Preparation method for heterocyclic compound capable of inhibiting il-17a, and use thereof

Abstract

The present invention relates to a heterocyclic compound capable of inhibiting IL-17A, a preparation method therefor, an intermediate, and a use thereof. In particular, the present invention relates to the compound shown in general formula (I), a preparation method therefor, an intermediate, a pharmaceutical composition including the compound shown in general formula (I), and a use of the compound shown in general formula (I) or the pharmaceutical composition thereof in preparing a drug which treats / prevents IL-17A-mediated diseases. The substituents in general formula (I) have the same definitions as in the description.

Description

Preparation and Uses of a Heterocyclic Compound that Inhibits IL-17A Technical Field

[0001] This invention relates to an IL-17A inhibitor and its use in the preparation of medicaments for treating psoriasis, arthritis and multiple sclerosis. Background Technology

[0002] Immune function is crucial for maintaining homeostasis and effective disease response, and abnormal immune responses are a well-established contributor to the pathophysiology of autoimmune diseases. In certain disease states, some key pathways leading to these abnormal autoimmune responses have been identified as effective avenues for therapeutic intervention. A recent example is the development of interleukin (IL)-17 inhibitors. IL-17A is a recognized pro-inflammatory cytokine that plays a key role in chronic inflammation and is a major driver of tissue damage. While IL-17A induces normal immune and inflammatory responses to pathogens, it can also contribute to chronic autoimmune diseases, including psoriasis, spondyloarthritis, rheumatoid arthritis, and multiple sclerosis.

[0003] The IL-17 family comprises six cytokines (IL-17A to IL-17F). IL-17A can form homodimers or heterodimers with its family member IL-17F. IL-17A binds to both IL-17RA and IL-17RC to mediate signal transduction. IL-17A transduces signals through its receptors, activating NF-κB transcription factors and various MAPKs. In the skin and joints, IL-17A acts on cellular targets, including keratinocytes, endothelial cells, fibroblasts, osteoclasts, chondrocytes, and osteoblasts, to stimulate the production of various antimicrobial peptides, chemokines, and pro-inflammatory and proliferative cytokines, which in turn promote tissue inflammation and bone remodeling. The critical importance of the IL-23 / IL-17A axis in the pathogenesis of psoriasis has led to numerous novel biological therapies targeting these cytokines. These biologics have significantly improved skin and joint symptoms in patients with moderate to severe psoriasis and psoriatic arthritis.

[0004] Currently, there are no effective oral treatments for moderate to severe psoriasis. Small molecule IL-17A inhibitors can provide efficacy comparable to anti-IL-17A antibodies used for psoriasis and / or other IL-17A-dependent diseases, such as psoriatic arthritis. While IL-17A inhibition can increase susceptibility to opportunistic infections in some cases, orally available small molecule inhibitors with relatively short half-lives offer improved agents for managing this risk. Oral administration allows patients to discontinue medication and rapidly clear the inhibitor from the body, resulting in a faster recovery of the ability to respond to infections. Furthermore, anti-drug antibodies against anti-IL-17A may develop in some patients and may decrease in efficacy over time. This inactivation pathway does not affect small molecule IL-17A inhibitors.

[0005] Small molecule IL-17A inhibitors remain needed to provide improved and / or orally available treatments for IL-17-mediated diseases. The compounds of this invention are potent modulators of human IL-17 activity and are therefore useful in the treatment and / or prevention of a variety of human diseases, including inflammatory and autoimmune disorders, and can be used to treat psoriasis, rheumatoid arthritis, and multiple sclerosis. Summary of the Invention

[0006] This invention provides an IL-17A inhibitory compound, its stereoisomer or a pharmaceutically acceptable salt thereof, its preparation method, intermediates, and applications. Specifically, this invention provides a compound of general formula (I), its preparation method, intermediates, a pharmaceutical composition comprising the compound of general formula (I), and the use of the compound of general formula (I) or a pharmaceutical composition thereof in the preparation of a medicament for treating / preventing IL-17A-mediated diseases. The compound exhibits excellent activity, superior physicochemical properties, ease of formulation, high bioavailability, and low toxicity.

[0007] This invention provides compounds represented by formulas (I), (II), (II-1), (II-1a), (II-1b), (II-2), (III), (III-1), (III-2), (IIIA), (IIIB), (IIIC), (IIIC-1), (IIIC-2), (IIIC-3), (IIIC-4), (IIIC-5), (IIIC-6), (IIID), (IIIE), (IIIF), (IV), (V), (VA), (V-Aa), (III-a), (III-1a), (III-2a), (VI-1), (VI-2), and (VI-a), their stereoisomers, deuterated derivatives, solvates, prodrugs, metabolites, pharmaceutically acceptable salts, or cocrystals.

[0008] Indicates a single or double bond;

[0009] Ring A and ring B are each independently C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups;

[0010] In some embodiments, ring A is selected from 5-membered heteroaryl, 5-membered heterocyclic alkyl, 3-6-membered cycloalkyl, 8-10-membered bicyclic heterocyclic alkyl, and 8-10-membered bicyclic heteroaryl; in some embodiments, ring A is selected from... In some implementations, ring A is selected from... In some implementations, ring A is selected from... In some implementations, ring A is selected from... In some implementations, ring A is selected from...

[0011] In some implementations, Selected from In some implementations, Selected from

[0012] In some implementations, ring B is C. 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 quinone heteroaryl, preferably C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, 5-6 membered heteroaryl, phenyl-5-6 membered heteroaryl, phenyl-C 3-6 Cycloalkyl or 5-6-membered heteroaryl; in some embodiments, ring B is selected from phenyl, 5-6-membered heteroaryl, benzo5-membered heteroaryl, benzocyclobutyl, benzocyclopentyl, 5-membered bridged cycloalkyl, 8-10-membered bicyclic heterocycloalkyl, 8-10-membered bicyclic heteroaryl; in some embodiments, ring B is selected from

[0013] In some implementations, Selected from Or selected from Or selected from

[0014] In some implementations, ring C is C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups;

[0015] In some implementations, ring C is selected from C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, 5-6 membered heteroaryl, phenyl-5-6 membered heteroaryl, phenyl-C 3-6 Cycloalkyl or 5-6-membered heteroaryl and 5-6-membered heteroaryl;

[0016] In some implementations, ring C is selected from...

[0017] In some implementations, ring C is selected from...

[0018] Ring D is C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups;

[0019] Ring Aa is C 3-8 Cycloalkyl; in some embodiments, cycloAa is C 3-6 Cycloalkyl; in some embodiments, cycloAa is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl;

[0020] In some implementations, ring D is selected from C. 3-8 Cycloalkyl, 3-8-membered heterocycloalkyl, 5-6-membered heteroaryl, 5-6-membered heteroaryl-5-6-membered heteroaryl, or 5-6-membered heteroaryl-4-6-membered heterocycloalkyl; in some embodiments, ring D is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, aziridine, oxacyclobutyl, pyrrolidinyl, imidazoalkyl, tetrahydrofuranyl, piperidinyl, piperazinyl, furanyl, thienyl, thiazolyl, isothiazolyl, imidazolyl, pyrazolyl, triazolyl, pyridinyl, In some embodiments, ring D is selected from cyclopropyl, oxacyclobutyl, thiazolyl, imidazolyl, pyrazolyl, and others.

[0021] Each R A and R B Each of these groups can be independently represented as hydrogen, deuterium, halogen, hydroxyl, mercapto, cyano, amino, nitro, oxo, =CH2, =CF2, =CHF, =CH(C) 1-3 Alkyl), =C(C)1-3 Alkyl)2, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 aryl or 5-10 heteroaryl, wherein the C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups may be further divided by 1-5 R groups. x Replaced; in some implementations, each R A and R B Each of these groups can be independently represented as hydrogen, deuterium, halogen, hydroxyl, mercapto, cyano, amino, nitro, oxo, or C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 aryl or 5-10 heteroaryl, wherein the C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups may be further divided by 1-5 R groups. x Replaced;

[0022] In some implementations, R A For H, C 1-6Alkyl, C 3-8 Cycloalkyl, =CH2, =CF2, =CHF, =CH(C 1-3 Alkyl), =C(C) 1- 3alkyl)2, wherein the cycloalkyl group is optionally further surrounded by 1-5 R x Replaced; in some implementations, R A C 1-6 Alkyl; in some embodiments, R A C 1-3 Alkyl; in some embodiments, R A It is methyl, ethyl, or isopropyl; in some embodiments, R A For H, C 1-6 Alkyl, C 3-8 cycloalkyl; in some embodiments, R A For H, C 1-3 Alkyl, C 3-6 cycloalkyl; in some embodiments, R A H, methyl, ethyl, cyclopropyl; in some embodiments, R A C 1-6 Alkyl, C 3-6 cycloalkyl; in some embodiments, R A C 1-3 Alkyl, C 3-4 Cycloalkyl, more preferably methyl, ethyl, isopropyl, cyclopropyl or cyclobutyl;

[0023] In some implementations, each R B Each of these elements independently represents hydrogen, deuterium, halogen, hydroxyl, cyano, amino, and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl, preferably hydrogen, halogen, cyano, C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl or 3-8 membered heterocyclic alkyl, more preferably hydrogen, halogen, cyano, C 1-3 Alkyl, C 2-4 alkenyl, C 1-3 Alkoxy, C 3-5Cycloalkyl or 4-6-membered heterocycloalkyl, more preferably hydrogen, fluorine, cyano, methyl, methoxy, vinyl, cyclopropyl, cyclobutyl, cyclopentyl, azircyclobutyl, azircyclopentyl, or azircyclohexyl; in some embodiments, each R B Each of these elements independently represents hydrogen, deuterium, halogen, hydroxyl, cyano, amino, and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3- 8-membered cycloalkyl, 3-8-membered heterocyclic alkyl, C 6-10 Aryl or 5-10 heteroaryl, preferably hydrogen, halogen, cyano, C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy or C 3-8 Cycloalkyl, more preferably hydrogen, halogen, cyano, C 1-3 Alkyl, C 2-4 alkenyl, C 1-3 Alkoxy or C 3-4 Cycloalkyl, more preferably hydrogen, fluorine, cyano, methyl, methoxy, vinyl, or cyclopropyl; in some embodiments, each R B Each is independently a halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 alkylthio or C 1-6 Alkylamine group; in some embodiments, each R B Each is independently hydrogen, deuterium, F, Cl, and C. 1-3 Alkyl, Halogenated C 1-3 Alkyl, deuterated C 1-3 Alkyl, C 3- 6-membered cycloalkyl, 3-6-membered heterocyclic alkyl; in some embodiments, each R B Each is independently hydrogen, F, and C. 3-5 Cycloalkyl, 4-6 member nitrogen-containing heterocyclic alkyl; in some embodiments, each R B Each is independently halogen or C 1-6 Alkyl; in some embodiments, each R B It is fluorine;

[0024] Or, any two R B The ring atoms connected to it form C 3-8Cycloalkyl or 3-8 membered heterocycloalkyl, optionally further surrounded by 1-5 R... x Replaced; in some implementations, any two R B The ring atoms connected to it form C 3-8 Cycloalkyl, optionally further surrounded by 1-3 R q Replaced; in some implementations, any two R B The ring atoms connected to it form C 3-6 Cycloalkyl, optionally further surrounded by 1-3 R q Replaced; in some implementations, two adjacent R B The ring atoms attached to it link to form cyclobutyl or cyclopentyl groups, which may optionally be further linked by 1-3 R groups. q Replaced;

[0025] X can be a key, N, O, or S, provided that when X is O or S, R1 or R2 does not exist; when X is a key, R1 or R2 is directly connected to L3.

[0026] In some implementations, X is a key, N, O, or S, provided that when X is O or S, R1 or R2 does not exist; when X is a key, R1 or R2 is directly connected to L3.

[0027] In some implementations, X1 is a key, N, O, or S; in some implementations, X1 is N or O; provided that when X1 is O, R1 or R2 does not exist; when X1 is a key, R1 or R2 is directly connected to L3.

[0028] L1, L2, and L3 are each independently a bond, -(CR a R b ) n1 (CH2) n2 -、-(CH2) n1 (CR a R b ) n2 -、-NR c (CH2) n1 -、-(CH2) n1 C(O)(CR a R b ) n2 -、-(CR a R b ) n1 C(O)(CR a R b ) n2 -、-C(O)(CR a R b ) n1 (CH2) n2 -、-(CR aR b ) n1 O(CH2) n2 -、-(CH2) n1 O(CR a R b ) n2 -、-(CR a R b ) n1 (CH2) n2 NR c -、-(CH2) n1 NR c (CR a R b ) n2 -、-NR c (CR a R b ) n1 (CH2) n2 -、-(CH2) n1 C(O)NR c -、-(CH2) n1 C(O)NR c (CR a R b ) n2 -、-(CR a R b ) n1 C(O)NR c (CH2) n2 -、-(CH2) n1 C(O)NR c (CR a R b ) n2 C(O)NR c (CH2) n1 -、-(CH2) n1 C(O)NR c (CR a R b ) n2 (CH2) n1 -、-(CH2) n1 C(O)NR c (CR a R b ) n2 NR c (CH2) n1 -、-(CH2) n1 NR c C(O)-、-(CR a =CR b ) n1 (CH2)n2 -、-(CR a =CR b ) n1 C(O)NR c (CR a R b ) n2 C(O)NR c (CH2) n1 -、-(CR a =CR b ) n1 C(O)NR c (CR a R b ) n2 (CH2) n1 -、-(CR a =CR b ) n1 C(O)NR c (CR a R b ) n2 NR c (CH2) n1 -、-(C≡C) n1 (CH2) n2 -、-(C≡C) n1 C(O)NR c (CH2) n2 -、-(C≡C) n1 C(O)NR c (CR a R b ) n2 C(O)NR c (CH2) n1 -、-(C≡C) n1 C(O)NR c (CR a R b ) n2 (CH2) n1 -、-(C≡C) n1 C(O)NR c (CR a R b ) n2 NR c (CH2) n1 -、-S(O)2-、 =CR a C(O)NR c (CR a R b ) n2 C(O)NR c (CH2)n1 -、=CR a C(O)NR c (CR a R b ) n2 -、-NR c (CR a R b ) n2 C(O)NR c (CH2) n1 -、-NR c C(O)NR c (CR a R b ) n2 C(O)NR c (CH2) n1 -、-OC(O)NR c (CR a R b ) n2 C(O)NR c (CH2) n1 -、C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 aryl or 5-10 heteroaryl, wherein the CH2, cycloalkyl, heterocycloalkyl, aryl or heteroaryl group is optionally further surrounded by 1-5 R groups. x Replaced; in some implementations, L1, L2, and L3 are each independently a bond, -(CR a R b ) n1 (CH2) n2 -、-(CH2) n1 (CR a R b ) n2 -、-NR c (CH2) n1 -、-(CH2) n1 C(O)(CR a R b ) n2 -、-(CR a R b ) n1 C(O)(CR a R b ) n2 -、-C(O)(CR a R b ) n1 (CH2) n2 -、-(CR a R b ) n1 O(CH2)n2 -、-(CH2) n1 O(CR a R b ) n2 -、-(CR a R b ) n1 (CH2) n2 NR c -、-(CH2) n1 NR c (CR a R b ) n2 -、-NR c (CR a R b ) n1 (CH2) n2 -、-(CH2) n1 C(O)NR c -、-(CH2) n1 C(O)NR c (CR a R b ) n2 -、-(CR a R b ) n1 C(O)NR c (CH2) n2 -、-(CH2) n1 C(O)NR c (CR a R b ) n2 C(O)NR c (CH2) n1 -、-(CH2) n1 C(O)NR c (CR a R b ) n2 (CH2) n1 -、-(CH2) n1 C(O)NR c (CR a R b ) n2 NR c (CH2) n1 -、-(CH2) n1 NR c C(O)-、-(CR a =CR b ) n1 (CH2) n2 -、-(CR a =CRb ) n1 C(O)NR c (CR a R b ) n2 C(O)NR c (CH2) n1 -、-(CR a =CR b ) n1 C(O)NR c (CR a R b ) n2 (CH2) n1 -、-(CR a =CR b ) n1 C(O)NR c (CR a R b ) n2 NR c (CH2) n1 -、-(C≡C) n1 (CH2) n2 -、-(C≡C) n1 C(O)NR c (CH2) n2 -、-(C≡C) n1 C(O)NR c (CR a R b ) n2 C(O)NR c (CH2) n1 -、-(C≡C) n1 C(O)NR c (CR a R b ) n2 (CH2) n1 -、-(C≡C) n1 C(O)NR c (CR a R b ) n2 NR c (CH2) n1 -、-S(O)2-、 =CR a C(O)NR c (CR a R b ) n2 C(O)NR c (CH2) n1 -、=CRaC(O)NR c(CR a R b ) n2 -、C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 aryl or 5-10 heteroaryl, wherein the CH2, cycloalkyl, heterocycloalkyl, aryl or heteroaryl group is optionally further surrounded by 1-5 R groups. x Replaced; in some implementations, L1, L2, and L3 are each independently a bond, -(CR a R b ) n1 (CH2) n2 -、-(CH2) n1 (CR a R b ) n2 -、-NR c (CH2) n1 -、-(CH2) n1 C(O)(CR a R b ) n2 -、-(CR a R b ) n1 C(O)(CR a R b ) n2 -、-C(O)(CR a R b ) n1 (CH2) n2 -、-(CR a R b ) n1 O(CH2) n2 -、-(CH2) n1 O(CR a R b ) n2 -、-(CR a R b ) n1 (CH2) n2 NR c -、-(CH2) n1 NR c (CR a R b ) n2 -、-NR c (CR a R b ) n1 (CH2) n2 -、-(CH2) n1 C(O)NR c -、-(CH2)n1 C(O)NR c (CR a R b ) n2 -、-(CR a R b ) n1 C(O)NR c (CH2) n2 -、-(CH2) n1 C(O)NR c (CR a R b ) n2 C(O)NR c (CH2) n1 -、-(CH2) n1 C(O)NR c (CR a R b ) n2 (CH2) n1 -、-(CH2) n1 C(O)NR c (CR a R b ) n2 NR c (CH2) n1 -、-(CH2) n1 NR c C(O)-、-(CR a =CR b ) n1 (CH2) n2 -、-(CR a =CR b ) n1 C(O)NR c (CR a R b ) n2 C(O)NR c (CH2) n1 -、-(CR a =CR b ) n1 C(O)NR c (CR a R b ) n2 (CH2) n1 -、-(CR a =CR b ) n1 C(O)NR c (CR a R b ) n2 NRc (CH2) n1 -、-(C≡C) n1 (CH2) n2 -、-(C≡C) n1 C(O)NR c (CH2) n2 -、-(C≡C) n1 C(O)NR c (CR a R b ) n2 C(O)NR c (CH2) n1 -、-(C≡C) n1 C(O)NR c (CR a R b ) n2 (CH2) n1 -、-(C≡C) n1 C(O)NR c (CR a R b ) n2 NR c (CH2) n1 -、-S(O)2-、 C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 aryl or 5-10 heteroaryl, wherein the CH2, cycloalkyl, heterocycloalkyl, aryl or heteroaryl group is optionally further surrounded by 1-5 R groups. x Replaced;

[0029] In some implementations, L1, L2, and L3 are each independently a key, -(CR) a R b ) n1 (CH2) n2 -、-(CH2) n1 (CR a R b ) n2 -、-NR c (CH2) n1 -、-(CH2) n1 C(O)(CR a R b ) n2 -、-(CR a R b ) n1 C(O)(CR a R b ) n2 -、-C(O)(CR a Rb ) n1 (CH2) n2 -、-(CR a R b ) n1 O(CH2) n2 -、-(CH2) n1 O(CR a R b ) n2 -、-(CR a R b ) n1 (CH2) n2 NR c -、-(CH2) n1 NR c (CR a R b ) n2 -、-NR c (CR a R b ) n1 (CH2) n2 -、-(CH2) n1 C(O)NR c -、-(CH2) n1 C(O)NR c (CR a R b ) n2 -、-(CR a R b ) n1 C(O)NR c (CH2) n2 -、-(CH2) n1 C(O)NR c (CR a R b ) n2 C(O)NR c (CH2) n1 -、-(CH2) n1 C(O)NR c (CR a R b ) n2 (CH2) n1 -、-(CH2) n1 C(O)NR c (CR a R b ) n2 NR c (CH2) n1 -、-(CH2) n1 NR cC(O)-、-(CR a =CR b ) n1 (CH2) n2 -、-(CR a =CR b ) n1 C(O)NR c (CR a R b ) n2 C(O)NR c (CH2) n1 -、-(CR a =CR b ) n1 C(O)NR c (CR a R b ) n2 (CH2) n1 -、-(CR a =CR b ) n1 C(O)NR c (CR a R b ) n2 NR c (CH2) n1 -、-(C≡C) n1 (CH2) n2 -、-(C≡C) n1 C(O)NR c (CH2) n2 -、-(C≡C) n1 C(O)NR c (CR a R b ) n2 C(O)NR c (CH2) n1 -、-(C≡C) n1 C(O)NR c (CR a R b ) n2 (CH2) n1 -、-(C≡C) n1 C(O)NR c (CR a R b ) n2 NR c (CH2) n1 -、C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10aryl or 5-10 heteroaryl, wherein the CH2, cycloalkyl, heterocycloalkyl, aryl or heteroaryl group is optionally further surrounded by 1-5 R groups. x Replaced;

[0030] In some implementations, L1, L2, and L3 are each independently a key, -(CR) a R b ) n1 (CH2) n2 -、-(CH2) n1 (CR a R b ) n2 -、-NR c (CH2) n1 -、-(CH2) n1 C(O)(CR a R b ) n2 -、-C(O)(CR a R b ) n1 (CH2) n2 -、-(CR a R b ) n1 O(CH2) n2 -、-(CH2) n1 O(CR a R b ) n2 -、-(CR a R b ) n1 (CH2) n2 NR c -、-(CH2) n1 NR c (CR a R b ) n2 -、-NR c (CR a R b ) n1 (CH2) n2 -、-(CH2) n1 C(O)NR c -、-(CH2) n1 C(O)NR c (CR a R b ) n2 -、-(CR a R b ) n1 C(O)NR c (CH2) n2-、-(CH2) n1 C(O)NR c (CR a R b ) n2 C(O)NR c (CH2) n1 -、-(CH2) n1 C(O)NR c (CR a R b ) n2 (CH2) n1 -、-(CH2) n1 C(O)NR c (CR a R b ) n2 NR c (CH2) n1 -、-(CH2) n1 NR c C(O)-、-(CR a =CR b ) n1 (CH2) n2 -、-(CR a =CR b ) n1 C(O)NR c (CR a R b ) n2 C(O)NR c (CH2) n1 -、-(CR a =CR b ) n1 C(O)NR c (CR a R b ) n2 (CH2) n1 -、-(CR a =CR b ) n1 C(O)NR c (CR a R b ) n2 NR c (CH2) n1 -、-(C≡C) n1 (CH2) n2 -、-(C≡C) n1 C(O)NR c (CH2) n2 -、-(C≡C) n1 C(O)NRc (CR a R b ) n2 C(O)NR c (CH2) n1 -、-(C≡C) n1 C(O)NR c (CR a R b ) n2 (CH2) n1 -、-(C≡C) n1 C(O)NR c (CR a R b ) n2 NR c (CH2) n1 -、C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups;

[0031] L4 is a bond, -(CH2) n1 C(O)NR c -、-(CR a =CR b ) n1 C(O)NR c -or-(C≡C) n1 C(O)NR c -; In some implementations, L4 is a bond, -C(O)NH- or -(C≡C)C(O)NH-;

[0032] In some implementations, L1 is selected from -(CH2). n1 C(O)NR c (CR a R b ) n2 -、-(CR a R b ) n1 C(O)NR c (CH2) n2 -、-(CH2) n1 C(O)NR c (CR a R b ) n2 C(O)NR c (CH2) n1 -、-(CR a =CR b ) n1 C(O)NR c (CR a Rb ) n2 C(O)NR c (CH2) n1 -、=CR a C(O)NR c (CR a R b ) n2 C(O)NR c (CH2) n1 -、=CR a C(O)NR c (CR a R b ) n2 -; In some implementations, L1 is selected from -C(O)NHCHR a -、-C(O)NHCHR a C(O)NH-、=CR a C(O)NHCHR a C(O)NH-、=CR a C(O)NHCHR a -; In some implementations, L1 is selected from C(O)NHCR a R b C(O)NH-、-C(O)NHCR a R b -; In some implementations, L1 is selected from -C(O)NHCR a R b -;

[0033] In some implementations, L1 or L4 is selected from...

[0034] In some implementations, L2 is the key, -(CR a R b ) n1 (CH2) n2 -、-NR c (CH2) n1 -、-(CR a R b ) n1 C(O)(CR a R b ) n2 -、-C(O)(CR a R b ) n1 (CH2) n2 -、-(CR a R b ) n1(CH2) n2 NR c -、-(CH2) n1 C(O)(CR a R b ) n2 -、-(CH2) n1 NR c (CR a R b ) n2 -、-(CR a R b ) n1 O(CH2) n2 -、-(CH2) n1 O(CR a R b ) n2 -、-(CH2) n1 C(O)NR c (CR a R b ) n2 -、-(CH2) n1 C(O)NR c (CR a R b ) n2 C(O)NR c (CH2) n1 -, 3-6 membered cycloalkyl, 4-6 membered heterocycloalkyl, 5-6 membered heteroaryl; in some embodiments, L2 is a bond, -(CR a R b ) n1 (CH2) n2 -、-NR c (CH2) n1 -、-(CR a R b ) n1 C(O)(CR a R b ) n2 -、-C(O)(CR a R b ) n1 (CH2) n2 -、-(CR a R b ) n1 (CH2) n2 NR c -、-(CH2) n1 C(O)NR c (CR a R b ) n2 -、-(CH2)n1 C(O)NR c (CR a R b ) n2 C(O)NR c (CH2) n1 -、=CR a C(O)NR c (CR a R b ) n2 C(O)NR c (CH2) n1 -、=CR a C(O)NR c (CR a R b ) n2 -; In some implementations, L2 is the key, -CR a R b -、-(CR a R b )2-、-(CR a R b )4-、-(CR a R b )3-、-NR c -、-NR c CH2-, -NR c (CHR a )2-、-NR c (CHR a )3-、-CHR a NR c -、-(CHR a )2NR c -、-(CHR a )3NR c -、-(CHR a )4NR c -、-OCHR a -、C(O)-、-C(R a R b )C(O)-、-(CR a R b )2C(O)-、-C(R a R b )C(O)C(R a R b )-、-(CR a R b )2C(O)(CR a R b )2-、-C(O)C(R a R b)-、-C(O)(CR a R b )2-、-C(O)NR c -、-C(O)NR c CR a R b -、-C(O)NR c (CR a R b )2-、-CH2C(O)NR c -、-CH2C(O)NR c CR a R b -、-CH2C(O)NR c (CR a R b )2-、-C(O)NR c C(R a R b )C(O)NR c -、-CH2C(O)NR c C(R a R b )C(O)NR c -、-CH2C(O)NR c C(R a R b )C(O)NR c CH2-、-CH2C(O)NR c (CR a R b )2C(O)NR c CH2-, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, piperidinyl, pyrrolyl, morpholinyl, tetrahydropyran;

[0035] In some implementations, L2 is the key, Where r is 0, 1, 2, or 3; in some implementations, L2 is the key, Where r is 0, 1, 2, or 3; in some implementations, L2 is the key, Where r is 0, 1, 2, or 3; in some implementations, L2 is the key, Where r is 0, 1, 2 or 3;

[0036] In some implementations, L2 is selected from the key, -CHR 5b -, -NH-, -N(CH3-) or selected from -NR 5b -;

[0037] In some implementations, L3 is the key, -(CRa R b ) n1 (CH2) n2 -、-NR c (CH2) n1 -、-(CR a R b ) n1 C(O)(CR a R b ) n2 -、-C(O)(CR a R b ) n1 (CH2) n2 -、-(CR a R b ) n1 (CH2) n2 NR c -、-(CH2) n1 C(O)NR c (CR a R b ) n2 -、-(CH2) n1 C(O)NR c (CR a R b ) n2 C(O)NR c (CH2) n1 -、=CR a C(O)NR c (CR a R b ) n2 C(O)NR c (CH2) n1 -、=CR a C(O)NR c (CR a R b ) n2 -、-S(O)2-、 6-10 aryl, 5-6 heteroaryl, C 3-8 Cycloalkyl, 4-8 membered heterocyclic alkyl; in some embodiments, L3 is a bond, -C(O), -C(O)NH-, -C(O)NH-CHR a -, Oxycyclic butyl, Piperazinyl, Morpholinyl, Phenyl, Cyclobutyl, -S(O)2-, In some implementations, L3 is the key, -(CR a R b ) n1 (CH2) n2 -、-NR c(CH2) n1 -、-(CR a R b ) n1 C(O)(CR a R b ) n2 -、-C(O)(CR a R b ) n1 (CH2) n2 -、-(CR a R b ) n1 (CH2) n2 NR c -、-(CH2) n1 C(O)NR c (CR a R b ) n2 -、-(CH2) n1 C(O)NR c (CR a R b ) n2 C(O)NR c (CH2) n1 -、=CR a C(O)NR c (CR a R b ) n2 C(O)NR c (CH2) n1 -、=CR a C(O)NR c (CR a R b ) n2 -; In some implementations, L3 is a bond, -C(O)-, -CR 7a R 7b -、-CR 7a R 7b -C(O)-, -S(O)2-, Preferred key, -C(O)-, -CHR 7a -、-CHR 7a -C(O)-; In some implementations, L3 is a bond, -C(O)-, -CR 7a R 7b -、-CR 7a R 7b -C(O)-, preferred bond, -C(O)-, -CHR 7a -、-CHR 7a -C(O)-;R a and Rb Each of these can be independently represented by hydrogen, deuterium, halogen, hydroxyl, cyano, amino, oxo, or C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl, 5-10 heteroaryl, -(CH2) n1 OR aa -(CH2) n1 C(O)R aa -(CH2) n1 C(O)OR aa -(CH2) n1 C(O)NR bb R cc -(CH2) n1 NR bb C(O)-R cc -(CH2) n1 C(Se)NR bb R cc 、-(CR bb R cc ) n1 NR bb R cc or -(CR) bb R cc ) n1 C(O)NR bb R cc The C mentioned therein 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups may be further divided by 1-5 R groups. x Replaced; in some implementations, L3 is selected from -CHR 7b -、-CHR 7b -C(O)-;

[0038] R a Selected from H, halogen, cyano, amino, C1-4 Alkyl, C 1-4 Deuterated alkyl, C 1-4 Alkoxy, C 1-4 Haloalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, -(CH2) n1 NR bb C(O)-R cc The C mentioned therein 3-8 Cycloalkyl groups, 3-8 membered heterocyclic alkyl groups, may optionally be further converted to =CH2, =CF2, =CHF, or =CH(C) 1-3 Alkyl), =C(C) 1-3 Alkyl)2 is substituted; in some embodiments, R a Selected from H, halogen, cyano, amino, C 1-4 Alkyl, C 1-4 Deuterated alkyl, C 1-4 Alkoxy, C 1-4 Haloalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, -(CH2) n1 NR bb C(O)-R cc In some implementations, R a Selected from H, halogen, cyano, amino, methyl, ethyl, methoxy, cyclopropyl, -(CH2). n1 NR bb C(O)-R cc In some implementations, R a Selected from H, halogen, cyano, amino, methyl, ethyl, methoxy, cyclopropyl, -NHC(O)-CH3, -NHC(O)CH2CH3, -NHC(O)H; in some embodiments, R a H, halogen, deuterium, amino, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 3-6 Cycloalkyl, 3-8 membered heterocyclic alkyl, preferably H, F, -CHF2, -CF3, cyclopropyl; in some embodiments, R a H, F, -CHF2, -CF3, cyclopropyl; in some embodiments, R b Selected from H, halogen, cyano, amino, C 1-4 Alkyl, C 1-4 Deuterated alkyl, C 1-4 Alkoxy, C 1-4 Haloalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, -(CH2) n1 NR bb C(O)-R ccThe C mentioned therein 3-8 Cycloalkyl groups, 3-8 membered heterocyclic alkyl groups, may optionally be further converted to =CH2, =CF2, =CHF, or =CH(C) 1-3 Alkyl), =C(C) 1-3 Alkyl)2 is substituted; in some embodiments, R a Each is independently hydrogen, deuterium, and C. 1-3 Alkyl, Halogenated C 1- 3-alkyl, deuterated C 1-3 alkyl;

[0039] In some implementations, R b Selected from methyl, ethyl, -CF3, -CH2CF3, -CH2CHF2;

[0040] In some implementations, R b Each independently is C 1-4 Alkyl, C 4-6 cycloalkyl, wherein the alkyl group or cycloalkyl group is further denoted by 1-3 R groups. x Replaced; in some implementations, R b Each independently is C 1-4 Alkyl, C 4-6 Cycloalkyl groups, wherein the alkyl group or cycloalkyl group is further composed of 1-3 radicals selected from deuterium, F, Cl, oxo group, =CH2, =CF2, =CHF, =CH(C) 1-3 Alkyl), =C(C) 1-3 Alkyl)2、=C 4-6 Cycloalkyl, =(4-6 membered heterocycloalkyl), C 1-4 Alkyl, C 3-6 Cycloalkyl groups, wherein the alkyl group or cycloalkyl group is optionally further selected from F, Cl, oxo group, =CH2, =CF2, =CHF, =CH(C) 1-2 Alkyl), =C(C) 1-2 The alkyl group is substituted; in some embodiments, R b Each independently is C 4-6 cycloalkyl group, wherein the cycloalkyl group is further composed of 1, 2, or 3 radicals selected from deuterium, F, Cl, oxo group, =CH2, =CF2, =CHF, =CH(C) 1-2 Alkyl), =C(C) 1-2 Alkyl)2、=C 4-6 Cycloalkyl, =(4-6 membered heterocycloalkyl), C 1-4 Alkyl, C 3-6 Cycloalkyl groups, wherein the alkyl group or cycloalkyl group is optionally further selected from F, Cl, oxo group, =CH2, =CF2, =CHF, =CH(C) 1-2 Alkyl), =C(C) 1-2The alkyl group is substituted; in some embodiments, R b Each is independently a C4 cycloalkyl, C5 cycloalkyl, or C6 cycloalkyl group, wherein the cycloalkyl group is further composed of 1, 2, or 3 groups selected from deuterium, F, Cl, oxoyl group, =CH2, =CF2, =CHF, =CH(CH3), =C(CH3)2, =C4 cycloalkyl, =C5 cycloalkyl, =C6 cycloalkyl, =(4-membered heterocycloalkyl), =(5-membered heterocycloalkyl), =(6-membered heterocycloalkyl), C 1-2 Alkyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, wherein the alkyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl may optionally be further substituted with a group selected from F, Cl, oxo, =CH2, =CF2, =CHF, =CH(CH3), =C(CH3)2;

[0041] R va H, halogen, deuterium, amino, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Halogenated alkyl groups, 3-8 membered heterocyclic alkyl groups; in some embodiments, R va The groups are H, F, -CHF2, -CF3, and cyclopropyl.

[0042] R c For hydrogen, deuterium, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups;

[0043] R 3a and R 3b Each of these elements independently represents hydrogen, deuterium, halogen, hydroxyl, cyano, amino, and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 alkylthio or C 1-6 Alkylamine group, preferably hydrogen, hydroxyl, cyano or C 1-3 Halogenated alkyl, more preferably hydrogen, hydroxyl, cyano or trifluoromethyl;

[0044] Or, R 3a and R 3b The carbon atom it is attached to links together to form an oxo group, C 3-8 Cycloalkyl or 3-8 membered heterocyclic alkyl, preferably oxo or C 4-6 Meta-heterocyclic alkyl, more preferably oxo- or oxo-heterocyclic butyl;

[0045] R 4a and R 4b Each of these can be independently represented by hydrogen, deuterium, halogen, hydroxyl, cyano, amino, oxo, or C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 alkylthio or C 1-6 Alkylamine group, preferably hydrogen, halogen or C 1-6 Alkyl, more preferably hydrogen, halogen or C 1-3 Alkyl; in some embodiments, R 4a and R 4b Each of these can be independently represented by hydrogen, deuterium, halogen, hydroxyl, cyano, amino, oxo, or C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 alkylthio or C 1-6 Alkylamine group, preferably hydrogen, halogen or C 1-3 Alkyl, more preferably hydrogen, fluorine or methyl, and even more preferably R 4a and R 4b Both can be hydrogen or both can be fluorine, or one can be hydrogen and the other can be methyl;

[0046] Or, R 4a and R 4b It links together with the carbon atoms it is attached to to form C 2-6 Alkenyl group, optionally further modified by halogen, hydroxyl group, C 1-6 Alkyl, C 1- 6-halogenated alkyl or C 1-6 Alkoxy groups are substituted, preferably 2-methylpropenyl, difluorovinyl, or monofluorovinyl;

[0047] In some implementations, R a and R b Each group is independently selected from: H, halogen, cyano, amino, methyl, ethyl, methoxy, cyclopropyl, -NHC(O)-CH3, -NHC(O)CH2CH3, -NHC(O)H, In some implementations, R a and R b Each is independently selected from: H, In some implementations, R a and R b Each is independently selected from: H, In some implementations, R a and R b Each is independently selected from: H, In some implementations, R a and R b Each is independently selected from: H,

[0048] Rv is selected from In some implementations, Rv is selected from

[0049] R1 and R2 are each independently hydrogen, deuterium, halogen, cyano, amino, oxo, or C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl, 5-10 heteroaryl, -(CH2) n1 R aa -(CH2) n1 OR aa -(CH2) n1 C(O)R aa -(CH2) n1 C(O)CH2R aa -(CH2) n1 C(O)OR aa -(CH2) n1 C(Se)R aa -(CH2) n1 C(O)NR bb R cc -C(O)(CH2) n1 NR bb R cc -(CH2) n1 C(Se)NR bb R cc -(CH2) n1C(O)C(O)NR bb R cc 、-(CR bb R cc ) n1 NR bb R cc or -(CR) bb R cc ) n1 C(O)NR bb R cc The C mentioned therein 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups may be further divided by 1-5 R groups. x Replaced; in some embodiments, R1 and R2 are each independently hydrogen, deuterium, halogen, cyano, amino, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl, 5-10 heteroaryl, -(CH2) n1 R aa -(CH2) n1 OR aa -(CH2) n1 C(O)R aa -(CH2) n1 C(O)CH2R aa -(CH2) n1 C(O)OR aa -(CH2) n1 C(Se)R aa -(CH2) n1 C(O)NR bb R cc -C(O)(CH2) n1 NR bb R cc -(CH2) n1C(Se)NR bb R cc -(CH2) n1 C(O)C(O)NR bb R cc 、-(CR bb R cc ) n1 NR bb R cc or -(CR) bb R cc ) n1 C(O)NR bb R cc The C mentioned therein 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups may be further substituted with 1-3 R groups. q Replaced; in some embodiments, R1 and R2 are each independently hydrogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups, 3-8 membered heterocyclic alkyl groups, 5-10 membered heteroaryl groups, -(CH2) n1 R aa -(CH2) n1 C(O)R aa -(CH2) n1 C(O)CH2R aa -(CH2) n1 C(O)OR aa -(CH2) n1 C(Se)R aa -(CH(CH3)) n1 C(O)NR bb R cc -(C(CH3)2) n1 C(O)NR bb R cc -C(O)(CH2) n1 NR bb R cc -(CH2) n1 C(O)C(O)NR bb R cc or The C mentioned therein 1-6Alkyl, C 1-6 Halogenated alkyl groups, 3-8 membered heterocyclic alkyl groups, and 5-10 membered heteroaryl groups may be further determinated by 1-3 R groups. q Replaced; in some embodiments, R1 and R2 are each independently hydrogen, C 1-3 Alkyl, C 1-3 Halogenated alkyl, 4-6 membered heterocyclic alkyl, 5-6 membered heteroaryl, -CH2R aa -C(O)R aa -CH2C(O)R aa -(CH2) n1 C(O)CH2R aa -(CH2) n1 C(O)OR aa -C(Se)R aa -CH(CH3)C(O)NR bb R cc -C(CH3)2C(O)NR bb R cc -C(O)NR bb R cc -C(O)CH2NR bb R cc -C(O)C(O)NR bb R cc or The C mentioned therein 1-3 Alkyl, C 1-3 The haloalkyl, 4-6 membered heterocyclic alkyl, and 5-6 membered heteroaryl groups are optionally further substituted with 1-3 Rqs; in some embodiments, R1 and R2 are each independently hydrogen, methyl, ethyl, -OCH3, -OCH2CH3, -OCF3, -OCH2CF3, -OCH2CH2CF3, -CH2CF3, -C(O)CH2CH3, -C(Se)CH2CH3, -C(O)CH2CF3, -C(O)CH2CH2CF3, -C(O)CH2N(CH3)2, -CH(CH3)C(O)NHCH2CF3, -CH(CH3)C(O)N(CH3)CH2CF3, -C(CH3)2C(O)NHCH2CF3, -C(O)C(O)NHCH2CF3 In some implementations, R1 and R2 are each independently... In some implementations, R1 and R2 are each independently...

[0050] In some embodiments, R1 and R2 are each independently hydrogen, methyl, ethyl, -OCH3, -OCH2CH3, -OCF3, -OCH2CF3, -OCH2CH2CF3, -CH2CF3, -C(O)CH2CH3, -C(Se)CH2CH3, -C(O)CH2CF3, -C(O)CH2CH2CF3, -C(O)CH2N(CH3)2, -CH(CH3)C(O)NHCH2CF3, -CH(CH3)C(O)N(CH3)CH2CF3, -C(CH3)2C(O)NHCH2CF3, -C(O)C(O)NHCH2CF3,

[0051] In some embodiments, R1 and R2 are each independently hydrogen, methyl, -OCH3, -OCF3, -OCH2CF3, -OCH2CH2CF3, -CH2CF3, -C(O)CH2CH3, -C(Se)CH2CH3, -C(O)CH2CF3, -C(O)CH2CH2CF3, -C(O)CH2N(CH3)2, -CH(CH3)C(O)NHCH2CF3, -CH(CH3)C(O)N(CH3)CH2CF3, -C(CH3)2C(O)NHCH2CF3, -C(O)C(O)NHCH2CF3,

[0052] In some embodiments, R1 and R2 are each independently hydrogen, methyl, -OCH3, -OCF3, -OCH2CF3, -OCH2CH2CF3, -CH2CF3, -C(O)CH2CH3, -C(Se)CH2CH3, -C(O)CH2CF3, -C(O)CH2CH2CF3, -C(O)CH2N(CH3)2, -CH(CH3)C(O)NHCH2CF3, -CH(CH3)C(O)N(CH3)CH2CF3, -C(CH3)2C(O)NHCH2CF3, -C(O)C(O)NHCH2CF3,

[0053] In some embodiments, R1 and R2 are each independently hydrogen, methyl, -CH2CF3, -C(O)CH2CH3, -C(Se)CH2CH3, -C(O)CH2CF3, -C(O)CH2CH2CF3, -C(O)CH2N(CH3)2, -CH(CH3)C(O)NHCH2CF3, -CH(CH3)C(O)N(CH3)CH2CF3, -C(CH3)2C(O)NHCH2CF3, -C(O)C(O)NHCH2CF3,

[0054] In some embodiments, R1 and R2 are each independently hydrogen, deuterium, halogen, cyano, amino, or C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl, 5-10 heteroaryl, -(CH2) n1 R aa -(CH2) n1 OR aa -(CH2) n1 C(O)R aa -(CH2) n1 C(O)OR aa -(CH2) n1 C(Se)R aa -(CH2) n1 C(O)NR bb R cc -(CH(CH3)) n1 C(O)NR bb R cc -(C(CH3)2) n1 C(O)NR bb R cc -(CH2) n1 C(Se)NR bb R cc -C(O)(CH2) n1 NR bb R cc -(CH2) n1 C(O)C(O)NR bb R cc 、-(CR bb R cc) n1 NR bb R cc or -(CR) bb R cc ) n1 C(O)NR bb R cc Preferably hydrogen or -(CH2) n1 C(O)R aa More preferably, one of R1 and R2 is hydrogen and the other is -C(O)R aa Further optimization involves selecting one of R1 and R2 as hydrogen and the other as -C(O)CH2CH3. Or -C(O)CH2CH2CF3;

[0055] Alternatively, R1 and R2 can be linked to form a 3-8 membered heterocyclic alkyl group, optionally further bonded by 1-3 R groups. y Replaced; in some embodiments, R1 is linked with R2 to form a 4-6 membered heterocyclic alkyl group, optionally further replaced by 1-3 R... y Replaced;

[0056] In some implementations, R1 and R2 are each independently hydrogen and C. 1-3 Alkyl, -C(O)R aa -CH(CH3)C(O)NR bb R cc -C(CH3)2C(O)NR bb R cc -C(O)C(O)NR bb R cc Preferably, hydrogen, methyl, -C(O)CH2CF3, -C(O)C(O)NHCH2CF3 or -CHCH3C(O)NHCH2CF3;

[0057] In some implementations, R1 and R2 are linked to form Optional further by 1-3 R y Replaced; in some implementations, R1 and R2 are linked to form Optional further by 1-3 R y Replaced; in some implementations, R1 and R2 are linked to form Optional further by 1-3 R y Replaced;

[0058] In some implementations, R1 and R2 are linked to form Optional further by 1-3 R y Replaced; in some implementations, R1 and R2 are linked to form Optional further by 1-3 R y Replaced;

[0059] Alternatively, R1 and R2 can be linked to form a 3-8 membered heterocyclic alkyl group, optionally further bonded by 1-3 R groups. y Instead, R1 and R2 are preferably linked to form C. 4- 6 heterocyclic alkyl groups, optionally further surrounded by 1-3 R groups y Replaced, better Optional further by 1-3 R y Replaced, further optimized

[0060] In some implementations, R1 and R2 are each independently C 1-4 Alkyl, C 1-4 Deuterated alkyl, C 1-4 Alkoxy, C 1-4 Halogenated alkoxy groups, C 1-4 Haloalkyl, C 3-8 cycloalkyl, wherein the C 3-8 Cycloalkyl groups may be further halogenated, =CH2, =CF2, =CHF, =CH(C) 1-3 Alkyl), =C(C) 1-3 Alkyl group substituted with 2, preferably R1 and R2 are each independently C1. 1-2 Alkyl, C 1-2 Alkoxy, C 1-2 Halogenated alkoxy groups, C 3-6 cycloalkyl, wherein the C 3-6 Cycloalkyl groups may be further halogenated, =CH2, =CF2, =CHF, =CH(C) 1-3 Alkyl), =C(C) 1-3 Alkyl group)2 is substituted, more preferably R1 and R2 are each independently methyl, ethyl, methoxy, ethoxy, trifluoroethoxy, In some implementations, R1 and R2 are each independently C 1-4 Alkyl, C 1-4 Deuterated alkyl, C 1- 4-alkoxy group, C 1-4 Halogenated alkoxy groups, C 1-4 Halogenated alkyl; in some embodiments, R1 and R2 are each independently C1. 1-2 Alkyl, C 1-2 Alkoxy, C 1-2Haloalkoxy; in some embodiments, R1 and R2 are each independently methyl, ethyl, methoxy, ethoxy, or trifluoroethoxy;

[0061] Alternatively, R1 and R2 may link to form a 3-8 membered heterocyclic alkyl group, which may be further coupled with =CH2, =CF2, =CHF, or =CH(C) 1-3 Alkyl), =C(C) 1-3 The alkyl group is replaced by R2; or R1 and R2 are linked to form a 3-8 membered heterocyclic alkyl group, which is further replaced by =CH2, =CF2, =CHF, =CH(C) ...CF2, =CH 1-3 Alkyl groups, =C(CH3)2 substituted;

[0062] R y Hydrogen, halogen, =O, =CH2, =CF2, =CHF, =CH(C) 1-3 Alkyl), =C(C) 1-3 Alkyl)2、=C 4-6 Cycloalkyl, =(4-6 membered heterocycloalkyl), C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 1-6 Alkoxy, the C 1-3 Alkyl, C 4-6 Cycloalkyl groups, 4-6 membered heterocyclic alkyl groups, optionally further halogenated, C 1-2 Alkyl, OH, CN, NH2 substitution;

[0063] In some implementations, R y For hydrogen, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 1-6 Alkoxy; in some embodiments, R y It is methyl, trifluoromethyl, or methoxy;

[0064] In some implementations, Selected from:

[0065] Or, R a and R b Linkage forms oxygen groups, C 3-8 Cycloalkyl or 3-8 membered heterocyclic alkyl, wherein the C 3-8 Cycloalkyl or 3-8 membered heterocycloalkyl optionally further surrounded by 1-5 R x Replaced;

[0066] Or, R a and R b It links together with the carbon atoms it is attached to to form C2-6 alkenyl, wherein the C 2-6 Alkenyl groups can be further selected by 1-5 R groups. x Replaced;

[0067] Or, R a and R b It links together with the carbon atoms it is attached to to form C 2-6 alkenyl, =C 4-6 cycloalkyl, wherein the C 2-6 Alkenyl or cycloalkyl groups may be further modified by 1-5 R groups. x Replaced;

[0068] Or, R a R b R1, R2 and R B Any two links in form C 3-8 Cycloalkyl or 3-8 membered heterocycloalkyl, optionally further surrounded by 1-5 R... x Replaced;

[0069] R aa R bb and R cc Each of these groups can be independently represented as hydrogen, deuterium, halogen, hydroxyl, mercapto, cyano, amino, nitro, oxo, or C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 aryl or 5-10 heteroaryl, wherein the C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups may be further divided by 1-5 R groups. x Replaced;

[0070] Or, R bb and R cc Link formation C 3-8 Cycloalkyl or 3-8 membered heterocycloalkyl, optionally further surrounded by 1-5 R...x Replaced;

[0071] R x For deuterium, halogen, hydroxyl, mercapto, cyano, amino, nitro, oxo, =CH2, =CF2, =CHF, =CH(C) 1-3 Alkyl), =CF(C) 1-3 Alkyl), =C(C) 1-3 Alkyl)2、=C 4-6 Cycloalkyl, =(4-6 membered heterocycloalkyl), C 1-6 Alkyl, C 2-6 alkenyl, ynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamine group, -(CH2) n1 -C 3-8 Cycloalkyl, -(CH2) n1 -(3-8 membered heterocyclic alkyl groups), C 6-10 aryl or 5-10 heteroaryl, wherein the C 1-3 Alkyl, C 4-6 Cycloalkyl, 4-6 membered heterocyclic alkyl, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups may be further converted to halogens, hydroxyl groups, mercapto groups, cyano groups, amino groups, nitro groups, oxo groups, =CH2, =CF2, =CHF, =CH(C) 1-3 Alkyl), =C(C) 1-3 Alkyl)2, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 alkylthio or C 1-6 Alkylamine group substituted; in some embodiments, R x For deuterium, halogen, hydroxyl, mercapto, cyano, amino, nitro, oxo, =CH2, =CF2, =CHF, =CH(C) 1-3 Alkyl), =C(C) 1-3 Alkyl)2、=C 4-6Cycloalkyl, =(4-6 membered heterocycloalkyl), C 1-6 Alkyl, C 2-6 alkenyl, ynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamine group, -(CH2) n1 -C 3-8 Cycloalkyl, -(CH2) n1 -(3-8 membered heterocyclic alkyl groups), C 6-10 aryl or 5-10 heteroaryl, wherein the C 1-3 Alkyl, C 4-6 Cycloalkyl, 4-6 membered heterocyclic alkyl, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1- 6-alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups may be further converted to halogens, hydroxyl groups, mercapto groups, cyano groups, amino groups, nitro groups, oxo groups, =CH2, =CF2, =CHF, =CH(C) 1-3 Alkyl), =C(C) 1-3 Alkyl)2, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 alkylthio or C 1-6 Alkylamine group substituted; in some embodiments, R x For deuterium, halogen, hydroxyl, mercapto, cyano, amino, nitro, oxo, =CH2, =CF2, =CHF, =CH(C) 1-3 Alkyl), =C(C) 1-3 Alkyl)2, C 1-6 Alkyl, C 2-6 alkenyl, ynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamine group, -(CH2) n1 -C 3-8 Cycloalkyl, -(CH2) n1-(3-8 membered heterocyclic alkyl groups), C 6-10 aryl or 5-10 heteroaryl, wherein the C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups may be further converted to halogens, hydroxyl groups, mercapto groups, cyano groups, amino groups, nitro groups, oxo groups, =CH2, =CF2, =CHF, =CH(C) 1-3 Alkyl), =C(C) 1-3 Alkyl)2, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 alkylthio or C 1-6 Alkylamine group substituted; in some embodiments, R x For deuterium, halogen, hydroxyl, mercapto, cyano, amino, nitro, oxo, C 1-6 Alkyl, C 2-6 alkenyl, ynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamine group, -(CH2) n1 -C 3-8 Cycloalkyl, -(CH2) n1 -(3-8 membered heterocyclic alkyl groups), C 6-10 aryl or 5-10 heteroaryl, wherein the C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups may be further converted to halogens, hydroxyl groups, mercapto groups, cyano groups, amino groups, nitro groups, oxo groups, =CH2, =CF2, =C(C) groups. 1-3 Alkyl)2, C 1-6Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 alkylthio or C 1-6 Alkylamine group substituted; in some embodiments, R x For deuterium, halogen, hydroxyl, mercapto, cyano, amino, nitro, oxo, C 1-6 Alkyl, C 2-6 alkenyl, ynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamine group, -(CH2) n1 -C 3-8 Cycloalkyl, -(CH2) n1 -(3-8 membered heterocyclic alkyl groups), C 6-10 aryl or 5-10 heteroaryl, wherein the C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups may be further converted to halogens, hydroxyl groups, mercapto groups, cyano groups, amino groups, nitro groups, oxo groups, C groups, etc. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 alkylthio or C 1-6 Alkylamine group substituted; in some embodiments, R x For deuterium, halogen, hydroxyl, mercapto, cyano, amino, nitro, oxo, C 1-6 Alkyl, C 2-6 alkenyl, ynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 aryl or 5-10 heteroaryl, wherein the C 1-6 Alkyl, C2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups may be further converted to halogens, hydroxyl groups, mercapto groups, cyano groups, amino groups, nitro groups, oxo groups, C groups, etc. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 alkylthio or C 1-6 Substituted with alkylamine group;

[0072] In some implementations, R x For deuterium, halogen, hydroxyl, oxo, cyano, amino, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamine group, -(CH2) n1 C 3-6 Cycloalkyl, -(CH2) n1 -(3-6 membered heterocyclic alkyl groups), =CH2, =CF2, =CHF, =CH(C 1-3 Alkyl), =C(C) 1-3 Alkyl)2, wherein the cycloalkyl, heterocycloalkyl optionally further converted to halogen, =CH2, =CF2, =CHF, =CH(C 1-3 Alkyl), =C(C) 1-3 Alkyl)2 is substituted, preferably halogen, C 1-3 Alkyl, Halogenated C 1-3 Alkyl, C 3-6 Cycloalkyl groups, wherein the cycloalkyl group is optionally further substituted with halogens, =CH2, =CF2, =CHF, =CHCH3, =C(CH3)2, more preferably fluorine, methyl, cyclobutyl, In some implementations, R x For deuterium, F, Cl, oxo groups, =CH2, =CF2, =CHF, =CH(C) 1-3 Alkyl), =C(C) 1-3 Alkyl)2、=C 4-6Cycloalkyl, =(4-6 membered heterocycloalkyl), C 1-4 Alkyl, C 3-6 Cycloalkyl groups, wherein the alkyl group or cycloalkyl group is optionally further selected from F, Cl, oxo group, =CH2, =CF2, =CHF, =CH(C) 1-2 Alkyl), =C(C) 1-2 The alkyl group is substituted; in some embodiments, R x For deuterium, F, Cl, oxo groups, =CH2, =CF2, =CHF, =CH(CH3), =C(CH3)2, =C 4-6 Cycloalkyl, =(4-6 membered heterocycloalkyl), C 1-2 Alkyl, C3 cycloalkyl, C4 cycloalkyl, C5 cycloalkyl, C6 cycloalkyl, wherein the alkyl or cycloalkyl group is optionally further selected from F, Cl, oxo, =CH2, =CF2, =CHF, =CH(C 1-2 Alkyl), =C(C) 1-2 Substituted with alkyl groups;

[0073] Or, two R atoms located on the same carbon atom x It links together with the carbon atoms it is attached to to form C 2-6 alkenyl, C 3-8 Cycloalkyl or 4-8 membered heterocyclic alkyl groups, wherein the alkenyl, cycloalkyl, or heterocyclic alkyl group is optionally further modified by halogen, hydroxyl, mercapto, cyano, amino, nitro, oxo, or C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 alkylthio or C 1-6 The alkylamine group is replaced; or, two R groups located on the same carbon atom are replaced. x It links together with the carbon atoms it is attached to to form C 2-6 Alkenyl group, wherein the alkenyl group is optionally further modified by halogen, hydroxyl, mercapto, cyano, amino, nitro, oxo, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 alkylthio or C 1-6 The alkylamine group is replaced;

[0074] R 5a and R 5b Each of these can be independently represented by hydrogen, deuterium, halogen, hydroxyl, cyano, amino, oxo, or C. 1-6 Alkyl, C 2-6 alkenyl, C2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl, 5-10 heteroaryl, -(CH2) n1 OR aa -(CH2) n1 C(O)R aa -(CH2) n1 NR bb C(O)R aa -(CH2) n1 C(O)OR aa -(CH2) n1 C(O)NR bb R cc Or -(CH2) n1 C(Se)NR bb R cc Preferred groups include hydrogen, cyano, and C. 1-6 Alkyl or -(CH2) n1 C(O)NR bb R cc More preferably hydrogen, cyano, C 1-3 Alkyl, -C(O)NR bb R cc or -CH2C(O)NR bb R cc ;

[0075] In some implementations, R 5a and R 5b Each of these can be independently represented by hydrogen, deuterium, halogen, hydroxyl, cyano, amino, oxo, or C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl, 5-10 heteroaryl, -(CH2) n1 OR aa -(CH2) n1 C(O)R aa -(CH2) n1 C(O)OR aa-(CH2) n1 C(O)NR bb R cc Or -(CH2) n1 C(Se)NR bb R cc Preferred groups include hydrogen, cyano, and C. 1-6 Alkyl or -(CH2) n1 C(O)NR bb R cc More preferably hydrogen, cyano, C 1-3 Alkyl, -C(O)NR bb R cc or -CH2C(O)NR bb R cc ;

[0076] In some implementations, R 5a It can be hydrogen, deuterium, halogen, hydroxyl, cyano, amino, oxo, or C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl, 5-10 heteroaryl, -(CH2) n1 OR aa -(CH2) n1 C(O)R aa -(CH2) n1 C(O)OR aa -(CH2) n1 C(O)NR bb R cc Or -(CH2) n1 C(Se)NR bb R cc Preferred hydrogen and C 1-6 Alkyl or -(CH2) n1 C(O)NR bb R cc More preferably hydrogen, C 1-3 Alkyl or -C(O)NR bb R cc Further preferred are hydrogen, methyl, or -C(O)NHCH2CF3; in some embodiments, R 5a It is hydrogen, cyano, C 1-6 Alkyl, C 3-6 Cycloalkyl or -(CH2)n1 C(O)NR bb R cc More preferably hydrogen, cyano, C 1-3 Alkyl, C 3-4 Cycloalkyl, -C(O)NR bb R cc or -CH2C(O)NR bb R cc ;

[0077] Or R 5a and R 5b It links together with the carbon atoms it is attached to to form C 2-6 Alkenyl group, optionally further divided by 1-2 halogens, C 1-3 Alkyl, C 3-6 Cycloalkyl substituted;

[0078] R6 is hydrogen, deuterium, or C. 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl, 5-10 quinone heteroaryl, preferably hydrogen or C 1-6 Alkyl, more preferably hydrogen or C 1-3 Alkyl groups, more preferably hydrogen or methyl groups;

[0079] R 7a and R 7b Each of these can be independently represented by hydrogen, deuterium, halogen, hydroxyl, cyano, amino, oxo, or C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl, 5-10 heteroaryl, -(CH2) n1 OR aa -(CH2) n1 C(O)R aa -(CH2) n1 NR bb C(O)-R cc -(CH2) n1 C(O)OR aa -(CH2) n1 C(O)NR bb R cc -(CH2)n1 C(Se)NR bb R cc 、-(CR bb R cc ) n1 NR bb R cc or -(CR) bb R cc ) n1 C(O)NR bb R cc The C mentioned therein 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3- 8-membered cycloalkyl, 3-8-membered heterocyclic alkyl, C 6-10 Aryl or 5-10 heteroaryl groups may be further substituted with 1-3 R groups. z The preferred substitutes are hydrogen, cyano, and C. 1- 6-alkyl, C 3-6 cycloalkyl, 5-6 membered heteroaryl, -C(O)NR bb R cc -C(Se)NR bb R cc or -(CR) bb R cc )NR bb R cc The C mentioned therein 1-6 Alkyl, C 3-6 Cycloalkyl or 5-6 heteroaryl groups may be further surrounded by 1-3 R groups. z Replaced;

[0080] In some implementations, R 7a and R 7b Each of these can be independently represented by hydrogen, deuterium, halogen, hydroxyl, cyano, amino, oxo, or C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl, 5-10 heteroaryl, -(CH2) n1 ORaa -(CH2) n1 C(O)R aa -(CH2) n1 C(O)OR aa -(CH2) n1 C(O)NR bb R cc -(CH2) n1 C(Se)NR bb R cc 、-(CR bb R cc ) n1 NR bb R cc or -(CR) bb R cc ) n1 C(O)NR bb R cc The C mentioned therein 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3- 8-membered cycloalkyl, 3-8-membered heterocyclic alkyl, C 6-10 Aryl or 5-10 heteroaryl groups may be further substituted with 1-3 R groups. z The preferred substitutes are hydrogen, cyano, and C. 1- 6-alkyl, C 3-6 cycloalkyl, 5-6 membered heteroaryl, -C(O)NR bb R cc -C(Se)NR bb R cc or -(CR) bb R cc )NR bb R cc The C mentioned therein 1-6 Alkyl, C 3-6 Cycloalkyl or 5-6 heteroaryl groups may be further surrounded by 1-3 R groups. z Replaced;

[0081] In some implementations, R 7a and R 7b Each of these can be independently represented by hydrogen, deuterium, halogen, hydroxyl, cyano, amino, oxo, or C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl, 5-10 heteroaryl, -(CH2) n1 OR aa -(CH2) n1 C(O)R aa -(CH2) n1 C(O)OR aa -(CH2) n1 C(O)NR bb R cc -(CH2) n1 C(Se)NR bb R cc 、-(CR bb R cc ) n1 NR bb R cc or -(CR) bb R cc ) n1 C(O)NR bb R cc Preferred groups include hydrogen, cyano, and C. 1-6 Alkyl, C 3-8 cycloalkyl, 5-6 membered heteroaryl, -C(O)NR bb R cc -C(Se)NR bb R cc or -(CR) bb R cc )NR bb R cc More preferably hydrogen or Further preference for hydrogen or

[0082] In some implementations, R 7a Halogen, cyano, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 aryl or 5-10 heteroaryl, wherein the C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C1-6 Alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups may be further substituted with 1-3 R groups. z Replaced;

[0083] Cyano and C are preferred 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 5-6 heteroaryl, 5-6 heteroaryl-5-6 heteroaryl or 5-6 heteroaryl-4-6 heterocycloalkyl, wherein the C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 5-6 heteroaryl, 5-6 heteroaryl-5-6 heteroaryl, or 5-6 heteroaryl-4-6 heterocycloalkyl optionally further surrounded by 1-3 R z Replaced;

[0084] More preferably cyano, C 1-3 Alkyl, C 3-6 Cycloalkyl, 4-6-membered heterocycloalkyl, 5-6-membered heteroaryl, 5-6-membered heteroaryl-5-6-membered heteroaryl or 5-6-membered heteroaryl-4-6-membered heterocycloalkyl, wherein the C 1-3 Alkyl, C 3-6 Cycloalkyl, 4-6-membered heterocycloalkyl, 5-6-membered heteroaryl, 5-6-membered heteroaryl and 5-6-membered heteroaryl or 5-6-membered heteroaryl and 4-6-membered heterocycloalkyl optionally further surrounded by 1-3 R z Replaced;

[0085] R8, R9, R 10 and R 11 It is hydrogen, halogen, cyano, C 1-6 Alkyl, C 2-6 alkenyl or C 1-6 Alkoxy, preferably hydrogen or halogen, more preferably hydrogen or fluorine;

[0086] R z For halogens, hydroxyl groups, cyano groups, amino groups, =CH2, =CF2, =CHF, =CH(C) 1-3 Alkyl), =C(C) 1-3 Alkyl)2, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 aryl or 5-10 heteroaryl, wherein the C 1-6 Alkyl, C2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups may be further converted to halogens, hydroxyl groups, cyano groups, amino groups, or C-terminal groups. 1-3 Alkyl, C 1-3 Halogenated alkyl or C 1-3 Alkoxy groups are preferred, with halogens and C being the most suitable. 1-3 Alkyl or 3-8 membered heterocyclic alkyl groups, optionally further modified by halogen, hydroxyl, cyano, amino, C 1-3 Alkyl, C 1-3 Halogenated alkyl or C 1-3 Alkoxy groups are substituted; in some embodiments, R z Halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 aryl or 5-10 heteroaryl, wherein the C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups may be further converted to halogens, hydroxyl groups, cyano groups, amino groups, or C-terminal groups. 1-3 Alkyl, C 1-3 Halogenated alkyl or C 1-3 Alkoxy groups are preferred, with halogens and C being the most suitable. 1-3 Alkyl or 4-6 membered heterocyclic alkyl, wherein the C 1-3 Alkyl or 4-6 membered heterocyclic alkyl groups may be further modified with halogens, hydroxyl groups, cyano groups, amino groups, or C-membered groups. 1-3 Alkyl, C 1-3 Halogenated alkyl or C 1-3 Alkyl groups are substituted;

[0087] Alternatively, R1 or R2 and R 7a Linkage forms 3-8 membered heterocyclic alkyl groups, optionally further bonded by 1-3 R groups. q The preferred replacements are R1 or R2 and R 7a Linkage forms 4-6 membered heterocyclic alkyl groups, optionally further bonded by 1-3 R groups. q Replaced;

[0088] Or, R 5a or R 5b Linked with R1 to form a 3-8 membered heterocyclic alkyl group, optionally further bonded by 1-3 R groups. q The substituted component is preferably a 4-6 membered heterocyclic alkyl group containing one nitrogen atom, optionally further replaced by 1-3 R atoms. q The substituted group, more preferably piperidinyl, butyrolactam or valproic acid, optionally further replaced by 1-3 R groups. q Replaced;

[0089] Or, R 5a or R 5b With R 7a or R 7b Link formation C 3-8 Cycloalkyl or 3-8 membered heterocycloalkyl, optionally further surrounded by 1-3 R q Replaced, preferably C 3-8 Cycloalkyl, optionally further surrounded by 1-3 R q Replaced, more preferably C 3-6 Cycloalkyl, optionally further surrounded by 1-3 R q The substituted group is preferably cyclopropyl, cyclobutyl, or cyclohexyl, and optionally further replaced by 1-3 R groups. q Replaced;

[0090] Or, R 5a or R 5b With R B Link formation C 3-8 Cycloalkyl or 3-8 membered heterocycloalkyl, optionally further surrounded by 1-3 R q Replaced, preferably C 3-8 Cycloalkyl, optionally further surrounded by 1-3 R q Replaced, more preferably C 3-6 Cycloalkyl, optionally further surrounded by 1-3 R q The substituted group is preferably cyclopentyl or cyclohexyl, optionally further replaced by 1-3 R groups. q Replaced;

[0091] Or, R 7a or R 7b Linked with R1 to form a 3-8 membered heterocyclic alkyl group, optionally further bonded by 1-3 R groups. q The substituted component is preferably a 4-6 membered heterocyclic alkyl group containing one nitrogen atom, optionally further replaced by 1-3 R atoms. q The substituted product, more preferably valproic acid, optionally further replaced by 1-3 R... q Replaced;

[0092] Or, R 7a or R 7b With R B Link formation C3-8 Cycloalkyl or 3-8 membered heterocycloalkyl, optionally further surrounded by 1-3 R q Replaced, preferably C 3-8 Cycloalkyl or 4-6 membered heterocyclic alkyl containing one nitrogen atom, optionally further substituted with 1-3 Rq, more preferably C 3-6 Cycloalkyl or 4-6 membered heterocycloalkyl containing 1 nitrogen atom, optionally further surrounded by 1-3 R atoms. q The substituted group is preferably cyclopentyl, cyclohexyl, tetrahydropyran, or valeramide, optionally further replaced by 1-3 R groups. q Replaced;

[0093] Or, R B Linked with R1 to form C 3-8 Cycloalkyl or 3-8 membered heterocycloalkyl, optionally further surrounded by 1-3 R q Replaced, preferably C 3-8 Cycloalkyl or 4-6 membered heterocycloalkyl containing 1 nitrogen atom, optionally further surrounded by 1-3 R atoms. q Replaced, more preferably C 3-6 Cycloalkyl or 4-6 membered heterocycloalkyl containing 1 nitrogen atom, optionally further surrounded by 1-3 R atoms. q The substituted compounds are preferably tetrahydropyrrole, piperidinyl, valproamide, or caprolactam, optionally further replaced by 1-3 R groups. q Replaced;

[0094] R aa R bb and R cc Each is independently hydrogen, halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 aryl or 5-10 heteroaryl, wherein the C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups may be further substituted with 1-3 R groups. q The preferred substitutes are hydrogen and C. 1-6 Alkyl, C 1-6 Halogenated alkyl or 3-8 membered heterocyclic alkyl, wherein the C 1-6 Alkyl, C 1-6 Halogenated alkyl or 3-8 membered heterocyclic alkyl may optionally be further denoted by 1-3 R groups. q The preferred alternatives are hydrogen and C. 1-3 Alkyl, C 1-3Halogenated alkyl or 5-6 membered heterocyclic alkyl, wherein the C 1-3 Alkyl, C 1-3 Halogenated alkyl or 5-6 membered heterocyclic alkyl may optionally be further denoted by 1-3 R groups. q Replaced;

[0095] In some implementations, R bb Selected from H, C 1-4 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic alkyl; in some embodiments, R bb Selected from H, methyl, ethyl, cyclopropyl, and cyclobutyl;

[0096] In some implementations, R cc Selected from H, C 1-4 Alkyl, C 1-4 Deuterated alkyl, C 1-4 Alkoxy, C 1-4 Haloalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic alkyl, wherein the C 3-8 Cycloalkyl groups, 3-8 membered heterocyclic alkyl groups, may optionally be further converted to =CH2, =CF2, =CHF, or =CH(C) 1-3 Alkyl), =C(C) 1-3 Alkyl)2-substituted, preferably R cc Selected from H, C 1-2 Alkyl, C 1-2 Alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocyclic alkyl, wherein the C 3-6 Cycloalkyl groups, 3-6 membered heterocyclic alkyl groups, may optionally be further converted to =CH2, =CF2, =CHF, or =CH(C) 1-3 Alkyl), =C(C) 1-3 Alkyl)2 is substituted, more preferably R cc Selected from H, methyl, ethyl, cyclopropyl,

[0097] In some implementations, R cc Selected from H, C 1-4 Alkyl, C 1-4 Deuterated alkyl, C 1-4 Alkoxy, C 1-4 Halogenated alkyl; in some embodiments, R cc Selected from H, C 1-2 Alkyl, C 1-2 Alkoxy; in some embodiments, R cc Selected from H, methyl, and ethyl;

[0098] Or, R bb and R ccLinkage forms 3-8 membered heterocyclic alkyl groups, optionally further bonded by 1-3 R groups. q Replaced;

[0099] R q For deuterium, halogen, hydroxyl, oxo, cyano, amino, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamine group, -(CH2) n1 C 3-6 Cycloalkyl, -(CH2) n1 -(3-6 membered heterocyclic alkyl groups), =CH2, =CF2, =CHF, =CH(C 1-3 Alkyl), =C(C) 1-3 Alkyl)2, wherein the cycloalkyl, heterocycloalkyl optionally further converted to halogen, =CH2, =CF2, =CHF, =CH(C 1-3 Alkyl), =C(C) 1-3 Alkyl)2 is substituted, preferably halogen, C 1-3 Alkyl, Halogenated C 1-3 Alkyl, C 3-6 Cycloalkyl groups, wherein the cycloalkyl group is optionally further substituted with halogens, =CH2, =CF2, =CHF, =CHCH3, =C(CH3)2, more preferably fluorine, methyl, cyclobutyl, Further optimization of halogens, C 1-3 Alkyl, Halogenated C 1-3 Alkyl groups, more preferably fluorine or methyl groups;

[0100] In some implementations, R q For deuterium, halogen, hydroxyl, oxo, cyano, amino, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamine group, -(CH2) n1 C 3-6 Cycloalkyl, =CH2, =CF2, =CHF, =CH(C 1-3 Alkyl), =C(C) 1-3 Alkyl)2, preferably halogen, C 1-3 Alkyl, Halogenated C 1-3 Alkyl, more preferably fluorine or methyl;

[0101] In some implementations, R q For deuterium, halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamine group, -(CH2) n1 C 3-6 Cycloalkyl, preferably halogen, C 1-3 Alkyl, Halogenated C 1-3 Alkyl, more preferably fluorine or methyl;

[0102] Or, two R atoms located on the same carbon atom q It links together with the carbon atoms it is attached to to form C 3-8 Cycloalkyl groups, optionally further modified by halogen, hydroxyl, cyano, amino, oxo, or C- group. 1-2 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-4 Haloalkyl, C 1-4 Alkoxy, C 1-4 alkylthio or C 1-4 The alkylamine group is replaced;

[0103] R 12 It is hydrogen, halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 alkylthio or C 1-6 Alkylamine group, preferably hydrogen or C 1-6 Alkyl, more preferably hydrogen or C 1-3 Alkyl groups, more preferably hydrogen or methyl groups;

[0104] M1 and M2 are each independently CR a Or N, preferably CH or N;

[0105] M3 is CH, NH, N or S, preferably CH, NH or N;

[0106] M4 is CH, NH, N, or S; preferably CH or NH.

[0107] M5 is CH, NH, N, O, or S; preferably CH, N, O, or S;

[0108] M6 is CH, NH, N, or S; preferably CH or N.

[0109] R 13 Halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 3-8 Cycloalkyl or 3-8 membered heterocyclic alkyl, wherein the C 1-6 Alkyl, C 3- 8-membered cycloalkyl or 3-8-membered heterocyclic alkyl groups may be further modified with halogen, hydroxyl, cyano, amino, C 1-3 Alkyl, C 1-3 Halogenated alkyl or C 1-3 Alkoxy groups are preferred, with halogens and C being the most suitable. 1-3 Alkyl or 4-6 membered heterocyclic alkyl, wherein the C 1-3 Alkyl or 4-6 membered heterocyclic alkyl groups may be further converted to halogen, cyano, C 1-3 Alkyl, C 1-3 Halogenated alkyl or C 1-3 Alkyl groups are substituted;

[0110] R 14 C 1-6 Alkyl groups, preferably methyl groups;

[0111] R 15 C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups, optionally further divided by 1-3 R groups p Replaced, preferably C 3-8 Cycloalkyl, 3-8-membered heterocycloalkyl or 5-10-membered heteroaryl, optionally further surrounded by 1-3 R p Replaced, better Optional further by 1-3 R p Replaced;

[0112] Or, R 15 -(CH2) n1 R aa -(CH2) n1 OR aa -(CH2) n1 C(O)R aa -(CH2)n1 C(O)OR aa -(CH2) n1 C(Se)R aa -(CH2) n1 C(O)NR bb R cc -(CH(CH3)) n1 C(O)NR bb R cc -(C(CH3)2) n1 C(O)NR bb R cc -(CH2) n1 C(Se)NR bb R cc -C(O)(CH2) n1 NR bb R cc -(CH2) n1 C(O)C(O)NR bb R cc 、-(CR bb R cc ) n1 NR bb R cc or -(CR) bb R cc ) n1 C(O)NR bb R cc Preferred -CH(CH3)C(O)NR bb R cc -C(CH3)2C(O)NR bb R cc or More preferably -CHCH3C(O)NHCH2CF3, -CH(CH3)C(O)N(CH3)CH2CF3, -C(CH3)2C(O)NHCH2CF3 or

[0113] R p For hydrogen, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 1-6 Alkoxy, preferably methyl;

[0114] t is an integer between 0 and 3;

[0115] s is 0 or 1;

[0116] n is an integer between 0 and 5;

[0117] m is an integer from 0 to 5; preferably m is an integer from 0 to 3, and more preferably 0, 1 or 2;

[0118] n1 is an integer between 0 and 3, preferably 0, 1 or 2;

[0119] n2 is an integer between 0 and 3, preferably 0, 1 or 2;

[0120] In some implementations, formula (IIIA) satisfies at least one of the following conditions:

[0121] (1)R 5a Linked with R1 to form a 3-8 membered heterocyclic alkyl group, optionally further substituted by 1-3 Rq, preferably a 4-6 membered heterocyclic alkyl group containing 1 nitrogen atom, optionally further substituted by 1-3 Rq. q The substituted group, more preferably piperidinyl, butyrolactam or valproic acid, optionally further replaced by 1-3 R groups. q Replaced;

[0122] (2)R 5a With R 7a or R 7b Link formation C 3-8 Cycloalkyl or 3-8 membered heterocycloalkyl, optionally further surrounded by 1-3 R q Replaced, preferably C 3-8 Cycloalkyl, optionally further surrounded by 1-3 R q Replaced, more preferably C 3-6 Cycloalkyl, optionally further surrounded by 1-3 R q The substituted group is preferably cyclopropyl, cyclobutyl, or cyclohexyl, and optionally further replaced by 1-3 R groups. q Replaced;

[0123] (3)R 5a With R 11 Link formation C 3-8 Cycloalkyl or 3-8 membered heterocycloalkyl, optionally further surrounded by 1-3 R q Replaced, preferably C 3-8 Cycloalkyl, optionally further surrounded by 1-3 R q Replaced, more preferably C 3-6 Cycloalkyl, optionally further surrounded by 1-3 R q The substituted group is preferably cyclopentyl or cyclohexyl, optionally further replaced by 1-3 R groups. q Replaced;

[0124] (4)R 7a or R 7b Linked with R1 to form a 3-8 membered heterocyclic alkyl group, optionally further bonded by 1-3 R groups. q The substituted component is preferably a 4-6 membered heterocyclic alkyl group containing one nitrogen atom, optionally further replaced by 1-3 R atoms. qThe substituted product, more preferably valproic acid, optionally further replaced by 1-3 R... q Replaced;

[0125] (5)R 7a or R 7b Linked with R8 to form C 3-8 Cycloalkyl or 3-8 membered heterocycloalkyl, optionally further surrounded by 1-3 R q Replaced, preferably C 3-8 Cycloalkyl or 4-6 membered heterocycloalkyl containing 1 nitrogen atom, optionally further surrounded by 1-3 R atoms. q Replaced, more preferably C 3-6 Cycloalkyl or 4-6 membered heterocycloalkyl containing 1 nitrogen atom, optionally further surrounded by 1-3 R atoms. q The substituted group is preferably cyclopentyl, tetrahydropyran, or valeramide, optionally further replaced by 1-3 R groups. q Replaced;

[0126] (6)R 11 Linked with R1 to form C 3-8 Cycloalkyl or 3-8 membered heterocycloalkyl, optionally further substituted with 1-3 Rq, preferably C 3-8 Cycloalkyl or 4-6 membered heterocycloalkyl containing 1 nitrogen atom, optionally further surrounded by 1-3 R atoms. q Replaced, more preferably C 3-6 Cycloalkyl or 4-6 membered heterocycloalkyl containing 1 nitrogen atom, optionally further surrounded by 1-3 R atoms. q The substituted compounds are preferably tetrahydropyrrole, piperidinyl, valproamide, or caprolactam, optionally further replaced by 1-3 R groups. q Replaced;

[0127] (7)R 10 With R 11 Link formation C 3-8 Cycloalkyl or 3-8 membered heterocycloalkyl, optionally further surrounded by 1-3 R q Replaced, preferably C 3-8 Cycloalkyl, optionally further surrounded by 1-3 R q Replaced, more preferably C 3-6 Cycloalkyl, optionally further surrounded by 1-3 R q The substituted group is preferably cyclobutyl, cyclopentyl, or cyclohexyl, and optionally further replaced by 1-3 R groups. q Replaced;

[0128] r is 0, 1, or 2;

[0129] In some implementations, the compound of general formula (V) is not

[0130] In some implementations, the general formula (VA) no

[0131] The object of this invention is to provide a compound of general formula (I), its stereoisomers, or a pharmaceutically acceptable salt thereof:

[0132] in:

[0133] Ring A and ring B are each independently C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups;

[0134] Each R A and R B Each of these groups can be independently represented as hydrogen, deuterium, halogen, hydroxyl, mercapto, cyano, amino, nitro, oxo, =CH2, =CF2, =CHF, =CH(C) 1-3 Alkyl), =C(C) 1-3 Alkyl)2, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 aryl or 5-10 heteroaryl, wherein the C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups may be further divided by 1-5 R groups. x Replaced;

[0135] Or, any two R B The ring atoms connected to it form C 3-8 Cycloalkyl or 3-8 membered heterocycloalkyl, optionally further surrounded by 1-5 R... x Replaced;

[0136] X is a key, N, O, or S, provided that when X is O or S, R1 or R2 does not exist; when X is a key, R1 or R2 is directly connected to L3; or X is N, O, or S, provided that when X is O or S, R1 or R2 does not exist.

[0137] L1, L2, and L3 are each independently a bond, -(CR a R b ) n1 (CH2) n2 -、-(CH2) n1 (CR a R b ) n2 -、-NR c (CH2) n1 -、-(CH2) n1 C(O)(CR a R b ) n2 -、-(CR a R b ) n1 C(O)(CR a R b ) n2 -、-C(O)(CR a R b ) n1 (CH2) n2 -、-(CR a R b ) n1 O(CH2) n2 -、-(CH2) n1 O(CR a R b ) n2 -、-(CR a R b ) n1 (CH2) n2 NR c -、-(CH2) n1 NR c (CR a R b ) n2 -、-NR c (CR a R b ) n1 (CH2) n2 -、-(CH2) n1 C(O)NR c -、-(CH2) n1 C(O)NR c (CR a R b )n2 -、-(CR a R b ) n1 C(O)NR c (CH2) n2 -、-(CH2) n1 C(O)NR c (CR a R b ) n2 C(O)NR c (CH2) n1 -、-(CH2) n1 C(O)NR c (CR a R b ) n2 (CH2) n1 -、-(CH2) n1 C(O)NR c (CR a R b ) n2 NR c (CH2) n1 -、-(CH2) n1 NR c C(O)-、-(CR a =CR b ) n1 (CH2) n2 -、-(CR a =CR b ) n1 C(O)NR c (CR a R b ) n2 C(O)NR c (CH2) n1 -、-(CR a =CR b ) n1 C(O)NR c (CR a R b ) n2 (CH2) n1 -、-(CR a =CR b ) n1 C(O)NR c (CR a R b ) n2 NR c (CH2) n1 -、-(C≡C) n1 (CH2)n2 -、-(C≡C) n1 C(O)NR c (CH2) n2 -、-(C≡C) n1 C(O)NR c (CR a R b ) n2 C(O)NR c (CH2) n1 -、-(C≡C) n1 C(O)NR c (CR a R b ) n2 (CH2) n1 -、-(C≡C) n1 C(O)NR c (CR a R b ) n2 NR c (CH2) n1 -、-S(O)2-、 =CR a C(O)NR c (CR a R b ) n2 C(O)NR c (CH2) n1 -、=CR a C(O)NR c (CR a R b ) n2 -、-NR c (CR a R b [[ID=​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​aryl or 5-10 heteroaryl, wherein the CH2, cycloalkyl, heterocycloalkyl, aryl or heteroaryl group is optionally further surrounded by 1-5 R groups. x Replaced; or

[0138] L1, L2, and L3 are each independently a bond, -(CR a R b ) n1 (CH2) n2 -、-(CH2) n1 (CR a R b ) n2 -、-NR c (CH2) n1 -、-(CH2) n1 C(O)(CR a R b ) n2 -、-(CR a R b ) n1 C(O)(CR a R b ) n2 -、-C(O)(CR a R b ) n1 (CH2) n2 -、-(CR a R b ) n1 O(CH2) n2 -、-(CH2) n1 O(CR a R b ) n2 -、-(CR a R b ) n1 (CH2) n2 NR c -、-(CH2) n1 NR c (CR a R b ) n2 -、-NR c (CR a R b ) n1 (CH2) n2 -、-(CH2) n1 C(O)NR c -、-(CH2) n1 C(O)NR c (CR a R b ) n2-、-(CR a R b ) n1 C(O)NR c (CH2) n2 -、-(CH2) n1 C(O)NR c (CR a R b ) n2 C(O)NR c (CH2) n1 -、-(CH2) n1 C(O)NR c (CR a R b ) n2 (CH2) n1 -、-(CH2) n1 C(O)NR c (CR a R b ) n2 NR c (CH2) n1 -、-(CH2) n1 NR c C(O)-、-(CR a =CR b ) n1 (CH2) n2 -、-(CR a =CR b ) n1 C(O)NR c (CR a R b ) n2 C(O)NR c (CH2) n1 -、-(CR a =CR b ) n1 C(O)NR c (CR a R b ) n2 (CH2) n1 -、-(CR a =CR b ) n1 C(O)NR c (CR a R b ) n2 NR c (CH2) n1 -、-(C≡C) n1 (CH2) n2-、-(C≡C) n1 C(O)NR c (CH2) n2 -、-(C≡C) n1 C(O)NR c (CR a R b ) n2 C(O)NR c (CH2) n1 -、-(C≡C) n1 C(O)NR c (CR a R b ) n2 (CH2) n1 -、-(C≡C) n1 C(O)NR c (CR a R b ) n2 NR c (CH2) n1 -、-S(O)2-、 =CRaC(O)NR c (CR a R b ) n2 C(O)NR c (CH2) n1 -、=CRaC(O)NR c (CR a R b ) n2 -、C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 aryl or 5-10 heteroaryl, wherein the CH2, cycloalkyl, heterocycloalkyl, aryl or heteroaryl group is optionally further surrounded by 1-5 R groups. x Replaced; or

[0139] L1, L2, and L3 are each independently a bond, -(CR a R b ) n1 (CH2) n2 -、-(CH2) n1 (CR a R b ) n2 -、-NR c (CH2) n1 -、-(CH2) n1 C(O)(CR a R b ) n2 -、-(CR a Rb ) n1 C(O)(CR a R b ) n2 -、-C(O)(CR a R b ) n1 (CH2) n2 -、-(CR a R b ) n1 O(CH2) n2 -、-(CH2) n1 O(CR a R b ) n2 -、-(CR a R b ) n1 (CH2) n2 NR c -、-(CH2) n1 NR c (CR a R b ) n2 -、-NR c (CR a R b ) n1 (CH2) n2 -、-(CH2) n1 C(O)NR c -、-(CH2) n1 C(O)NR c (CR a R b ) n2 -、-(CR a R b ) n1 C(O)NR c (CH2) n2 -、-(CH2) n1 C(O)NR c (CR a R b ) n2 C(O)NR c (CH2) n1 -、-(CH2) n1 C(O)NR c (CR a R b ) n2 (CH2) n1 -、-(CH2) n1 C(O)NR c (CR aR b ) n2 NR c (CH2) n1 -、-(CH2) n1 NR c C(O)-、-(CR a =CR b ) n1 (CH2) n2 -、-(CR a =CR b ) n1 C(O)NR c (CR a R b ) n2 C(O)NR c (CH2) n1 -、-(CR a =CR b ) n1 C(O)NR c (CR a R b ) n2 (CH2) n1 -、-(CR a =CR b ) n1 C(O)NR c (CR a R b ) n2 NR c (CH2) n1 -、-(C≡C) n1 (CH2) n2 -、-(C≡C) n1 C(O)NR c (CH2) n2 -、-(C≡C) n1 C(O)NR c (CR a R b ) n2 C(O)NR c (CH2) n1 -、-(C≡C) n1 C(O)NR c (CR a R b ) n2 (CH2) n1 -、-(C≡C) n1 C(O)NR c (CR a R b ) n2 NRc (CH2) n1 -、-S(O)2-、 C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 aryl or 5-10 heteroaryl, wherein the CH2, cycloalkyl, heterocycloalkyl, aryl or heteroaryl group is optionally further surrounded by 1-5 R groups. x Replaced; or

[0140] L1, L2, and L3 are each independently a bond, -(CR a R b ) n1 (CH2) n2 -、-(CH2) n1 (CR a R b ) n2 -、-NR c (CH2) n1 -、-(CH2) n1 C(O)(CR a R b ) n2 -、-(CR a R b ) n1 C(O)(CR a R b ) n2 -、-C(O)(CR a R b ) n1 (CH2) n2 -、-(CR a R b ) n1 O(CH2) n2 -、-(CH2) n1 O(CR a R b ) n2 -、-(CR a R b ) n1 (CH2) n2 NR c -、-(CH2) n1 NR c (CR a R b ) n2 -、-NR c (CR a R b ) n1 (CH2) n2 -、-(CH2) n1 C(O)NRc -、-(CH2) n1 C(O)NR c (CR a R b ) n2 -、-(CR a R b ) n1 C(O)NR c (CH2) n2 -、-(CH2) n1 C(O)NR c (CR a R b ) n2 C(O)NR c (CH2) n1 -、-(CH2) n1 C(O)NR c (CR a R b ) n2 (CH2) n1 -、-(CH2) n1 C(O)NR c (CR a R b ) n2 NR c (CH2) n1 -、-(CH2) n1 NR c C(O)-、-(CR a =CR b ) n1 (CH2) n2 -、-(CR a =CR b ) n1 C(O)NR c (CR a R b ) n2 C(O)NR c (CH2) n1 -、-(CR a =CR b ) n1 C(O)NR c (CR a R b ) n2 (CH2) n1 -、-(CR a =CR b ) n1 C(O)NR c (CR a R b) n2 NR c (CH2) n1 -、-(C≡C) n1 (CH2) n2 -、-(C≡C) n1 C(O)NR c (CH2) n2 -、-(C≡C) n1 C(O)NR c (CR a R b ) n2 C(O)NR c (CH2) n1 -、-(C≡C) n1 C(O)NR c (CR a R b ) n2 (CH2) n1 -、-(C≡C) n1 C(O)NR c (CR a R b ) n2 NR c (CH2) n1 -、C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 aryl or 5-10 heteroaryl, wherein the CH2, cycloalkyl, heterocycloalkyl, aryl or heteroaryl group is optionally further surrounded by 1-5 R groups. x Replaced; or

[0141] L1, L2, and L3 are each independently a bond, -(CR a R b ) n1 (CH2) n2 -、-(CH2) n1 (CR a R b ) n2 -、-NR c (CH2) n1 -、-(CH2) n1 C(O)(CR a R b ) n2 -、-C(O)(CR a R b ) n1 (CH2) n2 -、-(CR a R b ) n1 O(CH2) n2-、-(CH2) n1 O(CR a R b ) n2 -、-(CR a R b ) n1 (CH2) n2 NR c -、-(CH2) n1 NR c (CR a R b ) n2 -、-NR c (CR a R b ) n1 (CH2) n2 -、-(CH2) n1 C(O)NR c -、-(CH2) n1 C(O)NR c (CR a R b ) n2 -、-(CR a R b ) n1 C(O)NR c (CH2) n2 -、-(CH2) n1 C(O)NR c (CR a R b ) n2 C(O)NR c (CH2) n1 -、-(CH2) n1 C(O)NR c (CR a R b ) n2 (CH2) n1 -、-(CH2) n1 C(O)NR c (CR a R b ) n2 NR c (CH2) n1 -、-(CH2) n1 NR c C(O)-、-(CR a =CR b ) n1 (CH2) n2 -、-(CR a =CR b )n1 C(O)NR c (CR a R b ) n2 C(O)NR c (CH2) n1 -、-(CR a =CR b ) n1 C(O)NR c (CR a R b ) n2 (CH2) n1 -、-(CR a =CR b ) n1 C(O)NR c (CR a R b ) n2 NR c (CH2) n1 -、-(C≡C) n1 (CH2) n2 -、-(C≡C) n1 C(O)NR c (CH2) n2 -、-(C≡C) n1 C(O)NR c (CR a R b ) n2 C(O)NR c (CH2) n1 -、-(C≡C) n1 C(O)NR c (CR a R b ) n2 (CH2) n1 -、-(C≡C) n1 C(O)NR c (CR a R b ) n2 NR c (CH2) n1 -、C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups;

[0142] R a and R b Each of these can be independently represented by hydrogen, deuterium, halogen, hydroxyl, cyano, amino, oxo, or C. 1-6 Alkyl, C 2-6 alkenyl, C2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl, 5-10 heteroaryl, -(CH2) n1 OR aa -(CH2) n1 C(O)R aa -(CH2) n1 C(O)OR aa -(CH2) n1 C(O)NR bb R cc -(CH2) n1 NR bb C(O)-R cc -(CH2) n1 C(Se)NR bb R cc 、-(CR bb R cc ) n1 NR bb R cc or -(CR) bb R cc ) n1 C(O)NR bb R cc The C mentioned therein 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3- 8-membered cycloalkyl, 3-8-membered heterocyclic alkyl, C 6-10 Aryl or 5-10 heteroaryl groups may be further divided by 1-5 R groups. x Replaced; or

[0143] R a and R b Each of these can be independently represented by hydrogen, deuterium, halogen, hydroxyl, cyano, amino, oxo, or C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl, 5-10 heteroaryl, -(CH2) n1 OR aa -(CH2) n1 C(O)R aa -(CH2) n1 C(O)OR aa -(CH2) n1 C(O)NR bb R cc -(CH2) n1 C(Se)NR bb R cc 、-(CR bb R cc ) n1 NR bb R cc or -(CR) bb R cc ) n1 C(O)NR bb R cc The C mentioned therein 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups may be further divided by 1-5 R groups. x Replaced;

[0144] R c For hydrogen, deuterium, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups;

[0145] R1 and R2 are each independently hydrogen, deuterium, halogen, cyano, amino, oxo, or C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl, 5-10 heteroaryl, -(CH2) n1 R aa -(CH2) n1 OR aa -(CH2) n1 C(O)R aa -(CH2) n1 C(O)CH2R aa -(CH2) n1 C(O)OR aa -(CH2) n1 C(Se)R aa -(CH2) n1 C(O)NR bb R cc -C(O)(CH2) n1 NR bb R cc -(CH2) n1 C(Se)NR bb R cc -(CH2) n1 C(O)C(O)NR bb R cc 、-(CR bb R cc ) n1 NR bb R cc or -(CR) bb R cc ) n1 C(O)NR bb R cc The C mentioned therein 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups may be further divided by 1-5 R groups. x Replaced;

[0146] Or, R a and R b Linkage forms oxygen groups, C3-8 Cycloalkyl or 3-8 membered heterocyclic alkyl, wherein the C 3-8 Cycloalkyl or 3-8 membered heterocycloalkyl optionally further surrounded by 1-5 R x Replaced;

[0147] Or, R a and R b It links together with the carbon atoms it is attached to to form C 2-6 alkenyl, =C 4-6 cycloalkyl, wherein the C 2-6 Alkenyl or cycloalkyl groups may be further modified by 1-5 R groups. x Replaced; or, R a R b R1, R2 and R B Any two links in form C 3-8 Cycloalkyl or 3-8 membered heterocycloalkyl, optionally further surrounded by 1-5 R... x Replaced;

[0148] R aa R bb and R cc Each of these groups can be independently represented as hydrogen, deuterium, halogen, hydroxyl, mercapto, cyano, amino, nitro, oxo, or C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 aryl or 5-10 heteroaryl, wherein the C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups may be further divided by 1-5 R groups. x Replaced;

[0149] Or, R bb and R cc Link formation C 3-8 Cycloalkyl or 3-8 membered heterocycloalkyl, optionally further surrounded by 1-5 R... xReplaced; R x For deuterium, halogen, hydroxyl, mercapto, cyano, amino, nitro, oxo, =CH2, =CF2, =CHF, =CH(C) 1-3 Alkyl), =C(C) 1-3 Alkyl)2、=C 4-6 Cycloalkyl, =(4-6 membered heterocycloalkyl), C 1-6 Alkyl, C 2-6 alkenyl, ynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamine group, -(CH2) n1 -C 3-8 Cycloalkyl, -(CH2) n1 -(3-8 membered heterocyclic alkyl groups), C 6-10 aryl or 5-10 heteroaryl, wherein the C 1-3 Alkyl, C 4-6 Cycloalkyl, 4-6 membered heterocyclic alkyl, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups may be further converted to halogens, hydroxyl groups, mercapto groups, cyano groups, amino groups, nitro groups, oxo groups, =CH2, =CF2, =CHF, =CH(C) 1-3 Alkyl), =C(C) 1-3 Alkyl)2, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 alkylthio or C 1-6 Substituted with alkylamine group; or

[0150] R x For deuterium, halogen, hydroxyl, mercapto, cyano, amino, nitro, oxo, =CH2, =CF2, =CHF, =CH(C) 1-3 Alkyl), =C(C) 1-3 Alkyl)2, C 1-6 Alkyl, C 2-6 alkenyl, ynyl, C 1-6 Deuterated alkyl, C1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamine group, -(CH2) n1 -C 3-8 Cycloalkyl, -(CH2) n1 -(3-8 membered heterocyclic alkyl groups), C 6-10 aryl or 5-10 heteroaryl, wherein the C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups may be further converted to halogens, hydroxyl groups, mercapto groups, cyano groups, amino groups, nitro groups, oxo groups, =CH2, =CF2, =CHF, =CH(C) 1-3 Alkyl), =C(C) 1-3 Alkyl)2, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 alkylthio or C 1-6 Substituted with alkylamine group; or

[0151] R x For deuterium, halogen, hydroxyl, mercapto, cyano, amino, nitro, oxo, C 1-6 Alkyl, C 2-6 alkenyl, ynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamine group, -(CH2) n1 -C 3-8 Cycloalkyl, -(CH2) n1 -(3-8 membered heterocyclic alkyl groups), C 6-10 aryl or 5-10 heteroaryl, wherein the C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups may be further converted to halogens, hydroxyl groups, mercapto groups, cyano groups, amino groups, nitro groups, oxo groups, =CH2, =CF2, =C(C) groups. 1-3 Alkyl)2, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 alkylthio or C 1-6 Substituted with alkylamine group; or

[0152] R x For deuterium, halogen, hydroxyl, mercapto, cyano, amino, nitro, oxo, C 1-6 Alkyl, C 2-6 alkenyl, ynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamine group, -(CH2) n1 -C 3-8 Cycloalkyl, -(CH2) n1 -(3-8 membered heterocyclic alkyl groups), C 6-10 aryl or 5-10 heteroaryl, wherein the C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups may be further converted to halogens, hydroxyl groups, mercapto groups, cyano groups, amino groups, nitro groups, oxo groups, C groups, etc. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 alkylthio or C 1-6 Substituted with alkylamine group; or

[0153] R x For deuterium, halogen, hydroxyl, mercapto, cyano, amino, nitro, oxo, C 1-6 Alkyl, C 2-6alkenyl, ynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 aryl or 5-10 heteroaryl, wherein the C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1- 6-alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups may be further converted to halogens, hydroxyl groups, mercapto groups, cyano groups, amino groups, nitro groups, oxo groups, C groups, etc. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1- 6-alkylthio or C 1-6 Substituted with alkylamine group;

[0154] Or, two R atoms located on the same carbon atom x It links together with the carbon atoms it is attached to to form C 2-6 alkenyl, C 3-8 Cycloalkyl or 4-8 membered heterocyclic alkyl groups, wherein the alkenyl, cycloalkyl, or heterocyclic alkyl group is optionally further modified by halogen, hydroxyl, mercapto, cyano, amino, nitro, oxo, or C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 alkylthio or C 1-6 The alkylamine group is replaced;

[0155] Or, two R atoms located on the same carbon atom x It links together with the carbon atoms it is attached to to form C 2-6 Alkenyl group, wherein the alkenyl group is optionally further modified by halogen, hydroxyl, mercapto, cyano, amino, nitro, oxo, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1- 6-alkoxy, C1-6 alkylthio or C 1-6 The group substituted by the alkylamine group; n is an integer from 0 to 5;

[0156] m is an integer between 0 and 5;

[0157] n1 is an integer between 0 and 3;

[0158] n2 is an integer between 0 and 3.

[0159] The present invention also provides compounds of general formulas (II), (II-1), (II-1a), and (II-2), their stereoisomers, or pharmaceutically acceptable salts thereof.

[0160] in:

[0161] X1 can be a bond, N, O, or S, preferably N or O, provided that when X1 is O, R1 or R2 does not exist; when X1 is a bond, R1 or R2 is directly connected to L3.

[0162] X2 is CR a R b or NR c CH2 or NH are preferred;

[0163] L4 is a bond, -(CH2) n1 C(O)NR c -、-(CR a =CR b ) n1 C(O)NR c -or-(C≡C) n1 C(O)NR c -, preferred bond, -C(O)NH- or -(C≡C)C(O)NH-;

[0164] R 3a and R 3b Each of these elements independently represents hydrogen, deuterium, halogen, hydroxyl, cyano, amino, and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 alkylthio or C 1-6 Alkylamine group, preferably hydrogen, hydroxyl, cyano or C 1-3 Halogenated alkyl, more preferably hydrogen, hydroxyl, cyano or trifluoromethyl;

[0165] Or, R 3a and R 3b The carbon atom it is attached to links together to form an oxo group, C3-8 Cycloalkyl or 3-8 membered heterocyclic alkyl, preferably oxo or C 4-6 Meta-heterocyclic alkyl, more preferably oxo- or oxo-heterocyclic butyl;

[0166] R 4a and R 4b Each of these can be independently represented by hydrogen, deuterium, halogen, hydroxyl, cyano, amino, oxo, or C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 alkylthio or C 1-6 Alkylamine group, preferably hydrogen, halogen or C 1-6 Alkyl, more preferably hydrogen, halogen or C 1-3 alkyl;

[0167] Or, R 4a and R 4b It links together with the carbon atoms it is attached to to form C 2-6 Alkenyl group, optionally further modified by halogen, hydroxyl group, C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 1-6 Alkoxy groups are substituted, preferably 2-methylpropenyl, difluorovinyl, or monofluorovinyl;

[0168] The definitions of the remaining groups are the same as those in the above technical solution.

[0169] The present invention also provides a compound of general formula (II), its stereoisomer or a pharmaceutically acceptable salt thereof:

[0170] in:

[0171] X1 is N, O or S, preferably N or O, provided that R1 or R2 does not exist when X1 is O;

[0172] X2 is CR a R b or NR c CH2 or NH are preferred;

[0173] L4 is a bond, -(CH2) n1 C(O)NR c -、-(CR a =CR b ) n1 C(O)NR c -or-(C≡C) n1 C(O)NR c-, preferred bond, -C(O)NH- or -(C≡C)C(O)NH-;

[0174] R 3a and R 3b Each of these elements independently represents hydrogen, deuterium, halogen, hydroxyl, cyano, amino, and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 alkylthio or C 1-6 Alkylamine group, preferably hydrogen, hydroxyl, cyano or C 1-3 Halogenated alkyl, more preferably hydrogen, hydroxyl, cyano or trifluoromethyl;

[0175] Or, R 3a and R 3b Linkage forms oxygen groups, C 3-8 Cycloalkyl or 3-8 membered heterocyclic alkyl, preferably oxo or C 4-6 Metaheterocyclic alkyl, more preferably -CO- or oxocyclic butyl;

[0176] R 4a and R 4b Each of these can be independently represented by hydrogen, deuterium, halogen, hydroxyl, cyano, amino, oxo, or C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 alkylthio or C 1-6 Alkylamine group, preferably hydrogen, halogen or C 1-6 Alkyl, more preferably hydrogen, halogen or C 1-3 alkyl;

[0177] Or, R 4a and R 4b Link formation C 2-6 Alkenyl group, optionally further modified by halogen, hydroxyl group, C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 1-6 Alkyl groups are substituted, preferably 2-methylpropenyl groups;

[0178] Ring A, Ring B, R A R B L2, L3, R1, R2, R a R b R c n, m, n1, and n2 are as described above.

[0179] The present invention also provides a compound of general formula (II-1a), its stereoisomer, or a pharmaceutically acceptable salt thereof:

[0180] in:

[0181] X1 can be N, O, or S, with N being preferred;

[0182] Ring A, Ring B, R A R B L2, L3, R1, R2, R a R b R c R x n, m, n1, and n2 are as described above.

[0183] The present invention also provides compounds of general formulas (III), (III-1), (III-2), (VI-1), and (VI-2), their stereoisomers, or pharmaceutically acceptable salts thereof.

[0184] in:

[0185] R A C 1-6 Alkyl, C 3-6 Cycloalkyl, preferably C 1-3 Alkyl, C 3-4 Cycloalkyl, more preferably methyl, ethyl, isopropyl, cyclopropyl, or cyclobutyl; in some embodiments, R A C 1-6 Alkyl, preferably C 1-3 Alkyl, more preferably methyl, ethyl or isopropyl;

[0186] Ring B is C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 quinone heteroaryl, preferably C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, 5-6 membered heteroaryl, phenyl-5-6 membered heteroaryl, phenyl-C 3-6 Cycloalkyl or 5-6-membered heteroaryl and 5-6-membered heteroaryl;

[0187] Each R B Each of these elements independently represents hydrogen, deuterium, halogen, hydroxyl, cyano, amino, and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl, preferably hydrogen, halogen, cyano, C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy or C 3-8 Cycloalkyl, more preferably hydrogen, halogen, cyano, C 1-3 Alkyl, C 2-4 alkenyl, C 1-3 Alkoxy or C 3-4 Cycloalkyl, more preferably hydrogen, fluorine, cyano, methyl, methoxy, vinyl, or cyclopropyl; or, each R B Each of these elements independently represents hydrogen, deuterium, halogen, hydroxyl, cyano, amino, and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl, preferably hydrogen, halogen, cyano, C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl or 3-8 membered heterocyclic alkyl, more preferably hydrogen, halogen, cyano, C 1-3 Alkyl, C 2-4 alkenyl, C 1-3 Alkoxy, C 3-5 Cycloalkyl or 4-6-membered heterocycloalkyl, more preferably hydrogen, fluorine, cyano, methyl, methoxy, vinyl, cyclopropyl, cyclobutyl, cyclopentyl, aziridine, aziridine-pentyl, or aziridine-hexyl; wherein the alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamine, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl group is optionally further reinforced by 1-3 R groups. q Replaced;

[0188] Or, any two R B The ring atoms connected to it form C 3-8 Cycloalkyl, optionally further surrounded by 1-3 R q The replacement is preferably any two R. B The ring atoms connected to it form C 3-6 Cycloalkyl, optionally further surrounded by 1-3 R q The two adjacent Rs are replaced, or more preferably replaced. BThe ring atoms attached to it link to form cyclobutyl or cyclopentyl groups, which may optionally be further linked by 1-3 R groups. q Replaced;

[0189] X1 can be a bond, N, O, or S, preferably N or O, provided that when X1 is O, R1 or R2 does not exist; when X1 is a bond, R1 or R2 is directly connected to L3.

[0190] R1 and R2 are each independently hydrogen, deuterium, halogen, cyano, amino, or C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl, 5-10 heteroaryl, -(CH2) n1 R aa -(CH2) n1 OR aa -(CH2) n1 C(O)R aa -(CH2) n1 C(O)CH2R aa -(CH2) n1 C(O)OR aa -(CH2) n1 C(Se)R aa -(CH2) n1 C(O)NR bb R cc -C(O)(CH2) n1 NR bb R cc -(CH2) n1 C(Se)NR bb R cc -(CH2) n1 C(O)C(O)NR bb R cc 、-(CR bb R cc ) n1 NR bb R cc or -(CR) bb R cc ) n1 C(O)NR bb R cc The C mentioned therein 1-6 Alkyl, C2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups may be further substituted with 1-3 R groups. q The preferred substitutes are hydrogen and C. 1-6 Alkyl, C 1-6 Halogenated alkyl groups, 3-8 membered heterocyclic alkyl groups, 5-10 membered heteroaryl groups, -(CH2) n1 R aa -(CH2) n1 C(O)R aa -(CH2) n1 C(O)CH2R aa -(CH2) n1 C(O)OR aa -(CH2) n1 C(Se)R aa -(CH(CH3)) n1 C(O)NR bb R cc -(C(CH3)2) n1 C(O)NR bb R cc -C(O)(CH2) n1 NR bb R cc -(CH2) n1 C(O)C(O)NR bb R cc or The C mentioned therein 1-6 Alkyl, C 1-6 Halogenated alkyl groups, 3-8 membered heterocyclic alkyl groups, and 5-10 membered heteroaryl groups may be further determinated by 1-3 R groups. q The preferred substitutes are hydrogen and C. 1-3 Alkyl, C 1-3 Halogenated alkyl, 4-6 membered heterocyclic alkyl, 5-6 membered heteroaryl, -CH2R aa -C(O)R aa -(CH2) n1 C(O)CH2R aa -(CH2) n1 C(O)OR aa -CH2C(O)R aa -C(Se)R aa-CH(CH3)C(O)NR bb R cc -C(CH3)2C(O)NR bb R cc -C(O)NR bb R cc -C(O)CH2NR bb R cc -C(O)C(O)NR bb R cc or The C mentioned therein 1-3 Alkyl, C 1-3 The haloalkyl, 4-6 membered heterocyclic alkyl, and 5-6 membered heteroaryl groups may be further substituted with 1-3 Rqs, more preferably hydrogen, methyl, -CH2CF3, -C(O)CH2CH3, -C(Se)CH2CH3, -C(O)CH2CF3, -C(O)CH2CH2CF3, -C(O)CH2N(CH3)2, -CH(CH3)C(O)NHCH2CF3, -CH(CH3)C(O)N(CH3)CH2CF3, -C(CH3)2C(O)NHCH2CF3, -C(O)C(O)NHCH2CF3 -OCH3, -OCF3, -OCH2CF3, -OCH2CH2CF3, Ethyl, -OCH2CH3, or Or selected from

[0191] Alternatively, R1 and R2 can be linked to form a 3-8 membered heterocyclic alkyl group, optionally further bonded by 1-3 R groups. y Instead, R1 and R2 are preferably linked to form C. 4- 6 heterocyclic alkyl groups, optionally further surrounded by 1-3 R groups y Replaced, better Optional further by 1-3 R y Replaced;

[0192] R y Hydrogen, halogen, =O, =CH2, =CF2, =CHF, =CH(C) 1-3 Alkyl), =C(C) 1-3 Alkyl)2、=C 4-6 Cycloalkyl, =(4-6 membered heterocycloalkyl), C1-6 Alkyl, C 1-6 Halogenated alkyl or C 1-6 Alkoxy, the C 1-3 Alkyl, C 4-6 Cycloalkyl groups, 4-6 membered heterocyclic alkyl groups, optionally further halogenated, C 1-2 Alkyl, OH, CN, NH2 substitution, preferably methyl, trifluoromethyl or methoxy; or

[0193] R y For hydrogen, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 1-6 Alkoxy, preferably methyl, trifluoromethyl or methoxy;

[0194] R 3a and R 3b Each of these elements independently represents hydrogen, deuterium, halogen, hydroxyl, cyano, amino, and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 alkylthio or C 1-6 Alkylamine group, preferably hydrogen, hydroxyl, cyano or C 1-3 Halogenated alkyl, more preferably hydrogen, hydroxyl, cyano or trifluoromethyl;

[0195] Or, R 3a and R 3b Linkage forms oxygen groups, C 3-8 Cycloalkyl or 3-8 membered heterocyclic alkyl, preferably oxo or C 4-6 Meta-heterocyclic alkyl, more preferably oxo- or oxo-heterocyclic butyl;

[0196] R 4a and R 4b Each of these can be independently represented by hydrogen, deuterium, halogen, hydroxyl, cyano, amino, oxo, or C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 alkylthio or C 1-6 Alkylamine group, preferably hydrogen, halogen or C 1-3 Alkyl, more preferably hydrogen, fluorine or methyl, and even more preferably R 4a and R 4b Both can be hydrogen or both can be fluorine, or one can be hydrogen and the other can be methyl;

[0197] Or, R 4a and R 4b Link formation C 2-6 Alkenyl group, optionally further modified by halogen, hydroxyl group, C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 1-6 Alkyl groups are substituted, preferably 2-methylpropenyl groups;

[0198] L2 is the bond, Where r is 0, 1, 2, or 3; or

[0199] L2 is the bond, Where r is 0, 1, 2, or 3; or

[0200] L2 is the bond, Where r is 0, 1, 2 or 3;

[0201] L3 is a bond, -C(O)-, -CR 7a R 7b -、-CR 7a R 7b -C(O)-, preferred bond, -C(O)-, -CHR 7a -、-CHR 7a -C(O)-; or L3 as the bond, -C(O)-, -CR 7a R 7b -、-CR 7a R 7b -C(O)-, -S(O)2-, Preferred key, -C(O)-, -CHR 7a -、-CHR 7a -C(O)-;

[0202] R 5a and R 5b Each of these can be independently represented by hydrogen, deuterium, halogen, hydroxyl, cyano, amino, oxo, or C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl, 5-10 heteroaryl, -(CH2) n1 OR aa -(CH2) n1 C(O)R aa -(CH2) n1 NRbb C(O)R aa -(CH2) n1 C(O)OR aa -(CH2) n1 C(O)NR bb R cc Or -(CH2) n1 C(Se)NR bb R cc Preferred groups include hydrogen, cyano, and C. 1-6 Alkyl or -(CH2) n1 C(O)NR bb R cc More preferably hydrogen, cyano, C 1-3 Alkyl, -C(O)NR bb R cc or -CH2C(O)NR bb R cc ;or

[0203] R 5a and R 5b Each of these can be independently represented by hydrogen, deuterium, halogen, hydroxyl, cyano, amino, oxo, or C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl, 5-10 heteroaryl, -(CH2) n1 OR aa -(CH2) n1 C(O)R aa -(CH2) n1 C(O)OR aa -(CH2) n1 C(O)NR bb R cc Or -(CH2) n1 C(Se)NR bb R cc Preferred groups include hydrogen, cyano, and C. 1-6 Alkyl, C 3-6 Cycloalkyl or -(CH2) n1 C(O)NR bb R cc More preferably hydrogen, cyano, C 1-3 Alkyl, C 3-4 Cycloalkyl, -C(O)NRbb R cc or -CH2C(O)NR bb R cc ;or

[0204] R 5a and R 5b Each of these can be independently represented by hydrogen, deuterium, halogen, hydroxyl, cyano, amino, oxo, or C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl, 5-10 heteroaryl, -(CH2) n1 OR aa -(CH2) n1 C(O)R aa -(CH2) n1 NR bb C(O)R aa -(CH2) n1 C(O)OR aa -(CH2) n1 C(O)NR bb R cc Or -(CH2) n1 C(Se)NR bb R cc Preferred groups include hydrogen, cyano, and C. 1-6 Alkyl, C 3-6 Cycloalkyl or -(CH2) n1 C(O)NR bb R cc More preferably hydrogen, cyano, C 1-3 Alkyl, C 3-4 Cycloalkyl, -C(O)NR bb R cc or -CH2C(O)NR bb R cc The alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamine, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl groups are optionally further reinforced with 1-3 R groups. q Replaced;

[0205] Or R 5a and R 5b It links together with the carbon atoms it is attached to to form C 2-6 Alkenyl group, optionally further divided by 1-2 halogens, C1-3 Alkyl, C 3-6 Cycloalkyl substituted;

[0206] R6 is hydrogen, deuterium, or C. 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl, 5-10 quinone heteroaryl, preferably hydrogen or C 1-6 Alkyl, more preferably hydrogen or C 1-3 Alkyl groups, more preferably hydrogen or methyl groups;

[0207] R 7a and R 7b Each of these can be independently represented by hydrogen, deuterium, halogen, hydroxyl, cyano, amino, oxo, or C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl, 5-10 heteroaryl, -(CH2) n1 OR aa -(CH2) n1 C(O)R aa -(CH2) n1 NR bb C(O)-R cc -(CH2) n1 C(O)OR aa -(CH2) n1 C(O)NR bb R cc -(CH2) n1 C(Se)NR bb R cc 、-(CR bb R cc ) n1 NR bb R cc or -(CR) bb R cc ) n1 C(O)NR bb R cc The C mentioned therein 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3- 8-membered cycloalkyl, 3-8-membered heterocyclic alkyl, C 6-10 Aryl or 5-10 heteroaryl groups may be further substituted with 1-3 R groups. z The preferred substitutes are hydrogen, cyano, and C. 1- 6-alkyl, C 3-6 cycloalkyl, 5-6 membered heteroaryl, -C(O)NR bb R cc -C(Se)NR bb R cc or -(CR) bb R cc )NR bb R cc The C mentioned therein 1-6 Alkyl, C 3-6 Cycloalkyl or 5-6 heteroaryl groups may be further surrounded by 1-3 R groups. z Replaced; or

[0208] R 7a and R 7b Each of these can be independently represented by hydrogen, deuterium, halogen, hydroxyl, cyano, amino, oxo, or C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl, 5-10 heteroaryl, -(CH2) n1 OR aa -(CH2) n1 C(O)R aa -(CH2) n1 C(O)OR aa -(CH2) n1 C(O)NR bb R cc -(CH2) n1 C(Se)NR bb R cc 、-(CR bb R cc ) n1 NR bb R cc or -(CR)bb R cc ) n1 C(O)NR bb R cc The C mentioned therein 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups may be further substituted with 1-3 R groups. z The preferred substitutes are hydrogen, cyano, and C. 1-6 Alkyl, C 3-6 cycloalkyl, 5-6 membered heteroaryl, -C(O)NR bb R cc -C(Se)NR bb R cc or -(CR) bb R cc )NR bb R cc The C mentioned therein 1-6 Alkyl, C 3-6 Cycloalkyl or 5-6 heteroaryl groups may be further surrounded by 1-3 R groups. z Replaced;

[0209] R z For halogens, hydroxyl groups, cyano groups, amino groups, =CH2, =CF2, =CHF, =CH(C) 1-3 Alkyl), =C(C) 1-3 Alkyl)2, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 aryl or 5-10 heteroaryl, wherein the C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups may be further converted to halogens, hydroxyl groups, cyano groups, amino groups, or C-terminal groups. 1-3 Alkyl, C1-3 Halogenated alkyl or C 1-3 Alkoxy groups are preferred, with halogens and C being the most suitable. 1-3 Alkyl or 3-8 membered heterocyclic alkyl groups, optionally further modified by halogen, hydroxyl, cyano, amino, C 1-3 Alkyl, C 1-3 Halogenated alkyl or C 1-3 Alkyl groups are substituted;

[0210] Or, R 5a or R 5b Linked with R1 to form a 3-8 membered heterocyclic alkyl group, optionally further bonded by 1-3 R groups. q The substituted component is preferably a 4-6 membered heterocyclic alkyl group containing one nitrogen atom, optionally further replaced by 1-3 R atoms. q The substituted group, more preferably piperidinyl, butyrolactam or valproic acid, optionally further replaced by 1-3 R groups. q Replaced;

[0211] Or, R 5a or R 5b With R 7a or R 7b Link formation C 3-8 Cycloalkyl or 3-8 membered heterocycloalkyl, optionally further surrounded by 1-3 R q Replaced, preferably C 3-8 Cycloalkyl, optionally further surrounded by 1-3 R q Replaced, more preferably C 3-6 Cycloalkyl, optionally further surrounded by 1-3 R q The substituted group is preferably cyclopropyl, cyclobutyl, or cyclohexyl, and optionally further replaced by 1-3 R groups. q Replaced;

[0212] Or, R 5a or R 5b With R B Link formation C 3-8 Cycloalkyl or 3-8 membered heterocycloalkyl, optionally further surrounded by 1-3 R q Replaced, preferably C 3-8 Cycloalkyl, optionally further surrounded by 1-3 R q Replaced, more preferably C 3-6 Cycloalkyl, optionally further surrounded by 1-3 R q The substituted group is preferably cyclopentyl or cyclohexyl, optionally further replaced by 1-3 R groups. q Replaced;

[0213] Or, R 7a or R 7b Linked with R1 to form a 3-8 membered heterocyclic alkyl group, optionally further bonded by 1-3 R groups. qThe substituted component is preferably a 4-6 membered heterocyclic alkyl group containing one nitrogen atom, optionally further replaced by 1-3 R atoms. q The substituted product, more preferably valproic acid, optionally further replaced by 1-3 R... q Replaced;

[0214] Or, R 7a or R 7b With R B Link formation C 3-8 Cycloalkyl or 3-8 membered heterocycloalkyl, optionally further surrounded by 1-3 R q Replaced, preferably C 3-8 Cycloalkyl or 4-6 membered heterocyclic alkyl containing one nitrogen atom, optionally further substituted with 1-3 Rq, more preferably C 3-6 Cycloalkyl or 4-6 membered heterocycloalkyl containing 1 nitrogen atom, optionally further surrounded by 1-3 R atoms. q The substituted group is preferably cyclopentyl, cyclohexyl, tetrahydropyran, or valeramide, optionally further replaced by 1-3 R groups. q Replaced;

[0215] Or, R B Linked with R1 to form C 3-8 Cycloalkyl or 3-8 membered heterocycloalkyl, optionally further surrounded by 1-3 R q Replaced, preferably C 3-8 Cycloalkyl or 4-6 membered heterocycloalkyl containing 1 nitrogen atom, optionally further surrounded by 1-3 R atoms. q Replaced, more preferably C 3-6 Cycloalkyl or 4-6 membered heterocycloalkyl containing 1 nitrogen atom, optionally further surrounded by 1-3 R atoms. q The substituted compounds are preferably tetrahydropyrrole, piperidinyl, valproamide, or caprolactam, optionally further replaced by 1-3 R groups. q Replaced;

[0216] R aa R bb and R cc Each is independently hydrogen, halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 aryl or 5-10 heteroaryl, wherein the C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups may be further substituted with 1-3 R groups. qThe preferred substitutes are hydrogen and C. 1-6 Alkyl, C 1-6 Halogenated alkyl or 3-8 membered heterocyclic alkyl, wherein the C 1-6 Alkyl, C 1-6 Halogenated alkyl or 3-8 membered heterocyclic alkyl may optionally be further denoted by 1-3 R groups. q The preferred alternatives are hydrogen and C. 1-3 Alkyl, C 1-3 Halogenated alkyl or 5-6 membered heterocyclic alkyl, wherein the C 1-3 Alkyl, C 1-3 Halogenated alkyl or 5-6 membered heterocyclic alkyl may optionally be further denoted by 1-3 R groups. q Replaced;

[0217] Or, R bb and R cc Linkage forms 3-8 membered heterocyclic alkyl groups, optionally further bonded by 1-3 R groups. q Replaced;

[0218] R q For deuterium, halogen, hydroxyl, oxo, cyano, amino, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamine group, -(CH2) n1 C 3-6 Cycloalkyl, -(CH2) n1 -(3-6 membered heterocyclic alkyl groups), =CH2, =CF2, =CHF, =CH(C 1-3 Alkyl), =C(C) 1-3 Alkyl)2, wherein the cycloalkyl, heterocycloalkyl optionally further converted to halogen, =CH2, =CF2, =CHF, =CH(C 1-3 Alkyl), =C(C) 1-3 Alkyl)2 is substituted, preferably halogen, C 1-3 Alkyl, Halogenated C 1-3 Alkyl, C 3-6 Cycloalkyl groups, wherein the cycloalkyl group is optionally further substituted with halogens, =CH2, =CF2, =CHF, =CHCH3, =C(CH3)2, more preferably fluorine, methyl, cyclobutyl, or

[0219] R q For deuterium, halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 2-6 alkenyl, C2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamine group, -(CH2) n1 C 3-6 Cycloalkyl, preferably halogen, C 1-3 Alkyl, Halogenated C 1-3 Alkyl, more preferably fluorine or methyl; or

[0220] R q For deuterium, halogen, hydroxyl, oxo, cyano, amino, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamine group, -(CH2) n1 C 3-6 Cycloalkyl, =CH2, =CF2, =CHF, =CH(C 1-3 Alkyl), =C(C) 1-3 Alkyl)2, preferably halogen, C 1-3 Alkyl, Halogenated C 1-3 Alkyl, more preferably fluorine or methyl;

[0221] Or, two R atoms located on the same carbon atom q It links together with the carbon atoms it is attached to to form C 3-8 Cycloalkyl groups, optionally further modified by halogen, hydroxyl, cyano, amino, oxo, or C- group. 1-2 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-4 Haloalkyl, C 1-4 Alkoxy, C 1-4 alkylthio or C 1-4 The alkylamine group is replaced;

[0222] m is an integer from 0 to 3, preferably 0, 1 or 2;

[0223] n1 is an integer between 0 and 3, preferably 0, 1 or 2;

[0224] n2 is an integer between 0 and 3, preferably 0, 1 or 2;

[0225] The definitions of the remaining groups are the same as those of any of the above technical solutions.

[0226] The present invention also provides compounds of general formulas (III-a), (III-1a), and (III-2a), their stereoisomers, or pharmaceutically acceptable salts thereof:

[0227] in:

[0228] R A For H, C 1-6 Alkyl, C 3-8 Cycloalkyl groups, preferably H and C 1-3 Alkyl, C 3-6 Cycloalkyl, more preferably H, methyl, ethyl, or cyclopropyl;

[0229] Ring Aa is C 3-8 Cycloalkyl, preferably C 3-6 Cycloalkyl, more preferably cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl;

[0230] R a H, halogen, deuterium, amino, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 3-6 Cycloalkyl, 3-8 membered heterocycloalkyl, preferably H, F, -CHF2, -CF3, cyclopropyl;

[0231] Ring B is C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 quinone heteroaryl, preferably C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, 5-6 membered heteroaryl, phenyl-5-6 membered heteroaryl, phenyl-C 3-6 Cycloalkyl or 5-6-membered heteroaryl and 5-6-membered heteroaryl;

[0232] Each R B Each of these elements independently represents hydrogen, deuterium, halogen, hydroxyl, cyano, amino, and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl, preferably hydrogen, halogen, cyano, C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy or C 3-8 Cycloalkyl, more preferably hydrogen, halogen, cyano, C1-3 Alkyl, C 2-4 alkenyl, C 1-3 Alkoxy or C 3-4 Cycloalkyl, more preferably hydrogen, fluorine, cyano, methyl, methoxy, vinyl or cyclopropyl;

[0233] Or, any two R B The ring atoms connected to it form C 3-8 Cycloalkyl, optionally further surrounded by 1-3 R q The replacement is preferably any two R. B The ring atoms connected to it form C 3-6 Cycloalkyl, optionally further surrounded by 1-3 R q The two adjacent Rs are replaced, or more preferably replaced. B The ring atoms attached to it link to form cyclobutyl or cyclopentyl groups, which may optionally be further linked by 1-3 R groups. q Replaced;

[0234] X1 can be a bond, N, O, or S, preferably N or O, provided that when X1 is O, R1 or R2 does not exist; when X1 is a bond, R1 or R2 is directly connected to L3.

[0235] R1 and R2 are each independently hydrogen, deuterium, halogen, cyano, amino, or C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl, 5-10 heteroaryl, -(CH2) n1 R aa -(CH2) n1 OR aa -(CH2) n1 C(O)R aa -(CH2) n1 C(O)OR aa -(CH2) n1 C(Se)R aa -(CH2) n1 C(O)NR bb R cc -C(O)(CH2) n1 NR bb R cc -(CH2) n1 C(Se)NRbb R cc -(CH2) n1 C(O)C(O)NR bb R cc 、-(CR bb R cc ) n1 NR bb R cc or -(CR) bb R cc ) n1 C(O)NR bb R cc The C mentioned therein 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups may be further substituted with 1-3 R groups. q The preferred substitutes are hydrogen and C. 1-6 Alkyl, C 1-6 Halogenated alkyl groups, 3-8 membered heterocyclic alkyl groups, 5-10 membered heteroaryl groups, -(CH2) n1 R aa -(CH2) n1 C(O)R aa -(CH2) n1 C(Se)R aa -(CH(CH3)) n1 C(O)NR bb R cc -(C(CH3)2) n1 C(O)NR bb R cc -C(O)(CH2) n1 NR bb R cc -(CH2) n1 C(O)C(O)NR bb R cc or The C mentioned therein 1-6 Alkyl, C 1-6 Halogenated alkyl groups, 3-8 membered heterocyclic alkyl groups, and 5-10 membered heteroaryl groups may be further determinated by 1-3 R groups. q The preferred substitutes are hydrogen and C. 1-3 Alkyl, C 1-3Halogenated alkyl, 4-6 membered heterocyclic alkyl, 5-6 membered heteroaryl, -CH2R aa -C(O)R aa -CH2C(O)R aa -C(Se)R aa -CH(CH3)C(O)NR bb R cc -C(CH3)2C(O)NR bb R cc -C(O)NR bb R cc -C(O)CH2NR bb R cc -C(O)C(O)NR bb R cc or The C mentioned therein 1-3 Alkyl, C 1-3 The alkyl halogroup, 4-6-membered heterocyclic alkyl group, and 5-6-membered heteroaryl group may be further substituted with 1-3 Rqs, more preferably hydrogen, methyl, ethyl, -OCH3, -OCH2CH3, -OCF3, -OCH2CF3, -OCH2CH2CF3, -CH2CF3, -C(O)CH2CH3, -C(Se)CH2CH3, -C(O)CH2CF3, -C(O)CH2CH2CF3, -C(O)CH2N(CH3)2, -CH(CH3)C(O)NHCH2CF3, -CH(CH3)C(O)N(CH3)CH2CF3, -C(CH3)2C(O)NHCH2CF3, -C(O)C(O)NHCH2CF3

[0236] Alternatively, R1 and R2 can be linked to form a 3-8 membered heterocyclic alkyl group, optionally further bonded by 1-3 R groups. y Instead, R1 and R2 are preferably linked to form C. 4- 6 heterocyclic alkyl groups, optionally further surrounded by 1-3 R groups y Replaced, better Optional further by 1-3 R y Replaced;

[0237] R y For hydrogen, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 1-6 Alkoxy, preferably methyl, trifluoromethyl or methoxy;

[0238] R 3a and R 3bEach of these elements independently represents hydrogen, deuterium, halogen, hydroxyl, cyano, amino, and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 alkylthio or C 1-6 Alkylamine group, preferably hydrogen, hydroxyl, cyano or C 1-3 Halogenated alkyl, more preferably hydrogen, hydroxyl, cyano or trifluoromethyl;

[0239] Or, R 3a and R 3b Linkage forms oxygen groups, C 3-8 Cycloalkyl or 3-8 membered heterocyclic alkyl, preferably oxo or C 4-6 Meta-heterocyclic alkyl, more preferably oxo- or oxo-heterocyclic butyl;

[0240] R 4a and R 4b Each of these can be independently represented by hydrogen, deuterium, halogen, hydroxyl, cyano, amino, oxo, or C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 alkylthio or C 1-6 Alkylamine group, preferably hydrogen, halogen or C 1-3 Alkyl, more preferably hydrogen, fluorine or methyl, and even more preferably R 4a and R 4b Both can be hydrogen or both can be fluorine, or one can be hydrogen and the other can be methyl;

[0241] Or, R 4a and R 4b Link formation C 2-6 Alkenyl group, optionally further modified by halogen, hydroxyl group, C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 1-6 Alkyl groups are substituted, preferably 2-methylpropenyl groups;

[0242] L2 is the bond, Where r is 0, 1, 2 or 3;

[0243] L3 is a bond, -C(O)-, -CR 7a R 7b -、-CR 7a R 7b -C(O)-, -S(O)2-, Preferred key, -C(O)-, -CHR 7a -、-CHR 7a -C(O)-;

[0244] R 5a and R 5b Each of these can be independently represented by hydrogen, deuterium, halogen, hydroxyl, cyano, amino, oxo, or C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl, 5-10 heteroaryl, -(CH2) n1 OR aa -(CH2) n1 C(O)R aa -(CH2) n1 NR bb C(O)R aa -(CH2) n1 C(O)OR aa -(CH2) n1 C(O)NR bb R cc Or -(CH2) n1 C(Se)NR bb R cc Preferred groups include hydrogen, cyano, and C. 1-6 Alkyl or -(CH2) n1 C(O)NR bb R cc More preferably hydrogen, cyano, C 1-3 Alkyl, -C(O)NR bb R cc or -CH2C(O)NR bb R cc Or R 5a and R 5b It links together with the carbon atoms it is attached to to form C 2-6 Alkenyl group, optionally further divided by 1-2 halogens, C 1-3 Alkyl, C 3-6 Cycloalkyl substituted;

[0245] R6 is hydrogen, deuterium, or C. 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 3-8Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl, 5-10 quinone heteroaryl, preferably hydrogen or C 1-6 Alkyl, more preferably hydrogen or C 1-3 Alkyl groups, more preferably hydrogen or methyl groups;

[0246] R 7a and R 7b Each of these can be independently represented by hydrogen, deuterium, halogen, hydroxyl, cyano, amino, oxo, or C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl, 5-10 heteroaryl, -(CH2) n1 OR aa -(CH2) n1 C(O)R aa -(CH2) n1 NR bb C(O)-R cc -(CH2) n1 C(O)OR aa -(CH2) n1 C(O)NR bb R cc -(CH2) n1 C(Se)NR bb R cc 、-(CR bb R cc ) n1 NR bb R cc or -(CR) bb R cc ) n1 C(O)NR bb R cc The C mentioned therein 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3- 8-membered cycloalkyl, 3-8-membered heterocyclic alkyl, C 6-10Aryl or 5-10 heteroaryl groups may be further substituted with 1-3 R groups. z The preferred substitutes are hydrogen, cyano, and C. 1- 6-alkyl, C 3-6 cycloalkyl, 5-6 membered heteroaryl, -C(O)NR bb R cc -C(Se)NR bb R cc or -(CR) bb R cc )NR bb R cc The C mentioned therein 1-6 Alkyl, C 3-6 Cycloalkyl or 5-6 heteroaryl groups may be further surrounded by 1-3 R groups. z Replaced;

[0247] R z Halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 aryl or 5-10 heteroaryl, wherein the C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups may be further converted to halogens, hydroxyl groups, cyano groups, amino groups, or C-terminal groups. 1-3 Alkyl, C 1-3 Halogenated alkyl or C 1-3 Alkoxy groups are preferred, with halogens and C being the most suitable. 1-3 Alkyl or 3-8 membered heterocyclic alkyl groups, optionally further modified by halogen, hydroxyl, cyano, amino, C 1-3 Alkyl, C 1-3 Halogenated alkyl or C 1-3 Alkyl groups are substituted;

[0248] Or, R 5a or R 5b Linked with R1 to form a 3-8 membered heterocyclic alkyl group, optionally further bonded by 1-3 R groups. q The substituted component is preferably a 4-6 membered heterocyclic alkyl group containing one nitrogen atom, optionally further replaced by 1-3 R atoms. q The substituted group, more preferably piperidinyl, butyrolactam or valproic acid, optionally further replaced by 1-3 R groups.q Replaced;

[0249] Or, R 5a or R 5b With R 7a or R 7b Link formation C 3-8 Cycloalkyl or 3-8 membered heterocycloalkyl, optionally further surrounded by 1-3 R q Replaced, preferably C 3-8 Cycloalkyl, optionally further surrounded by 1-3 R q Replaced, more preferably C 3-6 Cycloalkyl, optionally further surrounded by 1-3 R q The substituted group is preferably cyclopropyl, cyclobutyl, or cyclohexyl, and optionally further replaced by 1-3 R groups. q Replaced;

[0250] Or, R 5a or R 5b With R B Link formation C 3-8 Cycloalkyl or 3-8 membered heterocycloalkyl, optionally further surrounded by 1-3 R q Replaced, preferably C 3-8 Cycloalkyl, optionally further surrounded by 1-3 R q Replaced, more preferably C 3-6 Cycloalkyl, optionally further surrounded by 1-3 R q The substituted group is preferably cyclopentyl or cyclohexyl, optionally further replaced by 1-3 R groups. q Replaced;

[0251] Or, R 7a or R 7b Linked with R1 to form a 3-8 membered heterocyclic alkyl group, optionally further bonded by 1-3 R groups. q The substituted component is preferably a 4-6 membered heterocyclic alkyl group containing one nitrogen atom, optionally further replaced by 1-3 R atoms. q The substituted product, more preferably valproic acid, optionally further replaced by 1-3 R... q Replaced;

[0252] Or, R 7a or R 7b With R B Link formation C 3-8 Cycloalkyl or 3-8 membered heterocycloalkyl, optionally further surrounded by 1-3 R q Replaced, preferably C 3-8 Cycloalkyl or 4-6 membered heterocyclic alkyl containing one nitrogen atom, optionally further substituted with 1-3 Rq, more preferably C 3-6 Cycloalkyl or 4-6 membered heterocycloalkyl containing 1 nitrogen atom, optionally further surrounded by 1-3 R atoms. qThe substituted group is preferably cyclopentyl, tetrahydropyran, or valeramide, optionally further replaced by 1-3 R groups. q Replaced;

[0253] Or, R B Linked with R1 to form C 3-8 Cycloalkyl or 3-8 membered heterocycloalkyl, optionally further surrounded by 1-3 R q Replaced, preferably C 3-8 Cycloalkyl or 4-6 membered heterocycloalkyl containing 1 nitrogen atom, optionally further surrounded by 1-3 R atoms. q Replaced, more preferably C 3-6 Cycloalkyl or 4-6 membered heterocycloalkyl containing 1 nitrogen atom, optionally further surrounded by 1-3 R atoms. q The substituted compounds are preferably tetrahydropyrrole, piperidinyl, valproamide, or caprolactam, optionally further replaced by 1-3 R groups. q Replaced;

[0254] R aa R bb and R cc Each is independently hydrogen, halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 aryl or 5-10 heteroaryl, wherein the C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups may be further substituted with 1-3 R groups. q The preferred substitutes are hydrogen and C. 1-6 Alkyl, C 1-6 Halogenated alkyl or 3-8 membered heterocyclic alkyl, wherein the C 1-6 Alkyl, C 1-6 Halogenated alkyl or 3-8 membered heterocyclic alkyl may optionally be further denoted by 1-3 R groups. q The preferred alternatives are hydrogen and C. 1-3 Alkyl, C 1-3 Halogenated alkyl or 5-6 membered heterocyclic alkyl, wherein the C 1-3 Alkyl, C 1-3 Halogenated alkyl or 5-6 membered heterocyclic alkyl may optionally be further denoted by 1-3 R groups. q Replaced;

[0255] Or, R bb and R ccLinkage forms 3-8 membered heterocyclic alkyl groups, optionally further bonded by 1-3 R groups. q Replaced;

[0256] R q For deuterium, halogen, hydroxyl, oxo, cyano, amino, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamine group, -(CH2) n1 C 3-6 Cycloalkyl, -(CH2) n1 -(3-6 membered heterocyclic alkyl groups), =CH2, =CF2, =CHF, =CH(C 1-3 Alkyl), =C(C) 1-3 Alkyl)2, wherein the cycloalkyl, heterocycloalkyl optionally further converted to =CH2, =CF2, =CHF, =CH(C 1-3 Alkyl), =C(C) 1-3 Alkyl)2 is substituted, preferably halogen, C 1-3 Alkyl, Halogenated C 1-3 Alkyl, more preferably fluorine or methyl;

[0257] m is an integer from 0 to 3, preferably 0, 1 or 2;

[0258] n1 is an integer between 0 and 3, preferably 0, 1 or 2;

[0259] n2 is an integer between 0 and 3, preferably 0, 1 or 2.

[0260] The definitions of the remaining groups are the same as those of any of the above technical solutions.

[0261] The present invention also provides a compound of general formula (III), its stereoisomer or a pharmaceutically acceptable salt thereof:

[0262] in:

[0263] R A C 1-6 Alkyl groups, preferably C1-3 alkyl groups, more preferably methyl, ethyl or isopropyl;

[0264] Ring B is C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 quinone heteroaryl, preferably C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, 5-6 membered heteroaryl, phenyl-5-6 membered heteroaryl, phenyl-C3-6 Cycloalkyl or 5-6-membered heteroaryl and 5-6-membered heteroaryl;

[0265] Each R B Each of these elements independently represents hydrogen, deuterium, halogen, hydroxyl, cyano, amino, and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl, preferably hydrogen, halogen, cyano, C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy or C 3-8 Cycloalkyl, more preferably hydrogen, halogen, cyano, C 1-3 Alkyl, C 2-4 alkenyl, C 1-3 Alkoxy or C 3-4 Cycloalkyl, more preferably hydrogen, fluorine, cyano, methyl, methoxy, vinyl or cyclopropyl;

[0266] Or, any two R B The ring atoms connected to it form C 3-8 Cycloalkyl, optionally further surrounded by 1-3 R q The replacement is preferably any two R. B The ring atoms connected to it form C 3-6 Cycloalkyl, optionally further surrounded by 1-3 R q The two adjacent Rs are replaced, or more preferably replaced. B The ring atoms attached to it link to form cyclobutyl or cyclopentyl groups, which may optionally be further linked by 1-3 R groups. q Replaced;

[0267] X1 is N, O or S, preferably N or O, provided that R1 or R2 does not exist when X1 is O;

[0268] R1 and R2 are each independently hydrogen, deuterium, halogen, cyano, amino, or C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl, 5-10 heteroaryl, -(CH2) n1 R aa -(CH2) n1 OR aa -(CH2) n1 C(O)R aa -(CH2) n1 C(O)OR aa -(CH2) n1 C(Se)R aa -(CH2) n1 C(O)NR bb R cc -C(O)(CH2) n1 NR bb R cc -(CH2) n1 C(Se)NR bb R cc -(CH2) n1 C(O)C(O)NR bb R cc 、-(CR bb R cc ) n1 NR bb R cc or -(CR) bb R cc ) n1 C(O)NR bb R cc The C mentioned therein 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups may be further substituted with 1-3 R groups. q The preferred substitutes are hydrogen and C. 1-6 Alkyl, C 1-6 Halogenated alkyl groups, 3-8 membered heterocyclic alkyl groups, 5-10 membered heteroaryl groups, -(CH2) n1 R aa -(CH2) n1 C(O)R aa -(CH2) n1 C(Se)R aa-(CH(CH3)) n1 C(O)NR bb R cc -(C(CH3)2) n1 C(O)NR bb R cc -C(O)(CH2) n1 NR bb R cc -(CH2) n1 C(O)C(O)NR bb R cc or The C mentioned therein 1-6 Alkyl, C 1-6 Halogenated alkyl groups, 3-8 membered heterocyclic alkyl groups, and 5-10 membered heteroaryl groups may be further determinated by 1-3 R groups. q The preferred substitutes are hydrogen and C. 1-3 Alkyl, C 1-3 Halogenated alkyl, 4-6 membered heterocyclic alkyl, 5-6 membered heteroaryl, -CH2R aa -C(O)R aa -CH2C(O)R aa -C(Se)R aa -CH(CH3)C(O)NR bb R cc -C(CH3)2C(O)NR bb R cc -C(O)NR bb R cc -C(O)CH2NR bb R cc -C(O)C(O)NR bb R cc or The C mentioned therein 1-3 Alkyl, C 1-3 The haloalkyl, 4-6 membered heterocyclic alkyl, and 5-6 membered heteroaryl groups may be further substituted with 1-3 Rqs, more preferably hydrogen, methyl, -CH2CF3, -C(O)CH2CH3, -C(Se)CH2CH3, -C(O)CH2CF3, -C(O)CH2CH2CF3, -C(O)CH2N(CH3)2, -CH(CH3)C(O)NHCH2CF3, -CH(CH3)C(O)N(CH3)CH2CF3, -C(CH3)2C(O)NHCH2CF3, -C(O)C(O)NHCH2CF3

[0269] Alternatively, R1 and R2 can be linked to form a 3-8 membered heterocyclic alkyl group, optionally further bonded by 1-3 R groups. y Instead, R1 and R2 are preferably linked to form C. 4- 6 heterocyclic alkyl groups, optionally further surrounded by 1-3 R groups y Replaced, better Optional further by 1-3 R y Replaced; R y For hydrogen, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 1-6 Alkoxy, preferably methyl, trifluoromethyl or methoxy;

[0270] R 3a and R 3b Each of these elements independently represents hydrogen, deuterium, halogen, hydroxyl, cyano, amino, and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 alkylthio or C 1-6 Alkylamine group, preferably hydrogen, hydroxyl, cyano or C 1-3 Halogenated alkyl, more preferably hydrogen, hydroxyl, cyano or trifluoromethyl;

[0271] Or, R 3a and R 3b Linkage forms oxygen groups, C 3-8 Cycloalkyl or 3-8 membered heterocyclic alkyl, preferably oxo or C 4-6 Metaheterocyclic alkyl, more preferably -CO- or oxocyclic butyl;

[0272] R 4a and R 4b Each of these can be independently represented by hydrogen, deuterium, halogen, hydroxyl, cyano, amino, oxo, or C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 alkylthio or C 1-6 Alkylamine group, preferably hydrogen, halogen or C 1-3 Alkyl, more preferably hydrogen, fluorine or methyl, and even more preferably R 4a and R 4b Both can be hydrogen or both can be fluorine, or one can be hydrogen and the other can be methyl;

[0273] Or, R4a and R 4b Link formation C 2-6 Alkenyl group, optionally further modified by halogen, hydroxyl group, C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 1-6 Alkyl groups are substituted, preferably 2-methylpropenyl groups;

[0274] L2 is the bond, Where r is 0, 1, 2, or 3; or L2 is the bond, Where r is 0, 1, 2 or 3;

[0275] L3 is a bond, -C(O)- or -CR 7a R 7b -, preferred key, -C(O)- or -CHR 7a -;

[0276] R 5a and R 5b Each of these can be independently represented by hydrogen, deuterium, halogen, hydroxyl, cyano, amino, oxo, or C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl, 5-10 heteroaryl, -(CH2) n1 OR aa -(CH2) n1 C(O)R aa -(CH2) n1 C(O)OR aa -(CH2) n1 C(O)NR bb R cc Or -(CH2) n1 C(Se)NR bb R cc Preferred groups include hydrogen, cyano, and C. 1-6 Alkyl or -(CH2) n1 C(O)NR bb R cc More preferably hydrogen, cyano, C 1-3 Alkyl, -C(O)NR bb R cc or -CH2C(O)NR bb R ccOr R 5a and R 5b Each of these can be independently represented by hydrogen, deuterium, halogen, hydroxyl, cyano, amino, oxo, or C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl, 5-10 heteroaryl, -(CH2) n1 OR aa -(CH2) n1 C(O)R aa -(CH2) n1 NR bb C(O)R aa -(CH2) n1 C(O)OR aa -(CH2) n1 C(O)NR bb R cc Or -(CH2) n1 C(Se)NR bb R cc Preferred groups include hydrogen, cyano, and C. 1-6 Alkyl or -(CH2) n1 C(O)NR bb R cc More preferably hydrogen, cyano, C 1-3 Alkyl, -C(O)NR bb R cc or -CH2C(O)NR bb R cc ;

[0277] R6 is hydrogen, deuterium, or C. 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl, 5-10 quinone heteroaryl, preferably hydrogen or C 1-6 Alkyl, more preferably hydrogen or C 1-3 Alkyl groups, more preferably hydrogen or methyl groups;

[0278] R 7a and R 7b Each of these can be independently represented by hydrogen, deuterium, halogen, hydroxyl, cyano, amino, oxo, or C. 1-6 Alkyl, C2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl, 5-10 heteroaryl, -(CH2) n1 OR aa -(CH2) n1 C(O)R aa -(CH2) n1 C(O)OR aa -(CH2) n1 C(O)NR bb R cc -(CH2) n1 C(Se)NR bb R cc 、-(CR bb R cc ) n1 NR bb R cc or -(CR) bb R cc ) n1 C(O)NR bb R cc The C mentioned therein 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups may be further substituted with 1-3 R groups. z The preferred substitutes are hydrogen, cyano, and C. 1-6 Alkyl, C 3-6 cycloalkyl, 5-6 membered heteroaryl, -C(O)NR bb R cc -C(Se)NR bb R cc or -(CR) bb R cc )NR bb R cc The C mentioned therein 1-6 Alkyl, C 3-6Cycloalkyl or 5-6 heteroaryl groups may be further surrounded by 1-3 R groups. z Replaced;

[0279] R z Halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 aryl or 5-10 heteroaryl, wherein the C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups may be further converted to halogens, hydroxyl groups, cyano groups, amino groups, or C-terminal groups. 1-3 Alkyl, C 1-3 Halogenated alkyl or C 1-3 Alkoxy groups are preferred, with halogens and C being the most suitable. 1-3 Alkyl or 3-8 membered heterocyclic alkyl groups, optionally further modified by halogen, hydroxyl, cyano, amino, C 1-3 Alkyl, C 1-3 Halogenated alkyl or C 1-3 Alkyl groups are substituted;

[0280] Or, R 5a or R 5b Linked with R1 to form a 3-8 membered heterocyclic alkyl group, optionally further bonded by 1-3 R groups. q The substituted component is preferably a 4-6 membered heterocyclic alkyl group containing one nitrogen atom, optionally further replaced by 1-3 R atoms. q The substituted group, more preferably piperidinyl, butyrolactam or valproic acid, optionally further replaced by 1-3 R groups. q Replaced;

[0281] Or, R 5a or R 5b With R 7a or R 7b Link formation C 3-8 Cycloalkyl or 3-8 membered heterocycloalkyl, optionally further surrounded by 1-3 R q Replaced, preferably C 3-8 Cycloalkyl, optionally further surrounded by 1-3 R q Replaced, more preferably C 3-6 Cycloalkyl, optionally further surrounded by 1-3 R qThe substituted group is preferably cyclopropyl, cyclobutyl, or cyclohexyl, and optionally further replaced by 1-3 R groups. q Replaced;

[0282] Or, R 5a or R 5b With R B Link formation C 3-8 Cycloalkyl or 3-8 membered heterocycloalkyl, optionally further surrounded by 1-3 R q Replaced, preferably C 3-8 Cycloalkyl, optionally further surrounded by 1-3 R q Replaced, more preferably C 3-6 Cycloalkyl, optionally further surrounded by 1-3 R q The substituted group is preferably cyclopentyl or cyclohexyl, optionally further replaced by 1-3 R groups. q Replaced;

[0283] Or, R 7a or R 7b Linked with R1 to form a 3-8 membered heterocyclic alkyl group, optionally further bonded by 1-3 R groups. q The substituted component is preferably a 4-6 membered heterocyclic alkyl group containing one nitrogen atom, optionally further replaced by 1-3 R atoms. q The substituted product, more preferably valproic acid, optionally further replaced by 1-3 R... q Replaced;

[0284] Or, R 7a or R 7b With R B Link formation C 3-8 Cycloalkyl or 3-8 membered heterocycloalkyl, optionally further surrounded by 1-3 R q Replaced, preferably C 3-8 Cycloalkyl or 4-6 membered heterocyclic alkyl containing one nitrogen atom, optionally further substituted with 1-3 Rq, more preferably C 3-6 Cycloalkyl or 4-6 membered heterocycloalkyl containing 1 nitrogen atom, optionally further surrounded by 1-3 R atoms. q The substituted group is preferably cyclopentyl, tetrahydropyran, or valeramide, optionally further replaced by 1-3 R groups. q Replaced;

[0285] Or, R B Linked with R1 to form C 3-8 Cycloalkyl or 3-8 membered heterocycloalkyl, optionally further surrounded by 1-3 R q Replaced, preferably C 3-8 Cycloalkyl or 4-6 membered heterocycloalkyl containing 1 nitrogen atom, optionally further surrounded by 1-3 R atoms. q Replaced, more preferably C 3-6Cycloalkyl or 4-6 membered heterocycloalkyl containing 1 nitrogen atom, optionally further surrounded by 1-3 R atoms. q The substituted compounds are preferably tetrahydropyrrole, piperidinyl, valproamide, or caprolactam, optionally further replaced by 1-3 R groups. q Replaced;

[0286] R aa R bb and R cc Each is independently hydrogen, halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 aryl or 5-10 heteroaryl, wherein the C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups may be further substituted with 1-3 R groups. q The preferred substitutes are hydrogen and C. 1-6 Alkyl, C 1-6 Halogenated alkyl or 3-8 membered heterocyclic alkyl, wherein the C 1-6 Alkyl, C 1-6 Halogenated alkyl or 3-8 membered heterocyclic alkyl may optionally be further denoted by 1-3 R groups. q The preferred alternatives are hydrogen and C. 1-3 Alkyl, C 1-3 Halogenated alkyl or 5-6 membered heterocyclic alkyl, wherein the C 1-3 Alkyl, C 1-3 Halogenated alkyl or 5-6 membered heterocyclic alkyl may optionally be further denoted by 1-3 R groups. q Replaced;

[0287] Or, R bb and R cc Linkage forms 3-8 membered heterocyclic alkyl groups, optionally further bonded by 1-3 R groups. q Replaced;

[0288] R q For deuterium, halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 alkylthio or C 1-6 Alkylamine group, preferably halogen or C 1-3Alkyl, more preferably fluorine or methyl;

[0289] m is an integer from 0 to 3, preferably 0, 1 or 2;

[0290] n1 is an integer between 0 and 3, preferably 0, 1 or 2;

[0291] n2 is an integer between 0 and 3, preferably 0, 1 or 2.

[0292] The present invention also provides a compound of general formula (IIIA), its stereoisomer, or a pharmaceutically acceptable salt thereof:

[0293] in:

[0294] R 5a It can be hydrogen, deuterium, halogen, hydroxyl, cyano, amino, oxo, or C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl, 5-10 heteroaryl, -(CH2) n1 OR aa -(CH2) n1 C(O)R aa -(CH2) n1 C(O)OR aa -(CH2) n1 C(O)NR bb R cc Or -(CH2) n1 C(Se)NR bb R cc Preferred hydrogen and C 1-6 Alkyl or -(CH2) n1 C(O)NR bb R cc More preferably hydrogen, C 1-3 Alkyl or -C(O)NR bb R cc Further preferred forms include hydrogen, methyl, or -C(O)NHCH2CF3;

[0295] R 7a and R 7b Each of these can be independently represented by hydrogen, deuterium, halogen, hydroxyl, cyano, amino, oxo, or C. 1-6 Alkyl, C 2-6 alkenyl, C2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl, 5-10 heteroaryl, -(CH2) n1 OR aa -(CH2) n1 C(O)R aa -(CH2) n1 C(O)OR aa -(CH2) n1 C(O)NR bb R cc -(CH2) n1 C(Se)NR bb R cc 、-(CR bb R cc ) n1 NR bb R cc or -(CR) bb R cc ) n1 C(O)NR bb R cc Preferred groups include hydrogen, cyano, and C. 1-6 Alkyl, C 3-8 cycloalkyl, 5-6 membered heteroaryl, -C(O)NR bb R cc -C(Se)NR bb R cc or -(CR) bb R cc )NR bb R cc More preferably hydrogen or Further preference for hydrogen or

[0296] R8, R9, R 10 and R 11 It is hydrogen, halogen, cyano, C 1-6 Alkyl, C 2-6 alkenyl or C 1-6 Alkoxy, preferably hydrogen or halogen, more preferably hydrogen or fluorine;

[0297] The prerequisite is that it satisfies at least one of the following conditions:

[0298] (1)R 5aLinked with R1 to form a 3-8 membered heterocyclic alkyl group, optionally further substituted by 1-3 Rq, preferably a 4-6 membered heterocyclic alkyl group containing 1 nitrogen atom, optionally further substituted by 1-3 Rq. q The substituted group, more preferably piperidinyl, butyrolactam or valproic acid, optionally further replaced by 1-3 R groups. q Replaced;

[0299] (2)R 5a With R 7a or R 7b Link formation C 3-8 Cycloalkyl or 3-8 membered heterocycloalkyl, optionally further surrounded by 1-3 R q Replaced, preferably C 3-8 Cycloalkyl, optionally further surrounded by 1-3 R q Replaced, more preferably C 3-6 Cycloalkyl, optionally further surrounded by 1-3 R q The substituted group is preferably cyclopropyl, cyclobutyl, or cyclohexyl, and optionally further replaced by 1-3 R groups. q Replaced;

[0300] (3)R 5a With R 11 Link formation C 3-8 Cycloalkyl or 3-8 membered heterocycloalkyl, optionally further surrounded by 1-3 R q Replaced, preferably C 3-8 Cycloalkyl, optionally further surrounded by 1-3 R q Replaced, more preferably C 3-6 Cycloalkyl, optionally further surrounded by 1-3 R q The substituted group is preferably cyclopentyl or cyclohexyl, optionally further replaced by 1-3 R groups. q Replaced;

[0301] (4)R 7a or R 7b Linked with R1 to form a 3-8 membered heterocyclic alkyl group, optionally further bonded by 1-3 R groups. q The substituted component is preferably a 4-6 membered heterocyclic alkyl group containing one nitrogen atom, optionally further replaced by 1-3 R atoms. q The substituted product, more preferably valproic acid, optionally further replaced by 1-3 R... q Replaced;

[0302] (5)R 7a or R 7b Linked with R8 to form C 3-8 Cycloalkyl or 3-8 membered heterocycloalkyl, optionally further surrounded by 1-3 R q Replaced, preferably C 3-8Cycloalkyl or 4-6 membered heterocycloalkyl containing 1 nitrogen atom, optionally further surrounded by 1-3 R atoms. q Replaced, more preferably C 3-6 Cycloalkyl or 4-6 membered heterocycloalkyl containing 1 nitrogen atom, optionally further surrounded by 1-3 R atoms. q The substituted group is preferably cyclopentyl, tetrahydropyran, or valeramide, optionally further replaced by 1-3 R groups. q Replaced;

[0303] (6)R 11 Linked with R1 to form C 3-8 Cycloalkyl or 3-8 membered heterocycloalkyl, optionally further substituted with 1-3 Rq, preferably C 3-8 Cycloalkyl or 4-6 membered heterocycloalkyl containing 1 nitrogen atom, optionally further surrounded by 1-3 R atoms. q Replaced, more preferably C 3-6 Cycloalkyl or 4-6 membered heterocycloalkyl containing 1 nitrogen atom, optionally further surrounded by 1-3 R atoms. q The substituted compounds are preferably tetrahydropyrrole, piperidinyl, valproamide, or caprolactam, optionally further replaced by 1-3 R groups. q Replaced;

[0304] (7)R 10 With R 11 Link formation C 3-8 Cycloalkyl or 3-8 membered heterocycloalkyl, optionally further surrounded by 1-3 R q Replaced, preferably C 3-8 Cycloalkyl, optionally further surrounded by 1-3 R q Replaced, more preferably C 3-6 Cycloalkyl, optionally further surrounded by 1-3 R q The substituted group is preferably cyclobutyl, cyclopentyl, or cyclohexyl, and optionally further replaced by 1-3 R groups. q Replaced;

[0305] r is 0, 1, or 2;

[0306] R A R1, R2, R 4a R 4b R a R bb R cc Rq and n1 are as described above.

[0307] The present invention also provides a compound of general formula (IIIB), its stereoisomer, or a pharmaceutically acceptable salt thereof:

[0308] in:

[0309] Ring C is C3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 quinone heteroaryl, preferably C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, 5-6 membered heteroaryl, phenyl-5-6 membered heteroaryl, phenyl-C 3-6 Cycloalkyl or 5-6-membered heteroaryl, more preferably: Further optimization

[0310] Each R B Each is independently a halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 alkylthio or C 1-6 Alkylamine group, preferably halogen or C 1-6 Alkyl, more preferably fluorine;

[0311] R 12 It is hydrogen, halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 alkylthio or C 1-6 Alkylamine group, preferably hydrogen or C 1-6 Alkyl, more preferably hydrogen or C 1-3 Alkyl groups, more preferably hydrogen or methyl groups;

[0312] s is 0 or 1;

[0313] R A R 4a R 4b And m as described above.

[0314] The present invention also provides a compound of general formula (IIIC), its stereoisomer, or a pharmaceutically acceptable salt thereof:

[0315] in:

[0316] M1 and M2 are each independently CR a Or N, preferably CH or N;

[0317] R1 and R2 are each independently hydrogen, deuterium, halogen, cyano, amino, or C. 1-6Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl, 5-10 heteroaryl, -(CH2) n1 R aa -(CH2) n1 OR aa -(CH2) n1 C(O)R aa -(CH2) n1 C(O)OR aa -(CH2) n1 C(Se)R aa -(CH2) n1 C(O)NR bb R cc -(CH(CH3)) n1 C(O)NR bb R cc -(C(CH3)2) n1 C(O)NR bb R cc -(CH2) n1 C(Se)NR bb R cc -C(O)(CH2) n1 NR bb R cc -(CH2) n1 C(O)C(O)NR bb R cc 、-(CR bb R cc ) n1 NR bb R cc or -(CR) bb R cc ) n1 C(O)NR bb R cc Preferably hydrogen or -(CH2) n1 C(O)R aa More preferably, one of R1 and R2 is hydrogen and the other is -C(O)R aa Further optimization involves selecting one of R1 and R2 as hydrogen and the other as -C(O)CH2CH3. Or -C(O)CH2CH2CF3;

[0318] Alternatively, R1 and R2 can be linked to form a 3-8 membered heterocyclic alkyl group, optionally further bonded by 1-3 R groups. y Instead, R1 and R2 are preferably linked to form C. 4- 6 heterocyclic alkyl groups, optionally further surrounded by 1-3 R groups y Replaced, better Optional further by 1-3 R y Replaced, further optimized

[0319] R 7a Halogen, cyano, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 aryl or 5-10 heteroaryl, wherein the C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups may be further substituted with 1-3 R groups. z Replaced;

[0320] Cyano and C are preferred 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 5-6 heteroaryl, 5-6 heteroaryl-5-6 heteroaryl or 5-6 heteroaryl-4-6 heterocycloalkyl, wherein the C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 5-6 heteroaryl, 5-6 heteroaryl-5-6 heteroaryl, or 5-6 heteroaryl-4-6 heterocycloalkyl optionally further surrounded by 1-3 R z Replaced;

[0321] More preferably cyano, C 1-3 Alkyl, C 3-6 Cycloalkyl, 4-6-membered heterocycloalkyl, 5-6-membered heteroaryl, 5-6-membered heteroaryl-5-6-membered heteroaryl or 5-6-membered heteroaryl-4-6-membered heterocycloalkyl, wherein the C 1-3 Alkyl, C 3-6Cycloalkyl, 4-6-membered heterocycloalkyl, 5-6-membered heteroaryl, 5-6-membered heteroaryl and 5-6-membered heteroaryl or 5-6-membered heteroaryl and 4-6-membered heterocycloalkyl optionally further surrounded by 1-3 R z Replaced;

[0322] R z Halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 aryl or 5-10 heteroaryl, wherein the C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups may be further converted to halogens, hydroxyl groups, cyano groups, amino groups, or C-terminal groups. 1-3 Alkyl, C 1-3 Halogenated alkyl or C 1-3 Alkoxy groups are preferred, with halogens and C being the most suitable. 1-3 Alkyl or 4-6 membered heterocyclic alkyl, wherein the C 1-3 Alkyl or 4-6 membered heterocyclic alkyl groups may be further modified with halogens, hydroxyl groups, cyano groups, amino groups, or C-membered groups. 1-3 Alkyl, C 1-3 Halogenated alkyl or C 1- Substituted with 3 alkoxy groups;

[0323] Alternatively, R1 or R2 and R 7a Linkage forms 3-8 membered heterocyclic alkyl groups, optionally further bonded by 1-3 R groups. q The preferred replacements are R1 or R2 and R 7a Linkage forms 4-6 membered heterocyclic alkyl groups, optionally further bonded by 1-3 R groups. q Replaced;

[0324] R 12 It is hydrogen, halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 alkylthio or C 1-6 Alkylamine group, preferably hydrogen or C 1-6 Alkyl, more preferably hydrogen or C1-3 Alkyl groups, more preferably hydrogen or methyl groups;

[0325] s is 0 or 1;

[0326] R A R 4a R 4b R B R a R aa R bb R cc R y R q m and n1 are as described above.

[0327] The present invention also provides a compound of general formula (IIIC-1), its stereoisomer, or a pharmaceutically acceptable salt thereof:

[0328] in:

[0329] Ring D is C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 quinone heteroaryl, preferred C3-8 Cycloalkyl, 3-8-membered heterocycloalkyl, 5-6-membered heteroaryl, 5-6-membered heteroaryl-5-6-membered heteroaryl or 5-6-membered heteroaryl-4-6-membered heterocycloalkyl, more preferably cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, aziridine, oxacyclobutyl, pyrrolidinyl, imidazoalkyl, tetrahydrofuranyl, piperidinyl, piperazinyl, furanyl, thienyl, thiazolyl, isothiazolyl, imidazolyl, pyrazolyl, triazolyl, pyridinyl Further preferred groups include cyclopropyl, oxacyclobutyl, thiazolyl, imidazolyl, and pyrazolyl.

[0330] R 13 Halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 3-8 Cycloalkyl or 3-8 membered heterocyclic alkyl, wherein the C 1-6 Alkyl, C 3- 8-membered cycloalkyl or 3-8-membered heterocyclic alkyl groups may be further modified with halogen, hydroxyl, cyano, amino, C 1-3 Alkyl, C 1-3 Halogenated alkyl or C 1-3 Alkoxy groups are preferred, with halogens and C being the most suitable. 1-3 Alkyl or 4-6 membered heterocyclic alkyl, wherein the C 1-3 Alkyl or 4-6 membered heterocyclic alkyl groups may be further converted to halogen, cyano, C 1-3 Alkyl, C1-3 Halogenated alkyl or C 1-3 Alkyl groups are substituted;

[0331] t is an integer between 0 and 3;

[0332] M1, M2, R A R1, R2, R 4a R 4b R B R 12 R q m and s are as described above.

[0333] The present invention also provides a compound of general formula (IIIC-2), general formula (IIIC-3) or general formula (IIIC-4), its stereoisomer or a pharmaceutically acceptable salt thereof:

[0334] in:

[0335] M3 is CH, NH, N or S, preferably CH, NH or N;

[0336] M4 is CH, NH, N, or S; preferably CH or NH.

[0337] M5 is CH, NH, N, O, or S; preferably CH, N, O, or S;

[0338] M6 is CH, NH, N, or S; preferably CH or N.

[0339] M1, M2, R A R1, R2, R 4a R 4b R B R 12 R 13 m, s, and t are as described above.

[0340] The present invention also provides a compound of general formula (IIIC-5) or general formula (IIIC-6), its stereoisomer, or a pharmaceutically acceptable salt thereof:

[0341] in:

[0342] R 14 C 1-6 Alkyl groups, preferably methyl groups;

[0343] R A R1, R2, R 4a R 4b R B R 12 m and s are as described above.

[0344] The present invention also provides a compound represented by general formula (IIID), general formula (IIIE) or general formula (IIIF), its stereoisomer or a pharmaceutically acceptable salt thereof:

[0345] in:

[0346] R 15 C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups, optionally further divided by 1-3 R groups p Replaced, preferably C 3-8 Cycloalkyl, 3-8-membered heterocycloalkyl or 5-10-membered heteroaryl, optionally further surrounded by 1-3 R p Replaced, better Optional further by 1-3 R p Replaced;

[0347] Or, R 15 -(CH2) n1 R aa -(CH2) n1 OR aa -(CH2) n1 C(O)R aa -(CH2) n1 C(O)OR aa -(CH2) n1 C(Se)R aa -(CH2) n1 C(O)NR bb R cc -(CH(CH3)) n1 C(O)NR bb R cc -(C(CH3)2) n1 C(O)NR bb R cc -(CH2) n1 C(Se)NR bb R cc -C(O)(CH2) n1 NR bb Rcc -(CH2) n1 C(O)C(O)NR bb R cc 、-(CR bb R cc ) n1 NR bb R cc or -(CR) bb R cc ) n1 C(O)NR bb R cc Preferred -CH(CH3)C(O)NR bb R cc -C(CH3)2C(O)NR bb R cc or More preferably -CHCH3C(O)NHCH2CF3, -CH(CH3)C(O)N(CH3)CH2CF3, -C(CH3)2C(O)NHCH2CF3 or

[0348] R p For hydrogen, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 1-6 Alkoxy, preferably methyl;

[0349] R A R1, R2, R 4a and R 4b As stated above.

[0350] In a further preferred embodiment of the invention, in the general formula (IIID) or general formula (IIIF), R1 and R2 are each independently hydrogen and C. 1-3 Alkyl, -C(O)R aa -CH(CH3)C(O)NR bb R cc -C(CH3)2C(O)NR bb R cc -C(O)C(O)NR bb R cc Preferably, hydrogen, methyl, -C(O)CH2CF3, -C(O)C(O)NHCH2CF3 or -CHCH3C(O)NHCH2CF3.

[0351] The present invention also provides a compound of general formula (IV) or (V), its stereoisomer or a pharmaceutically acceptable salt thereof:

[0352] in:

[0353] Indicates a single or double bond;

[0354] R a Selected from H, halogen, cyano, amino, C 1-4 Alkyl, C 1-4 Deuterated alkyl, C 1-4 Alkoxy, C 1-4 Haloalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, -(CH2) n1 NR bb C(O)-R cc ;or

[0355] R a Selected from H, halogen, cyano, amino, C 1-4 Alkyl, C 1-4 Deuterated alkyl, C 1-4 Alkoxy, C 1-4 Haloalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, -(CH2) n1 NR bb C(O)-R cc The C mentioned therein 3-8 Cycloalkyl groups, 3-8 membered heterocyclic alkyl groups, may optionally be further converted to =CH2, =CF2, =CHF, or =CH(C) 1-3 Alkyl), =C(C) 1-3 Alkyl)2-substituted; R bb Selected from H, C 1-4 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic alkyl;

[0356] R cc Selected from H, C 1-4 Alkyl, C 1-4 Deuterated alkyl, C 1-4 Alkoxy, C 1-4 Halogenated alkyl groups, preferably H or C 1-2 Alkyl, C 1-2 Alkoxy, more preferably H, methyl, or ethyl; or

[0357] R cc Selected from H, C 1-4 Alkyl, C 1-4 Deuterated alkyl, C 1-4 Alkoxy, C 1-4 Haloalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic alkyl, wherein the C 3-8 Cycloalkyl groups, 3-8 membered heterocyclic alkyl groups, may optionally be further converted to =CH2, =CF2, =CHF, or =CH(C)1-3 Alkyl), =C(C) 1-3 Alkyl)2-substituted, preferably R cc Selected from H, C 1-2 Alkyl, C 1-2 Alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocyclic alkyl, wherein the C 3-6 Cycloalkyl groups, 3-6 membered heterocyclic alkyl groups, may optionally be further converted to =CH2, =CF2, =CHF, or =CH(C) 1-3 Alkyl), =C(C) 1-3 Alkyl)2 is substituted, more preferably R cc Selected from H, methyl, ethyl, cyclopropyl, R1 and R2 are each independently C 1-4 Alkyl, C 1-4 Deuterated alkyl, C 1-4 Alkoxy, C 1- 4-Haloalkoxy, C 1-4 Halogenated alkyl groups, preferably C 1-2 Alkyl, C 1-2 Alkoxy, C 1-2 Halogenated alkoxy groups, more preferably methyl, ethyl, methoxy, ethoxy, or trifluoroethoxy; or

[0358] R1 and R2 are each independently C 1-4 Alkyl, C 1-4 Deuterated alkyl, C 1-4 Alkoxy, C 1-4 Halogenated alkoxy groups, C 1-4 Haloalkyl, C 3-8 cycloalkyl, wherein the C 3-8 Cycloalkyl groups may be further halogenated, =CH2, =CF2, =CHF, =CH(C) 1-3 Alkyl), =C(C) 1-3 Alkyl group substituted with 2, preferably R1 and R2 are each independently C1. 1-2 Alkyl, C 1-2 Alkoxy, C 1-2 Halogenated alkoxy groups, C 3-6 cycloalkyl, wherein the C 3-6 Cycloalkyl groups may be further halogenated, =CH2, =CF2, =CHF, =CH(C) 1-3 Alkyl), =C(C) 1-3 Alkyl group)2 is substituted, more preferably R1 and R2 are each independently methyl, ethyl, methoxy, ethoxy, trifluoroethoxy,

[0359] Alternatively, R1 and R2 may link to form a 3-8 membered heterocyclic alkyl group, which may be further coupled with =CH2, =CF2, =CHF, or =CH(C) 1-3 Alkyl), =C(C) 1-3 Alkyl)2-substituted;

[0360] s is 0 or 1;

[0361] n1 is selected from 0, 1, or 2;

[0362] The condition is that the compound is not

[0363] The present invention also provides a compound represented by general formula (VA), (V-Aa), its stereoisomer, or a pharmaceutically acceptable salt thereof:

[0364] in:

[0365] Indicates a single or double bond;

[0366] R A For H, C 1-6 Alkyl, preferably C 1-3 Alkyl, more preferably H, methyl, ethyl or isopropyl;

[0367] Ring Aa is C 3-8 Cycloalkyl, preferably C 3-6 Cycloalkyl, more preferably cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl;

[0368] R va H, halogen, deuterium, amino, C 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 3-6 Cycloalkyl, 3-8 membered heterocycloalkyl, preferably H, F, -CHF2, -CF3, cyclopropyl;

[0369] R a Selected from H, halogen, cyano, amino, C 1-4 Alkyl, C 1-4 Deuterated alkyl, C 1-4 Alkoxy, C 1-4 Haloalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, -(CH2) n1 NR bb C(O)-R cc The C mentioned therein 3-8 Cycloalkyl groups, 3-8 membered heterocyclic alkyl groups, may optionally be further converted to =CH2, =CF2, =CHF, or =CH(C) 1-3 Alkyl), =C(C)1-3 Alkyl)2-substituted; R bb Selected from H, C 1-4 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic alkyl;

[0370] R b Selected from H, halogen, cyano, amino, C 1-4 Alkyl, C 1-4 Deuterated alkyl, C 1-4 Alkoxy, C 1-4 Haloalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, -(CH2) n1 NR bb C(O)-R cc The C mentioned therein 3-8 Cycloalkyl groups, 3-8 membered heterocyclic alkyl groups, may optionally be further converted to =CH2, =CF2, =CHF, or =CH(C) 1-3 Alkyl), =C(C) 1-3 Alkyl)2-substituted; R bb Selected from H, C 1-4 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic alkyl; in some embodiments, R b Selected from methyl, ethyl, -CF3, -CH2CF3, -CH2CHF2;

[0371] Rv is selected from

[0372] R cc Selected from H, C 1-4 Alkyl, C 1-4 Deuterated alkyl, C 1-4 Alkoxy, C 1-4 Haloalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic alkyl, wherein the C 3-8 Cycloalkyl groups, 3-8 membered heterocyclic alkyl groups, may optionally be further converted to =CH2, =CF2, =CHF, or =CH(C) 1-3 Alkyl), =C(C) 1-3 Alkyl)2-substituted, preferably R cc Selected from H, C 1-2 Alkyl, C 1-2 Alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocyclic alkyl, wherein the C 3-6 Cycloalkyl groups, 3-6 membered heterocyclic alkyl groups, may optionally be further converted to =CH2, =CF2, =CHF, or =CH(C) 1-3 Alkyl), =C(C) 1-3Alkyl)2 is substituted, more preferably R cc Selected from H, methyl, ethyl, cyclopropyl,

[0373] R1 and R2 are each independently C 1-4 Alkyl, C 1-4 Deuterated alkyl, C 1-4 Alkoxy, C 1-4 Halogenated alkoxy groups, C 1-4 Haloalkyl, C 3-8 cycloalkyl, wherein the C 3-8 Cycloalkyl groups may be further halogenated, =CH2, =CF2, =CHF, =CH(C) 1-3 Alkyl), =C(C) 1-3 Alkyl group substituted with 2, preferably R1 and R2 are each independently C1. 1-2 Alkyl, C 1-2 Alkoxy, C 1-2 Halogenated alkoxy groups, C 3-6 cycloalkyl, wherein the C 3-6 Cycloalkyl groups may be further halogenated, =CH2, =CF2, =CHF, =CH(C) 1-3 Alkyl), =C(C) 1-3 Alkyl group)2 is substituted, more preferably R1 and R2 are each independently methyl, ethyl, methoxy, ethoxy, trifluoroethoxy,

[0374] Alternatively, R1 and R2 may link to form a 3-8 membered heterocyclic alkyl group, which may be further coupled with =CH2, =CF2, =CHF, or =CH(C) 1-3 Alkyl), =C(C) 1-3 Alkyl)2-substituted;

[0375] s is 0 or 1;

[0376] n1 is selected from 0, 1, or 2;

[0377] The condition is no

[0378] The compounds of the present invention, their stereoisomers or pharmaceutically acceptable salts thereof, wherein Selected from

[0379] Selected from The *site is the connection site between ring B and L2; when L2 is a bond, the *site is the connection site between ring B and L3; in some embodiments, the *site is the connection site between ring B and L3. Selected from The * site is the connection site between ring B and L2. When L2 is a bond, the * site is the connection site between ring B and L3.

[0380] L1 is selected from C(O)NHCR a R b C(O)NH-、-C(O)NHCR a R b -;

[0381] L2 is selected from the key, -CHR 5b -、-NH-、-N(CH3)-;

[0382] L3 is selected from -CHR 7b -、-CHR 7b -C(O)-;

[0383] When X is the key and N is the key, R2 is directly connected to L3.

[0384] R B Each is independently hydrogen, deuterium, F, Cl, and C. 1-3 Alkyl, Halogenated C 1-3 Alkyl, deuterated C 1-3 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, wherein the alkyl, cycloalkyl, or heterocycloalkyl group is optionally further surrounded by 1-3 F, Cl, oxo groups, =CH2, =CF2, =CHF, or =CH(C) groups. 1-2 Alkyl), =C(C) 1-2 Alkyl group substitution; in some embodiments, R B Each of the following is independently hydrogen, deuterium, F, Cl, CN, hydroxyl, C 1-3 Alkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkyl, deuterated C 1-3 alkyl;

[0385] R a Each is independently hydrogen, deuterium, and C. 1-3 Alkyl, Halogenated C 1-3 Alkyl, deuterated C 1-3 alkyl;

[0386] R b Each independently is C 1-4 Alkyl, C 3-6 cycloalkyl, wherein the alkyl group or cycloalkyl group is further denoted by 1-3 R groups. x Replaced;

[0387] R 5b R 7b Each is independently hydrogen, deuterium, halogen, and carbon. 1-3Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic alkyl, wherein the alkyl, cycloalkyl, or heterocyclic alkyl may optionally be further surrounded by 1-3 deuterium, F, Cl, CN, oxo, or C groups. 1-3 Alkoxy, halogenated C 1-3 Alkyl, =CH2, =CF2, =CHF, =CH(C 1-3 Alkyl), =C(C) 1-3 Alkyl)2、=C 4-6 Cycloalkyl, =(4-6 membered heterocycloalkyl) group substitution; in some embodiments, R 5b R 7b Each is independently hydrogen, deuterium, halogen, and carbon. 1-3 Alkyl, C 3-6 Cycloalkyl groups, wherein the alkyl group or cycloalkyl group is further surrounded by 1-3 deuterium, F, Cl, oxo groups, =CH2, =CF2, =CHF, =CH(C) groups. 1-3 Alkyl), =C(C) 1-3 Alkyl)2、=C 4-6 Substitution of cycloalkyl groups and (4-6 membered heterocycloalkyl) groups;

[0388] R1 is hydrogen, deuterium, or C. 1-4 alkyl;

[0389] R2 is -C(O)R aa -C(O)CH2R aa -C(O)OR aa -(CH2) n1 R aa 3-8 membered heterocyclic alkyl groups, halogenated C 1-4 Alkyl groups, wherein the heterocyclic alkyl groups are optionally further composed of 1-3 elements selected from deuterium, halogens, =CH2, =CF2, =CHF, =CH(C) 1-2 Alkyl), =C(C) 1-2 Alkyl group (R2), oxo group, or -CF3 group substitution; in some embodiments, R2 is -C(O)R aa -C(O)CH2R aa -OC(O)NHCH2R aa -C(O)NHCH2R aa -C(O)OR aa 3-8 membered heterocyclic alkyl groups, halogenated C 1-4 Alkyl groups, wherein the heterocyclic alkyl groups are optionally further composed of 1-3 groups selected from deuterium, halogen, oxo group, C 1-3 Alkyl, Halogenated C 1-3 Alkyl, =CH2, =CF2, =CHF, =CH(C 1-2 Alkyl), =C(C) 1-2 Substitution of alkyl groups;

[0390] R aa Each independently constitutes a halogenated C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, -(CH)=C 4-6 Cycloalkyl groups, wherein the cycloalkyl or heterocycloalkyl group is optionally further selected from 1-3 halogens, =CH2, =CF2, =CHF, =CH(C 1-3 Alkyl), =C(C) 1-3 Alkyl group substitution; in some embodiments, R aa Each independently constitutes a halogenated C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, wherein the cycloalkyl or heterocycloalkyl group is optionally further selected from 1-3 halogens, =CH2, =CF2, =CHF, =CH(C 1-3 Alkyl), =C(C) 1-3 Substitution of alkyl groups;

[0391] Alternatively, R1 and R2 may link to form a 3-8 membered heterocyclic alkyl group, which may optionally be further bonded by 1-3 elements selected from F, Cl, =O, =CH2, =CF2, =CHF, =CH(C) 1-2 Alkyl), =C(C) 1-2 Alkyl)2、=C 4-6 Substitution of cycloalkyl groups and (4-6 membered heterocycloalkyl) groups;

[0392] R x For deuterium, F, Cl, oxo groups, =CH2, =CF2, =CHF, =CH(C) 1-3 Alkyl), =CF(C) 1-3 Alkyl), =C(C) 1-3 Alkyl)2、=C 4-6 Cycloalkyl, =(4-6 membered heterocycloalkyl), C 1-4 Alkyl, C 3-6 Cycloalkyl groups, wherein the alkyl group or cycloalkyl group is optionally further selected from F, Cl, oxo group, =CH2, =CF2, =CHF, =CH(C) 1-2 Alkyl), =C(C) 1-2 The alkyl group is substituted; in some embodiments, R x For deuterium, F, Cl, oxo groups, =CH2, =CF2, =CHF, =CH(C) 1-3 Alkyl), =C(C) 1-3 Alkyl)2、=C 4-6 Cycloalkyl, =(4-6 membered heterocycloalkyl), C 1-4 Alkyl, C 3-6Cycloalkyl groups, wherein the alkyl group or cycloalkyl group is optionally further selected from F, Cl, oxo group, =CH2, =CF2, =CHF, =CH(C) 1-2 Alkyl), =C(C) 1-2 Substituted with alkyl groups;

[0393] Or, R 7b With R B Link formation C 3-8 cycloalkyl or 3-8 membered heterocyclic alkyl;

[0394] n1 is an integer between 0 and 3.

[0395] The compounds of the present invention, their stereoisomers or pharmaceutically acceptable salts thereof, wherein Selected from

[0396] Selected from Or selected from The * site is the connection site between ring B and L2. When L2 is a bond, the * site is the connection site between ring B and L3.

[0397] L1 is selected from C(O)NHCR a R b C(O)NH-、-C(O)NHCR a R b -;

[0398] L2 is selected from the key, -CHR 5b -, -NH-, -N(CH3-) or selected from -NR 5b -;

[0399] L3 is selected from -CHR 7b -、-CHR 7b -C(O)- or selected from -C(O)-;

[0400] When X is the key and N is the key, R2 is directly connected to L3.

[0401] R B Each is independently hydrogen, deuterium, F, Cl, and C. 1-3 Alkyl, Halogenated C 1-3 Alkyl, deuterated C 1-3 Alkyl; or

[0402] R B Each is independently hydrogen, deuterium, F, Cl, and C. 1-3 Alkyl, Halogenated C 1-3 Alkyl, deuterated C 1-3 Alkyl, C 3-6Cycloalkyl, 3-6 membered heterocycloalkyl, wherein the alkyl, cycloalkyl, or heterocycloalkyl group is optionally further surrounded by 1-3 F, Cl, oxo groups, =CH2, =CF2, =CHF, or =CH(C) groups. 1- 2 alkyl), = C(C 1-2 Substitution of alkyl groups;

[0403] R a Each is independently hydrogen, deuterium, and C. 1-3 Alkyl, Halogenated C 1-3 Alkyl, deuterated C 1-3 alkyl;

[0404] R b Each independently is C 1-4 Alkyl, C 4-6 cycloalkyl, wherein the alkyl group or cycloalkyl group is further denoted by 1-3 R groups. x Replaced;

[0405] R 5b R 7b Each is independently hydrogen, deuterium, halogen, and carbon. 1-3 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, wherein the alkyl, cycloalkyl, or heterocycloalkyl group is further surrounded by 1-3 deuterium, F, Cl, CN, oxo group, =CH2, =CF2, =CHF, =CH(C) groups. 1-3 Alkyl), =C(C) 1-3 Alkyl)2、=C 4-6 Cycloalkyl, =(4-6 membered heterocycloalkyl) group substitution; in some embodiments, R 5b R 7b Each is independently hydrogen, deuterium, halogen, and carbon. 1-3 Alkyl, C 3-6 Cycloalkyl groups, wherein the alkyl group or cycloalkyl group is further surrounded by 1-3 deuterium, F, Cl, oxo groups, =CH2, =CF2, =CHF, =CH(C) groups. 1-3 Alkyl), =C(C) 1-3 Alkyl)2、=C 4-6 Substitution of cycloalkyl groups and (4-6 membered heterocycloalkyl) groups;

[0406] R1 is hydrogen, deuterium, or C. 1-4 alkyl;

[0407] R2 is -C(O)R aa -C(O)CH2R aa -C(O)OR aa 3-8 membered heterocyclic alkyl groups, halogenated C 1-4 Alkyl groups or those selected from -(CH2) n1 R aaThe heterocyclic alkyl group is optionally further composed of 1-3 atoms selected from deuterium, halogen, =CH2, =CF2, =CHF, =CH(C) 1-2 Alkyl), =C(C) 1-2 Substitution with alkyl)2 or oxo, -CF3 groups;

[0408] R aa Each independently is C 3-8 Cycloalkyl, 3-8 membered heterocyclic alkyl, or selected from -(CH)=C 4-6 Cycloalkyl groups, wherein the cycloalkyl or heterocycloalkyl group is optionally further selected from 1-3 halogens, =CH2, =CF2, =CHF, =CH(C 1-3 Alkyl), =C(C) 1-3 Substitution of alkyl groups;

[0409] Alternatively, R1 and R2 may link to form a 3-8 membered heterocyclic alkyl group, which may optionally be further bonded by 1-3 elements selected from F, Cl, =O, =CH2, =CF2, =CHF, =CH(C) 1-2 Alkyl), =C(C) 1-2 Alkyl)2、=C 4-6 Substitution of cycloalkyl groups and (4-6 membered heterocycloalkyl) groups;

[0410] R x For deuterium, F, Cl, oxo groups, =CH2, =CF2, =CHF, =CH(C) 1-3 Alkyl), =C(C) 1-3 Alkyl)2、=C 4-6 Cycloalkyl, =(4-6 membered heterocycloalkyl), C 1-4 Alkyl, C 3-6 Cycloalkyl groups, wherein the alkyl group or cycloalkyl group is optionally further selected from F, Cl, oxo group, =CH2, =CF2, =CHF, =CH(C) 1-2 Alkyl), =C(C) 1-2 Substituted with alkyl groups;

[0411] Or, R 7b With R B Link formation C 3-8 cycloalkyl or 3-8 membered heterocyclic alkyl;

[0412] n1 is an integer between 0 and 3.

[0413] The compounds of the present invention, their stereoisomers or pharmaceutically acceptable salts thereof, wherein

[0414] L1 is selected from C(O)NHCR a R b C(O)NH-、-C(O)NHCRa R b -;

[0415] L2 is selected from the key, -CHR 5b -、-NH-、-N(CH3)-;

[0416] L3 is selected from -CHR 7b -、-CHR 7b -C(O)-;

[0417] When X is the key and N is the key, R2 is directly connected to L3.

[0418] R B Each of these can be independently identified as hydrogen, deuterium, F, Cl, -CH3, -CH2CH3, -CH2CH2CH3, -CH2F, -CHF2, -CF3, -CH2Cl, -CHCl2, -CCl3, -CHFCH3, -CF2CH3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CH2D, -CHD2, -CD3, -CHDCH3, -CD2CH3, -CH2CH2D, -CH2CHD2, -CH2CD3;

[0419] R a Each of these can be independently hydrogen, deuterium, -CH3, -CH2CH3, -CH2CH2CH3, -CH2F, -CHF2, -CF3, -CH2Cl, -CHCl2, -CCl3, -CHFCH3, -CF2CH3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CH2D, -CHD2, -CD3, -CHDCH3, -CD2CH3, -CH2CH2D, -CH2CHD2, -CH2CD3;

[0420] R b Each of the following groups is independently -CH3, -CH2CH3, -CH2CH2CH3, cyclobutyl, cyclopentyl, or cyclohexyl, wherein the -CH3, -CH2CH3, -CH2CH2CH3, cyclobutyl, cyclopentyl, or cyclohexyl groups are further bounded by 1-3 R groups. x Replaced;

[0421] R 5b R 7bEach of the following is independently hydrogen, deuterium, F, Cl, -CH3, -CH2CH3, -CH2CH2CH3, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 4-membered heterocyclic alkyl, 5-membered heterocyclic alkyl, 6-membered heterocyclic alkyl, wherein the -CH3, -CH2CH3, -CH2CH2CH3, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 4-membered heterocyclic alkyl, 5-membered heterocyclic alkyl, 6-membered heterocyclic alkyl is further surrounded by 1-3 deuterium, F, Cl, CN, oxo group, =CH2, =CF2, =CHF, =CH(C 1-3 Alkyl), =C(C) 1-3 Alkyl)2, =C4 cycloalkyl, =C5 cycloalkyl, =C6 cycloalkyl, =(4-membered heterocyclic alkyl), =(5-membered heterocyclic alkyl), =(6-membered heterocyclic alkyl) group substitution; in some embodiments, R 5b R 7b Each of the following groups is independently hydrogen, deuterium, F, Cl, -CH3, -CH2CH3, -CH2CH2CH3, cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, wherein the -CH3, -CH2CH3, -CH2CH2CH3, cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl groups are further surrounded by 1-3 deuterium, F, Cl, oxo groups, =CH2, =CF2, =CHF, or =CH(C 1-3 Alkyl), =C(C) 1-3 Substitution of groups such as alkyl groups (2), =C4 cycloalkyl, =C5 cycloalkyl, =C6 cycloalkyl, =(4-membered heterocyclic alkyl), =(5-membered heterocyclic alkyl), =(6-membered heterocyclic alkyl);

[0422] R1 can be hydrogen, deuterium, -CH3, -CH2CH3, or -CH2CH2CH3;

[0423] R2 is -C(O)R aa -C(O)CH2R aa -C(O)OR aa 4-membered heterocyclic alkyl, 5-membered heterocyclic alkyl, 6-membered heterocyclic alkyl, -CH2F, -CHF2, -CF3, -CHFCH3, -CF2CH3, -CH2CH2F, -CH2CHF2, -CH2CF3, wherein the 4-membered heterocyclic alkyl, 5-membered heterocyclic alkyl, and 6-membered heterocyclic alkyl may optionally be further selected from 1-3 elements selected from deuterium, F, Cl, =CH2, =CF2, =CHF, =CH(C 1-2 Alkyl), =C(C) 1-2 Substitution of alkyl groups;

[0424] R aaEach of the following is independently cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 4-membered heterocyclic alkyl, 5-membered heterocyclic alkyl, or 6-membered heterocyclic alkyl, wherein the cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 4-membered heterocyclic alkyl, 5-membered heterocyclic alkyl, or 6-membered heterocyclic alkyl may optionally be further selected from 1-3 of F, Cl, =CH2, =CF2, =CHF, or =CH(C 1-3 Alkyl), =C(C) 1-3 Substitution of alkyl groups;

[0425] Alternatively, R1 and R2 may be linked to form a 4-membered heterocyclic alkyl group, a 5-membered heterocyclic alkyl group, or a 6-membered heterocyclic alkyl group. The formed 4-membered, 5-membered, or 6-membered heterocyclic alkyl group may optionally be further bonded by 1-3 elements selected from F, Cl, =O, =CH2, =CF2, =CHF, and =CH(C). 1-2 Alkyl), =C(C) 1-2 Substitution of groups such as alkyl groups (2), =C4 cycloalkyl, =C5 cycloalkyl, =C6 cycloalkyl, =(4-membered heterocyclic alkyl), =(5-membered heterocyclic alkyl), =(6-membered heterocyclic alkyl);

[0426] R x For deuterium, F, Cl, oxo groups, =CH2, =CF2, =CHF, =CH(C) 1-3 Alkyl), =C(C) 1-3 Alkyl)2、=C 4-6 Cycloalkyl, =(4-6 membered heterocycloalkyl), -CH3, -CH2CH3, -CH2CH2CH3, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, wherein -CH3, -CH2CH3, -CH2CH2CH3, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl are optionally further selected from F, Cl, oxo, =CH2, =CF2, =CHF, =CH(C 1-2 Alkyl), =C(C) 1-2 Substituted with alkyl groups;

[0427] Or, R 7b With R B Linkages form cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 4-membered heterocyclic alkyl, 5-membered heterocyclic alkyl, and 6-membered heterocyclic alkyl.

[0428] The compounds, their stereoisomers, or pharmaceutically acceptable salts thereof, represented by general formulas (I), (II), (II-1), (II-1a), (II-1b), (II-2), (III), (III-1), (III-2), (IIIA), (IIIB), (IIIC), (IIIC-1), (IIIC-2), (IIIC-3), (IIIC-4), (IIIC-5), (IIIC-6), (IIID), (IIIE), (IIIF), (IV), (V), (VA), (V-Aa), (III-a), (III-1a), (III-2a), (VI-1), (VI-2), and (VI-a) of this invention are selected from, but not limited to, the structures shown in Tables 1 and 2 below:

[0429] Table 1:

[0430] Table 2:

[0431] The present invention further provides a pharmaceutical composition comprising a therapeutically effective dose of the compound as described above, its stereoisomer or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers or excipients.

[0432] Furthermore, the pharmaceutical composition or pharmaceutical preparation of the present invention contains 1-1500 mg of the compound described in any of the preceding embodiments, its stereoisomer or pharmaceutically acceptable salt, and a pharmaceutically acceptable carrier and / or excipient.

[0433] In some embodiments of the present invention, the above-described pharmaceutical compositions can be formulated in a conventional manner using one or more pharmaceutically acceptable carriers. The carriers refer to carriers conventional in the pharmaceutical field, such as: diluents like water; binders like cellulose derivatives, gelatin, polyvinylpyrrolidone, etc.; fillers like starch, etc.; disintegrants like calcium carbonate, sodium bicarbonate, etc.; lubricants like calcium stearate or magnesium stearate, etc. Additionally, other excipients such as sweeteners, flavoring agents, or coloring agents may be added to the composition.

[0434] In some embodiments of the invention, the pharmaceutical composition may be administered in any of the following ways: orally, by spray inhalation, rectal administration, nasal administration, buccal administration, topical administration, or parenteral administration such as subcutaneous, intravenous, intramuscular, intraperitoneal, intrathecal, intraventricular, intrasternal, or intracranial injection or infusion, or via an external implantation device. Oral administration is preferred.

[0435] When taken orally, the compounds of this application can be formulated into any orally acceptable dosage form, including but not limited to tablets, capsules, aqueous solutions or aqueous suspensions.

[0436] The present invention further provides the use of the compounds described above, their stereoisomers or pharmaceutically acceptable salts thereof, or pharmaceutical compositions thereof in the preparation of medicaments for the treatment / prevention of IL-17A-mediated diseases.

[0437] The present invention further provides a method for treating diseases in mammals or humans, comprising administering to the mammal a therapeutically effective dose of any of the indicated compounds, their stereoisomers, or pharmaceutically acceptable salts, esters, prodrugs, solvates, hydrates, or derivatives thereof, or pharmaceutical compositions thereof. The diseases are preferably psoriasis, arthritis, and multiple sclerosis, etc., and the therapeutically effective dose is preferably 1-1500 mg. In some embodiments, the mammals described in the present invention do not include humans.

[0438] The term "effective amount" or "therapeutic effective amount" as used in this application means that administering a sufficient amount of the compound disclosed in this application will alleviate, to some extent, one or more symptoms of the disease or condition being treated. In some embodiments, the result is a reduction and / or mitigation of the signs, symptoms, or causes of the disease, or any other desired alteration of the biological system. For example, an "effective amount" for therapeutic use is the amount of the compound disclosed in this application required to provide a clinically significant reduction in disease symptoms. Examples of therapeutically effective doses include, but are not limited to, 1-1500 mg, 1-1400 mg, 1-1300 mg, 1-1200 mg, 1-1000 mg, 1-900 mg, 1-800 mg, 1-700 mg, 1-600 mg, 1-500 mg, 1-400 mg, 1-300 mg, 1-250 mg, 1-200 mg, 1-150 mg, 1-125 mg, 1-100 mg, 1-80 mg, 1-60 mg, 1-50 mg, 1-40 mg, 1-25 mg, 1- 20mg, 5-1500mg, 5-1000mg, 5-900mg, 5-800mg, 5-700mg, 5-600mg, 5-500mg, 5-400mg, 5-300mg, 5-250mg, 5-200mg, 5 -150mg, 5-125mg, 5-100mg, 5-90mg, 5-70mg, 5-80mg, 5-60mg, 5-50mg, 5-40mg, 5-30mg, 5-25mg, 5-20mg, 10-1500mg, 10-1000mg, 10-900mg, 10-800mg, 10-700mg, 10-600mg, 10-500mg, 10-450mg, 10-400mg, 10-300mg, 10-250mg, 10-20 0mg, 10-150mg, 10-125mg, 10-100mg, 10-90mg, 10-80mg, 10-70mg, 10-60mg, 10-50mg, 10-40mg, 10-30mg, 10-20mg; 2 0-1500mg, 20-1000mg, 20-900mg, 20-800mg, 20-700mg, 20-600mg, 20-500mg, 20-400mg, 20-350mg, 20-300mg, 20-25 0mg, 20-200mg, 20-150mg, 20-125mg, 20-100mg, 20-90mg, 20-80mg, 20-70mg, 20-60mg, 20-50mg, 20-40mg, 20-30mg;50-1500mg, 50-1000mg, 50-900mg, 50-800mg, 50-700mg, 50-600mg, 50-500mg, 50-400mg, 50-300mg, 50-250mg, 50-200mg, 50-150mg, 50-125mg, 5 0-100mg; 100-1500mg, 100-1000mg, 100-900mg, 100-800mg, 100-700mg, 100-600mg, 100-500mg, 100-400mg, 100-300mg, 100-250mg, 100-200mg. ;

[0439] This invention relates to a pharmaceutical composition or pharmaceutical formulation comprising a therapeutically effective amount of the compound of the invention or its stereoisomers, deuterated derivatives, solvates, eutectics, or pharmaceutically acceptable salts, as well as a carrier and / or excipients. The pharmaceutical composition may be in unit dosage form (the amount of the active ingredient in a unit dosage form is also referred to as a "dosage strength"). In some embodiments, the pharmaceutical composition includes, but is not limited to, 1-1500 mg, 5-1000 mg, 10-800 mg, 20-600 mg, 25-500 mg, 40-200 mg, 50-100 mg, 1 mg, 1.25 mg, 2.5 mg, 5 mg, 10 mg, 12.5 mg, 15 mg, 20 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 55 mg, 60 mg, 65 mg, 70 mg, 75 mg, 80 mg, 85 mg, 90 mg, 95 mg, 100 mg, 110 mg, 120 mg, 125 mg, 130 mg, 140 mg, 150 mg, 160 mg, 170 mg, 180 mg, 190 mg, etc. The compounds of the present invention, or their stereoisomers, deuterated derivatives, solvates, eutectics, or pharmaceutically acceptable salts, in the amounts of g, 200 mg, 210 mg, 220 mg, 230 mg, 240 mg, 250 mg, 275 mg, 300 mg, 325 mg, 350 mg, 375 mg, 400 mg, 425 mg, 450 mg, 475 mg, 500 mg, 525 mg, 550 mg, 575 mg, 600 mg, 625 mg, 650 mg, 675 mg, 700 mg, 725 mg, 750 mg, 775 mg, 800 mg, 850 mg, 900 mg, 950 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, and 1500 mg.

[0440] A method for treating a disease in mammals, the method comprising administering to a subject a therapeutically effective amount of the compound of the present invention, its stereoisomer, deuterated form, solvate, eutectic or pharmaceutically acceptable salt, and a pharmaceutically acceptable carrier and / or excipient, the therapeutically effective amount preferably being 1-1500 mg, the disease preferably being psoriasis, arthritis and multiple sclerosis.

[0441] A method for treating a disease in mammals or humans. The method comprises administering a pharmaceutical compound of the invention, its stereoisomers, deuterated derivatives, solvates, cocrystals, or pharmaceutically acceptable salts, and pharmaceutically acceptable carriers and / or excipients, to a subject at a daily dose of 1-1500 mg / day. The daily dose may be a single dose or multiple doses. In some embodiments, the daily dose includes, but is not limited to, 10-1500 mg / day, 20-1500 mg / day, 25-1500 mg / day, 50-1500 mg / day, 75-1500 mg / day, 100-1500 mg / day, 200-1500 mg / day, 10-1000 mg / day, 20-1000 mg / day, 25-1000 mg / day, 50-1000 mg / day, and 75-1000 mg / day. / day, 100-1000mg / day, 200-1000mg / day, 25-800mg / day, 50-800mg / day, 100-800mg / day, 200-800mg / day, 25-400mg / day, 50-400mg / day, 100-400mg / day, 200-400mg / day, and in some embodiments, the daily dose includes, but is not limited to, 1mg / day, 5mg / day, 10mg / day, 20mg / day, 25mg / day, 50mg / day, 75mg / day, 100mg / day, 125mg / day, 150mg / day, 200mg / day, 400mg / day, 600mg / day, 800mg / day, 1000mg / day, 1200mg / day, 1400mg / day, and 1500mg / day.

[0442] This invention relates to a kit that may include a single-dose or multi-dose composition comprising a compound of the present invention or its stereoisomers, deuterated derivatives, solvates, eutectics, or pharmaceutically acceptable salts, wherein the amount of the compound of the present invention or its stereoisomers, deuterated derivatives, solvates, eutectics, or pharmaceutically acceptable salts is the same as that in the aforementioned pharmaceutical composition.

[0443] In this invention, the amount of the compound of the invention or its stereoisomers, deuterated derivatives, solvates, eutectics or pharmaceutically acceptable salts is converted in each case as free base.

[0444] "Product specification" refers to the weight of the active pharmaceutical ingredient contained in each vial, tablet, or other unit of preparation.

[0445] Detailed description of the invention

[0446] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. In case of any conflict, the definitions provided herein shall prevail. When trade names appear herein, they are intended to refer to the corresponding product or its active ingredient. All patents, published patent applications, and publications cited herein are incorporated herein by reference.

[0447] The term "alkyl" refers to a saturated, straight-chain or branched aliphatic hydrocarbon group having 1 to 20 (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) carbon atoms, i.e., "C". 1-20 Alkyl group. The alkyl group is preferably an alkyl group having 1 to 12 carbon atoms (i.e., C12). 1-12 Alkyl groups, more preferably alkyl groups having 1 to 8 carbon atoms (i.e., C14-C ... 1-8 Alkyl groups, more preferably alkyl groups having 1 to 6 carbon atoms (i.e., C14-C6 ... 1-6 Alkyl groups, most preferably alkyl groups having 1 to 3 carbon atoms (i.e., C14-C ... 1-3Alkyl groups). Non-limiting examples include: methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, 2-methylbutyl, 3-methylbutyl, n-hexyl, 1-ethyl-2-methylpropyl, 1,1,2-trimethylpropyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 2,2-dimethylbutyl, 1,3-dimethylbutyl, 2-ethylbutyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 2,3-dimethylbutyl, n-heptyl, 2-methylhexyl, 3-methylhexyl, 4-methylhexyl, 5-methylhexyl, 2 3-Dimethylpentyl, 2,4-Dimethylpentyl, 2,2-Dimethylpentyl, 3,3-Dimethylpentyl, 2-Ethylpentyl, 3-Ethylpentyl, n-Octyl, 2,3-Dimethylhexyl, 2,4-Dimethylhexyl, 2,5-Dimethylhexyl, 2,2-Dimethylhexyl, 3,3-Dimethylhexyl, 4,4-Dimethylhexyl, 2-Ethylhexyl, 3-Ethylhexyl, 4-Ethylhexyl, 2-Methyl-2-Ethylpentyl, 2-Methyl-3-Ethylpentyl, n-Nonyl, 2-Methyl-2-Ethylhexyl, 2-Methyl-3-Ethylhexyl, 2,2-Diethylpentyl, n-Decyl, 3,3-Diethylhexyl, 2,2-Diethylhexyl, and their various branched isomers, etc. The alkyl group can be substituted or unsubstituted. When substituted, the substituent can be replaced at any usable connection point. The substituent is preferably one or more of the following groups, independently selected from deuterium, halogen, hydroxyl, mercapto, cyano, amino, nitro, oxo, C... 1-6 Alkyl, C 2-6 alkenyl, ynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl compounds.

[0448] The term "alkenyl" refers to an alkyl group in which the molecule contains at least one carbon-carbon double bond, wherein the alkyl group, as defined above, has 2 to 12 (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12) carbon atoms (i.e., C atoms). 2-12 Alkenyl). The alkenyl group is preferably an alkenyl group having 2 to 6 carbon atoms (i.e., C). 2-6Alkenyl). Non-limiting examples include: vinyl, 1-propenyl, 2-propenyl, 2-methylpropenyl, 1-, 2-, or 3-butenyl, etc. The alkenyl group can be substituted or unsubstituted; when substituted, the substituent can be substituted at any usable connection point, preferably one or more of the following groups independently selected from deuterium, halogen, hydroxyl, mercapto, cyano, amino, nitro, oxo, C. 1-6 Alkyl, C 2-6 alkenyl, ynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl compounds.

[0449] The term "alkynyl" refers to an alkyl group in a molecule that contains at least one carbon-carbon triple bond, wherein the alkyl group, as defined above, has 2 to 12 (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12) carbon atoms (i.e., C atoms). 2-12 The alkynyl group is preferably an alkynyl group having 2 to 6 carbon atoms (i.e., C64). 2-6 Alkyne group). Non-limiting examples include: ethynyl, propynyl, butynyl, pentylyl, hexynyl, etc. The alkynyl group can be substituted or unsubstituted; when substituted, the substituent can be substituted at any usable linking point. The substituent is preferably one or more of the following groups, independently selected from deuterium, halogen, hydroxyl, mercapto, cyano, amino, nitro, oxo, C... 1-6 Alkyl, C 2-6 alkenyl, ynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl compounds.

[0450] The term "cycloalkyl" refers to a saturated or partially unsaturated monocyclic cyclic hydrocarbon substituent (i.e., monocyclic cycloalkyl) or polycyclic cyclic hydrocarbon substituent (i.e., polycyclic cycloalkyl) having 3 to 20 (e.g., 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) carbon atoms, i.e., C64. 3-20 Cycloalkyl group. The cycloalkyl group is preferably a cycloalkyl group having 3 to 12 carbon atoms (i.e., C12). 3-12cycloalkyl groups, more preferably cycloalkyl groups having 3 to 8 carbon atoms (i.e., C14-C ... 3-8 Cycloalkyl groups, more preferably cycloalkyl groups having 3 to 6 carbon atoms (i.e., C164-C ... 3-6 (Cycloalkyl). Non-limiting examples of monocyclic cycloalkyl groups include: cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cycloheptyl, cyclohepttrienyl, and cyclooctyl, etc. Non-limiting examples of polycyclic cycloalkyl groups include: spirocycloalkyl, fused cycloalkyl, and bridged cycloalkyl.

[0451] The term "spirocycloalkyl" refers to a polycyclic group in which the monocyclic rings share a single carbon atom (called the spiro atom). It may contain one or more double bonds, but none of the rings has a fully conjugated π-electron system. It has 5 to 20 (e.g., 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) ring atoms (i.e., C atoms). 5-20 Spirocycloalkyl. The spirocycloalkyl group is preferably a spirocycloalkyl group having 6 to 14 ring atoms (i.e., C14). 6-14 Spirocycloalkyl, more preferably spirocycloalkyl having 7 to 10 ring atoms (i.e., C14-C ... 7-10 Spirocycloalkyl. Based on the number of spiroatoms shared between rings, spirocycloalkyl is classified into monospirocycloalkyl, bispirocycloalkyl, or polyspirocycloalkyl, preferably monospirocycloalkyl or bispirocycloalkyl, more preferably 3 / 4, 3 / 5, 3 / 6, 4 / 4, 4 / 5, 4 / 6, 5 / 3, 5 / 4, 5 / 5, 5 / 6, 5 / 7, 6 / 3, 6 / 4, 6 / 5, 6 / 6, 6 / 7, 7 / 5, or 7 / 6 monospirocycloalkyl.

[0452] The term "fused-cycloalkyl" refers to a polycyclic aromatic hydrocarbon group in which each ring in a system shares an adjacent pair of carbon atoms with the other rings in the system, and has 5 to 20 (e.g., 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) ring atoms (i.e., C atoms). 5-20 Fused cyclic alkyl groups. They may contain one or more double bonds, but none of the rings has a fully conjugated π-electron system. Preferably, the fused cyclic alkyl group has 6 to 14 ring atoms (i.e., C14). 6-14 Fused cyclic alkyl groups, more preferably fused cyclic alkyl groups having 7 to 10 ring atoms (i.e., C14-C ... 7-10Fused cyclic alkyl groups are classified into bicyclic, tricyclic, tetracyclic, or polycyclic fused cyclic alkyl groups based on the number of constituent rings. Bicyclic or tricyclic fused cyclic alkyl groups are preferred, and ternary / quadrivalent, ternary / quinary, ternary / sixary, quadrivalent / quadrivalent, quadrivalent / quinary, quadrivalent / sixary, quinary / trivalent, quinary / quadrivalent, quinary / quinary, quinary / sixary, quinary / sevenary, quinary / trivalent, quinary / quadrivalent, quinary / quadrivalent, quinary / sixary, quinary / sevenary, quinary / trivalent, quinary / quadrivalent, quinary / sixary, quinary / sevenary, quinary / trivalent, or quinary / sixary bicyclic fused cyclic alkyl groups are more preferred.

[0453] The term "bridged cycloalkyl" refers to a fully carbon polycyclic group in which any two rings share two non-directly connected carbon atoms, having 5 to 20 (e.g., 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) ring atoms (i.e., C atoms). 5-20 Bridged cycloalkyl groups. They contain one or more double bonds, but none of the rings have a fully conjugated π-electron system. Preferably, the bridged cycloalkyl group has 6 to 14 ring atoms (i.e., C14). 6-14 Bridged cycloalkyl groups, more preferably bridged cycloalkyl groups having 7 to 10 ring atoms (i.e., C14-C ... 7-10 Bridged cycloalkyl groups are classified into bicyclic, tricyclic, tetracyclic, or polycyclic bridged cycloalkyl groups based on the number of rings, with bicyclic or tricyclic bridged cycloalkyl groups being preferred. Example structures are shown below:

[0454] The cycloalkyl group can be fused to an aryl, heteroaryl, or heterocycloalkyl ring, wherein the ring linked to the parent structure is a cycloalkyl group. The cycloalkyl group can be optionally substituted or unsubstituted; when substituted, the substituent can be substituted at any usable connection point. The substituent is preferably one or more of the following groups, independently selected from deuterium, halogen, hydroxyl, mercapto, cyano, amino, nitro, oxo, C... 1-6 Alkyl, C 2-6 alkenyl, ynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl compounds.

[0455] The term "heterocyclic alkyl" refers to a saturated or partially unsaturated monocyclic heterocyclic hydrocarbon substituent (i.e., monocyclic heterocyclic alkyl) or polycyclic heterocyclic hydrocarbon substituent (i.e., polycyclic heterocyclic alkyl) having 3 to 20 (e.g., 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20) ring atoms (i.e., 3-20 membered heterocyclic alkyl), wherein one or more (e.g., 1, 2, 3 or 4) ring atoms are selected from heteroatoms of nitrogen, oxygen, P(O)2, SO2 and S(O), but excluding the ring moiety of -OO-, -OS- or -SS-, and the remaining ring atoms are carbon. The heterocyclic alkyl group preferably has 3 to 12 ring atoms (i.e., 3-12 membered heterocyclic alkyl groups), wherein it contains 1 to 4 heteroatoms selected from N, O and S atoms; more preferably it has 3 to 8 ring atoms (i.e., 3-8 membered heterocyclic alkyl groups), wherein it contains 1 to 4, 1 to 3 or 1 to 2 heteroatoms selected from N, O and S atoms; even more preferably it has 3 to 6 ring atoms (i.e., 3-6 membered heterocyclic alkyl groups), wherein it contains 1 to 4, 1 to 3 or 1 to 2 heteroatoms selected from N, O and S atoms; and most preferably it has 4 to 6 ring atoms (i.e., 4-6 membered heterocyclic alkyl groups), wherein it contains 1 to 4, 1 to 3 or 1 to 2 heteroatoms selected from N, O and S atoms. Non-limiting examples of the monocyclic heterocyclic alkyl groups include: azirrobutyl, oxacyclobutyl, thiohexacyclobutyl, pyrrolyl, imidazoalkyl, tetrahydrofuranyl, tetrahydrothiophenyl, tetrahydropyranyl, dihydroimidazoyl, dihydrofuranyl, dihydropyrazolyl, piperidinyl, piperazinyl, morpholinyl, 1,3-dioxocyclopentyl, 2,2-difluoro-1,3-dioxocyclopentyl, cyclopentanone, 2,2-difluorocyclopentanone, acrylonitrile, oxacyclopentyl, azirropentyl, tetrahydropyrrolyl, butyrolactam, valeronyl, or caprolactam, etc. Example structures are as follows:

[0456] Non-limiting examples of the polycyclic heterocyclic alkyl groups include spirocyclic alkyl groups, fused heterocyclic alkyl groups, and bridged heterocyclic alkyl groups.

[0457] The term "spiroheteroalkyl" refers to a polycyclic heterocyclic alkyl group that shares a single atom (called a spiro atom) between monocyclic rings, having 5 to 20 (e.g., 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) ring atoms (i.e., 5-20-membered spiroheteroalkyl), wherein one or more (e.g., 1, 2, 3, or 4) ring atoms are selected from nitrogen, oxygen, P(O)₂, SO₂, and S(O) heteroatoms, but excluding the -OO-, -OS-, or -SS- ring moieties, and the remaining ring atoms are carbon. It may contain one or more double bonds, but no ring has a fully conjugated π-electron system. The spiroheteroalkyl group is preferably a spiroheteroalkyl group having 6 to 14 ring atoms (i.e., 6-14-membered spiroheteroalkyl), more preferably a spiroheteroalkyl group having 7 to 10 ring atoms (i.e., 7-10-membered spiroheteroalkyl). The spiroheterocyclic alkyl group is classified into monospiroheterocyclic alkyl, bispiroheterocyclic alkyl, or polyspiroheterocyclic alkyl based on the number of spiro atoms shared between the rings. It is preferred to be monospiroheterocyclic alkyl or bispiroheterocyclic alkyl, and more preferably 3-membered / 4-membered, 3-membered / 5-membered, 3-membered / 6-membered, 4-membered / 4-membered, 4-membered / 5-membered, 4-membered / 6-membered, 5-membered / 3-membered, 5-membered / 4-membered, 5-membered / 5-membered, 5-membered / 6-membered, 5-membered / 7-membered, 6-membered / 3-membered, 6-membered / 4-membered, 6-membered / 5-membered, 6-membered / 6-membered, 6-membered / 7-membered, 7-membered / 5-membered, or 7-membered / 6-membered monospiroheterocyclic alkyl.

[0458] The term "fused heterocyclic alkyl" refers to a polycyclic heterocyclic alkyl group in which each ring in a system shares an adjacent pair of atoms with other rings in the system. This group has 5 to 20 (e.g., 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) ring atoms (i.e., 5-20-membered fused heterocyclic alkyl), wherein one or more (e.g., 1, 2, 3, or 4) ring atoms are selected from nitrogen, oxygen, P(O)₂, SO₂, and S(O), but excludes the -OO-, -OS-, or -SS- ring moieties, and the remaining ring atoms are carbon. It may contain one or more double bonds, but no ring has a fully conjugated π-electron system. The fused heterocyclic alkyl group is preferably a fused heterocyclic alkyl group having 6 to 14 ring atoms (i.e., 6-14-membered fused heterocyclic alkyl), more preferably a fused heterocyclic alkyl group having 7 to 10 ring atoms (i.e., 7-10-membered fused heterocyclic alkyl). Based on the number of constituent rings, they are classified as bicyclic, tricyclic, tetracyclic, or polycyclic heterocyclic alkyl groups, with bicyclic or tricyclic heterocyclic alkyl groups being preferred, and ternary / quadrivalent, ternary / quinary, ternary / sixary, quadrivalent / quadrivalent, quadrivalent / quinary, quadrivalent / quinary, quadrivalent / sixary, quinary / trivalent, quinary / quadrivalent, quinary / quinary, quinary / sixary, quinary / sevenary, quinary / trivalent, quinary / quadrivalent, quinary / quadrivalent, quinary / sixary, quinary / sevenary, quinary / trivalent, quinary / quadrivalent, quinary / sixary, quinary / sevenary, quinary / trivalent, or quinary / sixary bicyclic heterocyclic alkyl groups.

[0459] The term "bridged heterocyclic alkyl" refers to a polycyclic heterocyclic alkyl group in which any two rings share two non-directly connected atoms, having 5 to 20 (e.g., 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) ring atoms (i.e., 5-20-membered bridged heterocyclic alkyl), wherein one or more (e.g., 1, 2, 3, or 4) ring atoms are selected from nitrogen, oxygen, P(O)₂, SO₂, and S(O), but excluding the -OO-, -OS-, or -SS- ring moieties, and the remaining ring atoms are carbon. It may contain one or more double bonds, but none of the rings has a fully conjugated π-electron system. The bridged heterocyclic alkyl is preferably a bridged heterocyclic alkyl with 6 to 14 ring atoms (i.e., 6-14-membered bridged heterocyclic alkyl), more preferably a bridged heterocyclic alkyl with 7 to 10 ring atoms (i.e., 7-10-membered bridged heterocyclic alkyl). Based on the number of constituent rings, they are classified as bicyclic, tricyclic, tetracyclic, or polycyclic bridged heterocyclic alkyl groups, with bicyclic bridged heterocyclic alkyl groups or tricyclic bridged heterocyclic alkyl groups being preferred.

[0460] The heterocyclic alkyl group can be fused to an aryl, heteroaryl, or cycloalkyl ring, wherein the ring connected to the parent structure is a heterocyclic alkyl group.

[0461] The heterocyclic alkyl group may be optionally substituted or unsubstituted. When substituted, the substituent may be substituted at any usable linker. The substituent is preferably one or more of the following groups, independently selected from deuterium, halogen, hydroxyl, mercapto, cyano, amino, nitro, oxo, and C. 1-6 Alkyl, C 2-6 alkenyl, ynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl compounds.

[0462] The In It refers to a heterocyclic alkyl group containing at least one nitrogen atom, wherein the heterocyclic alkyl group is as defined above.

[0463] The term "aryl" refers to an all-carbon monocyclic group (i.e., monocyclic aryl) or a fused polycyclic group (i.e., polycyclic aryl) having a conjugated π-electron system, having 6 to 14 (e.g., 6, 7, 8, 9, 10, 11, 12, 13, or 14) carbon atoms (i.e., C atoms). 6-14 Aryl group). The aryl group is preferably an aryl group having 6 to 12 carbon atoms (i.e., C64). 6-12 Aryl), more preferably aryl having 6 to 10 carbon atoms (i.e., C10). 6-10Aryl), further preferably phenyl or naphthyl, most preferably phenyl. The monocyclic aryl group is, for example, phenyl. Non-limiting examples of the polycyclic aryl group include: naphthyl, anthracene, phenanthryl, etc.

[0464] The aryl group can be fused to a cycloalkyl or heterocycloalkyl ring to form a fused aromatic ring system, wherein the ring connected to the parent structure is an aryl ring. The fused aromatic ring system is preferably a 6-10-membered aryl-3-8-membered cycloalkyl or a 6-10-membered aryl-3-8-membered heterocycloalkyl, more preferably a phenyl-3-8-membered cycloalkyl or a phenyl-3-8-membered heterocycloalkyl, and even more preferably a phenyl-4-6-membered cycloalkyl or a phenyl-4-6-membered heterocycloalkyl. Non-limiting examples include: indole, inzolyl, quinolinyl, isoquinolinyl, quinoxalinyl, phthalazinyl, benzimidazolyl, benzothiophenyl, thiophene, quinazolinyl, benzothiazolyl, carbazole, thiophenepyridyl, pyridothiophenyl, pyridopyrroleyl, etc. Example structures are as follows:

[0465] The aryl group can be optionally substituted or unsubstituted. When substituted, the substituent can be replaced at any usable linker. The substituent is preferably one or more of the following groups, independently selected from deuterium, halogen, hydroxyl, mercapto, cyano, amino, nitro, oxo, C... 1-6 Alkyl, C 2-6 alkenyl, ynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl compounds.

[0466] The term "heteroaryl" refers to a monocyclic heteroaryl group (i.e., monocyclic heteroaryl) or a fused polycyclic heteroaryl group (i.e., polycyclic heteroaryl) having a conjugated π-electron system, having 5 to 14 (e.g., 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14) ring atoms (i.e., 5-14-membered heteroaryl), wherein one or more (e.g., 1, 2, 3, or 4) ring atoms are heteroatoms selected from nitrogen, P(O)₂, SO₂, and S(O), preferably heteroatoms selected from nitrogen, oxygen, or sulfur, but excluding the -OO-, -OS-, or -SS- ring moieties, and the remaining ring atoms are carbon. The heteroaryl is preferably a heteroaryl having 5 to 10 ring atoms (i.e., 5-10-membered heteroaryl). The monocyclic heteroaryl group is preferably a heteroaryl group having 5 to 6 ring atoms (i.e., a 5-6 membered heteroaryl group). Non-limiting examples include: furanyl, pyranyl, thiophene, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, imidazole, pyrazolyl, triazolyl, tetrazolyl, pyrroleyl, pyridinyl, pyrimidinyl, pyridoneyl, pyrazinyl, pyridazinyl, etc.

[0467] The heteroaryl group can be fused to an aryl, heterocyclic alkyl, or cycloalkyl ring to form a fused heteroaryl ring system, wherein the ring connected to the parent structure can be a heteroaryl ring or an aryl ring. The fused heteroaryl ring system is preferably 5-6 membered heteroaryl-5-6 membered heteroaryl, 5-10 membered heteroaryl-C6-10 aryl, or C6-10 aryl-5-10 membered heteroaryl, more preferably 5-6 membered heteroaryl-5-6 membered heteroaryl, 5-6 membered heteroaryl-phenyl, or phenyl-5-6 membered heteroaryl. Non-limiting examples include: indole, inzolyl, quinolinyl, isoquinolinyl, quinoxalinyl, phthalazinyl, benzimidazolyl, benzothiophene, thiophene-phenyl, quinazolinyl, benzothiazolyl, carbazole, thiophene-pyridyl, pyridothiophene, pyridopyrrole, etc. Example structures are as follows:

[0468] The heteroaryl group can be optionally substituted or unsubstituted. When substituted, the substituent can be substituted at any usable linker. The substituent is preferably one or more of the following groups, independently selected from deuterium, halogen, hydroxyl, mercapto, cyano, amino, nitro, oxo, C... 1-6 Alkyl, C 2-6 alkenyl, ynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl compounds.

[0469] The term "alkoxy" refers to -O- (alkyl) or -O- (unsubstituted cycloalkyl), wherein alkyl and cycloalkyl are defined as above, having 1 to 10 (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10) carbon atoms (i.e., C atoms). 1-10 Alkoxy group). The alkoxy group is preferably an alkoxy group having 1 to 8 carbon atoms (i.e., C14). 1-8 Alkoxy groups, more preferably alkoxy groups having 1 to 6 carbon atoms (i.e., C14-C6 ... 1-6 Alkoxy groups, preferably alkoxy groups having 1 to 3 carbon atoms (i.e., C14-C ... 1-3 Alkoxy groups. Non-limiting examples include: methoxy, ethoxy, propoxy, butoxy, cyclopropoxy, cyclobutoxy, cyclopentoxy, cyclohexyloxy, etc. The alkoxy group may be optionally substituted or unsubstituted; when substituted, the substituent may be substituted at any usable linking point, preferably one or more of the following groups independently selected from deuterium, halogen, hydroxyl, mercapto, cyano, amino, nitro, oxo, C 1-6 Alkyl, C 2-6 alkenyl, ynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl compounds.

[0470] The term "alkathioyl" refers to -S- (alkyl) or -S- (unsubstituted cycloalkyl), wherein alkyl and cycloalkyl are defined as above and have 1 to 10 (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10) carbon atoms (i.e., C atoms). 1-10 Alkylthio group). The alkylthio group is preferably an alkylthio group having 1 to 8 carbon atoms (i.e., C12). 1-8 Alkylthioyl), more preferably alkylthioyl groups having 1 to 6 carbon atoms (i.e., C14-C ... 1-6 Alkylthio group), preferably alkylthio group with 1 to 3 carbon atoms (i.e., C12-C ... 1-3 Alkylthioyl). Non-limiting examples include: methylthioyl, ethylthioyl, propylthioyl, butylthioyl, cyclopropylthioyl, cyclobutylthioyl, cyclopentylthioyl, cyclohexylthioyl, etc. The alkylthioyl group may be optionally substituted or unsubstituted. When substituted, the substituent may be substituted at any usable linking point. The substituent is preferably one or more of the following groups, independently selected from deuterium, halogen, hydroxyl, mercapto, cyano, amino, nitro, oxo, C... 1-6 Alkyl, C 2-6 alkenyl, ynyl, C 1-6 Deuterated alkyl, C 1-6Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl compounds.

[0471] The terms “halogen” or “halogenated” should be understood to refer to fluorine (F), chlorine (Cl), bromine (Br) or iodine (I) atoms, preferably fluorine, chlorine or bromine atoms.

[0472] The term "halogenated alkyl" refers to an alkyl group substituted with one or more halogens, wherein the alkyl group is as defined above. Non-limiting examples include: fluoromethyl, chloromethyl, bromomethyl, iodomethyl, difluoromethyl, chlorofluoromethyl, dichloromethyl, bromofluoromethyl, trifluoromethyl, chlorodifluoromethyl, dichlorofluoromethyl, trichloromethyl, bromodifluoromethyl, bromochlorofluoromethyl, dibromofluoromethyl, 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 2,2-difluoroethyl, 2-chloro-2-fluoroethyl, 2,2-dichloroethyl, 2-bromo-2-fluoroethyl, 2,2,2-trifluoroethyl, 2-chloro-2,2-difluoroethyl, 2,2-dichloro-2-fluoroethyl, 2,2-dichloro-2-fluoroethyl, 2, 2,2-Trichloroethyl, 2-bromo-2,2-difluoroethyl, 2-bromo-2-chloro-2-fluoroethyl, 2-bromo-2,2-dichloroethyl, 1,1,2,2-tetrafluoroethyl, pentafluoroethyl, 1-chloro-1,2,2,2-tetrafluoroethyl, 2-chloro-1,1,2,2-tetrafluoroethyl, 1,2-dichloro-1,2,2-trifluoroethyl, 2-bromo-1,1,2,2-tetrafluoroethyl, etc., preferably fluoromethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 2,2-difluoroethyl. The alkyl halogroup may be optionally substituted or unsubstituted. When substituted, the substituent may be substituted at any usable linking point. The substituent is preferably one or more of the following groups, independently selected from deuterium, halogen, hydroxyl, mercapto, cyano, amino, nitro, oxo, C 1-6 Alkyl, C 2-6 alkenyl, ynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl compounds.

[0473] The term "haloalkoxy" refers to an alkoxy group substituted with one or more halogens, wherein the alkoxy group is as defined above. Non-limiting examples include: fluoromethoxy, chloromethoxy, bromomethoxy, iodomethoxy, difluoromethoxy, chlorofluoromethoxy, dichloromethoxy, bromofluoromethoxy, trifluoromethoxy, chlorodifluoromethoxy, dichlorofluoromethoxy, trichloromethoxy, bromodifluoromethoxy, bromochlorofluoromethoxy, dibromofluoromethoxy, etc.; preferably fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2-fluoroethoxy, 2-chloroethoxy, 2-bromoethoxy, 2,2-difluoroethoxy, 2-chloro-2-fluoroethoxy, 2,2-dichloroethoxy, 2-bromo-2-fluoroethoxy, 2,2,2-trifluoroethoxy, 2-chloro-2,2-difluoroethoxy, 2 2-Dichloro-2-fluoroethoxy, 2,2,2-trichloroethoxy, 2-bromo-2,2-difluoroethoxy, 2-bromo-2-chloro-2-fluoroethoxy, 2-bromo-2,2-dichloroethoxy, 1,1,2,2-tetrafluoroethoxy, pentafluoroethoxy, 1-chloro-1,2,2,2-tetrafluoroethoxy, 2-chloro-1,1,2,2-tetrafluoroethoxy, 1,2-dichloro-1,2,2-trifluoroethoxy, 2-bromo-1,1,2,2-tetrafluoroethoxy, preferably fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2-fluoroethoxy, 2-chloroethoxy, 2-bromoethoxy, 2,2-difluoroethoxy. The haloalkoxy group may be optionally substituted or unsubstituted. When substituted, the substituent may be substituted at any usable linker. The substituent is preferably one or more of the following groups, independently selected from deuterium, halogen, hydroxyl, mercapto, cyano, amino, nitro, oxo, C... 1-6 Alkyl, C 2-6 alkenyl, ynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl compounds.

[0474] The term "thiol" refers to -SH.

[0475] The term "hydroxyl group" refers to -OH.

[0476] The term "nitro" refers to -NO2.

[0477] The term "amino" refers to -NH2.

[0478] The term "cyano" refers to -CN.

[0479] The term "carboxyl group" refers to -C(O)OH.

[0480] The term "oxo" or "oxo group" refers to =O.

[0481] The term "carbonyl" refers to C=O.

[0482] The term "aminoacyl" refers to -C(O)NH2.

[0483] The term “deuterated alkyl” refers to an alkyl group that is substituted with one or more deuterium atoms, wherein the alkyl group is as defined above.

[0484] The term "hydroxyalkyl" refers to an alkyl group that is substituted with one or more hydroxyl groups, wherein the alkyl group is as defined above.

[0485] The terms “comprising,” “including,” “having,” “containing,” or “involving,” and their other variations herein, are inclusive or open-ended and do not exclude other elements or method steps not listed. Those skilled in the art will understand that the foregoing term “comprising” encompasses the meaning of “consisting of.”

[0486] The term "one or more species" or similar expression "at least one species" can mean, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more species.

[0487] When the lower and upper limits of a numerical range are disclosed, any numerical value falling within that range and any included range are specifically disclosed. In particular, each range of values ​​disclosed herein should be understood as representing each numerical value and range encompassed within a wider range.

[0488] In this article, "Z" and "-Z-" both refer to the same specific group and can be used interchangeably.

[0489] The expression mn used in this article refers to the range from m to n, as well as the subranges consisting of the individual point values ​​and the individual point values ​​themselves. For example, the expression "C2-C8" or "C2-8" covers the range of 2 to 8 carbon atoms, and should be understood to also cover any subranges within it and each point value, such as C2-C5, C3-C4, C2-C6, C3-C6, C4-C6, C4-C7, C4-C8, etc., and C2, C3, C4, C5, C6, C7, C8, etc. For example, the expression "C3-C10" or "C3-10" should be understood in a similar way, encompassing any subrange and point value included within it, such as C3-C9, C6-C9, C6-C8, C6-C7, C7-C10, C7-C9, C7-C8, C8-C9, etc., as well as C3, C4, C5, C6, C7, C8, C9, C10, etc. Similarly, the expression "C1-C6" or "C1-6" covers a range of 1-6 carbon atoms and should be understood to also encompass any subrange and each point value within it, such as C2-C5, C3-C4, C1-C2, C1-C3, C1-C4, C1-C5, C1-C6, etc., as well as C1, C2, C3, C4, C5, C6, etc. For example, the expression "three to ten yuan" should be understood as encompassing any subrange and each point value within it, such as three to five yuan, three to six yuan, three to seven yuan, three to eight yuan, four to five yuan, four to six yuan, four to seven yuan, four to eight yuan, five to seven yuan, five to eight yuan, six to seven yuan, six to eight yuan, nine to ten yuan, etc., as well as three, four, five, six, seven, eight, nine, ten yuan, etc. Other similar expressions in this article should also be understood in a similar manner.

[0490] The different expressions used in this article, such as "X is selected from A, B or C", "X is selected from A, B and C", "X is A, B or C", and "X is A, B and C", all express the same meaning, that is, X can be any one or more of A, B, and C.

[0491] The terms “optional” or “optionally” mean that an event or condition described below may or may not occur, including both the occurrence and non-occurrence of the event or condition. For example, “optionally (al) alkyl-substituted cycloalkyl” means that an alkyl group may but is not required to be present, and this description includes cases where the cycloalkyl group is substituted with an alkyl group and cases where the cycloalkyl group is not substituted with an alkyl group.

[0492] The terms "substitution" and "substituted" refer to the selective replacement of one or more (e.g., one, two, three, or four) hydrogen atoms on a specified atom by a chosen substituent from the indicated group, provided that the substitution does not exceed the normal valence of the specified atom in the present case and that the substitution forms a stable compound. Combinations of substituents and / or variables are permitted only if such combinations form a stable compound. When describing the absence of a substituent, it should be understood that the substituent can be one or more hydrogen atoms, provided that the structure allows the compound to reach a stable state. When describing the optional substitution of each carbon atom in a group with a heteroatom, the condition is that the substitution does not exceed the normal valence of all atoms in the group in the present case and that a stable compound is formed.

[0493] If a substituent is described as "optionally...substituted," the substituent may be unsubstituted or substituted. If an atom or group is described as being optionally substituted by one or more of the substituents in the list, one or more hydrogen atoms on that atom or group may be replaced by independently selected, optional substituents. When the substituent is oxo (i.e., =O), it means that two hydrogen atoms are substituted. When the substituent is hydrogen, this may also indicate that the corresponding group is "unsubstituted" or "unsubstituted." Unless otherwise specified, as used herein, the connection point of a substituent may be derived from any suitable position of the substituent.

[0494] When the bond of a substituent is such that it passes through the ring and connects two atoms, then such a substituent can be bonded to any cyclic atom in the substituted ring.

[0495] When any variable (e.g., R), and labeled variables (e.g., R1, R2, R3, R4, R5, R6, R7, etc.) appear more than once in the composition or structure of a compound, their definition is independent for each occurrence in each case. For example, if a group is substituted by 0, 1, 2, 3, or 4 R substituents, the group may optionally be substituted by up to four R substituents, and the options for each R substituent in each case are independent of each other.

[0496] The term "isomer" includes "stereoisomer" and "tautomer." A stereoisomer is a molecule whose atoms or groups of atoms have the same order of connection but different spatial arrangements. Stereoisomers include cis-trans isomers and optical isomers. A tautomer is a molecule that can interconvert through a reversible chemical reaction called tautomerization, typically caused by the migration of hydrogen atoms and π bonds (double or triple bonds), resulting in a transformation from one functional group to another. Examples include the following paired compounds: aldehyde / ketone – enol, imine – enamine.

[0497] The compounds of this invention can exist in specific geometric or stereoisomeric forms. All such compounds of this invention, including cis and trans isomers, (-)- and (+)- enantiomers, (R)- and (S)- enantiomers, diastereomers, (D)- isomers, (L)- isomers, and racemic mixtures thereof, as well as other mixtures, such as mixtures enriched with enantiomers or diastereomers, are within the scope of this invention. Additional asymmetric carbon atoms may be present in the substituents of the compounds of this invention. All such isomers and mixtures thereof are included within the scope of this invention. In some embodiments, the preferred compounds are those isomers exhibiting superior biological activity. Purified or partially purified isomers and stereoisomers of the compounds of this invention, or racemic mixtures or diastereomer mixtures, are also included within the scope of this invention. Purification and separation of such substances can be achieved using standard techniques known in the art.

[0498] All hydrogen atoms described in this invention can be replaced by their isotope deuterium, and any hydrogen atom in the compounds of the embodiments of this invention can also be replaced by a deuterium atom.

[0499] The compounds of the present invention include all suitable isotopic derivatives thereof. The term "isotopic derivative" refers to a compound in which at least one atom is replaced by an atom having the same atomic number but a different atomic mass. Examples of isotopes that may be introduced into the compounds of this disclosure include stable and radioactive isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, chlorine, bromine, and iodine, such as 2H (deuterium, D), 3H (tritium, T), 11C, 13C, 14C, 15N, 17O, 18O, 32P, 33P, 33S, 34S, 35S, 36S, 18F, 36Cl, 82Br, 123I, 124I, 125I, 129I, and 131I, preferably deuterium.

[0500] Compared to undeuterated drugs, deuterated drugs offer advantages such as reduced toxicity, increased drug stability, enhanced efficacy, and prolonged biological half-life. All isotopic variations of the compounds disclosed herein, regardless of radioactivity, are included within the scope of this disclosure. Each available hydrogen atom bonded to a carbon atom can be independently replaced by a deuterium atom, wherein the deuterium substitution can be partial or complete; partial deuterium substitution refers to the replacement of at least one hydrogen atom with at least one deuterium atom.

[0501] In the compounds of this invention, when a position is specifically designated as deuterium D, that position should be understood as having a deuterium abundance at least 1000 times greater than the native abundance (which is 0.015%) (i.e., at least 15% deuterium doping). In some embodiments, the deuterium abundance per designated deuterium atom is at least 1000 times greater than the native abundance of deuterium (i.e., at least 15% deuterium doping). In some embodiments, the deuterium abundance per designated deuterium atom is at least 2000 times greater than the native abundance of deuterium (i.e., at least 30% deuterium doping). In some embodiments, the deuterium abundance per designated deuterium atom is at least 3000 times greater than the native abundance of deuterium (i.e., at least 45% deuterium doping). In some embodiments, the deuterium abundance of each designated deuterium atom is at least 3340 times greater than the natural deuterium abundance (i.e., at least 50.1% deuterium doping). In some embodiments, the deuterium abundance of each designated deuterium atom is at least 3500 times greater than the natural deuterium abundance (i.e., at least 52.5% deuterium doping). In some embodiments, the deuterium abundance of each designated deuterium atom is at least 4000 times greater than the natural deuterium abundance (i.e., at least 60% deuterium doping). In some embodiments, the deuterium abundance of each designated deuterium atom is at least 4500 times greater than the natural deuterium abundance (i.e., at least 67.5% deuterium doping). In some embodiments, the deuterium abundance of each designated deuterium atom is at least 5000 times greater than the natural deuterium abundance (i.e., at least 75% deuterium doping). In some embodiments, the deuterium abundance of each designated deuterium atom is at least 5500 times greater than the natural deuterium abundance (i.e., at least 82.5% deuterium doping). In some embodiments, the deuterium abundance of each designated deuterium atom is at least 6000 times greater than the natural deuterium abundance (i.e., at least 90% deuterium doping). In some embodiments, the deuterium abundance of each designated deuterium atom is at least 6333.3 times greater than the natural deuterium abundance (i.e., at least 95% deuterium doping). In some embodiments, the deuterium abundance of each designated deuterium atom is at least 6466.7 times greater than the natural deuterium abundance (i.e., at least 97% deuterium doping). In some embodiments, the deuterium abundance of each designated deuterium atom is at least 6600 times greater than the natural deuterium abundance (i.e., at least 99% deuterium doping). In some implementations, the abundance of deuterium in each designated deuterium atom is at least 6633.3 times greater than the natural abundance of deuterium (i.e., at least 99.5% deuterium doping).

[0502] The term "pharmaceutically acceptable" refers to a substance that, within the bounds of normal medical judgment, is suitable for contact with a patient's tissues without causing undue toxicity, irritation, allergic reactions, etc., has a reasonable benefit-risk ratio, and is effective for its intended use.

[0503] The term "pharmaceutically acceptable salt" refers to a salt of the compounds of the present invention that is safe and effective when used in mammals and has the intended biological activity.

[0504] The term "pharmaceutical composition" refers to a composition containing one or more compounds described in this invention, or their physiologically / pharmaceutically acceptable salts or prodrugs, as well as other components such as physiologically / pharmaceutically acceptable carriers or excipients. The purpose of a pharmaceutical composition is to facilitate administration to a living organism, thereby promoting the absorption of the active ingredient and enabling it to exert its biological activity.

[0505] The term "pharmaceutically acceptable carrier" refers to substances that do not cause significant irritation to the organism and do not impair the biological activity and properties of the active compound. "Pharmaceutically acceptable carriers" include, but are not limited to, glidants, sweeteners, diluents, preservatives, dyes / colorants, flavoring agents, surfactants, wetting agents, dispersants, disintegrants, stabilizers, solvents, or emulsifiers.

[0506] The terms "administration" or "giving" refer to methods that enable the delivery of a compound or composition to a desired biological site of action. These methods include, but are not limited to, oral or parenteral administration (including intraventricular, intravenous, subcutaneous, intraperitoneal, intramuscular, and intravascular injection or infusion), local administration, and rectal administration. In particular, injection or oral administration.

[0507] As used herein, the term "treatment" includes relieving, reducing, or improving a disease or symptom; preventing other symptoms; improving or preventing underlying metabolic factors of symptoms; inhibiting a disease or symptom, for example, preventing the development of a disease or symptom; reducing a disease or symptom; promoting the remission of a disease or symptom; or causing the symptom of a disease or symptom to cease; and extends to include prevention. "Treatment" also includes achieving therapeutic and / or preventive benefits. A therapeutic benefit refers to the eradication or improvement of the condition being treated. Furthermore, a therapeutic benefit is achieved by eradicating or improving one or more physical symptoms associated with an underlying disease, and an improvement in the patient's condition can be observed even though the patient may still have the underlying disease. A preventive benefit refers to the use of a composition by a patient to prevent the risk of a certain disease, or the use by a patient when experiencing one or more physical symptoms of a disease, even though the disease has not yet been diagnosed.

[0508] The terms "active ingredient," "therapeutic agent," "active substance," or "active agent" refer to a chemical entity that can effectively treat or prevent a target disorder, disease, or symptom. The term "neuropsychiatric disorders" is a collective term for neurological and psychiatric disorders, encompassing both neurological and / or psychiatric conditions.

[0509] For the purposes of pharmaceuticals, pharmaceutical units, or active ingredients, the terms "effective amount," "therapeutic effective amount," or "preventive effective amount" refer to a sufficient quantity of a drug or agent that provides acceptable side effects while achieving the desired therapeutic effect. The determination of the effective amount varies from person to person, depending on the individual's age and general condition, as well as the specific active substance. The appropriate effective amount in a given case can be determined by a person skilled in the art based on routine testing.

[0510] As used herein, “individual” includes both human and non-human animals. Exemplary human individuals include human individuals suffering from a disease (such as the disease described herein) (referred to as patients) or normal individuals. In this invention, “non-human animals” includes all vertebrates, such as non-mammals (e.g., birds, amphibians, reptiles) and mammals, such as non-human primates, livestock, and / or domesticated animals (e.g., sheep, dogs, cats, cows, pigs, etc.).

[0511] The term "room temperature" refers to a temperature ranging from 10°C to 40°C. In some embodiments, "room temperature" refers to a temperature ranging from 15°C to 30°C; in other embodiments, "room temperature" refers to a temperature ranging from 18°C ​​to 25°C.

[0512] "Equivalent" or its abbreviation "eq" is the equivalent amount of other raw materials required based on the equivalence relationship of a chemical reaction, using the basic raw materials used in each step as a reference (1 equivalent).

[0513] In the context of this invention, when the terms "about" or "approximately" are used, whether or not they are used, it means within 10% of a given value or range, appropriately within 5%, and particularly within 1%. Alternatively, for those skilled in the art, the terms "about" or "approximately" mean within an acceptable standard error of the average. Whenever a number with a value of N is disclosed, any number having a value within N+ / -1%, N+ / -2%, N+ / -3%, N+ / -5%, N+ / -7%, N+ / -8%, or N+ / -10% is explicitly disclosed, where "+ / -" means addition or subtraction.

[0514] The following detailed description of the invention is intended to illustrate non-limiting embodiments, enabling other skilled in the art to more fully understand the technical solutions, principles, and practical applications of the invention, so that other skilled in the art can modify and implement the invention in many forms to best suit the requirements of a particular application. Beneficial effects

[0515] The compounds shown in this study have inhibitory effects on IL-17A receptors and / or good in vivo efficacy, namely, therapeutic or preventive effects on psoriasis, rheumatoid arthritis, and multiple sclerosis. Detailed Implementation

[0516] The present invention will be further illustrated below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Furthermore, it should be understood that after reading the teachings of this invention, those skilled in the art can make various alterations or modifications to the invention, and these equivalent forms also fall within the scope defined by the appended claims.

[0517] Example

[0518] The embodiments of the present invention will be described in detail below with reference to examples. However, those skilled in the art will understand that the following examples are for illustrative purposes only and should not be considered as limiting the scope of the invention. Unless otherwise specified, specific conditions in the examples are performed under conventional conditions or conditions recommended by the manufacturer. Reagents or instruments used, unless otherwise specified, are all commercially available conventional products. Unless otherwise specified, all proportions or percentages used herein are by weight.

[0519] The structure of the compounds was determined by nuclear magnetic resonance (NMR) and / or mass spectrometry (MS). NMR shifts (δ) are given in units of 10⁻⁶ (ppm). NMR measurements were performed using Bruker Avance III 400 and Bruker Avance 300 NMR spectrometers in the following solvents: deuterated dimethyl sulfoxide (DMSO-d₆), deuterated chloroform (CDCl₃), and deuterated methanol (CD₃OD). Tetramethylsilane (TMS) was used as the internal standard.

[0520] MS determination was performed using (Agilent 6120B (ESI) and Agilent 6120B (APCI));

[0521] HPLC determinations were performed using an Agilent 1260DAD high-performance liquid chromatograph (Zorbax SB-C18 100×4.6mm, 3.5μM).

[0522] Thin-layer chromatography silica gel plates are Yantai Huanghai HSGF254 or Qingdao GF254. The silica gel plates used in thin-layer chromatography (TLC) are 0.15mm-0.20mm in diameter, and the silica gel plates used for thin-layer chromatography separation and purification are 0.4mm-0.5mm in diameter.

[0523] Column chromatography typically uses Yantai Huanghai silica gel with a mesh size of 200-300 as the carrier.

[0524] Example 1

[0525] Step 1: Compound 1A (1 g, 6.02 mmol) was dissolved in DMF (15 mL), and compound 1B (0.94 g, 7.22 mmol) and DIPEA (1.55 g, 12.04 mmol) were added. Carter's condensing agent was then added, and the mixture was reacted at room temperature for 2 h. After the reaction was complete, water (30 mL) was added, followed by extraction with EA (20 mL x 3). The organic phase was washed with saturated brine, dried, and concentrated. The crude product was subjected to column chromatography (EA / PE = 0-50%) to obtain compound 1C (1.3 g, 78%). LC-MS (ESI): m / z = 279.2 [M+H] + .

[0526] Step 2: Compound 1C (0.5 g, 1.80 mmol) was dissolved in ethanol (16 mL) and water (8 mL), and ammonium chloride (481 mg, 9 mmol) and zinc powder (588 mg, 9 mmol) were added. The mixture was reacted at 50 °C for 1 hour. After cooling to room temperature, the reaction solution was filtered through diatomaceous earth, washed with EA, and the filtrate was extracted with saturated sodium bicarbonate solution and EA. The organic phase was concentrated and evaporated to dryness to obtain compound 1D (0.4 g, 90%), which did not require further purification. LC-MS (ESI): m / z = 249.1 [M+H] + .

[0527] Step 3: Dissolve (S)-2-((benzyloxy)carbonyl)amino)-2-(4,4-difluorocyclohexyl)acetic acid (0.6 g, 1.83 mmol) in DMF (10 mL), add DIPEA (395 mg, 3.06 mmol) and HATU (695 mg, 1.83 mmol), stir at room temperature for 20 minutes, then add compound 1D (380 mg, 1.52 mmol), and stir the reaction system at room temperature for 1 hour. After the reaction is complete, add water (30 mL), then extract with EA (20 mL x 3). Wash the organic phase with saturated brine, dry and concentrate the organic phase, and the crude product is subjected to column chromatography (EA / PE = 0-60%) to give compound 1E (0.8 g, 94%). LC-MS (ESI): m / z = 558.3 ​​[M+H] + .

[0528] Step 4: Dissolve compound 1E (0.2 g, 0.36 mmol) in methanol (8 mL), add 200 mg of 10% palladium hydroxide on carbon, then add 1N hydrochloric acid (0.36 mL), purging the mixture under a hydrogen atmosphere, and react overnight at room temperature. After the reaction is complete, add diatomaceous earth, stir, filter, wash the filter cake with methanol, concentrate the filtrate, and evaporate to dryness to obtain compound 1F (100 mg, 66%), which does not require further purification. LC-MS (ESI): m / z = 424.5 [M+H] + .

[0529] Step 5: Compound 1F (100 mg, 0.24 mmol) was dissolved in DMF (6 mL), compound 1G (40 mg, 0.29 mmol), triethylamine (49 mg, 0.48 mmol), and HATU (110 mg, 0.29 mmol) were added. The mixture was stirred at room temperature for 2 hours. After the reaction was complete, water (15 mL) was added, followed by extraction with EA (10 mL x 3). The organic phase was washed with saturated brine, dried, and concentrated. The crude product was subjected to column chromatography (MeOH / DCM = 0-25%) to give compound 1 (35 mg, 27%). LC-MS (ESI): m / z = 546.8 [M+H] + .

[0530] 1 H NMR(400MHz,DMSO-d6)δ10.19(s,1H),8.58(d,1H),8.12(d,1H),7.54(d,2H),7.4 8(d,1H),7.22(d,2H),7.01(d,1H),4.88–4.80(m,1H),4.52–4.38(m,3H),3.89–3. 71(m,2H),3.27(s,2H),2.44–2.31(m,1H),2.12-1.96(m,3H),1.95–1.85(m,1H),1 .83–1.64(m,3H),1.61-1.52(m,4H),1.51–1.34(m,2H),1.31(d,3H),1.27(t,3H).

[0531] Example 2

[0532] Step 1: Dissolve 2A (12.0 g, 49.7 mmol) in tetrahydrofuran (200.0 mL), then add lithium aluminum hydride (3.0 g, 74.0 mmol) under ice bath conditions. After slowly raising the temperature to room temperature for 2 hours, add water (3.0 mL), 15% sodium hydroxide solution (3.0 mL), and water (9.0 mL) sequentially. Stir for 20 minutes, then add anhydrous sodium sulfate to dry the mixture. Stir for 10 minutes, filter, and concentrate to obtain 2B (9.5 g, 89%), which is used directly in the next step. LCMS m / z = 214.1 [M+1] + .

[0533] Step 2: Dissolve 2B (8.0 g, 37.4 mmol) in dichloromethane (100.0 mL), then add triethylamine (7.6 g, 75.0 mmol), and finally add p-toluenesulfonyl chloride (8.6 g, 45.0 mmol). After reacting at room temperature for 2 h, concentrate to obtain compound 2C, which can be used directly in the next step.

[0534] Step 3: The crude product 2C was dissolved in acetone (100.0 mL), and then lithium bromide (4.6 g, 42.0 mmol) was added. The mixture was reacted at room temperature for 4 h, concentrated, and subjected to column chromatography (petroleum ether / ethyl acetate = 10 / 1 (v / v)) to give compound 2D (5.4 g, 74%). LCMS m / z = 276.0 [M+1] + .

[0535] Step 4: Diphenylmethylene glycine methyl ester (3.7 g, 14.6 mmol) was dissolved in DMF (50.0 mL). Potassium tert-butoxide (2.2 g, 19.5 mmol) was added under ice bath conditions. Stirring continued for 30 min, followed by the addition of 2D (2.7 g, 9.8 mmol). The reaction was slowly brought to room temperature and allowed to proceed for 4 h. The reaction was then quenched with saturated ammonium chloride solution, extracted with ethyl acetate, dried, concentrated, and subjected to column chromatography (petroleum ether / ethyl acetate = 10 / 1 (v / v)) to give compound 2E (3.6 g, 82%). LCMS m / z = 449.2 [M+1] + .

[0536] Step 5: Compound 2E (2.8 g, 6.2 mmol) was dissolved in methanol (50.0 mL), and palladium on carbon (0.3 g) was added. The mixture was purged with hydrogen three times and reacted overnight at room temperature. The solution was filtered and concentrated to give compound 2F (1.2 g, 67%). This compound was used directly in the next step. LCMS m / z = 285.2 [M+1] + .

[0537] Step 6: Dissolve 2F (1.2 g, 4.2 mmol) in dichloromethane (20.0 mL), then add triethylamine (1.3 g, 12.6 mmol), and finally add propionic anhydride (0.6 g, 4.6 mmol). After reacting at room temperature for 2 h, add saturated ammonium chloride solution, extract with dichloromethane, dry, filter, concentrate, and perform column chromatography (dichloromethane / methanol = 10 / 1 (v / v)) to give compound 2G (1.5 g, 100%). LCMS m / z = 285.2 [M-55] + .

[0538] Step 7: Dissolve 2g (1.5g, 4.2mmol) in 1,4-dioxane (10.0mL), then add hydrogen chloride (4M in 1,4-dioxane, 21.0mmol). React at room temperature for 2 hours, then concentrate to obtain compound 2H (1.5g, 100%), which can be used directly in the next step. LCMS m / z = 241.1 [M+1] + .

[0539] Step 8: Dissolve (S)-2-((benzyloxy)carbonyl)amino)-2-(4,4-difluorocyclohexyl)acetic acid (2.3 g, 6.8 mmol) in DMF (50.0 mL), then add HATU (3.6 g, 9.3 mmol) and DIPEA (2.4 g, 18.7 mmol). After stirring for 10 min, add compound 2H (1.5 g, 6.2 mmol). React at room temperature for 2 h, then add water, extract with ethyl acetate, dry, filter, concentrate, and perform column chromatography (petroleum ether / ethyl acetate = 2 / 1 (v / v)) to give compound 2I (1.8 g, 52%). LCMS m / z = 550.3 [M+1] + .

[0540] Step 9: Compound 2I (1.0 g, 1.8 mmol) was dissolved in ethanol (15.0 mL) and tetrahydrofuran (15.0 mL), followed by the addition of 1 M hydrochloric acid (1.8 mL, 1.8 mmol) and palladium hydroxide (0.2 g). The mixture was purged with hydrogen three times and reacted overnight at room temperature. The solution was concentrated and subjected to column chromatography (petroleum ether / ethyl acetate = 2 / 1 (v / v)) to give compound 2J (1.1 g, 100%), which was used directly in the next step. LCMS m / z = 416.2 [M+1] + .

[0541] Step 10: Compound 2J (1.1 g, 2.65 mmol) was dissolved in DMF (30.0 mL), followed by the addition of NMI (0.9 g, 10.6 mmol) and 1-ethyl-1H-pyrazole-5-carboxylic acid (0.45 g, 3.2 mmol). After stirring for 10 min, TCFH (0.9 g, 3.2 mmol) was added. The mixture was reacted at room temperature for 2 h, concentrated, and subjected to column chromatography (petroleum ether / ethyl acetate = 1 / 2 (v / v)) to give compound 2K (0.9 g, 63%). LCMS m / z = 538.3 [M+1] + .

[0542] Step 11: Dissolve compound 2K (0.2 g, 0.37 mmol) in tetrahydrofuran (10.0 mL) and methanol (5.0 mL), then add an aqueous solution of lithium hydroxide (35.0 mg, 1.5 mmol). After reacting at room temperature for 4 h, concentrate the solution, add 1 M hydrochloric acid to adjust the acidity, and a white solid precipitates. Filter the solution and dry it under vacuum to obtain compound 2L (0.19 g, 98%), which can be used directly in the next step.

[0543] Step 12: Compound 2L (0.19 g, 0.36 mmol) was dissolved in DMF (10.0 mL), followed by the addition of NMI (0.12 g, 1.44 mmol) and N-methylpiperidine (36.0 mg, 0.36 mmol). After stirring for 10 min, TCFH (0.12 g, 0.43 mmol) was added. The mixture was reacted at room temperature for 2 h, concentrated, and subjected to column chromatography (petroleum ether / ethyl acetate = 1 / 2 (v / v)) to give compound 2 (0.1 g, 45%). LCMS m / z = 606.3 [M+1] + .

[0544] 1 H NMR(400MHz,DMSO-d6)δ8.57(s,1H),8.32(d,1H),8.04(d,1H),7.46(d,1H),6.98(d,1H),4.69–4.64(m,1H),4.48–4.43(q,2H ),4.31–4.16(m,1H),3.50(s,2H),2.37–2.15(m,7H),2.11–1.96(m,4H),1.91–1.58(m,15H),1.38–1.18(m,5H),0.97(t,3H).

[0545] 19 F NMR(377MHz,DMSO-d6)δ-88.23(d).

[0546] Example 3

[0547] Step 1: methyl 6-nitroindole-3-carboxylic acid (1.5 g, 6.81 mmol) and tetrahydrofuran (30 mL) were added to a flask. Sodium hydride (0.82 g, 20.43 mmol) was then added in portions under ice bath conditions, and the reaction continued for half an hour. Di-tert-butyl dicarbonate (2.97 g, 13.62 mmol) was then added, and the reaction was carried out at room temperature for 1 hour. The mixture was extracted with water and ethyl acetate, washed, dried, concentrated, and purified by column chromatography (PE:EA = 1:5 (v / v)) to give the target compound 3B (1.5 g, yield: 68.7%). LC-MS (ESI): m / z = 321.1 [M+H] + .

[0548] Step 2: 3B (1.5 g, 6.81 mmol), methanol (20 ml), dichloromethane (10 ml), and palladium hydroxide (300 mg) were added to an autoclave, followed by the introduction of hydrogen gas (3 MPa). The reaction was carried out at 50°C for 16 hours. After cooling, the mixture was filtered and concentrated to obtain the target compound 3C (0.86 g, yield: 62.8%). LC-MS (ESI): m / z = 293.2 [M+H]+ .

[0549] Step 3: Add 3C (100 mg, 0.34 mmol) and N,N-dimethylformamide (10 mL) to a flask, followed by (S)-2-(((benzyloxy)carbonyl)amino)-2-(4,4-difluorocyclohexyl)acetic acid (167 mg, 0.51 mmol), HATU (194 mg, 0.51 mmol), and triethylamine (103 mg, 1.02 mmol). React at room temperature for 16 hours. Extract with water and ethyl acetate, wash, dry, concentrate, and purify by column chromatography (PE:EA = 1:3 (v / v)) to obtain the target compound 3D (201 mg, yield: 98.2%). LC-MS (ESI): m / z = 624.2 [M + Na] + .

[0550] Step 4: Add 3D (201 mg, 0.33 mmol), methanol (10 mL), and palladium on carbon (30 mg) to a flask, and then react at room temperature under hydrogen atmosphere for 16 hours. Filter and concentrate to obtain the target compound 3E (120 mg, 77.7%). LC-MS (ESI): m / z = 468.2 [M+H] + .

[0551] Step 5: Add 3E (120 mg, 0.26 mmol) and N,N-dimethylformamide (10 mL) to a flask, followed by 1-ethyl-1H-pyrazole-5-carboxylic acid (55 mg, 0.39 mmol), HATU (148 mg, 0.39 mmol), and triethylamine (79 mg, 0.78 mmol). React at room temperature for 2 hours. Extract with water and ethyl acetate, wash, dry, and concentrate to obtain crude target compound 3F (160 mg). LC-MS (ESI): m / z = 588.2 [MH] + .

[0552] Step 6: Add 3F (160 mg, 0.27 mmol), methanol (3 ml), tetrahydrofuran (3 ml), and water (3 ml) to a flask, followed by lithium hydroxide (32 mg, 1.35 mmol). React at room temperature for 2 hours. Add water to adjust the pH to approximately 5, extract with dichloromethane, wash, dry, and concentrate to obtain the crude target compound 3G (140 mg). LC-MS (ESI): m / z = 576.2 [M+H] + .

[0553] Step 7: Add 3G (140 mg, 0.24 mmol) and N,N-dimethylformamide (10 mL) to a flask, followed by 2,2,2-trifluoroethylamine (35 mg, 0.36 mmol), HATU (137 mg, 0.36 mmol), and triethylamine (73 mg, 0.72 mmol). React at room temperature for 2 hours. Extract with water and ethyl acetate, wash, dry, and concentrate to obtain the crude target compound 3H (185 mg). LC-MS (ESI): m / z = 655.5 [MH] + .

[0554] Step 8: Add crude 3H (185 mg, 0.31 mmol), dichloromethane (10 ml), and hydrochloric acid / dioxane (4 ml, 4 M) to a flask, and then react at room temperature for 2 hours. Concentrate under reduced pressure to obtain the crude target compound, which is then subjected to preparative HPLC to obtain compound 3 (24 mg, yield: 13.3%). Preparation method: Instrument: Waters 2767 preparative liquid chromatograph; Column: SunFire@Prep C18 (19mm × 250mm); Sample was dissolved in DMF and filtered through a 0.45μm filter to prepare the sample solution; Preparative chromatographic conditions: a. Composition of mobile phases A and B: Mobile phase A: acetonitrile, mobile phase B: water (containing 1 / 1000 trifluoroacetic acid); b. Gradient elution, mobile phase A content from 40% to 80%; c. Flow rate 15mL / min; d. Elution time 20min; Retention time: 7.24min. LC-MS (ESI): m / z = 557.2 [M+H] + .

[0555] 1 H NMR(400MHz,DMSO-d6)δ10.00(s,1H),8.80(t,1H),8.55(d,1H),7.47(d,1H),7.05-6.94(m,3H),6.78(q,1H),4.48-4.43(m,3H), 4.03(t,2H),3.70(t,1H),3.58(t,1H),3.42-3.69(m,1H),3.34-3.26(m,1H),2.05-1.63(m,7H),1.44-1.33(m,1H),1.27(t,3H).

[0556] Examples 4 and 5

[0557] Step 1: Dissolve cycloisopropyl malonate (4.4 g, 30.53 mmol) in ethyl acetate (120 mL), then add 4A (5.47 g, 32.36 mmol) and diphenylmethylene glycine ethyl ester (10.61 g, 39.69 mmol). React at room temperature for 24 hours. After the reaction is complete, extract the reaction solution three times with saturated sodium bicarbonate solution and ethyl acetate. Adjust the pH of the aqueous phase to 1-2 with hydrochloric acid (1 M), then extract with ethyl acetate. Concentrate the organic phase to obtain product 4B (crude product), which can be directly used in the next step. LCMS m / z = 341.1 [M+H] + .

[0558] Step 2: Dissolve 4B (crude product) in toluene (50 mL) and react at 110°C for 6 hours. After the reaction, cool the reaction solution, concentrate the residue, and purify by column chromatography (dichloromethane:methanol (v / v) = 10:1) to obtain the target compound 4C (6 g, 68%). LCMS m / z = 297.3 [M+H] + .

[0559] Step 3: Dissolve 4C (6 g, 20.25 mmol) in methanol (100 mL), then add zinc powder (13.25 g, 202.57 mmol) and ammonium chloride (6.5 g, 121.52 mmol) and react at room temperature for 1 hour. After the reaction is complete, filter and concentrate the reaction solution, then extract (with ethyl acetate), wash and concentrate again to obtain the target compound 4D (4.9 g, 90%). LCMS m / z = 267.1 [M+H] + .

[0560] Step 4: 4D (1.5 g, 5.63 mmol), (S)-2-((tert-butoxycarbonyl)amino)-2-(4,4-difluorocyclohexyl)acetic acid (2.48 g, 8.45 mmol), 2-(7-azobenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate (3.21 g, 8.45 mmol), and N,N-diisopropylethylamine (1.46 g, 11.26 mmol) were dissolved in N,N-dimethylformamide (15 mL), and the reaction was carried out at room temperature for 1 hour. After the reaction, the reaction solution was extracted (with ethyl acetate), washed, and concentrated. The residue was purified by column chromatography (ethyl acetate:petroleum ether (v / v) = 2:1) to give the target compound 4E (2.2 g, 72%). LCMS m / z = 486.2 [M+H-56] + .

[0561] Step 5: Dissolve 4E (2.2 g, 4.06 mmol) in dichloromethane (18 mL), then add trifluoroacetic acid (6 mL) and react at room temperature for 0.5 hours. After the reaction is complete, evaporate the reaction solution to dryness to obtain product 4F (1.79 g, crude product), which can be directly used for the next step. LCMS m / z = 442.1 [M+H] + .

[0562] Step 6: 4F (1.79 g, crude), 1-ethyl-1H-pyrazole-5-carboxylic acid (0.85 g, 6.07 mmol), 2-(7-azobenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate (2.31 g, 6.07 mmol), and triethylamine (0.82 g, 8.1 mmol) were dissolved in N,N-dimethylformamide (20 mL) and reacted at room temperature for 1 hour. After the reaction, the reaction solution was extracted (with ethyl acetate), washed, and concentrated. The residue was purified by column chromatography (ethyl acetate:petroleum ether (v / v) = 2:1) to give the target compound 4G (1.5 g, 65%). LCMS m / z = 564.3 [M+H] + .

[0563] Step 7: Dissolve 4G (200 mg, 0.35 mmol) in tetrahydrofuran (3 mL) and water (1 mL), then add lithium hydroxide monohydrate (44 mg, 1.05 mmol), and react at room temperature for 1 hour. After the reaction, adjust the pH to 3-4, then extract (with ethyl acetate), wash, and concentrate to obtain the target compound 4G (0.15 g, 80%). LCMS m / z = 536.6 [M+H] + .

[0564] Step 8: Dissolve 4g (0.15g, 0.28mmol), N-methylpiperazine (42mg, 0.42mmol), 2-(7-azobenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate (0.16g, 0.42mmol), and N,N-diisopropylethylamine (72mg, 0.56mmol) in N,N-dimethylformamide (5mL) and react at room temperature for 1 hour. After the reaction, filter and concentrate the residue for purification by preparative HPLC. Method: 1. Instrument: Waters 2767 preparative HPLC; column: SunFire@PrepC18 (19mm x 250mm). 2. Filter the sample through a 0.45µm filter to prepare the sample solution. 3. Preparative chromatographic conditions: a. Composition of mobile phases A and B: Mobile phase A: acetonitrile; Mobile phase B: water (containing 0.05% ammonia); b. Gradient elution, with mobile phase A content ranging from 25% to 75%; c. Flow rate: 15 mL / min; d. Elution time: 20 min. Retention time: 6.12 min (set for compound 4), retention time: 6.22 min (set for compound 5).

[0565] Compound 4 (17.1 mg, 9%) was isolated and purified, LCMS m / z = 618.3 [M+H] + ,1H NMR(400MHz,DMSO-d6)δ10.00(s,1H),8.56(d,1H),7.82-7.78(m,1H),7.67(s,1H),7.47(d,1H), 7.12(d,1H),7.06(d,1H),6.99(d,1H),4.86(d,1H),4.68(t,1H),4.46(q,2H),3.87(q,1H),3.36( The chromatogram values ​​were as follows: m, 1H; 3.18–3.13 (m, 1H); 2.99–2.97 (m, 2H); 2.38 (t, 1H); 2.16–2.02 (m, 7H); 1.93 (s, 3H); 1.73–1.64 (m, 4H); 1.48 (d, 1H); 1.36 (d, 1H); 1.28 (t, 3H); 1.17 (m, 1H). Compound 5 (39.8 mg, 23%) was obtained after isolation and purification. LCMS m / z = 618.3 [M+H] + ,1H NMR(400MHz,DMSO-d6)δ9.99(s,1H),8.57(d,1H),7.95(s,1H),7.80-7.76(m,1H),7 .47(d,1H),7.23(d,1H),7.12-7.09(dd,1H),6.99(d,1H),4.86-4.64(m,1H),4.56( d,1H),4.49-4.44(q,2H),3.55-3.41(m,4H),2.64-2.57(dd,1H),2.21-2.15(m,4H) ,2.12(s,3H),2.02-2.00(m,4H),1.88-1.72(m,5H),1.49-1.35(m,2H),1.28(t,3H).

[0566] Example 6

[0567] Step 1: In a single-necked flask, compound 6A (2.0 g, 9.05 mmol), 1-BOC-3,6-dihydro-2H-pyridine-5-boronic acid pinacol ester (3.36 g, 10.87 mmol), Pd(dppf)Cl2 (0.74 g, 0.91 mmol), potassium carbonate (1.88 g, 13.54 mmol), dioxane (20 mL), and water (2 mL) were added sequentially. The mixture was purged with nitrogen three times, and then heated to 100 °C with stirring for 18 hours. After cooling to room temperature, the mixture was filtered through a diatomaceous earth filter. The filtrate was poured into water and extracted three times with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude product. The crude product was purified using a Biotage Isolera One column (20 g silica gel column, eluent: 0-50% EA / PE) to obtain compound 6B (2.2 g, yield 75.42%). LC-MS (ESI): m / z = 267.1 [M-55] + .

[0568] Step 2: In a single-necked flask, compound 6B (2.2 g, 6.83 mmol), dichloromethane (10 mL), and 4N dioxane hydrochloride (5 mL) were added sequentially. The mixture was stirred at room temperature for 18 hours. The reaction solution was directly concentrated under reduced pressure to obtain the hydrochloride salt of compound 6C (1.7 g, 100% yield), which could be used directly for the next reaction without further purification. LC-MS (ESI): m / z = 223.1 [M+H] + .

[0569] Step 3: In a single-necked flask, the hydrochloride salt of compound 6C (1.7 g, 6.83 mmol), N,N-dimethylglycine (0.91 g, 8.88 mmol), N-methylimidazole (1.12 g, 13.66 mmol), TEA (0.76 g, 7.5 mmol), and DMF (20 mL) were added sequentially. The mixture was stirred at room temperature for half an hour, then TCFH (2.48 g, 8.88 mmol) was added, and the reaction was continued at room temperature for 2 hours. The reaction solution was poured into water and extracted three times with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the crude product. The crude product was purified using a Biotage Isolera One (12 g silica gel column, eluent: 0-4% MeOH / DCM) to obtain the target compound 6D (1.6 g, yield 76.3%). LC-MS (ESI): m / z = 308.2 [M+H] + .

[0570] Step 4: In a single-necked flask, compound 6D (1.60 g, 5.21 mmol), palladium on carbon (0.5 g), and methanol (10 mL) were added sequentially. The mixture was purged with hydrogen three times, and the reaction was continued at room temperature with stirring for 18 hours. The mixture was filtered through a diatomaceous earth liner, the solid was washed with methanol, and the filtrate was concentrated under reduced pressure to obtain compound 6E (1.45 g, 99.63% yield). No further purification was required, and it could be used directly in the next reaction. LC-MS (ESI): m / z = 280.3 [M+H] + .

[0571] Step 5: In a single-necked flask, add (S)-2-((benzyloxy)carbonyl)amino)-2-(4,4-difluorocyclohexyl)acetic acid (0.33 g, 1.01 mmol), N,N-diisopropylethylamine (0.19 g, 1.45 mmol), 2-(7-azobenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate (0.46 g, 1.21 mmol), and DMF (10 mL). After stirring for 10 minutes, add compound 6E (0.34 g, 1.21 mmol) and continue stirring for 2 hours. The reaction solution was poured into water and extracted three times with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude product. The crude product was purified using Biotage Isolera One (12 g silica gel column, eluent: 0-4% MeOH / DCM) to give compound 6F (0.28 g, yield 47.09%). LC-MS (ESI): m / z = 589.4 [M+H] + .

[0572] Step 6: In a single-necked flask, compound 6F (1.60 g, 5.21 mmol), palladium on carbon (0.5 g), and methanol (20 mL) were added sequentially. The mixture was purged with hydrogen three times, and the reaction was continued at room temperature with stirring for 18 hours. The mixture was filtered through a diatomaceous earth liner, the solid was washed with methanol, and the filtrate was concentrated under reduced pressure to obtain compound 6G (0.15 g, yield 68.75%), which could be used directly for the next reaction without further purification. LC-MS (ESI): m / z = 455.3 [M+H] + .

[0573] Step 7: In a single-necked flask, add 1-ethyl-1H-pyrazole-5-carboxylic acid (55 mg, 0.43 mmol), N,N-diisopropylethylamine (55 mg, 0.40 mmol), 2-(7-azobenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate (0.15 g, 0.40 mmol), and DMF (10 mL) sequentially. After stirring for 10 minutes, add compound 6G (0.15 g, 0.33 mmol) and continue stirring for 2 hours. Pour the reaction solution into water and extract three times with ethyl acetate. The combined organic phases are washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the crude product. The crude product is purified using a Biotage Isolera One (12 g silica gel column, eluent: 0-4% MeOH / DCM) to obtain the target compound 6 (20 mg, yield 10.51%). LC-MS (ESI): m / z = 577.3 [M+H] + .

[0574] 1 H NMR (400MHz, CDCl3): δ8.14–8.09(m,1H),7.91(s,1H),7.49–7.48(m,1H),7.0 3–7.01(m,2H),6.66–6.59(m,2H),4.68–4.56(m,4H),4.11–4.09(m,1H),3.29 –3.23(m,1H),3.07–2.88(m,2H),2.75–2.53(m,2H),2.39(s,3H),2.35(s,3H) ,2.16–2.03(m,5H),1.94–1.82(m,2H),1.72–1.50(m,5H),1.46–1.41(m,4H).

[0575] Example 7

[0576] Step 1: Dissolve 7A (5 g, 27.3 mmol) in methanol (50 mL), add sodium borohydride (1.55 g, 40.95 mmol) at 0°C, and react for 1 hour. After the reaction is complete, extract (with ethyl acetate), wash, dry, and concentrate to obtain the target compound 7B (5 g, 98%).

[0577] LCMS m / z = 186.1 [M+H] + .

[0578] Step 2: 7B (4 g, 21.6 mmol) was dissolved in dichloromethane (80 mL), followed by the addition of carbon tetrabromide (14.33 g, 43.24 mmol) and triphenylphosphine (11.33 g, 43.24 mmol). The reaction was carried out at room temperature for 3 hours. After the reaction was complete, the reaction solution was concentrated, and the residue was purified by column chromatography (petroleum ether:ethyl acetate (v / v) = 10:1) to obtain the target compound 7C (5 g, 93%). LCMS m / z = 248.0 [M+H] + .

[0579] Step 3: Diphenylmethyleneaminoacetonitrile (5.33 g, 24.2 mmol) was dissolved in tetrahydrofuran (50 mL) under nitrogen protection. Diisopropylaminolithium (24.2 mL, 48.41 mmol, 2 M / L) was added at -40°C, and the reaction was allowed to proceed for half an hour. Then, 7C (4 g, 16.13 mmol) was dissolved in tetrahydrofuran (10 mL) and added to the reaction solution, and the reaction was allowed to proceed for another 4 hours. After the reaction was completed, the reaction solution was quenched with saturated ammonium chloride solution, then extracted (with ethyl acetate), washed, and concentrated. The residue was purified by column chromatography (petroleum ether:ethyl acetate (v / v) = 5:1) to obtain the target compound 7D (2.16 g, 34%).

[0580] LCMS m / z = 388.2[M+H] + .

[0581] Step 4: Dissolve 7D (2.16 g, 5.58 mmol) in tetrahydrofuran (20 mL), then add hydrochloric acid (10 mL, 1 M), and react at room temperature for 1 hour. After the reaction, adjust the pH to 8, extract (with ethyl acetate), wash, concentrate, and purify the residue by column chromatography (petroleum ether:ethyl acetate (v / v) = 1:1) to obtain the target compound 7E (0.9 g, 72%). LCMS m / z = 224.1 [M+H-56] + .

[0582] Step 5: 7E (0.9 g, 4.03 mmol), 1-methylpiperidin-4-carboxylic acid (0.87 g, 6.04 mmol), 2-(7-azobenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate (2.3 g, 6.04 mmol), and N,N-diisopropylethylamine (1.04 g, 8.06 mmol) were dissolved in N,N-dimethylformamide (10 mL), and the reaction was carried out at room temperature for 1 hour. After the reaction was completed, the reaction solution was extracted (with ethyl acetate), washed, and concentrated. The residue was purified by column chromatography (dichloromethane:methanol (v / v) = 10:1) to give the target compound 7F (1 g, 71%). LCMS m / z = 349.4 [M+H] + .

[0583] Step 6: Dissolve 7F (1 g, 2.87 mmol) in methanol (10 mL), then add zinc powder (1.88 g, 28.7 mmol) and ammonium chloride (0.92 g, 17.22 mmol). React at 50°C for 1 hour. After the reaction is complete, filter and concentrate the reaction solution, then extract (with ethyl acetate), wash and concentrate again to obtain the target compound 7G (0.8 g, 87%). LCMS m / z = 319.7 [M+H] + .

[0584] Step 7: 7G (0.8 g, 2.51 mmol), (S)-2-((tert-butoxycarbonyl)amino)-2-(4,4-difluorocyclohexyl)acetic acid (1.1 g, 3.74 mmol), 2-(7-azobenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate (1.43 g, 3.74 mmol), and N,N-diisopropylethylamine (0.65 g, 5.02 mmol) were dissolved in N,N-dimethylformamide (10 mL), and the reaction was carried out overnight at 50°C. After the reaction, the reaction solution was extracted (with ethyl acetate), washed, and concentrated. The residue was purified by column chromatography (dichloromethane:methanol (v / v) = 5:1) to give the target compound 7H (0.65 g, 43%). LCMS m / z = 594.3 [M+H] + .

[0585] Step 8: Dissolve 7H (0.65 g, 1.09 mmol) in dichloromethane (6 mL), then add trifluoroacetic acid (2 mL) and react at room temperature for 0.5 hours. After the reaction is complete, evaporate the reaction solution to dryness to obtain product 7I (0.54 g, crude product), and proceed directly to the next step. LCMS m / z = 494.4 [M+H] + .

[0586] Step 9: Dissolve 7I (0.54 g, crude product), 1-ethyl-1H-pyrazole-5-carboxylic acid (230 mg, 1.65 mmol), 2-(7-azobenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate (0.62 g, 1.64 mmol), and N,N-diisopropylethylamine (220 mg, 2.17 mmol) in N,N-dimethylformamide (5 mL) and react at room temperature for 1 hour. After the reaction, filter and concentrate the residue for purification by preparative HPLC. Method: 1. Instrument: Waters 2767 preparative HPLC; column: SunFire@PrepC18 (19 mm x 250 mm). 2. Filter the sample through a 0.45 μm filter to prepare the sample solution. 3. Preparative chromatographic conditions: a. Composition of mobile phases A and B: Mobile phase A: acetonitrile; Mobile phase B: water (containing 0.05% ammonia); b. Gradient elution, with mobile phase A content ranging from 25% to 75%; c. Flow rate: 15 mL / min; d. Elution time: 20 min. Retention time: 6.94 min. Compound 7 was obtained after separation and purification. LCMS m / z = 616.3 [M+H] + . 1 H NMR(400MHz,DMSO-d6)δ9.99(d,1H),8.64-8.4(m,2H),7.81-7.70(m,1H),7.48(d,1H),7.31-7.17(dd,1H),7.15-7.03(dd,1H),7.0 0(d,1H),4.96(q,1H),4.64(q,1H),4.46(q,2H),2.77-2.67(m,2H),2.11(m,6H),1.91(s,3H),1.73-1.36(m,9H),1.30-1.24(m,8H).

[0587] Examples 8 and 9

[0588] Step 1: Isopropyltriphenylphosphine iodide (8.6 g, 20 mmol) was dissolved in toluene (100 mL), and then potassium bis(trimethylsilyl)amino (1 N, 20 mL) was added. The mixture was stirred at room temperature for 15 min, and then 8A (2.0 g, 10 mmol) was added. The mixture was heated to 100 °C and reacted for 4 h. After cooling to room temperature, the reaction solution was filtered through diatomaceous earth, washed with EA, and the organic phase was concentrated. The crude product was subjected to column chromatography (EA / PE = 1 / 9) to give compound 8B (1.5 g, 65%). LC-MS (ESI): m / z = 168.3 [M+H-56] + .

[0589] Step 2: Compound 8B (1.5 g, 6.7 mmol) was dissolved in dichloromethane (10 mL), and trifluoroacetic acid (5 mL) was added. The mixture was reacted at room temperature for 20 min. The reaction solution was concentrated and evaporated to dryness to obtain compound 8C (1.6 g, crude product), which did not require further purification. LC-MS (ESI): m / z = 126.2 [M+H] + .

[0590] Step 3: Diphenylmethylene glycine methyl ester (30.4 g, 120 mmol) was dissolved in DMF (300 mL) under nitrogen protection. Potassium tert-butoxide (13.4 g, 120 mmol) was added at 0°C, and the reaction was allowed to proceed for half an hour. Then, 7C (24.8 g, 100 mmol) was dissolved in tetrahydrofuran (50 mL) and added to the reaction solution, and the reaction was allowed to proceed for another 2 hours. After the reaction was completed, the reaction solution was quenched with saturated ammonium chloride solution, then extracted (with ethyl acetate), washed, and concentrated. The residue was purified by column chromatography (petroleum ether: ethyl acetate (v / v) = 5:1) to obtain the target compound 8D (12 g, 28%).

[0591] LCMS m / z = 421.1 [M+H] + .

[0592] Step 4: Dissolve 8D (12 g, 28.6 mmol) in tetrahydrofuran (100 mL), then add hydrochloric acid (20 mL, 4 M), and react at room temperature for 1 hour. After the reaction, adjust the pH to 8, then extract (with ethyl acetate), wash, concentrate, and purify the residue by column chromatography (petroleum ether:ethyl acetate (v / v) = 1:1) to obtain the target compound 8E (5.9 g, 80%). LCMS m / z = 257.1 [M+H] + .

[0593] Step 5: Dissolve 8E (5.9 g, 23 mmol) in DCM (20 mL), then add triethylamine (3.5 g, 35 mmol) and propionic anhydride (3.6 g, 28 mmol) sequentially, and react at room temperature for 1 hour. After the reaction, adjust the pH to 8, then extract (with ethyl acetate), wash, concentrate, and purify the residue by column chromatography (petroleum ether:ethyl acetate (v / v) = 4:1) to obtain the target compound 8F (6.8 g, 95%). LCMS m / z = 313.1 [M+H] + .

[0594] Step 6: Dissolve 8F (6.8 g, 22 mmol) in methanol (10 mL), then add zinc powder (5.7 g, 88 mmol) and ammonium chloride (4.7 g, 88 mmol) and react at room temperature for 2 hours. After the reaction is complete, filter and concentrate the reaction solution, then extract (with ethyl acetate). After washing and concentrating, the target compound 8G (5.6 g, 90%) is obtained. LCMS m / z = 283.1 [M+H] + .

[0595] Step 7: Dissolve 8g (5.6g, 20mmol) in DMF (30.0mL), add (S)-2-((tert-butoxycarbonyl)amino)-2-(4,4-difluorocyclohexyl)acetic acid (7.1g, 24mmol) and N-methylimidazolium (6.5g, 80mmol), and add N,N,N',N'-tetramethylchloroformamidin hexafluorophosphate (6.7g, 22mmol) at 0℃. Stir at room temperature for 1h. After the reaction is complete, add 30mL of water to the reaction solution, extract with ethyl acetate (40mL × 3), combine the organic layers, wash with saturated brine (20mL × 3), dry with anhydrous sodium sulfate, filter, concentrate, and purify the residue by silica gel column chromatography (petroleum ether:ethyl acetate (v / v) = 2:1) to give 8H (7.6g, 70%). LCMS m / z = 558.3 ​​[M+H] + .

[0596] Step 8: Compound 8H (560 mg, 1.0 mmol) was dissolved in tetrahydrofuran (10 mL) and water (2 mL), followed by the addition of lithium hydroxide (96 mg, 4 mmol). The reaction was carried out at room temperature for 4 hours, then concentrated. 1 M hydrochloric acid was added to adjust the pH to acidic, resulting in the precipitation of a white solid. This solid was filtered and dried under vacuum to obtain compound 8I (434 mg, 80%), which was used directly in the next step. LCMS m / z = 544.3 [M+H] + .

[0597] Step 9: Dissolve 8I (434 mg, 0.8 mmol) in DMF (10.0 mL), add 8C (200 mg, crude product) and N-methylimidazole (328 mg, 4 mmol), and add N,N,N',N'-tetramethylchloromethamphexane hexafluorophosphate (280 mg, 1 mmol) at 0 °C. Stir at room temperature for 1 h. After the reaction is complete, add 10 mL of water to the reaction solution, extract with ethyl acetate (20 mL × 2), combine the organic layers, wash with saturated brine (20 mL × 3), dry with anhydrous sodium sulfate, filter, concentrate, and purify the residue by silica gel column chromatography (petroleum ether:ethyl acetate (v / v) = 1:1) to obtain 8J (416 mg, 80%). LCMS m / z = 651.4 [M+H] + .

[0598] Step 10: Dissolve compound 8J (416 mg, 0.6 mmol) in dichloromethane (5 mL), add trifluoroacetic acid (2 mL), and react at room temperature for 20 min. Concentrate the reaction solution and evaporate to dryness to obtain compound 8K (420 mg, crude product), which does not require further purification. LC-MS (ESI): m / z = 551.3 [M+H] + .

[0599] Step 11: Dissolve 8K (320 mg, 0.6 mmol) in DMF (10.0 mL), add 1-ethyl-1H-pyrazole-5-carboxylic acid (140 mg, 1 mmol) and N-methylimidazole (328 mg, 4 mmol), and add N,N,N',N'-tetramethylchloromethamphexane hexafluorophosphate (280 mg, 1 mmol) at 0 °C. Stir at room temperature for 1 h. After the reaction is complete, add 10 mL of water to the reaction solution, extract with ethyl acetate (20 mL × 2), combine the organic layers, wash with saturated brine (20 mL × 3), dry with anhydrous sodium sulfate, concentrate, and separate by HPLC to obtain P1 (101 mg, 25%, HPLC purity peak time: 4.658 min, designated as compound 8) and P2 (101 mg, 25%, HPLC purity peak time: 4.847 min, designated as compound 9). HPLC preparation method: Column: Yuexu, column model: Ultimate C18 (4.6*50mm, 3μm); mobile phase: (phase A: 0.05% TFA aqueous solution, phase B: acetonitrile); gradient: 50% mobile phase B isocratic elution; flow rate: 1mL / min; column temperature: 35℃; wavelength: 254nm; cycle time: 10.0min; sample preparation: sample concentration 1mg / ml, injection: 2ul each time.

[0600] Compound 8, LCMS m / z = 673.4 [M+H] + .

[0601] 11H NMR (400 MHz, CDCl3) δ 8.25–8.05 (m, 2H), 7.48 (d, 1H), 7.07–6.94 (m, 2H), 6.89–6.81 (m, 1H), 6.64–6.61 (m, 1H), 6.55–6.37 (m, 1H), 5.19–5.13 (m, 1H), 4.72–4.68 (m, 1H), 4.62–4.56 (m, 2H), 3.48–3.41 (m, 2H), 3.35–3.28 (m, 1H), 3.17–3.00 (m, 2H), 2.31–2.21 (m, 2H), 2.20–2.10 (m, 3H), 2.07–1.98 (m, 2H), 1.95–1.85 (m, 3H), 1.67 (s, 4H), 1.62–1.55 (m, 6H), 1.43 (t, 3H), 1.31–1.27 (m, 4H), 1.19–1.12 (m, 3H).

[0602] 19 19F NMR (377 MHz, CDCl3) δ -88.40–-91.84 (m), -100.32 (m), -126.86 (d).

[0603] Compound 9, LCMS m / z = 673.4 [M+H] + .

[0604] 1 1H NMR (400 MHz, CDCl3) δ 8.37–8.26 (m, 1H), 8.15–7.94 (m, 1H), 7.46 (s, 1H), 7.15–7.06 (m, 1), 6.99–6.84 (m, 2H), 6.75–6.41 (m, 2H), 5.31–5.09 (m, 1H), 4.82–4.41 (m, 3H), 3.83–3.31 (m, 4H), 3.26–2.97 (m, 1H), 2.42–2.23 (m, 4H), 2.20–2.00 (m, 5H), 1.98–1.84 (m, 3H), 1.73–1.60 (m, 6H), 1.59–1.36 (m, 6H), 1.33–1.16 (m, 4H), 1.08–0.86 (m, 3H).

[0605] 19 19F NMR (377 MHz, CDCl3) δ -90.36 (d), -100.28 (m), -126.66 (d).

[0606] Example 10

[0607] Compound 10 (30 mg, 10%) was synthesized from 8I using the same method as compound 9. LCMS m / z = 609.3 [M+H] + .

[0608] 1 H NMR (400MHz, CDCl3) δ8.12–8.06(m,1H),7.99(s,1H),7.49(s,1H),7.05–6.96(m,2H),6 .70(t,1H),6.61(s,1H),6.17–6.08(m,1H),5.29(t,1H),4.71–4.53(m,3H),3.67(s,3H ),3.16–3.08(m,1H),3.01(d,3H),2.30–2.20(m,2H),2.19–2.12(m,2H),2.09–1.99(s, 1H),1.97–1.88(m,2H),1.55–1.49(m,1H),1.44(t,3H),1.36–1.23(m,6H),1.14(t,3H).

[0609] Example 11

[0610] Step 1: Compound 11A (0.5 g, 3.10 mmol), 1-methyl-1H-pyrazole-4-ol (0.24 g, 2.45 mmol), and potassium carbonate (0.86 g, 6.22 mmol) were dissolved in dimethyl sulfoxide (10 mL) and reacted at 110°C for 16 hours. After the reaction was completed, the reaction solution was extracted (with ethyl acetate), washed, and concentrated. The residue was purified by column chromatography (petroleum ether:ethyl acetate (v / v) = 1:1) to give compound 11B (0.27 g, 36%).

[0611] LC-MS (ESI): m / z = 238.1 [M+H] + .

[0612] Step 2: Compound 11B (0.27 g, 1.14 mmol) was dissolved in methanol (5 mL), followed by the addition of ammonium chloride (0.37 g, 6.92 mmol) and zinc powder (0.71 g, 10.92 mmol). The reaction was carried out at room temperature for 1 hour. After the reaction was complete, the reaction solution was filtered and concentrated. The residue was purified by column chromatography (dichloromethane:methanol (v / v) = 10:1) to obtain compound 11C (0.11 g, 46%). LC-MS (ESI): m / z = 208.2 [M+H] + .

[0613] Step 3: Compound 11C (0.11 g, 0.53 mmol), (S)-2-((tert-butoxycarbonyl)amino)-2-(4,4-difluorocyclohexyl)acetic acid (0.23 g, 0.80 mmol), 2-(7-azobenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate (0.30 g, 0.80 mmol), and N,N-diisopropylethylamine (0.21 g, 1.59 mmol) were dissolved in N,N-dimethylformamide (3 mL) and reacted at room temperature for 1 hour. After the reaction was complete, the reaction solution was extracted (with ethyl acetate), washed, and concentrated. The residue was purified by column chromatography (petroleum ether:ethyl acetate (v / v) = 1:1) to give compound 11D (0.25 g, 97%).

[0614] LC-MS(ESI):m / z=427.4[M+H-56] + .

[0615] Step 4: Compound 11D (0.25 g, 0.52 mmol) was dissolved in dichloromethane (3 mL), and then trifluoroacetic acid (1 mL) was added. The mixture was reacted at room temperature for 0.5 hours. After the reaction was complete, the reaction solution was evaporated to dryness to obtain compound 11E (crude product), which was then directly proceeded to the next step. LC-MS (ESI): m / z = 383.6 [M+H] + .

[0616] Step 5: Compound 11E (crude product), 1-ethyl-1H-pyrazole-5-carboxylic acid (0.11 g, 0.75 mmol), 2-(7-azobenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate (0.29 g, 0.77 mmol), and triethylamine (0.15 g, 1.48 mmol) were dissolved in N,N-dimethylformamide (3 mL) and reacted at room temperature for 1 hour. After the reaction, the mixture was filtered and concentrated, and the residue was purified by preparative HPLC. Method: 1. Instruments: Waters 2767 preparative HPLC; column: SunFire@PrepC18 (19 mm x 250 mm). 2. The sample was filtered through a 0.45 μm filter to prepare the sample solution. 3. Preparative chromatographic conditions: a. Composition of mobile phases A and B: Mobile phase A: acetonitrile; Mobile phase B: water (containing 0.05% ammonia); b. Gradient elution, with mobile phase A content ranging from 25% to 75%; c. Flow rate: 15 mL / min; d. Elution time: 20 min. Retention time: 8.72 min. Compound 11 (107.88 mg, 42%) was obtained after separation and purification.

[0617] LC-MS (ESI): m / z = 505.8 [M+H] + . 1H NMR(400MHz,DMSO-d6)δ9.76(s,1H),8.56(d,1H),7.87-7.83(m,1H),7.76(s,1H),7.47(d,1H),7.38(s,1H),6.98(d,1H),6.91-6.86(m ,1H),6.77-6.74(m,1H),4.73-4.69(m,1H),4.45(q,2H),3.81(s,3H),2.03(m,3H),1.88-1.70(m,4H),1.49-1.35(m,2H),1.27(t,3H).

[0618] Examples 12 and 13

[0619] Step 1: (S)-2-((benzyloxy)carbonyl)amino)-2-(4,4-difluorocyclohexyl)acetic acid (3.06 g, 9.36 mmol) was dissolved in DMF (25 mL), followed by the addition of HATU (3.56 g, 9.36 mmol) and N,N-diisopropylethylamine (2.41 g, 18.70 mmol). After stirring at room temperature for 10 min, compound 12A (1 g, 7.80 mmol) was added. The reaction was allowed to proceed for 2 h at room temperature, followed by extraction with water and ethyl acetate. The extract was dried, filtered, concentrated, and subjected to column chromatography (petroleum ether / ethyl acetate = 2 / 1 (v / v)) to give compound 12B (3 g, 88%). LCMS m / z = 438.5 [M+1] + .

[0620] Step 2: Compound 12B (1.5 g, 3.43 mmol) was dissolved in tetrahydrofuran (40 mL), cooled to -78 °C, and methyl magnesium bromide (6.85 mL, 1 M tetrahydrofuran solution) was slowly added. The mixture was then slowly raised to 0 °C and reacted for 1 hour. The reaction was quenched by slowly adding saturated ammonium chloride aqueous solution, followed by extraction with ethyl acetate, drying, filtration, concentration, and column chromatography (petroleum ether / ethyl acetate = 2 / 1 (v / v)) to give compound 12C (1.05 g, 68%). LCMS m / z = 454.1 [M+1] + .

[0621] Step 3: Compound 12C (1 g, 2.20 mmol) was dissolved in dichloromethane (20 mL), triethylamine (557 mg, 5.51 mmol) was added, the mixture was cooled to 0 °C, and p-toluenesulfonyl chloride (629 mg, 3.30 mmol) was added. The mixture was then stirred at room temperature for 5 hours. Water was added, and the mixture was extracted with dichloromethane. The extract was dried, filtered, concentrated, and subjected to column chromatography (petroleum ether / ethyl acetate = 5 / 1 (v / v)) to give compound 12D (650 mg, 49%). LCMS m / z = 608.6 [M+1] +.

[0622] Step 4: Diphenylmethylene glycine ethyl ester (428 mg, 1.60 mmol) was dissolved in tetrahydrofuran (10 mL) under nitrogen protection. Diisopropylaminolithium (1.6 mL, 3.20 mmol, 2 M / L) was added at -40°C, and the reaction was allowed to proceed for half an hour. Then, compound 12D (650 mg, 1.07 mmol) was dissolved in tetrahydrofuran (10 mL) and added to the reaction solution. The mixture was then allowed to naturally warm to room temperature for 4 hours. After the reaction was complete, the reaction solution was quenched with saturated ammonium chloride solution, extracted with ethyl acetate, dried, filtered, and concentrated. The residue was purified by column chromatography (petroleum ether:ethyl acetate = 5:1 (v / v)) to give compound 12E (440 mg, 58%). LCMS m / z = 703.2 [M+H] + .

[0623] Step 5: Compound 12E (440 mg, 0.62 mmol) was dissolved in tetrahydrofuran (8 mL), and then hydrochloric acid (1.3 mL, 1 M) was added. The mixture was reacted at room temperature for 1 hour. After the reaction, the pH was adjusted to 8, and the mixture was extracted with ethyl acetate. The extract was washed, concentrated, and the residue was purified by column chromatography (petroleum ether:ethyl acetate (v / v) = 1:1 (v / v)) to give compound 12F (0.3 g, 89%). LCMS m / z = 539.6 [M+H] + .

[0624] Step 6: Compound 12F (100 mg, 0.19 mmol) was dissolved in dichloromethane (5 mL), followed by the addition of triethylamine (38 mg, 0.37 mmol) and propionic anhydride (37 mg, 0.26 mmol). The mixture was reacted at room temperature for 1 hour. Water was added, followed by extraction with dichloromethane. The extract was dried, filtered, and concentrated to obtain compound 12G (110 mg, 98%), which did not require further purification. LCMS m / z = 595.7 [M+H] + .

[0625] Step 7: Compound 12G (110 mg, 0.18 mmol) was dissolved in tetrahydrofuran (2 mL), methanol (2 mL), and water (1 mL). Lithium hydroxide monohydrate (22 mg, 0.54 mmol) was then added, and the reaction was carried out at room temperature for 1 hour. After the reaction, the pH was adjusted to 3-4, and the mixture was extracted with ethyl acetate. The extract was washed and concentrated to obtain the target compound 12H (100 mg, 99%), which did not require further purification. LCMS m / z = 567.2 [M+H] + .

[0626] Step 8: Compound 12H (0.10 g, 0.17 mmol), N-methylpiperazine (34 mg, 0.34 mmol), HATU (97 mg, 0.26 mmol), and N,N-diisopropylethylamine (55 mg, 0.42 mmol) were dissolved in N,N-dimethylformamide (4 mL) and reacted at room temperature for 1 hour. Water was added, and the mixture was extracted with ethyl acetate. The extract was dried, filtered, and concentrated to obtain compound 12I (100 mg, 90%), which did not require further purification. LCMS m / z = 649.2 [M+1] + .

[0627] Step 9: Compound 12I (100 mg, 0.15 mmol) was dissolved in methanol (10 mL), and palladium hydroxide on carbon (0.1 g) and hydrochloric acid (0.15 mL, 1 N) were added. The mixture was then purged with hydrogen three times, and the reaction was continued with stirring at room temperature for 16 hours. The mixture was filtered through diatomaceous earth, the solid was washed with methanol, and the filtrate was concentrated under reduced pressure to obtain compound 12J (60 mg, 77%), which did not require further purification. LC-MS (ESI): m / z = 515.3 [M+H] + .

[0628] Step 10: Dissolve 1-ethyl-1H-pyrazole-5-carboxylic acid (25 mg, 0.18 mmol) in N,N-dimethylformamide (4 mL), add N,N-diisopropylethylamine (38 mg, 0.29 mmol) and HATU (68 mg, 0.18 mmol), stir at room temperature for 10 minutes, then add compound 12J (60 mg, 0.12 mmol) and react at room temperature for 2 hours. Concentrate under reduced pressure to obtain the crude target compound, and preparative HPLC yields compounds 12 (6 mg, 7%) and 13 (6 mg, 7%).

[0629] Preparation method: Instrument: Waters 2767 preparative liquid chromatograph; Column: SunFire@Prep C18 (19mm × 250mm); Sample was dissolved in DMF and filtered through a 0.45μm filter to prepare the sample solution; Preparative chromatographic conditions: a. Composition of mobile phases A and B: Mobile phase A: acetonitrile, mobile phase B: water (containing 1 / 1000 trifluoroacetic acid); b. Gradient elution, mobile phase A content from 3% to 50%; c. Flow rate 17mL / min; d. Elution time 20min. Retention time 8.232min (set for compound 12), retention time 8.244min (set for compound 13).

[0630] Compound 12 (6 mg, 7%): LC-MS (ESI): m / z = 637.8 [M+H] + . 1H NMR (400MHz, CD3OD) δ7.54–7.41(m,1H),7.29(d,1H),6.91–6.83(m,1H),4.97–4.88(m,2H),4.55–4.40(m,3H),3.59–3.45(m,2H),2.93(s,3 H),2.84(s,2H),2.36–2.22(m,1H),2.15-2.05(m,6H),1.96(d,1H),1 .74(t,3H),1.53–1.40(m,3H),1.36(t,5H),1.13(t,2H),0.96(t,3H).

[0631] Compound 13 (6 mg, 7%): LC-MS (ESI): m / z = 637.8 [M+H] + . 1 H NMR(400MHz,CD3OD)δ7.50(d,1H),7.21(s,1H),6.89(d,1H),4.92(d,2H),4.59–4.45(m,3H),3.58–3.46(m,2H),3.37-3.32(m,2H), 2.81(s,3H),2.29(td,2H),2.15–1.96(m,5H),1.89–1.69(m,3H),1.57–1.43(m,4H),1.39–1.27(m,6H),1.13(t,3H),0.93(dt,1H).

[0632] Examples 14 and 15

[0633] Following the synthetic method of compound 9, P1 (45 mg, 9%, peak time detected by HPLC: 4.158 min, designated as compound 14) and P2 (45 mg, 9%, peak time detected by HPLC: 4.105 min, designated as compound 15) were obtained.

[0634] HPLC preparation method: Column: Yuexu, column model: Ultimate C18 (4.6*50mm, 3μm); mobile phase: (phase A: 0.05% TFA aqueous solution, phase B: acetonitrile); gradient: 50% mobile phase B isocratic elution; flow rate: 1mL / min; column temperature: 35℃; wavelength: 254nm; cycle time: 10.0min; sample preparation: sample concentration 1mg / ml, injection: 2ul each time.

[0635] Compound 14, LC-MS (ESI): m / z = 617.3 [M+H] + .

[0636] 1 1H NMR (400 MHz, CDCl3) δ 8.23–7.99 (m, 2H), 7.50 (d, 1H), 7.02–6.96 (m, 2H), 6.88–6.81 (m, 1H), 6.64–6.61 (m, 1H), 6.40–6.20 (m, 1H), 5.08 (d, 2H), 4.94 (d, 1H), 4.72–4.41 (m, 7H), 3.21–3.12 (m, 1H), 2.22–2.10 (m, 3H), 1.92 (s, 2H), 1.83–1.59 (m, 2H), 1.58–1.46 (m, 2H), 1.43 (t, 3H), 1.33–1.18 (m, 5H), 1.03–0.95 (m, 3H). 19 19F NMR (377 MHz, CDCl3) δ -73.86 (s), -90.37 (d,), -126.64 (d).

[0637] Compound 15, LC-MS (ESI): m / z = 617.3 [M+H] + .

[0638] 1 1H NMR (400 MHz, CDCl3) δ 8.25–8.05 (m, 2H), 7.50 (d, 1H), 7.17–6.95 (m, 2H), 6.75–6.72 (m, 1H), 6.61 (d, 1H), 6.42–6.32 (m, 1H), 5.08–4.86 (m, 2H), 4.85–4.53 (m, 5H), 4.46 (d, 1H), 4.27 (d, 1H), 4.12 (d, 1H), 3.10–3.02 (m, 1H), 2.27 (q, 2H), 2.22–2.12 (m, 2H), 1.93–1.86 (m, 1H), 1.84–1.65 (m, 2H), 1.59–1.47 (m, 2H), 1.46–1.40 (m, 3H), 1.33–1.23 (m, 5H), 1.17 (m, 3H).

[0639] 19 19F NMR (377 MHz, CDCl3) δ -73.85 (s), -90.41 (d), -126.63 (d).

[0640] Example 16

[0641] Step 1: 16A (9 g, 35.42 mmol) and tetrahydrofuran (150 mL) were added to a flask. Sodium hydride (4.25 g, 106.26 mmol) was then added in portions under ice bath conditions, and the reaction continued for half an hour. Di-tert-butyl dicarbonate (15.46 g, 70.84 mmol) was then added, and the reaction was continued at room temperature for 2 hours. The mixture was extracted with water and ethyl acetate, washed, dried, concentrated, and purified by column chromatography (PE:EA = 10:1 (v / v)) to give compound 16B (12.2 g, 97.24%). LC-MS (ESI): m / z = 254.2 [M-99] + .

[0642] Step 2: 16B (12 g, 33.88 mmol), methanol (120 ml), and dichloromethane (40 ml) were added to a flask, followed by magnesium filings (4.12 g, 169.48 mmol). The mixture was reacted at room temperature for 16 hours under circulating water cooling. A saturated ammonium chloride solution was added, followed by water, extraction with dichloromethane, washing, drying, concentration, and purification by column chromatography (PE:EA = 10:1 (v / v)) to obtain compound 16C (10.1 g, 83.69%). LC-MS (ESI): m / z = 300.1 [M-55] + .

[0643] Step 3: 16C (500 mg, 1.40 mmol) and N,N-dimethylformamide (10 mL) were added to a flask, followed by methyl iodide (598 mg, 4.20 mmol). Sodium hydride (168 mg, 4.20 mmol) was added in portions at room temperature, and the reaction was continued for 3 hours. A saturated ammonium chloride solution was added, followed by water, extraction with ethyl acetate, washing, drying, concentration, and purification by column chromatography (PE:EA = 10:1 (v / v)) to give compound 16D (406 mg, 78.33%). LC-MS (ESI): m / z = 314.0 [M-55] + .

[0644] Step 4: 16D (340 mg, 0.92 mmol), benzophenone imine (333 mg, 1.84 mmol), cesium carbonate (899 mg, 2.76 mmol), and toluene (10 mL) were added to a flask, followed by 4,5-bis(diphenylphosphine-9,9-dimethyloxanthracene) (53 mg, 0.09 mmol) and tris(dibenzylindeneacetone)dipalladium (42 mg, 0.05 mmol). The mixture was then reacted at 110 °C for 4 hours under nitrogen protection. After cooling, water was added, and the mixture was extracted with ethyl acetate. The extract was washed, dried, concentrated, and purified by column chromatography (PE:EA = 10:1 (v / v)) to give compound 16E (360 mg, 83.16%). LC-MS (ESI): m / z = 471.1 [M+H] +.

[0645] Step 5: Add 16E (360 mg, 0.77 mmol), methanol (10 mL), and palladium on carbon (41 mg) to a flask, and then react at room temperature under hydrogen atmosphere for 4 hours. Filter and concentrate to give compound 16F (170 mg, 72.07%). LC-MS (ESI): m / z = 307.2 [M+H] + .

[0646] Step 6: Add 16F (170 mg, 0.55 mmol) and N,N-dimethylformamide (10 mL) to a flask, followed by (S)-2-(((benzyloxy)carbonyl)amino)-2-(4,4-difluorocyclohexyl)acetic acid (270 mg, 0.83 mmol), HATU (314 mg, 0.83 mmol), and triethylamine (167 mg, 1.65 mmol). React at room temperature for 16 hours. Extract with water and ethyl acetate, wash, dry, and concentrate to obtain crude compound 16G (310 mg). LC-MS (ESI): m / z = 516.2 [M-99] + .

[0647] Step 7: Add 16g (310mg, 0.50mmol), methanol (10ml), and palladium on carbon (53mg) to the flask, and then react at room temperature under hydrogen atmosphere for 16 hours. Filter and concentrate to give compound 16H (240mg). LC-MS (ESI): m / z = 426.2 [M-55] + .

[0648] Step 8: Add 16H (240 mg, 0.50 mmol) and N,N-dimethylformamide (10 mL) to a flask, followed by 1-ethyl-1H-pyrazole-5-carboxylic acid (105 mg, 0.75 mmol), HATU (285 mg, 0.75 mmol), and triethylamine (152 mg, 1.50 mmol). React at room temperature for 2 hours. Extract with water and ethyl acetate, wash, dry, and concentrate to obtain crude compound 16I (360 mg). LC-MS (ESI): m / z = 604.2 [M+H] + .

[0649] Step 9: Add 16I (360 mg, 0.60 mmol), methanol (3 ml), tetrahydrofuran (3 ml), and water (3 ml) to a flask, followed by lithium hydroxide (125 mg, 3 mmol). React at room temperature for 2 hours. Add water to adjust the pH to approximately 5, extract with dichloromethane, wash, dry, and concentrate to obtain crude compound 16J (310 mg). LC-MS (ESI): m / z = 588.2 [MH] + .

[0650] Step 10: Add 16J (310 mg, 0.53 mmol) and N,N-dimethylformamide (10 mL) to a flask, followed by 2,2,2-trifluoroethylamine (79 mg, 0.80 mmol), HATU (302 mg, 0.80 mmol), and triethylamine (161 mg, 1.59 mmol). React at room temperature for 2 hours. Extract with water and ethyl acetate, wash, dry, and concentrate to obtain crude compound 16K (320 mg). LC-MS (ESI): m / z = 615.2 [M-55] + .

[0651] Step 11: Add crude 16K (320 mg, 0.48 mmol), dichloromethane (10 ml), and hydrochloric acid / dioxane (4 ml, 4 M) to a flask, and then react at room temperature for 2 hours. Concentrate to obtain compound 16 (128 mg, 46.7%).

[0652] Preparation method: Instrument: Waters 2767 preparative liquid chromatograph; Column: SunFire@Prep C18 (19mm × 250mm); Sample was dissolved in DMF and filtered through a 0.45μm filter to prepare the sample solution; Preparative chromatographic conditions: a. Composition of mobile phases A and B: Mobile phase A: acetonitrile, mobile phase B: water (containing 1 / 1000 ammonia); b. Gradient elution, mobile phase A content from 40% to 80%; c. Flow rate 15mL / min; d. Elution time 20min; Retention time: 7.92min. LC-MS (ESI): m / z = 571.2 [M+H] + . 1 H NMR(400MHz,DMSO-d6)δ9.99(s,1H),8.54(d,1H),7.86(t,1H),7.47(s,1H),7.00(t,3H),6.80-6.77(m,1H),5.71(s,1 H),4.48-4.43(m,3H),3.90-3.80(m,3H),3.23-3.20(m,1H),2.06-1.65(m,7H),1.47-1.34(m,4H),1.29-1.26(m,4H).

[0653] Examples 17 and 18

[0654] Step 1: Compound 8 (68 mg) was chirally separated to obtain compounds 17 and 18.

[0655] Preparation method: Instrument: SFC Prep 150AP, column: Daicel AD-H (19mm*250mm), mobile phase: (phase A: CO2, phase B: MeOH); gradient: 30% mobile phase B isocratic elution; flow rate: 40mL / min, wavelength: 220nm. Sample preparation: sample concentration 5mg / ml, methanol solution injection: 2ml each time. After separation, the fractions were dried in a rotary evaporator at a bath temperature of 40℃ to obtain P1 (23mg, retention time: 5.20min, designated as compound 17) and P2 (24mg, retention time: 8.30min, designated as compound 18).

[0656] Compound 1: 7 1 H NMR (400MHz, CDCl3) δ8.16(s,1H),8.11(t,1H),7.49(s,1H),7.02(d,2H),6.81(d,1H),6. 65(s,1H),6.46(d,1H),5.17(s,1H),4.70(t,1H),4.60(q,2H),3.46(s,2H),3.36(s,1H), 3.12(s,2H),2.32–2.21(m,2H),2.20–2.12(m,2H),2.10–1.97(m,2H),1.97–1.85(m,3H), 1.60(s,3H),1.57(s,3H),1.54–1.47(m,1H),1.44(t,3H),1.38–1.22(m,8H),1.16(t,3H). 19 F NMR(377MHz, CDCl3)δ-90.02(s),-90.65(s),-100.06(s),-100.67(s),-126.75(s).

[0657] Compound 18: 1H NMR(400MHz, CDCl3)δ8.12(t,1H),7.98(s,1H),7.48(s,1H),7.04(t,2H),6.72(d,1H),6.60 (s,1H),6.32(d,1H),5.13(t,1H),4.65–4.55(m,3H),3.46–3.26(m,3H),3.18–3.08(m,1H),3 .07–2.95(m,1H),2.29–2.22(m,2H),2.21–2.08(m,4H),2.05–1.97(m,2H),1.95–1.82(m,3H ),1.59(s,3H),1.57(s,3H),1.54–1.49(s,1H),1.43(t,3H),1.33–1.24(m,6H),1.15(t,3H). 19 F NMR(377MHz, CDCl3)δ-90.04(s),-90.67(s),-100.15(s),-100.77(s),-127.22(s).

[0658] Example 19

[0659] Step 1: Add 19A (4.4 g, 23.6 mmol) and toluene (10.0 mL) to a 20 mL microwave-safe tube, followed by 2,5-hexanedione (2.9 g, 25.9 mmol) and anhydrous p-toluenesulfonic acid (0.4 g, 2.3 mmol). Microwave the mixture at 150 °C for 60 min, then cool to room temperature. Concentrate the mixture and purify the residue by silica gel column chromatography (petroleum ether:ethyl acetate (v / v) = 15:1) to obtain 19B (5.2 g, 83%). LCMS m / z = 265.1 [M+H] + .

[0660] Step 2: Compound 19B (5.0 g, 18.9 mmol) was dissolved in tetrahydrofuran (15 mL) and methanol (15 mL), followed by the addition of lithium hydroxide aqueous solution (1.8 g, 75.6 mmol). The reaction was carried out at room temperature for 2 hours, then concentrated. The solution was adjusted to acidity with 1 M hydrochloric acid, resulting in the precipitation of a white solid. This solid was filtered and dried under vacuum to obtain compound 19C (4.2 g, 93%), which was used directly in the next step. LCMS m / z = 237.1 [M+H] + .

[0661] Step 3: Dissolve 19C (4.2 g, 17.7 mmol) in DMF (30.0 mL), then add N-methyl-N-2,2,2-trifluoromethylethylamine hydrochloride (2.0 g, 17.7 mmol) and N-methylimidazole (5.8 g, 71.1 mmol). Add N,N,N',N'-tetramethylchloroformamidin hexafluorophosphate (6.0 g, 21.3 mmol) at 0 °C, and slowly raise the temperature to room temperature with stirring for 1 h. After the reaction is complete, add 30 mL of water to the reaction solution, extract with ethyl acetate (40 mL × 3), combine the organic layers, wash with saturated brine (20 mL × 3), dry with anhydrous sodium sulfate, filter, concentrate, and purify the residue by silica gel column chromatography (petroleum ether:ethyl acetate (v / v) = 10:1) to obtain 19D (4.2 g, 71%). LCMS m / z = 332.1 [M+H] + .

[0662] Step 4: Dissolve 19D (4.0 g, 12.7 mmol) in THF (30.0 mL), cool to -78 °C, then add LiHMDS (13.0 mL * 1.0 M, 13.0 mmol). After the addition is complete, continue stirring for 30 min, then add iodomethane (2.1 g, 14.5 mmol). Slowly raise the temperature to room temperature and react for 2 h. Quench with saturated ammonium chloride solution, extract with ethyl acetate (40 mL × 3...

Claims

1. A compound of general formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof: in: each of ring A and ring B is independently C 3-8 cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 aryl or 5-10 membered heteroaryl; each R A and R B is independently hydrogen, deuterium, halogen, hydroxyl, thiol, cyano, amino, nitro, oxo, =CH2, =CF2, =CH(C 1-3 alkyl), =C(C 1-3 alkyl)2, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuteroalkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkylamino, C 3-8 cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 aryl, or 5-10 membered heteroaryl, wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuteroalkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkylamino, C 3-8 cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 aryl, or 5-10 membered heteroaryl is optionally further substituted with 1-5 R x ; or, any two R B with the ring atom to which it is attached to form C 3-8 cycloalkyl or 3-8 membered heterocycloalkyl, optionally further substituted by 1-5 R x substituents; X can be a key, N, O, or S, provided that when X is O or S, R1 or R2 does not exist; when X is a key, R1 or R2 is directly connected to L3. L1, L2, and L3 are each independently a bond, -(CR a R b ) n1 (CH2) n2 -、-(CH2) n1 (CR a R b ) n2 -、-NR c (CH2) n1 -、-(CH2) n1 C(O)(CR a R b ) n2 -、-(CR a R b ) n1 C(O)(CR a R b ) n2 -、-C(O)(CR a R b ) n1 (CH2) n2 -、-(CR a R b ) n1 O(CH2) n2 -、-(CH2) n1 O(CR a R b ) n2 -、-(CR a R b ) n1 (CH2) n2 NR c -、-(CH2) n1 NR c (CR a R b ) n2 -、-NR c (CR a R b ) n1 (CH2) n2 -、-(CH2) n1 C(O)NR c -、-(CH2) n1 C(O)NR c (CR a R b ) n2 -、-(CR a R b ) n1 C(O)NR c (CH2) n2 -、-(CH2) n1 C(O)NR c (CR a R b ) n2 C(O)NR c (CH2) n1 -、-(CH2) n1 C(O)NR c (CR a R b ) n2 (CH2) n1 -、-(CH2) n1 C(O)NR c (CR a R b ) n2 NR c (CH2) n1 -、-(CH2) n1 NR c C(O)-、-(CR a =CR b ) n1 (CH2) n2 -、-(CR a =CR b ) n1 C(O)NR c (CR a R b ) n2 C(O)NR c (CH2) n1 -、-(CR a =CR b ) n1 C(O)NR c (CR a R b ) n2 (CH2) n1 -、-(CR a =CR b ) n1 C(O)NR c (CR a R b ) n2 NR c (CH2) n1 -、-(C≡C) n1 (CH2) n2 -、-(C≡C) n1 C(O)NR c (CH2) n2 -、-(C≡C) n1 C(O)NR c (CR a R b ) n2 C(O)NR c (CH2) n1 -、-(C≡C) n1 C(O)NR c (CR a R b ) n2 (CH2) n1 -、-(C≡C) n1 C(O)NR c (CR a R b ) n2 NR c (CH2) n1 -、-S(O)2-、 =CR a C(O)NR c (CR a R b ) n2 C(O)NR c (CH2) n1 -, =CR a C(O)NR c (CR a R b ) n2 -, -NR c (CR a R b ) n2 C(O)NR c (CH2) n1 -, -NR c C(O)NR c (CR a R b ) n2 C(O)NR c (CH2) n1 -, -O-C(O)NR c (CR a R b ) n2 C(O)NR c (CH2) n1 -, C 3-8 cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 aryl or 5-10 membered heteroaryl, said CH2, cycloalkyl, heterocycloalkyl, aryl or heteroaryl being optionally further substituted with 1-5 R x ; R a and R b are each independently hydrogen, deuterium, halogen, hydroxyl, cyano, amino, oxo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkylamino, C 3-8 cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, -(CH2) n1 OR aa , -(CH2) n1 C(O)R aa , -(CH2) n1 C(O)OR aa , -(CH2) n1 C(O)NR bb R cc , -(CH2) n1 NR bb C(O)-R cc , -(CH2) n1 C(Se)NR bb R cc , -(CR bb R cc ) n1 NR bb R cc , or -(CR bb R cc ) n1 C(O)NR bb R cc , wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkylamino, C 3- 8cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 aryl, or 5-10 membered heteroaryl is optionally further substituted with 1-5 R x ; R c is hydrogen, deuterium, C 1-6 alkyl, C 1-6 deuteroalkyl, C 1-6 haloalkyl, C 3-8 cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 aryl or 5-10 membered heteroaryl; R1and R2are each independently hydrogen, deuterium, halogen, cyano, amino, oxo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuteroalkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkylamino, C 3-8 cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, -(CH2) n1 R aa , -(CH2) n1 OR aa , -(CH2) n1 C(O)R aa , -(CH2) n1 C(O)CH2R aa , -(CH2) n1 C(O)OR aa , -(CH2) n1 C(Se)R aa , -(CH2) n1 C(O)NR bb R cc , -C(O)(CH2) n1 NR bb R cc , -(CH2) n1 C(Se)NR bb R cc , -(CH2) n1 C(O)C(O)NR bb R cc , -(CR bb R cc ) n1 NR bb R cc or -(CR bb R cc ) n1 C(O)NR bb R cc wherein the C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuteroalkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkylamino, C 3-8 cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 aryl or 5-10 membered heteroaryl is optionally further substituted by 1-5 R x substituents; or R a and R b linkage forms an oxo group, C 3-8 cycloalkyl or 3-8 membered heterocycloalkyl, wherein said C 3-8 cycloalkyl or 3-8 membered heterocycloalkyl is optionally further substituted with 1-5 R x groups; or R a and R b together with the carbon atom to which they are attached form a C 2-6 alkenyl, =C 4-6 cycloalkyl, wherein said C 2-6 alkenyl, cycloalkyl are optionally further substituted with 1-5 R x substituents; Or, R a R b R1, R2 and R B Any two links in form C 3-8 Cycloalkyl or 3-8 membered heterocycloalkyl, optionally further surrounded by 1-5 R... x Replaced; R aa R bb and R cc Each of these groups can be independently represented as hydrogen, deuterium, halogen, hydroxyl, mercapto, cyano, amino, nitro, oxo, or C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 aryl or 5-10 heteroaryl, wherein the C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups may be further divided by 1-5 R groups. x Replaced; Or, R bb and R cc Link formation C 3-8 Cycloalkyl or 3-8 membered heterocycloalkyl, optionally further surrounded by 1-5 R... x Replaced; R x For deuterium, halogen, hydroxyl, mercapto, cyano, amino, nitro, oxo, =CH2, =CF2, =CHF, =CH(C) 1-3 Alkyl), =CF(C) 1-3 Alkyl), =C(C) 1-3 Alkyl)2、=C 4-6 Cycloalkyl, =(4-6 membered heterocycloalkyl), C 1-6 Alkyl, C 2-6 alkenyl, ynyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamine group, -(CH2) n1 -C 3-8 Cycloalkyl, -(CH2) n1 -(3-8 membered heterocyclic alkyl groups), C 6-10 aryl or 5-10 heteroaryl, wherein the C 1-3 Alkyl, C 4-6 Cycloalkyl, 4-6 membered heterocyclic alkyl, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups may be further converted to halogens, hydroxyl groups, mercapto groups, cyano groups, amino groups, nitro groups, oxo groups, =CH2, =CF2, =CHF, =CH(C) 1-3 Alkyl), =C(C) 1-3 Alkyl)2, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 alkylthio or C 1-6 Substituted with alkylamine group; Or, two R atoms located on the same carbon atom x It links together with the carbon atoms it is attached to to form C 2-6 alkenyl, C 3-8 Cycloalkyl or 4-8 membered heterocyclic alkyl groups, wherein the alkenyl, cycloalkyl, or heterocyclic alkyl group is optionally further modified by halogen, hydroxyl, mercapto, cyano, amino, nitro, oxo, or C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 alkylthio or C 1-6 The alkylamine group is replaced; n is an integer between 0 and 5; m is an integer between 0 and 5; n1 is an integer between 0 and 3; n2 is an integer between 0 and 3.

2. The compound of formula (I) according to claim 1, its stereoisomers or pharmaceutically acceptable salts thereof, characterized in that, General formula (I) is further shown in general formulas (II), (II-1), (II-1a), and (II-2): in: X1 can be a bond, N, O, or S, preferably N or O, provided that when X1 is O, R1 or R2 does not exist; when X1 is a bond, R1 or R2 is directly connected to L3. X2 is CR a R b or NR c CH2 or NH are preferred; L4 is a bond, -(CH2) n1 C(O)NR c -、-(CR a =CR b ) n1 C(O)NR c -or-(C≡C) n1 C(O)NR c -, preferred bond, -C(O)NH- or -(C≡C)C(O)NH-; R 3a and R 3b Each of these elements independently represents hydrogen, deuterium, halogen, hydroxyl, cyano, amino, and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 alkylthio or C 1-6 Alkylamine group, preferably hydrogen, hydroxyl, cyano or C 1-3 Halogenated alkyl, more preferably hydrogen, hydroxyl, cyano or trifluoromethyl; Or, R 3a and R 3b The carbon atom it is attached to links together to form an oxo group, C 3-8 Cycloalkyl or 3-8 membered heterocyclic alkyl, preferably oxo or C 4-6 Meta-heterocyclic alkyl, more preferably oxo- or oxo-heterocyclic butyl; R 4a and R 4b Each of these can be independently represented by hydrogen, deuterium, halogen, hydroxyl, cyano, amino, oxo, or C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 alkylthio or C 1-6 Alkylamine group, preferably hydrogen, halogen or C 1-6 Alkyl, more preferably hydrogen, halogen or C 1-3 alkyl; Or, R 4a and R 4b It links together with the carbon atoms it is attached to to form C 2-6 Alkenyl group, optionally further modified by halogen, hydroxyl group, C 1-6 Alkyl, C 1- 6-halogenated alkyl or C 1-6 Alkoxy groups are substituted, preferably 2-methylpropenyl, difluorovinyl, or monofluorovinyl; Ring A, Ring B, R A R B L2, L3, R1, R2, R a R b R c n, m, n1 and n2 as described in claim 1.

3. The compound of formula (I) according to claim 1, its stereoisomers or pharmaceutically acceptable salts thereof, characterized in that, General formula (I) is further shown in general formulas (III), (III-1), (III-2), (VI-1), and (VI-2): in: R A C 1-6 Alkyl, C 3-6 Cycloalkyl, preferably C 1-3 Alkyl, C 3-4 Cycloalkyl, more preferably methyl, ethyl, isopropyl, cyclopropyl or cyclobutyl; Ring B is C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 quinone heteroaryl, preferably C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, 5-6 membered heteroaryl, phenyl-5-6 membered heteroaryl, phenyl-C 3-6 Cycloalkyl or 5-6-membered heteroaryl and 5-6-membered heteroaryl; Each R B Each of these elements independently represents hydrogen, deuterium, halogen, hydroxyl, cyano, amino, and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl, preferably hydrogen, halogen, cyano, C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl or 3-8 membered heterocyclic alkyl, more preferably hydrogen, halogen, cyano, C 1-3 Alkyl, C 2-4 alkenyl, C 1-3 Alkoxy, C 3-5 Cycloalkyl or 4-6-membered heterocycloalkyl, more preferably hydrogen, fluorine, cyano, methyl, methoxy, vinyl, cyclopropyl, cyclobutyl, cyclopentyl, aziridine, aziridine-pentyl, or aziridine-hexyl; wherein the alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamine, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl group is optionally further reinforced by 1-3 R groups. q Replaced; Or, any two R B The ring atoms connected to it form C 3-8 Cycloalkyl, optionally further surrounded by 1-3 R q The replacement is preferably any two R. B The ring atoms connected to it form C 3-6 Cycloalkyl, optionally further surrounded by 1-3 R q The two adjacent Rs are replaced, or more preferably replaced. B The ring atoms attached to it link to form cyclobutyl or cyclopentyl groups, which may optionally be further linked by 1-3 R groups. q Replaced; X1 can be a bond, N, O, or S, preferably N or O, provided that when X1 is O, R1 or R2 does not exist; when X1 is a bond, R1 or R2 is directly connected to L3. R1 and R2 are each independently hydrogen, deuterium, halogen, cyano, amino, or C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl, 5-10 heteroaryl, -(CH2) n1 R aa -(CH2) n1 OR aa -(CH2) n1 C(O)R aa -(CH2) n1 C(O)CH2R aa -(CH2) n1 C(O)OR aa -(CH2) n1 C(Se)R aa -(CH2) n1 C(O)NR bb R cc -C(O)(CH2) n1 NR bb R cc -(CH2) n1 C(Se)NR bb R cc -(CH2) n1 C(O)C(O)NR bb R cc 、-(CR bb R cc ) n1 NR bb R cc or -(CR) bb R cc ) n1 C(O)NR bb R cc The C mentioned therein 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups may be further substituted with 1-3 R groups. q Replaced by; preferably hydrogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups, 3-8 membered heterocyclic alkyl groups, 5-10 membered heteroaryl groups, -(CH2) n1 R aa -(CH2) n1 C(O)R aa -(CH2) n1 C(O)CH2R aa -(CH2) n1 C(O)OR aa -(CH2) n1 C(Se)R aa -(CH(CH3)) n1 C(O)NR bb R cc -(C(CH3)2) n1 C(O)NR bb R cc -C(O)(CH2) n1 NR bb R cc -(CH2) n1 C(O)C(O)NR bb R cc or The C mentioned therein 1-6 Alkyl, C 1-6 Halogenated alkyl groups, 3-8 membered heterocyclic alkyl groups, and 5-10 membered heteroaryl groups may be further determinated by 1-3 R groups. q Replaced by; preferably hydrogen, C 1-3 Alkyl, C 1-3 Halogenated alkyl, 4-6 membered heterocyclic alkyl, 5-6 membered heteroaryl, -CH2R aa -C(O)R aa -CH2C(O)R aa -(CH2) n1 C(O)CH2R aa -(CH2) n1 C(O)OR aa -C(Se)R aa -CH(CH3)C(O)NR bb R cc -C(CH3)2C(O)NR bb R cc -C(O)NR bb R cc -C(O)CH2NR bb R cc -C(O)C(O)NR bb R cc or The C mentioned therein 1-3 Alkyl, C 1-3 Halogenated alkyl, 4-6 membered heterocyclic alkyl, 5-6 membered heteroaryl, optionally further substituted with 1-3 R groups q The substituted substances are more preferably hydrogen, methyl, ethyl, -OCH3, -OCH2CH3, -OCF3, -OCH2CF3, -OCH2CH2CF3, -CH2CF3, -C(O)CH2CH3, -C(Se)CH2CH3, -C(O)CH2CF3, -C(O)CH2CH2CF3, -C(O)CH2N(CH3)2, -CH(CH3)C(O)NHCH2CF3, -CH(CH3)C(O)N(CH3)CH2CF3, -C(CH3)2C(O)NHCH2CF3, -C(O)C(O)NHCH2CF3, Alternatively, R1 and R2 can be linked to form a 3-8 membered heterocyclic alkyl group, optionally further bonded by 1-3 R groups. y Instead, R1 and R2 are preferably linked to form C. 4- 6 heterocyclic alkyl groups, optionally further surrounded by 1-3 R groups y Replaced, better Optional further by 1-3 R y Replaced; R y Hydrogen, halogen, =O, =CH2, =CF2, =CHF, =CH(C) 1-3 Alkyl), =C(C) 1-3 Alkyl)2、=C 4-6 Cycloalkyl, =(4-6 membered heterocycloalkyl), C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 1-6 Alkoxy, the C 1-3 Alkyl, C 4-6 Cycloalkyl groups, 4-6 membered heterocyclic alkyl groups, optionally further halogenated, C 1-2 Alkyl, OH, CN, NH2 substitution, preferably methyl, trifluoromethyl or methoxy; R 3a and R 3b Each of these elements independently represents hydrogen, deuterium, halogen, hydroxyl, cyano, amino, and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 alkylthio or C 1-6 Alkylamine group, preferably hydrogen, hydroxyl, cyano or C 1-3 Halogenated alkyl, more preferably hydrogen, hydroxyl, cyano or trifluoromethyl; Or, R 3a and R 3b Linkage forms oxygen groups, C 3-8 Cycloalkyl or 3-8 membered heterocyclic alkyl, preferably oxo or C 4-6 Meta-heterocyclic alkyl, more preferably oxo- or oxo-heterocyclic butyl; R 4a and R 4b Each of these can be independently represented by hydrogen, deuterium, halogen, hydroxyl, cyano, amino, oxo, or C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 alkylthio or C 1-6 Alkylamine group, preferably hydrogen, halogen or C 1-3 Alkyl, more preferably hydrogen, fluorine or methyl, and even more preferably R 4a and R 4b Both can be hydrogen or both can be fluorine, or one can be hydrogen and the other can be methyl; Or, R 4a and R 4b Link formation C 2-6 Alkenyl group, optionally further modified by halogen, hydroxyl group, C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 1-6 Alkyl groups are substituted, preferably 2-methylpropenyl groups; L2 is the bond, Where r is 0, 1, 2 or 3; L3 is a bond, -C(O)-, -CR 7a R 7b -, -CR 7a R 7b -C(O)-, -S(O)2-, Preferred key, -C(O)-, -CHR 7a -、-CHR 7a -C(O)-; R 5a and R 5b Each of these can be independently represented by hydrogen, deuterium, halogen, hydroxyl, cyano, amino, oxo, or C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl, 5-10 heteroaryl, -(CH2) n1 OR aa -(CH2) n1 C(O)R aa -(CH2) n1 NR bb C(O)R aa -(CH2) n1 C(O)OR aa -(CH2) n1 C(O)NR bb R cc Or -(CH2) n1 C(Se)NR bb R cc The alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamine, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl groups are optionally further reinforced with 1-3 R groups. q Replaced; R6 is hydrogen, deuterium, or C. 1-6 Alkyl, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C3-, C8-cycloalkyl, 3--8-membered heterocyclic alkyl, C 6-10 Aryl, 5-10 quinone heteroaryl, preferably hydrogen or C 1-6 Alkyl, more preferably hydrogen or C 1-3 Alkyl groups, more preferably hydrogen or methyl groups; R 7a and R 7b Each of these can be independently represented by hydrogen, deuterium, halogen, hydroxyl, cyano, amino, oxo, or C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 alkylamine group, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl, 5-10 heteroaryl, -(CH2) n1 OR aa -(CH2) n1 C(O)R aa -(CH2) n1 NR bb C(O)-R cc -(CH2) n1 C(O)OR aa -(CH2) n1 C(O)NR bb R cc -(CH2) n1 C(Se)NR bb R cc 、-(CR bb R cc ) n1 NR bb R cc or -(CR) bb R cc ) n1 C(O)NR bb R cc The C mentioned therein 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamine, C3-8 cycloalkyl, 3-8 membered heterocyclic alkyl, C 6-10 Aryl or 5-10 heteroaryl groups may be further substituted with 1-3 R groups. z Replaced; R z For halogens, hydroxyl groups, cyano groups, amino groups, =CH2, =CF2, =CHF, =CH(C) 1-3 Alkyl), =C(C) 1-3 Alkyl)2, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 aryl or 5-10 heteroaryl, wherein the C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups may be further converted to halogens, hydroxyl groups, cyano groups, amino groups, or C-terminal groups. 1-3 Alkyl, C 1-3 Halogenated alkyl or C 1-3 Alkyl groups are substituted; Or, R 5a or R 5b Linked with R1 to form a 3-8 membered heterocyclic alkyl group, optionally further bonded by 1-3 R groups. q The substituted component is preferably a 4-6 membered heterocyclic alkyl group containing one nitrogen atom, optionally further replaced by 1-3 R atoms. q The substituted group, more preferably piperidinyl, butyrolactam or valproic acid, optionally further replaced by 1-3 R groups. q Replaced; Or, R 5a or R 5b With R 7a or R 7b Link formation C 3-8 Cycloalkyl or 3-8 membered heterocycloalkyl, optionally further surrounded by 1-3 R q Replaced, preferably C 3-8 Cycloalkyl, optionally further surrounded by 1-3 R q Replaced, more preferably C 3-6 Cycloalkyl, optionally further surrounded by 1-3 R q The substituted group is preferably cyclopropyl, cyclobutyl, or cyclohexyl, and optionally further replaced by 1-3 R groups. q Replaced; Or, R 5a or R 5b With R B Link formation C 3-8 Cycloalkyl or 3-8 membered heterocycloalkyl, optionally further surrounded by 1-3 R q Replaced, preferably C 3-8 Cycloalkyl, optionally further surrounded by 1-3 R q Replaced, more preferably C 3-6 Cycloalkyl, optionally further surrounded by 1-3 R q The substituted group is preferably cyclopentyl or cyclohexyl, optionally further replaced by 1-3 R groups. q Replaced; Or, R 7a or R 7b Linked with R1 to form a 3-8 membered heterocyclic alkyl group, optionally further bonded by 1-3 R groups. q The substituted component is preferably a 4-6 membered heterocyclic alkyl group containing one nitrogen atom, optionally further replaced by 1-3 R atoms. q The substituted product, more preferably valproic acid, optionally further replaced by 1-3 R... q Replaced; Or, R 7a or R 7b With R B Link formation C 3-8 Cycloalkyl or 3-8 membered heterocycloalkyl, optionally further surrounded by 1-3 R q Replaced, preferably C 3-8 Cycloalkyl or 4-6 membered heterocyclic alkyl containing one nitrogen atom, optionally further substituted with 1-3 Rq, more preferably C 3-6 Cycloalkyl or 4-6 membered heterocycloalkyl containing 1 nitrogen atom, optionally further surrounded by 1-3 R atoms. q The substituted group is preferably cyclopentyl, cyclohexyl, tetrahydropyran, or valeramide, optionally further replaced by 1-3 R groups. q Replaced; Or, R B Linked with R1 to form C 3-8 Cycloalkyl or 3-8 membered heterocycloalkyl, optionally further surrounded by 1-3 R q Replaced, preferably C 3-8 Cycloalkyl or 4-6 membered heterocycloalkyl containing 1 nitrogen atom, optionally further surrounded by 1-3 R atoms. q Replaced, more preferably C 3-6 Cycloalkyl or 4-6 membered heterocycloalkyl containing 1 nitrogen atom, optionally further surrounded by 1-3 R atoms. q The substituted compounds are preferably tetrahydropyrrole, piperidinyl, valproamide, or caprolactam, optionally further replaced by 1-3 R groups. q Replaced; R aa R bb and R cc Each is independently hydrogen, halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 aryl or 5-10 heteroaryl, wherein the C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 Aryl or 5-10 heteroaryl groups may be further substituted with 1-3 R groups. q The preferred substitutes are hydrogen and C. 1-6 Alkyl, C 1-6 Halogenated alkyl or 3-8 membered heterocyclic alkyl, wherein the C 1-6 Alkyl, C 1-6 Halogenated alkyl or 3-8 membered heterocyclic alkyl may optionally be further denoted by 1-3 R groups. q The preferred alternatives are hydrogen and C. 1-3 Alkyl, C 1-3 Halogenated alkyl or 5-6 membered heterocyclic alkyl, wherein the C 1-3 Alkyl, C 1-3 Halogenated alkyl or 5-6 membered heterocyclic alkyl may optionally be further denoted by 1-3 R groups. q Replaced; Or, R bb and R cc Linkage forms 3-8 membered heterocyclic alkyl groups, optionally further bonded by 1-3 R groups. q Replaced; R q For deuterium, halogen, hydroxyl, oxo, cyano, amino, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Deuterated alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamine group, -(CH2) n1 C 3-6 Cycloalkyl, -(CH2) n1 -(3-6 membered heterocyclic alkyl groups), =CH2, =CF2, =CHF, =CH(C 1-3 Alkyl), =C(C) 1-3 Alkyl)2, wherein the cycloalkyl, heterocycloalkyl optionally further converted to halogen, =CH2, =CF2, =CHF, =CH(C 1-3 Alkyl), =C(C) 1-3 Alkyl)2 is substituted, preferably halogen, C 1-3 Alkyl, Halogenated C 1-3 Alkyl, C 3-6 Cycloalkyl groups, wherein the cycloalkyl group is optionally further substituted with halogens, =CH2, =CF2, =CHF, =CHCH3, =C(CH3)2, more preferably fluorine, methyl, cyclobutyl, Or, two R atoms located on the same carbon atom q It links together with the carbon atoms it is attached to to form C 3-8 Cycloalkyl groups, optionally further modified by halogen, hydroxyl, cyano, amino, oxo, or C- group. 1-2 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-4 Haloalkyl, C 1-4 Alkoxy, C 1-4 alkylthio or C 1-4 The alkylamine group is replaced; m is an integer from 0 to 3, preferably 0, 1 or 2; n1 is an integer between 0 and 3, preferably 0, 1 or 2; n2 is an integer between 0 and 3, preferably 0, 1 or 2.

4. The compound of general formula (I) according to any one of claims 1-3, its stereoisomers or pharmaceutically acceptable salts thereof, characterized in that, Ring B is:

5. The compound of formula (I) according to claim 1, its stereoisomers or pharmaceutically acceptable salts thereof, characterized in that, Selected from Selected from The * site is the connection site between ring B and L2. When L2 is a bond, the * site is the connection site between ring B and L3. L1 is selected from C(O)NHCR a R b C(O)NH-、-C(O)NHCR a R b -; L2 is selected from the key, -CHR 5b -、-NH-、-N(CH3)-、-NR 5b -; L3 is selected from -CHR 7b -、-CHR 7b -C(O)-、-C(O)-; When X is the key and N is the key, R2 is directly connected to L3. R B Each is independently hydrogen, deuterium, F, Cl, and C. 1-3 Alkyl, Halogenated C 1-3 Alkyl, deuterated C 1-3 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, wherein the alkyl, cycloalkyl, or heterocycloalkyl group is optionally further surrounded by 1-3 F, Cl, oxo groups, =CH2, =CF2, =CHF, or =CH(C) groups. 1- 2 alkyl), = C(C 1-2 Substitution of alkyl groups; R a Each is independently hydrogen, deuterium, and C. 1-3 Alkyl, Halogenated C 1-3 Alkyl, deuterated C 1-3 alkyl; R b Each independently is C 1-4 Alkyl, C 4-6 cycloalkyl, wherein the alkyl group or cycloalkyl group is further denoted by 1-3 R groups. x Replaced; R 5b R 7b Each is independently hydrogen, deuterium, halogen, and carbon. 1-3 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, wherein the alkyl, cycloalkyl, or heterocycloalkyl group is optionally further surrounded by 1-3 deuterium, F, Cl, CN, oxo group, =CH2, =CF2, =CHF, =CH(C) groups. 1-3 Alkyl), =C(C) 1-3 Alkyl)2、=C 4-6 Substitution of cycloalkyl groups and (4-6 membered heterocycloalkyl) groups; R1 is hydrogen, deuterium, or C. 1-4 alkyl; R2 is -C(O)R aa -C(O)CH2R aa -C(O)OR aa -(CH2) n1 R aa 3-8 membered heterocyclic alkyl groups, halogenated C 1-4 Alkyl groups, wherein the heterocyclic alkyl groups are optionally further composed of 1-3 elements selected from deuterium, halogens, =CH2, =CF2, =CHF, =CH(C) 1-2 Alkyl), =C(C) 1-2 Substitution with alkyl groups, oxo groups, or -CF3 groups; R aa Each independently constitutes a halogenated C 1-3 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, -(CH)=C 4-6 Cycloalkyl groups, wherein the cycloalkyl or heterocycloalkyl group is optionally further selected from 1-3 halogens, =CH2, =CF2, =CHF, =CH(C 1-3 Alkyl), =C(C) 1-3 Substitution of alkyl groups; Alternatively, R1 and R2 may link to form a 3-8 membered heterocyclic alkyl group, which may optionally be further bonded by 1-3 elements selected from F, Cl, =O, =CH2, =CF2, =CHF, =CH(C) 1-2 Alkyl), =C(C) 1-2 Alkyl)2、=C 4-6 Substitution of cycloalkyl groups and (4-6 membered heterocycloalkyl) groups; R x For deuterium, F, Cl, oxo groups, =CH2, =CF2, =CHF, =CH(C) 1-3 Alkyl), =CF(C) 1-3 Alkyl), =C(C) 1-3 Alkyl)2、=C 4-6 Cycloalkyl, =(4-6 membered heterocycloalkyl), C 1-4 Alkyl, C 3-6 Cycloalkyl groups, wherein the alkyl group or cycloalkyl group is optionally further selected from F, Cl, oxo group, =CH2, =CF2, =CHF, =CH(C) 1-2 Alkyl), =C(C) 1-2 Substituted with alkyl groups; Or, R 7b With R B Link formation C 3-8 cycloalkyl or 3-8 membered heterocyclic alkyl; n1 is an integer between 0 and 3.

6. The compound of formula (I) according to claim 5, its stereoisomers or pharmaceutically acceptable salts thereof, characterized in that, R 5b R 7b Each is independently hydrogen, deuterium, halogen, and carbon. 1-3 Alkyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, tetrahydrofuranyl, tetrahydropyranyl, azircyclopropyl, azircyclobutyl, azircyclopentyl, azircyclohexyl, wherein the alkyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, tetrahydrofuranyl, tetrahydropyranyl, azircyclopropyl, azircyclobutyl, azircyclopentyl, azircyclohexyl may optionally be further surrounded by 1-3 deuterium, F, Cl, CN, oxo, =CH2, =CF2, =CHF, =CH(C) groups. 1-3 Alkyl), =C(C) 1-3 Alkyl)2、=C 4-6 Substitution of cycloalkyl, =(4-6 membered heterocycloalkyl) groups; and / or, R a For hydrogen; and / or, R b for:

7. The compound of formula (I) according to any one of claims 1-6, its stereoisomers or pharmaceutically acceptable salts thereof, characterized in that, The compounds were selected from those listed in Tables 1 and 2.

8. A pharmaceutical composition comprising a therapeutically effective dose of the compound shown in any one of claims 1-7, its stereoisomer or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers or excipients.

9. The pharmaceutical composition according to claim 8, comprising 1-1500 mg of the compound or its stereoisomer or pharmaceutically acceptable salt according to any one of claims 1-7, and one or more pharmaceutically acceptable carriers or excipients.

10. Use of the compound, its stereoisomer, or a pharmaceutically acceptable salt thereof, as described in any one of claims 1-7, or the pharmaceutical composition of claim 8 or 9, in the preparation of a medicament for treating / preventing IL-17A-mediated diseases.

11. The use according to claim 10, wherein the IL-17A-mediated diseases are selected from psoriasis, arthritis, and multiple sclerosis.

12. A method for treating a disease in a mammal, the method comprising administering to a subject a therapeutically effective amount of the compound of any one of claims 1-6, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein the therapeutically effective amount is 1-1500 mg, and the disease is selected from psoriasis, arthritis, and multiple sclerosis.

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