Acryloyl compound and use thereof

Abstract

Disclosed are an acryloyl compound and a use thereof. The present invention provides a compound as shown in Formula (I), a stereoisomer thereof, an isotopically labeled compound thereof, a solvate thereof, a prodrug thereof, an N-oxide thereof or a pharmaceutically acceptable salt thereof. The compound of the present invention exhibits good therapeutic effects against cancer.

Description

Acryloyl compounds and uses thereof

[0001] This application claims priority to Chinese Patent Application No. 2024110645783, filed on August 2, 2024, Chinese Patent Application No. 202411199143X, filed on August 28, 2024, Chinese Patent Application No. 2024113307628, filed on September 23, 2024, Chinese Patent Application No. 2024114658231, filed on October 18, 2024, Chinese Patent Application No. 2024117251725, filed on November 27, 2024, Chinese Patent Application No. 2025100167224, filed on January 3, 2025, Chinese Patent Application No. 2025101696032, filed on February 14, 2025, Chinese Patent Application No. 2025105781458, filed on April 30, 2025, and Chinese Patent Application No. 2025110392500, filed on July 25, 2025. This application incorporates the entirety of the above-mentioned Chinese Patent Applications. TECHNICAL FIELD

[0002] The present application specifically relates to acryloyl compounds and uses thereof. BACKGROUND

[0003] Nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor. The protein level of NRF2 is tightly controlled by a specific E3 ligase complex consisting of Kelch-like ECH Associated Protein 1 (KEAP1), Cullin 3 (CUL3), and RING-box protein 1 (RBX1). Under normal conditions, KEAP1 acts as an oxidative sensor, promoting ubiquitination and subsequent degradation of NRF2. However, during oxidative or electrophilic stress, KEAP1 can be inactivated by covalent modification of sensor cysteine residues, allowing NRF2 levels to increase and regulate NRF2-dependent genes. In addition, KEAP1 mutations and NRF2 mutations contribute to the activation of NRF2 in cancer cells, for example, NRF2 activity is associated with poor prognosis in NSCLC. These genetic mutations can lead to the activation of the NRF2 pathway, promoting the cell-protective NRF2 transcriptional program. Even in patients without NRF2 pathway mutations, the NRF2 pathway is frequently activated. Therefore, targeting NRF2 can be an attractive therapeutic approach for tumors with aberrant NRF2 activation. Currently, Vividion Corporation has elucidated a new mechanism of action of a small molecule inhibitor of NRF2. The inhibitor covalently interacts with KEAP1 at the sensor cysteine residue, resulting in increased affinity between KEAP1 and CUL3, leading to increased KEAP1-mediated degradation of NRF2. By targeting the KEAP1-CUL3 interaction and promoting NRF2 degradation, a method for regulating NRF2 levels in NRF2-dependent cancers is provided, paving the way for the development of clinically relevant KEAP1 activators. SUMMARY

[0004] The technical problem to be solved by the present application is that the types of drugs for treating cancer in the prior art are relatively single. To this end, the present application provides a propenoyl compound and uses thereof. The compound of the present application has good therapeutic effect on cancer.

[0005] The present application provides a compound as shown in formula I, a stereoisomer thereof, an isotopically labeled compound thereof, a solvate thereof, a prodrug thereof, a nitroxide thereof or a pharmaceutically acceptable salt thereof,

[0006] wherein,

[0007] G is

[0008] ring G 1 is a 3-20 membered heterocycloalkyl or a partially saturated 3-20 membered heterocyclyl;

[0009] G2 -C(R 1 )2R 2 ; 3 or -C≡CR 2 ;

[0010] each R 1 , R 2 , and R 3 is independently H, D (deuterium), halogen, C 1-6 alkyl, or C 1-1 alkyl substituted with one or more R 1-6 ;

[0011] each R 1-1 is independently D, halogen, 3-10 membered heterocycloalkyl, or 3-10 membered heterocycloalkyl substituted with one or more R 1-1a ;

[0012] each R 1-1a is independently D, halogen, or C 1-6 alkyl;

[0013] R 4 is hydrogen or C 1-6 alkyl;

[0014] L is a single bond, C 1-6 alkylene, or C 1-6 alkylene substituted with C 1-6 alkyl;

[0015] k is 0, 1, 2, 3, or 4;

[0016] each R 5 is independently H, D, halogen, oxo (=0), C 1-6 alkyl, C 1-6 alkylene, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 3-10 membered heterocycloalkyl, C p alkyl substituted with one or more R 1-6 , C p alkylene substituted with one or more R 1-6 , C p alkenyl substituted with one or more R 2-6 , C p alkynyl substituted with one or more R 2-6 , C p cycloalkyl substituted with one or more R 3-10 , or 3-10 membered heterocycloalkyl substituted with one or more R p ;

[0017] or, any two R 5 and the atoms connected thereto form a 3-10 membered heterocyclic ring, a 5-10 membered heteroaromatic ring, a 3-10 membered heterocyclic ring substituted with one or more R 1-2 and the atoms connected thereto form a 3-10 membered heterocyclic ring, a 5-10 membered heteroaromatic ring, a 3-10 membered heterocyclic ring substituted with one or more R 1-3 and the atoms connected thereto form a 3-10 membered heterocyclic ring, a 5-10 membered heteroaromatic ring, a 3-10 membered heterocyclic ring substituted with one or more R

[0018] each R 1-2 and R 1-3 independently is D, amino, halogen, cyano, hydroxyl, oxo(=0), C 1-6 alkyl, C 1-6 alkylene, haloC 1-6 alkyl, -O-C 1-6 alkyl, C 3-6 cycloalkyl, or C 3-8 heteroalkyl; or two R 1-3 and the carbon atoms connected thereto form a saturated 3-6 membered heterocyclic ring or a saturated C 3-6 carbocyclic ring; or any two R 1- 2 and the atoms connected thereto form a 3-10 membered heterocyclic ring, a C 3-6 carbocyclic ring, a 3-10 membered heterocyclic ring substituted with one or more R 1-2a and the atoms connected thereto form a 3-10 membered heterocyclic ring, a C 1-2a carbocyclic ring substituted with one or more R 3-6 carbocyclic ring;

[0019] each R 1-2a independently is D, hydroxyl, cyano, halogen, C 1-6 alkyl, C 1-6 alkylene, -O-C 1-6 alkyl, C 2-6 alkenyl, C 2- alkynyl, C 3-6 cycloalkyl, or C 3-8 heteroalkyl; wherein the C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl is optionally substituted with a group selected from the group consisting of halogen, hydroxyl, cyano, -O-C 1-6 alkyl; the C 1-6 alkylene, C 3-6 cycloalkyl, C 3-8 heteroalkyl is optionally substituted with a group selected from the group consisting of halogen, hydroxyl, cyano, C 1-6 alkyl, -O-C 1-6 alkyl, haloC 1-6 alkyl, -O-haloC 1-6 alkyl;

[0020] Each R p Independent of D, halogen, C 1-6 Alkyl, C 1-6 Alkylene, C 2-6 alkenyl, C 2-6 acetylinyl Hydroxyl group, with one or more R p-1 Replacement C 1-6 Alkyl, with one or more R p-1 Replacement C 1-6 Alkylene, by one or more R p-1 Replacement C 2-6 alkenyl or with one or more R p-1 Replacement C 2-6 alkynyl group;

[0021] Each R p-1 Independent of D, halogen or C 1-6 alkyl;

[0022] Or, any two R p Together with the atoms attached to it, they form 3-10 membered heterocycles or are bounded by one or more R atoms. 1-2 Replaced 3-10 membered heterocycles;

[0023] Or, any two R p-1 Together with the atoms attached to it, they form 3-10 membered heterocycles or are bounded by one or more R atoms. 1-2 Replaced 3-10 membered heterocycles;

[0024] Ring A is a 3-10 membered heterocyclic ring, C 6-10 Aromatic rings, 5-10 quinone heterocyclic aromatic rings or Ring B is C 3-10 Carbon rings, 3-10 membered heterocycles, C 6-10 Aromatic rings or 5-10 heterocyclic aromatic rings;

[0025] Each R a Independently, it can be D, halogen, oxo (=O), cyano, hydroxyl, -C(O)-C 1-6 alkyl, C 1-6 Alkyl, Halogenated C 1-6 Alkyl, -OC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl or 3-6 membered heterocyclic alkyl;

[0026] Or, one of the R a One of the R 5Together with the atoms attached to it, they form partially saturated 3-10 membered heterocycles or are formed by one or more R atoms. 1-2 Substituted saturated 3-10 member heterocycles; and the R 5 Not on the carbon atom marked with an asterisk (*);

[0027] Y represents a single bond or -C(O)-CH=;

[0028] V is 3-10 membered heterocyclic alkyl groups, partially saturated 3-10 membered heterocyclic groups, C 6-10 Aryl, 5-10 membered heteroaryl or partially saturated 3-10 membered heterocyclic and 5-10 membered heteroaryl;

[0029] f1 and f2 are independently 0, 1, 2, 3, 4 or 5;

[0030] Each R g Independently D, amino, Halogen, oxo (=O), cyano, hydroxyl, C 1-6 Alkyl, -OC 1-6 Alkyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 3-8 Heteroalkyl, 5-10-membered heteroaryl, -OC 3-6 Cycloalkyl, -O-3-10 heterocyclic alkyl, -OC 3-8 Heteroalkyl, -O-5-10-membered heteroaryl, with one or more R 1-4 Replacement C 1-6 Alkyl, with one or more R 1-4 Replacement C 3-6 cycloalkyl, with one or more R 1-4 Substituted 3-10 membered heterocyclic alkyl groups, with one or more R 1-4 Replacement C 3-8 Heteroalkyl, by one or more R 1-4 The substituted 5-10 heteroaryl group, -O- is replaced by one or more R 1-4 Replacement C 1-6 Alkyl, -O- with one or more R 1-4 Replacement C 3-6 Cycloalkyl, -O- with one or more R 1-4 Substituted 3-10 membered heterocyclic alkyl groups, -O- with one or more R 1-4 Replacement C 3-8 Heteroalkyl, -O- with one or more R 1-4 Substituted 5-10 heteroaryl, -OC 1-6 alkyl-with one or more R 1-4 Replacement C 1-6 Alkyl, -OC 1-6alkyl- substituted by one or more R 1-4 substituted C 3-6 cycloalkyl, -O-C 1-6 alkyl- substituted by one or more R 1-4 substituted 3-10 membered heterocycloalkyl, -O-C 1-6 alkyl- substituted by one or more R 1-4 substituted C 3-8 heteroalkyl, -O-C 1-6 alkyl- substituted by one or more R 1-4 substituted 5-10 membered heteroaryl, -C(=O)R c ;

[0031] V is optionally substituted by one or more R 6 ;

[0032] each R 6 is independently H, D, halogen, oxo (=O), C 1-6 alkyl, C 1-6 alkylene, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 3-10 membered heterocycloalkyl, C p substituted C 1-6 alkyl, C p substituted C 1-6 alkylene, C p substituted C 2-6 alkenyl, C p substituted C 2-6 alkynyl, C p substituted C 3-10 cycloalkyl or 3-10 membered heterocycloalkyl; p substituted;

[0033] Alternatively, any two R 6 and the atom to which they are attached form a 3-10 membered heterocyclic ring, a 5-10 membered heteroaromatic ring, a 3-10 membered heterocyclic ring substituted by one or more R 1-2 substituted 3-10 membered heterocyclic ring or a 5-10 membered heteroaromatic ring substituted by one or more R 1-3 ;

[0034] R m and R n are independently C 1-6 alkyl;

[0035] R c and R d are independently hydrogen, C 1-6 alkyl, C 3-6cycloalkyl, 3-10 membered heterocycloalkyl, C 3-8 heteroalkyl, substituted C 1-4 alkyl, substituted C 1-6 alkyl, substituted C 1-4 alkyl, or -C(=O)-C 1-6 alkyl; or, R c , R d and the atom to which they are attached together form a 3-10 membered heterocycle or a substituted 3-10 membered heterocycle; 1-4 heterocycle;

[0036] each R 1-4 is independently deuterium (D), NH2, NH(C 1-6 alkyl), N(C 1-6 alkyl)2, hydroxyl, 3-8 membered heterocycloalkyl, C 1-6 alkyl, or substituted 3-8 membered heterocycloalkyl; p heterocycle;

[0037] or, one R a , one R g and the atom to which they are attached together form a partially saturated 3-10 membered heterocycle or a substituted partially saturated 3-10 membered heterocycle; 1-2 heterocycle;

[0038] or, one R 5 and one R g form a C 1-8 alkylene, C 1-8 heteroalkylene, C 2-8 alkenylene, C 2-8 heteroalkenylene, substituted C 1-2 alkylene, substituted C 1-8 alkylene, substituted C 1-2 alkylene, substituted C 1-8 heteroalkylene, substituted C 1- 2 alkylene, substituted C 2-8 alkylene, or substituted C 1-2 alkylene, or substituted C 2-8 heteroalkylene (i.e., one R 5 and one R g form T);

[0039] each heterocycloalkyl group (e.g., 3-10 membered heterocycloalkyl, 3-6 membered heterocycloalkyl, 3-8 membered heterocycloalkyl, 3-20 membered heterocycloalkyl, 5-12 membered heterocycloalkyl, 6 membered heterocycloalkyl, 6 membered heterocycloalkyl and 5 membered heterocycloalkyl, 6 membered heterocycloalkyl and 6 membered heterocycloalkyl), heterocycle (e.g., 3-10 membered heterocycle, saturated 3-6 membered heterocycle, partially saturated 3-10 membered heterocycle), heterocyclyl (e.g., partially saturated 3-10 membered heterocyclyl, partially saturated 3-20 membered heterocyclyl), C 3-8 heteroalkyl, C 1-8 heteroalkylene, and C 2-8 heteroalkenylene, the kind of heteroatom or heteroatomic group in each of the above groups is independently selected from one, two, three, four, or five of N, N(H), N(=0), O, C(=0), S, S(=0), S(=0)2, P, P(=0), and P(=0)2, and the total number of heteroatoms and heteroatomic groups is independently 1, 2, 3, 4, or 5;

[0040] the kind of heteroatom or heteroatomic group in each of the above groups is independently selected from one, two, or three of N, N(=0) ([N + (O) - ]), O, and S, and the total number of heteroatoms and heteroatomic groups is independently 1, 2, 3, or 4;

[0041] and the compound of Formula I satisfies any one of the following conditions:

[0042] condition (1) one of R a , one of R 5 , and the atoms to which they are attached together form a partially saturated 3-10 membered heterocycle or a saturated 3-10 membered heterocycle substituted with one or more R 1-2 ; and the R 5 is not on the carbon atom marked with an asterisk;

[0043] condition (2) one of R a , one of R g , and the atoms to which they are attached together form a partially saturated 3-10 membered heterocycle or a partially saturated 3-10 membered heterocycle substituted with one or more R 1-2 ;

[0044] condition (3) one of R 5 and one of R g are connected to form a C 1-8 alkylene, C 1-8 heteroalkylene, C 2-8 alkenylene, C 2-8 heteroalkenylene, C 1-2 alkyl substituted with one or more R 1-8alkylene, substituted C 1-2 substituted C 1-8 heteroalkylene, substituted C 1- 2 substituted C 2-8 alkenylene, substituted C 1-2 substituted C 2-8 heteroalkenylene.

[0045] In one aspect, the compound of Formula I is a compound of Formula I’:

[0046] G 1 is the carbon atom marked with an asterisk is in the R configuration, the S configuration, or a mixture thereof when it is a chiral carbon atom;

[0047] G 2 -C(R 1 )=CR 2 R 3 or -C≡CR 2 ;

[0048] each R 1 , R 2 , and R 3 is independently H, D (deuterium), halogen, C 1-6 alkyl, or substituted C 1-1 alkyl with one or more R 1-6 ;

[0049] each R 1-1 is independently D, halogen, 3-10 membered heterocycloalkyl, or 3-10 membered heterocycloalkyl substituted with one or more R 1-1a ;

[0050] each R 1-1a is independently D, halogen, or C 1-6 alkyl;

[0051] m and n are independently 0, 1, 2, or 3;

[0052] p1 is 0, 1, 2, or 3;

[0053] p2 is 0, 1, 2, or 3;

[0054] q is 0, 1, 2, or 3;

[0055] X is S(=O)(=NH), CH2, NH, or O;

[0056] X1 is CH2 or NH;

[0057] k is 1, 2, 3, or 4;

[0058] Each R 5 Independently, H, D, halogens, oxo (=O), C 1-6 Alkyl, C 1-6 Alkylene, C 2- 6-olefin, C 2-6 alkynyl group, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, with one or more R p Replacement C 1-6 Alkyl, with one or more R p Replacement C 1-6 Alkylene, by one or more R p Replacement C 2-6 alkenyl, with one or more R p Replacement C 2-6 alkynyl group, with one or more R p Replacement C 3-10 cycloalkyl or with one or more R p Substituted 3-10 membered heterocyclic alkyl groups;

[0059] Each R p Independent of D, halogen, C 1-6 Alkyl, C 1-6 Alkylene, C 2-6 alkenyl, C 2-6 acetylinyl Hydroxyl group, with one or more R p-1 Replacement C 1-6 Alkyl, with one or more R p-1 Replacement C 1-6 Alkylene, by one or more R p-1 Replacement C 2-6 alkenyl or with one or more R p-1 Replacement C 2-6 alkynyl group;

[0060] Each R p-1 Independent of D, halogen or C 1-6 alkyl;

[0061] Ring A is a 3-10 membered heterocyclic ring, C 6-10 Aromatic rings, 5-10 quinone heterocyclic aromatic rings or Ring B is C 3-10 Carbon rings, 3-10 membered heterocycles, C 6-10 Aromatic rings or 5-10 heterocyclic aromatic rings;

[0062] Each R a Independently, it can be D, halogen, oxo (=O), cyano, hydroxyl, -C(O)-C 1-6 alkyl, C 1-6 Alkyl, Halogenated C 1-6 Alkyl, -OC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl or 3-6 membered heterocyclic alkyl;

[0063] V is 3-10 membered heterocyclic alkyl groups, partially saturated 3-10 membered heterocyclic groups, C 6-10 Aryl, 5-10 membered heteroaryl or partially saturated 3-10 membered heterocyclic and 5-10 membered heteroaryl;

[0064] f1 is 0, 1, 2, 3, 4 or 5;

[0065] f2 is 1, 2, 3, 4 or 5;

[0066] Each R g Independently D, amino, Halogen, oxo (=O), cyano, hydroxyl, C 1-6 Alkyl, -OC 1-6 Alkyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 3-8 Heteroalkyl, 5-10-membered heteroaryl, -OC 3-6 Cycloalkyl, -O-3-10 heterocyclic alkyl, -OC 3-8 Heteroalkyl, -O-5-10-membered heteroaryl, with one or more R 1-4 Replacement C 1-6 Alkyl, with one or more R 1-4 Replacement C 3-6 cycloalkyl, with one or more R 1-4 Substituted 3-10 membered heterocyclic alkyl groups, with one or more R 1-4 Replacement C 3-8 Heteroalkyl, by one or more R 1-4 The substituted 5-10 heteroaryl group, -O- is replaced by one or more R 1-4 Replacement C 1-6 Alkyl, -O- with one or more R 1-4 Replacement C 3-6 Cycloalkyl, -O- with one or more R 1-4 Substituted 3-10 membered heterocyclic alkyl groups, -O- with one or more R 1-4 Replacement C 3-8 Heteroalkyl, -O- with one or more R 1-4 Substituted 5-10 heteroaryl, -OC 1-6 alkyl-with one or more R 1-4 Replacement C 1-6Alkyl, -OC 1-6 alkyl-with one or more R 1-4 Replacement C 3-6 cycloalkyl, -OC 1-6 alkyl-with one or more R 1-4 Substituted 3-10 membered heterocyclic alkyl groups, -OC 1-6 alkyl-with one or more R 1-4 Replacement C 3-8 Heteroalkyl, -OC 1-6 alkyl-with one or more R 1-4 Substituted 5-10 heteroaryl groups, -C(=O)R c ;

[0067] R m and R n Independently for C 1-6 alkyl;

[0068] R c and R d Independently hydrogen, C 1-6 Alkyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 3-8 Heteroalkyl, by one or more R 1-4 Replacement C 1-6 Alkyl, with one or more R 1-4 Substituted 3-10 membered heterocyclic alkyl groups or -C(=O)-C 1-6 Alkyl; or, R c R d Together with the atoms attached to it, they form 3-10 membered heterocycles or are bounded by one or more R atoms. 1-4 Replaced 3-10 membered heterocycles;

[0069] Each R 1-4 Independently, deuterium (D), NH2, and NH (C) 1-6 Alkyl), N(C) 1-6 Alkyl group, 2-hydroxyl group, 3-8 membered heterocyclic alkyl group, C 1-6 Alkyl or with one or more R p Substituted 3-8 membered heterocyclic alkyl groups;

[0070] One of the R 5 And one of the R g Connection forms C 1-8 Alkylene, C 1-8 Heteroalkyl, C 2-8 imidene group, C 2-8 Hesperyl, with one or more R 1-2 Replacement C 1-8 Alkylene, by one or more R 1-2 Replacement C1-8 Heteroalkyl, by one or more R 1-2 Replacement C 2-8 alkenyl groups or those with one or more R groups 1-2 Replacement C 2-8 Hesperyl;

[0071] Each R 1-2 Independently D, amino, Halogen, cyano, hydroxyl, oxo (=O), C 1-6 Alkyl, C 1-6 Alkylene, Halogenated C 1-6 Alkyl, -OC 1-6 Alkyl, C 3-6 cycloalkyl or C 3-8 Heteroalkyl; or any two Rs 1-2 Together with the atoms attached to it, they form 3-10 membered heterocycles, C 3-6 Carbon ring, with one or more R 1-2a The substituted 3-10-membered heterocycle or is replaced by one or more R 1-2a Replacement C 3-6 Carbon rings;

[0072] Each R 1-2a Independently D, hydroxyl, cyano, halogen, C 1-6 Alkyl, C 1-6 Alkylene, -OC 1-6 Alkyl, C 2-6 alkenyl, C 2- 6-acetylenic, C 3-6 cycloalkyl or C 3-8 Heteroalkyl; wherein, the C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 The alkynyl group may optionally be replaced by a group selected from the group consisting of: halogen, hydroxyl, cyano, -OC. 1-6 Alkyl; the C 1-6 Alkylene, C 3-6 cycloalkyl, C 3-8 The heteroalkyl group is optionally substituted with a group selected from the group consisting of: halogen, hydroxyl, cyano, C. 1-6 Alkyl, -OC 1-6 Alkyl, Halogenated C 1-6 Alkyl, -O-halogenated C 1-6 alkyl;

[0073] The various C 3-8 Heteroalkyl, 3-10 membered heterocyclic alkyl, 3-10 membered heterocycle, saturated 3-6 membered heterocycle, 3-6 membered heterocyclic alkyl, partially saturated 3-10 membered heterocyclic group, 3-8 membered heterocyclic alkyl, C 1-8 Heteroalkyl and C2-8 The heteroatoms or heterogroups in the hesene group are independently selected from one, two, three, four, or five of N, N(H), N(=O), O, C(=O), S, S(=O), S(=O)2, P, P(=O), and P(=O)2, and the total number of heteroatoms and heterogroups is independently 1, 2, 3, 4, or 5.

[0074] The types of heteroatoms or heterogroups in the 5-10 membered heteroaryl group and the 5-10 membered heteroaryl ring are independently selected from N, N(=O)([N + (O) - The total number of heteroatoms and heterogroups is 1, 2, 3 or 4, consisting of one, two or three of O and S.

[0075] This invention provides a compound of Formula I, its stereoisomers, its isotopically labeled compounds, its solvates, its prodrugs, its nitrides, or pharmaceutically acceptable salts thereof.

[0076] Where G is When a carbon atom is marked with an asterisk (*), it is a chiral carbon atom and is in the R configuration, S configuration, or a mixture thereof.

[0077] Each R 1 R 2 and R 3 Independently, H, D (deuterium), halogens, and C 1-6 Alkyl or with one or more R 1-1 Replacement C 1-6 alkyl;

[0078] Each R 1-1 Independently for D, halogen, 3-10 membered heterocyclic alkyl groups or those containing one or more R groups 1-1a Substituted 3-10 membered heterocyclic alkyl groups,

[0079] Each R 1-1a Independent of D, halogen or C 1-6 alkyl;

[0080] R 4 It is hydrogen or C 1-6 alkyl;

[0081] L represents a single bond, C 1-6 Alkylene or C 1-6 Alkyl-substituted C 1-6 Alkylene;

[0082] m and n are independently 0, 1, 2 or 3;

[0083] p1 is 0, 1, 2, or 3;

[0084] p2 is 0, 1, 2, or 3;

[0085] q can be 0, 1, 2, or 3;

[0086] X is S (=O) (=NH), CH2, NH or O;

[0087] X1 is CH2 or NH;

[0088] k can be 0, 1, 2, 3 or 4;

[0089] Each R 5 Independently, H, D, halogens, oxo (=O), C 1-6 Alkyl, C 1-6 Alkylene, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, with one or more R p Replacement C 1-6 Alkyl, with one or more R p Replacement C 1-6 Alkylene, by one or more R p Replacement C 2-6 alkenyl, with one or more R p Replacement C 2-6 alkynyl group, with one or more R p Replacement C 3-10 cycloalkyl or with one or more R p Substituted 3-10 membered heterocyclic alkyl groups;

[0090] Or, any two R 5 Together with the atoms attached to it, they form 3-10 membered heterocycles, 5-10 membered heteroaromatic rings, and are bonded by one or more R atoms. 1-2 The substituted 3-10-membered heterocycle or is replaced by one or more R 1-3 Replaced 5-10 heterocyclic aromatic rings;

[0091] When G is At that time, each R 5 Can be located at the same time Above, or simultaneously located Above, or part of R 5 lie in Above, the rest of R 5 lie in superior;

[0092] Each R 1-2 and R 1-3 Independently D, amino, Halogen, cyano, hydroxyl, oxo (=O), C 1-6 Alkyl, C 1-6 Alkylene, -OC 1-6 Alkyl, C 3-6 cycloalkyl or C 3-8 Heteroalkyl; or two R atoms on the same carbon atom 1- 3 Together with the carbon atom attached to it, it forms a saturated 3-6 membered heterocycle or a saturated C. 3-6 Carbon ring; or any two Rs 1-2 Together with the atoms attached to it, they form 3-10 membered heterocycles, C 3-6 Carbon ring, with one or more R 1-2a The substituted 3-10-membered heterocycle or is replaced by one or more R 1-2a Replacement C 3-6 Carbon rings;

[0093] Each R 1-2a Independently D, hydroxyl, cyano, halogen, C 1-6 Alkyl, C 1-6 Alkylene, -OC 1-6 Alkyl, C 2-6 alkenyl, C 2- 6-acetylenic, C 3-6 cycloalkyl or C 3-8 Heteroalkyl; wherein, the C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 The alkynyl group may optionally be replaced by a group selected from the group consisting of: halogen, hydroxyl, cyano, -OC. 1-6 Alkyl; the C 1-6 Alkylene, C 3-6 cycloalkyl, C 3-8 The heteroalkyl group is optionally substituted with a group selected from the group consisting of: halogen, hydroxyl, cyano, C. 1-6 Alkyl, -OC 1-6 Alkyl, Halogenated C 1-6 Alkyl, -O-halogenated C 1-6 alkyl;

[0094] Each R p Independent of D, halogen, C 1-6 Alkyl, C 1-6 Alkylene, C 2-6 alkenyl, C 2-6 acetylinyl Hydroxyl group, with one or more R p-1 Replacement C 1-6 Alkyl, with one or more R p-1 Replacement C 1-6Alkylene, by one or more R p-1 Replacement C 2-6 alkenyl or with one or more R p-1 Replacement C 2-6 alkynyl group;

[0095] Each R p-1 Independent of D, halogen or C 1-6 alkyl;

[0096] Or, any two R p Together with the atoms attached to it, they form 3-10 membered heterocycles or are bounded by one or more R atoms. 1-2 Replaced 3-10 membered heterocycles;

[0097] Or, any two R p-1 Together with the atoms attached to it, they form 3-10 membered heterocycles or are bounded by one or more R atoms. 1-2 Replaced 3-10 membered heterocycles;

[0098] Ring A is a 3-10 membered heterocyclic ring, C 6-10 Aromatic rings, 5-10 quinone heterocyclic aromatic rings or Ring B is C 3-10 Carbon rings, 3-10 membered heterocycles, C 6-10 Aromatic rings or 5-10 heterocyclic aromatic rings;

[0099] Each R a Independently, it can be D, halogen, oxo (=O), cyano, hydroxyl, -C(O)-C 1-6 alkyl, C 1-6 Alkyl, Halogenated C 1-6 Alkyl, -OC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl or 3-6 membered heterocyclic alkyl;

[0100] Or, one of the R a One of the R 5 Together with the atoms attached to it, they form partially saturated 3-10 membered heterocycles or are formed by one or more R atoms. 1-2 Substituted saturated 3-10 member heterocycles; and the R 5 Not on the carbon atom marked with an asterisk (*);

[0101] Y represents a single bond or -C(O)-CH=;

[0102] V is 3-10 membered heterocyclic alkyl groups, partially saturated 3-10 membered heterocyclic groups, C 6-10Aryl, 5-10 membered heteroaryl or partially saturated 3-10 membered heterocyclic and 5-10 membered heteroaryl;

[0103] f1 and f2 are independently 0, 1, 2, 3, 4 or 5;

[0104] Each R g Independently D, amino, Halogen, oxo (=O), cyano, hydroxyl, C 1-6 Alkyl, -OC 1-6 Alkyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 3-8 Heteroalkyl, 5-10-membered heteroaryl, -OC 3-6 Cycloalkyl, -O-3-10 heterocyclic alkyl, -OC 3-8 Heteroalkyl, -O-5-10-membered heteroaryl, with one or more R 1-4 Replacement C 1-6 Alkyl, with one or more R 1-4 Replacement C 3-6 cycloalkyl, with one or more R 1-4 Substituted 3-10 membered heterocyclic alkyl groups, with one or more R 1-4 Replacement C 3-8 Heteroalkyl, by one or more R 1-4 The substituted 5-10 heteroaryl group, -O- is replaced by one or more R 1-4 Replacement C 1-6 Alkyl, -O- with one or more R 1-4 Replacement C 3-6 Cycloalkyl, -O- with one or more R 1-4 Substituted 3-10 membered heterocyclic alkyl groups, -O- with one or more R 1-4 Replacement C 3-8 Heteroalkyl, -O- with one or more R 1-4 Substituted 5-10 heteroaryl, -OC 1-6 alkyl-with one or more R 1-4 Replacement C 1-6 Alkyl, -OC 1-6 alkyl-with one or more R 1-4 Replacement C 3-6 cycloalkyl, -OC 1-6 alkyl-with one or more R 1-4 Substituted 3-10 membered heterocyclic alkyl groups, -OC 1-6 alkyl-with one or more R 1-4 Replacement C 3-8 Heteroalkyl, -OC 1-6 alkyl-with one or more R 1-4Substituted 5-10 heteroaryl groups, -C(=O)R c ;

[0105] V is optionally controlled by one or more R 6 replace;

[0106] Each R 6 Independently, H, D, halogens, oxo (=O), C 1-6 Alkyl, C 1-6 Alkylene, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, with one or more R p Replacement C 1-6 Alkyl, with one or more R p Replacement C 1-6 Alkylene, by one or more R p Replacement C 2-6 alkenyl, with one or more R p Replacement C 2-6 alkynyl group, with one or more R p Replacement C 3-10 cycloalkyl or with one or more R p Substituted 3-10 membered heterocyclic alkyl groups;

[0107] Or, any two R 6 Together with the atoms attached to it, they form 3-10 membered heterocycles, 5-10 membered heteroaromatic rings, and are bonded by one or more R atoms. 1-2 The substituted 3-10-membered heterocycle or is replaced by one or more R 1-3 Replaced 5-10 heterocyclic aromatic rings;

[0108] R m and R n Independently for C 1-6 alkyl;

[0109] R c and R d Independently hydrogen, C 1-6 Alkyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 3-8 Heteroalkyl, by one or more R 1-4 Replacement C 1-6 Alkyl, with one or more R 1-4 Substituted 3-10 membered heterocyclic alkyl groups or -C(=O)-C 1-6 Alkyl; or, R c R d Together with the atoms attached to it, they form 3-10 membered heterocycles or are bounded by one or more R atoms. 1-4Replaced 3-10 membered heterocycles;

[0110] Each R 1-4 Independently, deuterium (D), NH2, and NH (C) 1-6 Alkyl), N(C) 1-6 Alkyl group, 2-hydroxyl group, 3-8 membered heterocyclic alkyl group, C 1-6 Alkyl or with one or more R p Substituted 3-8 membered heterocyclic alkyl groups;

[0111] Or, one of the R a One of the R g Together with the atoms attached to it, they form partially saturated 3-10 membered heterocycles or are formed by one or more R atoms. 1-2 The partially saturated 3-10 membered heterocycles are replaced;

[0112] Or, one of the R 5 And one of the R g Connection forms C 1-8 Alkylene, C 1-8 Heteroalkyl, C 2-8 imidene group, C 2-8 Hesperyl, with one or more R 1-2 Replacement C 1-8 Alkylene, by one or more R 1-2 Replacement C 1-8 Heteroalkyl, by one or more R 1- 2 Replacement C 2-8 alkenyl groups or those with one or more R groups 1-2 Replacement C 2-8 Hesperyl;

[0113] The various 3-10 membered heterocyclic alkyl groups, 3-10 membered heterocycles, saturated 3-6 membered heterocycles, 3-6 membered heterocyclic alkyl groups, partially saturated 3-10 membered heterocycles, partially saturated 3-10 membered heterocyclic groups, 3-8 membered heterocyclic alkyl groups, C 1-8 Heteroalkyl and C 2-8 The heteroatoms or heterogroups in the hesene group are independently selected from one, two, three, four, or five of N, N(H), N(=O), O, C(=O), S, S(=O), S(=O)2, P, P(=O), and P(=O)2, and the total number of heteroatoms and heterogroups is independently 1, 2, 3, 4, or 5.

[0114] The types of heteroatoms or heterogroups in the 5-10 membered heteroaryl group and the 5-10 membered heteroaryl ring are independently selected from N, N(=O)([N + (O) -The total number of heteroatoms and heterogroups is 1, 2, 3 or 4, consisting of one, two or three of O and S.

[0115] Each R 5 They can be located on the same atom or on different atoms.

[0116] Each R a They can be located on the same atom or on different atoms.

[0117] Each R g They can be located on the same atom or on different atoms.

[0118] In one embodiment, the compound as shown in Formula I satisfies any of the following conditions:

[0119] Condition (1) Ring A is a 3-10 member heterocyclic ring, a 5 member heteroaromatic ring, or Ring B is C 3-10 Carbon rings, 3-10 membered heterocycles, C 6-10 Aromatic ring or 5-10 membered heteroaromatic ring; the heteroatoms or heterogroups in the 5-membered heteroaromatic ring are selected from N, N(=O)([N + (O) - One, two, or three of O and S, and the total number of heteroatoms and heterogroups is 1, 2, or 3;

[0120] Condition (2) One of R a One of the R 5 Together with the atoms attached to it, they form partially saturated 3-10 membered heterocycles or are formed by one or more R atoms. 1-2 Substituted saturated 3-10 member heterocycles; and the R 5 Not on the carbon atom marked with an asterisk (*);

[0121] Condition (3) One of R a One of the R g Together with the atoms attached to it, they form partially saturated 3-10 membered heterocycles or are formed by one or more R atoms. 1-2 The partially saturated 3-10 membered heterocycles are replaced;

[0122] Condition (4) One of R 5 And one of the R g Connection forms C 1-8 Alkylene, C 1-8 Heteroalkyl, C 2-8 imidene group, C 2-8 Hesperyl, with one or more R 1-2 Replacement C 1-8 Alkylene, by one or more R 1-2 Replacement C1-8 Heteroalkyl, by one or more R 1- 2 Replacement C 2-8 alkenyl groups or those with one or more R groups 1-2 Replacement C 2-8 Hesperyl;

[0123] Condition (5) Any two R 5 Together with the atoms attached to it, they form 3-10 membered heterocycles, 5-10 membered heteroaromatic rings, and are bonded by one or more R atoms. 1-2 The substituted 3-10-membered heterocycle or is replaced by one or more R 1-3 Replaced 5-10 heterocyclic aromatic rings;

[0124] Condition (6) G is

[0125] Condition (7) k is 1, and R 5 Located on X, the R 5 for C 1-6 Alkylene, C 2-6 alkenyl, C 2- 6-acetylinyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, with one or more R p Replacement C 1-6 Alkylene, by one or more R p Replacement C 2-6 alkenyl, with one or more R p Replacement C 2-6 alkynyl group, with one or more R p Replacement C 3-10 cycloalkyl or with one or more R p Substituted 3-10 membered heterocyclic alkyl groups;

[0126] Condition (8) k is 1; and the R 5 Not on X, the R 5 C 1-6 Alkylene, C 2-6 alkenyl, C 2-6 alkynyl group, with one or more R p Replacement C 1-6 Alkylene, by one or more R p Replacement C 2-6 alkenyl or with one or more R p Replacement C 2-6 alkynyl group;

[0127] Condition (9) f1 is 1, R a -C(O)-C 1-6 alkyl, -OC1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl or 3-6 membered heterocyclic alkyl;

[0128] Condition (10) f1 is 2 or 3;

[0129] Condition (11) V is

[0130] Condition (12) Y is -C(O)-CH = ;

[0131] Condition (13) f2 is 1, 2 or 3, and at least one R g for

[0132] This invention provides a compound of Formula I, its stereoisomers, its isotopically labeled compounds, its solvates, its prodrugs, its nitrides, or pharmaceutically acceptable salts thereof.

[0133] Where G is When a carbon atom is marked with an asterisk (*), it is a chiral carbon atom and is in the R configuration, S configuration, or a mixture thereof.

[0134] Each R 1 R 2 and R 3 Independently, H, D (deuterium), halogens, and C 1-6 Alkyl or with one or more R 1-1 Replacement C 1-6 alkyl;

[0135] Each R 1-1 Independently for D, halogen, 3-10 membered heterocyclic alkyl groups or those containing one or more R groups 1-1a Substituted 3-10 membered heterocyclic alkyl groups,

[0136] Each R 1-1a Independent of D, halogen or C 1-6 alkyl;

[0137] R 4 It is hydrogen or C 1-6 alkyl;

[0138] L represents a single bond, C 1-6 Alkylene or C 1-6 Alkyl-substituted C 1-6 Alkylene;

[0139] m and n are independently 0, 1, 2 or 3;

[0140] p1 is 0, 1, 2, or 3;

[0141] p2 is 0, 1, 2, or 3;

[0142] q can be 0, 1, 2, or 3;

[0143] X is S (=O) (=NH), CH2, NH or O;

[0144] X1 is CH2 or NH;

[0145] k can be 0, 1, 2, 3 or 4;

[0146] Each R 5 Independently, H, D, halogens, oxo (=O), C 1-6 Alkyl, C 1-6 Alkylene, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, with one or more R p Replacement C 1-6 Alkyl, with one or more R p Replacement C 1-6 Alkylene, by one or more R p Replacement C 2-6 alkenyl, with one or more R p Replacement C 2-6 alkynyl group, with one or more R p Replacement C 3-10 cycloalkyl or with one or more R p Substituted 3-10 membered heterocyclic alkyl groups;

[0147] Or, any two R 5 Together with the atoms attached to it, they form 3-10 membered heterocycles, 5-10 membered heteroaromatic rings, and are bonded by one or more R atoms. 1-2 The substituted 3-10-membered heterocycle or is replaced by one or more R 1-3 Replaced 5-10 heterocyclic aromatic rings;

[0148] When G is At that time, each R 5 Can be located at the same time Above, or simultaneously located Above, or part of R 5 lie in Above, the rest of R 5 lie in superior;

[0149] Each R 1-2 and R 1-3 Independently D, amino, Halogen, cyano, hydroxyl, oxo (=O), C 1-6 Alkyl, C 1-6 Alkylene, -OC 1-6 Alkyl, C 3-6 cycloalkyl or C 3-8 Heteroalkyl; or two R atoms on the same carbon atom 1- 3 Together with the carbon atom attached to it, it forms a saturated 3-6 membered heterocycle or a saturated C. 3-6 Carbon ring; or any two Rs 1-2 Together with the atoms attached to it, they form 3-10 membered heterocycles, C 3-6 Carbon ring, with one or more R 1-2a The substituted 3-10-membered heterocycle or is replaced by one or more R 1-2a Replacement C 3-6 Carbon rings;

[0150] Each R 1-2a Independently D, hydroxyl, cyano, halogen, C 1-6 Alkyl, C 1-6 Alkylene, -OC 1-6 Alkyl, C 2-6 alkenyl, C 2- 6-acetylenic, C 3-6 cycloalkyl or C 3-8 Heteroalkyl; wherein, the C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 The alkynyl group may optionally be replaced by a group selected from the group consisting of: halogen, hydroxyl, cyano, -OC. 1-6 Alkyl; the C 1-6 Alkylene, C 3-6 cycloalkyl, C 3-8 The heteroalkyl group is optionally substituted with a group selected from the group consisting of: halogen, hydroxyl, cyano, C. 1-6 Alkyl, -OC 1-6 Alkyl, Halogenated C 1-6 Alkyl, -O-halogenated C 1-6 alkyl;

[0151] Each R p Independent of D, halogen, C 1-6 Alkyl, C 1-6 Alkylene, C 2-6 alkenyl, C 2-6 alkynyl group, with one or more R p-1 Replacement C 1-6 Alkyl, with one or more R p-1 Replacement C 1-6 Alkylene, by one or more R p-1 Replacement C2-6 alkenyl or with one or more R p-1 Replacement C 2-6 alkynyl group;

[0152] Each R p-1 Independent of D, halogen or C 1-6 alkyl;

[0153] Or, any two R p Together with the atoms attached to it, they form 3-10 membered heterocycles or are bounded by one or more R atoms. 1-2 Replaced 3-10 membered heterocycles;

[0154] Or, any two R p-1 Together with the atoms attached to it, they form 3-10 membered heterocycles or are bounded by one or more R atoms. 1-2 Replaced 3-10 membered heterocycles;

[0155] Ring A is a 3-10 membered heterocyclic ring, C 6-10 Aromatic rings, 5-10 quinone heterocyclic aromatic rings or Ring B is C 3-10 Carbon rings, 3-10 membered heterocycles, C 6-10 Aromatic rings or 5-10 heterocyclic aromatic rings;

[0156] Each R a Independently, it can be D, halogen, oxo (=O), cyano, hydroxyl, -C(O)-C 1-6 alkyl, C 1-6 Alkyl, -OC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl or 3-6 membered heterocyclic alkyl;

[0157] Or, one of the R a One of the R 5 Together with the atoms attached to it, they form partially saturated 3-10 membered heterocycles or are formed by one or more R atoms. 1-2 Substituted saturated 3-10 member heterocycles; and the R 5 Not on the carbon atom marked with an asterisk (*);

[0158] Y represents a single bond or -C(O)-CH=;

[0159] V is 3-10 membered heterocyclic alkyl groups, partially saturated 3-10 membered heterocyclic groups, C 6-10 Aryl, 5-10 membered heteroaryl or partially saturated 3-10 membered heterocyclic and 5-10 membered heteroaryl;

[0160] f1 and f2 are independently 0, 1, 2 or 3;

[0161] Each R g Independently D, amino, Halogen, oxo (=O), cyano, hydroxyl, C 1-6 Alkyl, -OC 1-6 Alkyl, C 3-6 cycloalkyl, C 3-8 Heteroalkyl, -O- with one or more R 1-4 Substituted 3-10 membered heterocyclic alkyl groups, -O- with one or more R 1-4 Replacement C 3-8 Heteroalkyl;

[0162] V is optionally controlled by one or more R 6 replace;

[0163] Each R 6 Independently, H, D, halogens, oxo (=O), C 1-6 Alkyl, C 1-6 Alkylene, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, with one or more R p Replacement C 1-6 Alkyl, with one or more R p Replacement C 1-6 Alkylene, by one or more R p Replacement C 2-6 alkenyl, with one or more R p Replacement C 2-6 alkynyl group, with one or more R p Replacement C 3-10 cycloalkyl or with one or more R p Substituted 3-10 membered heterocyclic alkyl groups;

[0164] Or, any two R 6 Together with the atoms attached to it, they form 3-10 membered heterocycles, 5-10 membered heteroaromatic rings, and are bonded by one or more R atoms. 1-2 The substituted 3-10-membered heterocycle or is replaced by one or more R 1-3 Replaced 5-10 heterocyclic aromatic rings;

[0165] R m and R n Independently for C 1-6 alkyl;

[0166] R c and R d Independently hydrogen, C 1-6 Alkyl, C 3-6Cycloalkyl, 3-10 membered heterocyclic alkyl, C 3-8 Heteroalkyl or by one or more R 1-4 Replacement C 1-6 alkyl;

[0167] Each R 1-4 Independently hydroxyl or 3-8 membered heterocyclic alkyl;

[0168] Or, one of the R a One of the R g Together with the atoms attached to it, they form partially saturated 3-10 membered heterocycles or are formed by one or more R atoms. 1-2 The partially saturated 3-10 membered heterocycles are replaced;

[0169] Or, one of the R 5 And one of the R g Connection forms C 1-8 Alkylene, C 1-8 Heteroalkyl, C 2-8 imidene group, C 2-8 Hesperyl, with one or more R 1-2 Replacement C 1-8 Alkylene, by one or more R 1-2 Replacement C 1-8 Heteroalkyl, by one or more R 1- 2 Replacement C 2-8 alkenyl groups or those with one or more R groups 1-2 Replacement C 2-8 Hesperyl;

[0170] The various 3-10 membered heterocyclic alkyl groups, 3-10 membered heterocycles, saturated 3-6 membered heterocycles, 3-6 membered heterocyclic alkyl groups, partially saturated 3-10 membered heterocycles, partially saturated 3-10 membered heterocyclic groups, 3-8 membered heterocyclic alkyl groups, C 1-8 Heteroalkyl and C 2-8 The heteroatoms or heterogroups in the hesene group are independently selected from one, two, three, four, or five of N, N(H), N(=O), O, C(=O), S, S(=O), S(=O)2, P, P(=O), and P(=O)2, and the total number of heteroatoms and heterogroups is independently 1, 2, 3, 4, or 5.

[0171] The types of heteroatoms or heterogroups in the 5-10 membered heteroaryl group and the 5-10 membered heteroaryl ring are independently selected from N, N(=O)([N + (O) - The total number of heteroatoms and heterogroups is 1, 2, 3 or 4, consisting of one, two or three of O and S.

[0172] And the compound shown in Formula I satisfies any of the following conditions:

[0173] Condition (1) Ring A is a 3-10 member heterocyclic ring, a 5 member heteroaromatic ring, or Ring B is C 3-10 Carbon rings, 3-10 membered heterocycles, C 6-10 Aromatic ring or 5-10 membered heteroaromatic ring; the heteroatoms or heterogroups in the 5-membered heteroaromatic ring are selected from N, N(=O)([N + (O) - One, two, or three of O and S, and the total number of heteroatoms and heterogroups is 1, 2, or 3;

[0174] Condition (2) One of R a One of the R 5 Together with the atoms attached to it, they form partially saturated 3-10 membered heterocycles or are formed by one or more R atoms. 1-2 Substituted saturated 3-10 member heterocycles; and the R 5 Not on the carbon atom marked with an asterisk (*);

[0175] Condition (3) One of R a One of the R g Together with the atoms attached to it, they form partially saturated 3-10 membered heterocycles or are formed by one or more R atoms. 1-2 The partially saturated 3-10 membered heterocycles are replaced;

[0176] Condition (4) One of R 5 And one of the R g Connection forms C 1-8 Alkylene, C 1-8 Heteroalkyl, C 2-8 imidene group, C 2-8 Hesperyl, with one or more R 1-2 Replacement C 1-8 Alkylene, by one or more R 1-2 Replacement C 1-8 Heteroalkyl, by one or more R 1- 2 Replacement C 2-8 alkenyl groups or those with one or more R groups 1-2 Replacement C 2-8 Hesperyl;

[0177] Condition (5) Any two R 5 Together with the atoms attached to it, they form 3-10 membered heterocycles, 5-10 membered heteroaromatic rings, and are bonded by one or more R atoms. 1-2 The substituted 3-10-membered heterocycle or is replaced by one or more R 1-3 Replaced 5-10 heterocyclic aromatic rings;

[0178] Condition (6) G is

[0179] Condition (7) k is 1, and R 5 Located on X, the R 5 for C 1-6 Alkylene, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, with one or more R p Replacement C 1-6 Alkylene, by one or more R p Replacement C 2-6 alkenyl, with one or more R p Replacement C 2-6 alkynyl group, with one or more R p Replacement C 3-10 cycloalkyl or with one or more R p Substituted 3-10 membered heterocyclic alkyl groups;

[0180] Condition (8) k is 1; and the R 5 Not on X, the R 5 C 1-6 Alkylene, C 2-6 alkenyl, C 2-6 alkynyl group, with one or more R p Replacement C 1-6 Alkylene, by one or more R p Replacement C 2-6 alkenyl or with one or more R p Replacement C 2-6 alkynyl group;

[0181] Condition (9) f1 is 1, R a -C(O)-C 1-6 alkyl, -OC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl or 3-6 membered heterocyclic alkyl;

[0182] Condition (10) f1 is 2 or 3;

[0183] Condition (11) V is

[0184] Condition (12) Y is -C(O)-CH = ;

[0185] Condition (13) f2 is 1, 2 or 3, and at least one Rg for

[0186] This invention provides a compound of Formula I, its stereoisomers, its isotopically labeled compounds, its solvates, its prodrugs, its nitrides, or pharmaceutically acceptable salts thereof.

[0187] Where G is When a carbon atom is marked with an asterisk (*), it is a chiral carbon atom and is in the R configuration, S configuration, or a mixture thereof.

[0188] Each R 1 R 2 and R 3 Independently, H, D (deuterium), halogens, and C 1-6 Alkyl or with one or more R 1-1 Replacement C 1-6 alkyl;

[0189] Each R 1-1 Independently for D, halogen, 3-10 membered heterocyclic alkyl groups or those containing one or more R groups 1-1a Substituted 3-10 membered heterocyclic alkyl groups,

[0190] Each R 1-1a Independent of D, halogen or C 1-6 alkyl;

[0191] R 4 It is hydrogen or C 1-6 alkyl;

[0192] L represents a single bond, C 1-6 Alkylene or C 1-6 Alkyl-substituted C 1-6 Alkylene;

[0193] m and n are independently 0, 1, 2 or 3;

[0194] p1 is 0, 1, 2, or 3;

[0195] p2 is 0, 1, 2, or 3;

[0196] q can be 0, 1, 2, or 3;

[0197] X is CH2, NH, or O;

[0198] X1 is CH2 or NH;

[0199] k can be 0, 1, 2, 3 or 4;

[0200] Each R 5 Independently, H, D, halogens, oxo (=O), C 1-6 Alkyl, C 1-6 Alkylene, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, with one or more R p Replacement C 1-6 Alkyl, with one or more R p Replacement C 1-6 Alkylene, by one or more R p Replacement C 2-6 alkenyl, with one or more R p Replacement C 2-6 alkynyl group, with one or more R p Replacement C 3-10 cycloalkyl or with one or more R p Substituted 3-10 membered heterocyclic alkyl groups;

[0201] Or, any two R 5 Together with the atoms attached to it, they form 3-10 membered heterocycles, 5-10 membered heteroaromatic rings, and are bonded by one or more R atoms. 1-2 The substituted 3-10-membered heterocycle or is replaced by one or more R 1-3 Replaced 5-10 heterocyclic aromatic rings;

[0202] When G is At that time, each R 5 Can be located at the same time Above, or simultaneously located Above, or part of R 5 lie in Above, the rest of R 5 lie in superior;

[0203] Each R 1-2 and R 1-3 Independently D, amino, Halogen, cyano, hydroxyl, oxo (=O), C 1-6 Alkyl, C 1-6 Alkylene, -OC 1-6 Alkyl, C 3-6 cycloalkyl or C 3-8 Heteroalkyl; or two R atoms on the same carbon atom 1- 3 Together with the carbon atom attached to it, it forms a saturated 3-6 membered heterocycle or a saturated C. 3-6 Carbon ring; or any two Rs 1-2 Together with the atoms attached to it, they form 3-10 membered heterocycles, C 3-6 Carbon ring, with one or more R 1-2aThe substituted 3-10-membered heterocycle or is replaced by one or more R 1-2a Replacement C 3-6 Carbon rings;

[0204] Each R 1-2a Independently D, hydroxyl, cyano, halogen, C 1-6 Alkyl, C 1-6 Alkylene, -OC 1-6 Alkyl, C 2-6 alkenyl, C 2- 6-acetylenic, C 3-6 cycloalkyl or C 3-8 Heteroalkyl; wherein, the C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 The alkynyl group may optionally be replaced by a group selected from the group consisting of: halogen, hydroxyl, cyano, -OC. 1-6 Alkyl; the C 1-6 Alkylene, C 3-6 cycloalkyl, C 3-8 The heteroalkyl group is optionally substituted with a group selected from the group consisting of: halogen, hydroxyl, cyano, C. 1-6 Alkyl, -OC 1-6 Alkyl, Halogenated C 1-6 Alkyl, -O-halogenated C 1-6 alkyl;

[0205] Each R p Independent of D, halogen, C 1-6 Alkyl, C 1-6 Alkylene, C 2-6 alkenyl, C 2-6 alkynyl group, with one or more R p-1 Replacement C 1-6 Alkyl, with one or more R p-1 Replacement C 1-6 Alkylene, by one or more R p-1 Replacement C 2-6 alkenyl or with one or more R p-1 Replacement C 2-6 alkynyl group;

[0206] Each R p-1 Independent of D, halogen or C 1-6 alkyl;

[0207] Or, any two R p Together with the atoms attached to it, they form 3-10 membered heterocycles or are bounded by one or more R atoms. 1-2 Replaced 3-10 membered heterocycles;

[0208] Or, any two R p-1Together with the atoms attached to it, they form 3-10 membered heterocycles or are bounded by one or more R atoms. 1-2 Replaced 3-10 membered heterocycles;

[0209] Ring A is a 3-10 membered heterocyclic ring, C 6-10 Aromatic rings, 5-10 quinone heterocyclic aromatic rings or Ring B is C 3-10 Carbon rings, 3-10 membered heterocycles, C 6-10 Aromatic rings or 5-10 heterocyclic aromatic rings;

[0210] Each R a Independently, it can be D, halogen, oxo (=O), cyano, hydroxyl, -C(O)-C 1-6 alkyl, C 1-6 Alkyl, -OC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl or 3-6 membered heterocyclic alkyl;

[0211] Or, one of the R a One of the R 5 Together with the atoms attached to it, they form partially saturated 3-10 membered heterocycles or are formed by one or more R atoms. 1-2 Substituted saturated 3-10 member heterocycles; and the R 5 Not on the carbon atom marked with an asterisk (*);

[0212] Y represents a single bond or -C(O)-CH=;

[0213] V is 3-10 membered heterocyclic alkyl groups, partially saturated 3-10 membered heterocyclic groups, C 6-10 Aryl, 5-10 membered heteroaryl or partially saturated 3-10 membered heterocyclic and 5-10 membered heteroaryl;

[0214] f1 and f2 are independently 0, 1, 2 or 3;

[0215] Each R g Independently D, amino, Halogen, oxo (=O), cyano, hydroxyl, C 1-6 Alkyl, -OC 1-6 Alkyl, C 3-6 cycloalkyl, C 3-8 Heteroalkyl, -O- with one or more R 1-4 Substituted 3-10 membered heterocyclic alkyl groups, -O- with one or more R 1-4 Replacement C 3-8 Heteroalkyl;

[0216] V is optionally controlled by one or more R 6 replace;

[0217] Each R 6 Independently, H, D, halogens, oxo (=O), C 1-6 Alkyl, C 1-6 Alkylene, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, with one or more R p Replacement C 1-6 Alkyl, with one or more R p Replacement C 1-6 Alkylene, by one or more R p Replacement C 2-6 alkenyl, with one or more R p Replacement C 2-6 alkynyl group, with one or more R p Replacement C 3-10 cycloalkyl or with one or more R p Substituted 3-10 membered heterocyclic alkyl groups;

[0218] Or, any two R 6 Together with the atoms attached to it, they form 3-10 membered heterocycles, 5-10 membered heteroaromatic rings, and are bonded by one or more R atoms. 1-2 The substituted 3-10-membered heterocycle or is replaced by one or more R 1-3 Replaced 5-10 heterocyclic aromatic rings;

[0219] R m and R n Independently for C 1-6 alkyl;

[0220] R c and R d Independently hydrogen, C 1-6 Alkyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 3-8 Heteroalkyl or by one or more R 1-4 Replacement C 1-6 alkyl;

[0221] Each R 1-4 Independently hydroxyl or 3-8 membered heterocyclic alkyl;

[0222] Or, one of the R a One of the R g Together with the atoms attached to it, they form partially saturated 3-10 membered heterocycles or are formed by one or more R atoms. 1-2 The partially saturated 3-10 membered heterocycles are replaced;

[0223] Or, one of the R 5 And one of the R g Connection forms C 1-8 Alkylene, C 1-8 Heteroalkyl, C 2-8 imidene group, C 2-8 Hesperyl, with one or more R 1-2 Replacement C 1-8 Alkylene, by one or more R 1-2 Replacement C 1-8 Heteroalkyl, by one or more R 1- 2 Replacement C 2-8 alkenyl groups or those with one or more R groups 1-2 Replacement C 2-8 Hesperyl;

[0224] The various 3-10 membered heterocyclic alkyl groups, 3-10 membered heterocycles, saturated 3-6 membered heterocycles, 3-6 membered heterocyclic alkyl groups, partially saturated 3-10 membered heterocycles, partially saturated 3-10 membered heterocyclic groups, 3-8 membered heterocyclic alkyl groups, C 1-8 Heteroalkyl and C 2-8 The heteroatoms or heterogroups in the hesene group are independently selected from one, two, three, four, or five of N, N(H), N(=O), O, C(=O), S, S(=O), S(=O)2, P, P(=O), and P(=O)2, and the total number of heteroatoms and heterogroups is independently 1, 2, 3, 4, or 5.

[0225] The types of heteroatoms or heterogroups in the 5-10 membered heteroaryl group and the 5-10 membered heteroaryl ring are independently selected from N, N(=O)([N + (O) - The total number of heteroatoms and heterogroups is 1, 2, 3 or 4, consisting of one, two or three of O and S.

[0226] And the compound shown in Formula I satisfies any of the following conditions:

[0227] Condition (1) Ring A is a 3-10 member heterocyclic ring, a 5 member heteroaromatic ring, or Ring B is C 3-10 Carbon rings, 3-10 membered heterocycles, C 6-10 Aromatic ring or 5-10 membered heteroaromatic ring; the heteroatoms or heterogroups in the 5-membered heteroaromatic ring are selected from N, N(=O)([N + (O) - One, two, or three of O and S, and the total number of heteroatoms and heterogroups is 1, 2, or 3;

[0228] Condition (2) One of R a One of the R 5 Together with the atoms attached to it, they form partially saturated 3-10 membered heterocycles or are formed by one or more R atoms. 1-2 Substituted saturated 3-10 member heterocycles; and the R 5 Not on the carbon atom marked with an asterisk (*);

[0229] Condition (3) One of R a One of the R g Together with the atoms attached to it, they form partially saturated 3-10 membered heterocycles or are formed by one or more R atoms. 1-2 The partially saturated 3-10 membered heterocycles are replaced;

[0230] Condition (4) One of R 5 And one of the R g Connection forms C 1-8 Alkylene, C 1-8 Heteroalkyl, C 2-8 imidene group, C 2-8 Hesperyl, with one or more R 1-2 Replacement C 1-8 Alkylene, by one or more R 1-2 Replacement C 1-8 Heteroalkyl, by one or more R 1- 2 Replacement C 2-8 alkenyl groups or those with one or more R groups 1-2 Replacement C 2-8 Hesperyl;

[0231] Condition (5) Any two R 5 Together with the atoms attached to it, they form 3-10 membered heterocycles, 5-10 membered heteroaromatic rings, and are bonded by one or more R atoms. 1-2 The substituted 3-10-membered heterocycle or is replaced by one or more R 1-3 Replaced 5-10 heterocyclic aromatic rings;

[0232] Condition (6) G is

[0233] Condition (7) k is 1, and R 5 Located on X, the R 5 for C 1-6 Alkylene, C 2-6 alkenyl, C 2- 6-acetylinyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, with one or more R p Replacement C 1-6 Alkylene, by one or more Rp Replacement C 2-6 alkenyl, with one or more R p Replacement C 2-6 alkynyl group, with one or more R p Replacement C 3-10 cycloalkyl or with one or more R p Substituted 3-10 membered heterocyclic alkyl groups;

[0234] Condition (8) k is 1; and the R 5 Not on X, the R 5 C 1-6 Alkylene, C 2-6 alkenyl, C 2-6 alkynyl group, with one or more R p Replacement C 1-6 Alkylene, by one or more R p Replacement C 2-6 alkenyl or with one or more R p Replacement C 2-6 alkynyl group;

[0235] Condition (9) f1 is 1, R a -C(O)-C 1-6 alkyl, -OC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl or 3-6 membered heterocyclic alkyl;

[0236] Condition (10) f1 is 2 or 3;

[0237] Condition (11) V is

[0238] Condition (12) Y is -C(O)-CH = ;

[0239] Condition (13) f2 is 1, 2 or 3, and at least one R g for

[0240] This invention provides a compound of Formula I, its stereoisomers, its isotopically labeled compounds, its solvates, its prodrugs, its nitrides, or pharmaceutically acceptable salts thereof.

[0241] Where G is When a carbon atom is marked with an asterisk (*), it is a chiral carbon atom and is in the R configuration, S configuration, or a mixture thereof.

[0242] Each R 1 R2 and R 3 Independently, H, D (deuterium), halogens, and C 1-6 Alkyl or with one or more R 1-1 Replacement C 1-6 alkyl;

[0243] Each R 1-1 Independently for D, halogen, 3-10 membered heterocyclic alkyl groups or those containing one or more R groups 1-1a Substituted 3-10 membered heterocyclic alkyl groups,

[0244] Each R 1-1a Independent of D, halogen or C 1-6 alkyl;

[0245] R 4 For H or C 1-6 alkyl;

[0246] L represents a single bond, C 1-6 Alkylene or C 1-6 Alkyl-substituted C 1-6 Alkylene;

[0247] m and n are independently 0, 1, 2 or 3;

[0248] X is CH2, NH, or O;

[0249] k can be 0, 1, 2, 3 or 4;

[0250] Each R 5 Independently, H, D, halogens, oxo (=O), C 1-6 Alkyl, C 1-6 Alkylene, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, with one or more R p Replacement C 1-6 Alkyl, with one or more R p Replacement C 1-6 Alkylene, by one or more R p Replacement C 2-6 alkenyl, with one or more R p Replacement C 2-6 alkynyl group, with one or more R p Replacement C 3-10 cycloalkyl or with one or more R p Substituted 3-10 membered heterocyclic alkyl groups;

[0251] Or, any two R 5Together with the atoms attached to it, they form 3-10 membered heterocycles, 5-10 membered heteroaromatic rings, and are bonded by one or more R atoms. 1-2 The substituted 3-10-membered heterocycle or is replaced by one or more R 1-3 Replaced 5-10 heterocyclic aromatic rings;

[0252] Each R 1-2 and R 1-3 Independently D, amino, Halogen, cyano, hydroxyl, oxo (=O), C 1-6 Alkyl, -OC 1-6 Alkyl, C 3-6 cycloalkyl or C 3-8 Heteroalkyl; or two R atoms on the same carbon atom 1-3 Together with the carbon atom attached to it, it forms a saturated 3-6 membered heterocycle or a saturated C. 3-6 Carbon ring; or any two Rs 1-2 Together with the atoms attached to it, they form 3-10 membered heterocycles, C 3-6 Carbon ring, with one or more R 1-2a The substituted 3-10-membered heterocycle or is replaced by one or more R 1-2a Replacement C 3-6 Carbon rings;

[0253] Each R 1-2a Independently D, hydroxyl, cyano, halogen, C 1-6 Alkyl, C 1-6 Alkylene, -OC 1-6 Alkyl, C 2-6 alkenyl, C 2- 6-acetylenic, C 3-6 cycloalkyl or C 3-8 Heteroalkyl; wherein, the C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 The alkynyl group may optionally be replaced by a group selected from the group consisting of: halogen, hydroxyl, cyano, -OC. 1-6 Alkyl; the C 1-6 Alkylene, C 3-6 cycloalkyl, C 3-8 The heteroalkyl group is optionally substituted with a group selected from the group consisting of: halogen, hydroxyl, cyano, C. 1-6 Alkyl, -OC 1-6 Alkyl, Halogenated C 1-6 Alkyl, -O-halogenated C 1-6 Alkyl groups; each R p Independent of D, halogen, C 1-6 Alkyl, C 1-6 Alkylene, C 2-6 alkenyl, C 2-6alkynyl group, with one or more R p-1 Replacement C 1-6 Alkyl, with one or more R p-1 Replacement C 1-6 Alkylene, by one or more R p-1 Replacement C 2-6 alkenyl or with one or more R p-1 Replacement C 2-6 alkynyl group;

[0254] Each R p-1 Independent of D, halogen or C 1-6 alkyl;

[0255] Or, any two R p Together with the atoms attached to it, they form 3-10 membered heterocycles or are bounded by one or more R atoms. 1-2 Replaced 3-10 membered heterocycles;

[0256] Or, any two R p-1 Together with the atoms attached to it, they form 3-10 membered heterocycles or are bounded by one or more R atoms. 1-2 Replaced 3-10 membered heterocycles;

[0257] Ring A is a 3-10 membered heterocyclic ring, C 6-10 Aromatic rings, 5-10 quinone heterocyclic aromatic rings or Ring B is C 3-10 Carbon rings, 3-10 membered heterocycles, C 6-10 Aromatic rings or 5-10 heterocyclic aromatic rings;

[0258] Each R a Independently, it can be D, halogen, oxo (=O), cyano, hydroxyl, -C(O)-C 1-6 alkyl, C 1-6 Alkyl, -OC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl or 3-6 membered heterocyclic alkyl;

[0259] Or, one of the R a One of the R 5 Together with the atoms attached to it, they form partially saturated 3-10 membered heterocycles or are formed by one or more R atoms. 1-2 Substituted saturated 3-10 member heterocycles; and the R 5 Not on the carbon atom marked with an asterisk (*);

[0260] Y represents a single bond or -C(O)-CH=;

[0261] V is 3-10 membered heterocyclic alkyl groups, partially saturated 3-10 membered heterocyclic groups, C 6-10 Aryl or 5-10 heteroaryl groups;

[0262] f1 and f2 are independently 0, 1, 2 or 3;

[0263] Each R g Independently D, amino, Halogen, oxo (=O), cyano, hydroxyl, C 1-6 Alkyl, -OC 1-6 Alkyl, C 3-6 cycloalkyl, C 3-8 Heteroalkyl, -O- with one or more R 1-4 The substituted 3-10 membered heterocyclic alkyl group or -O- is replaced by one or more R 1-4 Replacement C 3-8 Heteroalkyl;

[0264] R m and R n Independently for C 1-6 alkyl;

[0265] R c and R d Independently hydrogen, C 1-6 Alkyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 3-8 Heteroalkyl or by one or more R 1-4 Replacement C 1-6 alkyl;

[0266] Each R 1-4 Independently hydroxyl or 3-8 membered heterocyclic alkyl;

[0267] Or, one of the R a One of the R g Together with the atoms attached to it, they form partially saturated 3-10 membered heterocycles or are formed by one or more R atoms. 1-2 The partially saturated 3-10 membered heterocycles are replaced;

[0268] Or, one of the R 5 And one of the R g Connection forms C 1-8 Alkylene, C 1-8 Heteroalkyl, C 2-8 imidene group, C 2-8 Hesperyl, with one or more R 1-2 Replacement C 1-8 Alkylene, by one or more R 1-2 Replacement C 1-8 Heteroalkyl, by one or more R 1-2 Replacement C 2-8 alkenyl groups or those with one or more R groups 1-2 Replacement C 2-8 Hesperyl;

[0269] The various 3-10 membered heterocyclic alkyl groups, 3-10 membered heterocycles, saturated 3-6 membered heterocycles, 3-6 membered heterocyclic alkyl groups, partially saturated 3-10 membered heterocycles, partially saturated 3-10 membered heterocyclic groups, 3-8 membered heterocyclic alkyl groups, C 1-8 Heteroalkyl and C 2-8 The heteroatoms or heterogroups in the hesene group are independently selected from N, N(H), N(=O)([N + (O) - The total number of heteroatoms and heterogroups is 1, 2, 3, 4 or 5, of one, two, three, four or five of the following: O, C (=O), S, S (=O), S (=O)2, P, P (=O)2 and P (=O)2.

[0270] The types of heteroatoms or heterogroups in the 5-10 membered heteroaryl group and the 5-10 membered heteroaryl ring are independently selected from N, N(=O)([N + (O) - The total number of heteroatoms and heterogroups is 1, 2, 3 or 4, consisting of one, two or three of O and S.

[0271] And the compound shown in Formula I satisfies any of the following conditions:

[0272] Condition (1) Ring A is a 3-10 member heterocyclic ring, a 5 member heteroaromatic ring, or Ring B is C 3-10 Carbon rings, 3-10 membered heterocycles, C 6-10 Aromatic ring or 5-10 membered heteroaromatic ring; the heteroatoms or heterogroups in the 5-membered heteroaromatic ring are selected from N, N(=O)([N + (O) - One, two, or three of O and S, and the total number of heteroatoms and heterogroups is 1, 2, or 3;

[0273] Condition (2) One of R a One of the R 5 Together with the atoms attached to it, they form partially saturated 3-10 membered heterocycles or are formed by one or more R atoms. 1-2 Substituted saturated 3-10 member heterocycles; and the R 5 Not on the carbon atom marked with an asterisk (*);

[0274] Condition (3) One of R a One of the R gTogether with the atoms attached to it, they form partially saturated 3-10 membered heterocycles or are formed by one or more R atoms. 1-2 The partially saturated 3-10 membered heterocycles are replaced;

[0275] Condition (4) One of R 5 And one of the R g Connection forms C 1-8 Alkylene, C 1-8 Heteroalkyl, C 2-8 imidene group, C 2-8 Hesperyl, with one or more R 1-2 Replacement C 1-8 Alkylene, by one or more R 1-2 Replacement C 1-8 Heteroalkyl, by one or more R 1- 2 Replacement C 2-8 alkenyl groups or those with one or more R groups 1-2 Replacement C 2-8 Hesperyl;

[0276] Condition (5) Any two R 5 Together with the atoms attached to it, they form 3-10 membered heterocycles, 5-10 membered heteroaromatic rings, and are bonded by one or more R atoms. 1-2 The substituted 3-10-membered heterocycle or is replaced by one or more R 1-3 Replaced 5-10 heterocyclic aromatic rings;

[0277] Condition (6) G is

[0278] Condition (7) k is 1, and R 5 Located on X, the R 5 for C 1-6 Alkylene, C 2-6 alkenyl, C 2- 6-acetylinyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, with one or more R p Replacement C 1-6 Alkylene, by one or more R p Replacement C 2-6 alkenyl, with one or more R p Replacement C 2-6 alkynyl group, with one or more R p Replacement C 3-10 cycloalkyl or with one or more R p Substituted 3-10 membered heterocyclic alkyl groups;

[0279] Condition (8) k is 1; and the R 5 Not on X, the R5 C 1-6 Alkylene, C 2-6 alkenyl, C 2-6 alkynyl group, with one or more R p Replacement C 1-6 Alkylene, by one or more R p Replacement C 2-6 alkenyl or with one or more R p Replacement C 2-6 alkynyl group;

[0280] Condition (9) f1 is 1, R a -C(O)-C 1-6 alkyl, -OC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl or 3-6 membered heterocyclic alkyl;

[0281] Condition (10) f1 is 2 or 3;

[0282] Condition (11) V is

[0283] Condition (12) Y is -C(O)-CH = ;

[0284] Condition (13) at least one R g for

[0285] This invention provides a compound of Formula I, its stereoisomers, its isotopically labeled compounds, its solvates, its prodrugs, its nitrides, or pharmaceutically acceptable salts thereof.

[0286] Where G is When a carbon atom is marked with an asterisk (*), it is a chiral carbon atom and is in the R configuration, S configuration, or a mixture thereof.

[0287] Each R 1 R 2 and R 3 Independently, H, D (deuterium), halogens, and C 1-6 Alkyl or with one or more R 1-1 Replacement C 1-6 alkyl;

[0288] Each R 1-1 Independently for D, halogen, 3-10 membered heterocyclic alkyl groups or those containing one or more R groups 1-1a Substituted 3-10 membered heterocyclic alkyl groups,

[0289] Each R 1-1a Independent of D, halogen or C 1-6 alkyl;

[0290] R 4 For H or C 1-6 alkyl;

[0291] L represents a single bond, C 1-6 Alkylene or C 1-6 Alkyl-substituted C 1-6 Alkylene;

[0292] m and n are independently 0, 1, 2 or 3;

[0293] X is CH2, NH, or O;

[0294] k can be 0, 1, 2, 3 or 4;

[0295] Each R 5 Independently, H, D, halogens, oxo (=O), C 1-6 Alkyl, C 1-6 Alkylene, C 2- 6-olefin, C 2-6 alkynyl group, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, with one or more R p Replacement C 1-6 Alkyl, with one or more R p Replacement C 1-6 Alkylene, by one or more R p Replacement C 2-6 alkenyl, with one or more R p Replacement C 2-6 alkynyl group, with one or more R p Replacement C 3-10 cycloalkyl or with one or more R p Substituted 3-10 membered heterocyclic alkyl groups;

[0296] Or, any two R 5 Together with the atoms attached to it, they form 3-10 membered heterocycles, 5-10 membered heteroaromatic rings, and are bonded by one or more R atoms. 1-2 The substituted 3-10-membered heterocycle or is replaced by one or more R 1-3 Replaced 5-10 heterocyclic aromatic rings;

[0297] Each R 1-2 and R 1-3 Independently D, amino, Halogen, cyano, hydroxyl, C 1-6 Alkyl, -OC 1-6 Alkyl, C 3-6cycloalkyl or C 3-8 Heteroalkyl; or two R atoms on the same carbon atom 1-3 Together with the carbon atom attached to it, it forms a saturated 3-6 membered heterocycle or a saturated C. 3-6 Carbon rings;

[0298] Each R p Independent of D, halogen, C 1-6 Alkyl, C 1-6 Alkylene, C 2-6 alkenyl, C 2-6 alkynyl group, with one or more R p-1 Replacement C 1-6 Alkyl, with one or more R p-1 Replacement C 1-6 Alkylene, by one or more R p-1 Replacement C 2-6 alkenyl or with one or more R p-1 Replacement C 2-6 alkynyl group;

[0299] Each R p-1 Independent of D, halogen or C 1-6 alkyl;

[0300] Or, any two R p Together with the atoms attached to it, they form 3-10 membered heterocycles or are bounded by one or more R atoms. 1-2 Replaced 3-10 membered heterocycles;

[0301] Or, any two R p-1 Together with the atoms attached to it, they form 3-10 membered heterocycles or are bounded by one or more R atoms. 1-2 Replaced 3-10 membered heterocycles;

[0302] Ring A is a 3-10 membered heterocyclic ring, C 6-10 Aromatic rings, 5-10 quinone heterocyclic aromatic rings or Ring B is C 3-10 Carbon rings, 3-10 membered heterocycles, C 6-10 Aromatic rings or 5-10 heterocyclic aromatic rings;

[0303] Each R a Independently, it can be D, halogen, oxo (=O), cyano, hydroxyl, -C(O)-C 1-6 alkyl, C 1-6 Alkyl, -OC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl or 3-6 membered heterocyclic alkyl;

[0304] Or, one of the Ra One of the R 5 Together with the atoms attached to it, they form partially saturated 3-10 membered heterocycles or are formed by one or more R atoms. 1-2 Substituted saturated 3-10 member heterocycles; and the R 5 Not on the carbon atom marked with an asterisk (*);

[0305] Y represents a single bond or -C(O)-CH=;

[0306] V is 3-10 membered heterocyclic alkyl groups, partially saturated 3-10 membered heterocyclic groups, C 6-10 Aryl or 5-10 heteroaryl groups;

[0307] f1 and f2 are independently 0, 1, 2 or 3;

[0308] Each R g Independently D, amino, Halogen, oxo (=O), cyano, hydroxyl, C 1- 6-alkyl, -OC 1-6 Alkyl, C 3-6 cycloalkyl, C 3-8 Heteroalkyl, -O- with one or more R 1-4 The substituted 3-10 membered heterocyclic alkyl group or -O- is replaced by one or more R 1-4 Replacement C 3-8 Heteroalkyl;

[0309] R m and R n Independently for C 1-6 alkyl;

[0310] R c and R d Independently hydrogen, C 1-6 Alkyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 3-8 Heteroalkyl or by one or more R 1-4 Replacement C 1-6 alkyl;

[0311] Each R 1-4 Independently hydroxyl or 3-8 membered heterocyclic alkyl;

[0312] Or, one of the R a One of the R g Together with the atoms attached to it, they form partially saturated 3-10 membered heterocycles or are formed by one or more R atoms. 1-2 The partially saturated 3-10 membered heterocycles are replaced;

[0313] Or, one of the R 5And one of the R g Connection forms C 1-8 Alkylene, C 1-8 Heteroalkyl, C 2-8 imidene group, C 2-8 Hesperyl, with one or more R 1-2 Replacement C 1-8 Alkylene, by one or more R 1-2 Replacement C 1-8 Heteroalkyl, by one or more R 1- 2 Replacement C 2-8 alkenyl groups or those with one or more R groups 1-2 Replacement C 2-8 Hesperyl;

[0314] The various 3-10 membered heterocyclic alkyl groups, 3-10 membered heterocycles, saturated 3-6 membered heterocycles, 3-6 membered heterocyclic alkyl groups, partially saturated 3-10 membered heterocycles, partially saturated 3-10 membered heterocyclic groups, 3-8 membered heterocyclic alkyl groups, C 1-8 Heteroalkyl and C 2-8 The heteroatoms or heterogroups in the hesene group are independently selected from N, N(H), N(=O)([N + (O) - The total number of heteroatoms and heterogroups is 1, 2, 3, 4 or 5, of one, two, three, four or five of the following: O, C (=O), S, S (=O), S (=O)2, P, P (=O)2 and P (=O)2.

[0315] The types of heteroatoms or heterogroups in the 5-10 membered heteroaryl group and the 5-10 membered heteroaryl ring are independently selected from N, N(=O)([N + (O) - The total number of heteroatoms and heterogroups is 1, 2, 3 or 4, consisting of one, two or three of O and S.

[0316] And the compound shown in Formula I satisfies any of the following conditions:

[0317] Condition (1) Ring A is a 3-10 member heterocyclic ring, a 5 member heteroaromatic ring, or Ring B is C 3-10 Carbon rings, 3-10 membered heterocycles, C 6-10 Aromatic ring or 5-10 membered heteroaromatic ring; the heteroatoms or heterogroups in the 5-membered heteroaromatic ring are selected from N, N(=O)([N + (O) - One, two, or three of O and S, and the total number of heteroatoms and heterogroups is 1, 2, or 3;

[0318] Condition (2) One of R a One of the R 5 Together with the atoms attached to it, they form partially saturated 3-10 membered heterocycles or are formed by one or more R atoms. 1-2 Substituted saturated 3-10 member heterocycles; and the R 5 Not on the carbon atom marked with an asterisk (*);

[0319] Condition (3) One of R a One of the R g Together with the atoms attached to it, they form partially saturated 3-10 membered heterocycles or are formed by one or more R atoms. 1-2 The partially saturated 3-10 membered heterocycles are replaced;

[0320] Condition (4) One of R 5 And one of the R g Connection forms C 1-8 Alkylene, C 1-8 Heteroalkyl, C 2-8 imidene group, C 2-8 Hesperyl, with one or more R 1-2 Replacement C 1-8 Alkylene, by one or more R 1-2 Replacement C 1-8 Heteroalkyl, by one or more R 1- 2 Replacement C 2-8 alkenyl groups or those with one or more R groups 1-2 Replacement C 2-8 Hesperyl;

[0321] Condition (5) Any two R 5 Together with the atoms attached to it, they form 3-10 membered heterocycles, 5-10 membered heteroaromatic rings, and are bonded by one or more R atoms. 1-2 The substituted 3-10-membered heterocycle or is replaced by one or more R 1-3 Replaced 5-10 heterocyclic aromatic rings;

[0322] Condition (6) G is

[0323] Condition (7) k is 1, and R 5 Located on X, the R 5 for C 1-6 Alkylene, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, with one or more R p Replacement C 1-6 Alkylene, by one or more R pReplacement C 2-6 alkenyl, with one or more R p Replacement C 2-6 alkynyl group, with one or more R p Replacement C 3-10 cycloalkyl or with one or more R p Substituted 3-10 membered heterocyclic alkyl groups;

[0324] Condition (8) k is 1; and the R 5 Not on X, the R 5 C 1-6 Alkylene, C 2-6 alkenyl, C 2-6 alkynyl group, with one or more R p Replacement C 1-6 Alkylene, by one or more R p Replacement C 2-6 alkenyl or with one or more R p Replacement C 2-6 alkynyl group;

[0325] Condition (9) f1 is 1, R a -C(O)-C 1-6 alkyl, -OC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl or 3-6 membered heterocyclic alkyl;

[0326] Condition (10) f1 is 2 or 3;

[0327] Condition (11) V is

[0328] Condition (12) Y is -C(O)-CH = ;

[0329] Condition (13) at least one R g for

[0330] In a certain preferred solution, each R 1-2 and R 1-3 Independently D, amino, Halogen, cyano, hydroxyl, C 1-6 Alkyl, -OC 1-6 Alkyl, C 3-6 cycloalkyl or C 3-8 Heteroalkyl; or two R atoms on the same carbon atom 1-3 Together with the carbon atom attached to it, it forms a saturated 3-6 membered heterocycle or a saturated C. 3-6 Carbon ring; R c Rd R m R n The definitions of the remaining groups in Formula I are the same as before.

[0331] In a preferred embodiment, certain groups in the compound of Formula I, its stereoisomers, its isotopically labeled compounds, its solvates, its prodrugs, its nitrides or pharmaceutically acceptable salts thereof have the following definitions, and the definitions of groups not mentioned are as described in any embodiment of the present invention (hereinafter referred to as "in a certain embodiment").

[0332] In one embodiment, each halogen is independently fluorine, chlorine, bromine, or iodine; for example, fluorine or chlorine.

[0333] In one scheme, each of the C 1-6 Alkyl, -C(O)-C 1-6 C in alkyl 1-6 Alkyl and -OC 1-6 C in alkyl 1-6 Alkyl groups are independently C 1-4 Alkyl groups, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl, or sec-butyl; and methyl, for example.

[0334] In one scheme, each of the C 1-8 alkylene groups and the respective C 1-6 The alkylene group is independently a C1, C2, C3, C4, C5, or C6 alkylene group; for example, methylene,

[0335] In one scheme, each of the C 1-8 Alkylenes are straight-chain alkylenes, for example

[0336] In one scheme, each of the C 1-6 alkylene

[0337] In one scheme, each of the C 1-8 Heteroalkyl is C 1-6 Heteroalkyl, the C 1-8 The heteroalkyl group may be a straight-chain heteroalkyl group; the C 1-8 The heteroatoms or heterogroups in the heteroalkylene group can be selected from one, two, or three of N, C (=O), O, and S, and the number of heteroatoms can be 1, 2, or 3; for example, the heteroatoms or heterogroups can be selected from one or two of C (=O) and O, and the total number of heteroatoms and heterogroups can be 1, 2, or 3; as another example, the C 1-8 Heteroalkyl is (or ), (or ),

[0338] In one scheme, the C 1-8 Heteroalkyl is

[0339] In one scheme, each of the above is controlled by one or more R 1-2 Replacement C 1-8 Heteroalkylene is formed by one or more R 1-2 Replacement C 1-6 Heteroalkyl, the C 1-8 The heteroalkyl group may be a straight-chain heteroalkyl group; the C 1-8 The heteroatoms or heterogroups in the heteroalkylene group can be selected from one, two, or three of N, C (=O), O, and S, and the number of heteroatoms can be 1, 2, or 3; for example, the heteroatoms or heterogroups can be selected from one or two of C (=O) and O, and the total number of heteroatoms and heterogroups can be 1, 2, or 3; another example is the one or more R 1-2 Replacement C 1-8 Heteroalkyl is wait.

[0340] In one scheme, each of the C 2-6 The alkenyl group is independently C 2-4 Alkenyl groups, such as vinyl, allyl, methyl vinyl, propenyl, or butenyl.

[0341] In one scheme, each of the C 2-8 The sub-alkenyl group is independently C 2-6 alkenyl; the C 2-8 The subalkenyl group can be a straight-chain subalkenyl group; for example, the C... 2-8 imide For example (The alkene bond configuration can be cis or trans).

[0342] In one scheme, each of the C 2-8 The hesperidium group is independently C 2-6 Iso-alkenyl; the C 2-8 The hemibenyl group can be a straight-chain hemibenyl group; the C 2-8 The heteroatoms of the hesene group can be selected from one or both of N and O, and the number of heteroatoms can be one or two.

[0343] In one scheme, each of the C 2-6 The alkynyl group is independently C 2-4 Alkyne groups, such as ethynyl, propynyl, or methylpropynyl.

[0344] In one scheme, each of the C 3-10 cycloalkyl groups and the respective C 3-6 The cycloalkyl group is independently a C3, C4, C5, or C6 cycloalkyl group; for example, cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl.

[0345] In one scheme, the C 3-10 The carbon ring is a partially saturated C 3-6 Carbon ring.

[0346] In one embodiment, the heteroatoms or heterogroups of each of the 3-10-membered heterocyclic alkyl groups, the 3-8-membered heterocyclic alkyl groups, and the 3-6-membered heterocyclic alkyl groups are independently selected from one, two, or three of N, C (=O), and O, and the total number of heteroatoms and heterogroups is independently 1, 2, or 3; for example, the heteroatoms are independently selected from one or two of N and O, and the number of heteroatoms can be independently 1 or 2.

[0347] In one embodiment, each of the 3-10-membered heterocyclic alkyl groups, each of the 3-8-membered heterocyclic alkyl groups, and each of the 3-6-membered heterocyclic alkyl groups are independently 3, 4, 5, or 6-membered heterocyclic alkyl groups; for example... For example It can also be morpholino, piperazine, or aziridine.

[0348] In one scheme, the heteroatoms or heterogroups of each 3-10 member heterocycle are independently selected from one, two, or three of N, C (=O) and O, and the total number of heteroatoms and heterogroups is independently 1, 2, or 3; for example, the heteroatoms are independently selected from one or two of N and O, and the number of heteroatoms can be independently 1 or 2.

[0349] In one embodiment, each of the 3-10 member heterocycles is independently a saturated 3, 4, 5, 6, 7, 8, 9 or 10 member heterocycle or a partially saturated 3, 4, 5, 6, 7, 8, 9 or 10 member heterocycle;

[0350] The saturated 3-10 membered heterocycle may be a saturated 3-6 membered heterocycle; for example, a furan ring, a pyrrole ring, a piperidine ring, a piperazine ring, or a morpholine ring; or, for example, an azo-butane ring.

[0351] The number of alkene bonds in the partially saturated 3-10 membered heterocycles can independently be 1 or 2; the number of alkene bonds in the partially saturated 3-10 membered heterocycles can independently be It can also be used for

[0352] In one scheme, each of the C 6-10 The aromatic ring can be a benzene ring or a naphthalene ring, for example, a benzene ring.

[0353] In one scheme, each of the C 6-10 The aryl group can be phenyl or naphthyl, for example, phenyl.

[0354] In one embodiment, the heteroatoms or heterogroups of the 5-10 membered heteroaromatic ring are independently selected from one, two, or three of N, N(=O), and S, and the total number of heteroatoms and heterogroups is independently one, two, or three; for example, the heteroatoms are independently selected from one or two of N and S; the number of heteroatoms in the 5-10 membered heteroaromatic ring can be independently one or two; the 5-10 membered heteroaromatic ring can be independently a 5-6 membered heteroaromatic ring, such as a pyrazole ring, an imidazole ring, a thiophene ring, a pyridine ring, a pyrimidine ring, or a pyrazine ring.

[0355] In one embodiment, the heteroatoms or heterogroups of each 5-membered heteroaromatic ring are independently selected from one, two, or three of N, N(=O), and S, and the total number of heteroatoms and heterogroups is independently one, two, or three; for example, the heteroatoms are selected from one or two of N and S; the number of heteroatoms in the 5-membered heteroaromatic ring can be one; for example, a thiophene ring.

[0356] In one embodiment, the heteroatoms or heterogroups of each of the 5-10 member heteroaryl groups are independently selected from one, two, or three of N, N(=O), and S, and the total number of heteroatoms and heterogroups is independently one, two, or three; for example, the heteroatoms are independently selected from one or two of N and S, such as N; the number of heteroatoms in each of the 5-10 member heteroaryl groups can be independently one or two; the 5-10 member heteroaryl groups can be independently 5-6 member heteroaryl groups, such as pyrazolyl, pyridyl, pyrimidinyl, or pyrazinyl; and for another example... Or for example

[0357] In one embodiment, the 5-10 heteroaryl group is independently pyridazinyl, pyridoimidazolyl, pyridopyrazolyl, pyridotriazolyl, benzopyrazinyl, pyridopyridyl, pyridopyrroleyl, or pyridopyrazinyl; for example

[0358] In one scheme, each of the C 2-8 The hemibenyl group is independently a straight-chain hemibenyl group; for example, the C... 2-8 Hesperyl (The alkene bond configuration can be cis or trans).

[0359] In one embodiment, the 3-10 membered heterocyclic group and 5-10 membered heteroaryl group saturated in each part are independently piperidinopyrimidinyl, piperidinopyridinyl, piperazinopyrimidinyl, or piperazinopyridinyl; for example, it is...

[0360] In one embodiment, the 3-10 membered heterocyclic groups and 5-10 membered heteroaryl groups saturated in each part are independently azircyclopentenylpyridinyl or azircyclohexenylpyrimidinyl, for example...

[0361] In a certain scheme, each R 1 R 2 and R 3 Independently, it can be H or D, for example, H.

[0362] In one of the schemes, R 4 C 1-4 alkyl.

[0363] In one scheme, L is a single bond or C 1-4 Alkylene.

[0364] In one scheme, L represents a single bond.

[0365] In a given scheme, m and n are independently 1 or 2; for example, 1.

[0366] In one particular scheme, X is NH.

[0367] In one particular scheme, X is 0.

[0368] In one scheme, X is CH2.

[0369] In one particular scheme, k is 0.

[0370] In one particular scheme, k is 1.

[0371] In one scheme, ring A is a partially saturated 5-6 membered heterocycle, and C... 6-10 Aromatic rings, 5-membered heterocyclic aromatic rings or Ring B is a partially saturated 5-6 membered heterocyclic ring or a 5-6 membered heteroaromatic ring.

[0372] In one scheme, ring A is a partially saturated 3-10 membered heterocycle, 5 membered heteroaromatic ring, or... Ring B is a partially saturated 3-10 membered heterocycle or 5-10 membered heteroaromatic ring; preferably, ring A is a partially saturated 5-6 membered heterocycle, 5 membered heteroaromatic ring, or... Ring B is a partially saturated 5-6 membered heterocycle or 5-6 membered heteroaromatic ring; the types of heteroatoms in the partially saturated 5-6 membered heterocycle, 5 membered heteroaromatic ring and the 5-6 membered heteroaromatic ring are independently selected from one, two or three of N, O and S; the number of heteroatoms is independently one, two or three; the number of alkene bonds in the partially saturated 5-6 membered heterocycle is independently one or two.

[0373] In one scheme, ring A is Ring B is partially saturated with C 3-10 Carbon rings, partially saturated 3-10 membered heterocycles, C 6-10 Aromatic rings or 5-10 heterocyclic aromatic rings; for example, ring A is... Ring B is a partially saturated 5-6 membered heterocycle or a 5-6 membered heteroaromatic ring; the heteroatoms of the partially saturated 5-6 membered heterocycle and the 5-6 membered heteroaromatic ring are independently selected from one, two or three of N, O and S; the number of heteroatoms is independently one, two or three; the number of alkene bonds in the partially saturated 5-6 membered heterocycle is one or two.

[0374] In one scheme, ring A is C. 6-10 Aromatic ring.

[0375] In one scheme, ring A is C. 6-10 Aromatic rings or Ring B is a partially saturated 3-10 member heterocycle; for example, ring A is C. 6- 10 Aromatic rings or Ring B is a partially saturated 5-6 membered heterocycle, wherein the number of alkene bonds in the partially saturated 5-6 membered heterocycle is 1 or 2, and the heteroatom is selected from one or two of N and O; the number of heteroatoms is 1 or 2.

[0376] In one of the schemes, one of R a R 5 Together with the atoms attached to it, it forms a partially saturated 3-10 membered heterocycle; and R 5 Not on the carbon atom marked with "*"; the number of alkene bonds in the partially saturated 3-10 membered heterocycles is 1 or 2, the heteroatom or heterogroup is selected from one, two or three of N, C (=O) and O, and the total number of heteroatoms and heterogroups is 1, 2 or 3.

[0377] In one of the schemes, one of R a R g Together with the atoms attached thereto, they form a partially saturated 3-10 membered heterocycle; the number of alkene bonds in the partially saturated 3-10 membered heterocycle is 1 or 2, the type of heteroatom or heterogroup is selected from one, two or three of N, C (=O) and O, and the total number of heteroatoms and heterogroups is 1, 2 or 3.

[0378] In one of the schemes, one of R 5 And one of the R g Connection forms C 1-8 Alkylene, C 1-8 Heteroalkyl or C 2-8 Ideonyl, the C 1-8 The heteroatoms or heterogroups of the heteroalkylene group are selected from one, two, or three of N, C (=O), O, and S, and the total number of heteroatoms and heterogroups is 1, 2, or 3. For example, the heteroatoms or heterogroups are selected from one or two of C (=O) and O, and the total number of heteroatoms and heterogroups is 1, 2, or 3.

[0379] In a certain scheme, any two R 5 Together with the atoms attached thereto, they form 3-6 membered heterocycles or 5-6 membered heteroaromatic rings; the heteroatoms or heteroatomic groups of the 3-6 membered heterocycles are selected from one, two or three of N, C (=O) and O, and the total number of heteroatoms and heteroatomic groups is 1, 2 or 3; the heteroatoms of the 5-6 membered heteroaromatic rings are selected from one or two of N and O, and the number of heteroatoms is 1 or 2.

[0380] In one scheme, k is 1; R 5 Located on X, and the R on X 5 for C 1-6 Alkylene, 3-10 membered heterocyclic alkyl, with one or more R p Replacement C 1-6 alkylene or by one or more R p Substituted 3-10 membered heterocyclic alkyl groups; preferably, the R 5 for C 1-4 Alkylene, 3-6 heterocyclic alkyl, with one or more R p Replacement C 1- 4 alkylene groups or those containing one or more R p The substituted 3-6 membered heterocyclic alkyl group; the heteroatom of the 3-6 membered heterocyclic alkyl group is selected from one or two of N or O; the number of heteroatoms is one or two.

[0381] In one scheme, k is 1, and the R 5 Not on X, the R 5 C 1-6 alkylene or by one or more R p Replacement C 1-6 Alkylene; preferably, the R 5 C 1-4 alkylene or by one or more R p Replacement C1-4 Alkylene.

[0382] In a certain scheme, each R p Independent of halogen, C 1-6 alkylene or by one or more R p-1 Replacement C 1-6 Alkylene.

[0383] In a certain scheme, f1 is 0 or 1, for example, 1.

[0384] In a certain scheme, each R a Independently D, halogen, oxo, cyano, -C(O)-C 1-6 alkyl, -OC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl or C 3-6 cycloalkyl; for example, each R a Independently D, halogen, oxo, cyano, -C(O)-C 1-6 alkyl or For example, each R a It can be D or halogen independently.

[0385] In a certain scheme, f1 is 1, R a for -OC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl or C 3-6 Cycloalkyl.

[0386] In one scheme, V is C 6-10 Aryl or 5-10 heteroaryl; for example, V is C 6-10 Aryl or 5-6-membered heteroaryl, wherein the heteroatom of the 5-6-membered heteroaryl is N, and the number of heteroatoms is 1, 2 or 3; for example, V is a 5-6-membered heteroaryl, wherein the heteroatom of the 5-6-membered heteroaryl is N, and the number of heteroatoms is 1, 2 or 3.

[0387] In one scheme, V is C 6-10 Aryl or 5-10 heteroaryl; for example, V is C 6-10 The aryl or 5-6 heteroaryl group has N heteroatoms and the number of heteroatoms is 1, 2 or 3.

[0388] In one scheme, Y is -C(O)-CH=, and V is a 3-10 membered heterocyclic alkyl group or a partially saturated 3-10 membered heterocyclic group; for example, V is a 3-6 membered heterocyclic alkyl group, wherein the heteroatom type of the 3-6 membered heterocyclic alkyl group is selected from one or two of N and O, and the number of heteroatoms is 1 or 2.

[0389] In a certain scheme, each R g Independently D, amino, Halogen, C 1-6 Alkyl, C 3- 6-cycloalkyl, -OC 1-6 Alkyl, C 3-8 Heteroalkyl, -O- with one or more R 1-4 The substituted 3-10 membered heterocyclic alkyl group or -O- is replaced by one or more R 1-4 Replacement C 3-8 Heteroalkyl groups; for example, each R g Independently D, amino, Halogen, C 1-6 Alkyl, -OC 1-6 Alkyl, -O- with one or more R 1-4 The substituted 3-10 membered heterocyclic alkyl group or -O- is replaced by one or more R 1-4 Replacement C 3-8 Heteroalkyl groups; for example, D, amino, Halogen or C 1-6 Alkyl groups; for example, D, amino, halogen, or C. 1-6 Alkyl groups; for example, D-, amino groups, or halogens; for example, Halogen, -OC 1-6 Alkyl, -O- with one or more R 1-4 The substituted 3-10 membered heterocyclic alkyl group or -O- is replaced by one or more R 1-4 Replacement C 3-8 Heteroalkyl groups.

[0390] In a certain scheme, each R g Independently D or C 1-6 alkyl.

[0391] In a certain scheme, each R g Independently D, amino or

[0392] In one of the schemes, R c and R d Independently hydrogen or C 1-4 Alkyl group; for example, H.

[0393] In one of the schemes, R m and R n Independently for C 1-4 alkyl.

[0394] In one scheme, the carbon atom with the asterisk (*) has an R configuration.

[0395] In one of the schemes, one of R 5 Located adjacent to the carbon atom marked with an asterisk (*), for example... With the R 5 The configuration of directly bonded carbon atoms is the R configuration.

[0396] In one of the schemes, for The carbon atom marked with an asterisk (*) has an R configuration. In and the R 5 The directly bonded carbon atoms have an R or S configuration; preferably, In and the R 5 The configuration of directly bonded carbon atoms is the R configuration.

[0397] In one of the schemes, R 2 For H or C 1-6 alkyl.

[0398] In a certain scheme, each R 1-1 Halogens are independent of each other.

[0399] In a certain scheme, p1 is either 0 or 1, for example, 1.

[0400] In one particular scheme, p2 is 0.

[0401] In one particular scheme, q is 1.

[0402] In one scheme, X is CH2, NH or O.

[0403] In one of the plans, X 1 It is NH.

[0404] In a certain scheme, each R p Independently for D, halogen, Or hydroxyl group.

[0405] In one of the schemes, R c and R d Independently hydrogen or C 1-6 alkyl.

[0406] In one of the schemes, R c C 1-6 alkyl.

[0407] In one scheme, ring A is C. 6-10 Aromatic rings or 5-10 heterocyclic aromatic rings, such as C 6-10Aromatic rings or 5-6-membered heteroaromatic rings, such as benzene rings or 5-6-membered heteroaromatic rings, preferably benzene rings.

[0408] In one of the schemes, R a Independent of halogen or halogenated C 1-6 alkyl.

[0409] In one scheme, V is C 6-10 aryl, 5-10-membered heteroaryl, or partially saturated 5-6-membered heterocyclic benzo[5-6-membered heteroaryl], preferably, V is C 6-10 The aryl or 5-10 heteroaryl group is preferably N heteroatom, and the number of heteroatoms is 1, 2, 3 or 4.

[0410] In one possible solution, f2 can be 1, 2, 3, or 4.

[0411] In a certain scheme, each R g Independently amino, halogen, -OC 1-6 alkyl, -C(=O)R c -O- is controlled by one or more R 1-4 Replacement C 1-6 Alkyl or -O- with one or more R 1-4 Substituted 3-6 membered heterocyclic alkyl groups.

[0412] In a certain scheme, each R 1-4 Independently NH2, NH(C) 1-6 Alkyl), N(C) 1-6 Alkyl)2 or C 1-6 alkyl.

[0413] In a certain scheme, each R 1-2 Independently halogen, hydroxyl or C 1-6 alkyl.

[0414] In a certain scheme, each R 1-2a Halogens are independent of each other.

[0415] In a certain scheme, k is 1, 2, or 3, for example, 1 or 2.

[0416] In one embodiment, ring G1 is a 5-12 membered heterocyclic alkyl group; preferably, ring G1 is a 6-membered heterocyclic alkyl group, a 6-membered heterocyclic alkyl group fused with a 5-membered heterocyclic alkyl group, or a 6-membered heterocyclic alkyl group fused with a 6-membered heterocyclic alkyl group; more preferably, ring G1 is piperazinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazin-imidazolinidyl, piperazin-pyrrolidinyl, piperazin-piperazinyl, or piperidin-piperidinyl.

[0417] In one of the schemes, for

[0418] In one of the schemes, for The carbonyl group is attached at position "1", the ring A is attached at position "2", and one of the R groups is attached at position "3". g Connect the carbon atoms marked with "*" so that their configurations are independently R, S, or a mixture thereof;

[0419] Better place, for

[0420] In a certain scheme, each R 5 It can be H, oxo (=O) or C independently. 1-6 Alkyl, preferably, R 5 Independently H or C 1-6 alkyl.

[0421] In one of the schemes, one of R 5 And one of the R g Connection forms C 1-8 Alkylene, C 1-8 Heteroalkyl, C 2-8 Hesperyl, with one or more R 1-2 Replacement C 1-8 Alkylene, by one or more R 1-2 Replacement C 1-8 Heteroalkyl or by one or more R 1-2 Replacement C 2-8 Hesperyl; each R 1-2 Independently halogen, hydroxyl or C 1-6 Alkyl group; or any two R groups 1-2 Together with the atoms attached to it, it forms a 3-6 membered heterocycle; the C 1-8 Heteroalkyl and C 2-8 The heteroatoms or heterogroups in the hesene group are independently selected from one, two, or three of N (H), O, and C (=O), and the total number of heteroatoms and heterogroups is independently 1, 2, 3, 4, or 5; the heteroatoms in the 3-6 membered heterocycles are selected from one or two of N and O, and the number of heteroatoms is 1 or 2;

[0422] Preferably, one of the R 5 And one of the R g Connection forms C 1-8 Heteroalkyl, C 2-8 Hesperidinyl or with one or more R 1-2 Replacement C 1-8 Heteroalkylene; each R 1-2 Independently halogen, hydroxyl or C 1-6Alkyl group; or any two R groups 1-2 Together with the atoms attached to it, it forms a 3-6 membered heterocycle; the C 1-8 Heteroalkyl and C 2-8 The heteroatoms or heterogroups in the heteroene group are independently selected from one, two, or three of N (H), O, and C (=O), and the total number of heteroatoms and heterogroups is independently 1, 2, 3, 4, or 5; the heteroatoms in the 3-6 membered heterocyclic alkyl group are selected from one or two of N and O, and the number of heteroatoms is 1 or 2;

[0423] Better yet, one of the R 5 And one of the R g Connection forms C 2-8 Hesperidinyl or with one or more R 1-2 Replacement C 1-8 Heteroalkylene; each R 1-2 Independently halogen, hydroxyl or C 1-6 Alkyl group; or any two R groups 1-2 Together with the atoms attached to it, it forms a 3-6 membered heterocycle; the C 1-8 Heteroalkyl and C 2-8 The heteroatoms or heterogroups in the heteroene group are independently selected from one, two, or three of N (H), O, and C (=O), and the total number of heteroatoms and heterogroups is independently 1, 2, 3, 4, or 5; the heteroatoms in the 3-6 membered heterocyclic alkyl group are selected from one or two of N and O, and the number of heteroatoms is 1 or 2.

[0424] In one of the schemes, one of R 5 And one of the R g Connection formation

[0425] T 1 Independently for O, C 3-6 Cycloalkylene, 3-6 membered heterocycloalkylene, -C(R) a1 R a2 )-、-N(R b1 )-、-C(O)N(R b1 )-、-N(R b1 C(O)-, by one or more R 1-2a Replacement C 3-6 cycloalkyl or with one or more R 1-2a Substituted 3-6 membered heterocyclic alkyl groups;

[0426] T 2 Independently a single bond, O or -C(R) a1 Ra2 )-;

[0427] T 3 Independently for C 3-6 Cycloalkylene, 3-6 membered heterocycloalkylene, -C(R) a1 R a2 )-、-N(R b1 )-、-C(O)N(R b1 )-、-N(R b1 C(O)-, by one or more R 1-2a Replacement C 3-6 cycloalkyl or with one or more R 1-2a Substituted 3-6 membered heterocyclic alkyl groups;

[0428] The heteroatoms in each of the 3-6 membered heterocyclic alkyl groups are selected from one or two of N and O, and the number of heteroatoms is one or two;

[0429] R a1 and R a2 Independently, it is H, F, Cl, Br, hydroxyl group, C 1-3 Alkyl or -N(R) b1 R b2 ), or R a1 and R a2 Together they form a methylene group (=CH2);

[0430] R b1 and R b2 Independently for H and C 1-3 Alkyl or halogenated C 1-3 alkyl;

[0431] Each R 1-2a Independently, it can be F, Cl, or Br;

[0432] s1 can be 1, 2, 3, 4, 5, 6, 7 or 8;

[0433] s2 can be 1, 2, 3, 4, 5, 6 or 7 independently;

[0434] s3 can be 1, 2, 3, or 4 independently;

[0435] s4 can be 0, 1, 2, 3 or 4 independently.

[0436] In one of the schemes, one of R 5 And one of the R g Connection formation (T) (The two s4 values ​​are not both 0) (The two s4 values ​​are not both 0) or (The two s4 values ​​are not both 0 at the same time);

[0437] T 1 For O, or -C(R) a1 R a2 )-;

[0438] R a1 and R a2 Independently, it can be H, F, or a hydroxyl group;

[0439] T 2 It is a single bond;

[0440] T 3 Independently 3-6 membered heterocyclic alkylene, -C(HR) a2 )-、-N(R b1 )-、-C(O)N(R b1 - or -N(R) b1 )C(O)-, wherein the heteroatom in the 3-6 membered heterocyclic alkyl group is selected from one or two of N and O, and the number of heteroatoms is one or two;

[0441] R b1 Independently H or C 1-3 alkyl;

[0442] s2 can be 1, 2, 3, 4, 5, 6 or 7 independently;

[0443] s3 can be 1, 2, 3, or 4 independently;

[0444] s4 can be 0, 1, 2, 3 or 4 independently.

[0445] In one embodiment, the compound shown in Formula I is the compound shown in Formula I-1:

[0446] The compound shown in Formula I-1 optionally satisfies conditions (1), (2), (3) or (4); G, ring A, f1, R a V, f2, R g The definition is as described in any embodiment of this invention;

[0447] Preferably, where G is Carbon atoms marked with "*" are chiral carbon atoms, which have the R configuration;

[0448] Each R 1 R 2 and R 3 Independently H or D;

[0449] R 4 C 1-6 alkyl;

[0450] m and n are independently 1 or 2;

[0451] X is CH2, NH, or O;

[0452] k is 0 or 1;

[0453] f1 and f2 are independently 0, 1, 2 or 3;

[0454] Ring A is a partially saturated 5-6 membered heterocycle, C 6-10 Aromatic rings, 5-membered heterocyclic aromatic rings or Ring B is a partially saturated 5-6 membered heterocyclic ring or a 5-10 membered heteroaromatic ring;

[0455] Each R a Independently D, halogen, oxo, cyano, -C(O)-C 1-6 alkyl or

[0456] V is C 6-10 Aryl or 5-10 heteroaryl groups;

[0457] Each R g Independently D, amino, Halogen, C 1-6 Alkyl, C 3-6 cycloalkyl, -OC 1-6 Alkyl, C 3-8 Heteroalkyl, 5-10-membered heteroaryl, -O- with one or more R 1-4 The substituted 3-10 membered heterocyclic alkyl group or -O- is replaced by one or more R 1-4 Replacement C 3-8 Heteroalkyl;

[0458] R c and R d Independently hydrogen, C 1-6 Alkyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 3-8 Heteroalkyl, by one or more R 1-4 Replacement C 1-6 Alkyl, with one or more R 1-4 Substituted 3-10 membered heterocyclic alkyl groups or -C(=O)-C 1-6 alkyl;

[0459] Each R 1-4 Independently, deuterium (D), NH2, and NH (C) 1-6 Alkyl), N(C) 1-6 Alkyl)2, hydroxyl or 3-8 membered heterocyclic alkyl;

[0460] And the compound shown in Formula I-1 satisfies any of the following conditions:

[0461] (1) k is 0; ring A is a partially saturated 5-6 membered heterocycle, 5 membered heteroaromatic ring, or... Ring B is a partially saturated 5-6 membered heterocycle or a 5-6 membered heteroaromatic ring;

[0462] (2) Ring A is C 6-10 Aromatic rings;

[0463] One of the R a R 5 Together with the atoms attached to it, it forms a partially saturated 3-10 membered heterocycle, and R 5 Not on the carbon atom marked with an asterisk (*);

[0464] (3) k is 0; ring A is C 6-10 Aromatic rings;

[0465] One of the R a One of the R g Together with the atoms attached to it, they form partially saturated 3-10 membered heterocycles;

[0466] (4) Ring A is C 6-10 Aromatic rings; R 5 And one of the R g Connection forms C 1-8 Alkylene, C 1-8 Heteroalkyl or C 2-8 alkenyl;

[0467] The heteroatoms in the 5-membered heteroaromatic ring, 5-6-membered heteroaromatic ring and 5-6-membered heteroaryl group are independently selected from one, two or three of N, O and S, and the number of heteroatoms is independently 1, 2 or 3.

[0468] The number of alkene bonds in each of the partially saturated 5-6 membered heterocycles and partially saturated 3-10 membered heterocycles is independently 1 or 2, the types of heteroatoms or heterogroups are independently selected from one, two or three of N, C (=O) and O, and the total number of heteroatoms and heterogroups is independently 1, 2 or 3.

[0469] The C 1-8 The heteroatoms or heterogroups of the heteroalkylene group are selected from one, two or three of N, C (=O) and O, and the total number of heteroatoms and heterogroups is 1, 2 or 3;

[0470] Better yet, each R g Independently D, amino, Halogen, C 1-6 Alkyl, -OC 1-6 Alkyl, -O- with one or more R 1-4The substituted 3-10 membered heterocyclic alkyl group or -O- is replaced by one or more R 1-4 Replacement C 3-8 Heteroalkyl;

[0471] R c and R d Independently hydrogen or C 1-6 alkyl.

[0472] In one embodiment, the compound shown in Formula I is a compound shown in Formula I-2D, a compound shown in Formula I-2E, a compound shown in Formula 2F, or a compound shown in Formula 2G.

[0473] R 1 R 2 R 3 R 5 f1, R a V, f2, R g The T definition in any embodiment of the invention refers to the configuration of the carbon atom marked with "*" as R, S, or a mixture thereof.

[0474] In one embodiment, the compound represented by Formula I is a compound represented by Formula I-2D-1, I-2D-2, I-2E-1, I-2E-2, I-2E-3, I-2E-4, I-2E-5, I-2E-6, I-2E-7, I-2F-1, I-2F-2, I-2F-3, I-2F-4, I-2F-5, I-2G-1, I-2G-2, I-2G-3, or I-2G-4;

[0475] In a certain scheme, the compound shown in Formula I-2D, the compound shown in Formula I-2E, the compound shown in Formula 2F, or the compound shown in Formula 2G,

[0476] R 1 R 2 and R 3 For H;

[0477] Ring A is a benzene ring;

[0478] f1 is 1;

[0479] R a Halogen or halogenated C 1-6 alkyl;

[0480] V is C 6-10 Aryl or 5-10 heteroaryl, wherein the heteroatom of the 5-10 aryl group is N, and the number of heteroatoms is 1, 2, 3 or 4;

[0481] f2 is 1, 2, 3 or 4;

[0482] Each R g Independently amino, halogen, -OC 1-6 alkyl, -C(=O)R c -O- is controlled by one or more R 1-4 Replacement C 1-6 Alkyl or -O- with one or more R 1-4 The substituted 3-6-membered heterocyclic alkyl group, wherein the heteroatom in the 3-6-membered heterocyclic alkyl group is selected from one, two or three of N, O and S, and the number of heteroatoms is one, two or three;

[0483] R c and R d Independently hydrogen or C 1-6 alkyl;

[0484] Each R 1-4 Independently NH2, NH(C) 1-6 Alkyl), N(C) 1-6 Alkyl)2 or C 1-6 alkyl;

[0485] T is C 1-8 Alkylene, C 1-8 Heteroalkyl, C 2-8 Hesperyl, with one or more R 1-2 Replacement C 1-8 Alkylene, by one or more R 1-2 Replacement C 1-8 Heteroalkyl or by one or more R 1-2 Replacement C 2-8 Iso-alkenyl; the C 1-8 Heteroalkyl and C 2-8 The heteroatoms or heterogroups in the hesene group are independently selected from one, two, or three of N (H), O, and C (=O), and the total number of heteroatoms and heterogroups is independently 1, 2, 3, 4, or 5.

[0486] Each R 1-2 Independently halogen, hydroxyl or C 1-6 alkyl;

[0487] Or any two R 1-2 Together with the atoms attached thereto, they form a 3-6 membered heterocycle, wherein the heteroatom in the 3-6 membered heterocyclic alkane is selected from one or two of N and O, and the number of heteroatoms is one or two;

[0488] R 5 H or C independently 1-6 alkyl;

[0489] Ideally, T is

[0490] T 1 For O, or -C(R) a1 R a2 )-;

[0491] R a1 and R a2 Independently, it can be H, F, or a hydroxyl group;

[0492] T 2 It is a single bond;

[0493] T 3 Independently 3-6 membered heterocyclic alkylene, -C(HR) a2 )-、-N(R b1 )-、-C(O)N(R b1 - or -N(R) b1 )C(O)-, wherein the heteroatom in the 3-6 membered heterocyclic alkyl group is selected from one or two of N and O, and the number of heteroatoms is one or two;

[0494] R b1 Independently H or C 1-3 alkyl;

[0495] s2 can be 1, 2, 3, 4, 5, 6 or 7 independently;

[0496] s3 can be 1, 2, 3, or 4 independently;

[0497] s4 can be 0, 1, 2, 3 or 4 independently.

[0498] In one embodiment, the compound shown in Formula I is a compound shown in Formula I-2(IA):

[0499] Where T is C 1-8 Alkylene, C 1-8 Heteroalkyl, C 2-8 imidene group, C 2-8 Hesperyl, with one or more R 1-2 Replacement C 1- 8 alkylene groups, with one or more R 1-2 Replacement C 1-8 Heteroalkyl, by one or more R 1-2 Replacement C 2-8 alkenyl groups or those with one or more R groups 1-2 Replacement C 2-8 Hesperyl;

[0500] V is C6-10 Aryl or 5-10 heteroaryl groups;

[0501] The various C 1-8 Heteroalkyl and C 2-8 The heteroatoms or heterogroups in the hesene group are independently selected from one, two, three, four, or five of N, N(H), N(=O), O, C(=O), S, S(=O), S(=O)2, P, P(=O), and P(=O)2, and the total number of heteroatoms and heterogroups is independently 1, 2, 3, 4, or 5.

[0502] R 1 R 2 R 3 R 5 m, n, X, ring A, f1, R a f2, R g R 1-2 The definition is as described in any of the previous schemes; f3 is 0, 1, 2 or 3; when a carbon atom is marked with "*", it is a chiral carbon atom, and it is an R configuration, an S configuration or a mixture thereof;

[0503] Preferably, the compound shown in Formula I is a compound shown in Formula I-2, a compound shown in Formula I-2a, a compound shown in Formula I-2b, or a compound shown in Formula I-2c.

[0504] T, V, R 1 R 2 R 3 m, n, X, ring A, f1, R a f2, R g The definition is as described in Formula I-2(IA); when a carbon atom marked with "*" is a chiral carbon atom, it is in the R configuration, S configuration, or a mixture thereof;

[0505] Preferably, the compound shown in Formula I is a compound shown in Formula I-2:

[0506] Where T is C 1-8 Alkylene, C 1-8 Heteroalkyl, C 2-8 imidene group, C 2-8 Hesperyl, with one or more R 1-2 Replacement C 1- 8 alkylene groups, with one or more R 1-2 Replacement C 1-8 Heteroalkyl, by one or more R 1-2 Replacement C 2-8 alkenyl groups or those with one or more R groups 1-2Replacement C 2-8 Hesperyl;

[0507] V is C 6-10 Aryl or 5-10 heteroaryl groups;

[0508] The various C 1-8 Heteroalkyl and C 2-8 The heteroatoms or heterogroups in the hesene group are independently selected from one, two, three, four, or five of N, N(H), N(=O), O, C(=O), S, S(=O), S(=O)2, P, P(=O), and P(=O)2, and the total number of heteroatoms and heterogroups is independently 1, 2, 3, 4, or 5.

[0509] R 1 R 2 R 3 m, n, X, ring A, f1, R a f2, R g R 1-2 The definition is as described in any embodiment of this invention; when a carbon atom marked with "*" is a chiral carbon atom, it is an R configuration, an S configuration, or a mixture thereof;

[0510] (T can be with) (The ring atoms are connected, and the ring atoms are not the *-marked ring atoms)

[0511] Preferably, the compound shown in Formula I-2 is the compound shown in Formula I-2a.

[0512] Carbon atoms marked with "*" are chiral carbon atoms, which have the R configuration;

[0513] R 1 R 2 and R 3 Independently H or D;

[0514] X is CH2, NH, or O;

[0515] T is C 1-8 Alkylene, C 1-8 Heteroalkyl or C 2-8 alkenyl; the C 1-8 The heteroatoms or heterogroups in the heteroalkylene group can be selected from one, two, or three of N, C (=O), O, and S, and the number of heteroatoms can be one, two, or three.

[0516] Ring A is C 6-10 Aromatic rings or 5-10 heterocyclic aromatic rings;

[0517] R a It is D or halogen;

[0518] V is C 6-10 The aryl or 5-10 heteroaryl (or 5-6 heteroaryl) group, wherein the heteroatom of the 5-10 heteroaryl group is N, and the number of heteroatoms is 1, 2 or 3;

[0519] f2 is 1, 2, or 3;

[0520] Each R g Independently D, amino, Halogen, C 1-6 Alkyl, C 3-6 cycloalkyl, -OC 1-6 Alkyl, C 3-8 Heteroalkyl, 5-10-membered heteroaryl, -O- with one or more R 1-4 The substituted 3-10 membered heterocyclic alkyl group or -O- is replaced by one or more R 1-4 Replacement C 3-8 Heteroalkyl;

[0521] R c and R d Independently hydrogen, C 1-6 Alkyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 3-8 Heteroalkyl, by one or more R 1-4 Replacement C 1-6 Alkyl, with one or more R 1-4 Substituted 3-10 membered heterocyclic alkyl groups or -C(=O)-C 1-6 alkyl;

[0522] Each R 1-4 Independently, deuterium (D), NH2, and NH (C) 1-6 Alkyl), N(C) 1-6 Alkyl)2, hydroxyl or 3-8 membered heterocyclic alkyl;

[0523] Better yet, each R g Independently D, amino, Halogen, -OC 1-6 Alkyl, -O- with one or more R 1-4 The substituted 3-10 membered heterocyclic alkyl group or -O- is replaced by one or more R 1-4 Replacement C 3-8 Heteroalkyl;

[0524] R c and R d Independently hydrogen or C 1-6 alkyl.

[0525] (T can be with) (The ring atoms are connected, and the ring atoms are not the *-marked ring atoms)

[0526] Preferably, the compound shown in Formula I-2 is the compound shown in Formula I-2a.

[0527] Carbon atoms marked with "*" are chiral carbon atoms, which have the R configuration;

[0528] R 1 R 2 and R 3 Independently H or D;

[0529] X is CH2, NH, or O;

[0530] T is C 1-8 Alkylene, C 1-8 Heteroalkyl or C 2-8 alkenyl; the C 1-8 The heteroatoms or heterogroups in the heteroalkylene group can be selected from one, two, or three of N, C (=O), O, and S, and the number of heteroatoms can be one, two, or three.

[0531] Ring A is C 6-10 Aromatic rings;

[0532] R a It is D or halogen;

[0533] V is C 6-10 Aryl or 5-6-membered heteroaryl, wherein the heteroatom of the 5-6-membered heteroaryl is N, and the number of heteroatoms is 1 or 2;

[0534] f2 is 1 or 2;

[0535] Each R g Independently D, amino, Halogen, C 1-6 Alkyl, C 3-6 cycloalkyl, -OC 1-6 Alkyl or C 3-8 Heteroalkyl;

[0536] R c and R d Independently hydrogen, C 1-6 Alkyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 3-8 Heteroalkyl or by one or more R 1-4 Replacement C 1-6 alkyl;

[0537] Each R 1-4 Independently hydroxyl or 3-8 membered heterocyclic alkyl;

[0538] Better yet, each R g Independently D, amino, Or halogen;

[0539] R c and R d Independently hydrogen or C 1-6 alkyl.

[0540] Preferably, the compound shown in Formula I-2 is the compound shown in Formula I-2b.

[0541] Carbon atoms marked with "*" are chiral carbon atoms, which have the R configuration;

[0542] R 1 R 2 and R 3 Independently H or D;

[0543] T is C 1-8 Alkylene, C 1-8 Heteroalkyl or C 2-8 alkenyl; the C 1-8 The heteroatoms or heterogroups in the heteroalkylene group can be selected from one, two, or three of N, C (=O), O, and S, and the number of heteroatoms can be one, two, or three; or T is C. 2-8 Hesperidinyl or with one or more R 1-2 Replacement C 1-8 Heteroalkylene; each R 1-2 Independently halogen, hydroxyl or C 1-6 Alkyl group; or any two R groups 1-2 Together with the atoms attached to it, it forms a 3-6 membered heterocycle; the C 1-8 Heteroalkyl and C 2-8 The heteroatoms or heterogroups in the hesene group are independently selected from one, two, or three of N (H), O, and C (=O), and the total number of heteroatoms and heterogroups is independently one, two, or three.

[0544] Ring A is C 6-10 Aromatic rings or 5-10 heterocyclic aromatic rings;

[0545] R a It is D or halogen;

[0546] V is C 6-10 The aryl or 5-10 heteroaryl (or 5-6 heteroaryl) group, wherein the heteroatom of the 5-10 heteroaryl group is N, and the number of heteroatoms is 1, 2 or 3;

[0547] f2 is 1, 2, or 3;

[0548] Each R g Independently D, amino, Halogen, C 1-6 Alkyl, C 3-6 cycloalkyl, -OC 1-6 Alkyl, C 3-8 Heteroalkyl, 5-10-membered heteroaryl, -O- with one or more R 1-4 The substituted 3-10 membered heterocyclic alkyl group or -O- is replaced by one or more R 1-4 Replacement C 3-8 Heteroalkyl;

[0549] R c and R d Independently hydrogen, C 1-6 Alkyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 3-8 Heteroalkyl, by one or more R 1-4 Replacement C 1-6 Alkyl, with one or more R 1-4 Substituted 3-10 membered heterocyclic alkyl groups or -C(=O)-C 1-6 alkyl;

[0550] Each R 1-4 Independently, deuterium (D), NH2, and NH (C) 1-6 Alkyl), N(C) 1-6 Alkyl)2, hydroxyl or 3-8 membered heterocyclic alkyl;

[0551] Better yet, each R g Independently D, amino, Halogen, -OC 1-6 Alkyl, -O- with one or more R 1-4 The substituted 3-10 membered heterocyclic alkyl group or -O- is replaced by one or more R 1-4 Replacement C 3-8 Heteroalkyl;

[0552] R c and R d Independently hydrogen or C 1-6 alkyl.

[0553] Preferably, the compound shown in Formula I-2 is the compound shown in Formula I-2c.

[0554] Carbon atoms marked "*a" are chiral carbon atoms with an R configuration; carbon atoms marked "*b" are chiral carbon atoms with an R configuration, an S configuration, or a mixture of both.

[0555] R 1 R 2 and R 3Independently H or D;

[0556] T is C 1-8 Alkylene, C 1-8 Heteroalkyl or C 2-8 alkenyl; the C 1-8 The heteroatoms or heterogroups in the heteroalkylene group can be selected from one, two, or three of N, C (=O), O, and S, and the number of heteroatoms can be one, two, or three; or T is C. 2-8 Hesperidinyl or with one or more R 1-2 Replacement C 1-8 Heteroalkylene; each R 1-2 Independently halogen, hydroxyl or C 1-6 Alkyl group; or any two R groups 1-2 Together with the atoms attached to it, it forms a 3-6 membered heterocycle; the C 1-8 Heteroalkyl and C 2-8 The heteroatoms or heterogroups in the hesene group are independently selected from one, two, or three of N (H), O, and C (=O), and the total number of heteroatoms and heterogroups is independently one, two, or three.

[0557] Ring A is C 6-10 Aromatic rings or 5-10 heterocyclic aromatic rings;

[0558] R a It is D or halogen;

[0559] V is C 6-10 The aryl or 5-10 heteroaryl (or 5-6 heteroaryl) group, wherein the heteroatom of the 5-10 heteroaryl group is N, and the number of heteroatoms is 1, 2 or 3;

[0560] f2 is 1, 2, or 3;

[0561] Each R g Independently D, amino, Halogen, C 1-6 Alkyl, C 3-6 cycloalkyl, -OC 1-6 Alkyl, C 3-8 Heteroalkyl, 5-10-membered heteroaryl, -O- with one or more R 1-4 The substituted 3-10 membered heterocyclic alkyl group or -O- is replaced by one or more R 1-4 Replacement C 3-8 Heteroalkyl;

[0562] R c and R d Independently hydrogen, C 1-6 Alkyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic alkyl, C3-8 Heteroalkyl, by one or more R 1-4 Replacement C 1-6 Alkyl, with one or more R 1-4 Substituted 3-10 membered heterocyclic alkyl groups or -C(=O)-C 1-6 alkyl;

[0563] Each R 1-4 Independently, deuterium (D), NH2, and NH (C) 1-6 Alkyl), N(C) 1-6 Alkyl)2, hydroxyl or 3-8 membered heterocyclic alkyl;

[0564] Better yet, each R g Independently D, amino, Halogen, -OC 1-6 Alkyl, -O- with one or more R 1-4 The substituted 3-10 membered heterocyclic alkyl group or -O- is replaced by one or more R 1-4 Replacement C 3-8 Heteroalkyl;

[0565] R c and R d Independently hydrogen or C 1-6 alkyl.

[0566] In one embodiment, the compound shown in Formula I is a compound shown in Formula I-3:

[0567] The compound shown in Formula I-3 optionally satisfies condition (5), R 1 R 2 R 3 m, n, X, ring A, f1, R a V, f2, R g The definition is as described in any embodiment of this invention;

[0568] Preferably, the carbon atom marked with "*" is a chiral carbon atom with an R configuration;

[0569] Each R 1 R 2 and R 3 Independently H or D;

[0570] m and n are independently 1 or 2;

[0571] X is CH2, NH, or O;

[0572] Two Rs 5Together with the atoms attached thereto, they form 3-6 membered heterocycles or 5-6 membered heteroaromatic rings; the heteroatoms or heterogroups of the 3-6 membered heterocycles are selected from one, two, or three of N, C (=O) and O, and the total number of heteroatoms and heterogroups is 1, 2, or 3; the heteroatoms of the 5-6 membered heteroaromatic rings are selected from one or two of N and O, and the number of heteroatoms is 1 or 2;

[0573] Ring A is C 6-10 Aromatic rings;

[0574] f1 is 0, 1, or 2;

[0575] Each R a Independently D or halogen;

[0576] V is a 5-6 membered heteroaryl group, wherein the heteroatom of the 5-6 membered heteroaryl group is N, and the number of heteroatoms is 1, 2 or 3;

[0577] f2 is 0, 1, or 2;

[0578] Each R g Independently D, amino, Halogen, -OC 1-6 Alkyl, -O- with one or more R 1-4 The substituted 3-10 membered heterocyclic alkyl group or -O- is replaced by one or more R 1-4 Replacement C 3-8 Heteroalkyl;

[0579] Ideally, two Rs 5 Together with the atoms attached thereto, they form 3-6 membered heterocycles or 5-6 membered heteroaromatic rings; the heteroatoms of the 3-6 membered heterocycles and 5-6 membered heteroaromatic rings are independently selected from one or two of N and O, and the number of heteroatoms is 1 or 2.

[0580] In one embodiment, the compound shown in Formula I is a compound shown in Formula I-4:

[0581] R 1 R 2 R 3 R 4 L, ring A, f1, R a V, f2, R g The definition is as described in any embodiment of this invention;

[0582] Preferably, the carbon atom marked with "*" is a chiral carbon atom with an R configuration;

[0583] R 1 R 2 and R 3 Independently H or D;

[0584] L represents a single bond or C represents a single bond. 1-4 Alkylene;

[0585] R 4 C 1-4 alkyl;

[0586] Ring A is C 6-10 Aromatic rings or Ring B is a partially saturated 5-6 membered heterocycle, wherein the number of alkene bonds in the partially saturated 5-6 membered heterocycle is 1 or 2, and the heteroatom is selected from one or two of N and O; the number of heteroatoms is 1 or 2.

[0587] f1 and f2 are independently 0, 1 or 2;

[0588] Each R a It is D or halogen;

[0589] V is a 5-6 membered heteroaryl group, wherein the heteroatom of the 5-6 membered heteroaryl group is N, and the number of heteroatoms is 1, 2 or 3;

[0590] Each R g It can be D, amino, or halogen.

[0591] In one embodiment, the compound shown in Formula I is a compound shown in Formulas I-5:

[0592] The compounds shown in Formula I-5 optionally satisfy condition (7) or (8), R 1 R 2 R 3 m, n, ring A, f1, R a V, f2, R g The definition is as described in any embodiment of this invention;

[0593] Preferably, the carbon atom marked with "*" is a chiral carbon atom with an R configuration;

[0594] R 1 R 2 and R 3 Independently H or D;

[0595] m and n are independently 1 or 2;

[0596] R 5 for C 1-4 Alkylene, 3-6 heterocyclic alkyl, with one or more R p Replacement C 1-4 alkylene or by one or more R pThe substituted 3-6 membered heterocyclic alkyl group; the heteroatom of the 3-6 membered heterocyclic alkyl group is selected from one or two of N or O; the number of heteroatoms is one or two;

[0597] Each R p Independent of halogen, C 1-6 alkylene or by one or more R p-1 Replacement C 1-6 alkyl;

[0598] Each R p-1 Independently D or halogen;

[0599] Ring A is C 6-10 Aromatic rings;

[0600] Each R a It is D or halogen;

[0601] V is a 5-6 membered heteroaryl group, wherein the heteroatom of the 5-6 membered heteroaryl group is N, and the number of heteroatoms is 1, 2 or 3;

[0602] Each R g It is D, amino, or halogen;

[0603] f1 and f2 are independently 0, 1 or 2;

[0604] More preferably, in the compounds shown in Formula I-5, for

[0605] In one embodiment, the compound shown in Formula I is a compound shown in Formulas I-6:

[0606] The compounds shown in Formula I-6 optionally satisfy condition (9), R 1 R 2 R 3 m, n, X, ring A, f1, R a V, f2, R g The definition is as described in any embodiment of this invention;

[0607] Preferably, the carbon atom marked with "*" is a chiral carbon atom with an R configuration;

[0608] R 1 R 2 and R 3 Independently H or D;

[0609] m and n are independently 1 or 2;

[0610] X is NH or O;

[0611] Ring A is C6-10 Argan

[0612] f1 is 1, R a for -OC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl or C 3-6 cycloalkyl;

[0613] R c and R d Independently hydrogen or C 1-4 alkyl;

[0614] V is a 5-6 membered heteroaryl group, wherein the heteroatom type of the 5-6 membered heteroaryl group is N, and the number of heteroatoms is 1, 2, or 3; f2 is 0, 1, or 2;

[0615] Each R g It can be D, amino, or halogen.

[0616] In one embodiment, the compound is the compound shown in Formula I-6.

[0617] The compounds shown in Formula I-6 optionally satisfy condition (10), R 1 R 2 R 3 m, n, X, ring A, R a V, f2, R g The definition is as described in any embodiment of this invention;

[0618] Preferably, the carbon atom marked with "*" is a chiral carbon atom with an R configuration;

[0619] R 1 R 2 and R 3 Independently H or D;

[0620] m and n are independently 1 or 2;

[0621] X is NH or O;

[0622] Ring A is C 6-10 Argan

[0623] f1 is 2, R a Independently D or halogen;

[0624] V is a 5-6 membered heteroaryl group, wherein the heteroatom of the 5-6 membered heteroaryl group is N, and the number of heteroatoms is 1, 2 or 3;

[0625] f2 is 1 or 2; each R g It can be halogen or amino on its own.

[0626] In one embodiment, the compound shown in Formula I is a compound shown in Formulas I-7:

[0627] The compounds shown in Formulas I-7 optionally satisfy condition (12), where V is a 3-10 membered heterocyclic alkyl group or a partially saturated 3-10 membered heterocyclic group; R 1 R 2 R 3 m, n, X, ring A, f1, R a f2, R g The definition is as described in any embodiment of this invention;

[0628] Preferably, the carbon atom marked with "*" is a chiral carbon atom with an R configuration;

[0629] R 1 R 2 and R 3 Independently H or D;

[0630] m and n are independently 1 or 2;

[0631] X is NH or O;

[0632] Ring A is C 6-10 Argan

[0633] f1 is 1, R a Independent of D or halogen;

[0634] f2 is 1;

[0635] V is a 3-6 membered heterocyclic alkyl group, wherein the heteroatom type of the 3-6 membered heterocyclic alkyl group is selected from one or two of N and O, and the number of heteroatoms is 1, 2 or 3;

[0636] R g D or C 1-6 alkyl.

[0637] In one embodiment, the compound is the compound shown in Formula I-6.

[0638] The compounds shown in Formula I-6 optionally satisfy condition (13), R 1 R 2 R 3 m, n, X, ring A, f1, R a V, f2, R g The definition is as described in any embodiment of this invention;

[0639] Preferably, the carbon atom marked with "*" is a chiral carbon atom with an R configuration;

[0640] R 1 R 2 and R 3 Independently H or D;

[0641] m and n are independently 1 or 2;

[0642] X is NH or O;

[0643] Ring A is C 6-10 Argan

[0644] f1 is 1, R a Independently D or halogen;

[0645] V is a 5-6 membered heteroaryl group, wherein the heteroatom of the 5-6 membered heteroaryl group is N, and the number of heteroatoms is 1, 2 or 3;

[0646] f2 is independently 1 or 2;

[0647] Each R g Independently amino or And at least one is R g for

[0648] R m and R n Independently for C 1-6 alkyl.

[0649] In one embodiment, the compound represented by Formula I is a compound represented by Formula I-8-1 (IA) or I-8-2 (IB):

[0650] Where T is C 1-8 Alkylene, C 1-8 Heteroalkyl, C 2-8 imidene group, C 2-8 Hesperyl, with one or more R 1-2 Replacement C 1- 8 alkylene groups, with one or more R 1-2 Replacement C 1-8 Heteroalkyl, by one or more R 1-2 Replacement C 2-8 alkenyl groups or those with one or more R groups 1-2 Replacement C 2-8 Hesperyl;

[0651] V is C 6-10 Aryl or 5-10 heteroaryl groups;

[0652] The various C 1-8 Heteroalkyl and C 2-8The heteroatoms or heterogroups in the hesene group are independently selected from one, two, three, four, or five of N, N(H), N(=O), O, C(=O), S, S(=O), S(=O)2, P, P(=O), and P(=O)2, and the total number of heteroatoms and heterogroups is independently 1, 2, 3, 4, or 5.

[0653] R 1 R 2 R 3 p1, p2, q, X1, ring A, f1, R a f2, R g R 1-2 The definition is as described in any of the previous schemes; f3 is 0, 1, 2 or 3; when a carbon atom is marked with "*", it is a chiral carbon atom, and it is an R configuration, an S configuration or a mixture thereof;

[0654] Preferably, the compound shown in Formula I is a compound shown in Formula I-8-1 or I-8-2:

[0655] Where T is C 1-8 Alkylene, C 1-8 Heteroalkyl, C 2-8 imidene group, C 2-8 Hesperyl, with one or more R 1-2 Replacement C 1- 8 alkylene groups, with one or more R 1-2 Replacement C 1-8 Heteroalkyl, by one or more R 1-2 Replacement C 2-8 alkenyl groups or those with one or more R groups 1-2 Replacement C 2-8 Hesperyl;

[0656] V is C 6-10 Aryl or 5-10 heteroaryl groups;

[0657] The various C 1-8 Heteroalkyl and C 2-8 The heteroatoms or heterogroups in the hesene group are independently selected from one, two, three, four, or five of N, N(H), N(=O), O, C(=O), S, S(=O), S(=O)2, P, P(=O), and P(=O)2, and the total number of heteroatoms and heterogroups is independently 1, 2, 3, 4, or 5.

[0658] R 1 R 2 R 3 p1, p2, q, X1, ring A, f1, R af2, R g R 1-2 The definition is as described in the previous scheme; when a carbon atom marked with "*" is a chiral carbon atom, it is in the R configuration, S configuration, or a mixture thereof;

[0659] (T can be with) (The ring atoms are connected, and the ring atoms are not the *-marked ring atoms)

[0660] Preferably, the compound shown in Formula I is a compound shown in Formula I-8a-1 or I-8a-2.

[0661] Where T is C 1-8 Alkylene, C 1-8 Heteroalkyl, C 2-8 imidene group, C 2-8 Hesperyl, with one or more R 1-2 Replacement C 1- 8 alkylene groups, with one or more R 1-2 Replacement C 1-8 Heteroalkyl, by one or more R 1-2 Replacement C 2-8 alkenyl groups or those with one or more R groups 1-2 Replacement C 2-8 Hesperyl;

[0662] V is C 6-10 Aryl or 5-10 heteroaryl groups;

[0663] The various C 1-8 Heteroalkyl and C 2-8 The heteroatoms or heterogroups in the hesene group are independently selected from one, two, three, four, or five of N, N(H), N(=O), O, C(=O), S, S(=O), S(=O)2, P, P(=O), and P(=O)2, and the total number of heteroatoms and heterogroups is independently 1, 2, 3, 4, or 5.

[0664] R 1 R 2 R 3 p1, q, X1, ring A, f1, R a f2, R g R 1-2 The definition is as described in the previous scheme; when a carbon atom marked with "*" is a chiral carbon atom, it is in the R configuration, S configuration, or a mixture thereof;

[0665] (T can be with) (The ring atoms are connected, and the ring atoms are not the *-marked ring atoms)

[0666] Preferably, the compound shown in Formula I is a compound shown in Formula I-8b-1 or I-8b-2.

[0667] Carbon atoms marked with "*" are chiral carbon atoms, which have the R configuration;

[0668] p1 is either 0 or 1;

[0669] R 1 R 2 and R 3 Independently H or D;

[0670] X1 is CH2 or NH;

[0671] T is C 1-8 Alkylene, C 1-8 Heteroalkyl or C 2-8 alkenyl; the C 1-8 The heteroatoms or heterogroups in the heteroalkylene group can be selected from one, two, or three of N, C (=O), O, and S, and the number of heteroatoms can be one, two, or three.

[0672] Ring A is C 6-10 Aromatic rings or 5-10 heterocyclic aromatic rings;

[0673] R a It is D or halogen;

[0674] V is C 6-10 The aryl or 5-10 heteroaryl (or 5-6 heteroaryl) group, wherein the heteroatom of the 5-10 heteroaryl group is N, and the number of heteroatoms is 1, 2 or 3;

[0675] f2 is 1, 2, or 3;

[0676] Each R g Independently D, amino, Halogen, C 1-6 Alkyl, C 3-6 cycloalkyl, -OC 1-6 Alkyl, C 3-8 Heteroalkyl, 5-10-membered heteroaryl, -O- with one or more R 1-4 The substituted 3-10 membered heterocyclic alkyl group or -O- is replaced by one or more R 1-4 Replacement C 3-8 Heteroalkyl;

[0677] R c and R d Independently hydrogen, C 1-6 Alkyl, C 3-6 Cycloalkyl, 3-10 membered heterocyclic alkyl, C 3-8Heteroalkyl, by one or more R 1-4 Replacement C 1-6 Alkyl, with one or more R 1-4 Substituted 3-10 membered heterocyclic alkyl groups or -C(=O)-C 1-6 alkyl;

[0678] Each R 1-4 Independently, deuterium (D), NH2, and NH (C) 1-6 Alkyl), N(C) 1-6 Alkyl)2, hydroxyl or 3-8 membered heterocyclic alkyl.

[0679] (T can be with) (The ring atoms are connected, and the ring atoms are not the *-marked ring atoms)

[0680] In one scheme, V is The "3" bit is connected to ring A, the "2" bit is connected to Rg, and the "1" bit is connected to T.

[0681] In one of the schemes, R 1 R 2 and R 3 For H.

[0682] In one of the schemes, R 4 It is a methyl group.

[0683] In one scheme, the L single bond or When a carbon atom marked with an asterisk (*) is a chiral carbon atom, it is in the R configuration, S configuration, or a mixture thereof; the S configuration is preferred.

[0684] In one of the schemes, R 5 for

[0685] In one of the schemes, R 5 H, methyl, Or oxy group.

[0686] In one scheme, ring A is

[0687] In one of the schemes, for Preferably, position "1" is connected to the carbon atom marked with an asterisk (*) or to the L atom, and position "2" is connected to the Y atom or to the V atom; more preferably, for The "1" position is connected to the carbon atom marked with an asterisk (*), and the "2" position is connected to V. Further, and even better, this...

[0688] In one of the schemes, for Preferably, position "1" is connected to the carbon atom marked with an asterisk (*) or to the L atom, and position "2" is connected to the Y atom or to the V atom; more preferably, for The "1" position is connected to the carbon atom marked with an asterisk (*), and the "2" position is connected to V. Further, and even better, this...

[0689] In one of the schemes, R a For oxo, fluorine, chlorine, cyano,

[0690] In one of the schemes, R a For Br, Methyl, cyano, CF3 or

[0691] In one scheme, Y is a single bond or Better place, The carbonyl group in the ring is connected to ring A.

[0692] In one scheme, V is V passed Connect to ring A.

[0693] In one scheme, V is V passed Connect to ring A.

[0694] In one of the schemes, for Bit "1" is connected to ring A, and bit "2" is connected to one of the R's. 5 Connect, f2-1 is 0, 1, 2 or 3 (f2-1 represents the number of 1s minus f2); In for

[0695] In one of the schemes, R g It is fluorine, amino, cyano, methyl, methoxy,

[0696] In one of the schemes, R g for

[0697] In one scheme, T is Ideally, the "1" position is... The ring atoms (not the *-marked ring atoms) are connected, and the "2" position is connected to V.

[0698] In one scheme, T is

[0699] In one embodiment, the compound represented by Formula I is any one of the following compounds: Z2, Z3, Z1-1, Z4, Z5, Z6, Z7, Z8, Z9, Z10, Z11, Z12-1, Z13, Z14, Z20, Z21, Z22, Z23, Z24, Z25, Z26, Z27, Z28, Z29, Z30, Z31, Z32, Z33, Z34, Z35, Z36, Z37, Z38, Z39, Z40, Z41, Z42, Z43, Z71, Z72, Z73, Z74, Z44, Z45, Z46, Z47, Z48, Z49, Z50, Z51, Z52, Z53, Z54, Z55, Z56, Z57, Z58, Z59. Z60, Z61, Z62, Z63, Z64, Z65, Z66, Z67, Z68, Z69, Z70, Z75, Z76, Z77, Z78, Z7 9. Z80, Z81, Z82, Z83, Z84, Z85, Z86, Z87, Z88, Z89, Z90, Z91, Z92, Z93, Z94, Z 95, Z96, Z97, Z98, Z99, Z101, Z102, Z103, Z104, Z105, Z106, Z107, Z108, Z10 9. Z110, Z111, Z112, Z113, Z114, Z115, Z116, Z117, Z118, Z119, Z120, Z121, Z 122, Z123, Z124, Z15, Z16, Z17, Z18, Z19, Z130, Z131, Z132, Z133, Z134, Z13 5. Z136, Z137, Z138, Z139, Z140, Z141, Z142, Z143, Z144, Z145, Z146, Z147, Z 148, Z149, Z150, Z151, Z152, Z153, Z154, Z155, Z156, Z157, Z158, Z159, Z16 0. Z161, Z162, Z163, Z164, Z166, Z175, Z165, Z167, Z168, Z169, Z67-1, Z171, Z172, Z173, Z174, Z45A, Z62A, Z125, Z126, Z127, Z170, Z122A, Z176, Z177, Z 178, Z209, Z210, Z211, Z212, Z214, Z213, Z215, Z216, Z217, Z218, Z219, Z220 , Z221, Z222, Z223, Z224, Z225, Z226, Z227, Z228, Z229, Z230, Z231, Z232, Z2 33. Z234, Z235, Z236, Z237, Z238, Z239, Z240, Z241, Z242, Z243, Z244, Z245,Z246、Z247、Z248、Z249、Z250、Z251、Z252、Z253、Z254、Z255、Z256、Z257、Z258、Z259、Z260、Z261、Z262、Z263、Z264、Z1、Z12、Z128、Z265、Z266、Z267、Z268、Z269、Z129、Z270、Z271、Z272、Z273、Z274、Z275、Z276、Z277A、Z277、Z300、Z278、Z279、Z280、Z288、Z281、Z282、Z283、Z284、Z285、Z286、Z287、Z293、Z289、Z290、Z291、Z292、Z297、Z298、Z295、Z296、Z331、Z332、Z333、Z335、Z336、Z337、Z348、Z338、Z318、Z340、Z339、Z342、Z334、Z334-A、Z334-B、Z343、Z344、Z345、Z346、Z347、Z341、Z319、Z349、Z315A、Z350、Z315、Z372、Z373、Z374、Z375、Z376、Z179、Z180、Z181、Z182、Z183、Z184、Z185、Z186、Z187、Z188、Z189、Z190、Z191、Z192、Z193、Z194、Z195、Z196、Z197、Z198、Z199、Z200、Z201、Z202、Z203、Z204、Z205、Z206、Z207、Z208、Z330、Z294、Z301、Z302、Z303、Z304、Z305、Z306、Z307、Z308、Z309、Z310、Z311、Z312、Z313、Z314、Z316、Z317、Z320、Z321、Z322、Z323、Z324、Z325、Z326、Z327、Z328、Z329、Z351、Z352、Z353、Z354、Z355、Z356、Z357、Z358、Z359、Z360、Z361、Z362、Z363、Z364、Z365、Z366、Z367、Z368、Z369、Z370、Z377、Z378、Z379、Z380、Z381、Z382、Z383、Z384、Z385、Z237A、Z386、Z303A、Z305A、Z303B、Z387、Z388、Z389、Z390、Z391、Z392、Z310A、Z310B、Z393、Z394、Z327A、Z327B、Z395、Z396、Z402、Z403、Z397、Z404, Z405, Z398, Z399, Z406, Z407, Z400A, Z400, Z401, Z408, Z409, Z410A, Z410, Z411, Z412, Z413, Z418, Z419, Z414, Z415, Z416A, Z416, Z417, Z438A, Z438, Z439, Z440, Z421, Z420, Z422, Z423, Z424, Z425, Z426, Z427, Z428, Z429, Z430, Z431, Z432, Z433, Z434, Z43 5. Z436, Z437, Z441, Z442, Z443, Z444, Z445, Z446, Z447, Z448, Z449, Z450, Z451, Z452, Z453, Z454, Z455, Z456, Z457, Z458, Z459, Z460, Z461, Z462, Z463, Z464, Z465, Z466, Z467, Z468, Z469, Z470, Z471, Z472, Z473, Z474, Z475, Z476, Z477, Z478, Z479, Z480, and Z481.

[0700] In one embodiment, the compound represented by Formula I is: IC under the following test method 50 The value ranges from 0.1 nM to 80 nM, for example, 0.2 nM to 15 nM, or 0.4 nM to 10 nM.

[0701] The test method was to use the FastScan Total NRF2 ELISA Kit to detect the level of Human NRF2 protein in KYSE70 cells.

[0702] In one embodiment, the compound represented by Formula I is any of the following compounds:

[0703] compound The first group of compounds to elute under chromatographic conditions A, wherein chromatographic conditions A are as follows: column: Welch Xtimate C18, 21.2*150mm, 5μm; mobile phase A: 0.1% formic acid aqueous solution; mobile phase B: acetonitrile; mobile phase gradient: the volume percentage of mobile phase B increases from 40% to 95%, gradient elution time is 13 min; flow rate: 15 mL / min; column temperature: room temperature; preferably, the retention time of the first group of compounds to elute is 6.642 min.

[0704] Or, compounds Preferably, the retention time of the group of compounds that elute later under the chromatographic conditions A is 7.058 min.

[0705] Or, compounds The group of compounds that elute first under chromatographic condition A, and then the group of compounds that elute first under chromatographic condition B, wherein chromatographic condition B is: column: Daicel IH 250*4.6mm, 5μm; Mobile phase A: n-hexane + 0.2% trifluoroacetic acid (V / V), Mobile phase B: ethanol + 0.2% trifluoroacetic acid (V / V); Mobile phase A: Mobile phase B = 30:70 (V / V), isocratic elution, detection wavelength: 254 / 214nm; Flow rate: 1mL / min; Column temperature: 30℃; Preferably, under the chromatographic conditions B, the retention time of the first eluting compound is 5.770min;

[0706] Alternatively, compound Z128 is the compound that first elutes under chromatographic conditions C, wherein chromatographic conditions C are: Daicel IA250*4.6mm, 5μm; mobile phase: carbon dioxide: ethanol = 50:50 (V:V); isocratic elution, flow rate: 3mL / min; column temperature 40℃; preferably, the retention time of the first eluting compound is 3.98min;

[0707] Alternatively, compound Z174 is the compound that first elutes under chromatographic conditions D, wherein chromatographic conditions D are... ID, 10 μm, 30*250 mm, mobile phase: acetonitrile:isopropanol = 85:15 (V / V), isocratic elution, flow rate: 25 mL / min, column temperature: room temperature; preferably, the retention time of the first eluting compound is 6.278 min;

[0708] Or, compounds The first group of compounds to elute under chromatographic conditions E are: Waters XBridge C18, 19*250mm, 5μm; mobile phase system: A: 0.1% formic acid aqueous solution; B: acetonitrile; flow rate: 15mL / min; mobile phase gradient: the volume percentage of mobile phase B increases from 20% to 100%; gradient elution time: 20min; column temperature: room temperature; preferably, the retention time of the first group of compounds to elute is 6.220min.

[0709] Alternatively, the compound Z217 that elutes later under chromatographic condition F, wherein chromatographic condition F is DAICEL. IB, 5μm, 4.6*250mm; Mobile phase A: n-hexane (0.2% diethylamine), Mobile phase B: isopropanol (0.2% diethylamine); Mobile phase A: Mobile phase B = 30:70 (V / V), isocratic elution, flow rate: 1mL / min; Column temperature 30℃; Preferably, the retention time of the later eluting compound is 9.89min;

[0710] Or, compounds The group of compounds that elute first under the chromatographic conditions A preferably has a retention time of 7.44 min.

[0711] Or, compounds Preferably, the retention time of the group of compounds that elute later under the chromatographic conditions A is 7.93 min.

[0712] Or, compounds A group of compounds that elute first under chromatographic condition A are then subjected to chromatographic condition G, where chromatographic condition G is DAICEL. IA, 150mm*4.6mm*5μm, mobile phase: n-hexane:isopropanol:diethylamine = 50:50:0.2 (V / V / V), isocratic elution, flow rate: 1mL / min, column temperature 30℃; preferably, under the chromatographic conditions G, the retention time of the first eluting compound is 7.090min;

[0713] Or, compounds The group of compounds that elute first under chromatographic condition A are then elute later under chromatographic condition G; preferably, the retention time of the compounds that elute later under chromatographic condition G is 8.153 min.

[0714] Or, compounds (For example, compound Z220) is a compound that elutes first under chromatographic condition I, where chromatographic condition I is Daicel. IH 250*4.6mm, 5μm; Mobile phase A: n-hexane + 0.2% TFA (V / V), Mobile phase B: ethanol + 0.2% TFA (V / V); Mobile phase A: Mobile phase B = 30:70 (V / V), isocratic elution, detection wavelength: 254 / 214nm; Flow rate: 1mL / min; Column temperature: 30℃; Preferably, the retention time of the first eluting compound is 6.347min;

[0715] Alternatively, the group of compounds that elute first under chromatographic conditions H for compound Z277A, wherein chromatographic conditions H are: Welch Ultimate C18, 21.2*150mm, 5μm; mobile phase A: 0.1% trifluoroacetic acid aqueous solution, mobile phase B: acetonitrile; flow rate: 15mL / min; volume percentage of mobile phase gradient B increasing from 40% to 95%; gradient elution time: 13min; column temperature: room temperature; preferably, the retention time of the group of compounds that elute first is 5.995min.

[0716] Alternatively, a group of compounds that elute later under chromatographic conditions H, preferably, the retention time of the group of compounds that elute earlier is 6.019 min;

[0717] Alternatively, a group of compounds that first elute under chromatographic condition H, and then the compound that first elutes under chromatographic condition J, wherein chromatographic condition J is DAICEL. IG, 5μm, 4.6*250mm; Mobile phase A: acetonitrile (0.2% diethylamine), mobile phase B: isopropanol (0.2% diethylamine); mobile phase A: mobile phase B = 70:30 (V / V), isocratic elution; flow rate: 1mL / min; column temperature 30℃. Preferably, under the chromatographic conditions J, the retention time of the first eluting compound is 5.187min.

[0718] Alternatively, the group of compounds that first elute under chromatographic condition H of compound Z277A is then subjected to chromatographic condition J, wherein the retention time of the compound that elutes later under chromatographic condition J is preferably 6.237 min.

[0719] Or, compounds The compound that elutes first under chromatographic condition A has the same carbon atom configuration as the group of compounds that elute first under chromatographic condition H for compound Z277A. Preferably, the retention time of the compound that elutes first is 8.093 min.

[0720] Or, compounds The compound that elutes later under chromatographic condition A has the same carbon atom configuration as the group of compounds that elute earlier under chromatographic condition H for compound 277A. Preferably, the retention time of the compound that elutes later is 8.751 min.

[0721] Alternatively, the compound Z280 that first elutes under chromatographic condition K, wherein chromatographic condition K is DAICEL. IE, 5μm, 4.6*250mm; Mobile phase A: n-hexane, Mobile phase B: isopropanol; A / B = 50 / 50 (v / v); Isocratic elution, Flow rate: 1mL / min; Column temperature 30℃, Preferably, the retention time of the first eluting compound is 11.913min;

[0722] Alternatively, compound Z280 is a compound that elutes later under the chromatographic conditions K, preferably, the retention time of the compound that elutes later is 14.474 min;

[0723] Alternatively, compound Z287 is the compound that first elutes under chromatographic condition L, where chromatographic condition L is DAICEL. IG, 5μm, 4.6*250mm; Mobile phase A: acetonitrile (0.2% diethylamine), mobile phase B: isopropanol (0.2% diethylamine); mobile phase A: mobile phase B = 70:30 (V / V); isocratic elution, flow rate: 1mL / min; column temperature 30℃, preferably, the retention time of the first eluting compound is 5.605min;

[0724] Alternatively, the compound Z292 is the first eluting compound under chromatographic conditions M, wherein chromatographic conditions M are: 150 mm * 4.6 mm * 5 μm, mobile phase: acetonitrile: isopropanol: diethylamine 80-20-02 (V / V / V), isocratic elution, flow rate: 1 mL / min, column temperature 30 °C, preferably, the retention time of the first eluting compound is 5.281 min;

[0725] Alternatively, the group of compounds that elute first under chromatographic condition N, and the group that elutes first under chromatographic condition O, are compounds Z334.

[0726] The chromatographic conditions N are: Column: Daicel IG 250*30mm, 10μm; Mobile phase A: HEX (n-hexane) + 0.2% FA (formic acid) (V / V), Mobile phase B: ETOH (ethanol) + 0.2% FA (V / V); Detection wavelength: 254 / 214nm; Flow rate: 25mL / min; Column temperature: 30℃; Isogradient elution program: Mobile phase A: Mobile phase B = 30:70 (V / V);

[0727] The chromatographic conditions O are: Daicel IE 250*30mm, 10μm; Mobile phase A: HEX + 0.2% FA (V / V), Mobile phase B: ETOH + 0.2% FA (V / V), Mobile phase A: Mobile phase B = 40:60 (V / V), isocratic elution, Detection wavelength: 254 / 214nm; Flow rate: 25mL / min; Column temperature: 30℃;

[0728] Preferably, the retention times of the first eluting compound under chromatographic condition N are 11.745 min and 12.094 min; the retention time of the first eluting compound under chromatographic condition O is 8.683 min.

[0729] Alternatively, compound Z334 is a compound that first elutes under chromatographic condition N and then elutes under chromatographic condition O. Preferably, the compound that elutes under chromatographic condition O elutes after 11.132 min.

[0730] Or, compounds The compound that elutes first under chromatographic conditions E, preferably, has a retention time of 5.149 min.

[0731] Alternatively, compound Z338 is the first compound to elute under the chromatographic conditions K, preferably, the retention time of the first-eluting compound is 7.089 min;

[0732] Alternatively, the compound Z341 is the first to elute under chromatographic conditions P, wherein chromatographic conditions P are: column ID, 150 mm * 4.6 mm * 5 μm, mobile phase: HEX:ETOH:DEA (n-hexane:ethanol:diethylamine) = 40:60:0.2 (V / V / V), isocratic elution, flow rate: 1 mL / min, column temperature 30 °C. Preferably, the retention time of the first-eluting compound is 7.456 min.

[0733] Or, compounds The compound that elutes first under chromatographic conditions Q, where Q is the separation column: DAICEL. IG, 150mm*4.6mm*5μm, mobile phase: ACN:ETOH:DEA (acetonitrile:ethanol:diethylamine) = 60:40:0.2 (V / V / V), isocratic elution, flow rate: 1mL / min, column temperature 30℃, preferably, the retention time of the first eluting compound is 7.042 min.

[0734] Or, compounds The compound that elutes first under the chromatographic conditions H preferably has a retention time of 5.044 min.

[0735] Alternatively, compound Z310A is the compound that elutes first under the chromatographic conditions E, preferably, the retention time of the first-eluting compound is 1.00 min;

[0736] Alternatively, compound Z396 is the compound that elutes first under the chromatographic conditions R, where R is the chromatographic column: IF, 10μm, 30*250mm; Mobile phase A: HEX + 0.2% DEA; Mobile phase B: ETOH + 0.2% DEA; Flow rate: 1.0mL / min; Isogradient elution program: Mobile phase A: Mobile phase B = 50:50 (V / V), Column temperature: 30℃; Preferably, the retention time of the first eluting compound is 6.363min.

[0737] Or, compounds The compound that elutes first under the chromatographic conditions S, wherein chromatographic conditions S is the chromatographic column: Column ID 30*250mm, 10μm; Mobile phase A: ACN, Mobile phase B: IPA (isopropanol); Mobile phase A: Mobile phase B = 60:40 (V / V), isocratic elution, detection wavelength: 254 / 214nm; Flow rate: 1.0mL / min; Column temperature: 30℃; Preferably, the retention time of the first eluting compound is 5.099min;

[0738] Or, compounds The compound that elutes later under the chromatographic conditions S preferably has a retention time of 5.121 min.

[0739] Alternatively, compound Z399 is the compound that elutes first under the chromatographic conditions T, where T is a DAICEL column. IF, 150mm*4.6mm*5μm, mobile phase: ACN:IPA:DEA=60:40:0.2(V / V / V), isocratic elution, flow rate: 1mL / min, column temperature=30℃, preferably, the retention time of the first eluted compound is 5.375min;

[0740] Alternatively, compound Z410A is the first eluting compound under the chromatographic conditions E, preferably, the retention time of the first eluting compound is 7.58 min;

[0741] Alternatively, compound Z410A is a compound that elutes later under the chromatographic conditions E, preferably, the retention time of the later-eluting compound is 7.99 min;

[0742] Alternatively, compound Z303A is the first eluting compound under the chromatographic condition H, and the retention time of the first eluting compound is 6.150 min;

[0743] Alternatively, compound Z303A is the second eluting compound under the chromatographic condition H, and the retention time of the second eluting compound is 6.245 min;

[0744] Alternatively, compound Z367 is the first eluting compound under the chromatographic conditions E, preferably, the retention time of the first eluting compound is 4.835 min;

[0745] Alternatively, compound Z367 is a compound that elutes later under the chromatographic conditions E, preferably, the retention time of the later-eluting compound is 4.789 min;

[0746] Alternatively, compound Z416 is the compound that elutes later under the chromatographic conditions U, where U is the chromatographic column: ID, 150mm*4.6mm*5μm, mobile phase: ACN:IPA:DEA=70:30:0.2(V / V / V), isocratic elution, flow rate: 1mL / min, column temperature=30℃, preferably, the retention time of the later eluting compound is 4.925min;

[0747] Or, compounds The compound that elutes later under the chromatographic conditions V, wherein the chromatographic conditions V are as follows: column type: IH 250 mm, 10 mm, 5 μm; mobile phase system: (A: n-hexane; B: ethanol; C: diethylamine); flow rate: 1 mL / min; A:B:C = 30 / 70 / 0.2 (V / V / V); isocratic elution; column temperature: 30 °C; preferably, the retention time of the compound that elutes later is 10.012 min.

[0748] Alternatively, compound Z438A is the first eluting compound under the chromatographic condition H, preferably, the retention time of the first eluting compound is 5.380 min;

[0749] Or, compounds (For example, compound Z479) is a compound that elutes first under the following chromatographic conditions: column: Daicel. IH 250*30mm, 10μm; Mobile phase A: HEX + 0.2% TFA (V / V), Mobile phase B: ETOH + 0.2% TFA (V / V), Mobile phase A: Mobile phase B = 20:80 (V / V), isocratic elution, Detection wavelength: 254 / 214nm; Flow rate: 25mL / min; Column temperature: room temperature; Preferably, the retention time of the first eluting compound is 5.703min.

[0750] In the above chromatographic conditions, the room temperature is 20-30°C, for example, 25°C.

[0751] The present invention provides a pharmaceutical composition comprising (therapeuticly effective amounts) a compound of Formula I as described in any of the preceding embodiments, its stereoisomers, its isotopically labeled compounds, its solvates, its prodrugs, its nitrides, or pharmaceutically acceptable salts thereof; and pharmaceutical excipients.

[0752] This invention provides the use of a compound of Formula I as described in any of the preceding embodiments, its stereoisomers, its isotopically labeled compounds, its solvates, its prodrugs, its nitrides or pharmaceutically acceptable salts thereof, or the above-described pharmaceutical compositions in the preparation of a medicament for the prevention or treatment of cancer, wherein the cancer may be esophageal cancer, pancreatic cancer, head and neck cancer, cervical cancer, uterine cancer, lung cancer, ovarian cancer, bladder cancer, liver cancer, bile duct cancer, colon cancer, breast cancer, gastric cancer or kidney cancer.

[0753] In one embodiment, the cancer may be non-small cell lung cancer, squamous non-small cell lung cancer, lung adenocarcinoma, esophageal squamous cell carcinoma, esophageal adenocarcinoma, head and neck squamous cell carcinoma, squamous cell bladder cancer, endometrial cancer, or cervical squamous cell carcinoma.

[0754] In one embodiment, the cancer may be esophageal squamous cell carcinoma, lung adenocarcinoma, lung squamous cell carcinoma, head and neck squamous cell carcinoma, cervical squamous cell carcinoma, or endometrial cancer.

[0755] In one embodiment, the lung cancer may be adenocarcinoma or squamous cell carcinoma of the lung.

[0756] In one embodiment, the lung cancer is either human small cell lung cancer or human non-small cell lung cancer.

[0757] The present invention provides the use of a compound of Formula I as described in any of the preceding embodiments, its stereoisomers, its isotopically labeled compounds, its solvates, its prodrugs, its nitrides or pharmaceutically acceptable salts thereof, or the above-described pharmaceutical compositions in the preparation of a medicament for the prevention or treatment of diseases associated with KEAP1 and / or NRF2 proteins, preferably, said disease being cancer.

[0758] In one embodiment, the cancer may be esophageal cancer, pancreatic cancer, head and neck cancer, cervical cancer, uterine cancer, lung cancer, ovarian cancer, bladder cancer, liver cancer, bile duct cancer, colon cancer, breast cancer, stomach cancer, or kidney cancer.

[0759] In one embodiment, the cancer may be non-small cell lung cancer, squamous non-small cell lung cancer, lung adenocarcinoma, esophageal squamous cell carcinoma, esophageal adenocarcinoma, head and neck squamous cell carcinoma, squamous cell bladder cancer, endometrial cancer, or cervical squamous cell carcinoma.

[0760] In one embodiment, the cancer is esophageal squamous cell carcinoma, lung adenocarcinoma, lung squamous cell carcinoma, head and neck squamous cell carcinoma, cervical squamous cell carcinoma, or endometrial cancer.

[0761] In one embodiment, the lung cancer may be adenocarcinoma or squamous cell carcinoma of the lung.

[0762] In one embodiment, the cancer is lung cancer, such as human small cell lung cancer or human non-small cell lung cancer.

[0763] In one embodiment, the cancer is a cancer associated with the KEAP1 and / or NRF2 proteins.

[0764] The present invention provides a method of treating cancer comprising administering to a subject (therapeuticly effective amount) a compound of Formula I as described in any embodiment of the present invention, its stereoisomer, its isotopically labeled compound, its solvate, its prodrug, its nitride, or a pharmaceutically acceptable salt thereof; or a pharmaceutical composition thereof.

[0765] Terminology Definition

[0766] Unless otherwise specified, use wedge-shaped solid line keys. and wedge-shaped dashed key The absolute configuration of the center of a solid is represented by a straight solid line key. and straight dashed key The relative configuration of the center of a solid is indicated by a wavy line. Indicates wedge-shaped solid line key or wedge-shaped dashed key Or use wavy lines Indicates a straight solid line key Or straight dashed key

[0767] The "-" at the end of a group indicates that the group is connected to the rest of the molecule through that site; the "-" at the end of a structural segment This refers to the structural segment being connected to the rest of the molecule through this site, for example, It refers to cyclohexyl.

[0768] If a linking group is indicated as "absent or single bond", then the structures on both sides of the linking group are directly connected by a single bond. For example, -ABC-, when B is a single bond, -ABC- is -AC-.

[0769] In this invention, any combination of variables is permitted only if such a combination produces a stable compound.

[0770] In this invention, when any variable appears more than once in the composition or structure of a compound, its definition is independent in each case. For example, when R is substituted by one or more groups, each substituent is an independent substituent, which can be the same or different.

[0771] The term "multiple" refers to 2, 3, 4 or 5, preferably 2 or 3.

[0772] The term "pharmaceutically acceptable" means that the salts, solvents, excipients, etc., are generally non-toxic, safe, and suitable for patient use. The term "patient" preferably refers to a mammal, and more preferably a human.

[0773] The term "pharmaceutically acceptable salt" refers to a salt prepared from the compounds of this invention with a relatively non-toxic, pharmaceutically acceptable acid or base.

[0774] The term "oxo group" refers to =O (e.g., when connected to C or S, it is C=O, S=O / SO2) or O - (For example, together with N to form N) + O - ).

[0775] The term "halogen" refers to fluorine, chlorine, bromine, or iodine.

[0776] The term "alkyl" refers to an alkyl group having a specified number of carbon atoms (e.g., C10, C20, C30, C40, C50, C60, C7 ...60, C70, C60, C60, C70, C60, C70, C60 1-6 Alkyl groups are straight-chain or branched alkyl groups. Alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl, sec-butyl, n-pentyl, and n-hexyl.

[0777] The term "alkylene" refers to a substituent formed by eliminating two hydrogen atoms from a saturated straight-chain or branched alkane. The two eliminated hydrogen atoms can be on the same carbon atom or on different carbon atoms (e.g., the two eliminated hydrogen atoms are on the carbon atoms at the two ends). For example, C1 alkylene (i.e., methylene) refers to -CH2- or CH2=, and C2 alkylene (i.e., ethylene) refers to -CH2-CH2- or -CH(CH3)-.

[0778] The term "heteroalkyl" refers to an alkyl group in which the methylene (-CH2-) is surrounded by a heteroatom or heterogroup (such as N, N(H), N(=O) or [N... + (O) - Substituted by ]), O, C(=O), S, S(=O), S(=O)2, P, P(=O), P(=O)2), including straight-chain or branched heteroalkylene groups; C 1-8 Heteroalkyl refers to an alkyl group containing 1-8 carbon atoms in which at least one methylene group is replaced by a heteroatom or heterogroup.

[0779] The term "heteroalkylene" refers to the alkylene group in which the methylene (-CH2-) is surrounded by a heteroatom or heterogroup (such as N, N(H), N(=O)) (or [N + (O) - Substituted by ]), O, C(=O), S, S(=O), S(=O)2, P, P(=O), P(=O)2), including straight-chain or branched heteroalkylene groups; C 1-8-heteroalkyl refers to an alkyl group containing 1-8 carbon atoms in which at least one methylene group is substituted by a heteroatom or heterogroup, for example...

[0780] The term "alkoxy group" refers to the group -OR X , where R X It is an alkyl group as defined above.

[0781] The term "alkenyl" refers to an alkenyl group having a specified number of carbon atoms (e.g., C10, C20, C30, C40, C50, C60, C70, C80, C9 ... 2-6 Alkenes are straight-chain or branched olefins containing one or more carbon-carbon double bonds and no carbon-carbon triple bonds. The one or more carbon-carbon double bonds can be internal or terminal. Examples of alkenes include vinyl, allyl, methyl vinyl, propenyl, butenyl, pentenyl, 1,1-dimethyl-2-propenyl, hexenyl, etc.

[0782] The term "alkenyl" refers to a group having a specific number of carbon atoms (e.g., C10, C20, C30, C40, C50, C60, C70, C80, C9 ... 2-6 A substituent is a substituent formed by eliminating two hydrogen atoms from a straight-chain or branched alkene containing one or more carbon-carbon double bonds and no carbon-carbon triple bonds. The carbon-carbon double bonds can be located anywhere within the alkenyl group, and the two eliminated hydrogen atoms can be on the same carbon atom or on different carbon atoms (e.g., the two eliminated hydrogen atoms are on the carbon atoms at opposite ends). Therefore, C2 alkenyl groups (i.e., vinylidenes) include, but are not limited to, -CH=CH-, and C3 alkenyl groups include, but are not limited to, -CH2-CH=CH-. and -C(CH3)=CH-,

[0783] The term "hemeigenyl" refers to the methylene (-CH2-) or CH unit in an ethylene group surrounded by a heteroatom or heterogroup (such as N, N(H), N(=O)) (or [N + (O) - Substituted by ]), O, C(=O), S, S(=O), S(=O)2, P, P(=O), P(=O)2), including straight-chain or branched heteroene groups; C 2-8 An imidene group refers to an imidene group containing 2-8 carbon atoms in which at least one of the methylene (-CH2-) or CH units is replaced by a heteroatom or heterogroup.

[0784] The term "alkynyl" refers to a group having a specified number of carbon atoms (e.g., C10, C20, C30, C40, C50, C60, C70, C80, C9 ... 2-6 One or more carbon-carbon triple bonds in a straight-chain or branched hydrocarbon group (e.g., C10, C20, C30, C40, C50, C60, C70, C80, C9 ... 2-6 (Alynyl group). The one or more carbon-carbon triple bonds can be internal or terminal, for example, propynyl group with the triple bond internal. Or a propynyl group at the end of the triple bond wait.

[0785] The term "cycloalkyl" refers to a ring with a specified number of carbon atoms (e.g., C15, C25, C35, C45, C5 ... 3-10 The monovalent saturated cyclic alkyl group, preferably having 3-6 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

[0786] The term "carbon ring" refers to a ring with only a specified number of carbon atoms (e.g., C15, C25, C35, C45, C55, C65, C7 ... 3-10 The cyclic system is saturated or partially saturated (e.g., having one or more double or triple bonds) and does not have an aromatic cyclic system, preferably a cyclic system with 3-6 carbon atoms, such as cyclopropane, cyclobutane, cyclopentane, cyclohexane, and cyclohexene. The carbon ring is connected to the rest of the molecule by a single bond; or shares one or more atoms and / or one or more bonds with the rest of the molecule.

[0787] The term "heterocyclic alkyl" refers to a heteroatom or heterogroup having a specified number of ring atoms (e.g., 3-10, 3-8, 3-6), a specified number of heteroatoms (e.g., 1, 2, or 3), or a specified number of heteroatoms or heterogroups (e.g., N, N(H), N(=O)) (or [N + (O) - Cyclic groups (one, two, three, four, or five of the following: ]), O, C(=O), S, S(=O), S(=O)2, P, P(=O), P(=O)2, preferably monocyclic. Heterocyclic alkyl groups include, but are not limited to, azaheterocyclic butyl, tetrahydropyrrolyl, tetrahydrofuranyl, morpholinyl, and piperidinyl.

[0788] The term "heterocycle" refers to a ring with a specified number of ring atoms (e.g., 3-10, 3-6), a specified number of heteroatoms (e.g., 1, 2, or 3), or a specified heteroatom or heterogroup (e.g., N, N(H), N(=O)) (or [N + (O) - A saturated or partially saturated cyclic system consisting of one, two, three, four, or five of the following: O, C(=O), S, S(=O), S(=O)2, P, P(=O), P(=O)2. The heterocycle is connected to the rest of the molecule by a single bond; or shares two or more atoms and one or more bonds with the rest of the molecule.

[0789] The definition of "saturated heterocycle" is the same as that of "heterocyclic alkyl".

[0790] A "partially saturated heterocycle" refers to a cyclic system having one or more double or triple bonds and lacking aromaticity. The heterocycle is preferably a monocyclic ring. Partially saturated heterocycles include, but are not limited to, those described above.

[0791] The term "aryl" refers to an aryl group having a specified number of carbon atoms (e.g., C36). 6-10Aryl groups are cyclic groups consisting solely of carbon atoms, which can be monocyclic or polycyclic, and all are aromatic (conforming to Hückel's rule). Aryl groups include, but are not limited to, phenyl and naphthyl groups.

[0792] The term "aromatic ring" is defined the same as "aryl," and the aromatic ring is connected to the rest of the molecule by a single bond; or shares two atoms and one bond with the rest of the molecule.

[0793] The term "heteroaryl" refers to a heteroaryl group containing a specified number of ring atoms (e.g., 5-10, 5-6), a specified number of heteroatoms (e.g., 1, 2, or 3), and a specified type of heteroatom or heterogroup (N, N(=O) (or [N]). + (O) - The aromatic group (one, two, or three of O and S) is a monocyclic or polycyclic aromatic group. When polycyclic, each ring is aromatic and has at least one heteroatom. Monocyclic is preferred; examples include, but are not limited to, pyrazolyl, imidazolyl, thiophene, pyridinyl, pyrimidinyl, or pyrazinyl.

[0794] The term "heteroaromatic ring" is defined the same as "heteroaryl," and the heteroaromatic ring is connected to the rest of the molecule by a single bond; or shares two atoms and one bond with the rest of the molecule.

[0795] The alkyl, alkylene, alkoxy, alkenyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, heteroalkane ring, olefin ring, heteroolefin ring, aryl, aromatic ring, heteroaryl, heteroaromatic ring, etc. groups described in this invention may be substituted or unsubstituted. When substituted, the substituent is preferably one or more of the substituent groups described in this application.

[0796] The compounds of this invention can exist in specific geometric or stereoisomeric forms. This invention contemplates all such compounds, including cis and trans isomers, (-)- and (+)- enantiomers, (R)- and (S)- enantiomers, diastereomers, (D)- isomers, (L)- isomers, and racemic mixtures thereof, as well as other mixtures, such as mixtures enriched with enantiomers or diastereomers, all of which are within the scope of this invention. Additional asymmetric carbon atoms may be present in substituents such as alkyl groups. All such isomers and mixtures thereof are included within the scope of this invention.

[0797] Unless otherwise specified, the structures described herein are also intended to include compounds that differ only in the presence of one or more isotopically enriched atoms. Exemplary isotopes that may be incorporated into the compounds of this invention include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, chlorine, and iodine, such as 2H, 3H, 11C, 13C, 14C, 13N, 15N, 15O, 17O, 18O, 32P, 33P, 35S, 18F, 36Cl, 123I, and 125I. Isotope-labeled compounds (e.g., compounds labeled with 3H and 14C) can be used in compound or substrate tissue distribution assays. Tritium (i.e., 3H) and carbon-14 (i.e., 14C) isotopes are available due to their ease of preparation and detection. Additionally, substitution with heavier isotopes, such as deuterium (i.e., 2H), may provide certain therapeutic benefits due to enhanced metabolic stability (e.g., increased in vivo half-life or reduced dose requirement). In some embodiments, one or more hydrogen atoms are replaced by 2H or 3H, or one or more carbon atoms are replaced by carbon enriched with 13C or 14C. Positron emission isotopes, such as 15O, 13N, 11C, and 18F, can be used in positron emission tomography (PET) studies to examine substrate-acceptor occupancy. The preparation of isotopically labeled compounds is known to those skilled in the art. For example, isotopically labeled compounds can generally be prepared by following a procedure similar to that disclosed with respect to the compounds of the invention described herein, by replacing unlabeled reagents with isotopically labeled reagents.

[0798] The term "pharmaceutical excipients" refers to the excipients and additives used in the production of pharmaceuticals and the preparation of prescriptions. They are all substances contained in pharmaceutical preparations, excluding the active ingredient.

[0799] The term “treatment” refers to a therapeutic approach. When a specific condition is involved, treatment means: (1) alleviating one or more biological manifestations of the disease or condition; (2) interfering with (a) one or more points in a biological cascade that causes or precipitates the condition or (b) one or more biological manifestations of the condition; (3) improving one or more symptoms, effects or side effects associated with the condition, or one or more symptoms, effects or side effects associated with the condition or its treatment; or (4) slowing the development of the condition or one or more biological manifestations of the condition.

[0800] The term "prevention" refers to the reduction of the risk of acquiring or developing a disease or disorder.

[0801] The term "therapeutic effective amount" refers to an amount of compound sufficient to effectively treat the disease or condition described herein when administered to a patient. The "therapeutic effective amount" will vary depending on the compound, the condition and its severity, and the age of the patient to be treated, but may be adjusted as needed by those skilled in the art.

[0802] The term "patient" refers to any animal, preferably a mammal and human, that is about to or has already been administered the compound or composition according to embodiments of the invention.

[0803] Based on common knowledge in the field, the above-mentioned preferred conditions can be combined arbitrarily to obtain various preferred embodiments of the present invention.

[0804] The reagents and raw materials used in this invention are all commercially available.

[0805] The positive and progressive effect of this invention is that the compounds of this invention have a good inhibitory effect on cancer. Detailed Implementation

[0806] The present invention is further illustrated below by way of embodiments, but the invention is not limited to the scope of the embodiments described herein. Experimental methods in the following embodiments that do not specify specific conditions were performed according to conventional methods and conditions, or as selected according to the product instructions.

[0807] Unless otherwise specified, the preparative HPLC used in the following examples may be performed under the following conditions:

[0808] Preparative HPLC (ammonium bicarbonate method): Column: Welch Xtimate C18, 21.2*150mm, 5μm; Mobile phase A: 5mmol / L ammonium bicarbonate aqueous solution, Mobile phase B: acetonitrile; Flow rate: 15mL / min; B% = 40%-95%; Time: 13min; Column temperature: room temperature.

[0809] Preparative HPLC (formic acid method 1): Column type: Waters XBridge C18, 19*250mm, 5μm; Mobile phase system: A: 0.1% formic acid aqueous solution; B: preparative grade acetonitrile; Flow rate: 15mL / min; B% = 20%-100%; Time: 20min; Column temperature: room temperature.

[0810] Preparative HPLC (formic acid method 2): Column: Welch Xtimate C18, 21.2*150mm, 5μm; Mobile phase A: 0.1% formic acid aqueous solution, Mobile phase B: acetonitrile; Flow rate: 15mL / min; B% = 40%-95%; Time: 13min; Column temperature: room temperature.

[0811] Preparative HPLC (trifluoroacetic acid method): Column: Welch Xtimate C18, 21.2*150mm, 5μm; Mobile phase A: 0.1% trifluoroacetic acid aqueous solution, Mobile phase B: acetonitrile; Flow rate: 15mL / min; B% = 40%-95%; Time: 13min; Column temperature: room temperature.

[0812] Retention time test conditions: Sunfire C18, 4.6*150mm, 3.5μm; Mobile phase A: water (containing 0.05% trifluoroacetic acid); Mobile phase B: acetonitrile (containing 0.05% trifluoroacetic acid); Flow rate: 1mL / min; Chromatographic conditions: 10%-95% B, 15min; Column temperature: 40℃.

[0813] Example 1: Synthesis of Compound Z1

[0814] Step 1: 1-(3-bromo-5-chlorophenyl)ethyl-1-one (1900 mg, 8.1 mmol) was dissolved in 5 mL of methanol, and methylamine tetrahydrofuran solution (20 mL, 40.5 mmol, 2 M) and acetic acid (2 drops) were added. The reaction mixture was stirred at room temperature for 10 minutes and then sealed in a tube. Sodium cyanoborocyanate (1506 mg, 24.3 mmol) was added to the reaction mixture, and the reaction was carried out at room temperature for 16 hours. The reaction mixture was extracted with dichloromethane (3 x 50 mL), dried, concentrated, and the concentrate was purified by rapid silica gel column chromatography (petroleum ether / ethyl acetate = 30%) to give a yellow oily compound 1-1 (835 mg, yield 41%). LC-MS (ESI) m / z: [M+H] + =250.

[0815] Step 2: Compound 1-1 (300 mg, 1.2 mmol) was dissolved in dichloromethane (30 mL), followed by the addition of triethylamine (242 mg, 2.4 mmol), di-tert-butyl dicarbonate (523 mg, 2.4 mmol), and p-methylaminopyridine (15 mg, 0.12 mmol). The reaction mixture was allowed to react at room temperature for 16 hours. The reaction mixture was extracted with dichloromethane (3 x 50 mL), dried, concentrated, and the concentrate was purified by rapid silica gel column chromatography (petroleum ether / ethyl acetate = 10%) to give a yellow oily compound 1-2 (300 mg, 71% yield). LC-MS (ESI) m / z: [M+H] + =350. 1 HNMR (400MHz, CDCl3) δ7.34(s,1H),7.22(s,1H),7.11(s,1H),2.54(s,3H),2.35(s,1H),1.35-1.41(m,12H).

[0816] Step 3: Compounds 1-2 (240 mg, 0.69 mmol) were dissolved in dioxane (20 mL), and bis(pinacol)boronic acid ester (350 mg, 1.38 mmol), potassium acetate (135 mg, 1.38 mmol), and dichloro[1,1'-bis(diphenylphosphine)ferrocene]palladium dichloromethane complex (56 mg, 0.069 mmol) were added. The reaction solution was reacted at 95 °C for 16 hours under nitrogen protection. The reaction solution was extracted with ethyl acetate (3 x 50 mL), dried, concentrated, and the concentrate was purified by rapid silica gel column chromatography (petroleum ether / ethyl acetate = 10%) to give a yellow oily compound 1-3 (300 mg, 100% yield). LC-MS (ESI) m / z: [M+Na] + =418.

[0817] Step 4: Compounds 1-3 (340 mg, 0.86 mmol) were dissolved in dioxane / water (20 / 2 mL), and 2-bromopyrimidine-5-amine (150 mg, 0.86 mmol), potassium acetate (168 mg, 1.72 mmol), and dichloro[1,1'-bis(diphenylphosphine)ferrocene]palladium dichloromethane complex (140 mg, 0.172 mmol) were added. The reaction mixture was reacted at 100 °C for 16 hours under nitrogen protection. The reaction mixture was extracted with ethyl acetate (3 x 50 mL), dried, concentrated, and the concentrate was purified by rapid silica gel column chromatography (petroleum ether / ethyl acetate = 30%) to give a yellow oily compound 1-4 (170 mg, 55% yield). LC-MS (ESI) m / z: [M+Na] + =385.

[0818] Step 5: Compounds 1-4 (57 mg, 0.16 mmol) were dissolved in dichloromethane (10.0 mL), and trifluoroacetic acid (1 mL) was added. The reaction mixture was allowed to react at room temperature for 1.5 hours. The reaction mixture was concentrated, and the pH of the concentrate was adjusted to 9 with saturated sodium bicarbonate. The concentrate was extracted with dichloromethane (3 x 50 mL), dried, and concentrated to obtain a yellow oily compound 1-5 (60 mg, crude product), which was directly proceeded to the next step without purification. LC-MS (ESI) m / z: [M+H] + =263.

[0819] Step Six: Compounds 1-6 (60 mg, 0.23 mmol) were dissolved in dichloromethane (10.0 mL), and triethylamine (46 mg, 0.46 mmol) and acryloyl chloride (20 mg, 0.23 mmol) were added to the reaction mixture at 0 °C. The reaction mixture was reacted at room temperature for 20 minutes. The reaction mixture was extracted with dichloromethane (3 x 50 mL), dried, concentrated, and purified by preparative HPLC (ammonium bicarbonate method) to give a white solid compound N-(1-(3-(5-aminopyrimidin-2-yl)-5-chlorophenyl)ethyl)-N-methylacrylamide (Z1, 12.5 mg, yield 17%). LC-MS (ESI) m / z: [M+H] + =317. 1 HNMR(400MHz,DMSO-d6)δ8.21(s,1H),8.08(s,1H),8.03(s,1H),7.29(s,1H),6.78-7. 00(m,1H),6.23-6.13(m,1H),5.48-5.91(m,4H),2.65-2.79(m,3H),1.49-1.57(m,3H).

[0820] Example 2: Synthesis of Compound Z12

[0821] Step 1: 3-Bromo-5-chloro-2-hydroxypyridine (1 g, 4.8 mmol) and 2-bromopyrimidine-5-amine (840 g, 4.8 mmol) were dissolved in 1,4-dioxane (20 mL), and potassium phosphate (3053 mg, 14.4 mmol), N,N-dimethylethylenediamine (85 mg, 0.96 mmol), and cuprous iodide (182 mg, 0.96 mmol) were added. The reaction mixture was reacted at 110 °C for 24 hours under nitrogen protection. The reaction mixture was extracted with dichloromethane (3 x 50 mL), dried, concentrated, and purified by rapid silica gel column chromatography (petroleum ether / ethyl acetate = 100%) to give a yellow oily compound 12-1 (450 mg, yield 31%). LC-MS (ESI) m / z: [M+H] + =301.

[0822] Step 2: Compound 12-1 (200 mg, 0.67 mmol) and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)-2,3-dihydro-4H-1,4-oxazine-4-carboxylic acid tert-butyl ester (208 mg, 0.67 mmol) were dissolved in 1,4-dioxane:water (5:1, 10 mL). Potassium carbonate (277 mg, 2 mmol) and dichloro[1,1'-bis(diphenylphosphine)ferrocene]palladium dichloromethane complex (51 mg, 0.067 mmol) were added. The reaction mixture was reacted at 100 °C for 16 hours under nitrogen protection. The reaction mixture was extracted with dichloromethane (3 x 50 mL), dried, concentrated, and purified by rapid silica gel column chromatography (petroleum ether / ethyl acetate = 100%) to give a yellow oily compound 12-2 (200 mg, 74% yield). LC-MS(ESI)m / z:[M+H] + =406.

[0823] Step 3: Compound 12-2 (200 mg, 0.49 mmol) was added to dioxane hydrochloride (5 mL) in an ice bath. The reaction was carried out for 2 hours, and the mixture was concentrated to give a yellow oily compound 12-3 (160 mg, 100% yield). LC-MS (ESI) m / z: [M+H] + =306.

[0824] Step 4: Compound 12-3 (160 mg, 0.39 mmol) was dissolved in anhydrous methanol (10 mL), and sodium borohydride (72 mg, 1.95 mmol) was added under ice bath conditions. The reaction mixture was reacted at 0-25 °C for 1 hour under nitrogen protection. The reaction mixture was extracted with dichloromethane:methanol (10:1, 3 x 50 mL), dried, and concentrated. The concentrate was purified by rapid silica gel column chromatography (dichloromethane / methanol = 20%) to give a yellow oily compound 12-4 (130 mg, 80% yield). LC-MS (ESI) m / z: [M+H] + =308.

[0825] Step 5: Compound 12-4 (70 mg, 0.23 mmol) was dissolved in dichloromethane (10.0 mL), and triethylamine (46 mg, 0.46 mmol) and acryloyl chloride (20 mg, 0.23 mmol) were added under ice bath conditions. The reaction solution was reacted at 0 °C for 30 minutes. The reaction solution and the small-scale test were extracted together with dichloromethane:methanol (10:1, 3 x 50 mL), dried, concentrated, and the concentrate was purified by preparative HPLC (ammonium bicarbonate method) to obtain the white solid compound 3-(4-acryloylmorpholin-3-yl)-1-(5-aminopyrimidin-2-yl)-5-chloropyridin-2(1H)-one (Z12, 8 mg, yield 9.7%). LC-MS (ESI) m / z: [M+H] + =362.1 HNMR (400MHz, DMSO-d6) δ8.17(s,2H),8.01(s,1H),7.43(d,J=119.4Hz,1H),6.88(dd,J=16.3,10.8Hz,1H),6.14(d, J=16.5Hz,1H),5.96(s,2H),5.68(s,1H),5.17(d,J=76.7Hz,1H),4.27(d,J=11.8Hz,2H),3.93(s,2H),3.67(s,2H).

[0826] Example 3: Synthesis of compounds Z68, Z128, and Z165

[0827] Step 1: Methyl 5-bromopentanoate (4.43 g, 22.725 mmol) was added to acetonitrile (30 mL) containing 3-bromo-4-hydroxycyanobenzene (3 g, 15.150 mmol), sodium iodide (2.27 g, 15.150 mmol), and potassium carbonate (4.19 g, 30.300 mmol). The reaction was stirred at 90 °C for 5 hours. The reaction was quenched with water and extracted with ethyl acetate. The organic phase was washed with saturated brine. The organic phase was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated, and the crude product was purified by rapid silica gel column chromatography (ethyl acetate / petroleum ether: 0-20%) to give compound 128-1 (4.7 g, 99.3% yield). ES-API: [M+H] + =312.0.

[0828] Step 2: Add [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloride dichloromethane complex (261.61 mg, 0.320 mmol) to a dimethyl sulfoxide mixture of compound 128-1 (1000 mg, 3.203 mmol), pinacol diborate (1100 mg, 4.332 mmol), and potassium acetate (943 mg, 9.609 mmol). Stir the reaction mixture at 100 °C for 16 hours under nitrogen protection. Add water to the reaction mixture and extract with ethyl acetate. Wash the organic phase with saturated brine. Dry the organic phase with anhydrous sodium sulfate and filter. Concentrate the filtrate to obtain compound 128-2 (1.15 g, crude product), which can be used directly in the next step. ES-API: [M+Na] + =382.1.

[0829] Step 3: Add [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloromethane complex (32 mg, 0.039 mmol) to a mixture of compound 129-4 (200 mg, 0.392 mmol), compound 128-2 (352 mg, crude), and sodium carbonate (125 mg, 1.179 mmol) in N,N-dimethylformamide (6 mL) / water (1.5 mL). After purging the reaction mixture with nitrogen for 5 minutes, place it in a microwave reactor and stir at 85 °C for 40 minutes. Quench the reaction with water and extract with ethyl acetate. Wash the organic phase with saturated brine. Dry the organic phase with anhydrous sodium sulfate and filter. Concentrate the filtrate, and purify the crude product using a rapid silica gel column chromatography (ethyl acetate / petroleum ether: 0-30%) to give compound 128-3 (230 mg, 88.5% yield). ES-API: [M-99] + =562.2.

[0830] Step 4: Triethylsilane (0.29 mL, 1.816 mmol) was added dropwise to a dichloromethane solution (8 mL) of compound 128-3 (200 mg, 0.302 mmol), triethylamine (0.084 mL, 0.604 mmol), and palladium chloride (8.03 mg, 0.045 mmol). The reaction was stirred at room temperature for 5 hours under nitrogen protection. The reaction solution was filtered through diatomaceous earth, and the filtrate was concentrated to obtain compound 128-4 (159 mg, crude product). ES-API: [M+H] + =528.3.

[0831] Step 5: Add 0.6 mL of 3 M sodium hydroxide aqueous solution (1,800 mmol) to a methanol (2 mL) / tetrahydrofuran (2 mL) solution of compound 128-4 (159 mg, crude). Stir the reaction mixture at room temperature for 3 hours. Adjust the pH of the reaction mixture to 7 with 1 M hydrochloric acid. Concentrate the reaction mixture to obtain compound 128-5 (154 mg, crude).

[0832] Step Six: To a dichloromethane solution (8 mL) of compound 128-5 (150 mg, crude) and N,N-diisopropylethylamine (10.06 mg, 0.078 mmol), a 50% ethyl acetate solution of 1-propylphosphonic anhydride (0.16 mL, 0.302 mmol) was added dropwise. The reaction was stirred at room temperature for 1 hour. The reaction was quenched with water and extracted with ethyl acetate. The organic phase was washed with saturated brine. The organic phase was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated, and the crude product was purified by rapid silica gel column chromatography (tetrahydrofuran / petroleum ether: 0-50%) to give compound 128-6 (120 mg, 82.9% yield). ES-API: [M+H] + =496.1.

[0833] Step 7: Add 1M sodium hydroxide aqueous solution (1 mL, 1 mmol) to ethanol (2 mL) / dimethyl sulfoxide (2 mL) of compound 128-6 (100 mg, 0.202 mmol). Add 35% hydrogen peroxide aqueous solution (0.21 mL, 2.377 mmol). Stir the reaction mixture at room temperature for 2 hours. Add saturated sodium sulfite aqueous solution (20 mL) to the reaction mixture. Extract with ethyl acetate (20 mL). Wash the organic phase with saturated brine. Dry the organic phase with anhydrous sodium sulfate and filter. Concentrate the filtrate to give compound 128-7 (100 mg, crude product), which can be used directly in the next step. ES-API: [M-55] + =458.1.

[0834] Step 8: Add trifluoroacetic acid (1 mL) to dichloromethane (4 mL) containing compound 128-7 (100 mg, crude). Stir the reaction mixture at room temperature for 1 hour. Concentrate the reaction solution to obtain compound 128-8 (80 mg, crude), which can be used directly in the next step. ES-API: [M+H] + =414.3.

[0835] Step 9: Add 3 mL of saturated sodium bicarbonate aqueous solution to 3 mL of a tetrahydrofuran solution of compound 128-8 (80 mg, crude). Cool the reaction solution to 0°C and add acryloyl chloride (26 mg, 0.287 mmol). Stir the reaction at room temperature for 1 hour. The reaction solution was purified by preparative HPLC (formic acid method 1) to give 11-acryloyl-25-chloro-9-oxo-4-oxa-1(2,4)-piperazine-2(1,3),3(1,2)-dibenzocyclononane-35-carboxamide (Z128, 45 mg, yield 49.7%), a white solid. ES-API: [M+H] + =468.3.

[0836] Step 10: Compound Z128 (45 mg) was chirally separated (separation column: Daicel). IA250*4.6mm, 5μm; mobile phase: carbon dioxide: ethanol = 50:50 (V / V); flow rate: 3mL / min; column temperature 40℃) yielded two enantiomers. One of them was arbitrarily designated as: (1 2 R)-1 1 -Acryloyl-2 5 -Chloro-9-oxo-4-oxa-1(2,4)-piperazine-2(1,3),3(1,2)-dibenzocyclononane-3 5 2-Formamide (Z68, 10.2 mg, retention time: 3.98 min), white solid. ES-API: [M+H] + =468.1. 1HNMR: (400MHz, DMSO-d6) δ 7.93-7.73 (m, 4H), 7.38-7.35 (m, 1H), 7.25-7.22 (m, 2H), 7.03-6.34 (m, 2H), 6.40-6.10 (m, 1H), 5.84-5.44 (m, 2H), 4.68-4.61 (m, 1H), 4.30-3.82 (m, 4H), 3.63-3.33 (m, 1H), 3.20-3.10 (m, 1H), 3.05-2.77 (m, 2H), 2.21-2.13 (m, 1H), 1.90-1.45 (m, 4H). Another arbitrary designation is: (1 2 S)-1 1 -Acryloyl-2 5 -Chloro-9-oxo-4-oxa-1(2,4)-piperazine-2(1,3),3(1,2)-dibenzocyclononane-3 5 1,4-Formamide (Z165, 11.5 mg, peak 2, retention time: 6.32 min), white solid. ES-API: [M+H] + =468.1. 1 HNMR: (400MHz, DMSO-d6) δ8.30-7.67(m,4H),7.38-7.25(m,3H),7.03-6.63(m,2H),6.33-6.10(m,1H),5.91-5.43(m,2H),4.81- 4.55(m,1H),4.33-3.81(m,4H),3.68-3.35(m,1H),3.20-3.10(m,1H),3.07-2.79(m,2H),2.27-2.13(m,1H),1.90-1.44(m,4H).

[0837] Example 4: Synthesis of compound Z129

[0838] Z129 is A mixture.

[0839] Step 1: Add [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloride dichloromethane complex (824.81 mg, 1.010 mmol) to a dioxane solution of 3-bromo-4-hydroxycyanobenzene (2000 mg, 10.100 mmol), pinacol diboronate (3847.19 mg, 15.150 mmol), and potassium acetate (2973.64 mg, 30.300 mmol). Stir the reaction mixture at 100 °C for 16 hours under nitrogen protection. Filter the reaction mixture with diatomaceous earth, add water to the filtrate, and extract with ethyl acetate. Wash the organic phase with saturated brine. Dry the organic phase with anhydrous sodium sulfate and filter. Concentrate the filtrate, and purify the crude product by rapid silica gel column chromatography (ethyl acetate / petroleum ether: 0-20%) to give compound 129-1 (600 mg, yield 36.4%). ES-API: [M+H] + =164.1.

[0840] Step 2: Cool 120 mL of a tetrahydrofuran solution of 1-bromo-3-chloro-5-iodobenzene (22.54 g, 71.029 mmol) to -40 °C. Add dropwise a tetrahydrofuran solution of isopropyl magnesium chloride-lithium chloride (54.638 mL, 71.029 mmol). After the addition is complete, stir the reaction mixture at -40 °C for 30 minutes. Then add dropwise a tetrahydrofuran solution of 4-benzyl-1-tert-butyl-2-oxomethylenepiperazine-1,4-dicarboxylate (12.5 g, 37.384 mmol). After the addition is complete, slowly raise the temperature to 5 °C over 30 minutes. Stir the reaction mixture at 5 °C for 1 hour. Pour the reaction mixture into an ice-cold saturated ammonium chloride aqueous solution. Extract with ethyl acetate. Wash the organic phase with saturated brine. Dry the organic phase with anhydrous sodium sulfate and filter. The filtrate was concentrated, and the crude product was purified by rapid silica gel column chromatography (ethyl acetate / petroleum ether: 0-25%) to give compound 129-2 (10.5 g, yield 53.4%). ES-API: [M-55] + =425.0.

[0841] Step 3: Add 2 mL of trifluoroacetic acid (26.118 mmol) to a dichloromethane solution (500 mg, 0.951 mmol) of compound 129-2. Stir the reaction mixture at room temperature for 30 minutes under nitrogen protection. Cool the reaction mixture to 0°C and add acetonitrile (8 mL) and sodium cyanoborohydride (298.77 mg, 4.754 mmol). Stir the reaction mixture at room temperature for 16 hours. Concentrate the reaction mixture to dryness and add saturated sodium bicarbonate. Extract with ethyl acetate. Wash the organic phase with saturated brine. Dry the organic phase with anhydrous sodium sulfate and filter. Concentrate the filtrate, and purify the crude product by rapid silica gel column chromatography (ethyl acetate / petroleum ether: 0-30%) to give compound 129-3 (500 mg, yield 64.1%). ES-API: [M+H] + =409.0.

[0842] Step 4: To a dichloromethane solution (7 mL) of compound 129-3 (450 mg, 1.098 mmol), 4-dimethylaminopyridine (13.42 mg, 0.110 mmol), and N,N-diisopropylethylamine (0.384 mL, 2.197 mmol), di-tert-butyl dicarbonate (0.429 mL, 1.867 mmol) was added. The reaction was stirred at room temperature for 16 hours. The reaction solution was concentrated to dryness, and the crude product was purified by rapid silica gel column chromatography (tetrahydrofuran / petroleum ether: 0-20%) to give compound 129-4 (300 mg, yield 53.5%). 1 HNMR(400MHz, CDCl3):7.34-7.10(m,8H),5.22-5.03(m,3H),4.49-4.25(m,1H),4. 03-3.80(m,2H),3.50-3.25(m,1H),3.16-2.93(m,2H),1.48(s,9H).ES-API:[M+Na] + =531.0.

[0843] Step 5: Add [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloromethane dichloride complex (86.50 mg, 0.106 mmol) to a mixture of N,N-dimethylformamide (8 mL) / water (2 mL) of compound 129-4 (600 mg, 1.177 mmol), compound 129-1 (375.85 mg, 2.307 mmol), and sodium carbonate (374.21 mg, 3.531 mmol). Purge the reaction mixture with nitrogen for 5 minutes, then place it in a microwave reactor and stir at 85°C for 1 hour. Quench the reaction with water and extract with ethyl acetate. Wash the organic phase with saturated brine. Dry the organic phase with anhydrous sodium sulfate and filter. Concentrate the filtrate, and purify the crude product by rapid silica gel column chromatography (tetrahydrofuran / petroleum ether: 0-30%) to give compound 129-5 (540 mg, yield 83.7%). ES-API: [M-55] + =492.1.

[0844] Step Six: Triethylsilane (1 mL, 6.261 mmol) was added dropwise to a dichloromethane solution (5 mL) of compound 129-5 (740 mg, 1.350 mmol), triethylamine (0.375 mL, 2.701 mmol), and palladium chloride (35.91 mg, 0.203 mmol). The reaction was stirred at room temperature for 2 hours under nitrogen protection. A tetrahydrofuran solution of tetrabutylammonium fluoride (1 mL, 1.000 mmol) was added to the reaction solution. The reaction was stirred at room temperature for 30 minutes. The reaction was quenched with water and extracted with dichloromethane. The organic phase was washed with saturated brine. The organic phase was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated, and the crude product was purified by rapid silica gel column chromatography (methanol / dichloromethane: 0–3.5%) to give compound 129-6 (400 mg, 71.5% yield). ES-API: [M+H] + =414.1.

[0845] Step 7: Add sodium triacetoxyborohydride (214.04 mg, 1.015 mmol) to a mixture of compound 129-6 (140 mg, 0.338 mmol), 4-(tert-butyldimethylsiloxy)-n-butyraldehyde (15 mg, 0.080 mmol), and acetic acid (0.120 mL, 0.676 mmol) in 1,2-dichloroethane (4 mL) / acetonitrile (4 mL). Stir the reaction at room temperature for 2 hours. Quench the reaction with saturated sodium bicarbonate solution and extract with ethyl acetate. Wash the organic phase with saturated brine. Dry the organic phase with anhydrous sodium sulfate and filter. Concentrate the filtrate, and purify the crude product by rapid silica gel column chromatography (ethyl acetate / petroleum ether: 0-20%) to give compound 129-7 (200 mg, 98.5% yield). ES-API: [M+H] + =600.3.

[0846] Step 8: Add a tetrahydrofuran solution (2 mL) of tetrabutylammonium fluoride in tetrahydrofuran (2.000 mmol) to a tetrahydrofuran solution (2 mL). Stir the reaction at room temperature for 1 hour. Quench the reaction with water and extract with ethyl acetate. Wash the organic phase with saturated brine. Dry the organic phase with anhydrous sodium sulfate and filter. Concentrate the filtrate and purify the crude product by rapid silica gel column chromatography (ethyl acetate / petroleum ether: 0-5%) to give compound 129-8 (100 mg, yield 61.7%). ES-API: [M+H] + =486.2.

[0847] Step 9: Add cyanomethylenetri-n-butylphosphine (200 mg, 0.829 mmol) to a toluene solution of compound 129-8 (90 mg, 0.185 mmol) in 10 mL. Under nitrogen protection, stir at 70 °C for 5 hours. Quench the reaction with water and extract with ethyl acetate. Wash the organic phase with saturated brine. Dry the organic phase with anhydrous sodium sulfate and filter. Concentrate the filtrate, and purify the crude product using a rapid silica gel column chromatography (tetrahydrofuran / petroleum ether: 0-40%) to give compound 129-9 (170 mg, crude). ES-API: [M+H] + =468.2.

[0848] Step 10: Add 3 mL of 1 M sodium hydroxide aqueous solution (3.000 mmol) to ethanol (6 mL) / dimethyl sulfoxide (2 mL) of compound 129-9 (160 mg, crude). Cool the reaction solution to 0°C and add 1 mL of 35% hydrogen peroxide aqueous solution (11.632 mmol). Stir the reaction at room temperature for 5 hours. Add 50 mL of saturated sodium sulfite aqueous solution to the reaction solution. Extract with ethyl acetate. Wash the organic phase with saturated brine. Dry the organic phase with anhydrous sodium sulfate and filter. Concentrate the filtrate, and purify the crude product by rapid silica gel column chromatography (methanol / dichloromethane: 0-10%) to give compound 129-10 (35 mg). ES-API: [M+H] + =486.1.

[0849] Step 11: Add 4M hydrogen chloride-dioxane solution (1 mL, 4.000 mmol) to a methanol (1 mL) / dichloromethane (1 mL) solution of compound 129-10 (30 mg, 0.062 mmol). Stir the reaction at room temperature for 1 hour. Concentrate the reaction solution. Add saturated sodium bicarbonate aqueous solution (2 mL) / tetrahydrofuran (2 mL) to the crude product. Add acryloyl chloride (28.06 mg, 0.310 mmol) to the solution, and stir the reaction at room temperature for 30 minutes. Quench the reaction with saturated sodium bicarbonate aqueous solution and extract with dichloromethane. Purify the crude product by preparative HPLC (formic acid method 1) to give 11-acryloyl-25-chloro-4-oxa-1(2,4)-piperazine-2(1,3),3(1,2)-dibenzocyclooctane-35-carboxamide (Z129, 1.2 mg, yield 3.9%), a white solid. ES-API: [M+H] + =440.1.

[0850] Example 5: Synthesis of compounds Z65, Z125, Z126, and Z127

[0851] Step 1: Cool 30 mL of anhydrous tetrahydrofuran solution of 1-bromo-3-chloro-5-iodobenzene (2.0 g, 6.302 mmol) to -40 °C. Under nitrogen protection, slowly add 4.7 mL of lithium chloride solution of magnesium isopropyl chloride (6.113 mmol, 1.3 M) dropwise to the reaction solution. After the addition is complete, stir the reaction solution at -40 °C for 1 hour. Then, slowly raise the temperature of the reaction solution to -10 °C and add 4-methoxypyridine (598 mg, 5.483 mmol) and benzyl chloroformate (0.8 mL, 5.609 mmol). Stir the reaction solution at -10 °C for 0.5 hours. LCMS analysis confirmed the reaction was complete. The reaction was quenched by adding 5M dilute hydrochloric acid to the reaction solution under ice-water bath conditions. Then, ethyl acetate (30 mL) was added to the reaction solution. The organic phase was washed with saturated sodium bicarbonate solution (20 mL x 2) and saturated brine (20 mL x 2). The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated to dryness. The residue was purified by automated rapid chromatography on silica gel (tetrahydrofuran / petroleum ether = 0-20%) to give compound 63-1 (1.69 g, yield: 64%). ES-API: [M+H] + =420.0.

[0852] Step 2: Under nitrogen protection, zinc powder (788 mg, 12.052 mmol) was added to a solution of compound 63-1 (1.69 g, 4.017 mmol) in glacial acetic acid (15 mL). The reaction mixture was heated to 100 °C and stirred overnight. LC-MS analysis confirmed the reaction was complete. The reaction mixture was cooled to room temperature, filtered to remove insoluble matter, and ethyl acetate and petroleum ether (50 mL, V / V = 1:10) were added to the filtrate. The organic phase was washed with saturated sodium bicarbonate solution (20 mL * 2) and saturated brine (20 mL * 2). The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated to dryness. The residue was purified by automated rapid chromatography on silica gel (tetrahydrofuran / petroleum ether = 0-40%) to obtain compound 63-2 (1.27 g, yield: 75%). ES-API: [M+H] + =422.0.

[0853] Step 3: Under nitrogen protection, sodium borohydride (341 mg, 9.013 mmol) was added to a tetrahydrofuran (15 mL) solution of compound 63-2 (1.27 g, 3.004 mmol) in an ice-water bath. The reaction mixture was stirred at 0-5 °C for 0.5 h. LCMS confirmed the reaction was complete. The reaction was quenched by adding saturated sodium bicarbonate solution (30 mL), and extracted with ethyl acetate (20 mL * 3). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated to dryness. The residue was purified by automated rapid chromatography on silica gel (tetrahydrofuran / petroleum ether = 0-40%) to give compound 63-3 (1.00 g, yield: 78%). ES-API: [M+H] + =424.0.

[0854] Step 4: Sodium hydroxide (283 mg, 7.063 mmol, 60% dispersed in oil) was added to a solution of compound 63-3 (1.0 g, 2.354 mmol) in N,N-dimethylformamide (15 mL) under an ice-water bath. The reaction mixture was stirred at 0°C for 0.5 h. Tert-butyl(4-iodobutoxy)dimethylsilane (2.96 g, 9.418 mmol) was then added to the reaction mixture. The reaction mixture was heated to 50°C and stirred for 30 h. LC-MS analysis showed product formation, but some starting material remained. The reaction mixture was cooled to 0°C, and the reaction was quenched with saturated ammonium chloride solution (30 mL). Extraction was performed with ethyl acetate (20 mL x 3). The combined organic phases were washed with saturated brine (20 mL x 3), dried over anhydrous sodium sulfate, filtered, and concentrated to dryness. The residue was purified by automated rapid chromatography on silica gel (tetrahydrofuran / petroleum ether = 0-50%) to give compound 63-4 (646 mg, yield: 45%). ES-API:[M+H] + =610.2.

[0855] Step 5: Under nitrogen protection, compound 63-4 (114 mg, 0.187 mmol), pinacol diborate (57 mg, 0.224 mmol), potassium acetate (46 mg, 0.466 mmol), and [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloride (14 mg, 0.019 mmol) were dissolved in anhydrous dioxane (5 mL). The reaction mixture was heated to 80 °C and stirred for 3 h. LC-MS analysis confirmed the reaction was complete, yielding the reaction solution of compound 63-5, which could be directly proceeded to the next step without purification. ES-API: [M+H] + =658.3.

[0856] Step Six: Under nitrogen protection, 3-bromo-4-hydroxycyanobenzene (92 mg, 0.463 mmol), sodium carbonate (49 mg, 0.463 mmol), [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloride (14 mg, 0.019 mmol), and water (1 mL) were added to the reaction solution of compound 63-5. The reaction mixture was heated to 85 °C and stirred for 1 h. The reaction was confirmed to be complete by LCMS, and the reaction solution was concentrated to dryness under reduced pressure. The residue was purified by automated rapid chromatography on silica gel (tetrahydrofuran / petroleum ether = 0-20%) to give compound 63-6 (51 mg, yield: 42%). ES-API: [M+H] + =649.1.

[0857] Step 7: Add tetrabutylammonium fluoride solution (0.62 mL, 0.619 mmol, 1 M tetrahydrofuran solution) to a tetrahydrofuran (6 mL) solution of compound 63-6 (134 mg, 0.206 mmol). Heat the reaction mixture to 60 °C and stir for 2 h. LCMS was used to confirm the completeness of the reaction. Add ethyl acetate (15 mL) to the reaction mixture, wash with saturated brine (15 mL * 3), dry the organic phase with anhydrous sodium sulfate, filter, and concentrate to dryness. Purify the residue by automated rapid chromatography on silica gel (tetrahydrofuran / petroleum ether = 0-70%) to obtain crude compound 63-7 (138 mg). ES-API: [M+H] + =535.0.

[0858] Step 8: Under nitrogen protection, cyanomethylenetri-n-butylphosphine (242 mg, 0.449 mmol) was added to a toluene (3 mL) solution of compound 63-7 (120 mg, 0.224 mmol). The reaction mixture was heated to 65 °C and stirred for 3 h. LC-MS was used to confirm the completeness of the reaction. The reaction mixture was concentrated to dryness under reduced pressure. The residue was purified by automated rapid chromatography on silica gel (tetrahydrofuran / petroleum ether = 0-25%) to give compound 63-8 (87 mg, yield: 75%). ES-API: [M+H] + =517.2.

[0859] Step 8: Under ice-water bath conditions, sodium hydroxide (242 mg, 0.449 mmol) and H₂O₂ (1.5 mL) were added sequentially to a solution of compound 63-8 (179 mg, 4.468 mmol) in ethanol (5 mL), dimethyl sulfoxide (1 mL), and water (1.5 mL). The reaction mixture was stirred at room temperature for 2 h. The reaction was confirmed to be complete by LCMS. A saturated sodium sulfite solution (10 mL) was added to the reaction mixture, and the mixture was concentrated under reduced pressure to remove some of the organic solvent. The residue was washed with ethyl acetate (20 mL) and saturated brine (10 mL x 3). The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated to dryness. The residue was purified by automated rapid chromatography on silica gel (tetrahydrofuran / petroleum ether = 0-100%) to obtain compound 63-9 (71 mg, yield: 89%). ES-API: [M+H] + =535.2.

[0860] Step 9: Under nitrogen protection, compound 63-9 (60 mg, 0.112 mmol), triethylamine (45.39 mg, 0.449 mmol), and palladium dichloride (6.00 mg, 0.034 mmol) were dissolved in dichloromethane solution (2 mL). Triethylsilane (0.27 mL, 1.682 mmol) was added to the reaction solution, and the reaction was stirred at room temperature for 1 h. The reaction was confirmed to be complete by LCMS. The reaction was quenched by adding water (10 mL), extracted with dichloromethane (10 mL * 3), and the organic phase was washed with saturated brine (10 mL * 3), dried over anhydrous sodium sulfate, filtered, and concentrated to dryness. The residue was purified by automated rapid chromatography on silica gel (methanol / dichloromethane = 0-100%) to obtain crude compound 63-10 (58 mg). ES-API: [M+H] + =401.2.

[0861] Step 10: Under an ice-water bath, triethylamine (22 mg, 0.217 mmol) and acryloyl chloride (14.4 mg, 0.160 mmol) were added sequentially to a solution of compound 63-10 (58 mg, 0.145 mmol) in dichloromethane (5 mL). The reaction solution was stirred at 0 °C for 10 minutes. LCMS confirmed the reaction was complete. Dichloromethane (10 mL) and water (10 mL) were added to the reaction solution, and the mixture was extracted with dichloromethane (10 mL * 2). The organic phases were combined and washed with saturated brine (10 mL * 2). The mixture was dried over anhydrous sodium sulfate, filtered, and concentrated to dryness. The residue was purified by preparative HPLC (formic acid method 2) to obtain two isomers. One of the structures was arbitrarily designated as trans-(1 2 ,1 4 )-1 1 -Acryloyl-2 5-Chloro-4,9-dioxa-1(2,4)-piperidine-2(1,3),3(1,2)-dibenzocyclononane-3 5 -Formamide (Z126, 7.42 mg, yield 11.25%, retention time: 6.642 min). ES-API: [M+H] + =455.2.

[0862] Another structure is arbitrarily specified as cis-(1 2 ,1 4 )-1 1 -Acryloyl-2 5 -Chloro-4,9-dioxa-1(2,4)-piperidine-2(1,3),3(1,2)-dibenzocyclononane-3 5 -Formamide (Z125, 0.70 mg, yield 1.03%, retention time: 7.058 min). ES-API: [M+H] + =455.2.

[0863] Step 11: Chiral separation of compound Z126 (Column: Daicel) IH 250*4.6mm, 5μm; Mobile phase A: n-hexane + 0.2% trifluoroacetic acid (V / V), Mobile phase B: ethanol + 0.2% trifluoroacetic acid (V / V); Detection wavelength: 254 / 214nm; Flow rate: 1mL / min; Column temperature: 30℃; Isogradient elution program: Mobile phase A: Mobile phase B = 30:70 (V / V)) Purification yielded two isomers. One of them was arbitrarily designated as (1 2 S,1 4 S)-1 1 -Acryloyl-2 5 -Chloro-4,9-dioxa-1(2,4)-piperidine-2(1,3),3(1,2)-dibenzocyclononane-3 5 -Formamide (Z65, 2.20 mg, retention time: 5.770 min). ES-API: [M+H] + =455.2. 1HNMR(400MHz,DMSO-d6)δ8.02-8.00(m,4H),7.56-7.53(m,1H),7.28(m,1H),7.18(d, J=8.8Hz,1H),7.06-6.81(m,2H),6.25-6.20(m,1H),6.02-5.62(m,2H),4.60-4.12(m ,2H), 3.96-3.90(m,1H), 3.61-3.57(m,1H), 3.52-3.46(m,2H), 2.99-2.57(m,2H), 2.16-2.07(m,1H), 1.96-1.94(m,2H), 1.80-1.60(m,2H), 1.36-1.32(m,2H). Another arbitrarily designated as (1 2 R,1 4 R)-1 1 -Acryloyl-2 5 -Chloro-4,9-dioxa-1(2,4)-piperidine-2(1,3),3(1,2)-dibenzocyclononane-3 5 -Formamide (Z127, 3.74 mg, retention time: 8.750 min). ES-API: [M+H] + =455.2. 1 HNMR(400MHz,DMSO-d6)δ8.02-7.90(m,4H),7.56-7.53(m,1H),7.28(m,1H), 7.18(d,J=8.8Hz,1H),7.06-6.81(m,2H),6.25-6.20(m,1H),6.02-5.62(m,2H ),4.60-4.12(m,2H),3.96-3.90(m,1H),3.60-3.46(m,3H),2.99-2.68(m,2H) ,2.16-2.07(m,1H),1.96-1.94(m,2H),1.80-1.60(m,2H),1.36-1.29(m,2H).

[0864] Example 6 Synthesis of Compound Z7

[0865] Step 1: 3-Bromo-5-chloroacetophenone (1.4 g, 6.0 mmol) was dissolved in tetrahydrofuran (30 mL), and phenyltrimethylammonium tribromide (2.48 g, 6.60 mmol) was added at room temperature. The reaction mixture was stirred at room temperature for 4 hours. The reaction mixture was filtered, and the filtrate was concentrated. The crude product was purified by rapid silica gel column chromatography (ethyl acetate / petroleum ether: 0-10%) to give compound 7-1 (1.7 g, yield 90.8%), a pale yellow liquid.

[0866] Step 2: N-[(3S)-3-morpholinylmethyl]carbamate tert-butyl ester (900 mg, 4.16 mmol) was dissolved in acetonitrile (40 mL). Compound 7-1 (1689.87 mg, 5.410 mmol) and potassium carbonate (1.44 g, 10.40 mmol) were added sequentially at 0 °C, and the reaction mixture was stirred at room temperature for 18 hours. The reaction mixture was extracted with water (80 mL) and saturated ethyl acetate (150 mL). The organic phase was washed with saturated brine (80 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The crude product was purified by rapid silica gel column chromatography (ethyl acetate / petroleum ether: 0-40%) to give compound 7-2 (1.3 g, 70.0% yield), a yellow solid. ES-API: [M+H] + =447.0,449.0.

[0867] Step 3: Compound 7-2 (1.2 g, 2.68 mmol) was dissolved in dichloromethane (15 mL), and trifluoroacetic acid (5 mL, 26.118 mmol) was added at 0 °C. The reaction mixture was stirred at room temperature for 1 hour under nitrogen protection. The reaction mixture was concentrated, and 1,2-dichloroethane (30 mL) was added. The reaction mixture was cooled to 0 °C, and sodium triacetoxyborohydride (0.85 g, 4.02 mmol) was added. The reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated to dryness with dichloromethane (80 mL), and washed successively with saturated sodium bicarbonate (25 mL) and saturated brine (25 mL). The organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to obtain crude compound 7-3 (888 mg, crude product), a pale brown liquid, which was used directly for the next reaction. ES-API: [M+H] + =331.0,333.1.

[0868] Step 4: Compound 7-3 (888 mg, crude) and di-tert-butyl dicarbonate (1.85 mL, 8.03 mmol) were dissolved in dichloromethane (25 mL). 4-Dimethylaminopyridine (33 mg, 0.27 mmol) and triethylamine (1.12 mL, 8.03 mmol) were added at °C, and the reaction was stirred at room temperature for 1 hour. The reaction solution was concentrated, and ethyl acetate (60 mL) was added. The mixture was washed successively with water (30 mL x 2) and saturated brine (30 mL). The organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The crude product was purified by rapid silica gel column chromatography (tetrahydrofuran / petroleum ether: 0-30%) to give compound 7-4 (620 mg, two-step yield 53.6%), a pale yellow liquid. 1HNMR(400MHz, CDCl3)δ7.39(s,1H),7.31(s,1H),7.20(s,1H),4.53-4.30(m,1H),3.95-3.62(m,4H),3.42-3.21 (m,1H),2.99-2.75(m,2H),2.73-2.60(m,1H),2.53-2.30(m,2H),2.25-2.08(m,1H),1.19(s,9H).ES-API:[M+H] + =431.1,433.0.

[0869] Step 5: Compound 7-4 (300 mg, 0.695 mmol) was dissolved in 1,4-dioxane (10 mL) and bis(pinacol)boronic acid ester (353 mg, 1.39 mmol), [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloride (51 mg, 0.069 mmol), and potassium acetate (170 mg, 1.73 mmol) were added. The mixture was purged with nitrogen three times, and the reaction was carried out at 90 °C for 12 hours. The reaction solution was filtered through diatomaceous earth, and the filtrate was concentrated. The crude product was purified by rapid silica gel column chromatography (tetrahydrofuran / petroleum ether: 0-40%) to give compound 7-5 (332 mg, 100% yield), a pale yellow liquid. ES-API: [M+H] + =479.2.

[0870] Step Six: Compound 7-5 (100 mg, 0.209 mmol) and 5-amino-2-chloropyrimidine (54 mg, 0.418 mmol) were dissolved in 1,4-dioxane (2.5 mL) and water (0.5 mL). Potassium carbonate (72 mg, 0.522 mmol) and 1,1'-bis(diphenylphosphine)ferrocene palladium(II) dichloride (15 mg, 0.021 mmol) were added. The reaction mixture was stirred at 90 °C for 3 hours under a nitrogen atmosphere. Ethyl acetate (30 mL) was added to the reaction mixture, followed by washing with water (10 mL) and saturated brine (10 mL) successively. The mixture was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The crude product was purified by rapid silica gel column chromatography (tetrahydrofuran / petroleum ether: 0-60%) to give compound 7-6 (80 mg, yield 85.9%), a pale yellow solid. ES-API: [M+H] + =446.2.

[0871] Step 7: Compound 7-6 (65 mg, 0.146 mmol) was dissolved in anhydrous methanol (1 mL), and 4.0 M dioxane hydrochloride (3 mL, 12.0 mmol) was added at 0 °C. The reaction mixture was stirred at room temperature for 1 hour. The reaction solution was concentrated under reduced pressure to give compound 7-7 (66 mg, 100% yield), a white solid. ES-API: [M+H] + =346.1.

[0872] Step 8: Compound 7-7 (66 mg, 0.145 mmol) and triethylamine (117 mg, 1.16 mmol) were dissolved in dichloromethane (5 mL). Acryloyl chloride (13 mg, 0.145 mmol) was added at 0 °C, and the reaction was stirred at 0 °C for 10 minutes. Dichloromethane (10 mL) was added to the reaction solution, followed by washing with water (5 mL) and saturated brine (5 mL). The solution was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The crude product was subjected to preparative HPLC (ammonium bicarbonate method) to obtain the target product 1-((7R,9aS)-7-(3-(5-aminopyrimidin-2-yl)-5-chlorophenyl)hexahydropyrazino[2,1-c][1,4]oxazin-8(1H)-yl)propyl-2-en-1-one (Z7, 15 mg, yield 25.9%), a white solid. 1 HNMR(400MHz,DMSO-d6)δ8.20(s,2H),8.06-7.98(m,2H),7.32(s,1H),6.72(dd,J=1 6.8,10.4Hz,1H),6.08(dd,J=16.8,2.4Hz,1H),5.82(s,2H),5.65(dd,J=10.4,2.4Hz ,1H),5.18-5.06(m,1H),3.69-3.51(m,4H),3.41(dd,J=13.2,6.0Hz,1H),3.31-3.21 (m,2H),2.72(d,J=12.0Hz,1H),2.60-2.52(m,1H),2.50-2.39(m,2H).ES-API:[M+H] + =400.1.

[0873] Example 7 Synthesis of compound Z167

[0874] Step 1: Add sodium triacetoxyborohydride (231 mg, 1.09 mmol) to a mixture of compound 129-6 (150 mg, 0.362 mmol), 3-(tert-butyldimethylsilyloxy)-n-propionaldehyde (102 mg, 0.542 mmol), 1,2-dichloroethane (3 mL), and acetonitrile (3 mL). Stir the reaction at room temperature for 2 hours. Quench the reaction with saturated sodium bicarbonate solution and extract with ethyl acetate. Wash the organic phase with saturated brine. Dry the organic phase with anhydrous sodium sulfate and filter. Concentrate the filtrate, and purify the crude product by rapid silica gel column chromatography (tetrahydrofuran / petroleum ether: 0-30%) to give compound 167-1 (180 mg, yield 84.7%). ES-API: [M+H] + =586.2.

[0875] Step 2: Add a tetrahydrofuran solution (2 mL) of tetrabutylammonium fluoride in tetrahydrofuran (2.000 mmol) to a tetrahydrofuran solution (2 mL). Stir the reaction at room temperature for 1 hour. Quench the reaction with water and extract with ethyl acetate. Wash the organic phase with saturated brine. Dry the organic phase with anhydrous sodium sulfate and filter. Concentrate the filtrate and purify the crude product by rapid silica gel column chromatography (tetrahydrofuran / petroleum ether: 0-40%) to give compound 167-2 (140 mg, yield 96.6%). ES-API: [M+H] + =472.1.

[0876] Step 3: To a toluene solution (130 mg, 0.275 mmol) of compound 167-2 (20 mL), add cyanomethylenetri-n-butylphosphine (332.40 mg, 1.377 mmol). Under nitrogen protection, the reaction was stirred at 70 °C for 3 hours. The reaction was quenched with water and extracted with ethyl acetate. The organic phase was washed with saturated brine. The organic phase was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated, and the crude product was purified by rapid silica gel column chromatography (methanol / dichloromethane: 0-1%) to give compound 167-3 (75 mg, 60% yield). ES-API: [M+H] + =454.1.

[0877] Step 4: Add 1M sodium hydroxide aqueous solution (0.82 mL, 0.82 mmol) to ethanol (2 mL) / dimethyl sulfoxide (2 mL) of compound 167-3 (75 mg, 0.165 mmol). Cool the reaction solution to 0°C and add 35% hydrogen peroxide aqueous solution (0.15 mL, 1.67 mmol). Stir the reaction at room temperature for 3 hours. Add saturated sodium sulfite aqueous solution (20 mL) to the reaction solution. Extract with ethyl acetate. Wash the organic phase with saturated brine. Dry the organic phase with anhydrous sodium sulfate and filter. Concentrate the filtrate to give compound 167-4 (75 mg, crude). ES-API: [M+H] + =472.1.

[0878] Step 5: Add 0.5 mL of trifluoroacetic acid to 3 mL of dichloromethane containing compound 167-4 (75 mg, crude). Stir the reaction mixture at room temperature for 1 hour. Concentrate the reaction solution to obtain compound 167-5 (59 mg, crude). ES-API: [M+H] + =372.1.

[0879] Step Six: Add saturated sodium bicarbonate aqueous solution (3 mL) / tetrahydrofuran (3 mL) to compound 167-5 (59 mg, crude). Add acryloyl chloride (26 mg, 0.287 mmol), and stir the reaction at room temperature for 60 minutes. Quench the reaction with saturated sodium bicarbonate aqueous solution and extract with dichloromethane. Purify the crude product by preparative HPLC (ammonium bicarbonate method) to 11-acryloyl-25-chloro-4-oxa-1(2,4)-piperazine-2(1,3),3(1,2)-dibenzocycloheptane-35-carboxamide (Z167, 0.4 mg, yield 0.59%), white solid. ES-API: [M+H] + =426.1.

[0880] Example 8: Synthesis of compounds Z67-1, Z168, Z169, and Z170

[0881] Step 1: Sodium hydroxide (310 mg, 7.749 mmol, 60% dispersed in oil) was added to a solution of compound 63-3 (1.097 g, 2.583 mmol) in N,N-dimethylformamide (15 mL) under an ice-water bath. The reaction mixture was stirred at 0°C for 0.5 h. Tert-butyl(3-iodopropoxy)dimethylsilane (2.327 g, 7.749 mmol) was then added to the reaction mixture. The reaction mixture was heated to 50°C and stirred overnight. LC-MS analysis showed product formation, but some starting material remained. The reaction mixture was cooled to 0°C, and the reaction was quenched with saturated ammonium chloride solution (30 mL). Extraction was performed with ethyl acetate (20 mL x 3). The combined organic phases were washed with saturated brine (20 mL x 3), dried over anhydrous sodium sulfate, filtered, and concentrated to dryness. The residue was purified by automated rapid chromatography on silica gel (tetrahydrofuran / petroleum ether = 0-40%) to give compound 67-1 (695 mg, yield: 45%). ES-API:[M+H] + =596.1.

[0882] Step 2: Under nitrogen protection, compound 67-1 (695 mg, 1.164 mmol), pinacol diborate (355 mg, 1.397 mmol), potassium acetate (228 mg, 2.328 mmol), and [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloride (85 mg, 0.116 mmol) were dissolved in anhydrous dioxane (20 mL). The reaction mixture was heated to 80 °C and stirred for 3 h. LC-MS analysis confirmed the reaction was complete, yielding the reaction solution of compound 67-2, which could be directly proceeded to the next step without purification. ES-API: [M+H] + =644.2.

[0883] Step 3: Under nitrogen protection, 3-bromo-4-hydroxybenzonitrile (691 mg, 3.488 mmol), sodium carbonate (370 mg, 3.488 mmol), [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloride (85 mg, 0.116 mmol), and water (4 mL) were added to the above reaction solution. The reaction mixture was heated to 85 °C and stirred for 1 h. The reaction was confirmed to be complete by LCMS, and the reaction solution was concentrated to dryness under reduced pressure. The residue was purified by automated rapid chromatography on silica gel (tetrahydrofuran / petroleum ether = 0-20%) to give compound 67-3 (190 mg, yield: 26%). ES-API: [M+H] + =635.3.

[0884] Step 4: Add tetrabutylammonium fluoride solution (0.90 mL, 0.897 mmol, 1 M tetrahydrofuran solution) to a tetrahydrofuran (6 mL) solution of compound 67-3 (190 mg, 0.299 mmol). Heat the reaction solution to 60 °C and stir for 2 h. LCMS was used to confirm the completeness of the reaction. Add ethyl acetate (15 mL) to the reaction solution, wash with saturated brine (15 mL * 3), dry the organic phase with anhydrous sodium sulfate, filter, and concentrate to dryness. Purify the residue by automated rapid chromatography on silica gel (tetrahydrofuran / petroleum ether = 0-75%) to obtain crude compound 67-4 (126 mg). ES-API: [M+H] + =521.2.

[0885] Step 5: Under nitrogen protection, cyanomethylenetri-n-butylphosphine (290 mg, 1.200 mmol) was added to a toluene (10 mL) solution of compound 67-4 (125 mg, 0.240 mmol). The reaction mixture was heated to 65 °C and stirred for 3 h. The reaction was confirmed to be complete by LC-MS. The reaction mixture was concentrated to dryness under reduced pressure. The residue was purified by automated rapid chromatography on silica gel (tetrahydrofuran / petroleum ether = 0-75%) to obtain crude compound 67-5 (170 mg). ES-API: [M+H] + =503.1.

[0886] Step Six: Under ice-water bath conditions, sodium hydroxide (406 mg, 10.139 mmol) and H₂O₂ (1.5 mL) were added sequentially to a solution of compound 67-5 (170 mg, 0.149 mmol) in ethanol (5 mL), dimethyl sulfoxide (1 mL), and water (1.5 mL). The reaction mixture was stirred at room temperature for 1 h. The reaction was confirmed to be complete by LCMS. A saturated sodium sulfite solution (10 mL) was added to the reaction mixture, and the mixture was concentrated under reduced pressure to remove some of the organic solvent. The residue was then treated with ethyl acetate (20 mL), washed with saturated brine (10 mL x 3), dried over anhydrous sodium sulfate, filtered, and concentrated to dryness. The residue was purified by automated rapid chromatography on silica gel (tetrahydrofuran / petroleum ether = 0-85%) to give compound 67-6 (119 mg, 3-step yield: 76%). ES-API: [M+H] + =521.2.

[0887] Step 7: Under nitrogen protection, compound 67-6 (119 mg, 0.228 mmol), triethylamine (92 mg, 0.914 mmol), and palladium dichloride (12 mg, 0.069 mmol) were dissolved in dichloromethane solution (5 mL). Triethylsilane (398 mg, 3.426 mmol) was added to the reaction solution, and the mixture was stirred at room temperature for 1 h. The reaction was confirmed to be complete by LCMS. The reaction was quenched by adding water (10 mL), extracted with dichloromethane (10 mL * 3), and the organic phase was washed with saturated brine (10 mL * 3), dried over anhydrous sodium sulfate, filtered, and concentrated to dryness. The residue was purified by automated rapid chromatography on silica gel (methanol / dichloromethane = 0-100%) to give compound 67-7 (80 mg, yield: 91%). ES-API: [M+H] + =387.1.

[0888] Step 8: Under an ice-water bath, triethylamine (0.04 mL, 0.310 mmol) and acryloyl chloride (22 mg, 0.248 mmol) were added sequentially to a solution of compound 67-7 (80 mg, 0.207 mmol) in dichloromethane (10 mL). The reaction mixture was stirred at 0 °C for 10 minutes. LCMS confirmed the reaction was complete. Dichloromethane (10 mL) and water (10 mL) were added to the reaction mixture, and the mixture was extracted with dichloromethane (10 mL * 2). The organic phases were combined and washed with saturated brine (10 mL * 2). The mixture was dried over anhydrous sodium sulfate, filtered, and concentrated to dryness. The residue was purified by preparative HPLC (formic acid method 2) to obtain two isomers. One of them was arbitrarily designated as trans-(1 2 S,1 4 R)-1 1 -Acryloyl-2 5 -Chloro-4,8-dioxa-1(2,4)-piperidine-2(1,3),3(1,2)-dibenzocyclooctane-35 -Formamide (Z168, 33.75 mg, yield: 37%, retention time: 6.385 min). ES-API: [M+H] + =441.1. 1 H NMR (400MHz, DMSO-d6) δ 8.08–7.95 (m, 1H), 7.88–7.80 (m, 3H), 7.32 (s, 1H), 7.17 (s, 1H), 7.10–7.00 (m, 2H), 6.87–6.78 (m, 1H), 6.14–6.10 (m, 1H), 5.71–5.33 (m, 2H), 4.18–3.72 (m, 3H), 3.64–3.50 (m, 3H), 3.19–3.12 (m, 1H), 2.85–2.51 (m, 1H), 1.98–1.75 (m, 4H), 1.60–1.47 (m, 1H). Another arbitrarily designated cis-1 1 -Acryloyl-2 5 -Chloro-4,8-dioxa-1(2,4)-piperidine-2(1,3),3(1,2)-dibenzocyclooctane-3 5 -Formamide (Z169, 6.75 mg, yield: 7.4%, retention time: 6.756 min). ES-API: [M+H] + =441.1. 1 HNMR(400MHz,DMSO-d6)δ8.08-7.95(m,1H),7.88-7.80(m,3H),7.32(s,1H),7.17(s,1H),7.10-7.00(m,2H),6.87-6.78(m,1H),6.14-6.10( m,1H),5.71-5.33(m,2H),4.18-3.72(m,3H),3.64-3.50(m,3H),3.19- 3.12(m,1H),2.85-2.51(m,1H),1.98-1.75(m,4H),1.60-1.47(m,1H).

[0889] Step 9: Chiral separation of compound Z168 (Column: Daicel) IH 250*4.6mm, 5μm; Mobile phase A: HEX + 0.2% TFA (V / V), Mobile phase B: ETOH + 0.2% TFA (V / V); Detection wavelength: 254 / 214nm; Flow rate: 1mL / min; Column temperature: 30℃; Isogradient elution program: Mobile phase A: Mobile phase B = 30:70 (V / V)) Purification yielded two isomers. One of them was arbitrarily designated as (1 2 S,1 4 S)-11 -Acryloyl-2 5 -Chloro-4,8-dioxa-1(2,4)-piperidine-2(1,3),3(1,2)-dibenzocyclooctane-3 5 -Formamide (Z67-1, 12.66 mg, retention time: 5.862 min). ES-API: [M+H] + =441.1. 1 HNMR(400MHz,DMSO-d6)δ8.07-8.00(m,3H),7.94-7.91(m,1H),7.53(d,J=7.9Hz,1H ),7.28(s,1H),7.15(d,J=8.8Hz,1H),7.00(dd,J=16.7,10.5Hz,1H),6.88-6.86(m,1 H), 6.30-6.24(m,1H), 6.08-5.66(m,2H), 4.10-3.71(m,6H), 3.10-3.06(m,1H), 2.87-2.59(m,1H), 2.28-2.19(m,1H), 1.73-1.70(m,2H), 1.51-1.36(m,2H). Another arbitrarily designated as (1 2 R,1 4 R)-1 1 -Acryloyl-2 5 -Chloro-4,8-dioxa-1(2,4)-piperidine-2(1,3),3(1,2)-dibenzocyclooctane-3 5 -Formamide (Z170, 14.24 mg, retention time: 13.329 min). ES-API: [M+H] + =441.1. 1 HNMR(400MHz,DMSO-d6)δ8.07-8.00(m,3H),7.94-7.91(m,1H),7.53(d,J=7.9Hz, 1H),7.28(s,1H),7.15(d,J=8.8Hz,1H),7.00(dd,J=16.8,10.3Hz,1H),6.88-6.8 6(m,1H),6.30-6.23(m,1H),6.08-5.65(m,2H),4.10-3.68(m,6H),3.12-3.06(m, 1H),2.87-2.80(m,1H),2.28-2.22(m,1H),1.73-1.66(m,2H),1.50-1.38(m,2H).

[0890] Example 9: Synthesis of Compound Z171

[0891] Step 1: 100 mL of an aqueous solution of potassium iodide (24 g, 144.578 mmol) was added to 140 mL of a 25% ammonia solution of 2-bromo-4-chlorophenol (10 g, 48.204 mmol). The reaction mixture was stirred at room temperature for 4 hours. LC-MS analysis confirmed the reaction was complete. 100 mL of water was added to quench the reaction, followed by the addition of concentrated hydrochloric acid (150 mL). Extraction was performed with ethyl acetate (40 mL x 3). The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated to dryness. The residue was purified by automated rapid chromatography on silica gel (tetrahydrofuran / petroleum ether = 0-10%) to give compound 171-1 (12.8 g, yield: 80%).

[0892] Step 2: Triethylamine (8.3 mL, 59.889 mmol) and tert-butyldimethylchlorosilane (13.54 g, 89.834 mmol) were added sequentially to an anhydrous N,N-dimethylformamide solution (50 mL) of compound 171-1 (9.982 g, 29.945 mmol). The reaction mixture was stirred at room temperature for 0.5 hours. LCMS confirmed the reaction was complete. Ethyl acetate (150 mL) was added to the reaction mixture. The organic phase was washed with saturated sodium bicarbonate solution (50 mL x 2) and saturated brine (20 mL x 2). The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated to dryness. The residue was purified by automated rapid chromatography on silica gel (tetrahydrofuran / petroleum ether = 0-0.4%) to give compound 171-2 (12.132 g, yield: 91%).

[0893] Step 3: Cool 50 mL of anhydrous tetrahydrofuran solution of compound 171-2 (6.0 g, 13.405 mmol) to -40 °C. Under nitrogen protection, slowly add 10 mL of lithium chloride solution of isopropyl magnesium chloride (13.002 mmol, 1.3 M) to the reaction solution. After the addition is complete, stir the reaction solution at -40 °C for 1 hour. Then, slowly heat the reaction solution to -10 °C and add 4-methoxypyridine (1.27 g, 11.662 mmol) and benzyl chloroformate (1.7 mL, 11.930 mmol). Stir the reaction solution at -10 °C for 0.5 hours. LCMS analysis confirmed the reaction was complete. The reaction was quenched by adding 5M dilute hydrochloric acid to the reaction solution under ice-water bath conditions. Then, ethyl acetate (30 mL) was added to the reaction solution. The organic phase was washed with saturated sodium bicarbonate solution (20 mL x 2) and saturated brine (20 mL x 2). The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated to dryness. The residue was purified by automated rapid chromatography on silica gel (tetrahydrofuran / petroleum ether = 0-18%) to give compound 171-3 (1.639 g, yield: 22%). ES-API: [M+H] + =550.0.

[0894] Step 4: Under nitrogen protection, zinc powder (973 mg, 14.874 mmol) was added to a solution of compound 171-3 (1.639 g, 2.978 mmol) in glacial acetic acid (10 mL). The reaction mixture was heated to 105 °C and stirred overnight. LC-MS analysis confirmed the reaction was complete. The reaction mixture was cooled to room temperature, filtered to remove insoluble matter, and ethyl acetate and petroleum ether (50 mL, V / V = 1:10) were added to the filtrate. The organic phase was washed with saturated sodium bicarbonate solution (20 mL * 2) and saturated brine (20 mL * 2). The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated to dryness. The residue was purified by automated rapid chromatography on silica gel (tetrahydrofuran / petroleum ether = 0-10%) to give compound 171-4 (1.3 g, yield: 79%). ES-API: [M+H] + =552.0.

[0895] Step 5: Under nitrogen protection, sodium borohydride (267 mg, 7.053 mmol) was added to a tetrahydrofuran (20 mL) solution of compound 171-4 (1.3 g, 2.351 mmol) in an ice-water bath. The reaction mixture was stirred at 0-5 °C for 0.5 h. LCMS confirmed the reaction was complete. The reaction was quenched by adding saturated sodium bicarbonate solution (30 mL), and extracted with ethyl acetate (20 mL * 3). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated to dryness. The residue was purified by automated rapid chromatography on silica gel (tetrahydrofuran / petroleum ether = 0-20%) to give compound 171-5 (981 mg, yield: 75%). ES-API: [M+H] + =554.0.

[0896] Step Six: Sodium hydroxide (212 mg, 5.303 mmol, 60% dispersed in oil) was added to a solution of compound 171-5 (981 mg, 1.768 mmol) in N,N-dimethylformamide (15 mL) under an ice-water bath. The reaction mixture was stirred at 0°C for 0.5 h. Tert-butyl(2-iodoethoxy)dimethylsilane (2.024 g, 7.071 mmol) was added to the reaction mixture, and the reaction mixture was heated to 50°C and stirred overnight. LC-MS analysis showed product formation, but some starting material remained. The reaction mixture was cooled to 0°C, and the reaction was quenched with saturated ammonium chloride solution (30 mL). Extraction was performed with ethyl acetate (20 mL x 3). The combined organic phases were washed with saturated brine (20 mL x 3), dried over anhydrous sodium sulfate, filtered, and concentrated to dryness. The residue was purified by automated rapid chromatography on silica gel (tetrahydrofuran / petroleum ether = 0-22%) to give compound 171-6 (380 mg, yield: 36%). ES-API:[M+H] + =598.1.

[0897] Step 7: Add tetrabutylammonium fluoride solution (3 mL, 3.000 mmol, 1 M in THF) to a tetrahydrofuran (6 mL) solution of compound 171-6 (380 mg, 0.634 mmol), and stir the reaction mixture at room temperature for 1.5 h. The reaction was confirmed to be complete by LCMS. Ethyl acetate (15 mL) was added to the reaction mixture, and the mixture was washed with saturated brine (15 mL * 3). The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated to dryness. The residue was purified by automated rapid chromatography on silica gel (tetrahydrofuran / petroleum ether = 0-55%) to give compound 171-7 (305 mg, yield: 99%). ES-API: [M+H] + =484.0.

[0898] Step 8: Under nitrogen protection, cyanomethylenetri-n-butylphosphine (0.33 mL, 1.258 mmol) was added to a 5 mL solution of compound 171-7 (305 mg, 0.629 mmol) in toluene. The reaction mixture was heated to 65 °C and stirred for 3 h. The reaction was confirmed to be complete by LC-MS. The reaction mixture was concentrated to dryness under reduced pressure. The residue was purified by automated rapid chromatography on silica gel (tetrahydrofuran / petroleum ether = 0-25%) to give compound 171-8 (115 mg, yield: 39%). ES-API: [M+H] + =466.0.

[0899] Step 9: Under nitrogen protection, compound 171-8 (115 mg, 0.246 mmol), pinacol diborate (75 mg, 0.296 mmol), potassium acetate (60 mg, 0.616 mmol), and [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloride (18 mg, 0.025 mmol) were dissolved in anhydrous dioxane (10 mL). The reaction mixture was heated to 100 °C and stirred overnight. The reaction was confirmed to be complete by LCMS. The reaction solution was concentrated to dryness under reduced pressure. The residue was purified by automated rapid chromatography on silica gel (tetrahydrofuran / petroleum ether = 0-25%) to give compound 171-9 (116 mg, yield: 92%). ES-API: [M+H] + =514.2.

[0900] Step 10: Under nitrogen protection, 2-bromopyrimidine-4-amine (59 mg, 0.339 mmol), sodium carbonate (48 mg, 0.452 mmol), [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloride (16 mg, 0.023 mmol), and water (0.6 mL) were added to an anhydrous dioxane (3 mL) solution of compound 171-9 (116 mg, 0.226 mmol). The reaction mixture was heated to 85 °C and stirred for 2 h. The reaction was confirmed to be complete by LCMS, and the reaction solution was concentrated to dryness under reduced pressure. The residue was purified by automated rapid chromatography on silica gel (tetrahydrofuran / petroleum ether = 0-75%) to give compound 171-10 (98 mg, yield: 90%). ES-API: [M+H] + =481.1.

[0901] Step 11: Under nitrogen protection, compound 171-10 (98 mg, 0.204 mmol), triethylamine (82 mg, 0.815 mmol), and palladium dichloride (11 mg, 0.061 mmol) were dissolved in dichloromethane solution (6 mL). Triethylsilane (355 mg, 3.056 mmol) was added to the reaction solution, and the mixture was stirred at room temperature for 2 h. The reaction was confirmed to be complete by LCMS. The reaction was quenched by adding water (10 mL), and extracted with dichloromethane (10 mL * 3). The organic phase was washed with saturated brine (10 mL * 3), dried over anhydrous sodium sulfate, filtered, and concentrated to dryness. The residue was purified by automated rapid chromatography on silica gel (methanol / dichloromethane = 0-100%) to obtain crude compound 171-11 (95 mg). ES-API: [M+H] + =347.2.

[0902] Step 12: Under ice-water bath conditions, triethylamine (0.06 mL, 0.411 mmol) and acryloyl chloride (12 mg, 0.137 mmol) were added sequentially to a dichloromethane (6 mL) solution of compound 171-11 (95 mg, 0.274 mmol). The reaction mixture was stirred at 0 °C for 10 minutes. LC-MS analysis confirmed the reaction was complete. Dichloromethane (10 mL) and water (10 mL) were added to the reaction mixture, and the mixture was extracted with dichloromethane (10 mL x 2). The organic phases were combined and washed with saturated brine (10 mL x 2). The solution was dried over anhydrous sodium sulfate, filtered, and concentrated to dryness. The residue was purified by preparative HPLC (formic acid method 2) to obtain the target compound: 1-(13-(4-aminopyrimidin-2-yl)-11-chloro-2,3,6,7-tetrahydro-5H-5,9-methoxybenzo[e][1,4]dioxa[8]azacycloundec-8-(9H)-yl)prop-2-en-1-one (Z171, 5.06 mg, yield: 4.6%). ES-API: [M+H + =401.2.

[0903] Example 10 Synthesis of compound Z172

[0904] Step 1: 4-Bromo-2-chlorophenol (10 g, 48.2 mmol) was added to 140 mL of 25% ammonia solution. Then, an aqueous solution of potassium iodide (24 g, 144.6 mmol) and iodine (12.2 g, 48.2 mmol) was slowly added dropwise to the ammonia solution. The reaction mixture was stirred at room temperature for 4 hours. The reaction mixture was then transferred to an ice-water bath, 100 mL of water was added, and the solution was adjusted to acidity with 150 mL of concentrated hydrochloric acid. Extraction was performed with ethyl acetate (50 mL x 3). The combined organic compounds were dried over anhydrous sodium sulfate, concentrated, and the concentrate was purified by flash silica gel column chromatography (petroleum ether: ethyl acetate = 10:1) to give a white solid compound 172-1 (10 g, yield 62%). LC-MS (ESI) m / z: 330.9 [MH] - Retention time = 1.59 min.

[0905] Step 2: Compound 172-1 (10 g, 30 mmol), N-BOC-serine alcohol (11.5 g, 60 mmol), and triphenylphosphine (11.8 g, 45 mmol) were added to 80 mL of anhydrous tetrahydrofuran. The reaction mixture was transferred to an ice-water bath, and diethyl azodicarbonate (7.8 g, 45 mmol) was slowly added dropwise to the reaction mixture under nitrogen protection. After the addition was complete, the reaction mixture was stirred at room temperature for 5 hours. 100 mL of water was added, and the mixture was extracted with ethyl acetate (50 mL * 3). The combined organic compounds were dried over anhydrous sodium sulfate, concentrated, and the concentrate was purified by flash silica gel column chromatography (petroleum ether: ethyl acetate = 2:1) to obtain a colorless oily compound 172-2 (13 g, yield 85%). LC-MS (ESI) m / z: 406.0; 408.0 [M-100+H] + Retention time = 2.02 min.

[0906] Step 3: Compound 172-2 (13 g, 25.66 mmol) and imidazole (4.4 g, 64.16 mmol) were added to 80 mL of dichloromethane. At room temperature, tert-butyldiphenylchlorosilane (9.2 g, 33.36 mmol) was slowly added dropwise to the reaction mixture. After the addition was complete, the reaction mixture was stirred at room temperature for 1 hour. 100 mL of water was added, and the mixture was extracted with dichloromethane (80 mL * 3). The combined organic compounds were dried over anhydrous sodium sulfate, concentrated, and the concentrate was purified by flash silica gel column chromatography (petroleum ether: ethyl acetate = 10:1) to obtain a colorless oily compound 172-3 (18 g, 95% yield). LC-MS (ESI) m / z: 644.0; 646.0 [M-100+H] +Retention time = 2.52 min.

[0907] Step 4: Compound 172-3 (18 g, 24.16 mmol) and potassium vinyltrifluoroborate (3.6 g, 26.58 mmol) were dissolved in 60 mL of dioxane and 10 mL of water. Then, potassium carbonate (10 g, 72.47 mmol) and 1,1'-bis(diphenylphosphine)ferrocene palladium(II) dichloride (0.88 g, 1.21 mmol) were added. The reaction mixture was stirred at 90 °C for 5 hours under nitrogen protection. After the reaction was complete, 100 mL of water was added, and the mixture was extracted with ethyl acetate (80 mL * 3). The combined organic compounds were dried over anhydrous sodium sulfate, concentrated, and the concentrate was purified by rapid silica gel column chromatography (petroleum ether: ethyl acetate = 10:1) to give a colorless oily compound 172-4 (18 g, 95% yield). LC-MS (ESI) m / z: 544.2; 546.2 [M-100+H] + Retention time = 2.46 min.

[0908] Step 5: Compound 172-4 (11 g, 17.05 mmol) was dissolved in 20 mL of tetrahydrofuran and 5 mL of water, followed by the addition of potassium osmium tetroxide dihydrate (3.00 g, 25.58 mmol) and N-methylmorpholine oxide (0.53 g, 1.71 mmol). The reaction mixture was allowed to react at room temperature for 16 hours. After the reaction was complete, 100 mL of water was added, and the mixture was extracted with ethyl acetate (80 mL * 3). The combined organic compounds were dried over anhydrous sodium sulfate, concentrated, and the concentrate was purified by rapid silica gel column chromatography (petroleum ether: ethyl acetate = 1:1) to give a colorless oily compound 172-5 (9.3 g, yield 81%). LC-MS (ESI) m / z: 578.1; 580.2 [M-100+H] + Retention time = 2.08 min.

[0909] Step Six: Compound 172-5 (8 g, 11.78 mmol) and imidazole (2.0 g, 29.45 mmol) were added to 80 mL of dichloromethane. At room temperature, tert-butyldiphenylchlorosilane (4.2 g, 15.31 mmol) was slowly added dropwise to the reaction mixture. After the addition was complete, the reaction mixture was stirred at room temperature for 1 hour. 100 mL of water was added, and the mixture was extracted with dichloromethane (80 mL * 3). The combined organic compounds were dried over anhydrous sodium sulfate, concentrated, and the concentrate was purified by rapid silica gel column chromatography (petroleum ether: ethyl acetate = 5:1) to give a colorless oily compound 172-6 (10 g, 93% yield). LC-MS (ESI) m / z: 816.3; 818.2 [M-100+H] + Retention time = 3.44 min.

[0910] Step 7: Compound 172-6 (10 g, 10.90 mmol) and triethylamine (3.3 g, 32.7 mmol) were added to 80 mL of dichloromethane. Methanesulfonyl chloride (1.5 g, 13.08 mmol) was slowly added dropwise to the reaction mixture under ice bath conditions. After the addition was complete, the reaction mixture was stirred at room temperature for 0.5 hours. 100 mL of water was added, and the mixture was extracted with dichloromethane (80 mL x 3). The combined organic compounds were dried over anhydrous sodium sulfate, concentrated, and the concentrate was purified by rapid silica gel column chromatography (petroleum ether: ethyl acetate = 10:1) to give a colorless oily compound 172-7 (9.5 g, 88% yield). LC-MS (ESI) m / z: 894.2; 896.2 [M-100+H] + Retention time = 3.36 min.

[0911] Step 8: Compound 172-7 (9.5 g, 9.54 mmol) was dissolved in 15 mL of dichloromethane. Under ice bath conditions, 5 mL of trifluoroacetic acid was added dropwise to the reaction solution. After the addition was complete, the reaction solution was stirred at room temperature for 2 hours. After the reaction was complete, the reaction solution was evaporated to dryness at room temperature, redissolved in 60 mL of ethyl acetate, and washed twice with saturated sodium bicarbonate. The combined organic compounds were dried over anhydrous sodium sulfate and concentrated to give a yellow oily compound 172-8 (5.8 g, 68% yield), which was used directly in the next step. LC-MS (ESI) m / z: 894.3; 896.3 [M+H] + Retention time = 1.84 min.

[0912] Step 9: Compound 172-8 (5.8 g, 6.48 mmol) was dissolved in 20 mL of N,N-dimethylformamide, followed by the addition of potassium carbonate (2.7 g, 19.43 mmol) and potassium iodide (108 mg, 0.65 mmol). The reaction mixture was stirred at 80 °C for 16 hours. After the reaction was complete, 100 mL of water was added, and the mixture was extracted with ethyl acetate (80 mL * 3). The combined organic compounds were dried over anhydrous sodium sulfate, concentrated, and the concentrate was purified by rapid silica gel column chromatography (petroleum ether: ethyl acetate = 10:1) to give a colorless oily compound 172-9 (4.8 g, 93% yield). LC-MS (ESI) m / z: 798.2; 800.3 [M+H] + Retention time = 2.04 min & 2.15 min (two peaks).

[0913] Step 10: Compound 172-9 (4.5 g, 5.63 mmol) was dissolved in 10 mL of methanol, and then di-tert-butyl dicarbonate (3.1 g, 14.07 mmol) was added. The reaction mixture was stirred at 50 °C for 5 hours. After the reaction was complete, the reaction mixture was directly evaporated to dryness, and the concentrate was purified by rapid silica gel column chromatography (petroleum ether: ethyl acetate = 10:1) to obtain a colorless oily compound 172-10 (5 g, 100% yield). LC-MS (ESI) m / z: 798.2; 800.2 [M-100+H] + Retention time = 4.15 min & 4.39 min (two peaks).

[0914] Step 11: Compound 172-10 (4.5 g, 5.63 mmol) was dissolved in 20 mL of tetrahydrofuran, and then 13.9 mL of 1 M tetrabutylammonium fluoride tetrahydrofuran solution was added. The reaction mixture was stirred at room temperature for 3 hours. After the reaction was complete, the reaction mixture was directly evaporated to dryness, and the concentrate was purified by rapid silica gel column chromatography (petroleum ether: ethyl acetate = 1:1) to give two isomers. One of them was arbitrarily designated as 172-11-P1 (480 mg, yield 20%), a white solid, LC-MS (ESI) m / z: 322.0; 324.0 [M-100+H] + Retention time = 1.65 min. Another arbitrarily designated product was 172-11-P2 (560 mg, yield 24%), a white solid. LC-MS (ESI) m / z: 322.1; 324.1 [M-100+H] + Retention time = 1.69 min.

[0915] Step 12: Compound 172-11-P2 (450 mg, 1.06 mmol) was dissolved in 10 mL of toluene and 6 mL of tetrahydrofuran, followed by the addition of zinc thiram (488 mg, 1.60 mmol) and triphenylphosphine (558 mg, 2.13 mmol). Under nitrogen protection, diethyl azodicarbonate (7.8 g, 45 mmol) was slowly added dropwise to the reaction solution. After the addition was complete, the reaction solution was stirred at room temperature for 2 hours. After the reaction was complete, the reaction solution was filtered through diatomaceous earth, and the filtrate was evaporated to dryness and purified by preparative HPLC (ammonium bicarbonate method) to obtain a white solid compound 172-12 (350 mg, yield 82%). LC-MS (ESI) m / z: 304.0; 306.1 [M-100+H] + Retention time = 1.83 min.

[0916] Step 13: Compound 172-12 (150 mg, 0.37 mmol) and bis(pinacol)boronic acid ester (113 mg, 0.44 mmol) were dissolved in 2 mL of dioxane, followed by the addition of potassium acetate (109 mg, 1.11 mmol) and 1,1'-bis(diphenylphosphino)ferrocene palladium(II) dichloride (0.14 mg, 0.02 mmol). The mixture was stirred at 90 °C for 1 hour under nitrogen protection. After the reaction was complete, the reaction solution was directly mixed and purified by rapid silica gel column chromatography (petroleum ether: ethyl acetate = 5:1), followed by preparative HPLC (ammonium bicarbonate method) to obtain a white solid compound 172-13 (120 mg, yield 72%). LC-MS (ESI) m / z: 352.2 [M-100+H] + Retention time = 1.92 min.

[0917] Step Fourteen: Compound 172-13 (120 mg, 0.27 mmol) and 4-amino-2-bromopyrimidine (51 mg, 0.29 mmol) were dissolved in 2 mL of dioxane and 0.2 mL of water. Then, potassium carbonate (110 mg, 0.80 mmol) and 1,1'-bis(diphenylphosphine)ferrocene palladium(II) dichloride (10 mg, 0.01 mmol) were added. The reaction mixture was stirred at 90 °C for 1 hour under nitrogen protection. After the reaction was complete, 20 mL of water was added, and the mixture was extracted with ethyl acetate (20 mL * 3). The combined organic compounds were dried over anhydrous sodium sulfate, concentrated, and the concentrate was purified by rapid silica gel column chromatography (dichloromethane:methanol = 10:1), followed by preparative HPLC purification (ammonium bicarbonate method) to obtain a white solid compound 172-14 (70 mg, yield 62%). LC-MS (ESI) m / z: 419.3 [M+H] + Retention time = 1.73 min.

[0918] Step 15: Dissolve compound 172-14 (40 mg, 0.10 mmol) in 1 mL of dichloromethane, then add 0.5 mL of trifluoroacetic acid dropwise to the reaction solution. Stir the reaction solution at room temperature for 0.5 hours. After the reaction is complete, evaporate the reaction solution to dryness at room temperature, redissolve it in 20 mL of ethyl acetate, and wash twice with saturated sodium bicarbonate. Dry the combined organic compounds with anhydrous sodium sulfate, concentrate, and give a yellow solid compound 172-15 (30 mg, 94% yield), which can be used directly in the next step of the reaction. LC-MS (ESI) m / z: 319.2 [M+H] + Retention time = 1.33 min.

[0919] Step 16: Compound 172-15 (30 mg, 0.09 mmol) and triethylamine (19 mg, 0.19 mmol) were added to 2 mL of dichloromethane. Then, acryloyl chloride (10 mg, 0.11 mmol) was added under ice bath conditions, and the reaction mixture was stirred at 0 °C for 0.5 hours. The reaction mixture was extracted with dichloromethane (20 mL * 3), dried over anhydrous sodium sulfate, concentrated, and purified by preparative HPLC (ammonium bicarbonate method) to obtain a white solid compound 1-(cis-9-(4-aminopyrimidin-2-yl)-11-chloro-3,4,6,7-tetrahydro-2H-3,7-cycloimine benzo[f][1,5]dioxane-12-yl)prop-2-en-1-one (Z172, 10 mg, yield 30%). LC-MS (ESI) m / z: 373.2 [M+H] + Retention time = 1.46 min. 1 HNMR(400MHz,DMSO-d6)δ8.42-7.98(m,3H),7.13-6.72(m,3H),6.37(dd,J=5.8,2.7Hz,1H),6.16(d dd,J=16.7,4.0,2.2Hz,1H),5.83-5.70(m,1H),5.47(s,1H),4.72-4.42(m,2H),4.20-3.74(m,5H).

[0920] Example 11 Synthesis of compound Z173

[0921] Step 1: Dissolve 10.00 g (54.95 mmol) of 6-chlorochrome-4-one in 100 mL of concentrated sulfuric acid and cool to 0 °C. Then, add NBS (10.50 g, 56.46 mmol) in portions. Stir the reaction mixture at room temperature for 3 hours. Transfer the reaction mixture to an ice-water bath, add 100 mL of ice water, and extract with ethyl acetate (80 mL x 3). Dry the combined organic phases with anhydrous sodium sulfate, concentrate, and slurry the crude product with methyl tert-butyl ether to give a white solid compound 173-1 (10.40 g, 73% yield). LC-MS (ESI) m / z: 261.0 [M+H] + Retention time = 2.04 min.

[0922] Step 2: Compound 173-1 (10.00 g, 38.46 mmol) was dissolved in dichloromethane (100 mL). The reaction was heated to 40 °C, and then liquid bromine (3.1 mL, 40.38 mmol) was slowly added dropwise. After the addition was complete, the mixture was stirred for another half hour. The reaction was quenched with saturated sodium sulfite solution, water (80 mL) was added, and the mixture was extracted with dichloromethane (50 mL x 3). The combined organic phases were dried over anhydrous sodium sulfate, concentrated, and the concentrate was purified by rapid silica gel column chromatography (petroleum ether: ethyl acetate = 5:1) to give a white solid compound 173-2 (9.50 g, 73% yield). LC-MS (ESI) m / z: 338.8 [M+H] + Retention time = 2.15 min.

[0923] Step 3: Compound 173-2 (9.50 g, 28.11 mmol) was dissolved in methanol (80 mL), cooled to 0 °C, and sodium borohydride (2.67 g, 70.27 mmol) was slowly added in batches. The reaction mixture was stirred at room temperature for half an hour. The reaction mixture was evaporated to dryness, water (80 mL) was added, and the mixture was extracted with ethyl acetate (80 mL * 3). The combined organic compounds were dried over anhydrous sodium sulfate, concentrated, and the concentrate was purified by rapid silica gel column chromatography (dichloromethane:methanol = 96:4) to obtain compound 173-3 (8.80 g, 92% yield), a yellow oil. LC-MS (ESI) m / z: 322.8 [M-OH] + Retention time = 1.98 min.

[0924] Step 4: Compound 173-3 (8.80 g, 25.88 mmol) was dissolved in acetonitrile (40 mL), and then concentrated sulfuric acid (5.07 g, 51.76 mmol) was added. The reaction mixture was stirred at 80 °C for 16 hours. After the reaction ceased to change, the solution was evaporated to dryness to obtain a yellow oily compound 173-4 (10.00 g, crude product), which was directly used in the next step of the reaction. LC-MS (ESI) m / z: 301.9 [M+H] + Retention time = 1.59 min.

[0925] Step 5: Compound 173-4 (10.00 g, crude product) was dissolved in acetonitrile (80 mL) and water (20 mL), and the mixture was refluxed and stirred for 48 hours. After the reaction was complete, the pH was adjusted to between 12 and 13 with 50% sodium hydroxide solution, and then extracted with ethyl acetate (80 mL * 3). The combined organic compounds were dried over anhydrous sodium sulfate, concentrated, and the concentrate was purified by preparative HPLC (ammonium bicarbonate method) to obtain a white solid compound 173-5 (1.00 g, overall yield of 14%). LC-MS (ESI) m / z: 278.1 [M+H] + Retention time = 1.03 min.

[0926] Step Six: Dissolve compound 173-5 (1.00 g, 3.61 mmol) and triethylamine (1.09 g, 10.83 mmol) in dichloromethane (10 mL), cool to 0 °C, and slowly add chloroacetyl chloride (0.45 g, 3.97 mmol). Stir the reaction mixture at room temperature for 1 hour. Reduce the solution to dryness to obtain a yellow oily compound 173-6 (1.05 g, crude product), which can be used directly in the next step. LC-MS (ESI) m / z: 353.9 [M+H] + Retention time = 1.60 min.

[0927] Step 7: Compound 173-6 (1.05 g, crude) was dissolved in tetrahydrofuran (10 mL). Potassium tert-butoxide (1 M, 9 mL, 9.03 mmol) was slowly added dropwise under ice bath conditions. After the addition was complete, the reaction mixture was stirred at room temperature for 3 hours. Water (20 mL) was added, and the mixture was extracted with ethyl acetate (30 mL x 3). The combined organic compounds were dried over anhydrous sodium sulfate, concentrated, and the concentrate was purified by rapid silica gel column chromatography (petroleum ether: ethyl acetate = 1:1) to give a pale yellow solid, compound 173-7 (0.42 g, overall yield of 37%). LC-MS (ESI) m / z: 318.0 [M+H] + Retention time = 1.54 min.

[0928] Step 8: Compound 173-7 (410 mg, 1.29 mmol) was dissolved in tetrahydrofuran (10 mL), and a borane tetrahydrofuran solution (1 M, 4 mL, 3.88 mmol) was added dropwise under ice bath conditions. After the addition was complete, the reaction mixture was stirred at room temperature for 6 hours. After the reaction was complete, the solution was quenched with methanol until no more bubbles were observed, and then concentrated. The concentrate was purified by rapid silica gel column chromatography (petroleum ether: ethyl acetate = 1:1) to give a pale yellow solid compound 173-8 (240 mg, yield 61%). LC-MS (ESI) m / z: 303.9 [M+H] + Retention time = 1.72 min.

[0929] Step 9: Compound 173-8 (240 mg, 0.79 mmol), diboron pinacol ester (242 mg, 0.95 mmol), and potassium acetate (194 mg, 1.98 mmol) were dissolved in 1,4-dioxane (8 mL) under nitrogen protection. Then, Pd(dppf)Cl2 (25 mg) was added, and the reaction mixture was stirred at 80 °C for 16 hours. After the reaction was complete, 20 mL of water was added, and the mixture was extracted with ethyl acetate (30 mL * 3). The combined organic compounds were dried over anhydrous sodium sulfate, concentrated, and the concentrate was purified by rapid silica gel column chromatography (petroleum ether: ethyl acetate = 1.5:1) to give compound 173-9 (160 mg, 70% yield) as a colorless oil. LC-MS (ESI) m / z: 352.2 [M+H] + Retention time = 1.33 min.

[0930] Step 10: Compound 173-9 (80 mg, 0.23 mmol) and 4-amino-2-bromopyrimidine (48 mg, 0.27 mmol) were dissolved in dioxane (2 mL) and water (0.2 mmol), followed by the addition of potassium carbonate (79 mg, 0.58 mmol) and Pd(dppf)Cl2 (8 mg). The reaction mixture was stirred at 100 °C for 2 hours under nitrogen protection. After the reaction was complete, 20 mL of water was added, and the mixture was extracted with ethyl acetate (20 mL * 3). The combined organic compounds were dried over anhydrous sodium sulfate, concentrated, and the concentrate was purified by preparative HPLC (ammonium bicarbonate method) to give a white solid compound 173-10 (40 mg, yield 55%). LC-MS (ESI) m / z: 319.0 [M+H] + Retention time = 1.04 min.

[0931] Step 11: Compound 173-10 (40 mg, 0.12 mmol) and triethylamine (24 mg, 0.24 mmol) were added to dichloromethane (2 mL). Acryloyl chloride (15 mg, 0.16 mmol) was then added under ice bath conditions, and the reaction mixture was stirred at 0 °C for 0.5 hours. The reaction mixture was extracted with dichloromethane (20 mL * 3), dried over anhydrous sodium sulfate, concentrated, and purified by preparative HPLC (ammonium bicarbonate method) to obtain a white solid 1-(7-(4-aminopyrimidin-2-yl)-9-chloro-2,3,4a,10b-tetrahydrochromene[3,4-b][1,4]oxazin-1(5H)-yl)prop-2-en-1-one (Z173, 10.8 mg, yield 23%). LC-MS (ESI) m / z: [M+H] + =373.0; Retention time =1.12min. 1HNMR(400MHz,DMSO-d6)δ:8.12(d,J=5.9Hz,1H),7.30(dd,J=13.2,2.6Hz,1H),7.06-6.85(m,3H),6.85-6.73 (m,1H),6.45-6.22(m,2H),6.00-5.50(m,2H),4.40-3.74(m,5H),3.59(p,J=11.8Hz,1H),3.01-2.54(m,1H).

[0932] Example 12 Synthesis of compound Z174

[0933] Step 1: 4-Benzylmorpholino-3-one (1 g, 5.23 mmol) was dissolved in tetrahydrofuran (15 mL). A 2.0 M solution of lithium diisopropylamino in tetrahydrofuran / n-hexane (3.40 mL, 6.80 mmol) was added dropwise at -70 °C. The reaction was stirred at -70 °C for 1 hour. Tert-butyl(3-iodopropoxy)dimethylsilane (2.04 g, 6.80 mmol) was slowly added dropwise, and the reaction was slowly brought to room temperature and stirred for 3 hours. The reaction mixture was quenched with saturated ammonium chloride solution (10 mL) and water (10 mL), and extracted with ethyl acetate (60 mL). The organic phase was washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The crude product was purified by rapid silica gel column chromatography (tetrahydrofuran / petroleum ether: 0-20%) to give compound 174-1 (1.05 g, yield 55.2%), a colorless liquid. ES-API: [M+H] + =364.3.

[0934] Step 2: 1-Bromo-3-chloro-5-iodobenzene (1.4 g, 4.40 mmol) was dissolved in tetrahydrofuran (4.5 mL), and a 1.3 M tetrahydrofuran solution of the magnesium chloride-lithium chloride complex (3.72 mL, 4.84 mmol) was slowly added dropwise at -70 °C. The reaction was stirred at -70 °C for 30 minutes, and then stirred at 0 °C for 30 minutes. Compound 174-1 (800 mg, 2.20 mmol) and carbonyl chloride bis(triphenylphosphine)iridium(I) (172 mg, 0.22 mmol) were dissolved in dichloromethane (10 mL), and 1,1,3,3-tetramethyldisiloxane (591 mg, 4.40 mmol) was added at room temperature. The reaction was stirred at room temperature for 15 minutes, then cooled to -70 °C, and the above organomagnesium mixture solution was slowly added dropwise. The reaction was stirred at -70 °C for 5 minutes, then heated to 0 °C, and then stirred at 0 °C for 2 hours. The reaction mixture was quenched with saturated ammonium chloride solution (15 mL) and water (15 mL), and extracted with dichloromethane (100 mL). The organic phase was washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The crude product was purified by rapid silica gel column chromatography (ethyl acetate / petroleum ether: 0-3%) to give compound 174-2 (650 mg, yield 54.8%), a pale yellow liquid. 1 HNMR (400MHz, CDCl3) δ7.56-7.34(m,3H),7.32-7.26(m,2H),7.25-7.16(m,3H),3.86(d,J=1 0.4Hz,1H),3.77-3.57(m,2H),3.57-3.42(m,2H),3.34(dd,J=12.8,7.6Hz,1H),2.98(d,J=8. 8Hz,1H),2.84(d,J=13.2Hz,1H),2.72(d,J=11.6Hz,1H),2.23(td,J=11.6,2.8Hz,1H),1.74- 1.59(m,1H),1.46-1.32(m,1H),1.28-1.23(m,2H),0.81(s,9H),-0.03(s,6H).ES-API:[M+H] + =538.2,540.1.

[0935] Step 3: Compound 174-2 (600 mg, 1.113 mmol) was dissolved in 1,4-dioxane (15 mL), and bis(pinacolborate) (367 mg, 1.45 mmol), [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloride (81 mg, 0.11 mmol), and potassium acetate (273 mg, 2.78 mmol) were added. The mixture was purged three times with nitrogen, and the reaction was carried out at 90 °C for 12 h. The reaction solution was filtered through diatomaceous earth, and the filtrate was concentrated. The crude product was purified by rapid silica gel column chromatography (tetrahydrofuran / petroleum ether: 0-10%) to give compound 139-3 (600 mg, 92.0% yield), a pale yellow solid. ES-API: [M+H] + =586.3.

[0936] Step 4: Compound 174-3 (600 mg, 1.02 mmol) and 3-bromo-4-hydroxybenzonitrile (608.16 mg, 3.07 mmol) were dissolved in 1,4-dioxane (12 mL) and water (3 mL). Potassium carbonate (424 mg, 3.07 mmol) and 1,1'-bis(diphenylphosphine)ferrocene palladium(II) dichloride (75 mg, 0.10 mmol) were added. The reaction mixture was stirred at 90 °C for 5 hours under a nitrogen atmosphere. Ethyl acetate (80 mL) was added to the reaction mixture, followed by washing with water (15 mL) and saturated brine (15 mL) successively. The mixture was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The crude product was purified by rapid silica gel column chromatography (tetrahydrofuran / petroleum ether: 0-25%) to give compound 174-4 (590 mg, crude product), a white solid. ES-API: [M+H] + =577.2.

[0937] Step 5: Compound 174-4 (590 mg, 1.02 mmol) was dissolved in tetrahydrofuran (5 mL), and 1.0 M tetrabutylammonium fluoride tetrahydrofuran solution (3 mL, 3.0 mmol) was added at room temperature. The reaction mixture was stirred at 55 °C for 18 hours. The reaction solution was cooled to room temperature, concentrated under reduced pressure, and ethyl acetate (100 mL) was added. The mixture was washed successively with saturated sodium bicarbonate solution (25 mL) and saturated brine (25 mL). The organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The crude product was purified by rapid silica gel column chromatography (methanol / dichloromethane: 0-2%) to give compound 174-5 (210 mg, two-step yield 44.4%), a white solid. ES-API: [M+H] + =463.1.

[0938] Step Six: Compound 174-5 (210 mg, 0.45 mmol) was dissolved in toluene (15 mL), and cyanomethylenetri-n-butylphosphine (547 mg, 2.27 mmol) was added at room temperature. The reaction was carried out under nitrogen protection and stirred at 65 °C for 3 hours. The reaction solution was cooled to room temperature and concentrated under reduced pressure. The crude product was purified by rapid silica gel column chromatography (tetrahydrofuran / petroleum ether: 0-20%) to give compound 174-6 (22 mg, yield 10.9%), a colorless liquid. ES-API: [M+H] + =445.1.

[0939] Step 7: Compound 174-6 (22 mg, 0.049 mmol) was dissolved in dimethyl sulfoxide (1.5 mL), and potassium carbonate (34 mg, 0.247 mmol) and 30% hydrogen peroxide iodide (56 mg, 0.494 mmol) were added at room temperature. The reaction mixture was stirred at room temperature for 2 hours. Water (5 mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate (15 mL * 3). The combined organic phases were washed with saturated brine (5 mL * 3), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to give compound 174-7 (22 mg, 96.1% yield), a white solid. ES-API: [M + H] + =463.1.

[0940] Step 8: Compound 174-7 (22 mg, 0.048 mmol) was dissolved in acetonitrile (1.5 mL) and water (0.3 mL). Cerium ammonium nitrate (78 mg, 0.143 mmol) was added at room temperature, and the reaction was stirred at room temperature for 18 hours. The reaction mixture was then extracted with saturated sodium carbonate solution (2 mL) and ethyl acetate (15 mL × 2). The combined organic phases were dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The crude product was purified by rapid silica gel column chromatography (methanol / dichloromethane: 0-10%) to give the target product compound 174-8 (10 mg, yield 56.4%) as a white solid. ES-API: [M+H] + =373.1.

[0941] Step 9: Compound 174-8 (10 mg, 0.027 mmol) and triethylamine (8 mg, 0.080 mmol) were dissolved in dichloromethane (3 mL). Acryloyl chloride (3 mg, 0.027 mmol) was added at 0 °C, and the reaction was stirred at 0 °C for 10 minutes. Dichloromethane (10 mL) was added to the reaction solution, followed by washing with water (5 mL) and saturated brine (5 mL). The solution was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The crude product was subjected to preparative HPLC (ammonium bicarbonate method) to obtain trans-1-acryloyl-15-chloro-1,2,3,4a,5,6,7,17a-octahydro-13,17-(methylene)benzo[12,13][1]oxetanetridecano[5,6-b][1,4]oxazine-11-carboxamide (Z174, 2 mg, yield 17.5%), a white solid. ES-API:[M+H] + =427.1.

[0942] Example 13 Synthesis of compound Z62A

[0943] Step 1: 3-Morphyrinone (6 g, 59.34 mmol) was dissolved in N,N-dimethylformamide (100 mL). 60% sodium hydride (2.85 g, 71.21 mmol) was added at 0 °C. The reaction mixture was stirred at room temperature for 1 hour, followed by dropwise addition of 4-methoxybenzyl chloride (10.46 mL, 77.14 mmol). The reaction mixture was stirred at room temperature for another 2 hours. The reaction solution was quenched with saturated ammonium chloride solution (150 mL) and water (50 mL), and extracted with ethyl acetate (200 mL × 2). The combined organic phases were washed with saturated brine (150 mL × 3), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The crude product was purified by rapid silica gel column chromatography (ethyl acetate / petroleum ether: 0-100%) to give the target product 62-1 (11.6 g, yield 88.4%), a white solid. 1 HNMR(400MHz, CDCl3)δ7.20(d,J=8.8Hz,2H),6.87(d,J=8.8Hz,2H),4.56(s,2H),4.23(s,2H),3.88-3.75(m,5H),3.30-3.21(m,2H).ES-API:[M+H] + =222.1.

[0944] Step 2: Compound 62-1 (6 g, 27.12 mmol) was dissolved in tetrahydrofuran (75 mL). A 2.0 M solution of lithium diisopropylamino in tetrahydrofuran / n-hexane (17.63 mL, 35.26 mmol) was added dropwise at -70 °C. The reaction was stirred at -70 °C for 1 hour. Tert-butyl(3-iodopropoxy)dimethylsilane (10.58 g, 35.25 mmol) was slowly added dropwise, and the reaction was slowly brought to room temperature and stirred for 3 hours. The reaction mixture was quenched with saturated ammonium chloride solution (50 mL) and water (50 mL), and extracted with ethyl acetate (200 mL). The organic phase was washed with saturated brine (80 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The crude product was purified by rapid silica gel column chromatography (tetrahydrofuran / petroleum ether: 0-20%) to give the target product, 62-2 (5.2 g, yield 48.7%), a colorless liquid. ES-API:[M+H] + =394.2.

[0945] Step 3: Dissolve 1-bromo-3-chloro-5-iodobenzene (3.14 g, 9.91 mmol) in tetrahydrofuran (12 mL) in a 50 mL three-necked flask. Under nitrogen protection, slowly add a 1.3 M tetrahydrofuran solution of the isopropyl magnesium chloride-lithium chloride complex (7.62 mL, 9.91 mmol) at -70 °C. Stir the reaction at -70 °C for 30 minutes, and then stir at 0 °C for 30 minutes. In another 100 mL three-necked flask, compound 62-2 (3 g, 7.62 mmol) and 2,6-di-tert-butyl-4-methylpyridine (1.88 g, 9.15 mmol) were dissolved in dichloromethane (40 mL). Under nitrogen protection, Tf₂O (2.58 g, 9.146 mmol) was added dropwise at -70 °C. The reaction was stirred at -70 °C for 45 minutes. The above organomagnesium mixture was slowly added dropwise, and the reaction was slowly brought to room temperature for approximately 3 hours. Acetic acid (12.87 mL, 228.66 mmol) was added, followed by sodium borohydride (0.87 g, 22.87 mmol) in portions. The reaction was stirred at room temperature for 1 hour. The reaction mixture was filtered, and the filter cake was washed with dichloromethane (100 mL). The filtrate was washed with saturated sodium bicarbonate solution (100 mL × 2), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by rapid silica gel column chromatography (tetrahydrofuran / petroleum ether: 0-3%) to obtain the target product 62-4-a (2.1 g, retention time 2.40 min, yield 48.4%), a pale yellow liquid. 1HNMR (400MHz, CDCl3) δ7.50 (s, 1H), 7.45-7.34 (m, 2H), 7.10 (d, J = 8.4Hz, 2H), 6.82 (d, J = 8.4Hz, 2H) ,3.86(dd,J=11.2,1.6Hz,1H),3.78(s,3H),3.72-3.63(m,1H),3.58-3.42(m,3H),3.36-3.26(m,1H) ,2.95(d,J=8.8Hz,1H),2.78(d,J=13.2Hz,1H),2.72(d,J=11.8Hz,1H),2.21(td,J=11.8,3.2Hz,1H) ,1.71-1.60(m,1H),1.45-1.35(m,1H),1.31–1.21(m,2H),0.81(s,9H),-0.04(s,6H).ES-API:[M+H] + =568.2,570.1;

[0946] The target product 62-4-b (690 mg, retention time 2.36 min, yield 15.9%) is a pale yellow liquid. 1 HNMR (400MHz, CDCl3) δ7.53-7.32(m,3H),7.19(d,J=6.0Hz,2H),6.87(d,J=8.4H z,2H),4.08-3.97(m,1H),3.90-3.71(m,5H),3.58-3.43(m,3H),3.30(d,J=12.8 Hz,1H),3.20(d,J=13.2Hz,1H),2.75(t,J=10.8Hz,1H),2.36(d,J=10.8Hz,1H), 1.55-1.47(m,1H),1.34-1.21(m,3H),0.82(s,9H),-0.02(s,6H).ES-API:[M+H] + =568.2,570.1.

[0947] Step 4: Compound 62-4-b (650 mg, 1.14 mmol) and 4-[(methoxymethyl)oxy]-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)phenyl-1-onitrile (446 mg, 1.54 mmol, preparation method according to US2021 / 299070, Compound C8-3) were dissolved in 1,4-dioxane (8 mL) and water (2 mL). Potassium carbonate (395 mg, 2.86 mmol) and 1,1'-bis(diphenylphosphine)ferrocene palladium(II) dichloride (84 mg, 0.11 mmol) were added. The mixture was purged with nitrogen for 30 seconds, and the reaction was stirred at 85°C for 45 minutes in a microwave reactor. Ethyl acetate (80 mL) was added to the reaction solution, followed by washing with water (15 mL) and saturated brine (15 mL) successively. The mixture was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The crude product was purified by rapid silica gel column chromatography (ethyl acetate / petroleum ether: 0-20%) to give the target product 62-5 (690 mg, yield 92.7%), a pale yellow liquid. ES-API: [M+H] + =651.3.

[0948] Step 5: Compound 62-5 (640 mg, 0.98 mmol) was dissolved in dichloromethane (10 mL) and anhydrous methanol (1 mL). A 4.0 M dioxane hydrochloride solution (5 mL, 20.0 mmol) was added at 0 °C, and the reaction was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure, alkalized with saturated sodium bicarbonate solution, and extracted with dichloromethane (30 mL). The organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The crude product was purified by rapid silica gel column chromatography (methanol / dichloromethane: 0-3%) to give the target product 62-6 (400 mg, yield 82.6%) as a white solid. ES-API: [M+H] + =493.1.

[0949] Step Six: Compound 62-6 (400 mg, 0.811 mmol) was dissolved in toluene (100 mL), and cyanomethylenetri-n-butylphosphine (979 mg, 4.06 mmol) was added at room temperature. The reaction mixture was refluxed and stirred for 18 hours under nitrogen protection. The reaction solution was cooled to room temperature and concentrated under reduced pressure. The crude product was purified by rapid silica gel column chromatography (tetrahydrofuran / petroleum ether: 0-20%) to give the target product 62-7 (70 mg, yield 18.2%), a colorless liquid. ES-API: [M+H] + =475.1.

[0950] Step 7: Compound 62-7 (70 mg, 0.147 mmol) was dissolved in dimethyl sulfoxide (3 mL), and potassium carbonate (61 mg, 0.442 mmol) and 30% hydrogen peroxide iodide (83 mg, 0.737 mmol) were added at room temperature. The reaction mixture was stirred at room temperature for 2 hours. Water (5 mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate (20 mL * 3). The combined organic phases were washed with saturated brine (5 mL * 3), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to give the target product 62-8 (70 mg, yield 96.3%) as a white solid. ES-API: [M + H] + =493.2.

[0951] Step 8: Compound 62-8 (70 mg, 0.142 mmol) was dissolved in acetonitrile (7 mL) and water (3.5 mL). Cerium ammonium nitrate (311 mg, 0.568 mmol) was added at room temperature, and the reaction was stirred for 2 hours at room temperature. Then, additional cerium ammonium nitrate (311 mg, 0.568 mmol) was added, and the reaction was stirred for another 2 hours at room temperature. The reaction mixture was then extracted with 10 mL of saturated sodium carbonate solution and ethyl acetate (30 mL × 2). The combined organic phases were dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The crude product was purified by rapid silica gel column chromatography (methanol / dichloromethane: 0-10%) to give the target product 62-9 (20 mg, yield 37.8%) as a white solid. ES-API: [M+H] + =373.1.

[0952] Step 9: Compound 62-9 (20 mg, 0.054 mmol) and triethylamine (16 mg, 0.161 mmol) were dissolved in dichloromethane (3 mL). Acryloyl chloride (5 mg, 0.054 mmol) was added at 0 °C, and the reaction was stirred at 0 °C for 10 minutes. Dichloromethane (10 mL) was added to the reaction solution, followed by washing with water (5 mL) and saturated brine (5 mL). The solution was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The crude product was subjected to preparative HPLC (ammonium bicarbonate method) to obtain the target product cis-1-acryloyl-15-chloro-1,2,3,4a,5,6,7,17a-octahydro-13,17-(methylene)benzo[12,13][1]oxetanetridecano[5,6-b][1,4]oxazine-11-carboxamide (Z62A, 10 mg, yield 43.7%), a white solid. ES-API:[M+H] + =427.1. 1HNMR(400MHz,DMSO-d6)δ8.13-7.78(m,4H),7.45(s,1H),7.39-7.20(m,3H),7.10-6.76(m,1H),6.25-6.12(m,1H),5.80-5.6 5(m,1H),5.46-5.24(m,1H),4.53-4.34(m,1H),4.23-3.79(m,4H),3.64-3.49(m,1H),3.43-3.14(m,1H),2.17-1.29(m,4H).

[0953] Example 14 Synthesis of compounds Z122 and Z122A

[0954] Step 1: Compound Z174 (26 mg, 0.061 mmol) was chirally separated (separation column: (ID, 10 μm, 30*250 mm, mobile phase: acetonitrile:isopropanol = 85:15 (V / V), flow rate: 25 mL / min, column temperature: room temperature) Two isomers were obtained. One of the structures was arbitrarily designated as (4aR,17aR)-1-acryloyl-15-chloro-1,2,3,4a,5,6,7,17a-octahydro-13,17-(methylene)benzo[12,13][1]oxetanetridecano[5,6-b][1,4]oxazine-11-carboxamide (Z122, 8 mg, retention time 6.278 min, yield 30.8%), white solid. ES-API: [M+H] + =427.1. 1HNMR(400MHz,DMSO-d6)δ8.16(d,J=2.4Hz,1H),8.09-7.94(m,2H),7.87(dd,J=8.4,2.4Hz,1H),7.51(s,1H),7.37(s,1H),7.30-7.18(m,2H),6.7 8(dd,J=16.8,10.4Hz,1H),6.17(dd,J=16.8,2.4Hz,1H),5.69(dd,J=10.4,2.4Hz,1H),4.97(d,J=9.6Hz,1H),4.18-4.03(m,1H),3.95-3.84(m,2 3.83-3.76 (m, 1H), 3.73-3.52 (m, 3H), 2.23-2.09 (m, 1H), 1.92-1.79 (m, 1H), 1.75-1.60 (m, 1H), 1.37-1.25 (m, 1H). Another structure is arbitrarily designated as (4aS, 17aS)-1-acryloyl-15-chloro-1,2,3,4a,5,6,7,17a-octahydro-13,17-(methylene)benzo[12,13][1]oxetanetridecano[5,6-b][1,4]oxazine-11-carboxamide (Z122A, 9 mg, retention time 7.337 min, yield 34.6%), white solid. ES-API: [M+H] + =427.1. 1 HNMR(400MHz, DMSO-d6)δ8.16(d,J=2.4Hz,1H),8.07-7.94(m,2H),7.87(dd,J=8.4,2.4Hz,1H),7.51( s,1H),7.36(s,1H),7.30-7.20(m,2H),6.77(dd,J=16.8,10.4Hz,1H),6.17(dd,J=16.8,2.4Hz,1H),5 .69(dd,J=10.4,2.4Hz,1H),4.97(d,J=9.6Hz,1H),4.15-4.02(m,1H),3.94-3.84(m,2H),3.84-3.76( m,1H),3.74-3.54(m,3H),2.21-2.08(m,1H),1.96-1.79(m,1H),1.74-1.61(m,1H),1.35-1.26(m,1H).

[0955] Example 15 Synthesis of compound Z176

[0956] Step 1: Sodium hydroxide (3.27 g, 136.19 mmol, 60% dispersed in oil) was added to a tetrahydrofuran (15 mL) solution of (2E)-but-2-ene-1,4-diol (4 g, 45.398 mmol) under ice-water bath conditions. The reaction mixture was stirred at 0°C for 0.5 h. Then, tert-butyldiphenylchlorosilane (12.44 g, 45.40 mmol) was added to the reaction mixture, and the reaction mixture was stirred at room temperature for 6 h. The reaction mixture was cooled to 0°C, and the reaction was quenched with a saturated ammonium chloride solution (30 mL). Extraction was performed with ethyl acetate (20 mL x 3). The combined organic phases were washed with saturated brine (20 mL x 3), dried over anhydrous sodium sulfate, filtered, and concentrated to dryness. The residue was purified by automated rapid chromatography (tetrahydrofuran / petroleum ether = 0-50%) to give compound 176-1 (6.7 g, 20.520 mmol, yield 45.20%), a colorless oily liquid.

[0957] Step 2: Triphenylphosphine (1.37 g, 5.2 mmol) was added to a solution of compound 176-1 (1.7 g, 5.207 mmol) in dichloromethane (55 mL) under an ice-water bath. The reaction mixture was stirred at 0 °C for 0.5 h. Carbon tetrabromide (2.76 g, 8.33 mmol) was then added. The reaction mixture was stirred at room temperature for 2 h. The mixture was concentrated under reduced pressure. The residue was purified by automated rapid chromatography (tetrahydrofuran / petroleum ether = 0-10%) to obtain compound 176-2 (1500 mg, 3.852 mmol, yield 73.98%), a colorless oily liquid.

[0958] Step 3: Compound 63-2 (8 g, 18.926 mmol) was dissolved in tetrahydrofuran (40 mL), ethanol (40 mL), and sodium borohydride (1.07 g, 28.389 mmol). The mixture was stirred at -40 °C for 1 h. A saturated ammonium chloride solution (20 mL) was added in an ice-water bath, and the mixture was concentrated. Ethyl acetate (30 mL x 3) was added, and the organic phase was washed with saturated brine. The solution was dried over anhydrous sodium sulfate and purified by rapid silica gel column chromatography (petroleum ether / ethyl acetate = 0:30%) to obtain compound 63-3-A (2.5 g, 5.886 mmol, yield 31.10%), a colorless oily liquid (TLC: PE:EA = 3:1, Rf = 0.55), ES-API: [M+H]. + =424.4. 1¹H NMR (400 MHz, CDCl₃) δ 7.34–7.26 (m, 4H), 7.25–7.19 (m, 3H), 7.13 (s, 1H), 5.22 (dd, J = 6.2, 3.4 Hz, 1H), 5.16–5.03 (m, 2H), 4.18–3.93 (m, 2H), 3.35–3.27 (m, 1H), 2.25–2.22 (m, 1H), 2.09–2.02 (m, 1H), 1.86–1.73 (m, 1H), 1.64–1.50 (m, 1H). Compound 63-3-B (3.2 g, 7.534 mmol, yield 39.81%) was a colorless oily liquid (TLC: PE:EA = 3:1, Rf = 0.5), ES-API: [M+H]. + =424.4. 1 HNMR(400MHz, CDCl3)δ7.46-7.29(m,6H),7.26-7.22(m,1H),7.15-7.12(m,1H),5.59-5.58(m,1H),5.24-5.05(m,2H), 4.25(d,J=13.6Hz,1H),3.75-3.71(m,1H),2.85-2.78(m,1H),2.60-2.37(m,1H),1.94-1.74(m,2H),1.56-1.41(m,1H).

[0959] Step 4: A solution of compound 63-3-B (800 mg, 1.884 mmol) in N,N-dimethylformamide (15 mL) was added to sodium hydroxide (226 mg, 5.65 mmol, 60% dispersed in oil). The reaction mixture was stirred at 0°C for 0.5 h. Compound 176-2 (1246.93 mg, 3.202 mmol) was then added to the reaction mixture, and the reaction mixture was stirred at room temperature for 3 h. The reaction mixture was cooled to 0°C, and the reaction was quenched by adding saturated ammonium chloride solution (20 mL). Extraction was performed with ethyl acetate (20 mL x 3). The combined organic phases were washed with saturated brine (20 mL x 3), dried over anhydrous sodium sulfate, filtered, and concentrated to dryness. The residue was purified by automated rapid chromatography (tetrahydrofuran / petroleum ether = 0-50%) to give compound 176-3 (330 mg, 0.450 mmol, yield 23.89%), a colorless oily liquid. ES-API: [M+Na] + =754.2.

[0960] Step 5: Under nitrogen protection, compound 176-3 (250 mg, 0.341 mmol), 4-[(methoxymethyl)oxy]-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)phenyl-1-onitrile (177.45 mg, 0.614 mmol, preparation method according to US2021 / 299070, Compound C8-3), potassium carbonate (130 mg, 0.675 mmol), and [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloride (24 mg, 0.034 mmol) were dissolved in 1,4-dioxane (5 mL) and water (1 mL). The reaction mixture was heated to 85 °C and stirred for 1 h. The reaction was confirmed to be complete by LCMS, and the reaction solution was concentrated to dryness under reduced pressure. The residue was purified by automated rapid chromatography (tetrahydrofuran / petroleum ether = 0-40%) to give compound 176-4 (120 mg, 0.147 mmol, yield 43.16%), a colorless oily liquid. ES-API: [M+Na] + =837.2.

[0961] Step Six: Compound 176-4 (15 mg, 0.018 mmol) was dissolved in methanol (1 mL), and concentrated hydrochloric acid (0.1 mL) was added. The mixture was reacted at room temperature for 2 hours, followed by the addition of saturated sodium bicarbonate solution (10 mL). The mixture was concentrated and extracted with ethyl acetate (20 mL x 3). The combined organic phases were washed with saturated brine (20 mL x 3), dried over anhydrous sodium sulfate, filtered, and concentrated to dryness. The residue was purified by automated rapid chromatography (tetrahydrofuran / petroleum ether = 0-50%) to give compound 176-5 (6 mg, 0.011 mmol, yield 61.20%), a colorless oily liquid. ES-API: [M+H] + =533.1.

[0962] Step 7: Under nitrogen protection, cyanomethylenetri-n-butylphosphine (52 mg, 0.15 mmol) was added to a toluene (3 mL) solution of compound 176-5 (55 mg, 0.100 mmol). The reaction mixture was heated to 100 °C and stirred for 1 h. The reaction was confirmed to be complete by LC-MS. The reaction mixture was concentrated to dryness under reduced pressure. The residue was purified by automated rapid chromatography on silica gel (tetrahydrofuran / petroleum ether = 0-55%) to give compound 176-6 (40 mg, 0.075 mmol, yield 75.19%) as a white solid. ES-API: [M+H] + =515.2

[0963] Step 8: Compound 176-6 (10 mg, 0.019 mmol) was dissolved in dimethyl sulfoxide (2 mL) under an ice-water bath. Potassium carbonate (36.17 mg, 0.262 mmol) and hydrogen peroxide (49.51 mg, 0.437 mmol) were added, and the reaction was carried out at room temperature for 2 hours. Water (5 mL) was added, and the mixture was extracted with ethyl acetate (10 mL * 3). The combined organic phases were washed with saturated brine (10 mL * 3), dried over anhydrous sodium sulfate, filtered, and concentrated to dryness to give compound 176-7 (8 mg, 0.015 mmol, yield 77.29%), a white solid. ES-API: [M + H] + =533.1.

[0964] Step 9: Compound 176-7 (5 mg, 0.009 mmol) was dissolved in hexafluoroisopropanol (2 mL) under ice-water bath conditions. Aluminum trichloride (23.94 mg, 0.180 mmol) was added, and the reaction was carried out at room temperature for 3 hours. Saturated sodium bicarbonate solution (10 mL) was added, and the mixture was extracted with dichloromethane (10 mL x 3). The combined organic phases were washed with saturated brine (10 mL x 3), dried over anhydrous sodium sulfate, filtered, and concentrated to dryness to give compound 176-8 (3 mg, 0.008 mmol, yield 80.21%), a white solid. ES-API: [M+H] + =399.1.

[0965] Step 10: Under ice-water bath conditions, N,N-diisopropylethylamine (4.86 mg, 0.038 mmol) and acryloyl chloride (0.68 mg, 0.008 mmol) were added sequentially to a solution of compound 176-8 (3 mg, 0.008 mmol) in dichloromethane (2 mL). The reaction mixture was stirred at 0 °C for 10 minutes. LCMS analysis confirmed the reaction was complete. Dichloromethane (10 mL) and water (10 mL) were added to the reaction mixture, and the mixture was extracted with dichloromethane (10 mL * 2). The organic phases were combined and washed with saturated brine (10 mL * 2). The mixture was dried over anhydrous sodium sulfate, filtered, and concentrated to dryness. The residue was purified by preparative HPLC (formic acid method 1) to obtain trans-(E)-1. 1 -Acryloyl-2 5 -Chloride-1 2 λ 3 ,1 4 λ 3 -4,9-Dioxa-1(2,4)-piperidine-2(1,3),3(1,2)-dibenzocyclononane-6-ene-3 5 Formamide (Z176, 0.7 mg, 0.002 mmol, yield 21.1%), retention time 6.694 min, white solid. ES-API: [M+H] + =453.1.

[0966] Example 16 Synthesis of compounds Z177 and Z178

[0967] Step 1: Sodium hydroxide (470 mg, 11.772 mmol, 60% dispersed in oil) was added to a solution of compound 63-3 (1.0 g, 2.354 mmol) in N,N-dimethylformamide (15 mL) under ice-water bath conditions. The reaction mixture was stirred at 0°C for 0.5 h. Then, 1-iodo-4,4,5,5-tetramethyl-3-oxa-4-silane (3369.63 mg, 11.772 mmol) was added. The reaction mixture was heated to 50°C and stirred for 16 h. LC-MS analysis showed product formation, but some starting material remained. The reaction mixture was cooled to 0°C, and the reaction was quenched with saturated ammonium chloride solution (30 mL). Extraction was performed with ethyl acetate (20 mL x 3). The combined organic phases were washed with saturated brine (20 mL x 3), dried over anhydrous sodium sulfate, filtered, and concentrated to dryness. The residue was purified by automated rapid chromatography (tetrahydrofuran / petroleum ether = 0-50%) to give compound 177-1 (560 mg, 0.960 mmol, yield 40.79%), a colorless oily liquid. ES-API: [M+Na] + =604.0.

[0968] Step 2: Add tetrabutylammonium fluoride solution (1.39 mL, 1.39 mmol, 1M tetrahydrofuran solution) to a tetrahydrofuran (6 mL) solution of compound 177-1 (540 mg, 0.926 mmol). Stir the reaction mixture at room temperature for 5 h. Monitor the reaction for completeness using LCMS. Add ethyl acetate (15 mL) to the reaction mixture, wash with saturated brine (15 mL * 3), dry the organic phase with anhydrous sodium sulfate, filter, and concentrate to dryness. Purify the residue by automated rapid chromatography (tetrahydrofuran / petroleum ether = 0-70%) to obtain compound 177-2 (360 mg, 0.768 mmol, yield 82.92%), a colorless oily liquid. ES-API: [M+H] + =468.0.

[0969] Step 3: Sodium hydroxide (51 mg, 2.13 mmol, 60% dispersed in oil) was added to a solution of compound 177-2 (250 mg, 0.533 mmol) in N,N-dimethylformamide (5 mL) under ice-water bath conditions. The reaction mixture was stirred at 0°C for 0.5 h. Then, 1-iodo-4,4,5,5-tetramethyl-3-oxa-4-silane (610.60 mg, 2.133 mmol) was added. The reaction mixture was heated to 50°C and stirred for 16 h. LC-MS analysis showed product formation, but some starting material remained. The reaction mixture was cooled to 0°C, and the reaction was quenched with saturated ammonium chloride solution (10 mL). Extraction was performed with ethyl acetate (20 mL x 3). The combined organic phases were washed with saturated brine (20 mL x 3), dried over anhydrous sodium sulfate, filtered, and concentrated to dryness. The residue was purified by automated rapid chromatography (tetrahydrofuran / petroleum ether = 0-50%) to give compound 177-3 (130 mg, 0.207 mmol, yield 38.87%), a colorless oily liquid. ES-API: [M+Na] + =648.1.

[0970] Step 4: Under nitrogen protection, compound 177-3 (110 mg, 0.175 mmol), 4-[(methoxymethyl)oxy]-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)phenyl-1-onitrile (91.29 mg, 0.316 mmol, preparation method according to US2021 / 299070, Compound C8-3), potassium carbonate (34 mg, 0.175 mmol), and [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloride (14 mg, 0.019 mmol) were dissolved in 1,4-dioxane (5 mL) and water (1 mL). The reaction mixture was heated to 85 °C and stirred for 1 h. The reaction was confirmed to be complete by LCMS, and the reaction solution was concentrated to dryness under reduced pressure. The residue was purified by automated rapid chromatography (tetrahydrofuran / petroleum ether = 0-20%) to give compound 177-4 (90 mg, 0.127 mmol, yield 72.33%), a colorless oily liquid. ES-API: [M+Na] + =731.2.

[0971] Step 5: Compound 177-4 (90 mg, 0.127 mmol) was dissolved in methanol (5 mL), concentrated hydrochloric acid (1 mL) was added, and the mixture was reacted at room temperature for 2 hours. Saturated sodium bicarbonate solution (10 mL) was added, and the mixture was concentrated and extracted with ethyl acetate (20 mL * 3). The combined organic phases were washed with saturated brine (20 mL * 3), dried over anhydrous sodium sulfate, filtered, and concentrated to dryness. The residue was purified by automated rapid chromatography (tetrahydrofuran / petroleum ether = 0-50%) to give compound 177-5 (55 mg, 0.100 mmol, yield 78.67%), a colorless oily liquid. ES-API: [M+H] + =551.1.

[0972] Step Six: Under nitrogen protection, cyanomethylenetri-n-butylphosphine (52 mg, 0.15 mmol) was added to a 3 mL solution of compound 177-5 (55 mg, 0.100 mmol) in toluene. The reaction mixture was heated to 100 °C and stirred for 1 h. The reaction was confirmed to be complete by LC-MS. The reaction mixture was concentrated to dryness under reduced pressure. The residue was purified by automated rapid chromatography on silica gel (tetrahydrofuran / petroleum ether = 0-55%) to give compound 177-6 (40 mg, 0.075 mmol, yield 75.19%) as a white solid. ES-API: [M+H] + =533.2.

[0973] Step 7: Compound 177-6 (40 mg, 0.075 mmol) was dissolved in dimethyl sulfoxide (2 mL) under an ice-water bath. Potassium carbonate (36.17 mg, 0.262 mmol) and hydrogen peroxide (49.51 mg, 0.437 mmol) were added, and the reaction was carried out at room temperature for 2 hours. Water (5 mL) was added, and the mixture was extracted with ethyl acetate (10 mL * 3). The combined organic phases were washed with saturated brine (10 mL * 3), dried over anhydrous sodium sulfate, filtered, and concentrated to dryness to give compound 177-7 (35 mg, 0.064 mmol, yield 84.64%), a white solid. ES-API: [M + H] + =551.1.

[0974] Step 8: Compound 177-7 (10 mg, 0.018 mmol) was dissolved in hexafluoroisopropanol (2 mL) under ice-water bath conditions. Aluminum trichloride (23.94 mg, 0.180 mmol) was added, followed by saturated sodium bicarbonate solution (10 mL). Extraction was performed with dichloromethane (20 mL x 3). The combined organic phases were washed with saturated brine (20 mL x 3), dried over anhydrous sodium sulfate, filtered, and concentrated to dryness to obtain compound 177-8 (6 mg, 0.014 mmol, yield 79.26%), a white solid. ES-API: [M+H] + =417.2.

[0975] Step 9: Under ice-water bath conditions, N,N-diisopropylethylamine (9.3 mg, 0.072 mmol) and acryloyl chloride (2.1 mg, 0.024 mmol) were added sequentially to a solution of compound 177-8 (10 mg, 0.024 mmol) in dichloromethane (5 mL). The reaction mixture was stirred at 0 °C for 10 minutes. LCMS analysis confirmed the reaction was complete. Dichloromethane (10 mL) and water (10 mL) were added to the reaction mixture, and the mixture was extracted with dichloromethane (10 mL x 2). The organic phases were combined and washed with saturated brine (10 mL x 2). The mixture was dried over anhydrous sodium sulfate, filtered, and concentrated to dryness. The residue was purified by preparative HPLC (formic acid method 1) to obtain two isomers. One of the structures was arbitrarily designated as trans-1. 1 -Acryloyl-2 5 -Chloro-4,7,10-trioxa-1(2,4)-piperidine-2(1,3),3(1,2)-dibenzocyclodecadecane-3 5 1,2-Formamide (Z177, 2.1 mg, 0.004 mmol, yield 18.58%, retention time: 6.220 min), white solid. ES-API: [M+H] + =471.1. Another structure can be arbitrarily specified as cis-1. 1 -Acryloyl-2 5 -Chloro-4,7,10-trioxa-1(2,4)-piperidine-2(1,3),3(1,2)-dibenzocyclodecadecane-3 5 1,4-Formamide (Z178, 0.47 mg, 0.001 mmol, yield 4.16%, retention time: 6.439 min), white solid. ES-API: [M+H] + =471.1.

[0976] Example 17 Synthesis of compound Z209

[0977] Step 1: A solution of cis-1,2-dihydroxymethylethylene (4 g, 45.398 mmol) in tetrahydrofuran (15 mL) was reacted with sodium hydroxide (3.27 g, 136.19 mmol, 60% dispersed in oil) in an ice-water bath. The reaction mixture was stirred at 0°C for 0.5 h. Then, tert-butyldiphenylchlorosilane (12.44 g, 45.40 mmol) was added to the reaction mixture, and the mixture was stirred at room temperature for 6 h. The reaction mixture was cooled to 0°C, and the reaction was quenched with saturated ammonium chloride solution (30 mL). Extraction was performed with ethyl acetate (20 mL x 3). The combined organic phases were washed with saturated brine (20 mL x 3), dried over anhydrous sodium sulfate, filtered, and concentrated to dryness. The residue was purified by automated rapid chromatography (tetrahydrofuran / petroleum ether = 0-50%) to give compound 209-1 (8.3 g, 25.420 mmol, yield 55.99%), a colorless oily liquid.

[0978] Step 2: Triphenylphosphine (1.37 g, 5.2 mmol) was added to a solution of compound 209-1 (1.7 g, 5.207 mmol) in dichloromethane (55 mL) under an ice-water bath. The reaction mixture was stirred at 0 °C for 0.5 h. Carbon tetrabromide (2.76 g, 8.33 mmol) was then added. The reaction mixture was stirred at room temperature for 2 h. The mixture was concentrated under reduced pressure. The residue was purified by automated rapid chromatography (tetrahydrofuran / petroleum ether = 0-10%) to obtain compound 209-2 (1500 mg, 3.852 mmol, yield 73.98%), a colorless oily liquid.

[0979] Step 3: A solution of compound 63-3-B (800 mg, 1.884 mmol) in N,N-dimethylformamide (20 mL) was added to sodium hydroxide (300 mg, 7.53 mmol, 60% dispersed in oil). The reaction mixture was stirred at 0°C for 0.5 h. Compound 209-2 (2200 mg, 5.65 mmol) was then added to the reaction mixture, and the reaction mixture was stirred at room temperature for 3 h. The reaction mixture was cooled to 0°C, and the reaction was quenched by adding saturated ammonium chloride solution (20 mL). Extraction was performed with ethyl acetate (20 mL x 3). The combined organic phases were washed with saturated brine (20 mL x 3), dried over anhydrous sodium sulfate, filtered, and concentrated to dryness. The residue was purified by automated rapid chromatography (tetrahydrofuran / petroleum ether = 0-50%) to give compound 209-3 (870 mg, 1.18 mmol, yield 62.89%), a colorless oily liquid. ES-API: [M+Na] + =754.1.

[0980] Step 4: Under nitrogen protection, compound 209-3 (250 mg, 0.341 mmol), 4-[(methoxymethyl)oxy]-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)phenyl-1-onitrile (700 mg, 0.955 mmol, preparation method according to US2021 / 299070, Compound C8-3), potassium carbonate (330 mg, 2.387 mmol), and [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloride (70 mg, 0.095 mmol) were dissolved in 1,4-dioxane (10 mL) and water (2 mL). The reaction mixture was heated to 85 °C and stirred for 1 h. The reaction was confirmed to be complete by LCMS, and the reaction solution was concentrated to dryness under reduced pressure. The residue was purified by automated rapid chromatography (tetrahydrofuran / petroleum ether = 0-40%) to give compound 209-4 (690 mg, 0.846 mmol, yield 88.63%), a colorless oily liquid. ES-API: [M+Na] + =837.1.

[0981] Step 5: Compound 209-4 (690 mg, 0.846 mmol) was dissolved in dichloromethane (10 mL), methanol (1 mL), and dioxane (4 M, 1 mL) solution of hydrogen chloride was added. The mixture was reacted at room temperature for 2 hours, followed by the addition of saturated sodium bicarbonate solution (10 mL), concentration, and extraction with ethyl acetate (20 mL * 3). The combined organic phases were washed with saturated brine (20 mL * 3), dried over anhydrous sodium sulfate, filtered, and concentrated to dryness. The residue was purified by automated rapid chromatography (tetrahydrofuran / petroleum ether = 0-50%) to give compound 209-5 (290 mg, 0.544 mmol, yield 64.30%), a colorless oily liquid. ES-API: [M+H] + =533.2.

[0982] Step Six: Under nitrogen protection, cyanomethylenetri-n-butylphosphine (177 mg, 0.62 mmol) was added to a 3 mL solution of compound 209-5 (220 mg, 0.413 mmol) in toluene. The reaction mixture was heated to 100 °C and stirred for 1 h. The reaction was confirmed to be complete by LC-MS. The reaction mixture was concentrated to dryness under reduced pressure. The residue was purified by automated rapid chromatography on silica gel (tetrahydrofuran / petroleum ether = 0-55%) to give compound 209-6 (120 mg, 0.233 mmol, yield 56.45%) as a white solid. ES-API: [M+H] + =515.2.

[0983] Step 7: Compound 209-6 (40 mg, 0.075 mmol) was dissolved in dimethyl sulfoxide (2 mL) under ice-water bath conditions. Potassium carbonate (53.57 mg, 0.388 mmol) and hydrogen peroxide (53.59 mg, 0.388 mmol) were added, and the reaction was carried out at room temperature for 2 hours. Water (5 mL) was added, and the mixture was extracted with ethyl acetate (10 mL * 3). The combined organic phases were washed with saturated brine (10 mL * 3), dried over anhydrous sodium sulfate, filtered, and concentrated to dryness to give compound 209-7 (40 mg, 0.075 mmol, yield 96.62%) as a white solid. ES-API: [M+H] + =533.1.

[0984] Step 8: Compound 209-7 (20 mg, 0.039 mmol) was dissolved in hexafluoroisopropanol (2 mL) under an ice-water bath. Aluminum trichloride (20 mg, 0.150 mmol) was added, and the reaction was carried out at room temperature for 3 hours. Saturated sodium bicarbonate solution (10 mL) was added, and the mixture was extracted with dichloromethane (10 mL x 3). The combined organic phases were washed with saturated brine (10 mL x 3), dried over anhydrous sodium sulfate, filtered, and concentrated to dryness to give compound 209-8 (14 mg, 0.035 mmol, yield 93.53%), a white solid. ES-API: [M+H] +=399.1.

[0985] Step 9: Under ice-water bath conditions, N,N-diisopropylethylamine (11.64 mg, 0.09 mmol) and acryloyl chloride (2.72 mg, 0.03 mmol) were added sequentially to a solution of compound 209-8 (12 mg, 0.03 mmol) in dichloromethane (2 mL). The reaction mixture was stirred at 0 °C for 10 minutes. LCMS analysis confirmed the reaction was complete. Dichloromethane (10 mL) and water (10 mL) were added to the reaction mixture, and the mixture was extracted with dichloromethane (10 mL * 2). The organic phases were combined and washed with saturated brine (10 mL * 2). The mixture was dried over anhydrous sodium sulfate, filtered, and concentrated to dryness. The residue was purified by preparative HPLC (formic acid method 2) to obtain trans-(Z)-1. 1 -Acryloyl-2 5 -Chloro-4,9-dioxa-1(2,4)-piperidine-2(1,3),3(1,2)-dibenzocyclononane-6-ene-3 5 1,3-Formamide (Z209, 4.3 mg, 0.009 mmol, yield 31.56%), retention time 7.414 min, white solid. ES-API: [M+H] + =453.1.

[0986] Example 18 Synthesis of compound Z210

[0987] Step 1: Add sodium carbonate (22.24 mg, 2.097 mmol), 1,1'-bis(diphenylphosphino)ferrocene palladium(II) dichloride (76.71 mg, 0.105 mol), compound 63-5 (460.0 mg, 0.699 mol), and 2,4-dichloropyrimidin-5-ol (180.0 mg, 1.091 mmol) to a microwave tube. Finally, add dioxane and water (24 mL, 5:1, v / v) and microwave the mixture at 85 °C for 90.0 minutes under a nitrogen atmosphere. After the reaction was complete, the reactants were diluted with 30 mL of water and 150 mL of ethyl acetate, extracted with ethyl acetate (100 mL * 3), and the combined organic compounds were washed with saturated brine (50 mL * 2). The mixture was then concentrated to dryness, and the residue was purified by rapid silica gel column chromatography (tetrahydrofuran / petroleum ether = 0-30%) to give compound 210-1 (235.0 mg, yield: 50.89%). ES-API: [M+H] + =660.2.

[0988] Step 2: To a tetrahydrofuran (6 mL) solution of compound 210-1 (235.0 mg, 0.356 mmol), tetrabutylammonium fluoride solution (5.0 mL, 5.0 mmol, 1 M) was added, and the reaction mixture was stirred at room temperature for 3 h. The reaction was confirmed to be complete by LC-MS. Ethyl acetate (40.0 mL) was added to the reaction mixture, followed by washing with saturated brine (30.0 mL x 3). The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated to dryness. The residue was purified by automated rapid chromatography on silica gel (methanol / dichloromethane = 0-10%) to give compound 210-2 (150.0 mg, yield: 77.18%). ES-API: [M+H] + =546.2.

[0989] Step 3: Under nitrogen protection, cyanomethylenetri-n-butylphosphine (0.36 mL, 1.372 mmol) was added to a toluene (10.0 mL) solution of compound 210-2 (150.0 mg, 0.274 mmol). The reaction mixture was heated to 70.0 °C and stirred for 6 h. LC-MS was used to confirm the completeness of the reaction. The reaction mixture was concentrated to dryness under reduced pressure. The residue was purified by automated rapid chromatography on silica gel (tetrahydrofuran / petroleum ether = 0-70%) to obtain compound 210-3 (120.0 mg, yield: 82.73%). ES-API: [M+H] + =528.1.

[0990] Step 4: Ammonia (6.0 mL, 155.71 mmol) was added to a dioxane (1.0 mL) solution of compound 210-3 (120.0 mg, 0.227 mmol), and the mixture was microwaved at 150 °C for 2 h. After the reaction was complete, the cooled solution was extracted with ethyl acetate (2 x 100 mL) and saturated brine (100 mL). The organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated. Then, compound 210-4 (60.0 mg, yield: 51.91%) was purified by rapid silica gel column chromatography [methanol (0.05% ammonia) / dichloromethane = 0-30%, (v / v)]. ES-API: [M+H] + =509.2.

[0991] Step 5: Under nitrogen protection, compound 210-4 (60.0 mg, 0.118 mmol), triethylamine (0.13 mL, 0.943 mmol), and palladium dichloride (12.54 mg, 0.071 mmol) were dissolved in dichloromethane solution (5.0 mL). Triethylsilane (0.40 mL, 2.50 mmol) was added to the reaction solution, and the reaction was stirred at room temperature for 1 h. The reaction was confirmed to be complete by LCMS. The reaction was quenched by adding water (10 mL), extracted with dichloromethane (20.0 mL * 3), and the organic phase was washed with saturated brine (20.0 mL * 3), dried over anhydrous sodium sulfate, filtered, and concentrated to dryness. The residue was purified by automated rapid chromatography on silica gel (methanol / dichloromethane = 0-10%) to give compound 210-5 (30.0 mg, yield: 67.89%). ES-API: [M+H] + =375.1.

[0992] Step Six: Under an ice-water bath, triethylamine (88.0 mg, 0.863 mmol) and acryloyl chloride (8.00 mg, 0.088 mmol) were added sequentially to a dichloromethane (5 mL) solution of compound 210-5 (30.0 mg, 0.080 mmol). The reaction solution was stirred at 0 °C for 10 minutes. LCMS confirmed that the reaction was complete. Dichloromethane (20.0 mL) and water (10 mL) were added to the reaction solution, and the mixture was extracted with dichloromethane (30.0 mL * 2). The organic phases were combined and washed with saturated brine (30.0 mL * 2). The mixture was dried over anhydrous sodium sulfate, filtered, and concentrated to dryness. The residue was purified by preparative HPLC (formic acid method 2) to obtain 1-(1 2 -amino-2 5 -Chloro-4,9-dioxa-1(4,5)-pyrimidine-3(2,4)-piperidine-2(1,3)-phenylcyclononane-3 1 (-yl)prop-2-en-1-one (Z210, 2.88 mg, yield: 8.39%, including peaks at retention times of 6.642 min and 7.137 min). ES-API: [M+H] + =429.2.

[0993] Example 19 Synthesis of compounds Z211 and Z212

[0994] Step 1: Fuming nitric acid (6.8 mL) was slowly added to a solution of 10 g (57.471 mmol) of 2-bromo-3-hydroxypyridine in 60 mL of concentrated sulfuric acid under an ice-water bath. The reaction mixture was slowly heated to room temperature and stirred overnight. The reaction was confirmed to be complete by LC-MS. The reaction mixture was then slowly added dropwise to an ice-water bath with stirring. The aqueous phase was extracted with ethyl acetate (30 mL x 3). The combined organic phases were washed with saturated brine (20 mL x 3), dried over anhydrous sodium sulfate, filtered, and concentrated to dryness. The residue was purified by automated rapid chromatography on silica gel (ethyl acetate / petroleum ether = 0-100%) to give compound 211-1A (2 g, yield: 16%), retention time: 6.172 min, ES-API: [M+H]. + =219.1. 1 HNMR (400MHz, DMSO-d6) δ12.64(bs,1H),8.27(d,J=8.8Hz,1H),7...

Claims

1. A compound as shown in Formula I, a stereoisomer thereof, an isotopically-labeled compound thereof, a solvate thereof, a prodrug thereof, a nitroxide thereof, or a pharmaceutically acceptable salt thereof, Formula I wherein, G is the carbon atom marked "*" represents R configuration, S configuration or a mixture thereof when it is a chiral carbon atom; ring G1is 3-20 membered heterocycloalkyl or partially saturated 3-20 membered heterocyclyl; G2is -C(R 1 )2R 2 )2R 3 or -C≡CR 2 ; each R 1 , R 2 , and R 3 are independently H, D (deuterium), halogen, C 1-6 1-6alkyl or C 1-1 1-6alkyl substituted with one or more R 1-6 ; each R 1-1 independently D, halogen, 3-10 membered heterocycloalkyl or substituted 3-10 membered heterocycloalkyl, each of which is substituted with one or more R 1-1a substituted 3-10 membered heterocycloalkyl, each R is independently D, halogen, or C 1-1a independently D, halogen, or C 1-6 alkyl; R 4 is hydrogen or C 1-6 alkyl; L is a single bond, C 1-6 alkylene or C 1-6 alkyl-substituted C 1-6 alkylene; k is 0, 1, 2, 3 or 4; each R 5 independently H, D, halogen, oxo (=0), C 1-6 Alkyl, C 1-6 Alkylene, C 2- 6-olefin, C 2-6 alkynyl group, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, with one or more R p Replacement C 1-6 Alkyl, with one or more R p Replacement C 1-6 Alkylene, by one or more R p Replacement C 2-6 alkenyl, with one or more R p Replacement C 2-6 alkynyl group, with one or more R p Replacement C 3-10 cycloalkyl or with one or more R p Substituted 3-10 membered heterocyclic alkyl groups; or, any two R 5 and the atom to which they are attached form a 3-10 membered heterocyclic ring, a 5-10 membered heteroaromatic ring, a 3-10 membered heterocyclic ring substituted with one or more R 1-2 or a 5-10 membered heteroaromatic ring substituted with one or more R 1-3 substituted with one or more R each R 1-2 and R 1-3 independently D, amino, halogen, cyano, hydroxyl, oxo (=0), C 1-6 alkyl, halo-C 1-6 alkyl, C 1-6 alkylene, -0-C 1-6 alkyl, C 3-6 cycloalkyl or C 3-8 heteroalkyl; or two R 1-3 groups on the same carbon atom together with the carbon atom to which they are attached form a saturated 3-6 membered heterocyclic ring or a saturated C 3-6 carbocyclic ring; or any two R 1- 2 groups together with the atom to which they are attached form a 3-10 membered heterocyclic ring, a C 3-6 carbocyclic ring, a 3-10 membered heterocyclic ring substituted by one or more R 1-2a groups or a C 1-2a carbocyclic ring substituted by one or more R 3-6 carbocyclic ring; each R 1-2a independently D, hydroxyl, cyano, halo, C 1-6 alkyl, C 1-6 alkylene, -O-C 1-6 alkyl, C 2-6 alkenyl, C 2- 6alkynyl, C 3-6 cycloalkyl or C 3-8 heteroalkyl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl is optionally substituted with a member selected from the group consisting of halogen, hydroxy, cyano, -O- 1-6 alkyl; said C 1-6 alkylene, C 3-6 cycloalkyl, C 3-8 heteroalkyl is optionally substituted with a member selected from the group consisting of halogen, hydroxy, cyano, C 1-6 alkyl, -O- 1-6 alkyl, haloC 1-6 alkyl, -O-haloC 1-6 alkyl; each R p independently D, halogen, C 1-6 alkyl, C 1-6 alkylene, C 2-6 alkenyl, C 2-6 alkynyl, hydroxy, substituted C p-1 alkyl, substituted C 1-6 alkyl, substituted C p-1 alkyl, substituted C 1-6 alkylene, substituted C p-1 alkylene, substituted C 2-6 alkenyl or substituted C p-1 alkenyl or substituted C 2-6 alkynyl; each R is independently D, halogen, or C p-1 is independently D, halogen, or C 1-6 alkyl; or, any two R p and the atom to which they are attached form a 3-10 membered heterocycle or a 3-10 membered heterocycle substituted with one or more R 1-2 substituted with one or more R or, any two R p-1 and the atom to which they are attached form a 3-10 membered heterocycle or a 3-10 membered heterocycle substituted with one or more R 1-2 substituted 3-10 membered heterocycle; Ring A is a 3-10 membered heterocycle, C 6-10 aromatic ring, 5-10 membered heteroaromatic ring, or Ring B is C 3-10 carbocyclic, 3-10 membered heterocyclic, C 6-10 aromatic ring or 5-10 membered heteroaromatic ring; each R a independently D, halogen, oxo (=0), cyano, hydroxyl, -C(O)-C 1-6 alkyl, C 1-6 alkyl, haloC 1-6 alkyl, -O-C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl or 3-6 membered heterocycloalkyl; or one of the R a groups is 5 and the atom to which it is attached, together with the carbon atom marked with an asterisk, forms a partially saturated 3-10 membered heterocyclic ring or a saturated 3-10 membered heterocyclic ring substituted with one or more R 1-2 groups; and the R 5 group is not on the carbon atom marked with an asterisk; Y is a single bond or -C(O)-CH=; V is 3-10 membered heterocycloalkyl, partially saturated 3-10 membered heterocyclyl, C 6-10 aryl, 5-10 membered heteroaryl, or partially saturated 3-10 membered heterocyclyl and 5-10 membered heteroaryl; f1and f2are independently 0, 1, 2, 3, 4 or 5; each R g independently D, amino, halogen, oxo (=0), cyano, hydroxy, C 1-6 alkyl, -0-C 1-6 alkyl, -0-C 3-6 cycloalkyl, 3-10 membered heterocycloalkyl, C 3-8 heteroalkyl, 5-10 membered heteroaryl, -0-C 3-6 cycloalkyl, -0-3-10 membered heterocycloalkyl, -0-C 3-8 heteroalkyl, -0-5-10 membered heteroaryl, substituted with one or more R 1-4 substituted C 1-6 alkyl, substituted with one or more R 1-4 substituted C 3-6 cycloalkyl, substituted with one or more R 1-4 substituted 3-10 membered heterocycloalkyl, substituted with one or more R 1-4 substituted C 3-8 heteroalkyl, substituted with one or more R 1-4 substituted 5-10 membered heteroaryl, -0-substituted with one or more R 1-4 substituted C 1-6 alkyl, -0-substituted with one or more R 1-4 substituted C 3-6 cycloalkyl, -0-substituted with one or more R 1-4 substituted 3-10 membered heterocycloalkyl, -0-substituted with one or more R 1-4 substituted C 3-8 heteroalkyl, -0-substituted with one or more R 1-4 substituted 5-10 membered heteroaryl, -0-C 1-6 alkyl-substituted with one or more R 1-4 substituted C 1-6 alkyl, -0-C 1-6 alkyl-substituted with one or more R 1-4 substituted C 3-6 cycloalkyl, -0-C 1-6 alkyl-substituted with one or more R 1-4 substituted 3-10 membered heterocycloalkyl, -0-C 1-6 alkyl-substituted with one or more R 1-4 substituted C 3-8 heteroalkyl, -0-C 1-6 alkyl-substituted with one or more R 1-4 substituted 5-10 membered heteroaryl, -C(=0)R c ; V is optionally substituted with one or more R 6 substituted; each R 6 independently H, D, halogen, oxo (=0), C 1-6 Alkyl, C 1-6 Alkylene, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, with one or more R p Replacement C 1-6 Alkyl, with one or more R p Replacement C 1-6 Alkylene, by one or more R p Replacement C 2-6 alkenyl, with one or more R p Replacement C 2-6 alkynyl group, with one or more R p Replacement C 3-10 cycloalkyl or with one or more R p Substituted 3-10 membered heterocyclic alkyl groups; or, any two R 6 and the atom to which they are attached form a 3-10 membered heterocyclic ring, a 5-10 membered heteroaromatic ring, a 3-10 membered heterocyclic ring substituted with one or more R 1-2 or a 5-10 membered heteroaromatic ring substituted with one or more R 1-3 substituted with one or more R R m and R n independently C 1-6 alkyl; R c and R d are independently hydrogen, C 1-6 alkyl, C 3-6 cycloalkyl, 3-10 membered heterocycloalkyl, C 3-8 heteroalkyl, C 1-4 alkyl substituted with one or more R 1-6 , 3-10 membered heterocycloalkyl substituted with one or more R 1-4 , or -C(=O)-C 1-6 alkyl; or, R c , R d and the atom to which they are attached together form a 3-10 membered heterocycle or a 3-10 membered heterocycle substituted with one or more R 1-4 ; each R is independently deuterium (D), NH2, NH(C 1-4 independently deuterium (D), NH2, NH(C 1-6 alkyl), N(C 1-6 alkyl)2, hydroxyl, 3-8 membered heterocycloalkyl, C 1-6 alkyl or 3-8 membered heterocycloalkyl substituted with one or more R p substituted C1-C6alkyl; or one of the R a , wherein one R g and the atom to which it is attached form a partially saturated 3-10 membered heterocyclic ring or a partially saturated 3-10 membered heterocyclic ring substituted with one or more R 1-2 ; or one of the R 5 and one of the R g form a C 1-8 alkylene, C 1-8 heteroalkylene, C 2-8 alkenylene, C 2-8 heteroalkenylene, C 1-2 substituted C 1-8 alkylene, C 1-2 substituted C 1-8 heteroalkylene, C 1- 2 substituted C 2-8 alkenylene, or C 1-2 substituted C 2-8 heteroalkenylene; The various heterocyclic alkyl groups, heterocycles, heterocyclic groups, and C 3-8 Heteroalkyl, C 1-8 Heteroalkyl and C 2-8 The heteroatoms or heterogroups in the hesene group are independently selected from one, two, three, four, or five of N, N(H), N(=O), O, C(=O), S, S(=O), S(=O)2, P, P(=O), and P(=O)2, and the total number of heteroatoms and heterogroups is independently 1, 2, 3, 4, or 5. the kind of heteroatoms or heteroatom groups in the 5-10 membered heteroaryl and 5-10 membered heteroaryl ring is independently selected from N, N(=0) ([N + (O) - ]), O and S, one, two or three of which, the total number of heteroatoms and heteroatom groups being independently 1, 2, 3 or 4; and the compound of Formula I satisfies any one of the following conditions: one of R a wherein one of R 5 and the atom to which it is attached form a partially saturated 3-10 membered heterocyclic ring or a saturated 3-10 membered heterocyclic ring substituted with one or more R 1-2 ; and said R 5 is not on the carbon atom marked with an asterisk; one of R a one of R g and together with the atom to which it is attached forms a partially saturated 3-10 membered heterocyclic ring or a partially saturated 3-10 membered heterocyclic ring substituted with one or more R 1-2 substituted with one or more R one of R 5 and one of R g to form C 1-8 alkylene, C 1-8 heteroalkylene, C 2-8 alkenylene, C 2-8 heteroalkenylene, C 1-2 substituted with one or more R 1-8 alkylene, C 1-2 substituted with one or more R 1-8 heteroalkylene, C 1- 2 substituted with one or more R 2-8 alkenylene, or C 1-2 substituted with one or more R 2-8 heteroalkenylene.

2. The compound of Formula I as claimed in claim 1, its stereoisomers, its isotopically labeled compounds, its solvates, its prodrugs, its nitrides, or its pharmaceutically acceptable salts thereof, characterized in that, The compound as shown in Formula I is a compound as shown in Formula I': G1is the carbon atom marked "*" represents R configuration, S configuration or a mixture thereof when it is a chiral carbon atom; G2is -C(R 1 ) = CR 2 R 3 or -C≡CR 2 ; Each R 1 R 2 and R 3 Independently, H, D (deuterium), halogens, and C 1-6 Alkyl or with one or more R 1-1 Replacement C 1-6 alkyl; each R 1-1 independently D, halogen, 3-10 membered heterocycloalkyl or substituted 3-10 membered heterocycloalkyl, each of which is substituted with one or more R 1-1a substituted 3-10 membered heterocycloalkyl, each R is independently D, halogen, or C 1-1a is independently D, halogen, or C 1-6 alkyl; m and n are independently 0, 1, 2 or 3; p1is 0, 1, 2 or 3; p2is 0, 1, 2 or 3; q is 0, 1, 2 or 3; X is S(=O)(=NH), CH2, NH or O; X 1 CH2or NH; k is 0, 1, 2, 3 or 4; each R 5 independently H, D, halogen, oxo (=0), C 1-6 Alkyl, C 1-6 Alkylene, C 2- 6-olefin, C 2-6 alkynyl group, C 3-10 Cycloalkyl, 3-10 membered heterocyclic alkyl, with one or more R p Replacement C 1-6 Alkyl, with one or more R p Replacement C 1-6 Alkylene, by one or more R p Replacement C 2-6 alkenyl, with one or more R p Replacement C 2-6 alkynyl group, with one or more R p Replacement C 3-10 cycloalkyl or with one or more R p Substituted 3-10 membered heterocyclic alkyl groups; each R p independently D, halogen, C 1-6 alkyl, C 1-6 alkylene, C 2-6 alkenyl, C 2-6 alkynyl, hydroxy, substituted C p-1 alkyl, substituted C 1-6 alkyl, substituted C p-1 alkyl, substituted C 1-6 alkyl, substituted C p-1 alkyl, substituted C 2-6 alkenyl or substituted C p-1 alkenyl or substituted C 2-6 alkynyl; each R is independently D, halogen, or C p-1 is independently D, halogen, or C 1-6 alkyl; Ring A is a 3-10 membered heterocycle, C 6-10 an aromatic ring, a 5-10 membered heteroaromatic ring, or Ring B is C 3-10 carbocyclic, 3-10 membered heterocyclic, C 6-10 aromatic ring or 5-10 membered heteroaromatic ring; each R a independently D, halogen, oxo (=0), cyano, hydroxyl, -C(O)-C 1-6 alkyl, C 1-6 alkyl, haloC 1-6 alkyl, -O-C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl or 3-6 membered heterocycloalkyl; V is 3-10 membered heterocycloalkyl, partially saturated 3-10 membered heterocyclyl, C 6-10 aryl, 5-10 membered heteroaryl, or partially saturated 3-10 membered heterocyclyl and 5-10 membered heteroaryl; f1is 0, 1, 2, 3, 4 or 5; f2is 1, 2, 3, 4 or 5; each R g independently D, amino, halogen, oxo (=0), cyano, hydroxy, C 1-6 alkyl, -0-C 1-6 alkyl, C 3-6 cycloalkyl, 3-10 membered heterocycloalkyl, C 3-8 heteroalkyl, 5-10 membered heteroaryl, -0-C 3-6 cycloalkyl, -0-3-10 membered heterocycloalkyl, -0-C 3-8 heteroalkyl, -0-5-10 membered heteroaryl, substituted with one or more R 1-4 substituted C 1-6 alkyl, substituted with one or more R 1-4 substituted C 3-6 cycloalkyl, substituted with one or more R 1-4 substituted 3-10 membered heterocycloalkyl, substituted with one or more R 1-4 substituted C 3-8 heteroalkyl, substituted with one or more R 1-4 substituted 5-10 membered heteroaryl, -0-substituted with one or more R 1-4 substituted C 1-6 alkyl, -0-substituted with one or more R 1-4 substituted C 3-6 cycloalkyl, -0-substituted with one or more R 1-4 substituted 3-10 membered heterocycloalkyl, -0-substituted with one or more R 1-4 substituted C 3-8 heteroalkyl, -0-substituted with one or more R 1-4 substituted 5-10 membered heteroaryl, -0-C 1-6 alkyl-substituted with one or more R 1-4 substituted C 1-6 alkyl, -0-C 1-6 alkyl-substituted with one or more R 1-4 substituted C 3-6 cycloalkyl, -0-C 1-6 alkyl-substituted with one or more R 1-4 substituted 3-10 membered heterocycloalkyl, -0-C 1-6 alkyl-substituted with one or more R 1-4 substituted C 3-8 heteroalkyl, -0-C 1-6 alkyl-substituted with one or more R 1-4 substituted 5-10 membered heteroaryl, -C(=0)R c ; R m and R n are independently C 1-6 alkyl; R c and R d are independently hydrogen, C 1-6 alkyl, C 3-6 cycloalkyl, 3-10 membered heterocycloalkyl, C 3-8 heteroalkyl, C 1-4 alkyl substituted with one or more R 1-6 , 3-10 membered heterocycloalkyl substituted with one or more R 1-4 , or -C(=O)-C 1-6 alkyl; or, R c , R d and the atom to which they are attached together form a 3-10 membered heterocycle or a 3-10 membered heterocycle substituted with one or more R 1-4 ; each R 1-4 independently deuterium (D), NH2, NH(C 1-6 alkyl), N(C 1-6 alkyl)2, hydroxyl, 3-8 membered heterocycloalkyl, C 1-6 alkyl or 3-8 membered heterocycloalkyl substituted with one or more R p substituents; one of R 5 and one of R g to form C 1-8 alkylene, C 1-8 heteroalkylene, C 2-8 alkenylene, C 2-8 heteroalkenylene, C 1-2 substituted C 1-8 alkylene, C 1-2 substituted C 1-8 heteroalkylene, C 1-2 substituted C 2-8 alkenylene, or C 1-2 substituted C 2-8 heteroalkenylene; each R 1-2 independently D, amino, halogen, cyano, hydroxy, oxo (=0), C 1-6 alkyl, C 1-6 alkylene, halogenated C 1-6 alkyl, -O-C 1-6 alkyl, C 3-6 cycloalkyl or C 3-8 heteroalkyl; or any two R 1-2 and the atom to which they are attached form a 3-10 membered heterocyclic ring, C 3-6 carbocyclic, substituted 3-10 membered heterocyclic ring or C 1-2a substituted 3-10 membered heterocyclic ring or C 1-2a substituted C 3-6 carbocyclic; each R 1-2a independently D, hydroxyl, cyano, halo, C 1-6 alkyl, C 1-6 alkylene, -O-C 1-6 alkyl, C 2-6 alkenyl, C 2- 6alkynyl, C 3-6 cycloalkyl or C 3-8 heteroalkyl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl is optionally substituted with a member selected from the group consisting of halogen, hydroxy, cyano, -O- 1-6 alkyl; said C 1-6 alkylene, C 3-6 cycloalkyl, C 3-8 heteroalkyl is optionally substituted with a member selected from the group consisting of halogen, hydroxy, cyano, C 1-6 alkyl, -O- 1-6 alkyl, haloC 1-6 alkyl, -O-haloC 1-6 alkyl; each C 3-8 heteroalkyl, 3-10 membered heterocycloalkyl, 3-10 membered heterocycle, saturated 3-6 membered heterocycle, 3-6 membered heterocycloalkyl, partially saturated 3-10 membered heterocyclyl, 3-8 membered heterocycloalkyl, C 1-8 heteroalkyl, 3-10 membered heterocycloalkyl, 3-10 membered heterocycle, saturated 3-6 membered heterocycle, 3-6 membered heterocycloalkyl, partially saturated 3-10 membered heterocyclyl, 3-8 membered heterocycloalkyl, C 2-8 the kind of heteroatom or heteroatomic group in the heteroalkylene and heteroalkenylene is independently selected from one, two, three, four, or five of N, N(H), N(=0), O, C(=0), S, S(=0), S(=0)2, P, P(=0), and P(=0)2, the total number of heteroatoms and heteroatomic groups is independently 1, 2, 3, 4, or 5; the kind of heteroatoms or heteroatom groups in the 5-10 membered heteroaryl and 5-10 membered heteroaryl ring is independently selected from N, N(=0) ([N + (O) - ]), O and S, one, two or three of which, the total number of heteroatoms and heteroatom groups being independently 1, 2, 3 or 4.

3. The compound of claim 1 or 2, a stereoisomer thereof, an isotopically-labeled compound thereof, a solvate thereof, a prodrug thereof, a nitroxide thereof, or a pharmaceutically acceptable salt thereof, characterized in that, satisfies one or more of the following conditions: (1) each halo is independently fluorine, chlorine, bromine or iodine; (2) each C 1-6 alkyl, -C(O)-C 1-6 alkyl, -C(O)-C 1-6 alkyl and -O-C 1-6 alkyl, -C(O)-C 1-6 alkyl is independently C 1-4 alkyl; (3) each C 1-8 alkylene and each C 1-6 alkylene is independently Ci, C2, C3, C4, C5, or C6alkylene; (4) each C 1-8 heteroalkylene is C 1-6 heteroalkylene is C 1-8 heteroalkylene can be straight-chain heteroalkylene; the C 1-8 the kind of heteroatom or heteroatom group in the heteroalkylene can be selected from one, two or three of N, C(=0), O and S, the number of heteroatoms can be 1, 2 or 3; for example the kind of heteroatom or heteroatom group is selected from one or two of C(=0) and O, the total number of heteroatoms and heteroatom groups is 1, 2 or 3; (5) each C 2-6 alkenyl is independently C 2-4 alkenyl; (6) each C 2-8 alkylene is independently C 2-6 alkylene; (7) each C 2-8 heteroalkenylene is independently C 2-6 heteroalkenylene; each C 2-8 heteroalkenylene can be straight-chain heteroalkenylene; each C 2-8 the heteroatom species of the heteroalkenylene can be selected from one or both of N and O, and the number of heteroatoms can be one or two; (8) each C 2-6 alkynyl is independently C 2-4 alkynyl; (9) each C 3-10 cycloalkyl and each C 3-6 cycloalkyl is independently C3, C4, C5, and C6 cycloalkyl; (10) said C 3-10 carbocyclic is partially saturated C 3-6 carbocyclic; (11) the heteroatoms or heteroatom groups of each 3-10 membered heterocycloalkyl, each 3-8 membered heterocycloalkyl and each 3-6 membered heterocycloalkyl are independently selected from one, two or three of N, C(=O) and O, and the total number of heteroatoms and heteroatom groups is independently 1, 2 or 3; for example, the heteroatom species are independently selected from one or two of N and O, and the number of heteroatoms is independently 1 or 2; (12) each 3-10 membered heterocycloalkyl, each 3-8 membered heterocycloalkyl and each 3-6 membered heterocycloalkyl is independently a 3, 4, 5 or 6 membered heterocycloalkyl; (13) the heteroatoms or heteroatom groups of each 3-10 membered heterocycle are independently selected from one, two or three of N, C(=O) and O, and the total number of heteroatoms and heteroatom groups is independently 1, 2 or 3; for example, the heteroatom species are independently selected from one or two of N and O, and the number of heteroatoms is independently 1 or 2; (14) each 3-10 membered heterocycle is independently a saturated 3, 4, 5, 6, 7, 8, 9 or 10 membered heterocycle or a partially saturated 3, 4, 5, 6, 7, 8, 9 or 10 membered heterocycle; the saturated 3-10 membered heterocycle can be a saturated 3-6 membered heterocycle; the number of alkenes in the partially saturated 3-10 membered heterocycle is independently 1 or 2; (15) each C 6-10 the aromatic ring is independently a benzene ring or a naphthalene ring; (16) each C 6-10 aryl is independently phenyl or naphthyl; (17) the heteroatoms or heteroatom groups of each 5-10 membered heteroaromatic ring are independently selected from one, two or three of N, N(=O) and S, and the total number of heteroatoms and heteroatom groups is independently 1, 2 or 3; for example, the heteroatom species are independently selected from one or two of N and S; the number of heteroatoms of each 5-10 membered heteroaromatic ring is independently 1 or 2; each 5-10 membered heteroaromatic ring is independently a 5-6 membered heteroaromatic ring; (18) the heteroatom or heteroatom group species of each 5-membered heteroaromatic ring is independently selected from one, two or three of N, N(=0) and S, the total number of heteroatoms and heteroatom groups is independently 1, 2 or 3; for example, the heteroatom species is selected from one or two of N and S; the number of heteroatoms of the 5-membered heteroaromatic ring can be 1; (19) the heteroatom or heteroatom group species of each 5-10 membered heteroaryl is independently selected from one, two or three of N, N(=0) and S, the total number of heteroatoms and heteroatom groups is independently 1, 2 or 3; for example, the heteroatom species is independently selected from one or two of N and S, for example N; the number of heteroatoms of the 5-10 membered heteroaryl is independently 1 or 2; the 5-10 membered heteroaryl is independently 5-6 membered heteroaryl; Preferably, the compound of Formula I satisfies one or more of the following conditions: (1) each halo is independently fluoro or chloro; (2) each C 1-6 alkyl, -C(O)-C 1-6 alkyl, -C(O)-C 1-6 alkyl, and -O-C 1-6 alkyl, and -O-C 1-6 alkyl is independently methyl, ethyl, n-propyl, i-propyl, n-butyl, t-butyl, i-butyl, or s-butyl; again, for example, methyl; (3) each C 1-8 alkylene and each C 1-6 alkylene is independently methylene, (4) each C 1-8 heteroalkylene is or said C 1-8 heteroalkylene is (5) each C 2-6 alkenyl is independently vinyl, allyl, methylvinyl, propenyl, or butenyl; (6) each C 2-8 alkenylene is independently a straight chain alkenylene; for example the C 2-8 alkenylene is For example (7) each C 2-6 alkynyl is independently ethynyl, propynyl, or methylpropynyl; (8) each 3-10 membered heterocycloalkyl and each 3-6 membered heterocycloalkyl is independently For example or each 3-10 membered heterocycloalkyl and each 3-6 membered heterocycloalkyl is independently morpholinyl, piperazinyl or azetidinyl; (9) the saturated 3-10 membered heterocycle is a furan ring, a pyrrole ring, a piperidine ring, a piperazine ring or a morpholine ring; or the saturated 3-10 membered heterocycle is an azetidine ring; (10) said partially saturated 3-10 membered heterocyclic ring is independently (11) each C 6-10 the aromatic ring is a benzene ring; (12) each C 6-10 aryl is phenyl; (13) the 5-10 membered heteroaromatic ring is independently a pyrazole ring, an imidazole ring, a thiophene ring, a pyridine ring, a pyrimidine ring or a pyrazine ring; preferably, the 5-membered heteroaromatic ring is a thiophene ring; (14) said 5-10 membered heteroaryl group is independently pyrazolyl, pyridyl, pyrimidinyl, or pyrazinyl; and further examples or the 5-10 membered heteroaryl is independently pyridazinyl, pyridimidazinyl, pyridopyrazolyl, pyridotriazolyl, benzopyrazinyl, pyridopyridinyl, pyridopyrrolyl or pyridopyrazinyl; (15) each C 2-8 heteroalkenylene is independently straight-chain heteroalkenylene; for example, the C 2-8 heteroalkenylene (16) each partially saturated 3-10 membered heterocyclyl and 5-10 membered heteroaryl is independently piperidinopyrimidinyl, piperidinopyridinyl, piperazinopyrimidinyl or piperazinopyridinyl; or azacyclopentenylpyridinyl or azacyclohexenylpyrimidinyl; (17) each of the partially saturated 3-10 membered heterocyclyl and 5-10 membered heteroaryl groups is independently 4. The compound of claim 1 or 2, a stereoisomer thereof, an isotopically-labeled compound thereof, a solvate thereof, a prodrug thereof, a nitroxide thereof, or a pharmaceutically acceptable salt thereof, wherein, satisfies one or more of the following conditions: ​ (1) each R 1 , R 2 , and R 3 is independently H or D, for example H; (2) m and n are independently 1 or 2; for example, 1; (3) X is NH; (4) X is O; (5) X is CH2; (6) k is 1; (7) Ring A is a partially saturated 5-6 membered heterocyclic ring, C 6-10 aromatic ring, 5-membered heteroaromatic ring, or Ring B is a partially saturated 5-6 membered heterocycle or a 5-6 membered heteroaromatic ring; Alternatively, ring A is a partially saturated 3-10 membered heterocyclic ring, 5 membered heteroaromatic ring or Ring B is a partially saturated 3-10 membered heterocyclic ring or 5-10 membered heteroaromatic ring; preferably, Ring A is a partially saturated 5-6 membered heterocyclic ring, 5 membered heteroaromatic ring or Ring B is a partially saturated 5-6 membered heterocycle or a 5-6 membered heteroaromatic ring; the heteroatom species of the partially saturated 5-6 membered heterocycle, the 5-membered heteroaromatic ring and the 5-6 membered heteroaromatic ring is independently selected from one, two or three of N, O and S; the number of heteroatoms is independently 1, 2 or 3; the number of alkenes in the partially saturated 5-6 membered heterocycle is independently 1 or 2; For example, ring A is C 6-10 Aromatic ring; (8) one of R 5 and one of R g to form C 1-8 alkylene, C 1-8 heteroalkylene or C 2-8 alkenylene, the heteroatom or heteroatom group species of the C 1-8 heteroalkylene is selected from one, two or three of N, C(=0), O and S, the total number of heteroatoms and heteroatom groups being 1, 2 or 3, for example the heteroatom or heteroatom group species is selected from one or two of C(=0) and O, the total number of heteroatoms and heteroatom groups being 1, 2 or 3; (9) each R p independently halogen, C 1-6 alkylene or C p-1 substituted C 1-6 alkylene; (10) f1 is 0 or 1; (11) each R a independently D, halogen, oxo, cyano, -C(O)-C 1-6 alkyl, -O-C 1- 6alkyl, C 2-6 alkenyl, C 2-6 alkynyl or C 3-6 cycloalkyl; for example each R a independently D, halogen, oxo, cyano, -C(O)-C 1-6 alkyl or For example, each R a independently D or halogen; Alternatively, when f1 is 1, R a is -O-C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl or C 3-6 cycloalkyl; (12) V is a 5-6 membered heteroaryl, the heteroatom species of the 5-6 membered heteroaryl is N, the number of heteroatoms is 1 or 2 or 3; or V is C 6-10 aryl or 5-10 membered heteroaryl; for example V is C 6-10 aryl or 5-6 membered heteroaryl, the heteroatom species of which is N, the number of heteroatoms being 1 or 2 or 3; (13) each R g independently D, amino, halogen, C 1-6 alkyl, C 3-6 cycloalkyl, -O-C 1-6 alkyl, C 3-8 heteroalkyl or -O- is substituted by one or more R 1-4 substituted C 3-8 heteroalkyl, -O- is substituted by one or more R 1-4 substituted 3-10 membered heterocycloalkyl; for example, each R g independently D, amino, halogen or C 1-6 alkyl, -O-C 1-6 alkyl, -O- substituted by one or more R 1-4 substituted C 3-8 heteroalkyl, -O- substituted by one or more R 1-4 substituted 3-10 membered heterocycloalkyl; also, for example, D, amino, halogen or C 1-6 alkyl, -O-C 1-6 alkyl, -O- substituted by one or more R 1-4 substituted C 3- 8heteroalkyl, -O- substituted by one or more R 1-4 substituted 3-10 membered heterocycloalkyl; further for example D, amino, halogen or C 1-6 alkyl; further for example D, amino or halogen; or each R g independently D or C 1-6 alkyl, further or each R g independently D, amino or For example halogen, -O-C 1-6 alkyl, -O-substituted C 1-4 substituted C 3-8 heteroalkyl, -O-substituted C 1-4 substituted 3-10 membered heterocycloalkyl; (14) R c and R d independently hydrogen or C 1-4 alkyl; for example H; (15) R m and R n independently C 1-4 alkyl; (16) the configuration of the carbon atom marked with an asterisk is the R configuration; (17) one of R 5 located ortho to the carbon atom marked with an "*, e.g. with the R 5 the configuration of the directly attached carbon atom is the R configuration; Preferably, in the compound of formula I, For the configuration of the asterisked carbon atom is the R configuration, R 5 the configuration of the directly attached carbon atom is either the R configuration or the S configuration; preferably, The R 5 The configuration of the directly attached carbon atom is the R configuration.

5. The compound of Formula I as claimed in claim 1 or 2, its stereoisomers, its isotopically labeled compounds, its solvates, its prodrugs, its nitrides, or its pharmaceutically acceptable salts thereof, characterized in that, satisfies one or more of the following conditions: (1) R 2 is H or C 1-6 alkyl; (2) each R 1-1 independently halogen; (3) p1 is 0 or 1, for example, 1; (4) p2 is 0; (5) q is 1; (6) X is CH2, NH or O; (7) X 1 is NH; (8) each R p independently D, halogen, or hydroxyl; (9) R c independently hydrogen or C 1-6 alkyl, for example C 1-6 alkyl; (10) R d independently hydrogen or C 1-6 alkyl; (11) Ring A is C 6-10 an aromatic ring or a 5-10 membered heteroaromatic ring, for example C 6-10 an aromatic ring or a 5-6 membered heteroaromatic ring, for example a benzene ring or a 5-6 membered heteroaromatic ring, more preferably a benzene ring; (12) R a independently halogen or haloalkyl; 1-6 alkyl; (13) V is C 6-10 aryl, 5-10 membered heteroaryl, or partially saturated 5-6 membered heterocyclyl and 5-6 membered heteroaryl, preferably V is C 6-10 aryl or 5-10 membered heteroaryl, preferably the heteroatom species of the 5-10 aryl is N, the number of heteroatoms is 1, 2, 3, or 4; (14) f2 is 1, 2, 3 or 4; (15) each R g independently amino, halogen, -O-C 1-6 alkyl, -C(=O)R c , -O- substituted by one or more R 1- 4 substituted C 1-6 alkyl or -O- substituted by one or more R 1-4 substituted 3-6 membered heterocycloalkyl; (16) each R 1-4 independently NH2, NH(C 1-6 alkyl), N(C 1-6 alkyl)2, or C 1-6 alkyl; (17) each R 1-2 independently halogen, hydroxyl, or C 1-6 alkyl; (18) each R 1-2a independently halogen; (19) k is 1, 2, or 3, for example 1 or 2; (20) For (21) each R 5 independently H, oxo, or C 1-6 alkyl, preferably, R 5 independently H or C 1-6 alkyl.

6. The compound of Formula I as claimed in claim 1 or 2, its stereoisomers, its isotopically labeled compounds, its solvates, its prodrugs, its nitrides, or its pharmaceutically acceptable salts, characterized in that, which satisfies one or both of the following conditions: (1) ring G1is a 5-12 membered heterocycloalkyl; preferably, ring G1is a 6 membered heterocycloalkyl, a 6 membered heterocycloalkyl and a 5 membered heterocycloalkyl, or a 6 membered heterocycloalkyl and a 6 membered heterocycloalkyl; more preferably, ring G1is a piperazinyl, a piperidinyl, a morpholinyl, a thiomorpholinyl, a piperazinoimidazolidinyl, a piperazinopyrrolidinyl, a piperazinopiperazinyl, or a piperidinopiperidinyl; Preferably, For wherein the "1 " position is attached to the carbonyl group, the "2" position is attached to ring A, the "3" position and one of R g configuration of the carbon atom marked "*" is independently R, S or a mixture thereof; Preferably, For (2) One of R 5 And one of the R g Connection forms C 1-8 Alkylene, C 1-8 Heteroalkyl, C 2-8 Hesperyl, with one or more R 1-2 Replacement C 1-8 Alkylene, by one or more R 1-2 Replacement C 1-8 Heteroalkyl or by one or more R 1-2 Replacement C 2-8 Hesperyl; each R 1-2 Independently halogen, hydroxyl or C 1-6 Alkyl group; or any two R groups 1-2 Together with the atoms attached to it, it forms a 3-6 membered heterocycle; the C 1-8 Heteroalkyl and C 2-8 The heteroatoms or heterogroups in the heteroene group are independently selected from one, two, or three of N (H), O, and C (=O), and the total number of heteroatoms and heterogroups is independently 1, 2, 3, 4, or 5; the heteroatoms in the 3-6 membered heterocyclic alkyl group are selected from one or two of N and O, and the number of heteroatoms is 1 or 2; Preferably, one of the R 5 And one of the R g Connection forms C 1-8 Heteroalkyl, C 2-8 Hesperidinyl or with one or more R 1-2 Replacement C 1-8 Heteroalkylene; each R 1-2 Independently halogen, hydroxyl or C 1-6 Alkyl group; or any two R groups 1-2 Together with the atoms attached to it, it forms a 3-6 membered heterocycle; the C 1-8 Heteroalkyl and C 2-8 The heteroatoms or heterogroups in the heteroene group are independently selected from one, two, or three of N (H), O, and C (=O), and the total number of heteroatoms and heterogroups is independently 1, 2, 3, 4, or 5; the heteroatoms in the 3-6 membered heterocyclic alkyl group are selected from one or two of N and O, and the number of heteroatoms is 1 or 2; Better yet, one of the R 5 And one of the R g Connection forms C 2-8 Hesperidinyl or with one or more R 1-2 Replacement C 1-8 Heteroalkylene; each R 1-2 Independently halogen, hydroxyl or C 1-6 Alkyl group; or any two R groups 1-2 Together with the atoms attached to it, it forms a 3-6 membered heterocycle; the C 1-8 Heteroalkyl and C 2-8 The heteroatoms or heterogroups in the heteroene group are independently selected from one, two, or three of N (H), O, and C (=O), and the total number of heteroatoms and heterogroups is independently 1, 2, 3, 4, or 5; the heteroatoms in the 3-6 membered heterocyclic alkyl group are selected from one or two of N and O, and the number of heteroatoms is 1 or 2; or one of the R 5 and one of the R g to form T 1 is O, or -C(R a1 R a2 )-; R a1 and R a2 are independently H, F or hydroxyl; T 2 is a single bond; T 3 independently 3-6 membered heterocycloalkylene, -C(HR a2 )-, -N(R b1 )-, -C(O)N(R b1 )- or -N(R b1 )C(O)-, the heteroatoms in the 3-6 membered heterocycloalkylene being selected from one or two of N and O, the number of heteroatoms being one or two; R b1 independently H or C 1-3 alkyl; s2is independently 1, 2, 3, 4, 5, 6, or 7; s3is independently 1, 2, 3, or 4; s4is independently 0, 1, 2, 3, or 4.

7. The compound of Formula I, a stereoisomer thereof, an isotopically-labeled compound thereof, a solvate thereof, a prodrug thereof, a nitroxide thereof, or a pharmaceutically acceptable salt thereof, according to claim 1 or 2, wherein, as the compound of Formula I-2a: The compound as shown in formula I is a compound as shown in formula I-2 (IA): wherein T is C 1-8 alkylene, C 1-8 heteroalkylene, C 2-8 alkenylene, C 2-8 heteroalkenylene, C 1-2 substituted C 1- 8alkylene, C 1-2 substituted C 1-8 heteroalkylene, C 1-2 substituted C 2-8 alkenylene, C 1-2 substituted C 2-8 heteroalkenylene; V is C 6-10 aryl or 5-10 membered heteroaryl; each C 1-8 heteroalkylene and C 2-8 the kind of heteroatom or heteroatomic group in the heteroalkylene and heteroalkenylene is independently selected from one, two, three, four or five of N, N(H), N(=0), O, C(=0), S, S(=0), S(=0)2, P, P(=0) and P(=0)2, the total number of heteroatoms and heteroatomic groups is independently 1, 2, 3, 4 or 5; R 1 , R 2 , R 3 , R 5 , m, n, X, ring A, f1, R a , f2, R g , R 1-2 are as defined in any one of claims 1 to 6; f3 is 0, 1, 2 or 3; the carbon atom marked with an asterisk is in the R configuration, the S configuration or a mixture thereof, if it is a chiral carbon atom; Preferably, the compound of Formula I is a compound of Formula I-2: wherein T is C 1-8 alkylene, C 1-8 heteroalkylene, C 2-8 alkenylene, C 2-8 heteroalkenylene, C 1-2 substituted C 1- 8alkylene, C 1-2 substituted C 1-8 heteroalkylene, C 1-2 substituted C 2-8 alkenylene, C 1-2 substituted C 2-8 heteroalkenylene; V is C 6-10 aryl or 5-10 membered heteroaryl; each C 1-8 heteroalkylene and C 2-8 the kind of heteroatom or heteroatomic group in the heteroalkylene and heteroalkenylene is independently selected from one, two, three, four or five of N, N(H), N(=0), O, C(=0), S, S(=0), S(=0)2, P, P(=0) and P(=0)2, the total number of heteroatoms and heteroatomic groups is independently 1, 2, 3, 4 or 5; R 1 , R 2 , R 3 , m, n, X, ring A, f1, R a , f2, R g , R 1-2 are as defined in any one of claims 1 to 6; the carbon atom marked with an asterisk is in the R configuration, in the S configuration or as a mixture thereof, if it is a chiral carbon atom; Preferably, the compound of formula I-2 is a compound of formula I-2a, I-2b or I-2c the carbon atom marked "*" is a chiral carbon atom, which is in the R configuration; X is CH2, NH, or O; R 1 , R 2 and R 3 are independently H or D; f2is 1, 2, or 3; T is C 1-8 alkylene, C 1-8 heteroalkylene or C 2-8 alkenylene; the C 1-8 the kind of the heteroatom or heteroatom group in the heteroalkylene can be selected from one, two or three of N, C(=0), O and S, and the number of heteroatoms can be 1, 2 or 3; Ring A is C 6-10 an aromatic or 5-10 membered heteroaromatic ring; R a is D or halogen; V is C 6-10 aryl or 5-10 membered heteroaryl (or 5-6 membered heteroaryl), the heteroatom species of which is N, the number of heteroatoms being 1 or 2 or 3; as the compound of Formula I-2a: each R g independently D, amino, halogen, oxo (=0), cyano, hydroxy, C 1-6 alkyl, -0-C 1-6 alkyl, -0-C 3-6 cycloalkyl, 3-10 membered heterocycloalkyl, C 3-8 heteroalkyl, 5-10 membered heteroaryl, -0-C 3-6 cycloalkyl, -0-3-10 membered heterocycloalkyl, -0-C 3-8 heteroalkyl, -0-5-10 membered heteroaryl, substituted with one or more R 1-4 C(=0)R 1-6 alkyl, substituted with one or more R 1-4 C(=0)R 3-6 cycloalkyl, substituted with one or more R 1-4 3-10 membered heterocycloalkyl, substituted with one or more R 1-4 C(=0)R 3-8 heteroalkyl, substituted with one or more R 1-4 5-10 membered heteroaryl, -0-substituted with one or more R 1-4 C(=0)R 1-6 alkyl, -0-substituted with one or more R 1-4 C(=0)R 3-6 cycloalkyl, -0-substituted with one or more R 1-4 3-10 membered heterocycloalkyl, -0-substituted with one or more R 1-4 C(=0)R 3-8 heteroalkyl, -0-substituted with one or more R 1-4 5-10 membered heteroaryl, -0-C 1-6 alkyl-substituted with one or more R 1-4 C(=0)R 1-6 alkyl, -0-C 1-6 alkyl-substituted with one or more R 1-4 C(=0)R 3-6 cycloalkyl, -0-C 1-6 alkyl-substituted with one or more R 1-4 3-10 membered heterocycloalkyl, -0-C 1-6 alkyl-substituted with one or more R 1-4 C(=0)R 3-8 heteroalkyl, -0-C 1-6 alkyl-substituted with one or more R 1-4 5-10 membered heteroaryl, -C(=0)R c ; R c and R d are independently hydrogen, C 1-6 alkyl, C 3-6 cycloalkyl, 3-10 membered heterocycloalkyl, C 3-8 heteroalkyl, C 1-4 alkyl substituted with one or more R 1-6 cycloalkyl, 3-10 membered heterocycloalkyl, or -C(=O)-C 1-4 alkyl substituted with one or more R 1-6 cycloalkyl, 3-10 membered heterocycloalkyl, or -C(=O)-C each R is independently deuterium (D), NH2, NH(C 1-4 independently deuterium (D), NH2, NH(C 1-6 alkyl), N(C 1-6 alkyl)2, hydroxyl, or 3-8 membered heterocycloalkyl; the carbon atom marked "*" is a chiral carbon atom, which is in the R configuration; f2is 1, 2, or 3; R 1 , R 2 and R 3 are independently H or D; T is C 1-8 alkylene, C 1-8 heteroalkylene or C 2-8 alkenylene; the kind of heteroatom or heteroatom group in the C 1-8 heteroalkylene can be selected from one, two or three of N, C(=0), O and S, and the number of heteroatoms can be 1, 2 or 3; or T is C 2-8 heteroalkenylene or C 1-2 substituted C 1-8 heteroalkylene; each R 1-2 independently is halogen, hydroxyl or C 1-6 alkyl; or any two R 1-2 and the atom to which they are attached together form a 3-6 membered heterocyclic ring; said C 1-8 heteroalkylene and C 2-8 the kind of heteroatom or heteroatom group in the heteroalkylene or heteroalkenylene is independently selected from one, two or three of N(H), O and C(=O), the total number of heteroatoms and heteroatom groups is independently 1, 2 or 3; the heteroatom in the 3-6 membered heterocyclic ring is selected from one or two of N and O, the number of heteroatoms is 1 or 2; Ring A is C 6-10 an aromatic or 5-10 membered heteroaromatic ring; R a is D or halogen; V is C 6-10 aryl or 5-10 membered heteroaryl (or 5-6 membered heteroaryl), the heteroatom species of which is N, the number of heteroatoms being 1 or 2 or 3; as the compound of Formula I-2c: each R g independently D, amino, halogen, C 1-6 alkyl, C 3-6 cycloalkyl, -O-C 1-6 alkyl, C 3-8 heteroalkyl, 5-10 membered heteroaryl, -O- substituted with one or more R 1-4 substituted 3-10 membered heterocycloalkyl or -O- substituted with one or more R 1-4 C 3-8 heteroalkyl; R c and R d are independently hydrogen, C 1-6 alkyl, C 3-6 cycloalkyl, 3-10 membered heterocycloalkyl, C 3-8 heteroalkyl, C 1-4 alkyl substituted with one or more R 1-6 heterocycloalkyl substituted with one or more R 1-4 alkyl, or -C(=O)-C 1-6 alkyl; each R is independently deuterium, NH2, NH(C 1-4 independently deuterium, NH2, NH(C 1-6 alkyl), N(C 1-6 alkyl)2, hydroxyl, or 3-8 membered heterocycloalkyl; the carbon atom marked "*a" is a chiral carbon atom, which is in the R configuration; the carbon atom marked "*b" is a chiral carbon atom, which is in the R configuration, the S configuration, or a mixture of the two; f2is 1, 2, or 3; R 1 , R 2 , and R 3 are independently H or D; T is C 1-8 alkylene, C 1-8 heteroalkylene or C 2-8 alkenylene; the kind of heteroatom or heteroatom group in the C 1-8 heteroalkylene can be selected from one, two or three of N, C(=0), O and S, and the number of heteroatoms can be 1, 2 or 3; Or T is C 2-8 Hesperidinyl or with one or more R 1-2 Replacement C 1-8 Heteroalkylene; each R 1-2 Independently halogen, hydroxyl or C 1-6 Alkyl group; or any two R groups 1-2 Together with the atoms attached to it, it forms a 3-6 membered heterocycle; the C 1-8 Heteroalkyl and C 2-8 The heteroatoms or heterogroups in the hesene group are independently selected from one, two, or three of N (H), O, and C (=O), and the total number of heteroatoms and heterogroups is independently 1, 2, or 3; the heteroatoms in the 3-6 membered heterocycles are selected from one or two of N and O, and the number of heteroatoms is 1 or 2. Ring A is C 6-10 an aromatic or 5-10 membered heteroaromatic ring; R a is D or halogen; V is C 6-10 aryl or 5-10 membered heteroaryl (or 5-6 membered heteroaryl), the heteroatom species of which is N, the number of heteroatoms being 1 or 2 or 3; 8. The compound of Formula I, a stereoisomer thereof, an isotopically-labeled compound thereof, a solvate thereof, a prodrug thereof, a nitroxide thereof, or a pharmaceutically acceptable salt thereof, according to claim 1 or 2, wherein, each R g independently D, amino, halogen, C 1-6 alkyl, C 3-6 cycloalkyl, -O-C 1-6 alkyl, C 3-8 heteroalkyl, 5-10 membered heteroaryl, -O- substituted with one or more R 1-4 substituted 3-10 membered heterocycloalkyl or -O- substituted with one or more R 1-4 C 3-8 heteroalkyl; R c and R d are independently hydrogen, C 1-6 alkyl, C 3-6 cycloalkyl, 3-10 membered heterocycloalkyl, C 3-8 heteroalkyl, C 1-4 alkyl substituted with one or more R 1-6 cycloalkyl, 3-10 membered heterocycloalkyl, or -C(=O)-C 1-4 alkyl substituted with one or more R 1-6 heterocycloalkyl; each R is independently deuterium (D), NH2, NH(C 1-4 independently deuterium (D), NH2, NH(C 1-6 alkyl), N(C 1-6 alkyl)2, hydroxyl, or 3-8 membered heterocycloalkyl. the carbon atom marked "*" is a chiral carbon atom, which is in the R configuration; The compound as shown in formula I is a compound as shown in formula I-8-1 (IA) or I-8-2 (IB): wherein T is C 1-8 alkylene, C 1-8 heteroalkylene, C 2-8 alkenylene, C 2-8 heteroalkenylene, C 1-2 substituted C 1- 8alkylene, C 1-2 substituted C 1-8 heteroalkylene, C 1-2 substituted C 2-8 alkenylene, C 1-2 substituted C 2-8 heteroalkenylene; V is C 6-10 aryl or 5-10 membered heteroaryl; each C 1-8 heteroalkylene and C 2-8 the kind of heteroatom or heteroatomic group in the heteroalkylene and heteroalkenylene is independently selected from one, two, three, four or five of N, N(H), N(=0), O, C(=0), S, S(=0), S(=0)2, P, P(=0) and P(=0)2, the total number of heteroatoms and heteroatomic groups is independently 1, 2, 3, 4 or 5; R 1 , R 2 , R 3 , p1, p2, q, X1, ring A, f1, R a , f2, R g , R 1-2 are as defined in any one of claims 1 to 6; f3 is 0, 1, 2 or 3; the carbon atom marked with an asterisk is in the R configuration, in the S configuration or as a mixture thereof, if it is a chiral carbon atom; Preferably, the compound of Formula I is a compound of Formula I-8-1 or I-8-2: wherein T is C 1-8 alkylene, C 1-8 heteroalkylene, C 2-8 alkenylene, C 2-8 heteroalkenylene, C 1-2 substituted with one or more R 1- 8alkylene, C 1-2 substituted with one or more R 1-8 heteroalkylene, C 1-2 substituted with one or more R 2-8 alkenylene, or C 1-2 substituted with one or more R 2-8 heteroalkenylene; V is C 6-10 aryl or 5-10 membered heteroaryl; each C 1-8 heteroalkylene and C 2-8 the kind of heteroatom or heteroatomic group in the heteroalkylene and heteroalkenylene is independently selected from one, two, three, four or five of N, N(H), N(=0), O, C(=0), S, S(=0), S(=0)2, P, P(=0) and P(=0)2, the total number of heteroatoms and heteroatomic groups is independently 1, 2, 3, 4 or 5; R 1 , R 2 , R 3 , p1, p2, q, X1, ring A, f1, R a , f2, R g , R 1-2 are as defined in any one of claims 1 to 6; the carbon atom marked with an asterisk is in the R configuration, in the S configuration or as a mixture thereof, if it is a chiral carbon atom; Preferably, the compound of Formula I is a compound of Formula I-8a-1 or I-8a-2 wherein T is C 1-8 alkylene, C 1-8 heteroalkylene, C 2-8 alkenylene, C 2-8 heteroalkenylene, C 1-2 substituted C 1- 8alkylene, C 1-2 substituted C 1-8 heteroalkylene, C 1-2 substituted C 2-8 alkenylene, C 1-2 substituted C 2-8 heteroalkenylene; V is C 6-10 aryl or 5-10 membered heteroaryl; each C 1-8 heteroalkylene and C 2-8 the kind of heteroatom or heteroatomic group in the heteroalkylene and heteroalkenylene is independently selected from one, two, three, four or five of N, N(H), N(=0), O, C(=0), S, S(=0), S(=0)2, P, P(=0) and P(=0)2, the total number of heteroatoms and heteroatomic groups is independently 1, 2, 3, 4 or 5; R 1 , R 2 , R 3 , p1, q, X1, ring A, f1, R a , f2, R g , R 1-2 are as defined in any one of claims 1 to 6; the carbon atom marked with an asterisk is in the R configuration, in the S configuration or as a mixture thereof, if it is a chiral carbon atom; Preferably, the compound of formula I is a compound of formula I-8b-1 or I-8b-2 p1is 0 or 1; X1is CH2or NH; R 1 , R 2 and R 3 are independently H or D; f2is 1, 2, or 3; T is C 1-8 alkylene, C 1-8 heteroalkylene or C 2-8 alkenylene; the kind of the heteroatom or heteroatom group in the C 1-8 heteroalkylene can be selected from one, two or three of N, C(=0), O and S, and the number of heteroatoms can be 1, 2 or 3; Ring A is C 6-10 an aromatic or 5-10 membered heteroaromatic ring; R a is D or halogen; V is C 6-10 aryl or 5-10 membered heteroaryl (or 5-6 membered heteroaryl), the heteroatom species of which is N, the number of heteroatoms being 1 or 2 or 3; wherein the "3" position is connected to ring A, the "2" position is connected to Rg, and the "1" position is connected to T. each R g independently D, amino, halogen, C 1-6 alkyl, C 3-6 cycloalkyl, -O-C 1-6 alkyl, C 3-8 heteroalkyl or 5-10 membered heteroaryl, -O- substituted by one or more R 1-4 substituted C 3-8 heteroalkyl or -O- substituted by one or more R 1-4 substituted 3-10 membered heterocycloalkyl; R c and R d are independently hydrogen, C 1-6 alkyl, C 3-6 cycloalkyl, 3-10 membered heterocycloalkyl, C 3-8 heteroalkyl, C 1-4 alkyl substituted with one or more R 1-6 cycloalkyl, 3-10 membered heterocycloalkyl, or -C(=O)-C 1-4 alkyl substituted with one or more R 1-6 cycloalkyl, 3-10 membered heterocycloalkyl, or -C(=O)-C each R is independently deuterium (D), NH2, NH(C 1-4 independently deuterium (D), NH2, NH(C 1-6 alkyl), N(C 1-6 alkyl)2, hydroxyl, or 3-8 membered heterocycloalkyl; Preferably, V is 10. The compound of Formula I, a stereoisomer thereof, an isotopically-labeled compound thereof, a solvate thereof, a prodrug thereof, a nitroxide thereof, or a pharmaceutically acceptable salt thereof, according to claim 9, wherein, 9. The compound of Formula I as claimed in claim 1 or 2, its stereoisomers, its isotopically labeled compounds, its solvates, its prodrugs, its nitrides, or its pharmaceutically acceptable salts, characterized in that: the compound of Formula I is a compound of Formula I-2D, a compound of Formula I-2E, a compound of Formula 2F, or a compound of Formula 2G; R 1 , R 2 , R 3 , R 5 , f1, R a , V, f2, R g and T are as defined in any one of claims 1-8, the configuration of the carbon atom marked "*" is independently R, S or a mixture thereof; Preferably, the compound of Formula I is a compound of Formula I-2D-1, I-2D-2, I-2E-1, I-2E-2, I-2E-3, I-2E-4, I-2E-5, I-2E-6, I-2E-7, I-2F-1, I-2F-2, I-2F-3, I-2F-4, I-2F-5, I-2G-1, I-2G-2, I-2G-3, or I-2G-4; as the compound of Formula I-2D, as the compound of Formula I-2E, as the compound of Formula 2F, or as the compound of Formula 2G, ring A is a phenyl ring; R 1 , R 2 , and R 3 are H; f1is 1; f2is 1, 2, 3, or 4; R a halo or haloC 1-6 alkyl; V is C 6-10 aryl or 5-10 membered heteroaryl, the heteroatom species of which is N, the number of heteroatoms being 1, 2, 3 or 4; s2is independently 1, 2, 3, 4, 5, 6, or 7; each R g independently amino, halogen, -O-C 1-6 alkyl, -C(=O)R c , -O- substituted by one or more R 1-4 substituted C 1-6 alkyl or -O- substituted by one or more R 1-4 3-6 membered heterocycloalkyl, the heteroatoms in said 3-6 membered heterocycloalkyl being selected from one, two or three of N, O and S, the number of heteroatoms being 1, 2 or 3; R c and R d independently hydrogen or C 1-6 alkyl; each R 1-4 independently NH2, NH(C 1-6 alkyl), N(C 1-6 alkyl)2, or C 1-6 alkyl; T is C 1-8 Alkylene, C 1-8 Heteroalkyl, C 2-8 Hesperyl, with one or more R 1-2 Replacement C 1-8 Alkylene, by one or more R 1-2 Replacement C 1-8 Heteroalkyl or by one or more R 1-2 Replacement C 2-8 Iso-alkenyl; the C 1-8 Heteroalkyl and C 2-8 The heteroatoms or heterogroups in the hesene group are independently selected from one, two, or three of N (H), O, and C (=O), and the total number of heteroatoms and heterogroups is independently 1, 2, 3, 4, or 5. each R is independently halogen, hydroxyl, or C 1-2 independently halogen, hydroxyl, or C 1-6 alkyl; or any two R 1-2 and together with the atoms to which they are attached form a 3-6 membered heterocyclic ring, the 3-6 membered heterocyclic ring having one or two heteroatoms selected from N and O, the number of heteroatoms being one or two; R 5 independently H or C 1-6 alkyl; Preferably, T is T 1 is O, or -C(R a1 R a2 )-; R a1 and R a2 independently H, F or hydroxyl; T 2 is a single bond; T 3 independently 3-6 membered heterocycloalkylene, -C(HR a2 )-, -N(R b1 )-, -C(O)N(R b1 )- or -N(R b1 )C(O)-, the heteroatoms in the 3-6 membered heterocycloalkylene being selected from one or two of N and O, the number of heteroatoms being one or two; R b1 independently H or C 1-3 alkyl; s3is independently 1, 2, 3, or 4; s4is independently 0, 1, 2, 3, or 4. which satisfies one or more of the following conditions:

11. The compound of Formula I as claimed in claim 1 or 2, its stereoisomers, its isotopically labeled compounds, its solvates, its prodrugs, its nitrides, or its pharmaceutically acceptable salts, characterized in that, or oxo; (1) R 1 , R 2 , and R 3 are H; (2) R 5 For or R 5 is H, methyl, is connected to ring A; (3) Ring A is (4) R a is oxo, fluoro, chloro, bromo, cyano, methyl or trifluoromethyl; or R a Br, methyl, cyano, CF3or (5) V is (wherein the wavy line indicates the position of attachment to Y or to ring A); or, V is V by 13. A pharmaceutical composition comprising the compound of Formula I, a stereoisomer thereof, an isotopically-labeled compound thereof, a solvate thereof, a prodrug thereof, a nitroxide thereof, or a pharmaceutically acceptable salt thereof according to any one of claims 1-12; and, a pharmaceutically acceptable excipient. Preferably, For wherein "1" is attached to ring A and "2" is attached to one of R 5 f2-1 is 0, 1, 2, or 3; in the For (6) R g fluoro, amino, cyano, methyl, methoxy, or R g is (7) T is Preferably, the "1" bit is in the In the ring atom connection, the "2" position is connected to V; or, T is... Preferably, in the compound of formula I, For More preferably, For the "1 " position is attached to the carbon atom marked, the "2" position is attached to V, further more preferably, for Preferably, position "1" is connected to the carbon atom marked with an asterisk (*) or to the L atom, and position "2" is connected to either Y or V; more preferably, For Preferably, position "1" is connected to the carbon atom marked with an asterisk (*) or to the L atom, and position "2" is connected to either Y or V; more preferably, For the "1 " position is attached to the carbon atom marked, the "2" position is attached to V, further more preferably, for 12. A compound, a stereoisomer thereof, an isotopically-labeled compound thereof, a solvate thereof, a prodrug thereof, a nitroxide thereof, or a pharmaceutically acceptable salt thereof, characterized in that, The compound is any one of the following compounds: ​ 14. Use of a compound of Formula I, a stereoisomer thereof, an isotopically-labeled compound thereof, a solvate thereof, a prodrug thereof, a nitroxide thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of claim 13, in the manufacture of a medicament for the prevention or treatment of a cancer, which can be esophageal cancer, pancreatic cancer, head and neck cancer, cervical cancer, uterine cancer, lung cancer, ovarian cancer, bladder cancer, liver cancer, bile duct cancer, colon cancer, breast cancer, stomach cancer, or kidney cancer; or, which can be non-small cell lung cancer, squamous non-small cell lung cancer, lung adenocarcinoma, esophageal squamous carcinoma, esophageal adenocarcinoma, head and neck squamous carcinoma, squamous cell bladder cancer, endometrial cancer, or cervical squamous cell carcinoma; or, which can be esophageal squamous carcinoma, lung adenocarcinoma, lung squamous carcinoma, head and neck squamous carcinoma, cervical squamous carcinoma, or endometrial carcinoma; or, which can be lung adenocarcinoma or lung squamous carcinoma; or, which can be human small cell lung cancer or human non-small cell lung cancer.

15. Use of a compound of Formula I, a stereoisomer thereof, an isotopically-labeled compound thereof, a solvate thereof, a prodrug thereof, a nitroxide thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of claim 13, in the manufacture of a medicament for the prevention or treatment of a disease associated with KEAP1 and / or NRF2 protein, preferably, which can be a cancer, which can be esophageal cancer, pancreatic cancer, head and neck cancer, cervical cancer, uterine cancer, lung cancer, ovarian cancer, bladder cancer, liver cancer, bile duct cancer, colon cancer, breast cancer, stomach cancer, or kidney cancer; or, which can be non-small cell lung cancer, squamous non-small cell lung cancer, lung adenocarcinoma, esophageal squamous carcinoma, esophageal adenocarcinoma, head and neck squamous carcinoma, squamous cell bladder cancer, endometrial cancer, or cervical squamous cell carcinoma; or, which can be esophageal squamous carcinoma, lung adenocarcinoma, lung squamous carcinoma, head and neck squamous carcinoma, cervical squamous carcinoma, endometrial carcinoma, or lung cancer; which can be lung adenocarcinoma or lung squamous carcinoma; which can be human small cell lung cancer or human non-small cell lung cancer.

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