Protein translation inhibitor

Abstract

The present invention relates to the field of pharmaceutical chemistry, and in particular to a protein translation inhibitor as represented by formula (II) and a use thereof in treatment and / or prevention of diseases.

Description

Protein translation inhibitors

[0001] This application is based on the application with CN application number 202311459664.X and application date November 3, 2023, the application with CN application number 202410063442.4 and application date January 16, 2024, and the application with CN application number 202411479439.7 and application date October 22, 2024, and claims priority. The disclosed contents of the aforementioned CN applications are hereby introduced as a whole into this application. Technical Field

[0002] The present invention belongs to the field of medicinal chemistry, and specifically relates to a protein translation inhibitor and its use in treating and / or preventing diseases. Background Art

[0003] Aberrant protein translation is a common feature of malignant tumors, manifested by the upregulation of oncoproteins, growth factors, and signaling proteins associated with proliferation, survival, and metastasis. The expression of oncogenic drivers is regulated by the eukaryotic translation initiation factor 4F (eIF4F) complex, which mediates the recruitment of ribosomes to mRNA and initiates the translation of mRNA into protein.

[0004] The eIF4F complex consists of three subunits: the mRNA 5' cap-binding protein eIF4E, the scaffolding protein eIF4G, and the RNA helicase eIF4A. Natural products have been reported to inhibit eIF4A-mediated translation and exhibit antiproliferative and anti-tumor phenotypes in vitro and in vivo. Rocaglamide, for example, has been shown to bind and stabilize the untranslated RNA / eIF4A complex, blocking scanning ribosomes and thereby inhibiting the translation of target mRNAs and regulating the expression of related oncogenic factors.

[0005] Currently, more protein translation inhibitors need to be developed to meet the clinical needs of tumor diseases.

[0006] Summary of the Invention

[0007] The first aspect of the present invention provides a compound of formula II or its racemate, enantiomer, diastereomer, pharmaceutically acceptable salt, isotope-labeled compound, or a mixture thereof

[0008] in,

[0009] X 1 Selected from N and C(R 1 ), R 1is selected from hydrogen, halogen, cyano, -OH, -(C1-C6)alkyl and -O-(C1-C6)alkyl;

[0010] X 2 Selected from N and C(R 2 ), R 2 is selected from hydrogen, halogen, cyano, -OH, -(C1-C6)alkyl and -O-(C1-C6)alkyl;

[0011] R 3 -(C3-C6)cycloalkyl, -(3-8 membered)heterocyclyl, -(C6-C 10 )aryl and -(5-12 membered)heteroaryl, the -(C3-C6)cycloalkyl, -(3-8 membered)heterocyclyl, -(C6-C 10 )aryl and -(5-12 membered)heteroaryl are optionally substituted with one or more R 31 replace;

[0012] R 31 each independently selected from oxo, hydrogen, halogen, cyano, nitro, -OH, -SH, -NH2, -(C1-C6)alkyl, -(C1-C6)alkylene-OH, -(C1-C6)alkylene-NH2, -(C1-C6)alkylene-NH[(C1-C6)alkyl], -(C1-C6)alkylene-N[(C1-C6)alkyl]2, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C1-C6)haloalkyl, -O-(C1-C6)alkyl, -O-(C1-C6)haloalkyl, -S-(C1-C6)alkyl, -NH (C1-C6) alkyl, -N[(C1-C6) alkyl]2, -(C3-C6) cycloalkyl, -(4-10 membered) heterocyclyl, -O-(C3-C6) cycloalkyl, -O-(4-10 membered) heterocyclyl, -C(=O)-(C1-C6) alkyl, -C(=O)-(C3-C6) cycloalkyl, -C(=O)-O-(C1-C6) alkyl, -C(=O)-O-(C3-C6) cycloalkyl, -C(=O)-NH2, -C(=O)-NH(C1-C6) alkyl, -C(=O)-N[(C1-C6) alkyl]2, -(C6-C 10)aryl, -(5-12 membered)heteroaryl, -S(=O)2-NH2, -S(=O)2-NH(C1-C6)alkyl, -S(=O)2-N[(C1-C6)alkyl]2, -NH-C(=O)H, -NH-C(=O)-(C1-C6)alkyl, -N[(C1-C6)alkyl]-C(=O)-(C1-C6)alkyl, N[(C1-C6)alkyl]-C(=O)H, -NH-S(=O)2-(C1-C6)alkyl, -N[(C1-C6)alkyl] -S(=O)2-(C1-C6)alkyl, -P(=O)[(C1-C6)alkyl]2, -P(=O)[(C1-C6)alkyl]-NH2, -P(=O)[(C1-C6)alkyl]-NH(C1-C6)alkyl and -P(=O)[(C1-C6)alkyl]-N[(C1-C6)alkyl]2, the -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C6)cycloalkyl, -(4-10 membered)heterocyclyl, -(C6-C 10 ) aryl and -(5-12 membered) heteroaryl are optionally substituted by one or more radicals selected from hydrogen, halogen, -OH, -O-(C1-C4) alkyl, -(C1-C6) alkylene-OH, -NH2, -NH(C1-C4) alkyl, -N[(C1-C4) alkyl]2, -(C1-C6) alkylene-NH2, -(C1-C6) alkylene-NH[(C1-C6) alkyl], -(C1-C6) alkylene-N[(C1-C6) alkyl]2, -(C6-C 10 ) aryl and -(5-12 membered) heteroaryl, -(C1-C6) alkylene-O(C1-C6) alkyl, oxo group;

[0013] R 4 is selected from hydrogen, halogen, cyano, -OH, -NH2, -(C1-C6)alkyl, -(C1-C6)haloalkyl, -O-(C1-C6)alkyl, -O-(C1-C6)haloalkyl, -(C3-C6)cycloalkyl, -O-(C3-C6)cycloalkyl, -(4-10 membered)heterocyclyl, -O-(4-10 membered)heterocyclyl, -(C6 ... 10 )aryl, -O-(C6-C 10 )aryl, -(5-12 membered)heteroaryl, and -O-(5-12 membered)heteroaryl;

[0014] X is selected from O, S, NH, N[(C1-C6)alkyl], N[C(=O)-R c ]、C(R a )(R b )、C(=O)、C[=C(R a )R b], S(=O) and S(=O)2;

[0015] R a and R b are independently selected from hydrogen, halogen, cyano, -OR c 、-SR c 、-N(R c )R c , -(C1-C6)alkyl and -(C1-C6)haloalkyl;

[0016] R c selected from hydrogen, -(C1-C6)alkyl, -(C1-C6)haloalkyl, -O-(C1-C6)alkyl, -O-(C1-C6)haloalkyl, -(C3-C6)cycloalkyl, -O-(C3-C6)cycloalkyl, -(4-10 membered)heterocyclyl, -O-(4-10 membered)heterocyclyl, -(C6-C 10 )aryl, -O-(C6-C 10 )aryl, -(5-12 membered)heteroaryl, and -O-(5-12 membered)heteroaryl;

[0017] Ring B is selected from -(C6-C 10 )aryl and -(5-12 membered)heteroaryl;

[0018] R 5 and R 6 each independently selected from hydrogen, halogen, cyano, nitro, -OH, -SH, -NH2, -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C1-C6)haloalkyl, -O-(C1-C6)alkyl, -O-(C1-C6)haloalkyl, -S-(C1-C6)alkyl, -NH(C1-C6)alkyl, -N[(C1-C6)alkyl]2, -(C3-C6)cycloalkyl, -(4-10 membered)heterocyclyl, -O-(C3-C6)cycloalkyl, -O-(4-10 membered)heterocyclyl, -C(=O)-(C1-C6)alkyl, -C(=O)-(C3-C6)cycloalkyl, -C(=O -C(═O)-O-(C1-C6)alkyl, -C(═O)-O-(C3-C6)cycloalkyl, -C(═O)-NH2, -C(═O)-NH(C1-C6)alkyl, -C(═O)-N[(C1-C6)alkyl]2, -C(═O)-H and -C(═N-OH)-H, said -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C6)cycloalkyl and -(4-10 membered)heterocyclyl being optionally substituted by one or more groups selected from hydrogen, halogen, oxo, -OH, -O-(C1-C4)alkyl, -NH2, -NH(C1-C4)alkyl and N[(C1-C4)alkyl]2, or,

[0019] R 5 and R 6 The carbon atom to which it is attached forms a 5-membered heterocyclic group;

[0020] Ring C is selected from -(C6-C 10 )aryl and -(5-12 membered)heteroaryl;

[0021] R 7 each independently selected from hydrogen, halogen, cyano, nitro, -OH, -SH, -NH2, -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C1-C6)haloalkyl, -O-(C1-C6)alkyl, -O-(C1-C6)haloalkyl, -S-(C1-C6)alkyl, -NH(C1-C6)alkyl, -N[(C1-C6)alkyl]2, -(C3-C6)cycloalkyl, -(4-10 membered)heterocyclyl, -O-(C3-C6)cycloalkyl, -O-(4-10 membered)heterocyclyl, -C(=O)-(C1-C6)alkyl, -C(=O)-(C3-C6)cycloalkyl, -C( -(C1-C6)alkyl, -C(=O)-O-(C1-C6)alkyl, -C(=O)-O-(C3-C6)cycloalkyl, -C(=O)-NH2, -C(=O)-NH(C1-C6)alkyl, -C(=O)-N[(C1-C6)alkyl]2 and -NHC(=O)-(C1-C6)alkyl, said -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C6)cycloalkyl and -(4-10 membered)heterocyclyl being optionally substituted with one or more groups selected from hydrogen, halogen, oxo, -OH, -O-(C1-C4)alkyl, -NH2, -NH(C1-C4)alkyl and -N[(C1-C4)alkyl]2;

[0022] m is 1, 2, 3, 4, 5, 6, 7, 8 or 9;

[0023] R 8a 、R 8b 、R 9a and R 9beach independently selected from hydrogen, halogen, cyano, -(C1-C6)alkyl, -(C1-C6)haloalkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -OR, -N(R)R, -[(C1-C8)alkylene]R, -[(C1-C8)alkylene]OR, -[(C1-C8)alkylene]N(R)R, -[(C1-C8)alkylene]N(R)C(=O)R, -[(C1-C8)alkylene]N( R)C(=O)N(R)R, -C(=O)R, -C(=O)N(R)R, -C(=O)[(C1-C8)alkylene]N(R)R, -C(=O)OR, -C(=S)N(R)R, -S R, -S(=O)R, -S(=O)2R, -S(=O)2N(R)R, -N(R)C(=O)R, -N(R)C(=O)N(R)R, -P(=O)(OR)(OR), -(C6-C 10 )aryl, -(5-12 membered)heteroaryl, -(C3-C6)cycloalkyl and -(4-10 membered)heterocyclyl,

[0024] R is each independently selected from hydrogen, -OH, -NH2, -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C1-C6)haloalkyl, -O-(C1-C6)alkyl, -(C1-C4)alkylene-O-(C1-C6)alkyl, -O-(C1-C6)haloalkyl, -S-(C1-C6)alkyl, -S(=O)2-(C1-C6)alkyl, -(C3-C6)cycloalkyl, -(4-10 membered)heterocyclyl, -O-(C3-C6)cycloalkyl, -O-(4-10 membered)heterocyclyl, ) heterocyclic group, -C(=O)-H, -C(=O)-(C1-C6) alkyl, -C(=O)-(C3-C6) cycloalkyl, -C(=O)-O-(C1-C6) alkyl, -C(=O)-O-(C3-C6) cycloalkyl, -C(=O)-NH2, -C(=O)-NH(C1-C6) alkyl, -C(=O)-N[(C1-C6) alkyl]2, -[(C1-C6) alkylene]-(C3-C6) cycloalkyl, -[(C1-C6) alkylene]-(4-10 membered) heterocyclic group, -(C6-C 10 )aryl, -[(C1-C6)alkylene]-(C6-C 10 )aryl and -(5-12 membered)heteroaryl, the -(C1-C6)alkylene-, -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C6)cycloalkyl, -(4-10 membered)heterocyclyl, -(C6-C 10)aryl, -(5-12 membered)heteroaryl, optionally substituted by one or more groups selected from hydrogen, halogen, -OH, -O-(C1-C4)alkyl, -NH2, -NH(C1-C4)alkyl, N[(C1-C4)alkyl]2 and (C1-C4)alkyl,

[0025] Or, R 8a and R 8b Combined to form oxo, -(C2-C6)alkenyl, -(C3-C6)cycloalkyl or -(4-10 membered)heterocyclyl,

[0026] Or, R 9a and R 9b Combined to form oxo, -(C2-C6)alkenyl, -(C3-C6)cycloalkyl or -(4-10 membered)heterocyclyl,

[0027] Or, R 8a and R 9a The carbon atoms to which it is attached together form a (C3-C6)cycloalkyl, a (4-10-membered)heterocyclyl or a (5-10-membered)heteroaryl, wherein the aforementioned groups are optionally substituted by one or more selected from hydrogen, halogen, -OH, -O-(C1-C4)alkyl, -NH2, -NH(C1-C4)alkyl, -N[(C1-C4)alkyl]2, -(C3-C6)cycloalkyl, -(4-8-membered)heterocyclyl, -(5-6-membered)heteroaryl and -(C6-C 10 ) aryl radical substitution,

[0028] Or, R 8b and R 9b The carbon atoms to which it is attached together form a (C3-C6)cycloalkyl, a (4-10-membered)heterocyclyl or a (5-10-membered)heteroaryl, wherein the aforementioned groups are optionally substituted by one or more selected from hydrogen, halogen, -OH, -O-(C1-C4)alkyl, -NH2, -NH(C1-C4)alkyl, -N[(C1-C4)alkyl]2, -(C3-C6)cycloalkyl, -(4-8-membered)heterocyclyl, -(5-6-membered)heteroaryl and -(C6-C 10 ) aryl radical substitution;

[0029] R 10 is selected from hydrogen, cyano, -OH and -NH2, or R 10 and R 9a The atoms to which it is attached form a (5-6 membered) heterocyclic group, which is optionally substituted by one or more groups selected from hydrogen, halogen, -OH, -(C1-C4)alkyl, -(C3-C6)cycloalkyl, -O-(C1-C4)alkyl, -NH2, -NH(C1-C4)alkyl and -N[(C1-C4)alkyl]2.

[0030] The first aspect of the present invention also provides a compound of formula II or a racemate, enantiomer, diastereomer, pharmaceutically acceptable salt, isotope-labeled compound, or a mixture thereof.

[0031] in,

[0032] X 1 Selected from N and C(R 1 ), R 1 is selected from hydrogen, halogen, cyano, -OH, -(C1-C6)alkyl and -O-(C1-C6)alkyl;

[0033] X 2 Selected from N and C(R 2 ), R 2 is selected from hydrogen, halogen, cyano, -OH, -(C1-C6)alkyl and -O-(C1-C6)alkyl;

[0034] R 3 -(C3-C6)cycloalkyl, -(3-8 membered)heterocyclyl, -(C6-C 10 )aryl and -(5-12 membered)heteroaryl, said R 3 Optionally one or more R 31 replace;

[0035] R 31each independently selected from oxo, hydrogen, halogen, cyano, nitro, -OH, -SH, -NH2, -(C1-C6)alkyl, -(C1-C6)alkylene-OH, -(C1-C6)alkylene-NH2, -(C1-C6)alkylene-NH[(C1-C6)alkyl], -(C1-C6)alkylene-N[(C1-C6)alkyl]2, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C1-C6) C6)haloalkyl, -O-(C1-C6)alkyl, -O-(C1-C6)haloalkyl, -S-(C1-C6)alkyl, -NH(C1-C6)alkyl, -N[(C1-C6)alkyl]2, -(C3-C6)cycloalkyl, -(4-10 membered)heterocyclyl, -O-(C3-C6)cycloalkyl, -O-(4-10 membered)heterocyclyl, -C(=O)-(C1-C6)alkyl, -C(=O)-(C1-C6)alkyl, -C(=O)-O-(C1-C6)alkyl, -C(=O)-O-(C3-C6)cycloalkyl, -C(=O)-NH2, -C(=O)-NH(C1-C6)alkyl and -C(=O)-N[(C1-C6)alkyl]2, the said -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C6)cycloalkyl and -(4-10 membered)heteroalkyl The cyclic group is optionally substituted with one or more groups selected from hydrogen, halogen, -OH, -O-(C1-C4)alkyl, -(C1-C6)alkylene-OH, -NH2, -NH(C1-C4)alkyl, -N[(C1-C4)alkyl]2, -(C1-C6)alkylene-NH2, -(C1-C6)alkylene-NH[(C1-C6)alkyl] and -(C1-C6)alkylene-N[(C1-C6)alkyl]2;

[0036] R 4 is selected from hydrogen, halogen, cyano, -OH, -NH2, -(C1-C6)alkyl, -(C1-C6)haloalkyl, -O-(C1-C6)alkyl, -O-(C1-C6)haloalkyl, -(C3-C6)cycloalkyl, -O-(C3-C6)cycloalkyl, -(4-10 membered)heterocyclyl, -O-(4-10 membered)heterocyclyl, -(C6 ... 10 )aryl, -O-(C6-C 10 )aryl, -(5-12 membered)heteroaryl, and -O-(5-12 membered)heteroaryl;

[0037] X is selected from O, S, NH, N[(C1-C6)alkyl], N[C(=O)-R c ]、C(R a )(R b )、C(=O)、C[=C(R a )Rb ], S(=O) and S(=O)2;

[0038] R a and R b are independently selected from hydrogen, halogen, cyano, -OR c 、-SR c 、-N(R c )R c , -(C1-C6)alkyl and -(C1-C6)haloalkyl;

[0039] R c selected from hydrogen, -(C1-C6)alkyl, -(C1-C6)haloalkyl, -O-(C1-C6)alkyl, -O-(C1-C6)haloalkyl, -(C3-C6)cycloalkyl, -O-(C3-C6)cycloalkyl, -(4-10 membered)heterocyclyl, -O-(4-10 membered)heterocyclyl, -(C6-C 10 )aryl, -O-(C6-C 10 )aryl, -(5-12 membered)heteroaryl, and -O-(5-12 membered)heteroaryl;

[0040] Ring B is selected from -(C6-C 10 )aryl and -(5-12 membered)heteroaryl;

[0041] R 5 and R 6each independently selected from hydrogen, halogen, cyano, nitro, -OH, -SH, -NH2, -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C1-C6)haloalkyl, -O-(C1-C6)alkyl, -O-(C1-C6)haloalkyl, -S-(C1-C6)alkyl, -NH(C1-C6)alkyl, -N[(C1-C6)alkyl]2, -(C3-C6)cycloalkyl, -(4-10 membered)heterocyclyl, -O-(C3-C6)cycloalkyl, -O-(4-10 membered)heterocyclyl, -C(=O)-(C1-C6)alkyl, -C(=O)-(C3-C6)cycloalkyl, -C(= -C(═O)-O-(C-C)alkyl, -C(═O)-O-(C-C)alkyl, -C(═O)-O-(C-C)cycloalkyl, -C(═O)-NH, -C(═O)-NH(C-C)alkyl, -C(═O)-N[(C-C)alkyl], -C(═O)-H and -C(═N-OH)-H, said -(C-C)alkyl, -(C-C)alkenyl, -(C-C)alkynyl, -(C-C)cycloalkyl and -(4-10 membered)heterocyclyl being optionally substituted with one or more groups selected from hydrogen, halogen, -OH, -O-(C-C)alkyl, -NH, -NH(C-C)alkyl and N[(C-C)alkyl], or,

[0042] R 5 and R 6 The carbon atom to which it is attached forms a 5-membered heterocyclic group;

[0043] Ring C is selected from -(C6-C 10 )aryl and -(5-12 membered)heteroaryl;

[0044] R 7each independently selected from hydrogen, halogen, cyano, nitro, -OH, -SH, -NH2, -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C1-C6)haloalkyl, -O-(C1-C6)alkyl, -O-(C1-C6)haloalkyl, -S-(C1-C6)alkyl, -NH(C1-C6)alkyl, -N[(C1-C6)alkyl]2, -(C3-C6)cycloalkyl, -(4-10 membered)heterocyclyl, -O-(C3-C6)cycloalkyl, -O-(4-10 membered)heterocyclyl, -C(=O)-(C1-C6)alkyl, -C(=O)-(C3 -C6)alkyl, -C(=O)-O-(C1-C6)alkyl, -C(=O)-O-(C3-C6)cycloalkyl, -C(=O)-NH2, -C(=O)-NH(C1-C6)alkyl and -C(=O)-N[(C1-C6)alkyl]2, said -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C6)cycloalkyl and -(4-10 membered)heterocyclyl being optionally substituted with one or more groups selected from hydrogen, halogen, -OH, -O-(C1-C4)alkyl, -NH2, -NH(C1-C4)alkyl and -N[(C1-C4)alkyl]2;

[0045] m is 1, 2, 3, 4, 5, 6, 7, 8 or 9;

[0046] R 8a 、R 8b 、R 9a and R 9b each independently selected from hydrogen, halogen, cyano, -(C1-C6)alkyl, -(C1-C6)haloalkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -OR, -N(R)R, -[(C1-C8)alkylene]R, -[(C1-C8)alkylene]OR, -[(C1-C8)alkylene]N(R)R, -C(=O)R, -C(=O )N(R)R, -C(=O)[(C1-C8)alkylene]N(R)R, -C(=O)OR, -C(=S)N(R)R, -SR, -S(=O)R, -S( =O)2R, -S(=O)2N(R)R, -N(R)C(=O)R, -N(R)C(=O)N(R)R, -P(=O)(OR)(OR), -(C6-C 10 )aryl, -(5-12 membered)heteroaryl, -(C3-C6)cycloalkyl and -(4-10 membered)heterocyclyl,

[0047] R is each independently selected from hydrogen, -OH, -NH2, -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C1-C6)haloalkyl, -O-(C1-C6)alkyl, -O-(C1-C6)haloalkyl, -S-(C1-C6)alkyl, -(C3-C6)cycloalkyl, -(4-10 membered)heterocyclyl, -O-(C3-C6)cycloalkyl, -O-(4-10 membered)heterocyclyl, -C( =O)-H, -C(=O)-(C1-C6)alkyl, -C(=O)-(C3-C6)cycloalkyl, -C(=O)-O-(C1-C6)alkyl, -C(=O)-O-(C3-C6)cycloalkyl, -C(=O)-NH2, -C(=O)-NH(C1-C6)alkyl, -C(=O)-N[(C1-C6)alkyl]2, -[(C1-C6)alkylene]-(4-10 membered)heterocyclyl, -(C6-C 10 )aryl, -[(C1-C6)alkylene]-(C6-C 10 )aryl and -(5-12 membered)heteroaryl, the -(C1-C6)alkylene-, -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C6)cycloalkyl, -(4-10 membered)heterocyclyl, -(C6-C 10 )aryl, -(5-12 membered)heteroaryl are optionally substituted by one or more groups selected from hydrogen, halogen, -OH, -O-(C1-C4)alkyl, -NH2, -NH(C1-C4)alkyl, N[(C1-C4)alkyl]2,

[0048] Or, R 8a and R 8b , and R 9a and R 9b independently combine to form oxo, -(C2-C6)alkenyl, -(C3-C6)cycloalkyl or -(4-10 membered)heterocyclyl,

[0049] Or, R 8a and R 9a , R 8b and R 9b The carbon atoms to which it is attached together form a (C3-C6)cycloalkyl, a (4-10-membered)heterocyclyl or a (5-10-membered)heteroaryl, wherein the aforementioned groups are optionally substituted by one or more selected from hydrogen, halogen, -OH, -O-(C1-C4)alkyl, -NH2, -NH(C1-C4)alkyl, -N[(C1-C4)alkyl]2, -(C3-C6)cycloalkyl, -(4-8-membered)heterocyclyl, -(5-6-membered)heteroaryl and -(C6-C 10 ) aryl radical substitution;

[0050] R 10is selected from hydrogen, cyano, -OH and -NH2, or R 10 and R 9b The atoms to which it is attached form a (5-6 membered) heterocyclic group, which is optionally substituted by one or more groups selected from hydrogen, halogen, -OH, -(C1-C4)alkyl, -(C3-C6)cycloalkyl, -O-(C1-C4)alkyl, -NH2, -NH(C1-C4)alkyl and -N[(C1-C4)alkyl]2.

[0051] In certain embodiments, the compound is selected from the compound represented by Formula I,

[0052] in,

[0053] X 1 Selected from N and C(R 1 ), R 1 is selected from hydrogen, halogen, cyano, -OH, -(C1-C6)alkyl and -O-(C1-C6)alkyl;

[0054] X 2 Selected from N and C(R 2 ), R 2 is selected from hydrogen, halogen, cyano, -OH, -(C1-C6)alkyl and -O-(C1-C6)alkyl;

[0055] R 3 -(C3-C6)cycloalkyl, -(3-8 membered)heterocyclyl, -(C6-C 10 )aryl and -(5-12 membered)heteroaryl, the -(C3-C6)cycloalkyl, -(3-8 membered)heterocyclyl, -(C6-C 10 )aryl and -(5-12 membered)heteroaryl are optionally substituted with one or more R 31 replace;

[0056] R 31each independently selected from oxo, hydrogen, halogen, cyano, nitro, -OH, -SH, -NH2, -(C1-C6)alkyl, -(C1-C6)alkylene-OH, -(C1-C6)alkylene-NH2, -(C1-C6)alkylene-NH[(C1-C6)alkyl], -(C1-C6)alkylene-N[(C1-C6)alkyl]2, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C1-C6)haloalkyl, -O-(C1-C6)alkyl, -O-(C1-C6)haloalkyl, -S-(C1-C6)alkyl, -NH (C1-C6) alkyl, -N[(C1-C6) alkyl]2, -(C3-C6) cycloalkyl, -(4-10 membered) heterocyclyl, -O-(C3-C6) cycloalkyl, -O-(4-10 membered) heterocyclyl, -C(=O)-(C1-C6) alkyl, -C(=O)-(C3-C6) cycloalkyl, -C(=O)-O-(C1-C6) alkyl, -C(=O)-O-(C3-C6) cycloalkyl, -C(=O)-NH2, -C(=O)-NH(C1-C6) alkyl, -C(=O)-N[(C1-C6) alkyl]2, -(C6-C 10 )aryl, -(5-12 membered)heteroaryl, -S(=O)2-NH2, -S(=O)2-NH(C1-C6)alkyl, -S(=O)2-N[(C1-C6)alkyl]2, -NH-C(=O)H, -NH-C(=O)-(C1-C6)alkyl, -N[(C1-C6)alkyl]-C(=O)-(C1-C6)alkyl, N[(C1-C6)alkyl]-C(=O)H, -NH-S(=O)2-(C1-C6)alkyl, -N[(C1-C6)alkyl] -S(=O)2-(C1-C6)alkyl, -P(=O)[(C1-C6)alkyl]2, -P(=O)[(C1-C6)alkyl]-NH2, -P(=O)[(C1-C6)alkyl]-NH(C1-C6)alkyl and -P(=O)[(C1-C6)alkyl]-N[(C1-C6)alkyl]2, the -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C6)cycloalkyl, -(4-10 membered)heterocyclyl, -(C6-C 10 ) aryl and -(5-12 membered) heteroaryl are optionally substituted by one or more radicals selected from hydrogen, halogen, -OH, -O-(C1-C4) alkyl, -(C1-C6) alkylene-OH, -NH2, -NH(C1-C4) alkyl, -N[(C1-C4) alkyl]2, -(C1-C6) alkylene-NH2, -(C1-C6) alkylene-NH[(C1-C6) alkyl], -(C1-C6) alkylene-N[(C1-C6) alkyl]2, -(C6-C 10) aryl and -(5-12 membered) heteroaryl, -(C1-C6) alkylene-O(C1-C6) alkyl, oxo group;

[0057] R 4 is selected from hydrogen, halogen, cyano, -OH, -NH2, -(C1-C6)alkyl, -(C1-C6)haloalkyl, -O-(C1-C6)alkyl, -O-(C1-C6)haloalkyl, -(C3-C6)cycloalkyl, -O-(C3-C6)cycloalkyl, -(4-10 membered)heterocyclyl, -O-(4-10 membered)heterocyclyl, -(C6 ... 10 )aryl, -O-(C6-C 10 )aryl, -(5-12 membered)heteroaryl, and -O-(5-12 membered)heteroaryl;

[0058] X is selected from O, S, NH, N[(C1-C6)alkyl], N[C(=O)-R c ]、C(R a )(R b )、C(=O)、C[=C(R a )R b ], S(=O) and S(=O)2;

[0059] R a and R b are independently selected from hydrogen, halogen, cyano, -OR c 、-SR c 、-N(R c )R c , -(C1-C6)alkyl and -(C1-C6)haloalkyl;

[0060] R c selected from hydrogen, -(C1-C6)alkyl, -(C1-C6)haloalkyl, -O-(C1-C6)alkyl, -O-(C1-C6)haloalkyl, -(C3-C6)cycloalkyl, -O-(C3-C6)cycloalkyl, -(4-10 membered)heterocyclyl, -O-(4-10 membered)heterocyclyl, -(C6-C 10 )aryl, -O-(C6-C 10 )aryl, -(5-12 membered)heteroaryl, and -O-(5-12 membered)heteroaryl;

[0061] Ring B is selected from -(C6-C 10 )aryl and -(5-12 membered)heteroaryl;

[0062] R 5 and R 6each independently selected from hydrogen, halogen, cyano, nitro, -OH, -SH, -NH2, -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C1-C6)haloalkyl, -O-(C1-C6)alkyl, -O-(C1-C6)haloalkyl, -S-(C1-C6)alkyl, -NH(C1-C6)alkyl, -N[(C1-C6)alkyl]2, -(C3-C6)cycloalkyl, -(4-10 membered)heterocyclyl, -O-(C3-C6)cycloalkyl, -O-(4-10 membered)heterocyclyl, -C(=O)-(C1-C6)alkyl, -C(=O)-(C3-C6)cycloalkyl, -C(=O -C(═O)-O-(C1-C6)alkyl, -C(═O)-O-(C3-C6)cycloalkyl, -C(═O)-NH2, -C(═O)-NH(C1-C6)alkyl, -C(═O)-N[(C1-C6)alkyl]2, -C(═O)-H and -C(═N-OH)-H, said -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C6)cycloalkyl and -(4-10 membered)heterocyclyl being optionally substituted by one or more groups selected from hydrogen, halogen, oxo, -OH, -O-(C1-C4)alkyl, -NH2, -NH(C1-C4)alkyl and N[(C1-C4)alkyl]2, or,

[0063] R 5 and R 6 The carbon atom to which it is attached forms a 5-membered heterocyclic group;

[0064] Ring C is selected from -(C6-C 10 )aryl and -(5-12 membered)heteroaryl;

[0065] R 7each independently selected from hydrogen, halogen, cyano, nitro, -OH, -SH, -NH2, -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C1-C6)haloalkyl, -O-(C1-C6)alkyl, -O-(C1-C6)haloalkyl, -S-(C1-C6)alkyl, -NH(C1-C6)alkyl, -N[(C1-C6)alkyl]2, -(C3-C6)cycloalkyl, -(4-10 membered)heterocyclyl, -O-(C3-C6)cycloalkyl, -O-(4-10 membered)heterocyclyl, -C(=O)-(C1-C6)alkyl, -C(=O)-(C3-C6)cycloalkyl, -C( -(C1-C6)alkyl, -C(=O)-O-(C1-C6)alkyl, -C(=O)-O-(C3-C6)cycloalkyl, -C(=O)-NH2, -C(=O)-NH(C1-C6)alkyl, -C(=O)-N[(C1-C6)alkyl]2 and -NHC(=O)-(C1-C6)alkyl, said -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C6)cycloalkyl and -(4-10 membered)heterocyclyl being optionally substituted with one or more groups selected from hydrogen, halogen, oxo, -OH, -O-(C1-C4)alkyl, -NH2, -NH(C1-C4)alkyl and -N[(C1-C4)alkyl]2;

[0066] m is 1, 2, 3, 4, 5, 6, 7, 8 or 9;

[0067] R 8a 、R 8b 、R 9a and R 9b each independently selected from hydrogen, halogen, cyano, -(C1-C6)alkyl, -(C1-C6)haloalkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -OR, -N(R)R, -[(C1-C8)alkylene]R, -[(C1-C8)alkylene]OR, -[(C1-C8)alkylene]N(R)R, -[(C1-C8)alkylene]NHC(=O)R, -[(C1-C8)alkylene]N(R )C(=O)N(R)R, -C(=O)R, -C(=O)N(R)R, -C(=O)[(C1-C8)alkylene]N(R)R, -C(=O)OR, -C(=S)N(R)R, -SR , -S(=O)R, -S(=O)2R, -S(=O)2N(R)R, -N(R)C(=O)R, -N(R)C(=O)N(R)R, -P(=O)(OR)(OR), -(C6-C 10 )aryl, -(5-12 membered)heteroaryl, -(C3-C6)cycloalkyl and -(4-10 membered)heterocyclyl,

[0068] R is each independently selected from hydrogen, -OH, -NH2, -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C1-C6)haloalkyl, -O-(C1-C6)alkyl, -(C1-C4)alkylene-O-(C1-C6)alkyl, -O-(C1-C6)haloalkyl, -S-(C1-C6)alkyl, -S(=O)2-(C1-C6)alkyl, -(C3-C6)cycloalkyl, -(4-10 membered)heterocyclyl, -O-(C3-C6)cycloalkyl, -O-(4-10 membered)heterocyclyl, ) heterocyclic group, -C(=O)-H, -C(=O)-(C1-C6) alkyl, -C(=O)-(C3-C6) cycloalkyl, -C(=O)-O-(C1-C6) alkyl, -C(=O)-O-(C3-C6) cycloalkyl, -C(=O)-NH2, -C(=O)-NH(C1-C6) alkyl, -C(=O)-N[(C1-C6) alkyl]2, -[(C1-C6) alkylene]-(C3-C6) cycloalkyl, -[(C1-C6) alkylene]-(4-10 membered) heterocyclic group, -(C6-C 10 )aryl, -[(C1-C6)alkylene]-(C6-C 10 )aryl and -(5-12 membered)heteroaryl, the -(C1-C6)alkylene-, -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C6)cycloalkyl, -(4-10 membered)heterocyclyl, -(C6-C 10 )aryl, -(5-12 membered)heteroaryl, optionally substituted by one or more groups selected from hydrogen, halogen, -OH, -O-(C1-C4)alkyl, -NH2, -NH(C1-C4)alkyl, N[(C1-C4)alkyl]2 and (C1-C4)alkyl,

[0069] Or, R 8a and R 8b Combined to form oxo, -(C2-C6)alkenyl, -(C3-C6)cycloalkyl or -(4-10 membered)heterocyclyl,

[0070] Or, R 9a and R 9b Combined to form oxo, -(C2-C6)alkenyl, -(C3-C6)cycloalkyl or -(4-10 membered)heterocyclyl,

[0071] Or, R 8a and R 9aThe carbon atoms to which it is attached together form a (C3-C6)cycloalkyl, a (4-10-membered)heterocyclyl or a (5-10-membered)heteroaryl, wherein the aforementioned groups are optionally substituted by one or more selected from hydrogen, halogen, -OH, -O-(C1-C4)alkyl, -NH2, -NH(C1-C4)alkyl, -N[(C1-C4)alkyl]2, -(C3-C6)cycloalkyl, -(4-8-membered)heterocyclyl, -(5-6-membered)heteroaryl and -(C6-C 10 ) aryl radical substitution,

[0072] Or, R 8b and R 9b The carbon atoms to which it is attached together form a (C3-C6)cycloalkyl, a (4-10-membered)heterocyclyl or a (5-10-membered)heteroaryl, wherein the aforementioned groups are optionally substituted by one or more selected from hydrogen, halogen, -OH, -O-(C1-C4)alkyl, -NH2, -NH(C1-C4)alkyl, -N[(C1-C4)alkyl]2, -(C3-C6)cycloalkyl, -(4-8-membered)heterocyclyl, -(5-6-membered)heteroaryl and -(C6-C 10 ) aryl radical substitution;

[0073] R 10 is selected from hydrogen, cyano, -OH and -NH2, or R 10 and R 9a The atoms to which it is attached form a (5-6 membered) heterocyclic group, which is optionally substituted by one or more groups selected from hydrogen, halogen, -OH, -(C1-C4)alkyl, -(C3-C6)cycloalkyl, -O-(C1-C4)alkyl, -NH2, -NH(C1-C4)alkyl and -N[(C1-C4)alkyl]2.

[0074] In certain embodiments, the compound is selected from the compound represented by Formula I,

[0075] in,

[0076] X 1 Selected from N and C(R 1 ), R 1 is selected from hydrogen, halogen, cyano, -OH, -(C1-C6)alkyl and -O-(C1-C6)alkyl;

[0077] X 2 Selected from N and C(R 2 ), R 2 is selected from hydrogen, halogen, cyano, -OH, -(C1-C6)alkyl and -O-(C1-C6)alkyl;

[0078] R 3-(C3-C6)cycloalkyl, -(3-8 membered)heterocyclyl, -(C6-C 10 )aryl and -(5-12 membered)heteroaryl, said R 3 Optionally one or more R 31 replace;

[0079] R 31 each independently selected from oxo, hydrogen, halogen, cyano, nitro, -OH, -SH, -NH2, -(C1-C6)alkyl, -(C1-C6)alkylene-OH, -(C1-C6)alkylene-NH2, -(C1-C6)alkylene-NH[(C1-C6)alkyl], -(C1-C6)alkylene-N[(C1-C6)alkyl]2, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C1-C6) C6)haloalkyl, -O-(C1-C6)alkyl, -O-(C1-C6)haloalkyl, -S-(C1-C6)alkyl, -NH(C1-C6)alkyl, -N[(C1-C6)alkyl]2, -(C3-C6)cycloalkyl, -(4-10 membered)heterocyclyl, -O-(C3-C6)cycloalkyl, -O-(4-10 membered)heterocyclyl, -C(=O)-(C1-C6)alkyl, -C(=O)-(C1-C6)alkyl, -C(=O)-O-(C1-C6)alkyl, -C(=O)-O-(C3-C6)cycloalkyl, -C(=O)-NH2, -C(=O)-NH(C1-C6)alkyl and -C(=O)-N[(C1-C6)alkyl]2, the said -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C6)cycloalkyl and -(4-10 membered)heteroalkyl The cyclic group is optionally substituted with one or more groups selected from hydrogen, halogen, -OH, -O-(C1-C4)alkyl, -(C1-C6)alkylene-OH, -NH2, -NH(C1-C4)alkyl, -N[(C1-C4)alkyl]2, -(C1-C6)alkylene-NH2, -(C1-C6)alkylene-NH[(C1-C6)alkyl] and -(C1-C6)alkylene-N[(C1-C6)alkyl]2;

[0080] R 4 is selected from hydrogen, halogen, cyano, -OH, -NH2, -(C1-C6)alkyl, -(C1-C6)haloalkyl, -O-(C1-C6)alkyl, -O-(C1-C6)haloalkyl, -(C3-C6)cycloalkyl, -O-(C3-C6)cycloalkyl, -(4-10 membered)heterocyclyl, -O-(4-10 membered)heterocyclyl, -(C6 ... 10 )aryl, -O-(C6-C 10 )aryl, -(5-12 membered)heteroaryl, and -O-(5-12 membered)heteroaryl;

[0081] X is selected from O, S, NH, N[(C1-C6)alkyl], N[C(=O)-R c ]、C(R a )(R b )、C(=O)、C[=C(R a )R b ], S(=O) and S(=O)2;

[0082] R a and R b are independently selected from hydrogen, halogen, cyano, -OR c 、-SR c 、-N(R c )R c , -(C1-C6)alkyl and -(C1-C6)haloalkyl;

[0083] R c selected from hydrogen, -(C1-C6)alkyl, -(C1-C6)haloalkyl, -O-(C1-C6)alkyl, -O-(C1-C6)haloalkyl, -(C3-C6)cycloalkyl, -O-(C3-C6)cycloalkyl, -(4-10 membered)heterocyclyl, -O-(4-10 membered)heterocyclyl, -(C6-C 10 )aryl, -O-(C6-C 10 )aryl, -(5-12 membered)heteroaryl, and -O-(5-12 membered)heteroaryl;

[0084] Ring B is selected from -(C6-C 10 )aryl and -(5-12 membered)heteroaryl;

[0085] R 5 and R 6each independently selected from hydrogen, halogen, cyano, nitro, -OH, -SH, -NH2, -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C1-C6)haloalkyl, -O-(C1-C6)alkyl, -O-(C1-C6)haloalkyl, -S-(C1-C6)alkyl, -NH(C1-C6)alkyl, -N[(C1-C6)alkyl]2, -(C3-C6)cycloalkyl, -(4-10 membered)heterocyclyl, -O-(C3-C6)cycloalkyl, -O-(4-10 membered)heterocyclyl, -C(=O)-(C1-C6)alkyl, -C(=O)-(C3-C6)cycloalkyl, -C(= -C(═O)-O-(C-C)alkyl, -C(═O)-O-(C-C)alkyl, -C(═O)-O-(C-C)cycloalkyl, -C(═O)-NH, -C(═O)-NH(C-C)alkyl, -C(═O)-N[(C-C)alkyl], -C(═O)-H and -C(═N-OH)-H, said -(C-C)alkyl, -(C-C)alkenyl, -(C-C)alkynyl, -(C-C)cycloalkyl and -(4-10 membered)heterocyclyl being optionally substituted with one or more groups selected from hydrogen, halogen, -OH, -O-(C-C)alkyl, -NH, -NH(C-C)alkyl and N[(C-C)alkyl], or,

[0086] R 5 and R 6 The carbon atom to which it is attached forms a 5-membered heterocyclic group;

[0087] Ring C is selected from -(C6-C 10 )aryl and -(5-12 membered)heteroaryl;

[0088] R 7each independently selected from hydrogen, halogen, cyano, nitro, -OH, -SH, -NH2, -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C1-C6)haloalkyl, -O-(C1-C6)alkyl, -O-(C1-C6)haloalkyl, -S-(C1-C6)alkyl, -NH(C1-C6)alkyl, -N[(C1-C6)alkyl]2 , -(C3-C6)cycloalkyl, -(4-10 membered)heterocyclyl, -O-(C3-C6)cycloalkyl, -O-(4-10 membered)heterocyclyl, -C(=O)-(C1-C6)alkyl, -C(=O)-(C3-C6)cycloalkyl, -C(=O)-O-(C1-C6)alkyl, -C(=O)-O-(C3-C6)cycloalkyl, -C(=O)-NH2, -C(=O)- NH(C1-C6)alkyl and -C(=O)-N[(C1-C6)alkyl]2, said -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C6)cycloalkyl and -(4-10 membered)heterocyclyl being optionally substituted with one or more groups selected from hydrogen, halogen, -OH, -O-(C1-C4)alkyl, -NH2, -NH(C1-C4)alkyl and -N[(C1-C4)alkyl]2;

[0089] m is 1, 2, 3, 4, 5, 6, 7, 8 or 9;

[0090] R 8a 、R 8b 、R 9a and R 9b each independently selected from hydrogen, halogen, cyano, -(C1-C6)alkyl, -(C1-C6)haloalkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -OR, -N(R)R, -[(C1-C8)alkylene]R, -[(C1-C8)alkylene]OR, -[(C1-C8)alkylene]N(R)R, -C(=O)R, -C(=O )N(R)R, -C(=O)[(C1-C8)alkylene]N(R)R, -C(=O)OR, -C(=S)N(R)R, -SR, -S(=O)R, -S( =O)2R, -S(=O)2N(R)R, -N(R)C(=O)R, -N(R)C(=O)N(R)R, -P(=O)(OR)(OR), -(C6-C 10 )aryl, -(5-12 membered)heteroaryl, -(C3-C6)cycloalkyl and -(4-10 membered)heterocyclyl,

[0091] R is each independently selected from hydrogen, -OH, -NH2, -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C1-C6)haloalkyl, -O-(C1-C6)alkyl, -O-(C1-C6)haloalkyl, -S-(C1-C6)alkyl, -(C3-C6)cycloalkyl, -(4-10 membered)heterocyclyl, -O-(C3-C6)cycloalkyl, -O-(4-10 membered)heterocyclyl, -C( =O)-H, -C(=O)-(C1-C6)alkyl, -C(=O)-(C3-C6)cycloalkyl, -C(=O)-O-(C1-C6)alkyl, -C(=O)-O-(C3-C6)cycloalkyl, -C(=O)-NH2, -C(=O)-NH(C1-C6)alkyl, -C(=O)-N[(C1-C6)alkyl]2, -[(C1-C6)alkylene]-(4-10 membered)heterocyclyl, -(C6-C 10 )aryl, -[(C1-C6)alkylene]-(C6-C 10 )aryl and -(5-12 membered)heteroaryl, the -(C1-C6)alkylene-, -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C6)cycloalkyl, -(4-10 membered)heterocyclyl, -(C6-C 10 )aryl, -(5-12 membered)heteroaryl are optionally substituted by one or more groups selected from hydrogen, halogen, -OH, -O-(C1-C4)alkyl, -NH2, -NH(C1-C4)alkyl, N[(C1-C4)alkyl]2,

[0092] Or, R 8a and R 8b , and R 9a and R 9b independently combine to form oxo, -(C2-C6)alkenyl, -(C3-C6)cycloalkyl or -(4-10 membered)heterocyclyl,

[0093] Or, R 8a and R 9a , R 8b and R 9b The carbon atoms to which it is attached together form a (C3-C6)cycloalkyl, a (4-10-membered)heterocyclyl or a (5-10-membered)heteroaryl, wherein the aforementioned groups are optionally substituted by one or more selected from hydrogen, halogen, -OH, -O-(C1-C4)alkyl, -NH2, -NH(C1-C4)alkyl, -N[(C1-C4)alkyl]2, -(C3-C6)cycloalkyl, -(4-8-membered)heterocyclyl, -(5-6-membered)heteroaryl and -(C6-C 10 ) aryl radical substitution;

[0094] R 10is selected from hydrogen, cyano, -OH and -NH2, or R 10 and R 9b The atoms to which it is attached form a (5-6 membered) heterocyclic group, which is optionally substituted by one or more groups selected from hydrogen, halogen, -OH, -(C1-C4)alkyl, -(C3-C6)cycloalkyl, -O-(C1-C4)alkyl, -NH2, -NH(C1-C4)alkyl and -N[(C1-C4)alkyl]2.

[0095] In certain embodiments, the compound is selected from the compound represented by Formula I,

[0096] in,

[0097] X 1 Selected from N and C(R 1 ), R 1 is selected from hydrogen, halogen, cyano, -OH, -(C1-C6)alkyl and -O-(C1-C6)alkyl;

[0098] X 2 Selected from N and C(R 2 ), R 2 is selected from hydrogen, halogen, cyano, -OH, -(C1-C6)alkyl and -O-(C1-C6)alkyl;

[0099] R 3 -(C3-C6)cycloalkyl, -(4-8 membered)heterocyclyl, -(C6-C 10 )aryl and -(5-12 membered)heteroaryl, said R 3 Optionally one or more R 31 replace;

[0100] R 31each independently selected from oxo, hydrogen, halogen, cyano, nitro, -OH, -SH, -NH2, -(C1-C6)alkyl, -(C1-C6)alkylene-OH, -(C1-C6)alkylene-NH2, -(C1-C6)alkylene-NH[(C1-C6)alkyl], -(C1-C6)alkylene-N[(C1-C6)alkyl]2, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C1-C6) C6)haloalkyl, -O-(C1-C6)alkyl, -O-(C1-C6)haloalkyl, -S-(C1-C6)alkyl, -NH(C1-C6)alkyl, -N[(C1-C6)alkyl]2, -(C3-C6)cycloalkyl, -(4-10 membered)heterocyclyl, -O-(C3-C6)cycloalkyl, -O-(4-10 membered)heterocyclyl, -C(=O)-(C1-C6)alkyl, -C(=O)-(C1-C6)alkyl, -C(=O)-O-(C1-C6)alkyl, -C(=O)-O-(C3-C6)cycloalkyl, -C(=O)-NH2, -C(=O)-NH(C1-C6)alkyl and -C(=O)-N[(C1-C6)alkyl]2, the said -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C6)cycloalkyl and -(4-10 membered)heteroalkyl The cyclic group is optionally substituted with one or more groups selected from hydrogen, halogen, -OH, -O-(C1-C4)alkyl, -(C1-C6)alkylene-OH, -NH2, -NH(C1-C4)alkyl, -N[(C1-C4)alkyl]2, -(C1-C6)alkylene-NH2, -(C1-C6)alkylene-NH[(C1-C6)alkyl] and -(C1-C6)alkylene-N[(C1-C6)alkyl]2;

[0101] R 4 is selected from hydrogen, halogen, cyano, -OH, -NH2, -(C1-C6)alkyl, -(C1-C6)haloalkyl, -O-(C1-C6)alkyl, -O-(C1-C6)haloalkyl, -(C3-C6)cycloalkyl, -O-(C3-C6)cycloalkyl, -(4-10 membered)heterocyclyl, -O-(4-10 membered)heterocyclyl, -(C6 ... 10 )aryl, -O-(C6-C 10 )aryl, -(5-12 membered)heteroaryl, and -O-(5-12 membered)heteroaryl;

[0102] X is selected from O, S, NH, N[(C1-C6)alkyl], N[C(=O)-R c ]、C(R a )(R b )、C(=O)、C[=C(R a )Rb ], S(=O) and S(=O)2;

[0103] R a and R b are independently selected from hydrogen, halogen, cyano, -OR c 、-SR c 、-N(R c )R c , -(C1-C6)alkyl and -(C1-C6)haloalkyl;

[0104] R c selected from hydrogen, -(C1-C6)alkyl, -(C1-C6)haloalkyl, -O-(C1-C6)alkyl, -O-(C1-C6)haloalkyl, -(C3-C6)cycloalkyl, -O-(C3-C6)cycloalkyl, -(4-10 membered)heterocyclyl, -O-(4-10 membered)heterocyclyl, -(C6-C 10 )aryl, -O-(C6-C 10 )aryl, -(5-12 membered)heteroaryl, and -O-(5-12 membered)heteroaryl;

[0105] Ring B is selected from -(C6-C 10 )aryl and -(5-12 membered)heteroaryl;

[0106] R 5 and R 6each independently selected from hydrogen, halogen, cyano, nitro, -OH, -SH, -NH2, -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C1-C6)haloalkyl, -O-(C1-C6)alkyl, -O-(C1-C6)haloalkyl, -S-(C1-C6)alkyl, -NH(C1-C6)alkyl, -N[(C1-C6)alkyl]2, -(C3-C6)cycloalkyl, -(4-10 membered)heterocyclyl, -O-(C3-C6)cycloalkyl, -O-(4-10 membered)heterocyclyl, -C(=O)-(C1-C6)alkyl, -C(=O)-(C3-C6)cycloalkyl, -C(= -C(═O)-O-(C-C)alkyl, -C(═O)-O-(C-C)alkyl, -C(═O)-O-(C-C)cycloalkyl, -C(═O)-NH, -C(═O)-NH(C-C)alkyl, -C(═O)-N[(C-C)alkyl], -C(═O)-H and -C(═N-OH)-H, said -(C-C)alkyl, -(C-C)alkenyl, -(C-C)alkynyl, -(C-C)cycloalkyl and -(4-10 membered)heterocyclyl being optionally substituted with one or more groups selected from hydrogen, halogen, -OH, -O-(C-C)alkyl, -NH, -NH(C-C)alkyl and N[(C-C)alkyl], or,

[0107] R 5 and R 6 The carbon atom to which it is attached forms a 5-membered heterocyclic group;

[0108] Ring C is selected from -(C6-C 10 )aryl and -(5-12 membered)heteroaryl;

[0109] R 7Each is independently selected from hydrogen, halogen, cyano, nitro, -OH, -SH, -NH2, -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C1-C6)haloalkyl, -O-(C1-C6)alkyl, -O-(C1-C6)haloalkyl, -S-(C1-C6)alkyl, -NH(C1-C6)alkyl, -N[(C1-C6)alkyl]2, -(C3-C6)cycloalkyl, -(4-10 membered)heterocyclyl, -O-(C3-C6)cycloalkyl, -O-(4-10 membered)heterocyclyl, -C(=O)-(C1-C6)alkyl, -C(=O)-(C3-C6)cycloalkyl, -C(=O)-O-(C1-C6)alkyl, -C(=O)-O-(C3-C6)cycloalkyl, -C(=O) -NH2, -C(=O)-NH(C1-C6)alkyl and -C(=O)-N[(C1-C6)alkyl]2, wherein the -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C6)cycloalkyl and -(4-10 membered)heterocyclyl are optionally substituted with one or more groups selected from hydrogen, halogen, -OH, -O-(C1-C4)alkyl, -NH2, -NH(C1-C4)alkyl and -N[(C1-C4)alkyl]2;

[0110] m is 1, 2, 3, 4, 5, 6, 7, 8 or 9;

[0111] R 8a 、R 8b 、R 9a and R 9b each independently selected from hydrogen, halogen, cyano, -(C1-C6)alkyl, -(C1-C6)haloalkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -OR, -N(R)R, -[(C1-C8)alkylene]R, -[(C1-C8)alkylene]OR, -[(C1-C8)alkylene]N(R)R, -C(=O)R, -C(=O )N(R)R, -C(=O)[(C1-C8)alkylene]N(R)R, -C(=O)OR, -C(=S)N(R)R, -SR, -S(=O)R, -S( =O)2R, -S(=O)2N(R)R, -N(R)C(=O)R, -N(R)C(=O)N(R)R, -P(=O)(OR)(OR), -(C6-C 10 )aryl, -(5-12 membered)heteroaryl, -(C3-C6)cycloalkyl and -(4-10 membered)heterocyclyl,

[0112] R is independently selected from hydrogen, -OH, -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C1-C6)haloalkyl, -O-(C1-C6)alkyl, -O-(C1-C6)haloalkyl, -S-(C1-C6)alkyl, -(C3-C6)cycloalkyl, -(4-10 membered)heterocyclyl, -O-(C3-C6)cycloalkyl, -O-(4-10 membered)heterocyclyl, -C(=O) -H, -C(=O)-(C1-C6)alkyl, -C(=O)-(C3-C6)cycloalkyl, -C(=O)-O-(C1-C6)alkyl, -C(=O)-O-(C3-C6)cycloalkyl, -C(=O)-NH2, -C(=O)-NH(C1-C6)alkyl, -C(=O)-N[(C1-C6)alkyl]2, -[(C1-C6)alkylene]-(4-10 membered)heterocyclyl, -(C6-C 10 )aryl, -[(C1-C6)alkylene]-(C6-C 10 )aryl and -(5-12 membered)heteroaryl, the -(C1-C6)alkylene-, -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C6)cycloalkyl, -(4-10 membered)heterocyclyl, -(C6-C 10 )aryl, -(5-12 membered)heteroaryl are optionally substituted by one or more groups selected from hydrogen, halogen, -OH, -O-(C1-C4)alkyl, -NH2, -NH(C1-C4)alkyl, N[(C1-C4)alkyl]2,

[0113] Or, R 8a and R 8b , and R 9a and R 9b independently combine to form oxo, -(C2-C6)alkenyl, -(C3-C6)cycloalkyl or -(4-10 membered)heterocyclyl,

[0114] Or, R 8a and R 9a , R 8b and R 9b The carbon atoms to which it is attached together form a (C3-C6)cycloalkyl, a (4-10-membered)heterocyclyl or a (5-10-membered)heteroaryl, wherein the aforementioned groups are optionally substituted by one or more selected from hydrogen, halogen, -OH, -O-(C1-C4)alkyl, -NH2, -NH(C1-C4)alkyl, -N[(C1-C4)alkyl]2, -(C3-C6)cycloalkyl, -(4-8-membered)heterocyclyl, -(5-6-membered)heteroaryl and -(C6-C 10 ) aryl radical substitution;

[0115] R 10is selected from hydrogen, cyano, -OH and -NH2, or R 10 and R 9b The atoms to which it is attached form a (5-6 membered) heterocyclic group, which is optionally substituted by one or more groups selected from hydrogen, halogen, -OH, -(C1-C4)alkyl, -(C3-C6)cycloalkyl, -O-(C1-C4)alkyl, -NH2, -NH(C1-C4)alkyl and -N[(C1-C4)alkyl]2.

[0116] In certain embodiments, the -N(R c )R c NHR c .

[0117] In certain embodiments, the -N(R)R is -NHR.

[0118] In certain embodiments, the -[(C1-C8)alkylene]N(R)R is -[(C1-C8)alkylene]NHR.

[0119] In certain embodiments, the -C(=O)N(R)R is -C(=O)NHR.

[0120] In certain embodiments, the -C(=O)[(C1-C8)alkylene]N(R)R is -C(=O)[(C1-C8)alkylene]NHR.

[0121] In certain embodiments, the -C(=S)N(R)R is -C(=S)NHR.

[0122] In certain embodiments, the -S(=O)2N(R)R is -S(=O)2NHR.

[0123] In certain embodiments, the -N(R)C(=O)R is -NHC(=O)R.

[0124] In certain embodiments, the -N(R)C(=O)N(R)R is -NHC(=O)N(R)R, -N(R)C(=O)NHR-, or NHC(=O)NHR.

[0125] In certain embodiments, the -P(=O)(OR)(OR) is -P(=O)(OH)(OR).

[0126] In certain embodiments, the R 1 is selected from hydrogen, halogen, cyano, -OH, -(C1-C4)alkyl and -O-(C1-C4)alkyl.

[0127] In certain embodiments, the R 1is selected from the group consisting of hydrogen, fluorine, chlorine, cyano, -OH, methyl, ethyl, propyl, -O-methyl, -O-ethyl and -O-propyl.

[0128] In certain embodiments, the R 1 is selected from hydrogen and -O-methyl.

[0129] In certain embodiments, the R 1 is -O-methyl, X 1 Selected from N and C(OCH3).

[0130] In certain embodiments, the X 1 Selected from C(R 1 ), R1 is as defined in any embodiment of the present invention.

[0131] In certain embodiments, the X 1 is C(OCH3).

[0132] In certain embodiments, the X 1 is N.

[0133] In certain embodiments, the R 2 is selected from hydrogen, halogen, cyano, -OH, -(C1-C4)alkyl and -O-(C1-C4)alkyl.

[0134] In certain embodiments, the R 2 is selected from the group consisting of hydrogen, fluorine, chlorine, cyano, -OH, methyl, ethyl, propyl, -O-methyl, -O-ethyl and -O-propyl.

[0135] In certain embodiments, the R 2 is hydrogen, X 2 Selected from N and CH.

[0136] In certain embodiments, the X 2 Selected from C(R 2 ).

[0137] In certain embodiments, the X 2 Selected from CH.

[0138] In certain embodiments, the R 31is selected from the group consisting of oxo, hydrogen, halogen, cyano, nitro, -OH, -SH, -NH2, -(C1-C4)alkyl, -(C1-C4)alkylene-OH, -(C1-C4)alkylene-N[(C1-C4)alkyl]2, -(C2-C4)alkenyl, -(C2-C4)alkynyl, -(C1-C4)haloalkyl, -O-(C1-C4)alkyl, -O-(C1-C4)haloalkyl, -S-(C1-C4)alkyl, -NH(C1-C4)alkyl, -N[(C1-C4)alkyl]2 -C(=O)-(C1-C4)alkyl]2, -(C3-C6)cycloalkyl, -(4-8 membered)heterocyclyl, -O-(C3-C6)cycloalkyl, -O-(4-8 membered)heterocyclyl, -C(=O)-(C1-C4)alkyl, -C(=O)-(C3-C6)cycloalkyl, -C(=O)-O-(C1-C4)alkyl, -C(=O)-O-(C3-C6)cycloalkyl, -C(=O)-NH2, -C(=O)-NH(C1-C4)alkyl and -C(=O)-N[(C1-C4)alkyl]2.

[0139] In certain embodiments, the R 31Selected from oxo, hydrogen, halogen, cyano, nitro, -OH, -SH, -NH2, methyl, ethyl, propyl, -methylene-OH, -ethylene-OH, -propylene-OH, -methylene-N(methyl)2, -ethylene-N(methyl)2, -propylene-N(methyl)2, vinyl, propenyl, ethynyl, propynyl, halomethyl, haloethyl, halopropyl, -O-methyl, -O-ethyl, -O-propyl, -O-halomethyl, -O-halo Ethyl, -O-halopropyl, -S-methyl, -S-ethyl, -S-propyl, -NH-methyl, -NH-ethyl, -NH-propyl, -N(methyl)2, -N(methyl)-ethyl, -N(methyl)-propyl, -N(ethyl)2, -N(ethyl)-propyl, cyclopropyl, cyclopentyl, cyclohexyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, 1,4-dioxane, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, homopiperidinyl, homo piperazinyl, morpholinyl, -O-cyclopropyl, -O-cyclopentyl, -O-cyclohexyl, -O-tetrahydrofuranyl, -O-tetrahydropyranyl, -O-1,4-dioxanyl, -O-pyrrolidinyl, -O-piperidinyl, -O-piperazinyl, -O-morpholinyl, -C(=O)-methyl, -C(=O)-ethyl, -C(=O)-propyl, -C(=O)-cyclopropyl, -C(=O)-cyclopentyl, -C(=O)-cyclohexyl, -C(=O)-O -methyl, -C(=O)-O-ethyl, -C(=O)-O-propyl, -C(=O)-O-cyclopropyl, -C(=O)-O-cyclopentyl, -C(=O)-O-cyclohexyl, -C(=O)-NH2, -C(=O)-NH-methyl, -C(=O)-NH-ethyl, -C(=O)-NH-propyl, -C(=O)-N(methyl)2, -C(=O)-N(methyl)-ethyl and -C(=O)-N(ethyl)2.

[0140] In certain embodiments, the R 31 Selected from oxo, hydrogen, fluoro, chloro, cyano, -OH, -SH, -NH2, methyl, halomethyl, -O-methyl, -S-methyl, -NH-methyl, -CH2OH, -CH2CH2N(CH3)2, -C(=O)-NH2 and cyclopropyl.

[0141] In certain embodiments, R 31 is selected from the group consisting of oxo, hydrogen, fluoro, cyano, -NH2, -CH2OH, -CH2NH2, methyl, trifluoromethyl and -O-methyl.

[0142] In certain embodiments, the R 31 is selected from oxo, hydrogen, -NH2, -CH2OH and methyl.

[0143] In certain embodiments, the R 31Selected from hydrogen, fluorine, chlorine, cyano, -OH, -SH, -NH2, -(C1-C4)alkyl, -O-(C1-C4)alkyl, -NH-(C1-C4)alkyl, -(C1-C4)alkylene-OH, -(C1-C4)haloalkyl, -(C1-C4)alkylene-NH2, -(C1-C4)alkylene-NH(C1-C4)alkyl and -(C1-C4)alkylene-N[(C1-C4)alkyl]2.

[0144] In certain embodiments, the R 31 Selected from hydrogen, fluorine, chlorine, cyano, -OH, -SH, -NH2, -(C1-C4)alkyl, -(C1-C4)alkylene-OH, -(C1-C4)haloalkyl, -(C1-C4)alkylene-NH2, -(C1-C4)alkylene-NH(C1-C4)alkyl and -(C1-C4)alkylene-N[(C1-C4)alkyl]2.

[0145] In certain embodiments, the R 31 Selected from hydrogen, fluorine, chlorine, cyano, -OH, -SH, -NH2, -(C1-C4)alkyl, -(C1-C4)haloalkyl, -O-(C1-C4)alkyl and -(C1-C4)alkylene-OH.

[0146] In certain embodiments, the R 31 is selected from hydrogen, fluorine, chlorine, cyano, -OH, -SH, -NH2, -(C1-C4)alkyl and -(C1-C4)alkylene-OH.

[0147] In certain embodiments, the R 31 Selected from hydrogen, fluorine, chlorine, cyano, -OH, -SH, -NH2, methyl, halomethyl, -O-methyl, -CH2OH, -CH2NH2 and -CH2CH2N(CH3)2.

[0148] In certain embodiments, the R 31 Selected from hydrogen, fluorine, chlorine, cyano, -OH, -SH, -NH2, methyl, halomethyl, -CH2OH and -CH2CH2N(CH3)2.

[0149] In certain embodiments, the R 31 is selected from the group consisting of hydrogen, fluorine, chlorine, cyano, -OH, -SH and -NH2.

[0150] In certain embodiments, the R 31 Selected from hydrogen, fluorine, chlorine, cyano, -OH, -SH, -NH2, -(C1-C4)alkyl, -O-(C1-C4)alkyl, -(C1-C4)alkylene-OH and -(C1-C4)haloalkyl.

[0151] In certain embodiments, the R 31 is selected from the group consisting of hydrogen, fluorine, cyano, -NH2, methyl, trifluoromethyl, -O-methyl and -CH2OH.

[0152] In certain embodiments, the R 3 -(C3-C6)cycloalkyl, -(3-6 membered)heterocyclyl, -(C6-C 10 )aryl and -(5-12 membered)heteroaryl, the -(C3-C6)cycloalkyl, -(3-6 membered)heterocyclyl, -(C6-C 10 )aryl and -(5-12 membered)heteroaryl are optionally substituted with one or more R 31 Replacement, R 31 is as defined in any embodiment of the present invention.

[0153] In certain embodiments, the R 3 Selected from -(3-6 membered) heterocyclic group, -(C6-C 10 )aryl and -(5-12 membered)heteroaryl, the -(3-6 membered)heterocyclyl, -(C6-C 10 )aryl and -(5-12 membered)heteroaryl are optionally substituted with one or more R 31 Replacement, R 31 is as defined in any embodiment of the present invention.

[0154] In certain embodiments, the R 3 Selected from -(C6-C 10 )aryl and -(5-12 membered)heteroaryl, the -(C6-C 10 )aryl and -(5-12 membered)heteroaryl are optionally substituted with one or more R 31 Replacement, R 31 is as defined in any embodiment of the present invention.

[0155] In certain embodiments, the R 3 is selected from phenyl and -(5-10 membered)heteroaryl, wherein the phenyl and -(5-10 membered)heteroaryl are optionally substituted by one or more R 31 Replacement, R 31 is as defined in any embodiment of the present invention.

[0156] In certain embodiments, the R 3 is selected from phenyl and -(5-9 membered)heteroaryl, wherein the phenyl and -(5-9 membered)heteroaryl are optionally substituted by one or more R 31 Replacement, R 31 is as defined in any embodiment of the present invention.

[0157] In certain embodiments, the R3 -(5-6 membered)heteroaryl, wherein the -(5-6 membered)heteroaryl is optionally substituted by 1, 2, 3 or 4 R 31 Replacement, R 31 is as defined in any embodiment of the present invention.

[0158] In certain embodiments, the R 3 is selected from the group consisting of oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, isothiazolyl, imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyrazinyl, pyridazinyl, pyrimidinyl, pyridazinoimidazolyl, pyrazinoimidazolyl and pyrimidinonyl, wherein the oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, isothiazolyl, imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyrazinyl, pyridazinyl, pyrimidinyl, pyridazinoimidazolyl, pyrazinoimidazolyl and pyrimidinonyl are optionally substituted by 1, 2 or 3 R 31 Replacement, R 31 is as defined in any embodiment of the present invention.

[0159] In certain embodiments, the R 3 is selected from the group consisting of oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, isothiazolyl, imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyrazinyl, pyridazinyl and pyrimidinyl, wherein the oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, isothiazolyl, imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyrazinyl, pyridazinyl and pyrimidinyl are optionally substituted by 1, 2 or 3 R 31 Replacement, R 31 is as defined in any embodiment of the present invention.

[0160] In certain embodiments, the R 3 Selected from described Optional 1, 2 or 3 R 31 Replacement, R 31 is as defined in any embodiment of the present invention.

[0161] In certain embodiments, the R 3 Selected from described Optional 1, 2 or 3 R 31 Replacement, R 31 is as defined in any embodiment of the present invention.

[0162] In certain embodiments, the R 3Selected from described Optional 1, 2 or 3 R 31 Replacement, R 31 is as defined in any embodiment of the present invention.

[0163] In certain embodiments, the R 3 Selected from Optional 1, 2 or 3 R 31 Replacement, R 31 is as defined in any embodiment of the present invention.

[0164] In certain embodiments, the R 3 Selected from

[0165] In certain embodiments, the R 3 Selected from

[0166] In certain embodiments, the R 3 Selected from

[0167] In certain embodiments, the R 3 Selected from

[0168] In certain embodiments, the R 3 is selected from oxazolyl, pyrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyridazinoimidazolyl, pyrazinoimidazolyl, wherein the oxazolyl, pyrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyridazinoimidazolyl, pyrazinoimidazolyl is optionally substituted by 1, 2 or 3 R 31 Replacement, R 31 is as defined in any embodiment of the present invention.

[0169] In certain embodiments, the R 3 Selected from

[0170] In certain embodiments, the R 3 Selected from

[0171] In certain embodiments, the R 3 is selected from oxazolyl, pyrazolyl, pyrimidinyl and pyrazinyl, wherein the oxazolyl, pyrazolyl, pyrimidinyl and pyrazinyl are optionally substituted by 1, 2 or 3 R 31 (as defined in any embodiment of the invention) substituted, for example, by fluoro, cyano, amino, methyl, trifluoromethyl, -methylene-OH and -O-methyl.

[0172] In certain embodiments, the R 3 is selected from oxazolyl, pyrazolyl and pyrimidinyl, wherein the oxazolyl, pyrazolyl and pyrimidinyl are optionally substituted by 1, 2 or 3 R 31 Substitution, such as methyl substitution.

[0173] In certain embodiments, the R 3 Selected from described Optional 1, 2 or 3 R 31 (as defined in any embodiment of the invention) substituted, for example, by fluoro, cyano, amino, methyl, trifluoromethyl, -methylene-OH and -O-methyl.

[0174] In certain embodiments, the R 3 Selected from described Optional 1, 2 or 3 R 31 Substitution, such as methyl substitution.

[0175] In certain embodiments, the R 3 Selected from

[0176] In certain embodiments, the R 3 Selected from

[0177] In certain embodiments, the R 3 is selected from oxazolyl, said oxazolyl being optionally substituted with 1, 2 or 3 R 31 substituted, for example, optionally substituted with 1, 2 or 3 methyl groups.

[0178] In certain embodiments, the R 3 Selected from

[0179] In certain embodiments, the R 3 -(C3-C6)cycloalkyl and -(4-6 membered)heterocyclyl, wherein the -(C3-C6)cycloalkyl and -(4-6 membered)heterocyclyl are optionally substituted by one or more R 31 Replacement, R31 is as defined in any embodiment of the present invention.

[0180] In certain embodiments, the R 3 is selected from cyclopropyl, oxetanyl, azetidinyl, tetrahydrofuranyl, pyrrolidinyl, tetrahydropyranyl, piperidinyl, piperazinyl and morpholinyl, the foregoing groups being optionally substituted with one or more R 31 Replacement, R 31 is as defined in any embodiment of the present invention.

[0181] In certain embodiments, the R 3 Selected from

[0182] In certain embodiments, the R 3 -(3-6 membered) heterocyclyl, wherein the -(3-6 membered) heterocyclyl is optionally substituted by one or more R 31 Replacement, R 31 is as defined in any embodiment of the present invention.

[0183] In certain embodiments, the R 3 is selected from oxetanyl, azetidinyl, tetrahydrofuranyl, pyrrolidinyl, tetrahydropyranyl, piperidinyl, piperazinyl and morpholinyl, the aforementioned groups being optionally substituted by one or more R 31 Replacement, R 31 is as defined in any embodiment of the present invention.

[0184] In certain embodiments, the R 3 for

[0185] In certain embodiments, the R 3 for

[0186] In certain embodiments, the R 4 is selected from hydrogen, halogen, cyano, -OH, -NH2, -(C1-C4)alkyl, -(C1-C4)haloalkyl, -O-(C1-C4)alkyl, -O-(C1-C4)haloalkyl, -(C3-C6)cycloalkyl, -O-(C3-C6)cycloalkyl, -(4-8 membered)heterocyclyl, -O-(4-8 membered)heterocyclyl, -(C6-C 10 )aryl, -O-(C6-C 10 )aryl, -(5-10 membered)heteroaryl and -O-(5-10 membered)heteroaryl.

[0187] In certain embodiments, the R 4selected from hydrogen, halogen, cyano, -OH, -NH2, methyl, ethyl, propyl, halomethyl, haloethyl, halopropyl, -O-methyl, -O-ethyl, -O-propyl, -O-halomethyl, -O-haloethyl, -O-halopropyl, cyclopropyl, cyclopentyl, cyclohexyl, -O-cyclopropyl, -O-cyclopentyl, -O-cyclohexyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, 1,4-dioxane, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, homopiperidinyl, homopiperazinyl, morpholinyl, -O-tetrahydrofuranyl, pyrimidinyl, indolyl, quinolinyl, -O-oxazolyl, -O-thiazolyl, -O-pyrazolyl, -O-imidazolyl, -O-triazolyl, -O-tetrazolyl, -O-pyridinyl, -O-pyrimidinyl, -O-indolyl, and -O-quinolinyl.

[0188] In certain embodiments, the R 4 is selected from hydrogen, fluorine, chlorine, cyano, -OH, -NH2, methyl, halomethyl, -O-methyl, -NH-methyl and cyclopropyl.

[0189] In certain embodiments, the R 4 is selected from hydrogen, fluorine, chlorine, cyano, -OH and -NH2.

[0190] In certain embodiments, the R 4 For hydrogen.

[0191] In certain embodiments, the R c selected from hydrogen, -(C1-C4)alkyl, -(C1-C4)haloalkyl, -O-(C1-C4)alkyl, -O-(C1-C4)haloalkyl, -(C3-C6)cycloalkyl, -O-(C3-C6)cycloalkyl, -(4-8 membered)heterocyclyl, -O-(4-8 membered)heterocyclyl, -(C6-C 10 )aryl, -O-(C6-C 10 )aryl, -(5-10 membered)heteroaryl and -O-(5-10 membered)heteroaryl.

[0192] In certain embodiments, the R cselected from hydrogen, methyl, ethyl, propyl, halomethyl, haloethyl, halopropyl, -O-methyl, -O-ethyl, -O-propyl, -O-halomethyl, -O-haloethyl, -O-halopropyl, cyclopropyl, cyclopentyl, cyclohexyl, -O-cyclopropyl, -O-cyclopentyl, -O-cyclohexyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, 1,4-dioxane, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, homopiperidinyl, homopiperazinyl, morpholinyl, -O-tetrahydrofuranyl, -O-tetrahydro pyranyl, -O-1,4-dioxanyl, -O-pyrrolidinyl, -O-piperidinyl, -O-piperazinyl, -O-morpholinyl, phenyl, naphthyl, -O-phenyl, -O-naphthyl, oxazolyl, thiazolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, indolyl, quinolinyl, -O-oxazolyl, -O-thiazolyl, -O-pyrazolyl, -O-imidazolyl, -O-triazolyl, -O-tetrazolyl, -O-pyridinyl, -O-pyrimidinyl, -O-indolyl, and -O-quinolinyl.

[0193] In certain embodiments, the R c is selected from hydrogen, methyl, ethyl, halomethyl, -O-methyl, -NH-methyl and cyclopropyl.

[0194] R a and R b are independently selected from hydrogen, halogen, cyano, -OR c 、-SR c 、-N(R c )R c , -(C1-C4)alkyl and -(C1-C4)haloalkyl, R c is as defined in any embodiment of the present invention.

[0195] In certain embodiments, the R a and R b are independently selected from hydrogen, halogen, cyano, -OR c 、-SR c 、-N(R c )R c , methyl, ethyl, propyl, halomethyl, haloethyl and halopropyl, R c is as defined in any embodiment of the present invention.

[0196] In certain embodiments, the R a and R b Each is independently selected from hydrogen, fluorine, chlorine, cyano, -OH, -O-methyl, -SH, -S-methyl, -NH2, -N(methyl)2, -N(methyl)-ethyl, -N(ethyl)2, methyl, ethyl, propyl, halomethyl, haloethyl and halopropyl.

[0197] X is selected from O, S, NH, N[(C1-C4)alkyl], N[C(=O)-R c ]、C(R a )(R b )、C(=O)、C[=C(R a )R b ], S(=O) and S(=O)2, R a 、R b and R c is as defined in any embodiment of the present invention.

[0198] In certain embodiments, X is selected from O, S, NH, N(CH3), N(CH2CH3), N[C(=O)-CH3], CH2, C(CH3)2, C(CH3)(CH2CH3), C(CH2CH3)2, C(=O), C(=CH2), C(=CF2), C(=CHCF3), S(=O) and S(=O)2.

[0199] In certain embodiments, said X is selected from O, S, and NH.

[0200] In certain embodiments, said X is selected from O and S.

[0201] In certain embodiments, X is O.

[0202] In certain embodiments, the ring B is selected from -(C6-C 10 )aryl and 5-10 membered heteroaryl.

[0203] In certain embodiments, the ring B is selected from phenyl, naphthyl, oxazolyl, thiazolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, benzofuranyl, benzothiophenyl, indolyl, quinolinyl, and isoquinolinyl.

[0204] In certain embodiments, Ring B is phenyl.

[0205] In certain embodiments, the structural unit for

[0206] In certain embodiments, R 5 and R 6each independently selected from hydrogen, halogen, cyano, nitro, -OH, -SH, -NH2, -(C1-C4)alkyl, -(C2-C4)alkenyl, -(C2-C4)alkynyl, -(C1-C4)haloalkyl, -O-(C1-C4)alkyl, -O-(C1-C4)haloalkyl, -S-(C1-C4)alkyl, -NH(C1-C4)alkyl, -N[(C1-C4)alkyl]2, -(C3-C6)cycloalkyl, -(4-8 membered)heterocyclyl, -O-(C3-C6)cycloalkyl, -O-(4-8 membered)heterocyclyl, -C(=O)-(C1-C4)alkyl, -C(=O)-(C3-C6)cycloalkyl, -C(=O)-O-(C1-C4)alkyl, -C(=O)-O- -(C3-C6)cycloalkyl, -C(═O)-NH2, -C(═O)-NH(C1-C4)alkyl, -C(═O)-N[(C1-C4)alkyl]2, -C(═O)-H and -C(═N-OH)-H, said -(C1-C4)alkyl, -(C2-C4)alkenyl, -(C2-C4)alkynyl, -(C3-C6)cycloalkyl and -(4-8 membered)heterocyclyl are optionally substituted by 1, 2, 3, 4 or 5 groups selected from hydrogen, halogen, -OH, -O-methyl, -O-ethyl, -O-propyl, -NH2, -NH-methyl, -NH-ethyl, -NH-propyl, -N(methyl), -N(methyl)-ethyl, -N(methyl)-propyl, -N(ethyl)2 and -N(ethyl)-propyl.

[0207] In certain embodiments, the R 5 and R 6Each is independently selected from hydrogen, fluorine, chlorine, bromine, cyano, nitro, -OH, -SH, -NH2, methyl, ethyl, propyl, vinyl, propenyl, ethynyl, propynyl, halomethyl, haloethyl, halopropyl, -O-methyl, -O-ethyl, -O-propyl, -O-halomethyl, -O-haloethyl, -O-halopropyl, -S-methyl, -S-ethyl, -S-propyl, -NH-methyl, -NH-ethyl, -NH- Propyl, -N(methyl)2, -N(methyl)-ethyl, -N(methyl)-propyl, -N(ethyl)2, -N(ethyl)-propyl, cyclopropyl, cyclopentyl, cyclohexyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, 1,4-dioxane, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, homopiperidinyl, homopiperazinyl, morpholinyl, -O-cyclopropyl, -O-cyclopentyl, -O-cyclohexyl, -O-tetrahydrofuranyl, -O-tetrahydropyranyl, -O-1,4-dioxanyl, -O-pyrrolidinyl, -O-piperidinyl, -O-piperazinyl, -O-morpholinyl, -C(=O)-methyl, -C(=O)-ethyl, -C(=O)-propyl, -C(=O)-cyclopropyl, -C(=O)-cyclopentyl, -C(=O)-cyclohexyl, -C(=O)-O-methyl, -C(=O)-O-ethyl, -C(=O)-O-propyl, -C(=O)- (=O)-O-cyclopropyl, -C(=O)-O-cyclopentyl, -C(=O)-O-cyclohexyl, -C(=O)-NH2, -C(=O)-NH-methyl, -C(=O)-NH-ethyl, -C(=O)-NH-propyl, -C(=O)-N(methyl)2, -C(=O)-N(methyl)-ethyl, -C(=O)-N(ethyl)2, -C(=O)-H and -C(=N-OH)-H.

[0208] In certain embodiments, the R 5 and R 6 Each is independently selected from hydrogen, fluorine, chlorine, bromine, cyano, -OH, -NH2, methyl, ethyl, -O-methyl, -NH-methyl, -N(methyl)2, -N(methyl)-ethyl, cyclopropyl, azetidinyl, -O-cyclopropyl, -C(=O)-methyl, -C(=O)-cyclopropyl, -C(=O)-H and -C(=N-OH)-H.

[0209] In certain embodiments, the R 5 and R 6 Each is independently selected from hydrogen, fluorine, chlorine, bromine, cyano, -OH, -NH2, -(C1-C4)alkyl, -(C1-C4)alkyl-OH, -(C1-C4)alkyl-NH2, -(C1-C4)haloalkyl, -O-(C1-C4)alkyl, -O-(C1-C4)haloalkyl and -(C3-C6)cycloalkyl.

[0210] In certain embodiments, the R 5 and R 6 Each is independently selected from hydrogen, fluorine, chlorine, bromine, cyano, -OH, -NH2, -(C1-C4)alkyl, -(C1-C4)haloalkyl, -O-(C1-C4)alkyl, -O-(C1-C4)haloalkyl and -(C3-C6)cycloalkyl.

[0211] In certain embodiments, the R 5 is selected from the group consisting of hydrogen, fluorine, chlorine, bromine, cyano, -OH, -NH2 and -CH2NH2.

[0212] In certain embodiments, the R 5 is selected from the group consisting of hydrogen, fluorine, chlorine, bromine, cyano, -OH and -NH2.

[0213] In certain embodiments, the R 5 is selected from hydrogen and -NH2.

[0214] In certain embodiments, the R 5 For hydrogen.

[0215] In certain embodiments, the R 6 is selected from hydrogen, fluorine, chlorine, bromine, cyano, -OH, -NH2, -O-methyl and cyclopropyl.

[0216] In certain embodiments, the R 6 Selected from cyano, bromo, -NH2, -O-methyl and cyclopropyl.

[0217] In certain embodiments, the R 6 Selected from hydrogen, fluorine, chlorine, bromine, cyano, -OH, -NH2, -O-methyl.

[0218] In certain embodiments, the R 6 Selected from cyano, -O-methyl and cyclopropyl.

[0219] In certain embodiments, the R 6 is selected from hydrogen, cyano and -O-methyl.

[0220] In certain embodiments, the R 6 Selected from cyano and -O-methyl.

[0221] In certain embodiments, the R 5 and R 6 The atoms connected to it form Where * indicates the positions of connected atoms.

[0222] In certain embodiments, the ring C is selected from -(C6-C 10)aryl and -(5-10 membered)heteroaryl.

[0223] In certain embodiments, the ring C is selected from phenyl, naphthyl, oxazolyl, thiazolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, benzofuranyl, benzothiophenyl, indolyl, quinolinyl, and isoquinolinyl.

[0224] In certain embodiments, Ring C is phenyl.

[0225] In certain embodiments, the structural unit for

[0226] In certain embodiments, the structural unit for

[0227] In certain embodiments, the structural unit for

[0228] In certain embodiments, the R 7 each independently selected from hydrogen, halogen, cyano, nitro, -OH, -SH, -NH2, -(C1-C4)alkyl, -(C2-C4)alkenyl, -(C2-C4)alkynyl, -(C1-C4)haloalkyl, -O-(C1-C4)alkyl, -O-(C1-C4)haloalkyl, -S-(C1-C4)alkyl, -NH(C1-C4)alkyl, -N[(C1-C4)alkyl]2, -(C3-C6)cycloalkyl, -(4-8 membered)heterocyclyl, -O-(C3-C6)cycloalkyl, -O-(4-8 membered)heterocyclyl, -C(=O)-(C1-C4)alkyl, -C(=O)-(C3-C6)cycloalkyl, -C(=O)-O-(C1-C4)alkyl, -C(=O)-O -(C3-C6)cycloalkyl, -C(=O)-NH2, -C(=O)-NH(C1-C4)alkyl, -C(=O)-N[(C1-C4)alkyl]2 and -NHC(=O)-(C1-C4)alkyl, said -(C1-C4)alkyl, -(C2-C4)alkenyl, -(C2-C4)alkynyl, -(C3-C6)cycloalkyl and -(4-8 membered)heterocyclyl are optionally substituted by 1, 2, 3, 4 or 5 groups selected from hydrogen, halogen, -OH, -O-methyl, -O-ethyl, -O-propyl, -NH2, -NH-methyl, -NH-ethyl, -NH-propyl, -N(methyl), -N(methyl)-ethyl, -N(methyl)-propyl, -N(ethyl)2 and -N(ethyl)-propyl.

[0229] In certain embodiments, the R 7Each is independently selected from hydrogen, halogen, cyano, nitro, -OH, -SH, -NH2, -(C1-C4)alkyl, -(C2-C4)alkenyl, -(C2-C4)alkynyl, -(C1-C4)haloalkyl, -O-(C1-C4)alkyl, -O-(C1-C4)haloalkyl, -S-(C1-C4)alkyl, -NH(C1-C4)alkyl, -N[(C1-C4)alkyl]2, -(C3-C6)cycloalkyl, -(4-8 membered)heterocyclyl, -O-(C3-C6)cycloalkyl, -O-(4-8 membered)heterocyclyl , -C(=O)-(C1-C4)alkyl, -C(=O)-(C3-C6)cycloalkyl, -C(=O)-O-(C1-C4)alkyl, -C(=O)-O-(C3-C6)cycloalkyl, -C(=O)-NH2, -C(=O)-NH(C1-C4)alkyl and -C(=O)-N[(C1-C4)alkyl]2, wherein the -(C1-C4)alkyl, -(C2-C4)alkenyl, -(C2-C4)alkynyl, -(C3-C6)cycloalkyl and -(4-8 membered)heterocyclyl are optionally substituted by 1, 2, 3, 4 or 5 The present invention is substituted with a group selected from the group consisting of hydrogen, halogen, -OH, -O-methyl, -O-ethyl, -O-propyl, -NH2, -NH-methyl, -NH-ethyl, -NH-propyl, -N(methyl)2, -N(methyl)-ethyl, -N(methyl)-propyl, -N(ethyl)2 and -N(ethyl)-propyl.

[0230] In certain embodiments, the R 7Each is independently selected from hydrogen, halogen, cyano, nitro, -OH, -SH, -NH2, methyl, ethyl, propyl, -methylene-OH, -ethylene-OH, -propylene-OH, -methylene-NH2, -ethylene-NH2, -propylene-NH2, vinyl, propenyl, ethynyl, propynyl, halomethyl, haloethyl, halopropyl, -O-methyl, -O-ethyl, -O-propyl, -O-halomethyl, -O-haloethyl, -O-halopropyl, -S-methyl, -S -ethyl, -S-propyl, -NH-methyl, -NH-ethyl, -NH-propyl, -N(methyl)2, -N(methyl)-ethyl, -N(methyl)-propyl, -N(ethyl)2, -N(ethyl)-propyl, cyclopropyl, cyclopentyl, cyclohexyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, 1,4-dioxane, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, homopiperidinyl, homopiperazinyl, morpholinyl, -O-cyclopropyl, -O-cyclopentyl, -O-cyclohexyl, -O -tetrahydrofuranyl, -O-tetrahydropyranyl, -O-1,4-dioxanyl, -O-pyrrolidinyl, -O-piperidinyl, -O-piperazinyl, -O-morpholinyl, -C(=O)-methyl, -C(=O)-ethyl, -C(=O)-propyl, -C(=O)-cyclopropyl, -C(=O)-cyclopentyl, -C(=O)-cyclohexyl, -C(=O)-O-methyl, -C(=O)-O-ethyl, -C(=O)-O-propyl, -C(=O)-O-cyclopropyl, -C(=O)-O-cyclopentyl, -C(=O)-O-cyclohexyl, -C(=O)-O-methyl, -C(=O)-O-ethyl, -C(=O)-O-propyl, -C(=O)-O-cyclopropyl, -C(=O)-O- (=O)-O-cyclopentyl, -C(=O)-O-cyclohexyl, -C(=O)-NH2, -C(=O)-NH-methyl, -C(=O)-NH-ethyl, -C(=O)-NH-propyl, -C(=O)-N(methyl)2, -C(=O)-N(methyl)-ethyl, -C(=O)-N(ethyl)2, -C(=O)-H, -C(=N-OH)-H, -NHC(=O)-methylene-NH2 and -NHC(=O)-ethylidene-NH2.

[0231] In certain embodiments, the R 7Each is independently selected from hydrogen, halogen, cyano, nitro, -OH, -SH, -NH2, methyl, ethyl, propyl, -methylene-OH, -ethylene-OH, -propylene-OH, -methylene-NH2, -ethylene-NH2, -propylene-NH2, vinyl, propenyl, ethynyl, propynyl, halomethyl, haloethyl, halopropyl, -O-methyl, -O-ethyl, -O-propyl, -O-halomethyl, -O-haloethyl, -O-halopropyl, -S-methyl, -S-ethyl, -S-propyl, -NH-methyl, -NH-ethyl, -NH-propyl, -N(methyl)2, -N(methyl)-ethyl, -N(methyl)-propyl, -N(ethyl)2, -N(ethyl)-propyl, cyclopropyl, cyclopentyl, cyclohexyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, 1,4-dioxane, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, homopiperidinyl, homopiperazinyl, morpholinyl, -O-cyclopropyl , -O-cyclopentyl, -O-cyclohexyl, -O-tetrahydrofuranyl, -O-tetrahydropyranyl, -O-1,4-dioxanyl, -O-pyrrolidinyl, -O-piperidinyl, -O-piperazinyl, -O-morpholinyl, -C(=O)-methyl, -C(=O)-ethyl, -C(=O)-propyl, -C(=O)-cyclopropyl, -C(=O)-cyclopentyl, -C(=O)-cyclohexyl, -C(=O)-O-methyl, -C(=O)-O-ethyl, -C (=O)-O-propyl, -C(=O)-O-cyclopropyl, -C(=O)-O-cyclopentyl, -C(=O)-O-cyclohexyl, -C(=O)-NH2, -C(=O)-NH-methyl, -C(=O)-NH-ethyl, -C(=O)-NH-propyl, -C(=O)-N(methyl)2, -C(=O)-N(methyl)-ethyl, -C(=O)-N(ethyl)2, -C(=O)-H and -C(=N-OH)-H.

[0232] In certain embodiments, the R 7 Each is independently selected from hydrogen, fluorine, chlorine, bromine, cyano, -OH, -NH2, -(C1-C4)alkylene-OH, -(C1-C4)alkylene-NH(C1-C4)alkyl, -(C1-C4)alkylene-N[(C1-C4)alkyl]2, -(C1-C4)alkylene-NH2 and -NHC(=O)-(C1-C4)alkylene-NH2.

[0233] In certain embodiments, the R 7 Each is independently selected from hydrogen, fluorine, chlorine, bromine, cyano, -OH, -NH2, -(C1-C4)alkylene-OH, -(C1-C4)alkylene-NH(C1-C4)alkyl, -(C1-C4)alkylene-N[(C1-C4)alkyl]2 and -(C1-C4)alkylene-NH2.

[0234] In certain embodiments, the R 7 Each is independently selected from hydrogen, fluorine, chlorine, bromine, -OH, -NH2, -methylene-OH, -ethylene-OH, -propylene-OH, -methylene-NH2, -ethylene-NH2, -propylene-NH2, -NHC(=O)-methylene-NH2 and -NHC(=O)-ethylene-NH2.

[0235] In certain embodiments, the R 7 Each is independently selected from hydrogen, fluorine, chlorine, bromine, cyano, -OH, -NH2, -methylene-OH, -ethylene-OH, -propylene-OH, -methylene-NH2, -ethylene-NH2 and -propylene-NH2.

[0236] In certain embodiments, the R 7 Each is independently selected from hydrogen, fluorine, -OH, -NH2, -NHC(=O)CH2NH2, -CH2OH and -CH2NH2.

[0237] In certain embodiments, the R 7 Each is independently selected from hydrogen, fluorine, -OH, -NH2, -CH2OH and -CH2NH2.

[0238] In certain embodiments, the R 7 Each is independently selected from hydrogen, fluorine, chlorine, bromine, -OH, -NH2.

[0239] In certain embodiments, the R 7 Each is independently selected from hydrogen, -OH, and -NH2.

[0240] In certain embodiments, the R 7 are each independently selected from hydrogen and -NH2.

[0241] In certain embodiments, m is 1, 2, 3, 4, or 5.

[0242] In certain embodiments, m is 1, 2, or 3.

[0243] In certain embodiments, m is 1.

[0244] In certain embodiments, each of the R groups is independently selected from hydrogen, -OH, -NH2, -(C1-C4)alkyl, -(C2-C4)alkenyl, -(C2-C4)alkynyl, -(C1-C4)haloalkyl, -O-(C1-C4)alkyl, -(C1-C4)alkylene-O-(C1-C4)alkyl, -O-(C1-C4)haloalkyl, -S-(C1-C4)alkyl, -S(=O)2-(C1-C4)alkyl, -(C3-C6)cycloalkyl, -(4-8 membered)heterocyclyl, -O-(C3-C6)cycloalkyl, -O- (4-8 membered) heterocyclyl, -C(=O)-H, -C(=O)-(C1-C4) alkyl, -C(=O)-(C3-C6) cycloalkyl, -C(=O)-O-(C1-C4) alkyl, -C(=O)-O-(C3-C6) cycloalkyl, -C(=O)-NH2, -C(=O)-NH(C1-C4) alkyl, -C(=O)-N[(C1-C4) alkyl]2, -[(C1-C4) alkylene]-(C3-C6) cycloalkyl, -[(C1-C4) alkylene]-(4-8 membered) heterocyclyl, -(C6-C 10 )aryl, -[(C1-C4)alkylene]-(C6-C 10 )aryl and -(5-10 membered)heteroaryl, the -(C1-C4)alkylene-, -(C1-C4)alkyl, -(C2-C4)alkenyl, -(C2-C4)alkynyl, -(C3-C6)cycloalkyl, -(4-8 membered)heterocyclyl, -(C6-C 10 )aryl and -(5-10 membered)heteroaryl are optionally substituted with 1, 2, 3, 4, 5, 6 or 7 groups selected from hydrogen, halogen, -OH, -O-(C1-C4)alkyl, -NH2, -NH(C1-C4)alkyl, N[(C1-C4)alkyl]2 and (C1-C4)alkyl.

[0245] In certain embodiments, each of the R groups is independently selected from hydrogen, -OH, -NH2, -(C1-C4)alkyl, -(C2-C4)alkenyl, -(C2-C4)alkynyl, -(C1-C4)haloalkyl, -O-(C1-C4)alkyl, -O-(C1-C4)haloalkyl, -S-(C1-C4)alkyl, -(C3-C6)cycloalkyl, -(4-8 membered)heterocyclyl, -O-(C3-C6)cycloalkyl, -O-(4-8 membered)heterocyclyl -C(=O)-H, -C(=O)-(C1-C4)alkyl, -C(=O)-(C3-C6)cycloalkyl, -C(=O)-O-(C1-C4)alkyl, -C(=O)-O-(C3-C6)cycloalkyl, -C(=O)-NH2, -C(=O)-NH(C1-C4)alkyl, -C(=O)-N[(C1-C4)alkyl]2, -[(C1-C4)alkylene]-(4-8 membered)heterocyclyl, -(C6-C 10 )aryl, -[(C1-C4)alkylene]-(C6-C 10 )aryl and -(5-10 membered)heteroaryl, the -(C1-C4)alkylene-, -(C1-C4)alkyl, -(C2-C4)alkenyl, -(C2-C4)alkynyl, -(C3-C6)cycloalkyl, -(4-8 membered)heterocyclyl, -(C6-C 10 )aryl and -(5-10 membered)heteroaryl are optionally substituted with 1, 2, 3, 4, 5, 6 or 7 groups selected from hydrogen, halogen, -OH, -O-(C1-C4)alkyl, -NH2, -NH(C1-C4)alkyl, N[(C1-C4)alkyl]2.

[0246] In certain embodiments, each of the R groups is independently selected from hydrogen, -OH, -NH2, -(C1-C4)alkyl, -(C1-C4)haloalkyl, -O-(C1-C4)alkyl, -(C1-C4)alkylene-O-(C1-C6)alkyl, -O-(C1-C4)haloalkyl, -S(=O)2-(C1-C4)alkyl, -(C3-C6)cycloalkyl, -(4-8 membered)heterocyclyl, -C(=O)-H, -C(=O)-(C1-C4)alkyl, -C(=O)-(C3-C6)cycloalkyl, -[(C1-C4)alkylene]-( -(C-C)cycloalkyl and -[(C-C)alkylene]-(4-8 membered)heterocyclyl, said -(C-C)alkylene-, -(C-C)alkyl, -(C-C)cycloalkyl and -(4-8 membered)heterocyclyl being optionally substituted by 1, 2, 3, 4 or 5 groups selected from hydrogen, halogen, -OH, -O-methyl, -O-ethyl, -O-propyl, -NH2, -NH-methyl, -NH-ethyl, -NH-propyl, -N(methyl), -N(methyl)-ethyl, -N(methyl)-propyl, -N(ethyl), -N(ethyl)-propyl, methyl and ethyl.

[0247] In certain embodiments, each of the R groups is independently selected from hydrogen, -OH, -NH2, -(C1-C4)alkyl, -(C1-C4)haloalkyl, -O-(C1-C4)alkyl, -O-(C1-C4)haloalkyl, -(C3-C6)cycloalkyl, -(4-8 membered)heterocyclyl, -C(=O)-H, -C(=O)-(C1-C4)alkyl, -C(=O)-(C3-C6)cycloalkyl, and -[(C1-C4)alkylene]-(4-8 membered)heterocyclyl. Cyclic group, said -(C1-C4)alkylene-, -(C1-C4)alkyl, -(C3-C6)cycloalkyl and -(4-8 membered)heterocyclyl are optionally substituted by 1, 2, 3, 4 or 5 groups selected from hydrogen, halogen, -OH, -O-methyl, -O-ethyl, -O-propyl, -NH2, -NH-methyl, -NH-ethyl, -NH-propyl, -N(methyl)2, -N(methyl)-ethyl, -N(methyl)-propyl, -N(ethyl)2 and -N(ethyl)-propyl.

[0248] In certain embodiments, each of the R groups is independently selected from hydrogen, -OH, -NH2, methyl, ethyl, propyl, halomethyl, haloethyl, halopropyl, -methylene-O-methyl, -methylene-O-ethyl, -ethylidene-O-methyl, -ethylidene-O-ethyl, -O-methyl, -O-ethyl, -O-propyl, -O-halomethyl, -O-haloethyl, -O-halopropyl, -C(=O)-H, -C(=O)-methyl, -C(=O)-ethyl, -C(=O)-propyl, -S(=O)2-methyl, -S(=O)2-ethyl, -S(=O)2-propyl , cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, -methylene-cyclobutyl, -methylene-oxetanyl and -methylene-azetidinyl, the methyl, ethyl, propyl, , cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl and morpholinyl are optionally substituted with 1, 2 or 3 groups selected from -OH, -OCH3, -NH2, NHCH3, N(CH3)2 and -CH3.

[0249] In certain embodiments, each of the R groups is independently selected from hydrogen, -OH, -NH2, methyl, ethyl, propyl, halomethyl, haloethyl, halopropyl, -O-methyl, -O-ethyl, -O-propyl, -O-halomethyl, -O-haloethyl, -O-halopropyl, -C(=O)-H, -C(=O)-methyl, -C(=O)-ethyl, -C(=O)-propyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl and morpholinyl, and the methyl, ethyl, propyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl and morpholinyl are optionally substituted with 1, 2 or 3 groups selected from -OH and -NH2.

[0250] In certain embodiments, each of the R groups is independently selected from hydrogen, -OH, -NH2, -CH3, -CH2CH3, -CH2OH, -CH2CH2OH, -CH2OCH3, -CH2NH2, -CH2CH2NH2, -CH2CH2NHCH3, -CH2N(CH3)2, -CH(N(CH3)2)CH2OH, -CH2OCH2CH2OH, -OCH3, -C(=O)-H, -C(=O)CH3, -C(=O)CH2OH, -S(=O)2CH3, cyclobutyl-OH, oxetanyl, azetidinyl, azetidinyl-OH, pyrrolidinyl, piperazinyl, azetidinyl-CH3, piperazinyl-CH3, and -CH2-azetidinyl.

[0251] In certain embodiments, each of the R groups is independently selected from hydrogen, -OH, -NH2, -CH3, -CH2OH, -CH2CH2OH, -CH2NH2, -CH2CH2NH2, -OCH3, -C(=O)-H, -C(=O)CH2OH, oxetanyl, and azetidinyl-OH.

[0252] In certain embodiments, each of the R groups is independently selected from hydrogen, -OH, -(C1-C4)alkyl, -(C2-C4)alkenyl, -(C2-C4)alkynyl, -(C1-C4)haloalkyl, -O-(C1-C4)alkyl, -O-(C1-C4)haloalkyl, -S-(C1-C4)alkyl, -(C3-C6)cycloalkyl, -(4-8 membered)heterocyclyl, -O-(C3-C6)cycloalkyl, -O-(4-8 membered)heterocyclyl, - C(=O)-H, -C(=O)-(C1-C4)alkyl, -C(=O)-(C3-C6)cycloalkyl, -C(=O)-O-(C1-C4)alkyl, -C(=O)-O-(C3-C6)cycloalkyl, -C(=O)-NH2, -C(=O)-NH(C1-C4)alkyl, -C(=O)-N[(C1-C4)alkyl]2, -[(C1-C4)alkylene]-(4-8 membered)heterocyclyl, -(C6-C 10 )aryl, -[(C1-C4)alkylene]-(C6-C 10 )aryl and -(5-10 membered)heteroaryl, the -(C1-C4)alkylene-, -(C1-C4)alkyl, -(C2-C4)alkenyl, -(C2-C4)alkynyl, -(C3-C6)cycloalkyl, -(4-8 membered)heterocyclyl, -(C6-C 10 )aryl and -(5-10 membered)heteroaryl are optionally substituted with 1, 2, 3, 4, 5, 6 or 7 groups selected from hydrogen, halogen, -OH, -O-(C1-C4)alkyl, -NH2, -NH(C1-C4)alkyl, N[(C1-C4)alkyl]2.

[0253] In certain embodiments, each of the R groups is independently selected from hydrogen, -OH, -(C1-C4)alkyl, -(C1-C4)haloalkyl, -O-(C1-C4)alkyl, -O-(C1-C4)haloalkyl, -(C3-C6)cycloalkyl, -(4-8 membered)heterocyclyl, -C(=O)-H, -C(=O)-(C1-C4)alkyl, -C(=O)-(C3-C6)cycloalkyl, and -[(C1-C4)alkylene]-(4-8 membered)heterocyclyl , the -(C1-C4)alkylene-, -(C1-C4)alkyl, -(C3-C6)cycloalkyl and -(4-8 membered)heterocyclyl are optionally substituted by 1, 2, 3, 4 or 5 groups selected from hydrogen, halogen, -OH, -O-methyl, -O-ethyl, -O-propyl, -NH2, -NH-methyl, -NH-ethyl, -NH-propyl, -N(methyl)2, -N(methyl)-ethyl, -N(methyl)-propyl, -N(ethyl)2 and -N(ethyl)-propyl.

[0254] In certain embodiments, each of the R groups is independently selected from hydrogen, -OH, methyl, ethyl, propyl, halomethyl, haloethyl, halopropyl, -O-methyl, -O-ethyl, -O-propyl, -O-halomethyl, -O-haloethyl, -O-halopropyl, -C(=O)-H, -C(=O)-methyl, -C(=O)-ethyl, -C(=O)-propyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, and morpholinyl, and the methyl, ethyl, propyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, and morpholinyl groups are optionally substituted with 1, 2, or 3 groups selected from -OH and -NH2.

[0255] In certain embodiments, each of the R groups is independently selected from hydrogen, -OH, -CH3, -CH2OH, -CH2CH2OH, -CH2CH2NH2, -OCH3, -C(=O)-H, -C(=O)CH2OH, oxetanyl, azetidinyl, and azetidinyl-OH.

[0256] In certain embodiments, each of the R groups is independently selected from hydrogen, -OH, -CH3, -CH2OH, -CH2CH2OH, -CH2CH2NH2, -OCH3, -C(=O)-H, -C(=O)CH2OH, oxetanyl, and azetidinyl-OH.

[0257] In certain embodiments, each of the R groups is independently selected from hydrogen, -OH, -NH2, -(C1-C4)alkyl, -O-(C1-C4)alkyl, -C(=O)-(C1-C4)alkyl, -S(=O)2(C1-C4)alkyl, -(C3-C6)cycloalkyl, -(4-8 membered)heterocyclyl, -methylene-(C3-C6)cycloalkyl, and -methylene-(4-8 membered)heterocyclyl, and the -(C1-C4)alkyl, -(C3-C6)cycloalkyl, and -(4-8 membered)heterocyclyl are optionally substituted with 1, 2, 3, 4, or 5 groups selected from hydrogen, halogen, -OH, -NH2, -NH(C1-C4)alkyl, -N[(C1-C4)alkyl]2, -O-(C1-C4)alkyl, and -(C1-C4)alkyl.

[0258] In certain embodiments, each of the R groups is independently selected from hydrogen, -OH, -NH2, -(C1-C4)alkyl, -O-(C1-C4)alkyl, and -(4-8 membered)heterocyclyl, and the -(C1-C4)alkyl and -(4-8 membered)heterocyclyl groups are optionally substituted with 1, 2, 3, 4, or 5 groups selected from hydrogen, halogen, -OH, -NH2, -NH(C1-C4)alkyl, -N[(C1-C4)alkyl]2, and -O-(C1-C4)alkyl.

[0259] In certain embodiments, the R groups are each independently selected from hydrogen, -OH, -(C1-C4)alkyl and -O-(C1-C4)alkyl, and the foregoing groups are each independently optionally substituted with 1, 2 or 3 groups selected from hydrogen, halogen, -OH, -NH2, -NH-methyl and -N(methyl)2.

[0260] In certain embodiments, each of the R groups is independently selected from hydrogen, -OH, methyl, ethyl, propyl, -O-methyl, -O-ethyl, -O-propyl, -methylene-O-ethyl, -C(=O)-methyl, -S(=O)2-methyl, cyclobutyl, oxetanyl, azetidinyl, pyrrolidinyl, piperazinyl, -methylene-cyclobutyl, -methylene-oxetanyl, and -methylene-azetidinyl, each of the foregoing groups being optionally substituted with 1, 2, or 3 groups selected from -OH, -NH2, OCH3, NHCH3, , N(CH3)2, and CH3.

[0261] In certain embodiments, each of the R groups is independently selected from methyl, ethyl, propyl, -O-methyl, -O-ethyl, -O-propyl, oxetanyl, and azetidinyl, each of which is independently optionally substituted with 1, 2, or 3 groups selected from -OH and -NH2.

[0262] In certain embodiments, the R 8a 、R 8b 、R 9aand R 9b each independently selected from hydrogen, halogen, cyano, -(C1-C4)alkyl, -(C1-C4)haloalkyl, -(C2-C4)alkenyl, -(C2-C4)alkynyl, -OR, -N(R)R, -[(C1-C6)alkylene]R, -[(C1-C6)alkylene]OR, -[(C1-C6)alkylene]N(R)R, -[(C1-C6)alkylene]N(R)C(=O)R, -[(C1-C6)alkylene]N( R)C(=O)N(R)R, -C(=O)R, -C(=O)N(R)R, -C(=O)[(C1-C6)alkylene]N(R)R, -C(=O)OR, -C(=S)N(R)R, -S R, -S(=O)R, -S(=O)2R, -S(=O)2N(R)R, -N(R)C(=O)R, -N(R)C(=O)N(R)R, -P(=O)(OR)(OR), -(C6-C 10 )aryl, -(5-10 membered)heteroaryl, -(C3-C6)cycloalkyl and -(4-8 membered)heterocyclyl, R is as defined in any embodiment of the present invention.

[0263] R 8a 、R 8b 、R 9a and R 9b each independently selected from hydrogen, halogen, cyano, -(C1-C4)alkyl, -(C1-C4)haloalkyl, -(C2-C4)alkenyl, -(C2-C4)alkynyl, -OR, -N(R)R, -[(C1-C6)alkylene]R, -[(C1-C6)alkylene]OR, -[(C1-C6)alkylene]N(R)R, -C(=O)R, -C(=O )N(R)R, -C(=O)[(C1-C6)alkylene]N(R)R, -C(=O)OR, -C(=S)N(R)R, -SR, -S(=O)R, -S( =O)2R, -S(=O)2N(R)R, -N(R)C(=O)R, -N(R)C(=O)N(R)R, -P(=O)(OR)(OR), -(C6-C 10 )aryl, -(5-10 membered)heteroaryl, -(C3-C6)cycloalkyl and -(4-8 membered)heterocyclyl, R is as defined in any embodiment of the present invention.

[0264] In certain embodiments, the R 8a 、R 8b 、R 9a and R 9bEach is independently selected from hydrogen, cyano, -OR, -N(R)R, -[(C1-C4)alkylene]R, -[(C1-C4)alkylene]OR, -[(C1-C4)alkylene]N(R)R, -[(C1-C4)alkylene]N(R)C(=O)R, -[(C1-C4)alkylene]N(R)C(=O)N(R)R, -C(=O)R, -C(=O)N(R)R, -C(=O)[(C1-C4)alkylene]N(R)R, -C(=O)OR, -C(=S)N(R)R, -S(=O)R, -S(=O)2R, -S(=O)2N(R)R, -N(R)C(=O)R and -N(R)C(=O)N(R)R, and R is defined as described in any embodiment of the present invention.

[0265] In certain embodiments, the R 8a 、R 8b 、R 9a and R 9b Each is independently selected from hydrogen, -OR, -N(R)R, -[(C1-C4)alkylene]R, -[(C1-C4)alkylene]OR, -[(C1-C4)alkylene]N(R)R, -C(=O)R, -C(=O)N(R)R, -C(=O)[(C1-C4)alkylene]N(R)R, -C(=O)OR, -C(=S)N(R)R, -S(=O)R, -S(=O)2R, -S(=O)2N(R)R, -N(R)C(=O)R and -N(R)C(=O)N(R)R, and R is defined as described in the present invention.

[0266] In certain embodiments, the R 8a and R 8b Each is independently selected from hydrogen, -methylene-R, -ethylene-R, -propylene-R, -methylene-OR, -ethylene-OR, -propylene-OR, -methylene-N(R)R, -ethylene-N(R)R, -propylene-N(R)R, -C(=O)R, -C(=O)N(R)R and -C(=O)OR, and R is defined as described in any embodiment of the present invention.

[0267] In certain embodiments, the R 8a and R 8bEach is independently selected from hydrogen, -methylene-R, -methylene-OR, -methylene-N(R)R, -C(=O)R, -C(=O)OR and -C(=O)N(R)R, and R is defined as described in the present invention. For example, R is independently selected from hydrogen, -OH, -NH2, -(C1-C4)alkyl, -O-(C1-C4)alkyl, -C(=O)-(C1-C4)alkyl, -S(=O)2(C1-C4)alkyl and -(4-8 membered)heterocyclyl, and the -(C1-C4)alkyl and -(4-8 membered)heterocyclyl are optionally substituted with 1, 2, 3, 4 or 5 groups selected from hydrogen, halogen, -OH, -NH2, -NHCH3 and CH3.

[0268] In certain embodiments, the R 8a and R 8b Each is independently selected from hydrogen, -methylene-R, -methylene-OR, -methylene-N(R)R, -C(=O)R, -C(=O)OR and -C(=O)N(R)R, and R is as defined in any embodiment of the present invention.

[0269] In certain embodiments, the R 8a For hydrogen.

[0270] In certain embodiments, the R 8a for

[0271] In certain embodiments, the R 8b Selected from hydrogen,

[0272] In certain embodiments, the R 8b Selected from hydrogen,

[0273] In certain embodiments, the R 8b Selected from hydrogen,

[0274] In certain embodiments, the R 8b Selected from hydrogen,

[0275] In certain embodiments, the R 8b Selected from hydrogen,

[0276] In certain embodiments, the R 8b Selected from hydrogen,

[0277] In certain embodiments, the R 8b is selected from hydrogen, -methylene-R, -methylene-N(R)R, -C(=O)OR, -C(=O)N(R)R and -C(=O)R, R is defined as described in any embodiment of the present invention, for example, R is independently selected from hydrogen, -OH, methyl, ethyl, -O-methyl, -C(=O)-methyl, -S(=O)2-methyl, azetidinyl, pyrrolidinyl and piperazinyl, and the foregoing groups are each independently optionally substituted by 1, 2 or 3 groups selected from -OH and -NH2.

[0278] In certain embodiments, the R 8b is selected from -methylene-R, -C(=O)OR, -C(=O)N(R)R and -C(=O)R, wherein R is as defined in any embodiment of the present invention.

[0279] In certain embodiments, the R 8b Selected from hydrogen,

[0280] In certain embodiments, the R 8b Selected from

[0281] In certain embodiments, the R 8b Selected from hydrogen,

[0282] In certain embodiments, the R 8b Selected from hydrogen,

[0283] In certain embodiments, the R 8b Selected from hydrogen,

[0284] In certain embodiments, the R 9a and R 9b each is independently selected from hydrogen, -CN, -OR, -NHR, -N(R)R, -NHC(=O)R, -methylene-R, -ethylene-R, -propylene-R, -methylene-N(R)R, -ethylene-N(R)R, -propylene-N(R)R, -methylene-NHC(=O)R and -methylene-NHC(=O)NHR, and R is defined as described in any embodiment of the present invention.

[0285] In certain embodiments, the R 9a and R 9bEach is independently selected from hydrogen, -OR, -NHR, -methylene-R, -ethylene-R, -propylene-R, -methylene-N(R)R, -ethylene-N(R)R, -propylene-N(R)R and -NHC(=O)R, and R is defined as described in any embodiment of the present invention.

[0286] In certain embodiments, the R 9a and R 9b Each is independently selected from hydrogen, -CN, -OR, -N(R)R, -NHC(=O)R, -methylene-N(R)R, -methylene-NHC(=O)R and -methylene-NHC(=O)NHR, R is defined as described in any embodiment of the present invention, for example, R is independently selected from hydrogen, -OH, -(C1-C4)alkyl, -(C1-C4)alkylene-O-(C1-C4)alkyl, -S(=O)2(C1-C4)alkyl, -(C3-C6) Cycloalkyl, -(4-8 membered)heterocyclyl, -methylene-(C3-C6)cycloalkyl and -methylene-(4-8 membered)heterocyclyl, wherein the -(C1-C4)alkyl, -(C3-C6)cycloalkyl and -(4-8 membered)heterocyclyl are optionally substituted by 1, 2, 3, 4 or 5 groups selected from hydrogen, halogen, -OH, -NH2, -NH(C1-C4)alkyl, -N[(C1-C4)alkyl]2, -O-(C1-C4)alkyl and -(C1-C4)alkyl.

[0287] In certain embodiments, the R 9a and R 9b Each is independently selected from hydrogen, -OR, -N(R)R, -methylene-N(R)R and -NHC(=O)R, and R is as defined in any embodiment of the present invention.

[0288] In certain embodiments, the R 9a is selected from hydrogen, -CN, -N(R)R, -NHC(=O)R, -methylene-N(R)R, -methylene-NHC(=O)R and -methylene-NHC(=O)NHR, R is defined as described in any embodiment of the present invention, for example, R is independently selected from hydrogen, -OH, methyl, ethyl, -methylene-O-ethyl, -S(=O)2-methyl, cyclobutyl, azetidinyl, -methylene-cyclobutyl and -methylene-azetidinyl, and the foregoing groups are each independently optionally substituted by 1, 2 or 3 groups selected from -OH, OCH3, NHCH3, N(CH3)2 and CH3.

[0289] In certain embodiments, the R 9a is selected from hydrogen and -methylene-N(R)R, R is as defined in any embodiment of the present invention.

[0290] In certain embodiments, the R 9a Selected from hydrogen, -CN, -NHCH3, -N(CH3)2, -NHC(=O)H, -NHC(=O)CH2OH, -NHC(=O)CH2OCH3, -NHC(=O)CH2NHCH3, -NHC(=O)CH2N(CH3)2, -CH2NH2, -CH2NHCH3, -CH2N(CH 3)2, -CH2N(CH2CH3)2, -CH2N(CH3)(CH2CH3), -CH2NHC(=O)CH2OH, -CH2NHC(=O)CH2OCH3, -CH2NHC(=O)CH2NHCH3, -CH2NHC(=O)CH2N(CH3)2, -CH2NHC(=O )H, -CH2NHC(=O)CH3, -CH2NHC(=O)NHOH, -CH2NHC(=O)NHCH2CH2OH, -CH2NHC(=O)CH(N(CH3)2)CH2OH, -CH2NHC(=O)CH2NHCH3, -CH2NHC(=O)CH2N(CH3)2, -CH2NHC(=O)CH2N(CH2CH3)2, -CH2NHC(=O)CH2OCH2CH2OH, -CH2NHS(=O)2CH3, -CH2NHC(=O)cyclobutyl-OH, -CH2NHC(=O)-azetidinyl-CH3 and -CH2NHC(=O)CH2-azetidinyl.

[0291] In certain embodiments, the R 9a Selected from hydrogen, -CH2NH2, -CH2NHCH3, -NHC(=O)H, -NHC(=O)CH2OH and -CH2NHC(=O)CH2OH.

[0292] In certain embodiments, the R 9a is selected from hydrogen, -CH2NH2, -NHC(=O)H, -NHC(=O)CH2OH and -CH2NHC(=O)CH2OH.

[0293] In certain embodiments, the R 9a Selected from hydrogen,

[0294] In certain embodiments, the R 9a Selected from hydrogen,

[0295] In certain embodiments, the R 9a Selected from hydrogen,

[0296] In certain embodiments, the R 9a Selected from hydrogen,

[0297] In certain embodiments, the R 9a Selected from hydrogen,

[0298] In certain embodiments, the R 9a Selected from hydrogen,

[0299] In certain embodiments, the R 9a Selected from hydrogen,

[0300] In certain embodiments, the R 9a Selected from hydrogen and

[0301] In certain embodiments, the R 9a For hydrogen.

[0302] In certain embodiments, the R 9a for

[0303] In certain embodiments, the R 9b It is -OH.

[0304] In certain embodiments, the R 9b Selected from hydrogen and

[0305] In certain embodiments, the R 9b for

[0306] In certain embodiments, the R 9b Selected from hydrogen,

[0307] In certain embodiments, the R 8a and R 8b , and R 9a and R 9b Independently combine to form oxo, -(C2-C4)alkenyl, -(C3-C6)cycloalkyl or -(4-8 membered)heterocyclyl.

[0308] In certain embodiments, the R 8a and R 8b The groups are combined to form oxo, -(C2-C4)alkenyl, -(C3-C6)cycloalkyl or -(4-8 membered)heterocyclyl.

[0309] In certain embodiments, the R 9a and R 9b The groups are combined to form oxo, -(C2-C4)alkenyl, -(C3-C6)cycloalkyl or -(4-8 membered)heterocyclyl.

[0310] In certain embodiments, the R 8a and R 8b , and R 9a and R 9b Independently combine to form oxo, vinyl, propenyl, cyclopropyl, cyclobutyl, cyclopentyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl or piperazinyl.

[0311] In certain embodiments, the R 8a and R 8b The combination forms oxo, vinyl, propenyl, cyclopropyl, cyclobutyl, cyclopentyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl or piperazinyl.

[0312] In certain embodiments, the R 9a and R 9b The combination forms oxo, vinyl, propenyl, cyclopropyl, cyclobutyl, cyclopentyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl or piperazinyl.

[0313] In certain embodiments, the R 8a and R 9a , R 8b and R 9b The carbon atoms to which it is attached together form a (C3-C6)cycloalkyl, a (4-8) membered heterocyclyl or a (5-9 membered)heteroaryl, wherein the aforementioned groups are optionally substituted by 1, 2, 3, 4, 5, 6 or 7 groups selected from hydrogen, halogen, -OH, -O-(C1-C4)alkyl, -NH2, -NH(C1-C4)alkyl, -N[(C1-C4)alkyl]2, -(C3-C6)cycloalkyl and -(C6-C 10 ) aryl group substitution.

[0314] In certain embodiments, the R 8a and R 9a The carbon atoms to which it is attached together form a (C3-C6)cycloalkyl, a (4-8) membered heterocyclyl or a (5-9 membered)heteroaryl, wherein the aforementioned groups are optionally substituted by 1, 2, 3, 4, 5, 6 or 7 groups selected from hydrogen, halogen, -OH, -O-(C1-C4)alkyl, -NH2, -NH(C1-C4)alkyl, -N[(C1-C4)alkyl]2, -(C3-C6)cycloalkyl and -(C6-C10 ) aryl group substitution.

[0315] In certain embodiments, the R 8b and R 9b The carbon atoms to which it is attached together form a (C3-C6)cycloalkyl, a (4-8) membered heterocyclyl or a (5-9 membered)heteroaryl, wherein the aforementioned groups are optionally substituted by 1, 2, 3, 4, 5, 6 or 7 groups selected from hydrogen, halogen, -OH, -O-(C1-C4)alkyl, -NH2, -NH(C1-C4)alkyl, -N[(C1-C4)alkyl]2, -(C3-C6)cycloalkyl and -(C6-C 10 ) aryl group substitution.

[0316] In certain embodiments, the R 8a and R 9a , R 8b and R 9b The carbon atoms to which they are attached together form a (4-8 membered) heterocyclyl or a (5-9 membered) heteroaryl, the aforementioned groups being optionally substituted by 1, 2, 3, 4 or 5 groups selected from hydrogen, fluorine, chlorine, -OH, -O-methyl, -O-ethyl, -NH2, -NH-methyl, -NH-ethyl, -N(methyl)2, -N(methyl)-ethyl, -N(ethyl)2, cyclopropyl, cyclobutyl, cyclopentyl, phenyl and naphthyl.

[0317] In certain embodiments, the R 8a and R 9a The carbon atoms to which they are attached together form a (4-8 membered) heterocyclyl or a (5-9 membered) heteroaryl, and the aforementioned groups are optionally substituted by 1, 2, 3, 4 or 5 groups selected from hydrogen, fluorine, chlorine, -OH, -O-methyl, -O-ethyl, -NH2, -NH-methyl, -NH-ethyl, -N(methyl)2, -N(methyl)-ethyl, -N(ethyl)2, cyclopropyl, cyclobutyl, cyclopentyl, phenyl and naphthyl.

[0318] In certain embodiments, the R 8b and R 9b The carbon atoms to which they are attached together form a (4-8 membered) heterocyclyl or a (5-9 membered) heteroaryl, and the aforementioned groups are optionally substituted by 1, 2, 3, 4 or 5 groups selected from hydrogen, fluorine, chlorine, -OH, -O-methyl, -O-ethyl, -NH2, -NH-methyl, -NH-ethyl, -N(methyl)2, -N(methyl)-ethyl, -N(ethyl)2, cyclopropyl, cyclobutyl, cyclopentyl, phenyl and naphthyl.

[0319] In certain embodiments, the R 8a and R 9a , R 8b and R 9bThe carbon atom to which it is attached together forms an oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, pyridonyl, pyrimidonyl, oxazolyl, thiazolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, benzothiophenyl or indolyl, and the foregoing groups are optionally substituted with 1, 2 or 3 groups selected from hydrogen, fluorine, chlorine, -OH, -O-methyl, -O-ethyl, -NH2, -NH-methyl, -NH-ethyl, -N(methyl)2, -N(methyl)-ethyl, -N(ethyl)2, cyclopropyl, cyclobutyl, cyclopentyl, phenyl and naphthyl.

[0320] In certain embodiments, the R 8a and R 9a The carbon atom to which it is attached together forms an oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, pyridonyl, pyrimidonyl, oxazolyl, thiazolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, benzothiophenyl or indolyl, and the foregoing groups are optionally substituted with 1, 2 or 3 groups selected from hydrogen, fluorine, chlorine, -OH, -O-methyl, -O-ethyl, -NH2, -NH-methyl, -NH-ethyl, -N(methyl)2, -N(methyl)-ethyl, -N(ethyl)2, cyclopropyl, cyclobutyl, cyclopentyl, phenyl and naphthyl.

[0321] In certain embodiments, the R 8b and R 9b The carbon atom to which it is attached together forms an oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, pyridonyl, pyrimidonyl, oxazolyl, thiazolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, benzothiophenyl or indolyl, and the foregoing groups are optionally substituted with 1, 2 or 3 groups selected from hydrogen, fluorine, chlorine, -OH, -O-methyl, -O-ethyl, -NH2, -NH-methyl, -NH-ethyl, -N(methyl)2, -N(methyl)-ethyl, -N(ethyl)2, cyclopropyl, cyclobutyl, cyclopentyl, phenyl and naphthyl.

[0322] In certain embodiments, the R 8a and R 9a Does not exist, R 8b and R 9b The atoms connected to it form Where * indicates the positions of connected atoms.

[0323] In certain embodiments, the R 10 Selected from -OH, or R 10 and R 9bThe atoms to which it is attached form a 5-membered nitrogen-containing heterocyclic group, and the 5-membered nitrogen-containing heterocyclic group is optionally substituted by 1, 2, 3, 4 or 5 groups selected from hydrogen, halogen, -OH, methyl, ethyl, -O-methyl, -O-ethyl, -NH2, -NH-methyl, -NH-ethyl, -N(methyl)2, -N(methyl)-ethyl and -N(ethyl)2.

[0324] In certain embodiments, the R 10 is -OH, or R 10 and R 9b The atoms to which it is attached form an imidazolinyl group which is optionally substituted with 1, 2 or 3 groups selected from halogen, -OH, methyl, -NH2, -NH-methyl and -N(methyl)2.

[0325] In certain embodiments, the R 10 is -OH, or R 10 and R 9b The atoms connected to it form Where * indicates the positions of connected atoms.

[0326] In certain embodiments, the R 10 Selected from -OH, or R 10 and R 9a The atoms to which it is attached form a 5-membered nitrogen-containing heterocyclic group, and the 5-membered nitrogen-containing heterocyclic group is optionally substituted by 1, 2, 3, 4 or 5 groups selected from hydrogen, halogen, -OH, methyl, ethyl, -O-methyl, -O-ethyl, -NH2, -NH-methyl, -NH-ethyl, -N(methyl)2, -N(methyl)-ethyl and -N(ethyl)2.

[0327] In certain embodiments, the R 10 is -OH, or R 10 and R 9a The atoms to which it is attached form an imidazolinyl group, which is optionally substituted with 1, 2 or 3 groups selected from halogen, -OH, methyl, -NH2, -NH-methyl and -N(methyl)2.

[0328] In certain embodiments, the R 10 is -OH, or R 10 and R 9a The atoms connected to it form Where * indicates the positions of connected atoms.

[0329] In certain embodiments, the R 10 It is -OH.

[0330] In certain embodiments, the R 10 for

[0331] In certain embodiments, the compound of the structure shown in Formula I, wherein,

[0332] X 1 Selected from N and C(R 1 ), R 1 is selected from hydrogen, halogen, cyano, -OH, -(C1-C4)alkyl and -O-(C1-C4)alkyl;

[0333] X 2 Selected from C(R 2 ), R 2 is selected from hydrogen, halogen, cyano, -OH, -(C1-C4)alkyl and -O-(C1-C4)alkyl;

[0334] R 31 is selected from the group consisting of oxo, hydrogen, fluorine, chlorine, cyano, -OH, -SH, -NH2, -(C1-C4)alkyl, -O-(C1-C4)alkyl, -NH-(C1-C4)alkyl, -(C1-C4)alkylene-OH, -(C1-C4)haloalkyl, -(C1-C4)alkylene-NH2, -(C1-C4)alkylene-NH(C1-C4)alkyl and -(C1-C4)alkylene-N[(C1-C4)alkyl]2;

[0335] R 3 is selected from -(C3-C6)cycloalkyl, -(3-6 membered)heterocyclyl and -(5-9 membered)heteroaryl, wherein R 3 Optional 1, 2, 3 or 4 R 31 replace;

[0336] R 4 is selected from hydrogen, fluorine, chlorine, cyano, -OH, -NH2, methyl, halomethyl, -O-methyl, -NH-methyl and cyclopropyl;

[0337] X is selected from O, S, NH and N[(C1-C4)alkyl];

[0338] Ring B is phenyl;

[0339] R 5 and R 6 R is each independently selected from hydrogen, fluorine, chlorine, bromine, cyano, -OH, -NH2, -(C1-C4)alkyl, -(C1-C4)alkyl-OH, -(C1-C4)alkyl-NH2, -(C1-C4)haloalkyl, -O-(C1-C4)alkyl, -O-(C1-C4)haloalkyl and -(C3-C6)cycloalkyl; or R 5 and R 6 The atoms connected to it form Where * indicates the connected atomic positions;

[0340] Ring C is phenyl;

[0341] R 7 each independently selected from hydrogen, fluorine, chlorine, bromine, cyano, -OH, -NH2, -(C1-C4)alkylene-OH, -(C1-C4)alkylene-NH(C1-C4)alkyl, -(C1-C4)alkylene-N[(C1-C4)alkyl]2 and -(C1-C4)alkylene-NH2;

[0342] m is 1, 2, or 3;

[0343] R is each independently selected from hydrogen, -OH, NH2, -(C1-C4)alkyl, -(C1-C4)haloalkyl, -O-(C1-C4)alkyl, -O-(C1-C4)haloalkyl, -(C3-C6)cycloalkyl, -(4-8 membered)heterocyclyl, -C(=O)-H, -C(=O)-(C1-C4)alkyl, -C(=O)-(C3-C6)cycloalkyl and -[(C1-C4)alkylene]-(4-8 membered)heterocyclyl, wherein the -(C1-C4)alkyl group is selected from hydrogen, -OH, NH2, -(C1-C4)alkyl, -(C1-C4)haloalkyl, -O-(C1-C4)alkyl, -O-(C1-C4)haloalkyl, -(C3-C6)cycloalkyl, -(4-8 membered)heterocyclyl, -C4)alkylene-, -(C1-C4)alkyl, -(C3-C6)cycloalkyl and -(4-8 membered)heterocyclyl are optionally substituted by 1, 2, 3, 4 or 5 groups selected from hydrogen, halogen, -OH, -O-methyl, -O-ethyl, -O-propyl, -NH2, -NH-methyl, -NH-ethyl, -NH-propyl, -N(methyl), -N(methyl)-ethyl, -N(methyl)-propyl, -N(ethyl), -N(ethyl)-propyl, methyl and ethyl;

[0344] R 8a for

[0345] R 8b is selected from the group consisting of hydrogen, -methylene-R, -ethylene-R, -propylene-R, -methylene-OR, -ethylene-OR, -propylene-OR, -methylene-N(R)R, -ethylene-N(R)R, -propylene-N(R)R, -C(=O)R, -C(=O)N(R)R, and -C(=O)OR;

[0346] R 9a is selected from hydrogen, -OR, -N(R)R, -methylene-N(R)R, -methylene-NHC(=O)R, and -NHC(=O)R;

[0347] R 9b Selected from hydrogen and

[0348] R 10 for

[0349] In certain embodiments, the compound of the structure shown in Formula I, wherein,

[0350] X 1 Selected from N and C(R 1 ), R 1 is selected from hydrogen, halogen, cyano, -OH, -(C1-C4)alkyl and -O-(C1-C4)alkyl;

[0351] X 2 Selected from C(R 2 ), R 2 is selected from hydrogen, halogen, cyano, -OH, -(C1-C4)alkyl and -O-(C1-C4)alkyl;

[0352] R 31 is selected from the group consisting of oxo, hydrogen, fluorine, chlorine, cyano, -OH, -SH, -NH2, -(C1-C4)alkyl, -O-(C1-C4)alkyl, -NH-(C1-C4)alkyl, -(C1-C4)alkylene-OH, -(C1-C4)haloalkyl, -(C1-C4)alkylene-NH2, -(C1-C4)alkylene-NH(C1-C4)alkyl and -(C1-C4)alkylene-N[(C1-C4)alkyl]2;

[0353] R 3 is selected from -(C3-C6)cycloalkyl, -(3-6 membered)heterocyclyl and -(5-9 membered)heteroaryl, wherein R 3 Optional 1, 2, 3 or 4 R 31 replace;

[0354] R 4 is selected from hydrogen, fluorine, chlorine, cyano, -OH, -NH2, methyl, halomethyl, -O-methyl, -NH-methyl and cyclopropyl;

[0355] X is selected from O, S, NH and N[(C1-C4)alkyl];

[0356] Ring B is phenyl;

[0357] R 5 and R 6 R is each independently selected from hydrogen, fluorine, chlorine, bromine, cyano, -OH, -NH2, -(C1-C4)alkyl, -(C1-C4)alkyl-OH, -(C1-C4)alkyl-NH2, -(C1-C4)haloalkyl, -O-(C1-C4)alkyl, -O-(C1-C4)haloalkyl and -(C3-C6)cycloalkyl; or R 5 and R 6 The atoms connected to it form Where * indicates the connected atomic positions;

[0358] Ring C is phenyl;

[0359] R 7 each independently selected from hydrogen, fluorine, chlorine, bromine, cyano, -OH, -NH2, -(C1-C4)alkylene-OH, -(C1-C4)alkylene-NH(C1-C4)alkyl, -(C1-C4)alkylene-N[(C1-C4)alkyl]2 and -(C1-C4)alkylene-NH2;

[0360] m is 1, 2, or 3;

[0361] R is each independently selected from hydrogen, -OH, NH2, -(C1-C4)alkyl, -(C1-C4)haloalkyl, -O-(C1-C4)alkyl, -O-(C1-C4)haloalkyl, -(C3-C6)cycloalkyl, -(4-8 membered)heterocyclyl, -C(=O)-H, -C(=O)-(C1-C4)alkyl, -C(=O)-(C3-C6)cycloalkyl and -[(C1-C4)alkylene]-(4-8 membered)heterocyclyl, wherein - (C1-C4)alkylene-, -(C1-C4)alkyl, -(C3-C6)cycloalkyl and -(4-8 membered)heterocyclyl are optionally substituted by 1, 2, 3, 4 or 5 groups selected from hydrogen, halogen, -OH, -O-methyl, -O-ethyl, -O-propyl, -NH2, -NH-methyl, -NH-ethyl, -NH-propyl, -N(methyl), -N(methyl)-ethyl, -N(methyl)-propyl, -N(ethyl)2 and -N(ethyl)-propyl;

[0362] R 8a for

[0363] R 8b is selected from the group consisting of hydrogen, -methylene-R, -ethylene-R, -propylene-R, -methylene-OR, -ethylene-OR, -propylene-OR, -methylene-N(R)R, -ethylene-N(R)R, -propylene-N(R)R, -C(=O)R, -C(=O)N(R)R, and -C(=O)OR;

[0364] R 9a is selected from hydrogen, -OR, -N(R)R, -methylene-N(R)R, and -NHC(=O)R;

[0365] R 9b Selected from hydrogen and

[0366] R 10 for

[0367] In certain embodiments, the compound of the structure shown in Formula I, wherein,

[0368] X 1 Selected from N and C(R 1 ), R 1 is selected from hydrogen, halogen, cyano, -OH, -(C1-C4)alkyl and -O-(C1-C4)alkyl;

[0369] X 2 Selected from N and C(R 2 ), R 2 is selected from hydrogen, halogen, cyano, -OH, -(C1-C4)alkyl and -O-(C1-C4)alkyl;

[0370] R 31 is selected from the group consisting of hydrogen, fluorine, chlorine, cyano, -OH, -SH, -NH2, -(C1-C4)alkyl, -(C1-C4)alkylene-OH, -(C1-C4)haloalkyl, -(C1-C4)alkylene-NH2, -(C1-C4)alkylene-NH(C1-C4)alkyl and -(C1-C4)alkylene-N[(C1-C4)alkyl]2;

[0371] R 3 is selected from -(5-6 membered)heteroaryl, wherein R 3 Optional 1, 2, 3 or 4 R 31 replace;

[0372] R 4 is selected from hydrogen, fluorine, chlorine, cyano, -OH, -NH2, methyl, halomethyl, -O-methyl, -NH-methyl and cyclopropyl;

[0373] X is selected from O, S, NH and N[(C1-C4)alkyl];

[0374] Ring B is phenyl;

[0375] R 5 and R 6 Each is independently selected from hydrogen, fluorine, chlorine, bromine, cyano, -OH, -NH2, -(C1-C4)alkyl, -(C1-C4)haloalkyl, -O-(C1-C4)alkyl, -O-(C1-C4)haloalkyl and -(C3-C6)cycloalkyl; or R 5 and R 6 The atoms connected to it form Where * indicates the connected atomic positions;

[0376] Ring C is phenyl;

[0377] R 7each independently selected from hydrogen, fluorine, chlorine, bromine, cyano, -OH, -NH2, -(C1-C4)alkylene-OH, -(C1-C4)alkylene-NH(C1-C4)alkyl, -(C1-C4)alkylene-N[(C1-C4)alkyl]2 and -(C1-C4)alkylene-NH2;

[0378] m is 1, 2, or 3;

[0379] R is each independently selected from hydrogen, -OH, -(C1-C4)alkyl, -(C1-C4)haloalkyl, -O-(C1-C4)alkyl, -O-(C1-C4)haloalkyl, -(C3-C6)cycloalkyl, -(4-8 membered)heterocyclyl, -C(=O)-H, -C(=O)-(C1-C4)alkyl, -C(=O)-(C3-C6)cycloalkyl and -[(C1-C4)alkylene]-(4-8 membered)heterocyclyl, wherein -(C -(C1-C4)alkylene-, -(C1-C4)alkyl, -(C3-C6)cycloalkyl and -(4-8 membered)heterocyclyl are optionally substituted by 1, 2, 3, 4 or 5 groups selected from hydrogen, halogen, -OH, -O-methyl, -O-ethyl, -O-propyl, -NH2, -NH-methyl, -NH-ethyl, -NH-propyl, -N(methyl), -N(methyl)-ethyl, -N(methyl)-propyl, -N(ethyl)2 and -N(ethyl)-propyl;

[0380] R 8a for

[0381] R 8b is selected from the group consisting of hydrogen, -methylene-R, -ethylene-R, -propylene-R, -methylene-OR, -ethylene-OR, -propylene-OR, -methylene-N(R)R, -ethylene-N(R)R, -propylene-N(R)R, -C(=O)R, -C(=O)N(R)R, and -C(=O)OR;

[0382] R 9a is selected from hydrogen, -OR, -N(R)R, -methylene-N(R)R, and -NHC(=O)R;

[0383] R 9b Selected from hydrogen and

[0384] R 10 for

[0385] In certain embodiments, the compound of the structure shown in Formula I, wherein,

[0386] X 1 Selected from N and C(R 1 ), R1 is selected from the group consisting of hydrogen, fluorine, chlorine, cyano, -OH, methyl, ethyl, propyl, -O-methyl, -O-ethyl, and -O-propyl;

[0387] X 2 Selected from C(R 2 ), R 2 is selected from the group consisting of hydrogen, fluorine, chlorine, cyano, -OH, methyl, ethyl, propyl, -O-methyl, -O-ethyl, and -O-propyl;

[0388] R 31 is selected from the group consisting of hydrogen, fluorine, chlorine, cyano, -OH, -SH, -NH2, methyl, halomethyl, -O-methyl, -CH2OH, -CH2NH2 and -CH2CH2N(CH3)2;

[0389] R 3 is selected from cyclopropyl, oxetanyl, piperazinyl, piperazinonyl, morpholinyl, morpholinonyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, isothiazolyl, imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyrazinyl, pyridazinyl, pyrimidinyl, pyridazinoimidazolyl, pyrazinoimidazolyl and pyrimidonyl, wherein R 3 Optional 1, 2 or 3 R 31 replace;

[0390] R 4 is selected from hydrogen, fluorine, chlorine, cyano, -OH and -NH2;

[0391] X is selected from O and S;

[0392] Structural unit for

[0393] R 5 selected from hydrogen -OH, -NH2 and -CH2NH2;

[0394] R 6 is selected from hydrogen, fluorine, chlorine, bromine, cyano, -OH, -NH2, cyclopropyl and -O-methyl;

[0395] or R 5 and R 6 The atoms connected to it form Where * indicates the connected atomic positions;

[0396] Structural unit for

[0397] R 7each independently selected from hydrogen, fluorine, chlorine, bromine, cyano, -OH, -NH2, -(C1-C4)alkylene-OH, -(C1-C4)alkylene-NH(C1-C4)alkyl, -(C1-C4)alkylene-N[(C1-C4)alkyl]2 and -(C1-C4)alkylene-NH2;

[0398] m is 1, 2, or 3;

[0399] R 8a for

[0400] R 8b selected from hydrogen, -methylene-R, -methylene-N(R)R, -C(=O)OR, -C(=O)N(R)R and -C(=O)R, R is as defined in any embodiment of the present invention, for example, each R is independently selected from hydrogen, -OH, methyl, ethyl, -O-methyl, -C(=O)-methyl, -S(=O)2-methyl, azetidinyl, pyrrolidinyl and piperazinyl, each of the foregoing groups being independently optionally substituted with 1, 2 or 3 groups selected from -OH and -NH2;

[0401] R 9a is selected from hydrogen, -CN, -N(R)R, -NHC(=O)R, -methylene-N(R)R, -methylene-NHC(=O)R and -methylene-NHC(=O)NHR, R is as defined in any embodiment of the present invention, for example, each R is independently selected from hydrogen, -OH, methyl, ethyl, -methylene-O-ethyl, -S(=O)2-methyl, cyclobutyl, azetidinyl, -methylene-cyclobutyl and -methylene-azetidinyl, each of the foregoing groups being optionally substituted with 1, 2 or 3 groups selected from -OH, OCH3, NHCH3, N(CH3)2 and CH3;

[0402] R 9b is selected from hydrogen and

[0403] R 10 for

[0404] In certain embodiments, the compound of the structure shown in Formula I, wherein,

[0405] X 1 Selected from N and C(R 1 ), R 1 is selected from the group consisting of hydrogen, fluorine, chlorine, cyano, -OH, methyl, ethyl, propyl, -O-methyl, -O-ethyl, and -O-propyl;

[0406] X 2 Selected from C(R 2 ), R2 is selected from the group consisting of hydrogen, fluorine, chlorine, cyano, -OH, methyl, ethyl, propyl, -O-methyl, -O-ethyl, and -O-propyl;

[0407] R 31 is selected from the group consisting of hydrogen, fluorine, chlorine, cyano, -OH, -SH, -NH2, methyl, halomethyl, -O-methyl, -CH2OH and -CH2CH2N(CH3)2;

[0408] R 3 is selected from cyclopropyl, oxetanyl, piperazinyl, piperazinonyl, morpholinyl, morpholinonyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, isothiazolyl, imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyrazinyl, pyridazinyl, pyrimidinyl, pyridazinoimidazolyl, pyrazinoimidazolyl and pyrimidonyl, wherein R 3 Optional 1, 2 or 3 R 31 replace;

[0409] R 4 is selected from hydrogen, fluorine, chlorine, cyano, -OH and -NH2;

[0410] X is selected from O and S;

[0411] Structural unit for

[0412] R 5 selected from hydrogen -OH, -NH2 and -CH2NH2;

[0413] R 6 is selected from hydrogen, fluorine, chlorine, bromine, cyano, -OH, -NH2 and -O-methyl;

[0414] or R 5 and R 6 The atoms connected to it form Where * indicates the connected atomic positions;

[0415] Structural unit for

[0416] R 7 each independently selected from hydrogen, fluorine, chlorine, bromine, cyano, -OH, -NH2, -(C1-C4)alkylene-OH, -(C1-C4)alkylene-NH(C1-C4)alkyl, -(C1-C4)alkylene-N[(C1-C4)alkyl]2 and -(C1-C4)alkylene-NH2;

[0417] m is 1, 2, or 3;

[0418] Each R is independently selected from hydrogen, -OH, -(C1-C4)alkyl, -O-(C1-C4)alkyl, -C(=O)-H, -C(=O)CH2OH, oxetanyl and azetidinyl-OH, each of the foregoing groups being optionally substituted with 1, 2 or 3 groups selected from hydrogen, halogen, -OH, -NH2, -NH-methyl and -N(methyl);

[0419] R 8a for

[0420] R 8b is selected from the group consisting of H, -methylene-R, -methylene-N(R)R, -C(=O)OR, -C(=O)N(R)R, and -C(=O)R;

[0421] R 9a is selected from hydrogen, -methylene-N(R)R and -NHC(=O)R;

[0422] R 9b is selected from hydrogen and

[0423] R 10 for

[0424] In certain embodiments, the compound of the structure shown in Formula I, wherein,

[0425] X 1 Selected from N and C(R 1 ), R 1 is selected from the group consisting of hydrogen, fluorine, chlorine, cyano, -OH, methyl, ethyl, propyl, -O-methyl, -O-ethyl, and -O-propyl;

[0426] X 2 Selected from N and C(R 2 ), R 2 is selected from the group consisting of hydrogen, fluorine, chlorine, cyano, -OH, methyl, ethyl, propyl, -O-methyl, -O-ethyl, and -O-propyl;

[0427] R 31 is selected from the group consisting of hydrogen, fluorine, chlorine, cyano, -OH, -SH, -NH2, methyl, halomethyl, -CH2OH and -CH2CH2N(CH3)2;

[0428] R 3 is selected from oxazolyl, pyrazolyl and pyrimidinyl, wherein R 3 Optional 1, 2 or 3 R 31 replace;

[0429] R 4 is selected from hydrogen, fluorine, chlorine, cyano, -OH and -NH2;

[0430] X is selected from O;

[0431] Structural unit for

[0432] R 5 selected from hydrogen and -NH2;

[0433] R 6 is selected from hydrogen, fluorine, chlorine, bromine, cyano, -OH, -NH2 and -O-methyl;

[0434] Structural unit for

[0435] R 7 each independently selected from hydrogen, fluorine, chlorine, bromine, cyano, -OH, -NH2, -(C1-C4)alkylene-OH, -(C1-C4)alkylene-NH(C1-C4)alkyl, -(C1-C4)alkylene-N[(C1-C4)alkyl]2 and -(C1-C4)alkylene-NH2;

[0436] m is 1, 2, or 3;

[0437] Each R is independently selected from hydrogen, -OH, -(C1-C4)alkyl and -O-(C1-C4)alkyl, each of the foregoing groups being independently optionally substituted with 1, 2 or 3 groups selected from hydrogen, halogen, -OH, -NH2, -NH-methyl and -N(methyl)2;

[0438] R 8a for

[0439] R 8b is selected from -methylene-R, -C(=O)OR, -C(=O)N(R)R, and -C(=O)R;

[0440] R 9a is selected from hydrogen and -methylene-N(R)R;

[0441] R 9b is selected from hydrogen and

[0442] R 10 for

[0443] In certain embodiments, the compound of the structure shown in Formula I, wherein,

[0444] X 1 C(R 1 );

[0445] R 1is selected from the group consisting of hydrogen, fluorine, chlorine, cyano, -OH, methyl, ethyl, propyl, -O-methyl, -O-ethyl, and -O-propyl;

[0446] X 2 Selected from CH;

[0447] R 31 is selected from the group consisting of hydrogen, fluorine, chlorine, cyano, -OH, -SH, -NH2, -CH2OH, -CH2NH2, methyl, trifluoromethyl and -O-methyl;

[0448] R 3 Selected from The R 3 Optional 1, 2 or 3 R 31 replace;

[0449] R 4 is hydrogen;

[0450] X is O;

[0451] Structural unit for

[0452] R 5 is selected from hydrogen, -OH, -NH2 and -CH2NH2;

[0453] R 6 is selected from hydrogen, fluorine, chlorine, bromine, cyano, -OH, -NH2, cyclopropyl and -O-methyl;

[0454] or R 5 and R 6 The atoms connected to it form Where * indicates the connected atomic positions;

[0455] Structural unit for

[0456] R 7 are each independently selected from hydrogen, fluorine, chlorine, bromine, -OH and -NH2;

[0457] R 8a for

[0458] R 8b Selected from hydrogen,

[0459] R 9a Selected from hydrogen,

[0460] R 9b Selected from hydrogen and

[0461] R 10 for

[0462] In certain embodiments, the compound of the structure shown in Formula I, wherein,

[0463] X 1 C(R 1 );

[0464] R 1 is selected from the group consisting of hydrogen, fluorine, chlorine, cyano, -OH, methyl, ethyl, propyl, -O-methyl, -O-ethyl, and -O-propyl;

[0465] X 2 Selected from CH;

[0466] R 31 is selected from the group consisting of hydrogen, fluorine, chlorine, cyano, -OH, -SH, -NH2, -CH2OH, methyl, trifluoromethyl and -O-methyl;

[0467] R 3 Selected from The R 3 Optional 1, 2 or 3 R 31 replace;

[0468] R 4 is hydrogen;

[0469] X is O;

[0470] Structural unit for

[0471] R 5 is selected from hydrogen, -OH, -NH2 and -CH2NH2;

[0472] R 6 is selected from hydrogen, fluorine, chlorine, bromine, cyano, -OH, -NH2 and -O-methyl;

[0473] or R 5 and R 6 The atoms connected to it form Where * indicates the connected atomic positions;

[0474] Structural unit for

[0475] R 7are each independently selected from hydrogen, fluorine, chlorine, bromine, -OH and -NH2;

[0476] R 8a for

[0477] R 8b Selected from hydrogen,

[0478] R 9a Selected from hydrogen,

[0479] R 9b Selected from hydrogen and

[0480] R 10 for

[0481] In certain embodiments, the compound of the structure shown in Formula I, wherein,

[0482] X 1 C(R 1 );

[0483] R 1 is selected from the group consisting of hydrogen, fluorine, chlorine, cyano, -OH, methyl, ethyl, propyl, -O-methyl, -O-ethyl, and -O-propyl;

[0484] X 2 Selected from CH;

[0485] R 31 is selected from hydrogen, fluorine, chlorine, cyano, -OH, -SH and -NH2;

[0486] R 3 Selected from The R 3 Optional 1, 2 or 3 R 31 replace;

[0487] R 4 is hydrogen;

[0488] X is O;

[0489] Structural unit for

[0490] R 5 selected from hydrogen;

[0491] R 6 is selected from hydrogen, fluorine, chlorine, bromine, cyano, -OH, -NH2 and -O-methyl;

[0492] Structural unit for

[0493] R 7 are each independently selected from hydrogen, fluorine, chlorine, bromine, -OH and -NH2;

[0494] R 8a for

[0495] R 8b Selected from

[0496] R 9a Selected from hydrogen and

[0497] R 9b Selected from hydrogen and

[0498] R 10 for

[0499] In certain embodiments, the racemate is a racemate.

[0500] In certain embodiments, the compound is selected from the compound represented by formula I-1,

[0501] in,

[0502] X, X 1 、X 2 , Ring B, Ring C, R 31 、R 4 、R 5 、R 6 、R 7 、R 8a 、R 8b 、R 9a 、R 9b 、R 10 and m are as defined in any embodiment of the present invention,

[0503] n is 0, 1, 2, 3, 4 or 5,

[0504] Ring A is selected from 5-10 membered heteroaryl groups.

[0505] In certain embodiments, the structural fragment The definition of R 3 As defined, R 3 is as defined in any embodiment of the present invention.

[0506] In certain embodiments, Ring A is a 5-9 membered heteroaryl.

[0507] In certain embodiments, Ring A is a 5-6 membered heteroaryl.

[0508] In certain embodiments, the ring A is selected from the group consisting of oxazolyl, thiazolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, pyridinyl, and pyrimidinyl.

[0509] In certain embodiments, the ring A is selected from

[0510] In certain embodiments, the ring A is selected from

[0511] In certain embodiments, the ring A is selected from oxazolyl and pyrimidinyl.

[0512] In certain embodiments, the ring A is selected from

[0513] In certain embodiments, the compound is selected from the compound represented by formula I-1-A,

[0514] in,

[0515] X, X 1 、X 2 、R 31 、R 4 、R 5 、R 6 、R 7 、R 8a 、R 8b 、R 9a 、R 9b 、R 10 and m are as defined in any embodiment of the present invention, and ring A and n are as defined in any embodiment of the present invention.

[0516] In certain embodiments, the structural unit for

[0517] In certain embodiments, the structural unit for

[0518] In certain embodiments, the compound is selected from the compound represented by formula I-1-B,

[0519] in,

[0520] X, X 1 、X 2, Ring B, Ring C, R 31 、R 4 、R 5 、R 6 、R 7 、R 8b 、R 9a 、R 9b 、R 10 and m are as defined in any embodiment of the present invention, and ring A and n are as defined in any embodiment of the present invention.

[0521] In certain embodiments, the compound is selected from the compound represented by formula I-1-AB-1,

[0522] in,

[0523] X, X 1 、X 2 、R 31 、R 4 、R 5 、R 6 、R 7 、R 8b 、R 9b 、R 10 and m are as defined in any embodiment of the present invention, and ring A and n are as defined in any embodiment of the present invention.

[0524] In certain embodiments, the compound is selected from the compound represented by formula I-1-AB-1A or formula I-1-AB-1B.

[0525] in,

[0526] X, X 1 、X 2 、R 31 、R 4 、R 5 、R 6 、R 7 、R 9b 、R 10 and m are as defined in any embodiment of the present invention, ring A and n are as defined in any embodiment of the present invention, R 8b1 is selected from R and N(R)R, and R is as defined in any embodiment of the present invention.

[0527] In certain embodiments, the compound is selected from the compound represented by formula I-1-AB-1C or formula I-1-AB-1D,

[0528] in,

[0529] R 31、R 1 、R 4 、R 5 、R 6 、R 7 、R 8b 、R 9b 、R 9a and m are as defined in any embodiment of the present invention, ring A and n are as defined in any embodiment of the present invention, R 8b1 is selected from R and N(R)R, and R is as defined in any embodiment of the present invention.

[0530] In certain embodiments, the compound is selected from the compound represented by formula I-1-AB-1D,

[0531] in,

[0532] R 1 is selected from hydrogen, halogen, cyano, -OH, -(C1-C4)alkyl and -O-(C1-C4)alkyl, preferably selected from hydrogen, fluorine, chlorine, cyano, -OH, methyl, ethyl, propyl, -O-methyl, -O-ethyl and -O-propyl;

[0533] Ring A is selected from oxazolyl, pyrazolyl and pyrimidinyl, preferably selected from Ring A is optionally substituted with 1, 2 or 3 R 31 replace;

[0534] R 31 each independently selected from hydrogen, fluorine, chlorine, cyano, -OH, -SH, -NH2, -(C1-C4)alkyl, -O-(C1-C4)alkyl, -(C1-C4)alkylene-OH, -(C1-C4)alkylene-NH2 and -(C1-C4)haloalkyl, preferably selected from hydrogen, fluorine, chlorine, cyano, -OH, -SH, -NH2, -CH2OH, -CH2NH2, -CH3, -CF3 and -OCH3;

[0535] Alternatively, a structural fragment Selected from

[0536] R 4 is hydrogen;

[0537] R 5 is hydrogen or -NH2;

[0538] R 6Selected from hydrogen, fluorine, chlorine, bromine, cyano, -OH, -NH2, -(C1-C4)alkyl, -(C1-C4)alkyl-OH, -(C1-C4)alkyl-NH2, -(C1-C4)haloalkyl, -O-(C1-C4)alkyl, -O-(C1-C4)haloalkyl and -(C3-C6)cycloalkyl, preferably selected from hydrogen, fluorine, chlorine, bromine, cyano, -OH, -NH2, cyclopropyl and -O-methyl;

[0539] R 7 are each independently selected from hydrogen, fluorine, chlorine, bromine, -OH and -NH2;

[0540] m is 0, 1, 2, or 3;

[0541] R 8b is selected from hydrogen, -methylene-R, -methylene-OR, -methylene-N(R)R, -C(=O)R, -C(=O)OR and -C(=O)N(R)R, R is defined as described in any embodiment of the present invention, for example, each R is independently selected from hydrogen, -OH, -NH2, -(C1-C4)alkyl, -O-(C1-C4)alkyl, -C(=O)-(C1-C4)alkyl, -S(=O)2(C1-C4)alkyl and -(4-8 membered)heterocyclyl, wherein the -(C1-C4)alkyl and -(4-8 membered)heterocyclyl are optionally substituted with 1, 2, 3, 4 or 5 groups selected from hydrogen, halogen, -OH, -NH2, -NHCH3 and CH3; 8b Preferably selected from hydrogen,

[0542] R 9a is selected from hydrogen, -CN, -N(R)R, -NHC(=O)R, -methylene-N(R)R, -methylene-NHC(=O)R and -methylene-NHC(=O)NHR, R is defined as described in any embodiment of the present invention, for example, each R is independently selected from hydrogen, -OH, methyl, ethyl, -methylene-O-ethyl, -S(=O)2-methyl, cyclobutyl, azetidinyl, -methylene-cyclobutyl and -methylene-azetidinyl, each of the foregoing groups is optionally substituted by 1, 2 or 3 groups selected from -OH, OCH3, NHCH3, N(CH3)2 and CH3; R 9a Preferably selected from hydrogen,

[0543] R 9b Selected from hydrogen and

[0544] In certain embodiments, the compound is selected from

[0545] In certain embodiments, the compound is a racemate of a compound represented by Formula I, Formula I-1, Formula I-1-A, Formula I-1-B, I-1-AB-1, I-1-AB-1A, Formula I-1-AB-1B, I-1-AB-1C, or Formula I-1-AB-1D.

[0546] In certain embodiments, the compound is a mixture of a compound represented by Formula I, Formula I-1, Formula I-1-A, Formula I-1-B, I-1-AB-1, I-1-AB-1A, Formula I-1-AB-1B, I-1-AB-1C or Formula I-1-AB-1D and its enantiomers.

[0547] In certain embodiments, the content of the compound represented by Formula I, Formula I-1, Formula I-1-A, Formula I-1-B, I-1-AB-1, I-1-AB-1A, Formula I-1-AB-1B, I-1-AB-1C or Formula I-1-AB-1D in the mixture of the compound represented by Formula I, Formula I-1, Formula I-1-A, Formula I-1-B, I-1-AB-1, I-1-AB-1A, Formula I-1-AB-1B, I-1-AB-1C or Formula I-1-AB-1D and its enantiomer is ≥60%, or ≥70%, or ≥80%, or ≥85%, or ≥90%, or ≥91%, or ≥92%, or ≥93%, or ≥94%, or ≥95%, or ≥96%, or ≥97%, or ≥98%, or ≥99%.

[0548] The second aspect of the present invention provides a pharmaceutical composition comprising at least one compound of the first aspect of the present invention, or its racemate, enantiomer, diastereomer, pharmaceutically acceptable salt, isotopically labeled compound, or mixtures thereof, and one or more pharmaceutically acceptable carriers and / or excipients. In certain embodiments, the compound, or its racemate, enantiomer, diastereomer, pharmaceutically acceptable salt, isotopically labeled compound, or mixtures thereof, is present in the pharmaceutical composition in an effective amount, preferably a therapeutically effective amount, or a prophylactically effective amount.

[0549] The third aspect of the present invention provides the use of the compound described in the first aspect of the present invention or its racemate, enantiomer, diastereomer, pharmaceutically acceptable salt, isotope-labeled compound, or mixture of the foregoing forms, or the pharmaceutical composition described in the second aspect of the present invention in the preparation of a medicament for treating and / or preventing a disease or condition or alleviating the severity of the disease or condition, wherein the disease or condition is a tumor or cancer.

[0550] The third aspect of the present invention also provides the compound described in the first aspect of the present invention or its racemate, enantiomer, diastereomer, pharmaceutically acceptable salt, isotope-labeled compound, or mixture of the foregoing forms, or the pharmaceutical composition described in the second aspect of the present invention, which is used to treat and / or prevent a disease or condition or alleviate the severity of the disease or condition, wherein the disease or condition is a tumor or cancer.

[0551] The third aspect of the present invention also provides a method for treating and / or preventing a disease or condition or alleviating the severity of the disease or condition, which comprises administering to an individual in need thereof an effective amount of the compound of the first aspect of the present invention or its racemate, enantiomer, diastereomer, pharmaceutically acceptable salt, isotope-labeled compound, or a mixture of the foregoing forms, or the pharmaceutical composition of the second aspect of the present invention, wherein the disease or condition is a tumor or cancer.

[0552] In certain embodiments, the tumor or cancer is selected from leukemia, malignant lymphoma, multiple myeloma, gastric cancer, colorectal cancer, pancreatic cancer, colon cancer, breast cancer, ovarian cancer, liver cancer, and lung cancer.

[0553] In certain embodiments, the tumor or cancer is selected from leukemia, malignant lymphoma, multiple myeloma, gastric cancer, colorectal cancer, breast cancer, ovarian cancer, liver cancer, and lung cancer.

[0554] In certain embodiments, the tumor or cancer is selected from gastric cancer, colorectal cancer, breast cancer, ovarian cancer, and liver cancer.

[0555] In certain embodiments, the colorectal cancer is selected from colorectal adenocarcinoma and colon cancer.

[0556] In certain embodiments, the breast cancer is selected from ductal carcinoma.

[0557] Definition of terms

[0558] The various terms and phrases used in this application have general meanings known to those skilled in the art. Even so, this application still hopes to provide a more detailed description and explanation of these terms and phrases. If the mentioned terms and phrases are inconsistent with the known meanings, the meanings expressed in this application shall prevail.

[0559] As used herein, the term "pharmaceutically acceptable salt" refers to a salt of a compound of the invention that is pharmaceutically acceptable and possesses the desired pharmacological activity of the parent compound. Such salts include acid addition salts formed with inorganic or organic acids, or coordination compounds formed by the substitution of acidic protons present in the parent compound with metal ions or organic bases.

[0560] As used herein, the term "isotopically labeled compound" refers to a compound in which one or more atoms are replaced by atoms having the same atomic number but an atomic mass or mass number different from the atomic mass or mass number predominant in nature. Examples of suitable isotopes for inclusion in the compounds of the present invention include, but are not limited to, hydrogen isotopes such as 2 H, 3 H; carbon isotopes such as 11 C, 13 C and 14 C; chlorine isotopes such as 36 Cl; fluorine isotopes such as 18 F; iodine isotopes such as 123 I and 125 I; Nitrogen isotopes such as 13 N and 15 N; oxygen isotopes such as 15 O, 17 O and 18 O; and sulfur isotopes such as 35 S.

[0561] As used in this application, the term "racemate" includes "racemate". The term "racemate" refers to an equimolar mixture of an optically active chiral molecule and its enantiomer; the term "enantiomer" refers to one of a pair of molecular entities that are mirror images of each other and are non-superimposable. A mixture of enantiomers can be separated under conditions such as chiral resolution; the term "diastereomer" refers to stereoisomers that are not related to each other as mirror images. Diastereomers are characterized by some differences in physical and chemical properties. A mixture of diastereomers can be separated under conditions such as chromatography or crystallization.

[0562] As used in this application, "optionally substituted by..." means that the group may be unsubstituted or substituted by a substituent. For example, -(C1-C6)alkyl is optionally substituted by halogen, which means that -(C1-C6)alkyl may be unsubstituted or substituted by halogen to obtain a haloalkyl. It should be understood that when a group consists of multiple parts, one of which can be substituted, then this part in the group can also be substituted. For example, when it is expressed that the group is selected from -(C1-C6)alkyl, -O-(C1-C6)alkyl and -NH(C1-C6)alkyl, and the -(C1-C6)alkyl is optionally substituted by halogen, it is used to indicate that the (C1-C6)alkyl in -(C1-C6)alkyl, -O-(C1-C6)alkyl and -NH(C1-C6)alkyl are all optionally substituted by halogen. For example, "R is selected from methyl, -O-methyl, -NH-methyl, -S-methyl, -C(=O)-methyl and -C(=O)NH-methyl, and the methyl is optionally substituted by 1 hydroxyl or amino group" means that the methyl group and the methyl groups in -O-methyl, -NH-methyl, -S-methyl, -C(=O)-methyl and -C(=O)NH-methyl are all optionally substituted by 1 hydroxylamino group.

[0563] As used herein, the term "halogen" refers to fluorine, chlorine, bromine, and iodine.

[0564] As used herein, the term "alkyl" refers to a linear or branched monovalent saturated hydrocarbon group, for example, a (C1-C6) alkyl group has 1 to 6 carbon atoms, such as 1, 2, 3, 4, 5, or 6 carbon atoms; a (C1-C4) alkyl group has 1 to 4 carbon atoms, such as 1, 2, 3, or 4 carbon atoms. Non-limiting examples of alkyl groups include, but are not limited to, methyl, ethyl, propyl, propyl, butyl, and the like.

[0565] As used herein, the term "alkylene" refers to a linear or branched divalent saturated hydrocarbon group, for example, (C1-C8)alkylene refers to a group having 1 to 8 carbon atoms, such as 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms; (C1-C4)alkylene refers to a group having 1 to 4 carbon atoms, such as 1, 2, 3 or 4 carbon atoms; (C1-C8)alkylene includes (C1-C7), (C1-C6), (C1-C5), (C1-C4)alkylene, etc. Non-limiting examples of alkylene include, but are not limited to, methylene, ethylene, propylene, butylene, etc.

[0566] As used herein, the term "halo" refers to a group that is substituted with one or more halogens, such as 1, 2, 3, 4, 5, or 6 halogens. For example, "(C1-C6)haloalkyl" refers to a (C1-C6)alkyl group as defined above that is substituted with one or more halogens, non-limiting examples of which include but are not limited to CF3, CHF2, or CF2CF3.

[0567] As used herein, the term "alkenyl" refers to a straight or branched unsaturated hydrocarbon group containing at least one double bond. (C2-C6)alkenyl refers to a group having 2 to 6 (e.g., 2, 3, 4, 5, or 6) carbon atoms, including (C2-C5)alkenyl, (C2-C4)alkenyl, (C2-C3)alkenyl, and the like. Non-limiting examples include, but are not limited to, -CH=CH2, -CH=CH-CH=CH2, or -CH=C(CH)3-CH3, and the like.

[0568] As used herein, the term "alkynyl" refers to a straight-chain or branched unsaturated hydrocarbon group containing at least one triple bond, such as (C 2- C6) alkynyl refers to a group having 2 to 6 (such as 2, 3, 4, 5 or 6) carbon atoms, including (C 2- C5) alkynyl, (C 2- C4) alkynyl, (C 2- C3) alkynyl, etc. Non-limiting examples include but are not limited to ethynyl or propynyl, etc.

[0569] As used herein, the term "cycloalkyl" refers to a monovalent saturated hydrocarbon group consisting of carbon atoms, for example, a (C3-C6) cycloalkyl group consisting of 3-6 (e.g., 3, 4, 5, or 6) carbon atoms. The cycloalkyl group includes a monocyclic, bicyclic, or polycyclic ring, including a spirocyclic, cyclocyclic, or bridged ring. Non-limiting examples include, but are not limited to, cyclobutyl, cyclopentyl, or cyclohexyl.

[0570] As used herein, the term "heterocyclyl" refers to a saturated or partially unsaturated monovalent cyclic group consisting of ring atoms, wherein 1, 2, 3 or 4 of the ring atoms are heteroatoms and the rest are carbon atoms; preferably, the heteroatoms are selected from N, O or S, wherein the nitrogen atom is optionally quaternized, and the nitrogen and sulfur heteroatoms are optionally oxidized; preferably, the carbon atoms are optionally substituted with =O. For example, a (4-10 membered) heterocyclyl refers to a group consisting of 4, 5, 6, 7, 8, 9 or 10 ring atoms, and a (4-10 membered) heterocyclyl includes a (4-9 membered) heterocyclyl, a (4-8 membered) heterocyclyl, a (4-7 membered) heterocyclyl, a (4-6 membered) heterocyclyl, a 5-membered heterocyclyl, a 6-membered heterocyclyl, etc. The heterocyclyl includes a monocyclic, bicyclic or polycyclic ring, including a spirocyclic, fused or bridged ring. Non-limiting examples include, but are not limited to, oxetanyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, or imidazolinyl, and the like.

[0571] As used herein, the term "aryl" refers to an unsaturated carbocyclic group having a conjugated π electron system, such as (C6-C 10 ) aryl consists of 6 to 10 (e.g., 6, 7, 8, 9 or 10) carbon atoms. Non-limiting examples include, but are not limited to, phenyl and the like.

[0572] As used herein, the term "heteroaryl" refers to an unsaturated group having a conjugated π electron system consisting of ring atoms, wherein 1, 2, 3 or 4 of the ring atoms are heteroatoms and the rest are carbon atoms; preferably, the heteroatoms are selected from N, O or S, wherein the nitrogen atom is optionally quaternized, and the nitrogen and sulfur heteroatoms are optionally oxidized. For example, a (5-12 membered) heteroaryl group is composed of 5 to 12 (e.g., 5, 6, 7, 8, 9, 10, 11 or 12) ring atoms, including 5-10 membered, 5-9 membered, 6-9 membered, 5-6 membered heteroaryl groups, etc. The heteroaryl group includes monocyclic and polycyclic rings, non-limiting examples of which include, but are not limited to, imidazolyl or pyridyl groups.

[0573] As used herein, the term "pharmaceutically acceptable carrier and / or excipient" refers to a carrier and / or excipient that is pharmacologically and / or physiologically compatible with the subject and the active ingredient, as is well known in the art (see, for example, Remington's Pharmaceutical Sciences. Edited by Gennaro AR, 19th ed. Pennsylvania: Mack Publishing Company, 1995). Pharmaceutically acceptable carriers and / or excipients include, but are not limited to, pH adjusters, surfactants, ionic strength enhancers, diluents, agents that maintain osmotic pressure, agents that delay absorption, preservatives, and stabilizers. For example, pH adjusters include, but are not limited to, phosphate buffers. Surfactants include, but are not limited to, cationic, anionic, or nonionic surfactants, such as Tween-80. Ionic strength enhancers include, but are not limited to, sodium chloride. Preservatives include, but are not limited to, various antibacterial and antifungal agents, such as parabens, chlorobutanol, phenol, sorbic acid, and the like. Agents that maintain osmotic pressure include, but are not limited to, sugars, NaCl, and their analogs. Agents that delay absorption include, but are not limited to, monostearate and gelatin. Diluents include, but are not limited to, water, aqueous buffers (such as buffered saline), alcohols and polyols (such as glycerol), etc. Preservatives include, but are not limited to, various antibacterial and antifungal agents, such as thimerosal, 2-phenoxyethanol, parabens, chlorobutanol, phenol, sorbic acid, etc. Stabilizers have the meanings generally understood by those skilled in the art, and are capable of stabilizing the desired activity of the active ingredient in the drug, including, but not limited to, sodium glutamate, gelatin, SPGA, sugars (such as sorbitol, mannitol, starch, sucrose, lactose, dextran, or glucose), amino acids (such as glutamic acid, glycine), proteins (such as dried whey, albumin, or casein), or degradation products thereof (such as lactalbumin hydrolysate), etc.

[0574] As used herein, the term "treatment" is intended to alleviate, mitigate, improve, or eliminate the disease state or condition being treated. If a subject receives a therapeutic amount of the ligand-conjugated drug or its racemate, enantiomer, diastereomer, pharmaceutically acceptable salt, or mixture of the foregoing forms according to the methods described herein, and the subject exhibits an observable and / or detectable reduction or improvement in one or more signs and symptoms, the subject is successfully "treated." It should also be understood that the treatment of the disease state or condition includes not only complete treatment, but also achieving some biologically or medically relevant results despite not achieving complete treatment.

[0575] As used herein, the term "prevention" is intended to avoid, reduce, prevent, or delay the onset of a disease or disease-related symptoms, provided that the disease or disease-related symptoms have not yet appeared before the administration of the relevant drug. "Prevention" does not necessarily require the complete prevention of the onset of a disease or disease-related symptoms. For example, if the administration of the relevant drug can reduce the risk of a subject developing a particular disease or disease-related symptom, or reduce the severity of related symptoms that later appear, it can be considered to have "prevented" the onset or development of the disease.

[0576] As used in this application, the DMSO solvent used to dissolve compounds in NMR structure identification is deuterated DMSO, namely DMSO-d6. Beneficial effects:

[0577] The compound provided by the present invention has the effect of inhibiting protein translation, and can obviously inhibit cell proliferation in vitro and inhibit tumor growth in vivo.

[0578] In the in vitro tumor cell proliferation inhibition test, the small molecule compound of the present application has significant proliferation inhibition activity against BT474, DLD-1, NCI-N87, NUGC-4, SNU-423, MKN-45, SK-OV-3, Ls174T and HCC1954.

[0579] The small molecule compounds of the present application have significant tumor inhibitory effects in BALB / c nude mouse subcutaneous xenograft tumor models, such as NCI-H716, BT474, DLD-1, NCI-N87, NUGC-4, SNU-423, MKN-45, SK-OV-3, Ls174T or HCC1954 xenograft tumor models.

[0580] The small molecule compound of the present application has a significant tumor inhibitory effect in in vitro and in vivo models of hematological tumors, such as the NCI-H929 and MM.1R hematological tumor models.

[0581] In addition, the compounds provided by the present invention have excellent pharmacokinetic properties. DETAILED DESCRIPTION

[0582] The embodiments of the present invention will be described in detail below with reference to the examples, but it will be understood by those skilled in the art that the following examples are merely illustrative of the present invention and should not be construed as limiting the scope of the invention. Where specific conditions are not specified in the examples, the methods were performed according to conventional conditions or the conditions recommended by the manufacturer. Where the manufacturers of the reagents or instruments are not specified, they are all conventional products that can be obtained commercially.

[0583] Table 1

[0584] General chiral column separation method

[0585] The racemic compound of the present invention was dissolved in methanol and separated using a chiral preparative chromatographic column (see the table below) to obtain the product compound.

[0586] Example 1

[0587] Compounds 1 and 1A

[0588] Compounds 1 and 1A were synthesized according to the literature Liu, Tao; Nair, Somarajan J.; Lescarbeau, André; Belani, Jitendra; Peluso, Stéphane; Conley, James et al. (2012): Synthetic silvestrol analogues as potent and selective protein synthesis inhibitors. In Journal of medicinal chemistry 55(20), pp.8859-8878. DOI: 10.1021 / jm3011542. See Supporting information, page 7, compound S2.

[0589] Compound 2

[0590] Step 1: Compound 1 (750 mg, 1.66 mmol) and compound 2A (2752 mg, 9.93 mmol) were dissolved in CHCl₃ / TFE = 7 / 3 (15 mL). The reaction mixture was pumped at a rate of 15 mL / h via a 20 mL syringe via a syringe pump into a coil wrapped around a jacketed glass cylinder equipped with a 250 W UV lamp. The temperature of the external circulating hydrazine was adjusted to maintain an internal reaction temperature of 0-5°C. The UV lamp was simultaneously turned on and the reaction mixture was irradiated for 1 hour. The solvent was removed under reduced pressure and the excess cinnamate was removed by column chromatography (EA / PE = 1 / 3). The desired racemic product 2B was obtained as a crude yellow oil (900 mg, yield: 75%). LCMS [M+H+18] + =748.5.

[0591] Step 2: Mix the racemate of compound 2B (5.2 g, 7.96 mmol) with MeOH (50 mL), add NaOMe (1.1 g, 19.91 mmol) at 0°C, and stir at 65°C for 1.5 h. The solution was concentrated, washed sequentially with H2O, aqueous NH4Cl solution, and saturated brine, dried over Na2SO4, concentrated under reduced pressure, and purified on a silica gel column (0.2% FA, EA / PE = 1 / 3) to obtain the racemate of compound 2C (3.8 g, yield: 65%). LCMS [M+H-18] + =714.4.

[0592] Step 3: Mix the racemate of compound 2C (3.8 g, 5.21 mmol) with MeCN / CHCl3 = 1 / 1 (100 mL / 100 mL). Add NaBH(OAc)3 (5.5 g, 26.03 mmol) and AcOH (3.1 g, 52.05 mmol) at 0°C and stir at room temperature for 2 h. Extract the reaction solution with EA. The organic phase is washed sequentially with water and saturated brine, dried over anhydrous Na2SO4, and purified on a silica gel column (PE:EA = 1 / 1) to obtain the racemate of compound 2D (1.9 g, yield: 50%). LCMS [M+H] + =716.5.

[0593] Step 4: The racemate of compound 2D (1.3 g, 1.78 mmol), Pd2(dba)3 (325.0 mg, 0.36 mmol), DPPF (393.6 mg, 0.71 mmol), and Zn(CN)2 (519.5 mg, 4.44 mmol) were heated to 150°C in NMP (20 mL) for 2 h. The solution was diluted with water, extracted with EA, washed sequentially with water and brine, dried over anhydrous Na2SO4, and purified on a silica gel column (EA / PE = 1 / 1) to afford the racemate of compound 2E (1.1 g, yield: 91%).

[0594] 1 H NMR (400MHz, CDCl3) δ7.48-7.40 (m, 6H), 7.37 (dt, J = 12.4, 5.3Hz, 3H), 6.96 (t, J=7.9Hz,1H),6.85(s,1H),6.51(d,J=7.7Hz,1H),6.45(s,1H),6.36(d,J=1.9Hz ,1H),6.22(d,J=1.9Hz,1H),5.09(d,J=1.7Hz,2H),5.01(d,J=6.4Hz,1H),4.35 (d,J=14.2Hz,1H),3.95-3.81(m,4H),3.66(d,J=3.8Hz,3H),1.53-1.47(m,9H). LCMS[M+H-18] + =605.4.

[0595] Step 5: Pd(OH)2 / C (10%, 250 mg) was added to a solution of the racemate of compound 2E (500.0 mg, 0.74 mol) in EA / MeOH / THF / DCM = 20:2:2:0.2 (40 mL). The atmosphere was replaced with hydrogen three times, and the mixture was stirred at room temperature for 16 hours. The suspension was filtered, and the filter cake was washed with MeOH / DCM (1 / 10). The filtrate was concentrated and purified on a silica gel column (DCM / MeOH = 10 / 1) to obtain the racemate of compound 2F (300 mg, yield: 69%).

[0596] 1 H NMR (400MHz, CDCl3) δ7.42(d,J=8.6Hz,2H),7.33(d,J=8.6Hz,2H),6.98(dd,J=16.1 ,8.2Hz,1H),6.87(s,1H),6.51(d,J=7.7Hz,1H),6.33(s,1H),6.24(d,J=1.8Hz,1H), 6.12(d,J=1.7Hz,1H),4.98(d,J=6.3Hz,1H),4.35(d,J=14.2Hz,1H),3.90(dd,J=14 .1, 6.4Hz, 1H), 3.83 (d, J = 15.4Hz, 3H), 3.67 (d, J = 4.5Hz, 3H), 1.50 (d, J = 4.8Hz, 9H). LCMS[M+H] + =515.4.

[0597] Step 6: The racemate of compound 2F (306.0 mg, 0.52 mmol) and K2CO3 (143.6 mg, 1.04 mmol) were stirred in DMF (10 mL). Compound 2G (185.8 mg, 0.52 mmol) was added, and the reaction mixture was stirred at 60°C for 20 min. The solution was diluted with water, extracted with EA, washed sequentially with water and brine, dried over anhydrous Na2SO4, and purified on a silica gel column (EA / PE = 1 / 1) to obtain the racemate of compound 2H (300 mg, yield: 80%).

[0598] 1 H NMR (400MHz, CDCl3) δ7.41(d,J=8.4Hz,2H),7.33(d,J=8.5Hz,2H),7.00-6.92(m,2H),6.69(d,J=1.7Hz,1H),6.53(d,J=7.6Hz,1H ), 6.45 (d, J = 1.7Hz, 1H), 6.39 (s, 1H), 4.99 (d, J = 5.9Hz, 1H), 4.39 (d, J = 14.2Hz, 1H), 3.99-3.91 (m, 4H), 3.68 (s, 3H), 1.50 (s, 9H). LCMS[MH] + =719.2.

[0599] Step 7: A solution of the racemate of compound 2H (30 mg, 0.042 mmol) was added to DMF (3 mL). Under nitrogen, compound 2I (60 mg, 0.167 mmol), Pd(PPh3)4 (4.8 mg, 0.0042 mmol), and CuI (1.6 mg, 0.0083 mmol) were added. The mixture was stirred at 100°C for 1 h. The suspension was filtered and purified on a silica gel column (DCM / MeOH = 10 / 1) to obtain the racemate of compound 2J (15 mg, yield: 56%). LCMS [M+H] + =640.3.

[0600] Step 8: To a solution of the racemate of compound 2J (15 mg, 0.02 mmol) was added THF / 6M HCl = 1 / 1 (4 mL) and stirred at room temperature for 1 h. The solution was concentrated and purified by silica gel chromatography (DCM / MeOH) to afford the racemate of 2 as a white solid (4.5 mg, yield: 35%). Further chiral column separation afforded compound 2.

[0601] LCMS [M+H] + =540.1.

[0602] 1H NMR (400MHz, DMSO) δ8.25(d,J=0.7Hz,1H),7.50(d,J=8.6Hz,2H),7.41(d,J=0.7Hz,1H),7. 31(d,J=8.6Hz,2H),7.19(d,J=1.1Hz,1H),7.14(d,J=1.0Hz,1H),6.67(t,J=7.7Hz,1H),6. 26(s,1H),6.19-6.10(m,2H),5.63(s,1H),5.45(d,J=5.4Hz,1H),4.83(s,2H),4.66(t,J=5 .1Hz,1H),4.27(d,J=14.0Hz,1H),3.97(dd,J=13.9,4.8Hz,1H),3.83(s,3H),3.58(s,3H).

[0603] Step 9: 60% NaH (21.87 g, 546.88 mmol) was added to THF (2.5 L) at 0°C. The mixture was stirred at 0°C for 1 h, followed by the dropwise addition of compound 2L (99.59 g, 546.88 mmol). The mixture was stirred at 0°C for 2 h, followed by the dropwise addition of a solution of compound 2K (100.00 g, 451.97 mmol) in THF (300 mL). The mixture was stirred at room temperature for 3 h, followed by the addition of 10% HCl and extraction with ethyl acetate. The combined organic phases were dried over NaSO, filtered, and concentrated to afford the crude product, which was slurried with MTBE to afford 2A (120 g, 95.73% yield) as a pale yellow solid.

[0604] 1 H NMR (400MHz, DMSO) δ9.47(s,1H),7.74(s,1H),7.58(d,J=16.0Hz,1H),7.49(d,J= 7.2Hz, 1H), 7.36-7.28 (m, 2H), 6.49 (d, J = 16.0Hz, 1H), 3.73 (s, 3H), 1.49 (s, 9H).

[0605] Compound 3

[0606] Step 1: To a solution of the racemate of compound 2H (50 mg, 0.07 mmol) in dioxane / water (2 mL / 0.5 mL) were added NaCO (48.8 mg, 0.14 mL), Pd(PPh) (4.88 mg, 0.01 mmol), and compound 3A (28.3 mg, 0.08 mmol). The mixture was reacted at 80°C under nitrogen for 2 hours. The mixture was filtered and concentrated under reduced pressure. The crude product was purified by flash column chromatography (DCM / EA = 1 / 1) to afford the racemate of compound 3B as a light yellow solid (40 mg, yield: 76%). LCMS: [M+H] + =796.4.

[0607] Step 2: The racemate of compound 3B (20 mg, 0.025 mmol) was dissolved in 6M HCl (1 mL) / THF (0.5 mL) and stirred for 3 hours. The reaction solution was purified by preparative HPLC (ACN / H2O from 0 to 100%) to obtain the racemate of 3 as a white solid (6 mg, yield: 45%). Further chiral column separation afforded compound 3.

[0608] LCMS: [M+H] + =540.2.

[0609] 1 H NMR (400MHz, DMSO) δ8.46 (s, 1H), 7.79 (s, 1H), 7.51 (d, J = 8.4Hz, 2H), 7.32 (d, J = 8.4Hz, 2H), 7.03-6.89 (m, 3H), 6. 68(s,3H),4.68(d,J=4.8Hz,1H),4.34(d,J=13.6Hz,1H),4.09(dd,J=14.0,4.8Hz,1H),3.83(s,3H),3.59(s,3H).

[0610] Compound 4

[0611] Step 1: A solution of the racemate of compound 2J (150 mg, 0.23 mmol) and LiOH (25 mg, 0.59 mmol) in THF / H2O / MeOH (10 mL) was stirred at room temperature for 3 h. The pH was adjusted to 5 with 3 M hydrochloric acid and the mixture was concentrated and purified on a silica gel column (DCM / MeOH) to obtain the racemate of compound 4A as a white solid (130 mg, yield: 88%). LCMS [M+1] + =626.1.

[0612] Step 2: HATU (61 mg, 0.16 mmol) and DIEA (31 mg, 0.24 mmol) were added separately to a solution of the racemate of compound 4A (50 mg, 0.08 mmol) in DMF (3 mL). N,O-dimethylhydroxylamine (16 mg, 0.16 mmol) was added under N2 conditions and stirred at room temperature for 3 h. The mixture was concentrated and purified on silica gel (DCM / MeOH) to obtain the racemate of compound 4B as a white solid (20 mg, yield: 38%). LCMS [M+1] + =669.2.

[0613] Step 3: The racemate of compound 4B (12 mg, 0.02 mmol) was dissolved in a 1 / 1 THF / 6M HCl solution (4 mL) and stirred at room temperature for 1 h. The solution was concentrated and purified on silica gel (DCM / MeOH) to afford the racemate of 4 as a white solid (2.2 mg, yield: 22%). This was further resolved on a chiral column to afford 4 as a white solid.

[0614] LCMS [M+H] + =569.1.

[0615] 1H NMR (400MHz, DMSO) δ8.25(s,1H),7.53(d,J=8.5Hz,2H),7.41(s,1H),7.31(d,J=8.5Hz,2 H),7.20(d,J=0.9Hz,1H),7.15(s,1H),6.66(t,J=7.7Hz,1H),6.21(s,1H),6.16(d,J=7.9 Hz,1H),6.06(d,J=7.5Hz,1H),5.61(s,1H),5.07(d,J=4.8Hz,1H),4.83(s,2H),4.78(t,J =4.8Hz,1H),4.32(d,J=13.9Hz,1H),4.16(s,1H),3.90(s,3H),3.84(s,3H),3.09(s,3H).

[0616] Compound 5

[0617] Step 1: HATU (36.4 mg, 0.1 mmol) and DIEA (18.6 mg, 0.14 mmol) were mixed with a DMF (3 mL) solution of the racemate of compound 4A (30 mg, 0.05 mmol) under N2, followed by the addition of O-methylhydroxylamine (8 mg, 0.10 mmol) and stirring at room temperature for 3 h. The mixture was concentrated and purified by silica gel (DCM / MeOH) chromatography to afford the racemate of compound 5A as a white solid (20 mg, yield: 65%). LCMS [M+1]+ =655.2.

[0618] Step 2: The racemate of compound 5A (12 mg, 0.03 mmol) was dissolved in a 1 / 1 THF / 6M HCl solution (4 mL) and stirred at room temperature for 1 h. The solution was concentrated and purified by silica gel (DCM / MeOH) chromatography to afford the racemate of 5 as a white solid (2.6 mg, 31% yield). This was then resolved by chiral column chromatography to afford compound 5.

[0619] LCMS [M+H] + =555.1.

[0620] 1 H NMR (400MHz, DMSO) δ11.27(s,1H),8.26(s,1H),7.54(d,J=8.5Hz,2H),7.42( s,1H),7.30(d,J=8.3Hz,2H),7.20(s,1H),7.16(s,1H),7.11(t,J=7.5Hz,1H) ,6.87(d,J=18.2Hz,3H),5.65(s,1H),5.27(s,1H),4.60(d,J=4.4Hz,1H),4. 46(d,J=13.9Hz,1H),3.84(s,3H),3.74(dd,J=14.1,4.1Hz,1H),3.54(s,3H).

[0621] Compound 6

[0622] Step 1: The racemate of compound 4A (30.0 mg, 0.05 mmol), HATU (36.5 mg, 0.10 mmol), and DIEA (18.6 mg, 0.14 mmol) were stirred in DMF (3 mL) for 5 min. Dimethylamine hydrochloride (7.8 mg, 0.10 mmol) was added to the mixture and stirred for 10 min.

[0623] The solution was extracted twice with EA. The organic layer was washed with saturated brine, dried over Na2SO4, concentrated under reduced pressure, and purified on a silica gel column (DCM / MeOH = 10 / 1) to obtain the racemate of compound 6A (16.0 mg, 51% yield). LCMS [M+H] + =653.2.

[0624] Step 2: Mix the racemate of compound 6A (16.0 mg, 0.02 mmol) with THF (0.5 mL), add 6M HCl (0.5 mL) at 0°C, and stir at room temperature for 4 hours. The concentrate was purified by preparative HPLC to afford the racemate of compound 6 (5.9 mg, 46% yield) as a white solid. Further chiral column separation afforded compound 6.

[0625] LCMS [M+H] + =553.2.

[0626] 1 H NMR (400MHz, DMSO) δ8.25(s,1H),7.51(d,J=8.4Hz,2H),7.41(s,1H),7.35(d,J=8.4Hz,2H),7.18(d,J=19.6Hz,2H),6.73(d,J=7.4Hz,1H),6.40- 6.17(m,3H),5.62(s,1H),4.98(s,1H),4.73(s,1H),4.39(d,J=13.4Hz,1 H), 4.15 (dd, J = 13.3, 4.9Hz, 1H), 3.84 (s, 3H), 3.29 (s, 3H), 2.79 (s, 3H).

[0627] Compound 7

[0628] Step 1: Dissolve the racemate of compound 2H (50 mg, 2.2 mmol), pyrazole (3.7 g, 13.3 mmol), tBuXPhos-Pd-G3 (4.8 mg, 0.01 mmol), tBuXPhos (12.78 mg, 0.03 mmol), and Cs2CO3 (67 mg, 0.21 mmol) in 1,4-dioxane (2 mL). The reaction mixture was stirred at 100°C under nitrogen for 16 hours. After completion of the reaction, the mixture was quenched with water, extracted with EA, and the layers were separated. The organic phase was concentrated and purified on a silica gel column (DCM / EA = 1 / 1) to obtain the racemate of 7A as a light yellow solid (10 mg, yield: 20%). LCMS [M+H] + =639.2.

[0629] Step 2: The racemate of compound 7A (10 mg, 0.016 mmol) was dissolved in THF (0.5 mL), 6 M HCl (0.5 mL) was added, and the mixture was stirred at room temperature for 4 hours. The reaction solution was purified by flash column chromatography (ACN-H2O = 0-100%) to give the racemate of white solid 7 (4 mg, yield: 47%), which was further resolved by chiral column to give compound 7.

[0630] LCMS [M+H] + =539.1.

[0631] 1H NMR (400MHz, DMSO) δ8.58(d,J=2.4Hz,1H),7.75(d,J=1.6Hz,1H),7.51(d,J=8.4Hz,2H),7 .31(d,J=8.4Hz,2H),7.13(d,J=1.6Hz,1H),7.05(d,J=1.6Hz,1H),6.68(t,J=7.6Hz,1H), 6.58-6.54(m,1H),6.23(s,1H),6.14(m,2H),5.54(s,1H),5.39(d,J=5.2Hz,1H),4.82(s, 2H), 4.64 (t, J = 5.2Hz, 1H), 4.26 (d, J = 14.0Hz, 1H), 3.95 (m, 1H), 3.82 (s, 3H), 3.58 (s, 3H).

[0632] Compound 8

[0633] Step 1: To a solution of the racemate of compound 2H (54 mg, 0.075 mmol) and compound 8A (215 mg, 0.6 mmol) in DMF (5 mL) were added Pd(PPh) (9 mg, 0.0075 mmol) and CuI (28.5 mg, 0.015 mmol). The atmosphere was then purged with nitrogen for 2 minutes and microwaved at 120°C for 2 hours. The crude product was concentrated and purified by preparative chromatography to afford the racemate of 8B (20 mg, 40.9%) as a white solid.

[0634] LCMS: [M+H-C4H8] + =595.2.

[0635] Step 2: To a solution of the racemate of compound 8B (20 mg, 0.0308 mmol) in THF (1 mL) was added aqueous HCl (0.5 mL, 6 M). The reaction mixture was allowed to react at room temperature for 3 hours. The crude product was concentrated and purified by preparative HPLC to afford the racemate of compound 8 as a white solid (9 mg, yield: 53.1%). Further chiral column separation afforded compound 8.

[0636] LCMS: [M+H] + =551.2.

[0637] 1H NMR (400MHz, DMSO) δ9.53(s,2H),8.94(d,J=4.9Hz,2H),7.64(d,J=2.8Hz,2H),7.55-7.43(m,3H),7.36(d,J=8.6Hz,2H),7.14(t,J=7.6Hz,1H ),7.06-6.82(m,3H),5.66(d,J=58.4Hz,2H),4.74(d,J=4.6Hz,1H),4.41(d,J=13.8Hz,1H),4.18(d,J=4.8Hz,1H),3.86(s,3H),3.60(s,3H).

[0638] Compound 9

[0639] Step 1: Compound 1 (1.00 g, 2.21 mmol) and compound 9A (3.58 g, 22.08 mmol) were dissolved in a TFE / chloroform solution (CHCl₃ / TFE = 9 / 1, 18 mL). A 20 mL syringe was mounted on a syringe pump, which was connected to FEP tubing. The FEP tubing was then wrapped around two quartz cylinders, each housing a 250 W UV lamp. Both cylinders were cooled to -5°C using a low-temperature circulating pump, and a room-temperature water bath was placed outside the entire lamp system. Once the UV lamps were stably energized, the syringe pump was turned on, and the reaction solution was injected into the FEP tubes at a rate of 30 mL / h. The reaction solution was illuminated for a stable period of 1 hour. After the reaction was completed, the reaction solution was concentrated and separated by column chromatography (ethyl acetate / petroleum ether = 3 / 1) to remove excess cinnamate starting material. The crude product was diluted with ethyl acetate and reacted at 65°C for 1 hour. After further concentration, the racemic form of the target crude product 9B (0.96 g, yield 71%) was obtained as a yellow oil.

[0640] LCMS [M+H] + =615.5.

[0641] Step 2: The racemate of compound 9B (1.4 g, 2.27 mmol) was dissolved in methanol (100 mL) and NaOMe (0.3 g, 5.7 mmol) was added at 0°C. The reaction mixture was then incubated at 65°C for 1 hour. The reaction mixture was concentrated and separated by column chromatography (0.5% formic acid in ethyl acetate / petroleum ether = 1 / 3) to afford the racemate of target product 9C (0.96 g, 68% yield) as a yellow oil.

[0642] LCMS [M+H] + =615.1.

[0643] Step 3: The racemate of compound 9C (0.60 g, 0.977 mmol) and AcOH (1.06 g, 17.586 mmol) were dissolved in MeCN (40 mL) and DCM (40 mL). The mixture was then cooled to 0°C and protected with N2. STAB (1.04 g, 4.89 mmol) was added portionwise and stirred at room temperature for 1 hour. The reaction mixture was quenched with water, and aqueous NaHCO3 was added. The mixture was extracted twice with DCM. The organic layer was dried, concentrated under reduced pressure, and purified on a silica gel column (PE:EA) to afford the racemate of compound 9D as a white solid (0.32 g, 53% yield).

[0644] LCMS: [M+H] + =617.2.

[0645] Step 4: The racemate of compound 9D (2.00 g, 3.24 mmol), Cs2CO3 (1.58 g, 4.86 mmol), and MeOH (0.21 g, 6.48 mmol) were dissolved in toluene (30 mL). tBuXPhosPdG3 (51 mg, 0.06 mmol) was added and heated to 85°C for 3 hours. The reaction mixture was concentrated, diluted with MeOH / DCM (MeOH / DCM = 1 / 1), and filtered. The filtrate was concentrated and separated by column chromatography (EA / PE = 60%) to afford the racemate of the desired product 9E (810 mg, 44% yield) as a brown oil.

[0646] LCMS: [MH] - =567.0.

[0647] Step 5: Dissolve the racemate of compound 9E (300 mg, 0.53 mmol) and Pd / C (10%, 150 mg) in MeOH (15 mL) and react under H₂ for 2 hours at room temperature. The reaction mixture was filtered, and the filtrate was concentrated and separated by column chromatography to afford the racemate of target product 9F (270 mg, crude product not included in yield) as a white solid.

[0648] LCMS: [M+H] + =479.4.

[0649] Step 6: To 5 mL of DMF was added the racemate of compound 9F (360 mg, 0.75 mmol), compound 2G (268 mg, 0.75 mmol), and KCO (207 mg, 1.5 mmol) and stirred at 60°C for 1.5 hours. After cooling to room temperature, the mixture was extracted with ethyl acetate and water. The organic phase was separated and dried over anhydrous NaSO. After filtration and concentration, the crude product was purified on a silica gel column (EA / DCM from 0 to 50%) to afford the racemate of 9G as a yellow solid (360 mg, yield: 78%).

[0650] LCMS: [MH] - =609.2.

[0651] Step 7: The racemate of compound 9G (340 mg, 0.56 mmol) was dissolved in DMF (5 mL), and compound 2I (1600 mg, 4.46 mmol), Pd(PPh3)4 (65 mg, 0.06 mmol), and CuI (21 mg, 0.11 mmol) were added. The mixture was reacted at 110°C under nitrogen for 16 hours. After cooling to room temperature, the reaction solution was directly purified on a silica gel column (PE / EA = 1 / 1) to obtain the racemate of 9H as a white solid (180 mg, yield: 61%).

[0652] LCMS [M+H] + =530.0.

[0653] Step 8: To a mixture of the racemate of compound 9H (80 mg, 0.15 mmol) and pyridine (0.5 mL) was added MsCl (171 mL, 1.5 mmol) at 0°C and reacted at 0°C for 1 hour. The mixture was diluted with ethyl acetate (5 mL), washed with 1M HCl (5 mL), and the layers separated. The organic phase was purified on a silica gel column (DCM / EA = 1 / 1) to afford the racemate of compound 9I as a white solid (90 mg, yield: 97%).

[0654] LCMS [M+H] + =608.1.

[0655] Step 9: Dissolve the racemate of compound 9I (90 mg, 0.15 mmol) in DMF (0.5 mL) and add NaCN (36 mg, 0.75 mmol). Stir at room temperature for 16 hours. Extract with ethyl acetate, separate the organic phase, and dry over anhydrous NaSO. Filter and concentrate. The crude product is purified on a silica gel column (DCM / EA = 1 / 1) to afford the racemate of compound 9J as a white solid (70 mg, yield: 88%).

[0656] LCMS [M+H] + =539.1.

[0657] Step 10: The racemate of compound 9J (10 mg, 0.016 mmol) was dissolved in THF (0.5 mL). A 2M solution of lithium aluminum hydride in THF (0.08 mL) was added at 0°C, the mixture was slowly warmed to room temperature, and stirred for 1 hour. NaSO·10HO was added to quench the mixture. The resulting mixture was filtered, and the filtrate was purified on a medium-pressure preparative column (ACN / HO = 0%-100%, containing 0.1% formic acid) to afford the racemate of 9J as a white solid (7 mg, yield: 70%). Compound 9 was further resolved on a chiral column to afford compound 9.

[0658] LCMS [M+H] + =515.1.

[0659] 1 H NMR (400MHz, DMSO) δ8.26(s,1H),7.42(s,1H),7.22(d,J=4.8Hz,2H),7.13(d,J=8.4Hz,2H),7.09-7.04(m,3H),6.8 1-6.76(m,2H),6.71(d,J=8.8Hz,2H),3.97(s,3H),3.66(s,3H),3.23(d,J=13.6Hz,5H),3.13(m,1H),2.93(s,1H).

[0660] Compound 10

[0661] Step 1: To a solution of 10A (12.11 g, 70 mmol) in THF (120 mL) was slowly added NaH (9.06 g, 234.6 mmol) at 0°C. The mixture was stirred at room temperature for 0.5 hours. BnOH (16.2 g, 150 mmol) was then added and stirred at room temperature for 3 hours. The mixture was slowly quenched with water at 0°C and extracted with EtOAc. The organic phase was separated, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to give 19.6 g of compound 10B, yield: 89%. LCMS [M+H] + =317.2.

[0662] Step 2: To a solution of 10B (13.16 g, 41.6 mmol) in THF (150 mL) was slowly added dropwise MeMgBr solution (124.9 mL, 124.9 mmol) at -30°C. The mixture was then stirred at room temperature for 4.3 hours. The mixture was quenched with 6N HCl and stirred for another 2 hours. The organic phase was washed with 1N NaOH and water, separated, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel chromatography to give 7.12 g of compound 10C, yield: 46%. LCMS [M+H] +=334.2.

[0663] Step 3: Dissolve compound 10C (8.5 g, 25.5 mmol) in EA (60 mL), add Pd(OH)2 (850 mg), and stir at room temperature under a hydrogen balloon for 18 h. Concentrate to give 3.9 g of 10D as a white solid (yield: 100%). LCMS [M+H] + =154.2.

[0664] Step 4: To a solution of compound 10D (3.9 g, 25.5 mmol) and K2CO3 (9.85 g, 71.4 mmol) in acetone (40 mL) was added dropwise BnBr (4.36 g, 25.5 mmol). The mixture was stirred at room temperature for 48 h, acidified with acetic acid, diluted with water, extracted with EA, and the organic layer concentrated and washed with petroleum ether to obtain 4.80 g of an off-white solid 10E (yield: 77%). LCMS [M+H] + =244.1.

[0665] Step 5: To a solution of compound 10E (4800 mg, 19.73 mmol) in MeOH (60 mL) were added NaOH (2.368 g, 59.2 mmol) and 4-bromobenzaldehyde (3.65 g, 19.73 mol). The reaction solution was stirred at 70 ° C for 18 hours. Cooled and acidified with AcOH. Extracted with dichloromethane. The organic layer was washed with water and brine, dried and concentrated. The crude product was slurried with PE / EA to obtain 5.0 g of white solid 10F, yield: 60%. LCMS [M+H] + =410.2.

[0666] Step 6: To a solution of compound 10F (1150 mg, 2.8 mmol, 1.0 eq) in MeOH / H2O (130 mL / 65 mL) was added NaOH (785 mg, 19.6 mmol, 7.0 eq) and H2O2 (12.5 mL). The reaction mixture was stirred at 50°C for 3 hours. The mixture was cooled and filtered, and the solid was washed with a small amount of dichloromethane. The solid was acidified with AcOH and extracted with DCM. The organic layer was washed with water and brine, dried, and concentrated to give 670 mg of 10G as a white solid, yield: 57%. LCMS [M+H] + =424.0.

[0667] 1H NMR (400MHz, DMSO) δ9.99 (s, 1H), 8.56 (d, J = 2.4Hz, 1H), 8.18 (d, J = 8.8Hz, 2H) ,7.94(d,J=2.4Hz,1H),7.80(d,J=8.8Hz,2H),7.60-7.37(m,5H),5.34(s,2H).

[0668] Step 7: Compound 10G (2.5 g, 5.9 mmol) and compound 2A (9.8 g, 35.38 mmol) were dissolved in CHCl3 / TFE (7 / 3, 20 mL), and the reaction mixture was injected into a coil wrapped around a jacketed glass cylinder equipped with a 250W UV lamp at a rate of 12 mL / h through a syringe pump. The temperature of the external circulating cold hydrazine was adjusted to make the internal reaction temperature 0-5°C. At the same time, the UV lamp was turned on and the reaction mixture was irradiated for 1 hour. The solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography (EtOAc / hexane) to remove excess cinnamate to obtain a racemate of the light yellow oily product 10H (3.6 g, 75% yield). LCMS [M+H] + =700.9.

[0669] Step 8: The racemate of compound 10H (2.5 g, 3.56 mmol) was dissolved in methanol (60 mL), and NaOMe (481 mg, 8.91 mmol) was added at 0°C. The reaction solution was then stirred at 65°C for 1.5 hours. After completion of the reaction, the reaction solution was concentrated and extracted with EA, washed with water, NH4Cl solution, and saturated brine, and finally dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification was performed on a silica gel column (0.2% FA, EA / PE = 1 / 3) to obtain the racemate of compound 10I (3.0 g, crude product). LCMS [M+H] + =701.0.

[0670] Step 9: The racemate of compound 10I (3.0 g, 4.28 mmol) was dissolved in a mixed solvent of ACN / CHCl3 = 1 / 1 (40 mL / 40 mL). Na(AcO)3BH (4.533 g, 21.38 mmol) and AcOH (2.566 g, 47.0 mmol) were added at 0°C, and the reaction solution was stirred at room temperature for 2 hours. After completion of the reaction, the reaction solution was concentrated and extracted with EA, washed with water and saturated brine, and finally dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification was performed on a silica gel column (0.2% FA, EA / PE = 3 / 2) to obtain 500 mg of the racemate of compound 10J. LCMS [M+H] + =703.0.

[0671] 1 H NMR (400MHz, CDCl3) δ8.06 (s, 1H), 7.86 (d, J = 1.9Hz, 1H), 7.43 (d, J = 4.4Hz, 4H), 7.40 (dd, J = 8. 2,5.0Hz,2H),7.28(s,2H),7.15(d,J=8.5Hz,1H),7.10(d,J=2.0Hz,1H),7.06(d,J=8.7Hz,2H) ,7.00(t,J=7.9Hz,1H),6.90(s,1H),6.57(d,J=7.6Hz,1H),6.35(s,1H),5.14(s,2H),5.06(d, J=6.0Hz, 1H), 4.41 (d, J=13.9Hz, 1H), 3.95 (dd, J=14.0, 6.0Hz, 1H), 3.67 (s, 3H), 1.51 (s, 9H).

[0672] Step 10: To a solution of the racemate of compound 10J (500 mg, 0.71 mmol), DPPF (155 mg, 0.28 mmol), and Zn(CN)2 (208 mg, 1.80 mmol) in NMP (25 mL) was added Pd2(dba)3 (128 mg, 0.14 mmol). The reaction mixture was heated to 150°C under N2 protection for 1.2 hours. The solution was diluted with water and extracted with EA. The organic layer was washed with water and brine, dried, concentrated, and purified on a silica gel column (EA / PE = 1 / 1) to obtain 300 mg of the racemate of 10K as a yellow solid, in a yield of 65%. LCMS: [M+H] + =650.0.

[0673] Step 11: To a solution of the racemate of compound 10K (300 mg, 0.46 mol) in EA / MeOH / THF / DCM = 20:2:2:0.2 (7 mL) was added Pd(OH)2 / C (10%, 0.1 g). The mixture was stirred at room temperature under a hydrogen balloon for 18 hours. The solid was removed by filtration, and the filter cake was washed with MeOH / DCM (1 / 10). The combined filtrates were concentrated to give 0.22 g of the racemate of 10L as a white solid, yield: 87.0%. LCMS: [M+H] + =560.2.

[0674] Step 12: To a solution of the racemate of compound 10L (220 mg, 0.39 mmol) and compound 2G (150 mg, 0.39 mmol) in DMF (3 mL) was added K2CO3 (116 mg, 0.78 mmol). The mixture was stirred at 60°C for 1 hour. Water was added to quench the mixture, and the mixture was extracted with EtOAc. The organic phase was separated, dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified by column chromatography (EA-PE / DCM=0-50%) to give 221 mg of the racemate of 10M as a yellow solid, yield: 82%. LCMS [M+H-C4H8] + =636.1.

[0675] Step 13: The racemate of compound 10M (70 mg, 0.1 mmol), compound 2I (280 mg, 0.8 mmol), Pd(PPh3)4 (12 mg, 0.01 mmol) and CuI (4 mg, 0.02 mmol) were added to DMF (3 mL), and then stirred at 135°C under N2 protection in a microwave for 5 hours. Water was added and extracted with EA. The organic layer was washed with water and saturated brine, then dried and concentrated. The crude product was dissolved in DCM, and Boc2O (2 equivalents) and DIPEA (3 equivalents) and DMAP (0.2 equivalents) were added. The mixture was stirred at 40°C for 18 hours. It was concentrated and purified by flash chromatography (DCM / EA=1:1, DCM:MeOH=20:1) to give 60 mg of the racemate of 10N as a white solid, yield: 98%. LCMS [M+H] + =611.2.

[0676] Step 14: To a solution of the racemate of compound 10N (60 mg, 0.1 mmol) in THF (2 mL) was added H2O (2 mL), MeOH (2 mL), and LiOH (12.6 mg, 0.30 mmol), followed by stirring at room temperature for 5 hours. Purification by reverse phase chromatography (MeCH / HCO2H / H2O) afforded 30 mg of the racemate of compound 10N as a white solid, yield: 51%. LCMS [M+H] + =597.2.

[0677] Step 15: The racemate of compound 10O (30 mg, 0.048 mmol), N,O-dimethylhydroxylamine (9 mg, 0.096 mmol), HATU (18 mg, 0.048 mmol), and TMP (24 mg, 0.192 mmol) were added to DMF (1 mL), and the solution was stirred at 50°C for 18 hours. Purification by reverse phase column chromatography (ACN / H2O = 0%-100%) afforded 10 mg of the racemate of compound 10P as a white solid, yield: 33%. LCMS: [M+H] + =640.3.

[0678] Step 16: To a solution of the racemate of compound 10P (10 mg, 0.016 mmol) in THF (0.5 mL) was added dropwise 6 M HCl (0.5 mL), and the solution was stirred at room temperature for 4 hours. The reaction solution was separated by reverse-phase preparative column chromatography using ACN / H2O (5%-95%, +0.1% NH4HCO3) to afford 1.1 mg of the racemate of compound 10 as a white solid, yield: 10%. Further chiral column separation afforded compound 10. LCMS: [M+H] + =540.2.

[0679] Compound 11

[0680] Step 1: A solution of the racemate of compound 4A (10 mg, 0.02 mmol), compound 11A (12.7 mg, 0.1 mmol), tert-dodecanethiol (38.4 mg, 0.2 mmol), TMP (0.4 mg, 0.04 mmol), and meso-tetraphenylporphyrin zinc (1.3 mg, 0.001 mmol) in DMF (1 mL) was transferred to a microwave tube. The microwave tube was irradiated with 25W red light and maintained at 80°C. EDCI (36.6 mg, 0.2 mmol dissolved in 1 mL DMF) was added dropwise to the reaction system. The reaction solution was stirred at 80°C under 25W red light for 30 minutes. The reaction mixtures from three parallel reactions were combined and purified by reverse phase column chromatography (H2O:ACN = 0-100%) to afford 9 mg of the racemate of 11B as a white solid in a yield of 33%. LCMS: [M+H-C4H8] + =526.2.

[0681] Step 2: To a solution of the racemate of compound 11B (25 mg, 0.04 mmol) in THF (1 mL) was added 6 M HCl (1 mL). The reaction mixture was stirred at room temperature overnight, concentrated under reduced pressure, and purified by reverse-phase column chromatography (H₂O:ACN = 0-100%) to afford 9 mg of the racemate of compound 11 as a white solid (yield: 40%). Further chiral column separation afforded compound 11. LCMS [M+H]⁺ = 482.0.

[0682] 1 H NMR (400MHz, DMSO) δ8.25 (s, 1H), 7.53 (d, J = 8.5Hz, 2H), 7.41 (s, 1H), 7.30 (d, J=8.5Hz,2H),7.16(d,J=12.3Hz,2H),6.73(t,J=7.7Hz,1H),6.35(s,1H),6.2 2(t,J=7.7Hz,2H),5.34(s,1H),4.90-4.73(m,3H),4.47(s,1H),4.03(dd,J=1 4.3, 6.1Hz, 1H), 3.85 (s, 3H), 2.78-2.60 (m, 1H), 2.08 (dd, J = 12.8, 6.1Hz, 1H).

[0683] Compound 12

[0684] Step 1: Dissolve the racemate of compound 9H (42.3 mg, 0.08 mmol) and LiOH (16.8 mg, 0.4 mmol) in MeOH / H₂O (5 mL / 1 mL), stir at room temperature for 12 h, adjust the pH to 2-3 with 1 M aqueous hydrochloric acid, and extract with ethyl acetate (20 mL). The organic phase is dried over sodium sulfate and concentrated to afford 35 mg of the racemate of compound 12A as a white solid, yield: 84.6%. LCMS [M+H] + =516.2.

[0685] Step 2: The racemate of compound 12A (31 mg, 0.06 mmol) was mixed with Boc-ethylenediamine (19 mg, 0.12 mmol), 2,4,6-trimethylpyridine (22 mg, 0.18 mmol), and HATU (34 mg, 0.09 mmol) in DMF (3 mL) and stirred at room temperature for 12 hours. 50 mL of water was then added to the reaction mixture, which was extracted with ethyl acetate, washed with saturated brine, dried, and concentrated. The crude product was purified on a silica gel column (PE / EA = 1 / 2) to obtain 33 mg of the racemate of compound 12B as a white solid, in a yield of 83.7%. LCMS [M+H] + =658.2.

[0686] Step 3: To a solution of the racemate of compound 12B (33 mg, 0.05 mmol) in THF (3 mL) was added aqueous HCl (1 mL, 6 M). The reaction mixture was allowed to react at room temperature for 12 hours. The crude product was concentrated and purified by preparative chromatography to afford 20 mg of the racemate of compound 12 as a white solid (yield: 71.4%). Further chiral column separation afforded compound 12.

[0687] LCMS [M+H] + =558.2.

[0688] 1 H NMR (400MHz, DMSO) δ8.45(s,2H),8.24(d,J=0.6Hz,1H),7.40(d,J=0.6Hz,1H),7. 19(d,J=1.0Hz,1H),7.14(d,J=0.9Hz,1H),7.10-7.01(m,4H),6.97(dd,J=10.1,7. 4Hz,3H),6.59(d,J=9.0Hz,2H),5.32(s,1H),4.65(d,J=4.8Hz,1H),4.30(d,J=14 .1Hz,1H),3.90-3.86(m,1H),3.84(s,3H),3.59(s,3H),3.14(s,2H),2.65(s,2H).

[0689] Compound 13

[0690] Step 1: Dissolve the racemate of compound 12A (350 mg, 0.68 mmol) in DMF (2 mL), then add N,O-dimethylhydroxylamine hydrochloride (132.5 mg, 1.36 mmol), HATU (310 mg, 0.82 mmol), and DIEA (263.2 mg, 2.04 mmol) in that order. Stir the reaction mixture at room temperature for 2 hours, then spin dry. Purify by reverse-phase chromatography (acetonitrile / water = 5%-95%, 214 nm, 20 min) to afford 300 mg of the racemate of compound 13A as a white solid, yield: 79%. LCMS [M+Na] + =581.2.

[0691] Step 2: Iodomethyl pivalate (2000 mg, 8.26 mmol) was dissolved in anhydrous tetrahydrofuran (15 mL) solution and isopropylmagnesium chloride (2.0 M, 8.26 mL, 16.52 mmol) was added at -70 ° C. The reaction mixture was stirred at -70 ° C for 2 hours to obtain a solution of compound 13B. The racemate of compound 13A (100 mg, 0.18 mmol) was dissolved in 1 mL of anhydrous tetrahydrofuran and a solution of compound 13B (5 mL) was added at -70 ° C. The reaction mixture was stirred at room temperature overnight. The reaction mixture was diluted with water (15 mL), extracted with dichloromethane (15 mL × 2), washed with brine (15 mL x 2), dried over anhydrous sodium sulfate, filtered and concentrated. The crude product was purified by preparative chromatography to obtain 5.5 mg of the racemate of white solid 13, with a yield of 5.8%. Further chiral column separation gave compound 13. LCMS [M+H] + =530.0.

[0692] 1 H NMR (400MHz, DMSO-d6) δ8.25 (d, J = 0.8Hz, 1H), 7.43-7.41 (m, 3H), 7.37-7. 35(m,2H),7.31-7.27(m,2H),7.22-7.24(m,1H),7.17(d,J=1.2Hz,1H),7.1 2(d,J=1.2Hz,1H),6.93-6.91(m,2H),5.40(s,1H),4.83(d,J=4.8Hz,1H), 4.40-4.36(m,1H),3.80(s,3H),3.76-3.73(m,4H),3.10(t,J=12.0Hz,2H).

[0693] Compound 14

[0694] Step 1: A solution of the racemate of compound 9D (2.30 g, 3.7 mmol), Zn(CN)2 (1.09 g, 9.3 mmol), Pd(dba)3 (0.68 g, 0.75 mmol) and DPPF (0.83 g, 1.49 mmol) in NMP (160 mL) was stirred at 150°C for 4 hours. The mixture was extracted with H2O and EA, and the combined organic layers were washed with brine (2 x 10 mL). The mixture was purified by flash column chromatography (PE / EA = 1 / 1) to afford the racemate of 14A as a yellow solid (1.9 g, 90% yield).

[0695] LCMS: [M+H] + =564.2.

[0696] Step 2: Pd(OH)2 / C (10%, 1.4 g) was added to a solution of the racemate of compound 14A (2.8 g, 4.97 mmol) in EA / MeOH / THF / DCM (EA / MeOH / THF / DCM=20:2:0.2:0.2, 120 mL) under N2 protection. The suspension was stirred at room temperature under H2 for 4 hours. The reaction mixture was filtered and the filter cake was washed with MeOH / DCM solution (MeOH / DCM=1 / 10). The combined filtrate was concentrated and purified by flash column chromatography (DCM / MeOH=10 / 1) to give the racemate of 14B (1.6 g, 68% yield) as a yellow solid.

[0697] LCMS: [MH] + =474.2.

[0698] Step 3: At 0 ° C, trifluoromethanesulfonic anhydride (1.1 g, 4.06 mmol, 1.2 equivalents) was slowly added dropwise to a 150 mL DCM solution of compound 14B (1.6 g, 3.38 mmol) and diisopropylethylamine (0.7 g, 5.75 mmol), and the mixture was stirred for 45 minutes. Washed with 25 mL saturated sodium bicarbonate, the organic layer was collected, and the aqueous layer was extracted with DCM (20 mL). The combined organic layers were washed with 10% citric acid (20 mL) and water (20 mL) and dried. The filtrate was concentrated under reduced pressure and purified by flash column chromatography (DCM / EA=10 / 1) to give the racemate of compound 14C (1.7 g, 83% yield) in the form of a white powder. LCMS: [M+H] + =606.2.

[0699] Step 4: The racemate of compound 14C (50 mg, 2.2 mmol), compound 14D (30.26 mg, 0.16 mmol), tBuXPhos-Pd-G3 (4.8 mg, 0.01 mmol), tBuXPhos (12.78 mg, 0.03 mmol), and Cs2CO3 (67 mg, 0.21 mmol) were dissolved in 1,4-dioxane (2 mL). The reaction mixture was stirred at 100°C under nitrogen for 16 hours. After the reaction, the mixture was extracted with EA and concentrated to obtain 50 mg of the racemate of compound 14E. The crude product was not included in the yield. LCMS [M+H] + =639.2.

[0700] Step 5: A solution of the racemate of compound 14E (50 mg) in THF (0.5 mL) was added with 6 M HCl (0.5 mL), and the mixture was stirred at room temperature for 4 h. The reaction solution was purified by flash column chromatography (ACN-H2O = 0-100%) to give 6 mg of the racemate of white solid 14, yield: 12%. Further chiral column separation gave compound 14.

[0701] LCMS [M+H] + =539.2.

[0702] 1 H NMR (400MHz, DMSO) δ7.78(s,1H),7.47(d,J=8.6Hz,2H),7.31(d,J=8.6Hz,2 H),7.26(s,1H),7.09-7.03(m,2H),7.02-6.94(m,4H),6.92(d,J=1.6Hz,1H) ,5.51(s,1H),5.39(d,J=5.3Hz,1H),4.67(t,J=5.1Hz,1H),4.39(d,J=13.9H z, 1H), 4.18 (d, J = 18.8Hz, 2H), 4.15-4.07 (m, 1H), 3.80 (s, 3H), 3.58 (s, 3H).

[0703] Compound 15

[0704] Step 1: HBF4 (0.85 mL, 4.79 mmol) was added dropwise to a solution of the racemate of compound 2 (170 mg, 0.32 mmol) in ethanol (5 mL) at room temperature. After stirring for 15 minutes, the reaction mixture became clear and was cooled to 0°C. Tert-butyl nitrite (65.0 mg, 0.63 mmol) was added. After 30 minutes, the reaction mixture was diluted with ether (8 mL). Filtering afforded a solid, which was washed twice with ether (5 mL) and dried. The solid was added to water (500 mL) containing copper nitrate (17.7 g, 94.5 mmol) and cuprous oxide (45.0 mg, 0.32 mmol) and stirred at room temperature for 1 hour. The aqueous solution was filtered to afford a brown solid, which was purified by flash column chromatography (ACN / H2O) to afford 20 mg of the racemate of 15A as a yellow solid in a yield of 12.3%. LCMS [M+H] + =541.0.

[0705] Step 2: The racemate of compound 15A (20.0 mg, 0.04 mmol) and LiOH (34.8 mg, 0.40 mmol) were dissolved in THF / H2O (5 mL / 1 mL) and stirred at room temperature for 6 h. Purification by flash column chromatography (ACN / H2O) afforded 17.0 mg of 15B as a white solid (yield: 85.3%). LCMS [M+H] + =527.0.

[0706] Step 3: Compound 15B (15.0 mg, 0.03 mmol), N,O-dimethylhydroxylamine hydrochloride (2.92 mg, 0.03 mmol), HATU (13.0 mg, 0.03 mmol), HOAT (2.25 mg, 0.03 mmol), and TMP (10.3 mg, 0.09 mmol) were added to DMF (1.0 mL) and stirred at room temperature for 16 h. The mixture was purified by flash column chromatography (ACN / H2O) to give 9.0 mg of the racemate of 15 as a white solid, in a yield of 55.4%. Compound 15 was further resolved by chiral column.

[0707] LCMS [M+H] + =570.0.

[0708] 1 H NMR: (400MHz, CDCl3) δ9.09 (s, 1H), 8.25 (s, 1H), 7.53 (d, J = 8.4Hz, 2H), 7.41 (s, 1 H),7.30(d,J=8.4Hz,2H),7.21(s,1H),7.15(s,1H),6.85(s,1H),6.83(d,J=8.4Hz ,1H),6.56-6.36(m,3H),5.63(s,1H),5.11(d,J=4.8Hz,1H),4.79(t,J=4.8Hz,1H) ,4.38(d,J=7.2Hz,1H),4.18-4.13(m,1H),3.90(s,3H),3.84(s,3H),3.09(s,3H).

[0709] Compound 16

[0710] Step 1: To a solution of the racemate of compound 14C (2.00 g, 3.30 mmol) in DMF (10 mL) were added compound 2I (8.04 g, 22.46 mmol), Pd(PPh3)4 (763.35 mg, 0.6 mmol), and CuI (629.03 mg, 3.30 mmol). The mixture was stirred in a microwave oven at 115°C under nitrogen for 2 h. The mixture was purified on a silica gel column (PE / EA = 1 / 1) to afford 1.5 g of the racemate of compound 16A as a white solid, in a yield of 86%. LCMS [M+H] + =525.0.

[0711] Steps 2 and 3: Dissolve the racemate of compound 16A (100.00 mg, 0.19 mmol) and LiOH (20.00 mg, 0.25 mmol) in MeOH / H₂O (5 mL / 1 mL), stir at room temperature for 12 h, adjust the pH to 2-3 with 1 M aqueous hydrochloric acid, and extract with ethyl acetate (20 mL). The organic phase is dried over sodium sulfate and concentrated to afford the crude racemate of compound 16B.

[0712] The crude racemate of product 16B was dissolved in DMF (3 mL), and HATU (144.50 mg, 0.38 mmol), compound 16C (27.78 mg, 0.38 mmol), and DIEA (73.67 mg, 0.57 mmol) were added. The mixture was stirred at room temperature for 12 hours. 50 mL of water was added to the reaction solution, which was extracted with ethyl acetate, washed with saturated brine, dried, and concentrated. The crude product was purified on a silica gel column (PE / EA = 1 / 2) to obtain 20 mg of the racemate of 16 as a white solid, in a yield of 17%. Compound 16 was further resolved on a chiral column.

[0713] LCMS [M+H] + =566.2.

[0714] 1H NMR (400MHz, DMSO) δ8.25(s,1H),7.47(d,J=7.3Hz,2H),7.41(s,1H),7.32(dd,J=8.0,5.0Hz,2H),7.23(s,1H),7 .15(s,1H),7.04(t,J=6.8Hz,2H),6.96(s,3H),5.77(dd,J=15.3,5.4Hz,1H),5.62(d,J=7.0Hz,1H),5.06(dd,J=1 1.7,5.0Hz,1H),4.77(t,J=7.8Hz,1H),4.67(s,1H),4.62-4.50(m,2H),4.47(d,J=13.8Hz,1H),4.34-4.06(m,1H) ,4.01(dd,J=16.6,9.9Hz,1H), 3.93(dd,J=12.8,6.8Hz,1H), 3.85(d,J=3.9Hz,3H), 3.59(dd,J=17.2,7.4Hz,1H).

[0715] Compound 17

[0716] Step 1: Dissolve compound 17A (5.0 g, 30.10 mmol) in chloroform (50 mL) under an ice-water bath, and add N,N-dimethylformamide (0.5 mL) and thionyl chloride (5.37 g, 45.14 mmol) in sequence. Stir the mixture at 75°C for 12 hours. Concentrate the reaction mixture to obtain 6.0 g of 17B as a yellow solid. LCMS [M+H] + =185.2.

[0717] Step 2: Compound 1A (4.0 g, 13.87 mmol) was dissolved in dichloromethane (30 mL) under an ice-water bath, and triethylamine (4.2 g, 41.61 mmol) and DMAP (1.69 g, 13.8 mmol) and compound 17B (5.63 g, 30.52 mmol) were added. The mixture was stirred at room temperature for 1.5 hours. The mixture was diluted with water (30 mL) and extracted with dichloromethane (30 mL×2). The organic phase was washed with brine (30 mL×2), dried over anhydrous sodium sulfate, filtered, concentrated and purified by silica gel chromatography (PE / EA=1 / 1) to obtain 6.92 g of 17C as a white solid, yield: 85%. LCMS [M+H] + =585.0.

[0718] Step 3: Compound 17C (3.5 g, 5.99 mmol) was dissolved in anhydrous tetrahydrofuran (30 mL), and a solution of LiHMDS in THF (1 M, 17.96 mL, 17.96 mmol) was added dropwise at -78°C, and the reaction was stirred at -78°C for 1 hour. The mixture was diluted with water (50 mL), extracted with ethyl acetate (50 mL x 2), washed with brine (50 mL x 2), dried over anhydrous sodium sulfate, filtered, concentrated, and stirred with diethyl ether to obtain 2.67 g of 17D as a white solid, yield: 78%. LCMS [M+H] + =585.0.

[0719] Step 4: Compound 17D (900 mg, 1.54 mmol) was dissolved in AcOH (15 mL), sodium acetate (316 mg, 3.85 mmol) was added, and the reaction was stirred at 100° C. overnight. The reaction mixture was concentrated and extracted with dichloromethane (20 mL), washed with water (20 mL×2), brine (20 mL×2), dried over anhydrous sodium sulfate, filtered and concentrated, and stirred with diethyl ether to obtain 800 mg of yellow solid 17E, yield: 92%.

[0720] Step 5: Compound 17E (100 mg, 0.24 mmol) and compound 2A (397 mg, 1.44 mmol) were dissolved in CHCl3 / TFE (7 / 3, 5 mL). The reaction mixture was injected via a syringe pump at a rate of 12 mL / h into a coil wrapped around a jacketed glass cylinder equipped with a 250W UV lamp. The temperature of the external circulating hydrazine was adjusted to maintain an internal reaction temperature of 0-5°C, while the UV lamp was turned on. The reaction mixture was irradiated for 1 hour, the solvent was removed under reduced pressure, and the residue was purified using a silica gel column (EtOAc / hexane) to remove excess compound 2A, yielding 190 mg of the racemate of 17F as a pale yellow solid, yield: 75%. LCMS [M+H] + =696.1.

[0721] Step 6: The racemate of compound 17F (4.8 g, 6.91 mmol) was dissolved in MeOH (40 mL). NaOMe (932.4 mg, 17.27 mmol) was added at 0°C and stirred at 65°C for 1.5 h. The solution was concentrated, washed with H2O, NH4Cl(aq), and brine, dried over anhydrous Na2SO4, concentrated under reduced pressure, and purified on a silica gel column (0.2% FA, EA / PE = 1 / 3) to afford 2.8 g of the racemate of compound 17G, yield: 58%. LCMS [M+H-H2O] + =677.9.

[0722] Step 7: The racemate of compound 17G (2.85 g, 4.10 mmol) was dissolved in ACN / CHCl₃ (1 / 1, 30 mL / 30 mL). Na(AcO)₃BH (4.3 g, 20.50 mmol) and AcOH (2.5 g, 41.01 mmol) were added at 0°C and stirred at room temperature for 2 h. The mixture was concentrated, extracted with EA, washed with water and brine, dried over anhydrous Na₂SO₄, and purified on a silica gel column (A:PE, B:0.2% FA, EA) to give 1.6 g of the racemate of compound 17H, in a 56% yield. LCMS [M+H-H₂O] + =680.0.

[0723] Step 8: Dissolve the racemate of compound 17H (400 mg, 0.57 mmol) in MeOH (10 mL). Add palladium hydroxide (40 mg) to the solution and stir overnight at room temperature under a hydrogen balloon. Filter the reaction mixture, wash with methanol (10 mL), and concentrate the filtrate to obtain 320 mg of the racemate of compound 17I as a yellow solid (yield: 91%). LCMS [M+H-H2O] + =590.0.

[0724] Step 9: The racemate of compound 17I (320 mg, 0.53 mmol) was dissolved in DMF (5 mL), and 1,1,1-trifluoro-N-phenyl-N-((trifluoromethyl)sulfonyl)methanesulfonamide (189.3 mg, 0.53 mmol) and potassium carbonate (146.3 mg, 1.06 mmol) were added to the mixture. The reaction solution was stirred at 60 ° C for 1 hour. The reaction solution was purified by reverse phase (acetonitrile / water = 5%-95%, 214 nm, 20 minutes) to obtain 320 mg of the racemate of white solid 17J, yield: 82%. LCMS [M+H] + =740.2.

[0725] Step 10: The racemate of compound 17J (50 mg, 0.07 mmol) was dissolved in DMF (1.5 mL), and 2-(tributyltin)oxazole (190 mg, 0.54 mmol), tetrakistriphenylphosphine palladium (8 mg, 0.007 mmol) and CuI (2.6 mg, 0.014 mmol) were added to the solution in sequence. The solution was stirred at 100 ° C for 1.5 hours under microwave. The reaction mixture was filtered, washed with MeOH (5 mL) and shrunk. The residue was purified by reverse phase (acetonitrile / water = 5%-95%, 214 nm, 20 minutes) to give 30 mg of the racemate of yellow solid 17K, yield: 34%. LCMS [M+H] + =659.2.

[0726] Step 11: The racemate of compound 17K (35 mg, 0.05 mmol) was dissolved in tetrahydrofuran / water (3 mL / 1 mL) and lithium hydroxide (4.20 mg, 0.1 mmol) was added to the solution. The reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated and purified by reverse phase chromatography (acetonitrile / water = 5%-95%, 214 nm, 20 minutes) to give 30 mg of the racemate of 17L as a yellow solid, yield: 88%. LCMS [M+H] + =645.2.

[0727] Step 12: In DMF (1.5 mL), the racemate of compound 17L (30 mg, 0.05 mmol), N,O-dimethylhydroxylamine (10 mg, 0.1 mmol), HATU (22.8 mg, 0.06 mmol) and DIEA (19.35 mg, 0.15 mmol) were added sequentially. The reaction mixture was stirred at room temperature for 2 hours. The racemate of compound 17M (15 mg, 47% yield) was obtained by reverse phase purification (acetonitrile / water = 5%-95%, 214 nm, 20 minutes). LCMS [M+H] + = 688.2

[0728] Step 13: To a solution of the racemate of compound 17M (15 mg, 0.02 mmol) in tetrahydrofuran (0.5 mL) was added 6N / HCl (0.3 mL). The mixture was stirred at room temperature for 12 hours. The mixture was purified by preparative chromatography to afford 3.8 mg of the racemate of 17M as a white solid (yield: 30%). Further chiral column separation afforded compound 17.

[0729] LCMS [M+H] + =588.2.

[0730] 1 H NMR (400MHz, DMSO-d6) δ8.36(s,1H),8.24(s,1H),7.41(s,1H),7.15(d,J=12.4Hz,2H),6.72-6.60(m,4H),6.23-6.18(m,3H),6.04(d,J=7.6Hz, 1H),5.86(d,J=3.2Hz,2H),5.37(s,1H),4.92(s,1H),4.83-4.73(m,3H) ,4.16(d,J=14.0Hz,1H),4.08(brs,1H),3.88-3.85(m,6H),3.06(s,3H).

[0731] Compound 18

[0732] Step 1: To a solution of the racemate of compound 2H (50 mg, 0.07 mmol) in dioxane (5 mL) were added bisborane (35.2 mg, 0.14 mmol), potassium acetate (20.4 mg, 0.21 mmol), and Pd(dppf)Cl2 (5.62 mg, 0.01 mmol). The mixture was degassed under reduced pressure and replaced with nitrogen three times. The mixture was stirred at 85°C for 10 h. The reaction solution was concentrated, and the residue was purified on a silica gel column using PE / EA = 5 / 1 to obtain the racemate of compound 18A (40.0 mg, 83% yield) as a yellow solid. LC-MS: (M+H) + =699.3. 1 H NMR: (400MHz, CDCl3) δ7.36(dd,J=8.4,28.4Hz,4H),7.22(s,1H),7.14(d,J=7.2Hz,1H),6.99-6.95(m,2H),6.86(s,1H),6.53(d,J=7.6 Hz,1H),6.30(s,1H),5.01(d,J=6.0Hz,1H),4.36(d,J=14.4Hz,1H),3.95(s,3H),3.66(s,3H),3.53(s,1H),1.51(s,9H),1.37(s,12H).

[0733] Step 2: To the racemate of compound 18A (40 mg, 0.06 mmol) in dioxane / H₂O (5 mL / 1 mL), 2-bromopyrimidine (9.1 mg, 0.09 mmol), Na₂CO₃ (18.2 mg, 0.17 mmol), and Pd(dppf)Cl₂ (4.62 mg, 0.01 mmol) were added. The mixture was stirred at 100°C under a nitrogen atmosphere in a microwave oven for 1 h. The reaction mixture was concentrated, and the residue was purified by flash column chromatography (ACN / H₂O) to afford the racemate of compound 18B (30.0 mg, 80.5% yield) as a white solid. LC-MS: (M+H) + =651.0. 1H NMR: (400MHz, CDCl3) δ8.92 (d, J = 4.8Hz, 2H), 7.92 (s, 1H), 7.86 (s, 1H), 7.40 (dd,J=8.4,22.0Hz,5H),7.14(d,J=7.6Hz,1H),7.01-6.96(m,1H),6.91(s,1H ),6.57(d,J=7.6Hz,1H),6.31(s,1H),5.05(d,J=6.0Hz,1H),4.45(d,J=14.0 Hz, 1H), 4.07 (s, 3H), 3.97 (dd, J = 6.0, 14.0Hz, 1H), 3.69 (s, 1H), 1.52 (s, 9H).

[0734] Step 3: Dissolve the racemate of compound 18B (30 mg, 0.05 mmol) and LiOH (20.2 mg, 0.23 mmol) in THF / H₂O (1 mL / 1 mL) and stir at room temperature for 6 h. Purify by flash column chromatography (ACN / H₂O) to obtain the racemate of compound 18C (21.0 mg, 69.0% yield) as a white solid. LC-MS: [M+H-C₄H₂] + =581.0.

[0735] Step 4: The racemate of compound 18C (20.0 mg, 0.03 mmol), N,O-dimethylhydroxylamine hydrochloride (3.22 mg, 0.03 mmol), HATU (14.3 mg, 0.04 mmol), HOAT (2.25 mg, 0.03 mmol), and TMP (11.4 mg, 0.09 mmol) were added to DMF (5.0 mL) and stirred for 16 h. The mixture was purified by flash column chromatography (ACN / H2O) to afford the racemate of compound 18D (20.0 mg, 93.6% yield) as a white solid. LCMS [M+1] + =680.1.

[0736] Step 5: To a solution of the racemate of compound 18D (43.0 mg, 0.08 mmol) in THF (1 mL) was added HCl (6N, 1 mL) and stirred at room temperature overnight. Purification by flash column chromatography (ACN / H2O) afforded the racemate of compound 18 (70 mg, yield: 41%). Further chiral column separation afforded compound 18 as a white solid. LCMS [M+H] + =580.0.

[0737] Compound 19

[0738] Step 1: Compound 1A (3.5 g, 12.1 mmol), DMAP (148 mg, 1.21 mmol), and TEA (3667 mg, 36.3 mmol) were dissolved in DCM (40 mL), cooled to 0°C, and compound 19A (5860 mg, 26.7 mmol) was added portionwise. The mixture was stirred at 25°C for 1 hour. The solution was concentrated and extracted with EA, washed with water and brine, dried over anhydrous Na2SO4, and purified on a silica gel column (PE:EA = 3 / 1) to obtain 19B (5 g, 63% yield) as a yellow solid. LCMS: [M+H] + =655.0.

[0739] Step 2: Compound 19B (5 g, 7.64 mmol) was dissolved in THF (50 mL), cooled to -78°C, and under N2 protection, LiHMDS (23 mL, 23 mmol) was added dropwise to the stirred solution. The mixture was stirred at -78°C for 2 hours. The reaction solution was quenched with saturated aqueous NH4Cl solution, extracted with EA, washed with water and saturated brine, and the organic layer was dried over anhydrous Na2SO4, dried by spin drying, and purified on a silica gel column (PE:EA = 3 / 1) to obtain a yellow solid 19C (4.1 g, yield 82%). LCMS: [M+H] + =654.9.

[0740] Step 3: Compound 19C (6.1 g, 9.32 mmol) and AcONa (1912 mg, 23.31 mmol) were dissolved in AcOH (183 mL) and stirred at 100°C overnight. TLC showed no starting material, but new spots were generated. The solution was spin-dried and extracted with EA, washed with water and brine, dried over anhydrous Na2SO4, concentrated, and purified on a silica gel column (PE:EA = 1 / 1) to give 19D (4 g, 67% yield) as a yellow solid. LCMS: [M+H] + =636.9.

[0741] Step 4: Compound 19D (4 g, 6.29 mmol) was dissolved in CHCl₃ (120 mL), cooled to 0°C, and MeONa (3396 mg, 18.86 mmol) was added. The mixture was stirred at 25°C for 1 hour. TLC showed the absence of starting material, with the formation of new spots. The reaction mixture was adjusted to pH 5 with acetic acid, dried, extracted with EA, and washed with MeOH to afford a filter cake as a gray solid, 19E (2.5 g, 88% yield).

[0742] LCMS: [M+H] + =453.0.

[0743] 1H NMR(400MHz, CDCl3)δ8.33(s,1H),8.17(d,J=7.9Hz,1H),7.55(d,J=7.9Hz,1H), 7.48-7.34(m,6H),6.66(d,J=1.4Hz,1H),6.44(s,1H),5.17(s,2H),3.97(s,3H).

[0744] Step 5: Compound 19E (1 g, 2.2 mmol) and compound 9A (2.1 g, 13.25 mmol) were dissolved in CHCl3 / TFE (7 / 3, 15 mL). The reaction mixture was injected into a coil wrapped around a jacketed glass cylinder equipped with a 250W UV lamp via a syringe at a rate of 12 mL / h via a syringe pump. The temperature of the external circulating hydrazine was adjusted to keep the internal reaction temperature at 0-5°C. The UV lamp was turned on and the reaction mixture was irradiated for 1 hour. The solvent was removed under reduced pressure, and the residue was purified on a silica gel column (EtOAc / hexane) to remove excess cinnamate to obtain the racemate of compound 19F (2.9 g, 64% yield) as a light yellow solid. LCMS [M+H+H2O] + =633.1.

[0745] Step 6: A mixture of the racemate of compound 19F (2.96 g, 4.81 mmol) in MeOH (50 mL) was added to MeONa (649.76 g, 12.03 mmol), stirred at 65°C for 2 h, concentrated and extracted with EA, washed with saturated NH4Cl solution and brine, dried over anhydrous Na2SO4, and separated and purified on a silica gel column (0.5% FA, EA / PE = 31 / 69) to obtain the racemate of compound 19G (1.2 g, 75% yield) as a light yellow solid. LCMS [M+H] + =597.1.

[0746] Step 7: The racemate of compound 19G (1.7 g, 2.76 mmol) was added with Na(AcO)BH (2.9 g, 13.82 mmol) and AcOH (1.7 g, 27.64 mmol) in MeCN / CHCl = 1 / 1 (50 mL / 50 mL) at 0°C and stirred at room temperature for 2 h. The solution was concentrated and extracted with EA, washed with water and brine, dried over anhydrous NaSO, and purified on a silica gel column (A:PE, B:DCM / EA = 1 / 1) to obtain the racemate of compound 19H (919 mg, 54% yield).

[0747] LCMS [M+H-H2O] + =599.0.

[0748] 1H NMR (400MHz, CDCl3) δ7.49-7.32 (m, 6H), 7.24 (ddd, J = 7.9, 2.0, 1.0Hz, 1H), 7.15-7 .11(m,1H),7.10-7.05(m,3H),7.00(dd,J=9.1,6.7Hz,1H),6.89(dd,J=7.0,2.2Hz ,2H),6.38(d,J=1.9Hz,1H),6.23(d,J=1.9Hz,1H),5.09(s,2H),5.02(d,J=6.5Hz, 1H), 4.36 (d, J = 14.2Hz, 1H), 3.95-3.88 (m, 1H), 3.86 (s, 3H), 3.66 (d, J = 3.6Hz, 3H).

[0749] Step 8: The racemate of compound 19H (300.0 mg, 0.49 mmol), NH2Boc (170.7 mg, 1.46 mmol), Pd2(dba)3 (44.5 mg, 0.05 mmol), Xantphos (56.2 mg, 0.10 mmol), and Cs2CO3 (316.0 mg, 0.97 mmol) were mixed in 1,4-dioxane (20 mL) and stirred at 100°C under N2 for 16 h. The mixture was concentrated and purified on a silica gel column (PE / EA) to obtain the racemate of compound 19I (219 mg, 69% yield).

[0750] LCMS[MH] - =652.2.

[0751] 1 H NMR (400MHz, CDCl3) δ7.48-7.35(m,6H),7.10-7.03(m,4H),6.96(t,J=1.8Hz,1H),6.92-6.83(m,3H),6.36(d,J=1.9Hz,1H),6.22(d,J=1.9Hz, 1H), 5.09 (s, 2H), 5.03 (d, J = 6.7Hz, 1H), 4.33 (d, J = 14.2Hz, 1H), 3.95 (dd, J = 14.2, 6.7Hz, 1H), 3.86 (s, 3H), 3.65 (d, J = 3.7Hz, 3H), 1.49 (s, 9H).

[0752] Step 9: Pd(OH)2 / C (10%, 200 mg) was added to a solution of the racemate of compound 19I (219.0 mg, 0.34 mmol) in EA / MeOH / THF / DCM = 20:2:2:0.2 (10 mL). The reaction mixture was replaced with H2 several times. The mixture was stirred at room temperature for 16 hours. The suspension was filtered, and the filter cake was washed with MeOH / DCM (1 / 10). The combined filtrate was concentrated to dryness to afford the racemate of compound 19J (180 mg, 95% yield).

[0753] 1 H NMR(400MHz, CDCl3)δ7.23-7.02(m,7H),6.95-6.86(m,3H),6.47(s,1H), 6.11(d,J=1.5Hz,1H),5.91(s,1H),4.99(d,J=7.1Hz,1H),4.31(d,J=14.1H z, 1H), 3.97 (dd, J = 14.1, 7.1Hz, 1H), 3.74 (s, 3H), 3.66 (s, 3H), 1.50 (s, 9H).

[0754] LCMS [M+Na] + =586.1.

[0755] Step 10: The racemate of compound 19J (180 mg, 0.32 mmol) and K2CO3 (88 mg, 0.64 mmol) were stirred in DMF (10 mL). N-phenylbis(trifluoromethanesulfonimide) (114 mg, 0.32 mmol) was added and stirred at 60°C for 20 min. The solution was concentrated and extracted with EA, washed with water and brine, dried over anhydrous Na2SO4, and purified on a silica gel column (DCM / MeOH = 10 / 1) to obtain the racemate of compound 19K (190 mg, 86% yield). LCMS: [M+Na] + =718.0.

[0756] Step 11: To a solution of the racemate of compound 19K (70 mg, 0.1 mmol) in DMF (3 mL) were added compound 2I (288.55 mg, 0.8 mmol), Pd(PPh3)4 (11.6 mg, 0.01 mmol), and CuI (3.84 mg, 0.02 mmol). The reaction mixture was purged with nitrogen three times and then reacted in a microwave reactor at 100°C for 1.5 hours. The reaction mixture was purified by reverse-phase column chromatography (H2O:ACN = 0-100%) to afford the racemate of compound 19 (2.3 mg, yield: 5%). Further chiral column separation afforded compound 19 as a white solid.

[0757] LCMS [M+H]+ =515.0.

[0758] 1 H NMR(400MHz,DMSO)δ8.25(s,1H),7.41(s,1H),7.21-7.10(m,2H),7.10-6.8 9(m,5H),6.64(t,J=7.9Hz,1H),6.48(s,1H),6.26(d,J=8.0Hz,1H),6.17(d, J=6.4Hz,1H),5.31(d,J=5.2Hz,1H),5.25(s,1H),4.70(t,J=5.2Hz,2H),4.2 0(d,J=14.1Hz,1H), 4.01(dd,J=14.0,5.2Hz,1H), 3.85(s,3H), 3.55(s,3H).

[0759] Compound 20

[0760] Step 1: Compound 1 (1000 mg, 2.21 mmol) and Cs2CO3 (1.08 g, 3.32 mmol) were dissolved in anhydrous methanol (10 mL) and anhydrous toluene (30 mL). t-BuXPhosPdG3 (35.13 mg, 0.04 mmol) was added and stirred at 85°C for 13 hours. The solution was concentrated and diluted with MeOH / DCM = 1 / 1. After filtration, the concentrated filtrate was purified on a silica gel column (DCM / MeOH = 10 / 1) to afford 0.65 g of 20A as a yellow solid in a 73% yield.

[0761] Step 2: Compound 20A (1 g, 2.2 mmol) and compound 2B (4.1 g, 13.3 mmol) were dissolved in CHCl3 / TFE (9 / 1, 15 mL). The reaction mixture was pumped via a 20 mL syringe at a rate of 12 mL / h via a syringe pump into a coil wrapped around a jacketed glass cylinder equipped with a 250 W UV lamp. The temperature of the external circulating hydrazine was adjusted to maintain an internal reaction temperature of 0-5°C. The UV lamp was simultaneously turned on and the reaction mixture was irradiated for 1 hour. The solvent was removed under reduced pressure and the excess cinnamate was removed by column chromatography (EA / PE = 1 / 3). The desired racemic product 20B (3.9 g, 80% yield) was obtained as a crude yellow oil. LCMS [M+H] + =682.3.

[0762] Step 3: The racemate of compound 20B (3.7 g, 5.43 mmol) was mixed with MeOH (50 mL), and NaOMe (733.5 mg, 13.58 mmol) was added at 0°C. The mixture was stirred at 65°C for 1.5 h. The solution was concentrated, washed with H2O, NH4Cl(aq), and brine, dried over Na2SO4, concentrated under reduced pressure, and purified on a silica gel column (0.2% FA, EA / PE = 1 / 3) to obtain 2.5 g of the racemate of compound 20C, in a yield of 67%. LCMS [M+H-H2O] + =664.2.

[0763] Step 4: The racemate of compound 20C (2.5 g, 3.67 mmol) was dissolved in MeCN / CHCl₃ (1 / 1, 50 mL / 50 mL). Na(AcO)₃BH (3.9 g, 18.36 mmol) and AcOH (2.2 g, 36.71 mmol) were added at 0°C and stirred at room temperature for 2 h. The reaction solution was extracted with EA, washed with water and brine, dried over anhydrous Na₂SO₄, and purified on a silica gel column (A:PE, B:EA = 1 / 1) to obtain 1.5 g of the racemate of compound 20D (yield: 60%). LCMS [M+H-H₂O] + =666.3.

[0764] Step 5: Pd(OH)2 / C (10%, 100 mg) was added to a solution of the racemate of compound 20D (200 mg, 0.29 mmol) in EA / MeOH / THF / DCM (20:2:2:2:0.2, 10 mL). The reaction mixture was replaced with H2 three times, and the mixture was stirred at room temperature for 16 hours. The suspension was filtered, and the filter cake was washed with MeOH / DCM (1 / 10). The filtrate was concentrated and purified on a silica gel column (DCM / MeOH = 10 / 1) to obtain 155 mg of the racemate of compound 20E, yield: 89%. LCMS [M+Na] + =616.1.

[0765] Step 6: The racemate of compound 20E (155.0 mg, 0.26 mmol) and K2CO3 (72.1 mg, 0.52 mmol) were stirred in DMF (2 mL). Compound 2G (93.3 mg, 0.26 mmol) was added, and the reaction mixture was stirred at 60°C for 20 min. The solution was diluted with water, extracted with EA, washed with water and brine, dried over anhydrous Na2SO4, and purified on a silica gel column (EA / PE = 1 / 1) to obtain 160 mg of the racemate of compound 20F, in an 84% yield. LCMS: [M+Na] + =748.1.

[0766] Step 7: The racemate of compound 20F (50 mg, 0.07 mmol) was dissolved in DMF (1.5 ml), and 2-(tributyltin)oxazole (190 mg, 0.54 mmol), tetrakistriphenylphosphine palladium (8 mg, 0.007 mmol) and CuI (2.6 mg, 0.014 mmol) were added to the solution in sequence. The solution was stirred at 100 ° C under microwave for 1.5 hours. The reaction mixture was filtered, washed with MeOH (5 mL) and concentrated. The residue was purified by reverse phase (acetonitrile / water = 5%-95%, 214 nm, 20 minutes) to give 17 mg of the racemate of 20G as a yellow solid, yield: 38%. LCMS: [M+Na] + =667.2.

[0767] Step 8: The racemate of compound 20G (35 mg, 0.05 mmol) was dissolved in tetrahydrofuran / water (3 ml / 1 ml), and lithium hydroxide (4.56 mg, 0.1 mmol) was added to the solution. The reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated and purified by reverse phase purification (acetonitrile / water = 5%-95%, 214 nm, 20 minutes) to give 21 mg of the racemate of 20H as a yellow solid, yield: 61%. LCMS: [M+Na] + =653.2.

[0768] Step 9: In DMF (1.5 ml), the racemate of compound 20H (21 mg, 0.03 mmol), N,O-dimethylhydroxylamine (3.25 mg, 0.06 mmol), HATU (17.1 mg, 0.05 mmol), and DIEA (11.61 mg, 0.09 mmol) were added. The reaction mixture was stirred at room temperature for 2 hours. Purification by reverse phase (acetonitrile / water = 5%-95%, 214 nm, 20 minutes) gave 12 mg of the racemate of 20I as a yellow solid, yield: 54%. LCMS: [M+Na] + =696.3.

[0769] Step 10: To a solution of the racemate of compound 20I (12 mg, 0.02 mmol) in tetrahydrofuran (0.5 mL) was added 6N / HCl (0.3 mL). The mixture was stirred at room temperature for 12 hours. The mixture was purified by preparative chromatography to afford 3.2 mg of the racemate of compound 20 as a white solid in a yield of 22%. Further chiral column separation afforded compound 20. LCMS: [M+H] + =574.2.

[0770] 1H NMR (400MHz, DMSO-d6) δ8.24(d,J=0.8Hz,1H),7.40(d,J=0.8Hz,1H),7.17(d,J=1.2H z,1H),7.14(d,J=1.2Hz,1H),7.08-7.05(m,2H),6.67-6.63(m,3H),6.23(brs,1H),6 .16(d,J=9.2Hz,1H),6.01(d,J=7.6Hz,1H),5.30(s,1H),4.86(d,J=4.4Hz,1H),4.80 -4.79(m,3H),4.15-4.08(m,2H),3.87(s,3H),3.85(s,3H),3.63(s,3H),3.06(s,3H).

[0771] Compound 21

[0772] Step 1: To a solution of the racemate of compound 14E (60 mg, 0.1 mol) in THF (2 mL) was added aqueous LiOH (12 mg, 0.3 mmol, 0.5 mL H₂O). The reaction mixture was stirred at room temperature for 18 hours. The reaction mixture was purified by reverse-phase column chromatography (H₂O:ACN = 0-100%) to afford 45 mg of the racemate of compound 21A as a white solid, yield: 77.5%. LCMS: [M+H] + =625.2.

[0773] Step 2: To a solution of the racemate of compound 21A (45 mg, 0.07 mmol), N,O-dimethylhydroxylamine (14 mg, 0.14 mmol), HATU (54.72 mg, 0.14 mmol), and HOAT (19.58 mg, 0.14 mmol) in DMF (4 mL) was added TMP (35 mg, 0.28 mmol). The reaction mixture was stirred at 50°C for 18 hours. The reaction mixture was purified by normal phase column chromatography (DCM / MeOH = 10 / 1) to give 24 mg of the racemate of compound 21B as a white solid, yield: 50%. LCMS: [M+H] + =668.2.

[0774] Step 3: To a solution of the racemate of compound 21B (24 mg, 0.03 mmol) in THF (1 mL) was added 6 M HCl (2 mL). The reaction was stirred at room temperature for 18 hours. The reaction was purified by reverse-phase column chromatography (H2O:ACN = 0-100%) to afford 14 mg of the racemate of 21 as a white solid (yield: 70%). Further chiral column separation afforded compound 21.

[0775] LCMS [M+H] +=568.2.

[0776] 1 H NMR (400MHz, DMSO) δ7.78(s,1H),7.52(d,J=8.6Hz,2H),7.34-7.24(m,3H),7.06(t,J=7.4Hz,2H),6.99(t,J=4.4Hz,2H),6.91(dd,J=18.8,4.5 Hz,3H),5.50(s,1H),5.01(d,J=4.8Hz,1H),4.80(t,J=5.1Hz,1H),4.43 (d,J=13.8Hz,1H),4.19(s,3H),3.91(s,3H),3.81(s,2H),3.09(s,3H).

[0777] Compound 22

[0778] Step 1: The racemate of compound 9G (50.0 mg, 0.08 mmol), compound 22A (24.8 mg, 0.25 mmol), t-BuXPhos PdG3 (13.0 mg, 0.02 mmol), t-Bune phos (7.7 mg, 0.02 mmol), and Na2CO3 (26.1 mg, 0.25 mmol) were dissolved in 1,4-dioxane (5 mL). The reaction mixture was stirred at 100°C under N2 protection for 16 hours. The concentrate was purified by preparative HPLC to afford 1.2 mg of the racemate of 22 as a white solid (yield: 6.7%). Compound 22 was further resolved on a chiral column.

[0779] LCMS [M+H] + =562.2.

[0780] 1 H NMR (400MHz, DMSO) δ7.11-6.94(m,5H),6.89(d,J=7.4Hz,2H),6.68(d,J=1.5Hz,1H),6.62-6.54(m,3H),5.29(s,1H),5.26(d,J=5.0Hz, 1H), 4.71 (t, J = 5.2Hz, 1H), 4.23-4.15 (m, 3H), 4.00-3.92 (m, 3H), 3.78 (dd, J = 11.2, 6.2Hz, 1H), 3.74 (s, 3H), 3.60 (s, 3H), 3.55 (s, 3H).

[0781] Compound 23

[0782] Step 1: To a solution of the racemate of compound 9J (200 mg, 0.37 mol) in THF (5 mL) was added a solution of LiOH (47 mg, 1.12 mmol) in water (0.5 mL). The reaction mixture was stirred at room temperature for 18 hours. The reaction mixture was purified by reverse phase column chromatography (H2O:ACN = 0-100%) to afford the racemate of compound 23A as a white solid (180 mg, yield: 92%). LCMS [M+H] + =525.3.

[0783] Step 2: Add a solution of the racemate of compound 23A (10 mg, 0.02 mmol), compound 11A (24.3 mg, 0.2 mmol), tert-dodecylmercaptan (38.4 mg, 0.2 mmol), and meso-tetraphenylporphyrin zinc (1.3 mg, 0.001 mmol) in DMF (1 mL) to a microwave tube. Place the microwave tube in an 80°C water bath and illuminate with a 25W red light lamp. Add EDCI (36.6 mg, 0.2 mmol, dissolved in DMF) dropwise to the reaction system. Stirring is continued for 30 minutes. Three reactions were performed in parallel, and the reaction solutions were combined and purified by reverse phase column chromatography (H2O:ACN = 0-100%) to obtain the racemate of 23B as a white solid (10 mg, yield: 30%). LCMS [M+H] + =481.2.

[0784] Step 3: A THF (2 mL) solution of the racemate of compound 23B (30 mg, 0.06 mmol) was cooled to 0°C. LiAlH4 (30 μL, 0.12 mmol) was added dropwise to the reaction system, and the reaction was continued at 0°C for 1 hour. Na2SO4·10H2O was added to the reaction system and stirred at room temperature for half an hour. The suspension was filtered and the filter cake was washed three times with MeOH / DCM (1 / 10). The filtrate was dried and purified by thin layer chromatography (DCM / MeOH=7 / 1) to give the racemate of 23C as a white solid (5 mg, yield: 16.7%). LCMS [M+H] + =485.2.

[0785] Step 4: To a solution of the racemate of compound 23C (4 mg, 0.008 mmol), glycolic acid (1.2 mg, 0.008 mmol), HATU (6.4 mg, 0.016 mmol), and HOAT (2.4 mg, 0.016 mmol) in DMF (1 mL) was added TMP (4 mg, 0.032 mmol) and allowed to react at room temperature for 1 hour. The reaction solution was purified by reverse-phase column chromatography (HO:ACN = 0-100%) to afford the racemate of compound 23 as a white solid (2.2 mg, 50% yield). Compound 23 was then separated by chiral column chromatography.

[0786] LCMS [M+H-H2O] + =525.0.

[0787] 1 H NMR (400MHz, DMSO) δ8.26 (d, J = 0.6Hz, 1H), 7.79 (t, J = 5.7Hz, 1H), 7.41 (d, J=0.7Hz, 1H), 7.22 (dd, J=8.9, 1.1Hz, 2H), 7.14 (d, J=8.9Hz, 2H), 7.11-7. 00(m,3H),6.91(d,J=6.8Hz,2H),6.69(d,J=9.0Hz,2H),5.64(t,J=5.5Hz,1H), 5.42(s,1H),3.96(s,3H),3.91(d,J=5.3Hz,2H),3.70(t,J=5.3Hz,2H),3.65( s,3H),3.39(d,J=6.2Hz,1H),2.90(td,J=14.0,6.8Hz,1H),2.24-2.01(m,2H).

[0788] Compound 24

[0789] Step 1: Dissolve the racemate of compound 2E (3200 mg, 4.715 mmol) in THF (30 mL), MeOH (10 mL), and H₂O (10 mL). Add LiOH (594 mg, 14.14 mmol) and stir at room temperature under nitrogen for 8 hours. The reaction mixture is adjusted to pH 5 with 3M HCl and concentrated to obtain the crude product. Silica gel column chromatography (DCM / MeOH = 10 / 1) afforded the racemate of compound 24A as a white solid (2.8 g, yield: 89%). LCMS [M+H] + =665.2.

[0790] Step 2: Dissolve the racemate of compound 24A (2800 mg, 4.2124 mmol) in DMF (120 mL). Add dimethylhydroxylamine hydrochloride (1233 mg, 12.6371 mmol), HATU (4802 mg, 12.6371 mmol), HOAT (1719 mg, 12.6371 mmol), and TMP (1539 mg, 12.6371 mmol). Heat to 50°C and stir under nitrogen for 16 hours. Add water (100 mL) to the reaction solution, extract twice with ethyl acetate (150 mL), combine the organic phases, wash with saturated brine (150 mL), and dry over anhydrous sodium sulfate. Filter and concentrate to obtain the crude product, which is purified by silica gel column chromatography (ethyl acetate / petroleum ether = 1 / 10) to obtain the racemate of 24B as a yellow solid (2.9 g, yield: 97%). LCMS [M+H-C4H8] + =652.2.

[0791] Step 3: Dissolve the racemate of compound 24B (2900 mg, 4.10 mmol) in a mixture of EA / MeOH / THF / DCM = 20:2:2:0.2 (40 mL). Add Pd(OH)2 (870 mg) and stir at room temperature under hydrogen for 16 hours. The reaction mixture was filtered and concentrated to give the crude product, which was purified by silica gel column chromatography (DCM / MeOH = 10 / 1) to give the racemate of compound 24C as a yellow solid (1.8 g, yield: 71%). LCMS [M+H-C4H8] + =562.2.

[0792] Step 4: Dissolve the racemate of compound 24C (1800 mg, 2.9142 mmol) in DMF (50 mL), add compound 2G (1041 mg, 2.9142 mmol) and K2CO3 (804 mg, 5.8284 mmol), and stir at 60°C under nitrogen for 40 minutes. Filter the reaction mixture, add water (100 mL), and extract twice with ethyl acetate (150 mL). Combine the organic phases, wash with saturated brine (150 mL), and dry over anhydrous sodium sulfate. Filter and concentrate to obtain the crude product, which is then purified by silica gel column chromatography (EA / PE = 1 / 1) to afford the racemate of 24D as a yellow oil (1.6 g, yield: 74%). LCMS [M+H-C4H8] + =694.1.

[0793] Step 5: Dissolve the racemate of compound 24D (860 mg, 1.15 mmol) in dioxane (12 mL) and add bis-pinacol boronate (876 mg, 3.45 mmol), Pd(dppf)Cl2 (188 mg, 0.23 mmol), and KOAc (432 mg, 4.60 mmol). Stir at 85°C under nitrogen for 4 hours. The reaction mixture was filtered and concentrated to obtain the crude product, which was then purified by silica gel column chromatography (EA / PE = 1 / 1) to afford the racemate of compound 24E as a yellow oil (700 mg, yield: 84%). LCMS [M+H-C4H8] + =672.2.

[0794] Step 6: Dissolve the racemate of compound 24E (20 mg, 0.0300 mmol) in dioxane (1.5 mL) and water (0.3 mL). Add 2-bromopyrazine (8.74 mg, 0.0500 mmol), Pd(dppf)Cl2 (2.24 mg, 0.0030 mmol), and Na2CO3 (11.65 mg, 0.1099 mmol). Microwave the mixture at 100°C under nitrogen for 1 hour. The reaction mixture was filtered and concentrated to afford the racemate of compound 24F as a yellow solid (17 g, yield: 84%). LCMS [M+H] + =680.4.

[0795] Step 7: Dissolve the racemate of compound 24F (17 mg, 0.250 mmol) in THF (1 mL) and add 6M HCl (1 mL). Stir at room temperature under nitrogen for 16 hours. The reaction mixture is filtered and concentrated to obtain the crude product, which is then purified on a reverse-phase column (H2O / ACN) to afford the racemate of 24F as a white solid (1.4 mg, 9.6% yield). Further chiral column separation affords compound 24.

[0796] LCMS [M+H] + =580.2.

[0797] 1H NMR (400MHz, DMSO) δ9.38 (d, J = 0.7Hz, 2H), 7.70 (d, J = 1.1Hz, 1H), 7.66 (d, J = 1.0Hz, 1H), 7. 54(d,J=8.6Hz,2H),7.33(d,J=8.6Hz,2H),6.66(t,J=7.8Hz,1H),6.23(s,1H),6.16(d,J=7 .8Hz,1H),6.05(d,J=7.4Hz,1H),5.65(s,1H),5.09(d,J=4.9Hz,1H),4.84-4.78(m,2H),4. 33(d,J=13.9Hz,1H),4.13(dd,J=15.2,9.8Hz,1H),3.91(s,3H),3.87(s,3H),3.09(s,3H).

[0798] Compound 25

[0799] Step 1: Dissolve the racemate of compound 24E (10 mg, 0.01 mmol) in dioxane / water (5 mL / 1 mL), add compound 25A (2.19 mg, 0.02 mmol), Na2CO3 (4.37 mg, 0.04 mmol), and Pd(dppf)Cl2 (1.11 mg, 0.001 mmol). Heat to 100°C in a microwave oven under nitrogen for 1 hour. Filter the reaction mixture, wash the filter cake with ethyl acetate (2 mL x 3), and concentrate to obtain the racemate of 25B (12 mg) as a yellow solid, which is used directly in the next step. LCMS [M+H-C4H8] + =624.3.

[0800] Step 2: To a solution of the racemate of compound 25B (12 mg, 0.02 mmol) in tetrahydrofuran (0.5 mL) was added 6N HCl (0.3 mL) and stirred at room temperature for 12 hours. The reaction solution was directly purified by preparative HPLC to afford the racemate of compound 25 as a white solid (6.3 mg, yield: 73%), which was further resolved by chiral column to afford compound 25.

[0801] LCMS [M+H] + =580.0.

[0802] 1H NMR(400MHz,DMSO-d6)δ9.25-9.23(m,1H),8.33-8.31(m,1H),7.83-7.80(m, 1H),7.55(d,J=8.4Hz,2H),7.40(d,J=4.8Hz,2H),7.34(d,J=8.8Hz,2H),6.68(t,J=7.6Hz,1H),6.22-6.17(m,2H),6.08(d,J=6. 0Hz,1H),5.59(s,1H),4.80(d,J=4.8Hz,1H),4.33(d,J=14.0Hz,1H),4.17-4.13(m,1H),3.91(s,3H),3.88(s,3H),3.09(s,3H).

[0803] Compound 26

[0804] Step 1: Dissolve the racemate of compound 24E (20 mg, 0.03 mmol) in dioxane / water (5 mL / 1 mL), add compound 26A (8.17 mg, 0.04 mmol), Na2CO3 (8.74 mg, 0.08 mmol), and Pd(dppf)Cl2 (2.23 mg, 0.001 mmol). Heat to 100°C in a microwave oven under nitrogen protection for 1 hour. The reaction mixture was filtered, and the filter cake was washed with ethyl acetate (2 mL x 3). After concentration, the racemate of 26B was obtained as a yellow solid (19 mg), which was used directly in the next reaction. LCMS [M+H] + =719.3.

[0805] Step 2: To a solution of the racemate of compound 26B (19 mg, 0.02 mmol) in tetrahydrofuran (0.5 mL) was added 6N HCl (0.3 mL) and stirred at room temperature for 12 hours. The reaction solution was directly purified by preparative HPLC to afford the racemate of compound 26 as a white solid (2.3 mg, yield: 17%), which was further resolved on a chiral column to afford compound 26.

[0806] LCMS [M+H] + =619.2.

[0807] 1H NMR (400MHz, DMSO-d6) δ9.32(d,J=1.6Hz,1H),9.19(s,1H),8.14(s,1H),7.88(d,J=0.8H z,1H),7.55(d,J=8.4Hz,2H),7.33(d,J=8.4Hz,3H),7.28(s,1H),6.67(t,J=7.8Hz,1H),6 .20-6.16(m,2H),6.05(d,J=7.6Hz,1H),5.53(s,1H),4.98(d,J=4.4Hz,1H),4.82-4.80( m,3H),4.30(d,J=14.0Hz,1H),4.15-4.11(m,1H),3.90(s,3H),3.87(s,3H),3.09(s,3H).

[0808] Compound 27

[0809] Step 1: Dissolve the racemate of compound 24E (20 mg, 0.03 mmol) in dioxane / water (5 mL / 1 mL), add compound 27A (8.17 mg, 0.04 mmol), Na2CO3 (8.74 mg, 0.08 mmol), and Pd(dppf)Cl2 (2.23 mg, 0.001 mmol). Heat to 100°C in a microwave oven under nitrogen protection for 1 hour. The reaction mixture was filtered, and the filter cake was washed with ethyl acetate (2 mL x 3). After concentration, the racemate of 27B was obtained as a yellow solid (18 mg), which was used directly in the next reaction. LCMS [M+H] + =719.3.

[0810] Step 2: To a solution of the racemate of compound 27B (18 mg, 0.03 mmol) in tetrahydrofuran (0.5 mL) was added 6N HCl (0.3 mL) and stirred at room temperature for 12 hours. The reaction solution was directly purified by preparative HPLC to afford the racemate of compound 27 as a white solid (1.5 mg, yield: 9.7%). Further chiral column separation afforded compound 27.

[0811] LCMS [M+H] + =619.2.

[0812] 1H NMR (400MHz, DMSO-d6) δ8.38(s,1H),8.24(d,J=9.6Hz,1H),7.91(d,J=9.6Hz,1H),7.84(s,1H ),7.55(d,J=8.4Hz,2H),7.35(s,2H),7.32(s,1H),7.23(s,1H),6.67(t,J=7.8Hz,1H),6.21(s ,1H),6.17(d,J=7.6Hz,1H),6.07(d,J=7.6Hz,1H),5.60(s,1H),5.05(d,J=4.8Hz,1H),4.82-4 .79(m,3H),4.33(d,J=14.0Hz,1H),4.17-4.09(m,1H),3.91(s,3H),3.88(s,3H),3.09(s,3H).

[0813] Compound 28

[0814] Step 1: Dissolve the racemate of compound 24E (20 mg, 0.03 mmol) in dioxane / water (3 mL / 1 mL), add compound 28A (7.13 mg, 0.04 mmol), Na2CO3 (8.74 mg, 0.08 mmol), and Pd(dppf)Cl2 (2.23 mg, 0.001 mmol). Heat to 100°C in a microwave under nitrogen protection for 1 hour. The reaction mixture was filtered, and the filter cake was washed with ethyl acetate (2 mL x 3). After concentration, the racemate of crude compound 28B (20 mg) was obtained as a yellow solid, which was used directly in the next reaction. LCMS [M+H-C4H8] + =638.2.

[0815] Step 2: To a solution of the racemate of compound 28B (20 mg, 0.03 mmol) in tetrahydrofuran (0.5 mL) was added 6N HCl (0.5 mL) and stirred at room temperature for 12 hours. The reaction solution was directly purified by preparative HPLC to afford the racemate of compound 28 as a white solid (3.8 mg, yield: 22%), which was further resolved on a chiral column to afford compound 28.

[0816] LCMS [M+H] + =594.0.

[0817] 1H NMR (400MHz, DMSO-d6) δ9.25 (s, 1H), 7.53 (d, J = 8.4Hz, 2H), 7.30 (d, J = 8.4Hz, 2H), 7.2 4(d,J=1.2Hz,1H),7.16(d,J=1.2Hz,1H),6.66(t,J=15.2Hz,1H),6.20(s,1H),6.16(d, J=8.0Hz,1H),6.06(d,J=7.6Hz,1H),5.67(s,1H),5.13(d,J=4.8Hz,1H),4.83-4.76(m, 3H), 4.34 (d, J = 14.0Hz, 1H), 4.17-4.10 (m, 1H), 3.90 (s, 3H), 3.85 (s, 3H), 3.09 (s, 3H).

[0818] Compound 29

[0819] Step 1: Dissolve the racemate of compound 24E (20 mg, 0.03 mmol) in dioxane / water (3 mL / 1 mL), add compound 29A (7.30 mg, 0.04 mmol), Na2CO3 (8.74 mg, 0.08 mmol), and Pd(dppf)Cl2 (2.23 mg, 0.001 mmol). Heat to 100°C in a microwave oven under nitrogen for 1 hour. The reaction mixture was filtered, and the filter cake was washed with ethyl acetate (2 mL x 3). After concentration, the racemate of compound 29B (20 mg) was obtained as a yellow solid, which was used directly in the next step. LCMS [M+H-C4H8] + =642.2.

[0820] Step 2: To a solution of the racemate of compound 29B (20 mg, 0.03 mmol) in tetrahydrofuran (0.5 mL) was added 6N HCl (0.3 mL) and stirred at room temperature for 12 hours. The reaction solution was directly purified by preparative HPLC to afford the racemate of compound 29 as a white solid (1.5 mg, 9% yield). Further chiral column separation afforded compound 29.

[0821] LCMS [M+H] + =598.2.

[0822] 1H NMR (400MHz, DMSO-d6) δ9.01 (s, 2H), 7.57-7.53 (m, 4H), 7.32 (d, J = 8.8Hz, 2H),6.66(t,J=7.6Hz,1H),6.23(s,1H),6.17(d,J=12.0Hz,1H),6.04(d,J= 7.6Hz,1H),5.59(s,1H),5.03(d,J=4.8Hz,1H),4.87-4.79(m,3H),4.30(d ,J=14.0Hz,1H),4.16-4.09(m,1H),3.90(s,3H),3.85(s,3H),3.09(s,3H).

[0823] Compound 30

[0824] Step 1: Dissolve the racemate of compound 24E (20 mg, 0.03 mmol) in dioxane / water (3 mL / 1 mL), add compound 30A (7.59 mg, 0.04 mmol), Na2CO3 (8.74 mg, 0.08 mmol), and Pd(dppf)Cl2 (2.23 mg, 0.001 mmol). Heat to 100°C in a microwave oven under nitrogen for 1 hour. The reaction mixture was filtered, and the filter cake was washed with ethyl acetate (2 mL x 3). After concentration, the racemate of compound 30B (20 mg) was obtained as a yellow solid, which was used directly in the next step. LCMS [M+H-C4H8] + =649.2.

[0825] Step 2: To a solution of the racemate of compound 30B (20 mg, 0.03 mmol) in tetrahydrofuran (0.5 mL) was added 6N HCl (0.3 mL) and stirred at room temperature for 12 hours. The reaction solution was directly purified by preparative HPLC to afford the racemate of compound 30 as a white solid (1.1 mg, yield: 6.4%), which was further resolved on a chiral column to afford compound 30.

[0826] LCMS [M+H] + =605.2.

[0827] 1H NMR(400MHz,DMSO-d6)δ8.68(s,2H),7.55-7.53(m,4H),7.33(d,J=8.8Hz,2H ),6.66(t,J=7.6Hz,1H),6.22(s,1H),6.17-6.15(m,1H),6.03(d,J=8.0Hz,1 H),5.54(s,1H),4.98(d,J=4.8Hz,1H),4.83-4.79(m,3H),4.29(d,J=14.0Hz ,1H),4.16-4.10(m,1H),3.98(s,3H),3.90(s,3H),3.85(s,3H),3.08(s,3H).

[0828] Compound 31

[0829] Step 1: Dissolve the racemate of compound 24E (20 mg, 0.03 mmol) in dioxane / water (3 mL / 1 mL), and add compound 31A (7.80 mg, 0.04 mmol), Na2CO3 (8.74 mg, 0.08 mmol), and Pd(dppf)Cl2 (2.23 mg, 0.001 mmol). Heat to 100°C in a microwave oven under nitrogen for 1 hour. The reaction mixture was filtered, and the filter cake was washed with ethyl acetate (2 mL x 3). After concentration, the racemate of compound 31B (20 mg) was obtained as a yellow solid, which was used directly in the next step. LCMS [M+H-C4H8] + =654.2.

[0830] Step 2: To a solution of the racemate of compound 31B (20 mg, 0.03 mmol) in tetrahydrofuran (0.5 mL) was added 6N HCl (0.3 mL) and stirred at room temperature for 12 hours. The reaction solution was directly purified by preparative HPLC to afford the racemate of 31 as a white solid (3.3 mg, yield: 19%), which was further resolved on a chiral column to afford compound 31.

[0831] LCMS [M+H] + =610.2.

[0832] 1H NMR(400MHz,DMSO-d6)δ8.68(s,2H),7.55-7.53(m,4H),7.33(d,J=8.8Hz,2H ),6.66(t,J=7.6Hz,1H),6.22(s,1H),6.17-6.15(m,1H),6.03(d,J=8.0Hz,1 H),5.54(s,1H),4.98(d,J=4.8Hz,1H),4.83-4.79(m,3H),4.29(d,J=14.0Hz ,1H),4.16-4.10(m,1H),3.98(s,3H),3.90(s,3H),3.85(s,3H),3.08(s,3H).

[0833] Compound 32

[0834] Step 1: Dissolve the racemate of compound 24E (20 mg, 0.0300 mmol) in dioxane (2.0 mL) and water (0.5 mL). Add compound 32A (9.00 mg, 0.0550 mmol), Pd(dppf)Cl2 (2.24 mg, 0.0027 mmol), and Na2CO3 (12.00 mg, 0.1099 mmol). Heat to 100°C in a microwave oven under nitrogen for 1 hour. The reaction mixture was filtered and concentrated to afford the racemate of 32B as a yellow solid (17 mg, yield: 84%). LCMS [M+H-C4H8] + =692.2.

[0835] Step 2: Dissolve the racemate of compound 32B (17 mg, 0269 mmol) in THF (1 mL) and add 6M HCl (1 mL). Stir at room temperature for 16 hours. The reaction mixture was filtered and concentrated to obtain a crude product, which was purified using a reverse-phase preparative column [H2O (containing 0.1% FA) / ACN] to afford the racemate of 32 as a white solid (1.1 mg, yield: 7.5%). Further chiral column separation afforded compound 32.

[0836] LCMS [M+H] + =648.2.

[0837] 1H NMR (400MHz, DMSO) δ9.38 (d, J = 0.7Hz, 2H), 7.70 (d, J = 1.1Hz, 1H), 7.66 (d, J = 1.0Hz, 1H), 7. 54(d,J=8.6Hz,2H),7.33(d,J=8.6Hz,2H),6.66(t,J=7.8Hz,1H),6.23(s,1H),6.16(d,J=7 .8Hz,1H),6.05(d,J=7.4Hz,1H),5.65(s,1H),5.09(d,J=4.9Hz,1H),4.84-4.78(m,2H),4. 33(d,J=13.9Hz,1H),4.13(dd,J=15.2,9.8Hz,1H),3.91(s,3H),3.87(s,3H),3.09(s,3H).

[0838] Compound 33

[0839] Step 1: Dissolve the racemate of compound 24E (20 mg, 0.03 mmol) in dioxane / water (3 mL / 1 mL), and add compound 33A (11.26 mg, 0.04 mmol), Na2CO3 (8.74 mg, 0.08 mmol), and Pd(dppf)Cl2 (2.23 mg, 0.001 mmol). Heat the mixture to 100°C in a microwave oven under nitrogen for 1 hour. The reaction mixture was filtered, and the filter cake was washed with ethyl acetate (2 mL x 3). After concentration, the racemate of compound 33B (23 mg) was obtained as a yellow solid, which was used directly in the next step. LCMS [M+H-C4H8] + =739.3.

[0840] Step 2: To a solution of the racemate of compound 33B (23 mg, 0.03 mmol) in tetrahydrofuran (0.5 mL) was added 6N HCl (0.5 mL) and stirred at room temperature for 12 hours. The reaction solution was directly purified by preparative HPLC to afford the racemate of compound 33 as a white solid (1.1 mg, yield: 6.4%), which was further resolved on a chiral column to afford compound 33.

[0841] LCMS [M+H] + =595.2.

[0842] 1H NMR (400MHz, DMSO-d6) δ8.22(s,2H),7.54(d,J=8.8Hz,2H),7.44(d,J=4.8Hz,2 H),7.32(d,J=8.8Hz,2H),6.65(t,J=7.8Hz,1H),6.22(s,1H),6.16(d,J=8.0Hz, 1H),6.01(d,J=7.6Hz,1H),5.75(s,2H),5.47(s,1H),4.89(d,J=4.4Hz,1H),4. 84-4.77(m,3H),4.26(d,J=13.6Hz,1H),3.89(s,3H),3.83(s,3H),3.08(s,3H).

[0843] Compound 34

[0844] Step 1: Dissolve the racemate of compound 24E (20 mg, 0.03 mmol) in dioxane / water (3 mL / 1 mL), and add compound 34A (6.51 mg, 0.04 mmol), Na2CO3 (5.83 mg, 0.08 mmol), and Pd(dppf)Cl2 (4.89 mg, 0.001 mmol). Heat to 100°C in a microwave oven under nitrogen for 1 hour. The reaction mixture was filtered, and the filter cake was washed with ethyl acetate (2 mL x 3). After concentration, the racemate of 34B was obtained as a yellow solid (20 mg), which was used directly in the next step. LCMS [M+H-C4H8] + =649.2.

[0845] Step 2: To a solution of the racemate of compound 34B (20 mg, 0.03 mmol) in tetrahydrofuran (0.5 mL) was added 6N HCl (0.5 mL) and stirred at room temperature for 12 hours. The reaction solution was directly purified by preparative HPLC to afford the racemate of compound 34 as a white solid (4.6 mg, yield: 27%), which was further resolved on a chiral column to afford compound 34.

[0846] LCMS [M+H] + =605.2.

[0847] 1H NMR (400MHz, DMSO-d6) δ9.26(d,J=4.8Hz,1H),8.10(d,J=4.8Hz,1H),7.62(d,J=1.0Hz ,1H),7.58-7.52(m,3H),7.33(d,J=8.4Hz,2H),6.66(t,J=7.6Hz,1H),6.23(s,1H),6.1 6(d,J=8.0Hz,1H),6.04(d,J=7.6Hz,1H),5.64(s,1H),5.08(d,J=4.8Hz,1H),4.93-4. 76(m,3H),4.31(d,J=14.0Hz,1H),4.17(s,1H),3.91(S,3H),3.89(s,3H),3.09(s,3H).

[0848] Compound 35

[0849] Step 1: Dissolve the racemate of compound 24E (20 mg, 0.0275 mmol) in dioxane (2.0 mL) and water (0.4 mL). Add compound 35A (9.00 mg, 0.0550 mmol), Pd(dppf)Cl2 (2.24 mg, 0.0027 mmol), and Na2CO3 (12.00 mg, 0.1099 mmol). Heat to 100°C in a microwave oven under nitrogen for 1 hour. The reaction mixture was filtered and concentrated to obtain the crude product, which was then purified on a reverse phase column (H2O / ACN) to afford the racemate of compound 35B as a yellow solid (12 mg, yield: 63%). LCMS [M+H-C4H8] + =638.2.

[0850] Step 2: Compound 35B (12 mg, 0.0173 mmol) was dissolved in THF (1 mL) and 6 M HCl (1 mL) was added. The mixture was stirred at room temperature for 16 hours. The reaction mixture was filtered and concentrated to obtain the crude product, which was purified using a reverse-phase column [H₂O (containing 0.1% FA) / ACN] to afford 35 as a white solid (2.6 mg, 25% yield). Further chiral column separation afforded compound 35.

[0851] LCMS [M+H] + =594.2.

[0852] 1H NMR (400MHz, DMSO) δ9.38 (d, J = 0.7Hz, 2H), 7.70 (d, J = 1.1Hz, 1H), 7.66 (d, J = 1.0Hz, 1H), 7. 54(d,J=8.6Hz,2H),7.33(d,J=8.6Hz,2H),6.66(t,J=7.8Hz,1H),6.23(s,1H),6.16(d,J=7 .8Hz,1H),6.05(d,J=7.4Hz,1H),5.65(s,1H),5.09(d,J=4.9Hz,1H),4.84-4.78(m,2H),4. 33(d,J=13.9Hz,1H),4.13(dd,J=15.2,9.8Hz,1H),3.91(s,3H),3.87(s,3H),3.09(s,3H).

[0853] Compound 36

[0854] Step 1: Compound 24E racemate (20 mg, 0.03 mmol) was dissolved in dioxane / H2O (2.5 mL / 0.5 mL) and added to compound 36A (9.8 mg, 0.05 mmol), Na2CO3 (8.8 mg, 0.08 mmol), and Pd(dppf)Cl2 (2.5 mg, 0.00 mmol). The mixture was heated to 100°C in a microwave oven under nitrogen for 1 hour. The reaction solution was concentrated and the crude product was purified by reverse phase column chromatography (ACN / H2O) to obtain the racemate 36B as a white solid (10.0 mg, yield: 52.1%). LCMS [M+H-C4H8] + =643.2.

[0855] Step 2: Add HCl (6N, 2 mL) to a solution of the racemate of compound 36B (10.0 mg, 0.01 mmol) in THF (2 mL) and stir at room temperature overnight. The reaction solution was directly purified using a reverse phase column (ACN / H2O) to obtain the racemate of compound 36 as a white solid (6.4 mg, yield: 74.7%). Further chiral column separation afforded compound 36. LCMS [M+H] + =599.3.

[0856] Compound 37

[0857] Step 1: The racemate of compound 10O (20 mg, 0.03 mmol), compound 11A (42.6 mg, 0.3 mmol), HOAT (6.12 mg, 0.045 mmol), tert-dodecylmercaptan (60.6 mg, 0.3 mmol), TMP (5.48 mg, 0.045 mmol), meso-tetraphenylporphyrin zinc (2.03 mg, 0.003 mmol), and DMF (2 mL) were added to a microwave vial. After nitrogen was replaced in the reaction system, the microwave vial was stirred in an 80°C hot water bath while irradiated with 25W red light. A solution of EDCI (57.3 mg, 0.3 mmol) in DMF (2 mL) was slowly added dropwise to the reaction mixture, followed by stirring for 30 minutes. After completion of the reaction, the reaction mixture was purified on a silica gel column (HO / ACN = 40%:60%) to obtain the racemate of compound 37A (8.6 mg, yield: 46%). LCMS [M+H] + =553.2.

[0858] Step 2: Dissolve the racemate of compound 37A (8.6 mg, 0.015 mmol) in THF (1 mL) and add 6 M HCl (2 mL). Stir the reaction mixture at room temperature (20°C) for 2 hours. The reaction mixture is spin-dried and purified on a silica gel column (H2O / ACN = 55:45) to obtain the racemate of compound 37 (3.7 mg, yield: 52%). Further chiral column separation affords compound 37.

[0859] LCMS [M+H] + =453.2.

[0860] 1 H NMR (400MHz, DMSO) δ8.80(d,J=1.7Hz,1H),8.33(s,1H),7.87(d,J=1.7Hz,1H),7.54 (d,J=8.6Hz,2H),7.47(d,J=0.6Hz,1H),7.30(d,J=8.6Hz,2H),6.88(s,1H),6.55(s ,1H),6.47(d,J=23.6Hz,2H),6.03(s,1H),5.21(s,1H),4.51(d,J=3.9Hz,1H),4.24 (dd,J=14.0,6.0Hz,1H),2.80(td,J=13.4,4.3Hz,1H),2.16(dd,J=12.6,6.3Hz,1H).

[0861] Compound 38

[0862] Step 1: To a solution of the racemate of compound 10O (24 mg, 0.04 mmol) in DMF (2 mL) were added dimethylamine solution (0.1 mL, 0.2 mmol), HATU (15 mg, 0.04 mmol), and TMP (5 mg, 0.04 mmol), and the mixture was stirred at 20°C for 2 hours. The reaction solution was directly purified by reverse phase chromatography (MeCN / H2O / FA) to afford the racemate of 38A as a white solid (12 mg, yield: 48%). LCMS [M+H] + =624.3.

[0863] Step 2: To a solution of the racemate of compound 38A (12 mg, 0.02 mmol) in THF (2 mL) was added 6 M HCl (2 mL) and stirred at 25°C for 18 hours. The reaction solution was directly purified by reverse-phase chromatography (MeCN / H2O / FA) to afford the racemate of 38 as a white solid (4.7 mg, 47% yield), which was further resolved by chiral column chromatography to afford compound 38.

[0864] LCMS [M+H] + =524.2.

[0865] 1 H NMR (400MHz, DMSO) δ8.78(d,J=1.7Hz,1H),8.33(s,1H),7.89(d,J=1.7Hz,1H),7.53(s,1H),7.51(s,1H),7.47(s,1H), 7.37(d,J=8.5Hz,2H),6.66(t,J=7.8Hz,1H),6.22(s,1H),6.20(s,1H),6.14(dd,J=17.3,7.6Hz,2H),5.28(d,J=5.5Hz, 1H), 4.79 (s, 2H), 4.73 (t, J = 5.3Hz, 1H), 4.54 (d, J = 13.3Hz, 1H), 4.21 (dd, J = 13.3, 5.3Hz, 1H), 3.28 (s, 3H), 2.79 (s, 3H).

[0866] Compound 39

[0867] Step 1: Compound 10G (1 g, 2.36 mmol) and compound 9A (2.3 g, 14.14 mmol) were dissolved in CHCl₃ / TFE = 7 / 3 (15 mL). The reaction mixture was pumped at a rate of 12 mL / h using a 20 mL syringe via a syringe pump into a coil wrapped around a jacketed glass cylinder equipped with a 250 W UV lamp. The temperature of the external circulating hydrazine was adjusted to maintain an internal reaction temperature of 0-5°C. The UV lamp was turned on and the reaction mixture was irradiated for 1 hour. The solvent was removed under reduced pressure and the excess cinnamate was removed by column chromatography (EA / PE = 1 / 3) to obtain the racemate of 39A as a pale yellow solid (7 g, yield: 51%). LCMS [M+H-H₂O] + =568.1.

[0868] Step 2: The racemate of compound 39A (4.9 g, 8.37 mmol) was dissolved in methanol (60 mL) and NaOMe (1.135 g, 20.94 mmol) was added at 0°C. The mixture was stirred at 65°C for 1.5 hours. The reaction solution was concentrated and extracted with EA, washed with water, NH4Cl solution, and saturated brine, and dried over anhydrous sodium sulfate. After filtration and concentration, the mixture was purified on a silica gel column (0.2% FA in EA / PE = 1 / 3) to obtain the racemate of compound 39B (3.6 g, 73%). LCMS [M+H] + =586.1.

[0869] Step 3: The racemate of compound 39B (3.6 g, 6.15 mmol) was dissolved in a mixed solvent of ACN / CHCl3 = 1 / 1 (40 mL / 40 mL). Na(AcO)3BH (6.525 g, 30.77 mmol) and AcOH (3.695 g, 61.53 mmol) were added at 0°C and stirred at room temperature for 2 hours. The reaction solution was concentrated and extracted with EA, washed with water and saturated brine, and dried over anhydrous sodium sulfate. After filtration and concentration, the product was purified on a silica gel column (0.2% FA in EA / PE = 3 / 2) to obtain the racemate of compound 39C (1.9 g, yield: 53%). LCMS [M+H] + =588.1.

[0870] Step 4: Under nitrogen, a solution of the racemate of compound 39C (1500 mg, 2.55 mmol), Zn(CN)2 (7745.6 mg, 6.37 mmol), Pd2(dba)3 (468 mg, 0.5 mmol), and DPPF (564 mg, 1.02 mmol) in DMP (30 mL) was stirred at 150°C for 1 hour. The mixture was diluted with water and extracted three times with EA (50 ml x 3). The organic phase was concentrated, and the crude product was purified using a FLASH column (medium-low pressure flash preparative liquid chromatography) (DCM / MEOH = 0-10%) to obtain the racemate of compound 39D as a yellow solid (1100 mg, yield: 80.7%). LCMS: [M+H] + =535.6.

[0871] Step 5: To a solution of EA / MeOH (20 / 20 mL) was added the racemate of 39D (1100 mg, 2.06 mmol) and Pd / C (700 mg), the hydrogen atmosphere was replaced three times, and the mixture was stirred at room temperature for 16 hours. The reaction solution was purified using a FLASH column (MeOH / DCM = 0-10%) to obtain the racemate of compound 39E (350 mg, yield: 38.2%). LCMS: [M+H] + =445.6.

[0872] Step 6: The racemate of compound 39E (350 mg, 0.79 mmol) and K2CO3 (108 mg, 0.79 mmol) were added to DMF (5 mL), followed by compound 2G (281 mg, 0.79 mmol) and stirred at 60°C for 1.5 hours. The reaction solution was diluted with EA (30 mL) and washed with H2O (20 mL*2). It was then purified using a FLASH column (medium-low pressure rapid preparative liquid phase) (MeOH / DCM = 0-10%) to obtain the racemate of compound 39F (310 mg, yield: 68.3%). LCMS [M+H] + =577.6.

[0873] Step 7: The racemate of compound 39F (300 mg, 0.7 mmol), compound 2I (756 mg, 2.1 mmol) and Pd(PPh3)4 (81 mg, 0.05 mmol) were added to DMF (4 mL), and CuI (26.5 mg, 0.14 mmol) was added, and the mixture was stirred at 135°C under microwave for 5 hours. The reaction solution was diluted with EA (30 mL) and the resulting mixture was washed with H2O (20 mL*2). The solution was purified by FLASH column (medium-low pressure rapid preparative liquid phase) (MeOH / DCM = 0-15%) to obtain the racemate of 39G as a yellow solid (250 mg, yield: 71%). LCMS [M+H]+ =496.2.

[0874] Step 8: The racemate of compound 39G (250 mg, 0.5 mmol) and LiOH·H2O (60 mg, 1.5 mmol) were added to a mixture of THF / MeOH / H2O (1.5 / 1.5 / 1.5 mL) and stirred at 20°C for 5 hours. The reaction solution was purified using a FLASH column (medium-low pressure flash preparative liquid chromatography) (ACN-H2O) to obtain the racemate of compound 39H as a yellow solid (170 mg, yield: 70%). LCMS [M+H] + =482.7.

[0875] Step 9: The racemate of compound 39H (20 mg, 0.04 mmol), HATU (16 mg, 0.04 mmol), and TMP (15 mg, 0.12 mmol) were dissolved in DMF (2 mL), and 3-hydroxyazetidine (5.8 mg, 0.08 mmol) was added. The mixture was stirred at 20°C for 2 hours. The reaction solution was purified using a FLASH column (MeOH / DCM = 0-10%) to obtain the racemate of 39 as a white solid (19 mg, yield: 86%). Compound 39 was further resolved using a chiral column.

[0876] LCMS [M+H] + =537.7.

[0877] 1 H NMR (400MHz, DMSO) δ8.79(s,1H),8.44(s,1H),8.33(s,1H),7.93(d,J=1.6Hz,1H),7.48(d,J=6.1Hz,3H),7.37-7.30(m,2H),7.06(t,J=6.8H z,2H),7.02-6.93(m,3H),6.28(d,J=10.8Hz,1H),5.82(s,1H),5.41(m ,1H),4.67(m,2H),4.53(m,2H),4.07-3.96(m,3H),3.62-3.55(m,1H).

[0878] Compound 40

[0879] Step 1: The racemate of compound 39D (20 mg, 0.04 mmol), HATU (12 mg, 0.04 mmol), and TMP (14.5 mg, 0.12 mmol) were stirred in DMF (2 mL). Compound 40A (12 mg, 0.04 mmol) was added and stirred at 20°C for 2 hours. The mixture was purified by normal phase chromatography (MeOH / DCM = 0-10%) to obtain the racemate of 40B as a white solid (30 mg, yield: 94%). LCMS [M+H] + =747.0.

[0880] Step 2: Dissolve the racemate of compound 40B (30 mg, 0.04 mmol) and piperidine (10 mg, 0.12 mol) in DMF (1 mL) and react at 20°C for 1 hour. The reaction solution was lyophilized to obtain the racemate of compound 40 as a white solid (20 mg, yield: 87%), which was further resolved on a chiral column to afford compound 40.

[0881] LCMS [M+H] + =524.2.

[0882] 1 H NMR (400MHz, DMSO) δ8.80(d,J=1.7Hz,1H),8.41(t,J=5.6Hz,1H),8.34(s,1H),7.93(d,J=1.7Hz,1H),7.52(d,J=8.6Hz,2H),7.48(s,1H),7.30(d, J=8.5Hz,2H),7.04(ddd,J=21.9,14.9,7.3Hz,6H),6.26(s,1H),4.67(dd,J=18.3,9.1Hz,2H),3.25(dd,J=12.6,6.5Hz,3H),2.75(t,J=6.6Hz,2H).

[0883] Compound 41

[0884] Step 1: To a solution of the racemate of compound 19I (100.0 mg, 0.15 mmol) in THF / H2O / MeOH (3 ml / 1 mL / 1 mL) was added LiOH·H2O (19.3 mg, 0.46 mmol) and stirred at 40°C for 3 hours. The pH of the reaction solution was adjusted to approximately 5 with 3M HCl, the reaction solution was spin-dried and purified by normal phase column chromatography (DCM / MeOH) to obtain the racemate of compound 41A (75 mg, yield: 77%). LCMS [MH] - =638.2.

[0885] Step 2: To a DMF (mL) solution of the racemate of compound 41A (75.0 mg, 0.12 mmol), dimethylhydroxylamine hydrochloride (22.8 mg, 0.23 mmol), HOAT (16.0 mg, 0.12 mmol), and HATU (89.2 mg, 0.23 mmol) was added TMP (56.8 mg, 0.47 mmol). The mixture was stirred at 40°C for 16 hours. The reaction mixture was purified by normal phase column chromatography (DCM / MeOH) to obtain the racemate of compound 41B (85 mg, yield: 110%). LCMS [M+H] + =683.1.

[0886] Step 3: To a solution of the racemate of compound 41B (85.0 mg, 0.13 mmol) in EA / MeOH / THF / DCM (20:2:2:0.2, 10 mL) was added Pd(OH)2 / C (10%, 50 mg). The mixture was replaced with hydrogen three times and stirred at room temperature for 16 hours. The reaction mixture was filtered, and the filter cake was rinsed three times with MeOH / DCM (1 / 10). The filtrate was dried to give the racemate of compound 41C (50 mg, crude product not included in yield), which was used directly in the next reaction. LCMS [M+H] + =593.1.

[0887] Step 4: Compound 2G (30.2 mg, 0.084 mmol) was added to a solution of the racemate of compound 41C (50.0 mg, 0.08 mmol) and K2CO3 (23.3 mg, 0.169 mmol) in DMF (2 mL). The mixture was stirred at 60°C for 1 hour. The reaction mixture was extracted with water and ethyl acetate, and the organic phase was dried over anhydrous sodium sulfate. After filtration and concentration, the crude product was purified by normal phase column chromatography (PE / EA) to obtain the racemate of compound 41D (45 mg, yield: 73%). LCMS: [M+H]+ = 725.1.

[0888] Step 5: The racemate of compound 41D (33.0 mg, 0.05 mmol) was dissolved in dioxane (5 mL) and Pin2B2 (34.5 mg, 0.14 mmol), Pd(dppf)Cl2 (7.4 mg, 0.01 mmol), and KOAc (13.4 mg, 0.18 mmol) were added. The mixture was stirred at 85°C under N2 protection for 16 hours. The reaction mixture was filtered, the filter cake was washed with EA, and the filtrate was concentrated and purified on a silica gel column (DCM / MeOH) to obtain the racemate of compound 41E (43 mg, crude product was not included in the yield), which was used directly in the next reaction. LCMS [M+H] + =703.3.

[0889] Step 6: The racemate of compound 41E (43.0 mg, 0.06 mmol), 2-bromooxazole (13.6 mg, 0.09 mmol), Na2CO3 (19.5 mg, 0.184 mmol) and Pd(dppf)Cl2 (5.0 mg, 0.01 mmol) were added to a dioxane / water (2 mL / 1 mL) solution. The reaction mixture was degassed under reduced pressure, replaced with N2 three times, and stirred at 100°C for 2 hours using a microwave. The reaction solution was concentrated and purified on a silica gel column (DCM / MeOH) to obtain the racemate of compound 41F (7 mg, yield: 17.7%). LCMS [M+H] + =644.1.

[0890] Step 7: The racemate of compound 41F (7.0 mg, 0.01 mmol) was mixed with THF (1 mL), 6 M HCl (2 mL) was added at 0°C, and the mixture was stirred at 10°C for 16 hours. The reaction solution was concentrated and purified by preparative HPLC to afford the racemate of compound 41 as a white solid (0.8 mg, yield: 13.5%), which was further resolved by chiral column to afford compound 41.

[0891] LCMS [M+H] + =544.2.

[0892] 1 H NMR (400MHz, DMSO) δ8.25(s,1H),7.41(s,1H),7.17(d,J=14.2Hz,2H),7.04(t,J= 7.4Hz,2H),6.98(d,J=7.2Hz,1H),6.89(d,J=7.6Hz,2H),6.69(t,J=7.8Hz,1H),6 .47(s,1H),6.28(d,J=7.9Hz,1H),6.19(d,J=8.2Hz,1H),5.23(s,1H),4.90(s,1H ),4.84(s,1H),4.76(s,1H),4.21(s,1H),3.89(s,3H),3.86(s,3H),3.06(s,3H).

[0893] Compound 42

[0894] Step 1: The racemate of compound 24D (50 mg, 0.07 mmol), t-BuXPhos-PdG3 (7.94 mg, 0.01 mmol), and K2CO3 (450 mg, 3.26 mmol) were added to DMF (3 mL), followed by compound 42A (582 mg, 1.63 mmol), and the mixture was reacted at 120°C for 5 hours. The reaction mixture was diluted with water and extracted three times with EA (10 mL x 3). The organic phase was concentrated and purified by preparative HPLC (ACN / H2O) to afford the racemate of 42B as a white solid (8 mg, yield: 18%). LCMS [M+H] + =682.1.

[0895] Step 2: Add the racemate of compound 42B (10 mg, 0.01 mmol) and 6M HCl (1.5 mol) to THF (1 mL) and react at 40°C for 5 hours. The reaction solution was lyophilized to obtain the racemate of compound 42B as a white solid (8 mg, yield: 94%). LCMS [M+H] + =582.1, and further chiral column separation gave compound 42.

[0896] 1 H NMR (400MHz, DMSO) δ8.36 (s, 1H), 7.63-7.50 (m, 3H), 7.31 (d, J = 8.5Hz, 2H), 7.13-6.98 (m, 3H), 6.80 (s, 3H), 5.60 (s, 1 H),4.81(s,1H),4.42(d,J=13.4Hz,1H),4.17(d,J=12.4Hz,1H),3.92(s,3H),3.83(s,3H),3.08(s,3H),2.12(s,3H).

[0897] Compound 43

[0898] Step 1: Dissolve the racemate of compound 24E (20 mg, 0.03 mmol) in dioxane / water (3 mL / 1 mL), add compound 43A (7.79 mg, 0.04 mmol), Na2CO3 (5.83 mg, 0.06 mmol), and Pd(dppf)Cl2 (4.89 mg, 0.001 mmol). Heat to 100°C in a microwave oven under nitrogen for 1 hour. Filter the reaction mixture, wash the filter cake with ethyl acetate (2 mL x 3), and concentrate to obtain the racemate of 43B (20 mg) as a yellow solid, which is used directly in the next step. LCMS [M+H] + =710.2.

[0899] Step 2: To a solution of the racemate of compound 43B (20 mg, 0.03 mmol) in tetrahydrofuran (0.5 mL) was added 6N HCl (0.5 mL) and stirred at room temperature for 12 hours. The reaction solution was directly purified by preparative HPLC to afford the racemate of compound 43 as a white solid (3.1 mg, yield: 18%), which was further resolved by chiral column to afford compound 43.

[0900] LCMS [M+H]+ = 610.2.

[0901] 1 H NMR (400MHz, DMSO-d6) δ8.89(d,J=1.2Hz,1H),8.41(d,J=1.2Hz,1H),7.54(d,J=8.4Hz ,2H),7.33(s,1H),7.31(s,2H),7.24(d,J=0.8Hz,1H),6.67(t,J=7.8Hz,1H),6.22-6.1 5(m,2H),6.05(d,J=8.0Hz,1H),5.51(s,1H),4.98(d,J=4.4Hz,1H),4.82-4.78(m,3H), 4.30(d,J=14.0Hz,1H),4.13(d,J=14.8Hz,1H),4.03(s,3H),3.90(s,3H),3.85(s,3H).

[0902] Compound 44

[0903] Step 1: Dissolve the racemate of compound 24E (20 mg, 0.03 mmol) in dioxane / water (3 mL / 1 mL), add compound 44A (7.59 mg, 0.04 mmol), Na2CO3 (5.83 mg, 0.08 mmol), and Pd(dppf)Cl2 (4.89 mg, 0.001 mmol). Heat to 100°C in a microwave oven under nitrogen for 1 hour. The reaction mixture was filtered, and the filter cake was washed with ethyl acetate (2 mL x 3). After concentration, the racemate of 44B (20 mg) was obtained as a yellow solid, which was used directly in the next step. LCMS [M+H] + =705.0.

[0904] Step 2: To a solution of the racemate of compound 44B (20 mg, 0.03 mmol) in tetrahydrofuran (0.5 mL) was added 6N HCl (0.5 mL) and stirred at room temperature for 12 hours. The reaction solution was directly purified by preparative HPLC to afford the racemate of compound 44 as a white solid (1.4 mg, yield: 8.2%), which was further resolved on a chiral column to afford compound 44.

[0905] LCMS [M+H]+ = 605.2.

[0906] 1 H NMR (400MHz, DMSO-d6) δ9.57(d,J=1.6Hz,1H),9.28(d,J=1.2Hz,1H),7.55-7.53( m,3H),7.42(s,1H),7.33-7.31(m,2H),6.67(t,J=7.8Hz,1H),6.20-6.15(m,2H),6 .07(d,J=8.0Hz,1H),5.64(s,1H),5.10(d,J=5.2Hz,1H),4.82-4.78(m,3H),4.34 (d,J=13.6Hz,1H),4.15(d,J=18.8Hz,1H),3.90(s,3H),3.87(s,3H),3.09(s,3H).

[0907] Compound 45

[0908] Step 1: Dissolve the racemate of compound 24E (20 mg, 0.03 mmol) in dioxane / water (3 mL / 1 mL), add compound 45A (6.51 mg, 0.04 mmol), NaCO (5.83 mg, 0.08 mmol), and Pd(dppf)Cl (4.89 mg, 0.001 mmol). Heat the mixture to 100°C in a microwave oven under nitrogen for 1 hour. Filter the reaction mixture, wash the filter cake with ethyl acetate (2 mL x 3), and concentrate to obtain the racemate of 45B (20 mg) as a yellow solid, which is used directly in the next step.

[0909] Step 2: To a solution of the racemate of compound 45B (20 mg, 0.03 mmol) in tetrahydrofuran (0.5 mL) was added 6N HCl (0.5 mL) and stirred at room temperature for 12 hours. The reaction solution was directly purified by preparative HPLC to obtain the racemate of compound 45 as a white solid (1.5 mg, yield: 8.8%). Further chiral column separation gave compound 45. LCMS [M+H] + =579.2

[0910] 1H NMR (400MHz, DMSO-d6) δ8.96(d,J=2.0Hz,1H),8.59(d,J=5.6Hz,1H),8.14(d,J=8.0Hz,1H) ,7.70-7.46(m,3H),7.33(d,J=8.4Hz,2H),7.00(s,1H),6.88(s,1H),6.79-6.57(m,1H),6. 23-6.12(m,2H),6.06(d,J=7.6Hz,1H),5.51(s,1H),4.99(d,J=4.4Hz,1H),4.88-4.64(m,3 H),4.30(d,J=13.9Hz,1H),4.14(d,J=10.5Hz,1H),3.90(s,3H),3.88(s,3H),3.09(s,3H).

[0911] Compound 46

[0912] Step 1: The racemate of compound 24E (20 mg, 0.03 mmol) was dissolved in dioxane / water (3 mL / 1 mL), and compound 46A (6.51 mg, 0.04 mmol), Na2CO3 (5.83 mg, 0.08 mmol), and Pd(dppf)Cl2 (4.89 mg, 0.001 mmol) were added. The reaction was microwaved at 100°C for 1 hour. The reaction mixture was filtered, the filter cake was washed with ethyl acetate (2 mL x 3), and the filtrates were combined and concentrated to obtain the racemate of 46B (20 mg) as a yellow solid, which was used directly in the next step. LCMS [M+H] + =679.0.

[0913] Step 2: To a solution of the racemate of compound 46B (20 mg, 0.03 mmol) in tetrahydrofuran (0.5 mL) was added 6N HCl (0.5 mL) and stirred at room temperature for 12 hours. The reaction solution was directly purified by preparative HPLC to afford the racemate of compound 46 as a white solid (1.4 mg, yield: 8.2%), which was further resolved by chiral column to afford compound 46.

[0914] LCMS [M+H] + =579.1.

[0915] 1H NMR (400MHz, DMSO-d6) δ8.69-8.68(m,1H),8.04(d,J=8.0Hz,1H),7.92-7.88(m,1 H),7.54(d,J=8.8Hz,2H),7.40-7.32(m,5H),6.66(t,J=7.8Hz,1H),6.20-6.15(m, 2H),6.05(d,J=7.2Hz,1H),5.52(s,1H),4.97(d,J=4.4Hz,1H),4.82-4.79(m,3H), 4.30(d,J=14.0Hz,1H),4.16-4.11(m,1H),3.90(s,3H),3.86(s,3H),3.09(s,3H).

[0916] Compound 47

[0917] Step 1: To a solution of the racemate of compound 6A (30 mg, 0.05 mmol) in tetrahydrofuran (5 mL) was added BH3·DMS (70 μL, 0.14 mmol). The reaction system was stirred at 60°C for 2 hours. Methanol (15 mL) was added to the reaction system and stirring was continued at 60°C for 18 hours. The reaction solution was spin-dried and then purified by normal phase column chromatography (DCM:MeOH) to obtain the racemate of compound 47A as a white solid (20 mg, yield: 69%). LCMS [M+H] + =639.2.

[0918] Step 2: To a solution of the racemate of compound 47A (20 mg, 0.03 mmol) in THF (1 mL) was added 6 M HCl (1 mL). The reaction was stirred at room temperature for 18 hours. The reaction solution was purified by reverse-phase column chromatography (HO / ACN) to afford the racemate of compound 47 as a white solid (14 mg, yield: 69%). Further chiral column separation afforded compound 47.

[0919] LCMS [M+H] + =539.2.

[0920] 1H NMR (400MHz, DMSO) δ9.68(s,1H),8.25(s,1H),7.57-7.36(m,5H),7.18(s,2H),6.85(s,1H),6.45(d,J=39.4Hz,3H),5.74(s,1H),5.30(d,J=5. 8Hz,1H),4.68(s,1H),3.87(s,3H),3.68(d,J=13.2Hz,1H),3.24(d,J=11.1Hz,1H),2.95(d,J=3.3Hz,3H),2.84(t,J=12.9Hz,4H),1.24(s,1H).

[0921] Compound 48

[0922] Step 1: Add the racemate of compound 9H (210 mg, 0.4 mmol) and LiOH·H2O (48 mg, 1.19 mmol) to THF / MeOH / H2O (1.5 / 1.5 / 1.5 mL). Stir at 20°C for 16 hours. The solution is purified by reverse phase column chromatography (MeCN / H2O / FA) to afford the racemate of compound 48A as a white solid (150 mg, yield: 75%). LCMS [M+H] + =516.7.

[0923] Step 2: The racemate of compound 48A (20 mg, 0.04 mmol), HATU (15 mg, 0.04 mmol), and TMP (14 mg, 0.12 mmol) were stirred in DMF (2 mL). The racemate of compound 48B (9 mg, 0.08 mmol) was added to the mixture, and the mixture was stirred at 20°C for 2 hours. The mixture was purified by silica gel column (MeOH / DCM = 0-10%) to obtain 48 as a white solid (10 mg, yield: 50%). The product was further resolved by chiral column to obtain compound 48.

[0924] LCMS [M+H] + =571.2.

[0925] 1H NMR (400MHz, DMSO) δ8.25 (s, 1H), 7.41 (s, 1H), 7.17 (d, J = 20.4Hz, 2H), 7.05 ( m,4H),7.00-6.94(m,1H),6.91(d,J=7.2Hz,2H),6.58(m,2H),5.77(m,1H),5 .34(d,J=7.2Hz,1H),4.91(t,J=4.4Hz,1H),4.72-4.45(m,3H),4.31(m,1H), 4.23-4.05(m,1H),4.03-3.93(m,1H),3.88-3.76(m,4H),3.61-3.50(m,4H).

[0926] Compound 49

[0927] Step 1: The racemate of compound 20H (25 mg, 0.04 mmol), compound 11A (50.38 mg, 0.4 mmol), HOAT (8.09 mg, 0.06 mmol), tert-dodecylmercaptan (80.13 mg, 0.40 mmol), TMP (7.25 mg, 0.06 mmol), and meso-tetraphenylporphyrin zinc (2.69 mg, 0.001 mmol) were mixed with DMF (2 mL) and placed in a microwave oven. After nitrogen was replaced in the reaction system, the microwave oven was stirred in 80°C hot water while irradiated with 25W red light. EDCI (75.77 mg, 0.40 mmol, dissolved in 2 mL of DMF) was slowly added dropwise to the reaction mixture, followed by stirring for 30 minutes. After completion of the reaction, the reaction mixture was purified on a silica gel column (HO / ACN = 40%:60%) to obtain the racemate of the target product 49A (16 mg, yield: 69%). LCMS[M+H-C4H8-H2O] + =513.2.

[0928] Step 2: Dissolve the racemate of compound 49A (13 mg, 0.02 mmol) in THF (2 mL) and add 6 M HCl (4 mL). Stir the reaction mixture at room temperature (20°C) for 4 hours. The reaction mixture is spin-dried and purified on a silica gel column (H2O / ACN = 55:45) to obtain the racemate of compound 49 (10 mg, yield: 93%). Further chiral column separation affords compound 49.

[0929] LCMS [M+H] + =487.2.

[0930] 1H NMR (400MHz, DMSO) δ8.24(d,J=0.7Hz,1H),7.40(d,J=0.7Hz,1H),7.14(dd,J=5.1,1.1Hz,2 H),7.04(d,J=9.0Hz,2H),6.75(t,J=7.7Hz,1H),6.62(d,J=9.0Hz,2H),6.40(s,1H),6.26(t ,J=6.3Hz,2H),5.06(s,1H),5.01(s,1H),4.65(d,J=3.7Hz,1H),4.47(s,1H),3.93-3.87(m ,1H),3.86(s,3H),3.62(s,3H),2.64(td,J=13.4,4.9Hz,1H),2.00(dd,J=12.7,6.1Hz,1H).

[0931] Compound 50

[0932] Step 1: Dissolve the racemate of compound 20F (2.8 g, 3.86 mmol) in dioxane (30 mL) and add Pin2B2 (2.9 g, 11.59 mmol), Pd(dppf)Cl2 (630.3 mg, 0.77 mmol), and KOAc (1.1 g, 15.45 mmol). Replace the atmosphere with nitrogen three times and stir at 85°C for 16 hours. The reaction mixture was filtered, and the filter cake was washed with EA. The filtrate was concentrated and purified on a silica gel column (DCM / MeOH) to obtain the racemate of compound 50A (1.8 g, yield: 66%). LCMS [M+Na] + =726.8.

[0933] Step 2, Step 3: Dissolve the racemate of compound 50A (200.0 mg, 0.28 mmol) in dioxane / water (2 mL / 1 mL), and add compound 46A (67.4 mg, 0.43 mmol), Na2CO3 (90.5 mg, 0.85 mmol), and Pd(dppf)Cl2 (23.0 mg, 0.03 mmol). The atmosphere was purged with nitrogen three times, and the reaction mixture was stirred at 130°C for 2 hours. After concentration, the mixture was purified on a silica gel column (DCM / MeOH) to obtain the racemate of compound 50C (110 mg, two-step yield: 60%). LCMS [M+H] + =641.8.

[0934] Step 4: HATU (26.7 mg, 0.07 mmol), DIEA (30.2 mg, 0.24 mmol), and the racemate of compound 50C (30.0 mg, 0.05 mmol) were dissolved in DMF (2 mL) and stirred at 10°C for 10 minutes. Dimethylamine (0.1 mL, 0.23 mmol, 2 M in THF) was added to the mixture and reacted at 10°C for 1 hour. The solution was diluted with water, extracted with EA, washed with water and brine, and dried over anhydrous Na2SO4. The mixture was filtered, concentrated, and purified on a silica gel column (DCM / MeOH) to obtain the racemate of compound 50D (20 mg, yield: 64%). LCMS [M+H] + =669.0.

[0935] Step 5: The racemate of compound 50D (20.0 mg, 0.02 mmol) was dissolved in THF (1 mL), 6 M HCl (1 mL) was added at 0°C, and the mixture was stirred at 25°C for 16 hours. The mixture was concentrated and purified by preparative HPLC to afford the racemate of compound 50 as a white solid (4.1 mg, yield: 24%), which was further resolved by chiral column to afford compound 50.

[0936] LCMS [M+H] + =568.2.

[0937] 1 H NMR (400MHz, DMSO) δ8.69(dd,J=4.7,0.9Hz,1H),8.05(d,J=8.1Hz,1H),7.90(td,J=7.8,1.8Hz,1H),7.41-7.3 4(m,1H),7.32(dd,J=6.4,1.1Hz,2H),7.10(d,J=8.9Hz,2H),6.69(t,J=7.8Hz,1H),6.64(d,J=9.0Hz,2H),6.3 2(s,1H),6.25(d,J=6.7Hz,1H),6.10(d,J=7.0Hz,1H),5.23(s,1H),4.79(d,J=5.5Hz,1H),4.73(d,J=3.6Hz,1 H), 4.20 (d, J = 13.4Hz, 1H), 4.01 (dd, J = 13.4, 6.1Hz, 1H), 3.88 (s, 3H), 3.63 (s, 3H), 3.25 (s, 3H), 2.76 (s, 3H).

[0938] Compound 51

[0939] Step 1: The racemate of compound 50C (25 mg, 0.04 mmol), compound 11A (49.59 mg, 0.39 mmol), HOAT (7.97 mg, 0.06 mmol), tert-dodecylmercaptan (78.88 mg, 0.39 mmol), TMP (7.13 mg, 0.06 mmol), and meso-tetraphenylporphyrin zinc (2.65 mg, 0.004 mmol) were mixed with DMF (2 mL) and placed in a microwave oven. After nitrogen was replaced in the reaction system, the microwave oven was stirred in 80°C hot water while irradiated with 25W red light. A solution of EDCI (74.58 mg, 0.39 mmol) in DMF (2 mL) was slowly added dropwise to the reaction mixture, followed by stirring for 30 minutes. After completion of the reaction, the reaction mixture was purified on a silica gel column (HO / ACN = 40:60) to obtain the racemate of the target product 51A (14 mg, yield: 60%). LCMS [M+H] + =597.2.

[0940] Step 2: Dissolve the racemate of compound 51A (12 mg, 0.02 mmol) in THF (2 mL) and add 6 M HCl (4 mL). Stir the reaction mixture at room temperature (20°C) for 4 hours. The reaction mixture is spin-dried and purified on a silica gel column (H2O / ACN = 55%:45%) to obtain the racemate of the target product 51 (3 mg, yield: 30%). Further chiral column separation affords compound 51.

[0941] LCMS [M+H] + =497.2.

[0942] 1 H NMR (400MHz, DMSO) δ8.68(d,J=3.9Hz,1H),8.03(d,J=8.1Hz,1H),7.89(td,J=7.8,1.8Hz,1H),7. 40-7.35(m,1H),7.33-7.27(m,2H),7.07(d,J=9.0Hz,2H),6.73(t,J=7.7Hz,1H),6.63(d,J=9.0H z,2H),6.37(s,1H),6.23(d,J=7.8Hz,2H),5.33(t,J=4.6Hz,1H),4.92(s,1H),4.80(s,1H),4.57 (d,J=3.6Hz,1H),4.50(d,J=4.1Hz,1H),3.87(s,3H),3.63(s,3H),2.00(dd,J=15.0,7.3Hz,3H).

[0943] Compound 52

[0944] Step 1: The racemate of compound 20H (30 mg, 0.048 mmol) was dissolved in DMF (3 mL). Dimethylamine solution (0.12 mL, 0.24 mmol, 2 M in THF), HATU (36.18 mg, 0.095 mmol), HOAT (12.95 mg, 0.095 mmol), and TMP (17.27 mg, 0.14 mmol) were added and stirred at 25°C for 2 hours. The reaction was quenched with water and extracted twice with ethyl acetate. The organic phase was concentrated and purified on a silica gel column (EA / PE) to afford the racemate of 52A as a yellow solid (20 mg, yield: 65%). LCMS [M+H] + =658.2.

[0945] Step 2: Dissolve the racemate of compound 52A (20 mg, 0.030 mmol) in THF (1 mL), add 6 M HCl (1 mL), and stir at 25°C for 16 hours. The reaction mixture was filtered and purified using a reverse-phase column (ACN: 0.1% FA-H2O) to afford the racemate of 52 as a yellow solid (9.4 mg, yield: 55%). Further chiral column separation afforded compound 52.

[0946] LCMS [M+H] + =558.2.

[0947] 1 H NMR (400MHz, DMSO) δ8.24(s,1H),7.40(s,1H),7.16(d,J=15.0Hz,2H),7.08(d,J=8.9Hz,2H),6.63(t,J=8.4Hz,3H),6.23(s,1H),6.15(d,J=7.9Hz,1H), 6.01(d,J=7.6Hz,1H),5.28(s,1H),4.80-4.69(m,4H),4.20(d,J=13.4Hz,1H),4 .02(dd,J=13.5,5.5Hz,1H),3.85(s,3H),3.62(s,3H),3.25(s,3H),2.77(s,3H).

[0948] Compound 53

[0949] Step 1: Dissolve the racemate of compound 50A (250 mg, 0.3553 mmol) in dioxane (3 mL) and water (0.6 mL). Add 2-bromooxazole (525.73 mg, 3.5532 mmol), Pd(dppf)Cl2 (28.99 mg, 0.0355 mmol), and Na2CO3 (150.78 mg, 1.4225 mmol). Stir in a microwave at 130°C for 2.5 hours. The reaction mixture is filtered, concentrated, and purified on a silica gel column (EA / PE) to obtain the racemate of compound 53A as a yellow solid (200 mg, yield: 87%). LCMS [M+H-C4H8] + =589.2.

[0950] Step 2: Dissolve the racemate of compound 53A (200 mg, 0.3102 mmol) in THF (6 mL) and H₂O (2 mL), add LiOH (40 mg, 0.9307 mmol), and stir at 20°C for 16 hours. The reaction mixture was adjusted to pH 5 with 3M HCl, concentrated, and purified on a silica gel column (DCM:MeOH = 10:1) to afford the racemate of compound 53B as a yellow solid (150 mg, yield: 77%). LCMS [M-C₄H₄+H] + =575.1.

[0951] Step 3: The racemate of compound 53B (150 mg, 0.238 mmol) was dissolved in DMF (5 mL). Dimethylamine solution (0.6 mL, 1.2 mmol, 2 M in THF), HATU (180.99 mg, 0.476 mmol), HOAT (64.79 mg, 0.476 mmol), and TMP (86.43 mg, 0.714 mmol) were added and stirred at 25°C for 2 hours. The reaction mixture was filtered, concentrated, and purified using a reverse phase column (ACN: 0.1% FA-H2O) to afford the racemate of compound 53C as a yellow solid (120 mg, yield: 77%). LCMS [M+H] + =658.2.

[0952] Step 4: Dissolve the racemate of compound 53C (60 mg, 0.091 mmol) in THF (2 mL). Add BH3·THF (0.45 mL) under nitrogen and stir at 60°C for 3 hours. Then add MeOH and stir at 60°C for 16 hours. The reaction mixture was concentrated and purified using a reverse phase column (ACN: 0.1% FA-H2O) to obtain the racemate of compound 53D as a yellow solid (30 mg, yield: 52%). LCMS [M+H] + =644.2.

[0953] Step 5: The racemate of compound 53D (30 mg, 0.05 mmol) was dissolved in THF (1 mL), 6 M HCl (1 mL) was added, and the mixture was stirred at 25°C for 16 hours. The reaction mixture was directly purified using a reverse phase column (ACN: 0.1% FA-H2O) to afford the racemate of compound 53 as a white solid (17 mg, yield: 68%). Compound 53 was then separated using a chiral column.

[0954] LCMS [M+H] + =544.2.

[0955] 1 H NMR (400MHz, DMSO) δ8.25(d,J=0.7Hz,1H),7.41(d,J=0.8Hz,1H),7.19-7.15(m,4H),6.88(s,3H),6.64(d,J=9.0Hz,3H),5.41(d ,J=111.7Hz,2H),4.71(s,1H),3.87(s,3H),3.62(s,3H),3.24(s,1H),2.95(d,J=4.3Hz,4H),2.81(d,J=4.7Hz,4H),1.24(s,1H).

[0956] Compound 54

[0957] Step 1: Dissolve the racemate of compound 50D (25.0 mg, 0.04 mmol) in THF (1 mL) and add BH3·DMS (0.04 mL, 0.11 mmol). Stir at 60°C for 2 hours. Add methanol (1 mL) and stir at 60°C for 18 hours. The reaction solution is concentrated and purified on a silica gel column (DCM / MeOH) to obtain the racemate of compound 54A (10 mg, yield: 41%). LCMS [M+H] + =654.2.

[0958] Step 2: The racemate of compound 54A (10.0 mg, 0.015 mmol) was mixed with THF (1 mL), 6 M HCl (1 mL) was added at 0°C, and the mixture was stirred at 25°C for 16 hours. The reaction solution was concentrated and purified by preparative HPLC to obtain the racemate of compound 54 as a white solid (1.2 mg, yield: 14%), which was further resolved by chiral column to afford compound 54.

[0959] LCMS [M+H]+ = 554.2.

[0960] 1H NMR (400MHz, DMSO) δ8.67(d,J=3.8Hz,1H),8.01(d,J=8.0Hz,1H),7.89(t,J=7.8Hz,1H),7.39-7.33 (m,1H),7.27(s,2H),7.18(d,J=8.9Hz,2H),6.70(d,J=7.8Hz,1H),6.62(d,J=9.0Hz,2H),6.30(s,1 H),6.20(d,J=8.3Hz,1H),6.10(d,J=7.6Hz,1H),5.33(d,J=4.7Hz,2H),5.14(s,1H),4.81(s,1H),4 .54(s,1H),3.86(s,3H),3.62(s,3H),3.48(d,J=13.7Hz,1H),2.04-1.98(m,8H),1.29-1.29(m,1H).

[0961] Compound 55

[0962] Step 1: To a mixture of the racemate of compound 2D (600 mg, 0.82 mmol) in toluene (25 mL) and H2O (10 mL) were added compound 55A (212 mg, 2.46 mmol), K3PO4 (695 mg, 3.28 mmol), Cy3P (92 mg, 0.33 mmol) and Pd(OAc)2 (37 mg, 0.164 mmol). The reaction mixture was stirred at 120°C for 3 hours under nitrogen. The reaction mixture was poured into water (20 mL) and extracted with EA (50 mL). The organic phase was washed with 20 mL of brine. The organic phase was dried and concentrated, and purified by silica gel column chromatography (PE / EA = 2 / 1) to give the racemate of 55B as a yellow oil (450 mg, yield: 79%). LCMS [M+Na] + =716.4.

[0963] Step 2: To a solution of the racemate of compound 55B (450 mg, 0.65 mol) in EA / MeOH (1:1, 25 mL) was added Pd(OH)2 / C (10%, 100 mg). The hydrogen atmosphere was evacuated three times and the mixture was stirred at 25°C for 18 hours. The operation was repeated three times until the starting material was completely consumed. The reaction mixture was filtered and the filter cake was washed with MeOH / DCM (1 / 10). The combined filtrates were concentrated to afford the racemate of compound 55C as a white solid (380 mg, yield: 97%). LCMS [M+Na] + =626.2.

[0964] Step 3: To a solution of the racemate of compound 55C (380 mg, 0.63 mmol) and compound 2G (225 mg, 0.63 mmol) in DMF (15 mL) was added KCO (174 mg, 1.26 mmol) and stirred at 60°C for 2 hours. The mixture was poured into HO (15 mL) and extracted with EtOAc (30 mL). The organic phase was washed with water (15 mL) and brine (15 mL) and dried over anhydrous NaSO. After filtration and concentration, the crude product was purified by silica gel column chromatography (DCM / EA=0-30%) to give the racemate of 55D (350 mg, yield: 76%) as a white solid. LCMS [M+Na] + =758.0.

[0965] Step 4: Under nitrogen, to a solution of the racemate of compound 55D (50 mg, 0.068 mmol) in dioxane (20 mL) were added bisboronic acid ester (69 mg, 0.272 mmol), potassium acetate (40 mg, 0.408 mmol), and Pd(dppf)Cl2·DCM (17 mg, 0.02 mmol). The mixture was stirred at 105°C for 18 hours. The reaction solution was concentrated and purified by silica gel column chromatography (DCM / EA = 3 / 1) to obtain the racemate of compound 55E as an oil (40 mg, yield: 83%). LCMS [M+Na] + =736.4.

[0966] Step 5: Under nitrogen, to a mixture of the racemate of compound 55E (58 mg, 0.084 mmol) in dioxane (4 mL) and H2O (2 mL) were added 2-bromooxazole (50 mg, 0.34 mmol), Pd(dppf)Cl2·DCM (14 mg, 0.017 mmol), and Na2CO3 (27 mg, 0.25 mmol). The mixture was stirred in a microwave at 90°C for 2 hours. Water (10 mL) was added and the mixture was extracted with EA (50 mL). The organic phase was washed with water (20 mL) and brine (20 mL), dried, and concentrated. The crude product was purified by flash silica gel column chromatography (DCM / EA = 2:1) to afford the racemate of compound 55F (38 mg, yield: 70%) as a white solid. LCMS [M+Na] + =677.3.

[0967] Step 6: To a solution of the racemate of compound 55F (38 mg, 0.058 mmol) in THF (2 mL) was added H2O (2 mL), MeOH (2 mL), and LiOH (8 mg, 0.174 mmol), and the mixture was stirred at 25°C for 18 hours. The reaction solution was directly purified by reverse phase column chromatography (MeCN / FA / H2O) to afford the racemate of compound 55G as a white solid (25 mg, yield: 68%). LCMS [M+Na] + =663.3.

[0968] Step 7: To a solution of the racemate of compound 55G (25 mg, 0.04 mmol) in DMF (2 mL) were added dimethylamine solution (0.1 mL, 0.2 mmol, 2 M in THF), HATU (15 mg, 0.04 mol), and TMP (10 mg, 0.08 mmol), and the mixture was stirred at 20°C for 2 hours. The reaction solution was directly purified using a reverse phase column (MeCN / H2O / FA) to obtain the racemate of compound 55H as a white solid (18 mg, yield: 69%). LCMS [M+H] + =668.3.

[0969] Step 8: The racemate of compound 55H (18 mg, 0.027 mmol) was dissolved in THF (2 mL), added to 6 M HCl (2 mL), and stirred at 25°C for 18 hours. The reaction solution was purified by reverse phase column chromatography (MeCH / FA / H2O) to afford the racemate of 55 as a white solid (6.0 mg, yield: 40%), which was further resolved on a chiral column to afford compound 55.

[0970] LCMS [M+H] + =568.3.

[0971] 1H NMR(400MHz,DMSO)δ8.25(s,1H),7.41(s,1H),7.18(s,1H),7.14(s,1H),7.0 4(d,J=8.3Hz,2H),6.76(d,J=8.3Hz,2H),6.63(t,J=7.7Hz,1H),6.24(s,1H), 6.15(d,J=7.5Hz,1H),6.02(d,J=7.4Hz,1H),5.29(s,1H),4.78(d,J=4.3Hz,2H),4.74(d,J=5.2Hz,1H),4.22(d,J=13.4Hz,1H ),4.08-4.00(m,1H),3.85(s,3H),3.26(s,3H),2.77(s,3H),1.74(d,J=4.9Hz,1H),0.87-0.81(m,2H),0.53(d,J=5.1Hz,2H).

[0972] Compound 56

[0973] Step 1: To a mixture of the racemate of compound 55H (3 mg, 0.004 mmol) in THF (1 mL) was added 1 M DIBAL-H solution (0.1 mL, 0.1 mmol). The mixture was stirred at 20°C for 5 hours. DIBAL-H solution (0.1 mL, 0.1 mmol) was added and stirring was continued at 60°C for 4 hours. The reaction was quenched with methanol and concentrated. The crude product was purified by preparative TLC (DCM / MeOH) to afford the racemate of compound 56A as a white solid (2.5 mg, yield: 80%). LCMS [M+H] + =654.3.

[0974] Step 2: To a solution of the racemate of compound 56A (3 mg, 0.005 mmol) in THF (2 mL) was added 6 M HCl (2 mL) and stirred at 25°C for 18 hours. The reaction solution was purified by reverse phase chromatography (MeCN / FA / H2O) to afford the racemate of compound 56 as a white solid (1.5 mg, yield: 60%), which was further resolved by chiral column chromatography to afford compound 56.

[0975] LCMS: [M+H] + =554.2.

[0976] 1H NMR(400MHz,DMSO)δ8.37(s,4H),8.22(s,1H),7.39(s,1H),7.21(s,1H),7.10(d,J=9.0Hz,4H), 6.75(d,J=8.5Hz,2H),6.68(t,J=7.7Hz,2H),6.28(s,1H),6.18(d,J=7.6Hz,1H),6.11(d,J=7.9H z,1H),5.33(t,J=4.6Hz,1H),5.16(s,1H),4.77(s,1H),4.46(d,J=4.4Hz,1H),3.83(s,3H),3.5 3(s,2H),2.20(s,6H),1.97(s,1H),1.73(d,J=5.4Hz,1H),0.85-0.83(m,2H),0.53-0.51(m,2H).

[0977] Compound 57

[0978] Step 1: Compound 57A (24 g, 99.06 mmol) and 4-methoxybenzaldehyde (16.19 g, 118.87 mmol) were dissolved in EtOH (1 L). 50% NaOH (80 mL) was added at 50°C, and the mixture was stirred at 50°C for 12 hours. The reaction solution was concentrated, and the resulting crude product was diluted with H2O (500 mL), extracted with DCM (500 mL x 2), washed with brine (500 mL x 2), and dried over Na2SO4. Filtration and concentration afforded 57B (19.87 g, yield: 56%) as a yellow solid. LCMS [M+H] + =361.2.

[0979] Step 2: Compound 57B (18.8 g, 52.16 mmol) was dissolved in MeOH / H2O (100 mL / 50 mL), and NaOH (14.61 g, 365.10 mmol) and H2O2 (80 mL) were added. The mixture was stirred at 50°C for 12 hours. The reaction mixture was filtered and the filter cake was washed with ether (100 mL). The filter cake was dissolved in 200 mL of DCM and the pH was adjusted to 5 with 1N HCl (100 mL). The mixture was washed with brine (100 mL x 2) and dried over Na2SO4. The mixture was filtered and concentrated to give 57C (8.9 g, yield: 46%) as a yellow solid. LCMS [M+H] + =375.0.

[0980] Step 3: Compound 57C (2 g, 5.35 mmol) and compound 9A (5.197 g, 32.09 mmol) were dissolved in CHCl3 / TFE = 7 / 3 (15 mL x 2). The reaction mixture was pumped (12 mL / h) via a syringe pump into a coil wrapped around a jacketed glass cylinder equipped with a 250 W UV lamp. The temperature was adjusted to maintain an internal reaction temperature of 0-5°C while the UV lamp was on. The reaction mixture was irradiated for 1 hour, the solvent was removed under reduced pressure, and the residue was purified using a silica gel plug (EtOAc / hexane) to remove excess cinnamate, affording the racemate of 57D as a pale yellow solid (8.1 g, total yield: 75%). LCMS [M+H] + =537.7.

[0981] Step 4: The racemate of compound 57D (8.6 g, 16.03 mmol) was dissolved in methanol (120 mL). Solid sodium methoxide (2.163 g, 40.07 mmol) was slowly added in an ice-water bath (0°C). The reaction solution was stirred in a 65°C oil bath for 1.5 hours. After completion of the reaction, the methanol in the reaction solution was removed by rotary evaporation and then extracted with ethyl acetate (200 mL x 3). The organic phase was washed once with ammonium chloride solution (100 mL) and once with saturated brine (100 mL), then dried over anhydrous sodium sulfate. After filtration and concentration, the product was purified on a silica gel column (0.2% FA in EA / PE (65% / 35%)) to obtain the racemate of compound 57E (7.0 g, yield: 81%). LCMS [M+H-H2O] + =519.7.

[0982] Step 5: The racemate of compound 57E (7.0 g, 9.39 mmol) was dissolved in a mixture of acetonitrile and chloroform (80 mL / 80 mL). Acetic acid (7.827 g, 130.46 mmol) and STAB (13.828 g, 65.23 mmol) were slowly added in an ice-water bath (0°C). The reaction solution was stirred at room temperature for 2 hours. After completion of the reaction, the solvent was removed from the reaction solution by spin drying, and the solution was extracted with ethyl acetate (200 mL x 3). The organic phase was washed with saturated brine (100 mL) and dried over anhydrous sodium sulfate. After filtration and concentration, the product was purified on a silica gel column (0.2% FA in EA / PE = 50% / 50%) to obtain the racemate of compound 57F (3.8 g, yield: 54%). LCMS [M+H-H2O] + =521.8.

[0983] Step 6: Dissolve the racemate of compound 57F (3.8 g, 7.06 mmol) in methanol (50 mL) and add 10% Pd / C (1.14 g). Replace the hydrogen atmosphere three times and stir at 20°C for 16 hours. The reaction mixture was filtered, concentrated, and purified on a silica gel column (PE:EA = 40:60) to obtain the racemate of compound 57G (3.0 g, yield: 85%). LCMS [M+H-H2O] + =431.2.

[0984] Step 7: Under nitrogen, the racemate of compound 57G (2.8 g, 6.24 mmol) was dissolved in DMF (30 mL), and compound 2G (2.23 g, 6.24 mmol) and K2CO3 (1.723 g, 12.49 mmol) were added. The mixture was heated at 60°C for 1 hour. After completion, the reaction was quenched with water (100 mL) and extracted three times with EA (200 mL). The organic phase was washed with saturated brine and dried over anhydrous sodium sulfate. After filtration and concentration, the product was purified on a silica gel column (PE:EA = 60:40) to obtain the racemate of compound 57H (2.7 g, yield: 75%). LCMS [M+H-H2O] + =563.0.

[0985] Step 8: Under nitrogen, the racemate of compound 57H (200.0 mg, 0.34 mmol) was dissolved in DMF (3 mL). Compound 2I (333.3 mg, 0.93 mmol), Pd(PPh3)4 (139.9 mg, 0.03 mmol), and CuI (13.1 mg, 0.069 mmol) were added and stirred at 100°C for 1 h. The mixture was quenched with water and extracted with EA. The organic layer was washed with water and brine, and dried over anhydrous Na2SO4. After filtration and concentration, the mixture was purified on a silica gel column (DCM / MeOH = 20:1) to afford the racemate of compound 57I (100 mg, yield: 58%). LCMS [M+H]+ = 500.7.

[0986] Step 9: Dissolve the racemate of compound 57I (100.0 mg, 0.20 mmol) in THF / H2O / MeOH (3 mL / 1 mL / 1 mL), add LiOH (25.3 mg, 0.60 mmol), and stir at 40°C for 3 h. Adjust the pH to 5 with 3 M hydrochloric acid, concentrate, and purify on a silica gel column (DCM / MeOH) to obtain the racemate of compound 57J (90 mg, yield: 92%). LCMS [M+H] + =486.7.

[0987] Step 10: The racemate of compound 57J (90.0 mg, 0.19 mmol), HATU (105.8 mg, 0.28 mmol), and DIEA (119.7 mg, 0.93 mmol) were dissolved in DMF (2 mL) and stirred at 25°C for 10 minutes. DMA (0.6 μL, 0.93 mmol, 2 M in THF) was added and the mixture was reacted at 25°C for 1 hour. The solution was diluted with water, extracted with EA, washed with water and brine, and dried over anhydrous NaSO. After filtration and concentration, the product was purified on a silica gel column (DCM / MeOH) to afford the racemate of compound 57 (6.5 mg, yield: 6.8%). Further chiral separation was performed to afford compound 57.

[0988] LCMS [M+H]+ = 513.8.

[0989] 1 H NMR (400MHz, DMSO) δ8.25(s,1H),7.73-7.50(m,3H),7.41(s,1H),7.12(d,J=8.8Hz,2H),7.06-6.95(m,3H),6.83(d,J=7.1Hz,2H),6.6 8(d,J=8.9Hz,2H),4.94(d,J=8.1Hz,1H),4.19(d,J=13.2Hz,1H),4.02(dd,J=13.1,8.1Hz,1H),3.65(s,3H),3.20(s,3H),2.72(s,3H).

[0990] Compound 58

[0991] Step 1: The racemate of compound 57J (30.0 mg, 0.06 mmol), HATU (70.5 mg, 0.19 mmol), and DIEA (39.9 mg, 0.31 mmol) were dissolved in DMF (2 mL) and stirred at 25°C for 10 minutes. Compound 16C (34.0 mg, 0.31 mmol) was added and reacted at 25°C for 1 hour. The reaction solution was diluted with water, extracted with EA, washed with water and brine, dried over anhydrous Na2SO4, and purified on a silica gel column (DCM / MeOH) to afford the racemate of compound 58 (14.1 mg, yield: 42%). The product was further resolved on a chiral column to afford compound 58.

[0992] LCMS [M+H] + =541.2.

[0993] 1H NMR (400MHz, DMSO) δ8.24(s,1H),7.58(d,J=14.3Hz,3H),7.40(s,1H),7.05(ddd,J=21.5,11.8,6.0Hz,5H),6.86(d, J=7.2Hz,2H),6.67(dd,J=8.6,7.0Hz,2H),5.73(dd,J=10.7,5.7Hz,1H),5.59(dd,J=5.8,2.5Hz,1H),5.53(d,J=3.3H z,1H),4.83(dt,J=10.3,7.7Hz,1H),4.53(dt,J=40.9,11.6Hz,2H),4.15(dd,J=13.2,7.7Hz,1H),4.10-4.03(m,1H) ,3.93(ddd,J=25.7,13.2,8.3Hz,1H),3.78-3.66(m,1H),3.65(t,J=5.7Hz,3H),3.50(ddd,J=33.5,10.0,4.2Hz,1H).

[0994] Compound 59

[0995] Step 1: Dissolve the racemate of compound 50A (100 mg, 0.1421 mmol) in dioxane (2 mL) and water (0.4 mL). Add 2-bromopyrimidine (112.98 mg, 0.7106 mmol), Pd(dppf)Cl2 (11.60 mg, 0.0142 mmol), and Na2CO3 (60.26 mg, 0.5685 mmol). Stir in a microwave at 130°C for 2 hours. The reaction mixture is filtered, concentrated, and purified on a silica gel column (EA / PE) to obtain the racemate of compound 59A as a yellow solid (70 mg, yield: 75%). LCMS [M+H-H2O] + =638.2.

[0996] Step 2: Dissolve the racemate of compound 59A (60 mg, 0.09 mmol) in THF (2 mL) and H₂O (0.7 mL), add LiOH (11.5 mg, 0.27 mmol), and stir at 20°C for 16 hours. The reaction mixture was adjusted to pH 5 with 3M HCl, concentrated, and purified on a silica gel column (DCM:MeOH = 10:1) to afford the racemate of compound 59B as a yellow solid (40 mg, yield: 69%). LCMS [M+H-C₄H₄] + =586.2.

[0997] Step 3: The racemate of compound 59B (40 mg, 0.062 mmol) was dissolved in DMF (2 mL). Dimethylamine solution (0.16 mL, 0.32 mmol, 2 M in THF), HATU (47.40 mg, 0.312 mmol), HOAT (16.97 mg, 0.125 mmol), and TMP (22.62 mg, 0.187 mmol) were added and stirred at 25°C for 2 h. The reaction mixture was filtered, concentrated, and purified on a reverse phase column (ACN: 0.1% FA-H2O) to afford the racemate of compound 59C as a yellow solid (31 mg, yield: 76%). LCMS [M+H] + =669.2.

[0998] Step 4: The racemate of compound 59C (7 mg, 0.01 mmol) was dissolved in THF (1 mL), 6 M HCl (0.5 mL) was added, and the mixture was stirred at 20°C for 16 h. The reaction solution was directly purified by reverse phase column (ACN: 0.1% FA-H2O) to obtain the racemate of white solid 59 (4.0 mg, yield: 67%), which was further resolved by chiral column to obtain compound 59.

[0999] LCMS [M+H] + =569.2.

[1000] 1 H NMR (400MHz, DMSO) δ8.94 (d, J = 4.9Hz, 2H), 7.65-7.61 (m, 2H), 7.48 (t, J=4.9Hz,1H),7.10(d,J=8.9Hz,2H),6.65-6.60(m,3H),6.27(s,1H),6.17(d,J=7.1Hz,1H),6.00(d,J=7.8Hz,1H),5.26(s,1H),4.78(d,J=5 .8Hz,1H),4.74(d,J=4.0Hz,1H),4.19(d,J=13.5Hz,1H),4.01(dd,J=13.6,6.0Hz,1H),3.87(s,3H),3.63(s,3H),3.25(s,3H),2.76(s,3H).

[1001] Compound 60

[1002] Step 1: Dissolve the racemate of compound 59C (10 mg, 0.015 mmol) in THF (1.5 mL). Add DIBAL-H (0.045 mL, 0.045 mmol) at 0°C under nitrogen protection and react at 22°C for 1 hour. Add DIBAL-H (0.045 mL, 0.045 mmol) at 0°C under nitrogen protection and react at 22°C for 1 hour. Add DIBAL-H (0.045 mL, 0.045 mmol) at 0°C under nitrogen protection and react at 22°C for 1 hour. The reaction mixture was quenched with ice water, concentrated, and purified on a reverse phase column (ACN: 0.1% FA-H2O) to obtain the racemate of compound 60A as a yellow solid (5 mg, yield: 51%). LCMS [M+H] + =655.5.

[1003] Step 2: Dissolve the racemate of compound 60A (5 mg, 0.008 mmol) in THF (1 mL), add 6 M HCl (1 mL), and stir at 25°C for 16 hours. The reaction mixture was directly purified using a reverse-phase column (ACN: 0.1% FA-H2O) to afford the racemate of compound 60 as a white solid (2.5 mg, 59% yield). Further chiral column separation afforded compound 60.

[1004] LCMS [M+H] + =555.5.

[1005] 1 H NMR(400MHz,)δ8.92(d,J=4.8Hz,2H),8.13(s,1H),7.57(d,J=16.0Hz,2H),7.46(t,J =4.8Hz,1H),7.17(d,J=8.9Hz,2H),6.69(t,J=7.7Hz,1H),6.62(d,J=8.9Hz,2H),6.2 8(s,1H),6.20(d,J=7.7Hz,1H),6.07(d,J=7.2Hz,1H),5.20(s,1H),4.81(s,2H),4.5 4(s,1H),3.86(s,3H),3.62(s,3H),3.47(d,J=13.8Hz,1H),3.06(s,2H),2.37(s,6H).

[1006] Compound 61

[1007] Step 1: To a solution of the racemate of compound 50A (100 mg, 0.142 mmol) in dioxane (2 mL) was added a solution of compound 61A (189 mg, 0.71 mmol), Pd(dppf)Cl2 (11.6 mg, 0.014 mmol), and Na2CO3 (30.13 mg, 0.2842 mmol) in water (0.4 mL). Under nitrogen, the mixture was stirred at 100°C for 16 hours. The reaction mixture was directly purified using a silica gel column (PE / EA) to obtain the racemate of compound 61B (50 mg, yield: 50%). LCMS [M+H] + =687.0.

[1008] Step 2: The racemate of compound 61B (50 mg, 0.07 mmol) and LiOH·H2O (9 mg, 0.22 mmol) were added to a mixture of THF / MeOH / H2O (1 / 1 / 1, 3 mL) and stirred at 20°C for 16 hours. The reaction solution was purified using a reverse phase column (ACN-H2O) (FA) to obtain the racemate of compound 61C as a white solid (34 mg, yield: 69%). LCMS [M+H] + =673.0.

[1009] Step 3: The racemate of compound 61C (34 mg, 0.05 mmol), HATU (19 mg, 0.05 mmol), and TMP (14 mg, 0.12 mmol) were stirred in DMF (2 mL). Dimethylamine (11 mg, 0.1 mmol) was added to the mixture, and the mixture was stirred at 20°C for 2 hours. The reaction solution was purified using a reverse phase column (ACN / H2O = 0-100%) to obtain the racemate of compound 61D as a white solid (10 mg, yield: 50%). LCMS [M+H] + =700.1.

[1010] Step 4: The racemate of compound 61D (6 mg, 0.0086 mmol) was dissolved in THF (1 mL), 6M HCl (1 mL) was added, and the mixture was stirred at 20°C for 5 h. The reaction solution was directly purified using a reverse phase column (ACN-H2O) to obtain the racemate of compound 61 as a white solid (3.8 mg, yield: 70%). Further chiral column separation gave compound 61. LCMS [M+H] + =600.0.

[1011] Compound 62

[1012] Step 1: To a solution of the racemate of compound 50A (70 mg, 0.1 mmol) in dioxane / water (3 mL / 0.6 mL) were added compound 62A (25.82 mg, 0.15 mmol), Na2CO3 (31.64 mg, 0.3 mmol), and Pd(dppf)Cl2 (8.06 mg, 0.01 mmol). The reaction system was purged with nitrogen three times and microwaved at 130°C for 1 hour. The reaction solution was purified by reverse phase column chromatography (H2O + 0.1% FA / ACN) to afford the racemate of 62B as a yellow solid (50 mg, yield: 75%). LCMS [M+H] + =670.9.

[1013] Step 2: To a solution of the racemate of compound 62B (50 mg, 0.08 mmol) in THF / H2O (1 / 1, 2 mL) was added LiOH·H2O (6.41 mg, 0.15 mmol) and stirred at room temperature for 18 hours. The reaction mixture was purified by reverse phase column chromatography (H2O / ACN) to afford the racemate of compound 62C as a white solid (25 mg, yield: 51%). LCMS [M+H-C4H8] + =600.9.

[1014] Step 3: To a solution of the racemate of compound 62C (20 mg, 0.03 mmol), dimethylamine (12.44 mg, 0.15 mmol), and HATU (17.4 mg, 0.05 mmol) in DMF (1 mL) was added DIEA (7.88 mg, 0.06 mmol) and stirred at room temperature for 1 hour. The reaction mixture was purified by reverse phase column chromatography (H2O / ACN) to afford the racemate of compound 62D as a white solid (25 mg, yield: 90%). LCMS [M+H] + =684.1.

[1015] Step 4: To a solution of the racemate of compound 62D (5 mg, 0.01 mmol) in THF (1 mL) was added 6 M HCl (1 mL) and stirred at room temperature for 5 hours. The reaction solution was purified by reverse-phase column chromatography (H2O / ACN) to afford the racemate of compound 62 as a white solid (2.5 mg, yield: 60%). Further chiral column separation afforded compound 62.

[1016] LCMS [M+H] + =583.2.

[1017] 1H NMR(400MHz,DMSO)δ8.78(s,2H),7.59(d,J=4.3Hz,2H),7.10(d,J=8.8Hz,2H) ,6.63(t,J=7.8Hz,3H),6.25(s,1H),6.16(d,J=7.6Hz,1H),5.98(d,J=7.4Hz, 1H),5.25(s,1H),4.86-4.63(m,4H),4.17(d,J=13.5Hz,1H),3.99(dd,J=13.4 ,6.0Hz,1H),3.87(s,3H),3.63(s,3H),3.25(s,3H),2.76(s,3H),2.34(s,3H).

[1018] Compound 63

[1019] Step 1: The racemate of compound 20F (200 mg, 0.28 mmol) was dissolved in 1,4-dioxane (20 mL), followed by the addition of K2CO3 (77.28 mg, 1.38 mmol), 4-methyl-1H-pyrazole (113.70 mg, 1.38 mol), Pd2(dba)3 (51.28 mg, 0.01 mmol), and t-Buxphos (67.31 mg, 0.14 mmol). The mixture was stirred at 120°C for 12 hours. The reaction solution was concentrated, and the crude product was purified by FLASH column (medium-low pressure rapid preparative liquid phase) (PE / EA = 2 / 1) to obtain the racemate of 63A as a yellow solid (133.7 mg, yield: 73%). LCMS [M+H-C4H8] + =602.2.

[1020] Step 2: The racemate of compound 63A (133.7 mg, 0.20 mmol) was dissolved in THF / H2O (3 mL / 1 mL) and LiOH was added. . H2O (25.60 mg, 0.60 mmol) was added and reacted at 15°C for 12 hours. The reaction solution was purified by preparative HPLC (H2O / ACN) to obtain the racemate 63B as a yellow solid (92.9 mg, yield: 71%). LCMS [M+H-C4H8] + =588.2.

[1021] Step 3: The racemate of compound 63B (92.9 mg, 0.14 mmol) was dissolved in DMF (2 mL), and dimethylamine / THF (0.1 mL, 0.29 mmol), HATU (65.86 mg, 0.17 mmol), HOAT (23.57 mg, 0.17 mol), and TMP (52.47 mg, 0.43 mmol) were added. The mixture was reacted at room temperature for 2 hours. The reaction solution was purified by preparative HPLC (H2O / ACN) to obtain the racemate of compound 63C as a white solid (71.9 mg, yield: 74%). LCMS [M+H] + =671.3.

[1022] Step 4: To a solution of the racemate of compound 63C (72 mg, 0.11 mmol) in THF (2.5 mL) were added BH3 / DMS (0.13 mL, 0.33 mmol) and TFA (12.50 mg, 0.11 mmol), and the mixture was reacted at 20°C for 12 hours. The reaction solution was purified by preparative HPLC (H2O / ACN) to afford the racemate of compound 63D as a yellow oil (28.4 mg, yield: 40%). LC-MS: [M+H] + =657.2.

[1023] Step 5: To a solution of the racemate of compound 63D (28.3 mg, 0.04 mmol) in THF (1 mL) was added 6N HCl (1 mL), and the mixture was reacted at 15°C for 12 hours. The reaction solution was purified by preparative HPLC (HO / ACN) to afford the racemate of compound 63 as a white solid (5.8 mg, yield: 24%), which was further resolved on a chiral column to afford compound 63.

[1024] LCMS [M+H] + =557.2.

[1025] 1 H NMR(400MHz,DMSO-d6)δ8.31(s,1H),8.24(s,1H),7.54(s,1H),7.14(d,J=8.8Hz,2H) ,6.95(s,2H),6.68(t,J=7.8Hz,1H),6.62(d,J=9.2Hz,2H),6.25(s,1H),6.19-6.17(m ,1H),6.07(d,J=7.6Hz,1H),5.05(s,1H),4.80(brs,1H),4.45(d,J=4.4Hz,1H),3.82 (s,1H),3.62(s,3H),3.48-3.44(m,2H),3.02-2.95(m,1H),2.33(s,6H),2.11(s,3H).

[1026] Compound 64

[1027] Step 1: To a mixture of the racemate of compound 9D (2300 mg, 3.73 mmol) in pyridine (30 mL) was added MsCl (4250 mg, 37.3 mmol) at 0°C and the mixture was allowed to react at 0°C for 3 hours. EA (50 mL) was added to the reaction solution, which was washed with water (20 mL) and the organic phase was dried. After filtration and concentration, the crude product was purified on a silica gel column (PE / EA = 2 / 1) to obtain the racemate of compound 64A as a white solid (2400 mg, yield: 93%). LCMS [M+Na] + =717.1.

[1028] Step 2: To a solution of the racemate of compound 64A (2.4 g, 3.45 mmol) in DMF (20 mL) was added NaCN (423 mg, 8.63 mmol) and the mixture was reacted at 25°C for 18 hours. EA (30 mL) was added to the reaction solution, and the mixture was washed with water (20 mL) and saturated brine, respectively. The organic phase was dried and concentrated, and purified by FLASH column (medium-low pressure rapid preparative liquid phase) (PE / EA = 2 / 1) to obtain the racemate of compound 64B as a white solid (2200 mg, yield: 100%). LCMS [M+H] + =626.1.

[1029] Step 3: To a solution of the racemate of compound 64B (2200 mg, 3.51 mmol) in THF (5 mL) were added H2O (5 mL), MeOH (5 mL), and LiOH·H2O (443 mg, 10.54 mmol), and the mixture was reacted at 25°C for 18 hours. The reaction solution was purified by reverse phase chromatography (MeCN / FA / H2O) to obtain the racemate of compound 64C as a white solid (1.9 g, yield: 88%). LCMS [M+H] + =612.2.

[1030] Step 4: The racemate of compound 64C (100 mg, 0.16 mmol), compound 11A (207.3 mg, 1.63 mmol), HOAT (33.3 mg, 0.24 mmol), tert-dodecylmercaptan (329.8 mg, 1.63 mmol), TMP (29.8 mg, 0.24 mmol), and meso-tetraphenylporphyrin zinc (11.0 mg, 0.02 mmol) were mixed with DMF (2 mL) and placed in a microwave oven. After the reaction system was purged with nitrogen, the microwave oven was stirred in hot water at 80°C while irradiated with 25 W red light. A solution of EDCI (311.8 mg, 1.63 mmol) in DMF (4 mL) was slowly added dropwise to the reaction mixture and stirred for 30 minutes. The mixture was purified by reverse-phase chromatography (HO / ACN = 40%-60%) to afford the racemate of 64D as a white solid (35 mg, yield: 38%). LCMS [M+H-H2O] + =550.4.

[1031] Step 5: To a mixture of the racemate of compound 64D (210 mg, 0.37 mmol) in THF (10 mL) was added 10 M BH3·DMS solution (0.4 mL, 3.7 mmol) and stirred at 70 ° C for 3 hours. The reaction solution was cooled, MeOH was slowly added, and the crude product was obtained after concentration. The crude product was dissolved in DCM (15 mL), DIPEA (90 mg, 0.70 mmol) and Boc2O (150 mg, 0.70 mmol) were added, and stirred at 25 ° C for 5 hours. The reaction solution was concentrated and purified by FLASH column (medium and low pressure rapid preparative liquid phase) (PE: EA = 5: 1) to obtain a white solid 64E racemate (200 mg, yield: 85%). LCMS [M+Na] + =694.2.

[1032] Step 6: The racemate of compound 64E (160 mg, 0.24 mmol), Pd2(dba)3 (46 mg, 0.05 mmol), DPPF (55 mg, 0.1 mmol) and Zn(CN)2 (74 mg, 0.63 mmol) were added to NMP (20 ml), heated to 140°C under N2 protection, and stirred for 2 hours. The reaction solution was diluted with water and extracted with EA. The organic phase was washed with water and brine respectively, dried and concentrated. The crude product was purified by FLASH column (medium and low pressure rapid preparative liquid phase) (PE:EA=2:1) ​​to obtain the racemate of 64F as a white solid (130 mg, yield: 88%). LCMS: [M+H-H2O-C4H8] + =545.3.

[1033] Step 7: To a solution of the racemate of compound 64F (130 mg, 0.21 mol) in EA / MeOH = 1:1 (25 mL) was added Pd(OH)2 / C (10%, 50 mg), replaced with H2 several times, and stirred at 25°C for 5 hours. The reaction solution was filtered and the filter cake was washed with MeOH / DCM (1 / 10). The combined filtrate was concentrated and purified by FLASH column (medium and low pressure rapid preparative liquid phase) to obtain the racemate of 64G as a white solid (60 mg, yield: 54%). LCMS: [M+Na] + =551.0.

[1034] Step 8: To a solution of the racemate of compound 64G (60 mg, 0.114 mmol) and compound 2G (41 mg, 0.114 mol) in DMF (5 mL) was added K2CO3 (32 mg, 0.228 mmol) and stirred at 60°C for 1 hour. The mixture was poured into water and extracted with EA. The organic phase was washed with water and brine, dried and concentrated. The concentrate was purified by silica gel column chromatography (EA-PE.DCM / 0-50%), and the crude product was purified again by reverse phase chromatography to obtain the racemate of 64H as a white solid (40 mg, yield: 53%). LCMS [M+H-CO2-C4H8] + =561.0.

[1035] Step 9: Compound 2I (11 mg, 0.03 mmol), Pd(PPh3)4 (3 mg, 0.002 mmol) and CuI (1 mg, 0.004 mmol) were added to a solution of the racemate of compound 64H (5 mg, 0.007 mmol) in DMF (1 mL), and stirred at 100 ° C for 2 hours under nitrogen protection. EA (10 mL) was added, and the mixture was washed with water (10 mL) and brine (10 mL), respectively. The organic phase was dried and concentrated. The crude product was purified by preparative silica gel plate to obtain a white solid racemate of 64I (3 mg, yield: 75%). LCMS [M+Na] + =602.2.

[1036] Step 10: The racemate of compound 64I (3 mg, 0.044 mmol) was dissolved in 6M HCl (1 ml) and THF (1 ml) and stirred at 25°C for 5 hours. The reaction solution was purified by reverse phase chromatography (MeCN / FA / H2O) to obtain the racemate of compound 64K as a white solid (3 mg, yield: 100%). LCMS [M+Na] + =480.2.

[1037] Step 11: To a mixture of the racemate of compound 64K (3 mg, 0.01 mmol) in DMF (1 mL) were added glycolic acid (4 mg, 0.05 mmol), HATU (4 mg, 0.01 mmol), and TMP (3 mg, 0.02 mmol), and the mixture was stirred at 20°C for 2 hours. The reaction solution was purified by reverse-phase column chromatography (MeCN / H2O / FA) to afford the racemate of 64 as a white solid (2 mg, yield: 59%), which was further resolved by chiral column chromatography to afford compound 64.

[1038] LCMS [M+Na] + =560.0.

[1039] 1 H NMR(400MHz,DMSO)δ8.41(s,1H),8.27(s,1H),7.79(s,1H),7.59(d,J=8.4Hz,2H),7 .45-7.37(m,3H),7.26(d,J=16.1Hz,2H),7.07(td,J=14.1,7.0Hz,3H),6.95(d,J=7 .2Hz,2H),5.66(s,2H),5.33(d,J=4.5Hz,1H),3.98-3.90(m,3H),3.92(d,J=5.0Hz, 2H),3.79(d,J=6.8Hz,1H),3.73-3.66(m,1H),2.29-2.20(m,1H),2.19-2.13(m,1H).

[1040] Compound 70

[1041] Step 1: To a mixture of the racemate of compound 9D (1900 mg, 3.18 mmol) in H2O / toluene (6 mL / 30 mL) was added DMAP (113 mg, 0.93 mmol), and the solution was stirred at 110°C for 2 hours. The mixture was concentrated and purified by silica gel column (PE / EA = 2 / 1) to obtain the racemate of the target product 70A (1200 mg, yield: 70%). LCMS [M+H] + =557.2.

[1042] Step 2: The racemate of compound 70A (1000 mg, 1.8 mmol) and dimethylhydroxylamine hydrochloride (500 mg, 5.4 mmol) were dissolved in pyridine (20 mL) and EtOH (20 mL), heated to 70°C under nitrogen and stirred for 4 hours. The solution was diluted with water, extracted with EA, and the organic phase was washed with brine, dried and concentrated. Purification was performed by silica gel column chromatography (EA / PE = 0-1 / 2) to obtain the racemate of 70B as a yellow solid (650 mg, yield: 71%). LCMS [M+H-H2O] + =568.1.

[1043] Step 3: To a solution of the racemate of compound 70B (650 mg, 0.17 mmol) in THF (10 mL) was added a BH3·DMS solution (2.78 mL, 5.55 mmol) and stirred at 65°C for 4 hours. The reaction mixture was cooled to room temperature, slowly quenched with MeOH, and concentrated to afford the racemate of compound 70C as a white solid (420 mg, yield: 68%). LCMS [M+H] + =558.2.

[1044] Step 4: To a solution of the racemate of compound 70C (420 mg, 0.75 mmol) in DCM (10 mL) was added DIPEA (291 mg, 2.26 mmol) and Boc2O (194 mg, 0.9 mmol) and stirred at 25°C for 4 hours. The mixture was concentrated and purified by flash chromatography to give the racemate of compound 70D as a white solid (300 mg, yield: 61%). LCMS [M+Na] + =680.2.

[1045] Step 5: The racemate of compound 70D (345 mg, 0.52 mmol), Pd2(dba)3 (92 mg, 0.1 mmol), DPPF (111 mg, 0.2 mmol), and Zn(CN)2 (152 mg, 1.3 mmol) were suspended in NMP (20 mL) and heated to 130°C under nitrogen and stirred for 2 hours. The mixture was diluted with water and extracted with EA. The organic phase was washed with water and brine, dried, concentrated, and purified by silica gel column chromatography (EA / DCM = 0-1 / 1) to obtain the racemate of 70E as a yellow solid (280 mg, yield: 89%). LCMS [M+H-H2O] + =587.2.

[1046] Step 6: A mixture of the racemate of compound 70E (230 mg, 0.38 mmol) and Pd(OH)2 (80 mg) in EA (10 mL) and MeOH (10 mL) was stirred at 25°C under hydrogen for 3 hours. The filtrate was filtered and concentrated to afford the racemate of compound 70F as a white solid (170 mg, yield: 87%). LCMS [M+Na] + =537.2.

[1047] Step 7: The racemate of compound 70F (200 mg, 0.39 mmol), K2CO3 (135 mg, 0.98 mmol) and compound 2G (167 mg, 0.47 mmol) were added to DMF (10 mL) and stirred at 60°C for 2 hours. 30 mL of EA was added and the mixture was washed with 10 mL of water. The organic phase was washed with 10 mL of water and 10 mL of brine, dried and concentrated, and purified by flash column chromatography (PE / EA = 3 / 1) to obtain the racemate of 70G as a white solid (150 mg, yield: 60%). LCMS [M+Na] + =669.0.

[1048] Step 8: To a mixture of the racemate of compound 70G (35 mg, 0.054 mmol) in DMF (3 mL) were added compound 2I (78 mg, 0.216 mmmol), Pd(PPh3)4 (12 mg, 0.01 mmol) and CuI (4 mg, 0.02 mmol), and stirred at 100°C under nitrogen for 1.5 hours. After cooling to room temperature, the reaction solution was poured into 30 mL of EA and washed with 10 mL of water. The organic phase was washed with 10 mL of water and 10 mL of brine, dried and concentrated. Preparative TLC purification gave the racemate of 70H as a white solid (25 mg, yield: 83%). LCMS [M+Na] + =588.2.

[1049] Step 9: The racemate of compound 70H (25 mg, 0.044 mmol) and 6M HCl (1 mL) were added to THF (1 mL) and stirred at 25°C for 5 hours. The reaction solution was directly purified by reverse phase chromatography (MeCN / FA / H2O) to obtain the racemate of compound 70I as a white solid (25 mg, yield: 100%). LCMS [M+Na] + =466.0.

[1050] Step 10: To a mixture of the racemate of compound 70I (5 mg, 0.01 mmol) in DMF (1 mL) were added glycolic acid (4 mg, 0.05 mmol), HATU (4 mg, 0.01 mmol) and TMP (3 mg, 0.02 mmol). The mixture was stirred at 20°C for 2 hours. The reaction solution was purified by reverse phase chromatography (MeCN / H2O / FA) to obtain the racemate of 70 as a white solid (4 mg, yield: 67%), which was further resolved by chiral column to obtain compound 70.

[1051] LCMS [M+Na] + =546.0.

[1052] 1 H NMR (400MHz, DMSO) δ8.26(s,1H),8.02(d,J=6.9Hz,1H),7.58(d,J=8.5Hz,2H),7.42(s,1H ),7.37(d,J=8.5Hz,2H),7.29(d,J=0.8Hz,1H),7.19(s,1H),7.12-7.07(m,2H),7.03(dd, J=15.2,7.3Hz,3H),6.15(s,1H),5.81(t,J=5.5Hz,1H),4.65-4.52(m,1H),3.95(d,J=5.5 Hz, 2H), 3.82 (s, 3H), 3.68 (dd, J = 14.3, 5.7Hz, 1H), 2.40-2.38 (m, 1H), 2.03-1.97 (m, 1H).

[1053] Compound 71

[1054] Step 1: Dissolve the racemate of compound 20G (197 mg, 0.31 mmol) in pyridine (2 mL) and add MsCl (1.07 g, 9.30 mmol) in an ice-water bath. Stir the reaction mixture at 10°C for 3 hours. Dilute the reaction mixture with 6N HCl (20 mL), extract with EA (20 mL x 2), wash with brine (20 mL), and purify by preparative HPLC (H2O (0.1% FA) / ACN) to obtain the racemate of 71A as a white solid (150 mg, yield: 68%). LCMS [M+H] + =723.2.

[1055] Step 2: The racemate of compound 71A (150 mg, 0.21 mmol) was dissolved in DMF (2 mL) and NaCN (51.45 mg, 1.05 mmol) was added. The reaction mixture was stirred at 10°C for 12 hours. The reaction mixture was diluted with NaHCO3 solution (20 mL), extracted with EA (20 mL x 2), washed with brine (20 mL), and purified by preparative HPLC (H2O (0.1% FA) / ACN) to obtain the racemate of 71B as a yellow solid (115 mg, yield: 85%). LCMS [M+H] + =654.2.

[1056] Step 3: The racemate of compound 71B (115 mg, 0.18 mmol) was dissolved in THF (2 mL) and LiOH was added. . H2O (22.68 mg, 0.54 mmol). The reaction mixture was stirred at 10°C for 3 hours. The reaction mixture was concentrated and purified by preparative HPLC (H2O (0.1% FA) / ACN) to obtain the racemate 71C as a yellow solid (95 mg, yield: 84%). LCMS [M+H-C4H8] + =584.7.

[1057] Step 4: A solution of the racemate of compound 71C (10 mg, 0.02 mmol), compound 11A (19.85 mg, 0.16 mmol), tert-dodecylmercaptan (31.58 mg, 0.16 mmol), TMP (2.86 mg, 0.02 mmol), and meso-tetraphenylporphyrin zinc (1.06 mg, 0.001 mmol) in DMF (1 mL) was placed in a Schlenk tube. The reaction system was under 25W red light and the reaction temperature was maintained at 80°C. EDCI (29.86 mg, 0.16 mmol) was dissolved in 1 mL of DMF and added dropwise to the reaction system. The reaction solution was stirred for 0.5 hours. The reaction solution was purified by reverse phase column chromatography (HO / ACN) to obtain the racemate of 71D as a white solid (20 mg, yield: 24.7%). LCMS [M+H-C4H8] + =541.2.

[1058] Step 5: A THF (1 mL) solution of the racemate of compound 71D (15 mg, 0.03 mmol) was cooled to 0°C. LiAlH4 (12.6 μL, 0.05 mmol) was added dropwise to the reaction system and stirred at 0°C for 1 hour. Na2SO4·10H2O was added to the reaction system and stirred at room temperature for 0.5 hours. The reaction solution was filtered and the filter cake was washed with DMF. The filtrate was dried to give the racemate of 71E as a yellow solid (20 mg, crude product was not included in the yield), which was used directly in the next reaction. LCMS [M+H] + =600.9.

[1059] Step 6: To a solution of the racemate of compound 71E (18 mg, 0.03 mmol), glycolic acid (4.57 mg, 0.06 mmol), HATU (22.84 mg, 0.06 mmol), and HOAT (8.17 mg, 0.06 mmol) in DMF (1 mL) was added TMP (14.64 mg, 0.121 mmol) and stirred at room temperature for 1 hour. The reaction mixture was purified by reverse phase column chromatography (H2O / ACN) to afford the racemate of compound 71F as a white solid (4 mg, yield: 13.8%). LCMS [M+H-H2O] + =640.9.

[1060] Step 7: To a solution of the racemate of compound 71F (4 mg, 0.01 mmol) in THF (1 mL) was added 6 M HCl (1 mL) and stirred at room temperature overnight. The reaction solution was purified by reverse-phase column chromatography (HO / ACN) to afford the racemate of compound 71 as a white solid (1.2 mg, yield: 36.4%). Compound 71 was further resolved by chiral column chromatography.

[1061] LCMS [M+H-H2O] + =540.9.

[1062] 1 H NMR (400MHz, DMSO) δ8.25(s,1H),7.76(s,1H),7.41(s,1H),7.19(dd,J=12.7,6.6Hz,4H),6.73(dd,J=18.4,7.8Hz,3H),6.42 -6.24(m,2H),6.16(s,1H),5.63(s,1H),5.35(s,1H),3.95(s,3H),3.90(s,3H),3.66(s,5H),2.86(s,1H),2.15-1.98(m,2H).

[1063] Compound 72

[1064] Step 1: To a solution of DMF (5 mL) was added the racemate of 53B (100 mg, 0.16 mmol), HATU (90 mg, 0.24 mmol), HOAT (32 mg, 0.24 mmol), and TMP (58 mg, 0.48 mmol), and the mixture was stirred at 17°C for 0.5 h. Methylamine hydrochloride (21 mg, 0.32 mmol) was added, and the mixture was stirred at 28°C for 1 h. The reaction mixture was purified on a silica gel column (DCM / MeOH) to afford the racemate of 72A as a yellow solid (90 mg, yield: 82%). LCMS [M+H] + =644.4.

[1065] Step 2: Dissolve the racemate of compound 72A (80 mg, 0.124 mmol) in THF (1 mL) and add a solution of BH3·DMS (0.19 mL, 2 M in THF). Stir at 60°C for 4 hours under nitrogen. Add MeOH (3 mL) and stir at 60°C for 16 hours. The reaction mixture is purified by silica gel column chromatography (DCM / MeOH) to obtain the racemate of 72B as a yellow solid (15 mg, yield: 19%). LCMS [M+H] + =630.4.

[1066] Step 3: To a solution of the racemate of compound 72B (15 mg, 0.023 mmol) and TEA (7.06 mg, 0.070 mmol) in DMF (1 mL) was added acetic anhydride (3.7 mg, 0.035 mmol) and stirred at 27°C for 2 hours. The reaction solution was purified by silica gel column chromatography (DCM / MeOH) to obtain the racemate of compound 72C as a yellow solid (8 mg, yield: 54%). LCMS [M+H] + =672.3.

[1067] Step 4: The racemate of compound 72C (8 mg, 0.008 mmol) was added to THF / 6M HCl = 1 / 1 (3 mL) and stirred at 28°C for 5 hours. The reaction solution was concentrated and purified using a reverse phase column (H2O / ACN) to obtain the racemate of compound 72 as a white solid (2.9 mg, yield: 39%). Compound 72 was further resolved using a chiral column. LCMS [M+H] + =572.4.

[1068] Compound 73

[1069] Step 1: Dissolve the racemate of compound 53B (50 mg, 0.08 mmol), HATU (60.29 mg, 0.16 mmol), and DIEA (30.74 mg, 0.24 mmol) in DMF (2 mL). Add diethylamine (5.8 mg, 0.08 mmol) and stir at room temperature for 0.5 hours. The reaction mixture is dried and purified on a reverse-phase silica gel column (FA-H2O / ACN = 45:55) to obtain the racemate of the target product 73A (35 mg, yield: 74%). LCMS [M+H] + =686.3.

[1070] Step 2: Dissolve the racemate of compound 73A (25 mg, 0.04 mmol) in THF (2 mL), add BH3·DMS (0.12 mL, 2 M in THF), and stir at 60°C for 2 hours. Add MeOH (2 mL) and stir for 14 hours. The reaction solution was dried and purified on a silica gel column (DCM:MeOH = 85:15) to obtain the racemate of compound 73B (20 mg, yield: 74.5%). LCMS [M+H] + =672.3.

[1071] Step 3: Dissolve the racemate of compound 73B (15 mg, 0.02 mmol) in THF (3 mL), add 6 M HCl (3 mL), and stir at room temperature for 2 hours. The reaction solution is spin-dried and purified on a reverse-phase silica gel column (FA-H2O / ACN = 70:30) to obtain the racemate of the target product 73 (1 mg, yield: 8.7%). Further chiral column separation affords compound 73.

[1072] LCMS [M+H] + =572.2.

[1073] 1H NMR (400MHz, DMSO) δ8.23 (s, 1H), 8.16 (s, 1H), 7.39 (d, J = 0.7Hz, 1H), 7.16 (d, J = 8.8 Hz,2H),7.11(s,2H),6.69(t,J=7.7Hz,1H),6.62(d,J=8.9Hz,2H),6.29(s,1H),6.19 (d,J=8.1Hz,1H),6.10(d,J=7.2Hz,1H),5.22(s,1H),4.81(s,1H),4.51(s,1H),3.8 5(s,3H),3.62(s,3H),3.05(s,2H),2.74(s,2H),1.24(s,4H),1.00(d,J=5.2Hz,6H).

[1074] Compound 74

[1075] Step 1: Add MsCl (1.5 mg, 0.014 mmol) to a solution of the racemate of 72B (6 mg, 0.009 mmol) and TEA (2.82 mg, 0.028 mmol) in DMF (1 mL) and stir at 27°C for 2 hours. The concentrate was purified by preparative TLC (DCM / MeOH = 10 / 1) to afford the racemate of 74A as a yellow solid (3.3 mg, yield: 50%). LCMS [M+H] + =708.5.

[1076] Step 2: The racemate of compound 74A (3 mg, 0.004 mmol) was dissolved in THF / 6M HCl (1 / 1, 3 mL) and stirred at 28°C for 5 hours. The reaction solution was concentrated and purified using a reverse phase column (HO / ACN) to afford the racemate of 74 as a white solid (1 mg, yield: 39%). Compound 74 was then separated using a chiral column.

[1077] LCMS [M+H] + =608.5.

[1078] 1 H NMR(400MHz,DMSO)δ8.23(s,1H),7.40(s,1H),7.21(s,1H),7.14(s,1H),7.1 1(d,J=2.1Hz,3H),6.70(t,J=7.8Hz,2H),6.61(d,J=9.0Hz,2H),6.32(s,1H), 6.22-6.18(m,2H),5.33(d,J=4.7Hz,1H),5.27(s,1H),4.78(d,J=5.0Hz,3H),4.47(s,1H),3.85(s ,3H),3.61(s,3H),2.90(s,3H),2.83(s,3H),2.00(dd,J=14.4,6.8Hz,6H),1.46(d,J=7.4Hz,3H).

[1079] Compound 75

[1080] Step 1: Dissolve the racemate of compound 20H (50 mg, 0.08 mmol), HATU (30.15 mg, 0.08 mmol), HOAT (10.79 mg, 0.08 mmol), and TMP (38.43 mg, 0.32 mmol) in DMF (2 mL). Add cyclobutylamine (4.53 mg, 0.08 mmol) and stir at room temperature for 2 hours. The reaction mixture was spin-dried and purified on a reverse-phase silica gel column (H2O / ACN = 50:50) to obtain the racemate of the target product 75A (25 mg, yield: 70%). LCMS [M+H] + =670.2.

[1081] Step 2: Dissolve the racemate of compound 75A (25 mg, 0.04 mmol) in THF (2 mL), add BH3·DMS (0.12 mL, 2N in THF), and stir at 60°C for 2 hours. Add MeOH (2 mL) and stir for 14 hours. The reaction mixture was dried and purified on a silica gel column (DCM:MeOH = 85:15) to obtain the racemate of compound 75B (9 mg, yield: 39%). LCMS [M+H] + =656.2.

[1082] Step 3: The racemate of compound 75B (9 mg, 0.01 mmol) was dissolved in THF (1 mL), 6M HCl (1 mL) was added, and the mixture was stirred at room temperature for 2 hours. The reaction solution was spin-dried and purified on a reverse-phase silica gel column (H2O / ACN = 70:30) to obtain the racemate of compound 75 (1 mg, yield: 18%). The product was further resolved on a chiral column to obtain compound 75.

[1083] LCMS [M+H] + =556.2.

[1084] 1H NMR (400MHz, DMSO) δ8.23(d,J=0.7Hz,1H),8.21(s,1H),7.39(d,J=0.7Hz,1H),7.15-7.08(m,4H),6.70(t ,J=7.7Hz,1H),6.61(d,J=9.0Hz,2H),6.27(s,1H),6.19(d,J=7.8Hz,1H),6.10(d,J=7.6Hz,1H),5.17(s, 1H),4.79(s,1H),4.43(d,J=4.2Hz,1H),...

Claims

1. A compound of formula II or its racemate, enantiomer, diastereomer, pharmaceutically acceptable salt, isotope-labeled compound, or a mixture of the foregoing forms in, X 1 Selected from N and C (R 1 ), R 1 is selected from hydrogen, halogen, cyano, -OH, -(C1-C6)alkyl and -O-(C1-C6)alkyl; X 2 Selected from N and C (R 2 ), R 2 is selected from hydrogen, halogen, cyano, -OH, -(C1-C6)alkyl and -O-(C1-C6)alkyl; R 3 -(C3-C6)cycloalkyl, -(3-8 membered)heterocyclyl, -(C6-C 10 )aryl and -(5-12 membered)heteroaryl, the -(C3-C6)cycloalkyl, -(3-8 membered)heterocyclyl, -(C6-C 10 )aryl and -(5-12 membered)heteroaryl are optionally substituted with one or more R 31 replace; R 31 each independently selected from oxo, hydrogen, halogen, cyano, nitro, -OH, -SH, -NH2, -(C1-C6)alkyl, -(C1-C6)alkylene-OH, -(C1-C6)alkylene-NH2, -(C1-C6)alkylene-NH[(C1-C6)alkyl], -(C1-C6)alkylene-N[(C1-C6)alkyl]2, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C1-C6)haloalkyl, -O-(C1-C6)alkyl, -O-(C1-C6)haloalkyl, -S-(C1-C6)alkyl, -NH -(C1-C6)alkyl, -N[(C1-C6)alkyl]2, -(C3-C6)cycloalkyl, -(4-10 membered)heterocyclyl, -O-(C3-C6)cycloalkyl, -O-(4-10 membered)heterocyclyl, -C(=O)-(C1-C6)alkyl, -C(=O)-(C3-C6)cycloalkyl, -C(=O)-O-(C1-C6)alkyl, -C(=O)-O-(C3-C6)cycloalkyl, -C(=O)-NH2, -C(=O)-NH(C1-C6)alkyl, -C(=O)-N[(C1-C6)alkyl]2, -(C6-C 10 )aryl, -(5-12 membered)heteroaryl, -S(=O)2-NH2, -S(=O)2-NH(C1-C6)alkyl, -S(=O)2-N[(C1-C6)alkyl]2, -NH-C(=O)H, -NH-C(=O)-(C1-C6)alkyl, -N[(C1-C6)alkyl]-C(=O)-(C1-C6)alkyl, N[(C1-C6)alkyl]-C(=O)H, -NH-S(=O)2-(C1-C6)alkyl, -N[(C1-C6)alkyl] -S(=O)2-(C1-C6)alkyl, -P(=O)[(C1-C6)alkyl]2, -P(=O)[(C1-C6)alkyl]-NH2, -P(=O)[(C1-C6)alkyl]-NH(C1-C6)alkyl and -P(=O)[(C1-C6)alkyl]-N[(C1-C6)alkyl]2, the -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C6)cycloalkyl, -(4-10 membered)heterocyclyl, -(C6-C 10 The -(5-12 membered)aryl and -(5-12 membered)heteroaryl groups are optionally substituted by one or more radicals selected from hydrogen, halogen, -OH, -O-(C1-C4)alkyl, -(C1-C6)alkylene-OH, -NH2, -NH(C1-C4)alkyl, -N[(C1-C4)alkyl]2, -(C1-C6)alkylene-NH2, -(C1-C6)alkylene-NH[(C1-C6)alkyl], -(C1-C6)alkylene-N[(C1-C6)alkyl]2, -(C6-C 10 )aryl and -(5-12 membered)heteroaryl, -(C1-C6)alkylene-O(C1-C6)alkyl, oxo-substituted; R 4 is selected from hydrogen, halogen, cyano, -OH, -NH2, -(C1-C6)alkyl, -(C1-C6)haloalkyl, -O-(C1-C6)alkyl, -O-(C1-C6)haloalkyl, -(C3-C6)cycloalkyl, -O-(C3-C6)cycloalkyl, -(4-10 membered)heterocyclyl, -O-(4-10 membered) heterocyclic group, -(C6-C 10 )aryl, -O-(C6-C 10 )aryl, -(5-12 membered)heteroaryl, and -O-(5-12 membered)heteroaryl; X is selected from O, S, NH, N[(C1-C6)alkyl], N[C(=O)-R c ]、C(R a )(R b )、C(=O)、C[=C(R a )R b ], S(=O) and S(=O)2; R a and R b are each independently selected from hydrogen, halogen, cyano, -OR c 、-SR c 、-N(R c )R c , -(C1-C6)alkyl and -(C1-C6)haloalkyl; R c is selected from hydrogen, -(C1-C6)alkyl, -(C1-C6)haloalkyl, -O-(C1-C6)alkyl, -O-(C1-C6)haloalkyl, -(C3-C6)cycloalkyl, -O-(C3-C6)cycloalkyl, -(4-10 membered)heterocyclyl, -O-(4-10 membered)heterocyclyl, -(C6-C 10 )aryl, -O-(C6-C 10 )aryl, -(5-12 membered)heteroaryl, and -O-(5-12 membered)heteroaryl; Ring B is selected from -(C6-C 10 )aryl and -(5-12 membered)heteroaryl; R 5 and R 6 each is independently selected from hydrogen, halogen, cyano, nitro, -OH, -SH, -NH2, -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C1-C6)haloalkyl, -O-(C1-C6)alkyl, -O-(C1-C6)haloalkyl, -S-(C1-C6)alkyl, -NH(C1-C6)alkyl, -N[(C1-C6)alkyl]2, -(C3-C6)cycloalkyl, -(4-10 membered)heterocyclyl, -O-(C3-C6)cycloalkyl, -O-(4-10 membered)heterocyclyl, -C(=O)-(C1-C6)alkyl, -C(=O)-(C3-C6)cycloalkyl, -C(=O -C(═O)-O-(C1-C6)alkyl, -C(═O)-O-(C3-C6)cycloalkyl, -C(═O)-NH2, -C(═O)-NH(C1-C6)alkyl, -C(═O)-N[(C1-C6)alkyl]2, -C(═O)-H and -C(═N-OH)-H, said -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C6)cycloalkyl and -(4-10 membered)heterocyclyl being optionally substituted by one or more groups selected from hydrogen, halogen, oxo, -OH, -O-(C1-C4)alkyl, -NH2, -NH(C1-C4)alkyl and N[(C1-C4)alkyl]2, or, R 5 and R 6 The carbon atom to which it is attached forms a 5-membered heterocyclic group; Ring C is selected from -(C6-C 10 )aryl and -(5-12 membered)heteroaryl; R 7 each independently selected from hydrogen, halogen, cyano, nitro, -OH, -SH, -NH2, -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C1-C6)haloalkyl, -O-(C1-C6)alkyl, -O-(C1-C6)haloalkyl, -S-(C1-C6)alkyl, -NH(C1-C6)alkyl, -N[(C1-C6)alkyl]2, -(C3-C6)cycloalkyl, -(4-10 membered)heterocyclyl, -O-(C3-C6)cycloalkyl, -O-(4-10 membered)heterocyclyl, -C(=O)-(C1-C6)alkyl, -C(=O)-(C3-C6)cycloalkyl, -C( -(C1-C6)alkyl, -C(=O)-O-(C1-C6)alkyl, -C(=O)-O-(C3-C6)cycloalkyl, -C(=O)-NH2, -C(=O)-NH(C1-C6)alkyl, -C(=O)-N[(C1-C6)alkyl]2 and -NHC(=O)-(C1-C6)alkyl, said -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C6)cycloalkyl and -(4-10 membered)heterocyclyl being optionally substituted with one or more groups selected from hydrogen, halogen, oxo, -OH, -O-(C1-C4)alkyl, -NH2, -NH(C1-C4)alkyl and -N[(C1-C4)alkyl]2; m is 1, 2, 3, 4, 5, 6, 7, 8 or 9; R 8a , R 8b , R 9a and R 9b each independently selected from hydrogen, halogen, cyano, -(C1-C6)alkyl, -(C1-C6)haloalkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -OR, -N(R)R, -[(C1-C8)alkylene]R, -[(C1-C8)alkylene]OR, -[(C1-C8)alkylene]N(R)R, -[(C1-C8)alkylene]N(R)C(=O)R, -[(C1-C8)alkylene]N( R)C(=O)N(R)R, -C(=O)R, -C(=O)N(R)R, -C(=O)[(C1-C8)alkylene]N(R)R, -C(=O)OR, -C(=S)N(R)R, -S R, -S(=O)R, -S(=O)2R, -S(=O)2N(R)R, -N(R)C(=O)R, -N(R)C(=O)N(R)R, -P(=O)(OR)(OR), -(C6-C 10 )aryl, -(5-12 membered)heteroaryl, -(C3-C6)cycloalkyl and -(4-10 membered)heterocyclyl, R is independently selected from hydrogen, -OH, -NH2, -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, - (C1-C6)haloalkyl, -O-(C1-C6)alkyl, -(C1-C4)alkylene-O-(C1-C6)alkyl, -O-(C1-C6)haloalkyl, -S-(C1-C6)alkyl, -S(=O)2-(C1-C6)alkyl, -(C3-C6)cycloalkyl, -(4-10 membered)heterocyclyl, -O-(C3-C6)cycloalkyl, -O-(4-10 membered)heterocyclyl, -C(=O)-H, -C(=O)-(C1-C6) 6) alkyl, -C(=O)-(C3-C6) cycloalkyl, -C(=O)-O-(C1-C6) alkyl, -C(=O)-O-(C3-C6) cycloalkyl, -C(=O)-NH2, -C(=O)-NH(C1-C6) alkyl, -C(=O)-N[(C1-C6) alkyl]2, -[(C1-C6) alkylene]-(C3-C6) cycloalkyl, -[(C1-C6) alkylene]-(4-10 membered) heterocyclyl, -(C6-C 10 )aryl, -[(C1-C6)alkylene]-(C6-C 10 )aryl and -(5-12 membered)heteroaryl, the -(C1-C6)alkylene-, -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C6)cycloalkyl, -(4-10 membered)heterocyclyl, -(C6-C 10 )aryl, -(5-12 membered)heteroaryl, optionally substituted by one or more groups selected from hydrogen, halogen, -OH, -O-(C1-C4)alkyl, -NH2, -NH(C1-C4)alkyl, N[(C1-C4)alkyl]2 and (C1-C4)alkyl, Or, R 8a and R 8b Combined to form oxo, -(C2-C6)alkenyl, -(C3-C6)cycloalkyl or -(4-10 membered)heterocyclyl, Or, R 9a and R 9b Combined to form oxo, -(C2-C6)alkenyl, -(C3-C6)cycloalkyl or -(4-10 membered)heterocyclyl, Or, R 8a and R 9a The carbon atoms to which it is attached together form a (C3-C6)cycloalkyl, (4-10-membered)heterocyclyl or (5-10-membered)heteroaryl, wherein the aforementioned groups are optionally substituted by one or more selected from hydrogen, halogen, -OH, -O-(C1-C4)alkyl, -NH2, -NH(C1-C4)alkyl, -N[(C1-C4)alkyl]2, -(C3-C6)cycloalkyl, -(4-8-membered)heterocyclyl, -(5-6-membered)heteroaryl and -(C6-C 10 ) aryl radical substitution, Or, R 8b and R 9b The carbon atoms to which it is attached together form a (C3-C6)cycloalkyl, (4-10-membered)heterocyclyl or (5-10-membered)heteroaryl, wherein the aforementioned groups are optionally substituted by one or more selected from hydrogen, halogen, -OH, -O-(C1-C4)alkyl, -NH2, -NH(C1-C4)alkyl, -N[(C1-C4)alkyl]2, -(C3-C6)cycloalkyl, -(4-8-membered)heterocyclyl, -(5-6-membered)heteroaryl and -(C6-C 10 ) aromatic radical substitution; R 10 is selected from hydrogen, cyano, -OH and -NH2, or R 10 and R 9a The atoms to which it is attached form a (5-6 membered) heterocyclic group, which is optionally substituted by one or more groups selected from hydrogen, halogen, -OH, -(C1-C4)alkyl, -(C3-C6)cycloalkyl, -O-(C1-C4)alkyl, -NH2, -NH(C1-C4)alkyl and -N[(C1-C4)alkyl]2.

2. The compound of claim 1 or its racemate, enantiomer, diastereomer, pharmaceutically acceptable salt, isotope-labeled compound, or mixture thereof, wherein: The compound is selected from the compound shown in formula I, in, X 1 Selected from N and C (R 1 ), R 1 is selected from hydrogen, halogen, cyano, -OH, -(C1-C6)alkyl and -O-(C1-C6)alkyl; X 2 Selected from N and C (R 2 ), R 2 is selected from hydrogen, halogen, cyano, -OH, -(C1-C6)alkyl and -O-(C1-C6)alkyl; R 3 -(C3-C6)cycloalkyl, -(3-8 membered)heterocyclyl, -(C6-C 10 )aryl and -(5-12 membered)heteroaryl, the -(C3-C6)cycloalkyl, -(3-8 membered)heterocyclyl, -(C6-C 10 )aryl and -(5-12 membered)heteroaryl are optionally substituted with one or more R 31 replace; R 31 each independently selected from oxo, hydrogen, halogen, cyano, nitro, -OH, -SH, -NH2, -(C1-C6)alkyl, -(C1-C6)alkylene-OH, -(C1-C6)alkylene-NH2, -(C1-C6)alkylene-NH[(C1-C6)alkyl], -(C1-C6)alkylene-N[(C1-C6)alkyl]2, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C1-C6)haloalkyl, -O-(C1-C6)alkyl, -O-(C1-C6)haloalkyl, -S-(C1-C6)alkyl, -NH -(C1-C6)alkyl, -N[(C1-C6)alkyl]2, -(C3-C6)cycloalkyl, -(4-10 membered)heterocyclyl, -O-(C3-C6)cycloalkyl, -O-(4-10 membered)heterocyclyl, -C(=O)-(C1-C6)alkyl, -C(=O)-(C3-C6)cycloalkyl, -C(=O)-O-(C1-C6)alkyl, -C(=O)-O-(C3-C6)cycloalkyl, -C(=O)-NH2, -C(=O)-NH(C1-C6)alkyl, -C(=O)-N[(C1-C6)alkyl]2, -(C6-C 10 )aryl, -(5-12 membered)heteroaryl, -S(=O)2-NH2, -S(=O)2-NH(C1-C6)alkyl, -S(=O)2-N[(C1-C6)alkyl]2, -NH-C(=O)H, -NH-C(=O)-(C1-C6)alkyl, -N[(C1-C6)alkyl]-C(=O)-(C1-C6)alkyl, N[(C1-C6)alkyl]-C(=O)H, -NH-S(=O)2-(C1-C6)alkyl, -N[(C1-C6)alkyl] -S(=O)2-(C1-C6)alkyl, -P(=O)[(C1-C6)alkyl]2, -P(=O)[(C1-C6)alkyl]-NH2, -P(=O)[(C1-C6)alkyl]-NH(C1-C6)alkyl and -P(=O)[(C1-C6)alkyl]-N[(C1-C6)alkyl]2, the -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C6)cycloalkyl, -(4-10 membered)heterocyclyl, -(C6-C 10 The -(5-12 membered)aryl and -(5-12 membered)heteroaryl groups are optionally substituted by one or more radicals selected from hydrogen, halogen, -OH, -O-(C1-C4)alkyl, -(C1-C6)alkylene-OH, -NH2, -NH(C1-C4)alkyl, -N[(C1-C4)alkyl]2, -(C1-C6)alkylene-NH2, -(C1-C6)alkylene-NH[(C1-C6)alkyl], -(C1-C6)alkylene-N[(C1-C6)alkyl]2, -(C6-C 10 )aryl and -(5-12 membered)heteroaryl, -(C1-C6)alkylene-O(C1-C6)alkyl, oxo-substituted; R 4 is selected from hydrogen, halogen, cyano, -OH, -NH2, -(C1-C6)alkyl, -(C1-C6)haloalkyl, -O-(C1-C6)alkyl, -O-(C1-C6)haloalkyl, -(C3-C6)cycloalkyl, -O-(C3-C6)cycloalkyl, -(4-10 membered)heterocyclyl, -O-(4-10 membered)heterocyclyl, -(C6-C 10 )aryl, -O-(C6-C 10 )aryl, -(5-12 membered)heteroaryl, and -O-(5-12 membered)heteroaryl; X is selected from O, S, NH, N[(C1-C6)alkyl], N[C(=O)-R c ]、C(R a )(R b )、C(=O)、C[=C(R a )R b ], S(=O) and S(=O)2; R a and R b are each independently selected from hydrogen, halogen, cyano, -OR c 、-SR c 、-N(R c )R c , -(C1-C6)alkyl and -(C1-C6)haloalkyl; R c is selected from hydrogen, -(C1-C6)alkyl, -(C1-C6)haloalkyl, -O-(C1-C6)alkyl, -O-(C1-C6)haloalkyl, -(C3-C6)cycloalkyl, -O-(C3-C6)cycloalkyl, -(4-10 membered)heterocyclyl, -O-(4-10 membered)heterocyclyl, -(C6-C 10 )aryl, -O-(C6-C 10 )aryl, -(5-12 membered)heteroaryl, and -O-(5-12 membered)heteroaryl; Ring B is selected from -(C6-C 10 )aryl and -(5-12 membered)heteroaryl; R 5 and R 6 each independently selected from hydrogen, halogen, cyano, nitro, -OH, -SH, -NH2, -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C1-C6)haloalkyl, -O-(C1-C6)alkyl, -O-(C1-C6)haloalkyl, -S-(C1-C6)alkyl, -NH(C1-C6)alkyl, -N[(C1-C6)alkyl]2, -(C3-C6)cycloalkyl, -(4-10 membered)heterocyclyl, -O-(C3-C6)cycloalkyl, -O-(4-10 membered)heterocyclyl, -C(=O) -(C1-C6)alkyl, -C(=O)-(C3-C6)cycloalkyl, -C(=O)-O-(C1-C6)alkyl, -C(=O)-O-(C3-C6)cycloalkyl, -C(=O)-NH2, -C(=O)-NH(C1-C6)alkyl, -C(=O)-N[(C1-C6)alkyl]2, -C(=O)-H and -C(=N-OH)-H, wherein the -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C6)cycloalkyl and -(4-10 membered)heterocyclyl are optionally substituted by one or more is substituted with a group selected from hydrogen, halogen, oxo, -OH, -O-(C1-C4)alkyl, -NH2, -NH(C1-C4)alkyl and N[(C1-C4)alkyl]2, or R 5 and R 6 The carbon atom to which it is attached forms a 5-membered heterocyclic group; Ring C is selected from -(C6-C 10 )aryl and -(5-12 membered)heteroaryl; R 7 each independently selected from hydrogen, halogen, cyano, nitro, -OH, -SH, -NH2, -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C1-C6)haloalkyl, -O-(C1-C6)alkyl, -O-(C1-C6)haloalkyl, -S-(C1-C6)alkyl, -NH(C1-C6)alkyl, -N[(C1-C6)alkyl]2, -(C3-C6)cycloalkyl, -(4-10 membered)heterocyclyl, -O-(C3-C6)cycloalkyl, -O-(4-10 membered)heterocyclyl, -C(=O)-(C1-C6)alkyl, -C(=O)-(C3-C6)cycloalkyl, -C( -(C1-C6)alkyl, -C(=O)-O-(C1-C6)alkyl, -C(=O)-O-(C3-C6)cycloalkyl, -C(=O)-NH2, -C(=O)-NH(C1-C6)alkyl, -C(=O)-N[(C1-C6)alkyl]2 and -NHC(=O)-(C1-C6)alkyl, said -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C6)cycloalkyl and -(4-10 membered)heterocyclyl being optionally substituted with one or more groups selected from hydrogen, halogen, oxo, -OH, -O-(C1-C4)alkyl, -NH2, -NH(C1-C4)alkyl and -N[(C1-C4)alkyl]2; m is 1, 2, 3, 4, 5, 6, 7, 8 or 9; R 8a , R 8b , R 9a and R 9b each independently selected from hydrogen, halogen, cyano, -(C1-C6)alkyl, -(C1-C6)haloalkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -OR, -N(R)R, -[(C1-C8)alkylene]R, -[(C1-C8)alkylene]OR, -[(C1-C8)alkylene]N(R)R, -[(C1-C8)alkylene]NHC(=O)R, -[(C1-C8)alkylene]N(R )C(=O)N(R)R, -C(=O)R, -C(=O)N(R)R, -C(=O)[(C1-C8)alkylene]N(R)R, -C(=O)OR, -C(=S)N(R)R, -SR , -S(=O)R, -S(=O)2R, -S(=O)2N(R)R, -N(R)C(=O)R, -N(R)C(=O)N(R)R, -P(=O)(OR)(OR), -(C6-C 10 )aryl, -(5-12 membered)heteroaryl, -(C3-C6)cycloalkyl and -(4-10 membered)heterocyclyl, R is each independently selected from hydrogen, -OH, -NH2, -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C1-C6)haloalkyl, -O-(C1-C6)alkyl, -(C1-C4)alkylene-O-(C1-C6)alkyl, -O-(C1-C6)haloalkyl, -S-(C1-C6)alkyl, -S(=O)2-(C1-C6)alkyl, -(C3-C6)cycloalkyl, -(4-10 membered)heterocyclyl, -O-(C3-C6)cycloalkyl, -O-(4-10 membered)heterocyclyl, ) heterocyclic group, -C(=O)-H, -C(=O)-(C1-C6) alkyl, -C(=O)-(C3-C6) cycloalkyl, -C(=O)-O-(C1-C6) alkyl, -C(=O)-O-(C3-C6) cycloalkyl, -C(=O)-NH2, -C(=O)-NH(C1-C6) alkyl, -C(=O)-N[(C1-C6) alkyl]2, -[(C1-C6) alkylene]-(C3-C6) cycloalkyl, -[(C1-C6) alkylene]-(4-10 membered) heterocyclic group, -(C6-C 10 )aryl, -[(C1-C6)alkylene]-(C6-C 10 )aryl and -(5-12 membered)heteroaryl, the -(C1-C6)alkylene-, -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C6)cycloalkyl, -(4-10 membered)heterocyclyl, -(C6-C 10 )aryl, -(5-12 membered)heteroaryl, optionally substituted by one or more groups selected from hydrogen, halogen, -OH, -O-(C1-C4)alkyl, -NH2, -NH(C1-C4)alkyl, N[(C1-C4)alkyl]2 and (C1-C4)alkyl, Or, R 8a and R 8b Combined to form oxo, -(C2-C6)alkenyl, -(C3-C6)cycloalkyl or -(4-10 membered)heterocyclyl, Or, R 9a and R 9b Combined to form oxo, -(C2-C6)alkenyl, -(C3-C6)cycloalkyl or -(4-10 membered)heterocyclyl, Or, R 8a and R 9a The carbon atoms to which it is attached together form a (C3-C6)cycloalkyl, (4-10-membered)heterocyclyl or (5-10-membered)heteroaryl, wherein the aforementioned groups are optionally substituted by one or more selected from hydrogen, halogen, -OH, -O-(C1-C4)alkyl, -NH2, -NH(C1-C4)alkyl, -N[(C1-C4)alkyl]2, -(C3-C6)cycloalkyl, -(4-8-membered)heterocyclyl, -(5-6-membered)heteroaryl and -(C6-C 10 ) aryl radical substitution, Or, R 8b and R 9b The carbon atoms connected to it together form a (C3-C6) cycloalkyl, (4-10 membered) heterocyclic group or (5- 10-membered) heteroaryl, the aforementioned groups are optionally substituted by one or more selected from hydrogen, halogen, -OH, -O-(C1-C4) alkyl, -NH2, -NH(C1-C4) alkyl, -N[(C1-C4) alkyl]2, -(C3-C6) cycloalkyl, -(4-8-membered) heterocyclyl, -(5-6-membered) heteroaryl and -(C6-C 10 ) aromatic radical substitution; R 10 is selected from hydrogen, cyano, -OH and -NH2, or R 10 and R 9a The atoms to which it is attached form a (5-6 membered) heterocyclic group, which is optionally substituted by one or more groups selected from hydrogen, halogen, -OH, -(C1-C4)alkyl, -(C3-C6)cycloalkyl, -O-(C1-C4)alkyl, -NH2, -NH(C1-C4)alkyl and -N[(C1-C4)alkyl]2.

3. The compound according to claim 1 or 2, or its racemate, enantiomer, diastereomer, pharmaceutically acceptable salt, isotope-labeled compound, or mixture thereof, wherein: R 1 is selected from hydrogen, halogen, cyano, -OH, -(C1-C4)alkyl and -O-(C1-C4)alkyl; Preferably, R 1 is selected from the group consisting of hydrogen, fluorine, chlorine, cyano, -OH, methyl, ethyl, propyl, -O-methyl, -O-ethyl and -O-propyl; Preferably, R 1 is selected from hydrogen and -O-methyl; Preferably, R 1 is -O-methyl, X 1 Selected from N and C(OCH3).

4. The compound according to any one of claims 1 to 3 or its racemate, enantiomer, diastereomer, pharmaceutically acceptable salt, isotope-labeled compound, or mixture thereof, wherein: R 2 is selected from hydrogen, halogen, cyano, -OH, -(C1-C4)alkyl and -O-(C1-C4)alkyl; Preferably, R 2 is selected from the group consisting of hydrogen, fluorine, chlorine, cyano, -OH, methyl, ethyl, propyl, -O-methyl, -O-ethyl and -O-propyl; Preferably, R 2 is hydrogen, X 2 is selected from N and CH.

5. The compound according to any one of claims 1 to 4 or its racemate, enantiomer, diastereomer, pharmaceutically acceptable salt, isotope-labeled compound, or mixture thereof, wherein: R 31 is selected from the group consisting of oxo, hydrogen, halogen, cyano, nitro, -OH, -SH, -NH2, -(C1-C4)alkyl, -(C1-C4)alkylene-OH, -(C1-C4)alkylene-N[(C1-C4)alkyl]2, -(C2-C4)alkenyl, -(C2-C4)alkynyl, -(C1-C4)haloalkyl, -O-(C1-C4)alkyl, -O-(C1-C4)haloalkyl, -S-(C1-C4)alkyl, -NH(C1-C4)alkyl, -N[(C1-C4)alkyl]2 [(C1-C4)alkyl]2, -(C3-C6)cycloalkyl, -(4-8-membered)heterocyclyl, -O-(C3-C6)cycloalkyl, -O-(4-8-membered)heterocyclyl, -C(=O)-(C1-C4)alkyl, -C(=O)-(C3-C6)cycloalkyl, -C(=O)-O-(C1-C4)alkyl, -C(=O)-O-(C3-C6)cycloalkyl, -C(=O)-NH2, -C(=O)-NH(C1-C4)alkyl and -C(=O)-N[(C1-C4)alkyl]2, Preferably, R 31 is selected from the group consisting of hydrogen, fluorine, chlorine, cyano, -OH, -SH, -NH2, -(C1-C4)alkyl, -O-(C1-C4)alkyl, -NH-(C1-C4)alkyl, -(C1-C4)alkylene-OH, -(C1-C4)haloalkyl, -(C1-C4)alkylene-NH2, -(C1-C4)alkylene-NH(C1-C4)alkyl and -(C1-C4)alkylene-N[(C1-C4)alkyl]2, Preferably, R 31 is selected from the group consisting of hydrogen, fluorine, chlorine, cyano, -OH, -SH, -NH2, methyl, halomethyl, -O-methyl, -CH2OH, -CH2NH2 and -CH2CH2N(CH3)2, Preferably, R 31 is selected from the group consisting of hydrogen, fluorine, chlorine, cyano, -OH, -SH and -NH2; R 3 is selected from -(C3-C6)cycloalkyl, -(3-6 membered)heterocyclyl, -(C6-C 10 )aryl and -(5-12 membered)heteroaryl, the -(C3-C6)cycloalkyl, -(3-6 membered)heterocyclyl, -(C6-C 10 )aryl and -(5-12 membered)heteroaryl are optionally substituted with one or more R 31 Replacement, R 31 As defined in this claim, Preferably, R 3 Selected from -(C6-C 10 )aryl and -(5-12 membered)heteroaryl, the -(C6-C 10 )aryl and -(5-12 membered)heteroaryl are optionally substituted with one or more R 31 Replacement, R 31 As defined in this claim, Preferably, R 3 is selected from phenyl and -(5-10 membered)heteroaryl, wherein the phenyl and -(5-10 membered)heteroaryl are optionally substituted by one or more R 31 Replacement, R 31 As defined in this claim, Preferably, R 3 is selected from -(5-6 membered)heteroaryl, wherein the -(5-6 membered)heteroaryl is optionally substituted by 1, 2, 3 or 4 R 31 Replacement, R 31 As defined in this claim, Preferably, R 3 is selected from the group consisting of oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, isothiazolyl, imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyrazinyl, pyridazinyl, pyrimidinyl, pyridazinoimidazolyl, pyrazinoimidazolyl and pyrimidinone, wherein the oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, isothiazolyl, imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyrazinyl, pyridazinyl, pyrimidinyl, pyridazinoimidazolyl, pyrazinoimidazolyl and pyrimidinone are optionally substituted by 1, 2 or 3 R 31 Replacement, R 31 As defined in this claim, Preferably, R 3 Selected from Said Optional 1, 2 or 3 R 31 Replacement, R 31 As defined in this claim, Preferably, R 3 Selected from More preferably, R 3 is selected from oxazolyl, pyrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyridazinomidazolyl, pyrazinomidazolyl, wherein the oxazolyl, pyrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyridazinomidazolyl, pyrazinomidazolyl are optionally substituted by 1, 2 or 3 R 31 Replacement, R 31 is as defined in this claim; More preferably, R 3 Selected from More preferably, R 3 is selected from oxazolyl, pyrazolyl, pyrimidinyl and pyrazinyl, wherein the oxazolyl, pyrazolyl, pyrimidinyl and pyrazinyl are optionally substituted by 1, 2 or 3 R 31 (as defined in the claims) substituted, for example, by fluoro, cyano, amino, methyl, trifluoromethyl, -methylene-OH and -O-methyl; More preferably, R 3 Selected from Said Optional 1, 2 or 3 R 31 (as defined in the claims) substituted, for example, by fluoro, cyano, amino, methyl, trifluoromethyl, -methylene-OH and -O-methyl; More preferably, R 3 Selected from Or, R 3 is selected from -(C3-C6)cycloalkyl and -(3-6-membered)heterocyclyl, wherein the -(C3-C6)cycloalkyl and -(3-6-membered)heterocyclyl are optionally substituted by one or more R 31 Replacement, R 31 is as defined in this claim; Preferably, R 3 is selected from cyclopropyl, oxetanyl, azetidinyl, tetrahydrofuranyl, pyrrolidinyl, tetrahydropyranyl, piperidinyl, piperazinyl, piperazinonyl, morpholinyl and morpholinonyl, the foregoing groups being optionally substituted by one or more R 31 Replacement, R 31 is as defined in this claim; Preferably, R 3 Selected from 6. The compound according to any one of claims 1 to 5 or its racemate, enantiomer, diastereomer, pharmaceutically acceptable salt, isotope-labeled compound, or mixture thereof, wherein: R 4 is selected from hydrogen, halogen, cyano, -OH, -NH2, -(C1-C4)alkyl, -(C1-C4)haloalkyl, -O-(C1-C4)alkyl, -O-(C1-C4)haloalkyl, -(C3-C6)cycloalkyl, -O-(C3-C6)cycloalkyl, -(4-8 membered)heterocyclyl, -O-(4-8 membered)heterocyclyl, -(C6-C 10 )aryl, -O-(C6-C 10 )aryl, -(5-10 membered)heteroaryl, and -O-(5-10 membered)heteroaryl; Preferably, R 4 is selected from the group consisting of hydrogen, fluorine, chlorine, cyano, -OH, -NH2, methyl, halomethyl, -O-methyl, -NH-methyl and cyclopropyl; Preferably, R 4 is selected from the group consisting of hydrogen, fluorine, chlorine, cyano, -OH and -NH2; Preferably, R 4 For hydrogen.

7. The compound according to any one of claims 1 to 6 or its racemate, enantiomer, diastereomer, pharmaceutically acceptable salt, isotope-labeled compound, or mixture thereof, wherein: Preferably, X is selected from O, S, NH, N(CH3), N(CH2CH3), N[C(═O)-CH3], CH2, C(CH3)2, C(CH3)(CH2CH3), C(CH2CH3)2, C(═O), C(═CH2), C(═CF2), C(═CHCF3), S(═O) and S(═O)2, Preferably, X is selected from O, S and NH, More preferably, X is O.

8. The compound according to any one of claims 1 to 7 or its racemate, enantiomer, diastereomer, pharmaceutically acceptable salt, isotope-labeled compound, or mixture thereof, wherein: Ring B is selected from -(C6-C 10 ) aryl and 5-10 membered heteroaryl, Preferably, ring B is selected from phenyl, naphthyl, oxazolyl, thiazolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, pyridyl, pyrimidinyl, benzofuranyl, benzothiophenyl, indolyl, quinolyl and isoquinolyl, Preferably, ring B is phenyl, Preferably, the structural unit for R 5 and R 6 each is independently selected from hydrogen, halogen, cyano, nitro, -OH, -SH, -NH2, -(C1-C4)alkyl, -(C2-C4)alkenyl, -(C2-C4)alkynyl, -(C1-C4)haloalkyl, -O-(C1-C4)alkyl, -O-(C1-C4)haloalkyl, -S-(C1-C4)alkyl, -NH(C1-C4)alkyl, -N[(C1-C4)alkyl]2, -(C3-C6)cycloalkyl, -(4-8 membered)heterocyclyl, -O-(C3-C6)cycloalkyl, -O-(4-8 membered)heterocyclyl, -C(=O)-(C1-C4)alkyl, -C(=O)-(C3-C6)cycloalkyl, -C(=O)-O-(C1-C4)alkyl, -C(=O)-O- -(C3-C6)cycloalkyl, -C(═O)—NH2, -C(═O)—NH(C1-C4)alkyl, -C(═O)—N[(C1-C4)alkyl]2, -C(═O)—H and -C(═N-OH)—H, said -(C1-C4)alkyl, -(C2-C4)alkenyl, -(C2-C4)alkynyl, -(C3-C6)cycloalkyl and -(4-8 membered)heterocyclyl being optionally substituted by 1, 2, 3, 4 or 5 groups selected from hydrogen, halogen, -OH, -O-methyl, -O-ethyl, -O-propyl, -NH2, -NH-methyl, -NH-ethyl, -NH-propyl, -N(methyl), -N(methyl)-ethyl, -N(methyl)-propyl, -N(ethyl)2 and -N(ethyl)-propyl, Preferably, R 5 and R 6 each independently selected from hydrogen, fluorine, chlorine, bromine, cyano, -OH, -NH2, methyl, ethyl, -O-methyl, -NH-methyl, -N(methyl), -N(methyl)-ethyl, cyclopropyl, azetidinyl, -O-cyclopropyl, -C(=O)-methyl, -C(=O)-cyclopropyl, -C(=O)-H and -C(=N-OH)-H; Preferably, R 5 and R 6 each independently selected from hydrogen, fluorine, chlorine, bromine, cyano, -OH, -NH2, -(C1-C4)alkyl, -(C1-C4)alkyl-OH, -(C1-C4)alkyl-NH2, -(C1-C4)haloalkyl, -O-(C1-C4)alkyl, -O-(C1-C4)haloalkyl and -(C3-C6)cycloalkyl, Preferably, R 5 is selected from hydrogen, fluorine, chlorine, bromine, cyano, -OH, -NH2 and -CH2NH2, Preferably, R 5 is selected from hydrogen and -NH2; Preferably, R 6 is selected from hydrogen, fluorine, chlorine, bromine, cyano, -OH, -NH2, -O-methyl and cyclopropyl; Or, R 5 and R 6 The atoms connected to it form The * indicates the positions of connected atoms.

9. The compound according to any one of claims 1 to 8 or its racemate, enantiomer, diastereomer, pharmaceutically acceptable salt, isotope-labeled compound, or mixture thereof, wherein: Ring C is selected from -(C6-C 10 )aryl and -(5-10 membered)heteroaryl, Preferably, ring C is selected from phenyl, naphthyl, oxazolyl, thiazolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, pyridyl, pyrimidinyl, benzofuranyl, benzothiophenyl, indolyl, quinolyl and isoquinolyl, Preferably, ring C is phenyl, Preferably, the structural unit for R 7 each independently selected from hydrogen, halogen, cyano, nitro, -OH, -SH, -NH2, -(C1-C4)alkyl, -(C2-C4)alkenyl, -(C2-C4)alkynyl, -(C1-C4)haloalkyl, -O-(C1-C4)alkyl, -O-(C1-C4)haloalkyl, -S-(C1-C4)alkyl, -NH(C1-C4)alkyl, -N[(C1-C4)alkyl]2, -(C -(4-8 membered) heterocyclyl, -O-(C3-C6) cycloalkyl, -O-(4-8 membered) heterocyclyl, -C(=O)-(C1-C4) alkyl, -C(=O)-(C3-C6) cycloalkyl, -C(=O)-O-(C1-C4) alkyl, -C(=O)-O-(C3-C6) cycloalkyl, -C(=O)-NH2, -C(=O)-NH(C1-C4) alkyl wherein -(C1-C4)alkyl, -(C2-C4)alkenyl, -(C2-C4)alkynyl, -(C3-C6)cycloalkyl and -(4-8 membered)heterocyclyl are optionally substituted by 1, 2, 3, 4 or 5 groups selected from hydrogen, halogen, -OH, -O-methyl, -O-ethyl, -O-propyl, -NH2, -NH-methyl, -NH-ethyl, -NH-propyl, -N(methyl), -N(methyl)-ethyl, -N(methyl)-propyl, -N(ethyl)2 and -N(ethyl)-propyl, Preferably, R 7 each independently selected from hydrogen, fluorine, chlorine, bromine, cyano, -OH, -NH2, -(C1-C4)alkylene-OH, -(C1-C4)alkylene-NH(C1-C4)alkyl, -(C1-C4)alkylene-N[(C1-C4)alkyl]2, -(C1-C4)alkylene-NH2 and -NHC(=O)-(C1-C4)alkylene-NH2, Preferably, R 7 each independently selected from hydrogen, fluorine, chlorine, bromine, -OH, -NH2, -methylene-OH, -ethylene-OH, -propylene-OH, -methylene-NH2, -ethylene-NH2, -propylene-NH2, -NHC(=O)-methylene-NH2 and -NHC(=O)-ethylene-NH2, Preferably, R 7 Each is independently selected from hydrogen, -OH, -NH2, More preferably, R 7 are each independently selected from hydrogen and -NH2; Preferably, m is 1, 2 or 3.

10. The compound according to any one of claims 1 to 9 or its racemate, enantiomer, diastereomer, pharmaceutically acceptable salt, isotope-labeled compound, or mixture thereof, wherein: R is each independently selected from hydrogen, -OH, -NH2, -(C1-C4)alkyl, -(C2-C4)alkenyl, -(C2-C4)alkynyl, -(C1-C4)haloalkyl, -O-(C1-C4)alkyl, -(C1-C4)alkylene-O-(C1-C4)alkyl, -O-(C1-C4)haloalkyl, -S-(C1-C4)alkyl, -S(=O)2-(C1-C4)alkyl, -(C3-C6)cycloalkyl, -(4-8 membered)heterocyclyl, -O-(C3-C6)cycloalkyl, -O-(4-8 membered)heterocyclyl, ) heterocyclyl, -C(=O)-H, -C(=O)-(C1-C4) alkyl, -C(=O)-(C3-C6) cycloalkyl, -C(=O)-O-(C1-C4) alkyl, -C(=O)-O-(C3-C6) cycloalkyl, -C(=O)-NH2, -C(=O)-NH(C1-C4) alkyl, -C(=O)-N[(C1-C4) alkyl]2, -[(C1-C4) alkylene]-(C3-C6) cycloalkyl, -[(C1-C4) alkylene]-(4-8 membered) heterocyclyl, -(C6-C 10 )aryl, -[(C1-C4)alkylene]-(C6-C 10 )aryl and -(5-10 membered)heteroaryl, the -(C1-C4)alkylene-, -(C1-C4)alkyl, -(C2-C4)alkenyl, -(C2-C4)alkynyl, -(C3-C6)cycloalkyl, -(4-8 membered)heterocyclyl, -(C6-C 10 )aryl and -(5-10 membered)heteroaryl are optionally substituted by 1, 2, 3, 4, 5, 6 or 7 groups selected from hydrogen, halogen, -OH, -O-(C1-C4)alkyl, -NH2, -NH(C1-C4)alkyl, N[(C1-C4)alkyl]2 and (C1-C4)alkyl, Preferably, each R is independently selected from hydrogen, -OH, -NH2, -(C1-C4)alkyl, -(C1-C4)haloalkyl, -O-(C1-C4)alkyl, -(C1-C4)alkylene-O-(C1-C6)alkyl, -O-(C1-C4)haloalkyl, -S(=O)2-(C1-C4)alkyl, -(C3-C6)cycloalkyl, -(4-8 membered)heterocyclyl, -C(=O)-H, -C(=O)-(C1-C4)alkyl, -C(=O)-(C3-C6)cycloalkyl, -[(C1-C4)alkylene]-(C3-C6)alkylene 6) cycloalkyl and -[(C1-C4)alkylene]-(4-8 membered)heterocyclyl, said -(C1-C4)alkylene-, -(C1-C4)alkyl, -(C3-C6)cycloalkyl and -(4-8 membered)heterocyclyl being optionally substituted by 1, 2, 3, 4 or 5 groups selected from hydrogen, halogen, -OH, -O-methyl, -O-ethyl, -O-propyl, -NH2, -NH-methyl, -NH-ethyl, -NH-propyl, -N(methyl), -N(methyl)-ethyl, -N(methyl)-propyl, -N(ethyl), -N(ethyl)-propyl, methyl and ethyl, Preferably, each R is independently selected from hydrogen, -OH, -NH2, methyl, ethyl, propyl, halomethyl, haloethyl, halopropyl, -methylene-O-methyl, -methylene-O-ethyl, -ethylidene-O-methyl, -ethylidene-O-ethyl, -O-methyl, -O-ethyl, -O-propyl, -O-halomethyl, -O-haloethyl, -O-halopropyl, -C(=O)-H, -C(=O)-methyl, -C(=O)-ethyl, -C(=O)-propyl, -S(=O)2-methyl, -S(=O)2-ethyl, - S(=O)2-propyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, -methylene-cyclobutyl, -methylene-oxetanyl and -methylene-azetidinyl, the methyl, ethyl, propyl,, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl and morpholinyl being optionally substituted with 1, 2 or 3 groups selected from -OH, -OCH3, -NH2, NHCH3, N(CH3)2 and -CH3, Preferably, each R is independently selected from hydrogen, -OH, -NH2, -CH3, -CH2CH3, -CH2OH, -CH2CH2OH, -CH2OCH3, -CH2NH2, -CH2CH2NH2, -CH2CH2NHCH3, -CH2N(CH3)2, -CH(N(CH3)2)CH2OH, -CH2OCH2CH2OH, -OCH3, -C(=O)-H, -C(=O)CH3, -C(=O)CH2OH, -S(=O)2CH3, cyclobutyl-OH, oxetanyl, azetidinyl, azetidinyl-OH, pyrrolidinyl, piperazinyl, azetidinyl-CH3, piperazinyl-CH3 and -CH2-azetidinyl; Further preferably, each R is independently selected from hydrogen, -OH, -NH2, -(C1-C4)alkyl, -O-(C1-C4)alkyl, -C(=O)-(C1-C4)alkyl, -S(=O)2(C1-C4)alkyl, -(C3-C6)cycloalkyl, -(4-8-membered)heterocyclyl, -methylene-(C3-C6)cycloalkyl and -methylene-(4-8-membered)heterocyclyl, and the -(C1-C4)alkyl, -(C3-C6)cycloalkyl and -(4-8-membered)heterocyclyl are optionally substituted by 1, 2, 3, 4 or 5 groups selected from hydrogen, halogen, -OH, -NH2, -NH(C1-C4)alkyl, -N[(C1-C4)alkyl]2, -O-(C1-C4)alkyl and -(C1-C4)alkyl, Further preferably, R is each independently selected from hydrogen, -OH, methyl, ethyl, propyl, -O-methyl, -O-ethyl, -O-propyl, -methylene-O-ethyl, -C(=O)-methyl, -S(=O)2-methyl, cyclobutyl, oxetanyl, azetidinyl, pyrrolidinyl, piperazinyl, -methylene-cyclobutyl, -methylene-oxetanyl and -methylene-azetidinyl, and the foregoing groups are each independently optionally substituted by 1, 2 or 3 groups selected from -OH, -NH2, OCH3, NHCH3, , N(CH3)2 and CH3; R 8a , R 8b , R 9a and R 9b each independently selected from hydrogen, halogen, cyano, -(C1-C4)alkyl, -(C1-C4)haloalkyl, -(C2-C4)alkenyl, -(C2-C4)alkynyl, -OR, -N(R)R, -[(C1-C6)alkylene]R, -[(C1-C6)alkylene]OR, -[(C1-C6)alkylene]N(R)R, -[(C1-C6)alkylene]N(R)C(=O)R, -[(C1-C6)alkylene]N( R)C(=O)N(R)R, -C(=O)R, -C(=O)N(R)R, -C(=O)[(C1-C6)alkylene]N(R)R, -C(=O)OR, -C(=S)N(R)R, -S R, -S(=O)R, -S(=O)2R, -S(=O)2N(R)R, -N(R)C(=O)R, -N(R)C(=O)N(R)R, -P(=O)(OR)(OR), -(C6-C 10 )aryl, -(5-10 membered)heteroaryl, -(C3-C6)cycloalkyl and -(4-8 membered)heterocyclyl, R is as defined in the claims, Preferably, R 8a , R 8b , R 9a and R 9b each independently selected from hydrogen, cyano, -OR, -N(R)R, -[(C1-C4)alkylene]R, -[(C1-C4)alkylene]OR, -[(C1-C4)alkylene]N(R)R, -[(C1-C4)alkylene]N(R)C(=O)R, -[(C1-C4)alkylene]N(R)C(=O)N(R)R, -C(=O)R, -C(=O)N(R)R, -C(=O)[(C1-C4)alkylene]N(R)R, -C(=O)OR, -C(=S)N(R)R, -S(=O)R, -S(=O)2R, -S(=O)2N(R)R, -N(R)C(=O)R and -N(R)C(=O)N(R)R, R being as defined in the claims; Preferably, R 8a and R 8b each independently selected from hydrogen, -methylene-R, -ethylene-R, -propylene-R, -methylene-OR, -ethylene-OR, -propylene-OR, -methylene-N(R)R, -ethylene-N(R)R, -propylene-N(R)R, -C(=O)R, -C(=O)N(R)R and -C(=O)OR, R being as defined in the claims, Preferably, R 8a and R 8b Each independently selected from hydrogen, -methylene-R, -methylene-OR, -methylene-N(R)R, -C(=O)R, -C(=O)OR and -C(=O)N(R)R, R is as defined in the claims, for example, R is ... independently selected from hydrogen, -OH, -NH2, -(C1-C4)alkyl, -O-(C1-C4)alkyl, -C(=O)-(C1-C4)alkyl, -S(=O)2(C1-C4)alkyl and -(4-8 membered)heterocyclyl, wherein -(C1-C4)alkyl and -(4-8 membered)heterocyclyl are optionally substituted by 1, 2, 3, 4 or 5 groups selected from hydrogen, halogen, -OH, -NH2, -NHCH3 and CH3; Preferably, R 8a is hydrogen, preferably Preferably, R 8b Selected from hydrogen, Preferably, R 8b Selected from hydrogen, Preferably, R 8b is selected from hydrogen, -methylene-R, -methylene-N(R)R, -C(=O)OR, -C(=O)N(R)R and -C(=O)R, R is as defined in the claims, for example, R is independently selected from hydrogen, -OH, methyl, ethyl, -O-methyl, -C(=O)-methyl, -S(=O)2-methyl, azetidinyl, pyrrolidinyl and piperazinyl, the foregoing groups are each independently optionally substituted by 1, 2 or 3 groups selected from -OH and -NH2, More preferably, R 8b Selected from hydrogen, More preferably, R 8b Selected from hydrogen, Preferably, R 9a and R 9b each independently selected from hydrogen, -CN, -OR, -NHR, -N(R)R, -NHC(=O)R, -methylene-R, -ethylene-R, -propylene-R, -methylene-N(R)R, -ethylene-N(R)R, -propylene-N(R)R, -methylene-NHC(=O)R and -methylene-NHC(=O)NHR, R being as defined in the claims; Preferably, R 9a and R 9b Each is independently selected from hydrogen, -CN, -OR, -N(R)R, -NHC(=O)R, -methylene-N(R)R, -methylene-NHC(=O)R and -methylene-NHC(=O)NHR, R is defined as described in the claims, for example, R is independently selected from hydrogen, -OH, -(C1-C4)alkyl, -(C1-C4)alkylene-O-(C1-C4)alkyl, -S(=O)2(C1-C4)alkyl, -(C3-C6)cycloalkane -(C1-C4)alkyl, -(C3-C6)cycloalkyl and -(4-8-membered)heterocyclyl, wherein -(C1-C4)alkyl, -(C3-C6)cycloalkyl and -(4-8-membered)heterocyclyl are each optionally substituted by 1, 2, 3, 4 or 5 groups selected from hydrogen, halogen, -OH, -NH2, -NH(C1-C4)alkyl, -N[(C1-C4)alkyl]2, -O-(C1-C4)alkyl and -(C1-C4)alkyl; Preferably, R 9a Selected from hydrogen, -CN, -N(R)R, -NHC(=O)R, -methylene-N(R)R, -methylene-NHC(=O)R and -methylene-NHC(=O)NHR, R is as defined in the claims, for example, R is independently selected from hydrogen, -OH, methyl, ethyl, -methylene-O-ethyl, -S(=O)2-methyl, cyclobutyl, azetidinyl, -methylene-cyclobutyl and -methylene-azetidinyl, the foregoing groups are each independently optionally substituted by 1, 2 or 3 groups selected from -OH, OCH3, NHCH3, N(CH3)2 and CH3; Preferably, R 9a Selected from hydrogen, -CN, -NHCH3, -N(CH3)2, -NHC(=O)H, -NHC(=O)CH2OH, -NHC(=O)CH2OCH3, -NHC(=O)CH2NHCH3, -NHC(=O)CH2N(CH3)2, -CH2NH2, -CH2NHCH3, -CH2N(CH 3)2, -CH2N(CH2CH3)2, -CH2N(CH3)(CH2CH3), -CH2NHC(=O)CH2OH, -CH2NHC(=O)CH2OCH3, -CH2NHC(=O)CH2NHCH3, -CH2NHC(=O)CH2N(CH3)2, -CH2NHC(=O )H, -CH2NHC(=O)CH3, -CH2NHC(=O)NHOH, -CH2NHC(=O)NHCH2CH2OH, -CH2NHC(=O)CH(N(CH3)2)CH2OH, -CH2NHC(=O)CH2NHCH3, -CH2NHC(=O)CH2N(CH3)2, -CH2NHC(=O)CH2N(CH2CH3)2, -CH2NHC(=O)CH2OCH2CH2OH, -CH2NHS(=O)2CH3, -CH2NHC(=O)cyclobutyl-OH, -CH2NHC(=O)-azetidinyl-CH3 and -CH2NHC(=O)CH2-azetidinyl, Preferably, R 9a Selected from hydrogen, Preferably, R 9a Selected from hydrogen, Preferably, R 9a for Preferably, R 9b Selected from hydrogen and Or, R 8a and R 8b Combined to form oxo, -(C2-C4)alkenyl, -(C3-C6)cycloalkyl or -(4-8 membered)heterocyclyl, Or, R 9a and R 9b Combined to form oxo, -(C2-C4)alkenyl, -(C3-C6)cycloalkyl or -(4-8 membered)heterocyclyl, Preferably, R 8a and R 8b Combined to form oxo, vinyl, propenyl, cyclopropyl, cyclobutyl, cyclopentyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl or piperazinyl, Preferably, R 9a and R 9b Combine to form oxo, vinyl, propenyl, cyclopropyl, cyclobutyl, cyclopentyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl or piperazinyl; Or, R 8a and R 9a The carbon atoms to which it is attached together form a (C3-C6)cycloalkyl, a (4-8 membered)heterocyclyl or a (5-9 membered)heteroaryl, wherein the aforementioned groups are optionally substituted by 1, 2, 3, 4, 5, 6 or 7 groups selected from hydrogen, halogen, -OH, -O-(C1-C4)alkyl, -NH2, -NH(C1-C4)alkyl, -N[(C1-C4)alkyl]2, -(C3-C6)cycloalkyl and -(C6-C 10 ) aryl radical substitution, Or, R 8b and R 9b The carbon atoms connected thereto together form a (C3-C6) cycloalkyl, a (4-8 membered) heterocyclyl or a (5-9 membered) heteroaryl, wherein the aforementioned groups are optionally substituted by 1, 2, 3, 4, 5, 6 or 7 atoms selected from hydrogen, halogen, -OH, -O-(C1-C4) alkyl, -NH2, -NH(C1-C4)alkyl, -N[(C1-C4)alkyl]2, -(C3-C6)cycloalkyl and -(C6-C 10 ) aryl radical substitution, Preferably, R 8a and R 9a The carbon atoms to which it is attached together form a (4-8 membered) heterocyclyl or a (5-9 membered) heteroaryl, the aforementioned groups are optionally substituted by 1, 2, 3, 4 or 5 groups selected from hydrogen, fluorine, chlorine, -OH, -O-methyl, -O-ethyl, -NH2, -NH-methyl, -NH-ethyl, -N(methyl)2, -N(methyl)-ethyl, -N(ethyl)2, cyclopropyl, cyclobutyl, cyclopentyl, phenyl and naphthyl, Preferably, R 8b and R 9b The carbon atoms to which it is attached together form a (4-8 membered) heterocyclyl or a (5-9 membered) heteroaryl, the aforementioned groups are optionally substituted by 1, 2, 3, 4 or 5 groups selected from hydrogen, fluorine, chlorine, -OH, -O-methyl, -O-ethyl, -NH2, -NH-methyl, -NH-ethyl, -N(methyl)2, -N(methyl)-ethyl, -N(ethyl)2, cyclopropyl, cyclobutyl, cyclopentyl, phenyl and naphthyl, Preferably, R 8a and R 9a The carbon atom to which it is attached together forms an oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, pyridonyl, pyrimidonyl, oxazolyl, thiazolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, benzothiophenyl or indolyl, the foregoing groups are optionally substituted by 1, 2 or 3 groups selected from hydrogen, fluorine, chlorine, -OH, -O-methyl, -O-ethyl, -NH2, -NH-methyl, -NH-ethyl, -N(methyl)2, -N(methyl)-ethyl, -N(ethyl)2, cyclopropyl, cyclobutyl, cyclopentyl, phenyl and naphthyl, Preferably, R 8b and R 9b The carbon atom to which it is attached together forms an oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, pyridonyl, pyrimidonyl, oxazolyl, thiazolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, benzothiophenyl or indolyl, the foregoing groups are optionally substituted by 1, 2 or 3 groups selected from hydrogen, fluorine, chlorine, -OH, -O-methyl, -O-ethyl, -NH2, -NH-methyl, -NH-ethyl, -N(methyl)2, -N(methyl)-ethyl, -N(ethyl)2, cyclopropyl, cyclobutyl, cyclopentyl, phenyl and naphthyl, Preferably, R 8a and R 9a Does not exist, R 8b and R 9b The atoms connected to it form The * indicates the positions of connected atoms.

11. The compound according to any one of claims 1 to 10 or its racemate, enantiomer, diastereomer, pharmaceutically acceptable salt, isotope-labeled compound, or mixture thereof, wherein: R 10 Selected from -OH, or R 10 and R 9a The atoms to which it is attached form a 5-membered nitrogen-containing heterocyclic group, which is optionally substituted by 1, 2, 3, 4 or 5 groups selected from hydrogen, halogen, -OH, methyl, ethyl, -O-methyl, -O-ethyl, -NH2, -NH-methyl, -NH-ethyl, -N(methyl)2, -N(methyl)-ethyl and -N(ethyl)2, Preferably, R 10 is -OH, or R 10 and R 9a The atom to which it is attached forms an imidazolinyl group, which is optionally substituted by 1, 2 or 3 groups selected from halogen, -OH, methyl, -NH2, -NH-methyl and -N(methyl)2, Preferably, R 10 is -OH, or R 10 and R 9a The atoms connected to it form Where * indicates the connected atomic positions; Preferably, R 10 is -OH, preferably 12. The compound according to any one of claims 1 to 11 or its racemate, enantiomer, diastereomer, pharmaceutically acceptable salt, isotope-labeled compound, or mixture thereof, wherein: The compound is selected from the compound represented by formula I-1, in, X, X 1 , X 2 , Ring B, Ring C, R 31 , R 4 , R 5 , R 6 , R 7 , R 8a , R 8b , R 9a , R 9b , R 10 and m is as defined in any one of claims 1 to 11, n is 0, 1, 2, 3, 4 or 5, Structure fragment The definition of R 3 As defined, R 3 The definition as in any one of claims 1 to 11, Preferably, ring A is selected from 5-10 membered heteroaryl, preferably 5-9 membered heteroaryl, preferably 5-6 membered heteroaryl, preferably oxazolyl, thiazolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, pyridinyl and pyrimidinyl, preferably Preferred are oxazolyl and pyrimidinyl, for example Preferably, the compound is selected from the compound represented by formula I-1-A, in, X, X 1 , X 2 , R 31 , R 4 , R 5 , R 6 , R 7 , R 8a , R 8b , R 9a , R 9b , R 10 The definitions of and m are as described in any one of claims 1 to 11, and the definitions of ring A and n are as described in the present claims, Structural unit Preferably Preferably Preferably, the compound is selected from the compound represented by formula I-1-B, in, X, X 1 , X 2 , Ring B, Ring C, R 31 , R 4 , R 5 , R 6 , R 7 , R 8b , R 9a , R 9b , R 10 and m are as defined in any one of claims 1 to 11, and ring A and n are as defined in the claims; Preferably, the compound is selected from the compound represented by formula I-1-AB-1D, in, R 31 , R 1 , R 4 , R 5 , R 6 , R 7 , R 8b , R 9a , R 9b and m is as defined in any one of claims 1 to 11 The definitions of ring A and n are as described in this claim; R 8b1 is selected from R and N(R)R, R is as defined in claim 1, 2 or 10.

13. The compound according to any one of claims 1 to 12 or its racemate, enantiomer, diastereomer, pharmaceutically acceptable salt, isotope-labeled compound, or mixture thereof, wherein: The compound is selected from 14. A pharmaceutical composition comprising at least one compound according to any one of claims 1 to 13 or its racemate, enantiomer, diastereomer, pharmaceutically acceptable salt, isotopically labeled compound, or a mixture of the foregoing forms, and one or more pharmaceutically acceptable carriers and / or excipients.

15. Use of the compound according to any one of claims 1 to 13 or its racemate, enantiomer, diastereomer, pharmaceutically acceptable salt, isotope-labeled compound, or mixture of the foregoing forms, or the pharmaceutical composition according to claim 14 in the preparation of a medicament for treating and / or preventing a disease or condition or alleviating the severity of the disease or condition, wherein the disease or condition is a tumor or cancer; Preferably, the tumor or cancer is selected from gastric cancer, colorectal cancer, breast cancer, ovarian cancer and liver cancer.