in -C(S)-; further preferably, Z 11 With Z 21 Same or different, and Z 11 With Z 21 At least one of them is a group containing -O-, -NH-, -S-, or -Se-, preferably, a group containing -O-, such as *-CH2O-, *-CH2CH2O-, * is the terminal connected to N; Still further preferably, Z 11 、Z 21 and *-C(X1)-(CH2) n1 -(X) n - has a molecular weight independently of one another of 14.0-107.1, preferably 14.0-60; preferably about 14, about 16, about 28, about 30, about 42, about 43, about 44, about 46, about 58, or about 60; still more preferably, Z 11 、Z 21 and Z 31 Selected from -CH2-, -CD2-, -CH2CH2-, -CD2CH2-, -C(O)-, -CH2C(O)-, -NHC(O)-, -OC(O)-, -CH2CH2O-, -OCH2C(O)-, -CH2OC(O)-, -CH2CH2CH2O-, -SC(O)-.

[0359] In particular, in the above formula (C-2) and formula (C-3), Z 11 and Z 31 There is only one group containing a double bond; the double bond is, for example, a double bond between C and O in -C(O)-, or a double bond between C and S in -C(S)-; further preferably, Z 11 and Z 31The group without double bond and *-(CH2) n2 -X2-(CH2) n3 - (* is the end connected to N) are the same or different; Still more preferably, Z 11 、-(CH2) n2 -X2-(CH2) n3 - and Z 31 The molecular weight of Z is independently 14.0-107.1, preferably 14.0-60; preferably about 14, about 16, about 28, about 30, about 42, about 43, about 44, about 46, about 58, or about 60; still more preferably, Z 11 、Z 21 and Z 31 Selected from -CH2-, -CD2-, -CH2CH2-, -CD2CH2-, -C(O)-, -CH2C(O)-, -NHC(O)-, -OC(O)-, -CH2CH2O-, -OCH2C(O)-, -CH2OC(O)-, -CH2CH2CH2O-, -SC(O)-.

[0360] In particular, in the above formula (D-2) and formula (D-3), Z 11 is a group not containing a double bond; the double bond is, for example, a double bond between C and O in -C(O)-, or a double bond between C and S in -C(S)-; further preferably, Z 11 With *-(CH2) n2 -X2-(CH2) n3 - (* is the end connected to N) are the same or different; Still more preferably, Z 11 、-C(X1)-(CH2) n1 -(X) n - and -(CH2) n2 -X2-(CH2) n3 - has a molecular weight independently of one another of 14.0-107.1, preferably 14.0-60; preferably about 14, about 16, about 28, about 30, about 42, about 43, about 44, about 46, about 58, or about 60; still more preferably, Z 11 、Z 21 and Z 31 Selected from -CH2-, -CD2-, -CH2CH2-, -CD2CH2-, -C(O)-, -CH2C(O)-, -NHC(O)-, -OC(O)-, -CH2CH2O-, -OCH2C(O)-, -CH2OC(O)-, -CH2CH2CH2O-, -SC(O)-.

[0361] The present invention also provides a compound represented by the following formula (E), formula (E-1), or formula (F), or a pharmaceutically acceptable salt thereof:

[0362] Wherein, L1 and L2 are as described in the compound of formula (I), formula (I-1-P1), formula (I-1-P2), formula (I-1-P3), formula (I-1-P4), formula (III), formula (III-1), formula (III-B), formula (B), formula (C) or formula (D), X is O, CH2, NH, R a Deuterium, halogen, -CN, -OH, -NH2, -CHO, C 1-3 Alkyl, C 1-3 Alkoxy, -N(C 1-3 Alkyl)2, -NH(C 1-3 alkyl), -C(O)C 1-3 Alkyl, n1 is 0 or 1, m is 0 or 1, n is 0 or 1; R 23 、R 24 are independently selected from H and deuterium.

[0363] In particular, in the above-mentioned formula (E) and formula (E-1),

[0364] L1 and L2 are the 11 and Z 21 groups, and

[0365] Z 11 and Z 21 are groups without double bonds; the double bond is, for example, a double bond between C and O in -C(O)-, or a double bond between C and S in -C(S)-; further preferably, Z 11 With Z 21 Same or different, and Z 11 With Z 21 At least one of them is *-C(O)-(CH2) n1 -(X) n -(* is the terminal connected to N) group; Still more preferably, Z 11 、Z 21 and -C(O)-(CH2) n1 -(X) n - has a molecular weight independently of one another of 14.0-107.1, preferably 14.0-60; preferably about 14, about 16, about 28, about 30, about 42, about 43, about 44, about 46, about 58, or about 60; still more preferably, Z 11 、Z 21 and Z 31Selected from -CH2-, -CD2-, -CH2CH2-, -CD2CH2-, -C(O)-, -CH2C(O)-, -NHC(O)-, -OC(O)-, -CH2CH2O-, -OCH2C(O)-, -CH2OC(O)-, -CH2CH2CH2O-, -SC(O)-.

[0366] In particular, in formula (F) as described above,

[0367] L1 and L2 are the 11 and Z 21 groups, and

[0368] Z 11 and Z 21 There is only one group containing a double bond; the double bond is, for example, a double bond between C and O in -C(O)-, or a double bond between C and S in -C(S)-; further preferably, Z 11 With Z 21 The one not containing a double bond is the same as or different from *-(CH2)2-O- (* is the end connected to N); Still further preferably, Z 11 and Z 21 The molecular weight of Z is independently 14.0-107.1, preferably 14.0-60; preferably about 14, about 16, about 28, about 30, about 42, about 43, about 44, about 46, about 58, or about 60; still more preferably, Z 11 、Z 21 and Z 31 Selected from -CH2-, -CD2-, -CH2CH2-, -CD2CH2-, -C(O)-, -CH2C(O)-, -NHC(O)-, -OC(O)-, -CH2CH2O-, -OCH2C(O)-, -CH2OC(O)-, -CH2CH2CH2O-, -SC(O)-.

[0369] In one embodiment of the present invention, R a is fluorine, chlorine, methyl, ethyl, methoxy, ethoxy; preferably R a For fluorine.

[0370] In one embodiment of the present invention, m is 1.

[0371] In one embodiment of the present invention, X is CH2.

[0372] In one embodiment of the present invention, X is selected from O, CH2, NH, S, n is 1, and n1 is 0; or X is O or CH2, n is 1, and n1 is 1.

[0373] In one embodiment of the present invention, the sum of n and n1 is 0, 1, or 2; preferably, the sum of n and n1 is 1 or 2 (i.e., n is 1, n1 is 0; or n is 0, n1 is 1; or n is 1, n1 is 1; or n is 0, n1 is 2; or n is 2, n1 is 0); preferably, the sum of n and n1 is 1 (i.e., n is 1, n1 is 0; or n is 0, n1 is 1).

[0374] In particular, in the above-mentioned formula (E), formula (E-1), and formula (F), R a is fluorine, chlorine, methyl, ethyl, methoxy, ethoxy, m is 1, X is selected from O, CH2, NH, S, and the sum of n and n1 is 0, 1, or 2.

[0375] More preferably, R a is fluorine or methoxy, m is 1, X is selected from O, CH2, NH, S, and the sum of n and n1 is 1 or 2.

[0376] In one embodiment of the present invention, L1 is L2 is * indicates the N-connected end; Rings W1 and W2 are independently selected from The phenyl group is optionally substituted by one or more independently selected from halogen, C 1-3 The group is substituted by an alkoxy group (preferably a fluorine group or a methoxy group).

[0377] In one embodiment of the present invention, Z 11 、Z 12 、Z 21 、Z 22 are independently selected from -C 1-2 Alkylene-, -OC 1-3 Alkylene-, -NH-C 1-2 Alkylene-, -SC 1-2 Alkylene-, -C 1-2 Alkylene-OC 1-2 Alkylene-, -C 1-2 Alkylene-C(O)-, -OC 1-2 Alkylene-C(O)-, -C 1-2 Alkylene-NH-C(O)-, -C 1-2 Alkylene-OC(O)-, -NH-C(O)-, -NH-C 1-2 Alkylene-C(O)-, -OC(O)-, -SC(O)-.

[0378] In one embodiment of the present invention, Z 11 、Z 12 、Z 21 、Z 22 are independently selected from methylene, ethylene,

[0379] In one embodiment of the present invention, L1 and L2 are independently selected from *Indicates the N-connection terminal.

[0380] The present invention also provides a compound represented by the following formula (E-2), formula (E-3), formula (E-4), formula (F-1), formula (F-2), or a pharmaceutically acceptable salt thereof:

[0381] Among them, L1, L2, X, m, n, n1, R in formula (E-2), formula (E-3) and formula (E-4) a As described in the compounds of formula (E) and formula (E-1); R in formula (E-4) 23 、R 24 As described for the compound of formula (E-1); L1 and L2 in formula (F-1) and formula (F-2) are as described for the compound of formula (F).

[0382] In particular, in the above-mentioned formula (E-2), formula (E-3) and formula (E-4),

[0383] L1 and L2 are the 11 and Z 21 groups, and

[0384] Z 11 and Z 21 are groups without double bonds; the double bond is, for example, a double bond between C and O in -C(O)-, or a double bond between C and S in -C(S)-; further preferably, Z 11 With Z 21 Same or different, and Z 11 With Z 21 At least one of them is *-C(O)-(CH2) n1 -(X) n -(* is the terminal connected to N) group; Still more preferably, Z 11 、Z 21 and -C(O)-(CH2) n1 -(X) n - has a molecular weight independently of one another of 14.0-107.1, preferably 14.0-60; preferably about 14, about 16, about 28, about 30, about 42, about 43, about 44, about 46, about 58, or about 60; still more preferably, Z 11 、Z 21 and Z 31Selected from -CH2-, -CD2-, -CH2CH2-, -CD2CH2-, -C(O)-, -CH2C(O)-, -NHC(O)-, -OC(O)-, -CH2CH2O-, -OCH2C(O)-, -CH2OC(O)-, -CH2CH2CH2O-, -SC(O)-.

[0385] Specifically, in formulae (F-1) and (F-2) as described above,

[0386] L1 and L2 are the 11 and Z 21 groups, and

[0387] Z 11 and Z 21 There is only one group containing a double bond; the double bond is, for example, a double bond between C and O in -C(O)-, or a double bond between C and S in -C(S)-; further preferably, Z 11 With Z 21 The one not containing a double bond is the same as or different from *-(CH2)2-O- (* is the end connected to N); Still further preferably, Z 11 and Z 21 The molecular weight of Z is independently 14.0-107.1, preferably 14.0-60; preferably about 14, about 16, about 28, about 30, about 42, about 43, about 44, about 46, about 58, or about 60; still more preferably, Z 11 、Z 21 and Z 31 Selected from -CH2-, -CD2-, -CH2CH2-, -CD2CH2-, -C(O)-, -CH2C(O)-, -NHC(O)-, -OC(O)-, -CH2CH2O-, -OCH2C(O)-, -CH2OC(O)-, -CH2CH2CH2O-, -SC(O)-.

[0388] The present invention also provides a compound represented by the following formula (G), or a pharmaceutically acceptable salt thereof:

[0389] wherein X, X1, X2, n, n1, n2, and n3 are as described for the compound of formula (I), formula (I-1-P1), formula (I-1-P2), formula (I-1-P3), formula (I-1-P4), formula (III), formula (III-1), formula (III-B), formula (B), formula (C), or formula (D); m is independently 0 or 1; n4 is 0, 1, 2, or 3; X3 is O, S, CH2, or NH; or X3 is O, S, CH2, NH, or CD2; and R aDeuterium, halogen, -CN, -OH, -NH2, -CHO, C 1-3 Alkyl, C 1- 3 alkoxy, -N(C 1-3 Alkyl)2, -NH(C 1-3 alkyl), -C(O)C 1-3 alkyl.

[0390] In one embodiment of the present invention, R a is fluorine, chlorine, methyl, ethyl, methoxy, ethoxy; preferably fluorine or methoxy.

[0391] In one embodiment of the present invention, m is 1.

[0392] In one embodiment of the present invention, n4 is 0, 1, or 2; preferably 0 or 1, and more preferably 0.

[0393] In one embodiment of the present invention, X3 is O, CH2 or X3 is O, CH2, CD2.

[0394] In one embodiment of the present invention, X3 is O, n4 is 2; or X3 is CH2, n4 is 0 or 1; or X3 is CH2, CD2, n4 is 0 or 1; further preferably, X3 is CH2, CD2, and n4 is 0.

[0395] In particular, in formula (G) as described above, R a is fluorine, chlorine, methyl, ethyl, methoxy, or ethoxy; m is 1; X2 is O, NH, S, or Se, and the sum of n2 and n3 is 1, 2, or 3; X1 is O or S, and X is selected from O, CH2, NH, or S, and the sum of n and n1 is 0, 1, or 2;

[0396] X3 is O, n4 is 2; or X3 is CH2, CD2, n4 is 0 or 1.

[0397] More preferably, R a is fluorine, chlorine, or methoxy; m is 1; X2 is O, and the sum of n2 and n3 is 2 or 3; X1 is O, and X is selected from O, CH2, NH, or S, and the sum of n and n1 is 1 or 2;

[0398] X3 is O, n4 is 2; or X3 is CH2, CD2, n4 is 0 or 1.

[0399] In particular, in formula (G) as described above, R a is fluorine, chlorine, methyl, ethyl, methoxy, ethoxy; m is 1;

[0400] X3 is O, n4 is 2; or X3 is CH2, CD2, n4 is 0 or 1;

[0401] n2 is 2 or 3, n3 is 0, X2 is O, NH, S; or n2 is 1 or 2, n3 is 1, X2 is O, NH, S; or n2 is 0 or 1, n3 is 0, X2 is CH2;

[0402] X1 is O or S, X is selected from O, CH2, NH, S, n is 1, and n1 is 0; or X1 is O or S, X is O or CH2, n is 1, and n1 is 1.

[0403] In particular, in formula (G) as described above, R a is fluorine, chlorine, or methoxy; m is 1;

[0404] X3 is O, n4 is 2; or X3 is CH2, CD2, n4 is 0 or 1;

[0405] n2 is 2 or 3, n3 is 0, and X2 is O; or n2 is 1 or 2, n3 is 1, and X2 is O; or n2 is 0 or 1, n3 is 0, and X2 is CH2;

[0406] X1 is O, X is selected from O, CH2, NH, S, n is 1, and n1 is 0; or X1 is O, X is O or CH2, n is 1, and n1 is 1.

[0407] The present invention also provides a compound represented by the following formula (G-1) or formula (G-2), or a pharmaceutically acceptable salt thereof:

[0408] Among them, X, X1, X2, X3, n, n1, n2, n3, n4, m, R a As described for the compound of formula (G).

[0409] The present invention also provides a compound represented by the following formula (G-3) or formula (G-4), or a pharmaceutically acceptable salt thereof:

[0410] Among them, X, X1, X2, X3, n, n1, n2, n3, n4, m, R a As described for the compound of formula (G), R 19 、R 20 、R 21 、R 22 、R 23 、R 24 are independently selected from H or deuterium.

[0411] In particular, in the above-mentioned formula (G), formula (G-1), formula (G-2), formula (G-3), and formula (G-4), *-(CH2) n4 -X3-, *-(CH2) n2 -X2-(CH2) n3-, and *-C(X1)-(CH2) n1 -(X) n - (* is the end connected to N) are the same or different from each other, and their molecular weights are independently 14.0-107.1, preferably 14.0-60; preferably about 14, about 16, about 28, about 30, about 42, about 43, about 44, about 46, about 58, or about 60; Still more preferably, Z 11 、Z 21 and Z 31 Selected from -CH2-, -CD2-, -CH2CH2-, -CD2CH2-, -C(O)-, -CH2C(O)-, -NHC(O)-, -OC(O)-, -CH2CH2O-, -OCH2C(O)-, -CH2OC(O)-, -CH2CH2CH2O-, -SC(O)-.

[0412] The present invention also provides a compound represented by the following formula (H), or a pharmaceutically acceptable salt thereof:

[0413] wherein X, X1, X2, n, n1, n2, and n3 are as described for compounds of formula (I), formula (I-1-P1), formula (I-1-P2), formula (I-1-P3), formula (I-1-P4), formula (III), formula (III-1), formula (III-B), formula (B), formula (C), formula (D), or formula (G); m is independently 0 or 1, n5 is 1, 2, 3, or 4, and R a Selected from deuterium, halogen, -CN, -OH, -NH2, -CHO, C 1-3 Alkyl, C 1-3 Alkoxy, -N(C 1-3 Alkyl)2, -NH(C 1-3 alkyl), -C(O)C1-3 alkyl.

[0414] In one embodiment of the present invention, R a is fluorine, chlorine, methyl, ethyl, methoxy, ethoxy; preferably, R a It is fluorine and methoxy.

[0415] In one embodiment of the present invention, m is 1.

[0416] In one embodiment of the present invention, n5 is 1, 2, or 3; preferably 1 or 2, and more preferably 1.

[0417] The present invention also provides a compound represented by the following formula (H-1) or formula (H-2), or a pharmaceutically acceptable salt thereof:

[0418] Among them, X, X1, X2, n, n1, n2, n3, n5, m, R a As described for the compound of formula (H).

[0419] The present invention also provides a compound represented by the following formula (H-3) or formula (H-4), or a pharmaceutically acceptable salt thereof:

[0420] Among them, X, X1, X2, n, n1, n2, n3, n5, m, R a As described for the compound of formula (H), R 13 、R 14 、R 19 、R 20 、R 21 、R 22 、R 23 、R 24 are independently selected from H or deuterium.

[0421] The present invention also provides a compound having a structure as shown in Formula (Dc), Formula (Df), Formula (Dg), or Formula (Dh), or a pharmaceutically acceptable salt of the compound:

[0422] Among them, Z 11 、Z 12 、Z 22 、Z 32 , X, X1, X2, n, n1, n2, n3, ring W1, W2, W3 are as described in the compounds of formula (I), formula (I-1-P1), formula (I-1-P2), formula (I-1-P3), formula (I-1-P4), and formula (D), Pg 1 、Pg 2 Preferably, Pg 1 Independently selected from tert-butyl, methyl, benzyl, Pg 2 Independently selected from tert-butyloxycarbonyl (Boc), 9-fluorenylmethoxycarbonyl (FMOC), benzyloxycarbonyl (Cbz); preferably Boc.

[0423] On the basis of conforming to the common sense in this field, the above-mentioned preferred conditions can be arbitrarily combined to obtain the preferred embodiments of the present invention.

[0424] In one embodiment of the present invention, the compound of the present invention or a pharmaceutically acceptable salt of said compound is selected from:

[0425] In one embodiment of the present invention, the compound of the present invention or a pharmaceutically acceptable salt of said compound is selected from:

[0426] In one embodiment of the present invention, the compound is 3-(3-(2-((3-(2-carboxy-2-(pyrrolidin-3-yl)ethyl)benzyl)(2-(3-(2-carboxy-2-(pyrrolidin-3-yl)ethyl)phenoxy)ethyl)amino)-2-oxoethyl)phenyl)-2-(pyrrolidin-3-yl)propanoic acid, or a pharmaceutically acceptable salt of the compound:

[0427] In one embodiment of the present invention, the compound is 3-(3-(2-((3-(2-carboxy-2-(pyrrolidin-3-yl)ethyl)benzyl)(2-(3-(2-carboxy-2-(pyrrolidin-3-yl)ethyl)phenoxy)ethyl)amino)-2-oxoethyl)phenyl)-2-(pyrrolidin-3-yl)propanoic acid, or a pharmaceutically acceptable salt of the compound, which has stereoisomeric forms:

[0428] In one embodiment of the present invention, the compound is (S)-3-(3-(2-((3-((S)-2-carboxy-2-(pyrrolidin-3-yl)ethyl)benzyl)(2-(3-((S)-2-carboxy-2-(pyrrolidin-3-yl)ethyl)phenoxy)ethyl)amino)-2-oxoethyl)phenyl)-2-(pyrrolidin-3-yl)propanoic acid, or a pharmaceutically acceptable salt of the compound:

[0429] In one embodiment of the present invention, the compound is (S)-3-(3-(2-((3-((S)-2-carboxy-2-((R)-pyrrolidin-3-yl)ethyl)benzyl)(2-(3-((S)-2-carboxy-2-((R)-pyrrolidin-3-yl)ethyl)phenoxy)ethyl)amino)-2-oxoethyl)phenyl)-2-((R)-pyrrolidin-3-yl)propanoic acid, or a pharmaceutically acceptable salt of the compound:

[0430] In one embodiment of the present invention, the compound is (S)-3-(3-(2-((3-((S)-2-carboxy-2-((R)-pyrrolidin-3-yl)ethyl)benzyl)(2-(3-((S)-2-carboxy-2-((R)-pyrrolidin-3-yl)ethyl)phenoxy)ethyl)amino)-2-oxoethyl)phenyl)-2-((R)-pyrrolidin-3-yl)propanoic acid, or a deuterated derivative of the compound, or a pharmaceutically acceptable salt of the compound:

[0431] In one embodiment of the present invention, the compound is (2S,2'S)-3,3'-(((((2-(3-((S)-2-carboxy-2-((R)-pyrrolidin-3-yl)ethyl)phenyl)acetyl)azanediyl)bis(ethane-2,1-diyl))bis(oxy))bis(3,1-phenylene))bis(2-((R)-pyrrolidin-3-yl)propanoic acid), or a deuterated derivative of the compound, or a pharmaceutically acceptable salt of the compound:

[0432] In one embodiment of the present invention, the compound is (S)-3-(3-(2-((3-((S)-2-carboxy-2-((R)-pyrrolidin-3-yl)ethyl)benzyl)((3-((S)-2-carboxy-2-((R)-pyrrolidin-3-yl)ethyl)phenoxy)carbonyl)amino)ethoxy)phenyl)-2-((R)-pyrrolidin-3-yl)propanoic acid, or a deuterated derivative of the compound, or a pharmaceutically acceptable salt of the compound:

[0433] In one embodiment of the present invention, the compound of the present invention or a pharmaceutically acceptable salt of said compound is selected from:

[0434] Among them, * is the terminal connected to N,

[0435] The present invention also provides the preparation of formula (I), formula (I-1-P1), formula (I-1-P2), formula (I-1-P3), formula (I-1-P4), formula (I-2), formula (I-3), formula (I'-1), (I'-2), (I'-3), formula (II), formula (II-A), formula (II-A'), formula (II-B), formula (II-B'), formula (II-C), formula (II-C'), formula (III), formula (III-1), formula (III-2), formula (III-1-1), formula (III-2-1), formula (III-A), formula (III-A'), formula (III-B), formula (III-B'), formula (III-B'-1), formula (III-C), formula (III-C'), formula (III-D), formula (III- -D'), formula (III-E), formula (III-E'), formula (IV), formula (A), formula (B), formula (B-1), formula (C), formula (C-1), formula (D), formula (D-1), formula (B-2), formula (B-3), formula (C-2), formula (C-3), formula (D-2), formula (D-3), formula (E), formula (F), formula (E-1), formula (E-2), formula (E-3), formula (E-4), formula (F-1), formula (F-2), formula (G), formula (G-1), formula (G-2), formula (G-3), formula (G-4), formula (H), formula (H-1), formula (H-2), formula (H-3), formula (H-4), formula (Dc), formula (Df), formula (Dg), and formula (Dh), or a pharmaceutically acceptable salt thereof.

[0436] The compound of the general formula can be prepared by a variety of methods, including but not limited to the following methods:

[0437] Option 1:

[0438] wherein Y1 and Y2 are each independently halogen (e.g., fluorine, chlorine, bromine), preferably bromine; Y is independently halogen (e.g., fluorine, chlorine, bromine) or oxo (oxo refers to ═O in —C(O)H), preferably bromine or oxo (oxo refers to ═O in —C(O)H); R′ is as defined in the compound of formula (II); W1, W2, and W3 are as defined in the compounds of formula (I), (I-1-P1), (I-1-P2), (I-1-P3), and (I-1-P4);

[0439] Under the action of a base, compound (a) and compound (b) are reacted at room temperature for 16 hours to obtain compound (c). The chiral auxiliary group of compound (c) is hydrolyzed under alkaline conditions of hydrogen peroxide, and then esterified to obtain intermediate (d). Intermediate (e) is inserted into the carbonyl group at normal pressure, and reduced with DIBAL-H to obtain intermediate (f). Intermediate (f) is reductively aminated in an ammonia solution in tetrahydrofuran to obtain intermediate (g). The intermediate is further reductively aminated or substituted to obtain intermediate (i), which is deprotected under acidic conditions to obtain a compound of formula (II-A'). Intermediate (g) and intermediate (f) undergo a substitution reaction or reductive amination to obtain intermediate (j), which is deprotected under acidic conditions to obtain a compound of formula (III-C').

[0440] Option 2:

[0441] Y3 is independently halogen (e.g., fluorine, chlorine, bromine) or oxo (oxo refers to ═O in —C(O)H), preferably bromine or oxo (oxo refers to ═O in —C(O)H); L3 is as described for the compounds of formula (I), formula (I-1-P1), formula (I-1-P2), formula (I-1-P3), and formula (I-1-P4);

[0442] Compound (k) is synthesized according to the conditions of patent CN114008021A. Compound (m) is obtained by reductive amination or substitution reaction of compound (k) and compound (l), and then deprotected under acidic conditions to obtain the compound of formula (III-A').

[0443] Option 3:

[0444] Wherein, W1, W2, and W3 are as described in the compounds of formula (I), formula (I-1-P1), formula (I-1-P2), formula (I-1-P3), and formula (I-1-P4);

[0445] In the presence of ammonia in tetrahydrofuran, compound (p) undergoes reductive amination to obtain compound (q); compound (q) and compound (s) undergo further reductive amination to obtain intermediate (t); intermediate (t) is deprotected under acidic conditions to obtain compound of formula (III-D').

[0446] Option 4:

[0447] Among them, Z 11 、Z 12 、Z 22 、Z 32 , X, X1, X2, n, n1, n2, n3, ring W1, W2, W3 are as described in the compounds of formula (I), formula (I-1-P1), formula (I-1-P2), formula (I-1-P3), formula (I-1-P4), and formula (D), Pg 1 、Pg 2 Preferably, Pg 1 are independently selected from tert-butyl, methyl, benzyl, Pg 2 They are independently selected from tert-butyloxycarbonyl (Boc), 9-fluorenylmethoxycarbonyl (FMOC), and benzyloxycarbonyl (Cbz); preferably Boc.

[0448] The present invention also provides a pharmaceutical composition comprising the compound of the present invention, or a pharmaceutically acceptable salt of the compound.

[0449] The present invention also provides a pharmaceutical composition comprising the compound of the present invention, or a pharmaceutically acceptable salt of the compound, and a pharmaceutically acceptable excipient.

[0450] In the above-mentioned pharmaceutical composition, the compound of the present invention, or the pharmaceutically acceptable salt of the compound accounts for 0.1-99.9% by weight of the weight of the pharmaceutical composition, for example, 0.5% by weight, 1% by weight, 2% by weight, 3% by weight, 4% by weight, 5% by weight, 6% by weight, 7% by weight, 8% by weight, 9% by weight, 10% by weight, 20% by weight, 30% by weight, 40% by weight, 50% by weight, 60% by weight, 70% by weight, 80% by weight, 90% by weight, 91% by weight, 92% by weight, 93% by weight, 94% by weight, 95% by weight, 96% by weight, 97% by weight, 98% by weight, 99% by weight, 99.5% by weight, or a range formed by a combination of any two of the above-mentioned point values, and the balance is pharmaceutically acceptable excipients.

[0451] In some embodiments of the present invention, the pharmaceutical composition acts as an inhibitor of Lp(a) assembly.

[0452] In some embodiments of the present invention, the pharmaceutical composition is used as a medicament for treating cardiovascular disease (CVD).

[0453] Administration of the compounds of the present invention, or pharmaceutically acceptable salts thereof, can be carried out in pure form or in the form of suitable pharmaceutical compositions by any acceptable route of administration for similarly used drugs. The pharmaceutical compositions of the present invention can be prepared by combining the compounds of the present invention with suitable pharmaceutically acceptable excipients. The pharmaceutical compositions of the present invention can be formulated into solid, semisolid, liquid, or gaseous formulations. Generally, the pharmaceutical compositions can be prepared using conventional excipients in the pharmaceutical formulation art by conventional preparation methods.

[0454] The present invention also provides use of the compound of the present invention, or a pharmaceutically acceptable salt of the compound, in the preparation of a medicament for preventing and / or treating cardiovascular disease (CVD).

[0455] In one embodiment of the present invention, provided is the use of the compound of the present invention, or a pharmaceutically acceptable salt thereof, in the preparation of a medicament for preventing and / or treating diseases or conditions associated with elevated plasma levels of Lp(a).

[0456] In one embodiment of the present invention, the disease or condition associated with elevated Lp(a) plasma levels is cardiovascular disease (CVD); the cardiovascular disease (CVD) includes but is not limited to atherosclerotic cardiovascular disease (ASCVD), coronary artery stenosis, coronary artery-related diseases, aortic valve stenosis, aortic valve stenosis-related diseases, heart failure, heart failure-related diseases, atrial fibrillation, atrial fibrillation-related diseases; the ASCVD includes peripheral vascular disease, peripheral artery-related diseases, coronary heart disease, ischemic stroke, and ischemic stroke-related diseases.

[0457] The term "elevated Lp(a) plasma levels" refers to plasma levels equal to or above normal levels. For humans, "elevated Lp(a) plasma levels" refers to plasma levels equal to or above about 30 mg / dL.

[0458] In one embodiment of the invention, for humans, "elevated plasma levels of Lp(a)" are plasma levels equal to or greater than about 50 mg / dL. The compounds provided herein are useful in therapies that lower Lp(a) plasma levels.

[0459] The present invention also provides use of the compound of the present invention, or a pharmaceutically acceptable salt of the compound, in the preparation of a medicament for preventing and / or treating diseases mediated by Lp(a).

[0460] Furthermore, the present invention provides a use, wherein the Lp(a)-mediated disease is cardiovascular disease (CVD).

[0461] Furthermore, the use provided by the present invention, wherein the cardiovascular disease (CVD) is atherosclerotic cardiovascular disease (ASCVD), coronary artery stenosis, coronary artery-related diseases, aortic valve stenosis, aortic valve stenosis-related diseases, heart failure, heart failure-related diseases, atrial fibrillation, atrial fibrillation-related diseases; the ASCVD includes peripheral vascular disease, peripheral artery-related diseases, coronary heart disease, ischemic stroke, and ischemic stroke-related diseases.

[0462] The present invention also provides a method for preventing and / or treating cardiovascular diseases, comprising administering to a patient a therapeutically effective dose of the compound of the present invention, or a pharmaceutically acceptable salt of the compound, or the pharmaceutical composition of the present invention.

[0463] In one embodiment of the present invention, a method for preventing and / or treating a disease or condition associated with elevated plasma levels of Lp(a) is provided, comprising administering to a patient a therapeutically effective dose of a compound of the present invention, or a pharmaceutically acceptable salt of the compound, or a pharmaceutical composition of the present invention. In one embodiment of the present invention, the disease or condition associated with elevated plasma levels of Lp(a) is a cardiovascular disease (CVD); the cardiovascular disease (CVD) includes, but is not limited to, atherosclerotic cardiovascular disease (ASCVD), coronary artery stenosis, coronary artery-related disease, aortic valve stenosis, aortic valve stenosis-related disease, heart failure, heart failure-related disease, atrial fibrillation, atrial fibrillation-related disease; the ASCVD includes peripheral vascular disease, peripheral artery-related disease, coronary heart disease, ischemic stroke, and ischemic stroke-related disease.

[0464] The present invention also provides a method for preventing and / or treating diseases mediated by Lp(a), which comprises administering to a patient a therapeutically effective dose of a compound of the present invention, or a pharmaceutically acceptable salt of the compound, or a pharmaceutical composition of the present invention; preferably, the Lp(a)-mediated disease is cardiovascular disease (CVD); the cardiovascular disease (CVD) includes atherosclerotic cardiovascular disease (ASCVD), coronary artery stenosis, coronary artery-related diseases, aortic valve stenosis, aortic valve stenosis-related diseases, heart failure, heart failure-related diseases, atrial fibrillation, and atrial fibrillation-related diseases; the ASCVD includes peripheral vascular disease, peripheral artery-related diseases, coronary heart disease, ischemic stroke, and ischemic stroke-related diseases.

[0465] Furthermore, the present invention provides uses or methods, wherein the compounds of the present invention, or pharmaceutically acceptable salts of the compounds, can be administered in combination with another compound for treating or preventing a disease mediated by Lp(a); the Lp(a)-mediated disease is such as cardiovascular disease (CVD).

[0466] The present invention also provides a compound of the present invention, or a pharmaceutically acceptable salt of the compound, or a pharmaceutical composition of the present invention for preventing and / or treating cardiovascular diseases.

[0467] The present invention also provides a use of the compound shown, or a pharmaceutically acceptable salt of the compound, or the pharmaceutical composition of the present invention as a medicine.

[0468] The present invention provides a compound as shown, or a pharmaceutically acceptable salt of the compound or a pharmaceutical composition as shown in the present invention for use in preventing and / or treating cardiovascular diseases. The present invention provides a compound as shown, or a pharmaceutically acceptable salt of the compound or a pharmaceutical composition as shown in the present invention for use in preventing and / or treating diseases or conditions associated with elevated plasma levels of Lp(a). In one embodiment of the present invention, the disease or condition associated with elevated plasma levels of Lp(a) is cardiovascular disease (CVD); the cardiovascular disease (CVD) includes but is not limited to atherosclerotic cardiovascular disease (ASCVD), coronary artery stenosis, coronary artery-related diseases, aortic valve stenosis, aortic valve stenosis-related diseases, heart failure, heart failure-related diseases, atrial fibrillation, atrial fibrillation-related diseases; the ASCVD includes peripheral vascular disease, peripheral artery-related diseases, coronary heart disease, ischemic stroke, and ischemic stroke-related diseases.

[0469] The present invention also provides a compound shown, or a pharmaceutically acceptable salt of the compound or the pharmaceutical composition of the present invention for use in preventing and / or treating diseases mediated by Lp(a); preferably, the Lp(a)-mediated disease is cardiovascular disease (CVD); further preferably, the cardiovascular disease (CVD) includes atherosclerotic cardiovascular disease (ASCVD), coronary artery stenosis, coronary artery-related diseases, aortic valve stenosis, aortic valve stenosis-related diseases, heart failure, heart failure-related diseases, atrial fibrillation, and atrial fibrillation-related diseases; the ASCVD includes peripheral vascular disease, peripheral artery-related diseases, coronary heart disease, ischemic stroke, and ischemic stroke-related diseases.

[0470] In one embodiment of the present invention, there is provided a compound of the present invention, or a pharmaceutically acceptable salt of the compound, or a pharmaceutical composition of the present invention for preventing and / or treating a disease or condition associated with elevated plasma levels of Lp(a). In one embodiment of the present invention, the disease or condition associated with elevated plasma levels of Lp(a) is cardiovascular disease (CVD); the cardiovascular disease (CVD) includes, but is not limited to, atherosclerotic cardiovascular disease (ASCVD), coronary artery stenosis, coronary artery-related disease, aortic stenosis, aortic stenosis-related disease, heart failure, heart failure-related disease, atrial fibrillation, atrial fibrillation-related disease; the ASCVD includes peripheral vascular disease, peripheral artery-related disease, coronary heart disease, ischemic stroke, and ischemic stroke-related disease.

[0471] On the other hand, the present application provides a compound of the present invention, or a pharmaceutically acceptable salt of the compound, or a pharmaceutical composition of the present invention for preventing and / or treating a disease mediated by Lp(a); preferably, the Lp(a)-mediated disease is cardiovascular disease (CVD); further preferably, the cardiovascular disease (CVD) is atherosclerotic cardiovascular disease (ASCVD), coronary artery stenosis, coronary artery-related disease, aortic valve stenosis, aortic valve stenosis-related disease, heart failure, heart failure-related disease, atrial fibrillation, atrial fibrillation-related disease; the ASCVD includes peripheral vascular disease, peripheral artery-related disease, coronary heart disease, ischemic stroke, and ischemic stroke-related disease.

[0472] Use of the compound of the present invention, or a pharmaceutically acceptable salt thereof, in the preparation of a medicament for preventing and / or treating cardiovascular diseases in combination with another compound for preventing and / or treating cardiovascular diseases.

[0473] In one embodiment of the present invention, the cardiovascular disease is a disease or disorder associated with elevated plasma levels of Lp(a).

[0474] In one embodiment of the present invention, the disease or condition associated with elevated Lp(a) plasma levels is cardiovascular disease (CVD); the cardiovascular disease (CVD) includes but is not limited to atherosclerotic cardiovascular disease (ASCVD), coronary artery stenosis, coronary artery-related diseases, aortic valve stenosis, aortic valve stenosis-related diseases, heart failure, heart failure-related diseases, atrial fibrillation, atrial fibrillation-related diseases; the ASCVD includes peripheral vascular disease, peripheral artery-related diseases, coronary heart disease, ischemic stroke, and ischemic stroke-related diseases.

[0475] The compounds of the present invention, or pharmaceutically acceptable salts of the compounds, are used in combination with other compounds to prevent and / or treat cardiovascular diseases. Furthermore, the other compounds are used to prevent and / or treat cardiovascular diseases. Furthermore, the cardiovascular diseases are diseases or conditions associated with elevated plasma levels of Lp(a). Furthermore, the diseases or conditions associated with elevated plasma levels of Lp(a) include, but are not limited to, atherosclerotic cardiovascular disease (ASCVD), coronary artery stenosis, coronary artery-related diseases, aortic valve stenosis, aortic valve stenosis-related diseases, heart failure, heart failure-related diseases, atrial fibrillation, and atrial fibrillation-related diseases; the ASCVD includes peripheral vascular disease, peripheral artery-related diseases, coronary heart disease, ischemic stroke, and ischemic stroke-related diseases.

[0476] The compounds described herein, or pharmaceutically acceptable salts thereof, are co-administered with a therapeutic agent. In certain embodiments, the therapeutic agent may include, but is not limited to, Lp(a) plasmapheresis. The drugs or therapies may be co-administered or administered simultaneously. The drugs or therapies may be administered sequentially or subsequently.

[0477] The present invention also provides a pharmaceutical composition, or a pharmaceutically acceptable salt of the compound and another compound for treating or preventing a disease mediated by Lp(a); preferably, the Lp(a)-mediated disease is such as cardiovascular disease (CVD).

[0478] When the compound of the present invention, or a pharmaceutically acceptable salt thereof, is administered in combination with another drug for treating, for example, cardiovascular disease (CVD), the compound of the present invention, or a pharmaceutically acceptable salt thereof, may provide a more effective effect in treating cardiovascular-related diseases.

[0479] definition

[0480] The terms "optional," "optionally," "optionally," or "optionally" mean that the subsequently described event or circumstance may but need not occur, and that the description includes instances where said event or circumstance occurs and instances where it does not.

[0481] The “multiple” in “optionally substituted with one or more substituents each independently selected from…” refers to 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; preferably 1, 2, 3 or 4; more preferably 1 or 2.

[0482] When "about" is used to describe a molecular weight, "about" is rounded to the nearest integer.

[0483] Unless otherwise specified, the term "alkyl" refers to a monovalent saturated aliphatic hydrocarbon group, a straight or branched chain group containing 1 to 20 carbon atoms, preferably containing 1 to 10 carbon atoms (i.e., C1-10 Alkyl), further preferably containing 1 to 8 carbon atoms (C 1-8 Alkyl), more preferably containing 1-6 carbon atoms (ie C 1-6 Alkyl), such as "C 1-6 "Alkyl" means that the group is an alkyl group and the number of carbon atoms in the carbon chain is between 1 and 6 (specifically 1, 2, 3, 4, 5 or 6). Examples include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, neopentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, 2-methylbutyl, 3-methylbutyl, n-hexyl, n-heptyl, n-octyl, and the like.

[0484] Unless otherwise specified, the term "alkylene" refers to a monovalent saturated aliphatic hydrocarbon group, a straight or branched chain group containing 1 to 20 carbon atoms, preferably containing 1 to 10 carbon atoms (i.e., C 1-10 Alkylene), further preferably containing 1 to 8 carbon atoms (C 1-8 Alkylene), more preferably containing 1-6 carbon atoms (ie C 1-6 Alkylene), such as "C 1-6 "Alkylene" means that the group is an alkylene group and the number of carbon atoms in the carbon chain is between 1 and 6 (specifically 1, 2, 3, 4, 5 or 6). Examples include, but are not limited to, methylene, ethylene, n-propylene, n-pentylene, n-hexylene, wait.

[0485] Unless otherwise specified, the term "alkenyl" refers to a straight or branched unsaturated aliphatic hydrocarbon group consisting of carbon atoms and hydrogen atoms and having at least one double bond. The alkenyl group may contain 2 to 20 carbon atoms, preferably 2 to 10 carbon atoms (i.e., C 2-10 alkenyl), further preferably containing 2 to 8 carbon atoms (C 2-8 alkenyl), more preferably containing 2 to 6 carbon atoms (ie, C 2-6 alkenyl), 2-5 carbon atoms (ie C 2-5 alkenyl), 2-4 carbon atoms (ie C 2- 4 alkenyl), 2-3 carbon atoms (ie C 2-3 alkenyl), 2 carbon atoms (i.e., C2 alkenyl), for example, "C 2-6 The term "alkenyl" refers to an alkenyl group, and the number of carbon atoms in the carbon chain is between 2 and 6 (specifically 2, 3, 4, 5 or 6). Non-limiting examples of alkenyl groups include, but are not limited to, ethenyl, 1-propenyl, 2-propenyl, 1-butenyl, isobutenyl and 1,3-butadienyl.

[0486] Unless otherwise specified, the term "alkynyl" refers to a straight or branched unsaturated aliphatic hydrocarbon group consisting of carbon atoms and hydrogen atoms and having at least one triple bond. The alkynyl group may contain 2 to 20 carbon atoms, preferably 2 to 10 carbon atoms (i.e., C 2-10 Alkynyl), further preferably containing 2 to 8 carbon atoms (C 2-8 Alkynyl), more preferably containing 2-6 carbon atoms (ie, C 2-6 Alkynyl), 2-5 carbon atoms (ie C 2-5 Alkynyl), 2-4 carbon atoms (ie C 2- 4 alkynyl), 2-3 carbon atoms (ie C 2-3 alkynyl), 2 carbon atoms (i.e., C2 alkynyl), for example, "C 2-6 "Alkynyl" means that the group is an alkynyl group, and the number of carbon atoms in the carbon chain is between 2 and 6 (specifically 2, 3, 4, 5 or 6). Non-limiting examples of alkynyl groups include, but are not limited to, ethynyl, 1-propynyl, 2-propynyl and 1-butynyl.

[0487] Unless otherwise specified, the term "cycloalkyl" refers to a monocyclic, bicyclic or polycyclic saturated aliphatic hydrocarbon group having the specified number of carbon atoms, preferably containing 3 to 14 carbon atoms (i.e., C 3-14 Cycloalkyl), preferably containing 4 to 14 carbon atoms (ie, C 4-14 Cycloalkyl), preferably containing 5 to 14 carbon atoms (ie, C 5-14 cycloalkyl), more preferably containing 6 to 14 carbon atoms (C 6-14 cycloalkyl), further preferably 6-12 carbon atoms (C 6-12 Examples include, but are not limited to, cyclohexyl, spiro[3.5]nonyl, and the like.

[0488] Unless otherwise specified, the term "oxaalkyl" refers to an alkyl residue in which one or more carbons (and their associated hydrogens) are replaced by oxygen, such as "alkoxy" or "alkoxyalkyl." For example, C3 oxaalkylene includes -OC 1-3 Alkoxy, -CH2OCH2CH3, -CH2CH2OCH3, etc. Examples include methoxy, ethoxy, propoxy, methoxypropyl, etc. The term oxaalkyl is understood in the art [see Nomenclature and Indexing of Chemical Substances for Chemical Extraction, published by the American Chemical Society, 196, but not limited to 127(a)], i.e., it refers to compounds in which oxygen is bonded to its adjacent atom by a single bond (forming an ether bond); it does not refer to the double-bonded oxygen found in a carbonyl group. The terms "thiaalkyl" and "seleniaalkyl" are similar to "oxaalkyl". The term "azaalkyl" refers to a group containing the radicals "NH", "-N(C 1-3For example, C3 azaalkylene includes -NHCH2CH2CH3, -CH2NHCH2CH3, -CH2CH2NHCH3, -CH2CH2N(CH3)CH3 and the like.

[0489] "Alkoxy" refers to an -O-alkyl group, wherein the alkyl group is as defined above, i.e., containing 1-20 carbon atoms, preferably 1-10 carbon atoms, more preferably 1-8 carbon atoms, and more preferably 1-6 carbon atoms (specifically 1, 2, 3, 4, 5, or 6). Representative examples include, but are not limited to, methoxy, ethoxy, propoxy, isopropoxy, butoxy, 1-methylpropoxy, 2-methylpropoxy, tert-butoxy, pentyloxy, 1-methylbutoxy, 2-methylbutoxy, 3-methylbutoxy, 1,1-dimethylpropoxy, 1,2-dimethylpropoxy, 2,2-dimethylpropoxy, 1-ethylpropoxy, and the like.

[0490] Unless otherwise specified, the term "halogen" or "halo" refers to F, Cl, Br, and I.

[0491] Unless otherwise specified, the term "heterocycle" or "heterocyclyl" refers to a saturated or partially unsaturated monocyclic, bicyclic or polycyclic hydrocarbon substituent, which is a non-aromatic structure and contains 3-20 ring atoms, wherein 1, 2, 3 or more ring atoms are selected from N, O or S, and the remaining ring atoms are C. Preferably, it contains 3-12 ring atoms, more preferably 3-10 ring atoms, or 3-8 ring atoms, or 3-6 ring atoms, or 4-6 ring atoms, or 5-6 ring atoms. The number of heteroatoms is preferably 1-4, more preferably 1-3 (i.e., 1, 2 or 3). Examples of monocyclic heterocyclic groups include pyrrolidinyl, imidazolidinyl, tetrahydrofuranyl, dihydropyrrolyl, piperidinyl, piperazinyl, pyranyl, etc. Bicyclic or polycyclic heterocyclic groups include spirocyclic, fused ring and bridged heterocyclic groups.

[0492] Unless otherwise specified, the term "aryl" refers to a monocyclic, bicyclic, or tricyclic aromatic carbocyclic ring system containing 6 to 16 carbon atoms, or 6 to 14 carbon atoms, or 6 to 12 carbon atoms, or 6 to 10 carbon atoms, preferably 6 to 10 carbon atoms. The term "aryl" can be used interchangeably with the term "aromatic ring." Examples of aryl groups include, but are not limited to, phenyl, naphthyl, anthracenyl, phenanthrenyl, or pyrenyl.

[0493] Unless otherwise specified, the term "heteroaryl" refers to an aromatic monocyclic, bicyclic, or polycyclic ring system containing 5-16 members, or 5-14 members, 5-12 members, 5-10 members, 5-8 members, or 5-6 members, wherein 1, 2, 3 or more of the ring atoms are heteroatoms and the remainder are carbon, the heteroatoms being independently selected from O, N, or S, and the number of heteroatoms being preferably 1, 2, or 3. Polycyclic heteroaryl is a fused heteroaryl. Examples of heteroaryl groups can include, but are not limited to, furyl, thienyl, oxazolyl, thiazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, thiodiazolyl, triazinyl, phthalazinyl, quinolyl, isoquinolyl, pteridinyl, purinyl, indolyl, isoindolyl, indazolyl, benzofuranyl, benzothiophenyl, benzopyridinyl, benzopyrimidinyl, benzo [1,2,4]triazolo[4,3-b]pyridazinyl, [1,2,4]triazolo[1,5-a]pyridinyl, [1,2,4]triazolo[1,5-a]pyridinyl, [1,2,4]triazolo[1,5-a]pyridinyl, etc.

[0494] Unless otherwise specified, the term "fused heteroaryl" refers to an aromatic ring system formed by two or more cyclic structures sharing two adjacent atoms. Each ring in the fused heteroaryl is an unsaturated aromatic ring, which may contain 5-20 ring atoms, preferably 6-14 ring atoms, more preferably 7-10 ring atoms, including 1-4 ring heteroatoms, preferably 1-3 (i.e., 1, 2 or 3) ring heteroatoms, and the heteroatoms are independently selected from N, O and S. Fused heteroaryl includes bicyclic, tricyclic, tetracyclic or polycyclic fused heteroaryl, preferably bicyclic, tricyclic or tetracyclic fused heteroaryl, more preferably bicyclic or tricyclic fused heteroaryl. Illustrative examples of fused heteroaryl include (but are not limited to) wait.

[0495] Unless otherwise specified, the term "pharmaceutically acceptable salt" or "pharmaceutically acceptable salt" refers to a salt that is suitable for use in contact with mammalian tissues, particularly human tissues, without excessive toxicity, irritation, allergic response, etc., and is commensurate with a reasonable benefit / risk ratio, within the scope of sound medical judgment. For example, pharmaceutically acceptable salts of amines, carboxylic acids, and other types of compounds are well known in the art. The salts can be prepared in situ during the final isolation and purification of the compounds of the present invention, or separately by reacting the free base or free acid with a suitable reagent.

[0496] Unless otherwise specified, the compounds of the present invention and pharmaceutically acceptable salts also include their "stereoisomers". The term "stereoisomer" refers to a compound having the same chemical structure but different arrangements of atoms or groups in space. Stereoisomers include enantiomers, diastereomers, conformers (rotamers), geometric isomers (cis / trans) isomers, atropisomers, etc. Any mixture of stereoisomers obtained can be separated into pure or substantially pure geometric isomers, enantiomers, diastereomers based on the differences in the physicochemical properties of the components, for example, by chromatography and / or fractional crystallization. The compounds and pharmaceutically acceptable salts described in this specification may include one or more chiral (i.e., asymmetric) centers. If a structure or chemical name in this specification does not indicate chirality, the structure or name is intended to include any single stereoisomer corresponding to the structure or name (i.e., any single chiral isomer), as well as any mixture of stereoisomers (e.g., racemates). In some embodiments, a single stereoisomer is obtained by isolating the single stereoisomer from a mixture of isomers (e.g., a racemate) using, for example, chiral chromatography. In other embodiments, a single stereoisomer is obtained by direct synthesis, for example, from chiral starting materials.

[0497] A specific enantiomer of a compound of the invention may be more active than other enantiomers of the same compound. In one embodiment, the compound or a pharmaceutically acceptable salt thereof is present in a single enantiomeric excess (%ee) of ≥90%, ≥95%, ≥96%, ≥97%, ≥98%, or ≥99%. In one aspect, a single enantiomer is present in an enantiomeric excess (%ee) of ≥99%.

[0498] A specific diastereomer of a compound of the invention may be more active than other diastereomers of the same compound. In one embodiment, the compound or a pharmaceutically acceptable salt thereof is a single diastereomer having a diastereomeric excess (% de) of ≥90%, ≥95%, ≥96%, ≥97%, ≥98%, or ≥99%. In one aspect, the diastereomeric excess (% de) of a single diastereomer is ≥99%.

[0499] Unless otherwise specified, the compounds of the present invention and pharmaceutically acceptable salts also include their "tautomers". The term "tautomer" refers to structural isomers with different energies that can be converted into each other through a low energy barrier. If tautomerism is possible (such as in solution), a chemical equilibrium of tautomers can be achieved. For example, proton tautomers (also known as prototropic tautomers) include interconversions that occur through proton migration, such as keto-enol isomerization and imine-enamine isomerization. Valence tautomers include interconversions that occur through the reorganization of some of the bonding electrons.

[0500] Unless otherwise specified, the compounds of the present invention and pharmaceutically acceptable salts also include "isotopic derivatives" thereof. The term "isotopic derivative" means that the compounds of the present invention may exist in an isotopically labeled or enriched form, containing one or more atoms whose atomic mass or mass number is different from the atomic mass or mass number of the largest atom found in nature. Isotopes may be radioactive or non-radioactive isotopes. Isotopes commonly used as isotopic labels are: hydrogen isotopes, 2 H and 3 H; Carbon isotope: 13 C and 14 C; Chlorine isotope: 35 Cl and 37 Cl; Fluorine isotope: 18 F; Iodine isotope: 123 I and 125 I; Nitrogen isotopes: 13 N and 15 N; oxygen isotopes: 15 O. 17 O and 18 O and sulfur isotopes 35 These isotope-labeled compounds can be used to study the distribution of pharmaceutical molecules in tissues. 3 H and 13 C, because they are easy to label and detect, they are more widely used. Some heavy isotopes, such as deuterium ( 2 H) substitution can enhance metabolic stability, prolong half-life, thereby achieving the purpose of reducing dosage and providing therapeutic advantages. Isotope-labeled compounds are generally synthesized from labeled starting materials using known synthetic techniques in the same way as non-isotope-labeled compounds. All compounds of the present invention in which one atom is replaced by one or more isotopes thereof (for example, in the compound of formula (I), one or more carbon atoms are 11 C or 13 C carbon isotope, or one or more hydrogen atoms are 2 H or 3 H isotopes) are encompassed herein.

[0501] Unless otherwise specified, the compounds of the present invention and pharmaceutically acceptable salts also include "solvates" or "solvates" thereof. The terms "solvate" and "solvate" mean a physical association of a compound of the present invention with one or more solvent molecules (whether organic or inorganic). This physical association includes hydrogen bonding. In certain cases, for example, when one or more solvent molecules are incorporated into the crystal lattice of a crystalline solid, the solvate will be able to be separated. The solvent molecules in the solvate may be present in a regular and / or disordered arrangement. The solvate may contain stoichiometric or non-stoichiometric amounts of solvent molecules. "Solvate" encompasses solution phase and separable solvates. Exemplary solvates include, but are not limited to, hydrates, ethanolates, methanolates, and isopropanolates. Solvation methods are well known in the art. The term "hydrate" refers to a substance formed by water molecules being bound to cations or anions in a compound by coordinate bonds or covalent bonds, or by water ions that are not directly bound to cations or anions but are present in a certain proportion at defined positions in the solid crystal lattice.

[0502] Unless otherwise specified, the compounds of the present invention and pharmaceutically acceptable salts also include "prodrugs" thereof. The term "prodrug" refers to a drug that is converted into the parent drug in vivo. Prodrugs are generally useful because they can improve certain, undesirable physical or biological properties. Physical properties are often related to solubility (excessive or insufficient lipid or water solubility) or stability, while problematic biological properties include rapid metabolism or poor bioavailability, which may themselves be related to physicochemical properties. For example, they may be bioavailable by oral administration, whereas the parent drug is not. Prodrugs also have improved solubility in pharmaceutical compositions compared to the parent drug. An example, but not limited to, of a prodrug is any compound of the present invention administered as an ester ("prodrug") to facilitate transport across cell membranes, where water solubility is detrimental to mobility, but once inside the cell, water solubility is beneficial, which is then metabolically hydrolyzed to the carboxylic acid, the active entity. Another example of a prodrug is a short peptide (polyamino acid) conjugated to an acid group, where the peptide is metabolized to reveal the active moiety.

[0503] The term "oxo" refers to two H groups at the same substitution position being replaced by the same O group to form a double bond.

[0504] The term "thio" refers to two H groups at the same substituent position being replaced by the same S group to form a double bond.

[0505] The term "therapeutically effective dose" refers to the amount of a compound or combination of compounds that provides the expected clinical or therapeutic benefit in the subject being treated. The therapeutically effective dose will depend on factors such as the general condition of the subject being treated (e.g., weight, age, and sex), the severity of the disease, the specific compound being administered, the dosing regimen, the use of concomitant medications, and can be determined by the prescribing physician according to conventional practice. For example, the pharmaceutical composition can be administered at a dose appropriate for the disease to be treated (or prevented), such as administering from about 0.5 μg to about 50 mg of at least one compound / kg subject body weight, preferably from about 10 μg to about 100 mg / kg body weight / day.

[0506] The term "pharmaceutically acceptable excipient" refers to a carrier that does not cause significant irritation to an organism and does not abrogate the biological activity and properties of the administered compound. Any conventional pharmaceutically acceptable carrier may be used, the selection of which depends on factors such as the specific mode of administration, the effect of the carrier on solubility and stability, and the nature of the dosage form and is within the ordinary skill of those skilled in the art. Examples of pharmaceutically acceptable excipients include, but are not limited to, conventional diluents, excipients, fillers, binders, wetting agents, disintegrants, lubricants, colorants, fragrances, absorption enhancers, surfactants, adsorption carriers, and the like.

[0507] Unless otherwise specified, the term "treat," "treatment," "treatment," or "treating" encompasses any treatment of a disease, disorder, or condition in a patient, including: (a) inhibiting the symptoms of the disease, disorder, or condition, i.e., arresting its development; or (b) relieving the symptoms of the disease, disorder, or condition, i.e., causing regression of the disease or symptoms; or (c) ameliorating or eliminating the disease, disorder, or condition or one or more symptoms associated with the disease.

[0508] Abbreviations used in the Preparation Examples, Examples, and elsewhere herein are:

[0509] THF: tetrahydrofuran; Dioxane: 1,4-dioxane; FA: formic acid; PE: petroleum ether; EA: ethyl acetate; DCM: dichloromethane; TFA: trifluoroacetic acid; XPhos Pd G2: chloro(2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II).

[0510] The beneficial effects of the present invention are one or more of the following:

[0511] This invention designs a class of novel compounds, offering a new direction for the development of drugs that lower plasma Lp(a) levels. In vitro activity studies have shown that the compounds of this invention have a strong inhibitory effect on Lp(a) assembly; they exhibit favorable pharmacokinetic properties; safety assessments have demonstrated excellent safety; and in vivo efficacy studies in mice have shown that the compounds of this invention can significantly lower serum Lp(a) levels. Therefore, they are promising compounds for the treatment of Lp(a)-mediated diseases. Furthermore, the invention develops a specific synthesis method that is simple and easy to operate, facilitating large-scale industrial production and application. DETAILED DESCRIPTION

[0512] The present invention will be further described below in conjunction with specific examples. It should be understood that these examples are intended to illustrate the present invention only and are not intended to limit the scope of the present invention. Experimental methods in the following examples where specific conditions are not specified are generally performed under conventional conditions or according to the conditions recommended by the manufacturer. Unless otherwise defined, all professional and scientific terms used herein have the same meanings as those familiar to professionals in the field. In addition, any methods and materials similar or equivalent to those described herein can be applied to the present invention. The preferred embodiments and materials shown herein are for demonstration purposes only.

[0513] The structures of the compounds of the present invention were determined by nuclear magnetic resonance (NMR) and / or liquid chromatography-mass spectrometry (LC-MS) and / or liquid chromatography (HPLC). NMR measurements were performed using a Bruker 400 MHz and / or Varian 400 MHz instrument; LC-MS measurements were performed using an Agilent 1260 Infinity II-6120 / 6125MSD; and HPLC measurements were performed using a Waters UPCC (CA-352) instrument.

[0514] The starting materials in the examples of the present invention are known and can be purchased commercially, or can be synthesized using or according to methods known in the art.

[0515] The present invention provides a method for preparing the compound. The compound can be prepared by the following steps.

[0516] Synthesis of tert-butyl (R)-3-((S)-1-(tert-butoxy)-3-(3-formylphenyl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (Intermediate 1-5):

[0517] Step 1: Synthesis of tert-butyl (R)-3-(2-((S)-4-benzyl-2-oxooxazolidin-3-yl)-2-oxoethyl)pyrrolidine-1-carboxylate (Intermediate 1-1):

[0518] Triethylamine (11.03 g, 109.04 mmol, 2.5 eq) was added to a solution of 2-[(3R)-1-tert-butoxycarbonylpyrrolidin-3-yl]acetic acid (10 g, 43.62 mmol, 1 eq) in tetrahydrofuran (150 mL) maintained at 10°C. After 5 minutes, pivaloyl chloride (6.57 g, 54.52 mmol, 1.25 eq) was added. After 15 minutes, lithium chloride (2.31 g, 54.52 mmol, 1.25 eq) and (4S)-4-benzyloxazolidin-2-one (7.73 g, 43.62 mmol, 1 eq) in tetrahydrofuran (50 mL) were added. The mixture was warmed to room temperature and stirred for 24 hours. After 24 hours, 1N aqueous HCl (50 mL) was added and the organic and aqueous phases were separated. The organic phase was washed with 1N aqueous sodium hydroxide solution (50 mL) and saturated aqueous NaCl solution (50 mL), dried over anhydrous sodium sulfate, filtered, and the solution was concentrated in vacuo. The title compound (15 g) was obtained by flash chromatography (Silica gel, petroleum ether:ethyl acetate = 5:1, volume ratio). LCMS (ESI) [M+H] + =332.7. 1 H NMR (400MHz, CDCl3) δ7.38-7.27(m,3H),7.23-7.17(m,2H),4.68(ddd,J=10.8,7.2,3 .2Hz,1H),4.26-4.16(m,2H),3.68(dd,J=10.8,7.2Hz,1H),3.48(ddd,J=11.6,8.4,3 .6Hz,1H),3.37-3.23(m,2H),3.12-2.94(m,3H),2.78(dd,J=13.2,9.6Hz,1H),2.67( dt,J=14.8,7.2Hz,1H),2.17-2.06(m,1H),1.63-1.55(m,1H),1.46(d,J=4.4Hz,9H).

[0519] Step 2: Synthesis of tert-butyl (R)-3-((S)-1-((S)-4-benzyl-2-oxooxazolidin-3-yl)-3-(3-bromophenyl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (Intermediate 1-2):

[0520] Under nitrogen, a solution of lithium bis(trimethylsilyl)amide (1 M in THF, 30.1 mL, 30.1 mmol, 1 eq) was added dropwise to a 0°C solution of (3R)-tert-butyl 3-[2-[(4S)-4-benzyl-2-oxo-oxazolidin-3-yl]-2-oxo-ethyl]pyrrolidine-1-carboxylate (12 g, 30.89 mmol, 1 eq) in tetrahydrofuran (100 mL). The mixture was stirred at 0°C for 30 minutes, then a solution of 1-bromo-3-(bromomethyl)benzene (8.49 g, 33.98 mmol, 1.1 eq) in tetrahydrofuran (20 mL) was slowly added. The reaction mixture was slowly warmed to room temperature and stirred overnight. The reaction mixture was cooled in an ice-water bath, and a saturated aqueous solution of ammonium chloride was added. Water was added to the mixture, and the mixture was extracted with ethyl acetate. The organic layer was then washed with a saturated aqueous sodium chloride solution. The organic material was dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to give the title compound (17 g). LCMS (ESI) [M-tert-butyl + H] + =501.1.

[0521] Step 3: Synthesis of (S)-3-(3-bromophenyl)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)propanoic acid (Intermediate 1-3):

[0522] A solution of hydrogen peroxide (0.88 M in water, 3.4 mL, 32.3 mmol, 1.5 eq) was added in one portion to a solution of tert-butyl (3R)-3-[(1S)-2-[(4S)-4-benzyl-2-oxo-oxazolidin-3-yl]-1-[(3-bromophenyl)methyl]-2-oxo-ethyl]pyrrolidine-1-carboxylate (12 g, 21.53 mmol, 1 eq) in tetrahydrofuran (120 mL). The mixture was cooled in an ice / water bath and a solution of lithium hydroxide monohydrate (0.77 g, 32.3 mmol, 1.5 eq) in water (10 mL) was added. The reaction temperature was raised to room temperature and stirred for 2.5 hours. The reaction mixture was cooled to 0°C, and an aqueous solution (20 mL) of sodium bisulfite (4.1 g) was added. An aqueous solution (5 N) of sodium hydroxide was added, and the pH of the reaction mixture was adjusted to >12. Water and methyl tert-butyl ether were then added to separate the layers, and the aqueous layer was extracted with methyl tert-butyl ether. The organic matter was combined and extracted with water. This aqueous extract was then added to the bulk aqueous solution, and the aqueous solution was stirred with methyl tert-butyl ether (100 mL). The mixture was cooled to 0°C, and hydrochloric acid (5 N) was added to adjust the pH of the solution to 3. The layers were separated, and the organic layer was washed with a mixture of water and a saturated aqueous sodium chloride solution. The organic matter was dried over anhydrous sodium sulfate, filtered, and concentrated to obtain the title compound (5.5 g). LCMS (ESI) [M-tert-butyl + H] + =341.6.

[0523] Step 4: Synthesis of tert-butyl (R)-3-((S)-3-(3-bromophenyl)-1-(tert-butoxy)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (Intermediate 1-4):

[0524] (S)-3-(3-bromophenyl)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)propanoic acid (5.5 g, 13.81 mmol, 1 eq) was dissolved in 2-methyltetrahydrofuran (80 mL). Under nitrogen, O-tert-butyl-N,N'-diisopropylisourea (13.83 g, 69.05 mmol, 5 eq) was added. The mixture was heated to 65°C and stirred for 16 hours. The insoluble material was filtered, and the filter cake was washed with methyl tert-butyl ether. The filtrate was concentrated and purified by flash chromatography (silica gel, petroleum ether:ethyl acetate = 10:1) to obtain the title compound (5 g). LCMS (ESI) [M-2×tert-butyl + H] + =343.6.

[0525] Step 5: Synthesis of tert-butyl (R)-3-((S)-1-(tert-butoxy)-3-(3-formylphenyl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (Intermediate 1-5):

[0526] A solution of tert-butyl (R)-3-((S)-3-(3-bromophenyl)-1-(tert-butoxy)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (3 g, 6.6 mmol, 1 eq) in toluene (25 mL) was added to an autoclave, followed by palladium(II) acetate (148.22 mg, 0.66 mmol, 0.1 eq), butyldi-1-adamantylphosphine (355.07 mg, 0.99 mmol, 0.15 eq), and N,N,N',N'-tetramethylethylenediamine (1.15 g, 9.9 mmol, 1.5 eq). The mixture was stirred at 100°C for 16 hours under a 2 MPa synthesis gas atmosphere (CO / H2 = 1:1). The insoluble material was filtered through celite, and the filter cake was washed with ethyl acetate. The filtrate was concentrated and purified by flash chromatography (silica gel, petroleum ether:ethyl acetate = 5:1) to obtain the title compound (3 g). LCMS(ESI)[M-Boc] + =303.8. 1H NMR (400MHz, CDCl3) δ9.99 (s, 1H), 7.72 (dd, J = 8.6, 4.5Hz, 2H), 7.44 (dd, J = 8.5 ,4.4Hz,2H),3.66(dd,J=10.3,7.7Hz,1H),3.50(t,J=8.6Hz,1H),3.26(td,J=10 .4,6.9Hz,1H),3.06-2.83(m,3H),2.56-2.48(m,1H),2.40(dd,J=16.5,7.1Hz,1 H), 2.01-1.90 (m, 1H), 1.68 (dt, J = 22.3, 10.2Hz, 1H), 1.47 (s, 9H), 1.26 (s, 5H).

[0527] Synthesis of 3,3'-((2S,2'S)-((azanediylbis(methylene))bis(3,1-phenylene))bis(3-(tert-butoxy)-3-oxopropane-1,2-diyl))(3R,3'R)-bis(tert-butyl pyrrolidine-1-carboxylate) (Intermediate 1-6):

[0528] Dissolve tert-butyl (R)-3-((S)-1-(tert-butoxy)-3-(3-formylphenyl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (1.6 g, 3.97 mmol, 1 eq) in tetrahydrofuran (10 mL). Add methanolic ammonia (0.62 mL, 4.36 mmol, 1.1 eq, 7 N) and stir at room temperature for 0.5 hour. Then, add sodium cyanoborohydride (0.49 g, 7.9.3 mmol, 2 eq) and stir at room temperature for 16 hours. Liquid chromatography-mass spectrometry confirmed the reaction was complete, and the reaction solution was directly concentrated and purified by flash chromatography (Silica gel, dichloromethane:methanol = 30:1) to obtain the title compound (400 mg). LCMS (ESI) [M+H] + =793.3.

[0529] Preparation of Intermediate 2

[0530] Step 1: Synthesis of methyl 1-benzofuran-5-carboxylate:

[0531] In a tempered autoclave, 5-bromo-1-benzofuran (20.00 g, 101.51 mmol, 1 eq), palladium acetate (2.28 g, 10.15 mmol, 0.1 eq), and triethylamine (2.05 g, 203.02 mmol, 2 eq) were added to a mixed solvent of dimethyl sulfoxide (100 mL) and methanol (100 mL). CO gas was introduced to a pressure of 20 atmospheres. The mixture was heated to 80°C in an oil bath and allowed to react for 18 hours. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic phases were combined, washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, concentrated, and separated using a normal phase separation column (petroleum ether:ethyl acetate = 10:1) to obtain the title compound (6.00 g). 1 HNMR (400MHz, CD3OD) δ8.35(d,J=1.6Hz,1H),8.01(dd,J=8.8,1.6Hz,1H),7.87(d,J=2.4Hz,1H),7.58(d,J=8.8Hz,1H),7.00-6.89(m,1H),3.94(s,3H).

[0532] Step 2: Synthesis of methyl 2,3-dibromo-2,3-dihydro-1-benzofuran-5-carboxylate:

[0533] Methyl 1-benzofuran-5-carboxylate (6.00 g, 34.06 mmol, 1 eq) was added to anhydrous dichloromethane (60 mL). Bromine (6.53 g, 40.87 mmol, 1.2 eq) was then slowly added dropwise. The mixture was allowed to react at 0°C under nitrogen for 2 hours. The reaction mixture was slowly added dropwise to a sodium sulfite solution, extracted with dichloromethane, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated to afford the crude title compound (11.44 g). This crude product was used directly in the next step without further purification. 1 H NMR (400MHz, CD3OD) δ8.14(s,1H),8.00(dd,J=8.4,1.6Hz,1H),7.15(s,1H),7.06(d,J=8.4Hz,1H),5.97(s,1H),3.82(d,J=3.6Hz,3H).

[0534] Step 3: Synthesis of 3-bromo-1-benzofuran-5-carboxylic acid:

[0535] Dissolve methyl 2,3-dibromo-2,3-dihydro-1-benzofuran-5-carboxylate (11.00 g, 32.74 mmol, 1 eq) in ethanol, add potassium hydroxide in ethanol (2.0 eq, 15%), and react at 80°C for 2 hours. Adjust the pH of the reaction solution to 2-3 with 2M hydrochloric acid. Extract with ethyl acetate, wash with saturated brine, dry over anhydrous sodium sulfate, and concentrate to obtain the title compound (10.00 g, crude product). The crude product is used directly in the next reaction without purification.

[0536] Step 4: Synthesis of (3-bromo-1-benzofuran-5-yl)methanol:

[0537] Dissolve 3-bromo-1-benzofuran-5-carboxylic acid (10.00 g, 41.49 mmol, 1.0 eq) in tetrahydrofuran and add a solution of borane in tetrahydrofuran (860 mg, 62.23 mmol, 1.5 eq) at 0°C. The mixture is allowed to react at 0°C for 2 hours. Slowly add methanol dropwise at low temperature to quench the reaction, followed by concentration to obtain the title compound (10.00 g, crude product). The crude product is used directly in the next reaction without purification. LCMS (ESI) [M-OH] + =209.2.

[0538] Step 5: Synthesis of 3-bromo-5-(bromomethyl)-1-benzofuran:

[0539] Dissolve (3-bromo-1-benzofuran-5-yl)methanol (10.00 g, 37.44 mmol, 1 eq) in dichloromethane (100 mL). Slowly add tribromophosphine (11.15 g, 41.18 mmol, 1.1 eq) dropwise at 0°C. React at 0°C for 2 hours. Slowly add the reaction solution to water, extract with dichloromethane, wash with saturated brine, dry over anhydrous sodium sulfate, filter, and concentrate to obtain the crude target compound (10.10 g). The crude product is used directly in the next reaction without purification.

[0540] Step 6: Synthesis of tert-butyl 3-{1-[(4S)-4-benzyl-2-oxo-1,3-oxazolidin-3-yl]-3-(3-bromo-1-benzofuran-5-yl)-1-oxopropan-2-yl}pyrrolidine-1-carboxylate:

[0541] Dissolve tert-butyl 3-{2-[(4S)-4-benzyl-2-oxo-1,3-oxazolidin-3-yl]-2-oxoethyl}pyrrolidine-1-carboxylate (10.25 g, 26.38 mmol, 1 eq) in tetrahydrofuran (100 mL). Slowly add lithium bis(trimethylsilyl)amide (5.30 g, 31.65 mmol, 1.2 eq) dropwise at -78°C. Allow to react for 1 hour. Then, dissolve 3-bromo-5-(bromomethyl)-1-benzofuran (9.00 g, 26.38 mmol, 1 eq) in tetrahydrofuran (30 mL) and slowly add dropwise to the reaction mixture. The reaction mixture is slowly warmed to room temperature and stirred for 12 hours. The reaction mixture is added to saturated ammonium chloride and extracted with ethyl acetate. The organic phases are combined, washed with saturated sodium chloride, dried over sodium sulfate, filtered, and concentrated to yield the title compound (12.00 g). The crude product was used directly in the next reaction without purification. LCMS (ESI) [M+Na] + =619.0.

[0542] Step 7: Synthesis of 3-(3-bromo-1-benzofuran-5-yl)-2-{1-[(tert-butoxy)carbonyl]pyrrolidin-3-yl}propionic acid:

[0543] Dissolve tert-butyl 3-{1-[(4S)-4-benzyl-2-oxo-1,3-oxazolidin-3-yl]-3-(3-bromo-1-benzofuran-5-yl)-1-oxopropan-2-yl}pyrrolidine-1-carboxylate (11.00 g, 18.41 mmol, 1 eq) in tetrahydrofuran (300 mL). Dissolve lithium hydroxide (440 mg, 18.41 mmol, 1 eq) in water (100 mL) and hydrogen peroxide (11 mL). Add the mixture to the reaction mixture at 0°C and allow to react at room temperature for 2 hours. Quench with sodium sulfite solution, extract with ethyl acetate, wash with saturated sodium chloride, dry with sodium sulfate, and filter and concentrate to obtain the target compound (5.50 g). The crude product was used directly in the next step without purification. LCMS (ESI) [M-Boc+H] + =339.0.

[0544] Step 8: Synthesis of tert-butyl 3-[3-(3-bromo-1-benzofuran-5-yl)-1-(tert-butoxy)-1-oxopropane-2-yl]pyrrolidine-1-carboxylate:

[0545] Dissolve 3-(3-bromo-1-benzofuran-5-yl)-2-{1-[(tert-butoxy)carbonyl]pyrrolidin-3-yl}propanoic acid (5.50 g, 12.55 mmol, 1.0 eq) and O-tert-butyl-N,N'-diisopropylisourea (7.54 g, 37.64 mmol, 3.0 eq) in 2-methyltetrahydrofuran (50 mL), heat to 80°C, and react for 3 hours. Ethyl acetate and water were added for extraction, and the organic phase was washed with saturated brine, dried over sodium sulfate, concentrated, and purified by column chromatography to obtain the title compound (2.50 g). LCMS (ESI) [M+Na] + =516.2,518.2.

[0546] Step 9: Synthesis of tert-butyl 3-[1-(tert-butoxy)-3-(3-formyl-1-benzofuran-5-yl)-1-oxopropan-2-yl]pyrrolidine-1-carboxylate:

[0547] In a high-pressure reactor, tert-butyl 3-[3-(3-bromo-1-benzofuran-5-yl)-1-(tert-butoxy)-1-oxopropan-2-yl]pyrrolidine-1-carboxylate (1.5 g, 3.03 mmol, 1.0 eq), palladium acetate (68 mg, 0.30 mmol, 0.1 eq), [2-(dimethylamino)ethyl]dimethylamine (704 mg, 6.06 mmol, 2.0 eq) and bis(adamantan-1-yl)(butyl)phosphine (217 mg, 0.61 mmol, 0.2 eq) were added to toluene (15 mL), and H2 / CO (volume ratio: 1 / 1) was introduced to a pressure of 1.3 MPa, and the reaction was carried out at 100°C for 18 hours. The reaction mixture was extracted with ethyl acetate and water, washed with saturated sodium chloride solution, dried over sodium sulfate, and subjected to normal phase separation (Silica gel, petroleum ether:ethyl acetate = 6:1, volume ratio) to obtain the title compound (700 mg). 1 H NMR (400MHz, CDCl3) δ10.09(s,1H),8.18(d,J=4.1Hz,1H),7.94(d,J=6.0Hz,1H),7.38(d,J=8.5Hz,1H),7.15(t,J=7.2Hz,1H),3.71-3.34(m,2H),3 .23-3.13(m,1H),3.02-2.77(m,3H),2.45(d,J=8.6Hz,1H),2.39-2.28(m, 1H), 1.92-1.84 (m, 1H), 1.57 (d, J = 13.9Hz, 1H), 1.40 (s, 9H), 1.21 (s, 9H).

[0548] Synthesis of tert-butyl (R)-3-((S)-1-(tert-butoxy)-3-(3-fluoro-5-formylphenyl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (Intermediate 3-5)

[0549] Synthesis of tert-butyl (R)-3-((S)-1-((S)-4-benzyl-2-oxooxazolidin-3-yl)-3-(3-bromo-5-fluorophenyl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (Intermediate 3-1):

[0550] The target product (21.9 g) was synthesized by referring to the method of intermediate 1-2 using 1-bromo-3-(bromomethyl)-5-fluorobenzene as the starting material. LCMS (ESI) [M-tert-butyl + H] + =521.2.

[0551] Synthesis of (S)-3-(3-bromo-5-fluorophenyl)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)propanoic acid (Intermediate 3-2):

[0552] The target product (8.8 g) was synthesized by referring to the method of intermediate 1-3. LCMS (ESI) [M-tert-butyl + H] + =359.9.

[0553] Synthesis of tert-butyl (R)-3-((S)-3-(3-bromo-5-fluorophenyl)-1-(tert-butoxy)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (Intermediate 3-3):

[0554] The target product (6.1 g) was synthesized by referring to the method of intermediate 1-4. LCMS (ESI) [M-2×tert-butyl+H] + =359.9.

[0555] Synthesis of tert-butyl (R)-3-((S)-1-(tert-butoxy)-3-(3-fluoro-5-vinylphenyl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (Intermediate 3-4):

[0556] In a three-necked flask, tert-butyl (R)-3-((S)-3-(3-bromo-5-fluorophenyl)-1-(tert-butoxy)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (5.6 g) was dissolved in 1,4-dioxane (45 mL). Potassium vinyl trifluoroborate (8 g), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium dichloromethane complex (922 mg), and triethylamine (3.6 g) were added sequentially. Water (15 mL) was added and the mixture was heated to 75°C and stirred for 5 hours under nitrogen. The reaction was complete after liquid chromatography-mass spectrometry analysis. The insoluble matter was filtered through celite, the filter cake was washed with an appropriate amount of ethyl acetate, and the filtrate was concentrated. The title compound (4.4 g) was isolated and purified by flash chromatography (Silica gel, PE:EA = 10:1, volume ratio) to obtain the title compound. LCMS (ESI) [M-2×tert-butyl + H] + =308.3.

[0557] Synthesis of tert-butyl (R)-3-((S)-1-(tert-butoxy)-3-(3-fluoro-5-formylphenyl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (Intermediate 3-5):

[0558] In a three-necked flask, tert-butyl (R)-3-((S)-1-(tert-butoxy)-3-(3-fluoro-5-vinylphenyl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (4.4 g, 10.53 mmol, 1 eq) was dissolved in tetrahydrofuran (44 mL). Water (12 mL) was added under nitrogen. Potassium osmate (388 mg, 1.05 mmol, 0.1 eq) and sodium periodate (6.76 g, 31.59 mmol, 3 eq) were then added sequentially under ice-cooling. The mixture was warmed to room temperature and stirred for 3 hours. The insoluble material was filtered off, and the filtrate was poured into water, followed by extraction with ethyl acetate. The organic phases were combined, washed with saturated aqueous NaCl, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The title compound (2.7 g) was isolated and purified by flash chromatography (Silica gel, PE:EA = 10:1, volume ratio) to obtain the title compound. LCMS (ESI) [M-2×tert-butyl+H] + =310.0. 1H NMR (400MHz, DMSO-d6) δ9.97(d,J=1.5Hz,1H),7.63(s,1H),7.46(d,J=9.8Hz,1H),3.52(q,J=10.5Hz,1H),3.42-3.34(m,1H),3.24-3.09(m,1H),3 .02(t,J=10.0Hz,1H),2.83(q,J=13.9Hz,2H),2.59(d,J=8.9Hz,1H),2.3 0(s,1H),1.91-1.76(m,1H),1.68-1.49(m,1H),1.40(s,9H),1.21(s,9H).

[0559] Synthesis of tert-butyl (3R)-3-[(2S)-1-(tert-butoxy)-3-(5-formylpyridin-3-yl)-1-oxopropan-2-yl]pyrrolidine-1-carboxylate (Intermediate 4-1):

[0560] Following the method of Intermediate 1-5, 3-bromo-5-bromomethylpyridine was used to replace 1-bromo-3-(bromomethyl)benzene to synthesize the target compound (320 mg). LCMS (ESI) [M+H] + =405.2; 1 H NMR (400MHz, DMSO-d6) δ10.11(s,1H),8.95(d,J=1.8Hz,1H),8.71(d,J=1. 9Hz,1H),8.09(s,1H),3.59-3.47(m,2H),3.21-3.12(m,1H),3.05(t,J=10. 0Hz,1H),2.96-2.88(m,1H),2.87-2.79(m,1H),2.65-2.56(m,1H),2.39-2. 27(m,1H),1.90-1.81(m,1H),1.64-1.54(m,1H),1.40(s,9H),1.19(s,9H).

[0561] Example 1 (Compound 5)

[0562] Preparation of (2S,2'S)-3,3'-(((((S)-5-amino-5-carboxypentyl)azanediyl)bis(methylene))bis(5-fluoro-3,1-phenylene))bis(2-((R)-pyrrolidin-3-yl)propanoic acid):

[0563] Step 1: N 6 ,N 6Synthesis of -bis(3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)-5-fluorobenzyl)-N2-(tert-butoxycarbonyl)-L-lysine:

[0564] Tert-butyl (R)-3-((S)-1-(tert-butoxy)-3-(3-fluoro-5-formylphenyl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (376 mg, 0.893 mmol, 2.2 eq) and (tert-butoxycarbonyl)-L-lysine (100 mg, 0.406 mmol, 1.0 eq) were dissolved in tetrahydrofuran (2 mL), and sodium cyanoborohydride (64 mg, 1.02 mmol, 2.5 eq) and one drop of acetic acid were added. The reaction mixture was stirred at room temperature overnight. Saturated ammonium chloride solution and dichloromethane were added. The organic phase solvent was spin-dried and purified by flash chromatography (Silica gel, DCM:MeOH = 15:1, volume ratio) to obtain the title compound (89 mg). LCMS (ESI) [M+H] + =1057.9.

[0565] Step 2: Synthesis of (2S,2'S)-3,3'-(((((S)-5-amino-5-carboxypentyl)azanediyl)bis(methylene))bis(5-fluoro-3,1-phenylene))bis(2-((R)-pyrrolidin-3-yl)propionic acid): 6 ,N 6 -bis(3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)-5-fluorobenzyl)-N2-(tert-butoxycarbonyl)-L-lysine (89 mg, 0.084 mmol, 1.0 eq) was dissolved in 1,4-dioxane (0.2 mL), and 4M HCl (1,4-dioxane) solution (0.2 mL) was added. The reaction solution was stirred at room temperature overnight. The reaction was monitored by LCMS to be complete. The solvent was dried and separated and purified by preparative HPLC (C 18 , 10mmol / L NH4HCO3 water / acetonitrile solution) to obtain the target compound (9.8mg). LCMS (ESI) [M+H] + =645.4; 1H NMR(400MHz,D2O)δ6.97-6.86(m,6H),3.78(s,4H),3.64-3.57(m,1H),3.51-3.42(m,2H),3.40-3.31(m,2H),3.23-3.13(m,2H),2. 97-2.87(m,2H),2.77-2.68(m,4H),2.66-2.53(m,2H),2.45-2.33(m,4H),2.10-2.00(m,2H),1.81-1.53(m,6H),1.32-1.17(m,2H).

[0566] Example 2 (Compound 6)

[0567] Preparation of (2S,2'S)-3,3'-(((((5-((S)-2-carboxy-2-((R)-pyrrolidin-3-yl)ethyl)benzofuran-3-yl)methyl)azanediyl)bis(methylene))bis(3,1-phenylene))bis(2-((R)-pyrrolidin-3-yl)propanoic acid):

[0568] Step 1: Synthesis of 3,3'-((2S,2'S)-(((((5-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)benzofuran-3-yl)methyl)azanediyl)bis(methylene))bis(3,1-phenylene))bis(3-(tert-butoxy)-3-oxopropane-1,2-diyl))(3R,3'R)-bis(tert-butyl pyrrolidine-1-carboxylate):

[0569] 3,3'-((2S,2'S)-((azanediylbis(methylene))bis(3,1-phenylene))bis(3-(tert-butoxy)-3-oxopropane-1,2-diyl))(3R,3'R)-bis(tert-butyl pyrrolidine-1-carboxylate) (50 mg, 0.063 mmol, 1.0 eq) and (R)-tert-butyl 3-((S)-1-(tert-butoxy)-3-(3-formylbenzofuran-5-yl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (33 mg, 0.076 mmol, 1.2 eq) were dissolved in tetrahydrofuran (0.2 mL), and sodium cyanoborohydride (6 mg, 0.095 mmol, 1.5 eq) and one drop of acetic acid were added. The reaction mixture was stirred at room temperature overnight. Saturated ammonium chloride solution and dichloromethane were added. The organic phase solvent was spin-dried and separated and purified by flash chromatography (Silica gel, DCM:MeOH=15:1, volume ratio) to obtain the title compound (45 mg).

[0570] Step 2: Synthesis of (2S,2'S)-3,3'-(((((5-((S)-2-carboxy-2-((R)-pyrrolidin-3-yl)ethyl)benzofuran-3-yl)methyl)azanediyl)bis(methylene))bis(3,1-phenylene))bis(2-((R)-pyrrolidin-3-yl)propionic acid):

[0571] 3,3'-((2S,2'S)-(((((5-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)benzofuran-3-yl)methyl)azanediyl)bis(methylene))bis(3,1-phenylene))bis(3-(tert-butoxy)-3-oxopropane-1,2-diyl))(3R,3'R)-bis(tert-butyl pyrrolidine-1-carboxylate)(tert-butoxycarbonyl) (45 mg, 0.037 mmol, 1.0 eq) was dissolved in 1,4-dioxane (0.2 mL), and 4M HCl (1,4-dioxane) solution (0.2 mL) was added. The reaction solution was stirred at room temperature overnight, the solvent was dried by spin drying, and the product was separated and purified by preparative HPLC (C 18 , 10mmol / L NH4HCO3 water / acetonitrile solution) to obtain the target compound (13mg). LCMS (ESI) [M+H] + =751.5, 1 H NMR(400MHz,D2O)δ7.45(s,1H),7.30(d,J=8.4Hz,1H),7.18(t,J=7.5Hz,2H),7.06(d,J=9.1Hz,4H),7.01(d,J=11.7Hz,4H),3.53-3.44(m, 3H),3.32-3.18(m,7H),3.12-3.05(m,3H),2.83-2.67(m,7H),2.65-2 .54(m,3H),2.38-2.27(m,7H),2.03-1.96(m,3H),1.68-1.60(m,3H).

[0572] Example 3 (Compound 12)

[0573] Preparation of (2S,2'S)-3,3'-((((3-((S)-2-carboxy-2-((R)-pyrrolidin-3-yl)ethyl)-5-fluorobenzoyl)azanediyl)bis(methylene))bis(3,1-phenylene))bis(2-((R)-pyrrolidin-3-yl)propanoic acid):

[0574] Step 1: Synthesis of 3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)-5-fluorobenzoic acid:

[0575] Dissolve tert-butyl (R)-3-((S)-1-(tert-butoxy)-3-(3-fluoro-5-formylphenyl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (50 mg), sodium hydroxide (8 mg), and potassium permanganate (30 mg) in acetonitrile (0.5 mL) and water (0.5 mL). The reaction mixture was stirred at 60°C overnight. Water and dichloromethane were added. The organic phase solvent was dried and purified by flash chromatography (Silica gel, DCM:MeOH = 30:1, volume ratio) to obtain the title compound (15 mg). LCMS (ESI) [M-Boc+H] + =338.49.

[0576] Step 2: Synthesis of 3,3'-((2S,2'S)-((((3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)-5-fluorobenzoyl)azanediyl)bis(methylene))bis(3,1-phenylene))bis(3-(tert-butoxy)-3-oxopropane-1,2-diyl))(3R,3'R)-bis(di-tert-butyl pyrrolidine-1-carboxylate):

[0577] 3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)-5-fluorobenzoic acid (15 mg) was dissolved in N,N-dimethylformamide (0.3 mL), and 3,3'-((2S,2'S)-((azanediylbis(methylene))bis(3,1-phenylene))bis(3-(tert-butoxy)-3-oxopropane-1,2-diyl))(3R,3'R)-bis(tert-butyl pyrrolidine-1-carboxylate) (27 mg), O-(7-azabenzotriazol-1-yl)-N,N,N,N-tetramethyluronium hexafluorophosphate (15 mg), and N,N-diisopropylethylamine (14 mg) were added. The reaction mixture was stirred at room temperature overnight. Water and ethyl acetate were then added. The organic phase solvent was dried by spin drying and purified by flash chromatography (Silica gel, DCM:MeOH=30:1, volume ratio) to obtain the target compound (20 mg). LCMS (ESI) [M-Boc+H] + =1111.92.

[0578] Step 3: Synthesis of (2S,2'S)-3,3'-((((3-((S)-2-carboxy-2-((R)-pyrrolidin-3-yl)ethyl)-5-fluorobenzoyl)azanediyl)bis(methylene))bis(3,1-phenylene))bis(2-((R)-pyrrolidin-3-yl)propionic acid): 3,3'-((2S,2'S)-((((3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)-5-fluorobenzoyl)azanediyl)bis(methylene))bis(3,1-phenylene))bis(3-(tert-butoxy)-3-oxopropane-1,2-diyl))(3R,3'R)-bis(tert-butyl pyrrolidine-1-carboxylate)

[0579] 3,3'-((2S,2'S)-((((3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)-5-fluorobenzoyl)azanediyl)bis(methylene))bis(3,1-phenylene))bis(3-(tert-butoxy)-3-oxopropane-1,2-diyl))(3R,3'R)-bis(tert-butyl pyrrolidine-1-carboxylate) (115 mg) was dissolved in 1,4-dioxane (0.2 mL), and 4M HCl (1,4-dioxane) solution (0.2 mL) was added. The reaction solution was stirred at room temperature overnight, the solvent was dried by spin drying, and the product was separated and purified by preparative HPLC (C 18 , 10mmol / L NH4HCO3 water / acetonitrile solution) to obtain the target compound (39.9mg). LCMS (ESI) [M+H] + =743.65; 1 H NMR(400MHz,D2O)δ7.30-7.18(m,2H),7.16-6.93(m,7H),6.92-6.81(m,2H),4.60(s,2H),4.41(s,2H),3.42- 3.23(m,6H),3.20-3.06(m,3H),2.88-2.60(m,9H),2.45-2.24(m,6H),2.11-1.93(m,3H),1.75-1.53(m,3H).

[0580] Example 4 (Compound 47)

[0581] Preparation of (2S,2'S,2"S)-3,3',3"-((nitrilotris(methylene))tris(benzofuran-3,5-diyl))tris(2-((R)-pyrrolidin-3-yl)propanoic acid):

[0582] Step 1: Synthesis of 3,3',3"-((2S,2'S,2"S)-((nitrilotris(methylene))tris(benzofuran-3,5-diyl))tris(3-(tert-butoxy)-3-oxopropane-1,2-diyl))(3R,3'R,3"R)-tris(tert-butyl pyrrolidine-1-carboxylate):

[0583] Tert-butyl (R)-3-((S)-1-(tert-butoxy)-3-(3-formylbenzofuran-5-yl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (600 mg, 1.38 mmol, 1 eq) was dissolved in isopropanol (6 mL), and methanolic ammonia (1.0 eq, 7.0 M) and sodium triacetylborohydride (436 mg, 2.10 mmol, 1.5 eq) were added. The mixture was reacted at 25°C for 16 hours. The reaction solution was concentrated and separated by silica gel column chromatography (petroleum ether / ethyl acetate = 1 / 1, volume ratio) to obtain the title compound (30 mg). LCMS (ESI) [M+H] + =1322.6.

[0584] Step 2: Synthesis of (2S,2'S,2"S)-3,3',3"-((nitrilotris(methylene))tris(benzofuran-3,5-diyl))tris(2-((R)-pyrrolidin-3-yl)propionic acid):

[0585] 3,3',3"-((2S,2'S,2"S)-((nitrilotris(methylene))tris(benzofuran-3,5-diyl))tris(3-(tert-butoxy)-3-oxopropane-1,2-diyl))(3R,3'R,3"R)-tris(tert-butyl pyrrolidine-1-carboxylate) (35 mg, 0.03 mmol, 1 eq) was dissolved in a solution of hydrogen chloride in dioxane (1 mL, 4 M) and stirred at room temperature for 1 hour. The reaction mixture was concentrated, water was added, and lyophilized to obtain the title compound (15.88 mg). LCMS (ESI) [M+H] + =831.4; 1 H NMR (400MHz, CD3OD) δ8.10 (s, 3H), 7.56-7.47 (m, 6H), 7.27 (d, J = 8.4Hz, 3H), 4.64 (s, 6H), 3.52-3.35 (m, 6H ),3.26-3.19(m,3H),3.08-2.93(m,12H),2.52(d,J=7.6Hz,3H),2.16(d,J=7.2Hz,3H),1.91-1.73(m,3H).

[0586] Example 5 (Compound 89)

[0587] Preparation of (2S,2'S)-3,3'-((((3-fluoro-5-methoxyphenethyl)azanediyl)bis(methylene))bis(3,1-phenylene))bis(2-((R)-pyrrolidin-3-yl)propanoic acid):

[0588] Step 1: Synthesis of (E)-1-(2-ethoxyvinyl)-3-fluoro-5-methoxybenzene:

[0589] Under nitrogen, a three-necked flask was charged with [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride (1.14 g), cesium carbonate (29.32 g), 1,4-dioxane (180 mL), and water (30 mL). 3-Fluoro-5-bromoanisole (6.15 g) and (E)-1-ethoxyvinyl-2-boronic acid pinacol ester (6.54 g) were added sequentially. The reaction mixture was heated to 100°C for 3 hours. After completion of the reaction, the mixture was quenched with saturated brine and extracted with ethyl acetate. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, concentrated, and separated by column chromatography (silica gel, petroleum ether:ethyl acetate = 3:1, volume ratio) to obtain the title compound (3.60 g).

[0590] Step 2: Synthesis of 2-(3-fluoro-5-methoxyphenyl)acetaldehyde:

[0591] (E)-1-(2-Ethoxyvinyl)-3-fluoro-5-methoxybenzene (500 mg) was dissolved in HCl / Dioxane (5 mL) and stirred at room temperature for 16 hours. The reaction was complete after liquid chromatography-mass spectrometry analysis. The reaction solution was directly concentrated and purified by flash chromatography (Silica gel, petroleum ether:ethyl acetate = 10:1, volume ratio) to obtain the title compound (150 mg). LCMS (ESI) [M+H] + =169.07.

[0592] Step 3: Synthesis of 3,3'-((2S,2'S)-((((3-fluoro-5-methoxyphenethyl)azanediyl)bis(methylene))bis(3,1-phenylene))bis(3-(tert-butoxy)-3-oxopropane-1,2-diyl))(3R,3'R)-bis(tert-butyl pyrrolidine-1-carboxylate):

[0593] 2-(3-Fluoro-5-methoxyphenyl)acetaldehyde (47 mg) was dissolved in methanol (5 mL), and 3,3'-((2S,2'S)-((azanediylbis(methylene))bis(3,1-phenylene))bis(3-(tert-butyloxy)-3-oxopropane-1,2-diyl))(3R,3'R)-bis(tert-butyl pyrrolidine-1-carboxylate) (200 mg) and two drops of acetic acid were added at room temperature. The mixture was stirred at room temperature for 16 hours. The reaction mixture was directly concentrated and purified by flash chromatography (Silica gel, petroleum ether:ethyl acetate = 5:1, volume ratio) to obtain the title compound (120 mg). LCMS (ESI) [M+H] + =944.89.

[0594] Step 4: Synthesis of (2S,2'S)-3,3'-((((3-fluoro-5-methoxyphenethyl)azanediyl)bis(methylene))bis(3,1-phenylene))bis(2-((R)-pyrrolidin-3-yl)propionic acid):

[0595] 3,3'-((2S,2'S)-((((3-fluoro-5-methoxyphenethyl) azanediyl)bis(methylene))bis(3,1-phenylene))bis(3-(tert-butoxy)-3-oxopropane-1,2-diyl))(3R,3'R)-bis(tert-butyl pyrrolidine-1-carboxylate)(tert-butoxycarbonyl) (120 mg) was dissolved in HCl / Dioxane (5 mL) and stirred at room temperature for 16 hours. The reaction solution was directly concentrated and separated and purified by preparative HPLC (C 18 , 0.1% FA in water / acetonitrile solution) to obtain the title compound (47.46 mg). LCMS (ESI) [M+H] + =632.4.

[0596] Example 6 (Compound 62)

[0597] Preparation of (2S,2'S)-3,3'-((((3-fluoro-5-methoxybenzyl)azanediyl)bis(ethane-2,1-diyl))bis(1H-indole-1,6-diyl))bis(2-((R)-pyrrolidin-3-yl)propanoic acid):

[0598] Step 1: Synthesis of 2-{[(3-fluoro-5-methoxyphenyl)methyl](2-hydroxyethyl)amino}ethan-1-ol:

[0599] 2-[(2-Hydroxyethyl)amino]ethan-1-ol (2.00 g) was added to a solution of dichloromethane (30 mL). 3-Fluoro-5-methoxybenzene-1-carbaldehyde (4.00 g) and sodium triacetylborohydride (12.00 g) were added at 25°C. The reaction was allowed to react at 25°C for 2 hours. The reaction was monitored by liquid chromatography-mass spectrometry. The reaction solution was extracted with dichloromethane and water. The organic phase was dried and purified (reverse column chromatography: acetonitrile / water = 10%) to obtain the title compound (4.00 g). LCMS (ESI) [M+H] + =244.2.

[0600] Step 2: Synthesis of [bis(2-chloroethyl)][(3-fluoro-5-methoxyphenyl)methyl]amine:

[0601] 2-{[(3-fluoro-5-methoxyphenyl)methyl](2-hydroxyethyl)amino}ethan-1-ol (1.50 g) was added to thionyl chloride (15 mL) and reacted at 70° C. overnight. LCMS detected the compound, and the thionyl chloride was spin-dried, slurried with ethyl acetate, and extracted with aqueous ammonium chloride. Without further purification, the title compound (1.8 g, crude product) was obtained and used directly in the next reaction without further purification.

[0602] Step 3: Synthesis of 3,3'-((2S,2'S)-((((3-fluoro-5-methoxybenzyl)azanediyl)bis(ethane-2,1-diyl))bis(1H-indole-1,6-diyl))bis(3-(tert-butoxy)-3-oxopropane-1,2-diyl))(3R,3'R)-bis(tert-butyl pyrrolidine-1-carboxylate):

[0603] (R)-tert-Butyl 3-((S)-1-(tert-butoxy)-3-(1H-indol-6-yl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (0.5 g) was added to N,N-dimethylformamide (5 mL). [Bis(2-chloroethyl)][(3-fluoro-5-methoxyphenyl)methyl]amine (338 mg) and cesium carbonate (1.2 g) were added at room temperature. The reaction solution was reacted at 100°C under nitrogen protection overnight. The reaction was detected by LCMS. Saturated brine was added, and the mixture was extracted with ethyl acetate and dried over anhydrous sodium sulfate. The organic phase was spin-dried and then washed with a normal phase column (pure ethyl acetate) to obtain the title compound (190 mg). LCMS (ESI) [M+H] + =1036.6.

[0604] Step 4: Synthesis of (2S,2'S)-3,3'-((((3-fluoro-5-methoxybenzyl)azanediyl)bis(ethane-2,1-diyl))bis(1H-indole-1,6-diyl))bis(2-((R)-pyrrolidin-3-yl)propionic acid):

[0605] 3,3'-((2S,2'S)-((((3-fluoro-5-methoxybenzyl)azanediyl)bis(ethane-2,1-diyl))bis(1H-indole-1,6-diyl))bis(3-(tert-butoxy)-3-oxopropane-1,2-diyl))(3R,3'R)-bis(tert-butyl pyrrolidine-1-carboxylate) (140 mg) was added to TFA (2 mL) and stirred at 25°C for 0.5 hours. LCMS detected the product signal. The reaction solution was dried by rotary evaporation, dissolved in acetonitrile, and separated and purified by preparative HPLC (FA) to obtain the target compound (13.6 mg). LCMS (ESI) [M+H] + =725.04; 1 H NMR (400MHz, MeOD-d4) δ8.42(s,1H),7.42(d,J=8.0Hz,2H),7.11(d,J=3.2Hz,2H),6.91(d,J=7.2Hz,2 H),6.87-6.84(m,2H),6.45-6.43(m,3H),6.29(t,J=2.8Hz,2H),4.07(d,J=6.2Hz,4H),3.63(d,J=3.2H z,3H),3.59(s,2H),3.21-3.18(m,4H),3.13-3.03(m,6H),2.99-2.92(m,2H),2.87(s,2H),2.78-2.66 (m,2H),2.60-2.54(m,2H),2.38-2.30(m,2H),2.01(d,J=24.0Hz,2H),1.85-1.76(m,1H),1.56(s,1H).

[0606] Example 7 (Compound 95)

[0607] Preparation of (2S,2'S)-3,3'-((((2-(3-((S)-2-carboxy-2-((R)-pyrrolidin-3-yl)ethyl)phenoxy)acetyl)azanediyl)bis(methylene))bis(3,1-phenylene))bis(2-((R)-pyrrolidin-3-yl)propanoic acid):

[0608] Step 1: Synthesis of (3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)phenyl)boronic acid:

[0609] Tert-butyl (R)-3-((S)-3-(3-bromophenyl)-1-(tert-butoxy)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (1.9 g, 4.18 mmol, 1 eq), (dihydroxyboryl)boronic acid (562.29 mg, 6.27 mmol, 1.5 eq), potassium acetate (1230.7 mg, 12.54 mmol, 3 eq), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (199.27 mg, 0.42 mmol, 0.1 eq) and X-Phos Pd G2 (164 mg, 0.21 mmol, 0.05 eq) was added to EtOH (20 mL), the atmosphere was replaced with nitrogen three times, and the reaction was carried out at 90°C for 16 hours. LCMS detected the presence of product. Ethyl acetate (20 mL) was added to the reaction system, and the mixture was filtered through Celite. The filtrate was then dried to give the title compound (2.0 g). The crude product was used directly in the next step without further purification. LCMS [M-2×tert-butyl + H] + =308.2.

[0610] Step 2: Synthesis of tert-butyl (R)-3-((S)-1-(tert-butoxy)-3-(3-hydroxyphenyl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate:

[0611] (3-((S)-3-(tert-Butoxy)-2-((R)-1-(tert-Butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)phenyl)boronic acid (2000 mg, 4.77 mmol, 1 eq) was dissolved in THF (20 mL), and hydrogen peroxide (8 mL, 235.2 mmol, 49.31 eq) was added. The mixture was reacted at 20°C for 16 hours. LCMS analysis indicated the presence of product. Saturated sodium bisulfite solution (20 mL) and ethyl acetate (20 mL) were added, and the mixture was separated and extracted. The organic phase was dried over sodium sulfate and dried by spin drying. The title compound (800 mg) was obtained by flash chromatography (Silica gel, PE:EtOAc = 4:1, volume ratio) using a 4:1 HPLC-MS (ESI) method. +＝ 392.2.

[0612] Step 3: Synthesis of tert-butyl (R)-3-((S)-3-(3-(2-(benzyloxy)-2-oxoethoxy)phenyl)-1-(tert-butoxy)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate:

[0613] tert-Butyl (R)-3-((S)-1-(tert-butoxy)-3-(3-hydroxyphenyl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (2.0 g, 5.11 mmol, 1 eq), benzyl 2-bromoacetate (2.34 g, 10.22 mmol, 2 eq), and dipotassium carbonate (2.12 g, 15.33 mmol, 3 eq) were added to acetonitrile (50 mL) and reacted at 90°C for 16 hours. LCMS confirmed the presence of the product, which was then separated and purified by flash chromatography (Silica gel, PE:EtOAc = 5:1, volume ratio) to obtain the title compound (2.5 g). LCMS (ESI) [M+Na] +＝ 561.9.

[0614] Step 4: Synthesis of 2-(3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)phenoxy)acetic acid:

[0615] Dissolve tert-butyl (R)-3-((S)-3-(3-(2-(benzyloxy)-2-oxoethoxy)phenyl)-1-(tert-butoxy)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (2.5 g, 4.63 mmol, 1 eq) in methanol (50 mL). Add palladium on carbon (300 mg, 10% content) and replace the hydrogen atmosphere three times. Stir at room temperature for 16 hours. LCMS indicates completion of the reaction. Filter and dry the filtrate to obtain the title compound (1.5 g). LCMS (ESI) [M+Na] +＝ 472.2.

[0616] Step 5:

[0617] Synthesis of 3,3'-((2S,2'S)-((((2-(3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)phenoxy)acetyl)azanediyl)bis(methylene))bis(3,1-phenylene))bis(3-(tert-butoxy)-3-oxopropane-1,2-diyl))(3R,3'R)-bis(tert-butyl pyrrolidine-1-carboxylate):

[0618] 3,3'-((2S,2'S)-((azanediylbis(methylene))bis(3,1-phenylene))bis(3-(tert-butoxy)-3-oxopropane-1,2-diyl))(3R,3'R)-bis(tert-butyl pyrrolidine-1-carboxylate) (88.1 mg, 0.11 mmol, 1 eq), 2-(3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)phenoxy)acetic acid (50 mg, 0.11 mmol, 1 eq), O-(7-azabenzotriazol-1-yl)-N,N,N,N-tetramethyluronium hexafluorophosphate (41.83 mg, 0.11 mmol, 1 eq), and N,N-diisopropylethylamine (43.12 mg, 0.33 mmol, 3 eq) were dissolved in N,N-dimethylformamide (3 mL); the reaction was stirred at room temperature for 16 hours. LCMS confirmed the completion of the reaction. The reaction solvent was dried and purified on a thin-layer silica gel plate (DCM:MeOH = 20:1, volume ratio) to obtain the title compound (100 mg). LCMS (ESI) [M+Na] +＝ 1245.8.

[0619] Step 6: Synthesis of (2S,2'S)-3,3'-((((2-(3-((S)-2-carboxy-2-((R)-pyrrolidin-3-yl)ethyl)phenoxy)acetyl)azanediyl)bis(methylene))bis(3,1-phenylene))bis(2-((R)-pyrrolidin-3-yl)propanoic acid)(tert-butoxycarbonyl):

[0620] 3,3'-((2S,2'S)-((((2-(3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)phenoxy)acetyl)azanediyl)bis(methylene))bis(3,1-phenylene))bis(3-(tert-butoxy)-3-oxopropane-1,2-diyl))(3R,3'R)-bis(tert-butyl pyrrolidine-1-carboxylate) (100 mg, 0.08 mmol, 1 eq) was added to hydrochloric acid-dioxane (2 mL, 4.0 M) and reacted at room temperature for 6 hours; the mixture was filtered and the filter cake was washed with dioxane to obtain the title compound (46 mg). LCMS (ESI) [M+H] +＝ 755.2. 1H NMR (400MHz, CD3OD) δ7.34-7.20(m,5H),7.18-7.10(m,4H),6.92-6.85(m,2H),6.7-6.75(m,1H),4.92(s,2H),4.61(s,4H),3.57- 3.40(m,6H),3.34-3.21(m,3H),2.99-2.81(m,11H),2.78-2.72(m,3H),2.56-2.49(m,3H),2.29-2.15(m,3H),1.87-1.81(m,3H).

[0621] Example 8 (Compound 96)

[0622] Preparation of (S)-3-(3-(2-((3-((S)-2-carboxy-2-((R)-pyrrolidin-3-yl)ethyl)benzyl)(2-(3-((S)-2-carboxy-2-((R)-pyrrolidin-3-yl)ethyl)phenoxy)ethyl)amino)-2-oxoethyl)phenyl)-2-((R)-pyrrolidin-3-yl)propanoic acid:

[0623] Step 1: Preparation of tert-butyl (R)-3-((S)-1-(tert-butoxy)-1-oxo-3-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propan-2-yl)pyrrolidine-1-carboxylate:

[0624] In a single-necked flask, tert-butyl (R)-3-((S)-3-(3-bromophenyl)-1-(tert-butoxy)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (1.5 g, 3.30 mmol, 1.0 eq) was dissolved in 1,4-dioxane (20 mL). 1,1-Bis(diphenylphosphino)ferrocenedichloropalladium dichloromethane complex (II) (270.0 mg, 0.33 mmol, 0.1 eq), bis(pinacolato)boronate (1.26 g, 4.95 mmol, 1.5 eq), and potassium acetate (972 mg, 9.9 mmol, 3 eq) were then added. The mixture was stirred at 90°C under nitrogen for 16 hours. The reaction was complete by liquid chromatography-mass spectrometry. The reaction solution was then concentrated and purified by flash chromatography (Silica gel, PE:EtOAc = 2:1) to afford the title compound (1.2 g). LCMS(ESI)[M-Boc+H] + =402.2.

[0625] Step 2: Preparation of tert-butyl (R)-3-((S)-1-(tert-butoxy)-3-(3-hydroxyphenyl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate:

[0626] In a single-necked flask, the product from the first step (1.2 g, 2.39 mmol, 1.0 eq) was dissolved in tetrahydrofuran (20 mL). Hydrogen peroxide (0.5 mL) was then added and stirred at room temperature for 16 hours. Liquid chromatography-mass spectrometry confirmed the reaction was complete. The reaction solution was then concentrated and purified by flash chromatography (Silica gel, PE:EtOAc = 1:1) to yield the title compound (800.0 mg). LCMS (ESI) [M-2x tert-butyl+H] + =280.0.

[0627] Step 3: Preparation of tert-butyl (R)-3-((S)-1-(tert-butoxy)-3-(3-(2-(1,3-dioxoisoindolin-2-yl)ethoxy)phenyl)-1-oxopropane-2-yl)pyrrolidine-1-carboxylate:

[0628] In a single-necked flask, the product from step 2 (500.0 mg, 1.28 mmol, 1.0 eq) was dissolved in N,N-dimethylformamide (5 mL). 2-(2-bromoethyl)isoindoline-1,3-dione (647.7 mg, 2.56 mmol, 2 eq) and potassium carbonate (530.7 mg, 3.83 mmol, 3 eq) were then added and stirred at 90°C for 2 hours. The reaction was complete by LC / MS / MS. The reaction solution was then concentrated and purified by flash chromatography (Silica gel, PE:EtOAc = 1:1) to obtain the title compound (280 mg). LCMS (ESI) [M+H] + =565.3.

[0629] Step 4: Preparation of tert-butyl (R)-3-((S)-3-(3-(2-aminoethoxy)phenyl)-1-(tert-butoxy)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate:

[0630] In a single-necked flask, the product from step 3 (280.0 mg, 0.5 mmol, 1.0 eq) was dissolved in ethanol (10 mL). Hydrazine hydrate (124 mg, 2.50 mmol, 5.0 eq) was then added and allowed to react at 90°C for 16 hours. The reaction was complete after LC / MS analysis. The reaction solution was then concentrated and purified by flash chromatography (Silica gel, PE:EtOAc = 1:5) to obtain the title compound (160 mg). LCMS (ESI) [M+H] + =435.3.

[0631] Step 5: Preparation of tert-butyl (R)-3-((S)-1-(tert-butoxy)-3-(3-(((2-(3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)phenoxy)ethyl)amino)methyl)phenyl)-1-oxopropane-2-yl)pyrrolidine-1-carboxylate:

[0632] In a single-necked flask, the product from step 4 (160 mg, 0.37 mmol, 1.0 eq) was dissolved in methanol (10 mL). Tert-butyl (R)-3-((S)-1-(tert-butoxy)-3-(3-formylphenyl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (178.1 mg, 0.44 mmol, 1.2 eq) was then added, followed by sodium cyanoborohydride (23.2 mg, 0.37 mmol, 1.0 eq). The mixture was stirred at room temperature for 16 hours. Liquid chromatography-mass spectrometry confirmed the reaction was complete, and the reaction solution was directly concentrated and purified by flash chromatography (Silica gel, PE:EtOAc = 1:5) to obtain the title compound (233 mg). LCMS (ESI) [M+H] + =822.6.

[0633] Step 6: Preparation of tert-butyl (R)-3-((S)-3-(3-allylphenyl)-1-(tert-butoxy)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate:

[0634] In a single-necked flask, tert-butyl (R)-3-((S)-3-(3-bromophenyl)-1-(tert-butoxy)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (7.0 g, 15.4 mmol, 1.0 eq) was dissolved in 1,4-dioxane (20 mL) and water (4 mL). 2-allyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (5.2 g, 30.8 mmol, 2 eq), potassium phosphate (9.8 g, 46.2 mmol, 3 eq) and 1,1-bis(diphenylphosphino)ferrocenepalladium dichloride dichloromethane complex (II) (1.25 g, 1.54 mmol, 0.1 eq) were then added. The mixture was stirred at 90°C under nitrogen protection for 16 hours. The reaction was complete after liquid chromatography-mass spectrometry, and the reaction solution was directly concentrated and purified by flash chromatography (Silica gel, PE:EtOAc=2:1) ​​to obtain the target compound (5.0 g). LCMS [M-2×tert-butyl+H] + =304.1.

[0635] Step 7: Preparation of 2-(3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)phenyl)acetic acid:

[0636] In a single-necked flask, the product from step 6 (6.0 g, 14.4 mmol, 1.0 eq) was dissolved in 1,4-dioxane (100 mL). Sodium periodate (12.3 g, 57.75 mmol, 4 eq) and potassium osmate dihydrate (532.0 mg, 1.44 mmol, 0.1 eq) were then added and stirred at room temperature for 16 hours. Liquid chromatography-mass spectrometry confirmed the reaction was complete, and the reaction solution was directly concentrated and purified by flash chromatography (Silica gel, PE:EtOAc = 1:1) to obtain the title compound (500 mg). LCMS (ESI) [M+H] +＝ 434.2.

[0637] Step 8: Preparation of tert-butyl (R)-3-((S)-1-(tert-butoxy)-3-(3-((N-(2-(3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)phenoxy)ethyl)-2-(3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)phenyl)acetamido)methyl)phenyl)-1-oxopropane-2-yl)pyrrolidine-1-carboxylate:

[0638] In a single-necked flask, the product from step 5 (70 mg, 0.0852 mmol, 1.0 eq) was dissolved in DMF (5 mL). The product from step 7 (44.3 mg, 0.102 mmol, 1.2 eq), O-(7-azabenzotriazol-1-yl)-N,N,N,N-tetramethyluronium hexafluorophosphate (64.7 mg, 0.17 mmol, 2.0 eq), and N,N-diisopropylethylamine (33.0 mg, 0.25 mmol, 3.0 eq) were then added. The mixture was stirred at room temperature for 16 hours. The reaction was complete after LC / MS analysis. The reaction solution was concentrated and purified by flash chromatography (Silica gel, PE:EtOAc = 1:8) to yield the title compound (70 mg). LCMS (ESI) [M+H] + =1237.9.

[0639] Step 9: Preparation of (S)-3-(3-(2-((3-((S)-2-carboxy-2-((R)-pyrrolidin-3-yl)ethyl)benzyl)(2-(3-((S)-2-carboxy-2-((R)-pyrrolidin-3-yl)ethyl)phenoxy)ethyl)amino)-2-oxoethyl)phenyl)-2-((R)-pyrrolidin-3-yl)propanoic acid:

[0640] In a single-necked flask, the product from step 8 (70.0 mg, 0.056 mmol) was dissolved in hydrochloric acid-dioxane (2 mL) and stirred at room temperature for 16 hours. Liquid chromatography-mass spectrometry confirmed the reaction was complete, and the reaction solution was directly concentrated and purified by preparative chromatography to obtain the title compound (27.2 mg). LCMS (ESI) [M+H] + =769.4. 1 H NMR(400MHz,Deuterium Oxide)δ7.20(dq,J=30.0,7.5Hz,3H),7.11-6.86(m,6H),6.81(s,1H),6.69-6.59(m,2H),4.59( d,J=4.6Hz,2H),4.10(t,J=5.0Hz,1H),4.00(d,J=5.2Hz,1H),3.88(s,1H),3.79(d,J=5.2Hz,1H ),3.69(d,J=5.2Hz,2H),3.29(dtt,J=13.1,9.3,4.6Hz,6H),3.12(dd,J=11.9,7.9Hz,3H),2.87 -2.58(m,8H),2.54-2.48(m,1H),2.41-2.23(m,6H),2.01(s,3H),1.63(dt,J=22.4,11.3Hz,3H).

[0641] Example 9 (Compound 8)

[0642] Preparation of 3,3'-(((((4-(2-carboxy-2-((R)-pyrrolidin-3-yl)ethyl)benzofuran-2-yl)methyl)azanediyl)bis(methylene))bis(3,1-phenylene))bis(2-((R)-pyrrolidin-3-yl)propanoic acid):

[0643] Step 1: Synthesis of methyl 3-hydroxy-2-iodobenzoate:

[0644] Methyl 2-amino-3-hydroxybenzoate (25 g, 149.65 mmol, 1 eq) was dissolved in a 1.0 M aqueous sulfuric acid solution (1000 mL). The solution was cooled to 0°C and a 100 mL aqueous solution of sodium nitrite (11.25 g, 163.0 mmol, 1.08 eq) was added. The mixture was stirred at 25°C for 20 minutes. A 100 mL aqueous solution of potassium iodide (111.7 g, 672.9 mmol, 4.5 eq) was added and stirred at 70°C for 1.5 hours. Liquid chromatography-mass spectrometry confirmed the reaction was complete. Water and ethyl acetate were added to the reaction mixture, and the mixture was separated. The organic phase was washed with saturated sodium chloride, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated to obtain the crude product, which was purified by flash chromatography (silica gel, petroleum ether:ethyl acetate = 5:1) to obtain the title compound (20.0 g). LCMS (ESI) [M+H] + =278.9.

[0645] Step 2: Synthesis of methyl 2-hydroxymethylbenzofuran-4-carboxylate:

[0646] The product from the first step (20.0 g, 71.94 mmol, 1.0 eq) was dissolved in N,N-dimethylformamide (200 mL). Cuprous iodide (1.37 g, 7.19 mmol, 0.1 eq), bistriphenylphosphine palladium dichloride (5 g, 7.19 mmol, 0.1 eq), triethylamine (21.86 g, 214.55 mmol, 3.0 eq), and propargyl alcohol (6.1 g, 108.81 mmol, 1.5 eq) were added. The mixture was stirred at 75°C for 16 hours under nitrogen. Liquid chromatography-mass spectrometry confirmed the reaction was complete. Water and ethyl acetate were added to the reaction mixture, and the mixture was separated. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain the crude product. This was then separated and purified by flash chromatography (silica gel, petroleum ether:ethyl acetate = 10:1) to yield the title compound (11 g). LCMS (ESI) [M+H] + =207.4.

[0647] Step 3: Synthesis of methyl 2-(((tert-butyldiphenylsilyl)oxy)methyl)benzofuran-4-carboxylate:

[0648] The product from step 2 (11.0 g, 53.38 mmol, 1.0 eq) was dissolved in dichloromethane (80 mL), and imidazole (4.5 g, 66.09 mmol, 1.5 eq) and tert-butyldiphenylsilyl chloride (13.0 g, 47.30 mmol, 0.8 eq) were added. The mixture was stirred at 25°C for 16 hours. LCMS confirmed the reaction was complete, and the mixture was filtered and the filtrate was directly dried. The mixture was then purified by flash chromatography (silica gel, petroleum ether:ethyl acetate = 10:1) to obtain the title compound (12.2 g). LCMS (ESI) [M+Na] + =467.4.

[0649] Step 4: Synthesis of (2-(((tert-butyldiphenylsilyl)oxy)methyl)benzofuran-4-yl)methanol:

[0650] The product from step 3 (12.2 g, 27.47 mmol, 1 eq) was dissolved in tetrahydrofuran (100 mL). Lithium borohydride (1.79 g, 82.41 mmol, 3.0 eq) was added at 0°C and stirred at 25°C for 16 hours. LCMS confirmed the reaction was complete. Water and ethyl acetate were added, and the mixture was separated. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated, and purified by flash chromatography (silica gel, petroleum ether:ethyl acetate = 2:1) to obtain the title compound (7.64 g). LCMS (ESI) [M+Na] + =439.4.

[0651] Step 5: Synthesis of ((4-(bromomethyl)benzofuran-2-yl)methoxy)(tert-butyl)diphenylsilane:

[0652] The product from step 4 (2.0 g, 4.81 mmol, 1.0 eq) was added to dichloromethane (20 mL), and phosphorus tribromide (1.95 g, 7.21 mmol, 1.5 eq) was added at 0°C and stirred for 2 hours. TLC confirmed the reaction was complete, and saturated aqueous ammonium chloride was added to quench the reaction. The mixture was extracted with ethyl acetate, and the organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated to afford the crude product. This was then separated and purified by flash chromatography (silica gel, petroleum ether:ethyl acetate = 100:1) to afford the title compound (1.42 g).

[0653] Step 6: Synthesis of tert-butyl (R)-3-(2-(tert-butoxy)-2-oxoethyl)pyrrolidine-1-carboxylate:

[0654] (R)-2-(1-(tert-Butoxycarbonyl)pyrrolidin-3-yl)acetic acid (25.0 g, 109.11 mmol, 1.0 eq) was dissolved in dichloromethane (200 mL). N,N'-dicyclohexylcarbodiimide (22.5 g, 109.11 mmol, 1.0 eq), tert-butyl alcohol (24.25 mL, 327.33 mmol, 3.0 eq), and 4-dimethylaminopyridine (13.3 g, 109.11 mmol, 1.0 eq) were added at 25°C. After addition, the mixture was stirred for 16 hours. Liquid chromatography-mass spectrometry confirmed the reaction was complete. Water and ethyl acetate were added, and the mixture was separated and extracted. The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated to obtain the crude product, which was then purified by flash chromatography (silica gel, petroleum ether:ethyl acetate = 10:1) to obtain the title compound (24.0 g).

[0655] Step 7: Synthesis of tert-butyl (3R)-3-(1-(tert-butoxy)-3-(2-(((tert-butyldiphenylsilyl)oxy)methyl)benzofuran-4-yl)-1-oxopropane-2-yl)pyrrolidine-1-carboxylate:

[0656] The product from step 6 (905 mg) was dissolved in tetrahydrofuran (10 mL) and lithium bis(trimethylsilylamide) (4.8 mL) was slowly added dropwise at 0°C. The mixture was stirred at 0°C for 30 minutes. The product from step 5 (1.42 gq) was dissolved in tetrahydrofuran (10 mL) and slowly added dropwise to the previous reaction mixture. The mixture was stirred at 25°C for 3 hours. Liquid chromatography-mass spectrometry confirmed the reaction was complete. The reaction was quenched by addition of saturated aqueous ammonium chloride and extracted with ethyl acetate. The organic phase was dried over anhydrous sodium sulfate, filtered, concentrated, and purified by flash chromatography (silica gel, petroleum ether:ethyl acetate = 3:1) to yield the title compound (1.67 g). LCMS (ESI) [M+H] + =684.2.

[0657] Step 8: Synthesis of tert-butyl (3R)-3-(1-(tert-butoxy)-3-(2-(hydroxymethyl)benzofuran-4-yl)-1-oxopropane-2-yl)pyrrolidine-1-carboxylate:

[0658] Dissolve tert-butyl (3R)-3-(1-(tert-butoxy)-3-(2-(((tert-butyldiphenylsilyl)oxy)methyl)benzofuran-4-yl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (1.67 g, 2.44 mmol, 1.0 eq) in tetrahydrofuran (10 mL). Add tetrabutylammonium fluoride (3.18 g, 12.2 mmol, 5.0 eq) at 25°C and stir at room temperature for 2 hours. LCMS analysis confirmed the reaction was complete, filtered, and the organic phase was dried to give the title compound (1.8 g). LCMS (ESI) [M+Na] +=468.4.

[0659] Step 9: Synthesis of tert-butyl (3R)-3-(1-(tert-butoxy)-3-(2-formylbenzofuran-4-yl)-1-oxopropane-2-yl)pyrrolidine-1-carboxylate:

[0660] The product from step 8 (1.8 g, 4.04 mmol, 1.0 eq) was dissolved in dichloromethane (10 mL). Manganese dioxide (1.75 g, 20.2 mmol, 5.0 eq) was added at 25°C. The reaction mixture was stirred at 60°C for 2 hours. The reaction was complete after HPLC-MS analysis. The organic phase was filtered, concentrated, and purified by flash chromatography (silica gel, petroleum ether:ethyl acetate = 5:1) to obtain the title compound (894 mg). LCMS (ESI) [M+Na] + =476.4.

[0661] Step 10: Synthesis of 3,3'-((((((4-(3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)benzofuran-2-yl)methyl)azanediyl)bis(methylene))bis(3,1-phenylene))bis(3-(tert-butoxy)-3-oxopropane-1,2-diyl))(3R,3'R)-bis(tert-butyl pyrrolidine-1-carboxylate):

[0662] The product from step 9 (100 mg, 0.23 mmol, 1.0 eq) was dissolved in methanol (5 mL). 3,3'-(((azanediylbis(methylene))bis(3,1-phenylene))bis(3-(tert-butoxy)-3-oxopropane-1,2-diyl))(3R,3'R)-bis(tert-butyl pyrrolidine-1-carboxylate) (197.8 mg, 0.25 mmol, 1.1 eq) was added at 25°C. The mixture was stirred at 25°C for 30 minutes. Sodium triacetylborohydride (146.2 mg, 0.69 mmol, 3.0 eq) was added, and the reaction was continued for 2 hours. Liquid chromatography-mass spectrometry confirmed the reaction was complete. Water and ethyl acetate were added, and the mixture was separated by extraction. The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated to obtain the crude product. The crude product was then purified on a silica gel plate (petroleum ether:ethyl acetate = 1:1) to obtain the title compound (65 mg). LCMS (ESI) [M+H] + =1220.1.

[0663] Step 11: Synthesis of 3,3'-(((((4-(2-carboxy-2-((R)-pyrrolidin-3-yl)ethyl)benzofuran-2-yl)methyl)azanediyl)bis(methylene))bis(3,1-phenylene))bis(2-((R)-pyrrolidin-3-yl)propionic acid):

[0664] The product obtained in step 10 (65 mg) was dissolved in hydrochloric acid / 1,4-dioxane (1 mL) and stirred at 25°C for 2 hours. LCMS confirmed the reaction was complete, and the crude product was concentrated. Prep-HPLC yielded the target compound (4 mg). LCMS (ESI) [M+H] + =751.5; 1 H NMR(400MHz,MeOD-d4)δ7.36-7.30(m,3H),7.26-7.21(m,4H),7.18-7.09(m,4H),6.85(s,1H),3.81-3.71(m,2H),3.67-3.60 (m,4H),3.26-2.96(m,14H),2.81-2.64(m,5H),2.51-2.42(m,2H),2.42-2.30(m,3H),2.10-2.01(m,3H),1.84-1.57(m,3H).

[0665] Example 10 (Compound 11)

[0666] Preparation of (2S,2'S)-3,3'-(((((6-((S)-2-carboxy-2-((R)-pyrrolidin-3-yl)ethyl)benzo[b]thiophen-2-yl)methyl)azanediyl)bis(methylene))bis(3,1-phenylene))bis(2-((R)-pyrrolidin-3-yl)propanoic acid):

[0667] Step 1: Synthesis of 3,3'-((2S,2'S)-(((((6-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)benzo[b]thiophen-2-yl)methyl)azanediyl)bis(methylene))bis(3,1-phenylene))bis(3-(tert-butoxy)-3-oxopropane-1,2-diyl))(3R,3'R)-bis(tert-butyl pyrrolidine-1-carboxylate):

[0668] (R)-tert-Butyl 3-((S)-1-(tert-butoxy)-3-(2-formylbenzo[b]thiophen-6-yl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (86.7 mg, 0.189 mmol, 1.5 eq) was dissolved in methanol (5 mL), and 3,3'-((2S,2'S)-((azanediylbis(methylene))bis(3,1-phenylene))bis(3-(tert-butoxy)-3-oxopropane-1,2-diyl))(3R,3'R)-bis(tert-butyl pyrrolidine-1-carboxylate) (100 mg, 0.126 mmol, 1.0 eq) and sodium cyanoborohydride (15.84 mg, 0.252 mmol, 2.0 eq) were added at room temperature. The mixture was stirred at room temperature for 36 hours. The reaction was complete after liquid chromatography-mass spectrometry analysis, and the reaction solution was directly concentrated and purified by flash chromatography (Silica gel, petroleum ether:ethyl acetate = 1:8) to obtain the target compound (90 mg). LCMS (ESI) [M+H] + =1235.8.

[0669] Step 2: Synthesis of (2S,2'S)-3,3'-(((((6-((S)-2-carboxy-2-((R)-pyrrolidin-3-yl)ethyl)benzo[b]thiophen-2-yl)methyl)azanediyl)bis(methylene))bis(3,1-phenylene))bis(2-((R)-pyrrolidin-3-yl)propionic acid):

[0670] 3,3'-((2S,2'S)-(((((6-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)benzo[b]thiophen-2-yl)methyl)azanediyl)bis(methylene))bis(3,1-phenylene))bis(3-(tert-butoxy)-3-oxopropane-1,2-diyl))(3R,3'R)-bis(tert-butyl pyrrolidine-1-carboxylate) (90 mg, 0.07 mmol) was dissolved in hydrochloric acid / 1,4-dioxane (2 mL) and stirred at room temperature for 16 hours. The reaction was complete after LC / MS analysis, and the reaction solution was directly concentrated and purified by preparative chromatography to obtain the title compound (32.96 mg). LCMS (ESI) [M+H] + =767.4; 1H NMR(400MHz,Deuterium Oxide)δ7.78(d,J=8.2Hz,1H),7.70(s,1H),7.43(s,1H),7.30(dd,J=18.7,7.5Hz,5H),7.17(d ,J=7.6Hz,2H),7.12(s,2H),4.59(s,2H),4.35(s,4H),3.56(ddd,J=16.4,11.8,7.9Hz,3H),3. 43-3.34(m,3H),3.27-3.16(m,3H),3.08-2.90(m,5H),2.86-2.69(m,5H),2.64(td,J=9.6,5.0 Hz,2H),2.51(dq,J=17.4,8.7Hz,3H),2.18-2.04(m,3H),1.72(ddd,J=18.5,13.0,9.2Hz,3H).

[0671] Example 11 (Compound 49)

[0672] Preparation of (2S,2'S,2"S)-3,3',3"-((nitrilotris(methylene))tris(benzo[b]thiophene-3,5-diyl))tris(2-((R)-pyrrolidin-3-yl)propanoic acid):

[0673] Step 1: Synthesis of 3,3',3"-((2S,2'S,2"S)-((nitrilotris(methylene))tris(benzo[b]thiophene-3,5-diyl))tris(3-(tert-butoxy)-3-oxopropane-1,2-diyl))(3R,3'R,3"R)-tris(tert-butylpyrrolidine-1-carboxylate):

[0674] 3,3'-((2S,2'S)-((azanediylbis(methylene))bis(benzo[b]thiophene-3,5-diyl))bis(3-(tert-butoxy)-3-oxopropane-1,2-diyl))(3R,3'R)-bis(tert-butyl pyrrolidine-1-carboxylate) (40 mg, 0.04 mmol, 1.0 eq) was dissolved in tetrahydrofuran (5 mL), followed by the addition of tert-butyl (R)-3-((S)-1-(tert-butoxy)-3-(3-formylbenzo[b]thiophen-5-yl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (22.36 mg, 0.05 mmol, 1.1 eq) and sodium cyanoborohydride (2.74 mg, 0.04 mmol, 1.0 eq). The mixture was stirred at room temperature for 16 hours. The reaction was complete after liquid chromatography-mass spectrometry analysis, and the reaction solution was directly concentrated and purified by flash chromatography (Silica gel, petroleum ether:ethyl acetate = 1:8) to obtain the target compound (40 mg). LCMS (ESI) [M+H]+ =1347.1.

[0675] Step 2: Synthesis of (2S,2'S,2"S)-3,3',3"-((nitrilotris(methylene))tris(benzo[b]thiophene-3,5-diyl))tris(2-((R)-pyrrolidin-3-yl)propionic acid):

[0676] 3,3',3"-((2S,2'S,2"S)-((nitrilotris(methylene))tris(benzo[b]thiophene-3,5-diyl))tris(3-(tert-butoxy)-3-oxopropane-1,2-diyl))(3R,3'R,3"R)-tris(tert-butyl pyrrolidine-1-carboxylate) (40 mg, 0.03 mmol) was dissolved in hydrochloric acid / 1,4-dioxane (2 mL) and stirred at room temperature for 16 hours. The reaction was complete after LC / MS analysis. The reaction solution was directly concentrated and purified by preparative chromatography to obtain the title compound (22.36 mg). LCMS (ESI) [M+H] + =879.0; 1 H NMR(400MHz,Deuterium Oxide)δ8.08-8.00(m,3H),7.92(d,J=8.3Hz,3H),7.23(dd,J=8.4,1.5Hz,3H),6.4 7(s,3H),4.86(d,J=13.7Hz,3H),4.75(s,3H),3.37(ddd,J=12.0,10.0,5.6Hz,6H) ,3.21-3.13(m,3H),2.91(t,J=11.0Hz,3H),2.53(ddd,J=44.9,11.3,5.5Hz,6H),2 .42-2.24(m,6H),2.05(dtd,J=13.6,7.0,3.3Hz,3H),1.65(dq,J=13.2,9.7Hz,3H).

[0677] Example 12 (Compound 65)

[0678] Preparation of (2S,2'S,2"S)-3,3',3"-((nitrilotris(ethane-2,1-diyl))tris(benzene-3,1-diyl))tris(2-((R)-pyrrolidin-3-yl)propanoic acid):

[0679] Step 1: Synthesis of tert-butyl (R)-3-((S)-3-(3-allylphenyl)-1-(tert-butoxy)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate:

[0680] Tert-butyl (R)-3-((S)-3-(3-bromophenyl)-1-(tert-butoxy)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (1500 mg, 3.3 mmol, 1.0 eq) was dissolved in 1,4-dioxane (20 mL). 2-allyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.11 g, 6.6 mmol, 2 eq) and potassium phosphate (2.1 g, 9.9 mmol, 3 eq) were then added, followed by water (4 mL). The mixture was stirred at 90°C under nitrogen for 16 hours. The reaction was complete by liquid chromatography-mass spectrometry (LC-MS / MS). The reaction solution was then concentrated and purified by flash chromatography (silica gel, petroleum ether:ethyl acetate = 2:1) to obtain the title compound (900 mg). LCMS (ESI) [M+H] + =416.3.

[0681] Step 2: Synthesis of tert-butyl (R)-3-((S)-1-(tert-butoxy)-1-oxo-3-(3-(2-oxoethyl)phenyl)propan-2-yl)pyrrolidine-1-carboxylate:

[0682] Dissolve tert-butyl (R)-3-((S)-3-(3-allylphenyl)-1-(tert-butoxy)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (900 mg, 2.17 mmol, 1.0 eq) in 1,4-dioxane (20 mL), add sodium periodate (1.85 g, 8.66 mmol, 4 eq) and potassium osmate dihydrate (80 mg, 0.22 mmol, 0.1 eq), and stir at room temperature for 16 hours. LCMS analysis confirmed the completion of the reaction. The reaction solution was then concentrated and purified by flash chromatography (Silica gel, petroleum ether:ethyl acetate c = 1:1) to obtain the title compound (600 mg). LCMS (ESI) [M+H] + =418.3.

[0683] Step 3: Synthesis of 3,3'-((2S,2'S)-((azanediylbis(ethane-2,1-diyl))bis(3,1-phenylene))bis(3-(tert-butoxy)-3-oxopropane-1,2-diyl))(3R,3'R)-bis(tert-butyl pyrrolidine-1-carboxylate):

[0684] Dissolve tert-butyl (R)-3-((S)-1-(tert-butoxy)-1-oxo-3-(3-(2-oxoethyl)phenyl)propan-2-yl)pyrrolidine-1-carboxylate (400 mg, 0.96 mmol, 1.0 eq) in methanol (10 mL). Add ammonia / methanol (16.31 mg, 0.96 mmol, 1.0 eq), two drops of acetic acid, and sodium cyanoborohydride (71 mg, 1.15 mmol, 1.2 eq). Stir at room temperature for 16 hours. LCMS analysis confirmed the completion of the reaction. The reaction solution was then concentrated and purified by flash chromatography (Silica gel, petroleum ether:ethyl acetate = 1:8) to obtain the title compound (100 mg). LCMS (ESI) [M+H] + =820.6.

[0685] Step 4: Synthesis of 3,3',3"-((2S,2'S,2"S)-((nitrilotris(ethane-2,1-diyl))tris(benzene-3,1-diyl))tris(3-(tert-butoxy)-3-oxopropane-1,2-diyl))(3R,3'R,3"R)-tris(tert-butyl pyrrolidine-1-carboxylate):

[0686] 3,3'-((2S,2'S)-((azanediylbis(ethane-2,1-diyl))bis(3,1-phenylene))bis(3-(tert-butoxy)-3-oxopropane-1,2-diyl))(3R,3'R)-bis(tert-butyl pyrrolidine-1-carboxylate) (100 mg, 0.12 mmol, 1.0 eq) was dissolved in methanol (5 mL), and tert-butyl (R)-3-((S)-1-(tert-butoxy)-1-oxo-3-(3-(2-oxoethyl)phenyl)propan-2-yl)pyrrolidine-1-carboxylate (51 mg, 0.12 mmol, 1.0 eq) was added, two drops of acetic acid, and sodium cyanoborohydride (7.5 mg, 0.12 mmol, 1.0 eq). The mixture was stirred at room temperature for 16 hours. The reaction was complete after liquid chromatography-mass spectrometry. The reaction solution was directly concentrated and purified by flash chromatography (Silica gel, petroleum ether:ethyl acetate = 1:8) to obtain (80 mg). LCMS (ESI) [M+H] + =1221.9.

[0687] Step 5: Synthesis of (2S,2'S,2"S)-3,3',3"-((nitrilotris(ethane-2,1-diyl))tris(benzene-3,1-diyl))tris(2-((R)-pyrrolidin-3-yl)propionic acid):

[0688] 3,3',3"-((2S,2'S,2"S)-((nitrilotris(ethane-2,1-diyl))tris(benzene-3,1-diyl))tris(3-(tert-butoxy)-3-oxopropane-1,2-diyl))(3R,3'R,3"R)-tris(tert-butyl pyrrolidine-1-carboxylate) (80 mg) was dissolved in hydrochloric acid / 1,4-dioxane (2 mL) and stirred at room temperature for 16 hours. The reaction was complete after LC / MS analysis. The reaction solution was directly concentrated and purified by preparative chromatography to obtain the title compound (9.7 mg). LCMS (ESI) [M+H] + =753.7; 1 H NMR(400MHz,Deuterium Oxide)δ7.21(t,J=7.5Hz,3H),7.09-6.99(m,9H),3.40-3.30(m,6H),3.14(ddd,J=11.7,9.9,7.3Hz,4H),2.96(d,J=7.5Hz,4H),2.85(dd,J=1 1.7,9.2Hz,4H),2.78(d,J=9.1Hz,7H),2.72-2.64(m,5H),2.39(dq,J=14.9,9.1,6.8Hz,6H),2.04(td,J=6.5,3.6Hz,3H),1.71-1.63(m,3H).

[0689] Example 13 (Compound 67)

[0690] Preparation of (2S,2'S,2"S)-3,3',3"-((nitrilotris(ethane-2,1-diyl))tris(benzofuran-3,5-diyl))tris(2-((R)-pyrrolidin-3-yl)propanoic acid):

[0691] Step 1: Synthesis of tert-butyl (R)-3-((S)-1-(tert-butoxy)-3-(3-((E)-2-(hydroxyimino)ethyl)benzofuran-5-yl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate:

[0692] Dissolve (R)-tert-butyl 3-((S)-1-(tert-butoxy)-1-oxo-3-(3-(2-oxoethyl)benzofuran-5-yl)propan-2-yl)pyrrolidine-1-carboxylate (120 mg, 0.26 mmol, 1.0 eq) in ethanol (10 mL), add hydroxylamine hydrochloride (37 mg, 0.52 mmol, 2.0 eq), and stir at room temperature for 16 hours. LCMS analysis confirmed the reaction was complete, and the reaction solution was filtered. The filtrate was concentrated and purified by flash chromatography (silica gel, petroleum ether:ethyl acetate = 1:8) to obtain the title compound (100 mg). LCMS (ESI) [M+H]+ =473.2.

[0693] Step 2: Synthesis of tert-butyl (R)-3-((S)-3-(3-(2-aminoethyl)benzofuran-5-yl)-1-(tert-butoxy)-1-oxopropane-2-yl)pyrrolidine-1-carboxylate:

[0694] Dissolve tert-butyl (R)-3-((S)-1-(tert-butoxy)-3-(3-((E)-2-(hydroxyimino)ethyl)benzofuran-5-yl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (100 mg, 0.21 mmol, 1.0 eq) in methanol (10 mL), add palladium on carbon (10 mg), and stir at room temperature under a hydrogen atmosphere for 16 hours. LCMS analysis confirmed the reaction was complete, and the reaction solution was filtered and dried. Purification by flash chromatography (silica gel, petroleum ether:ethyl acetate = 1:8) afforded the title compound (70 mg). LCMS (ESI) [M+H] + =459.2.

[0695] Step 3: Synthesis of 3,3',3"-((2S,2'S,2"S)-((nitrilotris(ethane-2,1-diyl))tris(benzofuran-3,5-diyl))tris(3-(tert-butoxy)-3-oxopropane-1,2-diyl))(3R,3'R,3"R)-tris(tert-butyl pyrrolidine-1-carboxylate):

[0696] Dissolve tert-butyl (R)-3-((S)-3-(3-(2-aminoethyl)benzofuran-5-yl)-1-(tert-butoxy)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (100 mg, 0.22 mmol, 1.0 eq) in methanol (10 mL). Add tert-butyl (R)-3-((S)-1-(tert-butoxy)-1-oxo-3-(3-(2-oxoethyl)benzofuran-5-yl)propan-2-yl)pyrrolidine-1-carboxylate (200 mg, 0.44 mmol, 2.0 eq) and sodium cyanoborohydride (27 mg, 0.44 mmol, 2.0 eq). Stir at room temperature for 16 hours. Liquid chromatography-mass spectrometry confirmed the reaction was complete. The reaction solution was cooled, concentrated, and purified by flash chromatography (silica gel, petroleum ether:ethyl acetate = 1:1) to obtain the title compound (100 mg).

[0697] Step 4: Synthesis of (2S,2'S,2"S)-3,3',3"-((nitrilotris(ethane-2,1-diyl))tris(benzofuran-3,5-diyl))tris(2-((R)-pyrrolidin-3-yl)propanoic acid):

[0698] 3,3',3"-((2S,2'S,2"S)-((nitrilotris(ethane-2,1-diyl))tris(benzofuran-3,5-diyl))tris(3-(tert-butoxy)-3-oxopropane-1,2-diyl))(3R,3'R,3"R)-tris(tert-butyl pyrrolidine-1-carboxylate) (100 mg, 0.07 mmol) was dissolved in hydrochloric acid / 1,4-dioxane (4 mL) and stirred at room temperature for 16 hours. The reaction was complete by LC / MS detection, and the reaction solution was directly concentrated and purified by preparative chromatography to obtain (6.58 mg). LCMS (ESI) [M+H] + =873.2; 1 H NMR(400MHz,Deuterium Oxide)δ7.26-7.14(m,6H),6.94(s,6H),3.17(d,J=33.2Hz,4H),2.95(d,J=26.8Hz,5H), 2.61(d,J=51.5Hz,22H),2.41-2.10(m,7H),1.73(dd,J=101.8,31.7Hz,3H),1.08(s,1H).

[0699] Example 14 (Compound 71)

[0700] Preparation of (2S,2'S)-3,3'-((((2-(3-((S)-2-carboxy-2-((R)-pyrrolidin-3-yl)ethyl)phenoxy)ethyl)azanediyl)bis(ethane-2,1-diyl))bis(3,1-phenylene))bis(2-((R)-pyrrolidin-3-yl)propanoic acid):

[0701] Step 1: Synthesis of tert-butyl (R)-3-((S)-1-(tert-butoxy)-1-oxo-3-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propan-2-yl)pyrrolidine-1-carboxylate:

[0702] Dissolve tert-butyl (R)-3-((S)-3-(3-bromophenyl)-1-(tert-butoxy)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (1.5 g) in 1,4-dioxane (20 mL), add pinacol diboron (1.75 g), 1,1-bis(diphenylphosphino)ferrocenepalladium(II) chloride (241.4 mg), and potassium acetate (972 mg), and add water (4 mL). Stir at 90°C under nitrogen for 16 hours. Liquid chromatography-mass spectrometry confirmed the completion of the reaction, and the reaction solution was directly concentrated and purified by flash chromatography (Silica gel, petroleum ether:ethyl acetate = 2:1) to obtain the title compound (1.2 g). LCMS (ESI) [M+H-Boc] +=402.2.

[0703] Step 2: Synthesis of tert-butyl (R)-3-((S)-1-(tert-butoxy)-3-(3-hydroxyphenyl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate:

[0704] Dissolve tert-butyl (R)-3-((S)-1-(tert-butyloxy)-1-oxo-3-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propan-2-yl)pyrrolidine-1-carboxylate (1200 mg) in tetrahydrofuran (20 mL), add hydrogen peroxide (0.5 mL), and stir at room temperature for 16 hours. LCMS analysis confirmed the completion of the reaction. The reaction solution was directly concentrated and purified by flash chromatography (silica gel, petroleum ether:ethyl acetate = 1:1) to obtain the title compound (800 mg). LCMS (ESI) [M-2 × tert-butyl] + =280.

[0705] Step 3: Synthesis of tert-butyl (R)-3-((S)-1-(tert-butoxy)-3-(3-(2-(1,3-dioxoisoindolin-2-yl)ethoxy)phenyl)-1-oxopropane-2-yl)pyrrolidine-1-carboxylate:

[0706] Dissolve tert-butyl (R)-3-((S)-1-(tert-butoxy)-3-(3-hydroxyphenyl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (500 mg) in N,N-dimethylformamide (5 mL), add 2-(2-bromoethyl)isoindoline-1,3-dione (649 mg) and potassium carbonate (530 mg), and stir at 90°C for 2 hours. LCMS analysis confirmed the completion of the reaction. The reaction solution was directly concentrated and purified by flash chromatography (silica gel, petroleum ether:ethyl acetate = 1:1) to obtain the title compound (280 mg). LCMS (ESI) [M+H] + =565.3.

[0707] Step 4: Synthesis of tert-butyl (R)-3-((S)-3-(3-(2-aminoethoxy)phenyl)-1-(tert-butoxy)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate:

[0708] Dissolve (R)-tert-butyl 3-((S)-1-(tert-butoxy)-3-(3-(2-(1,3-dioxoisoindolin-2-yl)ethoxy)phenyl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (280 mg) in ethanol (10 mL), add hydrazine hydrate (124 mg), and stir at 90°C for 16 hours. The reaction is complete after liquid chromatography-mass spectrometry. The reaction solution is directly concentrated and purified by flash chromatography (silica gel, petroleum ether:ethyl acetate = 1:5) to obtain the title compound (160 mg). LCMS (ESI) [M+H] + =435.3.

[0709] Step 5:

[0710] Synthesis of 3,3'-((2S,2'S)-((((2-(3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)phenoxy)ethyl)azanediyl)bis(ethane-2,1-diyl))bis(3,1-phenylene))bis(3-(tert-butoxy)-3-oxopropane-1,2-diyl))(3R,3'R)-bis(tert-butyl pyrrolidine-1-carboxylate):

[0711] Dissolve tert-butyl (R)-3-((S)-3-(3-(2-aminoethoxy)phenyl)-1-(tert-butoxy)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (80 mg) in methanol (10 mL), add tert-butyl (R)-3-((S)-1-(tert-butoxy)-1-oxo-3-(3-(2-oxoethyl)phenyl)propan-2-yl)pyrrolidine-1-carboxylate (154 mg) and sodium cyanoborohydride (23 mg). Stir at room temperature for 16 hours. LCMS analysis confirmed the completion of the reaction, and the reaction solution was directly concentrated and purified by flash chromatography (Silica gel, petroleum ether:ethyl acetate = 1:8) to obtain the title compound (100 mg). LCMS (ESI) [M+H] + =1237.9.

[0712] Step 6: Synthesis of (2S,2'S)-3,3'-((((2-(3-((S)-2-carboxy-2-((R)-pyrrolidin-3-yl)ethyl)phenoxy)ethyl)azanediyl)bis(ethane-2,1-diyl))bis(3,1-phenylene))bis(2-((R)-pyrrolidin-3-yl)propionic acid):

[0713] 3,3'-((2S,2'S)-((((2-(3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)phenoxy)ethyl)azanediyl)bis(ethane-2,1-diyl))bis(3,1-phenylene))bis(3-(tert-butoxy)-3-oxopropane-1,2-diyl))(3R,3'R)-bis(tert-butyl pyrrolidine-1-carboxylate) (100 mg) was dissolved in hydrochloric acid / 1,4-dioxane (2 mL) and stirred at room temperature for 16 hours. The reaction was complete after liquid chromatography-mass spectrometry analysis, and the reaction solution was directly concentrated and purified by preparative chromatography to obtain the title compound (27.9 mg). LCMS (ESI) [M+H] + =769.5; 1 H NMR(400MHz,Deuterium Oxide)δ7.24-7.09(m,4H),7.00(q,J=8.0Hz,5H),6.82(d,J=7.4Hz,1H),6.73(d,J=8.3Hz,2H),4.17-4.06(m,2H),3.39-3.28(m,6H),3.1 7-3.03(m,5H),2.90(d,J=9.4Hz,3H),2.86-2.58(m,14H),2.37(td,J=17.0,15.4,6.6Hz,6H),2.02(s,3H),1.66(dd,J=14.2,6.5Hz,3H).

[0714] Example 15 (Compound 80)

[0715] Preparation of (2S,2S)-3,3'-((2,2'-((2-(3-((S)-2-carboxy-2-((R)-pyrrolidin-3-yl)ethyl)phenoxy)ethyl)azanediyl)bis(acetyl))bis(3,1-phenylene))bis(2-((R)-pyrrolidin-3-yl)propanoic acid):

[0716] Step 1: Synthesis of (3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)phenyl)boronic acid:

[0717] Tert-butyl (3R)-3-[(2S)-3-(3-bromophenyl)-1-(tert-butoxy)-1-oxopropan-2-yl]pyrrolidine-1-carboxylate (1900 mg, 4.18 mmol, 1 eq), (dihydroxyboryl)boronic acid (562.29 mg, 6.27 mmol, 1.5 eq), potassium acetate (1230.7 mg, 12.54 mmol, 3 eq), dicyclohexyl[2',4',6'-tri(prop-2 -yl)-[1,1'-biphenyl]-2-yl]phosphine (199.27 mg, 0.42 mmol, 0.1 eq) and XPhosPdG2 (164 mg, 0.21 mmol, 0.05 eq) were added to ethanol (20 mL), and the reaction solution was replaced with nitrogen three times; stirred at 90 ° C for 16 hours; the reaction was complete by liquid chromatography-mass spectrometry, ethyl acetate was added, and the mixture was filtered through celite. The filtrate was dried to obtain the target compound (2000 mg) and used directly in the next step.

[0718] Step 2: Synthesis of tert-butyl (R)-3-((S)-1-(tert-butoxy)-3-(3-hydroxyphenyl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate:

[0719] {3-[(2S)-3-(tert-butoxy)-2-[(3R)-1-[(tert-butoxy)carbonyl]pyrrolidin-3-yl]-3-oxopropyl]phenyl}boronic acid (2000 mg, 4.77 mmol, 1 eq) was dissolved in tetrahydrofuran (30 mL), and hydrogen peroxide (8 mL) was added. The mixture was stirred at 20°C for 16 hours. LCMS analysis confirmed the reaction was complete. A saturated sodium bisulfite solution and ethyl acetate were added, and the mixture was separated and extracted. The organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated to give the crude product, which was purified by column chromatography (petroleum ether / ethyl acetate = 4:1) to obtain the title compound (800 mg). LCMS (ESI) [M+H] + =392.2.

[0720] Step 3: Synthesis of tert-butyl (R)-3-((S)-3-(3-(2-(((benzyloxy)carbonyl)amino)ethoxy)phenyl)-1-(tert-butoxy)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate:

[0721] Tert-butyl (3R)-3-[(2S)-1-(tert-butoxy)-3-(3-hydroxyphenyl)-1-oxopropan-2-yl]pyrrolidine-1-carboxylate (2 g, 5.11 mmol, 1 eq), benzyl (2-bromoethyl)carbamate (2.64 g, 10.22 mmol, 2 eq), and potassium carbonate (2.12 g, 15.33 mmol, 3 eq) were added to acetonitrile (50 mL) and stirred at 90°C for 16 hours. LCMS analysis confirmed the reaction was complete, and the reaction solution was directly purified by column chromatography (petroleum ether / ethyl acetate = 7:1) to obtain the title compound (3 g). LCMS (ESI) [M+H] + =569.0

[0722] Step 4: Synthesis of tert-butyl (R)-3-((S)-3-(3-(2-aminoethoxy)phenyl)-1-(tert-butoxy)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate:

[0723] Dissolve (R)-tert-butyl 3-((S)-3-(3-(2-(((benzyloxy)carbonyl)amino)ethoxy)phenyl)-1-(tert-butoxy)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (3 g, 5.27 mmol, 1 eq) in methanol (50 mL), add palladium (300 mg, 10%), and replace the hydrogen atmosphere three times. Stir at 25°C for 16 hours. The reaction is complete after LCMS analysis. The reaction mixture is filtered and the filtrate is concentrated to obtain the title compound (2 g). LCMS (ESI) [M+H] + =435.4

[0724] Step 5: Synthesis of tert-butyl (R)-3-((S)-1-(tert-butoxy)-3-(3-(2-chloroacetyl)phenyl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate:

[0725] Tert-butyl (R)-3-((S)-1-(tert-butoxy)-3-(3-(methoxycarbonyl)phenyl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (700 mg, 1.614 mmol, 1 eq) was dissolved in anhydrous tetrahydrofuran (10 mL), cooled to -78°C, and lithium diisopropylamide (1.0 M, 2.42 mL, 2.42 mmol, 1.5 eq) was added. The mixture was stirred at -78°C for 1 hour. Chloroiodomethane (854.03 mg, 4.84 mmol, 3 eq) was added, and stirring was continued at -78°C for 2 hours. LCMS analysis confirmed the completion of the reaction. Saturated aqueous ammonium chloride and ethyl acetate were added to the reaction solution, and the mixture was separated by extraction. The organic phase was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated to give the crude product, which was purified by column chromatography (petroleum ether / ethyl acetate = 4:1) to give the title compound (100 mg). LCMS(ESI)[M+H-Boc] +=352.4.

[0726] Step 6: Synthesis of 3,3'-((2S,2'S)-((2,2'-((2-(3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)phenoxy)ethyl)azanediyl)bis(acetyl))bis(3,1-phenylene))bis(1-(tert-butoxy)-1-oxopropane-3,2-diyl))(3R,3'R)-bis(tert-butyl pyrrolidine-1-carboxylate):

[0727] Tert-butyl (R)-3-((S)-3-(3-(2-aminoethoxy)phenyl)-1-(tert-butoxy)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (192.2 mg, 0.44 mmol, 2 eq) and tert-butyl (R)-3-((S)-1-(tert-butoxy)-3-(3-(2-chloroacetyl)phenyl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (100 mg, 0.22 mmol, 1 eq) were dissolved in acetonitrile (3 mL), and anhydrous potassium carbonate (91.1 mg, 0.66 mmol, 3 eq) was added. The mixture was stirred at 60°C for 2 hours. LCMS indicated that the reaction was complete, and the reaction solution was concentrated and purified on a silica gel plate (petroleum ether:ethyl acetate = 1:1) to obtain the title compound (50 mg). LCMS (ESI) [M+H] + =1265.3.

[0728] Step 7: Synthesis of (2S,2S)-3,3'-((2,2'-((2-(3-((S)-2-carboxy-2-((R)-pyrrolidin-3-yl)ethyl)phenoxy)ethyl)azanediyl)bis(acetyl))bis(3,1-phenylene))bis(2-((R)-pyrrolidin-3-yl)propionic acid):

[0729] Under ice, 3,3'-((2S,2'S)-((2,2'-((2-(3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)phenoxy)ethyl)azanediyl)bis(acetyl))bis(3,1-phenylene))bis(1-(tert-butoxy)-1-oxopropane-3,2-diyl))(3R,3'R)-bis(tert-butyl pyrrolidine-1-carboxylate) (50 mg, 0.04 mmol, 1 eq) was added to hydrochloric acid / 1,4-dioxane (2 mL, 4.0 M) and stirred at 25°C for 6 hours. The reaction was complete after LCMS analysis, and the reaction solution was directly concentrated to obtain the crude product, which was then purified by Prep-HPLC to obtain the title compound (6 mg). LCMS (ESI) [MH]- = 795.6; 1H NMR (400MHz, DMSO) δ7.90(s,2H),7.81(d,J=8.0Hz,2H),7.63(d,J=7.6Hz,2H),7.53(d,J=8.0Hz,2H),7.10(t,J=8.0Hz,1H),6.76(d,J=7.6Hz ,1H),6.53-6.45(m,2H),5.34(s,3H),4.46(s,2H),3.92(s,2H),3.34- 2.69(m,25H),2.41-2.32(m,3H),2.03-1.95(m,3H),1.69-1.62(m,3H).

[0730] Example 16 (Compound 81)

[0731] Preparation of (2S,2'S)-3,3'-((((2-(3-((S)-2-carboxy-2-((R)-pyrrolidin-3-yl)ethyl)phenoxy)acetyl)azanediyl)bis(ethane-2,1-diyl))bis(3,1-phenylene))bis(2-((R)-pyrrolidin-3-yl)propanoic acid):

[0732] Step 1: Synthesis of 3,3'-((2S,2'S)-((azanediylbis(ethane-2,1-diyl))bis(3,1-phenylene))bis(3-(tert-butoxy)-3-oxopropane-1,2-diyl))(3R,3'R)-bis(tert-butyl pyrrolidine-1-carboxylate):

[0733] Dissolve tert-butyl (R)-3-((S)-3-(3-(2-aminoethyl)phenyl)-1-(tert-butoxy)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (100 mg) in methanol (10 mL). Add tert-butyl (R)-3-((S)-1-(tert-butoxy)-1-oxo-3-(3-(2-oxoethyl)phenyl)propan-2-yl)pyrrolidine-1-carboxylate (100 mg) and sodium cyanoborohydride (15 mg). Stir at room temperature for 16 hours. LCMS analysis confirmed the completion of the reaction. The reaction solution was cooled, concentrated, and purified by flash chromatography (silica gel, petroleum ether:ethyl acetate = 1:1) to obtain the title compound (100 mg). LCMS (ESI) [M+H] + =820.6

[0734] Step 2: Synthesis of 3,3'-((2S,2'S)-((((2-(3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)phenoxy)acetyl)azanediyl)bis(ethane-2,1-diyl))bis(3,1-phenylene))bis(3-(tert-butoxy)-3-oxopropane-1,2-diyl))(3R,3'R)-bis(tert-butyl pyrrolidine-1-carboxylate):

[0735] To 3,3'-((2S,2'S)-((azanediylbis(ethane-2,1-diyl))bis(3,1-phenylene))bis(3-(tert-butoxy)-3-oxopropane-1,2-diyl))(3R,3'R)-bis(tert-butyl pyrrolidine-1-carboxylate) (100 mg) were added 2-(3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)phenoxy)acetic acid (82 mg), O-(7-azabenzotriazol-1-yl)-N,N,N,N-tetramethyluronium hexafluorophosphate (93 mg) and diisopropylethylamine (47 mg); the mixture was stirred at room temperature for 16 hours. The reaction was complete after liquid chromatography-mass spectrometry. The reaction solution was diluted with water and extracted with ethyl acetate. The organic phase was dried, filtered, and concentrated to obtain a crude product, which was then separated and purified by flash chromatography (silica gel, petroleum ether:ethyl acetate = 1:8) to obtain the title compound (70 mg). LCMS (ESI) [M+H-Boc] + =1152.0.

[0736] Step 3: Synthesis of (2S,2'S)-3,3'-((((2-(3-((S)-2-carboxy-2-((R)-pyrrolidin-3-yl)ethyl)phenoxy)acetyl)azanediyl)bis(ethane-2,1-diyl))bis(3,1-phenylene))bis(2-((R)-pyrrolidin-3-yl)propionic acid):

[0737] 3,3'-((2S,2'S)-((((2-(3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)phenoxy)acetyl)azanediyl)bis(ethane-2,1-diyl))bis(3,1-phenylene))bis(3-(tert-butoxy)-3-oxopropane-1,2-diyl))(3R,3'R)-bis(tert-butyl pyrrolidine-1-carboxylate) (70 mg) was dissolved in hydrochloric acid / 1,4-dioxane (4 mL) and stirred at room temperature for 16 hours. The reaction was complete after liquid chromatography-mass spectrometry analysis, and the reaction solution was directly concentrated and purified by preparative chromatography to obtain the title compound (13.41 mg). LCMS (ESI) [M+H] + =783.1;1 H NMR(400MHz,Deuterium Oxide)δ7.21(td,J=7.7,2.0Hz,2H),7.14-6.99(m,7H),6.80(d,J=7.6Hz,1H),6.57(t ,J=2.1Hz,1H),6.08(dd,J=8.2,2.6Hz,1H),4.14-4.04(m,2H),3.63-3.55(m,2H),3.4 1-3.26(m,7H),3.14(dddd,J=25.2,23.0,11.2,4.0Hz,4H),2.87-2.63(m,12H),2.60- 2.54(m,1H),2.43-2.25(m,6H),2.10-1.98(m,3H),1.66(td,J=12.8,11.1,7.5Hz,3H).

[0738] Example 17 (Compound 90)

[0739] Preparation of (2S,2'S,2"S)-3,3',3"-((nitrilotris(methylene-d2))tris(benzene-3,1-diyl))tris(2-((R)-pyrrolidin-3-yl)propanoic acid):

[0740] Step 1: Synthesis of tert-butyl (R)-3-((S)-1-(tert-butoxy)-3-(3-(hydroxymethyl-d2)phenyl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate:

[0741] Tert-butyl (R)-3-((S)-1-(tert-butoxy)-3-(3-(methoxycarbonyl)phenyl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (1.2 g, 2.77 mmol, 1 eq) was dissolved in a mixture of tetrahydrofuran (14.4 mL) and deuterated methanol (4.2 mL). Under nitrogen, sodium deuterated borohydride (695.19 mg, 16.61 mmol, 6 eq) was added portionwise. The mixture was stirred at 70°C for 3 hours. LCMS analysis confirmed the completion of the reaction. The mixture was cooled to room temperature, and deuterated water (5 mL) was added. The mixture was stirred for 10 minutes, and water and ethyl acetate were added. The mixture was separated by extraction. The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated to give the crude product, which was then purified on silica gel (petroleum ether / ethyl acetate = 2:1) to give the title compound (600 mg). LCMS (ESI) [M+Na] + =430.2.

[0742] Step 2: Synthesis of tert-butyl (R)-3-((S)-3-(3-(bromomethyl-d2)phenyl)-1-(tert-butoxy)-1-oxopropane-2-yl)pyrrolidine-1-carboxylate:

[0743] Dissolve tert-butyl (R)-3-((S)-1-(tert-butoxy)-3-(3-(hydroxymethyl-d2)phenyl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (600 mg, 1.47 mmol, 1 eq) in dichloromethane (5 mL) and cool to 0°C. Add triphenylphosphine (1158.47 mg, 4.42 mmol, 3 eq) and N-bromosuccinimide (786.09 mg, 4.42 mmol, 3 eq). Stirring is continued at room temperature for 2 hours. LCMS analysis indicates the reaction is complete. Add water and dichloromethane, extract, and separate the liquids. The organic phase is dried over anhydrous sodium sulfate, filtered, and the filtrate is concentrated to obtain the crude product, which is then purified on a silica gel plate (petroleum ether / ethyl acetate = 3:1) to obtain the title compound (400 mg). LCMS (ESI) [M+Na] + =492.7.

[0744] Step 3: Synthesis of 3,3',3"-((2S,2'S,2"S)-((nitrilotris(methylene-d2))tris(benzene-3,1-diyl))tris(3-(tert-butoxy)-3-oxopropane-1,2-diyl))(3R,3'R,3"R)-tris(tert-butyl pyrrolidine-1-carboxylate):

[0745] (R)-3-((S)-3-(3-(aminomethyl-d2)phenyl)-1-(tert-butoxy)-1-oxopropan-2-yl)pyrrolidine-1-carboxylic acid tert-butyl ester (30 mg, 0.07 mmol, 1 eq), (R)-3-((S)-3-(3-(bromomethyl-d2)phenyl)-1-(tert-butoxy)-1-oxopropan-2-yl)pyrrolidine-1-carboxylic acid tert-butyl ester (69.43 mg, 0.15 mmol, 2 eq) and potassium carbonate (30.6 mg, 0.22 mmol, 3 eq) were added to acetonitrile (1 mL), and the reaction was heated to 60°C and stirred for 4 hours. The reaction was completed by liquid chromatography-mass spectrometry. The reaction solution was filtered and the filtrate was directly purified on a silica gel plate (petroleum ether / ethyl acetate = 3:1) to obtain the title compound (55 mg); LCMS (ESI) [M+H] + =1185.8.

[0746] Step 4: Synthesis of (2S,2'S,2"S)-3,3',3"-((nitrilotris(methylene-d2))tris(benzene-3,1-diyl))tris(2-((R)-pyrrolidin-3-yl)propionic acid):

[0747] 3,3',3"-((2S,2'S,2"S)-((nitrilotris(methylene-d2))tris(benzene-3,1-diyl))tris(3-(tert-butoxy)-3-oxopropane-1,2-diyl))(3R,3'R,3"R)-tris(tert-butyl pyrrolidine-1-carboxylate) (50 mg, 0.04 mmol, 1 eq) was added to hydrochloric acid / 1,4-dioxane (3.0 mL, 4 M) and stirred at 25°C for 2 hours. The reaction was complete after HPLC-MS / MS analysis. The reaction mixture was filtered and the filter cake was lyophilized with acetonitrile and water to give the title compound (25.84 mg). LCMS (ESI) [MH] - =715.5; 1 H NMR(400MHz,D2O)δ7.38-7.27(m,6H),7.1-7.11(m,6H),3.61-3.51(m,3H),3.38-3.33(m,3H),3.28-3.16(m,3H),3.07-2.9 8(m,3H),2.91-2.87(m,3H),2.84-2.74(m,3H),2.68-2.58(m,3H),2.53-2.47(m,3H),2.15-2.09(m,3H),1.78-1.65(m,3H).

[0748] Example 18 (Compound 91)

[0749] Preparation of (2S,2'S,2"S)-3,3',3"-((nitrilotris(methylene))tris(benzene-3,1-diyl))tris(2-((R)-pyrrolidin-3-yl)propanoic acid-3,3-d2):

[0750] Step 1: Synthesis of tert-butyl (R)-3-((S)-1-((S)-4-benzyl-2-oxooxazolidin-3-yl)-3-(3-bromophenyl)-1-oxopropan-2-yl-3,3-d2)pyrrolidine-1-carboxylate:

[0751] Under nitrogen protection, a solution of lithium bis(trimethylsilyl)amide (7.08 mL, 7.08 mmol, 1.1 eq, 1.0 M) was added dropwise to a solution of tert-butyl (3R)-3-[2-[(4S)-4-benzyl-2-oxo-oxazolidin-3-yl]-2-oxo-ethyl]pyrrolidine-1-carboxylate (2.5 g, 6.44 mmol, 1 eq) in tetrahydrofuran (30 mL) in an ice bath. The mixture was stirred at 0°C for 30 minutes. A solution of 1-bromo-3-(chloromethyl-d2)benzene (1.47 g, 7.08 mmol, 1.1 eq) in tetrahydrofuran (2 mL) was then slowly added dropwise. After the addition was complete, the reaction temperature was slowly raised to room temperature and stirred for 16 hours. The reaction was complete after liquid chromatography-mass spectrometry. The reaction mixture was cooled in an ice-water bath, saturated aqueous ammonium chloride and water were added, and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated to obtain a crude product, which was purified by column chromatography to obtain the desired product (3.1 g). LCMS (ESI) [M+H-tert-butyl] + =503.2.

[0752] Step 2: Synthesis of (S)-3-(3-bromophenyl)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)propanoic acid-3,3-d2:

[0753] To a solution of tert-butyl (R)-3-((S)-1-((S)-4-benzyl-2-oxooxazolidin-3-yl)-3-(3-bromophenyl)-1-oxopropan-2-yl-3,3-d2)pyrrolidine-1-carboxylate (3 g, 5.28 mmol, 1 eq) in tetrahydrofuran (120 mL) was added hydrogen peroxide solution (275 mg, 8.1 mmol, 1.5 eq) and the mixture was cooled in an ice bath. An aqueous solution (10 mL) of lithium hydroxide (192 mg, 8.1 mmol, 1.5 eq) was added and the mixture was stirred at 25°C for 2.5 hours. Liquid chromatography-mass spectrometry confirmed the reaction was complete. The reaction solution was cooled to 0°C, and an aqueous solution (5 mL) of sodium bisulfite (1 g) and an aqueous solution (5 N) of sodium hydroxide were added to adjust the pH of the reaction solution to >12. Water and methyl tert-butyl ether were added, and the mixture was separated and extracted, with the organic phase discarded. Hydrochloric acid solution (5 N) was added to the aqueous phase to raise the pH to 3, and the mixture was extracted with methyl tert-butyl ether. The organic phase was washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain the title compound (1.8 g). LCMS (ESI) [M+H-Boc] + =300.20.

[0754] Step 3: Synthesis of tert-butyl (R)-3-((S)-3-(3-bromophenyl)-1-(tert-butoxy)-1-oxopropan-2-yl-3,3-d2)pyrrolidine-1-carboxylate:

[0755] (S)-3-(3-bromophenyl)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)propanoic acid-3,3-d 2( A solution of 1.8 g, 4.5 mmol, 1 eq) in 2-methyltetrahydrofuran (50 mL) was added, and O-tert-butyl-N,N'-diisopropylisourea (4.5 g, 22.5 mmol, 5 eq) was added. Under nitrogen, the mixture was heated to 65°C and stirred for 16 hours. The reaction was complete after liquid chromatography-mass spectrometry. The insoluble matter was filtered, and the filter cake was washed with methyl tert-butyl ether. The filtrate was concentrated to obtain the crude product, which was separated and purified by flash chromatography (silica gel, petroleum ether:ethyl acetate = 10:1) to obtain the title compound (0.6 g). LCMS (ESI) [M+H-2×tert-butyl] + =344.16.

[0756] Step 4: Synthesis of tert-butyl (R)-3-((S)-1-(tert-butoxy)-3-(3-formylphenyl)-1-oxopropan-2-yl-3,3-d2)pyrrolidine-1-carboxylate:

[0757] Dissolve tert-butyl (R)-3-((S)-3-(3-bromophenyl)-1-(tert-butoxy)-1-oxopropan-2-yl-3,3-d2)pyrrolidine-1-carboxylate (0.6 g, 1.31 mmol, 1 eq) in N,N-dimethylformamide (4 mL), add palladium acetate (59 mg, 0.26 mmol, 0.2 eq), 1,4-bis(diphenylphosphino)butane (112 mg, 0.26 mmol, 0.2 eq), N-formylsaccharin (691 mg, 3.296 mmol, 2.5 eq), sodium carbonate (418 mg, 3.94 mmol, 3 eq) and triethylsilane (305 mg, 2.63 mmol, 2 eq); heat to 75°C and stir under nitrogen for 16 hours. The reaction was complete after liquid chromatography-mass spectrometry analysis. The insoluble matter was filtered, the filter cake was washed with methyl tert-butyl ether, the filtrate was concentrated, and the product was purified by flash chromatography (Silica gel, petroleum ether:ethyl acetate = 10:1) to obtain the desired product (165 mg). LCMS (ESI) [M+H-Boc] + =306.35.

[0758] Step 5: Synthesis of 3,3',3"-((2S,2'S,2"S)-((nitrilotris(methylene))tris(benzene-3,1-diyl))tris(3-(tert-butoxy)-3-oxopropane-1,2-diyl-1,1-d2))(3R,3'R,3"R)-tris(tert-butyl pyrrolidine-1-carboxylate):

[0759] Dissolve tert-butyl (R)-3-((S)-1-(tert-butoxy)-3-(3-formylphenyl)-1-oxopropan-2-yl-3,3-d2)pyrrolidine-1-carboxylate (160 mg, 0.39 mmol, 1 eq) in tetrahydrofuran (5 mL). Add ammonia methanol (0.018 mL, 0.13 mmol, 0.33 eq, 7.0 M), sodium cyanoborohydride (61 mg, 0.97 mmol, 2.5 eq), and one drop of acetic acid. Stir overnight at room temperature. LCMS analysis indicates the reaction is complete. Saturated ammonium chloride solution is added to quench the reaction. Ethyl acetate and water are added, and the mixture is separated and extracted. The organic phase is dried over anhydrous sodium sulfate, filtered, and concentrated to give the crude product, which is then purified by column chromatography to yield the product (40 mg). LCMS (ESI) [M+H] + =1186.02.

[0760] Step 6: Synthesis of (2S,2'S,2"S)-3,3',3"-((nitrilotris(methylene))tris(benzene-3,1-diyl))tris(2-((R)-pyrrolidin-3-yl)propanoic acid-3,3-d2):

[0761] 3,3',3"-((2S,2'S,2"S)-((nitrilotris(methylene))tris(benzene-3,1-diyl))tris(3-(tert-butyloxy)-3-oxopropane-1,2-diyl-1,1-d2))(3R,3'R,3"R)-tris(tert-butyl pyrrolidine-1-carboxylate) (30 mg, 0.03 mmol, 1 eq) was dissolved in 1,4-dioxane (1 mL), and hydrochloric acid / 1,4-dioxane (1 mL, 4.0 M) was added; the mixture was stirred at room temperature overnight and the reaction was complete after liquid chromatography-mass spectrometry. The solvent was dried and the mixture was separated and purified by Prep-HPLC (C 18 ,10mmol / LNH4HCO3 in water,MeCN) to obtain the target compound (4.5mg). LCMS (ESI) [M+H] + =717.63; 1 H NMR(400MHz,Deuterium Oxide)δ8.37(s,2H),7.40-7.25(m,6H),7.24-7.09(m,6H),4.19(s,6H),3.56-3.43(m,3H),3.40-3.29 (m,3H),3.26-3.13(m,3H),3.00-2.87(m,3H),2.49-2.30(m,6H),2.15-1.97(m,3H),1.75-1.59(m,3H).

[0762] Example 19 (Compound 93)

[0763] Preparation of (2S,2'S)-3,3'-((((3-((S)-2-carboxy-2-((R)-pyrrolidin-3-yl)ethyl)benzyl)azanediyl)bis(methylene-d2))bis(3,1-phenylene))bis(2-((R)-pyrrolidin-3-yl)propanoic acid):

[0764] Step 1: Synthesis of tert-butyl (R)-3-((S)-1-(tert-butoxy)-3-(3-(hydroxymethyl-d2)phenyl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate:

[0765] Tert-butyl (R)-3-((S)-1-(tert-butoxy)-3-(3-(methoxycarbonyl)phenyl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (1.2 g, 2.77 mmol, 1 eq) was dissolved in a mixture of tetrahydrofuran (14.4 mL) and deuterated methanol (4.2 mL). Under nitrogen, sodium deuterated borohydride (695.19 mg, 16.61 mmol, 6 eq) was added portionwise. The mixture was stirred at 70°C for 3 hours. LCMS indicated that the reaction was complete. The reaction solution was cooled to room temperature, and heavy water (5 mL) was added and stirred for 10 minutes. Water and ethyl acetate were added, and the mixture was separated by extraction. The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated to give the crude product, which was purified by column chromatography (petroleum ether / ethyl acetate = 2:1) to give the title compound (600 mg). LCMS (ESI) [M+Na] + =430.2.

[0766] Step 2: Synthesis of tert-butyl (R)-3-((S)-3-(3-(bromomethyl-d2)phenyl)-1-(tert-butoxy)-1-oxopropane-2-yl)pyrrolidine-1-carboxylate:

[0767] Tert-butyl (R)-3-((S)-1-(tert-butoxy)-3-(3-(hydroxymethyl-d2)phenyl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (600 mg, 1.47 mmol, 1 eq) was dissolved in dichloromethane (5 mL) and cooled to 0°C. Triphenylphosphine (1158.47 mg, 4.42 mmol, 3 eq) and N-bromosuccinimide (786.09 mg, 4.42 mmol, 3 eq) were added under ice-cooling, and stirring was continued at room temperature for 2 hours. LCMS confirmed the reaction was complete, and water and dichloromethane were added. The mixture was separated by extraction, and the organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated to give the crude product, which was purified by column chromatography (petroleum ether / ethyl acetate = 3:1) to obtain the title compound (400 mg). LCMS (ESI) [M+Na] + =491.7.

[0768] Step 3: Synthesis of 3,3'-((2S,2'S)-((((3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)benzyl)azanediyl)bis(methylene-d2))bis(3,1-phenylene))bis(3-(tert-butoxy)-3-oxopropane-1,2-diyl))(3R,3'R)-bis(tert-butyl pyrrolidine-1-carboxylate):

[0769] (R)-tert-Butyl 3-((S)-3-(3-(aminomethyl)phenyl)-1-(tert-butoxy)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (40 mg, 0.1 mmol, 1 eq), tert-butyl 3-((S)-3-(3-(bromomethyl-d2)phenyl)-1-(tert-butoxy)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (93.03 mg, 0.2 mmol, 2 eq), and potassium carbonate (41 mg, 0.3 mmol, 3 eq) were added to acetonitrile (1 mL). The reaction solution was stirred at 60°C for 4 hours. LCMS determined that the reaction was complete. The reaction solution was filtered to obtain the crude product, which was then purified on a silica gel plate (petroleum ether / ethyl acetate = 3:1) to obtain (60 mg). LCMS (ESI) [M+Na] + =1205.6.

[0770] Step 4: Synthesis of (2S,2'S)-3,3'-((((3-((S)-2-carboxy-2-((R)-pyrrolidin-3-yl)ethyl)benzyl)azanediyl)bis(methylene-d2))bis(3,1-phenylene))bis(2-((R)-pyrrolidin-3-yl)propionic acid):

[0771] 3,3'-((2S,2'S)-((((3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)benzyl)azanediyl)bis(methylene-d2))bis(3,1-phenylene))bis(3-(tert-butoxy)-3-oxopropane-1,2-diyl))(3R,3'R)-bis(tert-butyl pyrrolidine-1-carboxylate) (70 mg, 0.06 mmol, 1 eq) was added to hydrochloric acid / 1,4-dioxane (3 mL, 4.0 M) and stirred at 25°C for 2 hours. The reaction was completed by LCMS. The reaction solution was filtered and lyophilized with acetonitrile and water to obtain the title compound (41.67 mg). LCMS (ESI) [M+H] + =715.2. 1HNMR(400MHZ,D2O)δ7.41-7.26(m,6H),7.15-7.11(m,6H),4.25-421(m,2H),3.59-353(m,3H)3.39-3.34(m,3H),3.27-3.17 (m,3H),3.08-2.98(m,3H),2.92-2.87(m,3H),2.85-2.64(m,6H),2.53-2.48(m,3H),2.21-2.02(m,3H),1.78-1.63(m,3H).

[0772] Example 20 (Compound 94)

[0773] Preparation of (2S,2'S)-3,3'-(((((3-((S)-2-carboxy-2-((R)-pyrrolidin-3-yl)ethyl)phenyl)methyl-d2)azanediyl)bis(methylene))bis(3,1-phenylene))bis(2-((R)-pyrrolidin-3-yl)propanoic acid) hydrochloride:

[0774] Step 1: Synthesis of tert-butyl (R)-3-((S)-1-(tert-butoxy)-3-(3-cyanophenyl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate:

[0775] Oxalyl chloride (365 mg) was added to acetonitrile (10 mL). Under nitrogen, the reaction mixture was cooled to 0°C and N,N-dimethylformamide (262 mg) was added. The mixture was stirred for 40 minutes. A solution of (R)-tert-butyl 3-((S)-1-(tert-butoxy)-3-(3-carbamoylphenyl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (1.0 g) in N,N-dimethylformamide (10 mL) was added. Stirring was continued for 3 hours. TLC confirmed the reaction was complete. Triethylamine (1 mL) was added, and the reaction mixture was dried to give the crude product. The product was purified by column chromatography (petroleum ether / ethyl acetate = 2:1) to obtain the title compound (500 mg). LCMS (ESI) [M+Na] + =423.2.

[0776] Step 2: Synthesis of tert-butyl (R)-3-((S)-3-(3-(aminomethyl-d2)phenyl)-1-(tert-butoxy)-1-oxopropane-2-yl)pyrrolidine-1-carboxylate:

[0777] Dissolve (R)-tert-butyl 3-((S)-1-(tert-butoxy)-3-(3-cyanophenyl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (190 mg) in deuterated methanol (2 mL), cool to 0°C, add anhydrous nickel chloride (30.74 mg) and sodium deuterated borohydride (107.68 mg), and under nitrogen, raise the temperature to 15°C and stir for 16 hours. LCMS analysis indicates the reaction is complete, and heavy water (1 mL) is added to quench the reaction. Stir for 10 minutes, then add ethyl acetate and water, extract, and separate the liquids. The organic phase is then dried and purified by column chromatography (dichloromethane / methanol = 10:1) to yield 90 mg. LCMS (ESI) [M+H] + =407.2.

[0778] Step 3: Synthesis of 3,3'-((2S,2'S)-(((((3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)phenyl)methyl-d2)azanediyl)bis(methylene))bis(3,1-phenylene))bis(3-(tert-butoxy)-3-oxopropane-1,2-diyl))(3R,3'R)-bis(tert-butyl pyrrolidine-1-carboxylate):

[0779] Tert-butyl (R)-3-((S)-3-(3-(aminomethyl-d2)phenyl)-1-(tert-butoxy)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (90 mg) and tert-butyl (R)-3-((S)-1-(tert-butoxy)-3-(3-formylphenyl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (223.31 mg) were dissolved in isopropanol (3 mL), sodium triacetylborohydride (232.03 mg) was added, and the mixture was stirred at 15°C for 16 hours. LCMS indicated that the reaction was complete, and water and ethyl acetate were added, followed by extraction. The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated to give the crude product, which was purified by column chromatography (petroleum ether / ethyl acetate = 2:1) to give the title compound (150 mg). LCMS (ESI) [M+Na] + =1203.6.

[0780] Step 4: Synthesis of (2S,2'S)-3,3'-(((((3-((S)-2-carboxy-2-((R)-pyrrolidin-3-yl)ethyl)phenyl)methyl-d2)azanediyl)bis(methylene))bis(3,1-phenylene))bis(2-((R)-pyrrolidin-3-yl)propionic acid) hydrochloride:

[0781] 3,3'-((2S,2'S)-(((((3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)phenyl)methyl-d2)azanediyl)bis(methylene))bis(3,1-phenylene))bis(3-(tert-butoxy)-3-oxopropane-1,2-diyl))(3R,3'R)-bis(tert-butyl pyrrolidine-1-carboxylate) (150 mg) was added to hydrochloric acid / 1,4-dioxane (5 mL, 4.0 M) and stirred at 25°C for 3 hours. The reaction mixture was filtered and lyophilized with acetonitrile and water to obtain the title compound (74 mg). LCMS(ESI)[MH] + =711.42; 1 H NMR(400MHz,MeOD)δ7.54(s,3H),7.45-7.34(m,9H),4.37-4.25(m,4H),3.61-3.53(m,3H),3.50-3.42(m,3H),3.32-3.26( m,3H),3.22-3.13(m,3H),3.10-2.98(m,6H),2.95-2.84(m,3H),2.67-2.58(m,3H),2.26-2.17(m,3H),1.94-1.79(m,3H).

[0782] Example 21 (Compound 97)

[0783] Preparation of (S)-3-(3-((3-((S)-2-carboxy-2-((R)-pyrrolidin-3-yl)ethyl)-N-(2-(3-((S)-2-carboxy-2-((R)-pyrrolidin-3-yl)ethyl)phenoxy)ethyl)benzamido)methyl)phenyl)-2-((R)-pyrrolidin-3-yl)propanoic acid:

[0784] Step 1: Synthesis of tert-butyl (R)-3-((S)-1-(tert-butoxy)-3-(3-((3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)-N-(2-(3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)phenoxy)ethyl)benzamido)methyl)phenyl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate:

[0785] (R)-tert-Butyl 3-((S)-1-(tert-butoxy)-3-(3-(((2-(3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)phenoxy)ethyl)amino)methyl)phenyl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (70 mg) was dissolved in N,N-dimethylformamide (5 mL), and 3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)benzoic acid (43 mg), O-(7-azabenzotriazol-1-yl)-N,N,N,N-tetramethyluronium hexafluorophosphate (32 mg) and N,N-diisopropoxyethylamine (17 mg) were added. The mixture was stirred at room temperature for 16 hours. The reaction was complete after liquid chromatography-mass spectrometry. The reaction solution was directly concentrated and purified by flash chromatography (Silica gel, petroleum ether:ethyl acetate = 1:8) to obtain the title compound (70 mg). LCMS (ESI) [M+H] + =1223.9.

[0786] Step 2: Synthesis of (S)-3-(3-((3-((S)-2-carboxy-2-((R)-pyrrolidin-3-yl)ethyl)-N-(2-(3-((S)-2-carboxy-2-((R)-pyrrolidin-3-yl)ethyl)phenoxy)ethyl)benzamido)methyl)phenyl)-2-((R)-pyrrolidin-3-yl)propanoic acid:

[0787] Tert-butyl (R)-3-((S)-1-(tert-butoxy)-3-(3-((3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)-N-(2-(3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)phenoxy)ethyl)benzamido)methyl)phenyl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (70 mg) was dissolved in hydrochloric acid / 1,4-dioxane (2 mL) and stirred at room temperature for 16 hours. The reaction was complete after liquid chromatography-mass spectrometry analysis, and the reaction solution was directly concentrated and purified by preparative chromatography to obtain the title compound (15.41 mg). LCMS (ESI) [M+H] + =755.4; 1H NMR(400MHz,Deuterium Oxide)δ7.32-7.15(m,4H),7.14-6.97(m,3H),6.94-6.74(m,3H),6.71-6.49(m,2H),4. 53(d,J=14.7Hz,2H),4.26(d,J=5.5Hz,1H),4.06(d,J=15.0Hz,1H),3.94(s,1H),3.82- 3.67(m,2H),3.32(dt,J=23.6,8.8Hz,5H),3.13(dt,J=18.8,9.5Hz,3H),2.73(dtd,J=4 1.0,21.0,9.8Hz,9H),2.34(t,J=11.9Hz,6H),2.02(d,J=9.2Hz,3H),1.72-1.55(m,3H).

[0788] Example 22 (Compound 98)

[0789] Preparation of (2S,2'S)-3,3'-((((3-((S)-2-carboxy-2-((R)-pyrrolidin-3-yl)ethyl-1,1-d2)benzyl)azanediyl)bis(methylene))bis(3,1-phenylene))bis(2-((R)-pyrrolidin-3-yl)propanoic acid):

[0790] Step 1: Synthesis of 3,3'-((2S,2'S)-((((3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl-1,1-d2)benzyl)azanediyl)bis(methylene))bis(3,1-phenylene))bis(3-(tert-butoxy)-3-oxopropane-1,2-diyl))(3R,3'R)-bis(tert-butyl pyrrolidine-1-carboxylate):

[0791] 3,3'-((2S,2'S)-((azanediylbis(methylene))bis(3,1-phenylene))bis(3-(tert-butoxy)-3-oxopropane-1,2-diyl))(3R,3'R)-bis(tert-butyl pyrrolidine-1-carboxylate) (117 mg, 0.15 mmol, 1 eq), (R)-tert-butyl 3-((S)-1-(tert-butoxy)-3-(3-formylphenyl)-1-oxopropan-2-yl-3,3-d2)pyrrolidine-1-carboxylate (60 mg, 0.15 mmol, 1 eq) and one drop of acetic acid were dissolved in tetrahydrofuran (2 mL) and stirred at room temperature for 0.5 hour. Sodium cyanoborohydride (18 mg, 0.30 mmol, 2 eq) was added and stirred at room temperature for 16 hours. Liquid chromatography-mass spectrometry confirmed the complete reaction. The reaction solution was concentrated, ethyl acetate was added, and the mixture was washed sequentially with saturated sodium bicarbonate aqueous solution and saturated brine. The organic phase was separated, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain the crude product, which was then separated and purified by flash chromatography (silica gel, dichloromethane:methanol = 40:1) to obtain the title compound (120 mg). LCMS (ESI) [M+H] + =1181.99.

[0792] Step 2: Synthesis of (2S,2'S)-3,3'-((((3-((S)-2-carboxy-2-((R)-pyrrolidin-3-yl)ethyl-1,1-d2)benzyl)azanediyl)bis(methylene))bis(3,1-phenylene))bis(2-((R)-pyrrolidin-3-yl)propionic acid):

[0793] 3,3'-((2S,2'S)-((((3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl-1,1-d2)benzyl)azanediyl)bis(methylene))bis(3,1-phenylene))bis(3-(tert-butoxy)-3-oxopropane-1,2-diyl))(3R,3'R)-bis(tert-butyl pyrrolidine-1-carboxylate) (110 mg, 0.09 mmol, 1 eq) was dissolved in 1,4-dioxane (2 mL), and hydrochloric acid / 1,4-dioxane (2 mL, 4.0 M) was added. The mixture was stirred at room temperature overnight and the reaction was complete after liquid chromatography-mass spectrometry monitoring. The solvent was dried and separated and purified by Prep-HPLC (C 18 ,10mmol / L NH4HCO3 in water,MeCN) to obtain the target compound (33mg). LCMS (ESI) [M+H] + =713.62; 1H NMR(400MHz,Deuterium Oxide)δ7.27(t,J=7.5Hz,3H),7.23-6.89(m,9H),3.59(s,6H),3.40-3.28(m,6H),3.17- 3.09(m,3H),2.88-2.69(m,7H),2.47-2.32(m,6H),2.10-1.97(m,3H),1.72-1.58(m,3H).

[0794] Example 23 (Compound 99)

[0795] Preparation of (S)-3-(3-(2-(3-((S)-2-carboxy-2-((R)-pyrrolidin-3-yl)ethyl)-N-(3-((S)-2-carboxy-2-((R)-pyrrolidin-3-yl)ethyl)benzyl)benzamido)ethyl)phenyl)-2-((R)-pyrrolidin-3-yl)propanoic acid:

[0796] Step 1: Synthesis of tert-butyl (R)-3-((S)-1-(tert-butoxy)-3-(3-(((3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)phenethyl)amino)methyl)phenyl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate:

[0797] Dissolve (R)-tert-butyl 3-((S)-1-(tert-butoxy)-3-(3-(2-((methylsulfonyl)oxy)ethyl)phenyl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (100 mg) in acetonitrile (10 mL), add (R)-tert-butyl 3-((S)-3-(3-(aminomethyl)phenyl)-1-(tert-butoxy)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (122 mg), and stir overnight at 75°C. LCMS analysis confirmed the reaction was complete. The solvent was dried and the product was purified by column chromatography to yield the title compound (70 mg). LCMS (ESI) [M+H] + =806.79.

[0798] Step 2: Synthesis of tert-butyl (R)-3-((S)-1-(tert-butoxy)-3-(3-((3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)-N-(3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)phenethyl)benzamido)methyl)phenyl)-1-oxopropane-2-yl)pyrrolidine-1-carboxylate:

[0799] Tert-butyl (R)-3-((S)-1-(tert-butoxy)-3-(3-(((3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)phenethyl)amino)methyl)phenyl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (70 mg) and 3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)benzoic acid (44 mg) were dissolved in N,N-dimethylformamide (0.5 mL), and O-(7-azabenzotriazol-1-yl)-N,N,N,N-tetramethyluronium hexafluorophosphate (50 mg) and triethylamine (34 mg) were added, and the reaction solution was stirred at room temperature for 16 hours. After TLC monitoring, the reaction was complete, ethyl acetate and water were added, and the liquid was separated. The organic phase was dried over anhydrous sodium sulfate, filtered, concentrated, and purified by column chromatography to obtain the target compound (75 mg). LCMS (ESI) [M+H-Boc] + =1107.97.

[0800] Step 3: Synthesis of (S)-3-(3-(2-(3-((S)-2-carboxy-2-((R)-pyrrolidin-3-yl)ethyl)-N-(3-((S)-2-carboxy-2-((R)-pyrrolidin-3-yl)ethyl)benzyl)benzamido)ethyl)phenyl)-2-((R)-pyrrolidin-3-yl)propanoic acid:

[0801] Tert-butyl (R)-3-((S)-1-(tert-butoxy)-3-(3-((3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)-N-(3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)phenethyl)benzamido)methyl)phenyl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (75 mg) was dissolved in 1,4-dioxane (2 mL), and hydrochloric acid / 1,4-dioxane (4.0 M, 2 mL) was added; stirred at room temperature for 16 hours; the reaction was complete after LCMS detection. The solvent was dried by spin drying and the product was separated and purified by Prep-HPLC (C 18 ,10mmol / LNH4HCO3 in water,MeCN) to obtain the target compound (17mg). LCMS (ESI) [M+H] + =739.4; 1H NMR(400MHz,Deuterium Oxide)δ7.33-6.83(m,10H),6.82-6.59(m,2H),3.70-3.07(m,12H),3.02 -2.50(m,12H),2.46-2.28(m,6H),2.10-1.99(m,3H),1.74-1.59(m,3H).

[0802] Example 24 (Compound 100)

[0803] Preparation of (S)-3-(3-(2-((3-((S)-2-carboxy-2-((R)-pyrrolidin-3-yl)ethyl)phenethyl)(2-(3-((S)-2-carboxy-2-((R)-pyrrolidin-3-yl)ethyl)phenoxy)ethyl)amino)-2-oxoethyl)phenyl)-2-((R)-pyrrolidin-3-yl)propanoic acid:

[0804] Step 1: Synthesis of tert-butyl (R)-3-((S)-1-(tert-butoxy)-3-(3-(2-hydroxyethyl)phenyl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate:

[0805] Dissolve tert-butyl (R)-3-((S)-1-(tert-butoxy)-1-oxo-3-(3-(2-oxoethyl)phenyl)propan-2-yl)pyrrolidine-1-carboxylate (300 mg) in ethanol (10 mL) and add sodium borohydride (55 mg). Stir at room temperature for 16 hours. LCMS analysis indicated that the reaction was complete, and the mixture was concentrated and purified by column chromatography to yield the title compound (280 mg). LCMS (ESI) [M+H] + =420.3.

[0806] Step 2: Synthesis of tert-butyl (R)-3-((S)-1-(tert-butoxy)-3-(3-(2-((methylsulfonyl)oxy)ethyl)phenyl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate:

[0807] Dissolve tert-butyl (R)-3-((S)-1-(tert-butoxy)-3-(3-(2-hydroxyethyl)phenyl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (280 mg) in dichloromethane (6 mL), add methanesulfonic anhydride (116 mg) and triethylamine (135 mg), and stir at room temperature for 16 hours. LCMS analysis confirmed the reaction was complete, and flash chromatography (silica gel, petroleum ether:ethyl acetate = 10:1) was used to obtain the title compound (300 mg). LCMS (ESI) [M+H] + =498.2.

[0808] Step 3: Synthesis of tert-butyl (R)-3-((S)-3-(3-(2-(((benzyloxy)carbonyl)amino)ethoxy)phenyl)-1-(tert-butoxy)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate:

[0809] Dissolve tert-butyl (R)-3-((S)-3-(3-hydroxyphenyl)-1-(tert-butoxy)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (2000 mg) in N,N-dimethylformamide (20 mL), add benzyl (2-bromoethyl)carbamate (3956 mg) and potassium carbonate (3530 mg), and stir at 90°C for 16 hours under nitrogen. LCMS analysis confirmed the completion of the reaction. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated. The title compound (1500 mg) was isolated and purified by flash chromatography (silica gel, petroleum ether:ethyl acetate = 2:1). LCMS (ESI) [M+H] + =569.3.

[0810] Step 4: Synthesis of tert-butyl (R)-3-((S)-3-(3-(2-aminoethoxy)phenyl)-1-(tert-butoxy)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate:

[0811] Dissolve tert-butyl (R)-3-((S)-3-(3-(2-(((benzyloxy)carbonyl)amino)ethoxy)phenyl)-1-(tert-butoxy)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (1500 mg) in methanol (10 mL), add palladium on carbon (150 mg), and stir at room temperature under a hydrogen atmosphere (hydrogen balloon) for 16 hours. LCMS analysis confirmed the completion of the reaction, and the reaction solution was directly concentrated and purified by flash chromatography (silica gel, petroleum ether:ethyl acetate = 1:1) to obtain the title compound (1100 mg). LCMS (ESI) [M+H] + =435.3.

[0812] Step 5: Synthesis of tert-butyl (R)-3-((S)-1-(tert-butoxy)-3-(3-(2-((2-(3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)phenoxy)ethyl)amino)ethyl)phenyl)-1-oxopropane-2-yl)pyrrolidine-1-carboxylate:

[0813] Tert-butyl (R)-3-((S)-3-(3-(2-aminoethoxy)phenyl)-1-(tert-butoxy)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (175 mg) was dissolved in acetonitrile (5 mL), and tert-butyl (R)-3-((S)-1-(tert-butoxy)-3-(3-(2-((methylsulfonyl)oxy)ethyl)phenyl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (200 mg) and potassium carbonate (156 mg) were added. The reaction mixture was stirred at 80°C for 16 hours. LCMS analysis confirmed the reaction was complete. The reaction mixture was cooled, concentrated, and purified by flash chromatography (Silica gel, petroleum ether:ethyl acetate = 1:1) to obtain the title compound (280 mg). LCMS (ESI) [M+H] + =836.6.

[0814] Step 6: Synthesis of tert-butyl (R)-3-((S)-1-(tert-butoxy)-3-(3-(2-((3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)phenethyl)(2-(3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)phenoxy)ethyl)amino)-2-oxoethyl)phenyl)-1-oxopropane-2-yl)pyrrolidine-1-carboxylate:

[0815] Tert-butyl (R)-3-((S)-1-(tert-butoxy)-3-(3-(2-((2-(3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)phenoxy)ethyl)amino)ethyl)phenyl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (140 mg) was dissolved in N,N-dimethylformamide. To the reaction mixture was added 2-(3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)phenyl)acetic acid (80 mg), O-(7-azabenzotriazol-1-yl)-N,N,N,N-tetramethyluronium hexafluorophosphate (64 mg), and diisopropylethylamine (32 mg); the reaction mixture was stirred at room temperature for 16 hours. LCMS analysis confirmed the completion of the reaction. Water and ethyl acetate were added to the reaction mixture, and the mixture was separated and extracted. The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated. The title compound (70 mg) was isolated and purified by flash chromatography (silica gel, petroleum ether:ethyl acetate = 1:8). LCMS (ESI) [M+H] + =1251.8.

[0816] Step 7: Synthesis of (S)-3-(3-(2-((3-((S)-2-carboxy-2-((R)-pyrrolidin-3-yl)ethyl)phenethyl)(2-(3-((S)-2-carboxy-2-((R)-pyrrolidin-3-yl)ethyl)phenoxy)ethyl)amino)-2-oxoethyl)phenyl)-2-((R)-pyrrolidin-3-yl)propanoic acid:

[0817] Tert-butyl (R)-3-((S)-1-(tert-butoxy)-3-(3-(2-((3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)phenethyl)(2-(3-((S)-3-(tert-butoxy)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-3-oxopropyl)phenoxy)ethyl)amino)-2-oxoethyl)phenyl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (70 mg) was dissolved in hydrochloric acid / 1,4-dioxane (4.0 M, 4 mL) and stirred at room temperature for 16 hours. The reaction was complete after liquid chromatography-mass spectrometry analysis, and the reaction solution was directly concentrated and purified by preparative chromatography to obtain the title compound (19.18 mg). LCMS (ESI) [M+H] + =783.4; 1 H NMR(400MHz,Deuterium Oxide)δ7.20-7.08(m,2H),7.07-6.98(m,2H),6.96-6.81(m,4H),6.74(d,J=7.6Hz,1H),6 .64(dt,J=6.7,2.8Hz,2H),6.61-6.54(m,1H),4.49(s,2H),4.08(t,J=5.2Hz,1H),3.79(d, J=5.6Hz,1H),3.63-3.50(m,3H),3.43(d,J=5.3Hz,1H),3.30-3.18(m,5H),3.14-2.97(m,5 H),2.75-2.49(m,10H),2.33-2.16(m,6H),1.94(qq,J=6.6,3.8Hz,3H),1.65-1.47(m,3H).

[0818] Example 25 (Compound 101)

[0819] Preparation of (2S,2'S,2"S)-3,3',3"-((nitrilotris(methylene))tris(benzo[b]thiophene-4,2-diyl))tris(2-((R)-pyrrolidin-3-yl)propanoic acid):

[0820] Step 1: Synthesis of (4-bromobenzo[b]thiophen-2-yl)methanol:

[0821] Dissolve 4-bromobenzothiophene-2-carboxylic acid (10 g, 38.9 mmol, 1.0 eq) in THF (100 mL). Slowly add a solution of borane in tetrahydrofuran (58.3 mL, 110 mmol, 1.5 eq, 1.0 M) at 0°C. Heat to 60°C under nitrogen and stir for 3 hours. LCMS indicates the reaction is complete. Quench the reaction with methanol, filter, and add water to the filtrate. Extract with ethyl acetate. Combine the organic phases, dry over anhydrous sodium sulfate, filter, and concentrate to obtain the crude product. Column chromatography (petroleum ether:ethyl acetate = 5:1) yields the title compound (4.0 g). LCMS (ESI) [M+H] + =242.6.

[0822] Step 2: Synthesis of 4-bromo-2-(bromomethyl)benzo[b]thiophene:

[0823] (4-Bromobenzo[b]thiophen-2-yl)methanol (4.0 g, 16.45 mmol, 1 eq) and hydrogen bromide (24 mL, 40%) were added to dichloromethane (32 mL). Under nitrogen, the mixture was heated to 46°C and stirred for 18 hours. LCMS confirmed the reaction was complete. Water and dichloromethane were added to the reaction mixture, and the mixture was separated by extraction. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain the crude product, which was purified by column chromatography (petroleum ether = 100%) to afford the title compound (3.7 g).

[0824] Step 3: Synthesis of tert-butyl (R)-3-((S)-1-((S)-4-benzyl-2-oxooxazolidin-3-yl)-3-(4-bromobenzo[b]thiophen-2-yl)-1-oxopropane-2-yl)pyrrolidine-1-carboxylate:

[0825] Tert-butyl (R)-3-(2-((S)-4-benzyl-2-oxooxazolidin-3-yl)-2-oxoethyl)pyrrolidine-1-carboxylate (7.16 g, 18.43 mmol, 1.2 eq) was dissolved in tetrahydrofuran (70 mL). Lithium hexamethyldisilazide (8.3 mL, 23.04 mmol, 1.5 eq) was added at 0°C and stirred for 0.5 h. 4-Bromo-2-(bromomethyl)benzo[b]thiophene (4.7 g, 15.36 mmol, 1.0 eq) was added and stirred for 2 h. LCMS confirmed the reaction was complete. The reaction mixture was poured into ice water and extracted with ethyl acetate. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to give the crude product, which was purified by flash chromatography (silica gel, petroleum ether:ethyl acetate = 5:1) to afford the desired product (3.7 g). LCMS (ESI) [M+H-Boc] + =513.4.

[0826] Step 4: Synthesis of (S)-3-(4-bromobenzo[b]thiophen-2-yl)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)propanoic acid:

[0827] Tert-butyl (R)-3-((S)-1-((S)-4-benzyl-2-oxooxazolidin-3-yl)-3-(4-bromobenzo[b]thiophen-2-yl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (8.5 g, 13.85 mmol, 1.0 eq) was added to tetrahydrofuran (90 mL), and hydrogen peroxide (22.4 mL, 30%) and an aqueous solution of lithium hydroxide (664 mg, 27.7 mmol, 2.0 eq) were added at 0°C. The reaction solution was warmed to room temperature and the reaction was continued for 2 hours. LCMS confirmed the reaction was complete and the product was quenched with sodium sulfate decahydrate. The pH was adjusted to 5-6 with dilute hydrochloric acid and extracted with ethyl acetate. The product was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to give the crude product, which was separated and purified by flash chromatography (silica gel, petroleum ether:ethyl acetate = 3:1) to give the title compound (6.0 g). LCMS (ESI) [M+H-tert-butyl] + =398.3

[0828] Step 5: Synthesis of tert-butyl (R)-3-((S)-3-(4-bromobenzo[b]thiophen-2-yl)-1-(tert-butoxy)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate:

[0829] (S)-3-(4-Bromobenzo[b]thiophen-2-yl)-2-((R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)propanoic acid (6 g, 13.2 mmol, 1.0 eq) was added to 2-methyltetrahydrofuran (70 mL), followed by O-tert-butyl-N,N'-diisopropylisourea (10.58 g, 52.82 mmol, 4.0 eq). The mixture was stirred at 70°C under nitrogen for 3 hours. LCMS confirmed the reaction was complete. Water was added to the reaction solution, which was extracted with ethyl acetate. The organic phase was washed sequentially with saturated sodium carbonate solution and saturated sodium chloride, dried over anhydrous sodium sulfate, filtered, and concentrated to give the crude product, which was then separated and purified by flash chromatography (silica gel, petroleum ether:ethyl acetate = 9:1) to yield the title compound (5.3 g). LCMS (ESI) [2M+Na] + =1041.2.

[0830] Step 6: Synthesis of tert-butyl (R)-3-((S)-1-(tert-butoxy)-3-(4-formylbenzo[b]thiophen-2-yl)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate:

[0831] Dissolve tert-butyl (R)-3-((S)-3-(4-bromobenzo[b]thiophen-2-yl)-1-(tert-butoxy)-1-oxopropan-2-yl)pyrrolidine-1-carboxylate (2.2 g, 4.31 mmol, 1.0 eq) in toluene (25 mL). Add palladium acetate (193.53 mg, 0.86...

Claims

1. A compound as represented by formula (I), or a pharmaceutically acceptable salt of the compound, having the following structure: in, is a single bond or a double bond; A is CR X ,P,P(O),N,C 6-12 Aryl, 5-14 membered heteroaryl, C 3-8 carbocyclic group, 5-18 membered heterocyclic group; the aryl, heteroaryl, carbocyclic group, heterocyclic group are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 Alkyl, C 1-3 substituted by an alkoxy substituent; when When it is a single bond; R X H, -OH, C 1-3 Alkoxy; when When it is a double bond; R X does not exist; L1 is selected from -C 1-3 Alkylene-C 6-10 Aryl-C 6-10 Aryl-C 1-3 Alkylene-, -C 1-3 Alkylene-C 6-10 Aryl-5-12 membered heteroaryl-C 1-3 Alkylene-, -C 1-3 Alkylene-5-12 membered heteroaryl-5-12 membered heteroaryl-C 1-3 Alkylene-, The C 1-3 The alkylene group is optionally substituted with one or more independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The aryl and heteroaryl groups are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 Alkoxy is substituted by a substituent; * is the connection end between L1 and A; L2 is selected from -C 1-3 Alkylene-C 6-10 Aryl-C 6-10 Aryl-C 1-3 Alkylene-, -C 1-3 Alkylene-C 6-10 Aryl-5-12 membered heteroaryl-C 1-3 Alkylene-, -C 1-3 Alkylene-5-12 membered heteroaryl-5-12 membered heteroaryl-C 1-3 Alkylene-, The C 1-3 The alkylene group is optionally substituted with one or more independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The aryl and heteroaryl groups are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 is substituted by an alkoxy substituent; * is the connecting end between L2 and A; R is selected from H, -C 1-3 Alkylene-C 6-10 Aryl, -C 1-3 Alkylene-5-12 membered heteroaryl, C 1-6 alkyl, The C 1-3 The alkylene group is optionally substituted with one or more independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The aryl and heteroaryl groups are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 Alkoxy, C 1-3 The substituent of aminoalkyl is substituted; the C 1-6 The alkyl group is optionally substituted with one or more independently selected from deuterium, halogen, oxo, carboxyl, -CN, -OH, -NH2, C 1-3 Alkyl, C 1-3 The substituent of the alkoxy group is substituted; * is the connecting end between R and A; L3 is selected from -C 1-6 Alkylene-, -C 2-6 Alkenylene-, -C 2-6 Alkynylidene-, -C 1-3 Alkylene-C 6-10 Aryl-C 6-10 Aryl-C 1-3 Alkylene-, -C 1-3 Alkylene-C 6-10 Aryl-5-12 membered heteroaryl-C 1-3 Alkylene-, -C 1-3 Alkylene-5-12 membered heteroaryl-C 6-10 Aryl-C 1-3 Alkylene-, -C 1-3 Alkylene-5-12 membered heteroaryl-5-12 membered heteroaryl-C 1-3 Alkylene-, The alkylene, alkenylene and alkynylene groups are optionally substituted by one or more groups independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The aryl and heteroaryl groups are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 Alkyl, C 1-3 is substituted by an alkoxy substituent; * is the connecting end between L3 and A; Rings W1, W2, and W3 are independently selected from C 6-12 Aryl, 5-12 membered heteroaryl, C 6-14 Cycloalkyl, 5-12 membered heterocyclic group; the aryl, heteroaryl, cycloalkyl, heterocyclic group are optionally substituted by one or more independently selected from deuterium, halogen, -CN, -OH, -NH2, -CHO, C 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Haloalkyl, C 1-3 Haloalkoxy, -N(C 1-3 Alkyl)2, -NH(C 1-3 Alkyl), -C(O)C 1-3 substituted by an alkyl substituent; Z 11 , Z 12 , Z 21 , Z 22 , Z 31 , Z 32 are independently selected from a bond, -O-, -S-, -NH-, -Se-, -C 1-4 Alkylene-, -C 1-8 Oxyalkylene-, -C 1-4 Thioalkylene-, -C 1-4 Azaalkylene-, -C 1-4 Selenylene-; the alkylene, oxaalkylene, thiaalkylene, azaalkylene, selenylene are optionally substituted by one or more selected from Z 41 Substituted by a substituent; Z 41 are independently selected from deuterium, halogen, oxo, thio, -CN, -OH, -NH2, C 1-3 Alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 haloalkoxy; or any two Z 41 Together with the atoms they are attached to form C 3-6 Cycloalkyl, 3-6 membered heterocyclyl, phenyl, 5-6 membered heteroaryl; R 31 , R 32 , R 33 are independently selected from hydrogen, deuterium, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Deuterated alkyl, C 1-6 Alkoxy, C 1- 6-haloalkoxy, C 1-6 deuterated alkoxy; h1, h2, h3, h4, h5, and h6 are independently 0, 1, and 2; R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 , R 11 , R 12 , R 41 , R 42 , R 43 , R 44 , R 45 , R 46 , R 47 , R 48 , R 49 are independently selected from H, deuterium, -CN, -OH, -NH2, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -N(C 1-3 Alkyl)2, -NH(C 1-3 alkyl); R 50 , R 51 , R 52 are independently selected from H, deuterium, C 1-6 Alkyl, C 2-6 Alkenyl, C 1-6 Alkoxy, -C 1-3 Alkylene OC 1-6 Alkyl, -C 1-3 Alkylene-OC(O)-C 1-6 Alkyl; the alkyl, alkenyl, alkoxy, alkylene are optionally substituted by one or more independently selected from deuterium, halogen, -OH, -NH2, -CN, oxo, C 1-3 Alkyl, C 1-3 substituted by an alkoxy substituent; The condition is that when A is N, R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 , R 11 , R 12 , R 41 , R 42 , R 43 , R 44 , R 45 , R 46 , R 47 , R 48 , R 49 When they are H at the same time, L1, L2, and L3 are not H at the same time. The condition is that when A is N and R is R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 , R 11 , R 12 , R 41 , R 42 When both are H, L1 and L2 are not * is the connection terminal between R and A; The condition is that it is not The heteroatoms in the heterocyclic group and heteroaryl group are independently selected from O, N or S, and the number of heteroatoms is 1, 2, 3 or 4; For example, R is a group including L3, L1, L2 and L3 are respectively 11 , Z 21 and Z 31 The group, and Z 11 , Z 21 and Z 31 There is only one group containing a double bond in -C(O)-; the double bond is, for example, a double bond between C and O in -C(O)-, or a double bond between C and S in -C(S)-; further preferably, Z 11 , Z 21 and Z 31 Different from each other, or Z 11 , Z 21 and Z 31 The two groups not containing a double bond in Z are identical, and the two identical groups contain -O-, -NH-, -S-, or -Se-, preferably, -O-; Still more preferably, Z 11 , Z 21 and Z 31 The molecular weight of Z is independently 14.0-107.1, preferably 14.0-60; preferably about 14, about 16, about 28, about 30, about 42, about 43, about 44, about 46, about 58, or about 60; still more preferably, Z 11 , Z 21 and Z 31 Selected from -CH2-, -CD2-, -CH2CH2-, -CD2CH2-, -C(O)-, -CH2C(O)-, -NHC(O)-, -OC(O)-, -CH2CH2O-, -OCH2C(O)-, -CH2OC(O)-, -CH2CH2CH2O-, -SC(O)-.

2. A compound represented by formula (I-1-P1), formula (I-1-P2), formula (I-1-P3) or formula (I-1-P4), or a pharmaceutically acceptable salt of the compound, in, is a single bond or a double bond; A is CR X , P, P(O) or N; when When it is a single bond; R X H, -OH, C 1-3 Alkoxy; when When it is a double bond; R X does not exist; L1 is selected from -C 1-3 Alkylene-C 6-10 Aryl-C 6-10 Aryl-C 1-3 Alkylene-, -C 1-3 Alkylene-C 6-10 Aryl-5-12 membered heteroaryl-C 1-3 Alkylene-, -C 1-3 Alkylene-5-12 membered heteroaryl-5-12 membered heteroaryl-C 1-3 Alkylene-, The C 1-3 The alkylene group is optionally substituted with one or more independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The aryl and heteroaryl groups are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 Alkoxy is substituted by a substituent; * is the connection end between L1 and A; L2 is selected from -C 1-3 Alkylene-C 6-10 Aryl-C 6-10 Aryl-C 1-3 Alkylene-, -C 1-3 Alkylene-C 6-10 Aryl-5-12 membered heteroaryl-C 1-3 Alkylene-, -C 1-3 Alkylene-5-12 membered heteroaryl-5-12 membered heteroaryl-C 1-3 Alkylene-, The C 1-3 The alkylene group is optionally substituted with one or more independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The aryl and heteroaryl groups are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 is substituted by an alkoxy substituent; * is the connecting end between L2 and A; R is selected from H, -C 1-3 Alkylene-C 6-10 Aryl, -C 1-3 Alkylene-5-12 membered heteroaryl, C 1-6 alkyl, The C 1-3 The alkylene group is optionally substituted with one or more independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The aryl and heteroaryl groups are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 Alkoxy, C 1-3 The substituent of aminoalkyl is substituted; the C 1-6 The alkyl group is optionally substituted with one or more independently selected from deuterium, halogen, oxo, carboxyl, -CN, -OH, -NH2, C 1-3 Alkyl, C 1-3 The substituent of the alkoxy group is substituted; * is the connecting end between R and A; L3 is selected from -C 1-6 Alkylene-, -C 2-6 Alkenylene-, -C 2-6 Alkynylidene-, -C 1-3 Alkylene-C 6-10 Aryl-C 6-10 Aryl-C 1-3 Alkylene-, -C 1-3 Alkylene-C 6-10 Aryl-5-12 membered heteroaryl-C 1-3 Alkylene-, -C 1-3 Alkylene-5-12 membered heteroaryl-C 6-10 Aryl-C 1-3 Alkylene-, -C 1-3 Alkylene-5-12 membered heteroaryl-5-12 membered heteroaryl-C 1-3 Alkylene-, The alkylene, alkenylene and alkynylene groups are optionally substituted by one or more groups independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The aryl and heteroaryl groups are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 Alkyl, C 1-3 is substituted by an alkoxy substituent; * is the connecting end between L3 and A; Rings W1, W2, and W3 are independently selected from C 6-12 Aryl, 5-12 membered heteroaryl, C 6-14 Cycloalkyl, 5-12 membered heterocyclic group; the aryl, heteroaryl, cycloalkyl, heterocyclic group are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 Alkyl, C 1-3 substituted by an alkoxy substituent; Z 11 , Z 12 , Z 21 , Z 22 , Z 31 , Z 32 are independently selected from a bond, -C 1-4 Alkylene-, -C 1-4 Oxyalkylene-; the alkylene and oxyalkylene are optionally substituted by one or more independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 Alkyl, C 1-3 substituted by an alkoxy substituent; R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 , R 11 , R 12 are independently selected from H and deuterium; The condition is that when A is N, L1, L2, and L3 are not simultaneously The condition is that when A is N and R is When L1 and L2 are not * is the connection terminal between R and A; The heteroatoms in the heterocyclic group and heteroaryl group are independently selected from O, N or S, and the number of heteroatoms is 1, 2 or 3; For example, in the compound represented by formula (I-1-P1), R is a group including L3, and L1, L2 and L3 are respectively 11 , Z 21 and Z 31 The group, and Z 11 , Z 21 and Z 31 There is only one group containing a double bond in -C(O)-; the double bond is, for example, a double bond between C and O in -C(O)-, or a double bond between C and S in -C(S)-; further preferably, Z 11 , Z 21 and Z 31 Different from each other, or Z 11 , Z 21 and Z 31 The two groups not containing a double bond in Z are identical, and the two identical groups contain -O-, -NH-, -S-, or -Se-, preferably, -O-; Still more preferably, Z 11 , Z 21 and Z 31 The molecular weight of Z is independently 14.0-107.1, preferably 14.0-60; preferably about 14, about 16, about 28, about 30, about 42, about 43, about 44, about 46, about 58, or about 60; still more preferably, Z 11 , Z 21 and Z 31 Selected from -CH2-, -CD2-, -CH2CH2-, -CD2CH2-, -C(O)-, -CH2C(O)-, -NHC(O)-, -OC(O)-, -CH2CH2O-, -OCH2C(O)-, -CH2OC(O)-, -CH2CH2CH2O-, -SC(O)-; or in, is a single bond or a double bond; A is CR X , P, P(O) or N; when When it is a single bond; R X H, -OH, C 1-3 Alkoxy; when When it is a double bond; R X does not exist; L1 is selected from -C 1-3 Alkylene-C 6-10 Aryl-C 6-10 Aryl-C 1-3 Alkylene-, -C 1-3 Alkylene-C 6-10 Aryl-5-12 membered heteroaryl-C 1-3 Alkylene-, -C 1-3 Alkylene-5-12 membered heteroaryl-5-12 membered heteroaryl-C 1-3 Alkylene-, The C 1-3 The alkylene group is optionally substituted with one or more independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The aryl and heteroaryl groups are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 Alkoxy is substituted by a substituent; * is the connection end between L1 and A; L2 is selected from -C 1-3 Alkylene-C 6-10 Aryl-C 6-10 Aryl-C 1-3 Alkylene-, -C 1-3 Alkylene-C 6-10 Aryl-5-12 membered heteroaryl-C 1-3 Alkylene-, -C 1-3 Alkylene-5-12 membered heteroaryl-5-12 membered heteroaryl-C 1-3 Alkylene-, The C 1-3 The alkylene group is optionally substituted with one or more independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The aryl and heteroaryl groups are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 is substituted by an alkoxy substituent; * is the connecting end between L2 and A; R is selected from H, -C 1-3 Alkylene-C 6-10 Aryl, -C 1-3 Alkylene-5-12 membered heteroaryl, C 1-6 alkyl, The C 1-3 The alkylene group is optionally substituted with one or more independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The aryl and heteroaryl groups are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 Alkoxy, C 1-3 The substituent of aminoalkyl is substituted; the C 1-6 The alkyl group is optionally substituted with one or more independently selected from deuterium, halogen, oxo, carboxyl, -CN, -OH, -NH2, C 1-3 Alkyl, C 1-3 The substituent of the alkoxy group is substituted; * is the connecting end between R and A; L3 is selected from -C 1-6 Alkylene-, -C 2-6 Alkenylene-, -C 2-6 Alkynylidene-, -C 1-3 Alkylene-C 6-10 Aryl-C 6-10 Aryl-C 1-3 Alkylene-, -C 1-3 Alkylene-C 6-10 Aryl-5-12 membered heteroaryl-C 1-3 Alkylene-, -C 1-3 Alkylene-5-12 membered heteroaryl-C 6-10 Aryl-C 1-3 Alkylene-, -C 1-3 Alkylene-5-12 membered heteroaryl-5-12 membered heteroaryl-C 1-3 Alkylene-, The alkylene, alkenylene and alkynylene groups are optionally substituted by one or more groups independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The aryl and heteroaryl groups are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 Alkyl, C 1-3 is substituted by an alkoxy substituent; * is the connecting end between L3 and A; Rings W1, W2, and W3 are independently selected from C 6-12 Aryl, 5-12 membered heteroaryl, C 6-14 Cycloalkyl, 5-12 membered heterocyclic group; the aryl, heteroaryl, cycloalkyl, heterocyclic group are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 Alkyl, C 1-3 substituted by an alkoxy substituent; Z 11 , Z 12 , Z 21 , Z 22 , Z 31 , Z 32 are independently selected from a bond, -C 1-4 Alkylene-, -C 1-4 Oxyalkylene-, -C 1-4 Thioalkylene-, -C 1- 4-azaalkylene-; the alkylene, oxaalkylene, thiaalkylene, and azaalkylene are optionally substituted by one or more independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 Alkyl, C 1-3 substituted by an alkoxy substituent; R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 , R 11 , R 12 are independently selected from H and deuterium; The condition is that when A is N, L1, L2, and L3 are not simultaneously The condition is that when A is N and R is When L1 and L2 are not * is the connection terminal between R and A; The heteroatoms in the heterocyclic group and heteroaryl group are independently selected from O, N or S, and the number of heteroatoms is 1, 2 or 3; For example, in the compound represented by formula (I-1-P2), R is a group including L3, and L1, L2 and L3 are respectively 11 , Z 21 and Z 31 The group, and Z 11 , Z 21 and Z 31 There is only one group containing a double bond in -C(O)-; the double bond is, for example, a double bond between C and O in -C(O)-, or a double bond between C and S in -C(S)-; further preferably, Z 11 , Z 21 and Z 31 Different from each other, or Z 11 , Z 21 and Z 31 The two groups not containing a double bond in Z are identical, and the two identical groups contain -O-, -NH-, -S-, or -Se-, preferably, -O-; Still more preferably, Z 11 , Z 21 and Z 31 The molecular weight of Z is independently 14.0-107.1, preferably 14.0-60; preferably about 14, about 16, about 28, about 30, about 42, about 43, about 44, about 46, about 58, or about 60; still more preferably, Z 11 , Z 21 and Z 31 Selected from -CH2-, -CD2-, -CH2CH2-, -CD2CH2-, -C(O)-, -CH2C(O)-, -NHC(O)-, -OC(O)-, -CH2CH2O-, -OCH2C(O)-, -CH2OC(O)-, -CH2CH2CH2O-, -SC(O)-; or in, is a single bond or a double bond; A is CR X ,P,P(O),N,C 6-12 aryl, 5-14 membered heteroaryl, 5-18 membered heterocyclic group; the aryl, heteroaryl, heterocyclic group are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 Alkyl, C 1-3 substituted by an alkoxy substituent; when When it is a single bond; R X H, -OH, C 1-3 Alkoxy; when When it is a double bond; R X does not exist; L1 is selected from -C 1-3 Alkylene-C 6-10 Aryl-C 6-10 Aryl-C 1-3 Alkylene-, -C 1-3 Alkylene-C 6-10 Aryl-5-12 membered heteroaryl-C 1-3 Alkylene-, -C 1-3 Alkylene-5-12 membered heteroaryl-5-12 membered heteroaryl-C 1-3 Alkylene-, The C 1-3 The alkylene group is optionally substituted with one or more independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The aryl and heteroaryl groups are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 Alkoxy is substituted by a substituent; * is the connection end between L1 and A; L2 is selected from -C 1-3 Alkylene-C 6-10 Aryl-C 6-10 Aryl-C 1-3 Alkylene-, -C 1-3 Alkylene-C 6-10 Aryl-5-12 membered heteroaryl-C 1-3 Alkylene-, -C 1-3 Alkylene-5-12 membered heteroaryl-5-12 membered heteroaryl-C 1-3 Alkylene-, The C 1-3 The alkylene group is optionally substituted with one or more independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The aryl and heteroaryl groups are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 is substituted by an alkoxy substituent; * is the connecting end between L2 and A; R is selected from H, -C 1-3 Alkylene-C 6-10 Aryl, -C 1-3 Alkylene-5-12 membered heteroaryl, C 1-6 alkyl, The C 1-3 The alkylene group is optionally substituted with one or more independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The aryl and heteroaryl groups are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 Alkoxy, C 1-3 The substituent of aminoalkyl is substituted; the C 1-6 The alkyl group is optionally substituted with one or more independently selected from deuterium, halogen, oxo, carboxyl, -CN, -OH, -NH2, C 1-3 Alkyl, C 1-3 The substituent of the alkoxy group is substituted; * is the connecting end between R and A; L3 is selected from -C 1-6 Alkylene-, -C 2-6 Alkenylene-, -C 2-6 Alkynylidene-, -C 1-3 Alkylene-C 6-10 Aryl-C 6-10 Aryl-C 1-3 Alkylene-, -C 1-3 Alkylene-C 6-10 Aryl-5-12 membered heteroaryl-C 1-3 Alkylene-, -C 1-3 Alkylene-5-12 membered heteroaryl-C 6-10 Aryl-C 1-3 Alkylene-, -C 1-3 Alkylene-5-12 membered heteroaryl-5-12 membered heteroaryl-C 1-3 Alkylene-, The alkylene, alkenylene and alkynylene groups are optionally substituted by one or more groups independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The aryl and heteroaryl groups are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 Alkyl, C 1-3 is substituted by an alkoxy substituent; * is the connecting end between L3 and A; Rings W1, W2, and W3 are independently selected from C 6-12 Aryl, 5-12 membered heteroaryl, C 6-14 Cycloalkyl, 5-12 membered heterocyclic group; the aryl, heteroaryl, cycloalkyl, heterocyclic group are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 Alkyl, C 1-3 substituted by an alkoxy substituent; Z 11 , Z 12 , Z 21 , Z 22 , Z 31 , Z 32 are independently selected from a bond, -C 1-4 Alkylene-, -C 1-4 Oxyalkylene-, -C 1-4 Thioalkylene-, -C 1- 4-azaalkylene-; the alkylene, oxaalkylene, thiaalkylene, and azaalkylene are optionally substituted by one or more independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 Alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 substituted by a haloalkoxy substituent; R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 , R 11 , R 12 are independently selected from H and deuterium; The condition is that when A is N, R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 , R 11 , R 12 When they are H at the same time, L1, L2, and L3 are not H at the same time. The condition is that when A is N and R is R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 , R 11 , R 12 When both are H, L1 and L2 are not * is the connection terminal between R and A; The condition is that it is not The heteroatoms in the heterocyclic group and heteroaryl group are independently selected from O, N or S, and the number of heteroatoms is 1, 2, 3 or 4; For example, in the compound represented by formula (I-1-P3), R is a group including L3, and L1, L2 and L3 are respectively 11 , Z 21 and Z 31 The group, and Z 11 , Z 21 and Z 31 There is only one group containing a double bond in -C(O)-; the double bond is, for example, a double bond between C and O in -C(O)-, or a double bond between C and S in -C(S)-; further preferably, Z 11 , Z 21 and Z 31 Different from each other, or Z 11 , Z 21 and Z 31 The two groups not containing a double bond in Z are identical, and the two identical groups contain -O-, -NH-, -S-, or -Se-, preferably, -O-; Still more preferably, Z 11 , Z 21 and Z 31 The molecular weight of Z is independently 14.0-107.1, preferably 14.0-60; preferably about 14, about 16, about 28, about 30, about 42, about 43, about 44, about 46, about 58, or about 60; still more preferably, Z 11 , Z 21 and Z 31 Selected from -CH2-, -CD2-, -CH2CH2-, -CD2CH2-, -C(O)-, -CH2C(O)-, -NHC(O)-, -OC(O)-, -CH2CH2O-, -OCH2C(O)-, -CH2OC(O)-, -CH2CH2CH2O-, -SC(O)-; Alternatively, a compound represented by the following formula (I-1-P4), or a pharmaceutically acceptable salt of the compound: in, is a single bond or a double bond; A is CR X ,P,P(O),N,C 6-12 aryl, 5-14 membered heteroaryl, 5-18 membered heterocyclic group; the aryl, heteroaryl, heterocyclic group are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 Alkyl, C 1-3 substituted by an alkoxy substituent; when When it is a single bond; R X H, -OH, C 1-3 Alkoxy; when When it is a double bond; R X does not exist; L1 is selected from -C 1-3 Alkylene-C 6-10 Aryl-C 6-10 Aryl-C 1-3 Alkylene-, -C 1-3 Alkylene-C 6-10 Aryl-5-12 membered heteroaryl-C 1-3 Alkylene-, -C 1-3 Alkylene-5-12 membered heteroaryl-5-12 membered heteroaryl-C 1-3 Alkylene-, The C 1-3 The alkylene group is optionally substituted with one or more independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The aryl and heteroaryl groups are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 Alkoxy is substituted by a substituent; * is the connection end between L1 and A; L2 is selected from -C 1-3 Alkylene-C 6-10 Aryl-C 6-10 Aryl-C 1-3 Alkylene-, -C 1-3 Alkylene-C 6-10 Aryl-5-12 membered heteroaryl-C 1-3 Alkylene-, -C 1-3 Alkylene-5-12 membered heteroaryl-5-12 membered heteroaryl-C 1-3 Alkylene-, The C 1-3 The alkylene group is optionally substituted with one or more independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The aryl and heteroaryl groups are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 is substituted by an alkoxy substituent; * is the connecting end between L2 and A; R is selected from H, -C 1-3 Alkylene-C 6-10 Aryl, -C 1-3 Alkylene-5-12 membered heteroaryl, C 1-6 alkyl, The C 1-3 The alkylene group is optionally substituted with one or more independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The aryl and heteroaryl groups are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 Alkoxy, C 1-3 The substituent of aminoalkyl is substituted; the C 1-6 The alkyl group is optionally substituted with one or more independently selected from deuterium, halogen, oxo, carboxyl, -CN, -OH, -NH2, C 1-3 Alkyl, C 1-3 The substituent of the alkoxy group is substituted; * is the connecting end between R and A; L3 is selected from -C 1-6 Alkylene-, -C 2-6 Alkenylene-, -C 2-6 Alkynylidene-, -C 1-3 Alkylene-C 6-10 Aryl-C 6-10 Aryl-C 1-3 Alkylene-, -C 1-3 Alkylene-C 6-10 Aryl-5-12 membered heteroaryl-C 1-3 Alkylene-, -C 1-3 Alkylene-5-12 membered heteroaryl-C 6-10 Aryl-C 1-3 Alkylene-, -C 1-3 Alkylene-5-12 membered heteroaryl-5-12 membered heteroaryl-C 1-3 Alkylene-, The alkylene, alkenylene and alkynylene groups are optionally substituted by one or more groups independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The aryl and heteroaryl groups are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 Alkyl, C 1-3 is substituted by an alkoxy substituent; * is the connecting end between L3 and A; Rings W1, W2, and W3 are independently selected from C 6-12 Aryl, 5-12 membered heteroaryl, C 6-14 Cycloalkyl, 5-12 membered heterocyclic group; the aryl, heteroaryl, cycloalkyl, heterocyclic group are optionally substituted by one or more independently selected from deuterium, halogen, -CN, -OH, -NH2, -CHO, C 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Haloalkyl, C 1-3 Haloalkoxy, -N(C 1-3 Alkyl)2, -NH(C 1-3 Alkyl), -C(O)C 1-3 substituted by an alkyl substituent; Z 11 , Z 12 , Z 21 , Z 22 , Z 31 , Z 32 are independently selected from a bond, -O-, -S-, -NH-, -Se-, -C 1-4 Alkylene-, -C 1-8 Oxyalkylene-, -C 1-4 Thioalkylene-, -C 1-4 Azaalkylene-, -C 1-4 Selenylene-; the alkylene, oxaalkylene, thiaalkylene, azaalkylene, selenylene are optionally substituted by one or more selected from Z 41 Substituted by a substituent; Z 41 are independently selected from deuterium, halogen, oxo, thio, -CN, -OH, -NH2, C 1-3 Alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 haloalkoxy; or any two Z 41 Together with the atoms they are attached to form C 3-6 Cycloalkyl, 3-6 membered heterocyclyl, phenyl, 5-6 membered heteroaryl; R 31 , R 32 , R 33 are independently selected from hydrogen, deuterium, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Deuterated alkyl, C 1-6 Alkoxy, C 1- 6-haloalkoxy, C 1-6 deuterated alkoxy; h1, h2, h3, h4, h5, and h6 are independently 0, 1, and 2; R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 , R 11 , R 12 are independently selected from H and deuterium; The condition is that when A is N, R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 , R 11 , R 12 When they are H at the same time, L1, L2, and L3 are not H at the same time. The condition is that when A is N and R is R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 , R 11 , R 12 When both are H, L1 and L2 are not * is the connection terminal between R and A; The condition is that it is not The heteroatoms in the heterocyclic group and heteroaryl group are independently selected from O, N or S, and the number of heteroatoms is 1, 2, 3 or 4; For example, in the compound represented by formula (I-1-P4), R is a group including L3, and L1, L2 and L3 are respectively 11 , Z 21 and Z 31 The group, and Z 11 , Z 21 and Z 31 There is only one group containing a double bond in -C(O)-; the double bond is, for example, a double bond between C and O in -C(O)-, or a double bond between C and S in -C(S)-; further preferably, Z 11 , Z 21 and Z 31 Different from each other, or Z 11 , Z 21 and Z 31 The two groups not containing a double bond in Z are identical, and the two identical groups contain -O-, -NH-, -S-, or -Se-, preferably, -O-; Still more preferably, Z 11 , Z 21 and Z 31 The molecular weight of Z is independently 14.0-107.1, preferably 14.0-60; preferably about 14, about 16, about 28, about 30, about 42, about 43, about 44, about 46, about 58, or about 60; still more preferably, Z 11 , Z 21 and Z 31 Selected from -CH2-, -CD2-, -CH2CH2-, -CD2CH2-, -C(O)-, -CH2C(O)-, -NHC(O)-, -OC(O)-, -CH2CH2O-, -OCH2C(O)-, -CH2OC(O)-, -CH2CH2CH2O-, -SC(O)-.

3. The compound according to any one of claims 1 to 2, or a pharmaceutically acceptable salt of the compound, characterized in that: A is CR X , P, P(O), N, phenyl, 5-6 membered heterocyclic group, 12 membered heterocyclic group; the heteroatom in the heterocyclic group is N, and the number of heteroatoms is 1, 2, 3 or 4; Preferably, A is CR X 、P、P(O)、N、phenyl、piperazinyl、 or A is CR X , P, P(O), N, Preferably A is N, or A is N; or A is P(O); or A is selected from CR X ; R X is H, -OH, methoxy; or A is selected from C-OH, C-OCH3; or A is a 6-membered heterocyclic group; preferably, A is a piperazinyl group; preferably or A is phenyl; preferably 4. The compound according to any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof, characterized in that: L1 is selected from -C 1- 3-Alkylene-phenyl-phenyl-C 1-3 Alkylene-, -C 1-3 Alkylene-5-6 membered heteroaryl-5-6 membered heteroaryl-C 1-3 Alkylene-, The C 1-3 The alkylene group is optionally substituted with one or more independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The phenyl and heteroaryl groups are optionally substituted by one or more groups independently selected from halogen, -CN, C 1-3 Alkoxy is substituted by a substituent; * is the connecting end between L1 and N; Preferably, L1 is selected from -methylene-phenyl-phenyl-methylene-, -ethylene-phenyl-phenyl-ethylene-, -methylene-5-6-membered heteroaryl-5-6-membered heteroaryl-methylene-, -ethylene-5-6-membered heteroaryl-5-6-membered heteroaryl-ethylene-, The methylene and ethylene groups are optionally replaced by one or more groups independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The phenyl and heteroaryl groups are optionally substituted by one or more groups independently selected from halogen, -CN, C 1-3 Alkoxy is substituted by a substituent; * is the connecting end between L1 and A; or L1 is selected from -methylene-phenyl-phenyl-methylene-, -methylene-6-membered heteroaryl-6-membered heteroaryl-methylene-, The methylene group is optionally replaced by one or more independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The phenyl and heteroaryl groups are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 Alkoxy is substituted by a substituent; * is the connecting end between L1 and A; or L1 is selected from -methylene-phenyl-phenyl-methylene-, -methylene-pyridyl-pyridyl-methylene-, * is the L1 and A connection terminal; or L1 is selected from * is the L1 and A connection terminal; or L1 is * is the L1 and A connection terminal; or L1 is selected from *Indicates the A connection terminal.

5. The compound according to any one of claims 1 to 4, or a pharmaceutically acceptable salt of the compound, characterized in that: L2 is selected from -C 1- 3-Alkylene-phenyl-phenyl-C 1-3 Alkylene-, -C 1-3 Alkylene-5-6 membered heteroaryl-5-6 membered heteroaryl-C 1-3 Alkylene-, The C 1-3 The alkylene group is optionally substituted with one or more independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The phenyl and heteroaryl groups are optionally substituted by one or more groups independently selected from halogen, -CN, C 1-3 Alkoxy is substituted by a substituent; * is the connection terminal between L2 and N; Preferably, L2 is selected from -methylene-phenyl-phenyl-methylene-, -ethylene-phenyl-phenyl-ethylene-, -methylene-5-6-membered heteroaryl-5-6-membered heteroaryl-methylene-, -ethylene-5-6-membered heteroaryl-5-6-membered heteroaryl-ethylene-, The methylene and ethylene groups are optionally replaced by one or more groups independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The phenyl and heteroaryl groups are optionally substituted by one or more groups independently selected from halogen, -CN, C 1-3 Alkoxy is substituted by a substituent; * is the connecting end between L2 and A; or L2 is selected from -methylene-phenyl-phenyl-methylene-, -methylene-6-membered heteroaryl-6-membered heteroaryl-methylene-, The methylene group is optionally replaced by one or more independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The phenyl and heteroaryl groups are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 Alkoxy is substituted by a substituent; * is the connecting end between L2 and A; or L2 is selected from -methylene-phenyl-phenyl-methylene-, -methylene-pyridyl-pyridyl-methylene-, * is the connection terminal between L2 and A; or L2 is selected from * is the connection terminal between L2 and A; or L2 is * is the connection terminal between L2 and A; or L2 is selected from *Indicates the A connection terminal.

6. The compound according to any one of claims 1 to 5, or a pharmaceutically acceptable salt thereof, characterized in that: Rings W1, W2, and W3 are each independently selected from C 6-12 Aryl, 5-12 membered heteroaryl, C 6-14 Cycloalkyl; the aryl, heteroaryl, cycloalkyl are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 Alkyl, C 1-3 substituted by an alkoxy substituent; Preferably, rings W1, W2, and W3 are each independently selected from C 6-10 Aryl, 5-10 membered heteroaryl, C 6-10 Cycloalkyl; the aryl, heteroaryl, cycloalkyl is optionally substituted by one or more substituents independently selected from fluorine, chlorine, bromine, -CN, methyl, ethyl, methoxy, ethoxy; or Rings W1, W2, and W3 are each independently selected from phenyl, naphthyl, 8-10 membered bicyclic heteroaryl, C 8-10 bicyclic cycloalkyl, 5-6 membered monocyclic heteroaryl; the phenyl, naphthyl, heteroaryl, cycloalkyl are optionally substituted by one or more independently selected from halogen, -CN, C 1-3 Alkyl, C 1-3 substituted by an alkoxy substituent; or Ring W1, W2, and W3 are independently selected from phenyl, naphthyl, 5-membered / 5-membered fused heteroaryl, 5-membered / 6-membered fused heteroaryl, 6-membered / 5-membered fused heteroaryl, 6-membered / 6-membered fused heteroaryl, 4-membered / 6-membered spirocycloalkyl, 6-membered / 4-membered spirocycloalkyl, 5-membered / 5-membered spirocycloalkyl, 5-membered / 6-membered spirocycloalkyl, 6-membered / 5-membered spirocycloalkyl, 6-membered / 6-membered spirocycloalkyl, and 5-6-membered monocyclic heteroaryl; the phenyl, naphthyl, fused heteroaryl, spirocycloalkyl, and monocyclic heteroaryl are optionally substituted with one or more substituents independently selected from fluorine, chlorine, bromine, -CN, methyl, ethyl, methoxy, and ethoxy; or Ring W1, W2, and W3 are independently selected from phenyl and 5-6-membered monocyclic heteroaryl; the phenyl and heteroaryl are optionally substituted by one or more independently selected from deuterium, halogen, -CN, -OH, -NH2, -CHO, C 1-3 Alkyl, C 1-3 Alkoxy, -N(C 1-3 Alkyl)2, -NH(C 1-3 Alkyl), -C(O)C 1-3 The heteroaryl group is substituted by a substituent of an alkyl group; the heteroatom in the heteroaryl group is O, N or S, and the number of heteroatoms is 1 or 2; or Rings W1, W2, and W3 are each independently selected from the following optionally substituted groups: The optional substitution refers to being unsubstituted or being substituted by one or more independently selected from deuterium, halogen, -CN, -OH, -NH2, -CHO, C 1-3 Alkyl, C 1-3 Alkoxy, -N(C 1-3 Alkyl)2, -NH(C 1-3 Alkyl), -C(O)C 1-3 substituted by an alkyl substituent; or Rings W1, W2, and W3 are each independently selected from the following optionally substituted groups: The optional substitution means being unsubstituted or being substituted by one or more substituents independently selected from deuterium, fluorine, chlorine, bromine, -CN, -OH, -NH2, -CHO, methyl, ethyl, methoxy, ethoxy, -N(CH3)2, -NH(CH3), -C(O)CH3; or Ring W1, W2, W3 are independently selected from phenyl and thienyl; the phenyl and thienyl are optionally substituted by one or more substituents independently selected from deuterium, fluorine, chlorine, bromine, -CN, -OH, -NH2, -CHO, methyl, ethyl, methoxy, ethoxy, -N(CH3)2, -NH(CH3), -C(O)CH3; or Rings W1, W2, and W3 are each independently selected from the following optionally substituted groups: The optional substitution means being unsubstituted or being substituted by one or more substituents independently selected from deuterium, fluorine, chlorine, bromine, -CN, -OH, -NH2, -CHO, methyl, ethyl, methoxy, ethoxy, -N(CH3)2, -NH(CH3), -C(O)CH3; or Ring W1, W2, W3 are independently selected from phenyl; the phenyl is optionally substituted by one or more substituents independently selected from fluorine, chlorine, bromine, methyl, ethyl, methoxy, ethoxy; or W1, W2, and W3 are independently selected from 7. The compound according to any one of claims 1 to 6, or a pharmaceutically acceptable salt thereof, characterized in that: R is selected from H, -C 1-3 Alkylene-C 6-10 Aryl, -C 1-3 Alkylene-5-10 membered heteroaryl, C 1-6 alkyl, The C 1-3 The alkylene group is optionally substituted with one or more substituents independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2; the aryl and heteroaryl groups are optionally substituted with one or more substituents independently selected from deuterium, halogen, -CN, methoxy, C 1-3 The substituent of aminoalkyl is substituted; the C 1- 6 alkyl is optionally substituted by one or more independently selected from deuterium, halogen, oxo, carboxyl, -CN, -OH, -NH2, C 1-3 Alkyl, C 1-3 The substituent of the alkoxy group is substituted; * is the connecting end between R and A; Preferably, R is selected from H, -methylene-phenyl, -ethylene-phenyl, -methylene-5-6 membered heteroaryl, -ethylene-5-6 membered heteroaryl, C 1-6 alkyl, The methylene and ethylene groups are optionally substituted by one or more substituents independently selected from halogen, oxo, -CN, -OH, and -NH2; the phenyl and heteroaryl groups are optionally substituted by one or more substituents independently selected from halogen, -CN, methoxy, Substituents substituted; said C 1-6 The alkyl group is optionally substituted by one or more substituents independently selected from halogen, oxo, carboxyl, -CN, -OH, -NH2; * is the connecting end of R and A; or R is selected from H, -methylene-phenyl, -ethylene-phenyl, -methylene-pyridyl, -ethylene-pyridyl, methyl, ethyl, n-propyl, isopropyl, n-butyl, n-pentyl, n-hexyl, The phenyl and pyridyl groups are optionally substituted by one or more groups independently selected from halogen, methoxy, The methyl, ethyl, n-propyl, isopropyl, n-butyl, n-pentyl and n-hexyl groups are optionally substituted by one or more substituents independently selected from carboxyl and -NH2; * is the connecting end of R and A; or R is selected from H, -C 1-3 Alkylene-phenyl, -C 1-3 Alkylene-5-6 membered heteroaryl, C 1-6 Alkyl; the C 1-3 The alkylene group is optionally substituted by one or more independently selected from halogen, oxo, -CN, -OH, -NH2, C 1-3 The phenyl and heteroaryl groups are optionally substituted by one or more groups independently selected from halogen, -CN, C 1-3 Alkoxy, C 1-3 The substituent of aminoalkyl is substituted; the C 1-6 Alkyl is optionally substituted with one or more substituents each independently selected from halogen, carboxyl, -NH2, methyl, methoxy; or R is selected from H, * is the connection terminal between R and A; or R is selected from H, Best Best Best Best Best Wherein, * is the end connected to A; or R is selected from H, *Indicates the A connection terminal.

8. The compound according to any one of claims 1 to 7, or a pharmaceutically acceptable salt thereof, characterized in that: L3 is selected from -C 1- 6-alkylene-, -C 2-6 Alkyne-, -methylene-phenyl-phenyl-methylene-, -ethylene-phenyl-phenyl-ethylene-, -methylene-5-6-membered heteroaryl-5-6-membered heteroaryl-methylene-, -ethylene-5-6-membered heteroaryl-5-6-membered heteroaryl-ethylene-, The alkylene, methylene, ethylene, alkynylene groups are optionally substituted by one or more substituents independently selected from halogen, oxo, -CN, -OH, -NH2, methyl, ethyl; the phenyl and heteroaryl groups are optionally substituted by one or more substituents independently selected from halogen, -CN, methyl, ethyl, methoxy, ethoxy; * is the connecting end of L3 and A; Preferably, L3 is selected from -C 1-6 Alkylene-, -C 2-6 Alkyne-, -methylene-phenyl-phenyl-methylene-, -methylene-6-membered heteroaryl-6-membered heteroaryl-methylene-, The alkylene group and the methylene group are optionally substituted by one or more substituents independently selected from fluorine, chlorine, bromine, oxo, -CN, -OH, and -NH2; the phenyl group and the heteroaryl group are optionally substituted by one or more substituents independently selected from fluorine, chlorine, bromine, -CN, methyl, ethyl, methoxy, and ethoxy; * is the connecting end of L3 and A; or L3 is selected from methylene, ethylene, n-propylene, isopropylene, n-butylene, n-pentylene, n-hexylene, n-propynylene, n-butynylene, n-pentynylene, n-hexynylene, -methylene-phenyl-phenyl-methylene-, -methylene-pyridyl-pyridyl-methylene-, * is the L3 and A connection terminal; or L3 is selected from * is the L3 and A connection terminal; or L3 is selected from *Indicates the A connection terminal.

9. The compound according to any one of claims 1 to 8, or a pharmaceutically acceptable salt thereof, characterized in that: Z 11 , Z 12 , Z 21 , Z 22 , Z 31 , Z 32 are independently selected from a bond, -O-, -S-, -NH-, -Se-, -C 1-4 Alkylene-, -C 1-6 Oxyalkylene-, -C 1-4 Thioalkylene-, -C 1-4 Azaalkylene-, -C 1-4 Selenylene-; the alkylene, oxaalkylene, thiaalkylene, azaalkylene, selenylene are optionally substituted by one or more selected from Z 41 Substituted by a substituent; Z 41 are independently selected from deuterium, halogen (e.g., fluorine, chlorine), oxo, thio, -CN, -OH, -NH2, C 1-3 Alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 haloalkoxy; or any two Z 41 Together with the atoms they are attached to form C 3-6 Cycloalkyl, 3-6 membered heterocyclic group (e.g. oxetanyl); the heteroatom in the heterocyclic group is O, N or S, and the number of heteroatoms is 1 or 2; Preferably, Z 11 , Z 12 , Z 21 , Z 22 , Z 31 , Z 32 are independently selected from a bond, -C 1-3 Alkylene-, -C 1-3 Oxyalkylene-, -C 1-3 Thioalkylene-, -C 1-3 Azaalkylene-; the alkylene, oxaalkylene, thiaalkylene, azaalkylene are optionally substituted with one or more substituents independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, methyl, methoxy; preferably, the alkylene, oxaalkylene, thiaalkylene, azaalkylene are optionally substituted with one or more substituents independently selected from deuterium, oxo; or Z 11 , Z 12 , Z 21 , Z 22 , Z 31 , Z 32 Each independently selected from -C 1-2 Alkylene-, -C 1-2 Oxyalkylene-, -C 1-2 Thioalkylene-, -C 1-2 Azaalkylene-; the alkylene, oxaalkylene, thiaalkylene, azaalkylene are optionally substituted by one or more substituents independently selected from deuterium and oxo; or Z 11 , Z 12 , Z 21 , Z 22 , Z 31 , Z 32 are independently selected from a bond, -C 1-3 Alkylene-, -C 1-3 Oxoalkylene-; the alkylene and oxoalkylene are optionally substituted with one or more substituents independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, methyl, methoxy; preferably, the alkylene and oxoalkylene are optionally substituted with one or more substituents independently selected from deuterium and oxo; or Z 11 , Z 12 , Z 21 , Z 22 , Z 31 , Z 32 are independently selected from -C 1-2 Alkylene-, -C 1-3 Oxyalkylene-, -C 1-3 Azaalkylene-; the alkylene, oxaalkylene, azaalkylene are optionally substituted by one or more substituents each independently selected from oxo; or When Z 11 , Z 21 and Z 31 When Z 11 , Z 21 and Z 31 The combination defined in the following comprises at least one heteroatom or heteroatom group selected from -O-, -S-, -Se-, -NH-, -CO-, -C(S)-; or When Z 11 , Z 21 and Z 31 When Z 11 , Z 21 and Z 31 The combination of the definition of contains at least one heteroatom or heteroatom group, wherein the heteroatom or heteroatom group is selected from -CO- or -C(S)-; or When Z 11 , Z 21 and Z 31 When Z 11 , Z 21 and Z 31 The combination of the definitions of one of * indicates the connection terminal to A; or When Z 11 , Z 21 and Z 31 When Z 11 , Z 21 and Z 31 The combination defined in the following comprises at least one heteroatom or heteroatom group selected from -O-, -NH-, -CO-; or When Z 11 , Z 21 and Z 31 When Z 11 , Z 21 and Z 31 The combination defined in the above definition comprises 1-4 heteroatoms or heteroatom groups, wherein the heteroatoms or heteroatom groups are selected from -O-, -S-, -Se-, -NH-, -CO-, -C(S)-, specifically 1, 2, 3, 4; preferably 1-3 heteroatoms or heteroatom groups, specifically 1, 2, 3; more preferably 2-4 heteroatoms or heteroatom groups, specifically 2, 3, 4; more preferably 2 or 3 heteroatoms or heteroatom groups; the heteroatoms or heteroatom groups are preferably -O-, -S-, -NH-, -CO-; the heteroatoms or heteroatom groups are more preferably -O-, -CO-; preferably, the heteroatoms or heteroatom groups contain at least -CO- or -C(S)-; or Z 21 contains a heteroatom or heteroatom group selected from -O-, -S-, -Se-, -NH-; and Z 31 contains a heteroatom or heteroatom group selected from -CO-, -C(S)-; and Z 21 and Z 31 In the combination, the total number of the heteroatoms or heteroatom groups is 1-4; or When Z 11 , Z 21 and Z 31 When Z 11 , Z 21 and Z 31 The combination defined in the above definition contains 1-4 heteroatoms or heteroatom groups, wherein the heteroatoms or heteroatom groups are selected from -O-, -NH-, -CO-; preferably 1-3; more preferably 2-3; preferably, the heteroatoms or heteroatom groups contain at least -CO-; or Z 11 , Z 21 and Z 31 Contains 1 to 4 heteroatoms or heteroatom groups in total, wherein the heteroatoms or heteroatom groups are selected from -O-, -NH-, and -CO-, specifically 1, 2, 3, or 4; or Z 11 , Z 21 and Z 31 Contains 1 to 3 heteroatoms or heteroatom groups in total, wherein the heteroatoms or heteroatom groups are selected from -O-, -NH-, and -CO-, specifically 1, 2, or 3; or Z 11 , Z 21 and Z 31 Contains 2-3 heteroatoms or heteroatom groups in total, wherein the heteroatoms or heteroatom groups are selected from -O-, -NH-, and -CO-, specifically 2 or 3; preferably, the heteroatoms or heteroatom groups contain at least -CO-; or Z 11 , Z 12 , Z 21 , Z 22 , Z 31 , Z 32 are independently selected from -CD2-, -C 1-4 Alkylene-, -OC 1-3 Alkylene-, -C(O)-, -C 1-3 Alkylene-C(O)-, -OC 1-3 Alkylene-C(O)-, -NH-C 1-3 Alkylene-C(O)-, -SC 1-3 Alkylene-C(O)-, -OC 1-2 Alkylene-C(O)-C 1-3 Alkylene-, -C 1-2 Alkyl-OC 1-3 Alkylene-, -NH-C 1-3 Alkylene-, -SC 1-3 Alkylene-, -C 1-3 Alkylene-NH-C(O)-, -C 1-3 Alkylene-OC(O)-, -NH-C(O)-, -OC(O)-, -SC(O)-, -C 1-3 Alkylene-C(S)-, -Se-C 1-3 Alkylene-, The alkylene, methylene and ethylene groups are optionally substituted by one or more substituents independently selected from deuterium, fluorine and chlorine; or Z 11 , Z 12 , Z 21 , Z 22 , Z 31 , Z 32 are independently selected from -CD2-, -C 1-3 Alkylene-, -OC 1-3 Alkylene-, -C(O)-, -C 1-3 Alkylene-C(O)-, -OC 1-3 Alkylene-C(O)-, -NH-C 1-3 Alkylene-C(O)-, -SC 1-3 Alkylene-C(O)-, -OC 1-3 Alkylene-C(O)-C 1-3 Alkylene-, -C 1-3 Alkylene-OC 1-3 Alkylene-, -NH-C 1-3 Alkylene-, -SC 1-3 Alkylene-, -C 1-3 Alkylene-NH-C(O)-, -C 1-3 Alkylene-OC(O)-, -NH-C(O)-, -OC(O)-, -SC(O)-; or Z 11 , Z 12 , Z 21 , Z 22 , Z 31 , Z 32 are independently selected from a bond, -CD2-, -C 1-3 Alkylene-, -OC 1-3 Alkylene-, -C(O)-, -C 1-3 Alkylene-C(O)-, -OC 1-3 Alkylene-C(O)-, -NH-C 1-3 Alkylene-C(O)-, -SC 1-3 Alkylene-C(O)-, -OC 1-3 Alkylene-C(O)-C 1-3 Alkylene-; or Z 11 , Z 12 , Z 21 , Z 22 , Z 31 , Z 32 Each independently selected from -C 1-3 Alkylene-, -OC 1-3 Alkylene-, -C 1-3 Alkylene-C(O)-, -OC 1-3 Alkylene-C(O)-, -NH-C(O)-, -OC(O)-; or Z 11 , Z 12 , Z 21 , Z 22 , Z 31 , Z 32 are independently selected from -CD2-, -C 1-2 Alkylene-, -OC 1-3 Alkylene-, -C(O)-, -C 1-2 Alkylene-C(O)-, -OC 1-2 Alkylene-C(O)-, -NH-C 1-2 Alkylene-C(O)-, -SC 1-2 Alkylene-C(O)-, -OC 1-2 Alkylene-C(O)-C 1-2 Alkylene-, -C 1-2 Alkylene-OC 1-2 Alkylene-, -NH-C 1-2 Alkylene-, -SC 1-2 Alkylene-, -C 1-2 Alkylene-NH-C(O)-, -C 1-2 Alkylene-OC(O)-, -NH-C(O)-, -OC(O)-, -SC(O)-; or Z 11 , Z 12 , Z 21 , Z 22 , Z 31 , Z 32 are independently selected from a bond, -CD2-, -C 1-2 Alkylene-, -OC 1-2 Alkylene-, -C(O)-, -C 1-2 Alkylene-C(O)-, -OC 1-2 Alkylene-C(O)-, -NH-C 1-2 Alkylene-C(O)-, -SC 1-2 Alkylene-C(O)-, -OC 1-2 Alkylene-C(O)-C 1-2 Alkylene-; or Z 11 , Z 12 , Z 21 , Z 22 , Z 31 , Z 32 are independently selected from a bond, a methylene group, an ethylene group, -CD2-, or Z 11 , Z 12 , Z 21 , Z 22 , Z 31 , Z 32 are independently selected from methylene, ethylene, or Z 11 , Z 12 , Z 21 , Z 22 , Z 31 , Z 32 are independently selected from methylene, ethylene, -CD2, * indicates the connection terminal to A; or Z 12 , Z 22 , Z 32 are independently selected from methylene, -CD2, and Z 11 Selected from methylene, ethylene, -CD2, And Z 21 Selected from methylene, ethylene, -CD2, And Z 31 Selected from For example, Z 31 Selected from * indicates the connection terminal to A; or Z 12 , Z 22 , Z 32 are independently selected from methylene, -CD2, and Z 11 Selected from methylene, ethylene, -CD2, And Z 21 Selected from methylene, ethylene, -CD2, And Z 31 Selected from * indicates the connection terminal to A; or Z 11 , Z 12 , Z 21 , Z 22 , Z 31 , Z 32 are independently selected from methylene, ethylene, or Z 11 , Z 12 , Z 21 , Z 22 are independently selected from -CD2, methylene; or methylene; or Z 12 , Z 22 , Z 32 Each independently selected from -CD2, methylene, ethylene; or Z 12 , Z 22 , Z 32 All are -CD2, methylene; or Z 11 Selected from -CD2, -C 1-3 Alkylene-, -OC 1-3 Alkylene-; or -C 1-3 Alkylene-; or -CD2, methylene, ethylene, methyleneoxy, ethyleneoxy; or methylene; or Z 21 Selected from -OC 1-3 Alkylene-, -NH-C 1-3 Alkylene-, -SC 1-3 Alkylene-, -Se-C 1-3 Alkylene-, -C 1-2 Alkylene-OC 1-3 Alkylene-; or -OC 1-3 Alkylene-, -NH-C 1-2 Alkylene-, -SC 1-2 Alkylene-, -C 1-2 Alkylene-OC 1-3 Alkylene-; or Z 31 Selected from -C(O)-, -C 1-3 Alkylene-C(O)-, -OC 1-3 Alkylene-C(O)-, -NH-C 1-3 Alkylene-C(O)-, -SC 1-3 Alkylene-C(O)-, -OC 1-2 Alkylene-C(O)-C 1-3 Alkylene-, -C 1-3 Alkylene-NH-C(O)-, -C 1-3 Alkylene-OC(O)-, -NH-C(O)-, -OC(O)-, -SC(O)-, -C 1-3 Alkylene-C(S)-; or -C(O)-, -C 1-2 Alkylene-C(O)-, -OC 1-2 Alkylene-C(O)-, -NH-C(O)-, -OC(O)-, -SC(O)-; or -C 1-2 Alkylene-C(O)-, -OC 1-2 Alkylene-C(O)-, -NH-C(O)-, -OC(O)-, -SC(O)-; or -CH2C(O)-; or Z 11 Independently selected from -OC 1-3 Alkyl-, -NH-C 1-3 Alkyl-, -SC 1-3 Alkyl-, -Se-C 1-3 Alkyl-, -C 1-3 Alkyl-OC 1-3 Alkyl-; and Z 21 Independently selected from -OC 1-3 Alkyl-, -NH-C 1-3 Alkyl-, -SC 1-3 Alkyl-, -Se-C 1-3 Alkyl-, -C 1-3 Alkyl-OC 1-3 Alkyl-; or Z 21 Selected from -OC 1-3 Alkylene-, -NH-C 1-3 Alkylene-, -SC 1-3 Alkylene-, -Se-C 1-3 Alkylene-, -C 1-2 Alkylene-OC 1-3 Alkylene-; and Z 31 Selected from -C(O)-, -C 1-3 Alkylene-C(O)-, -OC 1-3 Alkylene-C(O)-, -NH-C 1-3 Alkylene-C(O)-, -SC 1-3 Alkylene-C(O)-, -OC 1-2 Alkylene-C(O)-C 1-3 Alkyl-, -C 1-3 Alkylene-NH-C(O)-, -C 1-3 Alkylene-OC(O)-, -NH-C(O)-, -OC(O)-, -SC(O)-, -C 1-3 Alkylene-C(S)-; or Z 11 Selected from -CD2, -C 1-3 Alkylene-, -OC 1-3 Alkylene-; and Z 21 Selected from -OC 1-3 Alkylene-, -NH-C 1-3 Alkylene-, -SC 1-3 Alkylene-, -Se-C 1-3 Alkylene-, -C 1-2 Alkylene-OC 1-3 Alkylene-; and Z 31 Selected from -C(O)-, -C 1-3 Alkylene-C(O)-, -OC 1-3 Alkylene-C(O)-, -NH-C 1-3 Alkylene-C(O)-, -SC 1-3 Alkylene-C(O)-, -OC 1-2 Alkylene-C(O)-C 1-3 Alkylene-, -C 1-3 Alkylene-NH-C(O)-, -C 1-3 Alkylene-OC(O)-, -NH-C(O)-, -OC(O)-, -SC(O)-, -C 1-3 Alkylene-C(S)-; or Z 11 Selected from -C 1-3 Alkylene-, -OC 1-3 Alkylene-; and Z 21 Selected from -OC 1-3 Alkylene-, -NH-C 1-3 Alkylene-, -SC 1-3 Alkylene-, -Se-C 1-3 Alkylene-, -C 1-2 Alkylene-OC 1-3 Alkylene-; and Z 31 Selected from -C(O)-, -C 1-3 Alkylene-C(O)-, -OC 1-3 Alkylene-C(O)-, -NH-C 1-3 Alkylene-C(O)-, -SC 1-3 Alkylene-C(O)-, -OC 1-2 Alkylene-C(O)-C 1-3 Alkylene-, -C 1-3 Alkylene-NH-C(O)-, -C 1-3 Alkylene-OC(O)-, -NH-C(O)-, -OC(O)-, -SC(O)-, -C 1-3 Alkylene-C(S)-; or Z 11 Selected from -CD2, -C 1-3 Alkylene-, -OC 1-3 Alkylene-*; and Z 21 Selected from -OC 1-3 Alkylene-*, -NH-C 1-3 Alkylene-*, -SC 1-3 Alkylene-*, -Se-C 1-3 Alkylene-*, -C 1-2 Alkylene-OC 1-3 Alkylene-*; and Z 31 Selected from -C(O)-, -C 1-3 Alkylene-C(O)-*, -OC 1-3 Alkylene-C(O)-*, -NH-C 1-3 Alkylene-C(O)-*, -SC 1-3 Alkylene-C(O)-*, -OC 1-2 Alkylene-C(O)-C 1-3 Alkylene-*, -C 1-3 Alkylene-NH-C(O)-*, -C 1-3 Alkylene-OC(O)-*, -NH-C(O)-*, -OC(O)-*, -SC(O)-*, -C 1-3 Alkylene-C(S)-*; * indicates the end connected to A; or Z 11 Selected from -C 1-3 Alkylene-, -OC 1-3 Alkylene-*; and Z 21 Selected from -OC 1-3 Alkylene-*, -NH-C 1-3 Alkylene-*, -SC 1-3 Alkylene-*, -Se-C 1-3 Alkylene-*, -C 1-2 Alkylene-OC 1-3 Alkylene-*; and Z 31 Selected from -C(O)-, -C 1-3 Alkylene-C(O)-*, -OC 1-3 Alkylene-C(O)-*, -NH-C 1-3 Alkylene-C(O)-*, -SC 1-3 Alkylene-C(O)-*, -OC 1-2 Alkylene-C(O)-C 1-3 Alkylene-*, -C 1-3 Alkylene-NH-C(O)-*, -C 1-3 Alkylene-OC(O)-*, -NH-C(O)-*, -OC(O)-*, -SC(O)-*, -C 1-3 Alkylene-C(S)-*; * indicates the end connected to A; or Z 11 Selected from -CD2, -C 1-2 Alkylene-, -OC 1-2 Alkylene-*; and Z 21 Selected from -OC 1-2 Alkylene-*, -NH-C 1-2 Alkylene-*, -SC 1-2 Alkylene-*, -Se-C 1-2 Alkylene-*, -CH2-OC 1-2 Alkylene-*; and Z 31 Selected from -C(O)-, -C 1-2 Alkylene-C(O)-*, -OC 1-2 Alkylene-C(O)-*, -NH-C 1-2 Alkylene-C(O)-*, -SC 1-2 Alkylene-C(O)-*, -C 1-2 Alkylene-NH-C(O)-*, -C 1-2 Alkylene-OC(O)-*, -NH-C(O)-*, -OC(O)-*, -SC(O)-*, -C 1-2 Alkylene-C(S)-*; for example, Z 31 Selected from -C 1-2 Alkylene-C(O)-*, -OC 1-2 Alkylene-C(O)-*, -NH-C 1-2 Alkylene-C(O)-*, -SC 1-2 Alkylene-C(O)-*, -C 1-2 Alkylene-NH-C(O)-*, -C 1-2 Alkylene-OC(O)-*, -CH2NH-C(O)-*, -NH-C(O)-*, -OC(O)-*, -SC(O)-*, -C 1-2 Alkylene-C(S)-*; for example, Z 31 Selected from -C 1-2 Alkylene-C(O)-*, -OCH2-C(O)-*, -CH2-OC(O)-*, -NH-C(O)-*, -OC(O)-*, -SC(O)-*; for example, Z 31 Selected from -CH2C(O)-*; * represents the terminal connected to A.

10. The compound according to any one of claims 1 to 9, or a pharmaceutically acceptable salt thereof, characterized in that: The compound has a structure as shown in formula (I-2): Among them, A, L1, L2, R, R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 , R 11 , R 12 , R 31 , R 32 As defined in any one of claims 1 to 9; For example, in the compound represented by formula (I-2), R is a group including L3, L1, L2 and L3 are respectively 11 , Z 21 and Z 31 The group, and Z 11 , Z 21 and Z 31 There is only one group containing a double bond in -C(O)-; the double bond is, for example, a double bond between C and O in -C(O)-, or a double bond between C and S in -C(S)-; further preferably, Z 11 , Z 21 and Z 31 Different from each other, or Z 11 , Z 21 and Z 31 The two groups not containing a double bond in Z are identical, and the two identical groups contain -O-, -NH-, -S-, or -Se-, preferably, -O-; Still more preferably, Z 11 , Z 21 and Z 31 The molecular weight of Z is independently 14.0-107.1, preferably 14.0-60; preferably about 14, about 16, about 28, about 30, about 42, about 43, about 44, about 46, about 58, or about 60; still more preferably, Z 11 , Z 21 and Z 31 Selected from -CH2-, -CD2-, -CH2CH2-, -CD2CH2-, -C(O)-, -CH2C(O)-, -NHC(O)-, -OC(O)-, -CH2CH2O-, -OCH2C(O)-, -CH2OC(O)-, -CH2CH2CH2O-, -SC(O)-; or The compound has a structure as shown in formula (I-3): Among them, A, L1, L2, R, R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 , R 11 , R 12 As defined in any one of claims 1 to 9; For example, in the compound represented by formula (I-3), R is a group including L3, L1, L2 and L3 are respectively 11 , Z 21 and Z 31 The group, and Z 11 , Z 21 and Z 31 There is only one group containing a double bond in -C(O)-; the double bond is, for example, a double bond between C and O in -C(O)-, or a double bond between C and S in -C(S)-; further preferably, Z 11 , Z 21 and Z 31 Different from each other, or Z 11 , Z 21 and Z 31 The two groups not containing a double bond in Z are identical, and the two identical groups contain -O-, -NH-, -S-, or -Se-, preferably, -O-; Still more preferably, Z 11 , Z 21 and Z 31 The molecular weight of Z is independently 14.0-107.1, preferably 14.0-60; preferably about 14, about 16, about 28, about 30, about 42, about 43, about 44, about 46, about 58, or about 60; still more preferably, Z 11 , Z 21 and Z 31 Selected from -CH2-, -CD2-, -CH2CH2-, -CD2CH2-, -C(O)-, -CH2C(O)-, -NHC(O)-, -OC(O)-, -CH2CH2O-, -OCH2C(O)-, -CH2OC(O)-, -CH2CH2CH2O-, -SC(O)-; or The compound has a structure as shown in formula (I'-1), formula (I'-2), and formula (I'-3): Among them, A, L1, L2, R, R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 , R 11 , R 12 , R 31 , R 32 , R 41 , R 42 , R 50 , R 51 , h1, h2, h3, h4 as defined in any one of claims 1 to 9; For example, in the compounds represented by formula (I'-1), (I'-2), and (I'-3), R is a group including L3, and Z 11 , Z 21 and Z 31 There is only one group containing a double bond in -C(O)-; the double bond is, for example, a double bond between C and O in -C(O)-, or a double bond between C and S in -C(S)-; further preferably, Z 11 , Z 21 and Z 31 Different from each other, or Z 11 , Z 21 and Z 31 The two groups not containing a double bond in Z are identical, and the two identical groups contain -O-, -NH-, -S-, or -Se-, preferably, -O-; Still more preferably, Z 11 , Z 21 and Z 31 The molecular weight of Z is independently 14.0-107.1, preferably 14.0-60; preferably about 14, about 16, about 28, about 30, about 42, about 43, about 44, about 46, about 58, or about 60; still more preferably, Z 11 , Z 21 and Z 31 Selected from -CH2-, -CD2-, -CH2CH2-, -CD2CH2-, -C(O)-, -CH2C(O)-, -NHC(O)-, -OC(O)-, -CH2CH2O-, -OCH2C(O)-, -CH2OC(O)-, -CH2CH2CH2O-, -SC(O)-; or The compound has a structure as shown in formula (II): wherein L1 and L2 are as defined in any one of claims 1 to 9, and R' is selected from H, -C 1-3 Alkylene-C 6-10 Aryl, -C 1-3 Alkylene-5-12 membered heteroaryl, C 1-6 Alkyl; the C 1-3 The alkylene group is optionally substituted with one or more independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, C 1-3 The aryl and heteroaryl groups are optionally substituted by one or more independently selected from deuterium, halogen, -CN, C 1-3 Alkoxy, C 1-3 The substituent of aminoalkyl is substituted; the C 1-6 The alkyl group is optionally substituted with one or more independently selected from deuterium, halogen, oxo, carboxyl, -CN, -OH, -NH2, C 1-3 Alkyl, C 1-3 substituted by an alkoxy substituent; or The compound has a structure as shown in formula (II-A), formula (II-B), formula (II-C), formula (II-A'), formula (II-B'), and formula (II-C'): Wherein, W1, W2, R' are as defined in any one of claims 1 to 9; or The compound has a structure as shown in formula (III): Wherein, A, L1, L2, L3 are as defined in any one of claims 1 to 9; For example, in the compound represented by formula (III), L1, L2 and L3 are respectively 11 , Z 21 and Z 31 The group, and Z 11 , Z 21 and Z 31 There is only one group containing a double bond in -C(O)-; the double bond is, for example, a double bond between C and O in -C(O)-, or a double bond between C and S in -C(S)-; further preferably, Z 11 , Z 21 and Z 31 Different from each other, or Z 11 , Z 21 and Z 31 The two groups not containing a double bond in Z are identical, and the two identical groups contain -O-, -NH-, -S-, or -Se-, preferably, -O-; Still more preferably, Z 11 , Z 21 and Z 31 The molecular weight of Z is independently 14.0-107.1, preferably 14.0-60; preferably about 14, about 16, about 28, about 30, about 42, about 43, about 44, about 46, about 58, or about 60; still more preferably, Z 11 , Z 21 and Z 31 Selected from -CH2-, -CD2-, -CH2CH2-, -CD2CH2-, -C(O)-, -CH2C(O)-, -NHC(O)-, -OC(O)-, -CH2CH2O-, -OCH2C(O)-, -CH2OC(O)-, -CH2CH2CH2O-, -SC(O)-; or The compound has a structure as shown in formula (III-1): Among them, W1, W2, W3, Z 11 , Z 12 , Z 21 , Z 22 , Z 31 , Z 32 As defined in any one of claims 1 to 9; Preferably, Z 12 , Z 22 , Z 32 are independently selected from methylene and ethylene; Z 11 , Z 21 , Z 31 are independently selected from a bond, -C 1-4 Alkylene-, -C 1-6 Oxoalkylene-(e.g. -C 1-4 Oxyalkylene-), -C 1-4 Thioalkylene-, -C 1-4 Azaalkylene-, -C 1-4 Selenylene-; the alkylene, oxaalkylene, thiaalkylene, azaalkylene, selenylene are optionally substituted by one or more selected from Z 41 Substituted by a substituent; Z 41 are independently selected from deuterium, halogen (e.g., fluorine, chlorine), oxo, thio, -CN, -OH, -NH2, C 1-3 Alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 haloalkoxy; or any two Z 41 Together with the atoms they are attached to form C 3-6 Cycloalkyl, 3-6 membered heterocyclic group (e.g. oxetanyl); the heteroatom in the heterocyclic group is O, N or S, and the number of heteroatoms is 1; Ring W1, W2, and W3 are independently selected from phenyl and 5-6-membered monocyclic heteroaryl; the phenyl and heteroaryl are optionally substituted by one or more independently selected from deuterium, halogen, -CN, -OH, -NH2, -CHO, C 1-3 Alkyl, C 1-3 Alkoxy, -N(C 1-3 Alkyl)2, -NH(C 1-3 Alkyl), -C(O)C 1-3 The heteroaryl group is substituted by a substituent of an alkyl group; the heteroatom in the heteroaryl group is O, N or S, and the number of heteroatoms is 1 or 2; or Z 12 , Z 22 , Z 32 are all methylene; or When Z 11 , Z 21 and Z 31 When Z 11 , Z 21 and Z 31 , wherein the combination is 2 or 3 heteroatoms or heteroatom groups selected from -O-, -S-, -NH-, -CO-; or Ring W1, W2, W3 are independently selected from phenyl and thienyl; the phenyl and thienyl are optionally substituted by one or more independently selected from deuterium, halogen, -CN, -OH, -NH2, -CHO, C 1-3 Alkyl, C 1-3 Alkoxy, -N(C 1-3 Alkyl)2, -NH(C 1-3 Alkyl), -C(O)C 1-3 substituted by an alkyl substituent; or Rings W1, W2, and W3 are independently selected from The above groups are optionally substituted by one or more substituents each independently selected from deuterium, fluorine, chlorine, bromine, methyl, ethyl, methoxy, ethoxy; For example, Z 11 , Z 21 and Z 31 There is only one group containing a double bond in -C(O)-; the double bond is, for example, a double bond between C and O in -C(O)-, or a double bond between C and S in -C(S)-; further preferably, Z 11 , Z 21 and Z 31 Different from each other, or Z 11 , Z 21 and Z 31 The two groups not containing a double bond in Z are identical, and the two identical groups contain -O-, -NH-, -S-, or -Se-, preferably, -O-; Still more preferably, Z 11 , Z 21 and Z 31 The molecular weight of Z is independently 14.0-107.1, preferably 14.0-60; preferably about 14, about 16, about 28, about 30, about 42, about 43, about 44, about 46, about 58, or about 60; still more preferably, Z 11 , Z 21 and Z 31 Selected from -CH2-, -CD2-, -CH2CH2-, -CD2CH2-, -C(O)-, -CH2C(O)-, -NHC(O)-, -OC(O)-, -CH2CH2O-, -OCH2C(O)-, -CH2OC(O)-, -CH2CH2CH2O-, -SC(O)-; or The compound has a structure as shown in formula (III-2): Among them, W1, W2, W3, Z 11 , Z 12 , Z 21 , Z 22 , Z 31 , Z 32 , R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 , R 11 , R 12 , R 44 , R 45 , R 46 , R 47 , R 48 , R 49 , R 31 , R 32 , R 33 As defined in any one of claims 1 to 9; Preferably, Z 31 The heteroatom or heteroatom group contains -CO- or -C(S)-; or R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 , R 11 , R 12 , R 44 , R 45 , R 46 , R 47 , R 48 , R 49 , R 31 , R 32 , R 33 is selected from hydrogen or deuterium; For example, Z 11 , Z 21 and Z 31 There is only one group containing a double bond in -C(O)-; the double bond is, for example, a double bond between C and O in -C(O)-, or a double bond between C and S in -C(S)-; further preferably, Z 11 , Z 21 and Z 31 Different from each other, or Z 11 , Z 21 and Z 31 The two groups not containing a double bond in Z are identical, and the two identical groups contain -O-, -NH-, -S-, or -Se-, preferably, -O-; Still more preferably, Z 11 , Z 21 and Z 31 The molecular weight of Z is independently 14.0-107.1, preferably 14.0-60; preferably about 14, about 16, about 28, about 30, about 42, about 43, about 44, about 46, about 58, or about 60; still more preferably, Z 11 , Z 21 and Z 31 Selected from -CH2-, -CD2-, -CH2CH2-, -CD2CH2-, -C(O)-, -CH2C(O)-, -NHC(O)-, -OC(O)-, -CH2CH2O-, -OCH2C(O)-, -CH2OC(O)-, -CH2CH2CH2O-, -SC(O)-; or The compound has a structure as shown in formula (III-1-1) and formula (III-2-1): Among them, W1, W2, W3, Z 11 , Z 12 , Z 21 , Z 22 , Z 31 , Z 32 , R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 , R 11 , R 12 , R 44 , R 45 , R 46 , R 47 , R 48 , R 49 , R 31 , R 32 , R 33 As defined in any one of claims 1 to 9; For example, Z 11 , Z 21 and Z 31 There is only one group containing a double bond in -C(O)-; the double bond is, for example, a double bond between C and O in -C(O)-, or a double bond between C and S in -C(S)-; further preferably, Z 11 , Z 21 and Z 31 Different from each other, or Z 11 , Z 21 and Z 31 The two groups not containing a double bond in Z are identical, and the two identical groups contain -O-, -NH-, -S-, or -Se-, preferably, -O-; Still more preferably, Z 11 , Z 21 and Z 31 The molecular weight of Z is independently 14.0-107.1, preferably 14.0-60; preferably about 14, about 16, about 28, about 30, about 42, about 43, about 44, about 46, about 58, or about 60; still more preferably, Z 11 , Z 21 and Z 31 Selected from -CH2-, -CD2-, -CH2CH2-, -CD2CH2-, -C(O)-, -CH2C(O)-, -NHC(O)-, -OC(O)-, -CH2CH2O-, -OCH2C(O)-, -CH2OC(O)-, -CH2CH2CH2O-, -SC(O)-; or The compound has a structure as shown in formula (III-A) and formula (III-A'): Wherein, L3 is as defined in any one of claims 1 to 9; or The compound has a structure as shown in formula (III-B) and formula (III-B'-1): Wherein, L1 and L2 are as defined in any one of claims 1 to 9; Preferably, L1 is * indicates the connection terminal to N; or L2 is * indicates the connection terminal to N; or Z 11 , Z 12 , Z 21 , Z 22 are independently selected from -C 1-3 Alkylene-, -C 1-3 Oxyalkylene-, -C 1-3 Thioalkylene-, -C 1-3 Azaalkylene-; the alkylene, oxaalkylene, thiaalkylene, azaalkylene are optionally substituted with one or more substituents independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, methyl, methoxy; or Z 11 , Z 12 , Z 21 , Z 22 Each independently selected from -C 1-3 Alkylene-, -C 1-3 Oxoalkylene-; the alkylene and oxoalkylene are optionally substituted by one or more substituents independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, methyl, methoxy; or Z 11 , Z 12 , Z 21 , Z 22 are independently selected from -C 1-2 Alkylene-, -C 1-2 Oxyalkylene-, -C 1-2 Thioalkylene-, -C 1-2 Azaalkylene-; the alkylene, oxaalkylene, thiaalkylene, azaalkylene are optionally substituted with one or more substituents independently selected from deuterium, halogen, oxo, -CN, -OH, -NH2, methyl, methoxy; or Z 11 , Z 12 , Z 21 , Z 22 are independently selected from methylene, For example, L1 and L2 are the 11 and Z 21 The group, and Z 11 and Z 21 There is only one group containing a double bond in -C(O)-; the double bond is, for example, a double bond between C and O in -C(O)-, or a double bond between C and S in -C(S)-; preferably, the double bond is, for example, a double bond between C and O in -C(O)-; further preferably, Z 11 and Z 21 Neither methylene nor Z 11 and Z 21 The group not containing a double bond in Z contains -O-, -NH-, -S-, or -Se-, preferably, -O-; still more preferably, Z 11 and Z 21 The molecular weight of Z is independently 14.0-107.1, preferably 14.0-60; preferably about 14, about 16, about 28, about 30, about 42, about 43, about 44, about 46, about 58, or about 60; still more preferably, Z 11 , Z 21 and Z 31 Selected from -CH2-, -CD2-, -CH2CH2-, -CD2CH2-, -C(O)-, -CH2C(O)-, -NHC(O)-, -OC(O)-, -CH2CH2O-, -OCH2C(O)-, -CH2OC(O)-, -CH2CH2CH2O-, -SC(O)-; or The compound has a structure as shown in formula (III-C), formula (III-C'), formula (III-D), formula (III-D'), formula (III-E), and formula (III-E'): Wherein, W1, W2, and W3 are as defined in any one of claims 1 to 9; or The compound has a structure as shown in formula (IV): Among them, R3, R4, R9, R 10 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 , R 21 , R 22 , R 23 , R 24 , R 25 , R 26 are independently selected from H and deuterium, and R3, R4, R9, R 10 , R 13 -R 26 At least one is deuterium; or The compound has a structure as shown in formula (A): Among them, R3, R4, R9, R 10 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 , R 21 , R 22 , R 23 , R 24 , R 25 , R 26 are independently selected from H and deuterium, and R3, R4, R9, R 10 , R 13 -R 26 At least one is deuterium; R A , R B , R C are independently selected from hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 1-6 Alkoxy, -C 1-3 Alkylene OC 1-6 Alkyl, -C 1-3 Alkylene-OC(O)-C 1-6 Alkyl, wherein the alkyl, alkenyl, alkoxy, alkylene is optionally substituted by one or more independently selected from deuterium, halogen, -OH, -NH2, -CN, oxo, C 1-3 Alkyl, C 1- 3 is substituted by an alkoxy substituent; Preferably, R A , R B , R C Each independently selected from C 1-6 Alkyl, C 1-6 Alkoxy, -C 1-2 Alkylene-OC 1-4 Alkyl, -C 1-2 Alkylene-OC(O)-C 1-4 Alkyl, the alkyl, C 1-6 Alkoxy, alkylene is optionally substituted by one or more substituents independently selected from deuterium, fluorine, chlorine, bromine, -OH, -NH2, -CN, oxo, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy; or R A , R B , R C Each independently selected from C 1-3 Alkyl, -methylene-OC 1-4 Alkyl, -methylene-OC(O)-C 1-3 Alkyl, wherein the methylene group and the alkyl group are optionally substituted by one or more substituents independently selected from methyl, ethyl, n-propyl and isopropyl; or R A , R B , R C Each independently selected from methyl, ethyl, -CH2-OC(O)-CH(CH3)2; or The compound has a structure as shown in formula (B), formula (B-1), formula (C), formula (C-1), formula (D), formula (D-1), formula (B-2), formula (B-3), formula (C-2), formula (C-3), formula (D-2), and formula (D-3): in, Z 11 , Z 21 , Z 31 , R 31 , R 32 , R 33 , h1, h2, h3, h4, h5, h6 as defined in any one of claims 1 to 9, X is selected from O, CH2, NH, S, Se, or X is selected from O, CH2, NH, S; or X is CH2; X2 is selected from O, CH2, NH, S, Se or X2 is selected from O, NH, S; or X2 is O; X1 is independently selected from O, S, or X1 is O; n, n1, n3 are each independently 0 or 1, n2 is independently 0, 1, 2 or 3; Z 12 , Z 22 , Z 32 Each of them is independently selected from methylene, ethylene, -CD2-; or Z 12 , Z 22 , Z 32 are independently selected from methylene, -CD2-; or Z 12 , Z 22 , Z 32 All are methylene; Ring W1, W2, and W3 are independently selected from phenyl and 5-6-membered monocyclic heteroaryl; the phenyl and heteroaryl are optionally substituted by one or more independently selected from deuterium, halogen, -CN, -OH, -NH2, -CHO, C 1-3 Alkyl, C 1-3 Alkoxy, -N(C 1-3 Alkyl)2, -NH(C 1-3 Alkyl), -C(O)C 1-3 The heteroaryl group is substituted by a substituent of an alkyl group; the heteroatom in the heteroaryl group is O, N or S, and the number of heteroatoms is 1 or 2; or Rings W1, W2, and W3 are each independently selected from the following optionally substituted groups: The optional substitution refers to being unsubstituted or being substituted by one or more independently selected from deuterium, halogen, -CN, -OH, -NH2, -CHO, C 1-3 Alkyl, C 1-3 Alkoxy, -N(C 1-3 Alkyl)2, -NH(C 1-3 Alkyl), -C(O)C 1-3 substituted by an alkyl substituent; or Rings W1, W2, and W3 are each independently selected from the following optionally substituted groups: The optional substitution means being unsubstituted or substituted by one or more substituents independently selected from deuterium, fluorine, chlorine, bromine, methyl, ethyl, methoxy, ethoxy; Preferably, The sum of n2 and n3 is not greater than 3 (specifically 0, 1, 2, 3); for example, the sum of n2 and n3 is not greater than 2 (specifically 0, 1, 2); for example, the sum of n2 and n3 is 1 or 2 (i.e., n2 is 2 and n3 is 0; or n2 is 1 and n3 is 1; or n2 is 0 and n3 is 2); or The sum of n and n1 is 0, 1, or 2; for example, the sum of n and n1 is 1 or 2 (i.e., n is 1 and n1 is 0; or n is 0 and n1 is 1; or n is 1 and n1 is 1; or n is 0 and n1 is 2; or n is 2 and n1 is 0); or The sum of n and n1 is 1 (i.e., n is 1 and n1 is 0; or n is 0 and n1 is 1); For example: n2 is 0 or 1, n3 is 0, and X2 is CH2; or n2 is 2 or 3, n3 is 0, X2 is O, NH, S; or n2 is 1 or 2, n3 is 1, X2 is O, NH, S; or n2 is 2 or 3, n3 is 0, and X2 is 0; or n2 is 2, n3 is 1, and X2 is 0; or n2 is 2, n3 is 0, X2 is O, NH, S; or n2 is 2, n3 is 0, and X2 is 0; and / or for example: X is selected from O, CH2, NH, S, n is 1, n1 is 0; or X is O or CH2, n is 1, n1 is 1; or X1 is O, X is selected from O, CH2, NH, S, n is 1, n1 is 0; or X1 is O, X is O or CH2, n is 1, n1 is 1; or X1 is O, X is selected from O, CH2, n is 1, n1 is 0; or X1 is O, X is O or CH2, n is 1, n1 is 1; or X1 is O, X is selected from CH2, n is 1, and n1 is 0; and / or, preferably: Z 11 is -CD2-; or Z 11 Independently selected from -C 1-3 Alkylene-, -OC 1-3 Alkylene-, -NH-C 1-3 Alkylene-, -SC 1-3 Alkylene-, -Se-C 1-3 Alkylene-, -C 1-2 Alkylene-OC 1-3 Alkylene-; or, Z 11 Independently selected from -C 1-3 Alkylene-, -OC 1-3 Preferably, Z 11 is independently selected from methylene, ethylene, methyleneoxy, ethyleneoxy; or, Z 11 is independently selected from methylene, -CD2-; or, Z 11 are independently selected from methylene; and / or Z 21 is -CD2-; or Z 21 Independently selected from -C 1-3 Alkylene-, -OC 1-3 Alkylene-, -NH-C 1-3 Alkylene-, -SC 1-3 Alkylene-, -Se-C 1-3 Alkylene-, -C 1-2 Alkylene-OC 1-3 Alkylene-; or -OC 1-3 Alkylene-, -NH-C 1-2 Alkylene-, -SC 1-2 Alkylene-, -C 1-2 Alkylene-OC 1-3 Alkylene-; and / or, preferably: Z 31 are independently selected from -C(O)-, -C 1-3 Alkylene-C(O)-, -OC 1-3 Alkylene-C(O)-, -NH-C 1-3 Alkylene-C(O)-, -SC 1-3 Alkylene-C(O)-, -OC 1-2 Alkylene-C(O)-C 1-3 Alkylene-, -C 1-3 Alkylene-NH-C(O)-, -C 1-3 Alkylene-OC(O)-, -NH-C(O)-, -OC(O)-, -SC(O)-, -C 1-3 Alkylene-C(S)-; or -C(O)-, -C 1-2 Alkylene-C(O)-, -OC 1-2 Alkylene-C(O)-, -NH-C(O)-, -OC(O)-, -SC(O)-; For example, in the above-mentioned formula (B) and formula (B-1), Z 12 , Z 22 , Z 32 are independently selected from methylene, -CD2-; Z 11 , Z 21 are independently selected from -CD2-, -C 1-3 Alkylene-(e.g. -C 1-2 Alkylene-), -OC 1-3 Alkylene-* (e.g. -OC 1-2 Alkylene-*), -SC 1-3 Alkylene-*, -NHC 1-3 Alkylene-*, -Se-C 1-3 Alkylene-*, -CH2-OC 1-2 Alkylene-, *, is the terminal connected to N; X1 is O or S, X is selected from O, CH2, NH, S, n is 1, n1 is 0; or X1 is O or S, X is O or CH2, n is 1, n1 is 1; or X1 is O or S, n is 0, n1 is 0; or For example, in the above formula (B) and formula (B-1), Z 12 , Z 22 , Z 32 are independently selected from methylene, -CD2-; Z 11 Independently selected from -CD2-, -CH2-, -CH2CH2-, -OCH2-*, -OCH2CH2-*, and the terminal connected to N; Z 21 Independently selected from -OCH2CH2-*, -CH2OCH2CH2-*, -OCH2CH2CH2-*, *, is the terminal connected to N; X1 is O, X is selected from O, CH2, NH, S, n is 1, n1 is 0; or X1 is O, X is O or CH2, n is 1, n1 is 1; or For example, in the above formula (B) and formula (B-1), Z 12 , Z 22 , Z 32 are independently selected from methylene, -CD2-; Z 11 , Z 21 are independently selected from -CD2-, -C 1-3 Alkylene-(e.g. -C 1-2 Alkylene-), -OC 1-3 Alkylene-* (e.g. -OC 1-2 Alkylene-*), -SC 1-3 Alkylene-*, -NHC 1-3 Alkylene-*, -Se-C 1-3 Alkylene-*, -CH2-OC 1-2 Alkylene-, * is the terminal connected to N, X1 is O or S, X is selected from O, CH2, NH, S, The sum of n and n1 is 0, 1, 2; Further example, Z 21 Independently selected from -OCH2CH2-*, -CH2OCH2CH2-*, -OCH2CH2CH2-*, *, is the terminal connected to N; X1 is O, X is selected from O, CH2, NH, S, The sum of n and n1 is 1, 2; For example, for any of the above formulas (B), (B-1), (B-2), and (B-3), Z 11 and Z 21 are groups without double bonds; the double bond is, for example, a double bond between C and O in -C(O)-, or a double bond between C and S in -C(S)-; further preferably, Z 11 With Z 21 Same or different, and Z 11 With Z 21 At least one of them is a group containing -O-, -NH-, -S-, or -Se-, preferably, a group containing -O-, such as *-CH2O-, *-CH2CH2O-, * is the terminal connected to N; Still more preferably, Z 11 , Z 21 and *-C(X1)-(CH2) n1 -(X) n - has a molecular weight independently of each other of 14.0-107.1, preferably 14.0-60; preferably about 14, about 16, about 28, about 30, about 42, about 43, about 44, about 46, about 58, or about 60; still more preferably, Z 11 , Z 21 and Z 31 is selected from -CH2-, -CD2-, -CH2CH2-, -CD2CH2-, -C(O)-, -CH2C(O)-, -NHC(O)-, -OC(O)-, -CH2CH2O-, -OCH2C(O)-, -CH2OC(O)-, -CH2CH2CH2O-, -SC(O)-; for example, in the above-mentioned formula (C) and formula (C-1), Z 12 , Z 22 , Z 32 are independently selected from methylene, -CD2-; and / or Z 11 Independently selected from -CD2-, -C 1-3 Alkylene-(e.g. -C 1-2 Alkylene-), -OC 1-3 Alkylene-* (e.g. -OC 1-2 Alkylene-*), -SC 1-2 Alkylene-*, -NHC 1-2 Alkylene-*, -Se-C 1-2 Alkylene-*, -CH2-OC 1-2 Alkylene-, * is the terminal connected to N; and / or Z 31 are independently selected from -C(O)-, -C 1-3 Alkylene-C(O)-*, -OC 1-2 Alkylene-C(O)-*, -NHCH2-C(O)-*, -SCH2-C(O)-*, -CH2-NHC(O)-*, -C 1-2 Alkylene-OC(O)-*, -NH-C(O)-*, -OC(O)-*, -SC(O)-*, -C 1-2 Alkylene-C(S)-,* is the terminal connected to N; and / or n2 is 2 or 3, n3 is 0, X2 is O, NH, S; or n2 is 1 or 2, n3 is 1, X2 is O, NH, S; or n2 is 0 or 1, n3 is 0, and X2 is CH2; For example, in the above formula (C) and formula (C-1), Z 12 , Z 22 , Z 32 are independently selected from methylene, -CD2-; and / or Z 11 Independently selected from -CD2-, -CH2-, -CH2CH2-, -OCH2-*, -OCH2CH2-*, *, is connected to N; and / or Z 31 independently selected from -C(O)-, -CH2CH2C(O)-*, -CH2C(O)-*, -OCH2C(O)-*, -NHC(O)-*, -OC(O)-*, -SC(O)-*, *, and the like, is a terminal connected to N; and / or n2 is 2 or 3, n3 is 0, and X2 is 0; or n2 is 1 or 2, n3 is 1, and X2 is O; or n2 is 0 or 1, n3 is 0, and X2 is CH2; For example, in the above formula (C) and formula (C-1), Z 12 , Z 22 , Z 32 are independently selected from methylene, -CD2-; Z 11 Independently selected from -CD2-, -C 1-3 Alkylene-(e.g. -C 1-2 Alkylene-), -OC 1-3 Alkylene-* (e.g. -OC 1-2 Alkylene-*), -SC 1-2 Alkylene-*, -NHC 1-2 Alkylene-*, -Se-C 1-2 Alkylene-*, -CH2-OC 1- 2 alkylene-*, and / or Z 31 are independently selected from -C(O)-, -C 1-3 Alkylene-C(O)-*, -OC 1-2 Alkylene-C(O)-*, -NHCH2-C(O)-*, -SCH2-C(O)-*, -CH2-NHC(O)-*, -C 1-2 Alkylene-OC(O)-*, -NH-C(O)-*, -OC(O)-*, -SC(O)-*, -C 1-2 Alkylene-C(S)-, * is the terminal connected to N; further, for example, Z 31 independently selected from -CH2CH2C(O)-*, -CH2C(O)-*, -OCH2C(O)-*, -NHC(O)-*, -OC(O)-*, -SC(O)-*, *, and the like, is connected to N; and / or Z 11 Independently selected from -CD2-, -CH2-, -CH2CH2-, -OCH2CH2-, * is connected to N; and / or X2 is O, NH, S, Se, and the sum of n2 and n3 is 1, 2, or 3; for further example, X2 is O, and the sum of n2 and n3 is 2 or 3; For example, for any of the above formulas (C), (C-1), (C-2), and (C-3), Z 11 and Z 31 There is only one group containing a double bond in -C(O)-; the double bond is, for example, a double bond between C and O in -C(O)-, or a double bond between C and S in -C(S)-; further preferably, Z 11 and Z 31 The group without double bonds and *-(CH2) n2 -X2-(CH2) n3 - (* is the end connected to N) are the same or different; Still more preferably, Z 11 、-(CH2) n2 -X2-(CH2) n3 - and Z 31 The molecular weight of Z is independently 14.0-107.1, preferably 14.0-60; preferably about 14, about 16, about 28, about 30, about 42, about 43, about 44, about 46, about 58, or about 60; still more preferably, Z 11 , Z 21 and Z 31 Selected from -CH2-, -CD2-, -CH2CH2-, -CD2CH2-, -C(O)-, -CH2C(O)-, -NHC(O)-, -OC(O)-, -CH2CH2O-, -OCH2C(O)-, -CH2OC(O)-, -CH2CH2CH2O-, -SC(O)-; For example, in the above-mentioned formula (D) and formula (D-1), Z 12 , Z 22 , Z 32 are independently selected from methylene, -CD2-; and / or Z 11 Independently selected from -CD2-, -C 1-2 Alkylene-, -OC 1-2 Alkylene-*, -SC 1-2 Alkylene-*, -NHC 1-2 Alkylene-*, -Se-C 1-2 Alkylene-*, -CH2-OC 1-2 Alkylene-, * is the terminal connected to N; and / or n2 is 2 or 3, n3 is 0, X2 is O, NH, S; or n2 is 1 or 2, n3 is 1, X2 is O, NH, S; or n2 is 0 or 1, n3 is 0, X2 is CH2; and / or X1 is O or S, X is selected from O, CH2, NH, S, n is 1, n1 is 0; or X1 is O or S, X is O or CH2, n is 1, n1 is 1; Or for example, in the above-mentioned formula (D) and formula (D-1), Z 12 , Z 22 , Z 32 are independently selected from methylene, -CD2-; and / or Z 11 Independently selected from -CD2-, -CH2-, -CH2CH2-, -OCH2-*, -OCH2CH2-*, *, is connected to N; and / or n2 is 2 or 3, n3 is 0, and X2 is 0; or n2 is 1 or 2, n3 is 1, and X2 is O; or n2 is 0 or 1, n3 is 0, X2 is CH2; and / or X1 is O, X is selected from O, CH2, NH, S, n is 1, n1 is 0; or X1 is O, X is O or CH2, n is 1, n1 is 1; Or for example, in the above-mentioned formula (D) and formula (D-1), Z 12 , Z 22 , Z 32 are independently selected from methylene, -CD2-; and / or Z 11 Independently selected from -CD2-, -CH2-, -CH2CH2-, -OCH2CH2-, * is connected to N; and / or n2 is 2 or 3, n3 is 0, and X2 is 0; or n2 is 2, n3 is 1, X2 is 0; and / or X1 is O, X is selected from O, CH2, NH, S, n is 1, n1 is 0; Or for example, in the above-mentioned formula (D) and formula (D-1), Z 12 , Z 22 , Z 32 are independently selected from methylene, -CD2-; Z 11 Independently selected from -CD2-, -C 1-2 Alkylene-, -OC 1-2 Alkylene-*, -SC 1-2 Alkylene-*, -NHC 1-2 Alkylene-*, -Se-C 1-2 Alkylene-*, -CH2-OC 1-2 Alkylene-, * is the terminal connected to N; or, Z 11 Independently selected from -CD2-, -CH2-, -CH2CH2-, -OCH2CH2-, * is connected to N; and / or X2 is O, NH, S, Se, and the sum of n2 and n3 is 1, 2, or 3; or, X2 is O, and the sum of n2 and n3 is 2 or 3; and / or X1 is O or S, X is selected from O, CH2, NH, S, and the sum of n and n1 is 0, 1, or 2; or, X1 is O, X is selected from O, CH2, NH, S, and the sum of n and n1 is 1 or 2; and / or For example, for any of the above formulas (D), (D-1), (D-2), and (D-3), Z 11 is a group without a double bond; the double bond is, for example, a double bond between C and O in -C(O)-, or a double bond between C and S in -C(S)-; further preferably, Z 11 With *-(CH2) n2 -X2-(CH2) n3 - (* is the end connected to N) are the same or different; Still more preferably, Z 11 、-C(X1)-(CH2) n1 -(X) n - and -(CH2) n2 -X2-(CH2) n3 - has a molecular weight independently of each other of 14.0-107.1, preferably 14.0-60; preferably about 14, about 16, about 28, about 30, about 42, about 43, about 44, about 46, about 58, or about 60; still more preferably, Z 11 , Z 21 and Z 31 Selected from -CH2-, -CD2-, -CH2CH2-, -CD2CH2-, -C(O)-, -CH2C(O)-, -NHC(O)-, -OC(O)-, -CH2CH2O-, -OCH2C(O)-, -CH2OC(O)-, -CH2CH2CH2O-, -SC(O)-; or The compound has a structure as shown in formula (E), formula (F), formula (E-1), formula (E-2), formula (E-3), formula (E-4), formula (F-1), or formula (F-2): in, L1, L2 are as defined in any one of claims 1 to 9, X is O, CH2, NH, R a Deuterium, halogen, -CN, -OH, -NH2, -CHO, C 1-3 Alkyl, C 1-3 Alkoxy, -N(C 1-3 Alkyl)2, -NH(C 1-3 Alkyl), -C(O)C 1-3 Alkyl, n1 is 0 or 1, m is 0 or 1, n is 0 or 1; R 23 , R 24 are independently selected from H and deuterium; For example, L1 is L2 is * indicates the terminal connected to N; Rings W1 and W2 are independently selected from The phenyl group is optionally substituted by one or more independently selected from halogen, C 1-3 Alkoxy (preferably fluorine, methoxy) substituents are substituted; Z 11 , Z 12 , Z 21 , Z 22 are independently selected from -C 1-2 Alkylene-, -OC 1-3 Alkylene-, -NH-C 1-2 Alkylene-, -SC 1-2 Alkylene-, -C 1-2 Alkylene-OC 1-2 Alkylene-, -C 1-2 Alkylene-C(O)-, -OC 1-2 Alkylene-C(O)-, -C 1-2 Alkylene-NH-C(O)-, -C 1-2 Alkylene-OC(O)-, -NH-C(O)-, -NH-C 1-2 Alkylene-C(O)-, -OC(O)-, -SC(O)-; or Z 11 , Z 12 , Z 21 , Z 22 are independently selected from methylene, ethylene, Or, for example L1 and L2 are independently selected from * indicates the connection terminal with N; X is selected from O, CH2, NH, S, for example X is O, CH2, NH, such as X is CH2; and / or R a Deuterium, halogen, -CN, -OH, -NH2, -CHO, C 1-3 Alkyl, C 1-3 Alkoxy, -N(C 1-3 Alkyl)2, -NH(C 1-3 Alkyl), -C(O)C 1- 3 alkyl, for example, R a is fluorine, chlorine, methyl, ethyl, methoxy, ethoxy; for example, R a is fluorine; and / or n1 is 0 or 1, and / or m is 0 or 1, for example, m is 1, and / or n is 0 or 1; for example, the sum of n and n1 is 0, 1, or 2; for example, the sum of n and n1 is 1 or 2 (i.e., n is 1 and n1 is 0; or n is 0 and n1 is 1; or n is 1 and n1 is 1; or n is 0 and n1 is 2; or n is 2 and n1 is 0); for example, the sum of n and n1 is 1 (i.e., n is 1 and n1 is 0; or n is 0 and n1 is 1); Preferably, X is selected from O, CH2, NH, S, n is 1, n1 is 0; or X is O or CH2, n is 1, n1 is 1; Or, preferably, R a is fluorine, chlorine, methyl, ethyl, methoxy, ethoxy, m is 1, X is selected from O, CH2, NH, S, The sum of n and n1 is 0, 1, 2; Or, preferably, R a is fluorine, methoxy, m is 1, X is selected from O, CH2, NH, S, The sum of n and n1 is 1, 2; For example, for any of the above-mentioned formulas (E), (E-1), (E-2), (E-3) and (E-4), L1 and L2 are respectively Z 11 and Z 21 The group, and Z 11 and Z 21 are groups without double bonds; the double bond is, for example, a double bond between C and O in -C(O)-, or a double bond between C and S in -C(S)-; further preferably, Z 11 With Z 21 Same or different, and Z 11 With Z 21 At least one of them is *-C(O)-(CH2) n1 -(X) n - (* is the terminal connected to N) group; Still more preferably, Z 11 , Z 21 and -C(O)-(CH2) n1 -(X) n - has a molecular weight independently of each other of 14.0-107.1, preferably 14.0-60; preferably about 14, about 16, about 28, about 30, about 42, about 43, about 44, about 46, about 58, or about 60; still more preferably, Z 11 , Z 21 and Z 31 Selected from -CH2-, -CD2-, -CH2CH2-, -CD2CH2-, -C(O)-, -CH2C(O)-, -NHC(O)-, -OC(O)-, -CH2CH2O-, -OCH2C(O)-, -CH2OC(O)-, -CH2CH2CH2O-, -SC(O)-; or For any of the above formula (F), formula (F-1) and formula (F-2), L1 and L2 are respectively Z 11 and Z 21 The group, and Z 11 and Z 21 There is only one group containing a double bond in -C(O)-; the double bond is, for example, a double bond between C and O in -C(O)-, or a double bond between C and S in -C(S)-; further preferably, Z 11 With Z 21 The one not containing a double bond is the same as or different from *-(CH2)2-O- (* is the terminal connected to N); Still more preferably, Z 11 and Z 21 The molecular weight of Z is independently 14.0-107.1, preferably 14.0-60; preferably about 14, about 16, about 28, about 30, about 42, about 43, about 44, about 46, about 58, or about 60; still more preferably, Z 11 , Z 21 and Z 31 Selected from -CH2-, -CD2-, -CH2CH2-, -CD2CH2-, -C(O)-, -CH2C(O)-, -NHC(O)-, -OC(O)-, -CH2CH2O-, -OCH2C(O)-, -CH2OC(O)-, -CH2CH2CH2O-, -SC(O)-; Alternatively, the compound has a structure as shown in formula (G), formula (G-1), formula (G-2), formula (G-3), or formula (G-4): in, X, X1, X2, n, n1, n2, n3 are as defined in any one of formula (B), formula (C) or formula (D), m is independently 0 or 1, for example m is 1; n4 is 0, 1, 2 or 3, or n4 is 0, 1 or 2, or n4 is 0 or 1, or n4 is 0; X3 is O, S, CH2, NH, or X3 is O, S, CH2, NH, CD2, or X3 is O, CH2, or X3 is O, CH2, CD2; R a Deuterium, halogen, -CN, -OH, -NH2, -CHO, C 1-3 Alkyl, C 1-3 Alkoxy, -N(C 1-3 Alkyl)2, -NH(C 1-3 Alkyl), -C(O)C 1- 3 alkyl; for example, R a is fluorine, chlorine, methyl, ethyl, methoxy, ethoxy; for example, R a is fluorine, methoxy; R 19 , R 20 , R 21 , R 22 , R 23 , R 24 are independently selected from H and deuterium; Preferably, X3 is 0, n4 is 2; or X3 is CH2, n4 is 0 or 1; or or X3 is CH2, CD2, n4 is 0 or 1; or X3 is CH2, CD2, n4 is 0; or Or, preferably R a is fluorine, chlorine, methyl, ethyl, methoxy, ethoxy; m is 1; X2 is O, NH, S, Se, The sum of n2 and n3 is 1, 2, and 3; X1 is O or S, X is selected from O, CH2, NH, S, The sum of n and n1 is 0, 1, 2; X3 is 0, n4 is 2; or X3 is CH2, CD2, n4 is 0 or 1; or Or, preferably R a is fluorine, chlorine, methoxy; m is 1; X2 is O, the sum of n2 and n3 is 2, 3; X1 is O, X is selected from O, CH2, NH, S, The sum of n and n1 is 1, 2; X3 is 0, n4 is 2; or X3 is CH2, CD2, n4 is 0 or 1; or Or, preferably R a is fluorine, chlorine, methyl, ethyl, methoxy, ethoxy; m is 1; X3 is 0, n4 is 2; or X3 is CH2, CD2, n4 is 0 or 1; n2 is 2 or 3, n3 is 0, X2 is O, NH, S; or n2 is 1 or 2, n3 is 1, X2 is O, NH, S; or n2 is 0 or 1, n3 is 0, and X2 is CH2; X1 is O or S, X is selected from O, CH2, NH, S, n is 1, n1 is 0; or X1 is O or S, X is O or CH2, n is 1, n1 is 1; or Or, preferably R a is fluorine, chlorine, methoxy; m is 1; X3 is 0, n4 is 2; or X3 is CH2, CD2, n4 is 0 or 1; n2 is 2 or 3, n3 is 0, and X2 is 0; or n2 is 1 or 2, n3 is 1, and X2 is O; or n2 is 0 or 1, n3 is 0, and X2 is CH2; X1 is O, X is selected from O, CH2, NH, S, n is 1, n1 is 0; or X1 is O, X is O or CH2, n is 1, n1 is 1; For any of the above-mentioned formula (G), formula (G-1), formula (G-2), formula (G-3), and formula (G-4), *-(CH2) n4 -X3-, *-(CH2) n2 -X2-(CH2) n3 -, and *-C(X1)-(CH2) n1 -(X) n - (* is the end connected to N) are the same or different from each other, and their molecular weights are independently 14.0-107.1, preferably 14.0-60; preferably about 14, about 16, about 28, about 30, about 42, about 43, about 44, about 46, about 58, or about 60; Still more preferably, Z 11 , Z 21 and Z 31 Selected from -CH2-, -CD2-, -CH2CH2-, -CD2CH2-, -C(O)-, -CH2C(O)-, -NHC(O)-, -OC(O)-, -CH2CH2O-, -OCH2C(O)-, -CH2OC(O)-, -CH2CH2CH2O-, -SC(O)-; Alternatively, the compound has a structure as shown in formula (H), formula (H-1), formula (H-2), formula (H-3), or formula (H-4): in, X, X1, X2, n, n1, n2, n3 are as defined in any one of formula (B), formula (C), formula (D) or formula (G), m is independently 0 or 1, or m is 1; n5 is 1, 2, 3 or 4, or n5 is 1, 2 or 3, or n5 is 1 or 2, or n5 is 1; R a Deuterium, halogen, -CN, -OH, -NH2, -CHO, C 1-3 Alkyl, C 1-3 Alkoxy, -N(C 1-3 Alkyl)2, -NH(C 1-3 Alkyl), -C(O)C 1- 3 alkyl; or, R a is fluorine, chlorine, methyl, ethyl, methoxy, ethoxy; or, R a is fluorine, methoxy; R 13 , R 14 , R 19 , R 20 , R 21 , R 22 , R 23 , R 24 are independently selected from H and deuterium.

11. A compound, or a pharmaceutically acceptable salt thereof, characterized in that: The compound is selected from:

12. A compound, or a pharmaceutically acceptable salt thereof, characterized in that: The compound is selected from: Or the compound is selected from: Among them, * is the terminal connected to N, 13. A compound having a structure as shown in Formula (Dc), Formula (Df), Formula (Dg), or Formula (Dh), or a pharmaceutically acceptable salt of the compound: in, Pg 1 , Pg 2 are protecting groups; Z 11 , Z 12 , Z 22 , Z 32 , X, X1, X2, n, n1, n2, n3, ring W1, W2, W3 are as defined in any one of claims 1 to 12; Preferably, Pg 1 Independently selected from tert-butyl, methyl, benzyl, Pg 2 Independently selected from tert-butyloxycarbonyl (Boc), 9-fluorenylmethoxycarbonyl (FMOC), benzyloxycarbonyl (Cbz); or Pg 2 For Boc.

14. A pharmaceutical composition, characterized in that: The pharmaceutical composition comprises the compound according to any one of claims 1 to 12, and a pharmaceutically acceptable salt of the compound; optionally, the pharmaceutical composition further comprises a pharmaceutically acceptable excipient.

15. Use of a compound according to any one of claims 1 to 12, a pharmaceutically acceptable salt of the compound, or a pharmaceutical composition according to claim 14 in the preparation of a medicament for preventing and / or treating a disease or condition associated with an elevated plasma level of Lp(a); preferably, the disease or condition associated with an elevated plasma level of Lp(a) is a cardiovascular disease (CVD); preferably, the cardiovascular disease (CVD) includes but is not limited to atherosclerotic cardiovascular disease (ASCVD), coronary artery stenosis, aortic valve stenosis, heart failure, atrial fibrillation; the ASCVD includes peripheral vascular disease, coronary heart disease, ischemic stroke.

16. A method for preventing and / or treating a disease or condition associated with elevated plasma levels of Lp(a), comprising administering to a patient a therapeutically effective dose of a compound according to any one of claims 1 to 12, or a pharmaceutically acceptable salt of the compound, or a pharmaceutical composition according to claim 14; Preferably, the disease or condition associated with increased Lp(a) plasma levels is cardiovascular disease (CVD); preferably, the cardiovascular disease (CVD) includes but is not limited to atherosclerotic cardiovascular disease (ASCVD), coronary artery stenosis, aortic valve stenosis, heart failure, atrial fibrillation; the ASCVD includes peripheral vascular disease, coronary heart disease, ischemic stroke.

17. Use of the compound according to any one of claims 1 to 12, a pharmaceutically acceptable salt of the compound, or the pharmaceutical composition according to claim 14 as a drug.

18. The compound according to any one of claims 1 to 12, the pharmaceutically acceptable salt of the compound, or the pharmaceutical composition according to claim 14 for use in preventing and / or treating a disease or condition associated with elevated plasma levels of Lp(a); Preferably, the disease or condition associated with increased Lp(a) plasma levels is cardiovascular disease (CVD); preferably, the cardiovascular disease (CVD) includes but is not limited to atherosclerotic cardiovascular disease (ASCVD), coronary artery stenosis, aortic valve stenosis, heart failure, atrial fibrillation; the ASCVD includes peripheral vascular disease, coronary heart disease, ischemic stroke.

19. The compound according to any one of claims 1 to 12, or a pharmaceutically acceptable salt of the compound, or the pharmaceutical composition according to claim 14, used in combination with another compound to prevent and / or treat cardiovascular diseases; Preferably, the additional compound is for use in the prevention and / or treatment of cardiovascular disease; Preferably, the cardiovascular disease is a disease or condition associated with elevated plasma levels of Lp(a); Preferably, the diseases or conditions associated with elevated Lp(a) plasma levels include, but are not limited to, atherosclerotic cardiovascular disease (ASCVD), coronary artery stenosis, aortic valve stenosis, heart failure, and atrial fibrillation; the ASCVD includes peripheral vascular disease, coronary heart disease, and ischemic stroke.