DNA polymerase θ inhibitor and use thereof

Abstract

Provided are a DNA polymerase θ inhibitor and a use thereof. Specifically disclosed are a nitrogen-containing heterocyclic compound represented by formula (I), or a stereoisomer, deuterated compound, or pharmaceutically acceptable salt or co-crystal thereof, and a pharmaceutical composition comprising same. In addition, provided is a use in the preparation of a drug for treating DNA polymerase θ-mediated diseases. Groups in formula (I) are as defined in the description.

Description

DNA polymerase θ inhibitor and its use Technical Field

[0001] The present invention relates to an inhibitor of DNA polymerase θ and use thereof in preparing an inhibitor for treating tumors. Background Art

[0002] DNA polymerase θ (Polθ) is a unique and versatile DNA polymerase. Mammalian cells have evolved multiple pathways to repair DNA double-strand breaks (DSBs) to ensure genomic stability. DNA polymerase theta (Polθ) is a key component of the alternative end joining (alt-EJ) pathway, also known as microhomology-mediated end joining (MMEJ), involved in DSB repair. MMEJ is an alternative cellular repair pathway, in addition to non-homologous end joining (NHEJ) and homologous recombination (HR). DNA polymerase θ (Polθ) is crucial for repairing DNA breaks, particularly in homologous recombination-deficient (HRD) cells. HRD, including defects in the BRCA1 and BRCA2 genes, is a clinically significant feature of several important cancer types, including breast, ovarian, prostate, and pancreatic cancers. Polθ is highly expressed and directs DSB repair toward alt-EJ, initiating the microhomology-mediated end joining (MMEJ) DNA repair process. In the context of HR deficiency, inhibition of Polθ leads to cell death through the accumulation of toxic RAD51 intermediates and inhibition of the alt-EJ repair pathway. In addition, Polθ also has the function of reverse transcription of RNA and promoting DNA repair using RNA as a template[7]. Polθ is almost not expressed in normal tissues, but is highly expressed in many tumor types (such as breast cancer, ovarian cancer, HNSCC, and lung cancer). At the same time, homologous recombination repair deficiency (HRD) is common in these tumor types; therefore, there is a theoretical basis for the application of Polθ inhibitors in these tumor types.

[0003] Currently, HRD tumors can be treated with poly (ADP-ribose) polymerase (PARP) inhibitors, which represent a rapidly growing, multi-billion dollar global market. However, a significant proportion of patients initially do not respond to PARP inhibitor treatment, and the vast majority of treated patients eventually develop PARP inhibitor resistance. Polθ inhibitors have the potential to treat multiple tumor types both as monotherapy and in combination with PARP inhibitors, and their unique mechanism of action may help address both types of PARP resistance. Other clinical patient populations may also benefit from Polθ inhibitor combination therapy, including possible combination therapy with chemotherapy, radiotherapy, and immuno-oncology drugs.

[0004] Summary of the Invention

[0005] The present invention provides a Polθ inhibitor with novel structure and good efficacy, which is used to treat tumor-related diseases and has the excellent effects of high bioavailability and low toxic side effects.

[0006] The present invention relates to a compound represented by formula (I), (Ia), (II), (II-a), (II-b), (III), (III-a), (III-b), (IV-a), (IV-b), (Va), (Vb), (VI-a), (VI-b), (VII-a), (VII-b), (VIII), (VIII-a), (VIII-b), (VIII-c), and stereoisomers, deuterated compounds, solvates, or pharmaceutically acceptable salts or cocrystals thereof.

[0007] in,

[0008] X1 is selected from CH or N;

[0009] Ar1 is selected from pyridyl, pyridazinyl, phenyl, 5-membered heteroaryl, 8-10-membered bicyclic carbocyclic group, 8-10-membered bicyclic heterocyclic group, and the Ar1 is optionally substituted by 1-3 selected from R 1a In some embodiments, Ar1 is selected from pyridyl, phenyl, 5-membered heteroaryl, 8-10-membered bicyclic carbocyclic group, 8-10-membered bicyclic heterocyclic group, and the Ar1 is optionally substituted by 1-3 substituents selected from R 1a In some embodiments, Ar1 is selected from pyridyl, wherein Ar1 is optionally substituted by 1-3 substituents selected from halogen, hydroxyl, cyano, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-2 Alkyl, deuterated C 1-2 Alkoxy, hydroxy C 1-2 Alkyl, C 3-4 Cycloalkyl, -OC 3-4 In some embodiments, Ar1 is selected from pyridyl, wherein Ar1 is optionally substituted by 1-3 groups selected from halogen, hydroxyl, cyano, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-2 Alkyl, deuterated C 1-2 Alkoxy, hydroxy C 1-2 Alkyl, C 3-4 In some embodiments, Ar1 is selected from In some embodiments, Ar1 is selected from In some embodiments, Ar1 is selected from In some embodiments, Ar1 is selected from in Indicates that r2 The linking site of * indicates the linking site with the aminoacyl group;

[0010] R 1a Each independently selected from halogen, hydroxy, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, hydroxy C 1-6 Alkyl, C 3-8 Cycloalkyl, 4-8 membered heterocycloalkyl, -OC 3-8 Cycloalkyl, -O-(4-8 membered heterocycloalkyl), carboxyl, 5 membered heteroaryl, wherein the heteroaryl is optionally substituted by 1-3 halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, hydroxyl C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, C 3-6 Cycloalkyl, -SC 1-6 Alkyl, carboxyl group substitution; in some embodiments, R 1a Each independently selected from halogen, hydroxy, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, hydroxy C 1-6 Alkyl, C 3-8 Cycloalkyl, 4-8 membered heterocycloalkyl, -OC 3-8 Cycloalkyl, -O-(4-8 membered heterocycloalkyl), carboxyl, 5 membered heteroaryl, wherein the heteroaryl is optionally substituted by 1-3 halogen, hydroxyl, cyano, amino, C 1-2 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, hydroxyl C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C1-2 Alkyl, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkyl, deuterated C 1-2 Alkoxy, C 3-6 Cycloalkyl, -SC 1-2 Alkyl, carboxyl group substitution; in some embodiments, R 1a Each independently selected from halogen, hydroxy, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, hydroxy C 1-6 Alkyl, C 3-8 Cycloalkyl, 4-8 membered heterocycloalkyl, -OC 3-8 Cycloalkyl, -O-(4-8 membered heterocycloalkyl), carboxyl, 5 membered heteroaryl, wherein the heteroaryl is optionally substituted by 1-3 halogen, hydroxyl, cyano, amino, C 1-2 Alkyl, C 2-4 Alkenyl, C 2-4 In some embodiments, R 1a Each independently selected from halogen, hydroxy, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, hydroxy C 1-6 Alkyl, C 3-8 Cycloalkyl, 4-8 membered heterocycloalkyl, -OC 3-8 Cycloalkyl, -O-(4-8 membered heterocycloalkyl), carboxyl or 5 membered heteroaryl, wherein the heteroaryl is optionally substituted by methyl, ethyl or propyl; in some embodiments, R 1a Each independently selected from halogen, hydroxy, cyano, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-2 Alkyl, deuterated C 1-2 Alkoxy, hydroxy C 1-2 Alkyl, C 3-4 Cycloalkyl, 4-6 membered heterocycloalkyl, -OC 3-4 Cycloalkyl, -O-(4-6 membered heterocycloalkyl), carboxyl In some embodiments, R 1a Each independently selected from halogen, hydroxy, cyano, C 1-6 Alkyl, C 1-6Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, hydroxy C 1-6 Alkyl, C 3-8 Cycloalkyl, C 4-8 heterocycloalkyl, carboxyl; in some embodiments, each R 1a Each independently selected from halogen, hydroxy, cyano, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-2 Alkyl, deuterated C 1-2 Alkoxy, hydroxy C 1-2 Alkyl, C 3-4 In some embodiments, each R 1a each independently selected from F, Cl, hydroxy, cyano, methyl, ethyl, isopropyl, methoxy, ethoxy, isopropyloxy, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH2F, -CHFCHF2, -CHFCF3, -CF2CH2F, -CF2CHF2, -CF2CF3, -OCHF2, -OCH2F, -OCF3, -OCH2CH2F, -OCH2CHF2, -OCH2CF3, -OCHFCH2F, -OCHFCHF2, -OCHFCF3, -OCF2CH2F, -OCF2CHF2, -OCF2CF3, -CH2D, -CHD2, -CD3, -CH2CH2D, -CH -2CHD2, -CH2CD3, -CHDCH2D, -CHDCHD2, -CHDCD3, -CD2CH2D, -CD2CHD2, -CD2CD3, -OCHD2, -OCH2D, -OCD3, -OCH2CH2D, -OCH2CHD2, -OCH2CD3, -OCHDCH2D, -OCHDCHD2, -OCHDCD3, -OCD2CH2D, -OCD2CHD2, -OCD2CD3, cyclopropyl, cyclobutyl, cyclopentyl, 4-membered heterocycloalkyl, 5-membered heterocycloalkyl, 6-membered heterocycloalkyl, -O-cyclopropyl, -O-cyclobutyl, -O-cyclopentyl, -O-4-membered heterocycloalkyl, -O-5-membered heterocycloalkyl, -O-6-membered heterocycloalkyl, or carboxyl; In some embodiments, each R 1a Each is independently selected from methyl, -CH2F, -CHF2, -CF3, -CH2CH2F, cyclopropyl; in some embodiments, each R 1a are each independently selected from methyl;

[0011] Alternatively, R on adjacent carbon atoms 1a Forming 4-6 membered cycloalkyl, 4-6 membered heterocycloalkyl; in some embodiments, R on adjacent carbon atoms 1a Form 4-, 5-, 6-membered cycloalkyl, 4-, 5-, 6-membered heterocycloalkyl; In some embodiments, R on adjacent carbon atoms 1a Forming 5-membered cycloalkyl, 6-membered cycloalkyl; In some embodiments, R on adjacent carbon atoms 1a Forming a 5-membered cycloalkyl group;

[0012] Ar2 is selected from pyridyl, phenyl, 5-membered heteroaryl, 7-10-membered bicyclic carbocyclic group, 7-10-membered bicyclic heterocyclic group, 4-6-membered monocyclic heterocycloalkyl, 3-6-membered monocyclic cycloalkyl, and said Ar2 is optionally substituted by 1-3 members selected from R 2a In some embodiments, Ar2 is selected from pyridyl, phenyl, and the Ar2 is optionally substituted by 1-3 groups selected from halogen, hydroxyl, cyano, amino, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkyl, deuterated C 1-2 Alkoxy, cyclopropyl, oxetanyl, azetidinyl, -O-cyclopropyl, carboxyl, acetyl, aminoacetyl, aminopropionyl group substituted; In some embodiments, Ar2 is selected from pyridyl, phenyl, said Ar2 is optionally substituted by 1-3 selected from halogen, hydroxyl, cyano, amino, C 1-2 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkyl, deuterated C 1-2 In some embodiments, Ar2 is selected from pyridyl, phenyl, and Ar2 is optionally substituted with 1-2 groups selected from F, Cl, and methoxy; In some embodiments, Ar2 is selected from pyridyl, phenyl, and Ar2 is optionally substituted with 1-2 groups selected from F, Cl, methoxy, and ethynyl; In some embodiments, Ar2 is selected from In some embodiments, Ar2 is selected from In some embodiments, Ar2 is selected from in For A r1 The linking site;

[0013] R 2a Each independently selected from halogen, hydroxy, cyano, =O, amino, methylamino, dimethylamino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, C 3-8 Cycloalkyl, 4-6 membered heterocycloalkyl, -OC 3-8 Cycloalkyl, -O-(4-8 membered heterocycloalkyl), carboxyl, acetyl, aminoacetyl, aminopropionyl; in some embodiments, R 2a Each independently selected from halogen, hydroxy, cyano, amino, C 1-2 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkyl, deuterated C 1-2 substituted with alkoxy, cyclopropyl, oxetanyl, azetidinyl, -O-cyclopropyl, carboxyl, acetyl, aminoacetyl, aminopropionyl; in some embodiments, R 2a Each is independently selected from F, Cl, methoxy, ethynyl; in some embodiments, R 2a Each independently selected from halogen, hydroxy, cyano, =O, amino, methylamino, dimethylamino, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, C 3-8 Cycloalkyl, 4-6 membered heterocycloalkyl, -OC 3-8 Cycloalkyl, -O-(4-8 membered heterocycloalkyl), carboxyl, acetyl, aminoacetyl, aminopropionyl; in some embodiments, R 2a Each independently selected from halogen, hydroxy, cyano, amino, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkyl, deuterated C1-2 substituted with alkoxy, cyclopropyl, oxetanyl, azetidinyl, -O-cyclopropyl, carboxyl, acetyl, aminoacetyl, aminopropionyl; in some embodiments, R 2a each independently selected from F, Cl, hydroxy, cyano, amino, methylamino, dimethylamino, methyl, ethyl, isopropyl, methoxy, ethoxy, isopropyloxy, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH2F, -CHFCHF2, -CHFCF3, -CF2CH2F, -CF2CHF2, -CF2CF3, -OCHF2, -OCH2F, -OCF3, -OCH2CH2F, -OCH2CHF2, -OCH2CF3, -OCHFCH2F, -OCHFCHF2, -OCHFCF3, -OCF2CH2F, -OCF2CHF2, -OCF2CF3, -CH2D, -CHD2, -CD3, -CH2CH2D, -CH -2CHD2, -CH2CD3, -CHDCH2D, -CHDCHD2, -CHDCD3, -CD2CH2D, -CD2CHD2, -CD2CD3, -OCHD2, -OCH2D, -OCD3, -OCH2CH2D, -OCH2CHD2, -OCH2CD3, -OCHDCH2D, -OCHDCHD2, -OCHDCD3, -OCD2CH2D, -OCD2CHD2, -OCD2CD3, cyclopropyl, cyclobutyl, cyclopentyl, 4-membered heterocycloalkyl, 5-membered heterocycloalkyl, 6-membered heterocycloalkyl, -O-cyclopropyl, -O-cyclobutyl, -O-cyclopentyl, -O-4-membered heterocycloalkyl, -O-5-membered heterocycloalkyl, -O-6-membered heterocycloalkyl, carboxyl, acetyl, aminoacetyl, or aminopropanoyl; In some embodiments, R 2a Each is independently selected from F, Cl, methoxy;

[0014] L1 is selected from C 1-6 Alkylene, -OC 1-6 Alkylene, C 2-6 In some embodiments, L1 is selected from -OC 1-6 Alkylene, C 2-6 In some embodiments, L1 is selected from -OC 1-6 Alkylene, C 2-6Alkenyl, wherein 0-2 methylene groups in the alkylene group are optionally replaced by C=O, NH or O; in some embodiments, L1 is selected from -O-*, -N(CH3)-*, -OCH2-*, -OCH2CH2-*, -OCH2-C(O)-*, -CH=CH-* or is absent, * represents the connection site between L1 and Ar3; in some embodiments, L1 is selected from -OCH2-*, -OCH2CH2-*, -OCH2-C(O)-*, -CH=CH-*, * represents the connection site between L1 and Ar3;

[0015] In some embodiments, L1 is selected from -OCH2-*;

[0016] Ar3 is selected from the following groups:

[0017] (i) pyridyl, piperidyl, azacyclohexenyl, wherein the pyridyl, piperidyl, azacyclohexenyl is further substituted by 1-2 groups selected from R3, and optionally substituted by 1-2 groups selected from halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, hydroxyl C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, C 3-6 Cycloalkyl, -SC 1-6 Alkyl and carboxyl group substitution;

[0018] (ii) 5-membered heteroaryl, pyrimidinyl, pyrazinyl, pyridazinyl, piperazinyl, 4-5-membered heterocycloalkyl or 6-10-membered bicyclic heterocycloalkyl, wherein the 5-membered heteroaryl, pyrimidinyl, pyrazinyl, pyridazinyl, piperazinyl or heterocycloalkyl is further substituted by 1-3 groups selected from R6;

[0019] In some embodiments, Ar3 is selected from the following groups:

[0020] (i) pyridyl, piperidyl, azacyclohexenyl, wherein the pyridyl, piperidyl, azacyclohexenyl is further substituted by 1-2 groups selected from R3, and optionally substituted by 1-2 groups selected from halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, hydroxyl C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C1-6 Alkoxy, C 3-6 Cycloalkyl, -SC 1-6 Alkyl and carboxyl group substitution;

[0021] (ii) 5-membered heteroaryl, pyrimidinyl, pyrazinyl, pyridazinyl, 4-5-membered heterocycloalkyl or 6-10-membered bicyclic heterocycloalkyl, wherein the 5-membered heteroaryl, pyrimidinyl, pyrazinyl, pyridazinyl or heterocycloalkyl is further substituted by 1-3 groups selected from R6;

[0022] In some embodiments, Ar3 is selected from the following groups:

[0023] (i) pyridyl, piperidyl, azacyclohexenyl, wherein the pyridyl, piperidyl, azacyclohexenyl is further substituted by 1-2 groups selected from R3, and optionally substituted by 1-2 groups selected from halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, hydroxyl C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, C 3-6 Cycloalkyl, -SC 1-6 Alkyl and carboxyl group substitution;

[0024] (ii) 5-membered heteroaryl, pyrimidinyl, pyrazinyl, pyridazinyl, wherein the 5-membered heteroaryl, pyrimidinyl, pyrazinyl, pyridazinyl is further substituted by 1-3 groups selected from R6;

[0025] In some embodiments, Ar3 is selected from the following groups:

[0026] (i) pyridyl and piperidyl, wherein the pyridyl and piperidyl are further substituted by 1-2 groups selected from R3, and optionally substituted by 1-2 groups selected from halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, hydroxyl C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, C 3-6 Cycloalkyl, -SC 1-6 Alkyl and carboxyl group substitution;

[0027] (ii) 5-membered heteroaryl, pyrimidinyl, pyrazinyl, pyridazinyl, wherein the 5-membered heteroaryl, pyrimidinyl, pyrazinyl, pyridazinyl is further substituted by 1-3 groups selected from R6;

[0028] In some embodiments, Ar3 is selected from the following groups:

[0029] (i) pyridyl, piperidyl or azacyclohexenyl, wherein the pyridyl, piperidyl or azacyclohexenyl is further substituted by 1-2 groups selected from R3, and optionally substituted by 1-2 groups selected from halogen, hydroxyl, cyano, amino, C 1-2 Alkyl, hydroxyl C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkyl, deuterated C 1-2 Alkoxy, C 3-4 radical substitution of cycloalkyl groups;

[0030] (ii) 5-membered heteroaryl, pyrimidinyl, pyrazinyl, pyridazinyl, piperazinyl, 4-5-membered heterocycloalkyl or 6-10-membered bicyclic heterocycloalkyl, wherein the 5-membered heteroaryl, pyrimidinyl, pyrazinyl, pyridazinyl, piperazinyl or heterocycloalkyl is further substituted by 1-3 groups selected from R6;

[0031] In some embodiments, Ar3 is selected from the following groups:

[0032] (i) pyridyl and piperidyl, wherein the pyridyl and piperidyl are further substituted by 1-2 groups selected from R3, and optionally substituted by 1-2 groups selected from halogen, hydroxyl, cyano, amino, C 1-2 Alkyl, hydroxyl C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkyl, deuterated C 1-2 Alkoxy, C 3-4 radical substitution of cycloalkyl groups;

[0033] (ii) 5-membered heteroaryl, pyrimidinyl, pyrazinyl, pyridazinyl, wherein the 5-membered heteroaryl, pyrimidinyl, pyrazinyl, pyridazinyl is further substituted by 1-3 groups selected from R6;

[0034] In some embodiments, Ar3 is selected from the following groups:

[0035] (i) pyridyl, said pyridyl being further substituted by 1-2 groups selected from R3, and optionally substituted by 1-2 groups selected from halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C2-6 Alkenyl, C 2-6 Alkynyl, hydroxyl C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, C 3-6 Cycloalkyl, -SC 1-6 Alkyl and carboxyl group substitution;

[0036] (ii) 5-membered heteroaryl, pyrimidinyl, pyrazinyl, pyridazinyl, wherein the 5-membered heteroaryl, pyrimidinyl, pyrazinyl, pyridazinyl is further substituted by 1-3 groups selected from R6;

[0037] In some embodiments, Ar3 is selected from the following groups:

[0038] (i) pyridyl, said pyridyl being further substituted by 1-2 groups selected from R3, and optionally substituted by 1-2 groups selected from F, Cl, hydroxy, cyano, amino, C 1-2 Alkyl, hydroxyl C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkyl, deuterated C 1-2 Alkoxy, C 3-4 radical substitution of cycloalkyl groups;

[0039] (ii) 5-membered heteroaryl, pyrimidinyl, pyrazinyl, pyridazinyl, wherein the 5-membered heteroaryl, pyrimidinyl, pyrazinyl, pyridazinyl is further substituted by 1-3 groups selected from R6;

[0040] In some embodiments, Ar3 is selected from the following groups:

[0041] (i) The Further substituted by 1 group selected from R3, and optionally substituted by 1-2 groups selected from F, Cl, methyl, ethyl;

[0042] (ii) Imidazolyl, pyrrolyl, pyrimidinyl, pyrazinyl, pyridazinyl, The Imidazolyl, pyrrolyl, pyrimidinyl, pyrazinyl, pyridazinyl, is further substituted with 1 group selected from R6;

[0043] In some embodiments, Ar3 is selected from the following groups:

[0044] (i) The Further substituted by 1 group selected from R3, and optionally substituted by 1-2 groups selected from F, Cl, methyl, ethyl;

[0045] (ii) Imidazolyl, pyrrolyl, pyrimidinyl, pyrazinyl, pyridazinyl, The Imidazolyl, pyrrolyl, pyrimidinyl, pyrazinyl, pyridazinyl, is further substituted with 1 group selected from R6;

[0046] In some embodiments, Ar3 is selected from the following groups:

[0047] (i) The Further substituted by 1 group selected from R3, and optionally substituted by 1-2 groups selected from F, Cl, methyl, ethyl;

[0048] (ii) Imidazolyl, pyrrolyl, pyrimidinyl, pyrazinyl, pyridazinyl, the Imidazolyl, pyrrolyl, pyrimidinyl, pyrazinyl, pyridazinyl is further substituted with one group selected from R6;

[0049] In some embodiments, Ar3 is selected from the following groups:

[0050] (i) The Further substituted by 1 group selected from R3, and optionally substituted by 1-2 groups selected from F, Cl, methyl, ethyl;

[0051] (ii) Imidazolyl, pyrrolyl, pyrimidinyl, pyrazinyl, pyridazinyl, the Imidazolyl, pyrrolyl, pyrimidinyl, pyrazinyl, pyridazinyl is further substituted with one group selected from R6;

[0052] In some embodiments, Ar3 is selected from the following groups:

[0053] (i) The is further substituted with 1 group selected from R3;

[0054] (ii) Imidazolyl, pyrrolyl, pyrimidinyl, pyrazinyl, pyridazinyl, the Imidazolyl, pyrrolyl, pyrimidinyl, pyrazinyl, pyridazinyl is further substituted with one group selected from R6;

[0055] In some embodiments, Ar3 is selected from the following groups:

[0056] Ar3 is selected from the following groups:

[0057] (i) The is further substituted with 1 group selected from R3;

[0058] (ii) Imidazolyl, pyrrolyl, pyrimidinyl, pyrazinyl, pyridazinyl, the Imidazolyl, pyrrolyl, pyrimidinyl, pyrazinyl, pyridazinyl is further substituted with one group selected from R6;

[0059] In some embodiments, Ar3 is selected from the following groups:

[0060] (i) The is further substituted with 1 group selected from R3;

[0061] (ii) Imidazolyl, pyrrolyl, pyrimidinyl, pyrazinyl, pyridazinyl, the Imidazolyl, pyrrolyl, pyrimidinyl, pyrazinyl, pyridazinyl is further substituted with one group selected from R6;

[0062] R3 is selected from the following groups:

[0063] (1) a 4-6 membered monocyclic heterocycloalkyl group, wherein the 4-6 membered monocyclic heterocycloalkyl group is further substituted by 1-3 groups selected from R 3b The group substitution;

[0064] (2) 8-10 membered heterocyclic alkyl, 7-11 membered spiro heterocyclic alkyl, 5-8 membered bridged heterocyclic alkyl, wherein the heterocyclic alkyl, spiro heterocyclic alkyl, bridged heterocyclic alkyl are optionally further substituted by 1-3 groups selected from halogen, hydroxyl, cyano, amino, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkyl, deuterated C 1-2 Alkoxy, -C(O)C 1-2 Alkyl radical substitution;

[0065] (3) 8-10 membered paracycloalkyl, 7-11 membered spirocycloalkyl, 5-8 membered bridged cycloalkyl, wherein the paracycloalkyl, spirocycloalkyl, bridged cycloalkyl are optionally further substituted by 1-3 groups selected from halogen, hydroxyl, cyano, amino, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkyl, deuterated C 1-2 Alkoxy group substitution;

[0066] (4)-O-(CH2) m -(4-6 membered monocyclic heterocycloalkyl), -O-(CH2) m -(4-6 membered monocyclic cycloalkyl), -O-(CH2) m -(5-6 membered heteroaryl), -O-(CH2) m -(phenyl), the 4-6 membered monocyclic heterocycloalkyl, 4-6 membered monocyclic cycloalkyl, 5-6 membered heteroaryl, phenyl is further substituted by 1-3 members selected from R 3b The group substitution;

[0067] (5)-C 1-3 Alkylene-(4-6 membered monocyclic heterocycloalkyl), -C 0-3 Alkylene-(4-6 membered monocyclic cycloalkyl), -C 0-3 Alkylene-(5-6 membered heteroaryl), -C 0-3 Alkylene-phenyl, further substituted by 1-3 groups selected from R 3b The group substitution;

[0068] (6)C 2-4 Alkynyl, F, Cl, N3, the alkynyl is optionally further substituted by 1-2 selected from R 3b The group substitution;

[0069] (7)-C(O)-NR aa R4, -NR aa -C(O)R4, -C(O)-C 0-3 Alkylene-R4, -NR aa R4, -NR aa -C(O)C 1-3 Alkyl, -C(O)-N(R aa )2;

[0070] In some embodiments, R3 is selected from the following groups:

[0071] (1) a 4-6 membered monocyclic heterocycloalkyl group, wherein the 4-6 membered monocyclic heterocycloalkyl group is further substituted by 1-3 groups selected from R 3b The group substitution;

[0072] (2) 8-10 membered heterocyclic alkyl, 7-11 membered spiro heterocyclic alkyl, 5-8 membered bridged heterocyclic alkyl, wherein the heterocyclic alkyl, spiro heterocyclic alkyl, bridged heterocyclic alkyl are optionally further substituted by 1-3 groups selected from halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, -C(O)C 1-4 Alkyl radical substitution;

[0073] (3) 8-10 membered paracycloalkyl, 7-11 membered spirocycloalkyl, 5-8 membered bridged cycloalkyl; the paracycloalkyl, spirocycloalkyl, bridged cycloalkyl may be further substituted by 1-3 groups selected from halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy group substitution;

[0074] (4)-O-(CH2) m -(4-6 membered monocyclic heterocycloalkyl), -O-(CH2) m -(4-6 membered monocyclic cycloalkyl), -O-(CH2) m -(5-6 membered heteroaryl), -O-(CH2) m -phenyl), the 4-6 membered monocyclic heterocycloalkyl, 4-6 membered monocyclic cycloalkyl, 5-6 membered heteroaryl, phenyl is further substituted by 1-3 members selected from R 3b The group substitution;

[0075] (5)-C 1-3 Alkylene-(4-6 membered monocyclic heterocycloalkyl), -C 0-3 Alkylene-(4-6 membered monocyclic cycloalkyl), -C 0-3 Alkylene-(5-6 membered heteroaryl), -C 0-3 Alkylenephenyl, further substituted by 1-3 groups selected from R 3b The group substitution;

[0076] (6)C 2-6 Alkynyl, halogen, N3, the alkynyl is optionally further substituted by 1-2 groups selected from R 3b The group substitution;

[0077] (7)-C(O)-NR aa R4, -NR aa-C(O)R4, -C(O)-C 0-3 Alkylene-R4, -NR aa R4;

[0078] In some embodiments, R3 is selected from the following groups:

[0079] (1) a 4-6 membered monocyclic heterocycloalkyl group, wherein the 4-6 membered monocyclic heterocycloalkyl group is further substituted by 1-3 groups selected from R 3b The group substitution;

[0080] (2) 8-10 membered heterocyclic alkyl, 7-11 membered spiro heterocyclic alkyl, 5-8 membered bridged heterocyclic alkyl, wherein the heterocyclic alkyl, spiro heterocyclic alkyl, bridged heterocyclic alkyl are optionally further substituted by 1-3 groups selected from halogen, hydroxyl, cyano, amino, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkyl, deuterated C 1-2 Alkoxy, -C(O)C 1-2 Alkyl radical substitution;

[0081] (3) 8-10 membered paracycloalkyl, 7-11 membered spirocycloalkyl, 5-8 membered bridged cycloalkyl, wherein the paracycloalkyl, spirocycloalkyl, bridged cycloalkyl are optionally further substituted by 1-3 groups selected from halogen, hydroxyl, cyano, amino, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkyl, deuterated C 1-2 Alkoxy group substitution;

[0082] (4)-O-(CH2) m -(4-6 membered monocyclic heterocycloalkyl), -O-(CH2) m -(4-6 membered monocyclic cycloalkyl), -O-(CH2) m -(5-6 membered heteroaryl), -O-(CH2) m -(phenyl), the 4-6 membered monocyclic heterocycloalkyl, 4-6 membered monocyclic cycloalkyl, 5-6 membered heteroaryl, phenyl is further substituted by 1-3 members selected from R 3b The group substitution;

[0083] (5)-C 1-3 Alkylene-(4-6 membered monocyclic heterocycloalkyl), -C 0-3 Alkylene-(4-6 membered monocyclic cycloalkyl), -C 0-3 Alkylene-(5-6 membered heteroaryl), -C0-3 Alkylene-phenyl, further substituted by 1-3 groups selected from R 3b The group substitution;

[0084] (6)C 2-4 Alkynyl, F, Cl, N3, the alkynyl is optionally further substituted by 1-2 selected from R 3b The group substitution;

[0085] In some embodiments, R3 is selected from the following groups:

[0086] (1)

[0087] (2) Optionally further substituted by 1-2 groups selected from F, Cl, hydroxy, cyano, amino, methyl, ethyl, isopropyl, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH2F, -CHFCHF2, -CHFCF3, -CF2CH2F, -CF2CHF2, -CF2CF3, -CH2D, -CHD2, -CD3, -CH2CH2D, -CH2CHD2, -CH2CD3, -CHDCH2D, -CHDCHD2, -CHDCD3, -CD2CH2D, -CD2CHD2, -CD2CD3, -C(O)CH3;

[0088] (3) Further selected by 1 R 3b The group substitution;

[0089] (4) Pyridyl, phenyl, Further 1-3 selected from F, Cl, methyl, ethyl, isopropyl, cyclopropyl, cyclobutyl, oxetanyl, -NHC(O)CH3, CN, CHF2, CF3 group substitution; or Pyridyl, phenyl, Further 1-3 selected from F, Cl, methyl, ethyl, isopropyl, cyclopropyl, cyclobutyl, oxetanyl, -NHC(O)CH3, CN, CHF2, CF3 group substitution; or Pyridyl, phenyl, Further 1-3 selected from F, Cl, methyl, ethyl, isopropyl, cyclopropyl, cyclobutyl, oxetanyl, -NHC(O)CH3, CN, CF3 group substitution;

[0090] (5) ethynyl, propynyl, F, Cl, N3, wherein the ethynyl and propynyl groups are optionally further substituted by 1-2 groups selected from amino, methylamino, dimethylamino, The group substitution;

[0091] (6)-C(O)-NR aa R4, -NR aa -C(O)R4, -C(O)-R4, -NR aa R4, -NR aa -C(O)C 1-3 Alkyl, -C(O)-N(R aa )2;

[0092] In some embodiments, R3 is selected from the following groups:

[0093] (1)

[0094] (2) Optionally further substituted by 1-2 groups selected from F, Cl, hydroxy, cyano, amino, methyl, ethyl, isopropyl, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH2F, -CHFCHF2, -CHFCF3, -CF2CH2F, -CF2CHF2, -CF2CF3, -CH2D, -CHD2, -CD3, -CH2CH2D, -CH2CHD2, -CH2CD3, -CHDCH2D, -CHDCHD2, -CHDCD3, -CD2CH2D, -CD2CHD2, -CD2CD3, -C(O)CH3;

[0095] (3) Further selected by 1 R 3b The group substitution;

[0096] (4) Pyridyl, phenyl, Further 1-3 selected from F, Cl, methyl, ethyl, isopropyl, cyclopropyl, cyclobutyl, oxetanyl, -NHC(O)CH3, CN, CF3 group substitution;

[0097] (5) ethynyl, propynyl, F, Cl, N3, wherein the ethynyl and propynyl groups are optionally further substituted by 1-2 groups selected from amino, methylamino, dimethylamino, The group substitution;

[0098] (6)-C(O)-NR aa R4, -NR aa -C(O)R4, -C(O)-R4, -NR aa R4;

[0099] In some embodiments, R3 is selected from the following groups:

[0100] (1)

[0101] (2) Optionally further substituted with 1-2 groups selected from F, Cl, hydroxy, cyano, amino, methyl, ethyl, isopropyl, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH2F, -CHFCHF2, -CHFCF3, -CF2CH2F, -CF2CHF2, -CF2CF3, -CH2D, -CHD2, -CD3, -CH2CH2D, -CH2CHD2, -CH2CD3, -CHDCH2D, -CHDCHD2, -CHDCD3, -CD2CH2D, -CD2CHD2, -CD2CD3, -C(O)CH3;

[0102] (3) Further selected by 1 R 3b The group substitution;

[0103] (4) Pyridyl, phenyl, Further 1-3 selected from F, Cl, methyl, ethyl, isopropyl, cyclopropyl, cyclobutyl, oxetanyl, -NHC(O)CH3, The group substitution;

[0104] (5) ethynyl, propynyl, F, Cl, N3, wherein the ethynyl and propynyl groups are optionally further substituted by 1-2 groups selected from amino, methylamino, dimethylamino, The group substitution;

[0105] (6)-C(O)-NR aa R4, -NR aa -C(O)R4, -C(O)-R4, -NR aa R4;

[0106] In some embodiments, R3 is selected from the following groups:

[0107] (1)

[0108] (2) Optionally further substituted by 1-2 groups selected from F, Cl, hydroxy, cyano, amino, methyl, ethyl, isopropyl, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH2F, -CHFCHF2, -CHFCF3, -CF2CH2F, -CF2CHF2, -CF2CF3, -CH2D, -CHD2, -CD3, -CH2CH2D, -CH2CHD2, -CH2CD3, -CHDCH2D, -CHDCHD2, -CHDCD3, -CD2CH2D, -CD2CHD2, -CD2CD3, -C(O)CH3;

[0109] (3) Further selected by 1 R 3b The group substitution;

[0110] (4) Pyridyl, phenyl, further substituted by 1-3 groups selected from F, Cl, methyl, ethyl, isopropyl, cyclopropyl, cyclobutyl, -NHC(O)CH3;

[0111] (5) ethynyl, propynyl, F, Cl, N3, wherein the ethynyl and propynyl groups are optionally further substituted with 1-2 groups selected from amino, methylamino, and dimethylamino;

[0112] (6)-C(O)-NR aa R4, -NR aa -C(O)R4, -C(O)-R4, -NR aa R4;

[0113] In some embodiments, R3 is selected from the following groups:

[0114] (1) a 4-6 membered monocyclic heterocycloalkyl group, wherein the 4-6 membered monocyclic heterocycloalkyl group is further substituted by 1-3 groups selected from R 3b The group substitution;

[0115] (2) 8-10 membered heterocyclic alkyl, 7-11 membered spiro heterocyclic alkyl, 5-8 membered bridged heterocyclic alkyl, wherein the heterocyclic alkyl, spiro heterocyclic alkyl, bridged heterocyclic alkyl are optionally further substituted by 1-3 groups selected from halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy group substitution;

[0116] (3) 8-10 membered paracycloalkyl, 7-11 membered spirocycloalkyl, 5-8 membered bridged cycloalkyl; the paracycloalkyl, spirocycloalkyl, bridged cycloalkyl may be further substituted by 1-3 groups selected from halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy group substitution;

[0117] (4)-O-(CH2) m -(4-6 membered monocyclic heterocycloalkyl), -O-(CH2) m -(4-6 membered monocyclic cycloalkyl), -O-(CH2) m -(5-6 membered heteroaryl), -O-(CH2) m -phenyl), the 4-6 membered monocyclic heterocycloalkyl, 4-6 membered monocyclic cycloalkyl, 5-6 membered heteroaryl, phenyl is further substituted by 1-3 members selected from R 3b The group substitution;

[0118] (5)-C 1-3 Alkylene-(4-6 membered monocyclic heterocycloalkyl), -C 0-3 Alkylene-(4-6 membered monocyclic cycloalkyl), -C 0-3 Alkylene-(5-6 membered heteroaryl), -C 0-3 Alkylenephenyl, further substituted by 1-3 groups selected from R 3b The group substitution;

[0119] (6)C 2-6 Alkynyl, halogen, N3, the alkynyl is optionally further substituted by 1-2 groups selected from R 3b The group substitution;

[0120] (7)-C(O)-NR aa R4, -NR aa -C(O)R4, -C(O)-C 0-3 Alkylene-R4, -NR aa R4;

[0121] In some embodiments, R3 is selected from the following groups:

[0122] (1) a 4-6 membered monocyclic heterocycloalkyl group, wherein the 4-6 membered monocyclic heterocycloalkyl group is further substituted by 1-3 groups selected from R 3bThe group substitution;

[0123] (2) 8-10 membered heterocyclic alkyl, 7-11 membered spiro heterocyclic alkyl, 5-8 membered bridged heterocyclic alkyl, wherein the heterocyclic alkyl, spiro heterocyclic alkyl, bridged heterocyclic alkyl are optionally further substituted by 1-3 groups selected from halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy group substitution;

[0124] (3) 8-10 membered paracycloalkyl, 7-11 membered spirocycloalkyl, 5-8 membered bridged cycloalkyl; the paracycloalkyl, spirocycloalkyl, bridged cycloalkyl may be further substituted by 1-3 groups selected from halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy group substitution;

[0125] (4)-O-(CH2) m -(4-6 membered monocyclic heterocycloalkyl), -O-(CH2) m -(4-6 membered monocyclic cycloalkyl), -O-(CH2) m -(5-6 membered heteroaryl), wherein the 4-6 membered monocyclic heterocycloalkyl, 4-6 membered monocyclic cycloalkyl, 5-6 membered heteroaryl is further substituted by 1-3 members selected from R 3b The group substitution;

[0126] (5)-C 1-3 Alkylene-(4-6 membered monocyclic heterocycloalkyl), -C 0-3 Alkylene-(4-6 membered monocyclic cycloalkyl), -C 1-3 Alkylene-(5-6 membered heteroaryl), further substituted by 1-3 groups selected from R 3b The group substitution;

[0127] (6)C 2-6 Alkynyl, halogen, N3, the alkynyl is optionally further substituted by 1-2 groups selected from R 3b The group substitution;

[0128] (7)-C(O)-NR aa R4, -NR aa -C(O)R4, -C(O)-C 0-3 Alkylene-R4, -NR aaR4;

[0129] In some embodiments, R3 is selected from the following groups:

[0130] (1) a 4-6 membered monocyclic heterocycloalkyl group, wherein the 4-6 membered monocyclic heterocycloalkyl group is further substituted by 1-3 groups selected from R 3b The group substitution;

[0131] (2) 8-10 membered heterocyclic alkyl, 7-11 membered spiro heterocyclic alkyl, 5-8 membered bridged heterocyclic alkyl, wherein the heterocyclic alkyl, spiro heterocyclic alkyl, bridged heterocyclic alkyl are optionally further substituted by 1-3 groups selected from halogen, hydroxyl, cyano, amino, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkyl, deuterated C 1-2 Alkoxy group substitution;

[0132] (3) 8-10 membered paracycloalkyl, 7-11 membered spirocycloalkyl, 5-8 membered bridged cycloalkyl, wherein the paracycloalkyl, spirocycloalkyl, bridged cycloalkyl are optionally further substituted by 1-3 groups selected from halogen, hydroxyl, cyano, amino, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkyl, deuterated C 1-2 Alkoxy group substitution;

[0133] (4)-O-(CH2) m -(4-6 membered monocyclic heterocycloalkyl), -O-(CH2) m -(4-6 membered monocyclic cycloalkyl), -O-(CH2) m -(5-6 membered heteroaryl), -O-(CH2) m -(phenyl), the 4-6 membered monocyclic heterocycloalkyl, 4-6 membered monocyclic cycloalkyl, 5-6 membered heteroaryl, phenyl is further substituted by 1-3 members selected from R 3b The group substitution;

[0134] (5)-C 1-3 Alkylene-(4-6 membered monocyclic heterocycloalkyl), -C 0-3 Alkylene-(4-6 membered monocyclic cycloalkyl), -C 0-3 Alkylene-(5-6 membered heteroaryl), -C 0-3 Alkylene-phenyl, further substituted by 1-3 groups selected from R 3b The group substitution;

[0135] (6)C2-4 Alkynyl, F, Cl, N3, the alkynyl is optionally further substituted by 1-2 selected from R 3b The group substitution;

[0136] (7)-C(O)-NR aa R4, -NR aa -C(O)R4, -C(O)-C 0-3 Alkylene-R4, -NR aa R4;

[0137] In some embodiments, R3 is selected from the following groups:

[0138] (1) a 4-6 membered monocyclic heterocycloalkyl group, wherein the 4-6 membered monocyclic heterocycloalkyl group is further substituted by 1-3 groups selected from R 3b The group substitution;

[0139] (2) 8-10 membered heterocyclic alkyl, 7-11 membered spiro heterocyclic alkyl, 5-8 membered bridged heterocyclic alkyl, wherein the heterocyclic alkyl, spiro heterocyclic alkyl, bridged heterocyclic alkyl are optionally further substituted by 1-3 groups selected from halogen, hydroxyl, cyano, amino, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkyl, deuterated C 1-2 Alkoxy group substitution;

[0140] (3) 8-10 membered paracycloalkyl, 7-11 membered spirocycloalkyl, 5-8 membered bridged cycloalkyl; the paracycloalkyl, spirocycloalkyl, bridged cycloalkyl may be further substituted by 1-3 groups selected from halogen, hydroxyl, cyano, amino, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkyl, deuterated C 1-2 Alkoxy group substitution;

[0141] (4)-O-(CH2) m -(4-6 membered monocyclic heterocycloalkyl), -O-(CH2) m -(4-6 membered monocyclic cycloalkyl), -O-(CH2) m -(5-6 membered heteroaryl), wherein the 4-6 membered monocyclic heterocycloalkyl, 4-6 membered monocyclic cycloalkyl, 5-6 membered heteroaryl is further substituted by 1-3 members selected from R 3b The group substitution;

[0142] (5)-C 1-3Alkylene-(4-6 membered monocyclic heterocycloalkyl), -C 0-3 Alkylene-(4-6 membered monocyclic cycloalkyl), -C 0-3 Alkylene-(5-6 membered heteroaryl), further substituted by 1-3 groups selected from R 3b The group substitution;

[0143] (6)C 2-4 Alkynyl, said alkynyl optionally further substituted by 1-2 selected from R 3b The group substitution;

[0144] (7)-C(O)-NR aa R4, -NR aa -C(O)R4, -C(O)-C 0-3 Alkylene-R4, -NR aa R4;

[0145] In some embodiments, R3 is selected from 4-6 membered monocyclic heterocycloalkyl, said 4-6 membered monocyclic heterocycloalkyl being further substituted by 1-3 members selected from R 3b In some embodiments, R3 is selected from 4-membered monoheterocycloalkyl, 5-membered monoheterocycloalkyl, 6-membered monoheterocycloalkyl, and the monocyclic heterocycloalkyl is further substituted by 1-3 groups selected from R 3b In some embodiments, R3 is selected from oxetanyl, azetidinyl, oxolanyl, azopentyl, oxetanyl, azohexyl, morpholinyl, piperazinyl, and the oxetanyl, azetidinyl, oxolanyl, azopentyl, oxetanyl, azohexyl, morpholinyl, piperazinyl is further substituted by 1, 2 or 3 groups selected from R 3b In some embodiments, R3 is selected from In some embodiments, R3 is selected from

[0146] In some embodiments, R3 is selected from 8-10 membered heterocyclic alkyl, 7-11 membered spiro heterocyclic alkyl, 5-8 membered bridged heterocyclic alkyl, wherein the heterocyclic alkyl, spiro heterocyclic alkyl, bridged heterocyclic alkyl are optionally further substituted by 1-3 members selected from halogen, hydroxyl, cyano, amino, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkyl, deuterated C 1-2 Alkoxy group substitution;

[0147] In some embodiments, R3 is selected from: The above ring is further optionally replaced by 1-3 groups selected from F, Cl, hydroxy, cyano, amino, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkyl, deuterated C 1-2 Alkoxy, -C(O)C 1-2 Alkyl radical substitution;

[0148] In some embodiments, R3 is selected from 8-10 membered cycloalkyl, 7-11 membered spirocycloalkyl, 5-8 membered bridged cycloalkyl, and the cycloalkyl, spirocycloalkyl, bridged cycloalkyl are optionally further substituted by 1-3 groups selected from halogen, hydroxyl, cyano, amino, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkyl, deuterated C 1-2 In some embodiments, R3 is selected from the group consisting of 5-membered cycloalkyl and 5-membered cycloalkyl, 5-membered cycloalkyl and 6-membered cycloalkyl, 6-membered cycloalkyl and 5-membered cycloalkyl, 6-membered cycloalkyl and 6-membered cycloalkyl, 4-membered cycloalkyl spiro 4-membered cycloalkyl, 4-membered cycloalkyl spiro 5-membered cycloalkyl, 4-membered cycloalkyl spiro 6-membered cycloalkyl, 5-membered cycloalkyl spiro 4-membered cycloalkyl, 5-membered cycloalkyl spiro 5-membered cycloalkyl, 5-membered cycloalkyl spiro 6-membered cycloalkyl, 6-membered cycloalkyl spiro 4-membered cycloalkyl, 6-membered cycloalkyl spiro 5-membered cycloalkyl, 6-membered cycloalkyl spiro 6-membered cycloalkyl, Optionally further substituted by 1, 2, or 3 groups selected from halogen, hydroxy, cyano, amino, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkyl, deuterated C 1-2 Alkoxy group substitution;

[0149] In some embodiments, R3 is selected from -O-(CH2) m -(4-6 membered monocyclic heterocycloalkyl), -O-(CH2) m -(4-6 membered monocyclic cycloalkyl), -O-(CH2) m -(5-6 membered heteroaryl), -O-(CH2) m -(phenyl), the 4-6 membered monocyclic heterocycloalkyl, 4-6 membered monocyclic cycloalkyl, 5-6 membered heteroaryl, phenyl is further substituted by 1-3 members selected from R 3b In some embodiments, R3 is selected from -O-(CH2) m-(4-6 membered monocyclic heterocycloalkyl), -O-(CH2) m -(4-6 membered monocyclic cycloalkyl), -O-(CH2) m -(5-6 membered heteroaryl), wherein the 4-6 membered monocyclic heterocycloalkyl, 4-6 membered monocyclic cycloalkyl, 5-6 membered heteroaryl is further substituted by 1-3 members selected from R 3b In some embodiments, R3 is selected from -O-(4-membered monocyclic heterocycloalkyl), -O-CH2-(4-membered monocyclic heterocycloalkyl), -O-(5-membered monocyclic heterocycloalkyl), -O-CH2-(5-membered monocyclic heterocycloalkyl), -O-(6-membered monocyclic heterocycloalkyl), -O-CH2-(6-membered monocyclic heterocycloalkyl), -O-(4-membered monocyclic cycloalkyl), -O-CH2-(4-membered monocyclic cycloalkyl), -O-(5-membered monocyclic cycloalkyl), -O-CH2-(5-membered monocyclic cycloalkyl), -O-(6-membered monocyclic cycloalkyl), -O-CH2-(6-membered monocyclic cycloalkyl), -O-(5-membered heteroaryl), -O-CH2-(5-membered heteroaryl), -O-(6-membered heteroaryl), -O-CH2-(6-membered heteroaryl), wherein the monocyclic heterocycloalkyl, monocyclic cycloalkyl and heteroaryl are further substituted by 1-3 groups selected from R 3b In some embodiments, R3 is selected from Further selected by 1 R 3b In some embodiments, R3 is selected from Further selected by 1 R 3b The group substitution;

[0150] In some embodiments, R3 is selected from -C 1-3 Alkylene-(4-6 membered monocyclic heterocycloalkyl), -C 0-3 Alkylene-(4-6 membered monocyclic cycloalkyl), -C 0-3 Alkylene-(5-6 membered heteroaryl), further substituted by 1-3 groups selected from R 3b In some embodiments, R3 is selected from -C 0-2 Alkylene-(5-membered heteroaryl), -C 0-2 Alkylene-(6-membered heteroaryl), further substituted by 1-3 groups selected from R 3b In some embodiments, R3 is selected from Pyridyl, phenyl, further substituted by 1-3 groups selected from F, Cl, methyl, ethyl, isopropyl, cyclopropyl, cyclobutyl, -NHC(O)CH3; in some embodiments, R3 is selected from further substituted by 1-2 groups selected from methyl, ethyl, isopropyl, cyclopropyl, and cyclobutyl;

[0151] In some embodiments, R3 is selected from C2-4 Alkynyl, halogen, N3, the alkynyl is optionally further substituted by 1-2 groups selected from R 3b In some embodiments, R3 is selected from ethynyl, propynyl, F, Cl, N3, and the ethynyl and propynyl groups are optionally further substituted with 1-2 groups selected from amino, methylamino, and dimethylamino; In some embodiments, R3 is selected from ethynyl, and the ethynyl groups are optionally further substituted with 1-2 groups selected from amino, methylamino, and dimethylamino; In some embodiments, R3 is selected from F, Cl, N3;

[0152] In some embodiments, R3 is selected from -C(O)-NR aa R4, -NR aa -C(O)R4, -C(O)-C 0-3 Alkylene-R4, -NR aa R4; In some embodiments, R3 is selected from -C(O)-NR aa R4, -NR aa -C(O)R4, -C(O)R4, -C(O)CH2R4, -NR aa R4; In some embodiments, R3 is selected from -C(O)-NR aa R4, -NR aa -C(O)R4, -C(O)R4; in some embodiments, R3 is selected from -C(O)NHR4, -NHC(O)R4, -C(O)R4, R4 are each independently selected from tetrahydropyran, piperidine, cyclobutyl, pyrazole, imidazole, isoxazole, and the tetrahydropyran, piperidine, cyclobutyl, pyrazole, imidazole, isoxazole are optionally further substituted with 1-2 groups selected from methyl, ethyl, isopropyl, F, Cl; in some embodiments, R3 is selected from -C(O)NHR4, -NHC(O)R4, -C(O)R4, R4 is selected from oxacyclohexyl, piperazinyl, cyclobutyl, pyrazolyl, and the piperazinyl, cyclobutyl, pyrazolyl are optionally further substituted with 1-2 groups selected from methyl, ethyl, isopropyl, F, Cl;

[0153] In some embodiments, R3 is selected from the following groups:

[0154] (1)

[0155] (2) Optionally further substituted by 1-2 groups selected from F, Cl, hydroxy, cyano, amino, methyl, ethyl, isopropyl, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH2F, -CHFCHF2, -CHFCF3, -CF2CH2F, -CF2CHF2, -CF2CF3, -CH2D, -CHD2, -CD3, -CH2CH2D, -CH2CHD2, -CH2CD3, -CHDCH2D, -CHDCHD2, -CHDCD3, -CD2CH2D, -CD2CHD2, -CD2CD 3、 -C(O)CH3 group substitution;

[0156] (3) Further selected by 1 R 3b The group substitution;

[0157] (4) Pyridyl, phenyl, further substituted by 1-3 groups selected from F, Cl, methyl, ethyl, isopropyl, cyclopropyl, cyclobutyl, -NHC(O)CH3;

[0158] (5) ethynyl, propynyl, F, Cl, N3, wherein the ethynyl and propynyl groups are optionally further substituted with 1-2 groups selected from amino, methylamino, and dimethylamino;

[0159] (6)-C(O)-NR aa R4, -NR aa -C(O)R4, -C(O)-R4, -NR aa R4;

[0160] In some embodiments, R3 is selected from the following groups:

[0161] (1)

[0162] (2) Optionally further substituted with 1-2 groups selected from F, Cl, hydroxy, cyano, amino, methyl, ethyl, isopropyl, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH2F, -CHFCHF2, -CHFCF3, -CF2CH2F, -CF2CHF2, -CF2CF3, -CH2D, -CHD2, -CD3, -CH2CH2D, -CH2CHD2, -CH2CD3, -CHDCH2D, -CHDCHD2, -CHDCD3, -CD2CH2D, -CD2CHD2, or -CD2CD3;

[0163] (3) Further selected by 1 R 3b The group substitution;

[0164] (4) further substituted by 1-2 groups selected from methyl, ethyl, isopropyl, cyclopropyl, and cyclobutyl;

[0165] (5) ethynyl, propynyl, F, Cl, N3, wherein the ethynyl and propynyl groups are optionally further substituted with 1-2 groups selected from amino, methylamino, and dimethylamino;

[0166] (6)-C(O)-NR aa R4, -NR aa -C(O)R4, -C(O)-R4, -NR aa R4;

[0167] In some embodiments, R3 is selected from

[0168] Each R4 and R6 are independently selected from 3-15 membered carbocyclic rings and 4-15 membered heterocyclic rings, and the carbocyclic rings and heterocyclic rings are optionally further substituted by 1-5 members selected from R 3b The group substitution;

[0169] In some embodiments, each R4 is independently selected from 5-6 membered heteroaryl, 4-6 membered monocyclic heterocycloalkyl, 3-6 membered monocyclic cycloalkyl, 8-10 membered heterocycloalkyl, 7-11 membered spiro heterocycloalkyl, 5-8 membered bridged heterocycloalkyl, 8-10 membered heterocycloalkyl, 7-11 membered spirocycloalkyl, 5-8 membered bridged heterocycloalkyl, and the 5-6 membered heteroaryl, 4-6 membered monocyclic heterocycloalkyl, 3-6 membered monocyclic cycloalkyl, 8-10 membered heterocycloalkyl, 7-11 membered spirocycloalkyl, 5-8 membered bridged heterocycloalkyl, 8-10 membered heterocycloalkyl, 7-11 membered spirocycloalkyl, 5-8 membered bridged heterocycloalkyl, 8-10 membered heterocycloalkyl, 7-11 membered spirocycloalkyl, 5-8 membered bridged heterocycloalkyl, 3b In some embodiments, each R4 is independently selected from 4-6 membered monocyclic heterocycloalkyl, 4-6 membered monocyclic cycloalkyl, 5-6 membered heteroaryl, and the monocyclic heterocycloalkyl, monocyclic cycloalkyl, heteroaryl are optionally further substituted by 1, 2, or 3 members selected from R 3bIn some embodiments, each R4 is independently selected from tetrahydropyran, piperidine, cyclopropyl, cyclobutyl, pyrazole, imidazole, isoxazole, piperazine, and the tetrahydropyran, piperidine, cyclopropyl, cyclobutyl, pyrazole, imidazole, isoxazole, piperazine are optionally further substituted with 1-2 groups selected from methyl, ethyl, isopropyl, F, Cl; In some embodiments, each R4 is independently selected from tetrahydropyran, piperidine, cyclobutyl, pyrazole, imidazole, isoxazole, and the tetrahydropyran, piperidine, cyclobutyl, pyrazole, imidazole, isoxazole are optionally further substituted with 1-2 groups selected from methyl, ethyl, isopropyl, F, Cl;

[0170] In some embodiments, each R6 is independently selected from 3-6 membered cycloalkyl, 4-6 membered heterocycloalkyl, 8-10 membered heterocycloalkyl, 7-11 membered spiro heterocycloalkyl, 5-8 membered bridged heterocycloalkyl, 8-10 membered heterocycloalkyl, 7-11 membered spiro heterocycloalkyl, 5-8 membered bridged heterocycloalkyl or 5-10 membered heteroaryl, and the 3-6 membered cycloalkyl, 4-6 membered heterocycloalkyl, 8-10 membered heterocycloalkyl, 7-11 membered spiro heterocycloalkyl, 5-8 membered bridged heterocycloalkyl, 8-10 membered heterocycloalkyl, 7-11 membered spiro heterocycloalkyl, 5-8 membered bridged heterocycloalkyl, 8-10 membered heterocycloalkyl, 7-11 membered spiro heterocycloalkyl, 5-8 membered bridged heterocycloalkyl, heteroaryl are optionally further substituted by 1-5 members selected from R 3b In some embodiments, each R6 is independently selected from 3-6 membered cycloalkyl, 4-6 membered heterocycloalkyl, 8-10 membered heterocycloheterocycloalkyl, 7-11 membered spiro heterocycloalkyl, 5-8 membered bridged heterocycloalkyl, 8-10 membered heterocycloheterocycloalkyl, 7-11 membered spiro heterocycloalkyl, 5-8 membered bridged heterocycloalkyl, and the 3-6 membered cycloalkyl, 4-6 membered heterocycloalkyl, 8-10 membered heterocycloheterocycloalkyl, 7-11 membered spiro heterocycloalkyl, 5-8 membered bridged heterocycloalkyl, 8-10 membered heterocycloheterocycloalkyl, 7-11 membered spiro heterocycloalkyl, 5-8 membered bridged heterocycloalkyl, 8-10 membered heterocycloheterocycloalkyl, 7-11 membered spiro heterocycloalkyl, 5-8 membered bridged heterocycloalkyl, 3b In some embodiments, each R6 is independently selected from 4-6 membered monocyclic heterocycloalkyl, 4-6 membered monocyclic cycloalkyl, 5-6 membered heteroaryl, and the monocyclic heterocycloalkyl, monocyclic cycloalkyl, heteroaryl are optionally further substituted by 1, 2, or 3 members selected from R 3b In some embodiments, each R6 is independently selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, azetidinyl, oxolanyl, azopentyl, oxhexyl, azohexyl, morpholinyl, piperazinyl, optionally further substituted by 1-2 groups selected from R 3b In some embodiments, each R6 is independently selected from azacyclohexyl, optionally further selected from C 1-2 Alkyl radical substitution;

[0171] R 3b Selected from halogen, =O, Hydroxyl, cyano, amino, methylamino, dimethylamino, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, -(CH2) m -C 3-6 Cycloalkyl, -(CH2) m -(4-10 membered heterocycloalkyl), aryl, 5-10 membered heteroaryl, benzo(5-6 membered cycloalkyl), benzo(5-6 membered heterocycloalkyl), 5-6 membered heteroaryl and 5-6 membered cycloalkyl, -OC 3-8 Cycloalkyl, -O-(4-8 membered heterocycloalkyl), carboxyl, -C(O)-(CH2) m -C 1-6 Alkyl, -C(O)-(CH2) m -Deuterated C 1-6 Alkyl, -C(O)-(CH2) m -C 3-8 Cycloalkyl, -C(O)-(CH2) m -(4-6 membered heterocycloalkyl), -C(O)-(CH2) m -(5-6 membered heteroaryl), -NH-C(O)-(CH2) m -C 1-6 Alkyl, -NH-C(O)-(CH2) m -C 3-8 Cycloalkyl, -S(O)2-C 1-6 Alkyl, -S(O)-C 1-6 Alkyl or selected from -NH-C(O)-(CH2) m -(5-6 membered heteroaryl), wherein the cycloalkyl, heterocycloalkyl, aryl, or heteroaryl group is optionally further substituted by 1-3 members selected from R 3aa The group substitution;

[0172] In some embodiments, R 3b Selected from halogen, =O, Hydroxyl, cyano, amino, methylamino, dimethylamino, C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkyl, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkyl, deuterated C 1-4 Alkoxy, -(CH2) m -C 3-6 Cycloalkyl, -(CH2) m-(4-9 membered heterocycloalkyl), phenyl, 5-10 membered heteroaryl, benzo(5-6 membered cycloalkyl), benzo(5-6 membered heterocycloalkyl), 5-6 membered heteroaryl and 5-6 membered cycloalkyl, -OC 3-6 Cycloalkyl, -O-(4-6 membered heterocycloalkyl), -C(O)-(CH2) m -C 1-4 Alkyl, -C(O)-(CH2) m -C 3-6 Cycloalkyl, -C(O)-(CH2) m -(4-6 membered heterocycloalkyl), -C(O)-(CH2) m -(5-6 membered heteroaryl), -NH-C(O)-(CH2) m -C 1-4 Alkyl, -NH-C(O)-(CH2) m -C 3-6 Cycloalkyl, -S(O)2-C 1-2 Alkyl or selected from -NH-C(O)-(CH2) m -(5-6 membered heteroaryl), wherein the cycloalkyl, heterocycloalkyl, phenyl, heteroaryl are optionally further substituted by 1-3 groups selected from R 3aa The group substitution;

[0173] In some embodiments, R 3b Selected from F, Cl, =O, Hydroxyl, cyano, amino, methylamino, dimethylamino, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH2F, -CHFCHF2, -CHFCF3, -CF2CH2F, -CF2CHF2, -CF2CF3, -OCHF2, -OCH2F, -OCF3, -OCH2CH2F, -OCH2CHF2, -OCH2CF3, -OCHFCH2F, -OCHFCHF2, -OCHFCF3, -OCF2CH2F, -OCF2CHF2, -OCF2CF3, -CH2D, -CHD2, -CD3, -CH2CH2D, -CH2CHD2, -CH2CD3, -CHDCH2D, -CHDCHD2, -CHDCD 3. -CD2CH2D, -CD2CHD2, -CD2CD3, -OCHD2, -OCH2D, -OCD3, -OCH2CH2D, -OCH2CHD2, -OCH2CD3, -OCHDCH2D, -OCHDCHD2, -OCHDCD3, -OCD2CH2D, -OCD2CHD2, -OCD2CD3, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, Azetidinyl, oxolanyl, azetyl, oxhexyl, azetidinyl, -CH2-oxetanyl, -CH2-oxolanyl, -CH2-azetidinyl, -CH2-azacyclopentyl, morpholinyl, piperazinyl, phenyl, pyrrolyl, furyl, thienyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, triazole, pyridazinyl, pyridyl, pyrimidinyl, pyrazinyl, benzocyclopentyl, benzocyclohexyl, benzoazepanyl, -C(O)CH3, -C(O)CD3, -C(O)CH2CH3, -C(O)-cyclopropyl, -C(O)-CH2-cyclopropyl, -C(O)-cyclobutyl, -C(O)-CH2-cyclobutyl, -C(O)-cyclopentyl, -C(O)-CH2-cyclopentyl, -C(O)-cyclohexyl, -C(O)-CH2-cyclohexyl, -C(O)-oxacyclopentyl, -C(O) )-azetidinyl, -C(O)-oxetanyl, -C(O)-azetidinyl, -C(O)-oxetanyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-azetidinyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-azetidinyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-azetidinyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-azetidinyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-azetidinyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-azetidinyl, -C -C(O)-pyrazolyl, -C(O)-imidazolyl, -C(O)-pyrrolyl, -C(O)-furyl, -C(O)-oxazolyl, -C(O)-isoxazolyl, -C(O)-thiazolyl, -NHC(O)CH3, -NHC(O)-cyclopropyl, -NHC(O)-cyclobutyl, -S(O)2CH3, -S(O)CH3 or -NHCO-pyrazolyl, the cyclopropyl, cyclobutyl butyl, cyclopentyl, cyclohexyl, oxetanyl, azetidinyl, oxolanyl, azopentyl, oxhexyl, azohexyl, morpholinyl, piperazinyl, phenyl, pyrrolyl, furyl, thienyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, triazole, pyridazinyl, pyridyl, pyrimidinyl, pyrazinyl, benzocyclopentyl, benzocyclohexyl, benzoazepine, optionally further substituted by 1-3 groups selected from R 3aa The group substitution;

[0174] In some embodiments, R 3b Selected from F, Cl, =O, Hydroxyl, cyano, amino, methylamino, dimethylamino, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH2F, -CHFCHF2, -CHFCF3, -CF2CH2F, -CF2CHF2, -CF2CF3, -OCHF2, -OCH2F, -OCF3, -OCH2CH2F, -OCH2CHF2, -OCH2CF3, -OCHFCH2F, -OCHFCHF2, -OCHFCF3, -OCF2CH2F, -OCF2CHF2, -OCF2CF3, -CH2D, -CHD2, -CD3, -CH2CH2D, -CH2CHD2, -CH2CD3, -CHDCH2D, -CHDCHD2, -CHD CD3, -CD2CH2D, -CD2CHD2, -CD2CD3, -OCHD2, -OCH2D, -OCD3, -OCH2CH2D, -OCH2CHD2, -OCH2CD3, -OCHDCH2D, -OCHDCHD2, -OCHDCD3, -OCD2CH2D, -OCD2CHD2, -OCD2CD3, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxygen heterocycle butyl, azetidinyl, oxolanyl, azetyl, oxhexyl, azetidinyl, -CH2-oxetanyl, -CH2-oxolanyl, -CH2-azetidinyl, -CH2-azacyclopentyl, morpholinyl, piperazinyl, phenyl, pyrrolyl, furanyl, thienyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrazinyl, benzocyclopentyl, benzocyclohexyl, benzoazepanyl, -C(O)CH3, -C(O)CD3, -C(O)CH2CH3, -C(O)-cyclopropyl, -C(O)-CH2-cyclopropyl, -C(O)-cyclobutyl, -C(O)-CH2-cyclobutyl, -C(O)-cyclopentyl, -C(O)-CH2-cyclopentyl, -C(O)-cyclohexyl, -C(O)-CH2-cyclohexyl, -C(O)-oxolanyl, -C(O)-azetidinyl, -C(O)-oxetanyl, -C(O)-azetidinyl, -C(O)-oxetanyl, -C(O)-CH2-oxolanyl, -C(O)-CH2-azepanyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-azetidinyl, -C(O)-CH2-oxahexyl, -C(O)-CH2-azepanyl, -C(O)-CH2-oxahexyl, -C(O)-CH2-azepanyl, -C(O)-pyrazolyl, -C(O)-imidazolyl, -C(O)-pyrrolyl, -C(O)-furyl, -C(O)-oxazolyl, -C(O)-isoxazolyl, -C(O)-thiazolyl, -NHC(O)CH3, -NHC(O)- Cyclopropyl, -NHC(O)-cyclobutyl, -S(O)2CH3, or -S(O)CH3 or selected from -NHCO-pyrazolyl, wherein the cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, azetidinyl, oxolanyl, azopentyl, oxhexyl, azohexyl, morpholinyl, piperazinyl, phenyl, pyrrolyl, furyl, thienyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrazinyl, benzocyclopentyl, benzocyclohexyl, benzoazepine, benzophenone ... 3aa The group substitution;

[0175] In some embodiments, R 3b Selected from halogen, =O, hydroxy, cyano, amino, methylamino, dimethylamino, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, -(CH2) m -C 3-6 Cycloalkyl, -(CH2) m -(4-8 membered heterocycloalkyl), aryl, 5-10 membered heteroaryl, benzo(5-6 membered cycloalkyl), benzo(5-6 membered heterocycloalkyl), 5-6 membered heteroaryl and 5-6 membered cycloalkyl, -OC 3-8 Cycloalkyl, -O-(4-8 membered heterocycloalkyl), carboxyl, -C(O)-(CH2) m -C 1-6 Alkyl, -C(O)-(CH2)m -Deuterated C 1-6 Alkyl, -C(O)-(CH2) m -C 3-8 Cycloalkyl, -C(O)-(CH2) m -(4-6 membered heterocycloalkyl), -C(O)-(CH2) m -(5-6 membered heteroaryl), -NH-C(O)-(CH2) m -C 1-6 Alkyl, -S(O)2-C 1-6 Alkyl, -S(O)-C 1-6 Alkyl, the cycloalkyl, heterocycloalkyl, aryl, heteroaryl may be further substituted by 1-3 groups selected from R 3aa In some embodiments, R 3b Selected from halogen, =O, hydroxy, cyano, amino, methylamino, dimethylamino, C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkyl, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkyl, deuterated C 1-4 Alkoxy, -(CH2) m -C 3-6 Cycloalkyl, -(CH2) m -(4-8 membered heterocycloalkyl), phenyl, 5-10 membered heteroaryl, benzo(5-6 membered cycloalkyl), benzo(5-6 membered heterocycloalkyl), 5-6 membered heteroaryl and 5-6 membered cycloalkyl, -OC 3-6 Cycloalkyl, -O-(4-6 membered heterocycloalkyl), -C(O)-(CH2) m -C 1-4 Alkyl, -C(O)-(CH2) m -C 3-6 Cycloalkyl, -C(O)-(CH2) m -(4-6 membered heterocycloalkyl), -C(O)-(CH2) m -(5-6 membered heteroaryl), -NH-C(O)-(CH2) m -C 1-4 Alkyl, -S(O)2-C 1-2 Alkyl, the cycloalkyl, heterocycloalkyl, phenyl, heteroaryl may be further substituted by 1-3 groups selected from R 3aa In some embodiments, R 3bSelected from F, Cl, =O, hydroxy, cyano, amino, methylamino, dimethylamino, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH2F, -CHFCHF2, -CHFCF3, -CF2CH2F, -CF2CHF2, -CF2CF3, -OCHF2, -OCH2F, -OCF3, -OCH2CH2F, -OCH2CHF2, -OCH2CF3, -OCHFCH2F, -OCHFCHF2, -OCHFCF3, -OCF2CH2F, -OCF2CHF2, - OCF2CF3, -CH2D, -CHD2, -CD3, -CH2CH2D, -CH2CHD2, -CH2CD3, -CHDCH2D, -CHDCHD2, -CHDCD3, -CD2CH2D, -CD2CHD2, -CD2CD3, -OCHD2, -OCH2D, -OCD3, -OCH2CH2D, -OCH2CHD2, -OCH2CD3, -OCHDCH2D, -OCHDCHD2, -OCHDCD3, -OCD2CH2D, -OCD2CHD2, -OCD2CD3, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, azetidinyl, oxolanyl, azopentyl, Oxanyl, azetidinyl, -CH2-oxetanyl, -CH2-oxolanyl, -CH2-azetidinyl, -CH2-azacyclopentyl, morpholinyl, piperazinyl, phenyl, pyrrolyl, furyl, thienyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrazinyl, benzocyclopentyl, benzocyclohexyl, benzoazepanyl, -C(O)CH3, -C(O)CD3, -C(O)CH2CH3, -C(O)-cyclopropyl, -C(O)-CH2-cyclopropyl, -C(O)-cyclobutyl, -C(O)-CH2-cyclobutyl, -C(O)-cyclopentyl, -C(O)-CH2-cyclopentyl, -C(O)-cyclohexyl, -C (O)-CH2-cyclohexyl, -C(O)-oxolanyl, -C(O)-azepanyl, -C(O)-oxetanyl, -C(O)-azetidinyl, -C(O)-oxetanyl, -C(O)-CH2-oxolanyl, -C(O)-CH2-azepanyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-azetidinyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-azetidinyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-azetidinyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-azetidinyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-pyrazolyl, -C(O)-imidazolyl, -C(O)-pyrrolyl, -C(O)-furyl, -C(O)-oxazolyl, -C(O)-isoxazolyl, -C(O)-thiazolyl, -NHC(O)CH3,-S(O)2CH3, or -S(O)CH3, wherein the cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, azetidinyl, oxolanyl, azopentyl, oxetanyl, azohexyl, morpholinyl, piperazinyl, phenyl, pyrrolyl, furyl, thienyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrazinyl, benzocyclopentyl, benzocyclohexyl, benzoazacyclopentyl are optionally further substituted by 1-3 selected from R, 3aa The group substitution;

[0176] In some embodiments, R 3b Selected from halogen, hydroxy, cyano, amino, methylamino, dimethylamino, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, C 3-6 Cycloalkyl, 4-8 membered heterocycloalkyl, aryl, heteroaryl, benzo(5-6 membered cycloalkyl), benzo(5-6 membered heterocycloalkyl), 5-6 membered heteroaryl and 5-6 membered cycloalkyl, -OC 3-8 Cycloalkyl, -O-(4-8 membered heterocycloalkyl), carboxyl, -C(O)-(CH2) m -C 1-6 Alkyl, -C(O)-(CH2) m -Deuterated C 1-6 Alkyl, -C(O)-(CH2) m -C 3-8 Cycloalkyl, -C(O)-(CH2) m -(4-6 membered heterocycloalkyl), -C(O)-(CH2) m -(5-6 membered heteroaryl), -NH-C(O)-(CH2) m -C 1-6 Alkyl, -S(O)2-C 1-6 Alkyl, -S(O)-C 1-6 Alkyl, the cycloalkyl, heterocycloalkyl, aryl, heteroaryl may be further substituted by 1-3 groups selected from R 3aa In some embodiments, R 3b Selected from halogen, hydroxy, cyano, amino, methylamino, dimethylamino, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, C3-6 Cycloalkyl, 4-8 membered heterocycloalkyl, aryl, heteroaryl, benzo(5-6 membered cycloalkyl), benzo(5-6 membered heterocycloalkyl), 5-6 membered heteroaryl and 5-6 membered cycloalkyl, -OC 3-8 Cycloalkyl, -O-(4-8 membered heterocycloalkyl), carboxyl, -C(O)-(CH2) m -C 1-6 Alkyl, -C(O)-(CH2) m -C 3-8 Cycloalkyl, -C(O)-(CH2) m -(4-6 membered heterocycloalkyl), -C(O)-(CH2) m -(5-6 membered heteroaryl), -NH-C(O)-(CH2) m -C 1-6 Alkyl, -S(O)2-C 1-6 Alkyl, -S(O)-C 1-6 Alkyl, the cycloalkyl, heterocycloalkyl, aryl, heteroaryl may be further substituted by 1-3 groups selected from R 3aa In some embodiments, R 3b Selected from halogen, hydroxy, cyano, amino, methylamino, dimethylamino, C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkyl, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkyl, deuterated C 1-4 Alkoxy, C 3-6 Cycloalkyl, 4-8 membered heterocycloalkyl, phenyl, heteroaryl, benzo(5-6 membered cycloalkyl), benzo(5-6 membered heterocycloalkyl), 5-6 membered heteroaryl and 5-6 membered cycloalkyl, -OC 3-6 Cycloalkyl, -O-(4-6 membered heterocycloalkyl), -C(O)-(CH2) m -C 1-4 Alkyl, -C(O)-(CH2) m -C 3-6 Cycloalkyl, -C(O)-(CH2) m -(4-6 membered heterocycloalkyl), -C(O)-(CH2) m -(5-6 membered heteroaryl), -NH-C(O)-(CH2) m -C 1-4 Alkyl, -S(O)2-C 1-2 Alkyl, the cycloalkyl, heterocycloalkyl, phenyl, heteroaryl may be further substituted by 1-3 groups selected from R 3aa In some embodiments, R 3b Selected from C 1-6 Alkyl, C3-6 Cycloalkyl, aryl, benzo(5-6 membered cycloalkyl), -O-(4-8 membered heterocycloalkyl), -C(O)-(CH2) m -C 1-6 Alkyl, -C(O)-(CH2) m -C 3-8 Cycloalkyl, -C(O)-(CH2) m -(4-6 membered heterocycloalkyl), -C(O)-(CH2) m -(5-6 membered heteroaryl), -NH-C(O)-(CH2) m -C 1-6 Alkyl, -S(O)2-C 1-6 Alkyl, the cycloalkyl, heterocycloalkyl, aryl, heteroaryl may be further substituted by 1, 2, or 3 groups selected from R 3aa The group substitution;

[0177] In some embodiments, R 3bselected from F, Cl, hydroxy, cyano, amino, methylamino, dimethylamino, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH2F, -CHFCHF2, -CHFCF3, -CF2CH2F, -CF2CHF2, -CF2CF3, -OCHF2, -OCH2F, -OCF3, -OCH2CH2F, -OCH2CHF2, -OCH2CF3, -OCHFCH2F, -OCH CHFCHF2, -OCHFCF3, -OCF2CH2F, -OCF2CHF2, -OCF2CF3, -CH2D, -CHD2, -CD3, -CH2CH2D, -CH2CHD2, -CH2CD3, -CHDCH2D, -CHDCH D2, -CHDCD3, -CD2CH2D, -CD2CHD2, -CD2CD3, -OCHD2, -OCH2D, -OCD3, -OCH2CH2D, -OCH2CHD2, -OCH2CD3, -OCHDCH2D, -OCHDCHD 2, -OCHDCD3, -OCD2CH2D, -OCD2CHD2, -OCD2CD3, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, azetidinyl, oxolanyl, azacyclopentyl, oxhexyl, azacyclohexyl, morpholinyl, piperazinyl, phenyl, pyrrolyl, furyl, thienyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrazinyl, benzocyclopentyl, benzocyclohexyl, benzoazepine, -C(O)CH3, -C(O)CD3, -C(O)CH2CH3, -C(O)- Cyclopropyl, -C(O)-CH2-cyclopropyl, -C(O)-cyclobutyl, -C(O)-CH2-cyclobutyl, -C(O)-cyclopentyl, -C(O)-CH2-cyclopentyl, -C(O)-cyclohexyl, -C(O)-CH2-cyclohexyl, -C(O)-oxolanyl, -C(O)-azetidinyl, -C(O)-oxetanyl, -C(O)-azetidinyl, -C(O)-oxetanyl, -C(O)-CH2-oxolanyl, -C(O)-CH2-azetidinyl, -C(O)-CH2-oxetanyl, -C(O)-CH2- azetidinyl, -C(O)-CH2-oxacyclohexyl, -C(O)-CH2-azacyclohexyl, -C(O)-pyrazolyl, -C(O)-imidazolyl, -C(O)-pyrrolyl, -C(O)-furyl, -C(O)-oxazolyl, -C(O)-isoxazolyl, -C(O)-thiazolyl, -NHC(O)CH3, -S(O)2CH3, or -S(O)CH3,The cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, azetidinyl, oxolanyl, azopentyl, oxhexyl, azohexyl, morpholinyl, piperazinyl, phenyl, pyrrolyl, furyl, thienyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrazinyl, benzocyclopentyl, benzocyclohexyl, benzoazepine, optionally further substituted by 1-3 R, 3aa In some embodiments, R 3b is selected from phenyl, benzocyclopentyl, -C(O)CH3, -C(O)-CH2-azacyclohexyl, -C(O)-pyrazolyl, -S(O)2CH3, wherein the phenyl, benzocyclopentyl, monoheterocyclohexyl, pyrazolyl is optionally further substituted by 1, 2, or 3 groups selected from R 3aa In some embodiments, R 3b is selected from benzocyclopentyl, -C(O)CH3, -C(O)-CH2-azacyclohexyl, -C(O)-pyrazolyl, -S(O)2CH3, wherein the benzocyclopentyl, monoheterocyclohexyl, pyrazolyl is optionally further substituted by 1, 2, or 3 groups selected from halogen, hydroxyl, cyano, SF5, amino, methylamino, dimethylamino, C 1-6 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, -NR aa C(O)-C 1-4 Alkyl, -NR aa C(O)-C 3-6 Cycloalkyl, -C(O)NR aa -C 3-6 Cycloalkyl, -C(O)-C 3-6 Cycloalkyl, -C(O)-(4-6 membered heterocycloalkyl); in some embodiments, R 3bSelected from benzocyclopentyl, -C(O)CH3, -C(O)-CH2-azacyclohexyl, -C(O)-pyrazolyl, -S(O)2CH3, wherein the benzocyclopentyl, monoheterocyclohexyl, pyrazolyl is optionally further substituted by 1, 2, or 3 groups selected from F, Cl, hydroxyl, cyano, SF5, amino, methylamino, dimethylamino, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH2F, -CHFCHF2, -CHFCF3, -CF2CH2F, -CF2CHF2, -CF2CF3, -OCHF2, -OCH2F, -OCF3, -OCH2CH2F, -OCH2CHF2, -OCH2CF3, -OCHFCH2F, -OCHFC HF2, -OCHFCF3, -OCF2CH2F, -OCF2CHF2, -OCF2CF3, -CH2D, -CHD2, -CD3, -CH2CH2D, -CH2CHD2, -CH2CD3, -CHDCH2D, -CHDCHD2, -CHDCD3, -CD2CH2D, -CD2CHD2, -CD2CD3, -OCHD2, -OCH2D, -OCD3, -OCH2CH2D, -OCH2CHD2, -OCH2CD3, -OCHDCH2D, -OCHDCHD2, -OCHDCD3, -OCD2CH2D, -OCD2CHD2, -OCD2CD3, -NHC(O)CH3, -NHC(O)-cyclopropyl, -NHC(O)-cyclobutyl, -C(O)NH-cyclobutyl;

[0178] In some embodiments, R 3b is selected from phenyl, wherein the phenyl group is optionally further substituted by 1, 2, or 3 groups selected from R 3aa The group substitution;

[0179] In some embodiments, R 3b Selected from methyl, ethyl, cyclopropyl,

[0180] R 3aa Selected from halogen, hydroxyl, cyano, =O, SF5, amino, methylamino, dimethylamino, -NH-C 3-6 Cycloalkyl, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, acetyl, -NR aa C(O)-C1-6 Alkyl, -NR aa C(O)-OC 1-6 Alkyl, -NR aa C(O)-C 3-6 Cycloalkyl, -NR aa C(O)-(3-6 membered heterocycloalkyl), -NR aa C(O)-(5-6 membered heteroaryl), -C(O)NR aa -C 3-6 Cycloalkyl, -C(O)-C 3-6 Cycloalkyl, -C(O)-(4-6 membered heterocycloalkyl), 4-6 membered heterocycloalkyl, 5-6 membered heteroaryl, The alkyl, cycloalkyl, heterocycloalkyl, and heteroaryl groups are optionally further substituted by 1 to 3 groups selected from deuterium, halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, acetyl, =O group substitution;

[0181] In some embodiments, R 3aa Selected from halogen, hydroxyl, cyano, =O, SF5, amino, methylamino, dimethylamino, -NH-C 3-6 Cycloalkyl, C 1-6 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkyl, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkyl, deuterated C 1-4 Alkoxy, acetyl, -NR aa C(O)-C 1-4 Alkyl, -NR aa C(O)-OC 1-4 Alkyl, -NR aa C(O)-C 3-6 Cycloalkyl, -NR aa C(O)-(3-6 membered heterocycloalkyl), -NR aa C(O)-(5-6 membered heteroaryl), -C(O)NR aa -C 3-6 Cycloalkyl, -C(O)-C 3-6 Cycloalkyl, -C(O)-(4-6 membered heterocycloalkyl), 4-6 membered heterocycloalkyl, 5-6 membered heteroaryl, The alkyl, cycloalkyl, heterocycloalkyl, and heteroaryl groups are optionally further substituted by 1 to 3 groups selected from deuterium, halogen, hydroxyl, cyano, amino, C 1-2Alkyl, alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, acetyl, =O; in some embodiments, R 3aa Selected from F, Cl, hydroxy, cyano, =O, SF5, amino, methylamino, dimethylamino, -NH-cyclopropyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH2F, -CHFCHF2, -CHFCF3, -CF2CH2F, -CF2CHF2, -CF2CF3, -OCHF2, -OCH2F, -OCF3, -OCH2CH2F, -OCH2CHF2, -OCH2CF3, -OCHFCH2F, -OCHFCHF2, -OCHFCF3, -OCF2C H2F, -OCF2CHF2, -OCF2CF3, -CH2D, -CHD2, -CD3, -CH2CH2D, -CH2CHD2, -CH2CD3, -CHDCH2D, -CHDCHD2, -CHDCD3, -CD2CH2D, -CD2CHD2, -CD2CD3, -OC HD2, -OCH2D, -OCD3, -OCH2CH2D, -OCH2CHD2, -OCH2CD3, -OCHDCH2D, -OCHDCHD2, -OCHDCD3, -OCD2CH2D, -OCD2CHD2, -OCD2CD3, -NHC(O)CH3, acetyl, -NR aa C(O)-C 1-4 Alkyl, -NR aa C(O)-OC 1-4 Alkyl, -NR aa C(O)-deuterated C 1-4 Alkyl, -NHC(O)-cyclopropyl, -NHC(O)-cyclobutyl, -NHC(O)-oxetanyl, -NHC(O)pyrazolyl, -C(O)NH-cyclobutyl, -C(O)-cyclopropyl, -C(O)-cyclobutyl, -C(O)-cyclopentyl, -C(O)-cyclohexyl, -C(O)-azepanyl, -C(O)-azepanyl, -C(O)-oxetanyl, -C(O)-oxolanyl, -C(O)-oxetanyl, azetidinyl, azopentyl, morpholinyl, piperazinyl, phenyl, pyrrolyl, furyl, thienyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrazinyl, The alkyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, oxolanyl, oxhexyl, azetidinyl, Azopentyl, azohexyl, morpholinyl, piperazinyl, phenyl, pyrrolyl, furyl, thienyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrazinyl optionally further substituted by 1-3 groups selected from deuterium, F, Cl, hydroxyl, cyano, amino, methyl, ethyl, methoxy, ethoxy, halo C 1-2 Alkyl, halogenated C 1-2 Alkoxy, acetyl, =O group substitution;

[0182] In some embodiments, R 3aa Selected from halogen, hydroxyl, cyano, =O, SF5, amino, methylamino, dimethylamino, -NH-C 3-6 Cycloalkyl, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, acetyl, -NR aa C(O)-C 1-6 Alkyl, -NR aa C(O)-OC 1-6 Alkyl, -NR aa C(O)-C 3-6 Cycloalkyl, -NR aa C(O)-(3-6 membered heterocycloalkyl), -NR aa C(O)-(5-6 membered heteroaryl), -C(O)NR aa -C 3-6 Cycloalkyl, -C(O)-C 3-6 Cycloalkyl, -C(O)-(4-6 membered heterocycloalkyl), 4-6 membered heterocycloalkyl, 5-6 membered heteroaryl, The alkyl, cycloalkyl, heterocycloalkyl, and heteroaryl groups are optionally further substituted by 1 to 3 groups selected from deuterium, halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, acetyl, =O; in some embodiments, R 3aa Selected from halogen, hydroxyl, cyano, =O, SF5, amino, methylamino, dimethylamino, -NH-C 3-6 Cycloalkyl, C 1-6 Alkyl, C 1-4Alkoxy, halogenated C 1-4 Alkyl, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkyl, deuterated C 1-4 Alkoxy, acetyl, -NR aa C(O)-C 1-4 Alkyl, -NR aa C(O)-OC 1-4 Alkyl, -NR aa C(O)-C 3-6 Cycloalkyl, -NR aa C(O)-(3-6 membered heterocycloalkyl), -NR aa C(O)-(5-6 membered heteroaryl), -C(O)NR aa -C 3-6 Cycloalkyl, -C(O)-C 3-6 Cycloalkyl, -C(O)-(4-6 membered heterocycloalkyl), 4-6 membered heterocycloalkyl, 5-6 membered heteroaryl, The alkyl, cycloalkyl, heterocycloalkyl, and heteroaryl groups are optionally further substituted by 1 to 3 groups selected from deuterium, halogen, hydroxyl, cyano, amino, C 1-2 Alkyl, alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, acetyl, =O; in some embodiments, R 3aaSelected from F, Cl, hydroxy, cyano, =O, SF5, amino, methylamino, dimethylamino, -NH-cyclopropyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH2F, -CHFCHF2, -CHFCF3, -CF2CH2F, -CF2CHF2, -CF2CF3, -OCHF2, -OCH2F, -OCF3, -OCH2CH2F, -OCH2CHF2, -OCH2CF3, -OCHFCH2F, -OCHFCHF2, -OCHFCF3, -OCF2C H2F, -OCF2CHF2, -OCF2CF3, -CH2D, -CHD2, -CD3, -CH2CH2D, -CH2CHD2, -CH2CD3, -CHDCH2D, -CHDCHD2, -CHDCD3, -CD2CH2D, -CD2CHD2, -CD2CD3, -OC HD2, -OCH2D, -OCD3, -OCH2CH2D, -OCH2CHD2, -OCH2CD3, -OCHDCH2D, -OCHDCHD2, -OCHDCD3, -OCD2CH2D, -OCD2CHD2, -OCD2CD3, -NHC(O)CH3, acetyl, -NR aa C(O)-C 1-4 Alkyl, -NR aa C(O)-OC 1-4 Alkyl, -NR aa C(O)-deuterated C 1-4 alkyl, -NHC(O)-cyclopropyl, -NHC(O)-cyclobutyl, -NHC(O)-oxetanyl, -NHC(O)pyrazolyl, -C(O)NH-cyclobutyl, -C(O)-cyclopropyl, -C(O)-cyclobutyl, -C(O)-cyclopentyl, -C(O)-cyclohexyl, -C(O)-azepanyl, -C(O)-azepanyl, -C(O)-oxetanyl, -C(O)-oxolanyl, -C(O)-oxetanyl, azetidinyl, azopentyl, morpholinyl, piperazinyl, phenyl, pyrrolyl, furyl, thienyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrazinyl, The alkyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, oxolanyl, oxhexyl, azetidinyl, Azopentyl, azohexyl, morpholinyl, piperazinyl, phenyl, pyrrolyl, furyl, thienyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrazinyl optionally further substituted by 1-3 groups selected from deuterium, F, Cl, hydroxyl, cyano, amino, methyl, ethyl, methoxy, ethoxy, halo C 1-2 Alkyl, halogenated C 1-2 Alkoxy, acetyl, =O group substitution;

[0183] In some embodiments, R 3aa Selected from halogen, hydroxyl, cyano, SF5, amino, methylamino, dimethylamino, -NH-C 3-6 Cycloalkyl, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, acetyl, -NR aa C(O)-C 1-6 Alkyl, -NR aa C(O)-C 3-6 Cycloalkyl, -C(O)NR aa -C 3-6 Cycloalkyl, -C(O)-C 3-6 Cycloalkyl, -C(O)-(4-6 membered heterocycloalkyl), 4-6 membered heterocycloalkyl, 5-6 membered heteroaryl, The alkyl, cycloalkyl, heterocycloalkyl, and heteroaryl groups are optionally further substituted by 1 to 3 groups selected from deuterium, halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, acetyl, =O; in some embodiments, R 3aa Selected from halogen, hydroxyl, cyano, SF5, amino, methylamino, dimethylamino, -NH-C 3-6 Cycloalkyl, C 1-6 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkyl, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkyl, deuterated C 1-4 Alkoxy, acetyl, -NR aa C(O)-C 1-4 Alkyl, -NR aa C(O)-C 3-6Cycloalkyl, -C(O)NR aa -C 3-6 Cycloalkyl, -C(O)-C 3-6 Cycloalkyl, -C(O)-(4-6 membered heterocycloalkyl), 4-6 membered heterocycloalkyl, 5-6 membered heteroaryl, The alkyl, cycloalkyl, heterocycloalkyl, and heteroaryl groups are optionally further substituted by 1 to 3 groups selected from deuterium, halogen, hydroxyl, cyano, amino, C 1-2 Alkyl, alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, acetyl, =O; in some embodiments, R 3aa Selected from halogen, hydroxyl, cyano, SF5, amino, methylamino, dimethylamino, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, acetyl, -NR aa C(O)-C 1-6 Alkyl, -NR aa C(O)-C 3-6 Cycloalkyl, -C(O)NR aa -C 3-6 Cycloalkyl, -C(O)-C 3-6 Cycloalkyl, -C(O)-(4-6 membered heterocycloalkyl), wherein the alkyl, cycloalkyl, heterocycloalkyl may be further substituted by 1-3 groups selected from halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, acetyl group substituted; in some embodiments, R 3aa Selected from halogen, hydroxyl, cyano, SF5, amino, methylamino, dimethylamino, C 1-6 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkyl, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkyl, deuterated C 1-4 Alkoxy, acetyl, -NR aa C(O)-C 1-4 Alkyl, -NR aa C(O)-C 3-6 Cycloalkyl, -C(O)NR aa -C 3-6 Cycloalkyl, -C(O)-C 3-6Cycloalkyl, -C(O)-(4-6 membered heterocycloalkyl), wherein the alkyl, cycloalkyl, heterocycloalkyl may be further substituted by 1-3 groups selected from halogen, hydroxyl, cyano, amino, C 1-2 Alkyl, alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, acetyl group substituted; in some embodiments, R 3aa Selected from F, Cl, hydroxy, cyano, SF5, amino, methylamino, dimethylamino, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH2F, -CHFCHF2, -CHFCF3, -CF2CH2F, -CF2CHF2, -CF2CF3, -OCHF2, -OCH2F, -OCF3, -OCH2CH2F, -OCH2CHF2, -OCH2CF3, -OCHFCH2F, -OCHFCHF2, -OCHFCF3, -OCF2CH2F, -OCH CF2CHF2, -OCF2CF3, -CH2D, -CHD2, -CD3, -CH2CH2D, -CH2CHD2, -CH2CD3, -CHDCH2D, -CHDCHD2, -CHDCD3, -CD2CH2D, -CD2CHD2, -CD2CD3, -OCHD2 , -OCH2D, -OCD3, -OCH2CH2D, -OCH2CHD2, -OCH2CD3, -OCHDCH2D, -OCHDCHD2, -OCHDCD3, -OCD2CH2D, -OCD2CHD2, -OCD2CD3, -NHC(O)CH3, acetyl, -NR aa C(O)-C 1-4 Alkyl, -NR aa C(O)-deuterated C 1-4 alkyl, -NHC(O)-cyclopropyl, -NHC(O)-cyclobutyl, -C(O)NH-cyclobutyl, -C(O)-cyclopropyl, -C(O)-cyclobutyl, -C(O)-cyclopentyl, -C(O)-cyclohexyl, -C(O)-azepanyl, -C(O)-azepanyl, -C(O)-oxetanyl, -C(O)-oxolanyl, -C(O)-oxetanyl, azetidinyl, azopentyl, morpholinyl, piperazinyl, phenyl, pyrrolyl, furyl, thienyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrazinyl, The cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, oxolanyl, oxhexyl, azetidinyl, Azolidinyl, azetidinyl, azetidinyl, morpholinyl, piperazinyl, phenyl, pyrrolyl, furyl, thienyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrazinyl, Optionally further substituted by 1-3 groups selected from deuterated F, Cl, hydroxy, cyano, amino, methyl, ethyl, methoxy, ethoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, acetyl, =O group substitution;

[0184] In some embodiments, R 3aa is selected from methyl, ethyl, cyclopropyl, cyclobutyl, oxetanyl, azetidinyl;

[0185] R aa Selected from H, C 1-6 Alkyl, halogenated C 1-6 Alkyl or deuterated C 1-6 Alkyl; in some embodiments, R aa Selected from H, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl; in some embodiments, R aa Selected from H;

[0186] m is selected from 0, 1, 2, 3, or 4; in some embodiments, m is selected from 0, 1, or 2; in some embodiments, m is selected from 0 or 1; in some embodiments, m is selected from 0; in some embodiments, m is selected from 1;

[0187] The heteroaryl and heterocycloalkyl groups contain 1, 2, 3, 4 or 5 heteroatoms selected from N, O, S, S(O), S(O)2, P and Si;

[0188] q1, q2, q3, q4 are each independently selected from 0 or 1; in some embodiments, q2 is selected from 0; in some embodiments, q2 and q3 are selected from 0; in some embodiments, q2 and q4 are selected from 0;

[0189] The condition is,

[0190] a) when R3 is selected from halogen, L1 is not -O-CH2-;

[0191] b) R3 is not selected from oxetanyl, -CH2-oxetanyl, -O-oxetanyl;

[0192] c) When L1 is absent and Ar3 is pyridyl or pyrazolyl, R3 and R6 are not phenyl.

[0193] The first embodiment specifically relates to a compound represented by formula (I), and its stereoisomers, deuterated substances, solvates, or pharmaceutically acceptable salts or cocrystals,

[0194] in,

[0195] Ar1 is selected from pyridyl, pyridazinyl, phenyl, 5-membered heteroaryl, 8-10-membered bicyclic carbocyclic group, 8-10-membered bicyclic heterocyclic group, and the Ar1 is optionally substituted by 1-3 selected from R 1a Substituents substituted;

[0196] R 1a Each independently selected from halogen, hydroxy, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, hydroxy C 1-6 Alkyl, C 3-8 Cycloalkyl, 4-8 membered heterocycloalkyl, -OC 3-8 Cycloalkyl, -O-(4-8 membered heterocycloalkyl), carboxyl, 5 membered heteroaryl, wherein the heteroaryl is optionally substituted by 1-3 halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, hydroxyl C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, C 3-6 Cycloalkyl, -SC 1-6 Alkyl and carboxyl group substitution;

[0197] Alternatively, R on adjacent carbon atoms 1a Forming 4-6 membered cycloalkyl, 4-6 membered heterocycloalkyl;

[0198] Ar2 is selected from pyridyl, phenyl, 5-membered heteroaryl, 7-10-membered bicyclic carbocyclic group, 7-10-membered bicyclic heterocyclic group, 4-6-membered monocyclic heterocycloalkyl, 3-6-membered monocyclic cycloalkyl, and said Ar2 is optionally substituted by 1-3 members selected from R 2a The group substitution;

[0199] R 2a Each independently selected from halogen, hydroxy, cyano, =O, amino, methylamino, dimethylamino, C 1-6 Alkyl, C 2-6 Alkenyl, C2-6 Alkynyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, C 3-8 Cycloalkyl, 4-6 membered heterocycloalkyl, -OC 3-8 Cycloalkyl, -O-(4-8 membered heterocycloalkyl), carboxyl, acetyl, aminoacetyl, aminopropionyl;

[0200] L1 is selected from C 1-6 Alkylene, -OC 1-6 Alkylene, C 2-6 In some embodiments, L1 is selected from -OC 1-6 Alkylene, C 2-6 The alkenyl group is absent, and 0-2 methylene groups in the alkylene group are optionally replaced by C=O, NH or O;

[0201] Ar3 is selected from the following groups:

[0202] (i) pyridyl, piperidyl, azacyclohexenyl, wherein the pyridyl, piperidyl, azacyclohexenyl is further substituted by 1-2 groups selected from R3, and optionally substituted by 1-2 groups selected from halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, hydroxyl C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, C 3-6 Cycloalkyl, -SC 1-6 Alkyl and carboxyl group substitution;

[0203] (ii) 5-membered heteroaryl, pyrimidinyl, pyrazinyl, pyridazinyl, 4-5-membered heterocycloalkyl, 6-10-membered bicyclic heterocycloalkyl, piperazinyl, wherein the 5-membered heteroaryl, pyrimidinyl, pyrazinyl, pyridazinyl, heterocycloalkyl, piperazinyl is further substituted by 1-3 groups selected from R6; in some embodiments, selected from 5-membered heteroaryl, pyrimidinyl, pyrazinyl, pyridazinyl, 4-5-membered heterocycloalkyl, 6-10-membered bicyclic heterocycloalkyl, wherein the 5-membered heteroaryl, pyrimidinyl, pyrazinyl, pyridazinyl, heterocycloalkyl is further substituted by 1-3 groups selected from R6;

[0204] R3 is selected from the following groups:

[0205] (1) a 4-6 membered monocyclic heterocycloalkyl group, wherein the 4-6 membered monocyclic heterocycloalkyl group is further substituted by 1-3 groups selected from R 3b The group substitution;

[0206] (2) 8-10 membered heterocyclic alkyl, 7-11 membered spiro heterocyclic alkyl, 5-8 membered bridged heterocyclic alkyl, wherein the heterocyclic alkyl, spiro heterocyclic alkyl, bridged heterocyclic alkyl are optionally further substituted by 1-3 groups selected from halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, -C(O)C 1-4 Alkyl radical substitution;

[0207] (3) 8-10 membered paracycloalkyl, 7-11 membered spirocycloalkyl, 5-8 membered bridged cycloalkyl; the paracycloalkyl, spirocycloalkyl, bridged cycloalkyl may be further substituted by 1-3 groups selected from halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy group substitution;

[0208] (4)-O-(CH2) m -(4-6 membered monocyclic heterocycloalkyl), -O-(CH2) m -(4-6 membered monocyclic cycloalkyl), -O-(CH2) m -(5-6 membered heteroaryl), -O-(CH2) m -phenyl), the 4-6 membered monocyclic heterocycloalkyl, 4-6 membered monocyclic cycloalkyl, 5-6 membered heteroaryl, phenyl is further substituted by 1-3 members selected from R 3b The group substitution;

[0209] (5)-C 1-3 Alkylene-(4-6 membered monocyclic heterocycloalkyl), -C 0-3 Alkylene-(4-6 membered monocyclic cycloalkyl), -C 0-3 Alkylene-(5-6 membered heteroaryl), -C 0-3 Alkylenephenyl, further substituted by 1-3 groups selected from R 3b The group substitution;

[0210] (6)C 2-6Alkynyl, halogen, N3, the alkynyl is optionally further substituted by 1-2 groups selected from R 3b The group substitution;

[0211] (7)-C(O)-NR aa R4, -NR aa -C(O)R4, -C(O)-C 0-3 Alkylene-R4, -NR aa R4, -NR aa -C(O)C 1-3 Alkyl, -C(O)-N(R aa )2; In some embodiments, selected from -C(O)-NR aa R4, -NR aa -C(O)R4, -C(O)-C 0-3 Alkylene-R4, -NR aa R4;

[0212] R4 and R6 are each independently selected from a 3-15 membered carbocyclic ring or a 4-15 membered heterocyclic ring, wherein the carbocyclic ring or heterocyclic ring is optionally further substituted by 1-5 members selected from R 3b The group substitution;

[0213] R 3b Selected from halogen, =O, Hydroxyl, cyano, amino, methylamino, dimethylamino, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, -(CH2) m -C 3-6 Cycloalkyl, -(CH2) m -(4-10 membered heterocycloalkyl), aryl, 5-10 membered heteroaryl, benzo(5-6 membered cycloalkyl), benzo(5-6 membered heterocycloalkyl), 5-6 membered heteroaryl and 5-6 membered cycloalkyl, -OC 3-8 Cycloalkyl, -O-(4-8 membered heterocycloalkyl), carboxyl, -C(O)-(CH2) m -C 1-6 Alkyl, -C(O)-(CH2) m -Deuterated C 1-6 Alkyl, -C(O)-(CH2) m -C 3-8 Cycloalkyl, -C(O)-(CH2) m -(4-6 membered heterocycloalkyl), -C(O)-(CH2) m -(5-6 membered heteroaryl), -NH-C(O)-(CH2)m -C 1-6 Alkyl, -NH-C(O)-(CH2) m -C 3-8 Cycloalkyl, -S(O)2-C 1-6 Alkyl, -S(O)-C 1-6 Alkyl or -NH-C(O)-(CH2) m -(5-6 membered heteroaryl), wherein the cycloalkyl, heterocycloalkyl, aryl, or heteroaryl group is optionally further substituted by 1-3 members selected from R 3aa The group substitution;

[0214] R 3aa Selected from halogen, hydroxyl, cyano, =O, SF5, amino, methylamino, dimethylamino, -NH-C 3-6 Cycloalkyl, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, acetyl, -NR aa C(O)-C 1-6 Alkyl, -NR aa C(O)-OC 1-6 Alkyl, -NR aa C(O)-C 3-6 Cycloalkyl, -NR aa C(O)-(3-6 membered heterocycloalkyl), -NR aa C(O)-(5-6 membered heteroaryl), -C(O)NR aa -C 3-6 Cycloalkyl, -C(O)-C 3-6 Cycloalkyl, -C(O)-(4-6 membered heterocycloalkyl), 4-6 membered heterocycloalkyl, 5-6 membered heteroaryl, The alkyl, cycloalkyl, heterocycloalkyl, and heteroaryl groups are optionally further substituted by 1 to 3 groups selected from deuterium, halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, acetyl, =O group substitution;

[0215] Each R aa Each independently selected from H, C 1-6 Alkyl, halogenated C 1-6 Alkyl or deuterated C 1-6 alkyl;

[0216] m is selected from 0, 1, 2, 3 or 4;

[0217] The heteroaryl and heterocycloalkyl groups contain 1-5 heteroatoms selected from N, O, S, S(O), S(O)2, P, and Si;

[0218] The condition is,

[0219] When R3 is selected from halogen, L1 is not -O-CH2-;

[0220] R3 is not selected from oxetane, -CH2-oxetane, -O-oxetane;

[0221] When L1 is absent and Ar3 is pyridyl or pyrazolyl, R3 and R6 are not phenyl.

[0222] The second specific embodiment relates to the compound represented by formula (I), and its stereoisomers, deuterated substances, solvates, or pharmaceutically acceptable salts or cocrystals,

[0223] in,

[0224] Ar1 is selected from pyridyl, pyridazinyl, phenyl, 5-membered heteroaryl, 8-10-membered bicyclic carbocyclic group, 8-10-membered bicyclic heterocyclic group, and the Ar1 is optionally substituted by 1-3 selected from R 1a Substituents substituted;

[0225] R 1a Each independently selected from halogen, hydroxy, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, hydroxy C 1-6 Alkyl, C 3-8 Cycloalkyl, 4-8 membered heterocycloalkyl, -OC 3-8 Cycloalkyl, -O-(4-8 membered heterocycloalkyl), carboxyl, 5 membered heteroaryl, wherein the heteroaryl is optionally substituted by 1-3 halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, hydroxyl C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, C 3-6 Cycloalkyl, -SC 1-6 Alkyl and carboxyl group substitution;

[0226] Alternatively, R on adjacent carbon atoms 1a Forming 4-6 membered cycloalkyl, 4-6 membered heterocycloalkyl;

[0227] Ar2 is selected from pyridyl, phenyl, 5-membered heteroaryl, 7-10-membered bicyclic carbocyclic group, 7-10-membered bicyclic heterocyclic group, 4-6-membered monocyclic heterocycloalkyl, 3-6-membered monocyclic cycloalkyl, and said Ar2 is optionally substituted by 1-3 members selected from R 2a The group substitution;

[0228] R 2a Each independently selected from halogen, hydroxy, cyano, =O, amino, methylamino, dimethylamino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, C 3-8 Cycloalkyl, 4-6 membered heterocycloalkyl, -OC 3-8 Cycloalkyl, -O-(4-8 membered heterocycloalkyl), carboxyl, acetyl, aminoacetyl, aminopropionyl;

[0229] L1 is selected from -OC 1-6 Alkylene, C 2-6 Alkenyl, wherein 0-2 methylene groups in the alkylene group are optionally replaced by C=O, NH or O;

[0230] Ar3 is selected from the following groups:

[0231] (i) pyridyl, piperidyl, azacyclohexenyl, wherein the pyridyl, piperidyl, azacyclohexenyl is further substituted by 1-2 groups selected from R3, and optionally substituted by 1-2 groups selected from halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, hydroxyl C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, C 3-6 Cycloalkyl, -SC 1-6 Alkyl and carboxyl group substitution;

[0232] (ii) 5-membered heteroaryl, pyrimidinyl, pyrazinyl, pyridazinyl, wherein the 5-membered heteroaryl, pyrimidinyl, pyrazinyl, pyridazinyl is further substituted by 1-3 groups selected from R6;

[0233] R3 is selected from the following groups:

[0234] (1) a 4-6 membered monocyclic heterocycloalkyl group, wherein the 4-6 membered monocyclic heterocycloalkyl group is further substituted by 1-3 groups selected from R 3b The group substitution;

[0235] (2) 8-10 membered heterocyclic alkyl, 7-11 membered spiro heterocyclic alkyl, 5-8 membered bridged heterocyclic alkyl, wherein the heterocyclic alkyl, spiro heterocyclic alkyl, bridged heterocyclic alkyl are optionally further substituted by 1-3 groups selected from halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, -C(O)C 1-4 Alkyl radical substitution;

[0236] (3) 8-10 membered paracycloalkyl, 7-11 membered spirocycloalkyl, 5-8 membered bridged cycloalkyl; the paracycloalkyl, spirocycloalkyl, bridged cycloalkyl may be further substituted by 1-3 groups selected from halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy group substitution;

[0237] (4)-O-(CH2) m -(4-6 membered monocyclic heterocycloalkyl), -O-(CH2) m -(4-6 membered monocyclic cycloalkyl), -O-(CH2) m -(5-6 membered heteroaryl), -O-(CH2) m -phenyl), the 4-6 membered monocyclic heterocycloalkyl, 4-6 membered monocyclic cycloalkyl, 5-6 membered heteroaryl, phenyl is further substituted by 1-3 members selected from R 3b The group substitution;

[0238] (5)-C 1-3 Alkylene-(4-6 membered monocyclic heterocycloalkyl), -C 0-3 Alkylene-(4-6 membered monocyclic cycloalkyl), -C 0-3 Alkylene-(5-6 membered heteroaryl), -C 0-3Alkylenephenyl, further substituted by 1-3 groups selected from R 3b The group substitution;

[0239] (6)C 2-6 Alkynyl, halogen, N3, the alkynyl is optionally further substituted by 1-2 groups selected from R 3b The group substitution;

[0240] (7)-C(O)-NR aa R4, -NR aa -C(O)R4, -C(O)-C 0-3 Alkylene-R4, -NR aa R4;

[0241] R4 and R6 are each independently selected from a 3-15 membered carbocyclic ring or a 4-15 membered heterocyclic ring, wherein the carbocyclic ring or heterocyclic ring is optionally further substituted by 1-5 members selected from R 3b The group substitution;

[0242] R 3b Selected from halogen, =O, Hydroxyl, cyano, amino, methylamino, dimethylamino, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, -(CH2) m -C 3-6 Cycloalkyl, -(CH2) m -(4-10 membered heterocycloalkyl), aryl, 5-10 membered heteroaryl, benzo(5-6 membered cycloalkyl), benzo(5-6 membered heterocycloalkyl), 5-6 membered heteroaryl and 5-6 membered cycloalkyl, -OC 3-8 Cycloalkyl, -O-(4-8 membered heterocycloalkyl), carboxyl, -C(O)-(CH2) m -C 1-6 Alkyl, -C(O)-(CH2) m -Deuterated C 1-6 Alkyl, -C(O)-(CH2) m -C 3-8 Cycloalkyl, -C(O)-(CH2) m -(4-6 membered heterocycloalkyl), -C(O)-(CH2) m -(5-6 membered heteroaryl), -NH-C(O)-(CH2) m -C 1-6 Alkyl, -NH-C(O)-(CH2) m -C 3-8 Cycloalkyl, -S(O)2-C1-6 Alkyl, -S(O)-C 1-6 Alkyl, the cycloalkyl, heterocycloalkyl, aryl, heteroaryl may be further substituted by 1-3 groups selected from R 3aa The group substitution;

[0243] R 3aa Selected from halogen, hydroxyl, cyano, =O, SF5, amino, methylamino, dimethylamino, -NH-C 3-6 Cycloalkyl, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, acetyl, -NR aa C(O)-C 1-6 Alkyl, -NR aa C(O)-OC 1-6 Alkyl, -NR aa C(O)-C 3-6 Cycloalkyl, -NR aa C(O)-(3-6 membered heterocycloalkyl), -NR aa C(O)-(5-6 membered heteroaryl), -C(O)NR aa -C 3-6 Cycloalkyl, -C(O)-C 3-6 Cycloalkyl, -C(O)-(4-6 membered heterocycloalkyl), 4-6 membered heterocycloalkyl, 5-6 membered heteroaryl, The alkyl, cycloalkyl, heterocycloalkyl, and heteroaryl groups are optionally further substituted by 1 to 3 groups selected from deuterium, halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, acetyl, =O group substitution;

[0244] R aa Selected from H, C 1-6 Alkyl, halogenated C 1-6 Alkyl or deuterated C 1-6 alkyl;

[0245] m is selected from 0, 1, 2, 3 or 4;

[0246] The heteroaryl and heterocycloalkyl groups contain 1-5 heteroatoms selected from N, O, S, S(O), S(O)2, P, and Si;

[0247] The condition is,

[0248] When R3 is selected from halogen, L1 is not -O-CH2-;

[0249] R3 is not selected from oxetanyl, -CH2-oxetanyl, -O-oxetanyl.

[0250] The third embodiment relates to a compound represented by formula (I), and its stereoisomers, deuterated substances, solvates, or pharmaceutically acceptable salts or cocrystals.

[0251] in,

[0252] Ar1 is selected from pyridyl, pyridazinyl, phenyl, 5-membered heteroaryl, 8-10-membered bicyclic carbocyclic group, 8-10-membered bicyclic heterocyclic group, and the Ar1 is optionally substituted by 1-3 selected from R 1a Substituents substituted;

[0253] R 1a Each independently selected from halogen, hydroxy, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, hydroxy C 1-6 Alkyl, C 3-8 Cycloalkyl, 4-8 membered heterocycloalkyl, -OC 3-8 Cycloalkyl, -O-(4-8 membered heterocycloalkyl), carboxyl;

[0254] Alternatively, R on adjacent carbon atoms 1a Forming 4-6 membered cycloalkyl, 4-6 membered heterocycloalkyl;

[0255] Ar2 is selected from pyridyl, phenyl, 5-membered heteroaryl, 7-10-membered bicyclic carbocyclic group, 7-10-membered bicyclic heterocyclic group, 4-6-membered monocyclic heterocycloalkyl, 3-6-membered monocyclic cycloalkyl, and said Ar2 is optionally substituted by 1-3 members selected from R 2a The group substitution;

[0256] R 2a Each independently selected from halogen, hydroxy, cyano, =O, amino, methylamino, dimethylamino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, C 3-8 Cycloalkyl, 4-6 membered heterocycloalkyl, -OC3-8 Cycloalkyl, -O-(4-8 membered heterocycloalkyl), carboxyl, acetyl, aminoacetyl, aminopropionyl;

[0257] L1 is selected from -OC 1-6 Alkylene, C 2-6 Alkenyl, wherein 0-2 methylene groups in the alkylene group are optionally replaced by C=O, NH or O;

[0258] Ar3 is selected from the following groups:

[0259] (i) pyridyl and piperidyl, wherein the pyridyl and piperidyl are further substituted by 1-2 groups selected from R3, and optionally substituted by 1-2 groups selected from halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, hydroxyl C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, C 3-6 Cycloalkyl, -SC 1-6 Alkyl and carboxyl group substitution;

[0260] (ii) 5-membered heteroaryl, pyrimidinyl, pyrazinyl, pyridazinyl, wherein the 5-membered heteroaryl, pyrimidinyl, pyrazinyl, pyridazinyl is further substituted by 1-3 groups selected from R6;

[0261] R3 is selected from the following groups:

[0262] (1) a 4-6 membered monocyclic heterocycloalkyl group, wherein the 4-6 membered monocyclic heterocycloalkyl group is further substituted by 1-3 groups selected from R 3b The group substitution;

[0263] (2) 8-10 membered heterocyclic alkyl, 7-11 membered spiro heterocyclic alkyl, 5-8 membered bridged heterocyclic alkyl, wherein the heterocyclic alkyl, spiro heterocyclic alkyl, bridged heterocyclic alkyl are optionally further substituted by 1-3 groups selected from halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, -C(O)C 1-4 Alkyl radical substitution;

[0264] (3) 8-10 membered paracycloalkyl, 7-11 membered spirocycloalkyl, 5-8 membered bridged cycloalkyl; the paracycloalkyl, spirocycloalkyl, bridged cycloalkyl may be further substituted by 1-3 groups selected from halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy group substitution;

[0265] (4)-O-(CH2) m -(4-6 membered monocyclic heterocycloalkyl), -O-(CH2) m -(4-6 membered monocyclic cycloalkyl), -O-(CH2) m -(5-6 membered heteroaryl), -O-(CH2) m -phenyl), the 4-6 membered monocyclic heterocycloalkyl, 4-6 membered monocyclic cycloalkyl, 5-6 membered heteroaryl, phenyl is further substituted by 1-3 members selected from R 3b The group substitution;

[0266] (5)-C 1-3 Alkylene-(4-6 membered monocyclic heterocycloalkyl), -C 0-3 Alkylene-(4-6 membered monocyclic cycloalkyl), -C 0-3 Alkylene-(5-6 membered heteroaryl), -C 0-3 Alkylenephenyl, further substituted by 1-3 groups selected from R 3b The group substitution;

[0267] (6)C 2-6 Alkynyl, halogen, N3, the alkynyl is optionally further substituted by 1-2 groups selected from R 3b The group substitution;

[0268] (7)-C(O)-NR aa R4, -NR aa -C(O)R4, -C(O)-C 0-3 Alkylene-R4, -NR aa R4;

[0269] R4 and R6 are each independently selected from a 3-15 membered carbocyclic ring or a 4-15 membered heterocyclic ring, wherein the carbocyclic ring or heterocyclic ring is optionally further substituted by 1-5 members selected from R 3b The group substitution;

[0270] R 3b Selected from halogen, =O, Hydroxyl, cyano, amino, methylamino, dimethylamino, C 1-6 Alkyl, C 1-6Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, -(CH2) m -C 3-6 Cycloalkyl, -(CH2) m -(4-10 membered heterocycloalkyl), aryl, 5-10 membered heteroaryl, benzo(5-6 membered cycloalkyl), benzo(5-6 membered heterocycloalkyl), 5-6 membered heteroaryl and 5-6 membered cycloalkyl, -OC 3-8 Cycloalkyl, -O-(4-8 membered heterocycloalkyl), carboxyl, -C(O)-(CH2) m -C 1-6 Alkyl, -C(O)-(CH2) m -Deuterated C 1-6 Alkyl, -C(O)-(CH2) m -C 3-8 Cycloalkyl, -C(O)-(CH2) m -(4-6 membered heterocycloalkyl), -C(O)-(CH2) m -(5-6 membered heteroaryl), -NH-C(O)-(CH2) m -C 1-6 Alkyl, -NH-C(O)-(CH2) m -C 3-8 Cycloalkyl, -S(O)2-C 1-6 Alkyl, -S(O)-C 1-6 Alkyl, the cycloalkyl, heterocycloalkyl, aryl, heteroaryl may be further substituted by 1-3 groups selected from R 3aa In some embodiments, R 3b Selected from halogen, =O, hydroxy, cyano, amino, methylamino, dimethylamino, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, -(CH2) m -C 3-6 Cycloalkyl, -(CH2) m -(4-8 membered heterocycloalkyl), aryl, 5-10 membered heteroaryl, benzo(5-6 membered cycloalkyl), benzo(5-6 membered heterocycloalkyl), 5-6 membered heteroaryl and 5-6 membered cycloalkyl, -OC 3-8 Cycloalkyl, -O-(4-8 membered heterocycloalkyl), carboxyl, -C(O)-(CH2) m -C 1-6Alkyl, -C(O)-(CH2) m -Deuterated C 1-6 Alkyl, -C(O)-(CH2) m -C 3-8 Cycloalkyl, -C(O)-(CH2) m -(4-6 membered heterocycloalkyl), -C(O)-(CH2) m -(5-6 membered heteroaryl), -NH-C(O)-(CH2) m -C 1-6 Alkyl, -S(O)2-C 1-6 Alkyl, -S(O)-C 1-6 Alkyl, the cycloalkyl, heterocycloalkyl, aryl, heteroaryl may be further substituted by 1-3 groups selected from R 3aa The group substitution;

[0271] R 3aa Selected from halogen, hydroxyl, cyano, =O, SF5, amino, methylamino, dimethylamino, -NH-C 3-6 Cycloalkyl, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, acetyl, -NR aa C(O)-C 1-6 Alkyl, -NR aa C(O)-OC 1-6 Alkyl, -NR aa C(O)-C 3-6 Cycloalkyl, -NR aa C(O)-(3-6 membered heterocycloalkyl), -NR aa C(O)-(5-6 membered heteroaryl), -C(O)NR aa -C 3-6 Cycloalkyl, -C(O)-C 3-6 Cycloalkyl, -C(O)-(4-6 membered heterocycloalkyl), 4-6 membered heterocycloalkyl, 5-6 membered heteroaryl, The alkyl, cycloalkyl, heterocycloalkyl, and heteroaryl groups are optionally further substituted by 1 to 3 groups selected from deuterium, halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, acetyl, =O; in some embodiments, R 3aaSelected from halogen, hydroxyl, cyano, =O, SF5, amino, methylamino, dimethylamino, -NH-C 3-6 Cycloalkyl, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, acetyl, -NR aa C(O)-C 1-6 Alkyl, -NR aa C(O)-OC 1-6 Alkyl, -NR aa C(O)-C 3-6 Cycloalkyl, -NR aa C(O)-(3-6 membered heterocycloalkyl), -NR aa C(O)-(5-6 membered heteroaryl), -C(O)NR aa -C 3-6 Cycloalkyl, -C(O)-C 3-6 Cycloalkyl, -C(O)-(4-6 membered heterocycloalkyl), 4-6 membered heterocycloalkyl, 5-6 membered heteroaryl, The alkyl, cycloalkyl, heterocycloalkyl, and heteroaryl groups are optionally further substituted by 1 to 3 groups selected from deuterium, halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, acetyl, =O group substitution;

[0272] R aa Selected from H, C 1-6 Alkyl, halogenated C 1-6 Alkyl or deuterated C 1-6 alkyl;

[0273] m is selected from 0, 1, 2, 3 or 4;

[0274] The heteroaryl and heterocycloalkyl groups contain 1-5 heteroatoms selected from N, O, S, S(O), S(O)2, P, and Si;

[0275] The condition is,

[0276] a) when R3 is selected from halogen, L1 is not -O-CH2-;

[0277] b) R3 is not selected from oxetanyl, -CH2-oxetanyl, or -O-oxetanyl.

[0278] A specific fourth embodiment relates to a compound of formula (I), and stereoisomers, deuterated forms, solvates, or pharmaceutically acceptable salts or cocrystals thereof, wherein

[0279] in,

[0280] Ar1 is selected from pyridyl, phenyl, 5-membered heteroaryl, 8-10-membered bicyclic carbocyclic group, 8-10-membered bicyclic heterocyclic group, and said Ar1 is optionally replaced by 1-3 selected from R 1a Substituents substituted;

[0281] R 1a Each independently selected from halogen, hydroxy, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, hydroxy C 1-6 Alkyl, C 3-8 Cycloalkyl, 4-8 membered heterocycloalkyl, -OC 3-8 Cycloalkyl, -O-(4-8 membered heterocycloalkyl), carboxyl; in some embodiments, R 1a Each independently selected from halogen, hydroxy, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, hydroxy C 1-6 Alkyl, C 3-8 Cycloalkyl, C 4-8 Heterocycloalkyl, carboxyl;

[0282] Alternatively, R on adjacent carbon atoms 1a Forming 4-6 membered cycloalkyl, 4-6 membered heterocycloalkyl;

[0283] Ar2 is selected from pyridyl, phenyl, 5-membered heteroaryl, 7-10-membered bicyclic carbocyclic group, 7-10-membered bicyclic heterocyclic group, 4-6-membered monocyclic heterocycloalkyl, 3-6-membered monocyclic cycloalkyl, and said Ar2 is optionally substituted by 1-3 members selected from R 2a The group substitution;

[0284] R 2a Each independently selected from halogen, hydroxy, cyano, =O, amino, methylamino, dimethylamino, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C1-6 Alkyl, deuterated C 1-6 Alkoxy, C 3-8 Cycloalkyl, 4-6 membered heterocycloalkyl, -OC 3-8 Cycloalkyl, -O-(4-8 membered heterocycloalkyl), carboxyl, acetyl, aminoacetyl, aminopropionyl;

[0285] L1 is selected from -OC 1-6 Alkylene, C 2-6 Alkenyl, wherein 0-2 methylene groups in the alkylene group are optionally replaced by C=O, NH or O;

[0286] Ar3 is selected from the following groups:

[0287] (i) pyridyl and piperidyl, wherein the pyridyl and piperidyl are further substituted by 1-2 groups selected from R3, and optionally substituted by 1-2 groups selected from halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, hydroxyl C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, C 3-6 Cycloalkyl, -SC 1-6 Alkyl and carboxyl group substitution;

[0288] (ii) 5-membered heteroaryl, pyrimidinyl, pyrazinyl, pyridazinyl, wherein the 5-membered heteroaryl, pyrimidinyl, pyrazinyl, pyridazinyl is further substituted by 1-3 groups selected from R6; in some embodiments, Ar3 is selected from the following groups:

[0289] (i) pyridyl, said pyridyl being further substituted by 1-2 groups selected from R3, and optionally substituted by 1-2 groups selected from halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, hydroxyl C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, C 3-6 Cycloalkyl, -SC 1-6 Alkyl and carboxyl group substitution;

[0290] (ii) 5-membered heteroaryl, pyrimidinyl, pyrazinyl, pyridazinyl, wherein the 5-membered heteroaryl, pyrimidinyl, pyrazinyl, pyridazinyl is further substituted by 1-3 groups selected from R6;

[0291] R3 is selected from the following groups:

[0292] (1) a 4-6 membered monocyclic heterocycloalkyl group, wherein the 4-6 membered monocyclic heterocycloalkyl group is further substituted by 1-3 groups selected from R 3b The group substitution;

[0293] (2) 8-10 membered heterocyclic alkyl, 7-11 membered spiro heterocyclic alkyl, 5-8 membered bridged heterocyclic alkyl, wherein the heterocyclic alkyl, spiro heterocyclic alkyl, bridged heterocyclic alkyl are optionally further substituted by 1-3 groups selected from halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy group substitution;

[0294] (3) 8-10 membered paracycloalkyl, 7-11 membered spirocycloalkyl, 5-8 membered bridged cycloalkyl; the paracycloalkyl, spirocycloalkyl, bridged cycloalkyl may be further substituted by 1-3 groups selected from halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy group substitution;

[0295] (4)-O-(CH2) m -(4-6 membered monocyclic heterocycloalkyl), -O-(CH2) m -(4-6 membered monocyclic cycloalkyl), -O-(CH2) m -(5-6 membered heteroaryl), -O-(CH2) m -phenyl), the 4-6 membered monocyclic heterocycloalkyl, 4-6 membered monocyclic cycloalkyl, 5-6 membered heteroaryl, phenyl is further substituted by 1-3 members selected from R 3b In some embodiments, the group selected from -O-(CH2) m -(4-6 membered monocyclic heterocycloalkyl), -O-(CH2) m -(4-6 membered monocyclic cycloalkyl), -O-(CH2) m -(5-6 membered heteroaryl), wherein the 4-6 membered monocyclic heterocycloalkyl, 4-6 membered monocyclic cycloalkyl, 5-6 membered heteroaryl is further substituted by 1-3 members selected from R3b The group substitution;

[0296] (5)-C 1-3 Alkylene-(4-6 membered monocyclic heterocycloalkyl), -C 0-3 Alkylene-(4-6 membered monocyclic cycloalkyl), -C 0-3 Alkylene-(5-6 membered heteroaryl), -C 0-3 Alkylenephenyl, further substituted by 1-3 groups selected from R 3b In some embodiments, the group selected from -C 1-3 Alkylene-(4-6 membered monocyclic heterocycloalkyl), -C 0-3 Alkylene-(4-6 membered monocyclic cycloalkyl), -C 0-3 Alkylene-(5-6 membered heteroaryl), further substituted by 1-3 groups selected from R 3b The group substitution;

[0297] (6)C 2-6 Alkynyl, halogen, N3, the alkynyl is optionally further substituted by 1-2 groups selected from R 3b The group substitution;

[0298] (7)-C(O)-NR aa R4, -NR aa -C(O)R4, -C(O)-C 0-3 Alkylene-R4, -NR aa R4;

[0299] R4 and R6 are each independently selected from a 3-15 membered carbocyclic ring or a 4-15 membered heterocyclic ring, wherein the carbocyclic ring or heterocyclic ring is optionally further substituted by 1-5 members selected from R 3b The group substitution;

[0300] R 3b Selected from halogen, hydroxy, cyano, amino, methylamino, dimethylamino, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, C 3-6 Cycloalkyl, 4-8 membered heterocycloalkyl, aryl, heteroaryl, benzo(5-6 membered cycloalkyl), benzo(5-6 membered heterocycloalkyl), 5-6 membered heteroaryl and 5-6 membered cycloalkyl, -OC 3-8 Cycloalkyl, -O-(4-8 membered heterocycloalkyl), carboxyl, -C(O)-(CH2) m -C 1-6 Alkyl, -C(O)-(CH2) m -Deuterated C 1-6Alkyl, -C(O)-(CH2) m -C 3-8 Cycloalkyl, -C(O)-(CH2) m -(4-6 membered heterocycloalkyl), -C(O)-(CH2) m -(5-6 membered heteroaryl), -NH-C(O)-(CH2) m -C 1-6 Alkyl, -S(O)2-C 1-6 Alkyl, -S(O)-C 1-6 Alkyl, the cycloalkyl, heterocycloalkyl, aryl, heteroaryl may be further substituted by 1-3 groups selected from R 3aa In some embodiments, R 3b Selected from halogen, hydroxy, cyano, amino, methylamino, dimethylamino, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, C 3-6 Cycloalkyl, 4-8 membered heterocycloalkyl, aryl, heteroaryl, benzo(5-6 membered cycloalkyl), benzo(5-6 membered heterocycloalkyl), 5-6 membered heteroaryl and 5-6 membered cycloalkyl, -OC 3-8 Cycloalkyl, -O-(4-8 membered heterocycloalkyl), carboxyl, -C(O)-(CH2) m -C 1-6 Alkyl, -C(O)-(CH2) m -C 3-8 Cycloalkyl, -C(O)-(CH2) m -(4-6 membered heterocycloalkyl), -C(O)-(CH2) m -(5-6 membered heteroaryl), -NH-C(O)-(CH2) m -C 1-6 Alkyl, -S(O)2-C 1-6 Alkyl, -S(O)-C 1-6 Alkyl, the cycloalkyl, heterocycloalkyl, aryl, heteroaryl may be further substituted by 1-3 groups selected from R 3aa The group substitution;

[0301] R 3aa Selected from halogen, hydroxyl, cyano, SF5, amino, methylamino, dimethylamino, -NH-C 3-6 Cycloalkyl, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C1-6 Alkyl, deuterated C 1-6 Alkoxy, acetyl, -NR aa C(O)-C 1-6 Alkyl, -NR aa C(O)-C 3-6 Cycloalkyl, -C(O)NR aa -C 3-6 Cycloalkyl, -C(O)-C 3-6 Cycloalkyl, -C(O)-(4-6 membered heterocycloalkyl), 4-6 membered heterocycloalkyl, 5-6 membered heteroaryl, The alkyl, cycloalkyl, heterocycloalkyl, and heteroaryl groups are optionally further substituted by 1 to 3 groups selected from deuterium, halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, acetyl, =O; in some embodiments, R 3aa Selected from halogen, hydroxyl, cyano, SF5, amino, methylamino, dimethylamino, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, acetyl, -NR aa C(O)-C 1-6 Alkyl, -NR aa C(O)-C 3-6 Cycloalkyl, -C(O)NR aa -C 3-6 Cycloalkyl, -C(O)-C 3-6 Cycloalkyl, -C(O)-(4-6 membered heterocycloalkyl), wherein the alkyl, cycloalkyl, heterocycloalkyl may be further substituted by 1-3 groups selected from halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, acetyl group substitution;

[0302] R aa Selected from H, C 1-6 Alkyl, halogenated C 1-6 Alkyl or deuterated C 1-6 alkyl;

[0303] m is selected from 0, 1, 2, 3 or 4;

[0304] The heteroaryl and heterocycloalkyl groups contain 1-5 heteroatoms selected from N, O, S, S(O), S(O)2, P, and Si;

[0305] Provided that, when R3 is selected from halogen, L1 is not -O-CH2-, and R3 is not selected from oxetanyl.

[0306] A specific fifth embodiment relates to a compound of formula (I), and stereoisomers, deuterated forms, solvates, or pharmaceutically acceptable salts or cocrystals thereof, wherein

[0307] Ar1 is selected from pyridyl, pyridazinyl, and said Ar1 is optionally substituted by 1-3 groups selected from halogen, hydroxyl, cyano, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-2 Alkyl, deuterated C 1-2 Alkoxy, hydroxy C 1-2 Alkyl, C 3-4 Cycloalkyl, -OC 3-4 Cycloalkyl, -O-(4-6 membered heterocycloalkyl), carboxyl or 5 membered heteroaryl, wherein the heteroaryl is optionally substituted by 1-3 halogen, hydroxyl, cyano, amino, C 1-2 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, hydroxyl C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkyl, deuterated C 1-2 Alkoxy, C 3-4 Cycloalkyl, -SC 1-2 Alkyl and carboxyl group substitution;

[0308] Ar2 is selected from pyridyl, phenyl, and said Ar2 is optionally substituted by 1-3 groups selected from halogen, hydroxyl, cyano, amino, C 1-2 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkyl, deuterated C 1-2 Alkoxy, cyclopropyl, oxetanyl, azetidinyl, -O-cyclopropyl, carboxyl, acetyl, aminoacetyl, aminopropionyl group substitution;

[0309] L1 is selected from -O-*, -N(CH3)-*, -OCH2-*, -OCH2CH2-*, -OCH2-C(O)-*, -CH=CH-* or is absent, * represents the connection site between L1 and Ar3; In some embodiments, L1 is selected from -OCH2-*, -OCH2CH2-*, -OCH2-C(O)-*, -CH=CH-* or is absent, * represents the connection site between L1 and Ar3;

[0310] Ar3 is selected from the following groups:

[0311] (i) pyridyl, piperidyl or azacyclohexenyl, wherein the pyridyl, piperidyl or azacyclohexenyl is further substituted by 1-2 groups selected from R3, and optionally substituted by 1-2 groups selected from halogen, hydroxyl, cyano, amino, C 1-2 Alkyl, hydroxyl C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkyl, deuterated C 1-2 Alkoxy, C 3-4 radical substitution of cycloalkyl groups;

[0312] (ii) 5-membered heteroaryl, pyrimidinyl, pyrazinyl, pyridazinyl, 4-5-membered heterocycloalkyl, 6-10-membered bicyclic heterocycloalkyl, piperazinyl, wherein the 5-membered heteroaryl, pyrimidinyl, pyrazinyl, pyridazinyl, heterocycloalkyl, piperazinyl is further substituted by 1-3 groups selected from R6; in some embodiments, selected from 5-membered heteroaryl, pyrimidinyl, pyrazinyl, pyridazinyl, 4-5-membered heterocycloalkyl, 6-10-membered bicyclic heterocycloalkyl, wherein the 5-membered heteroaryl, pyrimidinyl, pyrazinyl, pyridazinyl, heterocycloalkyl is further substituted by 1-3 groups selected from R6;

[0313] R3 is selected from the following groups:

[0314] (1) a 4-6 membered monocyclic heterocycloalkyl group, wherein the 4-6 membered monocyclic heterocycloalkyl group is further substituted by 1-3 groups selected from R 3b The group substitution;

[0315] (2) 8-10 membered heterocyclic alkyl, 7-11 membered spiro heterocyclic alkyl, 5-8 membered bridged heterocyclic alkyl, wherein the heterocyclic alkyl, spiro heterocyclic alkyl, bridged heterocyclic alkyl are optionally further substituted by 1-3 groups selected from halogen, hydroxyl, cyano, amino, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkyl, deuterated C 1-2 Alkoxy, -C(O)C1-2 Alkyl radical substitution;

[0316] (3) 8-10 membered paracycloalkyl, 7-11 membered spirocycloalkyl, 5-8 membered bridged cycloalkyl, wherein the paracycloalkyl, spirocycloalkyl, bridged cycloalkyl are optionally further substituted by 1-3 groups selected from halogen, hydroxyl, cyano, amino, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkyl, deuterated C 1-2 Alkoxy group substitution;

[0317] (4)-O-(CH2) m -(4-6 membered monocyclic heterocycloalkyl), -O-(CH2) m -(4-6 membered monocyclic cycloalkyl), -O-(CH2) m -(5-6 membered heteroaryl), -O-(CH2) m -(phenyl), the 4-6 membered monocyclic heterocycloalkyl, 4-6 membered monocyclic cycloalkyl, 5-6 membered heteroaryl, phenyl is further substituted by 1-3 members selected from R 3b The group substitution;

[0318] (5)-C 1-3 Alkylene-(4-6 membered monocyclic heterocycloalkyl), -C 0-3 Alkylene-(4-6 membered monocyclic cycloalkyl), -C 0-3 Alkylene-(5-6 membered heteroaryl), -C 0-3 Alkylene-phenyl, further substituted by 1-3 groups selected from R 3b The group substitution;

[0319] (6)C 2-4 Alkynyl, F, Cl, N3, the alkynyl is optionally further substituted by 1-2 selected from R 3b The group substitution;

[0320] (7)-C(O)-NR aa R4, -NR aa -C(O)R4, -C(O)-C 0-3 Alkylene-R4, -NR aa R4, -NR aa -C(O)C 1-3 Alkyl, -C(O)-N(R aa )2; In some embodiments, selected from -C(O)-NR aa R4, -NR aa -C(O)R4, -C(O)-C 0-3 Alkylene-R4, -NRaa R4;

[0321] R4 is selected from 5-6 membered heteroaryl, 4-6 membered monocyclic heterocycloalkyl, 3-6 membered monocyclic cycloalkyl, 8-10 membered heterocycloalkyl, 7-11 membered spiro heterocycloalkyl, 5-8 membered bridged heterocycloalkyl, 8-10 membered heterocycloalkyl, 7-11 membered spiro heterocycloalkyl, 5-8 membered bridged heterocycloalkyl, and the 5-6 membered heteroaryl, 4-6 membered monocyclic heterocycloalkyl, 3-6 membered monocyclic cycloalkyl, 8-10 membered heterocycloalkyl, 7-11 membered spiro heterocycloalkyl, 5-8 membered bridged heterocycloalkyl, 8-10 membered heterocycloalkyl, 7-11 membered spiro heterocycloalkyl, 5-8 membered bridged heterocycloalkyl, 8-10 membered heterocycloalkyl, 7-11 membered spiro heterocycloalkyl, 5-8 membered bridged heterocycloalkyl, 3b The group substitution;

[0322] R6 is selected from 3-6 membered cycloalkyl, 4-6 membered heterocycloalkyl, 8-10 membered heterocycloalkyl, 7-11 membered spiro heterocycloalkyl, 5-8 membered bridged heterocycloalkyl, 8-10 membered heterocycloalkyl, 7-11 membered spiro heterocycloalkyl, 5-8 membered bridged heterocycloalkyl or 5-10 membered heteroaryl, and the 3-6 membered cycloalkyl, 4-6 membered heterocycloalkyl, 8-10 membered heterocycloalkyl, 7-11 membered spiro heterocycloalkyl, 5-8 membered bridged heterocycloalkyl, 8-10 membered heterocycloalkyl, 7-11 membered spiro heterocycloalkyl, 5-8 membered bridged heterocycloalkyl, 8-10 membered heterocycloalkyl, 7-11 membered spiro heterocycloalkyl, 5-8 membered bridged heterocycloalkyl, heteroaryl are optionally further substituted by 1-5 members selected from R 3b The group substitution;

[0323] R 3b Selected from halogen, =O, Hydroxyl, cyano, amino, methylamino, dimethylamino, C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkyl, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkyl, deuterated C 1-4 Alkoxy, -(CH2) m -C 3-6 Cycloalkyl, -(CH2) m -(4-9 membered heterocycloalkyl), phenyl, 5-10 membered heteroaryl, benzo(5-6 membered cycloalkyl), benzo(5-6 membered heterocycloalkyl), 5-6 membered heteroaryl and 5-6 membered cycloalkyl, -OC 3-6 Cycloalkyl, -O-(4-6 membered heterocycloalkyl), -C(O)-(CH2) m -C 1-4 Alkyl, -C(O)-(CH2) m -C 3-6 Cycloalkyl, -C(O)-(CH2) m -(4-6 membered heterocycloalkyl), -C(O)-(CH2) m-(5-6 membered heteroaryl), -NH-C(O)-(CH2) m -C 1-4 Alkyl, -NH-C(O)-(CH2) m -C 3-6 Cycloalkyl, -S(O)2-C 1-2 Alkyl or -NH-C(O)-(CH2) m -(5-6 membered heteroaryl), wherein the cycloalkyl, heterocycloalkyl, phenyl, heteroaryl are optionally further substituted by 1-3 members selected from R 3aa The group substitution;

[0324] R 3aa Selected from halogen, hydroxyl, cyano, =O, SF5, amino, methylamino, dimethylamino, -NH-C 3-6 Cycloalkyl, C 1-6 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkyl, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkyl, deuterated C 1-4 Alkoxy, acetyl, -NR aa C(O)-C 1-4 Alkyl, -NR aa C(O)-OC 1-4 Alkyl, -NR aa C(O)-C 3-6 Cycloalkyl, -NR aa C(O)-(3-6 membered heterocycloalkyl), -NR aa C(O)-(5-6 membered heteroaryl), -C(O)NR aa -C 3-6 Cycloalkyl, -C(O)-C 3-6 Cycloalkyl, -C(O)-(4-6 membered heterocycloalkyl), 4-6 membered heterocycloalkyl, 5-6 membered heteroaryl, The alkyl, cycloalkyl, heterocycloalkyl, and heteroaryl groups are optionally further substituted by 1 to 3 groups selected from deuterium, halogen, hydroxyl, cyano, amino, C 1-2 Alkyl, alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, acetyl, =O group substitution;

[0325] R aa Selected from H, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 alkyl;

[0326] m is selected from 0, 1, and 2;

[0327] The definitions of other groups are consistent with any of the above schemes.

[0328] The sixth specific embodiment relates to a compound represented by formula (I), and its stereoisomers, deuterated substances, solvates, or pharmaceutically acceptable salts or cocrystals, wherein

[0329] Ar1 is selected from pyridyl or pyridazinyl, and said Ar1 is optionally substituted by 1-3 groups selected from halogen, hydroxyl, cyano, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-2 Alkyl, deuterated C 1-2 Alkoxy, hydroxy C 1-2 Alkyl, C 3-4 Cycloalkyl, -OC 3-4 Cycloalkyl, -O-(4-6 membered heterocycloalkyl), carboxyl or 5 membered heteroaryl, wherein the heteroaryl is optionally substituted by 1-3 halogen, hydroxyl, cyano, amino, C 1-2 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, hydroxyl C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkyl, deuterated C 1-2 Alkoxy, C 3-4 Cycloalkyl, -SC 1-2 Alkyl and carboxyl group substitution;

[0330] Ar2 is selected from pyridyl, phenyl, and said Ar2 is optionally substituted by 1-3 groups selected from halogen, hydroxyl, cyano, amino, C 1-2 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkyl, deuterated C 1-2 Alkoxy, cyclopropyl, oxetanyl, azetidinyl, -O-cyclopropyl, carboxyl, acetyl, aminoacetyl, aminopropionyl group substitution;

[0331] L1 is selected from -OCH2-*, -OCH2CH2-*, -OCH2-C(O)-*, -CH=CH-*, * represents the connection site between L1 and Ar3;

[0332] Ar3 is selected from the following groups:

[0333] (i) pyridyl, piperidyl or azacyclohexenyl, wherein the pyridyl, piperidyl or azacyclohexenyl is further substituted by 1-2 groups selected from R3, and optionally substituted by 1-2 groups selected from halogen, hydroxyl, cyano, amino, C 1-2 Alkyl, hydroxyl C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkyl, deuterated C 1-2 Alkoxy, C 3-4 radical substitution of cycloalkyl groups;

[0334] (ii) 5-membered heteroaryl, pyrimidinyl, pyrazinyl, pyridazinyl, wherein the 5-membered heteroaryl, pyrimidinyl, pyrazinyl, pyridazinyl is further substituted by 1-3 groups selected from R6;

[0335] R3 is selected from the following groups:

[0336] (1) a 4-6 membered monocyclic heterocycloalkyl group, wherein the 4-6 membered monocyclic heterocycloalkyl group is further substituted by 1-3 groups selected from R 3b The group substitution;

[0337] (2) 8-10 membered heterocyclic alkyl, 7-11 membered spiro heterocyclic alkyl, 5-8 membered bridged heterocyclic alkyl, wherein the heterocyclic alkyl, spiro heterocyclic alkyl, bridged heterocyclic alkyl are optionally further substituted by 1-3 groups selected from halogen, hydroxyl, cyano, amino, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkyl, deuterated C 1-2 Alkoxy, -C(O)C 1-2 Alkyl radical substitution;

[0338] (3) 8-10 membered paracycloalkyl, 7-11 membered spirocycloalkyl, 5-8 membered bridged cycloalkyl, wherein the paracycloalkyl, spirocycloalkyl, bridged cycloalkyl are optionally further substituted by 1-3 groups selected from halogen, hydroxyl, cyano, amino, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkyl, deuterated C 1-2 Alkoxy group substitution;

[0339] (4)-O-(CH2) m -(4-6 membered monocyclic heterocycloalkyl), -O-(CH2) m-(4-6 membered monocyclic cycloalkyl), -O-(CH2) m -(5-6 membered heteroaryl), -O-(CH2) m -(phenyl), the 4-6 membered monocyclic heterocycloalkyl, 4-6 membered monocyclic cycloalkyl, 5-6 membered heteroaryl, phenyl is further substituted by 1-3 members selected from R 3b The group substitution;

[0340] (5)-C 1-3 Alkylene-(4-6 membered monocyclic heterocycloalkyl), -C 0-3 Alkylene-(4-6 membered monocyclic cycloalkyl), -C 0-3 Alkylene-(5-6 membered heteroaryl), -C 0-3 Alkylene-phenyl, further substituted by 1-3 groups selected from R 3b The group substitution;

[0341] (6)C 2-4 Alkynyl, F, Cl, N3, the alkynyl is optionally further substituted by 1-2 selected from R 3b The group substitution;

[0342] (7)-C(O)-NR aa R4, -NR aa -C(O)R4, -C(O)-C 0-3 Alkylene-R4, -NR aa R4;

[0343] R4 is selected from 5-6 membered heteroaryl, 4-6 membered monocyclic heterocycloalkyl, 3-6 membered monocyclic cycloalkyl, 8-10 membered heterocycloalkyl, 7-11 membered spiro heterocycloalkyl, 5-8 membered bridged heterocycloalkyl, 8-10 membered heterocycloalkyl, 7-11 membered spiro heterocycloalkyl, 5-8 membered bridged heterocycloalkyl, and the 5-6 membered heteroaryl, 4-6 membered monocyclic heterocycloalkyl, 3-6 membered monocyclic cycloalkyl, 8-10 membered heterocycloalkyl, 7-11 membered spiro heterocycloalkyl, 5-8 membered bridged heterocycloalkyl, 8-10 membered heterocycloalkyl, 7-11 membered spiro heterocycloalkyl, 5-8 membered bridged heterocycloalkyl, 8-10 membered heterocycloalkyl, 7-11 membered spiro heterocycloalkyl, 5-8 membered bridged heterocycloalkyl, 3b The group substitution;

[0344] R6 is selected from 3-6 membered cycloalkyl, 4-6 membered heterocycloalkyl, 8-10 membered heterocycloheterocycloalkyl, 7-11 membered spiro heterocycloalkyl, 5-8 membered bridged heterocycloalkyl, 8-10 membered heterocycloheterocycloalkyl, 7-11 membered spiro heterocycloalkyl, 5-8 membered bridged heterocycloalkyl, and the 3-6 membered cycloalkyl, 4-6 membered heterocycloalkyl, 8-10 membered heterocycloheterocycloalkyl, 7-11 membered spiro heterocycloalkyl, 5-8 membered bridged heterocycloalkyl, 8-10 membered heterocycloheterocycloalkyl, 7-11 membered spiro heterocycloalkyl, 5-8 membered bridged heterocycloalkyl, 8-10 membered heterocycloheterocycloalkyl, 7-11 membered spiro heterocycloalkyl, 5-8 membered bridged heterocycloalkyl, 3b The group substitution;

[0345] R 3b Selected from halogen, =O, Hydroxyl, cyano, amino, methylamino, dimethylamino, C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkyl, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkyl, deuterated C 1-4 Alkoxy, -(CH2) m -C 3-6 Cycloalkyl, -(CH2) m -(4-9 membered heterocycloalkyl), phenyl, 5-10 membered heteroaryl, benzo(5-6 membered cycloalkyl), benzo(5-6 membered heterocycloalkyl), 5-6 membered heteroaryl and 5-6 membered cycloalkyl, -OC 3-6 Cycloalkyl, -O-(4-6 membered heterocycloalkyl), -C(O)-(CH2) m -C 1-4 Alkyl, -C(O)-(CH2) m -C 3-6 Cycloalkyl, -C(O)-(CH2) m -(4-6 membered heterocycloalkyl), -C(O)-(CH2) m -(5-6 membered heteroaryl), -NH-C(O)-(CH2) m -C 1-4 Alkyl, -NH-C(O)-(CH2) m -C 3-6 Cycloalkyl, -S(O)2-C 1-2 Alkyl, the cycloalkyl, heterocycloalkyl, phenyl, heteroaryl may be further substituted by 1-3 groups selected from R 3aa In some embodiments, R 3b Selected from halogen, =O, hydroxy, cyano, amino, methylamino, dimethylamino, C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkyl, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkyl, deuterated C 1-4 Alkoxy, -(CH2) m -C 3-6 Cycloalkyl, -(CH2) m -(4-8 membered heterocycloalkyl), phenyl, 5-10 membered heteroaryl, benzo(5-6 membered cycloalkyl), benzo(5-6 membered heterocycloalkyl), 5-6 membered heteroaryl and 5-6 membered cycloalkyl, -OC 3-6Cycloalkyl, -O-(4-6 membered heterocycloalkyl), -C(O)-(CH2) m -C 1-4 Alkyl, -C(O)-(CH2) m -C 3-6 Cycloalkyl, -C(O)-(CH2) m -(4-6 membered heterocycloalkyl), -C(O)-(CH2) m -(5-6 membered heteroaryl), -NH-C(O)-(CH2) m -C 1-4 Alkyl, -S(O)2-C 1-2 Alkyl, the cycloalkyl, heterocycloalkyl, phenyl, heteroaryl may be further substituted by 1-3 groups selected from R 3aa The group substitution;

[0346] R 3aa Selected from halogen, hydroxyl, cyano, =O, SF5, amino, methylamino, dimethylamino, -NH-C 3-6 Cycloalkyl, C 1-6 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkyl, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkyl, deuterated C 1-4 Alkoxy, acetyl, -NR aa C(O)-C 1-4 Alkyl, -NR aa C(O)-OC 1-4 Alkyl, -NR aa C(O)-C 3-6 Cycloalkyl, -NR aa C(O)-(3-6 membered heterocycloalkyl), -NR aa C(O)-(5-6 membered heteroaryl), -C(O)NR aa -C 3-6 Cycloalkyl, -C(O)-C 3-6 Cycloalkyl, -C(O)-(4-6 membered heterocycloalkyl), 4-6 membered heterocycloalkyl, 5-6 membered heteroaryl, The alkyl, cycloalkyl, heterocycloalkyl, and heteroaryl groups are optionally further substituted by 1 to 3 groups selected from deuterium, halogen, hydroxyl, cyano, amino, C 1-2 Alkyl, alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, acetyl, =O; in some embodiments, R 3aa Selected from halogen, hydroxyl, cyano, =O, SF5, amino, methylamino, dimethylamino, -NH-C 3-6Cycloalkyl, C 1-6 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkyl, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkyl, deuterated C 1-4 Alkoxy, acetyl, -NR aa C(O)-C 1-4 Alkyl, -NR aa C(O)-OC 1-4 Alkyl, -NR aa C(O)-C 3-6 Cycloalkyl, -NR aa C(O)-(3-6 membered heterocycloalkyl), -NR aa C(O)-(5-6 membered heteroaryl), -C(O)NR aa -C 3-6 Cycloalkyl, -C(O)-C 3-6 Cycloalkyl, -C(O)-(4-6 membered heterocycloalkyl), 4-6 membered heterocycloalkyl, 5-6 membered heteroaryl, The alkyl, cycloalkyl, heterocycloalkyl, and heteroaryl groups are optionally further substituted by 1 to 3 groups selected from deuterium, halogen, hydroxyl, cyano, amino, C 1-2 Alkyl, alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, acetyl, =O group substitution;

[0347] R aa Selected from H, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 alkyl;

[0348] m is selected from 0, 1, and 2;

[0349] The definitions of other groups are consistent with any of the above schemes.

[0350] The seventh specific embodiment relates to a compound represented by formula (I), and its stereoisomers, deuterated substances, solvates, or pharmaceutically acceptable salts or cocrystals, wherein

[0351] Ar1 is selected from pyridyl, said Ar1 is optionally substituted by 1-3 groups selected from halogen, hydroxyl, cyano, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-2 Alkyl, deuterated C 1-2 Alkoxy, hydroxy C 1-2 Alkyl, C 3-4Cycloalkyl, -OC 3-4 In some embodiments, Ar1 is selected from pyridyl, wherein Ar1 is optionally substituted by 1-3 groups selected from halogen, hydroxyl, cyano, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-2 Alkyl, deuterated C 1-2 Alkoxy, hydroxy C 1-2 Alkyl, C 3-4 Substitution of cycloalkyl and carboxyl groups;

[0352] Ar2 is selected from pyridyl, phenyl, and said Ar2 is optionally substituted by 1-3 groups selected from halogen, hydroxyl, cyano, amino, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkyl, deuterated C 1-2 Alkoxy, cyclopropyl, oxetanyl, azetidinyl, -O-cyclopropyl, carboxyl, acetyl, aminoacetyl, aminopropionyl group substitution;

[0353] L1 is selected from -OCH2-*, -OCH2CH2-*, -OCH2-C(O)-*, -CH=CH-*, * represents the connection site between L1 and Ar3;

[0354] Ar3 is selected from the following groups:

[0355] (i) pyridyl and piperidyl, wherein the pyridyl and piperidyl are further substituted by 1-2 groups selected from R3, and optionally substituted by 1-2 groups selected from halogen, hydroxyl, cyano, amino, C 1-2 Alkyl, hydroxyl C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkyl, deuterated C 1-2 Alkoxy, C 3-4 radical substitution of cycloalkyl groups;

[0356] (ii) 5-membered heteroaryl, pyrimidinyl, pyrazinyl, pyridazinyl, wherein the 5-membered heteroaryl, pyrimidinyl, pyrazinyl, pyridazinyl is further substituted by 1-3 groups selected from R6;

[0357] In some embodiments, Ar3 is selected from the following groups:

[0358] (i) pyridyl, said pyridyl being further substituted by 1-2 groups selected from R3, and optionally substituted by 1-2 groups selected from halogen, hydroxyl, cyano, amino, C 1-2 Alkyl, hydroxyl C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkyl, deuterated C 1-2 Alkoxy, C 3-4 radical substitution of cycloalkyl groups;

[0359] (ii) 5-membered heteroaryl, pyrimidinyl, pyrazinyl, pyridazinyl, wherein the 5-membered heteroaryl, pyrimidinyl, pyrazinyl, pyridazinyl is further substituted by 1-3 groups selected from R6;

[0360] R3 is selected from the following groups:

[0361] (1) a 4-6 membered monocyclic heterocycloalkyl group, wherein the 4-6 membered monocyclic heterocycloalkyl group is further substituted by 1-3 groups selected from R 3b The group substitution;

[0362] (2) 8-10 membered heterocyclic alkyl, 7-11 membered spiro heterocyclic alkyl, 5-8 membered bridged heterocyclic alkyl, wherein the heterocyclic alkyl, spiro heterocyclic alkyl, bridged heterocyclic alkyl are optionally further substituted by 1-3 groups selected from halogen, hydroxyl, cyano, amino, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkyl, deuterated C 1-2 Alkoxy group substitution;

[0363] (3) 8-10 membered paracycloalkyl, 7-11 membered spirocycloalkyl, 5-8 membered bridged cycloalkyl, wherein the paracycloalkyl, spirocycloalkyl, bridged cycloalkyl are optionally further substituted by 1-3 groups selected from halogen, hydroxyl, cyano, amino, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkyl, deuterated C 1-2 Alkoxy group substitution;

[0364] (4)-O-(CH2) m -(4-6 membered monocyclic heterocycloalkyl), -O-(CH2) m -(4-6 membered monocyclic cycloalkyl), -O-(CH2) m -(5-6 membered heteroaryl), -O-(CH2)m -(phenyl), the 4-6 membered monocyclic heterocycloalkyl, 4-6 membered monocyclic cycloalkyl, 5-6 membered heteroaryl, phenyl is further substituted by 1-3 members selected from R 3b In some embodiments, the group selected from -O-(CH2) m -(4-6 membered monocyclic heterocycloalkyl), -O-(CH2) m -(4-6 membered monocyclic cycloalkyl), -O-(CH2) m -(5-6 membered heteroaryl), wherein the 4-6 membered monocyclic heterocycloalkyl, 4-6 membered monocyclic cycloalkyl, 5-6 membered heteroaryl is further substituted by 1-3 members selected from R 3b The group substitution;

[0365] (5)-C 1-3 Alkylene-(4-6 membered monocyclic heterocycloalkyl), -C 0-3 Alkylene-(4-6 membered monocyclic cycloalkyl), -C 0-3 Alkylene-(5-6 membered heteroaryl), -C 0-3 Alkylene-phenyl, further substituted by 1-3 groups selected from R 3b In some embodiments, the group selected from -C 1-3 Alkylene-(4-6 membered monocyclic heterocycloalkyl), -C 0-3 Alkylene-(4-6 membered monocyclic cycloalkyl), -C 0-3 Alkylene-(5-6 membered heteroaryl), further substituted by 1-3 groups selected from R 3b The group substitution;

[0366] (6)C 2-4 Alkynyl, F, Cl, N3, the alkynyl is optionally further substituted by 1-2 selected from R 3b The group substitution;

[0367] (7)-C(O)-NR aa R4, -NR aa -C(O)R4, -C(O)-C 0-3 Alkylene-R4, -NR aa R4;

[0368] R4 is selected from 5-6 membered heteroaryl, 4-6 membered monocyclic heterocycloalkyl, 3-6 membered monocyclic cycloalkyl, 8-10 membered heterocycloalkyl, 7-11 membered spiro heterocycloalkyl, 5-8 membered bridged heterocycloalkyl, 8-10 membered heterocycloalkyl, 7-11 membered spiro heterocycloalkyl, 5-8 membered bridged heterocycloalkyl, and the 5-6 membered heteroaryl, 4-6 membered monocyclic heterocycloalkyl, 3-6 membered monocyclic cycloalkyl, 8-10 membered heterocycloalkyl, 7-11 membered spiro heterocycloalkyl, 5-8 membered bridged heterocycloalkyl, 8-10 membered heterocycloalkyl, 7-11 membered spiro heterocycloalkyl, 5-8 membered bridged heterocycloalkyl, 8-10 membered heterocycloalkyl, 7-11 membered spiro heterocycloalkyl, 5-8 membered bridged heterocycloalkyl, 3b The group substitution;

[0369] R6 is selected from 3-6 membered cycloalkyl, 4-6 membered heterocycloalkyl, 8-10 membered heterocycloheterocycloalkyl, 7-11 membered spiro heterocycloalkyl, 5-8 membered bridged heterocycloalkyl, 8-10 membered heterocycloheterocycloalkyl, 7-11 membered spiro heterocycloalkyl, 5-8 membered bridged heterocycloalkyl, and the 3-6 membered cycloalkyl, 4-6 membered heterocycloalkyl, 8-10 membered heterocycloheterocycloalkyl, 7-11 membered spiro heterocycloalkyl, 5-8 membered bridged heterocycloalkyl, 8-10 membered heterocycloheterocycloalkyl, 7-11 membered spiro heterocycloalkyl, 5-8 membered bridged heterocycloalkyl, 8-10 membered heterocycloheterocycloalkyl, 7-11 membered spiro heterocycloalkyl, 5-8 membered bridged heterocycloalkyl, 3b The group substitution;

[0370] R 3b Selected from halogen, hydroxy, cyano, amino, methylamino, dimethylamino, C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkyl, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkyl, deuterated C 1-4 Alkoxy, C 3-6 Cycloalkyl, 4-8 membered heterocycloalkyl, phenyl, heteroaryl, benzo(5-6 membered cycloalkyl), benzo(5-6 membered heterocycloalkyl), 5-6 membered heteroaryl and 5-6 membered cycloalkyl, -OC 3-6 Cycloalkyl, -O-(4-6 membered heterocycloalkyl), -C(O)-(CH2) m -C 1-4 Alkyl, -C(O)-(CH2) m -C 3-6 Cycloalkyl, -C(O)-(CH2) m -(4-6 membered heterocycloalkyl), -C(O)-(CH2) m -(5-6 membered heteroaryl), -NH-C(O)-(CH2) m -C 1-4 Alkyl, -S(O)2-C 1-2 Alkyl, the cycloalkyl, heterocycloalkyl, phenyl, heteroaryl may be further substituted by 1-3 groups selected from R3aa The group substitution;

[0371] R 3aa Selected from halogen, hydroxyl, cyano, SF5, amino, methylamino, dimethylamino, -NH-C 3-6 Cycloalkyl, C 1-6 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkyl, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkyl, deuterated C 1-4 Alkoxy, acetyl, -NR aa C(O)-C 1-4 Alkyl, -NR aa C(O)-C 3-6 Cycloalkyl, -C(O)NR aa -C 3-6 Cycloalkyl, -C(O)-C 3-6 Cycloalkyl, -C(O)-(4-6 membered heterocycloalkyl), 4-6 membered heterocycloalkyl, 5-6 membered heteroaryl, The alkyl, cycloalkyl, heterocycloalkyl, and heteroaryl groups are optionally further substituted by 1 to 3 groups selected from deuterium, halogen, hydroxyl, cyano, amino, C 1-2 Alkyl, alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, acetyl, =O; in some embodiments, R 3aa Selected from halogen, hydroxyl, cyano, SF5, amino, methylamino, dimethylamino, C 1-6 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkyl, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkyl, deuterated C 1-4 Alkoxy, acetyl, -NR aa C(O)-C 1-4 Alkyl, -NR aa C(O)-C 3-6 Cycloalkyl, -C(O)NR aa -C 3-6 Cycloalkyl, -C(O)-C 3-6 Cycloalkyl, -C(O)-(4-6 membered heterocycloalkyl), wherein the alkyl, cycloalkyl, heterocycloalkyl may be further substituted by 1-3 groups selected from halogen, hydroxyl, cyano, amino, C 1-2 Alkyl, alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, acetyl group substitution;

[0372] R aa Selected from H, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 alkyl;

[0373] m is selected from 0, 1, and 2;

[0374] The definitions of other groups are consistent with any of the above schemes.

[0375] In a specific eighth embodiment, the compound of formula (I) of the present invention, and its stereoisomers, deuterated forms, solvates, or pharmaceutically acceptable salts or cocrystals, have the structures of formula (II), (III), (II-a), (II-b), (III-a), (III-b), (IV-a), (IV-b), (Va), (Vb), (VI-a), (VI-b), (VII-a), (VII-b), (VIII), (VIII-a), (VIII-b), and (VIII-c),

[0376] In some embodiments, the compound has the structure of Formula (II), (III), (II-a), (II-b), (III-a), (III-b), (IV-a), (IV-b), (Va), (Vb), (VI-a), (VI-b), (VII-a), (VII-b), (VIII), (VIII-a), (VIII-b),

[0377] In some embodiments, the compound has the structure of Formula (II), (III), (II-a), (II-b), (III-a), (III-b), (IV-a), (IV-b), (Va), (Vb), (VI-a), (VI-b), (VII-a), (VII-b),

[0378] In some embodiments, the compound of formula (II), (III), (II-a), (II-b), (III-a), (III-b)

[0379] In some embodiments, having the structure of formula (II), (III),

[0380] wherein q1, q2, q3, and q4 are each independently selected from 0 or 1;

[0381] X1 is selected from CH or N;

[0382] Each R 1a each independently selected from F, Cl, hydroxy, cyano, methyl, ethyl, isopropyl, methoxy, ethoxy, isopropyloxy, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH2F, -CHFCHF2, -CHFCF3, -CF2CH2F, -CF2CHF2, -CF2CF3, -OCHF2, -OCH2F, -OCF3, -OCH2CH2F, -OCH2CHF2, -OCH2CF3, -OCHFCH2F, -OCHFCHF2, -OCHFCF3, -OCF2CH2F, -OCF2CHF2, -OCF2CF3, -CH2D, -CHD2, -CD3, -CH2CH2D, -CH2CHD2, -C H2CD3, -CHDCH2D, -CHDCHD2, -CHDCD3, -CD2CH2D, -CD2CHD2, -CD2CD3, -OCHD2, -OCH2D, -OCD3, -OCH2CH2D, -OCH2CHD2, -OCH2CD3, -OCHDCH2D, -OCHDCHD2, -OCHDCD3, -OCD2CH2D, -OCD2CHD2, -OCD2CD3, cyclopropyl, cyclobutyl, cyclopentyl, 4-membered heterocycloalkyl, 5-membered heterocycloalkyl, 6-membered heterocycloalkyl, -O-cyclopropyl, -O-cyclobutyl, -O-cyclopentyl, -O-4-membered heterocycloalkyl, -O-5-membered heterocycloalkyl, -O-6-membered heterocycloalkyl or carboxyl or selected from 5-membered heteroaryl, said heteroaryl optionally substituted with methyl, ethyl or propyl;

[0383] Each R 2aEach is independently selected from F, Cl, hydroxy, cyano, amino, methylamino, dimethylamino, methyl, ethyl, isopropyl, methoxy, ethoxy, isopropyloxy, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH2F, -CHFCHF2, -CHFCF3, -CF2CH2F, -CF2CHF2, -CF2CF3, -OCHF2, -OCH2F, -OCF3, -OCH2CH2F, -OCH2CHF2, -OCH2CF3, -OCHFCH2F, -OCHF CHF2, -OCHFCF3, -OCF2CH2F, -OCF2CHF2, -OCF2CF3, -CH2D, -CHD2, -CD3, -CH2CH2D, -CH2CHD2, -CH2CD3, -CHDCH2D, -CHDCHD2, -CHDCD3, -CD2C H2D, -CD2CHD2, -CD2CD3, -OCHD2, -OCH2D, -OCD3, -OCH2CH2D, -OCH2CHD2, -OCH2CD3, -OCHDCH2D, -OCHDCHD2, -OCHDCD3, -OCD2CH2D, -OCD2CHD2, -OCD2CD3, cyclopropyl, cyclobutyl, cyclopentyl, 4-membered heterocycloalkyl, 5-membered heterocycloalkyl, 6-membered heterocycloalkyl, -O-cyclopropyl, -O-cyclobutyl, -O-cyclopentyl, -O-4-membered heterocycloalkyl, -O-5-membered heterocycloalkyl, -O-6-membered heterocycloalkyl, carboxyl, acetyl, aminoacetyl or aminopropanoyl; or

[0384] Each R 2aeach independently selected from F, Cl, hydroxy, cyano, amino, methylamino, dimethylamino, methyl, ethyl, isopropyl, vinyl, ethynyl, propenyl, propynyl, methoxy, ethoxy, isopropyloxy, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH2F, -CHFCHF2, -CHFCF3, -CF2CH2F, -CF2CHF2, -CF2CF3, -OCHF2, -OCH2F, -OCF3, -OCH2CH2F, -OCH2CHF2, -OCH2CF3, -OCHFCH2F, -OCHFCHF2, -OCHFCF3, -OCF2CH2F, -OCF2CHF2, -OCF2CF3, -CH2D, -CHD2, -CD3 , -CH2CH2D, -CH2CHD2, -CH2CD3, -CHDCH2D, -CHDCHD2, -CHDCD3, -CD2CH2D, -CD2CHD2, -CD2CD3, -OCHD2, -OCH2D, -OCD3, -OCH2CH2D, -OCH2CHD2, -OCH2CD3, -OCHDCH2D, -OCHDCHD2, -OCHDCD3, -OCD2CH2D, -OCD2CHD2, -OCD2CD3, cyclopropyl, cyclobutyl, cyclopentyl, 4-membered heterocycloalkyl, 5-membered heterocycloalkyl, 6-membered heterocycloalkyl, -O-cyclopropyl, -O-cyclobutyl, -O-cyclopentyl, -O-4-membered heterocycloalkyl, -O-5-membered heterocycloalkyl, -O-6-membered heterocycloalkyl, carboxyl, acetyl, aminoacetyl or aminopropanoyl;

[0385] In some embodiments:

[0386] Wherein, q1, q2, q3, q4 are each independently selected from 0 or 1; each R 1aeach independently selected from F, Cl, hydroxy, cyano, methyl, ethyl, isopropyl, methoxy, ethoxy, isopropyloxy, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH2F, -CHFCHF2, -CHFCF3, -CF2CH2F, -CF2CHF2, -CF2CF3, -OCHF2, -OCH2F, -OCF3, -OCH2CH2F, -OCH2CHF2, -OCH2CF3, -OCHFCH2F, -OCHFCHF2, -OCHFCF3, -OCF2CH2F, -OCF2CHF2, -OCF2CF3, -CH2D, -CHD2, -CD3, -CH2CH2D, -CH2CHD2, -C H2CD3, -CHDCH2D, -CHDCHD2, -CHDCD3, -CD2CH2D, -CD2CHD2, -CD2CD3, -OCHD2, -OCH2D, -OCD3, -OCH2CH2D, -OCH2CHD2, -OCH2CD3, -OCHDCH2D, -OCHDCHD2, -OCHDCD3, -OCD2CH2D, -OCD2CHD2, -OCD2CD3, cyclopropyl, cyclobutyl, cyclopentyl, 4-membered heterocycloalkyl, 5-membered heterocycloalkyl, 6-membered heterocycloalkyl, -O-cyclopropyl, -O-cyclobutyl, -O-cyclopentyl, -O-4-membered heterocycloalkyl, -O-5-membered heterocycloalkyl, -O-6-membered heterocycloalkyl or carboxyl or selected from 5-membered heteroaryl, said heteroaryl optionally substituted with methyl, ethyl or propyl;

[0387] Each R 2aEach is independently selected from F, Cl, hydroxy, cyano, amino, methylamino, dimethylamino, methyl, ethyl, isopropyl, methoxy, ethoxy, isopropyloxy, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH2F, -CHFCHF2, -CHFCF3, -CF2CH2F, -CF2CHF2, -CF2CF3, -OCHF2, -OCH2F, -OCF3, -OCH2CH2F, -OCH2CHF2, -OCH2CF3, -OCHFCH2F, -OCHFCHF2, -OCHFCF3, -OCF2CH2F, -OCF2CHF2, -OCF2CF3, -CH2D, -CHD2, -CD3, - CH2CH2D, -CH2CHD2, -CH2CD3, -CHDCH2D, -CHDCHD2, -CHDCD3, -CD2CH2D, -CD2CHD2, -CD2CD3, -OCHD2, -OCH2D, -OCD3, -OCH2CH2D, -OCH2CHD2, -OCH2CD3, -OCHDCH2D, -OCHDCHD2, -OCHDCD3, -OCD2CH2D, -OCD2CHD2, -OCD2CD3, cyclopropyl, cyclobutyl, cyclopentyl, 4-membered heterocycloalkyl, 5-membered heterocycloalkyl, 6-membered heterocycloalkyl, -O-cyclopropyl, -O-cyclobutyl, -O-cyclopentyl, -O-4-membered heterocycloalkyl, -O-5-membered heterocycloalkyl, -O-6-membered heterocycloalkyl, carboxyl, acetyl, aminoacetyl or aminopropanoyl; or

[0388] Each R 2aeach independently selected from F, Cl, hydroxy, cyano, amino, methylamino, dimethylamino, methyl, ethyl, isopropyl, vinyl, ethynyl, propenyl, propynyl, methoxy, ethoxy, isopropyloxy, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH2F, -CHFCHF2, -CHFCF3, -CF2CH2F, -CF2CHF2, -CF2CF3, -OCHF2, -OCH2F, -OCF3, -OCH2CH2F, -OCH2CHF2, -OCH2CF3, -OCHFCH2F, -OCHFCHF2, -OCHFCF3, -OCF2CH2F, -OCF2CHF2, -OCF2CF3, -CH2D, -CHD2, -CD3 , -CH2CH2D, -CH2CHD2, -CH2CD3, -CHDCH2D, -CHDCHD2, -CHDCD3, -CD2CH2D, -CD2CHD2, -CD2CD3, -OCHD2, -OCH2D, -OCD3, -OCH2CH2D, -OCH2CHD2, -OCH2CD3, -OCHDCH2D, -OCHDCHD2, -OCHDCD3, -OCD2CH2D, -OCD2CHD2, -OCD2CD3, cyclopropyl, cyclobutyl, cyclopentyl, 4-membered heterocycloalkyl, 5-membered heterocycloalkyl, 6-membered heterocycloalkyl, -O-cyclopropyl, -O-cyclobutyl, -O-cyclopentyl, -O-4-membered heterocycloalkyl, -O-5-membered heterocycloalkyl, -O-6-membered heterocycloalkyl, carboxyl, acetyl, aminoacetyl or aminopropanoyl;

[0389] The definitions of other groups are consistent with any of the above schemes.

[0390] In a specific ninth embodiment, the compound of formula (I) of the present invention, and its stereoisomers, deuterated substances, solvates, or pharmaceutically acceptable salts or cocrystals, wherein

[0391] Ar3 is selected from the following groups:

[0392] (i) The Further substituted by 1 group selected from R3, and optionally substituted by 1-2 groups selected from F, Cl, methyl, ethyl; in some embodiments, selected from The is further substituted with 1 group selected from R3;

[0393] (ii) Imidazolyl, pyrrolyl, pyrimidinyl, pyrazinyl, pyridazinyl, The Imidazolyl, pyrrolyl, pyrimidinyl, pyrazinyl, pyridazinyl, is further substituted with 1 group selected from R6; in some embodiments, selected from Imidazolyl, pyrrolyl, pyrimidinyl, pyrazinyl, pyridazinyl, The Imidazolyl, pyrrolyl, pyrimidinyl, pyrazinyl, pyridazinyl, is further substituted with 1 group selected from R6; in some embodiments, selected from Imidazolyl, pyrrolyl, pyrimidinyl, pyrazinyl, pyridazinyl, the Imidazolyl, pyrrolyl, pyrimidinyl, pyrazinyl, pyridazinyl is further substituted with one group selected from R6;

[0394] R3 is selected from the following groups:

[0395] (1) In some embodiments, selected from In some embodiments, selected from

[0396] (2) Optionally further substituted by 1-2 groups selected from F, Cl, hydroxy, cyano, amino, methyl, ethyl, isopropyl, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH2F, -CHFCHF2, -CHFCF3, -CF2CH2F, -CF2CHF2, -CF2CF3, -CH2D, -CHD2, -CD3, -CH2CH2D, -CH2CHD2, -CH2CD3, -CHDCH2D, -CHDCHD2, -CHDCD3, -CD2CH2D, -CD2CHD2, -CD2CD3, -C(O)CH3;

[0397] (3) Further selected by 1 R 3b The group substitution;

[0398] (4) Pyridyl, phenyl, Further 1-3 selected from F, Cl, methyl, ethyl, isopropyl, cyclopropyl, cyclobutyl, oxetanyl, -NHC(O)CH3, CN, CHF2, CF3; in some embodiments, selected from Pyridyl, phenyl, Further 1-3 selected from F, Cl, methyl, ethyl, isopropyl, cyclopropyl, cyclobutyl, oxetanyl, -NHC(O)CH3, CN, CHF2, CF3; in some embodiments, selected from Pyridyl, phenyl, Further 1-3 selected from F, Cl, methyl, ethyl, isopropyl, cyclopropyl, cyclobutyl, oxetanyl, -NHC(O)CH3, CN, CF3; in some embodiments, selected from Pyridyl, phenyl, Further 1-3 selected from F, Cl, methyl, ethyl, isopropyl, cyclopropyl, cyclobutyl, oxetanyl, -NHC(O)CH3, In some embodiments, the group selected from Pyridyl, phenyl, further substituted by 1-3 groups selected from F, Cl, methyl, ethyl, isopropyl, cyclopropyl, cyclobutyl, -NHC(O)CH3;

[0399] (5) ethynyl, propynyl, F, Cl, N3, wherein the ethynyl and propynyl groups are optionally further substituted by 1-2 groups selected from amino, methylamino, dimethylamino, In some embodiments, the ethynyl group and the propynyl group are substituted with 1-2 groups selected from amino, methylamino and dimethylamino;

[0400] (6)-C(O)-NR aa R4, -NR aa -C(O)R4, -C(O)-R4, -NR aa R4, -NR aa -C(O)C 1-3 Alkyl, -C(O)-N(R aa )2; in some embodiments selected from -C(O)-NR aa R4, -NR aa -C(O)R4, -C(O)-R4, -NR aa R4;

[0401] Each R4 is independently selected from tetrahydropyran, piperidine, cyclopropyl, cyclobutyl, pyrazole, imidazole, isoxazole, piperazine, and the tetrahydropyran, piperidine, cyclopropyl, cyclobutyl, pyrazole, imidazole, isoxazole, and piperazine are optionally further substituted with 1-2 groups selected from methyl, ethyl, isopropyl, F, and Cl; in some embodiments, each R4 is independently selected from tetrahydropyran, piperidine, cyclobutyl, pyrazole, imidazole, isoxazole, and piperazine, and the tetrahydropyran, piperidine, cyclobutyl, pyrazole, imidazole, isoxazole, and piperazine are optionally further substituted with 1-2 groups selected from methyl, ethyl, isopropyl, F, and Cl;

[0402] Each R aa Each is independently selected from H, methyl, -CH2F, -CHF2, -CF3, -CH2D, -CHD2, -CD3;

[0403] R6 is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, azetidinyl, oxolanyl, azopentyl, oxhexyl, azohexyl, morpholinyl, piperazinyl or pyrazolyl, optionally further substituted by 1-2 selected from R 3b The group substitution;

[0404] R 3b Selected from F, Cl, =O, Hydroxyl, cyano, amino, methylamino, dimethylamino, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH2F, -CHFCHF2, -CHFCF3, -CF2CH2F, -CF2CHF2, -CF2CF3, -OCHF2, -OCH2F, -OCF3, -OCH2CH2F, -OCH2CHF2, -OCH2CF3, -OCHFCH2F, - OCHFCHF2, -OCHFCF3, -OCF2CH2F, -OCF2CHF2, -OCF2CF3, -CH2D, -CHD2, -CD3, -CH2CH2D, -CH2CHD2, -CH2CD3, -CHDCH2D, -CHDCHD2, -CHDCD3, -CD2CH2D, -CD2CHD2, -CD2CD3, - OCHD2, -OCH2D, -OCD3, -OCH2CH2D, -OCH2CHD2, -OCH2CD3, -OCHDCH2D, -OCHDCHD2, -OCHDCD3, -OCD2CH2D, -OCD2CHD2, -OCD2CD3, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, azetidinyl, oxolanyl, azocyclo Pentyl, oxacyclohexyl, azetidinyl, -CH2-oxetanyl, -CH2-oxolanyl, -CH2-azetidinyl, -CH2-azacyclopentyl, morpholinyl, piperazinyl, phenyl, pyrrolyl, furyl, thienyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, triazole, pyridazinyl, pyridyl, pyrimidinyl, pyrazinyl, benzocyclopentyl, benzocyclohexyl, benzoazepine, -C(O)CH3, -C(O)CD3, -C(O)CH2CH3, -C(O)-cyclopropyl, -C(O)-CH2-cyclopropyl, -C(O)-cyclobutyl, -C(O)-CH2-cyclobutyl, -C(O)-cyclopentyl, -C(O)-CH2-cyclopentyl, -C(O)-cyclohexyl, -C(O)-CH2-cyclohexyl, -C(O)-oxacyclopentyl, -C(O) )-azetidinyl, -C(O)-oxetanyl, -C(O)-azetidinyl, -C(O)-oxetanyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-azetidinyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-azetidinyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-azetidinyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-azetidinyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-azetidinyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-azetidinyl, -C -C(O)-pyrazolyl, -C(O)-imidazolyl, -C(O)-pyrrolyl, -C(O)-furyl, -C(O)-oxazolyl, -C(O)-isoxazolyl, -C(O)-thiazolyl, -NHC(O)CH3, -NHC(O)-cyclopropyl, -NHC(O)-cyclobutyl, -S(O)2CH3, -S(O)CH3 or -NHCO-pyrazolyl, the cyclopropyl, cyclobutyl butyl, cyclopentyl, cyclohexyl, oxetanyl, azetidinyl, oxolanyl, azopentyl, oxhexyl, azohexyl, morpholinyl, piperazinyl, phenyl, pyrrolyl, furyl, thienyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, triazole, pyridazinyl, pyridyl, pyrimidinyl, pyrazinyl, benzocyclopentyl, benzocyclohexyl, benzoazepine, optionally further substituted by 1-3 groups selected from R 3aa In some embodiments, R 3b Selected from F, Cl, =O, Hydroxyl, cyano, amino, methylamino, dimethylamino, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH2F, -CHFCHF2, -CHFCF3, -CF2CH2F, -CF2CHF2, -CF2CF3, -OCHF2, -OCH2F, -OCF3, -OCH2CH2F, -OCH2CHF2, -OCH2CF3, -OCHFCH2F, -OCHFCHF2, -OCHFCF3, -OCF2CH2F, -OCF2CHF2, -OCF2CF3, -CH2D, -CHD2, -CD3, -CH2CH2D, -CH2CHD2, -CH2CD3, -CHDCH2D, -CHDCHD2, -CHD CD3, -CD2CH2D, -CD2CHD2, -CD2CD3, -OCHD2, -OCH2D, -OCD3, -OCH2CH2D, -OCH2CHD2, -OCH2CD3, -OCHDCH2D, -OCHDCHD2, -OCHDCD3, -OCD2CH2D, -OCD2CHD2, -OCD2CD3, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxygen heterocycle butyl, azetidinyl, oxolanyl, azetyl, oxhexyl, azetidinyl, -CH2-oxetanyl, -CH2-oxolanyl, -CH2-azetidinyl, -CH2-azacyclopentyl, morpholinyl, piperazinyl, phenyl, pyrrolyl, furanyl, thienyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrazinyl, benzocyclopentyl, benzocyclohexyl, benzoazepanyl, -C(O)CH3, -C(O)CD3, -C(O)CH2CH3, -C(O)-cyclopropyl, -C(O)-CH2-cyclopropyl, -C(O)-cyclobutyl, -C(O)-CH2-cyclobutyl, -C(O)-cyclopentyl, -C(O)-CH2-cyclopentyl, -C(O)-cyclohexyl, -C(O)-CH2-cyclohexyl, -C(O)-oxacyclopentyl, -C( O)-azetidinyl, -C(O)-oxetanyl, -C(O)-azetidinyl, -C(O)-oxetanyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-azetidinyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-azetidinyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-azetidinyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-azetidinyl, -C(O)-pyrazolyl, -C(O)-imidazolyl, -C(O)-pyrrolyl, -C(O)-furyl, -C(O)-oxazolyl, -C(O)-isoxazolyl, -C(O)-thiazolyl, -NHC(O)CH3, -NHC(O)-cyclopropyl, -NHC(O)-cyclobutyl, -S(O)2CH3, -S(O)CH3 or NHCO-pyrazolyl, wherein the cyclopropyl alkyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, azetidinyl, oxolanyl, azopentyl, oxetanyl, azohexyl, morpholinyl, piperazinyl, phenyl, pyrrolyl, furyl, thienyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrazinyl, benzocyclopentyl, benzocyclohexyl, benzoazepine, optionally further substituted by 1-3 groups selected from R 3aa In some embodiments, R 3bSelected from F, Cl, =O, hydroxy, cyano, amino, methylamino, dimethylamino, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH2F, -CHFCHF2, -CHFCF3, -CF2CH2F, -CF2CHF2, -CF2CF3, -OCHF2, -OCH2F, -OCF3, -OCH2CH2F, -OCH2CHF2, -OCH2CF3, -OCHFCH2F, -OCHFCHF2, -OCHFCF3, -OCF2CH2F, -OCF2CHF2, - OCF2CF3, -CH2D, -CHD2, -CD3, -CH2CH2D, -CH2CHD2, -CH2CD3, -CHDCH2D, -CHDCHD2, -CHDCD3, -CD2CH2D, -CD2CHD2, -CD2CD3, -OCHD2, -OCH2D, -OCD3, -OCH2CH2D, -OCH2CHD2, -OCH2CD3, -OCHDCH2D, -OCHDCHD2, -OCHDCD3, -OCD2CH2D, -OCD2CHD2, -OCD2CD3, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, azetidinyl, oxolanyl, azopentyl, Oxanyl, azetidinyl, -CH2-oxetanyl, -CH2-oxolanyl, -CH2-azetidinyl, -CH2-azacyclopentyl, morpholinyl, piperazinyl, phenyl, pyrrolyl, furyl, thienyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrazinyl, benzocyclopentyl, benzocyclohexyl, benzoazepanyl, -C(O)CH3, -C(O)CD3, -C(O)CH2CH3, -C(O)-cyclopropyl, -C(O)-CH2-cyclopropyl, -C(O)-cyclobutyl, -C(O)-CH2-cyclobutyl, -C(O)-cyclopentyl, -C(O)-CH2-cyclopentyl, -C(O)-cyclohexyl, -C (O)-CH2-cyclohexyl, -C(O)-oxolanyl, -C(O)-azepanyl, -C(O)-oxetanyl, -C(O)-azetidinyl, -C(O)-oxetanyl, -C(O)-CH2-oxolanyl, -C(O)-CH2-azepanyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-azetidinyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-azetidinyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-azetidinyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-azetidinyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-pyrazolyl, -C(O)-imidazolyl, -C(O)-pyrrolyl, -C(O)-furyl, -C(O)-oxazolyl, -C(O)-isoxazolyl, -C(O)-thiazolyl, -NHC(O)CH3,-S(O)2CH3, or -S(O)CH3, wherein the cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, azetidinyl, oxolanyl, azopentyl, oxetanyl, azohexyl, morpholinyl, piperazinyl, phenyl, pyrrolyl, furyl, thienyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrazinyl, benzocyclopentyl, benzocyclohexyl, benzoazacyclopentyl are optionally further substituted by 1-3 selected from R, 3aa The group substitution;

[0405] R 3aa Selected from F, Cl, hydroxy, cyano, =O, SF5, amino, methylamino, dimethylamino, -NH-cyclopropyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH2F, -CHFCHF2, -CHFCF3, -CF2CH2F, -CF2CHF2, -CF2CF3, -OCHF2, -OCH2F, -OCF3, -OCH2CH2F, -OCH2CHF2, -OCH2CF3, -OCHFCH2F, -OCHFCHF2, -OCHFCF3, -OCF2CH2F, -OCF2CHF2, -OCF2CF3, -CH2D, -CHD2, -CD3, -CH2CH2D, -CH2 CHD2, -CH2CD3, -CHDCH2D, -CHDCHD2, -CHDCD3, -CD2CH2D, -CD2CHD2, -CD2CD3, -OCHD2, -OCH2D, -OCD3, -OCH2CH2D, -OCH2CHD2, -OCH2CD3, -OCHDCH2D, -OCHDCHD2, -OCHDCD3, -OCD2CH2D, -OCD2CHD2, -OCD2CD3, -NHC(O)CH3, acetyl, -NR aa C(O)-C 1-4 Alkyl, -NR aa C(O)-OC 1-4 Alkyl, -NR aa C(O)-deuterated C 1-4 Alkyl, -NHC(O)-cyclopropyl, -NHC(O)-cyclobutyl, -NHC(O)-oxetanyl, -NHC(O)pyrazolyl, -C(O)NH-cyclobutyl, -C(O)-cyclopropyl, -C(O)-cyclobutyl, -C(O)-cyclopentyl, -C(O)-cyclohexyl, -C(O)-azepanyl, -C(O)-azepanyl, -C(O)-oxetanyl, -C(O)-oxolanyl, -C(O)-oxetanyl, azetidinyl, azopentyl, morpholinyl, piperazinyl, phenyl, pyrrolyl, furyl, thienyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrazinyl, The alkyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, oxolanyl, oxhexyl, azetidinyl, Azopentyl, azohexyl, morpholinyl, piperazinyl, phenyl, pyrrolyl, furyl, thienyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrazinyl optionally further substituted by 1-3 groups selected from deuterium, F, Cl, hydroxyl, cyano, amino, methyl, ethyl, methoxy, ethoxy, halo C 1-2 Alkyl, halogenated C 1-2 Alkoxy, acetyl, =O; in some embodiments, R 3aa Selected from F, Cl, hydroxy, cyano, =O, SF5, amino, methylamino, dimethylamino, -NH-cyclopropyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH2F, -CHFCHF2, -CHFCF3, -CF2CH2F, -CF2CHF2, -CF2CF3, -OCHF2, -OCH2F, -OCF3, -OCH2CH2F, -OCH2CHF2, -OCH2CF3, -OCHFCH2F, -OCHFCHF2, -OCHFCF3, -OCF2C H2F, -OCF2CHF2, -OCF2CF3, -CH2D, -CHD2, -CD3, -CH2CH2D, -CH2CHD2, -CH2CD3, -CHDCH2D, -CHDCHD2, -CHDCD3, -CD2CH2D, -CD2CHD2, -CD2CD3, -OC HD2, -OCH2D, -OCD3, -OCH2CH2D, -OCH2CHD2, -OCH2CD3, -OCHDCH2D, -OCHDCHD2, -OCHDCD3, -OCD2CH2D, -OCD2CHD2, -OCD2CD3, -NHC(O)CH3, acetyl, -NR aa C(O)-C 1-4 Alkyl, -NR aa C(O)-OC 1-4 Alkyl, -NR aaC(O)-deuterated C 1-4 alkyl, -NHC(O)-cyclopropyl, -NHC(O)-cyclobutyl, -NHC(O)-oxetanyl, -NHC(O)pyrazolyl, -C(O)NH-cyclobutyl, -C(O)-cyclopropyl, -C(O)-cyclobutyl, -C(O)-cyclopentyl, -C(O)-cyclohexyl, -C(O)-azepanyl, -C(O)-azepanyl, -C(O)-oxetanyl, -C(O)-oxolanyl, -C(O)-oxetanyl, azetidinyl, azopentyl, morpholinyl, piperazinyl, phenyl, pyrrolyl, furyl, thienyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrazinyl, The alkyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, oxolanyl, oxhexyl, azetidinyl, Azopentyl, azohexyl, morpholinyl, piperazinyl, phenyl, pyrrolyl, furyl, thienyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrazinyl optionally further substituted by 1-3 groups selected from deuterium, F, Cl, hydroxyl, cyano, amino, methyl, ethyl, methoxy, ethoxy, halo C 1-2 Alkyl, halogenated C 1-2 Alkoxy, acetyl, =O group substitution;

[0406] The definitions of other groups are consistent with any of the above schemes.

[0407] In a specific tenth embodiment, the compound of formula (I) of the present invention, and its stereoisomers, deuterated substances, solvates, or pharmaceutically acceptable salts or cocrystals, wherein

[0408] Ar3 is selected from the following groups:

[0409] (i) The is further substituted with 1 group selected from R3;

[0410] (ii) Imidazolyl, pyrrolyl, pyrimidinyl, pyrazinyl, pyridazinyl, the Imidazolyl, pyrrolyl, pyrimidinyl, pyrazinyl, pyridazinyl is further substituted with one group selected from R6;

[0411] In some embodiments, Ar3 is selected from the following groups:

[0412] (i) The is further substituted with 1 group selected from R3;

[0413] (ii) Imidazolyl, pyrrolyl, pyrimidinyl, pyrazinyl, pyridazinyl, the Imidazolyl, pyrrolyl, pyrimidinyl, pyrazinyl, pyridazinyl is further substituted with one group selected from R6;

[0414] R3 is selected from the following groups:

[0415] (1)

[0416] (2) Optionally further substituted with 1-2 groups selected from F, Cl, hydroxy, cyano, amino, methyl, ethyl, isopropyl, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH2F, -CHFCHF2, -CHFCF3, -CF2CH2F, -CF2CHF2, -CF2CF3, -CH2D, -CHD2, -CD3, -CH2CH2D, -CH2CHD2, -CH2CD3, -CHDCH2D, -CHDCHD2, -CHDCD3, -CD2CH2D, -CD2CHD2, or -CD2CD3;

[0417] (3) Further selected by 1 R 3b The group substitution;

[0418] (4) Pyridyl, phenyl, further substituted by 1-3 groups selected from F, Cl, methyl, ethyl, isopropyl, cyclopropyl, cyclobutyl, -NHC(O)CH3;

[0419] (5) ethynyl, propynyl, F, Cl, N3, wherein the ethynyl and propynyl groups are optionally further substituted with 1-2 groups selected from amino, methylamino, and dimethylamino;

[0420] (6)-C(O)-NR aa R4, -NR aa -C(O)R4, -C(O)-R4, -NR aa R4;

[0421] In some embodiments, R3 is selected from the following groups:

[0422] (1)

[0423] (2) Optionally further substituted with 1-2 groups selected from F, Cl, hydroxy, cyano, amino, methyl, ethyl, isopropyl, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH2F, -CHFCHF2, -CHFCF3, -CF2CH2F, -CF2CHF2, -CF2CF3, -CH2D, -CHD2, -CD3, -CH2CH2D, -CH2CHD2, -CH2CD3, -CHDCH2D, -CHDCHD2, -CHDCD3, -CD2CH2D, -CD2CHD2, or -CD2CD3;

[0424] (3) Further selected by 1 R 3b The group substitution;

[0425] (4) further substituted by 1-2 groups selected from methyl, ethyl, isopropyl, cyclopropyl, and cyclobutyl;

[0426] (5) ethynyl, propynyl, F, Cl, N3, wherein the ethynyl and propynyl groups are optionally further substituted with 1-2 groups selected from amino, methylamino, and dimethylamino;

[0427] (6)-C(O)-NR aa R4, -NR aa -C(O)R4, -C(O)-R4, -NR aa R4;

[0428] Each R4 is independently selected from tetrahydropyran, piperidine, cyclobutyl, pyrazole, imidazole, isoxazole, and the tetrahydropyran, piperidine, cyclobutyl, pyrazole, imidazole, isoxazole is optionally further substituted with 1-2 groups selected from methyl, ethyl, isopropyl, F, and Cl;

[0429] Each R aa Each is independently selected from H, methyl, -CH2F, -CHF2, -CF3, -CH2D, -CHD2, -CD3;

[0430] R6 is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, azetidinyl, oxolanyl, azopentyl, oxhexyl, azohexyl, morpholinyl, piperazinyl, optionally further substituted by 1-2 selected from R 3b The group substitution;

[0431] R 3bselected from F, Cl, hydroxy, cyano, amino, methylamino, dimethylamino, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH2F, -CHFCHF2, -CHFCF3, -CF2CH2F, -CF2CHF2, -CF2CF3, -OCHF2, -OCH2F, -OCF3, -OCH2CH2F, -OCH2CHF2, -OCH2CF3, -OCHFCH2F, -OCH CHFCHF2, -OCHFCF3, -OCF2CH2F, -OCF2CHF2, -OCF2CF3, -CH2D, -CHD2, -CD3, -CH2CH2D, -CH2CHD2, -CH2CD3, -CHDCH2D, -CHDCH D2, -CHDCD3, -CD2CH2D, -CD2CHD2, -CD2CD3, -OCHD2, -OCH2D, -OCD3, -OCH2CH2D, -OCH2CHD2, -OCH2CD3, -OCHDCH2D, -OCHDCHD 2, -OCHDCD3, -OCD2CH2D, -OCD2CHD2, -OCD2CD3, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, azetidinyl, oxolanyl, azacyclopentyl, oxhexyl, azacyclohexyl, morpholinyl, piperazinyl, phenyl, pyrrolyl, furyl, thienyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrazinyl, benzocyclopentyl, benzocyclohexyl, benzoazepine, -C(O)CH3, -C(O)CD3, -C(O)CH2CH3, -C(O)- Cyclopropyl, -C(O)-CH2-cyclopropyl, -C(O)-cyclobutyl, -C(O)-CH2-cyclobutyl, -C(O)-cyclopentyl, -C(O)-CH2-cyclopentyl, -C(O)-cyclohexyl, -C(O)-CH2-cyclohexyl, -C(O)-oxolanyl, -C(O)-azetidinyl, -C(O)-oxetanyl, -C(O)-azetidinyl, -C(O)-oxetanyl, -C(O)-CH2-oxolanyl, -C(O)-CH2-azetidinyl, -C(O)-CH2-oxetanyl, -C(O)-CH2- azetidinyl, -C(O)-CH2-oxacyclohexyl, -C(O)-CH2-azacyclohexyl, -C(O)-pyrazolyl, -C(O)-imidazolyl, -C(O)-pyrrolyl, -C(O)-furyl, -C(O)-oxazolyl, -C(O)-isoxazolyl, -C(O)-thiazolyl, -NHC(O)CH3, -S(O)2CH3, or -S(O)CH3,The cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, azetidinyl, oxolanyl, azopentyl, oxhexyl, azohexyl, morpholinyl, piperazinyl, phenyl, pyrrolyl, furyl, thienyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrazinyl, benzocyclopentyl, benzocyclohexyl, benzoazepine, optionally further substituted by 1-3 R, 3aa In some embodiments, R 3bSelected from F, Cl, hydroxy, cyano, amino, methylamino, dimethylamino, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH2F, -CHFCHF2, -CHFCF3, -CF2CH2F, -CF2CHF2, -CF2CF3, -OCHF2, -OCH2F, -OCF3, -OCH2CH2F, -OCH2CHF2, -OCH2CF3, -OCHFCH2F, -OCHFCHF2, -OCHFCF3, -OCF2CH2F, -OCF 2CHF2, -OCF2CF3, -CH2D, -CHD2, -CD3, -CH2CH2D, -CH2CHD2, -CH2CD3, -CHDCH2D, -CHDCHD2, -CHDCD3, -CD2CH2D, -CD2CHD2, -CD2CD3, -OCHD2, -OCH2D, -OCD3, -OCH2CH2D, -OCH2CHD2, -OCH2CD3, -OCHDCH2D, -OCHDCHD2, -OCHDCD3, -OCD2CH2D, -OCD2CHD2, -OCD2CD3, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, Azetidinyl, oxolanyl, azacyclopentyl, oxahinyl, azahexyl, morpholinyl, piperazinyl, phenyl, pyrrolyl, furyl, thienyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrazinyl, benzocyclopentyl, benzocyclohexyl, -C(O)CH3, -C(O)CH2CH3, -C(O)-cyclopropyl, -C(O)-CH2-cyclopropyl, -C(O)-cyclobutyl, -C(O)-CH2-cyclobutyl, -C(O)-cyclopentyl, -C(O)-CH2-cyclopentyl, -C(O)-cyclohexyl, -C(O)-CH2-cyclohexyl, -C(O)-oxolanyl, -C(O)-azepanyl, -C(O)-azepanyl cyclopentyl, -C(O)-oxetanyl, -C(O)-azetidinyl, -C(O)-oxetanyl, -C(O)-CH2-oxolanyl, -C(O)-CH2-azetidinyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-azetidinyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-azetidinyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-azetidinyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-azetidinyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-azetidinyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-azetidinyl, -C(O)-pyrazolyl, -C(O)-imidazolyl, -C(O)-pyrrolyl, -C(O)-furyl, -C(O)-oxazolyl, -C(O)-isoxazolyl, -C(O)-thiazolyl, -NHC(O)CH3, -S(O)2CH3, or -S(O)CH3,The cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, azetidinyl, oxolanyl, azopentyl, oxhexyl, azohexyl, morpholinyl, piperazinyl, phenyl, pyrrolyl, furyl, thienyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrazinyl, benzocyclopentyl, benzocyclohexyl are optionally further substituted by 1-3 R, 3aa The group substitution;

[0432] R 3aa Selected from F, Cl, hydroxy, cyano, SF5, amino, methylamino, dimethylamino, -NH-cyclopropyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH2F, -CHFCHF2, -CHFCF3, -CF2CH2F, -CF2CHF2, -CF2CF3, -OCHF2, -OCH2F, -OCF3, -OCH2CH2F, -OCH2CHF2, -OCH2CF3, -OCHFCH2F, -OCHFCHF2, -OCHFCF3, -OCF2CH2 F, -OCF2CHF2, -OCF2CF3, -CH2D, -CHD2, -CD3, -CH2CH2D, -CH2CHD2, -CH2CD3, -CHDCH2D, -CHDCHD2, -CHDCD3, -CD2CH2D, -CD2CHD2, -CD2CD3, -OCH D2, -OCH2D, -OCD3, -OCH2CH2D, -OCH2CHD2, -OCH2CD3, -OCHDCH2D, -OCHDCHD2, -OCHDCD3, -OCD2CH2D, -OCD2CHD2, -OCD2CD3, -NHC(O)CH3, acetyl, -NR aa C(O)-C 1-4 Alkyl, -NR aa C(O)-deuterated C 1-4 alkyl, -NHC(O)-cyclopropyl, -NHC(O)-cyclobutyl, -C(O)NH-cyclobutyl, -C(O)-cyclopropyl, -C(O)-cyclobutyl, -C(O)-cyclopentyl, -C(O)-cyclohexyl, -C(O)-azepanyl, -C(O)-azepanyl, -C(O)-oxetanyl, -C(O)-oxolanyl, -C(O)-oxetanyl, azetidinyl, azopentyl, morpholinyl, piperazinyl, phenyl, pyrrolyl, furyl, thienyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrazinyl, The cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, oxolanyl, oxhexyl, azetidinyl, Azopentyl, azohexyl, morpholinyl, piperazinyl, phenyl, pyrrolyl, furyl, thienyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrazinyl optionally further substituted by 1-3 groups selected from deuterium, F, Cl, hydroxyl, cyano, amino, methyl, ethyl, methoxy, ethoxy, halo C 1-2 Alkyl, halogenated C 1-2 Alkoxy, acetyl, =O; in some embodiments, R 3aa Selected from F, Cl, hydroxy, cyano, SF5, amino, methylamino, dimethylamino, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH2F, -CHFCHF2, -CHFCF3, -CF2CH2F, -CF2CHF2, -CF2CF3, -OCHF2, -OCH2F, -OCF3, -OCH2CH2F, -OCH2CHF2, -OCH2CF3, -OCHFCH2F, -OCHFCHF2, -OCHFCF3, -OCF2CH2F, -OCH CF2CHF2, -OCF2CF3, -CH2D, -CHD2, -CD3, -CH2CH2D, -CH2CHD2, -CH2CD3, -CHDCH2D, -CHDCHD2, -CHDCD3, -CD2CH2D, -CD2CHD2, -CD2CD3, -OCHD2 , -OCH2D, -OCD3, -OCH2CH2D, -OCH2CHD2, -OCH2CD3, -OCHDCH2D, -OCHDCHD2, -OCHDCD3, -OCD2CH2D, -OCD2CHD2, -OCD2CD3, -NHC(O)CH3, acetyl, -NR aa C(O)-C 1-4 alkyl, -NHC(O)-cyclopropyl, -NHC(O)-cyclobutyl, -C(O)NH-cyclobutyl, -C(O)-cyclopropyl, -C(O)-cyclobutyl, -C(O)-cyclopentyl, -C(O)-cyclohexyl, -C(O)-azacyclopentyl, -C(O)-azacyclohexyl, -C(O)-oxetanyl, -C(O)-oxetanyl or -C(O)-oxetanyl, the cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetan ... Azacyclopentyl and azacyclohexyl are optionally further substituted by 1-3 groups selected from F, Cl, hydroxy, cyano, amino, methyl, ethyl, methoxy, ethoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, acetyl group substitution.

[0433] The compound of the present invention, its stereoisomer, deuterated form, solvate, or pharmaceutically acceptable salt or cocrystal, wherein the compound is selected from one of the structures in Table 1 below:

[0434] Table 1

[0435] The present invention also provides a pharmaceutical composition comprising a therapeutically effective amount of any compound described in the present invention, or its stereoisomer, deuterated substance, solvate or pharmaceutically acceptable salt or cocrystal, and a pharmaceutically acceptable carrier and / or excipient.

[0436] Furthermore, the present invention provides a pharmaceutical composition or pharmaceutical preparation comprising 1-1000 mg of a compound according to any of the aforementioned technical solutions, its stereoisomers, deuterated forms, solvates, pharmaceutically acceptable salts, or cocrystals, and a pharmaceutically acceptable carrier and / or excipient. The pharmaceutical composition may be in the form of a unit dosage form (the amount of the active ingredient in a unit dosage form is also referred to as the "drug strength").

[0437] The present invention also relates to a pharmaceutical use, namely, use of any compound of the present invention, or its stereoisomers, deuterated compounds, pharmaceutically acceptable salts or cocrystals, or compositions containing them, in the preparation of a medicament for treating diseases mediated by Pol θ. The Pol θ-mediated diseases include, but are not limited to, liver cancer, breast cancer, ovarian cancer, lung cancer, kidney cancer, prostate cancer, skin cancer, bladder cancer, pancreatic cancer, or head and neck cancer.

[0438] The present invention also provides a method for treating a disease in a mammal, comprising administering to the mammal a therapeutically effective amount of a compound of the present invention, or a stereoisomer, deuterated form, solvate, pharmaceutically acceptable salt, cocrystal, or pharmaceutical composition thereof. In some embodiments, the mammal of the present invention comprises a human. The therapeutically effective amount is preferably 1-1000 mg, and the disease is preferably liver cancer, breast cancer, ovarian cancer, lung cancer, kidney cancer, prostate cancer, skin cancer, bladder cancer, pancreatic cancer, or head and neck cancer.

[0439] As used herein, an "effective amount" or "therapeutically effective amount" refers to the administration of a sufficient amount of a compound disclosed herein to 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 alleviation of the signs, symptoms, or causes of a disease, or any other desired alteration of a biological system. For example, an "effective amount" for therapeutic uses is the amount of a composition comprising a compound disclosed herein required to provide a clinically significant reduction in disease symptoms.Examples of therapeutically effective amounts include, but are not limited to, 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, 1-20 mg, 5-1000 mg, 5-900 mg, 5-800 mg, 5-700 mg, 5-600 mg, 5-500 mg, 5-400 mg, 5-300 mg, 5-25 0mg, 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, 10-1000mg, 10-900 mg, 10-800mg, 10-700mg, 10-600mg, 10-500mg, 10-450mg, 10-400mg, 10-300mg, 10-250mg, 10-200mg, 10-150mg, 10-125mg, 10-100mg, 10-90 mg, 10-80mg, 10-70mg, 10-60mg, 10-50mg, 10-40mg, 10-30mg, 10-20mg; 20-1000mg, 20-900mg, 20-800mg, 20-700mg, 20-600mg, 20-500mg, 2 0-400mg, 20-350mg, 20-300mg, 20-250mg, 20-200mg, 20-150mg, 20-125mg, 20-100mg, 20-90mg, 20-80mg, 20-70mg, 20-60mg, 20-50mg, 20-40 mg, 20-30mg; 50-1000mg, 50-900mg, 50-800mg, 50-700mg, 50-600mg, 50-500mg, 50-400mg, 50-300mg, 50-250mg, 50-200mg, 50-150mg, 50-1 25mg, 50-100mg; 100-1000mg, 100-900mg, 100-800mg, 100-700mg, 100-600mg, 100-500mg, 100-400mg, 100-300mg, 100-250mg, 100-200mg;.

[0440] In some embodiments, the pharmaceutical composition includes, but is not limited to, 1-1000 mg, 5-500 mg, 10-250 mg, 50-250 mg, 100-200 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, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 120 mg, 125 mg, 150 mg, 200 mg, 250 mg, 300 mg, 400 mg, 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, 1000 mg of a compound of the invention or a stereoisomer, deuterated form, solvate, pharmaceutically acceptable salt, or cocrystal thereof.

[0441] A method for treating a disease in a mammal, comprising administering to a subject a therapeutically effective amount of a compound of the present invention or a stereoisomer, deuterated form, solvate, pharmaceutically acceptable salt, or cocrystal thereof, preferably 1-1000 mg. The disease is preferably liver cancer, breast cancer, ovarian cancer, lung cancer, kidney cancer, prostate cancer, skin cancer, bladder cancer, pancreatic cancer, or head and neck cancer.

[0442] A method for treating a disease in a mammal, comprising administering to a subject a compound of the present invention or a stereoisomer, deuterated form, solvate, pharmaceutically acceptable salt, or cocrystal thereof at a daily dose of 1-1000 mg / day. The daily dose may be a single dose or divided doses. In some embodiments, the daily dose includes, but is not limited to, 1-1000 mg / day, 1-300 mg / day, 5-500 mg / day, 10-500 mg / day, , 10-400 mg / day, 10-300 mg / day, 10-100 mg / day, 20-400 mg / day, 20-200 mg / day, 20-100 mg / day, 50-500 mg / day, 50-250 mg / day, 50-200 mg / day, 50-150 mg / day, 50-100 mg / day, 100-500 mg / day, 100-300 mg / day, 100-200 mg / day;

[0443] In some embodiments, daily doses include but are not limited to: 1 mg / day, 2.5 mg / day, 5 mg / day, 10 mg / day, 12.5 mg / day, 15 mg / day, 20 mg / day, 25 mg / day, 30 mg / day, 35 mg / day, 40 mg / day, 45 mg / day, 50 mg / day, 60 mg / day, 70 mg / day, 80 mg / day, 90 mg / day, 100 mg / day, 120 mg / day, 150 mg / day, 200 mg / day, 250 mg / day, 300 mg / day, 400 mg / day, 500 mg / day, 1000 mg / day.

[0444] The present invention relates to a kit, which may include a composition in single-dose or multi-dose form, wherein the kit contains a compound of the present invention or a stereoisomer, deuterated form, solvate, pharmaceutically acceptable salt or cocrystal thereof, and the amount of the compound of the present invention or its stereoisomer, deuterated form, solvate, pharmaceutically acceptable salt or cocrystal is the same as that in the above-mentioned pharmaceutical composition.

[0445] The amount of the compound of the invention or its stereoisomer, deuterated form, solvate, pharmaceutically acceptable salt or cocrystal in the present invention is in each case calculated as the free base.

[0446] "Preparation specifications" refers to the weight of the main drug contained in each vial, tablet or other unit preparation.

[0447] Synthesis route

[0448] Those skilled in the art can prepare the compounds of the present invention by combining known organic synthesis techniques, using commercially available chemicals and / or compounds described in the chemical literature as starting materials. "Commercially available chemicals" are obtained from reputable commercial sources, including suppliers such as Titan Technology, Anage Chemical, Shanghai Demo, Chengdu Kelon Chemical, Shaoyuan Chemical Technology, Nanjing Yaoshi, WuXi AppTec, and J&K Technology.

[0449] Specific and similar reactants can be selectively identified by indexes of known chemical substances prepared by the American Chemical Society's Chemical Abstracts Service, which are available in most public and university libraries and online. Chemicals that are known but not commercially available in the catalog are optionally prepared by custom chemical synthesis facilities, many of which standard chemical supply facilities (e.g., those listed above) offer custom synthesis services.

[0450] the term

[0451] Unless otherwise specified in the present invention, the terms of the present invention have the following meanings:

[0452] The carbon, hydrogen, oxygen, sulfur, nitrogen or halogen involved in the groups and compounds of the present invention include their isotopes, and the carbon, hydrogen, oxygen, sulfur, nitrogen or halogen involved in the groups and compounds of the present invention are optionally further replaced by one or more of their corresponding isotopes, wherein the isotopes of carbon include 12 C. 13 C and 14 C, hydrogen isotopes include protium (H), deuterium (deuterium, also known as heavy hydrogen), tritium (T, also known as super tritium), oxygen isotopes include 16 O. 17 O and 18 O, sulfur isotopes include 32 S. 33 S. 34 S and 36 S, nitrogen isotopes include 14 N and 15 N, an isotope of fluorine 19 F, chlorine isotopes include 35 Cl and 37 Isotopes of Cl, bromine include 79 Br and 81 Br.

[0453] "Halogen" herein refers to F, Cl, Br, I, or isotopes thereof.

[0454] "Halo" or "halogen-substituted" refers to substitution with one or more halogens selected from F, Cl, Br, I, or isotopes thereof. The upper limit of the number of halogen substituents is equal to the sum of the number of hydrogen atoms that can be replaced by the substituted group. Unless otherwise specified, the number of halogen substituents is any integer between 1 and the upper limit. When the number of halogen substituents is greater than 1, they may be the same or different halogens. Typical examples include 1-5 halogen substitutions, 1-3 halogen substitutions, 1-2 halogen substitutions, and 1 halogen substitution.

[0455] “D” or “deuterium” refers to deuterium, an isotope of hydrogen (H).

[0456] "Deuterated" or "deuterated compound" refers to a situation where a hydrogen atom on an alkyl, cycloalkyl, alkylene, aryl, heteroaryl, thiol, heterocycloalkyl, alkenyl, alkynyl or other group is replaced by at least one deuterium atom. The upper limit of the number of deuterated groups is equal to the sum of the number of replaceable hydrogen atoms in the substituted group. Unless otherwise specified, the number of deuterated groups is any integer between 1 and the upper limit, for example, 1-20 deuterium atoms, 1-10 deuterium atoms, 1-6 deuterium atoms, 1-3 deuterium atoms, 1-2 deuterium atoms or 1 deuterium atom.

[0457] “C x-y " group refers to a group containing x to y carbon atoms, such as "C1-6 "Alkyl" refers to an alkyl group containing 1 to 6 carbon atoms.

[0458] "Alkyl" refers to a monovalent straight-chain or branched saturated aliphatic hydrocarbon group. Typically, it is an alkyl group having 1 to 20 carbon atoms, or an alkyl group having 1 to 8 carbon atoms, or an alkyl group having 1 to 6 carbon atoms, or an alkyl group having 1 to 4 carbon atoms. Non-limiting examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, neobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, and the like. The alkyl group may be further substituted with a substituent.

[0459] "Alkylene" refers to a divalent straight-chain or branched saturated alkyl group. Examples of alkylene groups include, but are not limited to, methylene, ethylene, and the like.

[0460] "Haloalkyl" refers to a situation where one or more hydrogen atoms in an alkyl group are replaced by one or more halogen atoms (such as fluorine, chlorine, bromine, iodine, or their isotopes). The upper limit of the number of halogen substituents is equal to the sum of the number of replaceable hydrogen atoms in the alkyl group. Unless otherwise specified, the number of halogen substituents is any integer between 1 and the upper limit. Typically, an alkyl group is substituted with 1-5 halogens, or 1-3 halogens, or 1-2 halogens, or 1 halogen. When the number of halogen substituents is greater than 1, they can be the same or different halogens. Specific examples include, but are not limited to, -CF3, -CH2Cl, -CH2CF3, -CCl2, CF3, etc.

[0461] "Alkoxy" or "alkyloxy" refers to an -O-alkyl group. For example, -OC 1-8 Alkyl, -OC 1-6 Alkyl, -OC 1-4 Alkyl or -OC 1-2 Specific non-limiting examples include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy, tert-butoxy, n-pentoxy, n-hexyloxy, cyclopropyloxy, and cyclobutyloxy, and the like; the alkoxy groups may be optionally substituted with substituents.

[0462] "Haloalkoxy" refers to an -O-haloalkyl group. For example, -O-haloC 1-8 Alkyl, -O-halogenated C 1-6 Alkyl, -O-halogenated C 1-4 Alkyl or -O-halogenated C 1-2Alkyl; the upper limit of the number of halogen substituents is equal to the sum of the number of hydrogen atoms that can be substituted by the substituted group. Unless otherwise specified, the number of halogen substituents is any integer between 1 and the upper limit, preferably 1-5 halogen substitutions, 1-3 halogen substitutions, 1-2 halogen substitutions, or 1 halogen substitution; when the number of halogen substituents is greater than 1, they may be the same or different halogen substitutions; non-limiting examples include monofluoromethoxy, difluoromethoxy, trifluoromethoxy, difluoroethyloxy, and the like.

[0463] "Alkenyl" refers to a straight or branched chain hydrocarbon group containing at least one carbon-carbon double bond (C=C), typically containing 2 to 18 carbon atoms, such as 2 to 8 carbon atoms, further such as 2 to 6 carbon atoms, and further such as 2 to 4 carbon atoms, examples of which include but are not limited to vinyl, allyl, 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-methyl-1-butenyl, 2-methyl-1-butenyl, 2-methyl-2-butenyl, 2-methyl-3-butenyl, 2-methyl-4-butenyl, 2-methyl-5-butenyl, 2-methyl-6-butenyl, 2-methyl-7-butenyl, 2-methyl-8-butenyl, 2-methyl-9-butenyl, 2-methyl-1-butenyl, 2-methyl-2-butenyl, 2-methyl-3 ... -methyl-3-butenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 1-methyl-1-pentenyl, 2-methyl-1-pentenyl, 1-heptenyl, 2-heptenyl, 3-heptenyl, 4-heptenyl, 1-octenyl, 3-octenyl, 1-nonenyl, 3-nonenyl, 1-decenyl, 4-decenyl, 1,3-butadiene, 1,3-pentadiene, 1,4-pentadiene and 1,4-hexadiene, etc.; the alkenyl group may be optionally further substituted with a substituent.

[0464] "Alkenylene" refers to a straight or branched divalent unsaturated hydrocarbon group containing at least one carbon-carbon double bond (C=C), typically containing 2 to 18 carbon atoms, such as 2 to 8 carbon atoms, further such as 2 to 6 carbon atoms, and further such as 2 to 4 carbon atoms. Non-limiting examples include ethynylene, and the alkenylene group may be optionally substituted with a substituent.

[0465] "Alkynyl" refers to a straight-chain or branched hydrocarbon group containing at least one carbon-carbon triple bond (C≡C), typically containing 2 to 18 carbon atoms, further containing 2 to 8 carbon atoms, further containing 2 to 6 carbon atoms, and further containing 2 to 4 carbon atoms. Examples include, but are not limited to, ethynyl, 1-propynyl, 2-propynyl, butynyl, 2-butynyl, 3-butynyl, 1-methyl-2-propynyl, 4-pentynyl, 3-pentynyl, 1-methyl-2-butynyl, 2-hexynyl, 3-hexynyl, 2-heptynyl, 3-heptynyl, 4-heptynyl, 3-octynyl, 3-nonynyl, and 4-decynyl. The alkynyl group may be optionally substituted with a substituent.

[0466] "Alkynylene" refers to a straight or branched divalent unsaturated hydrocarbon group containing a carbon-carbon triple bond (C≡C), typically containing 2 to 18 carbon atoms, further containing 2 to 8 carbon atoms, further containing 2 to 6 carbon atoms, further containing 2-4 carbon atoms, non-limiting examples include ethynylene, propynylene, butynylene, and the alkynylene group may be optionally substituted with a substituent.

[0467] "Cycloalkyl" refers to a saturated or partially unsaturated, non-aromatic carbocyclic hydrocarbon group containing no ring heteroatoms. Cycloalkyl can be monocyclic, bicyclic or polycyclic. Bicyclic or polycyclic can be cyclic, spirocyclic, bridged or a combination thereof. Usually, cycloalkyl contains 3 to 20 carbon atoms, further contains 3-12 carbon atoms, further contains 3-8 carbon atoms, further contains 3-6 carbon atoms; when it is a monocyclic cycloalkyl, it contains 3-15 carbon atoms, or 3-10 carbon atoms, or 3-8 carbon atoms, or 3-6 carbon atoms; when it is a bicyclic or polycyclic cycloalkyl, it contains 5-12 carbon atoms, or contains 5-11 carbon atoms, or contains 6-10 carbon atoms; non-limiting examples include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, butenyl, cyclopentenyl, cyclohexenyl, The cycloalkyl group may be optionally substituted with a substituent.

[0468] "Cycloalkylene" refers to a divalent radical of a cycloalkyl group.

[0469] "Aryl" refers to a carbocyclic ring having aromaticity and not containing heteroatoms, including monocyclic aryl and condensed ring aryl. It generally contains 6 to 14 carbon atoms, and further contains 6 to 10 carbon atoms. Non-limiting examples include phenyl, naphthyl, anthracenyl, and phenanthrenyl. Aryl can optionally be substituted with a substituent.

[0470] "Carbocycle" or "carbocyclyl" refers to a saturated, partially unsaturated, or aromatic carbocycle, including aryl and cycloalkyl. Carbocycles can be monocyclic, bicyclic, or polycyclic, including bridged, fused, and spirocyclic rings and combinations thereof. Carbocycles typically have 3 to 12 carbon atoms, or 3-10 carbon atoms, or 3-6 carbon atoms. In non-limiting examples, monocyclic carbocycles include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or phenyl, and bicyclic bridged rings include etc., double ring and ring include etc., bicyclic spiro ring includes The carbocyclic ring may be optionally substituted with a substituent.

[0471] "Heterocycloalkyl" refers to a saturated or partially unsaturated, non-aromatic carbocyclic ring containing 1, 2, 3, or 4 heteroatoms selected from N, S, and O. Heterocycloalkyl groups may be monocyclic, bicyclic, or polycyclic. Bicyclic or polycyclic groups may be bridged, fused, spirocyclic, or combinations thereof. Heterocycloalkyl groups typically have 3 to 20 members. Monocyclic heterocycloalkyl groups typically have 3 to 15 members, or 3 to 10 members, or 3 to 8 members, or 3 to 6 members. Bicyclic or polycyclic heterocycloalkyl groups typically have 5 to 12 members, or 5 to 11 members, or 6 to 9 members. The heteroatoms N and S include their oxidation states. Non-limiting examples of heterocycloalkyl groups include azetidinyl, morpholinyl, piperazinyl, piperidinyl, tetrahydropyranyl, oxetanyl, pyranyl, azolidinyl, azolinyl, oxolanyl, oxekinyl, and the like. Heterocycloalkyl groups may be optionally substituted with substituents.

[0472] "Heteroaromatic ring" or "heteroaryl" unless otherwise specified refers to a ring containing 1 to 4 heteroatoms selected from N, O or S and their oxidation states and having aromatic properties, which may be monocyclic, bicyclic or polycyclic, and the bicyclic or polycyclic rings may be bridged, parallel, spirocyclic or combinations thereof; when bicyclic or polycyclic, it may be a fusion of a heteroaryl and an aryl, or a fusion of a heteroaryl and a heteroaryl, wherein either the heteroaryl or the aryl may be a connection site. Non-limiting examples include furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, indolyl, purinyl, The heteroaryl group may be optionally substituted by a substituent.

[0473] "Heterocycle" or "heterocyclyl" refers to a saturated or unsaturated, aromatic or non-aromatic ring containing 1 to 4 heteroatoms selected from N, O, or S and their oxidation states, and includes heteroaryl and heterocycloalkyl. Heterocycles include monocyclic heterocycles, bicyclic bridged heterocycles, bicyclic heterocycles, and bicyclic spiro heterocycles, or combinations thereof. Heterocycles are typically 3- to 12-membered heterocycles, 5- to 12-membered heterocycles, or 5- to 7-membered heterocycles. The heterocyclic group may be attached to a heteroatom or a carbon atom, and non-limiting examples include oxirane, aziridine, oxetanyl, azetidinyl, 1,3-dioxolanyl, 1,4-dioxolanyl, 1,3-dioxanyl, piperazinyl, azepanyl, pyridinyl, furanyl, thienyl, pyranyl, N-alkylpyrrolyl, pyrimidinyl, pyrazinyl, pyrazolyl, pyridazinyl, imidazolyl, piperidinyl, piperidinyl, morpholinyl, thiomorpholinyl, 1,3-dithianyl , dihydrofuranyl, dihydropyranyl, dithiolanyl, tetrahydrofuranyl, tetrahydropyrrolyl, tetrahydroimidazolyl, oxazolyl, dihydrooxazolyl, tetrahydrooxazolyl, tetrahydrothiazolyl, tetrahydropyranyl, benzimidazolyl, benzopyridinyl, pyrrolopyridinyl, benzodihydrofuranyl, azabicyclo[3.2.1]octyl, azabicyclo[5.2.0]nonyl, oxatricyclo[5.3.1.1]dodecyl, azaadamantyl and oxaspiro[3.3]heptanyl, The heterocyclic ring may be optionally substituted with a substituent.

[0474] "Heterocyclylene" refers to a substituted or unsubstituted, saturated or unsaturated, aromatic or non-aromatic divalent heterocyclic group. Non-limiting examples include wait.

[0475] "Spiro" refers to a polycyclic group that shares a carbon atom (called a spiro atom) between the rings, which may contain 0 or more double bonds or triple bonds, and may contain 0 to 5 heteroatoms selected from N, O, S, P, Si and their oxidation states. Typically, the spiro ring is a 6- to 14-membered ring, or a 6- to 12-membered ring, or a 6- to 10-membered ring. Typically, the spiro ring is a trispirotri (representing a three-membered ring spirotricycle), a trispirotetra, a trispiropenta, a trispirohexa, a tetraspirotetra, a tetraspiropenta, a tetraspirohexa, a pentaspiropenta or a pentaspirohexa. Non-limiting examples of spiro rings include , the spiro ring may be optionally substituted by a substituent.

[0476] "Parallel ring" or "condensed ring" refers to a polycyclic group in which the rings share two adjacent ring atoms and a chemical bond, and may contain one or more double bonds or triple bonds, and the rings may contain 0 to 5 heteroatoms selected from N, S, O, P, Si and their oxidation states. Usually, the cyclic ring is a 5- to 20-membered ring, or a 5- to 14-membered ring, or a 5- to 12-membered ring, or a 5- to 10-membered ring. Usually, the cyclic ring is a three- to four-membered ring (representing a cyclic ring formed by a three-membered ring and a four-membered ring. According to the IUPC naming rules, it is possible to have a three-membered ring as the basic ring or a four-membered ring as the basic ring. The same applies below), a three- to five-ring ring, a three- to six-ring ring, a four- to four-ring ring, a four- to five-ring ring, a four- to six-ring ring, a five- to five-ring ring, a five- to six-ring ring, and a six- to six-ring ring. Non-limiting examples of cyclic rings include purine, quinoline, isoquinoline, benzopyran, benzofuran, benzothiophene, The cyclic ring may be aromatic or non-aromatic and may be optionally substituted with a substituent.

[0477] "Bicyclic heterocyclic ring" refers to a bicyclic group in which two rings share two adjacent ring atoms and a chemical bond, and may contain one or more double bonds or triple bonds, and contain 1 to 5 heteroatoms selected from N, S, O, P, Si and their oxidation states, and may be saturated, partially saturated or aromatic, and its meaning includes bicyclic heterocyclic alkyl and bicyclic heteroaryl. Usually, the ring is 5 to 20-membered, or 5 to 14-membered, or 5 to 12-membered, or 8 to 10-membered. Usually, the ring is six-membered and five-membered (representing a ring formed by a six-membered ring and a five-membered ring. According to the IUPC naming rules, it is possible to have a six-membered ring as the basic ring or a five-membered ring as the basic ring, and the same applies below), six-membered and six-membered rings, five-membered and five-membered rings, four-membered and four-membered rings, four-membered and six-membered rings, five-membered and five-membered rings, five-membered and six-membered rings, and six-membered and six-membered rings. The bicyclic heterocyclic ring is optionally substituted by a substituent.

[0478] "Bridged ring" means two rings that share two non-adjacent ring atoms and may contain one or more double or triple bonds. A bridged ring may contain 0 to 5 heteroatoms selected from N, S, O, P, Si and their oxidation states. Typically, the number of ring atoms in a bridged ring is 5 to 20, or 5 to 14, or 5 to 12, or 5 to 10. Non-limiting examples of bridged rings include adamantane,

[0479] "Cycloheterocycloalkyl" refers to a ring containing at least one heterocycloalkane, which may be a heterocycloalkane-heterocycloalkyl, a cycloalkyl-heterocycloalkyl, or a heterocycloalkyl-cycloalkyl;

[0480] "Spiroheterocycloalkyl" refers to a spirocyclic ring system containing at least one heterocycloalkane, which may be a heterocycloalkanespiroheterocycloalkyl, a cycloalkylspiroheterocycloalkyl, or a heterocycloalkylspirocycloalkyl;

[0481] "Substitution" or "substituent" unless otherwise specified refers to any substitution at a position permitted by chemical theory, and the number of substituents complies with the chemical bond rules. Exemplary substituents include but are not limited to: C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Heteroalkyl, C 5-12 Aryl, 5-12 membered heteroaryl, hydroxyl, C 1-6 Alkoxy, C 5-12 Aryloxy, thiol, C 1-6 Alkylthio, cyano, halogen, C 1-6 Alkylthiocarbonyl, C 1-6 Alkylcarbamoyl, N-carbamoyl, nitro, silyl, sulfinyl, sulfonyl, sulfoxide, halo 1-6 Alkyl, halogenated C 1-6 Alkoxy, amino, phosphonic acid, -CO2(C 1-6 alkyl), -OC(=O)(C 1-6 alkyl), -OCO2(C 1-6 alkyl), -C(=O)NH2, -C(=O)N(C 1-6 alkyl)2,-OC(=O)NH(C 1-6 alkyl), -NHC(=O)(C 1-6 alkyl), -N(C 1-6 alkyl)C(=O)(C 1-6 Alkyl), -NHCO2(C 1-6 alkyl), -NHC(=O)N(C 1-6 alkyl)2,-HC(=O)NH(C 1-6 alkyl), -NHC(=O)NH2, -NHSO2(C 1-6 alkyl), -SO2N(C 1-6 Alkyl)2,-SO2NH(C 1-6 alkyl), -SO2NH2, -SO2C 1-6 Alkyl, etc.

[0482] "Optional" or "optionally" means that the subsequently described event or circumstance may but need not occur, and the description includes instances where the event or circumstance occurs and instances where it does not. For example, "alkyl optionally substituted with F" means that the alkyl group may but need not be substituted with F, and the description includes instances where the alkyl group is substituted with F and instances where the alkyl group is not substituted with F.

[0483] "Pharmaceutically acceptable salts" refer to salts of the compounds of the present invention that retain the biological effectiveness and properties of the free acids or free bases, and the free acids are reacted with non-toxic inorganic or organic bases, or the free bases are reacted with non-toxic inorganic or organic acids.

[0484] A "pharmaceutical composition" refers to a mixture of one or more compounds described herein, or stereoisomers, deuterated forms, solvates, pharmaceutically acceptable salts, or cocrystals thereof, with other ingredients, wherein the other ingredients include physiologically / pharmaceutically acceptable carriers and / or excipients.

[0485] "Carrier" refers to a system that does not cause significant irritation to the organism and does not eliminate the biological activity and properties of the administered compound, and can change the way the drug enters the human body and its distribution in the body, control the release rate of the drug and deliver the drug to the target organ. Non-limiting examples include microcapsules and microspheres, nanoparticles, liposomes, etc.

[0486] An "excipient" is a substance that is not itself a therapeutic agent but serves as a diluent, adjuvant, binder, and / or vehicle that is added to a pharmaceutical composition to improve its handling or storage properties or to allow or facilitate the formation of a compound or pharmaceutical composition into a unit dosage form for administration. As known to those skilled in the art, pharmaceutical excipients can serve a variety of functions and can be described as wetting agents, buffers, suspending agents, lubricants, emulsifiers, disintegrants, absorbents, preservatives, surfactants, colorants, flavoring agents, and sweeteners. Examples of pharmaceutical excipients include, but are not limited to: (1) sugars such as lactose, glucose, and sucrose; (2) starches such as corn starch and potato starch; (3) cellulose and its derivatives such as sodium carboxymethylcellulose, ethylcellulose, cellulose acetate, hydroxypropyl methylcellulose, hydroxypropyl cellulose, microcrystalline cellulose, and cross-linked carboxymethylcellulose (e.g., cross-linked sodium carboxymethylcellulose); (4) tragacanth; (5) malt; (6) gelatin; (7) talc; (8) excipients such as cocoa butter and suppository waxes; (9) oils such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn starch, and maltodextrin. oil and soybean oil; (10) glycols such as propylene glycol; (11) polyols such as glycerol, sorbitol, mannitol and polyethylene glycol; (12) esters such as ethyl oleate and ethyl laurate; (13) agar; (14) buffers such as magnesium hydroxide and aluminum hydroxide; (15) alginic acid; (16) pyrogen-free water; (17) isotonic saline; (18) Ringer's solution; (19) ethanol; (20) pH buffer solutions; (21) polyesters, polycarbonates and / or polyanhydrides; and (22) other non-toxic compatible substances used in pharmaceutical preparations.

[0487] "Stereoisomers" refer to isomers resulting from different spatial arrangements of atoms in a molecule, including cis-trans isomers, enantiomers, and conformational isomers.

[0488] The compounds of the present invention also include their tautomers. For example, when the present invention describes a compound on the left side in which the pyrimidine ring is substituted with OH, it also includes the tautomer compound on the right side.

[0489] "Solvate" refers to a substance formed by a compound of the present invention or a salt thereof and a stoichiometric or non-stoichiometric amount of a solvent bound to the compound or salt thereof by non-covalent forces between the molecules. When the solvent is water, the solvate is a hydrate.

[0490] A "cocrystal" is a crystal formed by the active pharmaceutical ingredient (API) and cocrystal former (CCF) bound together by hydrogen bonds or other non-covalent bonds. Both the API and CCF are solid in their pure form at room temperature, and the components exist in a fixed stoichiometric ratio. A cocrystal is a multi-component crystal, encompassing both binary cocrystals formed between two neutral solids and multi-component cocrystals formed between a neutral solid and a salt or solvate. DETAILED DESCRIPTION

[0491] The technical solutions of the present invention are described in detail below in conjunction with the embodiments, but the protection scope of the present invention includes but is not limited to them.

[0492] The present invention will be described in detail below through examples. Where specific conditions are not specified in the examples, the experimental methods are carried out according to conventional conditions. The examples are provided to better illustrate the present invention, but it should not be understood that the present invention is limited to the examples. Any non-essential improvements and adjustments made by those skilled in the art to the embodiments based on the above invention are still within the scope of protection of the present invention.

[0493] Test Method

[0494] The structures of the compounds were determined by nuclear magnetic resonance (NMR) or / and mass spectrometry (MS). NMR shifts (δ) were expressed in 10 -6 The unit of (ppm) is given. NMR measurements were performed using a Bruker Avance III 400 and Bruker Avance 300 NMR spectrometer. The solvents used were deuterated dimethyl sulfoxide (DMSO-d6), deuterated chloroform (CDCl3), and deuterated methanol (CD3OD). The internal standard was tetramethylsilane (TMS).

[0495] MS was determined using (Agilent 6120B (ESI) and Agilent 6120B (APCI));

[0496] HPLC determination was performed using an Agilent 1260DAD high pressure liquid chromatograph (Zorbax SB-C 18 100 × 4.6 mm, 3.5 μM);

[0497] Thin layer chromatography silica gel plates used were Yantai Huanghai HSGF254 or Qingdao GF254 silica gel plates. The specifications of the silica gel plates used for thin layer chromatography (TLC) were 0.15 mm to 0.20 mm, and the specifications used for thin layer chromatography separation and purification products were 0.4 mm to 0.5 mm.

[0498] Column chromatography generally uses Yantai Huanghai silica gel 200-300 mesh silica gel as the carrier.

[0499] abbreviation

[0500] TBSCl: tert-butyldimethylsilyl chloride; HATU: 2-(7-azobenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate; TBAF: tetrabutylammonium fluoride; TsCl: p-toluenesulfonyl chloride; DIPEA: N,N-diisopropylethylamine; DBU: 1,8-diazabicyclo[5.4.0]undec-7-ene; Pd2(dba)3: tris(dibenzylideneacetone)dipalladium; Xantphos: 4,5-bis(diphenylphosphino-9,9-dimethylxanthene); XPhos Pd G2: chloro(2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II); HBTU: benzotriazole-N,N,N',N'-tetramethyluronium hexafluorophosphate; Pd(dppf)Cl2: 1,1'-bis(diphenylphosphino)ferrocenepalladium(II) dichloride; Selectfluor reagent: 1-chloromethyl-4-fluoro-1,4-diazotizedobicyclo[2.2.2]octane bis(tetrafluoroborate); TCFH: N,N,N',N'-tetramethylchloroformamidine hexafluorophosphate; RuPhos Pd G3: methanesulfonic acid (2-dicyclohexylphosphino-2',6'-diisopropyl-1,1'-biphenyl)(2-amino-1,1'-biphenyl-2-yl) palladium(II); RuPhos Pd G4: methanesulfonic acid (2-dicyclohexylphosphino-2',4',6'-tri-isopropyl-1,1'-biphenyl)(2'-amino-1,1'-biphenyl-2-yl) palladium(II); DMF: N,N-dimethylformamide

[0501] Example 1:

[0502] Step 1: Sodium hydride (0.52 g, 12.88 mmol, 60% wt) was dissolved in THF (30 mL). Compound 1A (2.51 g, 8.59 mmol) (synthesized by referring to the method described in CN112979655A) was added portionwise at 0°C. After complete addition, the mixture was stirred at room temperature for 20 minutes. Carbon disulfide (0.98 g, 12.88 mmol) was added dropwise. After complete addition, stirring was continued for 20 minutes. Methyl iodide (1.84 g, 12.88 mmol) was added dropwise. After complete addition, the reaction was continued for 30 minutes. Ethyl acetate and saturated aqueous sodium bicarbonate were added, and the mixture was extracted. The organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to obtain the target compound 1B (2.6 g, 79% yield).

[0503] Step 2: Dissolve compound 1B (2.6 g, 6.80 mmol) in methanol (30 mL). Add hydrazine hydrate (0.41 g, 8.16 mmol) at 0°C and stir at room temperature for 20 minutes. Concentrate under reduced pressure. Add methanol (30 mL) and triethylamine (1.37 g, 13.6 mmol) to the residue. After stirring, add cyanogen bromide (0.86 g, 8.16 mmol) in portions at 0°C and continue stirring for 20 minutes. Concentrate under reduced pressure. The residue is purified by silica gel column chromatography to obtain the target compound 1C (2.4 g, 90% yield). LC-MS (ESI): m / z = 392.2 [M+H] + .

[0504] Step 3: Dissolve 4-(2-chloro-5-methoxypyridin-4-yl)-6-methylpyridine-3-carboxylic acid (1D) (0.22 g, 0.79 mmol) (prepared according to the method described in WO2022118210) and compound 1C (0.31 g, 0.79 mmol) in DMF (10 mL). Add 1-methyl-1H-imidazole (0.20 g, 2.4 mmol). Stir thoroughly and add TCFH (0.27 g, 0.95 mmol) in portions under ice-cooling. React at room temperature for 1 hour. After the reaction, add saturated brine and extract with ethyl acetate. The organic phase is washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue is separated by silica gel column chromatography to obtain compound 1E (0.42 g, yield 81.5%). LC-MS (ESI): m / z = 652.2 [M+H] + .

[0505] Step 4: Dissolve compound 1E (0.42 g, 0.64 mmol) in dichloromethane (10 mL), stir until homogeneous, then add trifluoroacetic acid (2 mL) dropwise. After complete addition, react at room temperature for 1 hour. After completion of the reaction, concentrate under reduced pressure. Add methanol (3 mL) and toluene (10 mL) to the residue, mix thoroughly, and concentrate under reduced pressure. Repeat this process three times, then add DCM (20 mL) and methanol (2 mL). Stir thoroughly, add potassium carbonate (0.56 g, 4.0 mmol), continue stirring for 10 minutes, and filter. The filtrate is concentrated under reduced pressure to obtain the target compound 1F (0.32 g, 91% yield). LC-MS (ESI): m / z = 552.2 [M+H] + .

[0506] Step 5: Dissolve compound 1F (0.32 g, 0.58 mmol) and p-fluoronitrobenzene (0.16 g, 1.16 mmol) in DMSO (10 mL). Add triethylamine (0.20 g, 2 mmol), stir well, and react at 60°C for 6 hours. After the reaction, add saturated brine and extract with ethyl acetate. The organic phase is washed with saturated brine (60 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The residue is separated by silica gel column chromatography to obtain compound 1G (0.26 g, yield: 67%). LC-MS (ESI): m / z = 673.3 [M+H] + .

[0507] Step 6: Dissolve compound 1G (0.26 g, 0.39 mmol) in methanol (20 mL) and tetrahydrofuran (6 mL), add zinc powder (0.25 g, 3.9 mmol) and ammonium chloride (0.21 g, 3.9 mmol), and react at room temperature for 1 hour. After the reaction, add saturated brine and extract with ethyl acetate. The organic phase is dried over anhydrous sodium sulfate, filtered, and concentrated. The residue is separated by silica gel column chromatography to obtain compound 1H (0.15 g, 60% yield). LC-MS (ESI): m / z = 643.2 [M+H] + .

[0508] Step 7: Dissolve compound 1H (0.14 g, 0.22 mmol) in dichloromethane (10 mL), add triethylamine (88 mg, 0.88 mmol), and stir until uniform. Then, add acetic anhydride (45 mg, 0.44 mmol) under ice-cooling conditions. Warm the mixture to room temperature and react for 1 hour. After the reaction, concentrate the mixture under reduced pressure. The residue is separated by silica gel column chromatography to obtain compound 1 (52 mg, yield: 35%). LC-MS (ESI): m / z = 685.1 [M+H] + .

[0509] 1H NMR(400MHz,DMSO-d6)δ9.67(s,1H),8.81(s,1H),8.54(d,1H),8.17(s,1H),7.78(dd,1H),7.53(s,1H),7.49(d,1H),7.45-7.38( m,3H),6.95-6.88(m,2H),5.51(s,2H),3.72(d,2H),3.63(s,3H),2.78-2.63(m,3H),2.58(s,3H),1.99(s,3H),1.89-1.69(m,4H).

[0510] Example 2:

[0511] Step 1: Compound 1F (0.30 g, 0.54 mmol) and 3,4-difluoronitrobenzene were used as starting materials and the procedure of Step 5 of Example 1 was followed to obtain Compound 2A (0.31 g, yield 83%). LC-MS (ESI): m / z = 691.2 [M+H] + .

[0512] Step 2: Compound 2A (0.31 g, 0.45 mmol) was used as the starting material and the same procedure as in Step 6 of Example 1 was followed to obtain Compound 2B (0.16 g, yield 54%). LC-MS (ESI): m / z = 661.2 [M+H] + .

[0513] Step 3: Compound 2B (0.16 g, 0.24 mmol) was used as the starting material and the same procedure as in Step 7 of Example 1 was followed to obtain Compound 2 (48 mg, yield 28%). LC-MS (ESI): m / z = 703.1 [M+H] + .

[0514] 1 H NMR(400MHz,DMSO-d6)δ9.93(s,1H),8.80(s,1H),8.55(d,1H),8.17(s,1H),7.81(dd,1H),7.57-7.47(m,3H),7.43(s,1H),7.1 9(dd,1H),7.03(t,1H),5.51(s,2H),3.63(s,3H),3.39(d,2H),2.81-2.68(m,3H),2.59(s,3H),2.02(s,3H),1.89-1.79(m,4H).

[0515] Example 3:

[0516] Step 1: Compound 1C (1 g, 2.56 mmol) and 3A-1 (0.67 g, 2.56 mmol) (synthesized according to the method described in patent WO2022118210) were used as raw materials and the procedure of step 3 of Example 1 was followed to obtain compound 3A (1.5 g, yield 92%). LC-MS (ESI): m / z = 635.2 [M+H] + .

[0517] Step 2: Compound 3A (1.5 g, 2.36 mmol) was used as the starting material and the same procedure as in Step 4 of Example 1 was followed to obtain compound 3B (1.2 g, yield 95%). LC-MS (ESI): m / z = 535.2 [M+H] + .

[0518] Step 3: Compound 3B (0.4 g, 0.75 mmol) was used as the starting material and the same procedure as in Step 5 of Example 1 was followed to obtain compound 3C (0.3 g, yield 61%). LC-MS (ESI): m / z = 656.2 [M+H] + .

[0519] Step 4: Compound 3C (0.3 g, 0.46 mmol) was used as the starting material and the same procedure as in Step 6 of Example 1 was followed to obtain compound 3D (0.15 g, yield 52%). LC-MS (ESI): m / z = 626.2 [M+H] + .

[0520] Step 5: Compound 3D (0.15 g, 0.24 mmol) was used as the starting material and the same procedure as in Step 7 of Example 1 was followed to obtain compound 3 (30 mg, yield 19%). LC-MS (ESI): m / z = 668.2 [M+H] + .

[0521] 1 H NMR(400MHz,DMSO-d6)δ9.66(s,1H),8.81(s,1H),8.53-8.52(m,1H),7.78-7.75(m,1H),7.49-7.47(m,1H),7.43-7.37(m,3H),7.31(s,1H),6.9 3-6.87(m,4H),5.50(s,2H),3.73-3.70(m,2H),3.59(s,3H),3.27-3.26 (m,2H),2.77-2.68(m,3H),2.56(s,3H),1.99(s,3H),1.91-1.75(m,3H).

[0522] Example 4:

[0523] Step 1: Dissolve methyl 5-hydroxypyridine-2-carboxylate (4A) (2.45 g, 16.00 mmol) and 1-Boc-4-hydroxypiperidine (3.86 g, 19.2 mmol) in toluene (30 mL). Add triphenylphosphine (6.29 g, 24 mmol) and stir until uniform. Then, add diisopropyl azodicarboxylate (4.85 g, 24 mmol) dropwise at 0°C. After complete addition, warm to room temperature and react for 1 hour. After completion of the reaction, the system was directly concentrated under reduced pressure. The residue was separated by silica gel column chromatography to obtain compound 4B (3.03 g, 56% yield). LC-MS (ESI): m / z = 337.7 [M+H] + .

[0524] Step 2: Dissolve compound 4B (3.03 g, 9.01 mmol) in methanol (50 mL) and slowly add sodium borohydride (3.41 g, 90.1 mmol) in portions. After complete addition, allow to react at room temperature for 1 hour. After completion of the reaction, concentrate under reduced pressure, add ethyl acetate, and wash the organic phase with saturated brine, dry over anhydrous sodium sulfate, and filter. After concentration under reduced pressure, the residue was separated by silica gel column chromatography to yield compound 4C (1.35 g, yield: 49%). LC-MS (ESI): m / z = 309.2 [M+H] + .

[0525] Step 3: Dissolve sodium hydride (0.21 g, 5.34 mmol, 60% wt) in THF (30 mL), cool to 0°C, and add compound 4C (1.35 g, 4.38 mmol) portionwise. Continue at room temperature for 20 minutes, then add 5-bromo-1,3,4-thiadiazole-2-amine (1.03 g, 5.69 mmol) portionwise. Then, warm to room temperature and react for 5 hours. The reaction is quenched by adding saturated aqueous sodium bicarbonate solution, extracted with ethyl acetate, and the organic phase is dried over anhydrous sodium sulfate, filtered, and the filtrate is concentrated under reduced pressure and separated by column chromatography to yield the target compound 4D (0.71 g, yield: 39.78%). LC-MS (ESI): m / z = 408.1 [M+H] + .

[0526] Step 4: Compound 1D (0.24 g, 0.86 mmol) and compound 4D (0.35 g, 0.86 mmol) were used as starting materials and the same procedure as in Step 3 of Example 1 was used to obtain compound 4E (0.38 g, yield: 66.13%). LC-MS (ESI): m / z = 668.2 [M+H] + .

[0527] Step 5: Using compound 4E (0.38 g, 0.57 mmol) as starting material, the trifluoroacetic acid salt of target compound 4F was obtained by referring to the procedure of step 4 of Example 1. LC-MS (ESI): m / z = 568.2 [M+H] + .

[0528] Step 6: Compound 4F (0.32 g, 0.57 mmol) and p-fluoronitrobenzene (0.31 g, 1.12 mmol) were used as starting materials and the same procedure as in Step 5 of Example 1 was used to obtain compound 4G (271 mg, yield: 70%). LC-MS (ESI): m / z = 689.2 [M+H] + .

[0529] Step 7: Using compound 4G (271 mg, 0.39 mmol) as starting material, the target compound 4H (182 mg, yield: 70%) was obtained by referring to the procedure of step 6 of Example 1. LC-MS (ESI): m / z = 659.5 [M+H] + .

[0530] Step 8: Using compound 4H (90 mg, 0.20 mmol) as starting material, the target compound 4 (48 mg, yield: 45%) was obtained by referring to the operation method of step 7 of Example 1. LC-MS (ESI): m / z = 701.2 [M+H] + .

[0531] 1 H NMR(400MHz,Methanol-d4)δ8.78(s,1H),8.27(d,1H),8.07(s,1H),7.64-7.32(m,6H),6.97(d,2H),5.48(s,2H),4.6 5-4.63(m,1H),3.71(s,3H),3.54-3.42(m,2H),3.08-3.05(m,2H),2.66(s,3H),2.22-2.05(s,5H),1.96-1.83(m,2H).

[0532] Example 5:

[0533] Step 1: Methyl 5-hydroxypyridine-2-carboxylate (4A) (2.0 g, 13.0 mmol) and tert-butyl 3-iodoazetidine-1-carboxylate (7.4 g, 26.0 mmol) were dissolved in DMF (100 mL). Cesium carbonate (8.4 g, 26.0 mmol) and cuprous iodide (2.5 g, 13.0 mmol) were added sequentially. The mixture was then heated to 100°C and stirred overnight under a nitrogen atmosphere. After completion of the reaction, the reaction solution was cooled to room temperature, filtered through a pad of celite, and water was added to the filtrate. The filtrate was extracted with ethyl acetate. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was separated by silica gel column chromatography to obtain compound 5A (3.0 g, yield 74%). LC-MS (ESI): m / z = 309.1 [M+H] + .

[0534] Step 2: Compound 5A (3.0 g, 9.73 mmol) was used as the starting material and the same procedure as in Step 2 of Example 4 was followed to obtain compound 5B (2.3 g, yield 84%). LC-MS (ESI): m / z = 281.1 [M+H] + .

[0535] Step 3: Compound 5B (3.0 g, 9.73 mmol) was used as a raw material and the operation method of the first step of Example 1 was referred to obtain compound 5C (2.3 g, yield 58%).

[0536] Step 4: Compound 5C (3.0 g, 9.73 mmol) was used as the starting material and the same procedure as in Step 2 of Example 1 was followed to obtain compound 5D (2.5 g, yield 96%). LC-MS (ESI): m / z = 380.2 [M+H] + .

[0537] Step 5: Compound 5D (1.0 g, 2.64 mmol) and 3A-1 (0.69 g, 2.64 mmol) were used as starting materials and the same procedure as in Step 3 of Example 1 was followed to obtain compound 5E (1.1 g, yield 67%). LC-MS (ESI): m / z = 623.2 [M+H] + .

[0538] Step 6: Compound 5E (1.1 g, 1.77 mmol) was used as the starting material and the same procedure as in Step 4 of Example 1 was followed to obtain compound 5F (0.8 g, yield 87%). LC-MS (ESI): m / z = 523.2 [M+H] + .

[0539] Step 7: Compound 5F (0.8 g, 1.53 mmol) was used as a starting material and the same procedure as in Step 5 of Example 1 was followed to obtain compound 5G (0.65 g, yield 66%). LC-MS (ESI): m / z = 644.2 [M+H] + .

[0540] Step 8: Compound 5G (0.65 g, 1.01 mmol) was used as a starting material and the same procedure as in Step 6 of Example 1 was followed to obtain compound 5H (0.30 g, yield 48%). LC-MS (ESI): m / z = 614.2 [M+H] + .

[0541] Step 9: Compound 5H (0.1 g, 0.16 mmol) was used as a starting material and the same procedure as in Step 7 of Example 1 was followed to obtain compound 5 (50 mg, yield 66%). LC-MS (ESI): m / z = 656.2 [M+H] + .

[0542] 1 H NMR(400MHz, CDCl3)δ8.99(s,1H),8.22-8.21(m,1H),7.45-7.31(m,4H),7.23(s,1H),7.13-7. 12(m,2H),6.85-6.77(m,2H),6.46-6.44(m,2H),5.50(s,2H),5.13-5.08(m,1H),4.33-4.29(m, 2H),3.90-3.87(m,2H),3.74(s,3H),2.68(s,3H),2.14(s,3H),2.08(s,1H).

[0543] Example 6:

[0544] Compound 1F (0.15 g, 0.27 mmol) was used as the starting material and the seventh step of Example 1 was followed to obtain compound 6 (50 mg, yield 31%). LC-MS (ESI): m / z = 594.2 [M+H] + .

[0545] 1H NMR(400MHz, CDCl3)δ8.98(s,1H),8.51-8.50(m,1H),8.03(s,1H),7.58-7.56(m,1H),7.46-7.44(m,1H),7.24(s,1H),7.17(s,1H),5.52(s, 2H),3.98-3.95(m,1H),3.72(s,3H),3.23-3.16(m,2H),2.85-2.81(m ,3H),2.69(s,3H),2.65-2.61(m,1H),2.14(s,3H),1.95-1.87(m,3H).

[0546] Example 7:

[0547] Compound 7 (50 mg, yield 28%) was obtained by following the third step of Example 1 using compound 1F (0.15 g, 0.27 mmol) as the starting material. LC-MS (ESI): m / z = 660.2 [M+H] + .

[0548] 1 H NMR(400MHz, CDCl3)δ8.98(s,1H),8.53-8.52(m,1H),8.03(s,1H),7.73(s,1H),7.63-7.59(m,2H),7.47-7.45(m,1H),7.24(s,1H),7.17 (s,1H),5.53(s,2H),3.93(s,3H),3.72(s,3H),3.13-3.06(m,2H),2.91-2.85(m,2H),2.69(s,3H),1.96-1.92(m,3H),1.75-1.69(m,3H).

[0549] Example 8:

[0550] Step 1: Compound 8A (2.3 g, 8 mmol) (synthesized according to the method described in WO2021190727) was dissolved in dichloromethane (30 mL), trifluoroacetic acid (6 mL) was added, and the reaction was allowed to react at room temperature for 1 hour. After the reaction, the solvent was removed by concentration under reduced pressure. The residue was basified and separated by silica gel column chromatography to obtain compound 8B (1.2 g, 80% yield). LC-MS (ESI): m / z = 188.2 [M+H] + .

[0551] Step 2: Compound 8B (1.2 g, 6.4 mmol) was dissolved in methanol (50 mL), and aqueous formaldehyde (2.7 g, 36% wt, 32 mmol) and 2 drops of acetic acid were added. After reacting at room temperature for 2 hours, sodium triacetoxyborohydride (4 g, 19.2 mmol) was added and reacted at room temperature for 4 hours. After completion of the reaction, the solvent was removed by concentration under reduced pressure, and the residue was separated by silica gel column chromatography to obtain compound 8C (0.9 g, 72% yield). LC-MS (ESI): m / z = 202.2 [M+H] + .

[0552] Step 3: Compound 8C (0.9 g, 4.48 mmol) was dissolved in methanol (20 mL), water (20 mL), and tetrahydrofuran (20 mL). Lithium hydroxide monohydrate (0.56 g, 13.44 mmol) was added and allowed to react at room temperature for 3 hours. After completion of the reaction, the solvent was removed by concentration under reduced pressure. The residue was adjusted to pH 2 with 1 M dilute hydrochloric acid and then separated by silica gel column chromatography to obtain compound 8D (0.66 g, yield 85%). LC-MS (ESI): m / z = 132.2 [MH] - .

[0553] Step 4: Compound 8D (35 mg, 0.2 mmol) was dissolved in DMF (20 mL), and DIPEA (77 mg, 0.6 mmol) and HATU (76 mg, 0.2 mmol) were added. After stirring at room temperature for 20 minutes, compound 1F (110 mg, 0.2 mmol) was added and allowed to react at room temperature for 1 hour. After completion of the reaction, saturated brine was added, and the mixture was extracted with dichloromethane. The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was separated by silica gel column chromatography to obtain compound 8 (30 mg, yield 21%). LC-MS (ESI): m / z = 707.2 [M+H] + .

[0554] 1H NMR (400MHz, CDCl3) δ10.39(s,1H),8.91(s,1H),8.51(s,1H),8.05(s,1H),7.56-7.54(m,1H),7. 46-7.44(m,1H),7.24(s,1H),7.15(s,1H),5.62(s,1H),5.55(s,2H),4.80-4.77(m,1H),3.97-3.9 3(m,1H),3.76(s,3H),3.34-3.11(m,5H),2.88-2.82(m,1H),2.77(s,3H),2.69(s,3H),2.68-2.63 (m,1H),2.56(s,2H),2.38-2.32(m,1H),2.31-2.18(m,2H),2.02-1.93(m,4H),1.66-1.59(m,2H).

[0555] Example 9:

[0556] Step 1: Compound 9A (1.0 g, 3.18 mmol) (prepared according to the method described in WO2016054388) was used as the starting material and the same procedure as in Step 3 of Example 1 was followed to obtain compound 9B (1.1 g, yield 60%). LC-MS (ESI): m / z = 575.2 [M+H] + .

[0557] Step 2: Compound 9B (1.1 g, 1.91 mmol) was used as the starting material and the same procedure as in Step 4 of Example 1 was followed to obtain Compound 9C (0.9 g, yield 99%). LC-MS (ESI): m / z = 475.2 [M+H] + .

[0558] Step 3: Compound 9C (0.05 g, 0.10 mmol) was used as the starting material and the same procedure as in Step 3 of Example 1 was followed to obtain compound 9 (50 mg, yield 82%). LC-MS (ESI): m / z = 583.2 [M+H] + .

[0559] 1H NMR(400MHz, CDCl3)δ8.98(s,1H),8.03(s,1H),7.70(s,1H),7.59-7.58(m,1H),7.24(s,2H),7.17(s,1H),4.33-4.31(m, 2H),3.91(s,3H),3.73(s,2H),2.97-2.80(m,2H),2.68(s,3H),2.11-2.10(m,2H),1.73-1.58(m,4H),1.41-1.31(m,2H).

[0560] Example 10:

[0561] Step 1: Compound 4D (3.26 g, 8 mmol) and 3A-1 (2.09 g, 8 mmol) were used as starting materials and the procedure of Step 3 of Example 1 was followed to obtain Compound 10A (5.2 g, yield 99%). LC-MS (ESI): m / z = 651.2 [M+H] + .

[0562] Step 2: Compound 10A (5.2 g, 8 mmol) was used as the starting material and the same procedure as in Step 4 of Example 1 was followed to obtain Compound 10B (3.5 g, yield 80%). LC-MS (ESI): m / z = 551.2 [M+H] + .

[0563] Step 3: Using compound 10B (1.65 g, 3 mmol) as starting material, the target compound 10C (1.5 g, yield 75%) was obtained by following the procedure of step 5 of Example 1. LC-MS (ESI): m / z = 672.2 [M+H] + .

[0564] Step 4: Using compound 10C (1.5 g, 2.25 mmol) as starting material, the target compound 10D (0.6 g, yield 42%) was obtained by referring to the procedure of step 6 of Example 1. LC-MS (ESI): m / z = 642.2 [M+H] + .

[0565] Step 5: Using compound 10D (128 mg, 0.2 mmol) as starting material, the target compound 10 (82 mg, yield 60%) was obtained by referring to the operation method of step 7 of Example 1. LC-MS (ESI): m / z = 684.2 [M+H] + .

[0566] 1H NMR(400MHz, CDCl3)δ9.56(s,1H),8.98(s,1H),8.33(s,1H),7.44-7.38(m,2H),7.37-7 .33(m,2H),7.25-7.21(m,1H),7.18(s,1H),7.06-7.01(m,1H),6.97-6.88(m,2H),6.87 -6.82(m,1H),6.81-6.77(m,1H),5.50(s,2H),4.57-4.47(m,1H),3.78(s,3H),3.51-3.40( m,2H),3.14-3.03(m,2H),2.66(s,3H),2.15(s,3H),2.14-2.07(m,2H),1.99-1.90(m,2H).

[0567] Example 11:

[0568] Compound 11 (50 mg, yield 26%) was obtained by following the third step of Example 1 using compound 3B (0.15 g, 0.28 mmol) as the starting material. LC-MS (ESI): m / z = 690.2 [M+H] + .

[0569] 1 H NMR(400MHz, CDCl3)δ8.97(s,1H),8.50-8.48(m,1H),7.55-7.52(m,1H),7.73(s,1H),7.44-7 .35(m,2H),7.19(s,1H),6.85-6.77(m,2H),5.54(s,2H),4.82-4.78(m,1H),4.00-3.96(m,2H) ,3.76(s,3H),3.18-3.12(m,1H),2.85-2.82(m,3H),2.71-2.69(m,2H),2.65(s,3H),2.64-2. 63(m,1H),2.47(s,2H),2.42(s,3H),2.00-1.91(m,5H),1.66-1.56(m,2H),1.29-1.26(m,1H).

[0570] Example 12:

[0571] Compound 10B (110 mg, 0.2 mmol) was used as the starting material and the target compound 12 (40 mg, 34% yield) was obtained by referring to the seventh step of Example 1. LC-MS (ESI): m / z = 593.2 [M+H] + .

[0572] 1 H NMR(400MHz,Chloroform-d)δ9.92(s,1H),9.00(s,1H),8.32-8.31(m,1H),7.46-7.43(m ,1H),7.42-7.37(m,1H),7.25-7.24(m,1H),7.23-7.21(m,1H),6.88-6.83(m,1H),6.82-6 .78(m,1H),5.51(s,2H),4.61-4.58(m,1H),3.76(s,3H),3.75-3.71(m,1H),3.70-3.61(m ,2H),3.46-3.40(m,1H),2.70(s,3H),2.12(s,3H),1.98-1.91(m,2H),1.86-1.82(m,2H).

[0573] Example 13:

[0574] Compound 1H (129 mg, 0.2 mmol) was dissolved in methanol (30 mL). Aqueous formaldehyde (167 mg, 36% wt, 2 mmol) and 1 drop of acetic acid were added. The mixture was stirred at room temperature overnight. Sodium cyanoborohydride (101 mg, 1.6 mmol) was then added and allowed to react at room temperature for 2 hours. After the reaction, the solvent was concentrated and the residue was separated by silica gel column chromatography to obtain compound 13 (40 mg, 30% yield). LC-MS (ESI): m / z = 671.2 [M+H] + .

[0575] 1 H NMR(400MHz,Chloroform-d)δ11.13(s,1H),8.94(s,1H),8.56-8.55(m,1H),8.0 4(s,1H),7.66-7.64(m,1H),7.44-7.42(m,1H),7.24(s,1H),7.15(s,1H),7.09- 6.89(m,2H),6.84-6.69(m,2H),5.52(s,2H),3.74(s,3H),3.69-3.56(m,2H),2. 90(s,6H),2.85-2.74(m,2H),2.73-2.69(m,1H),2.68(s,3H),2.06-1.85(m,4H).

[0576] Example 14:

[0577] Step 1: Compound 4A (2.45 g, 16.00 mmol) and 1-Boc 4-(hydroxymethyl)piperidine (4.13 g, 19.2 mmol) were used as starting materials and the same procedure as in Step 1 of Example 4 was used to synthesize compound 14A (4.54 g, 75% yield). LC-MS (ESI): m / z = 351.8 [M+H] + .

[0578] Step 2: Compound 14A (4.2 g, 11.99 mmol) was used as the starting material and the procedure of Step 2 of Example 4 was followed to synthesize Compound 14B (2.58 g, yield: 67%). LC-MS (ESI): m / z = 323.4 [M+H] + .

[0579] Step 3: Compound 14B (2.58 g, 8.00 mmol) was used as the starting material and the target compound 14C (0.82 g, yield 24.32%) was synthesized by referring to the third step of Example 4. LC-MS (ESI): m / z = 422.1 [M+H] + .

[0580] Step 4: Compound 3A-1 (0.25 g, 0.95 mmol) and 14C (0.40 g, 0.95 mmol) were used as starting materials and the procedure of Step 3 of Example 1 was followed to obtain compound 14D (0.46 g, yield 73%). LC-MS (ESI): m / z = 665.3 [M+H] + .

[0581] Step 5: Compound 14E (0.38 g) was synthesized by referring to the fourth step of Example 1 using compound 14D (0.46 g, 0.69 mmol) as the starting material. LC-MS (ESI): m / z = 565.2 [M+H] + .

[0582] Step 6: Dissolve compound 14E (0.18 g, 0.32 mmol) in dichloromethane (10 mL), add triethylamine (100 mg, 1.0 mmol), and stir until uniform. Then, add acetic anhydride (41 mg, 0.40 mmol) in an ice bath. Warm the mixture to room temperature and react for 1 hour. After the reaction, concentrate the mixture under reduced pressure. The residue is separated by silica gel column chromatography to obtain compound 14 (98 mg, yield: 51%). LC-MS (ESI): m / z = 607.3 [M+H] + .

[0583] 1H NMR(400MHz,Chloroform-d)δ9.00(s,1H),8.29(d,1H),7.46-7.34(m,2H),7.24-7.15(m,2H),6.89-6.75(m,2H),5.49(s,2H),4.69(d ,1H),3.95-3.81(m,3H),3.75(s,3H),3.15-3.04(m,1H),2.67(s,3H),2.59(t,1H),2.11(s,3H),2.09-2.00(m,2H),1.98-1.80(m,3H).

[0584] Example 15:

[0585] Compound 15 (97 mg, yield 61%) was obtained by following the procedure of step 7 of Example 1 using compound 3B (150 mg, 0.28 mmol) as the starting material. LC-MS (ESI): m / z = 577.2 [M+H] + .

[0586] 1 H NMR(400MHz,Methanol-d4)δ8.74(s,1H),8.47(d,1H),7.79-7.76(m,1H),7.55(d,1H),7.46-7.30(m,2H),7.00-6.59(m,2H),5.52(s,2H),4 .69-4.65(m,1H),4.14-4.00(m,1H),3.65(s,3H),3.29-3.19(m,1H), 2.94-2.91(m,1H),2.80-2.58(m,4H),2.14(s,3H),2.03-1.51(m,4H).

[0587] Example 16:

[0588] On an ice bath, 1-methylpyrazole-4-carboxylic acid (35 mg, 0.28 mmol) was dissolved in DMF (4 mL). DIPEA (109 mg, 0.84 mmol) and HATU (138 mg, 0.36 mmol) were added. After stirring for 10 minutes, compound 3B (150 mg, 0.28 mmol) was added. The mixture was allowed to warm to room temperature and stirred for 1 hour. TLC confirmed the reaction was complete, and the mixture was cooled to room temperature. Water was added and extracted with ethyl acetate. The organic phase was washed with water and saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified using a Biotage Isolera One medium-pressure prep system to yield the title compound 16 (99 mg, 55%). LC-MS (ESI): m / z = 643.3 [M+H] + .

[0589] 1 H NMR(400MHz, Methanol-d4)δ8.74(s,1H),8.49(d,1H),7.96(s,1H),7.81-7.78(m,1H),7.73(s,1H),7.55(d,1H),7.46-7.32(m,2H ),6.92-6.78(m,2H),5.53(s,2H),4.70-4.30(m,2H),3.92(s,3H),3.65(s,3H),3.17-2.84(m,3H),2.63(s,3H),2.08-1.65(m,4H).

[0590] Example 17:

[0591] Compound 4F (200 mg, 0.35 mmol) and compound 8D (61.02 mg, 0.35 mmol) were used as starting materials and the third step of Example 1 was followed to obtain compound 17 (130 mg, yield 51%). LC-MS (ESI): m / z = 723.3 [M+H] + .

[0592] 1 H NMR(400MHz, Methanol-d4)δ8.79(s,1H),8.27(d,1H),8.06(s,1H),7.73-7.28(m,4H),5.48(s,2H),4.79-4.67(m, 1H),4.11-3.75(m,2H),3.71(s,3H),3.56-3.53(m,2H),3.23-2.98(m,4H),2.88-2.57(m,6H),2.23-1.67(m,10H).

[0593] Example 18:

[0594] Compound 4H (100 mg, 0.15 mmol) was dissolved in methanol (8 mL), and aqueous formaldehyde (37% in H2O, 0.45 mmol) was added. One drop of glacial acetic acid was then added dropwise. After stirring at room temperature for 10 h, sodium cyanoborohydride (19.15 mg, 0.30 mmol) was slowly added under ice. The mixture was then warmed to room temperature. TLC confirmed the reaction was complete. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated. The residue was purified by silica gel column chromatography to yield the target compound 18 (46 mg, 45%). LC-MS (ESI): m / z = 687.3 [M+H] + .

[0595] 1 H NMR(400MHz,Methanol-d4)δ8.78(s,1H),8.27(d,1H),8.07(s,1H),7.76-7.26(m,4H),7.13-6.68 (m,4H),5.48(s,2H),4.52(s,1H),3.71(s,3H),2.91-2.6(m,10H),2.66(s,3H),2.36-1.85(m,4H).

[0596] Example 19:

[0597] Step 1: Dissolve compound 19A (15 g, 84.27 mmol) and N,N-dimethylformamide dimethyl acetal (40 g, 337.08 mmol) in toluene (150 mL). The mixture was then heated to reflux and stirred overnight. TLC confirmed the reaction was complete. The reaction solution was cooled to room temperature and concentrated. The residue was purified by silica gel column chromatography to yield compound 19B (13 g, 65%). LC-MS (ESI): m / z = 235.3 [M+H] + .

[0598] Step 2: Compound 19C (1.0 g, 5.20 mmol) (synthesized by the method described in EP2311822A1) and 4-iodophenethyl ether (1.9 g, 7.80 mmol) were dissolved in ultra-dry dimethyl sulfoxide (15 mL). Cuprous iodide (0.2 g, 1.04 mmol), L-proline (0.24 mg, 2.08 mmol), and cesium carbonate (5.07 g, 15.6 mmol) were added sequentially. The mixture was then reacted at 100°C overnight under a nitrogen atmosphere. After TLC analysis, the reaction mixture was cooled to room temperature, water was added, and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated. The residue was isolated by silica gel column chromatography to yield the target compound 19D (0.81 g, 50%). LC-MS (ESI): m / z = 313.3 [M+H] + .

[0599] Step 3: Sodium hydride (0.32 g, 8.03 mmol, 60% wt) was dissolved in THF (30 mL) under a nitrogen atmosphere. Compound 19D (0.81 mg, 2.59 mmol) was added portionwise at 0°C. After stirring on an ice bath for 40 minutes, compound 19B (1.21 g, 5.18 mmol) was slowly added. The reaction mixture was allowed to warm to room temperature and stirred for 5 hours. After completion of the reaction, the reaction mixture was poured into ice water and extracted with ethyl acetate. The organic phase was washed with saturated sodium bicarbonate aqueous solution, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to yield the target compound 19E (0.64 g, 60% yield). LC-MS (ESI): m / z = 412.3 [M+H] + .

[0600] Step 4: Compound 19E (0.2 g, 0.73 mmol) was used as the starting material and the same procedure as in Step 3 of Example 1 was followed to obtain compound 19 (0.16 g, yield 50%). LC-MS (ESI): m / z = 672.3 [M+H] + .

[0601] 1 H NMR(400MHz,DMSO-d6)δ8.81(s,1H),8.54(d,1H),8.17(s,1H),7.78-7.74(m,1H),7.61-7.38(m,3H),7.05-6.74(m,4H ),5.51(s,2H),3.94(d,2H),3.63-3.60(m,5H),2.87-2.62(m,3H),2.58(s,3H),2.04-1.77(m,4H),1.42-1.19(m,3H).

[0602] Example 20:

[0603] Step 1: Compound 19C (1.0 g, 5.20 mmol) and 2,4-difluoroiodobenzene (1.87 g, 7.8 mmol) were used as starting materials and the procedure of Step 2 of Example 19 was followed to obtain Compound 20A (0.55 g, 35% yield). LC-MS (ESI): m / z = 305.3 [M+H] + .

[0604] Step 2: Compound 20A (0.55 g, 1.81 mmol) was used as the starting material and the same procedure as in Step 3 of Example 19 was followed to obtain Compound 20B (0.41 g, yield 55%). LC-MS (ESI): m / z = 404.3 [M+H] + .

[0605] Step 3: Compound 20 (0.15 g, 45% yield) was obtained by following the procedure of step 3 of Example 1 using compound 20B (0.2 g, 0.5 mmol) as the starting material. LC-MS (ESI): m / z = 664.3 [M+H] + .

[0606] 1 H NMR(400MHz,DMSO-d6)δ8.81(s,1H),8.55(d,1H),8.17(s,1H),7.81-7.78(m,1H),7.64-7.39(m,3H),7.2 6-6.96(m,3H),5.51(s,2H),3.63(s,3H),3.38(d,2H),2.89-2.69(m,3H),2.59(s,3H),2.03-1.78(m,4H).

[0607] Example 21:

[0608] Step 1: Compound 9C (0.5 g, 1.05 mmol) was used as the starting material and the same procedure as in Step 5 of Example 1 was followed to obtain compound 21A (0.5 g, yield 79%). LC-MS (ESI): m / z = 597.2 [M+H] + .

[0609] Step 2: Compound 21A (0.5 g, 0.84 mmol) was used as the starting material and the same procedure as in Step 6 of Example 1 was followed to obtain Compound 21B (0.25 g, yield 52%). LC-MS (ESI): m / z = 567.2 [M+H] + .

[0610] Step 3: Compound 21B (0.15 g, 0.26 mmol) was used as the starting material and the same procedure as in Step 7 of Example 1 was followed to obtain Compound 21 (50 mg, yield 31%). LC-MS (ESI): m / z = 609.2 [M+H] + .

[0611] 1 H NMR(400MHz, CDCl3)δ8.96(s,1H),8.13-8.12(m,1H),8.03(s,1H),7.91-7.88(m,1H),7.43(s,1H),7.24(s,1H),7.14(s,1H),6.99 -6.96(m,1H),4.37-4.26(m,4H),3.73(s,3H),2.92-2.85(m,2H),2.66(s,3H),2.17(s,3H),1.94-1.87(m,4H),1.45-1.35(m,2H).

[0612] Example 22:

[0613] Step 1: Compound 22A (1.82 g, 5.6 mmol) (synthesized by the method described in WO2008053031) and compound 19C (1.08 g, 5.6 mmol) were used as starting materials and the procedure of Step 2 of Example 19 was followed to obtain compound 22B (0.38 g, 17% yield). LC-MS (ESI): m / z = 388.4 [M+H] + .

[0614] Step 2: Compound 22B (0.38 g, 0.98 mmol) and compound 19B (0.35 g, 1.50 mmol) were used as starting materials and the same procedure as in Step 3 of Example 19 was followed to obtain compound 22C (0.16 g, 34% yield). LC-MS (ESI): m / z = 487.2 [M+H] + .

[0615] Step 3: Compound 22C (0.16 g, 0.33 mmol) and compound 1D (92 mg, 0.33 mmol) were used as starting materials and the same procedure as in Step 3 of Example 1 was followed to obtain compound 22 (0.16 g, yield 65%). LC-MS (ESI): m / z = 747.2 [M+H] + .

[0616] 1H NMR(400MHz,Chloroform-d)δ8.96(s,1H),8.54(d,1H),8.02(s,1H),7.62-7.55(m,3H),7.43(d,1H),7.23(s,1H),7.14(s,1H),6.96-6 .90(m,2H),5.51(s,2H),4.54(t,4H),4.03-3.95(m,2H),3.72(s,3H),2.97(t,2H),2.84-2.84(m,1H),2.68(s,3H),2.08-1.71(m,3H).

[0617] Example 23:

[0618] Step 1: 1-Methyl-1H-pyrazol-4-ol (23A) (1 g, 10.1 mmol), 5-bromo-2-hydroxymethylpyridine (1.27 g, 6.75 mmol), cesium carbonate (4.4 g, 13.5 mmol), cuprous iodide (257 mg, 1.35 mmol), and 2,2,6,6-tetramethyl-3,5-heptanedione (248 mg, 1.35 mmol) were dissolved in dioxane (50 mL) in this order. The mixture was then heated to 100°C and allowed to react overnight. After completion of the reaction, the mixture was cooled to room temperature, water was added, and the mixture was extracted with ethyl acetate. The organic phase was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated, and the residue was isolated by silica gel column chromatography to yield compound 23B (356 mg, 26% yield). LC-MS (ESI): m / z = 206.1 [M+H] + .

[0619] Step 2: Sodium hydride (0.050 g, 2.08 mmol, 60% wt) was dissolved in THF (20 mL). Compound 23B (0.356 g, 1.73 mmol) was added portionwise at 0°C. After complete addition, the mixture was stirred at room temperature for 20 minutes. Carbon disulfide (0.158 g, 2.08 mmol) was added dropwise. After complete addition, stirring was continued for 20 minutes. Methyl iodide (0.295 g, 2.08 mmol) was added dropwise. After complete addition, the reaction was continued for 30 minutes. Ethyl acetate was added, and the organic phase was washed with saturated sodium bicarbonate solution, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to obtain the target compound 23C (0.386 g, 75% yield). LC-MS (ESI): m / z = 296.2 [M+H] + .

[0620] Step 3: Dissolve compound 23C (0.386 g, 1.31 mmol) in methanol (10 mL). Add hydrazine hydrate (78 mg, 1.57 mmol) at 0°C and stir at room temperature for 2 hours. Concentrate under reduced pressure. Add methanol (10 mL) and triethylamine (0.265 g, 2.62 mmol) to the residue. After stirring, add cyanogen bromide (0.166 g, 1.57 mmol) in portions at 0°C and continue stirring for 30 minutes. Concentrate under reduced pressure. The residue is purified by silica gel column chromatography to obtain the target compound 23D (0.310 g, 78% yield). LC-MS (ESI): m / z = 305.2 [M+H] + .

[0621] Step 4: Dissolve 3A-1 (80 mg, 0.26 mmol) and compound 23D (57 mg, 0.22 mmol) in DMF (3 mL). Add 1-methyl-1H-imidazole (39 mg, 0.47 mmol). Stir thoroughly, then add TCFH (73 mg, 0.26 mmol) in portions under ice. React at room temperature for 12 hours. After completion of the reaction, add saturated brine and extract with ethyl acetate. The combined organic phases are washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue is separated by silica gel column chromatography to obtain compound 23 (34 mg, 29% yield). LC-MS (ESI): m / z = 548.2 [M+H] + .

[0622] 1 H NMR(400MHz,DMSO-d6)δ12.86(s,1H),8.81-8.61(m,1H),8.42-8.35(m,1H),7.84-7.78(m,1H),7.56-7.51(m,1H),7.47-7.44(m,1H) ),7.43-7.41(m,1H),7.41-7.36(m,1H),7.32(s,1H),6.95-6.85(m,2H),5.52-5.48(m,2H),3.81(s,3H),3.58(s,3H),2.56(s,3H).

[0623] Example 24:

[0624] Compound 4F (0.18 g, 0.32 mmol) was used as the starting material and the procedure of step 7 of Example 1 was followed to obtain the target compound 24 (98 mg, yield: 51%). LC-MS (ESI): m / z = 610.3 [M+H] + .

[0625] 1H NMR(400MHz,Chloroform-d)δ11.46(s,1H),8.96(s,1H),8.33(d,1H),8.03(s,1H),7.42(d,1H),7.25-7.20(m,2H),7.15( s,1H),5.47(s,2H),4.64-4.54(m,1H),3.82-3.60(m,6H),3.47-3.38(m,1H),2.67(s,3H),2.12(s,3H),2.03-1.76(m,4H).

[0626] Example 25:

[0627] Step 1: Compound 5D (1.3 g, 3.43 mmol) was used as the starting material and the same procedure as in Step 3 of Example 1 was used to obtain compound 25A (1.8 g, yield 82%). LC-MS (ESI): m / z = 640.1 [M+H] + .

[0628] Step 2: Compound 25A (1.8 g, 2.81 mmol) was used as the starting material and the same procedure as in Step 4 of Example 1 was followed to obtain Compound 25B (1.3 g, yield 86%). LC-MS (ESI): m / z = 540.1 [M+H] + .

[0629] Step 3: Compound 25B (0.1 g, 0.19 mmol) was used as the starting material and the same procedure as in Step 7 of Example 1 was followed to obtain Compound 25 (0.03 g, yield 27%). LC-MS (ESI): m / z = 582.2 [M+H] + .

[0630] 1 H NMR(400MHz, CDCl3)δ8.96(s,1H),8.22-8.21(m,1H),8.03(s,1H),7.47-7.44(m,1H), 7.25(s,1H),7.18(s,1H),7.12-7.09(m,1H),5.50(s,2H),5.02-4.97(m,1H),4.54-4.50(m,1H), 4.43-4.39(m,1H),4.21-4.19(m,1H),4.09-4.06(m,1H),3.74(s,3H),2.70(s,3H),1.92(s,3H).

[0631] Example 26:

[0632] Step 1: Dissolve compound 26A (6.5 g, 66.95 mmol) and 26B (10.38 g, 66.95 mmol) in methanol (60 mL). Add sodium carbonate (14.2 g, 134 mmol), stir thoroughly, and react at 60°C for 4 hours. After completion of the reaction, cool to room temperature, filter through celite, and concentrate the filtrate under reduced pressure. The residue is separated by silica gel column chromatography (EA) to obtain compound 26C (4.8 g, 40.00% yield). LC-MS (ESI): m / z = 180.2 [M+H] + .

[0633] 1 H NMR (400MHz, Chloroform-d) δ7.24(s,1H),7.00(s,1H),3.84(s,3H),3.31(t,4H),2.55(t,4H).

[0634] Step 2: Compound 26C (3.62 g, 19.97 mmol) and N-phenylbis(trifluoromethanesulfonimide) (10.70 g, 29.95 mmol) were dissolved in THF (80 mL). The mixture was then cooled to -78°C and slowly added dropwise with LiHMDS (30 mL, 1 M THF solution). The mixture was allowed to warm to room temperature after the addition was complete. After the reaction was complete, water (100 mL) was added and the mixture was extracted with ethyl acetate (100 mL x 2). The combined organic phases were dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure and the residue was separated by silica gel column chromatography (EA:PE (v / v) = 1:1) to afford compound 26D (4.2 g, 67.56% yield). LC-MS (ESI): m / z = 312.3 [M+H] + .

[0635] Step 3: Compound 26D (4.2 g, 13.49 mmol) and compound 26E (3.55 g, 13.49 mmol) were dissolved in 1,4-dioxane (60 mL) and water (10 mL). Pd(dppf)Cl2 (1.97 g, 2.70 mmol) and potassium carbonate (3.73 g, 26.98 mmol) were added, stirred, and reacted at 100°C under a nitrogen atmosphere for 6 hours. The reaction solution was cooled to room temperature, water (80 mL) was added, and the mixture was extracted with ethyl acetate (100 mL x 3). The combined organic phases were washed with saturated brine (150 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure and purified by silica gel column chromatography (DCM:MeOH (v / v) = 30:1) to obtain compound 26F (2.6 g, yield 64.6%). LC-MS (ESI): m / z = 299.2 [M+H] + .

[0636] Step 4: Compound 26F (2.6 g, 8.71 mmol) was dissolved in ethanol (30 mL), and sodium borohydride (1.65 g, 43.64 mmol) was slowly added portionwise. The mixture was then heated to 70°C for 2 hours. After the reaction, the mixture was cooled to room temperature and concentrated under reduced pressure to remove most of the ethanol. Saturated brine (60 mL) was added to the residue, and the mixture was extracted with dichloromethane (80 mL x 4). The combined organic phases were dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure, and the residue was separated by silica gel column chromatography (DCM:MeOH (v / v) = 10:1) to afford 26G (1.3 g, 55.21% yield). LC-MS (ESI): m / z = 271.0 [M+H] + .

[0637] Step 5: 26G (0.73 g, 2.7 mmol) was dissolved in methanol (10 mL), and palladium on carbon (0.2 g) was added. The reaction was allowed to proceed at room temperature under a hydrogen atmosphere for 3 hours. After completion of the reaction, the product was concentrated under reduced pressure. The residue was separated by silica gel column chromatography (DCM:MeOH (v / v) = 10:1) to obtain the target compound 26H (0.56 g, yield 76.15%). LC-MS (ESI): m / z = 273.1 [M+H] + .

[0638] Step 6: Sodium hydride (40 mg, 1.0 mmol, 60% wt) was dissolved in a mixture of THF (6 mL) and DMF (3 mL). Compound 26H (0.14 g, 0.51 mmol) and imidazole (2 mg) were added at 0°C. After complete addition, the mixture was stirred at room temperature for 30 minutes. Carbon disulfide (76 mg, 1.0 mmol) was added dropwise. After complete addition, stirring was continued for 1 hour. Methyl iodide (0.14 g, 1.0 mmol) was added dropwise. After complete addition, the reaction was continued for 30 minutes. Ethyl acetate and saturated aqueous sodium bicarbonate were added for extraction. The organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to obtain the target compound 26I (0.18 g, 97% yield). LC-MS (ESI): m / z = 363.0 [M+H] + .

[0639] Step 7: Compound 26I (0.18 g, 0.50 mmol) was dissolved in methanol (10 mL). Hydrazine hydrate (50 mg, 1 mmol) was added at 0°C and stirred at room temperature for 20 minutes. The mixture was concentrated under reduced pressure. Methanol (10 mL) and triethylamine (0.20 g, 2 mmol) were added to the residue and stirred until homogeneous. Cyanogen bromide (0.11 g, 1 mmol) was added portionwise at 0°C and stirred for another 20 minutes. The mixture was concentrated under reduced pressure and the residue was purified by silica gel column chromatography to obtain compound 26J (0.12 g, yield 64.61%). LC-MS (ESI): m / z = 372.0 [M+H]+ .

[0640] Step 8: Compound 26J (0.12 g, 0.32 mmol) and 1D (92 mg, 0.33 mmol) were dissolved in DMF (10 mL). 1-Methyl-1H-imidazole (82 mg, 1.0 mmol) was added and stirred. TCFH (0.11 g, 0.39 mmol) was added portionwise in an ice bath. The mixture was allowed to react at room temperature for 1 hour. After the reaction, saturated brine was added and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was separated by silica gel column chromatography to obtain compound 26 (96 mg, 46% yield). LC-MS (ESI): m / z = 632.0 [M+H] + .

[0641] 1 H NMR(400MHz,Chloroform-d)δ11.39(s,1H),8.95(s,1H),8.54(d,1H),8.03(s,1H),7.61(dd,1H),7.43(d,1H),7.23(s,2 H),7.15(s,1H),6.99(s,1H),5.52(s,2H),3.84(s,3H),3.73(s,3H),3.47(d,2H),2.73-2.62(m,6H),2.01-1.86(m,4H).

[0642] Example 27:

[0643] Step 1: Dissolve compound 26C (2.6 g, 14.51 mmol) in methanol (30 mL) and slowly add sodium borohydride (0.55 g, 14.51 mmol) in portions. The mixture was allowed to react at room temperature for 1 hour. After completion of the reaction, the mixture was concentrated under reduced pressure, and the residue was separated by silica gel column chromatography (DCM:MeOH (v / v) = 10:1) to afford 27A (2.3 g, 87.46% yield). LC-MS (ESI): m / z = 182.0 [M+H] + .

[0644] Step 2: Compound 27A (2.3 g, 12.65 mmol) and methyl 5-hydroxypyridine-2-carboxylate (4A) (1.94 g, 12.65 mmol) were used as starting materials and the same procedure as in Example 4 (step 1) was used to synthesize compound 27B (1.8 g, 45% yield). LC-MS (ESI): m / z = 317.2 [M+H] + .

[0645] Step 3: Compound 27B (1.8 g, 5.69 mmol) was used as the starting material and the procedure of Step 4 of Example 26 was followed to obtain Compound 27C (0.86 g, yield 52.42%). LC-MS (ESI): m / z = 289.2 [M+H] + .

[0646] Step 4: Using compound 27C (0.28 g, 0.97 mmol) as the starting material, compound 27D (0.37 g, yield 100%) was synthesized by referring to the first step of Example 1.

[0647] Step 5: Using compound 27D (0.37 g, 0.97 mmol) as the starting material, compound 27E (0.18 g, 48.5% yield) was synthesized by referring to the second step of Example 1. LC-MS (ESI): m / z = 194.6 [M / 2+H] + .

[0648] Step 6: Compound 27E (0.18 g, 0.46 mmol) and 1D (0.13 g, 0.46 mmol) were used as starting materials and the procedure of Step 3 of Example 1 was followed to obtain compound 27 (0.15 g, yield 50.31%). LC-MS (ESI): m / z = 324.6 [M / 2+H] + .

[0649] 1 H NMR(400MHz,DMSO-d6)δ12.91(s,1H),8.81(s,1H),8.31(t,1H),8.16(s,1H),7.53-7.48(m,3H),7.41(s,1H),7.24(d,1H),7.13(d,1H),5.45( s,2H),4.65-4.55(m,1H),3.72(s,3H),3.63(s,3H),3.20-3.10(m,2H) ,2.80-2.70(m,2H),2.58(s,3H),2.11-1.97(m,2H),1.80-1.68(m,2H).

[0650] Example 28:

[0651] Step 1: Compound 1F (552 mg, 1 mmol) and 2-chloro-5-nitropyridine (317 mg, 2 mmol) were used as starting materials and the procedure of Step 5 of Example 1 was followed to obtain Compound 28A (550 mg, 82% yield). LC-MS (ESI): m / z = 674.2 [M+H] + .

[0652] Step 2: Compound 28A (0.5 g, 0.82 mmol) was used as the starting material and the same procedure as in Step 6 of Example 1 was followed to obtain Compound 28B (210 mg, 40% yield). LC-MS (ESI): m / z = 644.2 [M+H] + .

[0653] Step 3: Compound 28B (210 mg, 0.33 mmol) was used as the starting material and the same procedure as in Step 7 of Example 1 was followed to obtain compound 28 (80 mg, yield 63%). LC-MS (ESI): m / z = 686.2 [M+H] + .

[0654] 1 H NMR(400MHz, CDCl3)δ11.05(s,1H),8.94(s,1H),8.52-8.51(m,1H),8.17(s,1H),8.03 (s,1H),8.02-7.92(m,1H),7.57-7.54(m,1H),7.43-7.41(m,1H),7.23(s,1H),7.15(s ,1H),6.75-6.73(m,1H),5.52(s,2H),4.43-4.40(m,2H),3.73(s,3H),3.01-2.95(m,2 H),2.85-2.79(m,1H),2.68(s,3H),2.19(s,3H),1.97-1.94(m,2H),1.83-1.76(m,2H).

[0655] Example 29:

[0656] Compound 2B (110 mg, 0.17 mmol) was dissolved in dry dichloromethane, replaced with nitrogen, and cooled to 0°C in an ice-water bath. Triethylamine (52 mg, 0.51 mmol) and cyclopropylcarbonyl chloride (27 mg, 0.26 mmol) were added, and the mixture was allowed to warm to room temperature for 1 hour. The reaction was monitored by TLC, quenched with water, extracted with dichloromethane, and the organic phase washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude product, which was purified using a Biotage Isolera One medium-pressure preparation instrument to yield compound 29 (30 mg, 24.20%). LC-MS (ESI): m / z = 729.2 [M+H] + .

[0657] 1H NMR(400MHz,DMSO-d6)δ12.91(s,1H),10.17(s,1H),8.81(s,1H),8.57-8.52(m, 1H),8.17(s,1H),7.84-7.78(m,1H),7.57-7.48(m,3H),7.42(s,1H),7.24-7.18( m,1H),7.06-6.99(m,1H),5.51(s,2H),3.63(s,3H),2.80-2.66(m,4H),2.59(s, 3H),2.04-1.96(m,1H),1.92-1.82(m,4H),1.77-1.69(m,1H),0.81-0.75(m,4H).

[0658] Example 30:

[0659] Compound 3C (200 mg, 0.37 mmol) and 3-bromopiperidine-2,6-dione (144 mg, 0.75 mmol) were dissolved in DMSO (6 mL). Triethylamine (112 mg, 1.11 mmol) was added, stirred, and reacted at 50°C for 6 hours. After completion of the reaction, saturated brine was added and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated, and the residue was separated by silica gel column chromatography to obtain compound 30 (74 mg, yield: 31%). LC-MS (ESI): m / z = 646.3 [M+H] + .

[0660] 1 H NMR(400MHz, Methanol-d4)δ8.75(s,1H),8.46(d,1H),7.79-7.76(m,1H),7.54(d,1H),7.39-7.36(m,2H),6.84-6.61(m,2H ),5.52(s,2H),3.65(s,3H),3.61-3.53(m,1H),3.03-2.91(m,2H),2.84-2.57(m,8H),2.22-2.06(m,2H),1.91-1.79(m,4H).

[0661] Example 31:

[0662] Step 1: Compound 4F (0.50 g, 0.88 mmol) and 3,4-difluoronitrobenzene (0.14 g, 0.88 mmol) were used as starting materials and the procedure of Step 5 of Example 1 was followed to obtain Compound 31A (0.41 g, yield 65%). LC-MS (ESI): m / z = 707.2 [M+H]+ .

[0663] Step 2: Compound 31A (0.41 g, 0.57 mmol) was used as the starting material and the same procedure as in Step 6 of Example 1 was followed to obtain compound 31B (0.21 g, yield 55%). LC-MS (ESI): m / z = 677.2 [M+H] + .

[0664] Step 3: Compound 31B (0.21 g, 0.31 mmol) was used as the starting material and the same procedure as in Step 1 of Example 13 was followed to obtain Compound 31 (76 mg, yield 35%). LC-MS (ESI): m / z = 705.1 [M+H] + .

[0665] 1 H NMR(400MHz,DMSO-d6)δ8.78(s,1H),8.31(d,1H),8.15(s,1H),7.53(d,3H),7.42(s,1H),6.98-6.96(m,1H),6.61-6.42(m,2H),5.4 6(s,2H),4.63-4.61(m,1H),3.63(s,3H),3.14-3.05(m,2H),2.90-2.75(m,8H),2.60(s,3H),2.14-2.07(m,2H),1.81-1.78(m,2H).

[0666] Example 32:

[0667] Step 1: Compound 32A (4 g, 11.94 mmol) (prepared according to the method described in WO2022194122), 5-bromo-2-hydroxymethylpyridine (2.24 g, 11.94 mmol), Pd(dppf)2Cl2 (0.88 g, 1.2 mmol), and potassium carbonate (4.94 g, 35.82 mmol) were added sequentially to a mixture of 1,4-dioxane (15 mL) and water (4 mL). The mixture was heated to 90°C under a nitrogen atmosphere for 12 hours. After the reaction was complete, the mixture was cooled to room temperature, filtered, and the filtrate was concentrated. The residue was then separated by silica gel column chromatography to obtain compound 32B (2.64 g, 70%). LC-MS (ESI): m / z = 317.2 [M+H] + .

[0668] Step 2: Compound 32B (1.0 g, 3.16 mmol) was dissolved in anhydrous ethanol (15 mL) and ethyl acetate (10 mL). Palladium on carbon (0.3 g) was added at room temperature and stirred under a hydrogen atmosphere for 2 hours. The reaction was terminated by TLC monitoring of the disappearance of the starting material. The filtrate was filtered, concentrated, and the residue was purified by silica gel column chromatography to yield 32C (0.85 g, 84%). LC-MS (ESI): m / z = 319.2 [M+H] + .

[0669] Step 3: Compound 32C (0.85 g, 2.66 mmol) and compound 19B (1.24 g, 5.32 mmol) were used as starting materials and the same procedure as in Step 3 of Example 19 was followed to obtain compound 32D (0.72 g, yield 65%). LC-MS (ESI): m / z = 418.2 [M+H] + .

[0670] Step 4: Compound 32D (0.5 g, 1.20 mmol) and compound 3A (0.31 g, 1.20 mmol) were used as starting materials and the same procedure as in Step 3 of Example 1 was followed to obtain compound 32E (0.48 g, yield 61%). LC-MS (ESI): m / z = 661.2 [M+H] + .

[0671] Step 5: Compound 32E (0.48 g, 0.73 mmol) was used as the starting material and the same procedure as in Step 4 of Example 1 was followed to obtain compound 32F (0.37 g, yield 90%). LC-MS (ESI): m / z = 561.2 [M+H] + .

[0672] Step 6: Compound 32F (0.11 g, 0.20 mmol) was used as the starting material and the same procedure as in Step 7 of Example 1 was followed to obtain compound 32 (38 mg, yield 32%). LC-MS (ESI): m / z = 603.2 [M+H] + .

[0673] 1H NMR(400MHz, Methanol-d4)δ8.74(s,1H),8.46(d,1H),7.81-7.78(m,1H),7.53(d,1H),7.39-7.36(m,2H),6.84-6.81(m,2H),5.52(s,2H),3.73-3 .71(m,1H),3.65(s,3H),3.63-3.43(m,3H),3.24-3.21(m,1H),2.89-2.8 6(m,2H),2.63(s,3H),2.41-2.38(m,2H),2.07(s,3H),1.55-1.51(m,2H).

[0674] Example 33:

[0675] Compound 1F (0.41 g, 0.57 mmol) was used as the starting material and the same procedure as in Example 30 was followed to obtain compound 33 (0.21 g, yield 55%). LC-MS (ESI): m / z = 663.2 [M+H] + .

[0676] 1 H NMR(400MHz,Methanol-d4)δ8.78(s,1H),8.47(d,1H),8.07(s,1H),7.80-7.77(m,1H),7.55(d, 1H),7.47(s,1H),7.41(s,1H),5.53(s,2H),3.71(s,3H),3.62-3.52(m,1H),3.08-2.92(m,2H), 2.88-2.57(m,8H),2.30-2.06(m,2H),1.92-1.75(m,4H).

[0677] Example 34:

[0678] Step 1: Dissolve compound 1D (87 mg, 0.31 mmol) and 6-(5-amino-1,3,4-thiadiazol-2-yl)oxy)methylpicolinate (100 mg, 0.38 mmol) in DMF (3 mL). Add 1-methyl-1H-imidazole (56 mg, 0.68 mmol). Stir thoroughly, then add TCFH (105 mg, 0.37 mmol) portionwise in an ice bath. React at room temperature for 12 hours. After completion of the reaction, add saturated brine (8 mL) and extract with ethyl acetate (8 mL x 2). The combined organic phases are washed with saturated brine (8 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The residue is isolated by silica gel column chromatography to afford compound 34B (145 mg, 88% yield). LC-MS (ESI): m / z = 527.4 [M+H] + .

[0679] Step 2: Compound 34B (145 mg, 0.27 mmol) was dissolved in methanol (3 mL) and water (1 mL). Lithium hydroxide (23 mg, 0.54 mmol) was added and the mixture was allowed to react at room temperature for 2 hours. The pH was adjusted to 2-3 with dilute hydrochloric acid. The precipitated solid was filtered, and the filter cake was washed with water and dried to obtain compound 34C (80 mg, 57% yield). LC-MS (ESI): m / z = 513.2 [M+H] + .

[0680] Step 3: Compound 34C (80 mg, 0.15 mmol) and N-methylpiperazine (20 mg, 0.18 mmol) were dissolved in DMF (3 mL). 1-Methyl-1H-imidazole (30 mg, 0.34 mmol) was added and stirred. TCFH (56 mg, 0.18 mmol) was added portionwise in an ice bath. The mixture was allowed to react at room temperature for 12 hours. After the reaction, saturated brine (3 mL) was added and the mixture was extracted with ethyl acetate (3 mL x 2). The combined organic phases were washed with saturated brine (4 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was isolated by silica gel column chromatography to yield compound 34 (32 mg, 35% yield). LC-MS (ESI): m / z = 596.2 [M+H] + .

[0681] 1H NMR(400MHz,DMSO-d6)δ13.05(s,1H),8.84-8.78(m,1H),8.64-8.57(m,1H),8.19-8.15(m,1H),7.92-7.86(m,1H),7.64-7.57(m,1H),7.55-7.4 8(m,1H),7.45-7.37(m,1H),5.64-5.54(m,2H),3.64-3.61(m,3H),3.29 -3.26(m,4H),2.61-2.54(m,3H),2.44-2.24(m,4H),2.23-2.17(m,3H).

[0682] Example 35:

[0683] Compound 1D (103 mg, 0.36 mmol) and compound 23D (123 mg, 0.40 mmol) were dissolved in DMF (5 mL). 1-Methyl-1H-imidazole (67 mg, 0.82 mmol) was added and stirred. TCFH (124 mg, 0.44 mmol) was added portionwise on ice. The mixture was allowed to react at room temperature for 12 hours. After completion of the reaction, saturated brine (8 mL) was added and the mixture was extracted with ethyl acetate (8 mL x 2). The combined organic phases were washed with saturated brine (8 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was separated by silica gel column chromatography (DCM:MeOH (v / v) = 20:1) to afford compound 35 (70 mg, 32% yield). LC-MS (ESI): m / z = 566.2 [M+H] + .

[0684] 1 H NMR(400MHz,DMSO-d6)δ13.15(s,1H),8.84-8.78(m,1H),8.41-8.36(m,1H),8.18-8.12 (m,1H),7.81-7.78(m,1H),7.56-7.52(m,1H),7.52-7.50(m,1H),7.48-7.43(m,1H),7.43 -7.38(m,2H),5.49-5.46(m,2H),3.84-3.79(m,3H),3.65-3.59(m,3H),2.60-2.56(m,3H)

[0685] Example 36:

[0686] 3-Oxetanecarboxylic acid (37 mg, 0.36 mmol), N,N-diisopropylethylamine (50 mg, 0.39 mmol), and HATU (0.14 g, 0.36 mmol) were dissolved in DMF (10 mL) in sequence and stirred for 10 minutes. Compound 2B (0.2 g, 0.30 mmol) was then added, and the reaction was stirred for 2 hours. The reaction solution was poured into water and extracted with ethyl acetate. The organic phase was 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 medium-pressure preparation instrument Biotage Isolera One to obtain compound 36 (20 mg, yield 8.95%). LC-MS (ESI): m / z = 745.9 [M+H] + .

[0687] 1 H NMR (400MHz, CDCl3): δ8.95(s,1H),8.57-8.56(m,1H),8.04(s,1H),7.70-7.68(m,1H),7.60(s,1H),7.49-7.47(m,1H),7.25(s,1H),7.18- 7.17(m,3H),5.56(s,2H),4.96-4.93(m,2H),4.89-4.86(m,2H),3.91 -3.88(m,1H),3.75(s,3H),3.59-3.57(m,2H),2.97-2.96(m,2H),2.77 -2.75(m,1H),2.70(s,3H),1.99-1.96(m,4H).

[0688] Example 37:

[0689] Compound 2B (200 mg, 0.30 mmol) was dissolved in dichloromethane (10 mL), and triethylamine (120 mg, 1.20 mmol) and propionyl chloride (55 mg, 0.60 mmol) were added sequentially. The mixture was allowed to react at room temperature under a nitrogen atmosphere for 5 h. After the reaction was complete, dichloromethane was added, and the organic phase was washed sequentially with water and saturated brine, dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated to obtain a residue that was purified by silica gel column chromatography to yield compound 37 (40 mg, 18%). LC-MS (ESI): m / z = 717.1 [M+H] + .

[0690] 1H NMR(400MHz, CDCl3)δ8.94(s,1H),8.56-8.55(m,1H),8.04(s,1H),7.65-7.63(m ,1H),7.45-7.43(m,2H),7.24(s,1H),7.15(s,1H),7.12-7.09(m,1H),7.04(s,1H ),6.96-6.93(m,1H),5.54(s,2H),3.75(s,3H),3.54-3.52(m,2H),2.83-2.77(m, 2H),2.73-2.69(m,4H),2.41-2.35(m,2H),2.01-1.93(m,4H),1.27-1.23(m,3H).

[0691] Example 38:

[0692] Step 1: Compound 25B (0.5 g, 0.92 mmol) was used as the starting material and the same procedure as in Step 5 of Example 1 was followed to obtain compound 38A (0.35 g, yield 56%). LC-MS (ESI): m / z = 679.1 [M+H] + .

[0693] Step 2: Compound 38A (0.35 g, 0.51 mmol) was used as the starting material and the same procedure as in Step 6 of Example 1 was followed to obtain compound 38B (0.18 g, yield 54%). LC-MS (ESI): m / z = 649.1 [M+H] + .

[0694] Step 3: Compound 38B (0.1 g, 0.15 mmol) was used as the starting material and the same procedure as in Step 7 of Example 1 was followed to obtain compound 38 (0.03 g, yield 29%). LC-MS (ESI): m / z = 691.2 [M+H] + .

[0695] 1 H NMR(400MHz,DMSO-d6)δ9.86(s,1H),8.81(s,1H),8.31-8.30(m,1H),8.17(s,1H),7.56-7.49(m,1H),7.46-7.39(m,3H),7.13-7.11(m,1H),6.6 0-6.55(m,1H),6.46-6.44(m,2H),5.48(s,2H),5.25-5.20(m,1H),4.39 -4.35(m,2H),3.83-3.80(m,2H),3.63(s,3H),2.59(s,3H),1.99(s,3H).

[0696] Example 39:

[0697] Using 1-methyl-1H-pyrazole-4-carboxylic acid (23 mg, 0.18 mmol) and 2B (100 mg, 0.15 mmol) as starting materials, compound 39 (54 mg, 47%) was obtained by following the synthetic procedure of Example 36, step 1. LC-MS (ESI): m / z = 769.4 [M+H] + .

[0698] 1 H NMR (400MHz, CDCl3): δ8.92(s,1H),8.56(s,1H),8.04(s,1H),7.92(s,1H),7.81(s,1 H),7.66-7.63(m,1H),7.53-7.47(m,1H),7.46-7.43(m,1H),7.35(s,1H),7.25(s,1H ),7.20-7.17(m,1H),7.15(s,1H),7.00-6.95(m,1H),5.55(s,2H),3.96(s,3H),3.76 (s,3H),3.57-3.53(m,2H),2.85-2.78(m,2H),2.74-2.68(m,4H),2.05-1.95(m,4H).

[0699] Example 40:

[0700] Using 2,2-difluoropropionic acid (20 mg, 0.18 mmol) and 2B (100 mg, 0.15 mmol) as starting materials, compound 40 (28 mg, 25%) was obtained by following the synthetic procedure of the first step of Example 36. LC-MS (ESI): m / z = 753.1 [M+H] + .

[0701] 1 H NMR (400MHz, CDCl3): δ8.98(s,1H),8.57(s,1H),8.03(s,1H),7.94(s,1H),7.70-7.65(m,1H),7.54-7.45(m,2H),7.24(s,1H),7.21-7.17(m ,2H),7.06(s,1H),5.54(s,2H),3.73(s,3H),3.59-3.55(m,2H),2.90- 2.84(m,2H),2.77-2.70(m,4H),2.07-1.99(m,2H),1.95-1.84(m,5H).

[0702] Example 41:

[0703] Using 1-fluorocyclopropane-1-carboxylic acid (19 mg, 0.18 mmol) and 2B (100 mg, 0.15 mmol) as starting materials, compound 41 (36 mg, 32%) was obtained by following the synthetic procedure of the first step of Example 36. LC-MS (ESI): m / z = 747.7 [M+H] + .

[0704] 1 H NMR (400MHz, CDCl3): δ8.95(s,1H),8.57-8.55(m,1H),8.04-8.01(m,3H),7.66-7.62(m,1H),7 .51-7.42(m,2H),7.24(s,1H),7.18-7.13(m,2H),7.00-6.95(m,1H),5.53(s,2H),3.74(s,3H), 3.57-3.53(m,2H),2.84-2.77(m,2H),2.75-2.68(m,4H),2.05-1.93(m,4H),1.51-1.38(m,4H).

[0705] Example 42:

[0706] Using 1-fluorocyclobutane-1-carboxylic acid (21 mg, 0.18 mmol) and 2B (100 mg, 0.15 mmol) as starting materials, compound 42 (36 mg, 32%) was obtained by following the synthetic procedure of the first step of Example 36. LC-MS (ESI): m / z = 761.7 [M+H] + .

[0707] 1 H NMR (400MHz, CDCl3): δ8.98(s,1H),8.56-8.55(m,1H),8.02(s,2H),7.89- 7.86(m,1H),7.65-7.62(m,1H),7.54-7.48(m,1H),7.45-7.42(m,1H),7.24 (s,1H),7.19-7.13(m,2H),6.99-6.94(m,1H),5.50(s,2H),3.72(s,3H),3 .57-3.51(m,2H),2.85-2.65(m,8H),2.55-2.39(m,2H),2.07-1.93(m,6H).

[0708] Example 43:

[0709] Compound 43 (0.017 g, 10.28%) was synthesized using 2B (0.15 g, 0.23 mmol) and methyl chloroformate (0.026 g, 0.28 mmol) as starting materials, following the synthetic method described in Example 37, step 1. LC-MS (ESI): m / z = 719.2 [M+H] + .

[0710] 1 H NMR (400MHz, CDCl3): δ8.95(s,1H),8.57-8.56(m,1H),8.03(s,1H),7.68-7. 65(m,1H),7.46-7.44(m,1H),7.31-7.28(m,1H),7.27(s,1H),7.15(s,1H),7 .00-6.97(m,1H),5.54(s,2H),3.78(s,3H),3.74(s,3H),3.54-3.51(m,2H), 2.86-2.84(m,2H),2.72-2.69(m,4H),2.10-2.03(m,2H),1.97-1.93(m,3H).

[0711] Example 44:

[0712] Compound 44 (72 mg, 33% yield) was obtained by referring to the synthesis method of Example 37 using compound 2B (200 mg, 0.30 mmol) and isobutyryl chloride (64 mg, 0.60 mmol) as starting materials. LC-MS (ESI): m / z = 731.1 [M+H] + .

[0713] 1 H NMR (400MHz, CDCl3) δ11.12(s,1H),8.95(s,1H),8.56(s,1H),8.04(s,1H),7.67-7.65(m,1H),7.52-7.44(m,2H),7.24(s,1H),7.16-7.10(m,3H ),7.03-6.95(m,1H),5.54(s,2H),3.74(s,3H),3.56-3.53(m,2H),2.84 -2.69(m,6H),2.53-2.46(m,1H),2.07-1.94(m,4H),1.26-1.25(m,6H).

[0714] Example 45:

[0715] Compound 2B (120 mg, 0.18 mmol) and 3,3-difluorocyclobutanecarboxylic acid were used as starting materials and the procedure of step 4 of Example 8 was followed to obtain compound 45 (51 mg, yield 36.36%). LC-MS (ESI): m / z = 779.9 [M+H] + .

[0716] 1 H NMR(400MHz,DMSO-d6)δ12.93(s,1H),10.10(s,1H),8.81(s,1H),8.57-8.53(m ,1H),8.17(s,1H),7.84-7.79(m,1H),7.58-7.52(m,2H),7.52-7.48(m,1H),7. 42(s,1H),7.26-7.20(m,1H),7.09-7.01(m,1H),5.51(s,2H),3.63(s,3H),3.4 2(s,1H),3.10-3.02(m,1H),2.86-2.70(m,8H),2.59(s,3H),1.91-1.83(m,4H).

[0717] Example 46:

[0718] Compound 2B (85 mg, 0.13 mmol) and acetyl chloride-d3 were used as starting materials and the procedure of step 7 of Example 1 was followed to obtain compound 46 (27 mg, yield 29.41%). LC-MS (ESI): m / z = 706.8 [M+H] + .

[0719] 1 H NMR(400MHz,DMSO-d6)δ13.16-12.50(m,1H),10.12-9.92(m,1H),8.82(s, 1H),8.57-8.54(m,1H),8.17(s,1H),7.83-7.79(m,1H),7.56-7.48(m,3H) ,7.41(s,1H),7.21-7.17(m,1H),7.08-7.00(m,1H),5.51(s,2H),3.63(s, 3H),3.44-3.35(m,4H),2.76-2.73(m,1H),2.58(s,3H),1.91-1.83(m,4H).

[0720] Example 47:

[0721] Compound 2B (150 mg, 0.23 mmol) and 3-methylenecyclobutanecarboxylic acid were used as starting materials and the procedure of step 4 of Example 8 was followed to obtain compound 47 (53 mg, yield 30.51%). LC-MS (ESI): m / z = 755.3 [M+H] + .

[0722] 1 H NMR(400MHz,DMSO-d6)δ12.92(s,1H),9.90(s,1H),8.82(s,1H),8.58-8.53(m,1H),8. 17(s,1H),7.85-7.77(m,1H),7.61-7.53(m,1H),7.52(s,1H),7.51-7.48(m,1H),7.41( s,1H),7.26-7.20(m,1H),7.07-7.00(m,1H),5.51(s,2H),4.82-4.76(m,2H),3.63(s,3 H),3.38(s,1H),3.23-3.14(m,1H),2.97-2.71(m,8H),2.58(s,3H),1.90-1.82(m,4H).

[0723] Example 48:

[0724] Step 1: Compound 2B (0.2 g, 0.30 mmol) and compound 48A (41.4 mg, 0.30 mmol) were used as starting materials and the procedure of step 3 of Example 1 was followed to obtain compound 48A (0.2 g, yield 84%). LC-MS (ESI): m / z = 781.1 [M+H] + .

[0725] Step 2: Compound 48A (0.2 g, 0.26 mmol) was dissolved in DMF (10 mL). Sodium hydride (16 mg, 0.39 mmol, 60% wt) was added at 0°C, and the mixture was stirred at room temperature overnight. Ethyl acetate was added, and the organic phase was washed with saturated aqueous sodium bicarbonate, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the target compound 48 (0.09 g, 46% yield). LC-MS (ESI): m / z = 745.2 [M+H] + .

[0726] 1H NMR(400MHz, CDCl3)δ8.97(s,1H),8.56-8.55(m,1H),8.03(s,1H),7.66-7.64(m,1H) ),7.46-7.44(m,1H),7.24(s,1H),7.16(s,1H),7.11-7.01(m,3H),5.52(s,2H),4.33 (s,2H),4.04-4.01(m,2H),3.75-3.73(m,2H),3.72(s,3H),3.60-3.57(m,2H),2.87 -2.81(m,2H),2.75-2.71(m,1H),2.69(s,3H),2.04-1.95(m,4H),1.29-1.26(m,1H).

[0727] Example 49:

[0728] Step 1: Dissolve zinc powder (4.53 g, 69.76 mmol) in DMA (100 mL) at room temperature. Add 1,2-dibromoethane (1.31 g, 6.97 mmol) and trimethylsilyl chloride (0.76 g, 6.97 mmol) dropwise to the reaction mixture under nitrogen atmosphere. After the addition, add 1-Boc-3-iodoazetidine (9.87 g, 34.88 mmol) and continue stirring at room temperature for 1 hour. Then, filter the reaction mixture and add raw material 49A (5.0 g, 23.25 mmol), CuI (0.66 g, 3.49 mmol), and Pd(dppf)2Cl2 (2.55 g, 3.49 mmol) to the filtrate in sequence. React at 85°C for 16 hours. After the reaction was complete, the mixture was cooled to room temperature, water was added, and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was separated by silica gel column chromatography to obtain the target compound 49B (3.0 g, yield 46%). LC-MS (ESI): m / z = 279.1 [M+H] + .

[0729] Step 2: Compound 49B (3.0 g, 10.79 mmol) was dissolved in methanol (30 mL). Thionyl chloride (3 mL) was added dropwise at 0°C. The temperature was then raised to 70°C and stirred overnight. After the reaction was complete, the mixture was cooled to room temperature and concentrated under reduced pressure. DCM (30 mL) and triethylamine (3.27 g, 32.37 mmol) were added to the residue. After stirring, Boc anhydride (3.53 g, 16.18 mmol) was added and stirring continued for 20 minutes. The mixture was concentrated under reduced pressure and the residue was purified by silica gel column chromatography to obtain the target compound 49C (2.4 g, 76% yield). LC-MS (ESI): m / z = 293.2 [M+H] + .

[0730] Step 3: Compound 49C (2.4 g, 8.21 mmol) was used as the starting material and the same procedure as in Step 2 of Example 4 was followed to obtain compound 49D (1.2 g, yield 55%). LC-MS (ESI): m / z = 265.2 [M+H] + .

[0731] Step 4: Compound 49D (1.2 g, 4.54 mmol) was used as the starting material and the same procedure as in Example 1 was followed to obtain compound 49E (1.2 g, yield 75%). LC-MS (ESI): m / z = 355.2 [M+H] + .

[0732] Step 5: Compound 49E (1.2 g, 3.39 mmol) was used as the starting material and the same procedure as in Step 2 of Example 1 was followed to obtain compound 49F (1.1 g, yield 89%). LC-MS (ESI): m / z = 364.2 [M+H] + .

[0733] Step 6: Compound 49F (1.2 g, 3.29 mmol) was used as the starting material and the same procedure as in Step 3 of Example 1 was followed to obtain compound 49G (1.5 g, yield 73%). LC-MS (ESI): m / z = 624.2 [M+H] + .

[0734] Step 7: Compound 49G (1.5 g, 2.41 mmol) was used as the starting material and the same procedure as in Step 4 of Example 1 was followed to obtain compound 49H (1.1 g, yield 87%). LC-MS (ESI): m / z = 524.2 [M+H] + .

[0735] Step 8: Compound 49H (0.5 g, 0.96 mmol) was used as the starting material and the same procedure as in Step 5 of Example 1 was followed to obtain compound 49I (0.3 g, yield 48%). LC-MS (ESI): m / z = 645.2 [M+H] + .

[0736] Step 9: Compound 49I (0.3 g, 0.47 mmol) was used as the starting material and the same procedure as in Step 6 of Example 1 was followed to obtain compound 49J (0.18 g, yield 62%). LC-MS (ESI): m / z = 615.2 [M+H] + .

[0737] Step 10: Compound 49J (0.1 g, 0.16 mmol) was used as the starting material and the same procedure as in Step 1 of Example 13 was followed to obtain compound 49 (0.03 g, yield 28%). LC-MS (ESI): m / z = 643.2 [M+H] + .

[0738] 1 H NMR (400MHz, CDCl3) δ8.94(s,1H),8.59-8.58(m,1H),8.03(s,1H),7.85-7.83(m,1H),7.48-7.46(m,1H),7.24(s,1H),7.15(s,1H),6.90-6. 87(m,2H),6.52-6.50(m,2H),5.54(s,2H),4.29-4.25(m,2H),3.93-3 .89(m,1H),3.84-3.82(m,2H),3.73(s,3H),2.88(s,6H),2.68(s,3H).

[0739] Example 50:

[0740] Step 1: Dissolve compound 4G (500 mg, 0.73 mmol) in di-tert-butyl dicarbonate (8 mL), add DMAP (9 mg, 0.07 mmol), and heat at 80°C for 3 h. TLC confirms the reaction is complete, cool to room temperature, and concentrate the reaction mixture. The residue is purified by silica gel column chromatography to yield the target compound 50A (419 mg, 77%). LC-MS (ESI): m / z = 745.3 [M+H] + .

[0741] Step 2: Using compound 50A (419 mg, 0.56 mmol) as starting material, the target compound 50B (261 mg, yield: 65%) was obtained by referring to the procedure of step 6 of Example 1. LC-MS (ESI): m / z = 715.3 [M+H] + .

[0742] Step 3: Dissolve compound 50B (216 mg, 0.37 mmol) in dichloromethane (30 mL), add triethylamine (111 mg, 1.1 mmol), and slowly add benzyl chloroformate (76 mg, 0.44 mmol) in an ice bath. After complete addition, warm to room temperature and continue stirring for 1 hour. After TLC analysis, the reaction mixture was poured into ice water and extracted with ethyl acetate. The organic phase was washed with saturated sodium bicarbonate solution, dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the target compound 50C (223 mg, 71% yield). LC-MS (ESI): m / z = 849.3 [M+H] + .

[0743] Step 4: Compound 50C (223 mg, 0.26 mmol) was dissolved in ultra-dry DMF (30 mL). Sodium hydride (32 mg, 0.79 mmol, 60% wt) was added under ice-cooling. After stirring for 0.5 h, iodomethane (48 mg, 0.34 mmol) was added and stirring continued for 2 h. After TLC analysis, the reaction mixture was poured into ice water and extracted with ethyl acetate. The organic phase was washed with saturated sodium bicarbonate solution, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the target compound 50D (152 mg, 68% yield). LC-MS (ESI): m / z = 863.3 [M+H] + .

[0744] Step 5: Dissolve compound 50D (152 mg, 0.18 mmol) in dichloromethane (50 mL). Slowly add trifluoromethanesulfonic acid (1 mL) dropwise under ice-cooling. After complete addition, stir for 1 hour. After TLC, pour the reaction mixture into ice water. Add saturated sodium bicarbonate solution dropwise to adjust the pH to 8-9. Extract with ethyl acetate. The organic phase is washed with saturated brine, dried over anhydrous sodium sulfate, and filtered. The filtrate is concentrated under reduced pressure, and the residue is purified by silica gel column chromatography to obtain the target compound 50 (46 mg, 39% yield). LC-MS (ESI): m / z = 673.2 [M+H] + .

[0745] 1 H NMR(400MHz,Methanol-d4)δ8.80(s,1H),8.26(d,1H),8.06(s,1H),7.60-7.30(m,4H),7.06-6.47(m,4H ),5.47(s,2H),4.67-4.50(m,1H),3.71(s,3H),3.31-3.16(m,3H),3.10-2.53(m,7H),2.23-1.79(m,4H).

[0746] Example 51:

[0747] Step 1: Compound 51A (synthesized according to the method described in patent WO2020243459) (5.00 g, 17.4 mmol) and compound 3A-1 (5.00 g, 19.2 mmol) were dissolved in DMF (100 mL), 1-methyl-1H-imidazole (4.29 g, 52.2 mmol) was added, and TCFH (5.86 g, 20.9 mmol) was added in batches under ice bath conditions after stirring. The mixture was reacted at room temperature for 3 hours. After the reaction, saturated brine was added and extracted with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was separated by silica gel column chromatography to obtain compound 51B (8.10 g, yield 87.7%). LC-MS (ESI): m / z = 530.0 [M+H] + .

[0748] Step 2: Compound 51B (4.00 g, 7.55 mmol), pinacol diboronate (5.75 g, 22.6 mmol), Pd(dppf)Cl2 (1.11 g, 1.51 mmol), and potassium acetate (2.59 g, 26.4 mmol) were dissolved in 1,4-dioxane (100 mL) and then heated to 100°C for overnight reaction. After completion of the reaction, the mixture was cooled to room temperature and concentrated under reduced pressure. The residue was purified by silica gel column chromatography and then C-18 reverse-phase silica gel column chromatography to obtain compound 51C (870 mg, 23.3% yield). LC-MS (ESI): m / z = 496.2 [M+H] + .

[0749] Step 3: Compound 51C (300 mg, 0.606 mmol), compound 51D (synthesized according to the method described in patent WO2022236272) (284 mg, 1.21 mmol), Pd(dppf)Cl2 (88.6 mg, 0.121 mmol), and potassium carbonate (209 mg, 1.51 mmol) were dissolved in 1,4-dioxane (10 mL) and water (1 mL). The temperature was then raised to 100°C and the reaction was allowed to react overnight. After the reaction was completed, the mixture was cooled to room temperature and concentrated under reduced pressure. The residue was purified by preparative HPLC to obtain compound 51 (67 mg, 19.8%). LC-MS (ESI): m / z = 558.2 [M+H] + .

[0750] 1H NMR(400MHz,Chloroform-d)δ9.02-8.93(m,2H),8.12(dd,1H),7.54-7.42(m,2H),7.38(td,1H),7.20(d,1H),6.84(t,1H), 6.78(d,1H),6.55(d,1H),5.57(s,2H),3.75(s,3H),3.69-3.61(m,1H),2.66(s,3H),1.21-1.14(m,2H),1.10-1.03(m,2H).

[0751] Example 52:

[0752] Step 1: Compound 52A (1 g, 2.55 mmol) (synthesized according to the method described in patent WO2023134708) and compound 1C (763 mg, 3.31 mmol) were used as starting materials and the procedure of step 3 of Example 1 was followed to obtain compound 52B (213 mg, yield 13.84%). LC-MS (ESI): m / z = 604.4 [M+H] + .

[0753] Step 2: Dissolve compound 52B (213 mg, 0.35 mmol) in dichloromethane (10 mL). Add trifluoroacetic acid (2 mL) at 0°C. Stir for 5 minutes, then warm to room temperature for 1 hour. After completion of the reaction, concentrate under reduced pressure to obtain crude compound 52C (431 mg), which was carried on to the next step without further purification.

[0754] Step 3: Using crude compound 52C (431 mg) and 3,4-difluoronitrobenzene (128 mg, 0.80 mmol) as starting materials, the procedure of step 5 of Example 1 was followed to obtain compound 52D (101 mg, 45% yield over two steps). LC-MS (ESI): m / z = 643.1 [M+H] + .

[0755] Step 4: Compound 52D (100 mg, 0.16 mmol) was dissolved in a methanol / water (1:1) mixture (10 mL). Na2CO3 (170 mg, 1.60 mmol) and Na2S2O4 (278 mg, 1.60 mmol) were added and stirred at room temperature under a nitrogen atmosphere for 1 hour. After completion of the reaction, water was added and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude product, which was purified using a Biotage Isolera One medium-pressure prep system to obtain the target compound 52E (88 mg, 89.77% yield). LC-MS (ESI): m / z = 613.5 [M+H] +.

[0756] Step 5: Compound 52E (88 mg, 0.14 mmol) and cyclopropylcarbonyl chloride (18 mg, 0.18 mmol) were used as starting materials and the same procedure as in Example 29 was followed to obtain compound 52 (28 mg, yield 29.38%). LC-MS (ESI): m / z = 681.4 [M+H] + .

[0757] 1 H NMR(400MHz,DMSO-d6)δ13.12(s,1H),10.18(s,1H),9.44-9.41(m,1H),9.38(s, 1H),8.57-8.53(m,1H),7.85-7.78(m,1H),7.58-7.44(m,4H),7.24-7.18(m,1H) ,7.16-7.10(m,1H),7.09-7.00(m,2H),5.52(s,2H),3.56(s,3H),3.42-3.35(m, 2H),2.82-2.70(m,3H),1.90-1.82(m,4H),1.76-1.69(m,1H),0.81-0.76(m,4H).

[0758] Example 53:

[0759] Compound 26J (0.12 g, 0.32 mmol) and 3A-1 (86 mg, 0.33 mmol) were dissolved in DMF (10 mL). 1-Methyl-1H-imidazole (82 mg, 1.0 mmol) was added and stirred. TCFH (0.11 g, 0.39 mmol) was added portionwise in an ice bath and allowed to react at room temperature for 1 hour. After completion of the reaction, saturated brine was added and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was separated by silica gel column chromatography to obtain compound 53 (102 mg, 52% yield). LC-MS (ESI): m / z = 615.3 [M+H] + .

[0760] 1H NMR(400MHz,Methanol-d4)δ8.75(s,1H),8.48(d,1H),7.81(dd,1H),7.56(d,1H),7.39(t,2H),7.27(dd,2H),6.8 4(t,2H),5.53(s,2H),3.81(s,3H),3.65(s,3H),3.49(d,2H),2.75-2.64(m,3H),2.63(s,3H),1.95-1.87(m,4H).

[0761] Example 54:

[0762] Compound 54 (0.11 g, 56% yield) was synthesized using compound 27E (0.12 g, 0.31 mmol) and 3A-1 (94 mg, 0.36 mmol) as starting materials, following the procedure described in step 3 of Example 1. LC-MS (ESI): m / z = 631.3 [M+H] + .

[0763] 1 H NMR(400MHz, Methanol-d4)δ8.75(s,1H),8.25(d,1H),7.57-7.44(m,2H),7.43-7.33(m,2H),7.25(dd,2H),6.88-6.80(m,2H),5.47(s,2 H),4.66-4.55m,1H),3.80(s,3H),3.65(s,3H),3.27-3.17(m,2H),2.94-2.84(m,2H),2.82(s,3H),2.16-2.07(m,2H),1.96-1.83(m,2H).

[0764] Example 55:

[0765] Step 1: Compound 26G (0.54 g, 2.0 mmol) was used as the starting material and the procedure of Step 1 of Example 1 was followed to obtain Compound 55A (0.56 g, yield 78%).

[0766] Step 2: Compound 55A (0.56 g, 1.55 mmol) was used as the starting material and the procedure of Step 2 of Example 1 was followed to obtain Compound 55B (0.52 g, yield 91%). LC-MS (ESI): m / z = 370.1 [M+H] + .

[0767] Step 3: Compound 55B (100 mg, 0.27 mmol) and 1D (92 mg, 0.33 mmol) were used as starting materials and the procedure described in Step 3 of Example 1 was followed to obtain compound 55 (82 mg, yield 48%). LC-MS (ESI): m / z = 630.4 [M+H] + .

[0768] 1 H NMR (400MHz, CDCl3) δ11.49(s,1H),8.96(s,1H),8.69(d,1H),8.03(s,1H),7.72(dd,1H),7.44(d,1H),7.27(s,1H),7.23(s,1H ),7.15(s,1H),7.02(s,1H),6.24-6.19(m,1H),5.53(s,2H),3.85(s,3H),3.73(s,3H),3.66(d,2H),3.24(t,2H),2.68(s,5H).

[0769] Example 56:

[0770] Compound 56 (91 mg, 55% yield) was synthesized using compound 55B (100 mg, 0.27 mmol) and 3A-1 (86 mg, 0.33 mmol) as starting materials, following the procedure of step 3 of Example 1. LC-MS (ESI): m / z = 613.3 [M+H] + .

[0771] 1 H NMR(400MHz, CDCl3)δ9.80(s,1H),8.99(s,1H),8.68(d,1H),7.72(dd,1H),7.48- 7.34(m,2H),7.28(s,1H),7.20(s,1H),7.07(s,1H),6.88-6.82(m,1H),6.79(d,1H),6.2 1(t,1H),5.56(s,2H),3.85(s,3H),3.77(s,3H),3.68(s,2H),3.26(t,2H),2.67(s,5H).

[0772] Example 57:

[0773] Step 1: Compound 57A (0.7 g, yield 69%) was obtained by following the procedure of Step 1 in Example 2 using compound 49H (0.8 g, 1.53 mmol) as the starting material. LC-MS (ESI): m / z = 663.2 [M+H] + .

[0774] Step 2: Compound 57A (0.7 g, 1.06 mmol) was used as the starting material and the same procedure as in Step 6 of Example 1 was followed to obtain Compound 57B (0.4 g, yield 59%). LC-MS (ESI): m / z = 633.2 [M+H] + .

[0775] Step 3: Compound 57B (0.05 g, 0.08 mmol) was used as the starting material and the same procedure as in Step 1 of Example 13 was followed to obtain Compound 57 (0.02 g, yield 37%). LC-MS (ESI): m / z = 661.2 [M+H] + .

[0776] 1 H NMR(400MHz, CDCl3)δ8.95(s,1H),8.59-8.58(m,1H),8.02(s,1H),7.87-7.84(m,1H),7.47-7.45(m,1H),7.23(s,1H),7. 15(s,1H),6.52-6.50(m,3H),5.53(s,2H),4.33-4.32(m,2H),3.93-3.89(m,3H),3.72(s,3H),2.88(s,6H),2.68(s,3H).

[0777] Example 58:

[0778] Step 1: Compound 57B (0.1 g, 0.16 mmol) and compound 48A (22.1 mg, 0.16 mmol) were used as starting materials and the same procedure as in Step 3 of Example 1 was followed to obtain compound 58A (0.1 g, yield 84%). LC-MS (ESI): m / z = 753.1 [M+H] + .

[0779] Step 2: Compound 58A (0.1 g, 0.13 mmol) was used as the starting material and the procedure of Step 2 of Example 48 was followed to obtain Compound 58 (0.05 g, yield 52%). LC-MS (ESI): m / z = 717.2 [M+H] + .

[0780] 1H NMR (400MHz, CDCl3) δ8.98(s,1H),8.61-8.60(m,1H),8.03(s,1H),7.89-7.85(m,1H),7.53-7.51(m,1H),7.24(s,1H),7.19(s,1H),7.02-6. 98(m,2H),6.55-6.50(m,1H),5.57(s,2H),4.45-4.41(m,2H),4.32(s ,2H),4.03-3.92(m,5H),3.73(s,3H),3.72-3.69(m,3H),2.72(s,3H).

[0781] Example 59:

[0782] Compound 57B (0.05 g, 0.08 mmol) was used as the starting material and the same procedure as in Example 29 was followed to obtain compound 59 (0.02 g, yield 36%). LC-MS (ESI): m / z = 701.2 [M+H] + .

[0783] 1 H NMR(400MHz, CDCl3)δ8.98(s,1H),8.61(s,1H),8.05(s,1H),7.95-7.93( m,1H),7.57-7.55(m,1H),7.41-7.32(m,2H),7.25-7.23(m,3H),7.05-7. 03(m,1H),5.63(s,2H),4.39-4.38(m,2H),3.95-3.94(m,2H),3.76(s,3H ),2.75(s,3H),1.74-1.70(m,3H),1.08-1.07(m,2H),0.85-0.84(m,2H).

[0784] Example 60:

[0785] Step 1: Compound 57B (0.05 g, 0.08 mmol) was used as the starting material and the same procedure as in Step 1 of Example 36 was followed to obtain compound 60 (0.02 g, yield 35%). LC-MS (ESI): m / z = 717.2 [M+H] + .

[0786] 1H NMR(400MHz, CDCl3)δ8.95(s,1H),8.59(s,1H),8.03(s,1H),7.88-7.85(m, 1H),7.52-7.49(m,1H),7.41-7.38(m,2H),7.24(s,1H),7.20-7.18(m,2H),7 .07-7.05(m,1H),5.57(s,2H),4.97-4.94(m,2H),4.88-4.84(m,2H),4.41-4 .39(m,2H),3.95-3.94(m,3H),3.85-3.80(m,2H),3.74(s,3H),2.71(s,3H).

[0787] Example 61:

[0788] Compound 57B (0.05 g, 0.08 mmol) and compound 9D (10.8 mg, 0.08 mmol) were used as starting materials and the same procedure as in step 3 of Example 1 was followed to obtain compound 61 (0.02 g, yield 33%). LC-MS (ESI): m / z = 741.2 [M+H] + .

[0789] 1 H NMR(400MHz,DMSO-d6)δ9.73(s,1H),8.81(s,1H),8.61-8.60(m,1H),8.2 6(s,1H),8.17(s,1H),7.98-7.95(m,2H),7.61-7.53(m,3H),7.42(s,2H), 7.33-7.30(m,1H),6.64-6.60(m,1H),5.54(s,2H),4.33-4.29(m,2H),4.0 3-3.97(m,1H),3.92-3.89(m,2H),3.63(s,3H),3.31(s,3H),2.59(s,3H).

[0790] Example 62:

[0791] Compound 62 (124 mg, 15%) was synthesized using 62A (370 mg, 1.38 mmol) (synthesized by the method described in WO2023202623) and 26J (510 mg, 1.38 mmol) as starting materials, following the third step of Example 1. LC-MS (ESI): m / z = 622.4 [M+H] + .

[0792] 1H NMR (400MHz, CDCl3): δ8.89(s,1H),8.55-8.53(m,1H),7.74-7.70(m,1H),7.63-7.60 (m,1H),7.59-7.57(m,1H),7.44-7.41(m,1H),7.22(s,1H),7.14(s,1H),6.99-6.95(m,2H) ,5.50(s,2H),3.84(s,3H),3.71(s,3H),3.48-3.42(m,2H),2.68(s,6H),1.98-1.87(m,4H).

[0793] Example 63:

[0794] Compound 63 (82 mg, 85% yield) was obtained by following the procedure of step 3 of Example 1 using compound 2B (100 mg, 0.15 mmol) and bicyclo[1.1.1]pentane-1-carboxylic acid (17 mg, 0.15 mmol) as starting materials. LC-MS (ESI): m / z = 756.2 [M+H] + .

[0795] 1 H NMR(400MHz, CDCl3)δ10.80(s,1H),8.95(s,1H),8.59-8.55(m,1H),8.05(s,1H), 8.73-8.71(m,1H),7.66-7.50(m,2H),7.49-7.47(m,1H),7.25(s,1H),7.17(s,1H ),7.15-7.07(m,2H),5.57(s,2H),3.76(s,3H),3.59-3.56(m,2H),3.06-2.87(m, 2H),2.82-2.74(m,1H),2.71(s,3H),2.54(s,1H),2.15(s,6H),2.05-1.86(m,4H).

[0796] Example 64:

[0797] Step 1: Dissolve compound 4A (1.53 g, 10 mmol) in DMF (80 mL), add cesium carbonate (6.52 g, 20 mmol) and 3,4-difluoronitrobenzene (1.91 g, 12 mmol) sequentially, and heat to 60°C for 3 hours. After completion, cool the reaction to room temperature and quench with saturated brine. Extract the mixture with ethyl acetate, dry the organic phase over anhydrous sodium sulfate, filter, and concentrate. The residue is purified by silica gel column chromatography to obtain the target compound 64A (2.66 g, 91% yield). LC-MS (ESI): m / z = 293.2 [M+H] + .

[0798] Step 2: Compound 64A (2.66 g, 9.1 mmol) was used as the starting material and the target compound 64B (2.3 g, yield 96%) was obtained by referring to the procedure of Step 2 of Example 4. LC-MS (ESI): m / z = 265.2 [M+H] + .

[0799] Step 3: Using compound 64B (2.3 g, 8.7 mmol) as starting material, the target compound 64C (3 g, yield 97%) was obtained by referring to the operation method of the first step of Example 1. LC-MS (ESI): m / z = 355.2 [M+H] + .

[0800] Step 4: Using compound 64C (3 g, 8.5 mmol) as starting material, the target compound 64D (1.25 g, 40% yield) was obtained by referring to the procedure of step 2 of Example 1. LC-MS (ESI): m / z = 364.2 [M+H] + .

[0801] Step 5: Using compound 64D (1.25 g, 3.4 mmol) as starting material, the target compound 64E (2.06 g, yield 99%) was obtained by referring to the procedure of step 3 of Example 1. LC-MS (ESI): m / z = 624.2 [M+H] + .

[0802] Step 6: Compound 64E (2.06 g, 3.3 mmol) was used as the starting material and the procedure of Step 6 of Example 1 was followed to obtain the target compound 64F (1.13 g, yield 50%). LC-MS (ESI): m / z = 594.2 [M+H] + .

[0803] Step 7: Compound 64F (119 mg, 0.2 mmol) was dissolved in dichloromethane (20 mL), and triethylamine (41 mg, 0.4 mmol) and cyclopropanecarbonyl chloride (25 mg, 0.24 mmol) were added. The reaction was allowed to react at room temperature for 1 hour. The mixture was quenched with water, extracted with dichloromethane, and the organic phase was dried over anhydrous sodium sulfate. After concentration, the residue was purified by silica gel column chromatography to obtain the target compound 64 (27 mg, 20% yield). LC-MS (ESI): m / z = 662.2 [M+H] + .

[0804] 1 H NMR (400MHz, CDCl3) δ11.71(s,1H),8.99(s,1H),8.36-8.35(m,1H),8.02(s,1H),7.66-7.63(m,1H),7.59(s,1H),7.40-7.38(m,1H),7.24(s ,1H),7.20-7.14(m,3H),7.08-7.03(m,1H),5.49(s,2H),3.70(s,3H), 2.69(s,3H),1.55-1.48(m,1H),1.13-1.09(m,2H),0.91-0.86(m,2H).

[0805] Example 65:

[0806] Compound 28B (129 mg, 0.2 mmol) was used as the starting material and the procedure of step 7 of Example 64 was followed to obtain the target compound 65 (40 mg, yield 28%). LC-MS (ESI): m / z = 712.2 [M+H] + .

[0807] 1 H NMR (400MHz, CDCl3) δ11.42(s,1H),8.98(s,1H),8.70-8.54(m,1H),8.47(s,1H),8.46-8.37(m, 1H),8.04(s,1H),7.52-7.46(m,1H),7.45-7.40(m,1H),7.24(s,1H),7.21(s,1H),7.17(s,1H), 6.88-6.86(m,1H),5.52(s,2H),4.46-4.43(m,2H),3.72(s,3H),3.17-3.10(m,2H),2.83-2.80( m,1H),2.70(s,3H),2.09-1.99(m,2H),1.90-1.77(m,3H),1.05-1.02(m,2H),0.88-0.85(m,2H).

[0808] Example 66:

[0809] Step 1: Compound 66A (7.5 g, 77.32 mmol) and 26B (17.86 g, 115.98 mmol) were used as starting materials and the same procedure as in Step 1 of Example 26 was followed to obtain compound 66B (6.23 g, 45% yield). LC-MS (ESI): m / z = 180.2 [M+H] + .

[0810] Step 2: Compound 66B (4.23 g, 23.5 mmol) was used as the starting material and the same procedure as in Step 2 of Example 26 was followed to obtain compound 66C (4.0 g, yield 55%). LC-MS (ESI): m / z = 312.3 [M+H] + .

[0811] Step 3: Compound 66C (4.0 g, 12.86 mmol) and 26E (4.4 g, 16.72 mmol) were used as starting materials and the same procedure as in Step 3 of Example 26 was followed to obtain compound 66D (3.27 g, yield 85%). LC-MS (ESI): m / z = 299.2 [M+H] + .

[0812] Step 4: Compound 66D (1.0 g, 3.36 mmol) was used as the starting material and the same procedure as in Step 4 of Example 26 was followed to obtain compound 66E (719 mg, yield 79%). LC-MS (ESI): m / z = 271.0 [M+H] + .

[0813] Step 5: Compound 66E (719 mg, 2.66 mmol) was used as the starting material and the same procedure as in Step 5 of Example 26 was followed to obtain compound 66F (613 mg, yield 85%). LC-MS (ESI): m / z = 273.1 [M+H] + .

[0814] Step 6: Compound 66F (613 mg, 2.25 mmol) was used as the starting material and the same procedure as in Step 3 of Example 19 was followed to obtain compound 66G (426 mg, yield 51%). LC-MS (ESI): m / z = 372.1 [M+H] + .

[0815] Step 7: Compound 66 (51 mg, 38% yield) was synthesized using compound 66G (80 mg, 0.22 mmol) and 1D (73 mg, 0.26 mmol) as starting materials, following the procedure of step 3 of Example 1. LC-MS (ESI): m / z = 632.2 [M+H] + .

[0816] 1 H NMR(400MHz, Methanol-d4)δ8.78(s,1H),8.48(d,1H),8.07(s,1H),7.80-7.78(m,1H),7.56(d,1H),7.47(s,1H),7.41(s,1H),7.34( d,1H),5.75(d,1H),5.54(s,2H),3.72(s,3H),3.71(s,3H),3.34-3.3.26(m,2H),2.87-2.75(m,3H),2.66(s,3H),1.93-1.82(m,4H).

[0817] Example 67:

[0818] Step 1: Dissolve 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (67A) (15.5 g, 79.8 mmol) in tetrahydrofuran (100 mL). Add sodium hydride (3.83 g, 159 mmol) under ice-cooling. Stir at 0°C for 30 minutes. Add deuterated iodomethane (23.2 g, 159 mmol) and react at room temperature for 12 hours. Add water and extract with ethyl acetate. The combined organic phases are dried over anhydrous sodium sulfate, filtered, and concentrated to yield compound 67B (15 g, 89% yield). LC-MS (ESI): m / z = 212.1 [M+H] + .

[0819] Step 2: Compound 67B (15 g, 71 mmol) was dissolved in 3M sodium hydroxide (51 mL, 142 mmol). Hydrogen peroxide (5.23 g, 142 mmol) was added dropwise under an ice bath and allowed to react at room temperature for 6 h. The pH was adjusted to 3-4 with hydrochloric acid, followed by extraction with dichloromethane. The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated to afford compound 67C (5.2 g, 73% yield). LC-MS (ESI): m / z = 102.1 [M+H] + .

[0820] Step 3: Compound 67C (5.2 g, 51 mmol) and (5-bromopyridin-2-yl)methanol (6.2 g, 34 mmol) were used as starting materials and the same procedure as in Example 23, Step 1, was used to obtain Compound 67D (1.2 g, yield: 18%). LC-MS (ESI): m / z = 209.2 [M+H] + .

[0821] Step 4: Compound 67D (0.454 g, 2.18 mmol) was used as the starting material and the same procedure as in Example 1 was followed to obtain compound 67E (0.651 g, yield 100%). LC-MS (ESI): m / z = 299.2 [M+H] + .

[0822] Step 5: Compound 67E (0.651 g, 2.18 mmol) was used as the starting material and the same procedure as in Step 2 of Example 1 was followed to obtain compound 67F (0.643 g, ...

Claims

1. A compound represented by formula (I) and its stereoisomers, deuterated substances, solvates, or pharmaceutically acceptable salts or cocrystals, in, Ar1 is selected from pyridyl, pyridazinyl, phenyl, 5-membered heteroaryl, 8-10-membered bicyclic carbocyclic group, 8-10-membered bicyclic heterocyclic group, and the Ar1 is optionally substituted by 1-3 selected from R 1a Substituents are substituted; R 1a Each independently selected from halogen, hydroxyl, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, hydroxyl C 1-6 Alkyl, C 3-8 Cycloalkyl, 4-8 membered heterocycloalkyl, -OC 3-8 Cycloalkyl, -O-(4-8 membered heterocycloalkyl), carboxyl, 5 membered heteroaryl, wherein the heteroaryl is optionally substituted by 1-3 halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, Hydroxyl C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, C 3-6 Cycloalkyl, -SC 1-6 Alkyl, carboxyl radical substitution; Alternatively, R on adjacent carbon atoms 1a Forming 4-6 membered cycloalkyl, 4-6 membered heterocycloalkyl; Ar2 is selected from pyridyl, phenyl, 5-membered heteroaryl, 7-10-membered bicyclic carbocyclic group, 7-10-membered bicyclic heterocyclic group, 4-6-membered monocyclic heterocycloalkyl, 3-6-membered monocyclic cycloalkyl, wherein Ar2 is optionally replaced by 1-3 selected from R 2a The group substitution; R 2a Each is independently selected from halogen, hydroxy, cyano, =O, amino, methylamino, dimethylamino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, C 3-8 Cycloalkyl, 4-6 membered heterocycloalkyl, -OC 3-8 Cycloalkyl, -O-(4-8 membered heterocycloalkyl), carboxyl, acetyl, aminoacetyl, aminopropionyl; L1 is selected from C 1-6 Alkylene, -OC 1-6 Alkylene, C 2-6 The alkenyl group is absent, and 0-2 methylene groups in the alkylene group are optionally replaced by C=O, NH, N(CH3) or O; Ar3 is selected from the following groups: (i) pyridyl, piperidyl, azacyclohexenyl, wherein the pyridyl, piperidyl, azacyclohexenyl is further substituted by 1-2 groups selected from R3, and optionally substituted by 1-2 groups selected from halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, Hydroxyl C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, C 3-6 Cycloalkyl, -SC 1-6 Alkyl, carboxyl radical substitution; (ii) 5-membered heteroaryl, pyrimidinyl, pyrazinyl, pyridazinyl, piperazinyl, 4-5-membered heterocycloalkyl or 6-10-membered bicyclic heterocycloalkyl, wherein the 5-membered heteroaryl, pyrimidinyl, pyrazinyl, pyridazinyl, piperazinyl or heterocycloalkyl is further substituted by 1-3 groups selected from R6; R3 is selected from the following groups: (1) a 4-6 membered monocyclic heterocycloalkyl group, wherein the 4-6 membered monocyclic heterocycloalkyl group is further substituted by 1-3 groups selected from R 3b The group substitution; (2) 8-10 membered heterocycloalkyl, 7-11 membered spiro heterocycloalkyl, 5-8 membered bridged heterocycloalkyl, wherein the heterocycloalkyl, spiro heterocycloalkyl, bridged heterocycloalkyl are optionally further substituted by 1-3 groups selected from halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, -C(O)C 1-4 Alkyl radical substitution; (3) 8-10 membered paracycloalkyl, 7-11 membered spirocycloalkyl, 5-8 membered bridged cycloalkyl; the paracycloalkyl, spirocycloalkyl, bridged cycloalkyl may be further substituted by 1-3 groups selected from halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy group substitution; (4)-O-(CH2) m -(4-6 membered monocyclic heterocycloalkyl), -O-(CH2) m -(4-6 membered monocyclic cycloalkyl), -O-(CH2) m -(5-6 membered heteroaryl), -O-(CH2) m -phenyl, the 4-6 membered monocyclic heterocycloalkyl, 4-6 membered monocyclic cycloalkyl, 5-6 membered heteroaryl, phenyl further substituted by 1-3 selected from R 3b The group substitution; (5)-C 1-3 Alkylene-(4-6 membered monocyclic heterocycloalkyl), -C 0-3 Alkylene-(4-6 membered monocyclic cycloalkyl), -C 0-3 Alkylene-(5-6 membered heteroaryl), -C 0-3 Alkylenephenyl, further substituted by 1 to 3 selected from R 3b The group substitution; (6)C 2-6 Alkynyl, halogen, N3, the alkynyl is optionally further substituted by 1-2 selected from R 3b The group substitution; (7)-C(O)-NR aa R4, -NR aa -C(O)R4, -C(O)-C 0-3 Alkylene -R4, -NR aa R4, -NR aa -C(O)C 1-3 Alkyl, -C(O)-N(R aa )2; R4 and R6 are each independently selected from a 3-15 membered carbocyclic ring or a 4-15 membered heterocyclic ring, wherein the carbocyclic ring or heterocyclic ring is optionally further substituted by 1-5 members selected from R 3b The group substitution; R 3b Selected from halogen, =O, Hydroxyl, cyano, amino, methylamino, dimethylamino, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, -(CH2) m -C 3-6 Cycloalkyl, -(CH2) m -(4-10 membered heterocycloalkyl), aryl, 5-10 membered heteroaryl, benzo(5-6 membered cycloalkyl), benzo(5-6 membered heterocycloalkyl), 5-6 membered heteroaryl and 5-6 membered cycloalkyl, -OC 3-8 Cycloalkyl, -O-(4-8 membered heterocycloalkyl), carboxyl, -C(O)-(CH2) m -C 1-6 Alkyl, -C(O)-(CH2) m -Deuterated C 1-6 Alkyl, -C(O)-(CH2) m -C 3-8 Cycloalkyl, -C(O)-(CH2) m -(4-6 membered heterocycloalkyl), -C(O)-(CH2) m -(5-6 membered heteroaryl), -NH-C(O)-(CH2) m -C 1-6 Alkyl, -NH-C(O)-(CH2) m -C 3-8 Cycloalkyl, -S(O)2-C 1-6 Alkyl, -S(O)-C 1-6 Alkyl or -NH-C(O)-(CH2) m -(5-6 membered heteroaryl), wherein the cycloalkyl, heterocycloalkyl, aryl, heteroaryl may be further substituted by 1-3 members selected from R 3aa The group substitution; R 3aa Selected from halogen, hydroxyl, cyano, =O, SF5, amino, methylamino, dimethylamino, -NH-C 3-6 Cycloalkyl, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-6 Alkyl, deuterated C 1-6 Alkoxy, acetyl, -NR aa C(O)-C 1-6 Alkyl, -NR aa C(O)-OC 1-6 Alkyl, -NR aa C(O)-C 3-6 Cycloalkyl, -NR aa C(O)-(3-6 membered heterocycloalkyl), -NR aa C(O)-(5-6 membered heteroaryl), -C(O)NR aa -C 3-6 Cycloalkyl, -C(O)-C 3-6 Cycloalkyl, -C(O)-(4-6 membered heterocycloalkyl), 4-6 membered heterocycloalkyl, 5-6 membered heteroaryl, The alkyl, cycloalkyl, heterocycloalkyl, and heteroaryl groups are optionally further substituted with 1 to 3 groups selected from deuterium, halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, acetyl, =O group substitution; Each R aa Each independently selected from H, C 1-6 Alkyl, halogenated C 1-6 Alkyl or deuterated C 1-6 alkyl; m is selected from 0, 1, 2, 3 or 4; The heteroaryl and heterocycloalkyl groups contain 1 to 5 heteroatoms selected from N, O, S, S(O), S(O)2, P, and Si; The condition is, a) when R3 is selected from halogen, L1 is not -O-CH2-; b) R3 is not selected from oxetane, -CH2-oxetane, -O-oxetane; c) When L1 is absent and Ar3 is pyridyl or pyrazolyl, R3 and R6 are not phenyl.

2. The compound of formula (I) according to claim 1, and its stereoisomers, deuterated substances, solvates, or pharmaceutically acceptable salts or cocrystals, wherein Ar1 is selected from pyridyl, pyridazinyl, and said Ar1 is optionally substituted by 1-3 groups selected from halogen, hydroxyl, cyano, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-6 Alkoxy, deuterated C 1-2 Alkyl, deuterated C 1-2 Alkoxy, hydroxyl C 1-2 Alkyl, C 3-4 Cycloalkyl, -OC 3-4 The heteroaryl group is optionally substituted by 1-3 halogen, hydroxyl, cyano, amino, C 1-2 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, Hydroxyl C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkyl, deuterated C 1-2 Alkoxy, C 3-4 Cycloalkyl, -SC 1-2 Alkyl, carboxyl radical substitution; Ar2 is selected from pyridyl, phenyl, and said Ar2 is optionally substituted by 1-3 groups selected from halogen, hydroxyl, cyano, amino, C 1-2 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkyl, deuterated C 1-2 Alkoxy, cyclopropyl, oxetanyl, azetidinyl, -O-cyclopropyl, carboxyl, acetyl, aminoacetyl, aminopropanoyl group substitution; L1 is selected from -O-, -N(CH3)-*, -OCH2-*, -OCH2CH2-*, -OCH2-C(O)-*, -CH=CH-* or does not exist, * represents the connection site between L1 and Ar3; Ar3 is selected from the following groups: (i) pyridyl, piperidyl or azacyclohexenyl, wherein the pyridyl, piperidyl or azacyclohexenyl is further substituted by 1-2 groups selected from R3, and optionally substituted by 1-2 groups selected from halogen, hydroxyl, cyano, amino, C 1-2 Alkyl, hydroxyl C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkyl, deuterated C 1-2 Alkoxy, C 3-4 radical substitution of cycloalkyl groups; (ii) 5-membered heteroaryl, pyrimidinyl, pyrazinyl, pyridazinyl, piperazinyl, 4-5-membered heterocycloalkyl or 6-10-membered bicyclic heterocycloalkyl, wherein the 5-membered heteroaryl, pyrimidinyl, pyrazinyl, pyridazinyl, piperazinyl or heterocycloalkyl is further substituted by 1-3 groups selected from R6; R3 is selected from the following groups: (1) a 4-6 membered monocyclic heterocycloalkyl group, wherein the 4-6 membered monocyclic heterocycloalkyl group is further substituted by 1-3 groups selected from R 3b The group substitution; (2) 8-10 membered heterocycloalkyl, 7-11 membered spiro heterocycloalkyl, 5-8 membered bridged heterocycloalkyl, wherein the heterocycloalkyl, spiro heterocycloalkyl, bridged heterocycloalkyl are optionally further substituted by 1-3 groups selected from halogen, hydroxyl, cyano, amino, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkyl, deuterated C 1-2 Alkoxy, -C(O)C 1-2 Alkyl radical substitution; (3) 8-10 membered paracycloalkyl, 7-11 membered spirocycloalkyl, 5-8 membered bridged cycloalkyl, wherein the paracycloalkyl, spirocycloalkyl, bridged cycloalkyl are optionally further substituted by 1-3 groups selected from halogen, hydroxyl, cyano, amino, C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkyl, deuterated C 1-2 Alkoxy group substitution; (4)-O-(CH2) m -(4-6 membered monocyclic heterocycloalkyl), -O-(CH2) m -(4-6 membered monocyclic cycloalkyl), -O-(CH2) m -(5-6 membered heteroaryl), -O-(CH2) m -(phenyl), the 4-6 membered monocyclic heterocycloalkyl, 4-6 membered monocyclic cycloalkyl, 5-6 membered heteroaryl, phenyl further substituted by 1-3 selected from R 3b The group substitution; (5)-C 1-3 Alkylene-(4-6 membered monocyclic heterocycloalkyl), -C 0-3 Alkylene-(4-6 membered monocyclic cycloalkyl), -C 0-3 Alkylene-(5-6 membered heteroaryl), -C 0-3 Alkylene-phenyl, further substituted by 1-3 selected from R 3b The group substitution; (6)C 2-4 Alkynyl, F, Cl, N3, the alkynyl group is optionally further substituted by 1-2 selected from R 3b The group substitution; (7)-C(O)-NR aa R4, -NR aa -C(O)R4, -C(O)-C 0-3 Alkylene -R4, -NR aa R4, -NR aa -C(O)C 1-3 Alkyl, -C(O)-N(R aa )2; R4 is selected from 5-6 membered heteroaryl, 4-6 membered monocyclic heterocycloalkyl, 3-6 membered monocyclic cycloalkyl, 8-10 membered cycloheterocycloalkyl, 7-11 membered spiro heterocycloalkyl, 5-8 membered bridged heterocycloalkyl, 8-10 membered cycloheterocycloalkyl, 7-11 membered spiro heterocycloalkyl, 5-8 membered bridged heterocycloalkyl, 8-10 membered cycloheterocycloalkyl, 7-11 membered spirocycloalkyl, 5-8 membered bridged heterocycloalkyl, the 5-6 membered heteroaryl, 4-6 membered monocyclic heterocycloalkyl, 3-6 membered monocyclic cycloalkyl, 8-10 membered cycloheterocycloalkyl, 7-11 membered spiro heterocycloalkyl, 5-8 membered bridged heterocycloalkyl, 8-10 membered cycloheterocycloalkyl, 7-11 membered spirocycloalkyl, 5-8 membered bridged heterocycloalkyl, 8-10 membered cycloheterocycloalkyl, 7-11 membered spirocycloalkyl, 5-8 membered bridged cycloalkyl 3b The group substitution; R6 is selected from 3-6 membered cycloalkyl, 4-6 membered heterocycloalkyl, 8-10 membered heterocycloalkyl, 7-11 membered spiro heterocycloalkyl, 5-8 membered bridged heterocycloalkyl, 8-10 membered heterocycloalkyl, 7-11 membered spiro heterocycloalkyl, 5-8 membered bridged heterocycloalkyl or 5-10 membered heteroaryl, wherein the 3-6 membered cycloalkyl, 4-6 membered heterocycloalkyl, 8-10 membered heterocycloalkyl, 7-11 membered spiro heterocycloalkyl, 5-8 membered bridged heterocycloalkyl, 8-10 membered heterocycloalkyl, 7-11 membered spiro heterocycloalkyl, 5-8 membered bridged heterocycloalkyl, 8-10 membered heterocycloalkyl, 7-11 membered spiro heterocycloalkyl, 5-8 membered bridged heterocycloalkyl, heteroaryl is optionally further substituted by 1-5 members selected from R 3b The group substitution; R 3b Selected from halogen, =O, Hydroxyl, cyano, amino, methylamino, dimethylamino, C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkyl, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkyl, deuterated C 1-4 Alkoxy, -(CH2) m -C 3-6 Cycloalkyl, -(CH2) m -(4-9 membered heterocycloalkyl), phenyl, 5-10 membered heteroaryl, benzo(5-6 membered cycloalkyl), benzo(5-6 membered heterocycloalkyl), 5-6 membered heteroaryl and 5-6 membered cycloalkyl, -OC 3-6 Cycloalkyl, -O-(4-6 membered heterocycloalkyl), -C(O)-(CH2) m -C 1-4 Alkyl, -C(O)-(CH2) m -C 3-6 Cycloalkyl, -C(O)-(CH2) m -(4-6 membered heterocycloalkyl), -C(O)-(CH2) m -(5-6 membered heteroaryl), -NH-C(O)-(CH2) m -C 1-4 Alkyl, -NH-C(O)-(CH2) m -C 3-6 Cycloalkyl, -S(O)2-C 1-2 Alkyl or -NH-C(O)-(CH2) m -(5-6 membered heteroaryl), wherein the cycloalkyl, heterocycloalkyl, phenyl, heteroaryl may be further substituted by 1-3 members selected from R 3aa The group substitution; R 3aa Selected from halogen, hydroxyl, cyano, =O, SF5, amino, methylamino, dimethylamino, -NH-C 3-6 Cycloalkyl, C 1-6 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkyl, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkyl, deuterated C 1-4 Alkoxy, acetyl, -NR aa C(O)-C 1-4 Alkyl, -NR aa C(O)-OC 1-4 Alkyl, -NR aa C(O)-C 3-6 Cycloalkyl, -NR aa C(O)-(3-6 membered heterocycloalkyl), -NR aa C(O)-(5-6 membered heteroaryl), -C(O)NR aa -C 3-6 Cycloalkyl, -C(O)-C 3-6 Cycloalkyl, -C(O)-(4-6 membered heterocycloalkyl), 4-6 membered heterocycloalkyl, 5-6 membered heteroaryl, The alkyl, cycloalkyl, heterocycloalkyl, and heteroaryl groups are optionally further substituted with 1 to 3 groups selected from deuterium, halogen, hydroxyl, cyano, amino, C 1-2 Alkyl, alkoxy, halogenated C 1-2 Alkyl, halogenated C 1-2 Alkoxy, acetyl, =O group substitution; R aa Selected from H, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 alkyl; m is selected from 0, 1, and 2.

3. The compound of formula (I) according to claim 1, and its stereoisomers, deuterated forms, solvates, or pharmaceutically acceptable salts or cocrystals, having the structures of formula (II), (III), (II-a), (II-b), (III-a), (III-b), (IV-a), (IV-b), (Va), (Vb), (VI-a), (VI-b), (VII-a), (VII-b), (VIII), (VIII-a), (VIII-b), (VIII-c), in, q1, q2, q3, q4 are each independently selected from 0 or 1; X1 is selected from CH or N; Each R 1a Each is independently selected from F, Cl, hydroxy, cyano, methyl, ethyl, isopropyl, methoxy, ethoxy, isopropyloxy, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH2F, -CHFCHF2, -CHFCF3, -CF2CH2F, -CF2CHF2, -CF2CF3, -OCHF2, -OCH2F, -OCF3, -OCH2CH2F, -OCH2CHF2, -OCH2CF3, -OCHFCH2F, -OCHFCHF2, -OCHFCF3, -OCF2CH2F, -OCF2CHF2, -OCF2CF3, -CH2D, -CHD2, -CD3, -CH2CH2D, -CH2CHD2, - CH2CD3, -CHDCH2D, -CHDCHD2, -CHDCD3, -CD2CH2D, -CD2CHD2, -CD2CD3, -OCHD2, -OCH2D, -OCD3, -OCH2CH2D, -OCH2CHD2, -OCH2CD3, -OCHDCH2D, -OCHDCHD2, -OCHDCD3, -OCD2CH2D, -OCD2CHD2, -OCD2CD3, cyclopropyl, cyclobutyl, cyclopentyl, 4-membered heterocycloalkyl, 5-membered heterocycloalkyl, 6-membered heterocycloalkyl, -O-cyclopropyl, -O-cyclobutyl, -O-cyclopentyl, -O-4-membered heterocycloalkyl, -O-5-membered heterocycloalkyl, -O-6-membered heterocycloalkyl, carboxyl or 5-membered heteroaryl, wherein the heteroaryl is optionally substituted with methyl, ethyl or propyl; Each R 2a Each is independently selected from F, Cl, hydroxy, cyano, amino, methylamino, dimethylamino, methyl, ethyl, isopropyl, vinyl, ethynyl, propenyl, propynyl, methoxy, ethoxy, isopropyloxy, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH2F, -CHFCHF2, -CHFCF3, -CF2CH2F, -CF2CHF2, -CF2CF3, -OCHF2, -OCH2F, -OCF3, -OCH2CH2F, -OCH2CHF2, -OCH2CF3, -OCHFCH2F, -OCHFCHF2, -OCHFCF3, -OCF2CH2F, -OCF2CHF2, -OCF2CF3, -CH2D, -CHD2, -CD3 , -CH2CH2D, -CH2CHD2, -CH2CD3, -CHDCH2D, -CHDCHD2, -CHDCD3, -CD2CH2D, -CD2CHD2, -CD2CD3, -OCHD2, -OCH2D, -OCD3, -OCH2CH2D, -OCH2CHD2, -OCH2CD3, -OCHDCH2D, -OCHDCHD2, -OCHDCD3, -OCD2CH2D, -OCD2CHD2, -OCD2CD3, cyclopropyl, cyclobutyl, cyclopentyl, 4-membered heterocycloalkyl, 5-membered heterocycloalkyl, 6-membered heterocycloalkyl, -O-cyclopropyl, -O-cyclobutyl, -O-cyclopentyl, -O-4-membered heterocycloalkyl, -O-5-membered heterocycloalkyl, -O-6-membered heterocycloalkyl, carboxyl, acetyl, aminoacetyl or aminopropanoyl.

4. The compound of formula (I) according to claim 1, and its stereoisomers, deuterated substances, solvates, or pharmaceutically acceptable salts or cocrystals, wherein Ar3 is selected from the following groups: (i) The Further substituted by 1 group selected from R3, and optionally substituted by 1-2 groups selected from F, Cl, methyl, ethyl; (ii) Imidazolyl, pyrrolyl, pyrimidinyl, pyrazinyl, pyridazinyl, The Imidazole, pyrrole pyrimidinyl, pyrazinyl, pyridazinyl, is further substituted with 1 group selected from R6; R3 is selected from the following groups: (1) (2) Optionally further substituted by 1-2 groups selected from F, Cl, hydroxy, cyano, amino, methyl, ethyl, isopropyl, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH2F, -CHFCHF2, -CHFCF3, -CF2CH2F, -CF2CHF2, -CF2CF3, -CH2D, -CHD2, -CD3, -CH2CH2D, -CH2CHD2, -CH2CD3, -CHDCH2D, -CHDCHD2, -CHDCD3, -CD2CH2D, -CD2CHD2, -CD2CD3, -C(O)CH3; (3) Further selected from R 3b The group substitution; (4) Pyridyl, phenyl, further 1-3 selected from F, Cl, methyl, ethyl, isopropyl, cyclopropyl, cyclobutyl, oxetanyl, -NHC(O)CH3, Group substitution of CN, CHF2, CF3; (5) ethynyl, propynyl, F, Cl, N3, wherein the ethynyl and propynyl groups are optionally further substituted with 1-2 groups selected from amino, methylamino, dimethylamino, The group substitution; (6)-C(O)-NR aa R4、-NR aa -C(O)R4、-C(O)-R4、-NR aa R4、-NR aa -C(O)C 1-3 alkyl、-C(O)-N(R aa )2; Each R4 is independently selected from tetrahydropyran, piperidine, cyclopropyl, cyclobutyl, pyrazole, imidazole, isoxazole, piperazine, wherein the tetrahydropyran, piperidine, cyclopropyl, cyclobutyl, pyrazole, imidazole, isoxazole, piperazine is optionally further substituted by 1-2 groups selected from methyl, ethyl, isopropyl, F, Cl; Each R aa Each is independently selected from H, methyl, -CH2F, -CHF2, -CF3, -CH2D, -CHD2, -CD3; R6 is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, azetidinyl, oxolyl, azopentyl, oxetanyl, azohexyl, morpholinyl, piperazinyl, pyrazolyl, optionally further substituted by 1-2 selected from R 3b The group substitution; R 3b Selected from F, Cl, =O, Hydroxyl, cyano, amino, methylamino, dimethylamino, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH2F, -CHFCHF2, -CHFCF3, -CF2CH2F, -CF2CHF2, -CF2CF3, -OCHF2, -OCH2F, -OCF3, -OCH2CH2F, -OCH2CHF2, -OCH2CF3, -OCHFCH2F, -OCHFCHF2, -OCHFCF3, -OCF2CH2F, -OCF2CHF2, -OCF2CF3, -CH2D, -CHD2, -CD3, -CH2CH2D, -CH2CHD2, -CH2CD3, -CHDCH2D, -CHDCHD2, -CHDCD 3. -CD2CH2D, -CD2CHD2, -CD2CD3, -OCHD2, -OCH2D, -OCD3, -OCH2CH2D, -OCH2CHD2, -OCH2CD3, -OCHDCH2D, -OCHDCHD2, -OCHDCD3, -OCD2CH2D, -OCD2CHD2, -OCD2CD3, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, azetidinyl, oxolanyl, azopentyl, oxacyclohexyl, azetidinyl, -CH2-oxetanyl, -CH2-oxolanyl, -CH2-azetidinyl, -CH2-azacyclopentyl, morpholinyl, piperazinyl, phenyl, pyrrolyl, furanyl, thienyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, triazole, pyridazinyl, pyridinyl, pyrimidinyl, pyrazinyl, benzocyclopentyl, benzocyclohexyl, benzoazepanyl, -C(O)CH3, -C(O)CD3, -C(O)CH2CH3, -C(O)-cyclopropyl, -C(O)-CH2-cyclopropyl, -C(O)-cyclobutyl, -C(O)-CH2-cyclobutyl, -C(O)-cyclopentyl, -C(O)-CH2-cyclopentyl, -C(O)-cyclohexyl, -C(O)-CH2-cyclohexyl, -C(O)-oxacyclopentyl, -C(O )-azetidinyl, -C(O)-oxetanyl, -C(O)-azetidinyl, -C(O)-oxetanyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-azetidinyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-azetidinyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-azetidinyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-azetidinyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-azetidinyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-azetidinyl, -C(O)-CH2-oxetanyl, -C(O)-CH2-azetidinyl, -C -C(O)-pyrazolyl, -C(O)-imidazolyl, -C(O)-pyrrolyl, -C(O)-furanyl, -C(O)-oxazolyl, -C(O)-isoxazolyl, -C(O)-thiazolyl, -NHC(O)CH3, -NHC(O)-cyclopropyl, -NHC(O)-cyclobutyl, -S(O)2CH3, -S(O)CH3 or -NHCO-pyrazolyl, wherein the cyclopropyl, cyclobutyl butyl, cyclopentyl, cyclohexyl, oxetanyl, azetidinyl, oxolanyl, azopentyl, oxetanyl, azohexyl, morpholinyl, piperazinyl, phenyl, pyrrolyl, furanyl, thienyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, triazole, pyridazinyl, pyridyl, pyrimidinyl, pyrazinyl, benzocyclopentyl, benzocyclohexyl, benzoazacyclopentyl, optionally further substituted by 1-3 selected from R 3aa The group substitution; R 3aa Selected from F, Cl, hydroxyl, cyano, =O, SF5, amino, methylamino, dimethylamino, -NH-cyclopropyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH2F, -CHFCHF2, -CHFCF3, -CF2CH2F, -CF2CHF2, -CF2CF3, -OCHF2, -OCH2F, -OCF3, -OCH2CH2F, -OCH2CHF2, -OCH2CF3, -OCHFCH2F, -OCHFCHF2, -OCHFCF3, -OCF2C H2F, -OCF2CHF2, -OCF2CF3, -CH2D, -CHD2, -CD3, -CH2CH2D, -CH2CHD2, -CH2CD3, -CHDCH2D, -CHDCHD2, -CHDCD3, -CD2CH2D, -CD2CHD2, -CD2CD3, -OC HD2, -OCH2D, -OCD3, -OCH2CH2D, -OCH2CHD2, -OCH2CD3, -OCHDCH2D, -OCHDCHD2, -OCHDCD3, -OCD2CH2D, -OCD2CHD2, -OCD2CD3, -NHC(O)CH3, acetyl, -NR aa C(O)-C 1-4 Alkyl, -NR aa C(O)-OC 1-4 Alkyl, -NR aa C(O)-deuterated C 1-4 Alkyl, -NHC(O)-cyclopropyl, -NHC(O)-cyclobutyl, -NHC(O)-oxetanyl, -NHC(O)pyrazolyl, -C(O)NH-cyclobutyl, -C(O)-cyclopropyl, -C(O)-cyclobutyl, -C(O)-cyclopentyl, -C(O)-cyclohexyl, -C(O)-azetyl, -C(O)-azetidinyl, -C(O)-oxetanyl, -C(O)-oxolyl, -C(O)-oxetanyl, azetidinyl, azopentyl, morpholinyl, piperazinyl, phenyl, pyrrolyl, furanyl, thienyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrazinyl, The alkyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, oxacyclopentyl, oxacyclohexyl, azetidinyl, azocyclopentyl, azocyclohexyl, morpholinyl, piperazinyl, phenyl, pyrrolyl, furanyl, thienyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrazinyl, optionally further substituted with 1-3 moieties selected from deuterium, F, Cl, hydroxyl, cyano, amino, methyl, ethyl, methoxy, ethoxy, halo C 1-2 Alkyl, halogenated C 1-2 Alkoxy, acetyl, =O is substituted.

5. The compound according to claim 1, its stereoisomer, deuterated form, solvate, or pharmaceutically acceptable salt or co-crystal, wherein the compound is selected from one of the structures in Table 1.

6. A pharmaceutical composition comprising the compound according to any one of claims 1 to 5, or a stereoisomer, deuterated product, pharmaceutically acceptable salt or cocrystal thereof, and a pharmaceutically acceptable carrier and / or excipient.

7. Use of the compound according to any one of claims 1 to 5, its stereoisomer, deuterated form, solvate, pharmaceutically acceptable salt or cocrystal, or the composition according to claim 6 in the preparation of a medicament for treating Polθ-mediated diseases.

8. The use according to claim 7, wherein The Polθ-mediated disease is liver cancer, breast cancer, ovarian cancer, lung cancer, kidney cancer, prostate cancer, skin cancer, bladder cancer, pancreatic cancer or head and neck cancer.

9. A pharmaceutical composition or pharmaceutical preparation comprising 1-1000 mg of the compound according to any one of claims 1-5 or its stereoisomer, deuterated form, solvate, pharmaceutically acceptable salt or cocrystal and a carrier and / or excipient.

10. A method for treating a disease in a mammal, the method comprising administering to a subject a therapeutically effective amount of a compound according to any one of claims 1 to 5 or a stereoisomer, deuterated form, solvate, pharmaceutically acceptable salt or cocrystal thereof, the therapeutically effective amount preferably being 1 to 1000 mg, and the disease preferably being liver cancer, breast cancer, ovarian cancer, lung cancer, kidney cancer, prostate cancer, skin cancer, bladder cancer, pancreatic cancer or head and neck cancer.

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