Protein translation inhibitors

Abstract

The present invention belongs to the field of pharmacochemistry and, specifically, relates to a protein translation inhibitor represented by Formula II and its use in the treatment and / or prevention of diseases.

Description

Technology Field

[0001] The present application is based on the application with CN application number 202311459664.X and a filing date of November 03, 2023, the application with CN application number 202410063442.4 and a filing date of January 16, 2024, and the application with CN application number 202411479439.7 and a filing date of October 22, 2024, and claims priority thereof, and the disclosures of the aforementioned CN applications are incorporated in their entirety into the present application.

[0002] The present invention belongs to the field of pharmacochemistry and, specifically, relates to protein translation inhibitors and their use in the treatment and / or prevention of diseases. Background Technology

[0003] Protein translation abnormalities are a common characteristic of malignant tumors, manifesting as 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 complex, which mediates the recruitment of ribosomes into mRNA and initiates the translation process from mRNA to protein.

[0004] The eIF4F complex consists of three subunits: eIF4E, an mRNA 5' cap binding protein; eIF4G, a scaffold protein; and eIF4A, an RNA helicase. Natural substances have been reported to inhibit translation mediated by eIF4A and to exhibit antiproliferative and antitumor phenotypes in vivo and in vitro. Taking rocaglamide as an example, it has been demonstrated that it can bind to and stabilize untranslated RNA / eIF4A complexes, block ribosome scanning to inhibit the translation of target mRNA, and regulate the expression of related oncogenic factors.

[0005] Currently, the development of more protein translation inhibitors is necessary to meet the clinical needs of oncological diseases.

[0006] The first aspect of the present invention provides a compound represented by Formula II or a racemic mixture thereof, enantiomer, diastereomer, pharmaceutically acceptable salt, isotope-labeled compound, or a mixture of the aforementioned forms, and

[0007]

[0008] Formula II

[0009] Here,

[0010] X 1 is N and C(R 1 Selected from ), and R 1 It is selected from hydrogen, halogen, cyano, -OH, -(C1-C6) alkyl and -O-(C1-C6) alkyl;

[0011] X 2 is N and C(R 2 Selected from ), and R 2 is selected from hydrogen, halogen, cyano, -OH, -(C1-C6) alkyl and -O-(C1-C6) alkyl;

[0012] R 3 -(C3-C6) cycloalkyl, -(3-8) heterocyclyl, -(C6-C 10 ) selected from aryl and -(5-12 member) heteroaryl, and the -(C3-C6) cycloalkyl, -(3-8 member) heterocyclyl, -(C6-C 10 ) aryls and -(5-12-membered) heteroaryls have one or more R 31 It is optionally substituted by;

[0013] R 31Each is independently 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 won) heterocyclyl, -O-(C3-C6) cycloalkyl, -O-(4-10 won) 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 moieties) 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) Selected from -(C1-C6) alkyl]-NH2, -P(=O)[(C1-C6) alkyl]-NH(C1-C6) alkyl and -P(=O)[(C1-C6) alkyl]-N[(C1-C6) alkyl]2, and the above -(C1-C6) alkyl, -(C2-C6) alkenyl, -(C2-C6) alkynyl, -(C3-C6) cycloalkyl, -(4-10 member) heterocyclyl, -(C6-C 10) Aryl and -(5-12) heteroaryls are 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 ) Optionally substituted by one or more groups selected from aryl and -(5-12-membered) heteroaryl, -(C1-C6) alkylene-O(C1-C6) alkyl, and oxo;

[0014] R 4 is 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 won) heterocyclyl, -O-(4-10 won) heterocyclyl, -(C6-C 10 ) Aryl, -O-(C6-C 10 Selected from ) aryl, -(5-12-membered) heteroaryl and -O-(5-12-membered) heteroaryl;

[0015] X is 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 Selected from ], S(=O) and S(=O)2;

[0016] R a and R b are each independently hydrogen, halogen, cyano, -OR c , -SR c , -N(R c )R c , selected from -(C1-C6) alkyl and -(C1-C6) haloalkyl;

[0017] R cis hydrogen, -(C1-C6) alkyl, -(C1-C6) haloalkyl, -O-(C1-C6) alkyl, -O-(C1-C6) haloalkyl, -(C3-C6) cycloalkyl, -O-(C3-C6) cycloalkyl, -(4-10 won) heterocyclyl, -O-(4-10 won) heterocyclyl, -(C6-C 10 ) Aryl, -O-(C6-C 10 Selected from ) aryl, -(5-12-membered) heteroaryl and -O-(5-12-membered) heteroaryl;

[0018] Ring B is -(C6-C 10 Selected from ) aryls and -(5-12-membered) heteroaryls;

[0019] R 5 and R 6 Each is independently 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 member) heterocyclyl, -O-(C3-C6) cycloalkyl, -O-(4-10 member) 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 groups selected from hydrogen, halogen, oxo, -OH, -O-(C1-C4) alkyl, -NH2, -NH(C1-C4) alkyl, and N[(C1-C4) alkyl]2, or,

[0020] R 5 and R 6 It forms a 5-membered heterocyclyl together with the carbon atom connected to it;

[0021] Ring C is -(C6-C 10 Selected from ) aryls and -(5-12-membered) heteroaryls;

[0022] R 7 Each is independently 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 member) heterocyclyl, -O-(C3-C6) cycloalkyl, -O-(4-10 member) 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 and -NHC(=O)-(C1-C6) alkyl, 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 groups selected from hydrogen, halogen, oxo, -OH, -O-(C1-C4) alkyl, -NH2, -NH(C1-C4) alkyl and -N[(C1-C4) alkyl]2;

[0023] m is 1, 2, 3, 4, 5, 6, 7, 8 or 9 and;

[0024] R 8a , R 8b , R 9a and R 9bEach is independently 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, -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 Selected from aryl, -(5-12 group) heteroaryl, -(C3-C6) cycloalkyl and -(4-10 group) heterocyclyl, and

[0025] R is independently 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) heterocyclyl, -O-(C3-C6) cycloalkyl, -O-(4-10) 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]-(C3-C6) cycloalkyl, -[(C1-C6) alkylene]-(4-10 members) heterocyclyl, -(C6-C 10 ) aryl, -[(C1-C6) alkylene]-(C6-C 10) selected from aryl and -(5-12 group) heteroaryl, and the above -(C1-C6) alkylene-, -(C1-C6) alkyl, -(C2-C6) alkenyl, -(C2-C6) alkynyl, -(C3-C6) cycloalkyl, -(4-10 group) heterocyclyl, -(C6-C 10 ) The aryl, -(5-12 group) heteroaryl is 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, and

[0026] Or, R 8a and R 8b They combine to form an oxo, -(C2-C6) alkenyl, -(C3-C6) cycloalkyl, or -(4-10 member) heterocyclyl, and

[0027] Or, R 9a and R 9b They combine to form an oxo, -(C2-C6) alkenyl, -(C3-C6) cycloalkyl, or -(4-10 member) heterocyclyl, and

[0028] Or, R 8a and R 9a together with the carbon atoms connected thereto, it forms (C3-C6) cycloalkyl, (4-10) heterocyclyl, or (5-10) heteroaryl, and the aforementioned groups are hydrogen, halogen, -OH, -O-(C1-C4) alkyl, -NH2, -NH(C1-C4) alkyl, -N[(C1-C4) alkyl]2, -(C3-C6) cycloalkyl, -(4-8) heterocyclyl, -(5-6) heteroaryl and -(C6-C 10 ) Optionally substituted by one or more groups selected from aryls, and

[0029] Or, R 8b and R 9btogether with the carbon atoms connected thereto, it forms (C3-C6) cycloalkyl, (4-10) heterocyclyl, or (5-10) heteroaryl, and the aforementioned groups are hydrogen, halogen, -OH, -O-(C1-C4) alkyl, -NH2, -NH(C1-C4) alkyl, -N[(C1-C4) alkyl]2, -(C3-C6) cycloalkyl, -(4-8) heterocyclyl, -(5-6) heteroaryl and -(C6-C 10 ) Optionally substituted by one or more groups selected from aryls;

[0030] R 10 Silver is selected from hydrogen, cyano, -OH and -NH2, or R 10 and R 9a It forms a (5-6 member) heterocyclyl together with the atoms connected thereto, and the (5-6 member) heterocyclyl 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.

[0031] The first aspect of the present invention also provides a compound represented by Formula II or a racemic mixture thereof, enantiomer, diastereomer, pharmaceutically acceptable salt, isotope-labeled compound, or a mixture of the aforementioned forms, and

[0032]

[0033] Formula II

[0034] Here,

[0035] X 1 is N and C(R 1 Selected from ), and R 1 It is selected from hydrogen, halogen, cyano, -OH, -(C1-C6) alkyl and -O-(C1-C6) alkyl;

[0036] X 2 is N and C(R 2 Selected from ), and R2 is selected from hydrogen, halogen, cyano, -OH, -(C1-C6) alkyl and -O-(C1-C6) alkyl;

[0037] R 3 -(C3-C6) cycloalkyl, -(3-8) heterocyclyl, -(C6-C 10 ) selected from aryls and -(5-12-membered) heteroaryls, and the R 3 is one or more R 31 It is optionally substituted by;

[0038] R 31Each is independently 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 won) heterocyclyl, -O-(C3-C6) cycloalkyl, -O-(4-10 won) 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 won) heterocyclyl are selected from hydrogen, halogen, -OH, Optionally substituted by one or more groups selected from -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;

[0039] R 4 is 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 won) heterocyclyl, -O-(4-10 won) heterocyclyl, -(C6-C 10 ) Aryl, -O-(C6-C10 Selected from ) aryl, -(5-12-membered) heteroaryl and -O-(5-12-membered) heteroaryl;

[0040] X is 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 Selected from ], S(=O) and S(=O)2;

[0041] R a and R b are each independently hydrogen, halogen, cyano, -OR c , -SR c , -N(R c )R c , selected from -(C1-C6) alkyl and -(C1-C6) haloalkyl;

[0042] R c is hydrogen, -(C1-C6) alkyl, -(C1-C6) haloalkyl, -O-(C1-C6) alkyl, -O-(C1-C6) haloalkyl, -(C3-C6) cycloalkyl, -O-(C3-C6) cycloalkyl, -(4-10 won) heterocyclyl, -O-(4-10 won) heterocyclyl, -(C6-C 10 ) Aryl, -O-(C6-C 10 Selected from ) aryl, -(5-12-membered) heteroaryl and -O-(5-12-membered) heteroaryl;

[0043] Ring B is -(C6-C 10 Selected from ) aryls and -(5-12-membered) heteroaryls;

[0044] R 5 and R 6Each is independently 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 member) heterocyclyl, -O-(C3-C6) cycloalkyl, -O-(4-10 member) 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 groups selected from hydrogen, halogen, -OH, -O-(C1-C4) alkyl, -NH2, -NH(C1-C4) alkyl, and N[(C1-C4) alkyl]2, or,

[0045] R 5 and R 6 It forms a 5-membered heterocyclyl together with the carbon atom connected to it;

[0046] Ring C is -(C6-C 10 Selected from ) aryls and -(5-12-membered) heteroaryls;

[0047] R 7Each is independently 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 member) heterocyclyl, -O-(C3-C6) cycloalkyl, -O-(4-10 member) 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 are selected from, 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 groups selected from hydrogen, halogen, -OH, -O-(C1-C4) alkyl, -NH2, -NH(C1-C4) alkyl, and -N[(C1-C4) alkyl]2;

[0048] m is 1, 2, 3, 4, 5, 6, 7, 8 or 9 and;

[0049] R 8a , R 8b , R 9a and R 9bEach is independently 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 Selected from aryl, -(5-12 group) heteroaryl, -(C3-C6) cycloalkyl and -(4-10 group) heterocyclyl, and

[0050] R is independently 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) heterocyclyl, -O-(C3-C6) cycloalkyl, -O-(4-10) 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 members) heterocyclyl, -(C6-C 10 ) aryl, -[(C1-C6) alkylene]-(C6-C 10 ) selected from aryl and -(5-12 group) heteroaryl, and the above -(C1-C6) alkylene-, -(C1-C6) alkyl, -(C2-C6) alkenyl, -(C2-C6) alkynyl, -(C3-C6) cycloalkyl, -(4-10 group) heterocyclyl, -(C6-C 10) The aryl, -(5-12 group) heteroaryl is 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

[0051] Or, R 8a and R 8b , and R 9a and R 9b They independently combine to form an oxo, -(C2-C6) alkenyl, -(C3-C6) cycloalkyl, or -(4-10 member) heterocyclyl, and

[0052] Or, R 8a and R 9a , R 8b and R 9b together with the carbon atoms connected thereto, it forms (C3-C6) cycloalkyl, (4-10) heterocyclyl, or (5-10) heteroaryl, and the aforementioned groups are hydrogen, halogen, -OH, -O-(C1-C4) alkyl, -NH2, -NH(C1-C4) alkyl, -N[(C1-C4) alkyl]2, -(C3-C6) cycloalkyl, -(4-8) heterocyclyl, -(5-6) heteroaryl and -(C6-C 10 ) Optionally substituted by one or more groups selected from aryls;

[0053] R 10 Silver is selected from hydrogen, cyano, -OH and -NH2, or R 10 and R 9b It forms a (5-6 member) heterocyclyl together with the atoms connected thereto, and the (5-6 member) heterocyclyl 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.

[0054] In certain embodiments, the compound is selected from compounds represented by Formula I, and

[0055]

[0056] Formula I

[0057] Here,

[0058] X 1 is N and C(R 1 Selected from ), and R 1 It is selected from hydrogen, halogen, cyano, -OH, -(C1-C6) alkyl and -O-(C1-C6) alkyl;

[0059] X 2 is N and C(R 2 Selected from ), and R 2 is selected from hydrogen, halogen, cyano, -OH, -(C1-C6) alkyl and -O-(C1-C6) alkyl;

[0060] R 3 -(C3-C6) cycloalkyl, -(3-8) heterocyclyl, -(C6-C 10 ) selected from aryl and -(5-12 member) heteroaryl, and the -(C3-C6) cycloalkyl, -(3-8 member) heterocyclyl, -(C6-C 10 ) aryls and -(5-12-membered) heteroaryls have one or more R 31 It is optionally substituted by;

[0061] R 31Each is independently 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 won) heterocyclyl, -O-(C3-C6) cycloalkyl, -O-(4-10 won) 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 moieties) 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) Selected from -(C1-C6) alkyl]-NH2, -P(=O)[(C1-C6) alkyl]-NH(C1-C6) alkyl and -P(=O)[(C1-C6) alkyl]-N[(C1-C6) alkyl]2, and the above -(C1-C6) alkyl, -(C2-C6) alkenyl, -(C2-C6) alkynyl, -(C3-C6) cycloalkyl, -(4-10 member) heterocyclyl, -(C6-C 10) Aryl and -(5-12) heteroaryls are 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 ) Optionally substituted by one or more groups selected from aryl and -(5-12-membered) heteroaryl, -(C1-C6) alkylene-O(C1-C6) alkyl, and oxo;

[0062] R 4 is 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 won) heterocyclyl, -O-(4-10 won) heterocyclyl, -(C6-C 10 ) Aryl, -O-(C6-C 10 Selected from ) aryl, -(5-12-membered) heteroaryl and -O-(5-12-membered) heteroaryl;

[0063] X is 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 Selected from ], S(=O) and S(=O)2;

[0064] R a and R b are each independently hydrogen, halogen, cyano, -OR c , -SR c , -N(R c )R c , selected from -(C1-C6) alkyl and -(C1-C6) haloalkyl;

[0065] R cis hydrogen, -(C1-C6) alkyl, -(C1-C6) haloalkyl, -O-(C1-C6) alkyl, -O-(C1-C6) haloalkyl, -(C3-C6) cycloalkyl, -O-(C3-C6) cycloalkyl, -(4-10 won) heterocyclyl, -O-(4-10 won) heterocyclyl, -(C6-C 10 ) Aryl, -O-(C6-C 10 Selected from ) aryl, -(5-12-membered) heteroaryl and -O-(5-12-membered) heteroaryl;

[0066] Ring B is -(C6-C 10 Selected from ) aryls and -(5-12-membered) heteroaryls;

[0067] R 5 and R 6 Each is independently 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 member) heterocyclyl, -O-(C3-C6) cycloalkyl, -O-(4-10 member) 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 groups selected from hydrogen, halogen, oxo, -OH, -O-(C1-C4) alkyl, -NH2, -NH(C1-C4) alkyl, and N[(C1-C4) alkyl]2, or,

[0068] R 5 and R 6 It forms a 5-membered heterocyclyl together with the carbon atom connected to it;

[0069] Ring C is -(C6-C 10 Selected from ) aryls and -(5-12-membered) heteroaryls;

[0070] R 7 Each is independently 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 member) heterocyclyl, -O-(C3-C6) cycloalkyl, -O-(4-10 member) 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 and -NHC(=O)-(C1-C6) alkyl, 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 groups selected from hydrogen, halogen, oxo, -OH, -O-(C1-C4) alkyl, -NH2, -NH(C1-C4) alkyl and -N[(C1-C4) alkyl]2;

[0071] m is 1, 2, 3, 4, 5, 6, 7, 8 or 9 and;

[0072] R 8a , R 8b , R 9a and R 9bEach is independently 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 Selected from aryl, -(5-12 group) heteroaryl, -(C3-C6) cycloalkyl and -(4-10 group) heterocyclyl, and

[0073] R is independently 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) heterocyclyl, -O-(C3-C6) cycloalkyl, -O-(4-10) 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]-(C3-C6) cycloalkyl, -[(C1-C6) alkylene]-(4-10 members) heterocyclyl, -(C6-C 10 ) aryl, -[(C1-C6) alkylene]-(C6-C 10) selected from aryl and -(5-12 group) heteroaryl, and the above -(C1-C6) alkylene-, -(C1-C6) alkyl, -(C2-C6) alkenyl, -(C2-C6) alkynyl, -(C3-C6) cycloalkyl, -(4-10 group) heterocyclyl, -(C6-C 10 ) The aryl, -(5-12 group) heteroaryl is 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, and

[0074] Or, R 8a and R 8b They combine to form an oxo, -(C2-C6) alkenyl, -(C3-C6) cycloalkyl, or -(4-10 member) heterocyclyl, and

[0075] Or, R 9a and R 9b They combine to form an oxo, -(C2-C6) alkenyl, -(C3-C6) cycloalkyl, or -(4-10 member) heterocyclyl, and

[0076] Or, R 8a and R 9a together with the carbon atoms connected thereto, it forms (C3-C6) cycloalkyl, (4-10) heterocyclyl, or (5-10) heteroaryl, and the aforementioned groups are hydrogen, halogen, -OH, -O-(C1-C4) alkyl, -NH2, -NH(C1-C4) alkyl, -N[(C1-C4) alkyl]2, -(C3-C6) cycloalkyl, -(4-8) heterocyclyl, -(5-6) heteroaryl and -(C6-C 10 ) Optionally substituted by one or more groups selected from aryls, and

[0077] Or, R 8b and R 9btogether with the carbon atoms connected thereto, it forms (C3-C6) cycloalkyl, (4-10) heterocyclyl, or (5-10) heteroaryl, and the aforementioned groups are hydrogen, halogen, -OH, -O-(C1-C4) alkyl, -NH2, -NH(C1-C4) alkyl, -N[(C1-C4) alkyl]2, -(C3-C6) cycloalkyl, -(4-8) heterocyclyl, -(5-6) heteroaryl and -(C6-C 10 ) Optionally substituted by one or more groups selected from aryls;

[0078] R 10 Silver is selected from hydrogen, cyano, -OH and -NH2, or R 10 and R 9a It forms a (5-6 member) heterocyclyl together with the atoms connected thereto, and the (5-6 member) heterocyclyl 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.

[0079] In certain embodiments, the compound is selected from compounds represented by Formula I, and

[0080]

[0081] Formula I

[0082] Here,

[0083] X 1 is N and C(R 1 Selected from ), and R 1 It is selected from hydrogen, halogen, cyano, -OH, -(C1-C6) alkyl and -O-(C1-C6) alkyl;

[0084] X 2 is N and C(R 2 Selected from ), and R 2 is selected from hydrogen, halogen, cyano, -OH, -(C1-C6) alkyl and -O-(C1-C6) alkyl;

[0085] R 3 -(C3-C6) cycloalkyl, -(3-8) heterocyclyl, -(C6-C 10 ) selected from aryls and -(5-12-membered) heteroaryls, and the R 3 is one or more R 31 It is optionally substituted by;

[0086] R 31 Each is independently 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 won) heterocyclyl, -O-(C3-C6) cycloalkyl, -O-(4-10 won) 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 won) heterocyclyl are selected from hydrogen, halogen, -OH, Optionally substituted by one or more groups selected from -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;

[0087] R 4 is 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 won) heterocyclyl, -O-(4-10 won) heterocyclyl, -(C6-C 10 ) Aryl, -O-(C6-C 10 Selected from ) aryl, -(5-12-membered) heteroaryl and -O-(5-12-membered) heteroaryl;

[0088] X is 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 Selected from ], S(=O) and S(=O)2;

[0089] R a and R b are each independently hydrogen, halogen, cyano, -OR c , -SR c , -N(R c )R c , selected from -(C1-C6) alkyl and -(C1-C6) haloalkyl;

[0090] R c is hydrogen, -(C1-C6) alkyl, -(C1-C6) haloalkyl, -O-(C1-C6) alkyl, -O-(C1-C6) haloalkyl, -(C3-C6) cycloalkyl, -O-(C3-C6) cycloalkyl, -(4-10 won) heterocyclyl, -O-(4-10 won) heterocyclyl, -(C6-C 10 ) Aryl, -O-(C6-C 10 Selected from ) aryl, -(5-12-membered) heteroaryl and -O-(5-12-membered) heteroaryl;

[0091] Ring B is -(C6-C 10 Selected from ) aryls and -(5-12-membered) heteroaryls;

[0092] R 5 and R 6 Each is independently 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 member) heterocyclyl, -O-(C3-C6) cycloalkyl, -O-(4-10 member) 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 groups selected from hydrogen, halogen, -OH, -O-(C1-C4) alkyl, -NH2, -NH(C1-C4) alkyl, and N[(C1-C4) alkyl]2, or,

[0093] R 5 and R 6 It forms a 5-membered heterocyclyl together with the carbon atom connected to it;

[0094] Ring C is -(C6-C 10 Selected from ) aryls and -(5-12-membered) heteroaryls;

[0095] R 7Each is independently 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 member) heterocyclyl, -O-(C3-C6) cycloalkyl, -O-(4-10 member) 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 are selected from, 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 groups selected from hydrogen, halogen, -OH, -O-(C1-C4) alkyl, -NH2, -NH(C1-C4) alkyl, and -N[(C1-C4) alkyl]2;

[0096] m is 1, 2, 3, 4, 5, 6, 7, 8 or 9 and;

[0097] R 8a , R 8b , R 9a and R 9bEach is independently 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 Selected from aryl, -(5-12 group) heteroaryl, -(C3-C6) cycloalkyl and -(4-10 group) heterocyclyl, and

[0098] R is independently 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) heterocyclyl, -O-(C3-C6) cycloalkyl, -O-(4-10) 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 members) heterocyclyl, -(C6-C 10 ) aryl, -[(C1-C6) alkylene]-(C6-C 10 ) selected from aryl and -(5-12 group) heteroaryl, and the above -(C1-C6) alkylene-, -(C1-C6) alkyl, -(C2-C6) alkenyl, -(C2-C6) alkynyl, -(C3-C6) cycloalkyl, -(4-10 group) heterocyclyl, -(C6-C 10) The aryl, -(5-12 group) heteroaryl is 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

[0099] Or, R 8a and R 8b , and R 9a and R 9b They independently combine to form an oxo, -(C2-C6) alkenyl, -(C3-C6) cycloalkyl, or -(4-10 member) heterocyclyl, and

[0100] Or, R 8a and R 9a , R 8b and R 9b together with the carbon atoms connected thereto, it forms (C3-C6) cycloalkyl, (4-10) heterocyclyl, or (5-10) heteroaryl, and the aforementioned groups are hydrogen, halogen, -OH, -O-(C1-C4) alkyl, -NH2, -NH(C1-C4) alkyl, -N[(C1-C4) alkyl]2, -(C3-C6) cycloalkyl, -(4-8) heterocyclyl, -(5-6) heteroaryl and -(C6-C 10 ) Optionally substituted by one or more groups selected from aryls;

[0101] R 10 Silver is selected from hydrogen, cyano, -OH and -NH2, or R 10 and R 9b It forms a (5-6 member) heterocyclyl together with the atoms connected thereto, and the (5-6 member) heterocyclyl 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.

[0102] In certain embodiments, the compound is selected from compounds represented by Formula I, and

[0103]

[0104] Formula I

[0105] Here,

[0106] X 1 is N and C(R 1 Selected from ), and R 1 It is selected from hydrogen, halogen, cyano, -OH, -(C1-C6) alkyl and -O-(C1-C6) alkyl;

[0107] X 2 is N and C(R 2 Selected from ), and R 2 is selected from hydrogen, halogen, cyano, -OH, -(C1-C6) alkyl and -O-(C1-C6) alkyl;

[0108] R 3 -(C3-C6) cycloalkyl, -(4-8) heterocyclyl, -(C6-C 10 ) selected from aryls and -(5-12-membered) heteroaryls, and the R 3 is one or more R 31 It is optionally substituted by;

[0109] R 31Each is independently 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 won) heterocyclyl, -O-(C3-C6) cycloalkyl, -O-(4-10 won) 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 won) heterocyclyl are selected from hydrogen, halogen, -OH, Optionally substituted by one or more groups selected from -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;

[0110] R 4 is 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 won) heterocyclyl, -O-(4-10 won) heterocyclyl, -(C6-C 10 ) Aryl, -O-(C6-C10 Selected from ) aryl, -(5-12-membered) heteroaryl and -O-(5-12-membered) heteroaryl;

[0111] X is 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 Selected from ], S(=O) and S(=O)2;

[0112] R a and R b are each independently hydrogen, halogen, cyano, -OR c , -SR c , -N(R c )R c , selected from -(C1-C6) alkyl and -(C1-C6) haloalkyl;

[0113] R c is hydrogen, -(C1-C6) alkyl, -(C1-C6) haloalkyl, -O-(C1-C6) alkyl, -O-(C1-C6) haloalkyl, -(C3-C6) cycloalkyl, -O-(C3-C6) cycloalkyl, -(4-10 won) heterocyclyl, -O-(4-10 won) heterocyclyl, -(C6-C 10 ) Aryl, -O-(C6-C 10 Selected from ) aryl, -(5-12-membered) heteroaryl and -O-(5-12-membered) heteroaryl;

[0114] Ring B is -(C6-C 10 Selected from ) aryls and -(5-12-membered) heteroaryls;

[0115] R 5 and R 6Each is independently 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 member) heterocyclyl, -O-(C3-C6) cycloalkyl, -O-(4-10 member) 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 groups selected from hydrogen, halogen, -OH, -O-(C1-C4) alkyl, -NH2, -NH(C1-C4) alkyl, and N[(C1-C4) alkyl]2, or,

[0116] R 5 and R 6 It forms a 5-membered heterocyclyl together with the carbon atom connected to it;

[0117] Ring C is -(C6-C 10 Selected from ) aryls and -(5-12-membered) heteroaryls;

[0118] R 7Each is independently 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 member) heterocyclyl, -O-(C3-C6) cycloalkyl, -O-(4-10 member) 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 are selected from, 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 groups selected from hydrogen, halogen, -OH, -O-(C1-C4) alkyl, -NH2, -NH(C1-C4) alkyl, and -N[(C1-C4) alkyl]2;

[0119] m is 1, 2, 3, 4, 5, 6, 7, 8 or 9 and;

[0120] R 8a , R 8b , R 9a and R 9bEach is independently 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 Selected from aryl, -(5-12 group) heteroaryl, -(C3-C6) cycloalkyl and -(4-10 group) heterocyclyl, and

[0121] R is independently 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) heterocyclyl, -O-(C3-C6) cycloalkyl, -O-(4-10) 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 members) heterocyclyl, -(C6-C 10 ) aryl, -[(C1-C6) alkylene]-(C6-C 10 ) selected from aryl and -(5-12 group) heteroaryl, and the above -(C1-C6) alkylene-, -(C1-C6) alkyl, -(C2-C6) alkenyl, -(C2-C6) alkynyl, -(C3-C6) cycloalkyl, -(4-10 group) heterocyclyl, -(C6-C 10) The aryl, -(5-12 group) heteroaryl is 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

[0122] Or, R 8a and R 8b , and R 9a and R 9b They independently combine to form an oxo, -(C2-C6) alkenyl, -(C3-C6) cycloalkyl, or -(4-10 member) heterocyclyl, and

[0123] Or, R 8a and R 9a , R 8b and R 9b together with the carbon atoms connected thereto, it forms (C3-C6) cycloalkyl, (4-10) heterocyclyl, or (5-10) heteroaryl, and the aforementioned groups are hydrogen, halogen, -OH, -O-(C1-C4) alkyl, -NH2, -NH(C1-C4) alkyl, -N[(C1-C4) alkyl]2, -(C3-C6) cycloalkyl, -(4-8) heterocyclyl, -(5-6) heteroaryl and -(C6-C 10 ) Optionally substituted by one or more groups selected from aryls;

[0124] R 10 Silver is selected from hydrogen, cyano, -OH and -NH2, or R 10 and R 9b It forms a (5-6 member) heterocyclyl together with the atoms connected thereto, and the (5-6 member) heterocyclyl 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.

[0125] In certain embodiments, the -N(R c )R c -NHRc am.

[0126] In a specific embodiment, -N(R)R is -NHR.

[0127] In certain embodiments, the -[(C1-C8)alkylene]N(R)R is -[(C1-C8)alkylene]NHR.

[0128] In a specific embodiment, -C(=O)N(R)R is -C(=O)NHR.

[0129] In certain embodiments, the -C(=O)[(C1-C8) alkylene]N(R)R is -C(=O)[(C1-C8) alkylene]NHR.

[0130] In a specific embodiment, -C(=S)N(R)R is -C(=S)NHR.

[0131] In a specific embodiment, -S(=O)2N(R)R is -S(=O)2NHR.

[0132] In a specific embodiment, the -N(R)C(=O)R is -NHC(=O)R.

[0133] In certain embodiments, -N(R)C(=O)N(R)R is -NHC(=O)N(R)R, -N(R)C(=O)NHR- or NHC(=O)NHR.

[0134] In a specific embodiment, the -P(=O)(OR)(OR) is -P(=O)(OH)(OR).

[0135] In a specific embodiment, the R 1 It is selected from hydrogen, halogen, cyano, -OH, -(C1-C4) alkyl and -O-(C1-C4) alkyl.

[0136] In a specific embodiment, the R 1 It is selected from hydrogen, fluorine, chlorine, cyano, -OH, methyl, ethyl, propyl, -O-methyl, -O-ethyl, and -O-propyl.

[0137] In a specific embodiment, the R 1 It is selected from hydrogen and -O-methyl.

[0138] In a specific embodiment, the R 1 It is -O-methyl, and X 1 is selected from N and C(OCH3).

[0139] In a specific embodiment, the X 1 is C(R 1 Selected from ), and the definition of R1 is as described in any one embodiment of the present invention.

[0140] In a specific embodiment, the X 1 is C(OCH3).

[0141] In a specific embodiment, the X 1 is N.

[0142] In a specific embodiment, the R 2 It is selected from hydrogen, halogen, cyano, -OH, -(C1-C4) alkyl and -O-(C1-C4) alkyl.

[0143] In a specific embodiment, the R 2 It is selected from hydrogen, fluorine, chlorine, cyano, -OH, methyl, ethyl, propyl, -O-methyl, -O-ethyl, and -O-propyl.

[0144] In a specific embodiment, the R 2 is hydrogen, and X 2 is selected from N and CH.

[0145] In a specific embodiment, the X 2 is C(R 2 It is selected from ).

[0146] In a specific embodiment, the X 2 is selected from CH.

[0147] In a specific embodiment, the R 31Silver, iodine, 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, -(C3-C6) cycloalkyl, -(4-8-membered) heterocyclyl, -O-(C3-C6) cycloalkyl, -O-(4-8-membered) heterocyclyl, It is selected from -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.

[0148] In a specific embodiment, the R 31Iodine, 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, ethinyl, 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, oxetanil, tetrahydrofuranil, Tetrahydropyranil, 1,4-dioxanil, azetidinil, pyrrolidinil, piperidinil, piperazinil, homopiperidinil, homopiperidinil, morpholinil, -O-cyclopropyl, -O-cyclopentyl, -O-cyclohexyl, -O-tetrahydrofuranil, -O-tetrahydropyranil, -O-1,4-dioxanil, -O-pyrrolidinil, -O-piperidinil, -O-piperirazinil, -O-morpholinil, -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, It is selected from -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.

[0149] In a specific embodiment, the R 31 It is selected from iodine, hydrogen, fluorine, chlorine, cyano, -OH, -SH, -NH2, methyl, halomethyl, -O-methyl, -S-methyl, -NH-methyl, -CH2OH, -CH2CH2N(CH3)2, -C(=O)-NH2 and cyclopropyl.

[0150] In certain embodiments, R 31 Silver is selected from iodine, hydrogen, fluorine, cyano, -NH2, -CH2OH, -CH2NH2, methyl, trifluoromethyl, and -O-methyl.

[0151] In a specific embodiment, the R 31 It is selected from iodine, hydrogen, -NH2, -CH2OH, and methyl.

[0152] In a specific embodiment, the R 31 It is selected 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.

[0153] In a specific embodiment, the R 31 It is 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.

[0154] In a specific embodiment, the R 31 It is selected from hydrogen, fluorine, chlorine, cyano, -OH, -SH, -NH2, -(C1-C4) alkyl, -(C1-C4) haloalkyl, -O-(C1-C4) alkyl and -(C1-C4) alkylene-OH.

[0155] In a specific embodiment, the R 31 It is selected from hydrogen, fluorine, chlorine, cyano, -OH, -SH, -NH2, -(C1-C4) alkyl and -(C1-C4) alkylene-OH.

[0156] In a specific embodiment, the R 31It is selected from hydrogen, fluorine, chlorine, cyano, -OH, -SH, -NH2, methyl, halomethyl, -O-methyl, -CH2OH, -CH2NH2 and -CH2CH2N(CH3)2.

[0157] In a specific embodiment, the R 31 It is selected from hydrogen, fluorine, chlorine, cyano, -OH, -SH, -NH2, methyl, halomethyl, -CH2OH and -CH2CH2N(CH3)2.

[0158] In a specific embodiment, the R 31 It is selected from hydrogen, fluorine, chlorine, cyano, -OH, -SH, and -NH2.

[0159] In a specific embodiment, the R 31 It is selected from hydrogen, fluorine, chlorine, cyano, -OH, -SH, -NH2, -(C1-C4) alkyl, -O-(C1-C4) alkyl, -(C1-C4) alkylene-OH and -(C1-C4) haloalkyl.

[0160] In a specific embodiment, the R 31 It is selected from hydrogen, fluorine, cyano, -NH2, methyl, trifluoromethyl, -O-methyl, and -CH2OH.

[0161] In a specific embodiment, the R 3 -(C3-C6) cycloalkyl, -(3-6 member) heterocyclyl, -(C6-C 10 ) selected from aryl and -(5-12 member) heteroaryl, and the -(C3-C6) cycloalkyl, -(3-6 member) heterocyclyl, -(C6-C 10 ) aryls and -(5-12-membered) heteroaryls have one or more R 31 It is optionally substituted by, and R 31 The definition is as described in any one embodiment of the present invention.

[0162] In a specific embodiment, the R 3 Silver -(3-6 units) heterocyclil, -(C6-C 10Selected from ) aryls and -(5-12 member) heteroaryls, and the -(3-6 member) heterocyclil, -(C6-C 10 ) aryls and -(5-12-membered) heteroaryls have one or more R 31 It is optionally substituted by, and R 31 The definition is as described in any one embodiment of the present invention.

[0163] In a specific embodiment, the R 3 -(C6-C 10 ) selected from aryls and -(5-12-membered) heteroaryls, and the -(C6-C 10 ) aryls and -(5-12-membered) heteroaryls have one or more R 31 It is optionally substituted by, and R 31 The definition is as described in any one embodiment of the present invention.

[0164] In a specific embodiment, the R 3 is selected from phenyl and -(5-10) heteroaryls, and said phenyl and -(5-10) heteroaryls are one or more R 31 It is optionally substituted by, and R 31 The definition is as described in any one embodiment of the present invention.

[0165] In a specific embodiment, the R 3 is selected from phenyl and -(5-9 member) heteroaryls, and said phenyl and -(5-9 member) heteroaryls are one or more R 31 It is optionally substituted by, and R 31 The definition is as described in any one embodiment of the present invention.

[0166] In a specific embodiment, the R 3 is selected from -(5-6 member) heteroaryls, and said -(5-6 member) heteroaryls have 1, 2, 3, or 4 R groups. 31 It is optionally substituted by, and R 31The definition is as described in any one embodiment of the present invention.

[0167] In a specific embodiment, the R 3 is selected from oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, isothiazolyl, imidazolyl, triazolyl, tetrazolyl, pyridyl, pyrazinyl, pyridazinyl, pyrimidinyl, pyridazinoimidazolyl, pyrazinoimidazolyl, and pyrimidinonyl, wherein the oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, isothiazolyl, imidazolyl, triazolyl, tetrazolyl, pyridyl, pyrazinyl, pyridazinyl, pyrimidinyl, pyridazinoimidazolyl, pyrazinoimidazolyl, and pyrimidinonyl have 1, 2, or 3 R 31 It is optionally substituted by, and R 31 The definition is as described in any one embodiment of the present invention.

[0168] In a specific embodiment, the R 3 is selected from oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, isothiazolyl, imidazolyl, triazolyl, tetrazolyl, pyridyl, pyrazinyl, pyridazinyl, and pyrimidinyl, wherein the oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, isothiazolyl, imidazolyl, triazolyl, tetrazolyl, pyridyl, pyrazinyl, pyridazinyl, and pyrimidinyl have 1, 2, or 3 R 31 It is optionally substituted by, and R 31 The definition is as described in any one embodiment of the present invention.

[0169] In a specific embodiment, the R 3 silver , , , , , , , , , , , , , , , , , , , , , and Selected from, and the above , , , , , , , , , , , , , , , , , , , , , and is 1, 2, or 3 R 31 It is optionally substituted by, and R 31 The definition is as described in any one embodiment of the present invention.

[0170] In a specific embodiment, the R 3 silver , , , , , , , , , , , , , , , , , , , , and Selected from, and the above , , , , , , , , , , , , , , , , , , , , and is 1, 2, or 3 R 31 It is optionally substituted by, and R 31 The definition is as described in any one embodiment of the present invention.

[0171] In a specific embodiment, the R 3 silver , , , , , , , , , , , , , , , , , , , and Selected from, and the above , , , , , , , , , , , , , , , , , , , and is 1, 2, or 3 R 31It is optionally substituted by, and R 31 The definition is as described in any one embodiment of the present invention.

[0172] In a specific embodiment, the R 3 silver , , , , , , , , , , , , , , , , and Selected from, and the above , , , , , , , , , , , , , , , , and is 1, 2, or 3 R 31 It is optionally substituted by, and R 31 The definition is as described in any one embodiment of the present invention.

[0173] In a specific embodiment, the R 3 silver , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , and Selected from.

[0174] In a specific embodiment, the R 3 silver , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , and Selected from.

[0175] In a specific embodiment, the R 3 silver , , , , , , , , , , , , , , , , , , , , , , , , , , , , and Selected from.

[0176] In a specific embodiment, the R 3 silver , , , , , , , , , , , , and Selected from.

[0177] In a specific embodiment, the R 3 is selected from oxazolyl, pyrazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyridazinoimidazolyl, and pyrazinoimidazolyl, wherein the oxazolyl, pyrazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyridazinoimidazolyl, and pyrazinoimidazolyl have 1, 2, or 3 R 31 It is optionally substituted by, and R 31 The definition is as described in any one embodiment of the present invention.

[0178] In a specific embodiment, the R 3 silver , , , , , , , , , , , , , , , , , , , , , , , , , and Selected from.

[0179] In a specific embodiment, the R 3 silver , , , , , , , , , , , , , , , , , , , , , , , , and Selected from.

[0180] In a specific embodiment, the R 3 is selected from oxazolyl, pyrazolyl, pyrimidinyl, and pyrazinyl, wherein the oxazolyl, pyrazolyl, pyrimidinyl, and pyrazinyl have 1, 2, or 3 R31 It is optionally substituted by (as defined in any one embodiment of the present invention), for example by fluorine, cyano, amino, methyl, trifluoromethyl, -methylene-OH and -O-methyl.

[0181] In a specific embodiment, the R 3 is selected from oxazolyl, pyrazolyl, and pyrimidinyl, and said oxazolyl, pyrazolyl, and pyrimidinyl have 1, 2, or 3 R 31 It is selectively substituted by, for example, by methyl.

[0182] In a specific embodiment, the R 3 silver , , , and Selected from, and the above , , , and is 1, 2, or 3 R 31 It is optionally substituted by (as defined in any one embodiment of the present invention), for example by fluorine, cyano, amino, methyl, trifluoromethyl, -methylene-OH and -O-methyl.

[0183] In a specific embodiment, the R 3 silver , , and Selected from, and the above , , and is 1, 2, or 3 R 31 It is selectively substituted by, for example, by methyl.

[0184] In a specific embodiment, the R 3 silver , , , , , , , , , , , and Selected from.

[0185] In a specific embodiment, the R 3 silver , , , and Selected from.

[0186] In a specific embodiment, the R 3 is selected from oxazolyl, said oxazolyl has 1, 2, or 3 R 31 It is optionally substituted by, for example, optionally by 1, 2, or 3 methyl groups.

[0187] In a specific embodiment, the R 3 silver and Selected from.

[0188] In a specific embodiment, the R 3 It is selected from -(C3-C6)cycloalkyl and -(4-6)heterocyclyl, and said -(C3-C6)cycloalkyl and -(4-6)heterocyclyl is one or more R 31 It is optionally substituted by, and R 31 The definition is as described in any one embodiment of the present invention.

[0189] In a specific embodiment, the R 3 ...is selected from cyclopropyl, oxetanil, azetidinil, tetrahydrofuranil, pyrrolidinil, tetrahydropyranil, piperidinil, piperazinil, and morpholinil, and the aforementioned group is one or more R 31 It is optionally substituted by, and R 31 The definition is as described in any one embodiment of the present invention.

[0190] In a specific embodiment, the R3 silver , , and Selected from.

[0191] In a specific embodiment, the R 3 is selected from -(3-6 member) heterocyclils, and said -(3-6 member) heterocyclils are one or more R 31 It is optionally substituted by, and R 31 The definition is as described in any one embodiment of the present invention.

[0192] In a specific embodiment, the R 3 ...is selected from oxetanil, azetidinil, tetrahydrofuranil, pyrrolidinil, tetrahydropyranil, piperidinil, piperazinil, and morpholinil, and the aforementioned group is one or more R 31 It is optionally substituted by, and R 31 The definition is as described in any one embodiment of the present invention.

[0193] In a specific embodiment, the R 3 silver or am.

[0194] In a specific embodiment, the R 3 silver am.

[0195] In a specific embodiment, the R 4 is 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 member) heterocyclyl, -O-(4-8 member) heterocyclyl, -(C6-C 10 ) Aryl, -O-(C6-C 10 ) is selected from aryl, -(5-10) heteroaryl and -O-(5-10) heteroaryl.

[0196] In a specific embodiment, the R 4hydrogen, 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, oxetanil, tetrahydrofuranil, tetrahydropyranil, 1,4-dioxanil, azetidinil, pyrrolidinyl, piperidinyl, piperazinil, homopiperidinil, homopiperidinil, morpholinil, -O-tetrahydrofuranil, -O-tetrahydropyranil, -O-1,4-dioxanil, -O-pyrrolidinyl, -O-piperidinyl, Selected from -O-piperazinyl, -O-morpholinyl, phenyl, naphthyl, -O-phenyl, -O-naphthyl, oxazolyl, thiazolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, pyridyl, pyrimidinyl, indolyl, quinolinyl, -O-oxazolyl, -O-thiazolyl, -O-pyrazolyl, -O-imidazolyl, -O-triazolyl, -O-tetrazolyl, -O-pyridyl, -O-pyrimidinyl, -O-indolyl and -O-quinolinyl.

[0197] In a specific embodiment, the R 4 It is selected from hydrogen, fluorine, chlorine, cyano, -OH, -NH2, methyl, halomethyl, -O-methyl, -NH-methyl, and cyclopropyl.

[0198] In a specific embodiment, the R 4 It is selected from hydrogen, fluorine, chlorine, cyano, -OH and -NH2.

[0199] In a specific embodiment, the R 4 is hydrogen.

[0200] In a specific embodiment, the R c is hydrogen, -(C1-C4) alkyl, -(C1-C4) haloalkyl, -O-(C1-C4) alkyl, -O-(C1-C4) haloalkyl, -(C3-C6) cycloalkyl, -O-(C3-C6) cycloalkyl, -(4-8 member) heterocyclyl, -O-(4-8 member) heterocyclyl, -(C6-C10 ) Aryl, -O-(C6-C 10 ) is selected from aryl, -(5-10) heteroaryl and -O-(5-10) heteroaryl.

[0201] In a specific embodiment, the R c 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, oxetanil, tetrahydrofuranil, tetrahydropyranil, 1,4-dioxanil, azetidinil, pyrrolidinil, piperidinil, piperazinil, homopiperidinil, homopiperidinil, morpholinil, -O-tetrahydrofuranil, -O-tetrahydropyranil, -O-1,4-dioxanil, -O-pyrrolidinil, -O-piperidinil, -O-piperidinil, -O-morpholinil, phenyl, naphthyl, Selected from -O-phenyl, -O-naphthyl, oxazolyl, thiazolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, pyridyl, pyrimidinyl, indolyl, quinolinyl, -O-oxazolyl, -O-thiazolyl, -O-pyrazolyl, -O-imidazolyl, -O-triazolyl, -O-tetrazolyl, -O-pyridyl, -O-pyrimidinyl, -O-indolyl and -O-quinolinyl.

[0202] In a specific embodiment, the R c It is selected from hydrogen, methyl, ethyl, halomethyl, -O-methyl, -NH-methyl, and cyclopropyl.

[0203] R a and R b are each independently hydrogen, halogen, cyano, -OR c , -SR c , -N(R c )R c , selected from -(C1-C4) alkyl and -(C1-C4) haloalkyl, and R c The definition is as described in any one embodiment of the present invention.

[0204] In a specific embodiment, the R a and R b are each independently hydrogen, halogen, cyano, -OR c , -SR c , -N(R c )R c Selected from , methyl, ethyl, propyl, halomethyl, haloethyl, and halopropyl, and R c The definition is as described in any one embodiment of the present invention.

[0205] In a specific embodiment, 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.

[0206] X is 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 ], selected from S(=O) and S(=O)2, and R a , R b and R c The definition is as described in any one embodiment of the present invention.

[0207] In a specific embodiment, 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)2 and S(=O)2.

[0208] In certain embodiments, X is selected from O, S and NH.

[0209] In a specific embodiment, X is selected from O and S.

[0210] In a specific embodiment, X is O.

[0211] In a specific embodiment, the ring B is -(C6-C 10 ) is selected from aryls and 5-10-membered heteroaryls.

[0212] In certain embodiments, the ring B is selected from phenyl, naphthyl, oxazolyl, thiazolyl, pyrazolyl, imidazolyl, triazolyl, tetrazollyl, pyridyl, pyrimidinyl, benzofuranyl, benzothienyl, indolyl, quinolinyl, and isoquinolinyl.

[0213] In a specific embodiment, the ring B is phenyl.

[0214] In a specific embodiment, the structural unit Is am.

[0215] In certain embodiments, R 5 and R 6Each is independently 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, wherein the -(C1-C4) alkyl, -(C2-C4) alkenyl, -(C2-C4) alkynyl, -(C3-C6) cycloalkyl, and -(4-8-membered) heterocyclyl are 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, It is optionally substituted by 1, 2, 3, 4, or 5 groups selected from -N(ethyl)2 and -N(ethyl)-propyl.

[0216] In a specific embodiment, the R 5 and R 6Each is independently hydrogen, fluorine, chlorine, bromine, cyano, nitro, -OH, -SH, -NH2, methyl, ethyl, propyl, vinyl, propene, ethinyl, 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, oxetanil, tetrahydrofuranil, tetrahydropyranil, 1,4-dioxanil, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, Homopiperidinyl, Homopiperazinyl, Morfollinyl, -O-cyclopropyl, -O-cyclopentyl, -O-cyclohexyl, -O-tetrahydrofuranil, -O-tetrahydropyranil, -O-1,4-dioxanil, -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, It is selected from -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.

[0217] In a specific embodiment, the R 5 and R 6Each 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.

[0218] In a specific embodiment, 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.

[0219] In a specific embodiment, 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.

[0220] In a specific embodiment, the R 5 It is selected from hydrogen, fluorine, chlorine, bromine, cyano, -OH, -NH2 and -CH2NH2.

[0221] In a specific embodiment, the R 5 It is selected from hydrogen, fluorine, chlorine, bromine, cyano, -OH and -NH2.

[0222] In a specific embodiment, the R 5 It is selected from hydrogen and -NH2.

[0223] In a specific embodiment, the R 5 is hydrogen.

[0224] In a specific embodiment, the R 6It is selected from hydrogen, fluorine, chlorine, bromine, cyano, -OH, -NH2, -O-methyl, and cyclopropyl.

[0225] In a specific embodiment, the R 6 It is selected from cyano, bromine, -NH2, -O-methyl, and cyclopropyl.

[0226] In a specific embodiment, the R 6 It is selected from hydrogen, fluorine, chlorine, bromine, cyano, -OH, -NH2, and -O-methyl.

[0227] In a specific embodiment, the R 6 It is selected from cyano, -O-methyl, and cyclopropyl.

[0228] In a specific embodiment, the R 6 It is selected from hydrogen, cyano, and -O-methyl.

[0229] In a specific embodiment, the R 6 It is selected from cyano and -O-methyl.

[0230] In a specific embodiment, the R 5 and R 6 Silver together with the atoms connected to it It forms, where * indicates the position of the connected atoms.

[0231] In a specific embodiment, the ring C is -(C6-C 10 ) is selected from aryls and -(5-10) heteroaryls.

[0232] In certain embodiments, the ring C is selected from phenyl, naphthyl, oxazolyl, thiazolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, pyridyl, pyrimidinyl, benzofuranyl, benzothienyl, indolyl, quinolinyl, and isoquinolinyl.

[0233] In a specific embodiment, the ring C is phenyl.

[0234] In a specific embodiment, the structural unit Is am.

[0235] In a specific embodiment, the structural unit Is or am.

[0236] In a specific embodiment, the structural unit Is am.

[0237] In a specific embodiment, the R 7 Each is independently 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, wherein the -(C1-C4) alkyl, -(C2-C4) alkenyl, -(C2-C4) alkynyl, -(C3-C6) cycloalkyl, and -(4-8-membered) heterocyclyl are 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, It is optionally substituted by 1, 2, 3, 4, or 5 groups selected from -N(ethyl)2 and -N(ethyl)-propyl.

[0238] In a specific embodiment, the R 7Each is independently 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 are selected from, and the -(C1-C4) alkyl, -(C2-C4) alkenyl, -(C2-C4) alkynyl, -(C3-C6) cycloalkyl, and -(4-8-membered) heterocyclyl are 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. It is selectively substituted by 2, 3, 4, or 5 groups.

[0239] In a specific embodiment, the R 7Each is independently hydrogen, halogen, cyano, nitro, -OH, -SH, -NH2, methyl, ethyl, propyl, -methylene-OH, -ethylene-OH, -propylene-OH, -methylene-NH2, -ethylene-NH2, -propylene-NH2, vinyl, prophenyle, ethinyl, 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, oxetanil, tetrahydrofuranil, tetrahydropyranil, 1,4-Dioxanyl, Azetidinyl, Pyrrolidinyl, Piperidinyl, Piperazinyl, Homopiperidinyl, Homopiperidinyl, Morfollinyl, -O-Cyclopropyl, -O-Cyclopentyl, -O-Cyclohexyl, -O-Tetrahydrofuranil, -O-Tetrahydropyranil, -O-1,4-Dioxanyl, -O-Pyrrolidinyl, -O-Pyrrolidinyl, -O-Piperidinyl, -O-Piperazinyl, -O-Morfollinyl, -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, It is selected from -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, -C(=N-OH)-H, -NHC(=O)-methylene-NH2 and -NHC(=O)-ethylene-NH2.

[0240] In a specific embodiment, the R 7Each is independently hydrogen, halogen, cyano, nitro, -OH, -SH, -NH2, methyl, ethyl, propyl, -methylene-OH, -ethylene-OH, -propylene-OH, -methylene-NH2, -ethylene-NH2, -propylene-NH2, vinyl, prophenyle, ethinyl, 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, oxetanil, tetrahydrofuranil, tetrahydropyranil, 1,4-Dioxanyl, Azetidinyl, Pyrrolidinyl, Piperidinyl, Piperazinyl, Homopiperidinyl, Homopiperidinyl, Morfollinyl, -O-Cyclopropyl, -O-Cyclopentyl, -O-Cyclohexyl, -O-Tetrahydrofuranil, -O-Tetrahydropyranil, -O-1,4-Dioxanyl, -O-Pyrrolidinyl, -O-Pyrrolidinyl, -O-Piperidinyl, -O-Piperazinyl, -O-Morfollinyl, -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, It is selected from -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.

[0241] In a specific embodiment, the R 7Each 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.

[0242] In a specific embodiment, 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.

[0243] In a specific embodiment, 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.

[0244] In a specific embodiment, 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.

[0245] In a specific embodiment, the R 7 Each is independently selected from hydrogen, fluorine, -OH, -NH2, -NHC(=O)CH2NH2, -CH2OH, and -CH2NH2.

[0246] In a specific embodiment, the R 7 Each is independently selected from hydrogen, fluorine, -OH, -NH2, -CH2OH, and -CH2NH2.

[0247] In a specific embodiment, the R7 Each is independently selected from hydrogen, fluorine, chlorine, bromine, -OH, and -NH2.

[0248] In a specific embodiment, the R 7 Each is independently selected from hydrogen, -OH, and -NH2.

[0249] In a specific embodiment, the R 7 Each is independently selected from hydrogen and -NH2.

[0250] In certain embodiments, m is 1, 2, 3, 4, or 5.

[0251] In certain embodiments, m is 1, 2, or 3.

[0252] In a specific embodiment, m is 1.

[0253] In certain embodiments, R is each independently 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 member) heterocyclyl, -(C6-C 10 ) aryl, -[(C1-C4) alkylene]-(C6-C 10) selected from aryl and -(5-10 member) heteroaryl, and the above -(C1-C4) alkylene-, -(C1-C4) alkyl, -(C2-C4) alkenyl, -(C2-C4) alkynyl, -(C3-C6) cycloalkyl, -(4-8 member) heterocyclyl, -(C6-C 10 ) Aryl and -(5-10) heteroaryls 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.

[0254] In certain embodiments, R is each independently 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 member) heterocyclyl, -(C6-C 10 ) aryl, -[(C1-C4) alkylene]-(C6-C 10 ) selected from aryl and -(5-10 member) heteroaryl, and the above -(C1-C4) alkylene-, -(C1-C4) alkyl, -(C2-C4) alkenyl, -(C2-C4) alkynyl, -(C3-C6) cycloalkyl, -(4-8 member) heterocyclyl, -(C6-C 10) aryl and -(5-10) 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.

[0255] In certain embodiments, R is each 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) cycloalkyl and -[(C1-C4) alkylene]-(4-8-membered) heterocyclyl, and the -(C1-C4) Alkylene-, -(C1-C4) alkyl, -(C3-C6) cycloalkyl and -(4-8) 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, -N(ethyl)-propyl, methyl, and ethyl.

[0256] In certain embodiments, 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) alkylene-, -(C1-C4) alkyl, -(C3-C6) cycloalkyl, and -(4-8-membered) heterocyclyl are hydrogen, halogen, -OH, -O-methyl, -O-ethyl, -O-propyl, It is optionally substituted by 1, 2, 3, 4, or 5 groups selected from -NH2, -NH-methyl, -NH-ethyl, -NH-propyl, -N(methyl)2, -N(methyl)-ethyl, -N(methyl)-propyl, -N(ethyl)2 and -N(ethyl)-propyl.

[0257] In certain embodiments, R is each independently hydrogen, -OH, -NH2, methyl, ethyl, propyl, halomethyl, haloethyl, halopropyl, -methylene-O-methyl, -methylene-O-ethyl, -ethylene-O-methyl, -methylene-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, oxetanil, tetrahydrofuranil, tetrahydropyranil, azetidinil, pyrrolidinil, piperidinil, piperazinil, morpholinil, Selected from -methylene-cyclobutyl, -methylene-oxetanyl and -methylene-azetidinyl, wherein the methyl, ethyl, propyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, tetrahydrofuranil, tetrahydropyranil, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl and morpholinyl are optionally substituted by 1, 2 or 3 groups selected from -OH, -OCH3, -NH2, NHCH3, N(CH3)2 and -CH3.

[0258] In certain embodiments, R is each 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 methyl, ethyl, propyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, and morpholinyl are optionally substituted by one, two, or three groups selected from -OH and -NH2.

[0259] In certain embodiments, R is each 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.

[0260] In certain embodiments, R is each independently selected from hydrogen, -OH, -NH2, -CH3, -CH2OH, -CH2CH2OH, -CH2NH2, -CH2CH2NH2, -OCH3, -C(=O)-H, -C(=O)CH2OH, oxetanyl, and azetidinyl-OH.

[0261] In certain embodiments, R is each independently 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 member) heterocyclyl, -(C6-C 10 ) aryl, -[(C1-C4) alkylene]-(C6-C 10) selected from aryl and -(5-10 member) heteroaryl, and the above -(C1-C4) alkylene-, -(C1-C4) alkyl, -(C2-C4) alkenyl, -(C2-C4) alkynyl, -(C3-C6) cycloalkyl, -(4-8 member) heterocyclyl, -(C6-C 10 ) aryl and -(5-10) 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.

[0262] In certain embodiments, 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 the -(C1-C4) alkylene-, -(C1-C4) alkyl, -(C3-C6) cycloalkyl, and -(4-8-membered) heterocyclyl are hydrogen, halogen, -OH, -O-methyl, -O-ethyl, -O-propyl, -NH2, It is optionally substituted by 1, 2, 3, 4, or 5 groups selected from -NH-methyl, -NH-ethyl, -NH-propyl, -N(methyl)2, -N(methyl)-ethyl, -N(methyl)-propyl, -N(ethyl)2, and -N(ethyl)-propyl.

[0263] In certain embodiments, R is each 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 methyl, ethyl, propyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, and morpholinyl are optionally substituted by one, two, or three groups selected from -OH and -NH2.

[0264] In certain embodiments, R is each independently selected from hydrogen, -OH, -CH3, -CH2OH, -CH2CH2OH, -CH2CH2NH2, -OCH3, -C(=O)-H, -C(=O)CH2OH, oxetanyl, azetidinyl, and azetidinyl-OH.

[0265] In certain embodiments, R is each independently selected from hydrogen, -OH, -CH3, -CH2OH, -CH2CH2OH, -CH2CH2NH2, -OCH3, -C(=O)-H, -C(=O)CH2OH, oxetanyl, and azetidinyl-OH.

[0266] In certain embodiments, R is each 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 each selected from hydrogen, halogen, -OH, -NH2, -NH(C1-C4) alkyl, -N[(C1-C4) alkyl]2, -O-(C1-C4) alkyl, and -(C1-C4) alkyl. It is selectively substituted by 1, 2, 3, 4, or 5 groups.

[0267] In certain embodiments, R is each independently selected from hydrogen, -OH, -NH2, -(C1-C4) alkyl, -O-(C1-C4) alkyl, and -(4-8) heterocyclyl, and the -(C1-C4) alkyl and -(4-8) 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, and -O-(C1-C4) alkyl.

[0268] In certain embodiments, R is each independently selected from hydrogen, -OH, -(C1-C4) alkyl and -O-(C1-C4) alkyl, and each of the aforementioned groups is selectively substituted by one, two, or three groups independently selected from hydrogen, halogen, -OH, -NH2, -NH-methyl and -N(methyl)2.

[0269] In certain embodiments, 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 each of the aforementioned groups is each independently optionally substituted by one, two, or three groups selected from -OH, -NH2, OCH3, NHCH3, N(CH3)2 and CH3.

[0270] In certain embodiments, R is each independently selected from methyl, ethyl, propyl, -O-methyl, -O-ethyl, -O-propyl, oxetanyl, and azetidinyl, and the aforementioned groups are each independently substituted by 1, 2, or 3 groups selected from -OH and -NH2.

[0271] In a specific embodiment, the R 8a , R 8b , R 9a and R 9b Each is independently 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, -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) selected from aryl, -(5-10 group) heteroaryl, -(C3-C6) cycloalkyl and -(4-8 group) heterocyclyl, and the definition of R is as described in any one embodiment of the present invention.

[0272] R 8a , R 8b , R 9a and R 9b Each is independently 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 ) selected from aryl, -(5-10 group) heteroaryl, -(C3-C6) cycloalkyl and -(4-8 group) heterocyclyl, and the definition of R is as described in any one embodiment of the present invention.

[0273] In a specific embodiment, 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 The definition of R is as described in any one embodiment of the present invention.

[0274] In a specific embodiment, 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 the definition of R is as described in the present invention.

[0275] In a specific embodiment, 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 the definition of R is as described in any one embodiment of the present invention.

[0276] In a specific embodiment, 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 the definition of R is 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 each optionally substituted by 1, 2, 3, 4, or 5 groups selected from hydrogen, halogen, -OH, -NH2, -NHCH3, and CH3.

[0277] In a specific embodiment, 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 the definition of R is as described in any one embodiment of the present invention.

[0278] In a specific embodiment, the R 8a is hydrogen.

[0279] In a specific embodiment, the R 8a Is am.

[0280] In a specific embodiment, the R 8b is hydrogen, , , , , , , , , , , , , , , , , , , , , , , , , , and Selected from.

[0281] In a specific embodiment, the R 8b is hydrogen, , , , , , , , , , , , , , , , and Selected from.

[0282] In a specific embodiment, the R 8b is hydrogen, , , , , , , , , , , , , , , and Selected from.

[0283] In a specific embodiment, the R 8b is hydrogen, , , , , , , , , , , , , , , , , , , , , , , , , , and Selected from.

[0284] In a specific embodiment, the R 8b is hydrogen, , , , , , , , , , , , , , and Selected from.

[0285] In a specific embodiment, the R 8b is hydrogen, , , , , , , , , , , , and Selected from.

[0286] In a specific embodiment, the R 8bis selected from hydrogen, -methylene-R, -methylene-N(R)R, -C(=O)OR, -C(=O)N(R)R and -C(=O)R, and the definition of R is as described in any one embodiment of the present invention, for example, R is each independently selected from hydrogen, -OH, methyl, ethyl, -O-methyl, -C(=O)-methyl, -S(=O)2-methyl, azetidinyl, pyrrolidinyl and piperazinyl, and each of the aforementioned groups is selectively substituted by one, two or three groups independently selected from -OH and -NH2.

[0287] In a specific embodiment, the R 8b is selected from -methylene-R, -C(=O)OR, -C(=O)N(R)R and -C(=O)R, and the definition of R is as described in any one embodiment of the present invention.

[0288] In a specific embodiment, the R 8b is hydrogen, , , , , , , , , , , , , , , , and Selected from.

[0289] In a specific embodiment, the R 8b Is , , , , , and Selected from.

[0290] In a specific embodiment, the R 8b is hydrogen, , , , , and Selected from.

[0291] In a specific embodiment, the R 8b is hydrogen, , , , , , and Selected from.

[0292] In a specific embodiment, the R 8b is hydrogen, and Selected from.

[0293] In a specific embodiment, 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 the definition of R is as described in any one embodiment of the present invention.

[0294] In a specific embodiment, the R 9a and R 9b Each 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 the definition of R is as described in any one embodiment of the present invention.

[0295] In a specific embodiment, the R 9a and R 9bEach 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, and the definition of R is as described in any one 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, and said -(C1-C4) alkyl, -(C3-C6) cycloalkyl, and -(4-8-membered) heterocyclyl Each is 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.

[0296] In a specific embodiment, 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 the definition of R is as described in any one embodiment of the present invention.

[0297] In a specific embodiment, the R 9ais selected from hydrogen, -CN, -N(R)R, -NHC(=O)R, -methylene-N(R)R, -methylene-NHC(=O)R and -methylene-NHC(=O)NHR, and the definition of R is as described in any one embodiment of the present invention, for example, R is each independently selected from hydrogen, -OH, methyl, ethyl, -methylene-O-ethyl, -S(=O)2-methyl, cyclobutyl, azetidinyl, -methylene-cyclobutyl and -methylene-azetidinyl, and each of the aforementioned groups is each independently selectively substituted by one, two or three groups selected from -OH, OCH3, NHCH3, N(CH3)2 and CH3.

[0298] In a specific embodiment, the R 9a is selected from hydrogen and -methylene-N(R)R, and the definition of R is as described in any one embodiment of the present invention.

[0299] In a specific embodiment, the R 9ais 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(CH3)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, It is selected from -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.

[0300] In a specific embodiment, the R 9a is selected from hydrogen, -CH2NH2, -CH2NHCH3, -NHC(=O)H, -NHC(=O)CH2OH and -CH2NHC(=O)CH2OH.

[0301] In a specific embodiment, the R 9a It is selected from hydrogen, -CH2NH2, -NHC(=O)H, -NHC(=O)CH2OH, and -CH2NHC(=O)CH2OH.

[0302] In a specific embodiment, the R 9a is hydrogen, , , , , , , , , , , , , , , , , , , , , , , , , , and Selected from.

[0303] In a specific embodiment, the R 9a is hydrogen, , , , , , , , , , , , , , , , and Selected from.

[0304] In a specific embodiment, the R 9a is hydrogen, , , , , , , , , , , , , , and Selected from.

[0305] In a specific embodiment, the R 9a is hydrogen, , , , and Selected from.

[0306] In a specific embodiment, the R 9a is hydrogen, , , and Selected from.

[0307] In a specific embodiment, the R 9a is hydrogen, , , and Selected from.

[0308] In a specific embodiment, the R 9a is hydrogen, and Selected from.

[0309] In a specific embodiment, the R 9a is hydrogen and Selected from.

[0310] In a specific embodiment, the R 9a is hydrogen.

[0311] In a specific embodiment, the R 9a Is am.

[0312] In a specific embodiment, the R 9b is -OH.

[0313] In a specific embodiment, the R 9b is hydrogen and Selected from.

[0314] In a specific embodiment, the R 9b Is am.

[0315] In a specific embodiment, the R 9b is hydrogen, , , , , , , , , , , , , , and Selected from.

[0316] In a specific embodiment, the R 8a and R 8b , and R 9a and R 9b It combines independently to form an oxo, -(C2-C4) alkenyl, -(C3-C6) cycloalkyl, or -(4-8 member) heterocyclyl.

[0317] In a specific embodiment, the R 8a and R 8b It combines to form an oxo, -(C2-C4) alkenyl, -(C3-C6) cycloalkyl, or -(4-8 member) heterocyclyl.

[0318] In a specific embodiment, the R 9a and R 9b It combines to form an oxo, -(C2-C4) alkenyl, -(C3-C6) cycloalkyl, or -(4-8 member) heterocyclyl.

[0319] In a specific embodiment, the R 8a and R 8b , and R 9a and R 9b It combines independently to form oxo, vinyl, propenyl, cyclopropyl, cyclobutyl, cyclopentyl, oxetanil, tetrahydrofuranil, tetrahydropyranil, azetidinil, pyrrolidinil, piperidinil, or piperazinil.

[0320] In a specific embodiment, the R 8a and R 8b It combines to form oxo, vinyl, propenyl, cyclopropyl, cyclobutyl, cyclopentyl, oxetanil, tetrahydrofuranil, tetrahydropyranil, azetidinil, pyrrolidinil, piperidinil, or piperazinil.

[0321] In a specific embodiment, the R 9a and R 9bIt combines to form oxo, vinyl, propenyl, cyclopropyl, cyclobutyl, cyclopentyl, oxetanil, tetrahydrofuranil, tetrahydropyranil, azetidinil, pyrrolidinil, piperidinil, or piperazinil.

[0322] In a specific embodiment, the R 8a and R 9a , R 8b and R 9b together with the carbon atoms connected thereto, it forms (C3-C6) cycloalkyl, (4-8) heterocyclyl, or (5-9) heteroaryl, and the aforementioned groups are hydrogen, halogen, -OH, -O-(C1-C4) alkyl, -NH2, -NH(C1-C4) alkyl, -N[(C1-C4) alkyl]2, -(C3-C6) cycloalkyl and -(C6-C 10 ) is selectively substituted by 1, 2, 3, 4, 5, 6, or 7 groups selected from aryls.

[0323] In a specific embodiment, the R 8a and R 9a together with the carbon atoms connected thereto, it forms (C3-C6) cycloalkyl, (4-8) heterocyclyl, or (5-9) heteroaryl, and the aforementioned groups are hydrogen, halogen, -OH, -O-(C1-C4) alkyl, -NH2, -NH(C1-C4) alkyl, -N[(C1-C4) alkyl]2, -(C3-C6) cycloalkyl and -(C6-C 10 ) is selectively substituted by 1, 2, 3, 4, 5, 6, or 7 groups selected from aryls.

[0324] In a specific embodiment, the R 8b and R 9b together with the carbon atoms connected thereto, it forms (C3-C6) cycloalkyl, (4-8) heterocyclyl, or (5-9) heteroaryl, and the aforementioned groups are hydrogen, halogen, -OH, -O-(C1-C4) alkyl, -NH2, -NH(C1-C4) alkyl, -N[(C1-C4) alkyl]2, -(C3-C6) cycloalkyl and -(C6-C10 ) is selectively substituted by 1, 2, 3, 4, 5, 6, or 7 groups selected from aryls.

[0325] In a specific embodiment, the R 8a and R 9a , R 8b and R 9b It forms a (4-8-membered) heterocyclyl or (5-9-membered) heteroaryl together with the carbon atoms connected thereto, and the aforementioned group is 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.

[0326] In a specific embodiment, the R 8a and R 9a It forms a (4-8-membered) heterocyclyl or (5-9-membered) heteroaryl together with the carbon atoms connected thereto, and the aforementioned group is 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.

[0327] In a specific embodiment, the R 8b and R 9b It forms a (4-8-membered) heterocyclyl or (5-9-membered) heteroaryl together with the carbon atoms connected thereto, and the aforementioned group is 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.

[0328] In a specific embodiment, the R 8a and R 9a , R 8b and R 9b The carbon atom connected thereto forms oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, pyridinonyl, pyrimidinonyl, oxazolyl, thiazolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, pyridyl, pyrimidinyl, benzothienyl or indolyl, and the aforementioned group is optionally substituted by one, two, or three 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.

[0329] In a specific embodiment, the R 8a and R 9a The carbon atom connected thereto forms oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, pyridinonyl, pyrimidinonyl, oxazolyl, thiazolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, pyridyl, pyrimidinyl, benzothienyl or indolyl, and the aforementioned group is optionally substituted by one, two, or three 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.

[0330] In a specific embodiment, the R 8b and R 9bThe carbon atom connected thereto forms oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, pyridinonyl, pyrimidinonyl, oxazolyl, thiazolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, pyridyl, pyrimidinyl, benzothienyl or indolyl, and the aforementioned group is optionally substituted by one, two, or three 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.

[0331] In a specific embodiment, the R 8a and R 9a is absent, and the above R 8b and R 9b together with the atoms connected to it It forms, where * indicates the position of the connected atoms.

[0332] In a specific embodiment, the R 10 is selected from -OH, or R 10 and R 9b It forms a pentatonic nitrogen-containing heterocyclyl together with an atom connected thereto, and the pentatonic nitrogen-containing heterocyclyl 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.

[0333] In a specific embodiment, the R 10 is selected from -OH, or R 10 and R 9b It forms imidazolinyl together with the atoms connected thereto, and said imidazolinyl is optionally substituted by one, two, or three groups selected from halogen, -OH, methyl, -NH2, -NH-methyl and -N(methyl)2.

[0334] In a specific embodiment, the R 10 is -OH, or, R 10 and R 9b together with the atoms connected to it It forms, where * indicates the position of the connected atoms.

[0335] In a specific embodiment, the R 10 is selected from -OH, or R 10 and R 9a It forms a pentatonic nitrogen-containing heterocyclyl together with an atom connected thereto, and the pentatonic nitrogen-containing heterocyclyl 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.

[0336] In a specific embodiment, the R 10 is selected from -OH, or R 10 and R 9a It forms imidazolinyl together with the atoms connected thereto, and said imidazolinyl is optionally substituted by one, two, or three groups selected from halogen, -OH, methyl, -NH2, -NH-methyl and -N(methyl)2.

[0337] In a specific embodiment, the R 10 is -OH, or, R 10 and R 9a together with the atoms connected to it It forms, where * indicates the position of the connected atoms.

[0338] In a specific embodiment, the R 10 It is -OH.

[0339] In a specific embodiment, the R 10 silver am.

[0340] In certain embodiments, in a compound having a structure represented by Formula I,

[0341] X 1 is N and C(R 1 Selected from ), and R 1 It is selected from hydrogen, halogen, cyano, -OH, -(C1-C4) alkyl and -O-(C1-C4) alkyl;

[0342] X 2 is C(R 2 Selected from ), and R 2 is selected from hydrogen, halogen, cyano, -OH, -(C1-C4) alkyl and -O-(C1-C4) alkyl;

[0343] R 31 It is selected from iodine, 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;

[0344] R 3 is selected from -(C3-C6) cycloalkyl, -(3-6 group) heterocyclyl, and -(5-9 group) heteroaryl, and R 3 is 1, 2, 3, or 4 Rs 31 It is optionally substituted by;

[0345] R 4 is selected from hydrogen, fluorine, chlorine, cyano, -OH, -NH2, methyl, halomethyl, -O-methyl, -NH-methyl, and cyclopropyl;

[0346] X is selected from O, S, NH and N[(C1-C4) alkyl];

[0347] Ring B is phenyl;

[0348] R 5 and R 6are 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 Silver together with the atoms connected to it It forms, where * indicates the position of the connected atoms;

[0349] Ring C is phenyl;

[0350] 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;

[0351] m is 1, 2, or 3 and;

[0352] 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) alkylene-, -(C1-C4) alkyl, -(C3-C6) cycloalkyl, and -(4-8-membered) heterocyclyl are hydrogen, halogen, -OH, -O-methyl, -O-ethyl, -O-propyl, -NH2, Optionally substituted by 1, 2, 3, 4, or 5 groups selected from -NH-methyl, -NH-ethyl, -NH-propyl, -N(methyl)2, -N(methyl)-ethyl, -N(methyl)-propyl, -N(ethyl)2, -N(ethyl)-propyl, methyl, and ethyl;

[0353] R 8a Is And;

[0354] R 8b is 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;

[0355] R 9a is selected from hydrogen, -OR, -N(R)R, -methylene-N(R)R, -methylene-NHC(=O)R and -NHC(=O)R;

[0356] R 9b is hydrogen and Selected from;

[0357] R 10 silver am.

[0358] In certain embodiments, in a compound having a structure represented by Formula I,

[0359] X 1 is N and C(R 1 Selected from ), and R 1 It is selected from hydrogen, halogen, cyano, -OH, -(C1-C4) alkyl and -O-(C1-C4) alkyl;

[0360] X 2 is C(R 2 Selected from ), and R 2 is selected from hydrogen, halogen, cyano, -OH, -(C1-C4) alkyl and -O-(C1-C4) alkyl;

[0361] R 31It is selected from iodine, 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;

[0362] R 3 is selected from -(C3-C6) cycloalkyl, -(3-6 group) heterocyclyl, and -(5-9 group) heteroaryl, and R 3 is 1, 2, 3, or 4 Rs 31 It is optionally substituted by;

[0363] R 4 is selected from hydrogen, fluorine, chlorine, cyano, -OH, -NH2, methyl, halomethyl, -O-methyl, -NH-methyl, and cyclopropyl;

[0364] X is selected from O, S, NH and N[(C1-C4) alkyl];

[0365] Ring B is phenyl;

[0366] R 5 and R 6 are 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 Silver together with the atoms connected to it It forms, where * indicates the position of the connected atoms;

[0367] Ring C is phenyl;

[0368] R 7Each 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;

[0369] m is 1, 2, or 3 and;

[0370] 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) alkylene-, -(C1-C4) alkyl, -(C3-C6) cycloalkyl, and -(4-8-membered) heterocyclyl are hydrogen, halogen, -OH, -O-methyl, -O-ethyl, -O-propyl, -NH2, Optionally substituted by 1, 2, 3, 4, or 5 groups selected from -NH-methyl, -NH-ethyl, -NH-propyl, -N(methyl)2, -N(methyl)-ethyl, -N(methyl)-propyl, -N(ethyl)2, and -N(ethyl)-propyl;

[0371] R 8a Is And;

[0372] R 8b is 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;

[0373] R 9a is selected from hydrogen, -OR, -N(R)R, -methylene-N(R)R and -NHC(=O)R;

[0374] R9b is hydrogen and Selected from;

[0375] R 10 silver am.

[0376] In certain embodiments, in a compound having a structure represented by Formula I,

[0377] X 1 is N and C(R 1 Selected from ), and R 1 It is selected from hydrogen, halogen, cyano, -OH, -(C1-C4) alkyl and -O-(C1-C4) alkyl;

[0378] X 2 is N and C(R 2 Selected from ), and R 2 is selected from hydrogen, halogen, cyano, -OH, -(C1-C4) alkyl and -O-(C1-C4) alkyl;

[0379] R 31 It is 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;

[0380] R 3 is selected from -(5-6 member) heteroaryls, and R 3 is 1, 2, 3, or 4 Rs 31 It is optionally substituted by;

[0381] R 4 is selected from hydrogen, fluorine, chlorine, cyano, -OH, -NH2, methyl, halomethyl, -O-methyl, -NH-methyl, and cyclopropyl;

[0382] X is selected from O, S, NH and N[(C1-C4) alkyl];

[0383] Ring B is phenyl;

[0384] R 5 and R 6 are each 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 Silver together with the atoms connected to it

[0385] It forms, where * indicates the position of the connected atoms;

[0386] Ring C is phenyl;

[0387] 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;

[0388] m is 1, 2, or 3 and;

[0389] 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 the -(C1-C4) alkylene-, -(C1-C4) alkyl, -(C3-C6) cycloalkyl, and -(4-8-membered) heterocyclyl are hydrogen, halogen, -OH, -O-methyl, -O-ethyl, -O-propyl, -NH2, -NH-methyl, Optionally substituted by 1, 2, 3, 4, or 5 groups selected from -NH-ethyl, -NH-propyl, -N(methyl)2, -N(methyl)-ethyl, -N(methyl)-propyl, -N(ethyl)2, and -N(ethyl)-propyl;

[0390] R 8a Is And;

[0391] R 8b is 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;

[0392] R 9a is selected from hydrogen, -OR, -N(R)R, -methylene-N(R)R and -NHC(=O)R;

[0393] R 9b is hydrogen and Selected from;

[0394] R 10 silver am.

[0395] In certain embodiments, in a compound having a structure represented by Formula I,

[0396] X 1 is N and C(R 1Selected from ), and R 1 It is selected from hydrogen, fluorine, chlorine, cyano, -OH, methyl, ethyl, propyl, -O-methyl, -O-ethyl, and -O-propyl;

[0397] X 2 is C(R 2 Selected from ), and R 2 is selected from hydrogen, fluorine, chlorine, cyano, -OH, methyl, ethyl, propyl, -O-methyl, -O-ethyl, and -O-propyl;

[0398] R 31 It is selected from hydrogen, fluorine, chlorine, cyano, -OH, -SH, -NH2, methyl, halomethyl, -O-methyl, -CH2OH, -CH2NH2 and -CH2CH2N(CH3)2;

[0399] R 3 is selected from cyclopropyl, oxetanil, piperazinil, piperazinonil, morpholinil, morpholinonil, oxazolil, thiazolil, pyrazolil, isoxazolil, isothiazollil, imidazollil, triazolil, tetrazollil, pyridyl, pyrazinil, pyridazinil, pyrimidinil, pyridazinoimidazolil, pyrazinoimidazolil, and pyrimidinonil, and R 3 is 1, 2, or 3 Rs 31 It is optionally substituted by;

[0400] R 4 is selected from hydrogen, fluorine, chlorine, cyano, -OH, and -NH2;

[0401] X is selected from O and S;

[0402] Structural unit Is And;

[0403] R 5 is selected from hydrogen, -OH, -NH2 and -CH2NH2;

[0404] R 6 It is selected from hydrogen, fluorine, chlorine, bromine, cyano, -OH, -NH2, cyclopropyl, and -O-methyl;

[0405] or R 5 and R 6 Silver together with the atoms connected to it It forms, where * indicates the position of the connected atoms;

[0406] Structural unit Is And;

[0407] 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;

[0408] m is 1, 2, or 3 and;

[0409] R 8a Is And;

[0410] R 8b is selected from hydrogen, -methylene-R, -methylene-N(R)R, -C(=O)OR, -C(=O)N(R)R, and -C(=O)R, and the definition of R is as described in any one embodiment of the present invention, for example, R is each independently selected from hydrogen, -OH, methyl, ethyl, -O-methyl, -C(=O)-methyl, -S(=O)2-methyl, azetidinyl, pyrrolidinyl, and piperazinyl, and each of the aforementioned groups is each independently optionally substituted by one, two, or three groups selected from -OH and -NH2;

[0411] R 9ais selected from hydrogen, -CN, -N(R)R, -NHC(=O)R, -methylene-N(R)R, -methylene-NHC(=O)R, and -methylene-NHC(=O)NHR, and the definition of R is as described in any one embodiment of the present invention, for example, R is each independently selected from hydrogen, -OH, methyl, ethyl, -methylene-O-ethyl, -S(=O)2-methyl, cyclobutyl, azetidinyl, -methylene-cyclobutyl, and -methylene-azetidinyl, and each of the aforementioned groups is each independently optionally substituted by one, two, or three groups selected from -OH, OCH3, NHCH3, N(CH3)2, and CH3;

[0412] R 9b is hydrogen and Selected from;

[0413] R 10 silver am.

[0414] In certain embodiments, in a compound having a structure represented by Formula I,

[0415] X 1 is N and C(R 1 Selected from ), and R 1 It is selected from hydrogen, fluorine, chlorine, cyano, -OH, methyl, ethyl, propyl, -O-methyl, -O-ethyl, and -O-propyl;

[0416] X 2 is C(R 2 Selected from ), and R 2 is selected from hydrogen, fluorine, chlorine, cyano, -OH, methyl, ethyl, propyl, -O-methyl, -O-ethyl, and -O-propyl;

[0417] R 31 It is selected from hydrogen, fluorine, chlorine, cyano, -OH, -SH, -NH2, methyl, halomethyl, -O-methyl, -CH2OH, and -CH2CH2N(CH3)2;

[0418] R 3is selected from cyclopropyl, oxetanil, piperazinil, piperazinonil, morpholinil, morpholinonil, oxazolil, thiazolil, pyrazolil, isoxazolil, isothiazollil, imidazollil, triazolil, tetrazollil, pyridyl, pyrazinil, pyridazinil, pyrimidinil, pyridazinoimidazolil, pyrazinoimidazolil, and pyrimidinonil, and R 3 is 1, 2, or 3 Rs 31 It is optionally substituted by;

[0419] R 4 is selected from hydrogen, fluorine, chlorine, cyano, -OH, and -NH2;

[0420] X is selected from O and S;

[0421] Structural unit Is And;

[0422] R 5 is selected from hydrogen, -OH, -NH2 and -CH2NH2;

[0423] R 6 It is selected from hydrogen, fluorine, chlorine, bromine, cyano, -OH, -NH2, and -O-methyl;

[0424] or R 5 and R 6 Silver together with the atoms connected to it It forms, where * indicates the position of the connected atoms;

[0425] Structural unit Is And;

[0426] 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;

[0427] m is 1, 2, or 3 and;

[0428] R is each independently selected from hydrogen, -OH, -(C1-C4) alkyl, -O-(C1-C4) alkyl, -C(=O)-H, -C(=O)CH2OH, oxetanyl, and azetidinyl-OH, and each of the aforementioned groups is each independently optionally substituted by one, two, or three groups selected from hydrogen, halogen, -OH, -NH2, -NH-methyl, and -N(methyl)2;

[0429] R 8a Is And;

[0430] R 8b is selected from H, -methylene-R, -methylene-N(R)R, -C(=O)OR, -C(=O)N(R)R and -C(=O)R;

[0431] R 9a is selected from hydrogen, -methylene-N(R)R and -NHC(=O)R;

[0432] R 9b is hydrogen and Selected from;

[0433] R 10 silver am.

[0434] In certain embodiments, in a compound having a structure represented by Formula I,

[0435] X 1 is N and C(R 1 Selected from ), and R 1 It is selected from hydrogen, fluorine, chlorine, cyano, -OH, methyl, ethyl, propyl, -O-methyl, -O-ethyl, and -O-propyl;

[0436] X 2 is N and C(R 2 Selected from ), and R 2 It is selected from hydrogen, fluorine, chlorine, cyano, -OH, methyl, ethyl, propyl, -O-methyl, -O-ethyl, and -O-propyl;

[0437] R 31It is selected from hydrogen, fluorine, chlorine, cyano, -OH, -SH, -NH2, methyl, halomethyl, -CH2OH, and -CH2CH2N(CH3)2;

[0438] R 3 is selected from oxazolyl, pyrazolyl, and pyrimidinyl, and R 3 is 1, 2, or 3 R 31 It is optionally substituted by;

[0439] R 4 is selected from hydrogen, fluorine, chlorine, cyano, -OH, and -NH2;

[0440] X is selected from O;

[0441] Structural unit Is And;

[0442] R 5 is selected from hydrogen and -NH2;

[0443] R 6 It is selected from hydrogen, fluorine, chlorine, bromine, cyano, -OH, -NH2, and -O-methyl;

[0444] Structural unit Is And;

[0445] 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;

[0446] m is 1, 2, or 3 and;

[0447] R is each independently selected from hydrogen, -OH, -(C1-C4) alkyl and -O-(C1-C4) alkyl, and each of the aforementioned groups is each independently optionally substituted by 1, 2, or 3 groups selected from hydrogen, halogen, -OH, -NH2, -NH-methyl and -N(methyl)2;

[0448] R 8a Is And;

[0449] R 8b is selected from -methylene-R, -C(=O)OR, -C(=O)N(R)R and -C(=O)R;

[0450] R 9a is selected from hydrogen and -methylene-N(R)R;

[0451] R 9b is hydrogen and Selected from;

[0452] R 10 silver am.

[0453] In certain embodiments, in a compound having a structure represented by Formula I,

[0454] X 1 is C(R 1 ) and;

[0455] R 1 It is selected from hydrogen, fluorine, chlorine, cyano, -OH, methyl, ethyl, propyl, -O-methyl, -O-ethyl, and -O-propyl;

[0456] X 2 is selected from CH;

[0457] R 31 It is selected from hydrogen, fluorine, chlorine, cyano, -OH, -SH, -NH2, -CH2OH, -CH2NH2, methyl, trifluoromethyl, and -O-methyl;

[0458] R 3 silver , , , , , , , , , , , , , , , , , , , , , , , and Selected from, and the above R 3 is 1, 2, or 3 R 31 It is optionally substituted by;

[0459] R 4 is hydrogen;

[0460] X is O and;

[0461] Structural unit Is And;

[0462] R 5 is selected from hydrogen, -OH, -NH2 and -CH2NH2;

[0463] R 6 It is selected from hydrogen, fluorine, chlorine, bromine, cyano, -OH, -NH2, cyclopropyl, and -O-methyl;

[0464] or R 5 and R 6 Silver together with the atoms connected to it It forms, where * indicates the position of the connected atoms;

[0465] Structural unit Is or And;

[0466] R 7 Each is independently selected from hydrogen, fluorine, chlorine, bromine, -OH, and -NH2;

[0467] R 8a Is And;

[0468] R 8b is hydrogen, , , , , , , , , , , , , , , , , , , and Selected from;

[0469] R 9a is hydrogen, , , , , , , , , , , , , , and Selected from;

[0470] R 9b is hydrogen and Selected from;

[0471] R 10 silver am.

[0472] In certain embodiments, in a compound having a structure represented by Formula I,

[0473] X 1 is C(R 1 ) and;

[0474] R 1 It is selected from hydrogen, fluorine, chlorine, cyano, -OH, methyl, ethyl, propyl, -O-methyl, -O-ethyl, and -O-propyl;

[0475] X 2 is selected from CH;

[0476] R 31 It is selected from hydrogen, fluorine, chlorine, cyano, -OH, -SH, -NH2, -CH2OH, methyl, trifluoromethyl, and -O-methyl;

[0477] R 3 silver , , , , , , , , , , , , , , , , , , , , , , , and Selected from, and the above R 3 is 1, 2, or 3 R 31 It is optionally substituted by;

[0478] R 4 is hydrogen;

[0479] X is O and;

[0480] Structural unit Is And;

[0481] R 5 is selected from hydrogen, -OH, -NH2 and -CH2NH2;

[0482] R 6 It is selected from hydrogen, fluorine, chlorine, bromine, cyano, -OH, -NH2, and -O-methyl;

[0483] or R 5 and R 6 Silver together with the atoms connected to it It forms, where * indicates the position of the connected atoms;

[0484] Structural unit Is or And;

[0485] R 7 Each is independently selected from hydrogen, fluorine, chlorine, bromine, -OH, and -NH2;

[0486] R 8a Is And;

[0487] R 8b is hydrogen, , , , , , , , , , , , , , , , and Selected from;

[0488] R 9a is hydrogen, , , , and Selected from;

[0489] R 9b is hydrogen and Selected from;

[0490] R 10 silver am.

[0491] In certain embodiments, in a compound having a structure represented by Formula I,

[0492] X 1 is C(R 1 ) and;

[0493] R 1 It is selected from hydrogen, fluorine, chlorine, cyano, -OH, methyl, ethyl, propyl, -O-methyl, -O-ethyl, and -O-propyl;

[0494] X 2 is selected from CH;

[0495] R 31 It is selected from hydrogen, fluorine, chlorine, cyano, -OH, -SH, and -NH2;

[0496] R 3 silver , , and Selected from, and the above R 3 is 1, 2, or 3 R 31 It is optionally substituted by;

[0497] R 4 is hydrogen;

[0498] X is O and;

[0499] Structural unit Is And;

[0500] R 5 is selected from hydrogen;

[0501] R 6 It is selected from hydrogen, fluorine, chlorine, bromine, cyano, -OH, -NH2, and -O-methyl;

[0502] Structural unit Is or And;

[0503] R 7 Each is independently selected from hydrogen, fluorine, chlorine, bromine, -OH, and -NH2;

[0504] R 8a Is And;

[0505] R 8b is hydrogen, , , , , , and Selected from;

[0506] R 9a is hydrogen and Selected from;

[0507] R 9b is hydrogen and Selected from;

[0508] R 10 silver am.

[0509] In certain embodiments, the racemic mixture is a racemic body.

[0510] In certain embodiments, the compound is selected from the compounds represented by Formula I-1, and

[0511]

[0512] Equation I-1

[0513] Here,

[0514] 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 The definitions of and m are as described in any one embodiment of the present invention, and

[0515] n is 0, 1, 2, 3, 4, or 5, and

[0516] Ring A is selected from 5-10 member heteroaryls.

[0517] In certain embodiments, structural fragments The definition of is R 3 As defined in, R 3 The definition is as described in any one embodiment of the present invention.

[0518] In certain embodiments, the ring A is a 5-9 member heteroaryl.

[0519] In certain embodiments, the ring A is a 5-6-membered heteroaryl.

[0520] In certain embodiments, the ring A is selected from oxazolyl, thiazolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, pyridyl, and pyrimidinyl.

[0521] In a specific embodiment, the ring A is , , , , , , , , , , and Selected from.

[0522] In a specific embodiment, the ring A is , , , , , , , , , and Selected from.

[0523] In a specific embodiment, the ring A is selected from oxazolyl and pyrimidinyl.

[0524] In a specific embodiment, the ring A is , , and Selected from.

[0525] In certain embodiments, the compound is selected from the compounds represented by Formula I-1-A, and

[0526]

[0527] Formula I-1-A

[0528] Here,

[0529] X, X 1 , X 2 , R 31 , R 4 , R 5 , R 6 , R 7 , R 8a , R 8b , R 9a , R 9b , R 10The definitions of and m are as described in any one embodiment of the present invention, and the definitions of ring A and ring n are as described in any one embodiment of the present invention.

[0530] In a specific embodiment, the structural unit Is or am.

[0531] In a specific embodiment, the structural unit Is am.

[0532] In certain embodiments, the compound is selected from the compounds represented by Formula I-1-B, and

[0533]

[0534] Formula I-1-B

[0535] Here,

[0536] 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 The definitions of and m are as described in any one embodiment of the present invention, and the definitions of ring A and ring n are as described in any one embodiment of the present invention.

[0537] In certain embodiments, the compound is selected from compounds represented by the formula I-1-AB-1, and

[0538]

[0539] Formula I-1-AB-1

[0540] Here,

[0541] X, X 1 , X 2 , R 31 , R 4, R 5 , R 6 , R 7 , R 8b , R 9b , R 10 The definitions of and m are as described in any one embodiment of the present invention, and the definitions of ring A and n are as described in any one embodiment of the present invention.

[0542] In certain embodiments, the compound is selected from compounds represented by the formula I-1-AB-1A or the formula I-1-AB-1B, and

[0543]

[0544] Here,

[0545] X, X 1 , X 2 , R 31 , R 4 , R 5 , R 6 , R 7 , R 9b , R 10 The definitions of and m are as described in any one embodiment of the present invention, and the definitions of ring A and n are as described in any one embodiment of the present invention, and R 8b1 is selected from R and N(R)R, and the definition of R is as described in any one embodiment of the present invention.

[0546] In certain embodiments, the compound is selected from compounds represented by the formula I-1-AB-1C or the formula I-1-AB-1D, and

[0547]

[0548] Here,

[0549] R 31 , R 1 , R 4 , R 5 , R 6 , R 7 , R 8b , R 9b , R 9aThe definitions of and m are as described in any one embodiment of the present invention, and the definitions of ring A and n are as described in any one embodiment of the present invention, and R 8b1 is selected from R and N(R)R, and the definition of R is as described in any one embodiment of the present invention.

[0550] In certain embodiments, the compound is selected from compounds represented by the formula I-1-AB-1D, and

[0551] Here,

[0552] R 1 It 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;

[0553] Ring A is selected from oxazolyl, pyrazolyl, and pyrimidinyl, preferably , , and Selected from, ring A is 1, 2, or 3 R 31 It is optionally substituted by;

[0554] R 31 Each is 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;

[0555] Or, structural fragments Is , , , , , , , , , , and Selected from;

[0556] R 4 is hydrogen;

[0557] R 5 is hydrogen or -NH2;

[0558] R 6 It is 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 selected from hydrogen, fluorine, chlorine, bromine, cyano, -OH, -NH2, cyclopropyl and -O-methyl;

[0559] R 7 Each is independently selected from hydrogen, fluorine, chlorine, bromine, -OH, and -NH2;

[0560] m is 0, 1, 2, or 3, and;

[0561] 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, and the definition of R is as described in any one embodiment of the present invention, for example, R is each 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 said -(C1-C4) alkyl and -(4-8-membered) heterocyclyl are each optionally substituted by 1, 2, 3, 4, or 5 groups selected from hydrogen, halogen, -OH, -NH2, -NHCH3, and CH3; R 8b is preferably hydrogen, , , , , , , , and Selected from;

[0562] 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, and the definition of R is as described in any one embodiment of the present invention, for example, R is each independently selected from hydrogen, -OH, methyl, ethyl, -methylene-O-ethyl, -S(=O)2-methyl, cyclobutyl, azetidinyl, -methylene-cyclobutyl, and -methylene-azetidinyl, and each of the aforementioned groups is each independently optionally substituted by one, two, or three groups selected from -OH, OCH3, NHCH3, N(CH3)2, and CH3; R 9a is preferably hydrogen, , , , , , , , , , , , , , , , and Selected from;

[0563] R 9b is hydrogen and Selected from.

[0564] In certain embodiments, the compound is

[0565]

[0566]

[0567]

[0568]

[0569]

[0570]

[0571]

[0572]

[0573]

[0574]

[0575]

[0576]

[0577]

[0578]

[0579]

[0580]

[0581]

[0582]

[0583]

[0584]

[0585]

[0586]

[0587]

[0588]

[0589]

[0590]

[0591]

[0592]

[0593]

[0594]

[0595]

[0596]

[0597] Selected from.

[0598] In certain embodiments, the compound is a racemic mixture of compounds 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.

[0599] In certain embodiments, the compound is a mixture of the compound represented by Formula I, Formula I-1, Formula I-1-A, Formula I-1-B, Formula I-1-AB-1, Formula I-1-AB-1A, Formula I-1-AB-1B, Formula I-1-AB-1C, or Formula I-1-AB-1D and its enantiomers.

[0600] In certain embodiments, in a 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, 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 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 It is ≥98% or ≥99%.

[0601] A second aspect of the present invention provides a pharmaceutical composition comprising at least one compound described in the first aspect of the present invention or a racemic mixture thereof, enantiomer, diastereomer, pharmaceutically acceptable salt, isotope-labeled compound, or mixture of the aforementioned forms, and one or more pharmaceutically acceptable carriers and / or excipients. In certain embodiments, said compound or a racemic mixture thereof, enantiomer, diastereomer, pharmaceutically acceptable salt, isotope-labeled compound, or mixture of the aforementioned forms is present in said pharmaceutical composition in an effective amount, preferably in a therapeutically effective amount, or in a prophylactically effective amount.

[0602] A third aspect of the present invention provides the use of a compound described in the first aspect of the present invention, or a racemic mixture thereof, enantiomer, diastereomer, pharmaceutically acceptable salt, isotope-labeled compound, or a mixture of the aforementioned forms, or a pharmaceutical composition described in the second aspect of the present invention, in the manufacture of a drug for the treatment and / or prevention of a disease or pathology or for alleviating the severity of said disease or pathology, wherein said disease or pathology is a tumor or cancer.

[0603] A third aspect of the present invention also provides for the use of the compound described in the first aspect of the present invention or a racemic mixture thereof, enantiomer, diastereomer, pharmaceutically acceptable salt, isotope-labeled compound, or mixture of the aforementioned forms, or a pharmaceutical composition described in the second aspect of the present invention, for the treatment and / or prevention of a disease or pathology or for alleviating the severity of said disease or pathology, wherein said disease or pathology is a tumor or cancer.

[0604] A third aspect of the present invention also provides a method for treating and / or preventing a disease or condition or alleviating the severity of said disease or condition, comprising the step of administering to an individual in need an effective amount of the compound described in the first aspect of the present invention or a racemic mixture thereof, enantiomer, diastereomer, pharmaceutically acceptable salt, isotope-labeled compound, or a mixture of the aforementioned forms, or a pharmaceutical composition described in the second aspect of the present invention, wherein said disease or condition is a tumor or cancer.

[0605] 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.

[0606] 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.

[0607] In certain embodiments, the tumor or cancer is selected from gastric cancer, colorectal cancer, breast cancer, ovarian cancer, and liver cancer.

[0608] In a specific embodiment, the colorectal cancer is selected from colorectal adenocarcinoma and colon cancer.

[0609] In a specific embodiment, the breast cancer is selected from ductal carcinoma.

[0610] Definition of Terms

[0611] Various terms and phrases used in this application have their general meanings known to those skilled in the art; however, this application will explain and clarify such terms and phrases in more detail, and if a mentioned term or phrase does not correspond to its known meaning, the meaning described in this invention shall be used as the basis.

[0612] As used in this application, the term “pharmaceuticalally acceptable salt” refers to a salt of the compound of the present invention that is pharmaceutically acceptable and has the desired pharmacological activity of the parent compound. Such salts include acid addition salts formed with an inorganic or organic acid, salts formed by replacing an acidic proton present in the parent compound with a metal ion, or coordination compounds formed with an organic base.

[0613] As used in this application, the term “isotope-labeled compound” refers to a compound in which one or more atoms have the same number of atoms but are replaced by atoms with an atomic mass or mass number different from the atomic mass or mass number dominant in nature. Examples of isotopes suitable for inclusion in the compounds of the present invention are 2 H, 3 Hydrogen isotopes such as H; 11 C, 13 C and 14 Carbon isotopes such as C; 36 Chlorine isotopes such as Cl; 18 Fluorine isotopes such as F; 123 I and 125 Iodine isotopes such as I; 13 N and 15 Nitrogen isotopes such as N; 15 O, 17 O and 18 Oxygen isotopes such as O; and 35 It includes, but is not limited to, sulfur isotopes such as S.

[0614] As used in this application, the term “racemic mixture” includes “racemics,” the term “racemics” refers to an equimolar mixture of a chiral molecule having optical activity and its enantiomer; the term “enantiomer” refers to one of a pair of molecular entities that are mirror images of each other but cannot be superimposed, and a mixture of enantiomers can be separated, for example, under chiral separation conditions; the term “diastereomer” refers to a stereoisomer that is not enantiomer, a diastereomer is characterized by some difference in physicochemical properties, and a mixture of diastereomers can be separated, for example, under chromatography or crystallization conditions.

[0615] As used in this application, "...optionally substituted by" indicates that the group may be substituted and may be substituted by a substituent, for example, that -(C1-C6) alkyl is optionally substituted by a halogen indicates that -(C1-C6) alkyl may be substituted and may be substituted by a halogen to obtain a haloalkyl. It must be understood that when a group consists of multiple parts, if one part can be substituted, this part of the group can also be substituted; for example, if the group is selected from -(C1-C6) alkyl, -O-(C1-C6) alkyl, and -NH(C1-C6) alkyl, and the -(C1-C6) alkyl is selectively substituted by a halogen, this indicates that the (C1-C6) alkyl of -(C1-C6) alkyl, -O-(C1-C6) alkyl, and -NH(C1-C6) alkyl are all selectively substituted by a halogen. Furthermore, 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 selectively substituted by one hydroxyl or amino group" implies methyl and -O-methyl, The methyl groups of -NH-methyl, -S-methyl, -C(=O)-methyl, and -C(=O)NH-methyl all indicate that they are selectively substituted by one hydroxyl or amino group.

[0616] As used in this application, the term "halogen" refers to fluorine, chlorine, bromine, and iodine.

[0617] As used in this application, the term “alkyl” refers to a straight-chain or branched-chain monovalent hydrocarbon group, for example, (C1-C6)alkyl refers to having 1 to 6 carbon atoms, e.g., 1, 2, 3, 4, 5, or 6 carbon atoms; (C1-C4)alkyl refers to having 1 to 4 carbon atoms, e.g., 1, 2, 3, or 4 carbon atoms. Non-limiting examples of alkyl include, but are not limited to, methyl, ethyl, propyl, propyl, butyl, etc.

[0618] As used in this application, the term “alkylene” refers to a straight-chain or branched-chain divalent hydrocarbon group, for example, (C1-C8)alkylene refers to having 1 to 8 carbon atoms, e.g., 1, 2, 3, 4, 5, 6, 7, or 8 carbon atoms; (C1-C4)alkylene refers to having 1 to 4 carbon atoms, e.g., 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.

[0619] As used in this application, the term “halo” indicates that the group modified thereby is substituted by one or more halogens, e.g., 1, 2, 3, 4, 5, or 6 halogens. For example, “(C1-C6) haloalkyl” indicates that the (C1-C6) alkyl defined above is substituted by one or more halogens, and non-limiting examples include but are not limited to CF3, CHF2, or CF2CF3, etc.

[0620] As used in this application, the term "alkenyl" refers to a straight-chain or branched-chain unsaturated hydrocarbon group containing at least one double bond. (C 2-C6) Alkenyl indicates having 2 to 6 carbon atoms (e.g., 2, 3, 4, 5, or 6), which is (C 2- C5) Alkenyl, (C 2- C4) Alkenyl, (C 2- C3) Includes alkenyls, etc., and non-limiting examples include but are not limited to CH=CH2, -CH=CH-CH=CH2 or -CH=C(CH)3-CH3.

[0621] As used in this application, the term "alkynyl" refers to a straight-chain or branched-chain unsaturated hydrocarbon group containing at least one triple bond, e.g. (C 2- C6) Alkynyl indicates having 2 to 6 carbon atoms (e.g., 2, 3, 4, 5, or 6), which is (C 2- C5) alkynyl, (C 2- C4) alkynyl, (C 2- C3) Includes alkynyl, etc., and non-limiting examples include but are not limited to ethinyl or propynyl.

[0622] As used in this application, the term “cycloalkyl” refers to a monovalent saturated hydrocarbon group composed of carbon atoms, for example, (C3-C6) cycloalkyl indicates that it is composed of 3 to 6 (e.g., 3, 4, 5, or 6) carbon atoms. The cycloalkyl comprises monocyclic, bicyclic, or polycyclic groups including a spiro ring, a fused ring, or a bridge ring. Non-limiting examples include, but are not limited to, cyclobutyl, cyclopentyl, or cyclohexyl.

[0623] As used in this application, the term “heterocyclil” refers to a saturated or partially unsaturated monovalent cyclic group composed of ring atoms, wherein 1, 2, 3, or 4 ring atoms are heteroatoms and the remainder are carbon atoms; preferably, the heteroatoms are selected from N, O, or S, wherein the nitrogen atoms may optionally be quaternized and the nitrogen and sulfur heteroatoms may optionally be oxidized; preferably, the carbon atoms are optionally substituted by =O. For example, (4-10) heterocyclil refers to a composition of 4, 5, 6, 7, 8, 9, or 10 ring atoms, and (4-10) heterocyclil includes (4-9) heterocyclil, (4-8) heterocyclil, (4-7) heterocyclil, (4-6) heterocyclil, 5-membered heterocyclil, 6-membered heterocyclil, etc. The heterocyclil includes a monocyclic, bicyclic, or polycyclic group comprising a spiro ring, a fused ring, or a bridge ring. Non-limiting examples include, but are not limited to, oxetanil, azetidinil, pyrrolidinil, piperidinil, piperazinil, morpholinil, or imidazolinil.

[0624] As used in this application, the term "aryl" refers to an unsaturated carbon ring group having a conjugated ð-electron system, for example (C6-C 10 ) Aryls consist of 6 to 10 (e.g., 6, 7, 8, 9, or 10) carbon atoms. Non-limiting examples include, but are not limited to, phenyls.

[0625] As used in this application, the term “heteroaryl” refers to an unsaturated group having a conjugated ð-electron system composed of ring atoms, wherein 1, 2, 3, or 4 ring atoms are heteroatoms and the remainder are carbon atoms; preferably, said heteroatoms are selected from N, O, or S, wherein the nitrogen atom is optionally quaternized and the nitrogen and sulfur heteroatoms may optionally be oxidized. For example, a (5-12-membered) heteroaryl is composed of 5 to 12 ring atoms (e.g., 5, 6, 7, 8, 9, 10, 11, or 12) and includes 5-10-membered, 5-9-membered, 6-9-membered, 5-6-membered heteroaryls, etc. The heteroaryls include monocyclic and polycyclic groups, and non-limiting examples include but are not limited to imidazolyl or pyridyl.

[0626] As used in this application, 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 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, osmotic pressure maintenance reagents, absorption delay reagents, 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 reagents such as parabens, chlorobutanol, phenol, and sorbic acid. Osmotic pressure maintenance reagents include, but are not limited to, sugars, NaCl, and analogs thereof. Absorption delay reagents include, but are not limited to, stearates and gelatin. Diluents include, but are not limited to, water, aqueous buffers (e.g., buffered saline), alcohols, and polyols (e.g., glycerol). Preservatives include, but are not limited to, various antibacterial and antifungal reagents such as thimerosal, 2-phenoxyethanol, parabens, chlorobutanol, phenol, and sorbic acid.Stabilizers have the meaning commonly understood by those skilled in the art and can stabilize the desired activity of the active ingredient of a drug, and include, but are not limited to, monosodium glutamate, gelatin, SPGA, sugars (e.g., sorbitol, mannitol, starch, sucrose, lactose, dextran, or glucose), amino acids (e.g., glutamic acid, glycine), proteins (e.g., dried whey, albumin, or casein), or degradation products thereof (e.g., lactalbumin hydrolysate).

[0627] As used in this application, the term “treatment” is intended to alleviate, reduce, improve, or eliminate a target disease state or pathology. A subject is successfully “treated” when, in accordance with the method described herein, a therapeutic dose of the ligand-conjugated drug or a racemic mixture, enantiomer, diastereomer, pharmaceutically acceptable salt, or mixture of the aforementioned forms is administered, and one or more of the subject’s signs and symptoms show an observable and / or detectable reduction or improvement. Furthermore, it should be understood that treatment of the said disease state or pathology includes not only complete cure but also achieving some biologically or medically relevant results even if complete cure is not achieved.

[0628] As used in this application, the term "prevention" is intended to avoid, reduce, prevent, or delay the appearance of symptoms related to a disease or pathology, provided that such disease or disease-related symptoms had not yet appeared prior to the administration of the relevant drug. "Prevention" does not mean the complete prevention of the appearance of the disease or disease-related symptoms; for example, if the risk of a specific disease or disease-related symptom appearing in a subject is reduced after the administration of the relevant drug, or if the severity of the related symptom that subsequently appears is alleviated, this may all be considered as "prevention" of the appearance or progression of the said disease.

[0629] As used in this application, the DMSO solvent used to dissolve compounds in the nuclear magnetic resonance structure determination process is deuteriumized DMSO, i.e., DMSO- d 6 am.

[0630] Beneficial effects:

[0631] The compound provided in the present invention has a protein translation inhibitory effect, significantly inhibits the proliferation of cell lines in vitro, and can inhibit tumor growth in vivo.

[0632] In an in vitro tumor cell proliferation inhibition test, the small molecule compound of the present application has significant proliferation inhibitory activity against BT474, DLD-1, NCI-N87, NUGC-4, SNU-423, MKN-45, SK-OV-3, Ls174T, and HCC1954.

[0633] The small molecule compounds of the present application have a significant tumor suppression effect 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.

[0634] The small molecule compound of the present application has a significant tumor-suppressing effect in in vivo and in vitro models of blood cancer, such as the NCI-H929 and MM.1R blood cancer models.

[0635] In addition, the compound provided in the present invention has excellent pharmacokinetic properties. Specific details for implementing the invention

[0636] The following describes embodiments of the present invention in combination with examples; however, those skilled in the art should understand that the following examples are intended only to illustrate the invention and not to limit the scope of the invention. Where specific conditions are not specified in the examples, they are based on general conditions or conditions suggested by the manufacturer. Where the manufacturer is not specified for any reagents or equipment used, they are all general products available on the market.

[0637]

[0638] Universal chiral column separation method

[0639] The racemic mixture of the present invention was dissolved in methanol, and the resulting compound was obtained by separating it using a chiral preparative chromatography column (see table below).

[0640]

[0641] Example 1

[0642] Compounds 1 and 1A

[0643]

[0644] Literature: Liu, Tao; Nair, Somarajan J.; Lescarbeau, Andr ; Belani, Jitendra; Peluso, St. Synthetic compounds 1 and 1A were synthesized according to phane; 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, and compound S2 was referred to on page 7 of the Supporting Information.

[0645] Compound 2

[0646]

[0647] 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 then injected via a 20 mL syringe at a rate of 15 mL / h using an injection pump into a coil wound around a jacketed glass cylinder equipped with a 250 W UV lamp. While controlling the internal reaction temperature to 0–5 °C by adjusting the external circulation cooler, the UV lamp was turned on and the reaction mixture was irradiated for 1 hour. After removing the solvent under reduced pressure, the mixture was separated by column chromatography (EA / PE=1 / 3) to remove excess cinnamate, yielding a racemic mixture (900 mg, yield: 75%) of the required yellow oil form crude product 2B. LCMS [M+H+18] + =748.5.

[0648] Step 2: The racemic mixture of Compound 2B (5.2 g, 7.96 mmol) was mixed with MeOH (50 mL), NaOMe (1.1 g, 19.91 mmol) was added at 0 °C, and the mixture was stirred at 65 °C for 1.5 hours. The solution was concentrated, washed sequentially with H2O, aqueous NH4Cl solution, and saturated saline, dried with Na2SO4, concentrated under reduced pressure, and purified using a silica gel column (0.2% FA, EA / PE=1 / 3) to obtain the racemic mixture of Compound 2C (3.8 g, yield: 65%). LCMS [M+H-18] + = 714.4.

[0649] Step 3: The racemic mixture of Compound 2C (3.8 g, 5.21 mmol) was mixed with MeCN / CHCl3=1 / 1 (100 mL / 100 mL), NaBH(OAc)3 (5.5 g, 26.03 mmol) and AcOH (3.1 g, 52.05 mmol) were added at 0°C, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was extracted with EA, the organic phase was washed sequentially with water and saturated saline, dried with anhydrous Na2SO4, and purified using a silica gel column (PE:EA=1 / 1) to obtain the racemic mixture of Compound 2D (1.9 g, yield: 50%). LCMS [M+H] + =716.5.

[0650] Step 4: A racemic mixture 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) was heated at 150°C for 2 hours in a 20 mL NMP solution. The solution was diluted with water, extracted with EA, washed sequentially with water and saline solution, dried with anhydrous Na2SO4, and purified using a silica gel column (EA / PE=1 / 1) to obtain a racemic mixture of Compound 2E (1.1 g, yield: 91%).

[0651] 1H NMR (400 MHz, CDCl3) δ 7.48 - 7.40 (m, 6H), 7.37 (dt, J = 12.4, 5.3 Hz, 3H), 6.96 (t, J = 7.9 Hz, 1H), 6.85 (s, 1H), 6.51 (d, J = 7.7 Hz, 1H), 6.45 (s, 1H), 6.36 (d, J = 1.9 Hz, 1H), 6.22 (d, J = 1.9 Hz, 1H), 5.09 (d, J = 1.7 Hz, 2H), 5.01 (d, J = 6.4 Hz, 1H), 4.35 (d, J = 14.2 Hz, 1H), 3.95 - 3.81 (m, 4H), 3.66 (d, J = 3.8 Hz, 3H), 1.53 - 1.47 (m, 9H). LCMS [M+H-18] + =605.4.

[0652] Step 5: Pd(OH)2 / C (10%, 250 mg) was added to a racemic solution of Compound 2E (500.0 mg, 0.74 mol) in EA / MeOH / THF / DCM = 20:2:2:0.2 (40 mL). The mixture was hydrogenated three times and 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 using a silica gel column (DCM / MeOH = 10 / 1) to obtain a racemic solution of Compound 2F (300 mg, yield: 69%).

[0653] 1H NMR (400 MHz, CDCl3) δ 7.42 (d, J = 8.6 Hz, 2H), 7.33 (d, J = 8.6 Hz, 2H), 6.98 (dd, J = 16.1, 8.2 Hz, 1H), 6.87 (s, 1H), 6.51 (d, J = 7.7) Hz, 1H), 6.33 (s, 1H), 6.24 (d, J = 1.8 Hz, 1H), 6.12 (d, J = 1.7 Hz, 1H), 4.98 (d, J = 6.3 Hz, 1H), 4.35 (d, J = 14.2 Hz, 1H), 3.90 (dd, J = 14.1, 6.4 Hz, 1H), 3.83 (d, J = 15.4 Hz, 3H), 3.67 (d, J = 4.5 Hz, 3H), 1.50 (d, J = 4.8 Hz, 9H). LCMS [M+H] + = 515.4.

[0654] Step 6: A racemic mixture of Compound 2F (306.0 mg, 0.52 mmol) and K2CO3 (143.6 mg, 1.04 mmol) was 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 minutes. The solution was diluted with water, extracted with EA, washed sequentially with water and saline solution, dried with anhydrous Na2SO4, and purified using a silica gel column (EA / PE=1 / 1) to obtain a racemic mixture of Compound 2H (300 mg, yield: 80%).

[0655] 1H NMR (400 MHz, CDCl3) δ 7.41 (d, J = 8.4 Hz, 2H), 7.33 (d, J = 8.5 Hz, 2H), 7.00 - 6.92 (m, 2H), 6.69 (d, J = 1.7 Hz, 1H), 6.53 (d, J = 7.6) Hz, 1H), 6.45 (d, J = 1.7 Hz, 1H), 6.39 (s, 1H), 4.99 (d, J = 5.9 Hz, 1H), 4.39 (d, J = 14.2 Hz, 1H), 3.99 - 3.91 (m, 4H), 3.68 (s, 3H), 1.50 (s, 9H). LCMS [MH] + =719.2.

[0656] Step 7: A solution of the racemic mixture of Compound 2H (30 mg, 0.042 mmol) was added to DMF (3 mL), and 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 under nitrogen protection, and the mixture was stirred at 100°C for 1 hour. After filtering the suspension, it was purified using a silica gel column (DCM / MeOH=10 / 1) to obtain the racemic mixture of Compound 2J (15 mg, yield: 56%). LCMS [M+H] + = 640.3.

[0657] Step 8: THF / 6M HCl = 1 / 1 (4 mL) was added to a racemic solution of Compound 2J (15 mg, 0.02 mmol) and stirred at room temperature for 1 hour. The solution was concentrated and purified by silica gel (DCM / MeOH) chromatography to obtain a racemic solution of white solid 2 (4.5 mg, yield: 35%), which was further separated using a chiral column to obtain Compound 2.

[0658] LCMS [M+H] + = 540.1.

[0659] 1 H NMR (400 MHz, DMSO) δ 8.25 (d, J= 0.7 Hz, 1H), 7.50 (d, J = 8.6 Hz, 2H), 7.41 (d, J = 0.7 Hz, 1H), 7.31 (d, J = 8.6 Hz, 2H), 7.19 (d, J = 1.1 Hz, 1H), 7.14 (d, J = 1.0 Hz, 1H), 6.67 (t, J = 7.7 Hz, 1H), 6.26 (s, 1H), 6.19 - 6.10 (m, 2H), 5.63 (s, 1H), 5.45 (d, J = 5.4 Hz, 1H), 4.83 (s, 2H), 4.66 (t, J = 5.1 Hz, 1H), 4.27 (d, J = 14.0 Hz, 1H), 3.97 (dd, J = 13.9, 4.8 Hz, 1H), 3.83 (s, 3H), 3.58 (s, 3H).

[0660] Step 9: 60% NaH (21.87 g, 546.88 mmol) was added to THF (2.5 L) at 0°C and the mixture was stirred at 0°C for 1 hour, then 2 L (99.59 g, 546.88 mmol) of compound was added dropwise, the mixture was stirred at 0°C for 2 hours, and a THF solution (300 mL) of compound 2K (100.00 g, 451.97 mmol) was added dropwise. The mixture was stirred at room temperature for 3 hours, then 10% HCl was added, followed by extraction with ethyl acetate, the organic phases were combined, dried with Na2SO4, and filtered and concentrated to obtain a crude product, which was slurried with MTBE to obtain a pale yellow solid 2A (120 g, yield: 95.73%).

[0661] 1 H NMR (400 MHz, DMSO) δ 9.47 (s, 1H), 7.74 (s, 1H), 7.58 (d, J = 16.0 Hz, 1H), 7.49 (d, J= 7.2 Hz, 1H), 7.36 - 7.28 (m, 2H), 6.49 (d, J = 16.0 Hz, 1H), 3.73 (s, 3H), 1.49 (s, 9H).

[0662] Compound 3

[0663]

[0664] Step 1: Na2CO3 (48.8 mg, 0.14 mL), Pd(PPh3)4 (4.88 mg, 0.01 mmol), and Compound 3A (28.3 mg, 0.08 mmol) were added to a dioxane / water (2 mL / 0.5 mL) solution of the racemic mixture of Compound 2H (50 mg, 0.07 mmol), and the mixture was reacted at 80 °C for 2 hours under nitrogen protection. The mixture was filtered, concentrated under reduced pressure, and the crude product was purified by high-speed column chromatography (DCM / EA=1 / 1) to obtain a racemic mixture of the pale yellow solid Compound 3B (40 mg, yield: 76%). LCMS: [M+H] + =796.4.

[0665] Step 2: A racemic mixture of Compound 3B (20 mg, 0.025 mmol) was dissolved in 6 M HCl (1 mL) / THF (0.5 mL) and stirred for 3 hours. The reaction mixture was purified by preparative HPLC (ACN / H2O 0 to 100%) to obtain a racemic mixture of white solid 3 (6 mg, yield: 45%), which was further separated using a chiral column to obtain Compound 3.

[0666] LCMS: [M+H] + =540.2.

[0667] 1 H NMR (400 MHz, DMSO) δ 8.46 (s, 1H), 7.79 (s, 1H), 7.51 (d, J = 8.4 Hz, 2H), 7.32 (d, J = 8.4 Hz, 2H), 7.03 - 6.89 (m, 3H), 6.68 (s, 3H), 4.68 (d, J= 4.8 Hz, 1H), 4.34 (d, J = 13.6 Hz, 1H), 4.09 (dd, J = 14.0, 4.8 Hz, 1H), 3.83 (s, 3H), 3.59 (s, 3H).

[0668] Compound 4

[0669]

[0670] Step 1: A 10 mL THF / H2O / MeOH solution of the racemic mixture of Compound 2J (150 mg, 0.23 mmol) and LiOH (25 mg, 0.59 mmol) was taken and stirred at room temperature for 3 hours. The pH was adjusted to 5 with 3 M hydrochloric acid, and the mixture was concentrated and purified using a silica gel column (DCM / MeOH) to obtain the racemic mixture of the white solid 4A (130 mg, yield: 88%). LCMS [M+1] + = 626.1.

[0671] Step 2: HATU (61 mg, 0.16 mmol) and DIEA (31 mg, 0.24 mmol) were each added to a 3 mL DMF solution of the racemic mixture of Compound 4A (50 mg, 0.08 mmol), N,O-dimethylhydroxylamine (16 mg, 0.16 mmol) was added under N2 conditions, and the mixture was stirred at room temperature for 3 hours. The mixture was concentrated with silica gel (DCM / MeOH) and purified to obtain a racemic mixture of the white solid Compound 4B (20 mg, yield: 38%). LCMS [M+1] + = 669.2.

[0672] Step 3: A racemic mixture of compound 4B (12 mg, 0.02 mmol) was dissolved in THF / 6M HCl = 1 / 1 (4 mL) and stirred at room temperature for 1 hour. The solution was concentrated and purified with silica gel (DCM / MeOH) to obtain a racemic mixture of white solid 4 (2.2 mg, yield: 22%), which was further separated using a chiral column to obtain white solid 4.

[0673] LCMS [M+H] + = 569.1.

[0674] 1H NMR (400 MHz, DMSO) δ 8.25 (s, 1H), 7.53 (d, J = 8.5 Hz, 2H), 7.41 (s, 1H), 7.31 (d, J = 8.5 Hz, 2H), 7.20 (d, J = 0.9 Hz, 1H), 7.15 (s, 1H), 6.66 (t, J = 7.7 Hz, 1H), 6.21 (s, 1H), 6.16 (d, J = 7.9 Hz, 1H), 6.06 (d, J = 7.5 Hz, 1H), 5.61 (s, 1H), 5.07 (d, J = 4.8 Hz, 1H), 4.83 (s, 2H), 4.78 (t, J = 4.8 Hz, 1H), 4.32 (d, J = 13.9 Hz, 1H), 4.16 (s, 1H), 3.90 (s, 3H), 3.84 (s, 3H), 3.09 (s, 3H).

[0675] Compound 5

[0676]

[0677] Step 1: HATU (36.4 mg, 0.1 mmol) and DIEA (18.6 mg, 0.14 mmol) were mixed under N2 with a DMF (3 mL) solution of the racemic mixture of Compound 4A (30 mg, 0.05 mmol), then O-methylhydroxylamine (8 mg, 0.10 mmol) was added and stirred at room temperature for 3 hours. The mixture was concentrated and purified by silica gel (DCM / MeOH) chromatography to obtain a racemic mixture of the white solid Compound 5A (20 mg, yield: 65%). LCMS [M+1] + = 655.2.

[0678] Step 2: A racemic mixture of compound 5A (12 mg, 0.03 mmol) was dissolved in THF / 6M HCl = 1 / 1 (4 mL) and stirred at room temperature for 1 hour. The solution was concentrated and purified by silica gel (DCM / MeOH) chromatography to obtain a racemic mixture of white solid compound 5 (2.6 mg, yield 31%), which was further separated using a chiral column to obtain compound 5.

[0679] LCMS [M+H] + = 555.1.

[0680] 1 H NMR (400 MHz, DMSO) δ 11.27 (s, 1H), 8.26 (s, 1H), 7.54 (d, J = 8.5 Hz, 2H), 7.42 (s, 1H), 7.30 (d, J = 8.3 Hz, 2H), 7.20 (s, 1H), 7.16 (s, 1H), 7.11 (t, J = 7.5 Hz, 1H), 6.87 (d, J = 18.2 Hz, 3H), 5.65 (s, 1H), 5.27 (s, 1H), 4.60 (d, J = 4.4 Hz, 1H), 4.46 (d, J = 13.9) Hz, 1H), 3.84 (s, 3H), 3.74 (dd, J = 14.1, 4.1 Hz, 1H), 3.54 (s, 3H).

[0681] Compound 6

[0682]

[0683] Step 1: A racemic mixture of compound 4A (30.0 mg, 0.05 mmol), HATU (36.5 mg, 0.10 mmol), and DIEA (18.6 mg, 0.14 mmol) was stirred in DMF (3 mL) for 5 minutes. Dimethylamine hydrochloride (7.8 mg, 0.10 mmol) was added to the mixture and stirred for 10 minutes.

[0684] The solution was extracted twice with EA. The organic layer was washed with saturated saline, dried with Na2SO4, concentrated under reduced pressure, and purified using a silica gel column (DCM / MeOH=10 / 1) to obtain a racemic mixture of Compound 6A (16.0 mg, yield 51%). LCMS [M + H] + = 653.2.

[0685] Step 2: A racemic mixture of Compound 6A (16.0 mg, 0.02 mmol) was mixed with THF (0.5 mL), 6 M HCl (0.5 mL) was added at 0°C, and the mixture was stirred at room temperature for 4 hours. The concentrate was purified by preparative high-performance liquid chromatography to obtain a racemic mixture of white solid 6 (5.9 mg, yield: 46%), which was further separated using a chiral column to obtain Compound 6.

[0686] LCMS[M+H] + =553.2.

[0687] 1 H NMR (400 MHz, DMSO) δ 8.25 (s, 1H), 7.51 (d, J = 8.4 Hz, 2H), 7.41 (s, 1H), 7.35 (d, J = 8.4 Hz, 2H), 7.18 (d, J = 19.6 Hz, 2H), 6.73 (d, J) = 7.4 Hz, 1H), 6.40 - 6.17 (m, 3H), 5.62 (s, 1H), 4.98 (s, 1H), 4.73 (s, 1H), 4.39 (d, J = 13.4 Hz, 1H), 4.15 (dd, J = 13.3, 4.9 Hz, 1H), 3.84 (s, 3H), 3.29 (s, 3H), 2.79 (s, 3H).

[0688] Compound 7

[0689]

[0690] Step 1: A racemic mixture 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) were dissolved in 1,4-dioxane (2 mL). The reaction was mixed under nitrogen protection and stirred at 100°C for 16 hours. After the reaction was complete, water was added, the mixture was quenched, extracted with EA, and separated. The organic phase was concentrated and purified using a silica gel column (DCM / EA=1 / 1) to obtain a racemic mixture of pale yellow solid 7A (10 mg, yield: 20%). LCMS [M+H] + = 639.2.

[0691] Step 2: A racemic mixture 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 mixture was purified by high-speed column chromatography (ACN-H2O=0~100%) to obtain a racemic mixture of white solid 7 (4 mg, yield: 47%), which was further separated by a chiral column to obtain compound 7.

[0692] LCMS [M+H] + = 539.1.

[0693] 1H NMR (400 MHz, DMSO) δ 8.58 (d, J = 2.4 Hz, 1H), 7.75 (d, J = 1.6 Hz, 1H), 7.51 (d, J = 8.4 Hz, 2H), 7.31 (d, J = 8.4 Hz, 2H), 7.13 (d, J = 8.4 Hz, 2H) 1.6 Hz, 1H), 7.05 (d, J = 1.6 Hz, 1H), 6.68 (t, J = 7.6 Hz, 1H), 6.58 - 6.54 (m, 1H), 6.23 (s, 1H), 6.14 (m, 2H), 5.54 (s, 1H), 5.39 (d, J = 5.2 Hz, 1H), 4.82 (s, 2H), 4.64 (t, J = 5.2 Hz, 1H), 4.26 (d, J = 14.0 Hz, 1H), 3.95 (m, 1H), 3.82 (s, 3H), 3.58 (s, 3H).

[0694] Compound 8

[0695]

[0696] Step 1: Pd(PPh3)4 (9 mg, 0.0075 mmol) and CuI (28.5 mg, 0.015 mmol) were added to a 5 mL DMF solution of a racemic mixture of compound 2H (54 mg, 0.075 mmol) and compound 8A (215 mg, 0.6 mmol), then the mixture was purged with nitrogen for 2 minutes and reacted in a microwave at 120°C for 2 hours. The crude product obtained by concentration was purified using a preparative chromatography column to obtain a racemic mixture of 8B in the form of a white solid (20 mg, 40.9%).

[0697] LCMS: [M+H-C4H8] + =595.2.

[0698] Step 2: An aqueous solution of HCl (0.5 mL, 6 M) was added to a THF (1 mL) solution of a racemic mixture of Compound 8B (20 mg, 0.0308 mmol), and the reaction mixture was reacted at room temperature for 3 hours. The crude product obtained by concentration was purified by preparative HPLC to obtain a racemic mixture of white solid 8 (9 mg, yield: 53.1%), which was further separated using a chiral column to obtain Compound 8.

[0699] LCMS: [M+H] + = 551.2.

[0700] 1 H NMR (400 MHz, DMSO) δ 9.53 (s, 2H), 8.94 (d, J = 4.9 Hz, 2H), 7.64 (d, J = 2.8 Hz, 2H), 7.55 - 7.43 (m, 3H), 7.36 (d, J = 8.6 Hz, 2H), 7.14 (t, J = 7.6 Hz, 1H), 7.06 - 6.82 (m, 3H), 5.66 (d, J = 58.4 Hz, 2H), 4.74 (d, J = 4.6 Hz, 1H), 4.41 (d, J = 13.8 Hz, 1H), 4.18 (d, J) = 4.8 Hz, 1H), 3.86 (s, 3H), 3.60 (s, 3H).

[0701] Compound 9

[0702]

[0703] Step 1: Compound 1 (1.00 g, 2.21 mmol) and Compound 9A (3.58 g, 22.08 mmol) were dissolved in a TFE / trichloromethane solution (CHCl3 / TFE=9 / 1, 18 mL), placed in a 20 mL syringe, and mounted on an injection pump. The injection pump was connected to an FEP tube, which was sequentially wound around two quartz column sleeves, with a single 250 W UV lamp tube placed inside each quartz column sleeve. The temperature of the two column sleeves was cooled to -5°C using a cold circulation pump, and a room temperature water bath was added outside the entire lamp column sleeve system. After the UV lamps were stably excited, the injection pump was operated to inject the reaction solution into the FEP tubes at a rate of 30 mL / h, and the irradiation time of the reaction solution was maintained for 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 raw material to obtain a crude product. Ethyl acetate was added to the crude product to dilute it, and the reaction was carried out for 1 hour under conditions of 65°C. After further concentration, a racemic mixture (0.96 g, yield 71%) of the target crude product 9B in the form of a yellow oil was obtained.

[0704] LCMS [M+H] + =615.5.

[0705] Step 2: A racemic mixture of compound 9B (1.4 g, 2.27 mmol) was dissolved in methanol (100 mL), then NaOMe (0.3 g, 5.7 mmol) was added at 0°C, and the reaction mixture was reacted at 65°C for 1 hour. After concentrating the reaction mixture, it was separated by column chromatography (0.5% formic acid dissolved in ethyl acetate / petroleum ether = 1 / 3) to obtain a racemic mixture of target product 9C in the form of a yellow oil (0.96 g, yield 68%).

[0706] LCMS [M+H] + =615.1.

[0707] Step 3: A racemic mixture of compound 9C (0.60 g, 0.977 mmol) and AcOH (1.06 g, 17.586 mmol) was dissolved in MeCN (40 mL) and DCM (40 mL), cooled to 0°C, protected with N2, and STAB (1.04 g, 4.89 mmol) was added in batches and stirred at room temperature for 1 hour. The reaction mixture was quenched with water, an aqueous solution of NaHCO3 was added, and the mixture was extracted twice with DCM. The organic layer was dried, concentrated under reduced pressure, and purified using a silica gel column (PE:EA) to obtain a racemic mixture of white solid 9D (0.32 g, yield 53%).

[0708] LCMS: [M+H] + =617.2.

[0709] Step 4: A racemic mixture 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), then tBuXPhos Pd G3 (51 mg, 0.06 mmol) was added, and the mixture was heated to 85°C and reacted for 3 hours. The reaction mixture was concentrated, diluted with a MeOH / DCM solution (MeOH / DCM=1 / 1), filtered, and the filtrate was concentrated and separated by column chromatography (EA / PE=60%) to obtain a racemic mixture of target product 9E in the form of a brown oil (810 mg, yield 44%).

[0710] LCMS: [MH] - =567.0.

[0711] Step 5: A racemic mixture of compound 9E (300 mg, 0.53 mmol) and Pd / C (10%, 150 mg) were dissolved in MeOH (15 mL) and reacted at room temperature for 2 hours under H2 conditions. The reaction mixture was filtered, the filtrate was concentrated, and then separated by column chromatography to obtain a racemic mixture of the white solid target product 9F (270 mg, crude product yield not calculated).

[0712] LCMS: [M+H] +=479.4.

[0713] Step 6: A racemic mixture of compound 9F (360 mg, 0.75 mmol), compound 2G (268 mg, 0.75 mmol), and K2CO3 (207 mg, 1.5 mmol) were added to 5 mL of DMF 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 with anhydrous Na2SO4. After filtration and concentration, the crude product was purified using a silica gel column (EA / DCM 0 to 50%) to obtain a racemic mixture of yellow solid 9G (360 mg, yield: 78%).

[0714] LCMS: [MH] - =609.2.

[0715] Step 7: A racemic mixture of compound 9G (340 mg, 0.56 mmol) was dissolved in DMF (5 mL), compound 2I (1600 mg, 4.46 mmol), Pd(PPh3)4 (65 mg, 0.06 mmol), and CuI (21 mg, 0.11 mmol) were added, and the mixture was reacted at 110°C for 16 hours under nitrogen protection. After cooling to room temperature, the reaction mixture was immediately purified using a silica gel column (PE / EA=1 / 1) to obtain a racemic mixture of white solid 9H (180 mg, yield: 61%).

[0716] LCMS [M+H] + =530.0.

[0717] Step 8: MsCl (171 mL, 1.5 mmol) was added to a mixture of a racemic mixture of compound 9H (80 mg, 0.15 mmol) and pyridine (0.5 mL) at 0°C and reacted for 1 hour at 0°C. The mixture was diluted with ethyl acetate (5 mL), washed with 1 M HCl (5 mL), and separated. The organic phase was purified using a silica gel column (DCM / EA=1 / 1) to obtain a racemic mixture of white solid 9I (90 mg, yield: 97%).

[0718] LCMS [M+H] + =608.1.

[0719] Step 9: A racemic mixture of compound 9I (90 mg, 0.15 mmol) was dissolved in DMF (0.5 mL), NaCN (36 mg, 0.75 mmol) was added, and the mixture was stirred at room temperature for 16 hours. The mixture was extracted with ethyl acetate, the organic phase was separated, and the solution was dried with anhydrous Na2SO4. After filtration and concentration, the crude product was purified using a silica gel column (DCM / EA=1 / 1) to obtain a racemic mixture of white solid 9J (70 mg, yield: 88%).

[0720] LCMS [M+H] + =539.1.

[0721] Step 10: A racemic mixture of compound 9J (10 mg, 0.016 mmol) was dissolved in THF (0.5 mL), a 2 M lithium aluminum hydride THF solution (0.08 mL) was added at 0°C, the temperature was slowly raised to room temperature, and the mixture was stirred for 1 hour. Na2SO4·10H2O was added and quenched, the resulting mixture was filtered, and the filtrate was purified using a medium-pressure preparative column (ACN / H2O = 0%~100%, containing 0.1% formic acid) to obtain a racemic mixture of white solid 9 (7 mg, yield: 70%), which was further separated using a chiral column to obtain compound 9.

[0722] LCMS [M+H] + =515.1.

[0723] 1 H NMR (400 MHz, DMSO) δ 8.26 (s, 1H), 7.42 (s, 1H), 7.22 (d, J = 4.8 Hz, 2H), 7.13 (d, J = 8.4 Hz, 2H), 7.09 - 7.04 (m, 3H), 6.81 - 6.76 (m, 2H), 6.71 (d, J = 8.8 Hz, 2H), 3.97 (s, 3H), 3.66 (s, 3H), 3.23 (d, J = 13.6 Hz, 5H), 3.13 (m, 1H), 2.93 (s, 1H).

[0724] Compound 10

[0725]

[0726] Step 1: NaH (9.06 g, 234.6 mmol) was slowly added to a 120 mL THF solution of 10A (12.11 g, 70 mmol) at 0 °C. The mixture was stirred at room temperature for 0.5 hours. BnOH (16.2 g, 150 mmol) was added again 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 with anhydrous Na2SO4, filtered, and concentrated under reduced pressure to obtain 19.6 g of compound 10B, with a yield of 89%. LCMS [M+H] + =317.2.

[0727] Step 2: MeMgBr solution (124.9 mL, 124.9 mmol) was slowly added dropwise to a THF solution (150 mL) containing 10B (13.16 g, 41.6 mmol) at -30 °C. The mixture was stirred again at room temperature for 4.3 hours. The mixture was quenched with 6 N HCl and stirred continuously for 2 hours. The organic phase was washed with 1 N NaOH and water, separated, dried with anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel chromatography to obtain 7.12 g of compound 10C, with a yield of 46%. LCMS [M+H] + =334.2.

[0728] Step 3: Compound 10C (8.5 g, 25.5 mmol) was dissolved in EA (60 mL), Pd(OH)2 (850 mg) was added, and the mixture was stirred at room temperature for 18 hours under hydrogen ballooning action. By concentration, 3.9 g of white solid 10D was obtained, and the yield was 100%. LCMS [M+H] + = 154.2.

[0729] Step 4: BnBr (4.36 g, 25.5 mmol) was added dropwise to a 40 mL acetone solution of compound 10D (3.9 g, 25.5 mmol) and K2CO3 (9.85 g, 71.4 mmol), stirred at room temperature for 48 hours, acidified with acetic acid, diluted with water, extracted with EA, concentrated the organic layer, and washed with petroleum ether to obtain 4.80 g of yellowish-white solid 10E, with a yield of 77%. LCMS [M+H] + = 244.1.

[0730] Step 5: NaOH (2.368 g, 59.2 mmol) and 4-bromobenzaldehyde (3.65 g, 19.73 mol) were added to a 60 mL MeOH solution of Compound 10E (4800 mg, 19.73 mmol). The reaction mixture was stirred at 70 °C for 18 hours. It was cooled and acidified with AcOH. Extraction was performed with dichloromethane. The organic layer was washed with water and saline solution, dried, and concentrated. The crude product was slurried with PE / EA to obtain 5.0 g of white solid 10F, with a yield of 60%. LCMS [M+H] + =410.2.

[0731] Step 6: NaOH (785 mg, 19.6 mmol, 7.0 eq) and H2O2 (12.5 mL) were added to a MeOH / H2O (130 mL / 65 mL) solution of Compound 10F (1150 mg, 2.8 mmol, 1.0 eq). 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 saline solution, dried, and concentrated to obtain 670 mg of white solid 10 G, with a yield of 57%. LCMS [M+H] + = 424.0.

[0732] 1 H NMR (400 MHz, DMSO) δ 9.99 (s, 1H), 8.56 (d, J= 2.4 Hz, 1H), 8.18 (d, J = 8.8 Hz, 2H), 7.94 (d, J = 2.4 Hz, 1H), 7.80 (d, J = 8.8 Hz, 2H), 7.60 - 7.37 (m, 5H), 5.34 (s, 2H).

[0733] Step 7: Compound 10G (2.5g, 5.9mmol) and Compound 2A (9.8g, 35.38mmol) were dissolved in CHCl3 / TFE (7 / 3, 20mL), and the reaction mixture was injected via a syringe at a rate of 12mL / h through an injection pump into a coil wound in a jacketed glass cylinder equipped with a 250W UV lamp. While controlling the internal reaction temperature to 0–5°C by adjusting the temperature of an external circulation cooler, 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, yielding a racemic mixture (3.6g, 75% yield) of the pale yellow oil-form product 10H. LCMS [M+H] + =700.9.

[0734] Step 8: A racemic mixture of Compound 10H (2.5 g, 3.56 mmol) was dissolved in methanol (60 mL), then NaOMe (481 mg, 8.91 mmol) was added at 0 °C, and the reaction mixture was subsequently stirred at 65 °C for 1.5 hours. After the reaction was complete, the reaction mixture was concentrated and extracted with EA, washed with water, NH4Cl solution, and saturated saline, and finally dried with anhydrous sodium sulfate and concentrated under reduced pressure. The mixture was then purified using a silica gel column (0.2% FA, EA / PE=1 / 3) to obtain a racemic mixture of Compound 10I (3.0 g, crude product). LCMS [M+H] + =701.0.

[0735] Step 9: The racemic mixture of Compound 10I (3.0 g, 4.28 mmol) was dissolved in an ACN / CHCl3=1 / 1 (40 mL / 40 mL) mixed solvent, and Na(AcO)3BH (4.533 g, 21.38 mmol) and AcOH (2.566 g, 47.0 mmol) were added at 0°C, followed by stirring the reaction mixture at room temperature for 2 hours. After the reaction was complete, the reaction mixture was concentrated, extracted with EA, washed with water and saturated saline, and finally dried with anhydrous sodium sulfate and concentrated under reduced pressure. It was then purified using a silica gel column (0.2% FA, EA / PE=3 / 2) to obtain 500 mg of the racemic mixture of Compound 10J. LCMS [M+H] + =703.0.

[0736] 1 H NMR (400 MHz, CDCl3) δ 8.06 (s, 1H), 7.86 (d, J = 1.9 Hz, 1H), 7.43 (d, J = 4.4 Hz, 4H), 7.40 (dd, J = 8.2, 5.0 Hz, 2H), 7.28 (s, 2H), 7.15 (d, J = 8.5 Hz, 1H), 7.10 (d, J = 2.0 Hz, 1H), 7.06 (d, J = 8.7 Hz, 2H), 7.00 (t, J = 7.9 Hz, 1H), 6.90 (s, 1H), 6.57 (d, J = 7.6 Hz, 1H), 6.35 (s, 1H), 5.14 (s, 2H), 5.06 (d, J = 6.0 Hz, 1H), 4.41 (d, J = 13.9 Hz, 1H), 3.95 (dd, J = 14.0, 6.0 Hz, 1H), 3.67 (s, 3H), 1.51 (s, 9H).

[0737] Step 10: Pd2(dba)3 (128 mg, 0.14 mmol) was added to a 25 mL NMP solution containing a racemic mixture of compound 10J (500 mg, 0.71 mmol), DPPF (155 mg, 0.28 mmol), and Zn(CN)2 (208 mg, 1.80 mmol). The reaction mixture was heated to 150 °C under N2 protection and reacted for 1.2 hours. The solution was diluted with water and extracted with EA, the organic layer was washed with water and saline solution, dried and concentrated, and purified using a silica gel column (EA / PE=1 / 1) to obtain 300 mg of a racemic mixture of yellow solid 10K, with a yield of 65%. LCMS: [M+H] + =650.0.

[0738] Step 11: Pd(OH)2 / C (10%, 0.1 g) was added to a 7 mL solution of EA / MeOH / THF / DCM = 20:2:2:0.2 of the racemic mixture of Compound 10K (300 mg, 0.46 mol). The mixture was stirred at room temperature for 18 hours under hydrogen ballooning. The solid was removed by filtration, and the filter cake was washed with MeOH / DCM (1 / 10). The combined filtrate was concentrated to obtain 0.22 g of a racemic mixture of 10 L of white solid, with a yield of 87.0%. LCMS: [M+H] + =560.2.

[0739] Step 12: K2CO3 (116 mg, 0.78 mmol) was added to a 3 mL DMF solution of a 10 L racemic mixture of Compound (220 mg, 0.39 mmol) and Compound 2 G (150 mg, 0.39 mmol). The mixture was stirred at 60 °C for 1 hour. Water was added for quenching, and the mixture was extracted with EtOAc. The organic phase was separated, dried with anhydrous Na2SO4, filtered, and concentrated. The residue was purified by column chromatography (EA-PE / DCM = 0–50%) to obtain 221 mg of a yellow solid 10 M racemic mixture, with a yield of 82%. LCMS [M+H-C4H8] + =636.1.

[0740] Step 13: A racemic mixture of 10 M compound (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 the mixture was stirred by microwave at 135°C for 5 hours under N2 protection. Water was added and extracted with EA, and the organic layer was washed with water and saturated saline, then dried and concentrated. The crude product was dissolved in DCM, and Boc2O (2 eq.), DIPEA (3 eq.), and DMAP (0.2 eq.) were added. The mixture was stirred at 40°C for 18 hours. This was concentrated and purified by high-speed chromatography (DCM / EA=1:1, DCM:MeOH=20:1) to obtain 60 mg of a white solid 10N racemic mixture, with a yield of 98%. LCMS [M+H] + =611.2.

[0741] Step 14: H2O (2 mL), MeOH (2 mL), and LiOH (12.6 mg, 0.30 mmol) were added to a THF (2 mL) solution of a 10N racemic mixture (60 mg, 0.1 mmol), and the mixture was stirred at room temperature for 5 hours. Purification by reverse-phase chromatography (MeCH / HCO2H / H2O) yielded 30 mg of a white solid 10N racemic mixture, with a yield of 51%. LCMS [M+H] + =597.2.

[0742] Step 15: A racemic mixture 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%) yielded 10 mg of a racemic mixture of the white solid 10P, with a yield of 33%. LCMS:[M+H] + =640.3.

[0743] Step 16: 6M HCl (0.5 mL) was added dropwise to a THF (0.5 mL) solution of the racemic mixture of Compound 10P (10 mg, 0.016 mmol), and the solution was stirred at room temperature for 4 hours. The reaction mixture was separated by reverse-phase preparative column chromatography ACN / H2O=(5%–95%, +0.1% NH4HCO3) to obtain 1.1 mg of the racemic mixture of the white solid 10, with a yield of 10%, which was further separated by a chiral column to obtain Compound 10. LCMS: [M+H] + =540.2.

[0744] Compound 11

[0745]

[0746] Step 1: A 1 mL DMF solution of the racemic mixture of Compound 4A (10 mg, 0.02 mmol), Compound 11A (12.7 mg, 0.1 mmol), tert-dodecyl mercaptan (38.4 mg, 0.2 mmol), TMP (0.4 mg, 0.04 mmol), and zinc meso-tetraphenylporphyrin (1.3 mg, 0.001 mmol) was transferred to a microwave tube. The microwave tube was irradiated under a 25 W red lamp and the temperature was maintained at 80°C. EDCI (36.6 mg, 0.2 mmol, dissolved in 1 mL DMF) was added to the reaction system dropwise. The reaction mixture was continuously stirred for 30 minutes at 80°C under a 25 W red lamp. The reaction solutions of the three parallel reactions were combined and purified by reverse-phase column chromatography (H2O:ACN=0–100%) to obtain 9 mg of a racemic mixture of white solid 11B, with a yield of 33%. LCMS: [M+H-C4H8] + =526.2.

[0747] Step 2: 1 mL of 6 M HCl was added to a 1 mL THF solution of the racemic mixture of Compound 11B (25 mg, 0.04 mmol). The reaction mixture was stirred overnight at room temperature and concentrated under reduced pressure. It was then purified by reverse-phase column chromatography (H2O:ACN=0–100%) to obtain 9 mg of the racemic mixture of the white solid 11, with a yield of 40%. This was further separated using a chiral column to obtain Compound 11. LCMS [M+H]+=482.0.

[0748] 1 H NMR (400 MHz, DMSO) δ 8.25 (s, 1H), 7.53 (d, J = 8.5 Hz, 2H), 7.41 (s, 1H), 7.30 (d, J = 8.5 Hz, 2H), 7.16 (d, J = 12.3 Hz, 2H), 6.73 (t, J = 7.7 Hz, 1H), 6.35 (s, 1H), 6.22 (t, J = 7.7 Hz, 2H), 5.34 (s, 1H), 4.90 - 4.73 (m, 3H), 4.47 (s, 1H), 4.03 (dd, J = 14.3, 6.1 Hz, 1H), 3.85 (s, 3H), 2.78 - 2.60 (m, 1H), 2.08 (dd, J = 12.8, 6.1 Hz, 1H).

[0749] Compound 12

[0750]

[0751] Step 1: A racemic mixture of compound 9H (42.3 mg, 0.08 mmol) and LiOH (16.8 mg, 0.4 mmol) was dissolved in MeOH / H2O (5 mL / 1 mL), stirred at room temperature for 12 hours, pH adjusted to 2–3 with 1 M aqueous hydrochloric acid, and extracted with ethyl acetate (20 mL). The organic phase was dried with sodium sulfate and concentrated to obtain 35 mg of a racemic mixture of the white solid 12A, with a yield of 84.6%. LCMS [M+H] + = 516.2.

[0752] Step 2: The racemic mixture 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), HATU (34 mg, 0.09 mmol), and DMF (3 mL), and stirred at room temperature for 12 hours. Then, 50 mL of water was added to the reaction mixture, extracted with ethyl acetate, washed with saturated saline, dried and concentrated, and the crude product was purified using a silica gel column (PE / EA=1 / 2) to obtain 33 mg of the racemic mixture of the white solid 12B, with a yield of 83.7%. LCMS [M+H] + =658.2.

[0753] Step 3: An aqueous solution of HCl (1 mL, 6 M) was added to a 3 mL THF solution of a racemic mixture of Compound 12 B (33 mg, 0.05 mmol), and the reaction mixture was reacted at room temperature for 12 hours. The crude product obtained by concentration was purified using a preparative chromatography column to obtain 20 mg of a racemic mixture of white solid 12, with a yield of 71.4%, and this was further separated using a chiral column to obtain Compound 12.

[0754] LCMS [M+H] + =558.2.

[0755] 1 H NMR (400 MHz, DMSO) δ 8.45 (s, 2H), 8.24 (d, J= 0.6 Hz, 1H), 7.40 (d, J = 0.6 Hz, 1H), 7.19 (d, J = 1.0 Hz, 1H), 7.14 (d, J = 0.9 Hz, 1H), 7.10 - 7.01 (m, 4H), 6.97 (dd, J = 10.1, 7.4 Hz, 3H), 6.59 (d, J = 9.0 Hz, 2H), 5.32 (s, 1H), 4.65 (d, J = 4.8 Hz, 1H), 4.30 (d, J = 14.1 Hz, 1H), 3.90 - 3.86 (m, 1H), 3.84 (s, 3H), 3.59 (s, 3H), 3.14 (s, 2H), 2.65 (s, 2H).

[0756] Compound 13

[0757]

[0758] Step 1: A racemic mixture of Compound 12A (350 mg, 0.68 mmol) was dissolved in DMF (2 mL), and then N,O-dimethylhydroxylamine hydrochloride (132.5 mg, 1.36 mmol), HATU (310 mg, 0.82 mmol), and DIEA (263.2 mg, 2.04 mmol) were added sequentially. The reaction mixture was stirred at room temperature for 2 hours, then immediately rotary dried and purified by reverse-phase chromatography (acetonitrile / water = 5%–95%, 214 nm, 20 min) to obtain 300 mg of a racemic mixture of the white solid Compound 13A, with a yield of 79%. LCMS [M+Na] + =581.2.

[0759] Step 2: Iodomethyl pivalate (2000 mg, 8.26 mmol) was dissolved in a solution of anhydrous tetrahydrofuran (15 mL), and isopropyl magnesium 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. A racemic mixture 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 overnight at room temperature. The reaction mixture was diluted with water (15 mL), extracted with dichloromethane (15 mL x 2), washed with saline solution (15 mL x 2), dried with anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified using a preparative chromatography column to obtain 5.5 mg of a racemic mixture of white solid 13, with a yield of 5.8%, which was further separated using a chiral column to obtain compound 13. LCMS[M+H] + =530.0.

[0760] 1 ¹H NMR (400 MHz, DMSO- d 6) δ 8.25 (d, J = 0.8 Hz, 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 = 1.2 Hz, 1H), 7.12 (d, J = 1.2 Hz, 1H), 6.93-6.91 (m, 2H), 5.40 (s, 1H), 4.83 (d, J = 4.8 Hz, 1H), 4.40-4.36 (m, 1H), 3.80 (s, 3H), 3.76-3.73 (m, 4H), 3.10 (t, J = 12.0 Hz, 2H).

[0761] Compound 14

[0762]

[0763] Step 1: A 160 mL NMP solution of a racemic mixture 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) was stirred at 150 °C for 4 hours. The mixture was extracted with H2O and EA, and the combined organic layer was washed with saline solution (2 × 10 mL). The mixture was purified by high-speed column chromatography (PE / EA=1 / 1) to obtain a racemic mixture of yellow solid 14A (1.9 g, 90% yield).

[0764] LCMS: [M+H] + =564.2.

[0765] Step 2: Pd(OH)2 / C (10%, 1.4 g) was added to an EA / MeOH / THF / DCM solution (EA / MeOH / THF / DCM = 20:2:0.2:0.2, 120 mL) of a racemic mixture of compound 14A (2.8 g, 4.97 mmol) under N2 protection. The suspension was stirred at room temperature for 4 hours under an H2 atmosphere. The reaction mixture was filtered, and the filter cake was washed with a MeOH / DCM solution (MeOH / DCM = 1 / 10). The combined filtrate was concentrated and purified by high-speed column chromatography (DCM / MeOH = 10 / 1) to obtain a racemic mixture of yellow solid 14B (1.6 g, 68% yield).

[0766] LCMS: [MH] + =474.2.

[0767] Step 3: At 0°C, trifluoromethanesulfonic acid anhydride (1.1 g, 4.06 mmol, 1.2 eq.) was slowly added dropwise to 150 mL of a DCM solution containing the racemic mixture 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. The organic layer was collected after washing with 25 mL of saturated sodium bicarbonate solution, and the aqueous layer was extracted with DCM (20 mL). The combined organic layer was sequentially washed with 10% citric acid (20 mL) and water (20 mL) and dried. The filtrate was concentrated under reduced pressure and purified by high-speed column chromatography (DCM / EA=10 / 1) to obtain the racemic mixture of Compound 14C in the form of a white powder (1.7 g, 83% yield). LCMS: [M+H] + =606.2.

[0768] Step 4: The racemic mixture 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 was mixed under nitrogen protection and stirred at 100°C for 16 hours. After the reaction was complete, the mixture was extracted with EA and concentrated to obtain 50 mg of the racemic mixture of Compound 14E; the crude product yield was not calculated. LCMS [M+H] + =639.2.

[0769] Step 5: 6M HCl (0.5mL) was added to a solution in which a racemic mixture (50mg) of compound 14E was dissolved in THF (0.5mL) and stirred at room temperature for 4 hours. The reaction mixture was purified by high-speed column chromatography (ACN-H2O=0~100%) to obtain 6mg of a racemic mixture of white solid 14, with a yield of 12%. This was further separated using a chiral column to obtain compound 14.

[0770] LCMS [M+H]+ =539.2.

[0771] 1 H NMR (400 MHz, DMSO) δ 7.78 (s, 1H), 7.47 (d, J = 8.6 Hz, 2H), 7.31 (d, J = 8.6 Hz, 2H), 7.26 (s, 1H), 7.09 - 7.03 (m, 2H), 7.02 - 6.94 (m, 4H), 6.92 (d, J = 1.6 Hz, 1H), 5.51 (s, 1H), 5.39 (d, J = 5.3 Hz, 1H), 4.67 (t, J = 5.1 Hz, 1H), 4.39 (d, J = 13.9 Hz, 1H), 4.18 (d, J = 18.8 Hz, 2H), 4.15 - 4.07 (m, 1H), 3.80 (s, 3H), 3.58 (s, 3H).

[0772] 화합물 15

[0773]

[0774] Step 1: At room temperature, HBF4 (0.85 mL, 4.79 mmol) was added dropwise to ethanol (5 mL) containing a racemic mixture of Compound 2 (170 mg, 0.32 mmol). After stirring for 15 minutes, the reaction mixture was cooled to 0°C once it became clear, and tert-butyl nitrite (65.0 mg, 0.63 mmol) was added. After 30 minutes, the reaction mixture was diluted with diethyl ether (8 mL). A solid was obtained by filtration, washed twice with diethyl 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. After filtering the aqueous solution, it was a brown solid. The solid was purified by high-speed column chromatography (ACN / H2O) to obtain 20 mg of a racemic mixture of yellow solid 15A, with a yield of 12.3%. LCMS [M+H] + = 541.0.

[0775] Step 2: The racemic mixture of compound 15A (20.0 mg, 0.04 mmol) and LiOH (34.8 mg, 0.40 mmol) was dissolved in THF / H2O (5 mL / 1 mL) and stirred at room temperature for 6 hours. Purification by high-speed column chromatography (ACN / H2O) yielded 17.0 mg of white solid 15B, with a yield of 85.3%. LCMS [M+H] + = 527.0.

[0776] 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 hours. The mixture was purified by high-speed column chromatography (ACN / H2O) to obtain 9.0 mg of a racemic mixture of white solid 15, with a yield of 55.4%. This was further separated by a chiral column to obtain compound 15.

[0777] LCMS [M+H] + = 570.0.

[0778] 1 H NMR: (400 MHz, CDCl3) δ 9.09 (s, 1H), 8.25 (s, 1H), 7.53 (d, J = 8.4 Hz, 2H), 7.41 (s, 1H), 7.30 (d, J = 8.4 Hz, 2H), 7.21 (s, 1H), 7.15 (s, 1H), 6.85 (s, 1H), 6.83 (d, J =8.4 Hz, 1H), 6.56 - 6.36 (m, 3H), 5.63 (s, 1H), 5.11 (d, J = 4.8 Hz, 1H), 4.79 (t, J = 4.8 Hz, 1H), 4.38 (d, J = 7.2 Hz, 1H), 4.18 - 4.13 (m, 1H), 3.90 (s, 3H), 3.84 (s, 3H), 3.09 (s, 3H).

[0779] Compound 16

[0780]

[0781] Step 1: 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) were added to a 10 mL DMF solution of the racemic mixture of Compound 14C (2.00 g, 3.30 mmol), stirred under nitrogen at 115 °C in a microwave for 2 hours, and purified using a silica gel column (PE / EA=1 / 1) to obtain 1.5 g of the racemic mixture of the white solid 16A, with a yield of 86%. LCMS [M + H] + =525.0.

[0782] Steps 2 and 3: A racemic mixture of compound 16A (100.00 mg, 0.19 mmol) and LiOH (20.00 mg, 0.25 mmol) were dissolved in MeOH / H2O (5 mL / 1 mL), stirred at room temperature for 12 hours, adjusted to pH 2–3 with a 1 M aqueous hydrochloric acid solution, and extracted with ethyl acetate (20 mL). The organic phase was dried with sodium sulfate and concentrated to obtain the racemic mixture of crude product 16B.

[0783] The racemic mixture of the crude product 16B was dissolved in DMF (3 mL), 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, and the mixture was stirred at room temperature for 12 hours. 50 mL of water was added to the reaction mixture, extracted with ethyl acetate, washed with saturated saline solution, dried and concentrated, and the crude product was purified using a silica gel column (PE / EA=1 / 2) to obtain 20 mg of the racemic mixture of white solid 16, with a yield of 17%, which was further separated using a chiral column to obtain compound 16.

[0784] LCMS [M+H] + = 566.2.

[0785] 1 H NMR (400 MHz, DMSO) δ 8.25 (s, 1H), 7.47 (d, J = 7.3 Hz, 2H), 7.41 (s, 1H), 7.32 (dd, J = 8.0, 5.0 Hz, 2H), 7.23 (s, 1H), 7.15 (s, 1H), 7.04 (t, J = 6.8 Hz, 2H), 6.96 (s, 3H), 5.77 (dd, J = 15.3, 5.4 Hz, 1H), 5.62 (d, J = 7.0 Hz, 1H), 5.06 (dd, J = 11.7, 5.0 Hz, 1H), 4.77 (t, J= 7.8 Hz, 1H), 4.67 (s, 1H), 4.62 - 4.50 (m, 2H), 4.47 (d, J = 13.8 Hz, 1H), 4.34 - 4.06 (m, 1H), 4.01 (dd, J = 16.6, 9.9 Hz, 1H), 3.93 (dd, J = 12.8, 6.8 Hz, 1H), 3.85 (d, J = 3.9 Hz, 3H), 3.59 (dd, J = 17.2, 7.4 Hz, 1H).

[0786] Compound 17

[0787]

[0788] Step 1: Compound 17A (5.0 g, 30.10 mmol) was dissolved in chloroform (50 mL) under an ice bath, and N,N-dimethylformamide (0.5 mL) and thionyl chloride (5.37 g, 45.14 mmol) were added sequentially. The mixture was stirred at 75 °C for 12 hours. The reaction mixture was concentrated to obtain 6.0 g of yellow solid 17B. LCMS [M+H] + = 185.2.

[0789] Step 2: Compound 1A (4.0 g, 13.87 mmol) was dissolved in dichloromethane (30 mL) under an ice bath, and triethylamine (4.2 g, 41.61 mmol), 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 x 2). The organic phase was washed with saline solution (30 mL x 2), dried with anhydrous sodium sulfate, filtered and concentrated, and purified by silica gel chromatography (PE / EA=1 / 1) to obtain 6.92 g of white solid 17C, with a yield of 85%. LCMS [M+H] + = 585.0.

[0790] Step 3: Compound 17C (3.5 g, 5.99 mmol) was dissolved in anhydrous tetrahydrofuran (30 mL), and a THF solution of LiHMDS (1 M, 17.96 mL, 17.96 mmol) was added dropwise at -78 °C and stirred for 1 hour. The mixture was diluted with water (50 mL), extracted with ethyl acetate (50 mL x 2), washed with saline solution (50 mL x 2), dried with anhydrous sodium sulfate, filtered, concentrated, and stirred with diethyl ether to obtain 2.67 g of white solid 17D, with a yield of 78%. LCMS [M+H] + = 585.0.

[0791] 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 mixture was stirred overnight at 100°C. The reaction mixture was concentrated and extracted with dichloromethane (20 mL), washed with water (20 mL x 2) and saline solution (20 mL x 2), dried with anhydrous sodium sulfate, filtered and concentrated, and stirred with diethyl ether to obtain 800 mg of yellow solid 17E, with a yield of 92%.

[0792] 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 at a rate of 12 mL / h using an injection pump into a coil wound in a jacketed glass cylinder equipped with a 250 W UV lamp. The internal reaction temperature was controlled from 0 to 5°C by adjusting the temperature of an external circulation cooler 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 a racemic mixture of pale yellow solid 17F with a yield of 75%. LCMS [M+H] + = 696.1.

[0793] Step 6: A racemic mixture 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 the mixture was stirred at 65 °C for 1.5 hours. The solution was concentrated, washed with H2O, NH4Cl(aq), and saline solution, dried with anhydrous Na2SO4, concentrated under reduced pressure, and purified using a silica gel column (0.2% FA, EA / PE=1 / 3) to obtain a racemic mixture of Compound 17G (2.8 g), with a yield of 58%. LCMS [M+H-H2O] + = 677.9.

[0794] Step 7: A racemic mixture 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 the mixture was stirred at room temperature for 2 hours. After concentration, the mixture was extracted with EA, washed with water and saline solution, dried with anhydrous Na2SO4, and purified using a silica gel column (A: PE, B: 0.2% FA, EA) to obtain 1.6 g of a racemic mixture of Compound 17H, with a yield of 56%. LCMS [M+H-H2O] + =680.0.

[0795] Step 8: A racemic mixture of compound 17H (400 mg, 0.57 mmol) was dissolved in MeOH (10 mL), palladium hydroxide (40 mg) was added to the solution, and the reaction mixture was stirred overnight at room temperature under a hydrogen balloon. The reaction mixture was filtered, washed with methanol (10 mL), and the filtrate was concentrated to obtain 320 mg of a racemic mixture of yellow solid 17I, with a yield of 91%. LCMS [M+H-H2O] + = 590.0.

[0796] Step 9: A racemic mixture 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 chromatography (acetonitrile / water = 5%–95%, 214 nm, 20 min) to obtain 320 mg of a racemic mixture of the white solid 17J, with a yield of 82%. LCMS [M+H] + = 740.2.

[0797] Step 10: A racemic mixture of compound 17J (50 mg, 0.07 mmol) was dissolved in DMF (1.5 mL), and 2-(tributyltinyl)oxazole (190 mg, 0.54 mmol), tetracysteine ​​palladium (8 mg, 0.007 mmol), and CuI (2.6 mg, 0.014 mmol) were sequentially added to the solution. The solution was stirred under microwave at 100 °C for 1.5 hours. The reaction mixture was filtered, washed with MeOH (5 mL), and shrunk. The residue was purified by reverse-phase chromatography (acetonitrile / water = 5%–95%, 214 nm, 20 min) to obtain 30 mg of a racemic mixture of yellow solid 17K, with a yield of 34%. LCMS [M+H] + = 659.2.

[0798] Step 11: A racemic mixture 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 min) to obtain 30 mg of a yellow solid racemic mixture in 17 L, with a yield of 88%. LCMS [M+H] + = 645.2.

[0799] Step 12: 17 L of the racemic mixture of compounds (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 to 1.5 mL of DMF. The reaction mixture was stirred at room temperature for 2 hours. Purification by reverse-phase chromatography (acetonitrile / water = 5%–95%, 214 nm, 20 min) yielded a yellow solid 17 M racemic mixture (15 mg, 47% yield). LCMS [M+H]+ = 688.2

[0800] Step 13: 6N / HCl (0.3 mL) was added to a tetrahydrofuran (0.5 mL) solution of a racemic mixture of Compound 17M (15 mg, 0.02 mmol). The mixture was stirred at room temperature for 12 hours. The mixture was purified using a preparative chromatography column to obtain 3.8 mg of a racemic mixture of white solid 17, with a yield of 30%, which was further separated using a chiral column to obtain Compound 17.

[0801] LCMS [M+H] + = 588.2.

[0802] 1 ¹H NMR (400 MHz, DMSO- d 6) δ 8.36 (s, 1H), 8.24 (s, 1H), 7.41 (s, 1H), 7.15 (d, J = 12.4 Hz, 2H), 6.72-6.60 (m, 4H), 6.23-6.18 (m, 3H), 6.04 (d, J = 7.6) Hz, 1H), 5.86 (d, J = 3.2 Hz, 2H), 5.37 (s, 1H), 4.92 (s, 1H), 4.83-4.73 (m, 3H), 4.16 (d, J = 14.0 Hz, 1H), 4.08 (brs, 1H), 3.88-3.85 (m, 6H), 3.06 (s, 3H).

[0803] Compound 18

[0804]

[0805] Step 1: Bis(pinacolato)diborone (35.2 mg, 0.14 mmol), potassium acetate (20.4 mg, 0.21 mmol), and Pd(dppf)Cl2 (5.62 mg, 0.01 mmol) were added to a 5 mL solution of a racemic mixture of Compound 2H (50 mg, 0.07 mmol) in dioxane. The mixture was degassed under reduced pressure and purged with nitrogen three times. The mixture was stirred at 85 °C for 10 hours, the reaction solution was concentrated, and the residue was purified using a silica gel column with PE / EA = 5 / 1 to obtain a racemic mixture of Compound 18A (40.0 mg, yield 83%), which is a yellow solid. LC-MS: (M+H) + = 699.3. 1 H NMR: (400 MHz, CDCl3) δ 7.36 (dd, J = 8.4, 28.4 Hz, 4H), 7.22 (s, 1H), 7.14 (d, J = 7.2 Hz, 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 = 6.0 Hz, 1H), 4.36 (d, J = 14.4 Hz, 1H), 3.95 (s, 3H), 3.66 (s, 3H), 3.53 (s, 1H), 1.51 (s, 9H), 1.37 (s, 12H).

[0806] Step 2: 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 to a dioxane / H2O (5 mL / 1 mL) solution of the racemic mixture of Compound 18A (40 mg, 0.06 mmol), heated to 100 °C by microwave, and stirred under nitrogen for 1 hour. The reaction mixture was concentrated, and the residue was purified by high-speed column chromatography (ACN / H2O) to obtain a racemic mixture of Compound 18B (30.0 mg, yield 80.5%), which is a white solid. LC-MS: (M+H) + = 651.0. 1H NMR: (400 MHz, CDCl3) δ 8.92 (d, J = 4.8 Hz, 2H), 7.92 (s, 1H), 7.86 (s, 1H), 7.40 (dd, J = 8.4, 22.0 Hz, 5H), 7.14 (d, J = 7.6 Hz, 1H), 7.01 - 6.96 (m, 1H), 6.91 (s, 1H), 6.57 (d, J=7.6 Hz, 1H), 6.31 (s, 1H), 5.05 (d, J = 6.0 Hz, 1H), 4.45 (d, J = 14.0 Hz, 1H), 4.07 (s, 3H), 3.97 (dd, J = 6.0, 14.0 Hz, 1H), 3.69 (s, 1H), 1.52 (s, 9H).

[0807] Step 3: A racemic mixture of Compound 18B (30 mg, 0.05 mmol) and LiOH (20.2 mg, 0.23 mmol) was dissolved in THF / H2O (1 mL / 1 mL) and stirred at room temperature for 6 hours. Purification by high-speed column chromatography (ACN / H2O) yielded a racemic mixture of Compound 18C (21.0 mg, yield 69.0%) as a white solid. LC-MS: [M+H-C4H8] + = 581.0.

[0808] Step 4: A racemic mixture 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), stirred for 16 hours, and purified by high-speed column chromatography (ACN / H2O) to obtain a racemic mixture of Compound 18D (20.0 mg, yield 93.6%), which is a white solid. LCMS [M+1] + = 680.1.

[0809] Step 5: 1 mL of 6N HCl was added to a 1 mL THF solution of the racemic mixture of Compound 18D (43.0 mg, 0.08 mmol) and stirred overnight at room temperature. Purification by high-speed column chromatography (ACN / H2O) yielded the racemic mixture of Compound 18 (70 mg, yield: 41%), which was further separated by a chiral column to obtain Compound 18, a white solid. LCMS [M+H] + = 580.0.

[0810] Compound 19

[0811]

[0812] 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) and cooled to 0 °C. Compound 19A (5860 mg, 26.7 mmol) was added in a batch, and the mixture was stirred at 25 °C for 1 hour. The solution was concentrated and extracted with EA, washed with water and saline solution, dried with anhydrous Na₂SO₄, and purified by a silica gel column (PE:EA=3 / 1) to obtain yellow solid 19B (5 g, yield 63%). LCMS: [M+H] + =655.0.

[0813] Step 2: Compound 19B (5 g, 7.64 mmol) was dissolved in THF (50 mL) and cooled to -78°C. Under N2 protection, LiHMDS (23 mL, 23 mmol) was added dropwise to the aforementioned stirred solution and stirred at -78°C for 2 hours. The reaction mixture was quenched with a saturated aqueous NH4Cl solution, extracted with EA, washed with water and saturated saline, the organic layer was dried with anhydrous Na2SO4, rotary dried, and purified using a silica gel column (PE:EA=3 / 1) to obtain the yellow solid 19C (4.1 g, yield 82%). LCMS: [M+H] + =654.9.

[0814] 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 overnight at 100°C. TLC indicated the absence of raw material and the formation of new spots. The solution was first rotary dried, then extracted with EA, washed with water and saline, dried with anhydrous Na2SO4, concentrated, and purified using a silica gel column (PE:EA=1 / 1) to obtain the yellow solid 19D (4 g, yield 67%). LCMS: [M+H] + =636.9.

[0815] Step 4: Compound 19D (4g, 6.29mmol) was dissolved in CHCl3 (120mL), cooled to 0°C, MeONa (3396mg, 18.86mmol) was added, and the mixture was stirred at 25°C for 1 hour. TLC indicated that no raw material was present and a new spot was formed. The reaction mixture was adjusted to pH=5 with acetic acid and rotary dried, extracted with EA, and washed with MeOH to obtain a filter cake, which was a gray solid 19E (2.5g, yield 88%).

[0816] LCMS: [M+H] + =453.0.

[0817] 1 H NMR (400 MHz, CDCl3) δ 8.33 (s, 1H), 8.17 (d, J = 7.9 Hz, 1H), 7.55 (d, J = 7.9 Hz, 1H), 7.48 - 7.34 (m, 6H), 6.66 (d, J = 1.4 Hz, 1H), 6.44 (s, 1H), 5.17 (s, 2H), 3.97 (s, 3H).

[0818] 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), and the reaction mixture was injected via a syringe at a rate of 12 mL / h through an injection pump into a coil wound in a jacketed glass cylinder equipped with a 250 W UV lamp. While controlling the internal reaction temperature to 0–5 °C by adjusting the temperature of an external circulation cooler, 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 using a silica gel column (EtOAc / hexane) to remove excess cinnamate, yielding a racemic mixture of Compound 19F (2.9 g, yield 64%), a pale yellow solid. LCMS [M+H+H2O] + = 633.1.

[0819] Step 6: A mixture of the racemic mixture 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 hours, concentrated and extracted with EA, washed with saturated NH4Cl solution and saline, dried with anhydrous Na2SO4, and separated and purified by a silica gel column (0.5% FA, EA / PE=31 / 69) to obtain the racemic mixture of Compound 19G (1.2 g, yield 75%), a pale yellow solid. LCMS [M+H] + = 597.1.

[0820] Step 7: A racemic mixture of compound 19G (1.7g, 2.76mmol) was mixed with Na(AcO)3BH (2.9g, 13.82mmol) and AcOH (1.7g, 27.64mmol) under MeCN / CHCl3=1 / 1 (50mL / 50mL) conditions at 0°C and stirred at room temperature for 2 hours. The solution was concentrated and extracted with EA, washed with water and saline solution, dried with anhydrous Na2SO4, and purified using a silica gel column (A:PE, B:DCM / EA=1 / 1) to obtain a racemic mixture of compound 19H (919mg, yield 54%).

[0821] LCMS [M+H-H2O] + =599.0.

[0822] 1 H NMR (400 MHz, CDCl3) δ 7.49 - 7.32 (m, 6H), 7.24 (ddd, J = 7.9, 2.0, 1.0 Hz, 1H), 7.15 - 7.11 (m, 1H), 7.10 - 7.05 (m, 3H), 7.00 (dd, J = 9.1, 6.7 Hz, 1H), 6.89 (dd, J = 7.0, 2.2 Hz, 2H), 6.38 (d, J = 1.9 Hz, 1H), 6.23 (d, J = 1.9 Hz, 1H), 5.09 (s, 2H), 5.02 (d, J = 6.5 Hz, 1H), 4.36 (d, J = 14.2 Hz, 1H), 3.95 - 3.88 (m, 1H), 3.86 (s, 3H), 3.66 (d, J = 3.6 Hz, 3H).

[0823] Step 8: A racemic mixture 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) was mixed in 1,4-dioxane (20 mL) and stirred under N2 at 100°C for 16 hours. The mixture was concentrated and purified using a silica gel column (PE / EA) to obtain a racemic mixture of compound 19I (219 mg, yield 69%).

[0824] LCMS [MH] - =652.2.

[0825] 1 H NMR (400 MHz, CDCl3) δ 7.48 - 7.35 (m, 6H), 7.10 - 7.03 (m, 4H), 6.96 (t, J= 1.8 Hz, 1H), 6.92 - 6.83 (m, 3H), 6.36 (d, J = 1.9 Hz, 1H), 6.22 (d, J = 1.9 Hz, 1H), 5.09 (s, 2H), 5.03 (d, J = 6.7 Hz, 1H), 4.33 (d, J = 14.2 Hz, 1H), 3.95 (dd, J = 14.2, 6.7 Hz, 1H), 3.86 (s, 3H), 3.65 (d, J = 3.7 Hz, 3H), 1.49 (s, 9H).

[0826] Step 9: Pd(OH)2 / C (10%, 200 mg) was added to a racemic solution of Compound 19I (219.0 mg, 0.34 mmol) in EA / MeOH / THF / DCM = 20:2:2:0.2 (10 mL). The mixture was substituted 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 mixed filtrate was concentrated and dried to obtain a racemic solution of Compound 19J (180 mg, 95% yield).

[0827] 1 H NMR (400 MHz, CDCl3) δ 7.23 - 7.02 (m, 7H), 6.95 - 6.86 (m, 3H), 6.47 (s, 1H), 6.11 (d, J = 1.5 Hz, 1H), 5.91 (s, 1H), 4.99 (d, J = 7.1 Hz, 1H), 4.31 (d, J = 14.1 Hz, 1H), 3.97 (dd, J = 14.1, 7.1 Hz, 1H), 3.74 (s, 3H), 3.66 (s, 3H), 1.50 (s, 9H).

[0828] LCMS[M+Na] + =586.1.

[0829] Step 10: The racemic mixture of Compound 19J (180 mg, 0.32 mmol) and K2CO3 (88 mg, 0.64 mmol) was stirred in DMF (10 mL). N-phenylbis(trifluoromethanesulfonylimide) (114 mg, 0.32 mmol) was added and stirred at 60°C for 20 minutes. The solution was concentrated and extracted with EA, washed with water and saline solution, dried with anhydrous Na2SO4, and purified by a silica gel column (DCM / MeOH=10 / 1) to obtain the racemic mixture of Compound 19K (190 mg, yield 86%). LCMS: [M+Na] + = 718.0.

[0830] Step 11: 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) were added to a DMF (3 mL) solution of a racemic mixture of Compound 19K (70 mg, 0.1 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 obtain a racemic mixture of Compound 19 (2.3 mg, yield: 5%), which was further separated by a chiral column to obtain Compound 19, a white solid.

[0831] LCMS [M+H] + = 515.0.

[0832] 1 H NMR (400 MHz, DMSO) δ 8.25 (s, 1H), 7.41 (s, 1H), 7.21 - 7.10 (m, 2H), 7.10 - 6.89 (m, 5H), 6.64 (t, J = 7.9 Hz, 1H), 6.48 (s, 1H), 6.26 (d, J = 8.0 Hz, 1H), 6.17 (d, J = 6.4 Hz, 1H), 5.31 (d, J = 5.2 Hz, 1H), 5.25 (s, 1H), 4.70 (t,J = 5.2 Hz, 2H), 4.20 (d, J = 14.1 Hz, 1H), 4.01 (dd, J = 14.0, 5.2 Hz, 1H), 3.85 (s, 3H), 3.55 (s, 3H).

[0833] Compound 20

[0834]

[0835] 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), a solution of t-BuXPhosPdG3 (35.13 mg, 0.04 mmol) was added, and the mixture was stirred at 85°C for 13 hours. The solution was concentrated and diluted to MeOH / DCM=1 / 1, filtered, and the filtrate was concentrated and purified using a silica gel column (DCM / MeOH=10 / 1) to obtain 0.65 g of yellow solid 20A, with a yield of 73%.

[0836] Step 2: Compound 20A (1 g, 2.2 mmol) and Compound 2A (4.1 g, 13.3 mmol) were dissolved in CHCl3 / TFE (9 / 1, 15 mL). The reaction mixture was then injected using a 20 mL syringe at a rate of 12 mL / h via an injection pump into a coil wound around a jacketed glass cylinder equipped with a 250 W UV lamp. The internal reaction temperature was controlled to 0–5 °C by adjusting the temperature of an external circulation cooler. Simultaneously, the UV lamp was turned on and the reaction mixture was irradiated for 1 hour. After removing the solvent under reduced pressure, the mixture was separated by column chromatography (EA / PE=1 / 3) to remove excess cinnamate, yielding the racemic mixture (3.9 g, yield 80%) of the required yellow oil-form crude product 20B. LCMS [M+H] + =682.3.

[0837] Step 3: The racemic mixture of Compound 20B (3.7 g, 5.43 mmol) was mixed with MeOH (50 mL), NaOMe (733.5 mg, 13.58 mmol) was added at 0 °C, and the mixture was stirred at 65 °C for 1.5 hours. The solution was concentrated, washed with H2O, NH4Cl(aq), and saline solution, dried with Na2SO4, concentrated under reduced pressure, and purified using a silica gel column (0.2% FA, EA / PE=1 / 3) to obtain 2.5 g of the racemic mixture of Compound 20C, with a yield of 67%. LCMS [M+H-H2O] + =664.2.

[0838] Step 4: A racemic mixture 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 the mixture was stirred at room temperature for 2 hours. The reaction mixture was extracted with EA, washed with water and saline solution, dried with anhydrous Na2SO4, and purified using a silica gel column (A:PE, B:EA=1 / 1) to obtain 1.5 g of a racemic mixture of Compound 20D, with a yield of 60%. LCMS [M+H-H2O] + =666.3.

[0839] Step 5: Pd(OH)2 / C (10%, 100 mg) was added to an EA / MeOH / THF / DCM (20:2:2:2:0.2, 10 mL) solution of the racemic mixture of Compound 20D (200 mg, 0.29 mmol). The mixture was purged with H2 three times and 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 using a silica gel column (DCM / MeOH=10 / 1) to obtain 155 mg of the racemic mixture of Compound 20E, with a yield of 89%. LCMS[M+Na] + = 616.1.

[0840] Step 6: A racemic mixture of Compound 20E (155.0 mg, 0.26 mmol) and K2CO3 (72.1 mg, 0.52 mmol) was 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 minutes. The solution was diluted with water, extracted with EA, washed with water and saline solution, dried with anhydrous Na2SO4, and purified using a silica gel column (EA / PE=1 / 1) to obtain 160 mg of a racemic mixture of Compound 20F, with a yield of 84%. LCMS: [M+Na] + =748.1.

[0841] Step 7: A racemic mixture of compound 20F (50 mg, 0.07 mmol) was dissolved in DMF (1.5 mL), and 2-(tributyltinyl)oxazole (190 mg, 0.54 mmol), tetracysteine ​​palladium (8 mg, 0.007 mmol), and CuI (2.6 mg, 0.014 mmol) were sequentially added to the solution. The solution was stirred under microwave at 100 °C for 1.5 hours. The reaction mixture was filtered, washed with MeOH (5 mL), and concentrated. The residue was purified by reverse-phase chromatography (acetonitrile / water = 5%–95%, 214 nm, 20 min) to obtain 17 mg of a racemic mixture of yellow solid 20 G, with a yield of 38%. LCMS: [M+Na] + =667.2.

[0842] Step 8: A racemic mixture of Compound 20G (35 mg, 0.05 mmol) was dissolved in tetrahydrofuran / water (3 mL / 1 mL), and then 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 chromatography (acetonitrile / water = 5%–95%, 214 nm, 20 min) to obtain 21 mg of a racemic mixture of the yellow solid 20H, with a yield of 61%. LCMS: [M+Na] + =653.2.

[0843] Step 9: A racemic mixture 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 to DMF (1.5 mL). The reaction mixture was stirred at room temperature for 2 hours. Purification by reverse-phase chromatography (acetonitrile / water = 5%–95%, 214 nm, 20 min) yielded 12 mg of a racemic mixture of yellow solid 20I, with a yield of 54%. LCMS: [M+Na] + =696.3.

[0844] Step 10: 6N / HCl (0.3 mL) was added to a tetrahydrofuran (0.5 mL) solution of the racemic mixture of Compound 20I (12 mg, 0.02 mmol). The mixture was stirred at room temperature for 12 hours. The mixture was purified by preparative chromatography to obtain 3.2 mg of the racemic mixture of the white solid 20, with a yield of 22%, which was further separated using a chiral column to obtain Compound 20. LCMS: [M+H] + =574.2.

[0845] 1H NMR (400 MHz, DMSO- d 6) δ 8.24 (d, J = 0.8 Hz, 1H), 7.40 (d, J = 0.8 Hz, 1H), 7.17 (d, J = 1.2 Hz, 1H), 7.14 (d, J = 1.2 Hz, 1H), 7.08-7.05 (m, 2H), 6.67-6.63 (m, 3H), 6.23 (brs, 1H), 6.16 (d, J = 9.2 Hz, 1H), 6.01 (d, J = 7.6 Hz, 1H), 5.30 (s, 1H), 4.86 (d, J= 4.4 Hz, 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).

[0846] Compound 21

[0847]

[0848] Step 1: An aqueous LiOH solution (12 mg, 0.3 mmol, 0.5 mL H2O) was added to a 2 mL THF solution of a racemic mixture of Compound 14E (60 mg, 0.1 mol). 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 obtain 45 mg of a racemic mixture of the white solid 21A, with a yield of 77.5%. LCMS:[M+H] + =625.2.

[0849] Step 2: TMP (35 mg, 0.28 mmol) was added to a 4 mL DMF solution of the racemic mixture 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). 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 obtain 24 mg of the racemic mixture of the white solid 21B, with a yield of 50%. LCMS: [M+H] + = 668.2.

[0850] Step 3: 6M HCl (2mL) was added to a THF (1mL) solution of the racemic mixture of Compound 21B (24mg, 0.03mmol). 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 obtain 14mg of the racemic mixture of white solid 21, with a yield of 70%, which was further separated by a chiral column to obtain Compound 21.

[0851] LCMS [M+H] + =568.2.

[0852] 1 H NMR (400 MHz, DMSO) δ 7.78 (s, 1H), 7.52 (d, J = 8.6 Hz, 2H), 7.34 - 7.24 (m, 3H), 7.06 (t, J = 7.4 Hz, 2H), 6.99 (t, J = 4.4 Hz, 2H), 6.91 (dd, J = 18.8, 4.5 Hz, 3H), 5.50 (s, 1H), 5.01 (d, J = 4.8 Hz, 1H), 4.80 (t, J = 5.1 Hz, 1H), 4.43 (d, J = 13.8 Hz, 1H), 4.19 (s, 3H), 3.91 (s, 3H), 3.81 (s, 2H), 3.09 (s, 3H).

[0853] Compound 22

[0854]

[0855] Step 1: A racemic mixture 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), and the reaction mixture was stirred at 100°C for 16 hours under N2 protection. The concentrate was purified by preparative high-performance liquid chromatography to obtain 1.2 mg of a racemic mixture of white solid 22, with a yield of 6.7%, which was further separated using a chiral column to obtain Compound 22.

[0856] LCMS [M+H] + =562.2.

[0857] 1H NMR (400 MHz, DMSO) δ 7.11 - 6.94 (m, 5H), 6.89 (d, J = 7.4 Hz, 2H), 6.68 (d, J = 1.5 Hz, 1H), 6.62 - 6.54 (m, 3H), 5.29 (s, 1H), 5.26 (d, J = 5.0 Hz, 1H), 4.71 (t, J = 5.2 Hz, 1H), 4.23 - 4.15 (m, 3H), 4.00 - 3.92 (m, 3H), 3.78 (dd, J = 11.2, 6.2 Hz, 1H), 3.74 (s, 3H), 3.60 (s, 3H), 3.55 (s, 3H).

[0858] Compound 23

[0859]

[0860] Step 1: An aqueous solution of LiOH (47 mg, 1.12 mmol) (0.5 mL) was added to a THF (5 mL) solution of a racemic mixture of Compound 9J (200 mg, 0.37 mol). 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 obtain a racemic mixture of 23A in the form of a white solid (180 mg, yield: 92%). LCMS [M+H] + = 525.3.

[0861] Step 2: A 1 mL DMF solution of the racemic mixture of Compound 23A (10 mg, 0.02 mmol), Compound 11A (24.3 mg, 0.2 mmol), tert-dodecyl mercaptan (38.4 mg, 0.2 mmol), and zinc meso-tetraphenylporphyrin (1.3 mg, 0.001 mmol) was added to a microwave tube. The microwave tube was placed in an 80°C water bath and irradiated using a 25 W red lamp. EDCI (36.6 mg, 0.2 mmol, dissolved in DMF) was added to the reaction system dropwise. The mixture was then stirred continuously for 30 minutes. The three reactions were added in parallel, the reaction mixtures were combined, and purified by reverse-phase column chromatography (H2O:ACN=0–100%) to obtain a racemic mixture of the white solid 23B (10 mg, yield: 30%). LCMS [M+H] + = 481.2.

[0862] Step 3: A 2 mL THF solution of the racemic mixture 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 the mixture was stirred at room temperature for 30 minutes. The suspension was filtered, and the filter cake was washed three times with MeOH / DCM (1 / 10). The obtained filtrate was rotary-dried and purified by thin-layer chromatography (DCM / MeOH=7 / 1) to obtain the racemic mixture of the white solid 23C (5 mg, yield: 16.7%). LCMS [M+H] + = 485.2.

[0863] Step 4: TMP (4 mg, 0.032 mmol) was added to a DMF (1 mL) solution of a racemic mixture 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), and the mixture was reacted at room temperature for 1 hour. The reaction mixture was purified by reverse-phase column chromatography (H2O:ACN = 0–100%) to obtain a racemic mixture of white solid 23 (2.2 mg, yield: 50%), which was further separated by a chiral column to obtain compound 23.

[0864] LCMS [M+H-H2O] + = 525.0.

[0865] 1 H NMR (400 MHz, DMSO) δ 8.26 (d, J = 0.6 Hz, 1H), 7.79 (t, J = 5.7 Hz, 1H), 7.41 (d, J = 0.7 Hz, 1H), 7.22 (dd, J = 8.9, 1.1 Hz, 2H), 7.14 (d, J = 8.9 Hz, 2H), 7.11 - 7.00 (m, 3H), 6.91 (d, J = 6.8 Hz, 2H), 6.69 (d, J = 9.0 Hz, 2H), 5.64 (t, J = 5.5 Hz, 1H), 5.42 (s, 1H), 3.96 (s, 3H), 3.91 (d, J = 5.3 Hz, 2H), 3.70 (t, J = 5.3 Hz, 2H), 3.65 (s, 3H), 3.39 (d, J = 6.2 Hz, 1H), 2.90 (td, J = 14.0, 6.8 Hz, 1H), 2.24 - 2.01 (m, 2H).

[0866] Compound 24

[0867]

[0868] Step 1: A racemic mixture of Compound 2E (3200 mg, 4.715 mmol) was dissolved in THF (30 mL), MeOH (10 mL), and H2O (10 mL). LiOH (594 mg, 14.14 mmol) was added, and the mixture was stirred at room temperature for 8 hours under nitrogen protection. The reaction mixture was adjusted to pH 5 with 3 M HCl and concentrated to obtain the crude product. A racemic mixture of the white solid 24A (2.8 g, yield: 89%) was obtained by silica gel column chromatography (DCM / MeOH = 10 / 1). LCMS [M+H] + = 665.2.

[0869] Step 2: A racemic mixture of compound 24A (2800 mg, 4.2124 mmol) was dissolved in DMF (120 mL), 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) were added, and the mixture was heated to 50°C under nitrogen protection and stirred for 16 hours. Water (100 mL) was added to the reaction mixture, extracted twice with ethyl acetate (150 mL), the organic phases were combined, washed with saturated saline (150 mL), and dried with anhydrous sodium sulfate. The crude product was filtered and concentrated, and purified by silica gel column chromatography (ethyl acetate / petroleum ether = 1 / 10) to obtain a racemic mixture (2.9 g, yield: 97%) of yellow solid 24B. LCMS [M+H-C4H8] + = 652.2.

[0870] Step 3: A racemic mixture of Compound 24B (2900 mg, 4.10 mmol) was dissolved in a mixed solution (40 mL) of EA / MeOH / THF / DCM = 20:2:2:0.2, Pd(OH)2 (870 mg) was added, and the mixture was stirred at room temperature under hydrogen conditions for 16 hours. The reaction mixture was filtered and concentrated to obtain the crude product, which was purified by silica gel column chromatography (DCM / MeOH = 10 / 1) to obtain a racemic mixture of the yellow solid 24C (1.8 g, yield: 71%). LCMS [M+H-C4H8] + = 562.2.

[0871] Step 4: A racemic mixture of Compound 24C (1800 mg, 2.9142 mmol) was dissolved in DMF (50 mL), Compound 2G (1041 mg, 2.9142 mmol) and K2CO3 (804 mg, 5.8284 mmol) were added, and the mixture was stirred at 60 °C for 40 minutes under nitrogen protection. The reaction mixture was filtered, water (100 mL) was added to the filtrate, and the mixture was extracted twice with ethyl acetate (150 mL). The organic phases were combined, washed with saturated saline (150 mL), and dried with anhydrous sodium sulfate. The crude product was obtained by filtration and concentration, and purified by silica gel column chromatography (EA / PE=1 / 1) to obtain a racemic mixture of the yellow oil-like substance 24D (1.6 g, yield: 74%). LCMS [M+H-C4H8] + = 694.1.

[0872] Step 5: A racemic mixture of compound 24D (860 mg, 1.15 mmol) was dissolved in dioxane (12 mL), and bis(pinacolato)diborone (876 mg, 3.45 mmol), Pd(dppf)Cl2 (188 mg, 0.23 mmol), and KOAc (432 mg, 4.60 mmol) were added. The mixture was stirred at 85°C for 4 hours under nitrogen protection. The reaction mixture was filtered and concentrated to obtain the crude product, which was purified by silica gel column chromatography (EA / PE=1 / 1) to obtain a racemic mixture of yellow oil-like substance 24E (700 mg, yield: 84%). LCMS [M+H-C4H8] + = 672.2.

[0873] Step 6: A racemic mixture of compound 24E (20 mg, 0.0300 mmol) was dissolved in dioxane (1.5 mL) and water (0.3 mL), and 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) were added. The mixture was reacted by microwave at 100 °C under nitrogen protection for 1 hour. The reaction mixture was filtered and concentrated to obtain a racemic mixture of yellow solid 24F (17 g, yield: 84%). LCMS [M+H] + = 680.4.

[0874] Step 7: A racemic mixture of compound 24F (17 mg, 0.250 mmol) was dissolved in THF (1 mL), 6 M-HCl (1 mL) was added, and the mixture was stirred at room temperature for 16 hours under nitrogen protection. The reaction mixture was filtered and concentrated to obtain the crude product, which was purified by a reverse-phase column (H2O / ACN) to obtain a racemic mixture of white solid 24 (1.4 mg, yield: 9.6%), which was further separated by a chiral column to obtain compound 24.

[0875] LCMS [M+H] + = 580.2.

[0876] 1H NMR (400 MHz, DMSO) δ 9.38 (d, J = 0.7 Hz, 2H), 7.70 (d, J = 1.1 Hz, 1H), 7.66 (d, J = 1.0 Hz, 1H), 7.54 (d, J = 8.6 Hz, 2H), 7.33 (d, J = 8.6) Hz, 2H), 6.66 (t, J = 7.8 Hz, 1H), 6.23 (s, 1H), 6.16 (d, J = 7.8 Hz, 1H), 6.05 (d, J = 7.4 Hz, 1H), 5.65 (s, 1H), 5.09 (d, J = 4.9 Hz, 1H), 4.84 - 4.78 (m, 2H), 4.33 (d, J = 13.9 Hz, 1H), 4.13 (dd, J = 15.2, 9.8 Hz, 1H), 3.91 (s, 3H), 3.87 (s, 3H), 3.09 (s, 3H).

[0877] Compound 25

[0878]

[0879] Step 1: A racemic mixture of Compound 24E (10 mg, 0.01 mmol) was dissolved in dioxane / water (5 mL / 1 mL), and 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) were added. The reaction was carried out for 1 hour by heating to 100°C in a microwave under nitrogen protection. The reaction mixture was filtered, the filter cake was washed with ethyl acetate (2 mL x 3), and after concentration, a racemic mixture (12 mg) of the yellow solid 25B was obtained, which was used immediately for the next reaction. LCMS [M+H-C4H8] + = 624.3.

[0880] Step 2: 6N HCl (0.3 mL) was added to a tetrahydrofuran (0.5 mL) solution of the racemic mixture of Compound 25B (12 mg, 0.02 mmol) and stirred at room temperature for 12 hours. The reaction mixture was immediately purified by preparative HPLC to obtain a racemic mixture of white solid 25 (6.3 mg, yield: 73%), which was further separated by a chiral column to obtain Compound 25.

[0881] LCMS [M+H] + = 580.0.

[0882] 1 ¹H NMR (400 MHz, DMSO- d 6) δ 9.25-9.23 (m, 1H), 8.33-8.31 (m, 1H), 7.83-7.80 (m, 1H), 7.55 (d, J = 8.4 Hz, 2H), 7.40 (d, J = 4.8 Hz, 2H), 7.34 (d, J = 8.8 Hz, 2H), 6.68 (t, J = 7.6 Hz, 1H), 6.22-6.17 (m, 2H), 6.08 (d, J = 6.0 Hz, 1H), 5.59 (s, 1H), 4.80 (d, J = 4.8 Hz, 1H), 4.33 (d, J = 14.0 Hz, 1H), 4.17-4.13 (m, 1H), 3.91 (s, 3H), 3.88 (s, 3H), 3.09 (s, 3H).

[0883] Compound 26

[0884]

[0885] Step 1: A racemic mixture of Compound 24E (20 mg, 0.03 mmol) was dissolved in dioxane / water (5 mL / 1 mL), and 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) were added. The reaction was carried out for 1 hour by heating to 100°C in a microwave under nitrogen protection. The reaction mixture was filtered, the filter cake was washed with ethyl acetate (2 mL x 3), and after concentration, a racemic mixture of yellow solid 26B (19 mg) was obtained, which was used immediately for the next reaction. LCMS [M+H] + = 719.3.

[0886] Step 2: 6N HCl (0.3 mL) was added to a tetrahydrofuran (0.5 mL) solution of the racemic mixture of Compound 26B (19 mg, 0.02 mmol) and stirred at room temperature for 12 hours. The reaction mixture was immediately purified by preparative HPLC to obtain a racemic mixture of the white solid 26 (2.3 mg, yield: 17%), which was further separated by a chiral column to obtain Compound 26.

[0887] LCMS [M+H] + = 619.2.

[0888] 1 ¹H NMR (400 MHz, DMSO- d 6) δ 9.32 (d, J = 1.6 Hz, 1H), 9.19 (s, 1H), 8.14 (s, 1H), 7.88 (d, J = 0.8 Hz, 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 = 7.6 Hz, 1H), 5.53 (s, 1H), 4.98 (d, J= 4.4 Hz, 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).

[0889] Compound 27

[0890]

[0891] Step 1: A racemic mixture of Compound 24E (20 mg, 0.03 mmol) was dissolved in dioxane / water (5 mL / 1 mL), and 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) were added. The reaction was carried out for 1 hour by heating to 100°C in a microwave under nitrogen protection. The reaction mixture was filtered, the filter cake was washed with ethyl acetate (2 mL x 3), and after concentration, a racemic mixture of yellow solid 27B (18 mg) was obtained, which was used immediately for the next reaction. LCMS [M+H] + = 719.3.

[0892] Step 2: 6N HCl (0.3 mL) was added to a tetrahydrofuran (0.5 mL) solution of the racemic mixture of Compound 27B (18 mg, 0.03 mmol) and stirred at room temperature for 12 hours. The reaction mixture was immediately purified by preparative HPLC to obtain a racemic mixture of the white solid 27 (1.5 mg, yield: 9.7%), which was further separated by a chiral column to obtain Compound 27.

[0893] LCMS [M+H] + = 619.2.

[0894] 1 ¹H NMR (400 MHz, DMSO- d 6) δ 8.38 (s, 1H), 8.24 (d, J = 9.6 Hz, 1H), 7.91 (d, J= 9.6 Hz, 1H), 7.84 (s, 1H), 7.55 (d, J = 8.4 Hz, 2H), 7.35 (s, 2H), 7.32 (s, 1H), 7.23 (s, 1H), 6.67 (t, J = 7.8 Hz, 1H), 6.21 (s, 1H), 6.17 (d, J = 7.6 Hz, 1H), 6.07 (d, J = 7.6 Hz, 1H), 5.60 (s, 1H), 5.05 (d, J = 4.8 Hz, 1H), 4.82-4.79 (m, 3H), 4.33 (d, J = 14.0 Hz, 1H), 4.17-4.09 (m, 1H), 3.91 (s, 3H), 3.88 (s, 3H), 3.09 (s, 3H).

[0895] Compound 28

[0896]

[0897] Step 1: A racemic mixture of Compound 24E (20 mg, 0.03 mmol) was dissolved in dioxane / water (3 mL / 1 mL), and 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) were added. The reaction was carried out for 1 hour by heating to 100°C in a microwave under nitrogen protection. The reaction mixture was filtered, the filter cake was washed with ethyl acetate (2 mL x 3), and after concentration, a racemic mixture (20 mg) of the yellow solid compound 28B was obtained, which was used immediately for the next reaction. LCMS [M+H-C4H8] + = 638.2.

[0898] Step 2: 6N HCl (0.5 mL) was added to a tetrahydrofuran (0.5 mL) solution of the racemic mixture of Compound 28B (20 mg, 0.03 mmol) and stirred at room temperature for 12 hours. The reaction mixture was immediately purified by preparative HPLC to obtain a racemic mixture of white solid 28 (3.8 mg, yield: 22%), which was further separated by a chiral column to obtain Compound 28.

[0899] LCMS [M+H] + = 594.0.

[0900] 1 ¹H NMR (400 MHz, DMSO- d 6) δ 9.25 (s, 1H), 7.53 (d, J = 8.4 Hz, 2H), 7.30 (d, J = 8.4 Hz, 2H), 7.24 (d, J = 1.2 Hz, 1H), 7.16 (d, J = 1.2 Hz, 1H), 6.66 (t, J = 15.2 Hz, 1H), 6.20 (s, 1H), 6.16 (d, J = 8.0 Hz, 1H), 6.06 (d, J = 7.6 Hz, 1H), 5.67 (s, 1H), 5.13 (d, J = 4.8 Hz, 1H), 4.83-4.76 (m, 3H), 4.34 (d, J = 14.0 Hz, 1H), 4.17-4.10 (m, 1H), 3.90 (s, 3H), 3.85 (s, 3H), 3.09 (s, 3H).

[0901] Compound 29

[0902]

[0903] Step 1: A racemic mixture of Compound 24E (20 mg, 0.03 mmol) was dissolved in dioxane / water (3 mL / 1 mL), and 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) were added. The reaction was carried out for 1 hour by heating to 100°C in a microwave under nitrogen protection. The reaction mixture was filtered, the filter cake was washed with ethyl acetate (2 mL x 3), and after concentration, a racemic mixture (20 mg) of the yellow solid 29B was obtained, which was used immediately for the next reaction. LCMS [M+H-C4H8] + = 642.2.

[0904] Step 2: 6N HCl (0.3 mL) was added to a tetrahydrofuran (0.5 mL) solution of the racemic mixture of Compound 29B (20 mg, 0.03 mmol) and stirred at room temperature for 12 hours. The reaction mixture was immediately purified by preparative HPLC to obtain a racemic mixture of the white solid 29 (1.5 mg, yield: 9%), which was further separated by a chiral column to obtain Compound 29.

[0905] LCMS [M+H] + = 598.2.

[0906] 1 ¹H NMR (400 MHz, DMSO- d 6) δ 9.01 (s, 2H), 7.57-7.53 (m, 4H), 7.32 (d, J = 8.8 Hz, 2H), 6.66 (t, J = 7.6 Hz, 1H), 6.23 (s, 1H), 6.17 (d, J = 12.0 Hz, 1H), 6.04 (d, J = 7.6 Hz, 1H), 5.59 (s, 1H), 5.03 (d, J = 4.8 Hz, 1H), 4.87-4.79 (m, 3H), 4.30 (d, J= 14.0 Hz, 1H), 4.16-4.09 (m, 1H), 3.90 (s, 3H), 3.85 (s, 3H), 3.09 (s, 3H).

[0907] Compound 30

[0908]

[0909] Step 1: A racemic mixture of Compound 24E (20 mg, 0.03 mmol) was dissolved in dioxane / water (3 mL / 1 mL), and 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) were added. The reaction was carried out for 1 hour by heating to 100°C in a microwave under nitrogen protection. The reaction mixture was filtered, the filter cake was washed with ethyl acetate (2 mL x 3), and after concentration, a racemic mixture of the yellow solid 30B (20 mg) was obtained, which was used immediately for the next reaction. LCMS [M+H-C4H8] + = 649.2.

[0910] Step 2: 6N HCl (0.3 mL) was added to a tetrahydrofuran (0.5 mL) solution of the racemic mixture of Compound 30B (20 mg, 0.03 mmol) and stirred at room temperature for 12 hours. The reaction mixture was immediately purified by preparative HPLC to obtain a racemic mixture of the white solid 30 (1.1 mg, yield: 6.4%), which was further separated by a chiral column to obtain Compound 30.

[0911] LCMS [M+H] + = 605.2.

[0912] 1 ¹H NMR (400 MHz, DMSO- d 6) δ 8.68 (s, 2H), 7.55-7.53 (m, 4H), 7.33 (d, J = 8.8 Hz, 2H), 6.66 (t, J = 7.6 Hz, 1H), 6.22 (s, 1H), 6.17-6.15 (m, 1H), 6.03 (d,J = 8.0 Hz, 1H), 5.54 (s, 1H), 4.98 (d, J = 4.8 Hz, 1H), 4.83-4.79 (m, 3H), 4.29 (d, J = 14.0 Hz, 1H), 4.16-4.10 (m, 1H), 3.98 (s, 3H), 3.90 (s, 3H), 3.85 (s, 3H), 3.08 (s, 3H).

[0913] Compound 31

[0914]

[0915] Step 1: A racemic mixture of Compound 24E (20 mg, 0.03 mmol) was dissolved in dioxane / water (3 mL / 1 mL), and 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) were added. The reaction was carried out for 1 hour by heating to 100°C in a microwave under nitrogen protection. The reaction mixture was filtered, the filter cake was washed with ethyl acetate (2 mL x 3), and after concentration, a racemic mixture of the yellow solid 31B (20 mg) was obtained, which was used immediately for the next reaction. LCMS [M+H-C4H8] + = 654.2.

[0916] Step 2: 6N HCl (0.3 mL) was added to a tetrahydrofuran (0.5 mL) solution of the racemic mixture of Compound 31B (20 mg, 0.03 mmol) and stirred at room temperature for 12 hours. The reaction mixture was immediately purified by preparative HPLC to obtain a racemic mixture of the white solid 31 (3.3 mg, yield: 19%), which was further separated by a chiral column to obtain Compound 31.

[0917] LCMS [M+H] + = 610.2.

[0918] 1 ¹H NMR (400 MHz, DMSO- d6) δ 8.68 (s, 2H), 7.55-7.53 (m, 4H), 7.33 (d, J = 8.8 Hz, 2H), 6.66 (t, J = 7.6 Hz, 1H), 6.22 (s, 1H), 6.17-6.15 (m, 1H), 6.03 (d, J = 8.0 Hz, 1H), 5.54 (s, 1H), 4.98 (d, J = 4.8 Hz, 1H), 4.83-4.79 (m, 3H), 4.29 (d, J = 14.0 Hz, 1H), 4.16-4.10 (m, 1H), 3.98 (s, 3H), 3.90 (s, 3H), 3.85 (s, 3H), 3.08 (s, 3H).

[0919] Compound 32

[0920]

[0921] Step 1: A racemic mixture of Compound 24E (20 mg, 0.0300 mmol) was dissolved in dioxane (2.0 mL) and water (0.5 mL), 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) were added, and the mixture was reacted for 1 hour at 100°C using a microwave under nitrogen protection. The reaction mixture was filtered and concentrated to obtain a racemic mixture of yellow solid 32B (17 mg, yield: 84%). LCMS [M+H-C4H8] + = 692.2.

[0922] Step 2: A racemic mixture of compound 32B (17 mg, 0.269 mmol) was dissolved in THF (1 mL), 6 M-HCl (1 mL) was added, and the mixture was stirred 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 obtain a racemic mixture of white solid 32 (1.1 mg, yield: 7.5%), which was further separated using a chiral column to obtain compound 32.

[0923] LCMS [M+H] + = 648.2.

[0924] 1 H NMR (400 MHz, DMSO) δ 9.38 (d, J = 0.7 Hz, 2H), 7.70 (d, J = 1.1 Hz, 1H), 7.66 (d, J = 1.0 Hz, 1H), 7.54 (d, J = 8.6 Hz, 2H), 7.33 (d, J = 8.6) Hz, 2H), 6.66 (t, J = 7.8 Hz, 1H), 6.23 (s, 1H), 6.16 (d, J = 7.8 Hz, 1H), 6.05 (d, J = 7.4 Hz, 1H), 5.65 (s, 1H), 5.09 (d, J = 4.9 Hz, 1H), 4.84 - 4.78 (m, 2H), 4.33 (d, J = 13.9 Hz, 1H), 4.13 (dd, J = 15.2, 9.8 Hz, 1H), 3.91 (s, 3H), 3.87 (s, 3H), 3.09 (s, 3H).

[0925] Compound 33

[0926]

[0927] Step 1: A racemic mixture of Compound 24E (20 mg, 0.03 mmol) was dissolved in dioxane / water (3 mL / 1 mL), and 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) were added. The reaction was carried out for 1 hour by heating to 100°C in a microwave under nitrogen protection. The reaction mixture was filtered, the filter cake was washed with ethyl acetate (2 mL x 3), and after concentration, a racemic mixture of the yellow solid 33B (23 mg) was obtained, which was used immediately for the next reaction. LCMS [M+H-C4H8] + = 739.3.

[0928] Step 2: 6N HCl (0.5 mL) was added to a tetrahydrofuran (0.5 mL) solution of the racemic mixture of Compound 33B (23 mg, 0.03 mmol) and stirred at room temperature for 12 hours. The reaction mixture was immediately purified by preparative HPLC to obtain a racemic mixture of the white solid 33 (1.1 mg, yield: 6.4%), which was further separated by a chiral column to obtain Compound 33.

[0929] LCMS [M+H] + = 595.2.

[0930] 1 ¹H NMR (400 MHz, DMSO- d 6) δ 8.22 (s, 2H), 7.54 (d, J = 8.8 Hz, 2H), 7.44 (d, J = 4.8 Hz, 2H), 7.32 (d, J = 8.8 Hz, 2H), 6.65 (t, J = 7.8 Hz, 1H), 6.22 (s, 1H), 6.16 (d, J = 8.0 Hz, 1H), 6.01 (d, J = 7.6 Hz, 1H), 5.75 (s, 2H), 5.47 (s, 1H), 4.89 (d, J= 4.4 Hz, 1H), 4.84-4.77 (m, 3H), 4.26 (d, J = 13.6 Hz, 1H), 3.89 (s, 3H), 3.83 (s, 3H), 3.08 (s, 3H).

[0931] Compound 34

[0932]

[0933] Step 1: A racemic mixture of Compound 24E (20 mg, 0.03 mmol) was dissolved in dioxane / water (3 mL / 1 mL), and 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) were added. The reaction was carried out for 1 hour by heating to 100°C in a microwave under nitrogen protection. The reaction mixture was filtered, the filter cake was washed with ethyl acetate (2 mL x 3), and after concentration, a racemic mixture (20 mg) of the yellow solid 34B was obtained and used immediately for the next reaction. LCMS [M+H-C4H8] + = 649.2.

[0934] Step 2: 6N HCl (0.5 mL) was added to a tetrahydrofuran (0.5 mL) solution of the racemic mixture of Compound 34B (20 mg, 0.03 mmol) and stirred at room temperature for 12 hours. The reaction mixture was immediately purified by preparative HPLC to obtain a racemic mixture of the white solid 34 (4.6 mg, yield: 27%), which was further separated by a chiral column to obtain Compound 34.

[0935] LCMS [M+H] + = 605.2.

[0936] 1 ¹H NMR (400 MHz, DMSO- d 6) δ 9.26 (d, J = 4.8 Hz, 1H), 8.10 (d, J = 4.8 Hz, 1H), 7.62 (d, J= 1.0 Hz, 1H), 7.58 - 7.52 (m, 3H), 7.33 (d, J = 8.4 Hz, 2H), 6.66 (t, J = 7.6 Hz, 1H), 6.23 (s, 1H), 6.16 (d, J = 8.0 Hz, 1H), 6.04 (d, J = 7.6 Hz, 1H), 5.64 (s, 1H), 5.08 (d, J = 4.8 Hz, 1H), 4.93 - 4.76 (m, 3H), 4.31 (d, J = 14.0 Hz, 1H), 4.17 (s, 1H), 3.91(S,3H), 3.89 (s, 3H), 3.09 (s, 3H).

[0937] Compound 35

[0938]

[0939] Step 1: A racemic mixture of Compound 24E (20 mg, 0.0275 mmol) was dissolved in dioxane (2.0 mL) and water (0.4 mL). 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) were added, and the mixture was reacted for 1 hour at 100°C using a microwave under nitrogen protection. The reaction mixture was filtered and concentrated to obtain the crude product, which was purified using a reverse-phase column (H2O / ACN) to yield a racemic mixture of the yellow solid 35B (12 mg, yield: 63%). LCMS [M+H-C4H8] + = 638.2.

[0940] Step 2: Compound 35B (12 mg, 0.0173 mmol) was dissolved in THF (1 mL), 6 M HCl (1 mL) was added, and 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 obtain a white solid 35 (2.6 mg, yield: 25%), which was further separated using a chiral column to obtain Compound 35.

[0941] LCMS [M+H] + = 594.2.

[0942] 1 H NMR (400 MHz, DMSO) δ 9.38 (d, J = 0.7 Hz, 2H), 7.70 (d, J = 1.1 Hz, 1H), 7.66 (d, J = 1.0 Hz, 1H), 7.54 (d, J = 8.6 Hz, 2H), 7.33 (d, J = 8.6) Hz, 2H), 6.66 (t, J = 7.8 Hz, 1H), 6.23 (s, 1H), 6.16 (d, J = 7.8 Hz, 1H), 6.05 (d, J = 7.4 Hz, 1H), 5.65 (s, 1H), 5.09 (d, J = 4.9 Hz, 1H), 4.84 - 4.78 (m, 2H), 4.33 (d, J = 13.9 Hz, 1H), 4.13 (dd, J = 15.2, 9.8 Hz, 1H), 3.91 (s, 3H), 3.87 (s, 3H), 3.09 (s, 3H).

[0943] Compound 36

[0944]

[0945] Step 1: 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) were added to a dioxane / H2O (2.5 mL / 0.5 mL) solution of the racemic mixture of Compound 24E (20 mg, 0.03 mmol), and the mixture was reacted for 1 hour at 100 °C using a microwave under nitrogen protection. The reaction mixture was concentrated, and the crude product was purified using a reverse-phase column (ACN / H2O) to obtain the racemic mixture of the white solid 36B (10.0 mg, yield: 52.1%). LCMS [M+H-C4H8] + = 643.2.

[0946] Step 2: 2 mL of 6N HCl was added to a 2 mL THF solution of the racemic mixture of Compound 36B (10.0 mg, 0.01 mmol), and the mixture was stirred overnight at room temperature. The reaction mixture was immediately purified using a reverse-phase column (ACN / H2O) to obtain a racemic mixture of the white solid 36 (6.4 mg, yield: 74.7%), which was further separated using a chiral column to obtain Compound 36. LCMS [M+H] + = 599.3.

[0947] Compound 37

[0948]

[0949] Step 1: A racemic mixture of compound 10O (20 mg, 0.03 mmol), compound 11A (42.6 mg, 0.3 mmol), HOAT (6.12 mg, 0.045 mmol), tert-dodecyl mercaptan (60.6 mg, 0.3 mmol), TMP (5.48 mg, 0.045 mmol), and zinc meso-tetraphenylporphyrin (2.03 mg, 0.003 mmol) were added to a microwave tube along with DMF (2 mL). After purging the reaction system with nitrogen, the microwave tube was placed in an 80°C hot water bath and stirred while simultaneously irradiating with a 25W red lamp. Then, a DMF (2 mL) solution of EDCI (57.3 mg, 0.3 mmol) was slowly added dropwise to the reaction mixture, followed by stirring for 30 minutes. After the reaction was complete, the reaction solution was purified using a silica gel column (H2O / ACN=40%:60%) to obtain a racemic mixture of compound 37A (8.6 mg, yield: 46%). LCMS [M+H] + = 553.2.

[0950] Step 2: A racemic mixture of Compound 37A (8.6 mg, 0.015 mmol) was dissolved in THF (1 mL), and 6 M HCl (2 mL) was added. The reaction mixture was stirred at room temperature (20°C) for 2 hours. The reaction mixture was rotary dried and purified using a silica gel column (H2O / ACN=55:45) to obtain a racemic mixture of Compound 37 (3.7 mg, yield: 52%), which was further separated using a chiral column to obtain Compound 37.

[0951] LCMS [M+H] + = 453.2.

[0952] 1 H NMR (400 MHz, DMSO) δ 8.80 (d, J = 1.7 Hz, 1H), 8.33 (s, 1H), 7.87 (d, J = 1.7 Hz, 1H), 7.54 (d, J = 8.6 Hz, 2H), 7.47 (d, J = 0.6 Hz, 1H), 7.30 (d,J = 8.6 Hz, 2H), 6.88 (s, 1H), 6.55 (s, 1H), 6.47 (d, J = 23.6 Hz, 2H), 6.03 (s, 1H), 5.21 (s, 1H), 4.51 (d, J = 3.9 Hz, 1H), 4.24 (dd, J = 14.0, 6.0 Hz, 1H), 2.80 (td, J = 13.4, 4.3 Hz, 1H), 2.16 (dd, J = 12.6, 6.3 Hz, 1H).

[0953] Compound 38

[0954]

[0955] Step 1: Dimethylamine solution (0.1 mL, 0.2 mmol), HATU (15 mg, 0.04 mmol), and TMP (5 mg, 0.04 mmol) were added to a DMF (2 mL) solution of a racemic mixture of Compound 10O (24 mg, 0.04 mmol), and the mixture was stirred at 20°C for 2 hours. The reaction mixture was immediately purified using a reverse-phase chromatography column (MeCN / H2O / FA) to obtain a racemic mixture of the white solid 38A (12 mg, yield: 48%). LCMS [M+H] + = 624.3.

[0956] Step 2: 6M HCl (2mL) was added to a THF (2mL) solution of the racemic mixture of Compound 38A (12mg, 0.02mmol) and stirred at 25°C for 18 hours. The reaction mixture was immediately purified using a reverse-phase chromatography column (MeCN / H2O / FA) to obtain a racemic mixture of the white solid 38 (4.7mg, yield: 47%), which was further separated using a chiral column to obtain Compound 38.

[0957] LCMS [M+H] + = 524.2.

[0958] 1 H NMR (400 MHz, DMSO) δ 8.78 (d, J= 1.7 Hz, 1H), 8.33 (s, 1H), 7.89 (d, J = 1.7 Hz, 1H), 7.53 (s, 1H), 7.51 (s, 1H), 7.47 (s, 1H), 7.37 (d, J = 8.5 Hz, 2H), 6.66 (t, J = 7.8 Hz, 1H), 6.22 (s, 1H), 6.20 (s, 1H), 6.14 (dd, J = 17.3, 7.6 Hz, 2H), 5.28 (d, J = 5.5 Hz, 1H), 4.79 (s, 2H), 4.73 (t, J = 5.3 Hz, 1H), 4.54 (d, J = 13.3 Hz, 1H), 4.21 (dd, J = 13.3, 5.3 Hz, 1H), 3.28 (s, 3H), 2.79 (s, 3H).

[0959] Compound 39

[0960]

[0961] Step 1: Compound 10G (1g, 2.36 mmol) and Compound 9A (2.3g, 14.14 mmol) were dissolved in CHCl3 / TFE=7 / 3 (15 mL). The reaction mixture was then injected using a 20 mL syringe at a rate of 12 mL / h via an injection pump into a coil wound around a jacketed glass cylinder equipped with a 250 W UV lamp. The internal reaction temperature was controlled from 0 to 5°C by adjusting the temperature of an external circulation cooler. Simultaneously, the UV lamp was turned on and the reaction mixture was irradiated for 1 hour. After removing the solvent under reduced pressure, the mixture was separated by column chromatography (EA / PE=1 / 3) to remove excess cinnamate, yielding a racemic mixture (7 g, yield: 51%) of the pale yellow solid 39A. LCMS [M+H-H2O] + =568.1.

[0962] Step 2: The racemic mixture of Compound 39A (4.9 g, 8.37 mmol) was dissolved in methanol (60 mL), NaOMe (1.135 g, 20.94 mmol) was added at 0 °C, and the mixture was stirred at 65 °C for 1.5 hours. The reaction mixture was concentrated and extracted with EA, washed with water, NH4Cl solution, and saturated saline, and dried with anhydrous sodium sulfate. After filtration and concentration, the mixture was purified using a silica gel column (0.2% FA in EA / PE=1 / 3) to obtain the racemic mixture of Compound 39B (3.6 g, 73%). LCMS [M+H] + = 586.1.

[0963] Step 3: The racemic mixture of Compound 39B (3.6 g, 6.15 mmol) was dissolved in an ACN / CHCl3=1 / 1 (40 mL / 40 mL) mixed solvent, Na(AcO)3BH (6.525 g, 30.77 mmol) and AcOH (3.695 g, 61.53 mmol) were added at 0 °C, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated and extracted with EA, washed with water and saturated saline, and dried with anhydrous sodium sulfate. After filtration and concentration, the mixture was purified using a silica gel column (EA / PE=3 / 2 with 0.2% FA) to obtain the racemic mixture of Compound 39C (1.9 g, yield: 53%). LCMS [M+H] + =588.1.

[0964] Step 4: Under nitrogen protection, a 30 mL DMP solution of the racemic mixture 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) was stirred at 150 °C for 1 hour. The mixture was diluted with water, extracted three times with EA (50 mL * 3), concentrated the organic phase, and the crude product was purified using a FLASH column (medium-low pressure rapid preparative liquid chromatography) (DCM / MEOH = 0–10%) to obtain a racemic mixture of the yellow solid 39D (1100 mg, yield: 80.7%). LCMS: [M+H]+ = 535.6.

[0965] Step 5: The racemic mixture of 39D (1100 mg, 2.06 mmol) and Pd / C (700 mg) were added to an EA / MeOH (20 / 20 mL) solution, hydrogenated three times, and stirred at room temperature for 16 hours. The reaction mixture was purified using a FLASH column (medium-low pressure high-speed preparative liquid chromatography) (MeOH / DCM = 0–10%) to obtain the racemic mixture of compound 39E (350 mg, yield: 38.2%). LCMS: [M+H] + = 445.6.

[0966] Step 6: The racemic mixture of Compound 39E (350 mg, 0.79 mmol) and K2CO3 (108 mg, 0.79 mmol) were added to DMF (5 mL), followed by the addition of Compound 2G (281 mg, 0.79 mmol) and stirring at 60 °C for 1.5 hours. The reaction mixture was diluted with EA (30 mL) and washed with H2O (20 mL x 2). It was then purified using a FLASH column (medium-low pressure high-speed preparative liquid chromatography) (MeOH / DCM = 0–10%) to obtain the racemic mixture of Compound 39F (310 mg, yield: 68.3%). LCMS [M+H] + =577.6.

[0967] Step 7: A racemic mixture 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), followed by the addition of CuI (26.5 mg, 0.14 mmol), and the mixture was stirred under microwave at 135 °C for 5 hours. The reaction mixture was diluted with EA (30 mL), and the resulting mixture was washed with H2O (20 mL x 2). The solution was purified using a FLASH column (medium-low pressure high-speed preparative liquid chromatography) (MeOH / DCM = 0–15%) to obtain a racemic mixture of the yellow solid 39G (250 mg, yield: 71%). LCMS [M+H] + =496.2.

[0968] Step 8: A racemic mixture of compound 39G (250 mg, 0.5 mmol) and LiOH·H2O (60 mg, 1.5 mmol) were added to a THF / MeOH / H2O (1.5 / 1.5 / 1.5 mL) mixture and stirred at 20°C for 5 hours. The reaction mixture was purified using a FLASH column (medium-low pressure high-speed liquid chromatography) (ACN-H2O) to obtain a racemic mixture of yellow solid 39H (170 mg, yield: 70%). LCMS [M+H] + =482.7.

[0969] Step 9: A racemic mixture 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 and stirred at 20°C for 2 hours. The reaction mixture was purified using a FLASH column (medium-low pressure high-speed preparative liquid chromatography) (MeOH / DCM = 0–10%) to obtain a racemic mixture of white solid 39 (19 mg, yield: 86%), which was further separated using a chiral column to obtain compound 39.

[0970] LCMS [M+H] + =537.7.

[0971] 1 H NMR (400 MHz, DMSO) δ 8.79 (s, 1H), 8.44 (s, 1H), 8.33 (s, 1H), 7.93 (d, J = 1.6 Hz, 1H), 7.48 (d, J = 6.1 Hz, 3H), 7.37 - 7.30 (m, 2H), 7.06 (t, J = 6.8 Hz, 2H), 7.02 - 6.93 (m, 3H), 6.28 (d, J= 10.8 Hz, 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).

[0972] Compound 40

[0973]

[0974] Step 1: A racemic mixture of Compound 39D (20 mg, 0.04 mmol), HATU (12 mg, 0.04 mmol), and TMP (14.5 mg, 0.12 mmol) was 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 using a normal-phase chromatography column (MeOH / DCM = 0–10%) to obtain a racemic mixture of the white solid 40B (30 mg, yield: 94%). LCMS [M+H] + = 747.0.

[0975] Step 2: A racemic mixture of compound 40B (30 mg, 0.04 mmol) and piperidine (10 mg, 0.12 mol) were dissolved in DMF (1 mL) and reacted at 20°C for 1 hour. The reaction mixture was freeze-dried to obtain a racemic mixture of white solid 40 (20 mg, yield: 87%), which was further separated using a chiral column to obtain compound 40.

[0976] LCMS [M+H] + = 524.2.

[0977] 1 H NMR (400 MHz, DMSO) δ 8.80 (d, J = 1.7 Hz, 1H), 8.41 (t, J = 5.6 Hz, 1H), 8.34 (s, 1H), 7.93 (d, J = 1.7 Hz, 1H), 7.52 (d, J = 8.6 Hz, 2H), 7.48 (s, 1H), 7.30 (d, J= 8.5 Hz, 2H), 7.04 (ddd, J = 21.9, 14.9, 7.3 Hz, 6H), 6.26 (s, 1H), 4.67 (dd, J = 18.3, 9.1 Hz, 2H), 3.25 (dd, J = 12.6, 6.5 Hz, 3H), 2.75 (t, J = 6.6 Hz, 2H).

[0978] Compound 41

[0979]

[0980] Step 1: LiOH·H2O (19.3 mg, 0.46 mmol) was added to a THF / H2O / MeOH (3 ml / 1 mL / 1 mL) solution of the racemic mixture of Compound 19I (100.0 mg, 0.15 mmol) and stirred at 40°C for 3 hours. The pH of the reaction mixture was adjusted to approximately 5 with 3 M HCl, the reaction mixture was rotary-dried, and purified by normal-phase column chromatography (DCM / MeOH) to obtain the racemic mixture of Compound 41A (75 mg, yield: 77%). LCMS[MH] - = 638.2.

[0981] Step 2: TMP (56.8 mg, 0.47 mmol) was added to a DMF (mL) solution of the racemic mixture 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). 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 racemic mixture of Compound 41B (85 mg, yield: 110%). LCMS[M+H] + = 683.1.

[0982] Step 3: Pd(OH)2 / C (10%, 50 mg) was added to a mixed solution of EA / MeOH / THF / DCM (20:2:2:0.2, 10 mL) of the racemic mixture of Compound 41B (85.0 mg, 0.13 mmol), hydrogenated three times, and stirred at room temperature for 16 hours. The reaction mixture was filtered, the filter cake was rinsed three times with MeOH / DCM (1 / 10), and the filtrate was rotary-dried to obtain the racemic mixture of Compound 41C (50 mg, crude product yield not calculated), which was used immediately in the next reaction. LCMS[M+H] + = 593.1.

[0983] Step 4: Compound 2G (30.2 mg, 0.084 mmol) was added to a 2 mL DMF solution of the racemic mixture of Compound 41C (50.0 mg, 0.08 mmol) and K2CO3 (23.3 mg, 0.169 mmol), and 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 with anhydrous sodium sulfate. The crude product obtained by filtration and concentration was purified by normal-phase column chromatography (PE / EA) to obtain the racemic mixture of Compound 41D (45 mg, yield: 73%). LCMS: [M+H] + = 725.1.

[0984] Step 5: The racemic mixture of Compound 41D (33.0 mg, 0.05 mmol) was dissolved in a solution of 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 using a silica gel column (DCM / MeOH) to obtain the racemic mixture of Compound 41E (43 mg, crude product yield not calculated), which was used directly in the next reaction. LCMS [M+H] + = 703.3.

[0985] Step 6: The racemic mixture 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, purged with N2 three times, and stirred by microwave at 100°C for 2 hours. The reaction mixture was concentrated and purified using a silica gel column (DCM / MeOH) to obtain the racemic mixture of Compound 41F (7 mg, yield: 17.7%). LCMS [M+H] + = 644.1.

[0986] Step 7: A racemic mixture 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 mixture was concentrated and purified by preparative HPLC to obtain a racemic mixture of white solid 41 (0.8 mg, yield: 13.5%), which was further separated by a chiral column to obtain compound 41.

[0987] LCMS [M+H] + = 544.2.

[0988] 1 H NMR (400 MHz, DMSO) δ 8.25 (s, 1H), 7.41 (s, 1H), 7.17 (d, J = 14.2 Hz, 2H), 7.04 (t, J = 7.4 Hz, 2H), 6.98 (d, J = 7.2 Hz, 1H), 6.89 (d, J = 7.6 Hz, 2H), 6.69 (t, J = 7.8 Hz, 1H), 6.47 (s, 1H), 6.28 (d, J = 7.9 Hz, 1H), 6.19 (d, J= 8.2 Hz, 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).

[0989] Compound 42

[0990]

[0991] Step 1: A racemic mixture 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), Compound 42A (582 mg, 1.63 mmol) was added, and the mixture was reacted at 120 °C for 5 hours. The reaction mixture was diluted with water, extracted three times with EA (10 mL * 3), the organic phase was concentrated, and purified by preparative HPLC (ACN / H2O) to obtain a racemic mixture of the white solid 42B (8 mg, yield: 18%). LCMS [M+H] + = 682.1.

[0992] Step 2: A racemic mixture of Compound 42B (10 mg, 0.01 mmol) and 6 M HCl (1.5 mol) were added to THF (1 mL) and reacted at 40 °C for 5 hours. The reaction mixture was freeze-dried to obtain a racemic mixture of the white solid 42 (8 mg, yield: 94%). LCMS [M+H] + = 582.1, and compound 42 was obtained by further separating this with a chiral column.

[0993] 1H NMR (400 MHz, DMSO) δ 8.36 (s, 1H), 7.63 - 7.50 (m, 3H), 7.31 (d, J = 8.5 Hz, 2H), 7.13 - 6.98 (m, 3H), 6.80 (s, 3H), 5.60 (s, 1H), 4.81 (s, 1H), 4.42 (d, J = 13.4 Hz, 1H), 4.17 (d, J = 12.4 Hz, 1H), 3.92 (s, 3H), 3.83 (s, 3H), 3.08 (s, 3H), 2.12 (s, 3H).

[0994] Compound 43

[0995]

[0996] Step 1: A racemic mixture of Compound 24E (20 mg, 0.03 mmol) was dissolved in dioxane / water (3 mL / 1 mL), and 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) were added. The reaction was carried out for 1 hour by heating to 100°C in a microwave under nitrogen protection. The reaction mixture was filtered, the filter cake was washed with ethyl acetate (2 mL x 3), and after concentration, a racemic mixture (20 mg) of the yellow solid 43B was obtained and used immediately for the next reaction. LCMS [M+H] + = 710.2.

[0997] Step 2: 6N HCl (0.5 mL) was added to a tetrahydrofuran (0.5 mL) solution of the racemic mixture of Compound 43B (20 mg, 0.03 mmol) and stirred at room temperature for 12 hours. The reaction mixture was immediately purified by preparative HPLC to obtain a racemic mixture of the white solid 43 (3.1 mg, yield: 18%), which was further separated by a chiral column to obtain Compound 43.

[0998] LCMS [M+H]+ = 610.2.

[0999] 1 ¹H NMR (400 MHz, DMSO-d 6) δ 8.89 (d, J = 1.2 Hz, 1H), 8.41 (d, J = 1.2 Hz, 1H), 7.54 (d, J = 8.4 Hz, 2H), 7.33 (s, 1H), 7.31 (s, 2H), 7.24 (d, J = 0.8 Hz, 1H), 6.67 (t, J = 7.8 Hz, 1H), 6.22-6.15 (m, 2H), 6.05 (d, J = 8.0 Hz, 1H), 5.51 (s, 1H), 4.98 (d, J = 4.4 Hz, 1H), 4.82-4.78 (m, 3H), 4.30 (d, J = 14.0 Hz, 1H), 4.13 (d, J = 14.8 Hz, 1H), 4.03 (s, 3H), 3.90 (s, 3H), 3.85 (s, 3H).

[1000] Compound 44

[1001]

[1002] Step 1: A racemic mixture of Compound 24E (20 mg, 0.03 mmol) was dissolved in dioxane / water (3 mL / 1 mL), and 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) were added. The reaction was carried out for 1 hour by heating to 100°C in a microwave under nitrogen protection. The reaction mixture was filtered, the filter cake was washed with ethyl acetate (2 mL x 3), and after concentration, a racemic mixture (20 mg) of the yellow solid 44B was obtained and used immediately for the next reaction. LCMS [M+H] + = 705.0.

[1003] Step 2: 6N HCl (0.5 mL) was added to a tetrahydrofuran (0.5 mL) solution of the racemic mixture of Compound 44B (20 mg, 0.03 mmol) and stirred at room temperature for 12 hours. The reaction mixture was immediately purified by preparative HPLC to obtain a racemic mixture of the white solid 44 (1.4 mg, yield: 8.2%), which was further separated by a chiral column to obtain Compound 44.

[1004] LCMS [M+H]+ = 605.2.

[1005] 1 ¹H NMR (400 MHz, DMSO- d 6) δ9.57 (d, J = 1.6 Hz, 1H), 9.28 (d, J = 1.2 Hz, 1H), 7.55-7.53 (m, 3H), 7.42 (s, 1H), 7.33-7.31 (m, 2H), 6.67 (t, J = 7.8 Hz, 1H), 6.20-6.15 (m, 2H), 6.07 (d, J = 8.0 Hz, 1H), 5.64 (s, 1H), 5.10 (d, J = 5.2 Hz, 1H), 4.82-4.78 (m, 3H), 4.34 (d, J = 13.6 Hz, 1H), 4.15 (d, J = 18.8 Hz, 1H), 3.90 (s, 3H), 3.87 (s, 3H), 3.09 (s, 3H).

[1006] Compound 45

[1007]

[1008] Step 1: A racemic mixture of compound 24E (20 mg, 0.03 mmol) was dissolved in dioxane / water (3 mL / 1 mL), and compound 45A (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 mixture was heated to 100°C in a microwave under nitrogen protection and reacted for 1 hour. The reaction mixture was filtered, the filter cake was washed with ethyl acetate (2 mL x 3), and after concentration, a racemic mixture (20 mg) of yellow solid 45B was obtained and used immediately for the next reaction.

[1009] Step 2: 6N HCl (0.5 mL) was added to a tetrahydrofuran (0.5 mL) solution of the racemic mixture of Compound 45B (20 mg, 0.03 mmol) and stirred at room temperature for 12 hours. The reaction mixture was immediately purified by preparative HPLC to obtain a racemic mixture of the white solid 45 (1.5 mg, yield: 8.8%), which was further separated using a chiral column to obtain Compound 45. LCMS [M+H] + = 579.2

[1010] 1 ¹H NMR (400 MHz, DMSO- d 6) δ 8.96 (d, J = 2.0 Hz, 1H), 8.59 (d, J = 5.6 Hz, 1H), 8.14 (d, J = 8.0 Hz, 1H), 7.70 - 7.46 (m, 3H), 7.33 (d, J = 8.4 Hz, 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 = 7.6 Hz, 1H), 5.51 (s, 1H), 4.99 (d, J = 4.4 Hz, 1H), 4.88 - 4.64 (m, 3H), 4.30 (d, J = 13.9 Hz, 1H), 4.14 (d,J = 10.5 Hz, 1H), 3.90 (s, 3H), 3.88 (s, 3H), 3.09 (s, 3H).

[1011] Compound 46

[1012]

[1013] Step 1: A racemic mixture 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 carried out in a microwave 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 a racemic mixture (20 mg) of the yellow solid 46B, which was used immediately for the next reaction. LCMS [M+H] + = 679.0.

[1014] Step 2: 6N HCl (0.5 mL) was added to a tetrahydrofuran (0.5 mL) solution of the racemic mixture of Compound 46B (20 mg, 0.03 mmol) and stirred at room temperature for 12 hours. The reaction mixture was immediately purified by preparative HPLC to obtain a racemic mixture of the white solid 46 (1.4 mg, yield: 8.2%), which was further separated by a chiral column to obtain Compound 46.

[1015] LCMS [M+H] + = 579.1.

[1016] 1 ¹H NMR (400 MHz, DMSO- d 6) δ 8.69-8.68 (m, 1H), 8.04 (d, J = 8.0 Hz, 1H), 7.92-7.88 (m, 1H), 7.54 (d, J = 8.8 Hz, 2H), 7.40-7.32 (m, 5H), 6.66 (t, J= 7.8 Hz, 1H), 6.20-6.15 (m, 2H), 6.05 (d, J = 7.2 Hz, 1H), 5.52 (s, 1H), 4.97 (d, J = 4.4 Hz, 1H), 4.82-4.79 (m, 3H), 4.30 (d, J = 14.0 Hz, 1H), 4.16-4.11 (m, 1H), 3.90 (s, 3H), 3.86 (s, 3H), 3.09 (s, 3H).

[1017] Compound 47

[1018]

[1019] Step 1: BH3·DMS (70 μL, 0.14 mmol) was added to a tetrahydrofuran solution (5 mL) of the racemic mixture of Compound 6A (30 mg, 0.05 mmol). The reaction system was stirred at 60 °C for 2 hours. Methanol (15 mL) was added to the reaction system and stirred continuously at 60 °C for 18 hours. The reaction mixture was rotary-dried and purified by normal-phase column chromatography (DCM:MeOH) to obtain a racemic mixture of the white solid 47A (20 mg, yield: 69%). LCMS [M+H] + = 639.2.

[1020] Step 2: 6M HCl (1 mL) was added to a THF (1 mL) solution of the racemic mixture of Compound 47A (20 mg, 0.03 mmol). The reaction system was stirred at room temperature for 18 hours. The reaction mixture was purified by reverse-phase column chromatography (H2O / ACN) to obtain a racemic mixture of the white solid 47 (14 mg, yield: 69%), which was further separated by a chiral column to obtain Compound 47.

[1021] LCMS [M+H] + = 539.2.

[1022] 1H NMR (400 MHz, DMSO) δ 9.68 (s, 1H), 8.25 (s, 1H), 7.57 - 7.36 (m, 5H), 7.18 (s, 2H), 6.85 (s, 1H), 6.45 (d, J = 39.4 Hz, 3H), 5.74 (s, 1H), 5.30 (d, J = 5.8 Hz, 1H), 4.68 (s, 1H), 3.87 (s, 3H), 3.68 (d, J = 13.2 Hz, 1H), 3.24 (d, J = 11.1 Hz, 1H), 2.95 (d, J = 3.3 Hz, 3H), 2.84 (t, J = 12.9 Hz, 4H), 1.24 (s, 1H).

[1023] Compound 48

[1024]

[1025] Step 1: A racemic mixture of compound 9H (210 mg, 0.4 mmol) and LiOH·H2O (48 mg, 1.19 mmol) was added to THF / MeOH / H2O (1.5 / 1.5 / 1.5 mL). The mixture was stirred at 20°C for 16 hours. The solution was purified using a reverse-phase column (MeCN / H2O / FA) to obtain a racemic mixture of the white solid 48A (150 mg, yield: 75%). LCMS [M+H] + = 516.7.

[1026] Step 2: A racemic mixture of Compound 48A (20 mg, 0.04 mmol), HATU (15 mg, 0.04 mmol), and TMP (14 mg, 0.12 mmol) was stirred in DMF (2 mL). A racemic mixture of Compound 48B (9 mg, 0.08 mmol) was added to the mixture and stirred at 20°C for 2 hours. The mixture was purified using a silica gel column (MeOH / DCM = 0–10%) to obtain a white solid 48 (10 mg, yield: 50%), which was further separated using a chiral column to obtain Compound 48.

[1027] LCMS [M+H] + = 571.2.

[1028] 1 H NMR (400 MHz, DMSO) δ 8.25 (s, 1H), 7.41 (s, 1H), 7.17 (d, J = 20.4 Hz, 2H), 7.05 (m, 4H), 7.00 - 6.94 (m, 1H), 6.91 (d, J = 7.2 Hz, 2H), 6.58 (m, 2H), 5.77 (m, 1H), 5.34 (d, J = 7.2 Hz, 1H), 4.91 (t, J = 4.4 Hz, 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).

[1029] Compound 49

[1030]

[1031] Step 1: A racemic mixture of compound 20H (25 mg, 0.04 mmol), compound 11A (50.38 mg, 0.4 mmol), HOAT (8.09 mg, 0.06 mmol), tert-dodecyl mercaptan (80.13 mg, 0.40 mmol), TMP (7.25 mg, 0.06 mmol), and zinc meso-tetraphenylporphyrin (2.69 mg, 0.001 mmol) were mixed with DMF (2 mL) and placed in a microwave tube. After purging the reaction system with nitrogen, the microwave tube was placed in hot water at 80°C and stirred while simultaneously irradiating with a 25W red lamp. Then, EDCI (75.77 mg, 0.40 mmol) was dissolved in 2 mL of DMF and slowly added dropwise to the reaction mixture, followed by stirring for 30 minutes. After the reaction was complete, the reaction mixture was purified using a silica gel column (H2O / ACN=40%:60%) to obtain a racemic mixture of target product 49A (16 mg, yield: 69%). LCMS [M+H-C4H8-H2O] + = 513.2.

[1032] Step 2: A racemic mixture of compound 49A (13 mg, 0.02 mmol) was dissolved in THF (2 mL), and 6 M HCl (4 mL) was added. The reaction mixture was stirred at room temperature (20 °C) for 4 hours. The reaction mixture was rotary dried and purified using a silica gel column (H2O / ACN=55:45) to obtain a racemic mixture of compound 49 (10 mg, yield: 93%), which was further separated using a chiral column to obtain compound 49.

[1033] LCMS [M+H] + = 487.2.

[1034] 1 H NMR (400 MHz, DMSO) δ 8.24 (d, J = 0.7 Hz, 1H), 7.40 (d, J = 0.7 Hz, 1H), 7.14 (dd, J = 5.1, 1.1 Hz, 2H), 7.04 (d, J = 9.0 Hz, 2H), 6.75 (t, J = 7.7 Hz, 1H), 6.62 (d, J = 9.0 Hz, 2H), 6.40 (s, 1H), 6.26 (t, J = 6.3 Hz, 2H), 5.06 (s, 1H), 5.01 (s, 1H), 4.65 (d, J = 3.7 Hz, 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, 4.9 Hz, 1H), 2.00 (dd, J = 12.7, 6.1 Hz, 1H).

[1035] Compound 50

[1036]

[1037] Step 1: A racemic mixture of Compound 20F (2.8 g, 3.86 mmol) was dissolved in dioxane (30 mL), and Pin2B2 (2.9 g, 11.59 mmol), Pd(dppf)Cl2 (630.3 mg, 0.77 mmol), and KOAc (1.1 g, 15.45 mmol) were added. The mixture was purged with nitrogen three times and stirred at 85°C for 16 hours. The reaction mixture was filtered, the filter cake was washed with EA, and the filtrate was concentrated and purified using a silica gel column (DCM / MeOH) to obtain a racemic mixture of Compound 50A (1.8 g, yield: 66%). LCMS [M+Na] + = 726.8.

[1038] Steps 2, 3: A racemic mixture of Compound 50A (200.0 mg, 0.28 mmol) was dissolved in dioxane / water (2 mL / 1 mL), and 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) were added. The mixture was purged with nitrogen three times, and the reaction mixture was stirred at 130°C for 2 hours. After concentration, the mixture was purified using a silica gel column (DCM / MeOH) to obtain a racemic mixture of Compound 50C (110 mg, Step 2 yield: 60%). LCMS [M+H] + = 641.8.

[1039] Step 4: HATU (26.7 mg, 0.07 mmol), DIEA (30.2 mg, 0.24 mmol), and the racemic mixture 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 saline solution, and dried with anhydrous Na2SO4. After filtration and concentration, the solution was purified using a silica gel column (DCM / MeOH) to obtain the racemic mixture of Compound 50D (20 mg, yield: 64%). LCMS [M+H] += 669.0.

[1040] Step 5: A racemic mixture of compound 50D (20.0 mg, 0.02 mmol) was dissolved in THF (1 mL), 6 M HCl (1 mL) was added under 0°C conditions, and the mixture was stirred at 25°C for 16 hours. After concentration, the mixture was purified by preparative HPLC to obtain a racemic mixture of white solid 50 (4.1 mg, yield: 24%), which was further separated using a chiral column to obtain compound 50.

[1041] LCMS [M+H] + = 568.2.

[1042] 1 H NMR (400 MHz, DMSO) δ 8.69 (dd, J = 4.7, 0.9 Hz, 1H), 8.05 (d, J = 8.1 Hz, 1H), 7.90 (td, J = 7.8, 1.8 Hz, 1H), 7.41 - 7.34 (m, 1H), 7.32 (dd, J = 6.4, 1.1 Hz, 2H), 7.10 (d, J = 8.9 Hz, 2H), 6.69 (t, J = 7.8 Hz, 1H), 6.64 (d, J = 9.0 Hz, 2H), 6.32 (s, 1H), 6.25 (d, J = 6.7 Hz, 1H), 6.10 (d, J = 7.0 Hz, 1H), 5.23 (s, 1H), 4.79 (d, J = 5.5 Hz, 1H), 4.73 (d, J = 3.6 Hz, 1H), 4.20 (d, J = 13.4 Hz, 1H), 4.01 (dd, J = 13.4, 6.1 Hz, 1H), 3.88 (s, 3H), 3.63 (s, 3H), 3.25 (s, 3H), 2.76 (s, 3H).

[1043] Compound 51

[1044]

[1045] Step 1: A racemic mixture of compound 50C (25 mg, 0.04 mmol), compound 11A (49.59 mg, 0.39 mmol), HOAT (7.97 mg, 0.06 mmol), tert-dodecyl mercaptan (78.88 mg, 0.39 mmol), TMP (7.13 mg, 0.06 mmol), and zinc meso-tetraphenylporphyrin (2.65 mg, 0.004 mmol) were mixed with DMF (2 mL) and placed in a microwave tube. After purging the reaction system with nitrogen, the microwave tube was placed in hot water at 80°C and stirred while simultaneously irradiating with a 25W red lamp. Then, 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 the reaction was complete, the reaction mixture was purified using a silica gel column (H2O / ACN=40:60) to obtain a racemic mixture of target product 51A (14 mg, yield: 60%). LCMS [M+H] + = 597.2.

[1046] Step 2: A racemic mixture of compound 51A (12 mg, 0.02 mmol) was dissolved in THF (2 mL), and 6 M HCl (4 mL) was added. The reaction mixture was stirred at room temperature (20 °C) for 4 hours. The reaction mixture was rotary dried and purified using a silica gel column (H2O / ACN = 55%:45%) to obtain a racemic mixture of target product 51 (3 mg, yield: 30%), which was further separated using a chiral column to obtain compound 51.

[1047] LCMS [M+H] + = 497.2.

[1048] 1H NMR (400 MHz, DMSO) δ 8.68 (d, J = 3.9 Hz, 1H), 8.03 (d, J = 8.1 Hz, 1H), 7.89 (td, J = 7.8, 1.8 Hz, 1H), 7.40 - 7.35 (m, 1H), 7.33 - 7.27 (m, 2H), 7.07 (d, J = 9.0 Hz, 2H), 6.73 (t, J = 7.7 Hz, 1H), 6.63 (d, J = 9.0 Hz, 2H), 6.37 (s, 1H), 6.23 (d, J = 7.8 Hz, 2H), 5.33 (t, J) = 4.6 Hz, 1H), 4.92 (s, 1H), 4.80 (s, 1H), 4.57 (d, J = 3.6 Hz, 1H), 4.50 (d, J = 4.1 Hz, 1H), 3.87 (s, 3H), 3.63 (s, 3H), 2.00 (dd, J = 15.0, 7.3 Hz, 3H).

[1049] Compound 52

[1050]

[1051] Step 1: A racemic mixture 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 the mixture was stirred at 25°C for 2 hours. The reaction was quenched by adding water, extracted twice with ethyl acetate, and the organic phase was concentrated and purified using a silica gel column (EA / PE) to obtain a racemic mixture of yellow solid 52A (20 mg, yield: 65%). LCMS [M+H] + = 658.2.

[1052] Step 2: A racemic mixture of compound 52A (20 mg, 0.030 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 filtered and purified using a reverse-phase column (ACN: 0.1% FA-H2O) to obtain a racemic mixture of yellow solid 52 (9.4 mg, yield: 55%), which was further separated using a chiral column to obtain compound 52.

[1053] LCMS [M+H] + = 558.2.

[1054] 1 H NMR (400 MHz, DMSO) δ 8.24 (s, 1H), 7.40 (s, 1H), 7.16 (d, J = 15.0 Hz, 2H), 7.08 (d, J = 8.9 Hz, 2H), 6.63 (t, J = 8.4 Hz, 3H), 6.23 (s, 1H), 6.15 (d, J = 7.9 Hz, 1H), 6.01 (d, J = 7.6 Hz, 1H), 5.28 (s, 1H), 4.80 - 4.69 (m, 4H), 4.20 (d, J = 13.4 Hz, 1H), 4.02 (dd, J = 13.5, 5.5 Hz, 1H), 3.85 (s, 3H), 3.62 (s, 3H), 3.25 (s, 3H), 2.77 (s, 3H).

[1055] Compound 53

[1056]

[1057] Step 1: A racemic mixture of Compound 50A (250 mg, 0.3553 mmol) was dissolved in dioxane (3 mL) and water (0.6 mL). Then, 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) were added, and the mixture was stirred by microwave at 130°C for 2.5 hours. The reaction mixture was filtered, concentrated, and purified using a silica gel column (EA / PE) to obtain a racemic mixture of the yellow solid 53A (200 mg, yield: 87%). LCMS [M+H-C4H8] + = 589.2.

[1058] Step 2: The racemic mixture of compound 53A (200 mg, 0.3102 mmol) was dissolved in THF (6 mL) and H2O (2 mL), and LiOH (40 mg, 0.9307 mmol) was added and stirred at 20°C for 16 hours. The pH of the reaction mixture was adjusted to 5 with 3 M HCl, concentrated, and purified using a silica gel column (DCM:MeOH=10:1) to obtain the racemic mixture of the yellow solid 53B (150 mg, yield: 77%). LCMS [M-C4H8+H] + = 575.1.

[1059] Step 3: A racemic mixture 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 the mixture was stirred at 25°C for 2 hours. The reaction mixture was filtered and concentrated, then purified using a reverse-phase column (ACN: 0.1% FA-H2O) to obtain a racemic mixture of the yellow solid 53C (120 mg, yield: 77%). LCMS [M+H] + = 658.2.

[1060] Step 4: A racemic mixture of compound 53C (60 mg, 0.091 mmol) was dissolved in THF (2 mL), BH3·THF (0.45 mL) was added under nitrogen protection, and the mixture was stirred at 60 °C for 3 hours; then, MeOH was added and the mixture was stirred 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 a racemic mixture of yellow solid 53D (30 mg, yield: 52%). LCMS [M+H] + = 644.2.

[1061] Step 5: A racemic mixture 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 immediately purified using a reverse-phase column (ACN: 0.1% FA-H2O) to obtain a racemic mixture of white solid 53 (17 mg, yield: 68%), which was further separated using a chiral column to obtain compound 53.

[1062] LCMS [M+H] + = 544.2.

[1063] 1 H NMR (400 MHz, DMSO) δ 8.25 (d, J = 0.7 Hz, 1H), 7.41 (d, J = 0.8 Hz, 1H), 7.19 - 7.15 (m, 4H), 6.88 (s, 3H), 6.64 (d, J = 9.0 Hz, 3H), 5.41 (d, J = 111.7 Hz, 2H), 4.71 (s, 1H), 3.87 (s, 3H), 3.62 (s, 3H), 3.24 (s, 1H), 2.95 (d, J = 4.3 Hz, 4H), 2.81 (d, J = 4.7 Hz, 4H), 1.24 (s, 1H).

[1064] Compound 54

[1065]

[1066] Step 1: A racemic mixture of Compound 50D (25.0 mg, 0.04 mmol) was dissolved in THF (1 mL), BH3·DMS (0.04 mL, 0.11 mmol) was added, and the mixture was stirred at 60°C for 2 hours. Methanol (1 mL) was added, and the mixture was stirred at 60°C for 18 hours. The reaction mixture was concentrated and purified using a silica gel column (DCM / MeOH) to obtain a racemic mixture of Compound 54A (10 mg, yield: 41%). LCMS [M+H] + = 654.2.

[1067] Step 2: A racemic mixture 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. After concentrating the reaction mixture, it was purified by preparative HPLC to obtain a racemic mixture of white solid 54 (1.2 mg, yield: 14%), which was further separated using a chiral column to obtain compound 54.

[1068] LCMS [M+H]+ = 554.2.

[1069] 1 H NMR (400 MHz, DMSO) δ 8.67 (d, J = 3.8 Hz, 1H), 8.01 (d, J = 8.0 Hz, 1H), 7.89 (t, J = 7.8 Hz, 1H), 7.39 - 7.33 (m, 1H), 7.27 (s, 2H), 7.18 (d, J = 8.9 Hz, 2H), 6.70 (d, J = 7.8 Hz, 1H), 6.62 (d, J = 9.0 Hz, 2H), 6.30 (s, 1H), 6.20 (d, J = 8.3 Hz, 1H), 6.10 (d, J = 7.6 Hz, 1H), 5.33 (d, J= 4.7 Hz, 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 = 13.7 Hz, 1H), 2.04 - 1.98 (m, 8H), 1.29 - 1.29 (m, 1H).

[1070] Compound 55

[1071]

[1072] Step 1: 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) were added to a mixture of toluene (25 mL) and H2O (10 mL) of the racemic mixture of Compound 2D (600 mg, 0.82 mmol), and the reaction mixture was stirred at 120 °C for 3 hours under nitrogen protection. The reaction mixture was poured into water (20 mL), extracted with EA (50 mL), and the organic phase was washed with 20 mL of saline solution. The organic phase was dried and concentrated, then purified by silica gel column chromatography (PE / EA=2 / 1) to obtain a racemic mixture of yellow oil-like substance 55B (450 mg, yield: 79%). LCMS [M+Na] + = 716.4.

[1073] Step 2: Pd(OH)2 / C (10%, 100 mg) was added to an EA / MeOH (1:1, 25 mL) mixed solution of the racemic mixture of Compound 55B (450 mg, 0.65 mol). The mixture was hydrogenated three times and stirred at 25°C for 18 hours. This process was repeated three times until the raw materials were completely consumed. The reaction mixture was filtered, and the filter cake was washed with MeOH / DCM (1 / 10). The combined filtrate was concentrated to obtain a racemic mixture of the white solid 55C (380 mg, yield: 97%). LCMS [M+Na] + = 626.2.

[1074] Step 3: K2CO3 (174 mg, 1.26 mmol) was added to a 15 mL DMF solution of the racemic mixture of Compound 55C (380 mg, 0.63 mmol) and Compound 2G (225 mg, 0.63 mmol), and the mixture was stirred at 60 °C for 2 hours. The mixture was poured into H2O (15 mL) and extracted with EtOAc (30 mL). The organic phase was washed with water (15 mL) and saline solution (15 mL) and dried with anhydrous Na2SO4. After filtration and concentration, the crude product was purified by silica gel column chromatography (DCM / EA = 0–30%) to obtain a racemic mixture of the white solid 55D (350 mg, yield: 76%). LCMS [M+Na] + = 758.0.

[1075] Step 4: Under nitrogen protection, bis(pinacolato)diborone (69 mg, 0.272 mmol), potassium acetate (40 mg, 0.408 mmol), and Pd(dppf)Cl2·DCM (17 mg, 0.02 mmol) were added to a 20 mL solution of the racemic mixture of compound 55D (50 mg, 0.068 mmol) in dioxane, and the mixture was stirred at 105 °C for 18 hours. The reaction mixture was concentrated and purified by silica gel column chromatography (DCM / EA=3 / 1) to obtain the racemic mixture of oil-form substance 55E (40 mg, yield: 83%). LCMS [M+Na] + = 736.4.

[1076] Step 5: Under nitrogen protection, 2-bromooxazole (50 mg, 0.34 mmol), Pd(dppf)Cl2·DCM (14 mg, 0.017 mmol), and Na2CO3 (27 mg, 0.25 mmol) were added to a mixture of dioxane (4 mL) and H2O (2 mL) of the racemic mixture of compound 55E (58 mg, 0.084 mmol), and the mixture was stirred by 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 saline solution (20 mL), dried, and concentrated. The crude product was purified by high-speed silica gel column chromatography (DCM / EA=2:1) ​​to obtain a racemic mixture of the white solid 55F (38 mg, yield: 70%). LCMS [M+Na] + = 677.3.

[1077] Step 6: H2O (2 mL), MeOH (2 mL), and LiOH (8 mg, 0.174 mmol) were added to a THF (2 mL) solution of the racemic mixture of Compound 55F (38 mg, 0.058 mmol), and the mixture was stirred at 25 °C for 18 hours. The reaction mixture was immediately purified using a reverse-phase column (MeCN / FA / H2O) to obtain a racemic mixture of the white solid 55G (25 mg, yield: 68%). LCMS [M+Na] + = 663.3.

[1078] Step 7: 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) were added to a DMF (2 mL) solution of the racemic mixture of Compound 55G (25 mg, 0.04 mmol), and the mixture was stirred at 20 °C for 2 hours. The reaction mixture was immediately purified using a reverse-phase column (MeCN / H2O / FA) to obtain a racemic mixture of the white solid 55H (18 mg, yield: 69%). LCMS [M+H] + = 668.3.

[1079] Step 8: A racemic mixture 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 mixture was purified by reverse-phase column chromatography (MeCH / FA / H2O) to obtain a racemic mixture of white solid 55 (6.0 mg, yield: 40%), which was further separated by a chiral column to obtain compound 55.

[1080] LCMS [M+H] + = 568.3.

[1081] 1 H NMR (400 MHz, DMSO) δ 8.25 (s, 1H), 7.41 (s, 1H), 7.18 (s, 1H), 7.14 (s, 1H), 7.04 (d, J = 8.3 Hz, 2H), 6.76 (d, J = 8.3 Hz, 2H), 6.63 (t, J = 7.7 Hz, 1H), 6.24 (s, 1H), 6.15 (d, J = 7.5 Hz, 1H), 6.02 (d, J = 7.4 Hz, 1H), 5.29 (s, 1H), 4.78 (d, J = 4.3 Hz, 2H), 4.74 (d, J = 5.2 Hz, 1H), 4.22 (d, J = 13.4 Hz, 1H), 4.08 - 4.00 (m, 1H), 3.85 (s, 3H), 3.26 (s, 3H), 2.77 (s, 3H), 1.74 (d, J = 4.9 Hz, 1H), 0.87 - 0.81 (m, 2H), 0.53 (d, J = 5.1 Hz, 2H).

[1082] Compound 56

[1083]

[1084] Step 1: 1 M DIBAL-H solution (0.1 mL, 0.1 mmol) was added to a THF (1 mL) mixture of the racemic mixture of Compound 55H (3 mg, 0.004 mmol). The mixture was stirred at 20°C for 5 hours. DIBAL-H solution (0.1 mL, 0.1 mmol) was continuously added, and stirring was continued at 60°C for 4 hours. The reaction was quenched with methanol, and the reaction mixture was concentrated. The crude product was purified by preparative TLC (DCM / MeOH) to obtain a racemic mixture of the white solid 56A (2.5 mg, yield: 80%). LCMS [M+H] + = 654.3.

[1085] Step 2: 6M HCl (2mL) was added to a THF (2mL) solution of the racemic mixture of compound 56A (3mg, 0.005mmol) and stirred at 25°C for 18 hours. The reaction mixture was purified using a reverse-phase chromatography column (MeCN / FA / H2O) to obtain a racemic mixture of white solid 56 (1.5mg, yield: 60%), which was further separated using a chiral column to obtain compound 56.

[1086] LCMS: [M+H] + = 554.2.

[1087] 1 H NMR (400 MHz, DMSO) δ 8.37 (s, 4H), 8.22 (s, 1H), 7.39 (s, 1H), 7.21 (s, 1H), 7.10 (d, J = 9.0 Hz, 4H), 6.75 (d, J = 8.5 Hz, 2H), 6.68 (t, J = 7.7 Hz, 2H), 6.28 (s, 1H), 6.18 (d, J = 7.6 Hz, 1H), 6.11 (d, J = 7.9 Hz, 1H), 5.33 (t, J = 4.6 Hz, 1H), 5.16 (s, 1H), 4.77 (s, 1H), 4.46 (d, J= 4.4 Hz, 1H), 3.83 (s, 3H), 3.53 (s, 2H), 2.20 (s, 6H), 1.97 (s, 1H), 1.73 (d, J = 5.4 Hz, 1H), 0.85-0.83 (m, 2H), 0.53-0.51 (m, 2H).

[1088] Compound 57

[1089]

[1090] 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 crude product obtained by concentrating the reaction solution was diluted with H2O (500 mL), extracted with DCM (500 mL x 2), washed with saline solution (500 mL x 2), and dried with Na2SO4. By filtration and concentration, yellow solid 57B (19.87 g, yield: 56%) was obtained. LCMS [M+H] + = 361.2.

[1091] Step 2: Compound 57B (18.8 g, 52.16 mmol) was dissolved in MeOH / H2O (100 mL / 50 mL), NaOH (14.61 g, 365.10 mmol) and H2O2 (80 mL) were added, and the mixture was stirred at 50 °C for 12 hours. The reaction solution was filtered, and the filter cake was washed with diethyl ether (100 mL). The filter cake was dissolved in 200 mL of DCM, the pH was adjusted to 5 with 1 N HCl (100 mL), washed with saline solution (100 mL × 2), and dried with Na2SO4. By filtration and concentration, the yellow solid 57C (8.9 g, yield: 46%) was obtained. LCMS [M+H] + = 375.0.

[1092] 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 * 2), and the reaction mixture (12 mL / h) was injected via a syringe and injection pump into a coil wound in a jacketed glass cylinder equipped with a 250 W UV lamp. The internal reaction temperature was controlled to 0–5°C by adjusting the temperature, 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 with a silica gel plug (EtOAc / hexane) to remove excess cinnamate, yielding a racemic mixture (8.1 g, total yield: 75%) of pale yellow solid 57D. LCMS [M+H] + = 537.7.

[1093] Step 4: The racemic mixture of Compound 57D (8.6 g, 16.03 mmol) was dissolved in methanol (120 mL), and sodium methoxide solid (2.163 g, 40.07 mmol) was slowly added in an ice bath (0 °C). The reaction mixture was then placed in an oil bath at 65 °C and stirred for 1.5 hours. After the reaction was complete, the methanol in the reaction mixture was rotary dried, then extracted with ethyl acetate (200 mL * 3). The organic phase was washed once each with ammonium chloride solution (100 mL) and saturated saline (100 mL), and dried with anhydrous sodium sulfate. After filtration and concentration, the mixture was purified using a silica gel column (FA in 0.2% EA / PE (65% / 35%)) to obtain the racemic mixture of Compound 57E (7.0 g, yield: 81%). LCMS [M+H-H2O] + = 519.7.

[1094] Step 5: A racemic mixture of Compound 57E (7.0 g, 9.39 mmol) was dissolved in an acetonitrile / chloroform (80 mL / 80 mL) mixed solution, and acetic acid (7.827 g, 130.46 mmol) and STAB (13.828 g, 65.23 mmol) were slowly added in an ice bath (0°C), and the reaction mixture was placed at room temperature and stirred for 2 hours. After the reaction was complete, the solvent of the reaction mixture was rotary dried, then extracted with ethyl acetate (200 mL * 3), the organic phase was washed with saturated saline (100 mL), and dried with anhydrous sodium sulfate. After filtration and concentration, the mixture was purified using a silica gel column (EA / PE = 50% / 50% with 0.2% FA) to obtain a racemic mixture of Compound 57F (3.8 g, yield: 54%). LCMS [M+H-H2O] + = 521.8.

[1095] Step 6: A racemic mixture of Compound 57F (3.8 g, 7.06 mmol) was dissolved in methanol (50 mL), 10% Pd / C (1.14 g) was added, the mixture was hydrogenated three times, and stirred at 20 °C for 16 hours. The reaction mixture was filtered and concentrated, and purified using a silica gel column (PE:EA=40:60) to obtain a racemic mixture of Compound 57G (3.0 g, yield: 85%). LCMS [ M+H-H2O ] + = 431.2.

[1096] Step 7: Under nitrogen protection, the racemic mixture of Compound 57G (2.8 g, 6.24 mmol) was dissolved in DMF (30 mL), Compound 2G (2.23 g, 6.24 mmol) and K2CO3 (1.723 g, 12.49 mmol) were added, and the reaction was carried out by heating at 60 °C for 1 hour. After the reaction was complete, water (100 mL) was added for quenching, extracted three times with EA (200 mL), the organic phase was washed with saturated saline solution, and dried with anhydrous sodium sulfate. After filtration and concentration, the mixture was purified using a silica gel column (PE:EA=60:40) to obtain the racemic mixture of Compound 57H (2.7 g, yield: 75%). LCMS [M+H-H2O]+ = 563.0.

[1097] Step 8: Under nitrogen protection, a racemic mixture 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 the mixture was stirred at 100°C for 1 hour. Water was added for quenching, extraction with EA was performed, the organic layer was washed with water and saline solution, and dried with anhydrous Na2SO4. After filtration and concentration, the mixture was purified using a silica gel column (DCM / MeOH=20:1) to obtain a racemic mixture of Compound 57I (100 mg, yield: 58%). LCMS [M+H]+ = 500.7.

[1098] Step 9: The racemic mixture of Compound 57I (100.0 mg, 0.20 mmol) was dissolved in THF / H2O / MeOH (3 mL / 1 mL / 1 mL), LiOH (25.3 mg, 0.60 mmol) was added, and the mixture was stirred at 40°C for 3 hours. The pH was adjusted to 5 with 3 M hydrochloric acid, and after concentration, the mixture was purified using a silica gel column (DCM / MeOH) to obtain the racemic mixture of Compound 57J (90 mg, yield: 92%). LCMS [M+H] + = 486.7.

[1099] Step 10: A racemic mixture 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. Then, DMA (0.6 μL, 0.93 mmol, 2 M in THF) was added and reacted at 25°C for 1 hour. The solution was diluted with water, extracted with EA, washed with water and saline solution, and dried with anhydrous Na2SO4. After filtration and concentration, the mixture was purified using a silica gel column (DCM / MeOH) to obtain a racemic mixture of Compound 57 (6.5 mg, yield: 6.8%), which was further separated using a chiral column to obtain Compound 57.

[1100] LCMS [M+H]+ = 513.8.

[1101] 1 H NMR (400 MHz, DMSO) δ 8.25 (s, 1H), 7.73 - 7.50 (m, 3H), 7.41 (s, 1H), 7.12 (d, J = 8.8 Hz, 2H), 7.06 - 6.95 (m, 3H), 6.83 (d, J = 7.1 Hz, 2H), 6.68 (d, J = 8.9 Hz, 2H), 4.94 (d, J = 8.1 Hz, 1H), 4.19 (d, J = 13.2 Hz, 1H), 4.02 (dd, J = 13.1, 8.1 Hz, 1H), 3.65 (s, 3H), 3.20 (s, 3H), 2.72 (s, 3H).

[1102] Compound 58

[1103]

[1104] Step 1: A racemic mixture 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 the mixture was reacted at 25°C for 1 hour. The reaction mixture was diluted with water, extracted with EA, washed with water and saline solution, dried with anhydrous Na2SO4, and purified by a silica gel column (DCM / MeOH) to obtain a racemic mixture of Compound 58 (14.1 mg, yield: 42%), which was further separated by a chiral column to obtain Compound 58.

[1105] LCMS [M+H] + = 541.2.

[1106] 1 H NMR (400 MHz, DMSO) δ 8.24 (s, 1H), 7.58 (d, J = 14.3 Hz, 3H), 7.40 (s, 1H), 7.05 (ddd, J = 21.5, 11.8, 6.0 Hz, 5H), 6.86 (d, J = 7.2 Hz, 2H), 6.67 (dd, J = 8.6, 7.0 Hz, 2H), 5.73 (dd, J = 10.7, 5.7 Hz, 1H), 5.59 (dd, J = 5.8, 2.5 Hz, 1H), 5.53 (d, J = 3.3 Hz, 1H), 4.83 (dt, J = 10.3, 7.7 Hz, 1H), 4.53 (dt, J = 40.9, 11.6 Hz, 2H), 4.15 (dd, J = 13.2, 7.7 Hz, 1H), 4.10 - 4.03 (m, 1H), 3.93 (ddd, J = 25.7, 13.2, 8.3 Hz, 1H), 3.78 - 3.66 (m, 1H), 3.65 (t, J= 5.7 Hz, 3H), 3.50 (ddd, J = 33.5, 10.0, 4.2 Hz, 1H).

[1107] Compound 59

[1108]

[1109] Step 1: A racemic mixture of compound 50A (100 mg, 0.1421 mmol) was dissolved in dioxane (2 mL) and water (0.4 mL), and 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) were added. The mixture was stirred by microwave at 130°C for 2 hours. The reaction mixture was filtered, concentrated, and purified using a silica gel column (EA / PE) to obtain a racemic mixture of the yellow solid 59A (70 mg, yield: 75%). LCMS [M+H-H2O] + = 638.2.

[1110] Step 2: A racemic mixture of compound 59A (60 mg, 0.09 mmol) was dissolved in THF (2 mL) and H2O (0.7 mL), and LiOH (11.5 mg, 0.27 mmol) was added and stirred at 20°C for 16 hours. The pH of the reaction mixture was adjusted to 5 with 3 M HCl, concentrated, and purified using a silica gel column (DCM:MeOH=10:1) to obtain a racemic mixture of the yellow solid 59B (40 mg, yield: 69%). LCMS [M+H-C4H8] + = 586.2.

[1111] Step 3: A racemic mixture 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 the mixture was stirred at 25°C for 2 hours. The reaction mixture was filtered and concentrated, then purified using a reverse-phase column (ACN: 0.1% FA-H2O) to obtain a racemic mixture of the yellow solid 59C (31 mg, yield: 76%). LCMS [M+H] + = 669.2.

[1112] Step 4: A racemic mixture of compound 59C (7 mg, 0.01 mmol) was dissolved in THF (1 mL), 6 M HCl (0.5 mL) was added and stirred at 20°C for 16 hours, and the reaction mixture was immediately purified using a reverse-phase column (ACN: 0.1% FA-H2O) to obtain a racemic mixture of white solid 59 (4.0 mg, yield: 67%), which was further separated using a chiral column to obtain compound 59.

[1113] LCMS [M+H] + = 569.2.

[1114] 1H NMR (400 MHz, DMSO) δ 8.94 (d, J = 4.9 Hz, 2H), 7.65 - 7.61 (m, 2H), 7.48 (t, J = 4.9 Hz, 1H), 7.10 (d, J = 8.9 Hz, 2H), 6.65 - 6.60 (m, 3H), 6.27 (s, 1H), 6.17 (d, J = 7.1 Hz, 1H), 6.00 (d, J = 7.8 Hz, 1H), 5.26 (s, 1H), 4.78 (d, J = 5.8 Hz, 1H), 4.74 (d, J = 4.0 Hz, 1H), 4.19 (d, J = 13.5 Hz, 1H), 4.01 (dd, J = 13.6, 6.0 Hz, 1H), 3.87 (s, 3H), 3.63 (s, 3H), 3.25 (s, 3H), 2.76 (s, 3H).

[1115] Compound 60

[1116]

[1117] Step 1: A racemic mixture of compound 59C (10 mg, 0.015 mmol) was dissolved in THF (1.5 mL), and DIBAL-H (0.045 mL, 0.045 mmol) was added under nitrogen protection at 0°C and reacted at 22°C for 1 hour. DIBAL-H (0.045 mL, 0.045 mmol) was added again under nitrogen protection at 0°C and reacted at 22°C for 1 hour. DIBAL-H (0.045 mL, 0.045 mmol) was added again under nitrogen protection at 0°C and reacted at 22°C for 1 hour. The reaction mixture was quenched with ice water, concentrated, and purified using a reverse-phase column (ACN: 0.1% FA-H2O) to obtain a racemic mixture of yellow solid 60A (5 mg, yield: 51%). LCMS [M+H] + = 655.5.

[1118] Step 2: A racemic mixture of compound 60A (5 mg, 0.008 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 immediately purified using a reverse-phase column (ACN: 0.1% FA-H2O) to obtain a racemic mixture of white solid 60 (2.5 mg, yield: 59%), which was further separated using a chiral column to obtain compound 60.

[1119] LCMS [M+H] + = 555.5.

[1120] 1 H NMR (400 MHz, ) δ 8.92 (d, J = 4.8 Hz, 2H), 8.13 (s, 1H), 7.57 (d, J = 16.0 Hz, 2H), 7.46 (t, J = 4.8 Hz, 1H), 7.17 (d, J = 8.9 Hz, 2H), 6.69 (t, J = 7.7 Hz, 1H), 6.62 (d, J = 8.9 Hz, 2H), 6.28 (s, 1H), 6.20 (d, J = 7.7 Hz, 1H), 6.07 (d, J = 7.2 Hz, 1H), 5.20 (s, 1H), 4.81 (s, 2H), 4.54 (s, 1H), 3.86 (s, 3H), 3.62 (s, 3H), 3.47 (d, J = 13.8 Hz, 1H), 3.06 (s, 2H), 2.37 (s, 6H).

[1121] Compound 61

[1122]

[1123] Step 1: An aqueous solution (0.4 mL) 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) was added to a dioxane (2 mL) solution of the racemic mixture of Compound 50A (100 mg, 0.142 mmol). The mixture was stirred at 100 °C for 16 hours under nitrogen protection. The reaction mixture was immediately purified using a silica gel column (PE / EA) to obtain the racemic mixture of Compound 61B (50 mg, yield: 50%). LCMS [M+H] + = 687.0.

[1124] Step 2: The racemic mixture of compound 61B (50 mg, 0.07 mmol) and LiOH·H2O (9 mg, 0.22 mmol) were added to a THF / MeOH / H2O (1 / 1 / 1, 3 mL) mixed solution and stirred at 20°C for 16 hours. The reaction mixture was purified using a reverse-phase column (ACN-H2O) (FA) to obtain the racemic mixture of the white solid 61C (34 mg, yield: 69%). LCMS [M+H] + = 673.0.

[1125] Step 3: A racemic mixture of compound 61C (34 mg, 0.05 mmol), HATU (19 mg, 0.05 mmol), and TMP (14 mg, 0.12 mmol) was stirred in DMF (2 mL). Dimethylamine (11 mg, 0.1 mmol) was added to the mixture and stirred at 20°C for 2 hours. The reaction mixture was purified using a reverse-phase column (ACN / H2O = 0–100%) to obtain a racemic mixture of white solid 61D (10 mg, yield: 50%). LCMS [M+H] + = 700.1.

[1126] Step 4: The racemic mixture of Compound 61D (6 mg, 0.0086 mmol) was dissolved in THF (1 mL), and 6 M HCl (1 mL) was added and stirred at 20 °C for 5 hours. The reaction mixture was immediately purified using a reverse-phase column (ACN-H2O) to obtain a racemic mixture of the white solid 61 (3.8 mg, yield: 70%), which was further separated using a chiral column to obtain Compound 61. LCMS [M+H] + = 600.0.

[1127] Compound 62

[1128]

[1129] Step 1: 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) were added to a dioxane / water (3 mL / 0.6 mL) solution of the racemic mixture of Compound 50A (70 mg, 0.1 mmol). The reaction system was purged with nitrogen three times and reacted in a microwave at 130 °C for 1 hour. The reaction mixture was purified by reverse-phase column chromatography (H2O + 0.1% FA / ACN) to obtain the racemic mixture of the yellow solid 62B (50 mg, yield: 75%). LCMS [M+H] + = 670.9.

[1130] Step 2: LiOH·H2O (6.41 mg, 0.15 mmol) was added to a THF / H2O (1 / 1, 2 mL) solution of the racemic mixture of Compound 62B (50 mg, 0.08 mmol) and stirred at room temperature for 18 hours. The reaction mixture was purified by reverse-phase column chromatography (H2O / ACN) to obtain the racemic mixture of the white solid 62C (25 mg, yield: 51%). LCMS [M+H-C4H8] + = 600.9.

[1131] Step 3: DIEA (7.88 mg, 0.06 mmol) was added to a 1 mL DMF solution of a racemic mixture of compound 62C (20 mg, 0.03 mmol), dimethylamine (12.44 mg, 0.15 mmol), and HATU (17.4 mg, 0.05 mmol), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was purified by reverse-phase column chromatography (H2O / ACN) to obtain a racemic mixture of the white solid 62D (25 mg, yield: 90%). LCMS [M+H] + = 684.1.

[1132] Step 4: 6M HCl (1 mL) was added to a THF (1 mL) solution of a racemic mixture of compound 62D (5 mg, 0.01 mmol) and stirred at room temperature for 5 hours. The reaction mixture was purified by reverse-phase column chromatography (H2O / ACN) to obtain a racemic mixture of white solid 62 (2.5 mg, yield: 60%), which was further separated by a chiral column to obtain compound 62.

[1133] LCMS [M+H] + = 583.2.

[1134] 1 H NMR (400 MHz, DMSO) δ 8.78 (s, 2H), 7.59 (d, J = 4.3 Hz, 2H), 7.10 (d, J = 8.8 Hz, 2H), 6.63 (t, J = 7.8 Hz, 3H), 6.25 (s, 1H), 6.16 (d, J = 7.6 Hz, 1H), 5.98 (d, J = 7.4 Hz, 1H), 5.25 (s, 1H), 4.86 - 4.63 (m, 4H), 4.17 (d, J = 13.5 Hz, 1H), 3.99 (dd, J = 13.4, 6.0 Hz, 1H), 3.87 (s, 3H), 3.63 (s, 3H), 3.25 (s, 3H), 2.76 (s, 3H), 2.34 (s, 3H).

[1135] Compound 63

[1136]

[1137] Step 1: A racemic mixture of compound 20F (200 mg, 0.28 mmol) was dissolved in 1,4-dioxane (20 mL), then 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) were added, and the mixture was stirred at 120°C for 12 hours. The crude product obtained by concentrating the reaction mixture was purified using a FLASH column (medium-low pressure high-speed preparative liquid chromatography) (PE / EA=2 / 1) to obtain a racemic mixture of yellow solid 63A (133.7 mg, yield: 73%). LCMS [M+H-C4H8] + = 602.2.

[1138] Step 2: Dissolve the racemic mixture of Compound 63A (133.7 mg, 0.20 mmol) in THF / H2O (3 mL / 1 mL), and LiOH . H2O (25.60 mg, 0.60 mmol) was added, and the reaction was carried out at 15°C for 12 hours. The reaction mixture was purified by preparative HPLC (H2O / ACN) to obtain a racemic mixture (92.9 mg, yield: 71%) of yellow solid 63B. LCMS [M+H-C4H8] + = 588.2.

[1139] Step 3: A racemic mixture of Compound 63B (92.9 mg, 0.14 mmol) was dissolved in DMF (2 mL), 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, and the mixture was reacted at room temperature for 2 hours. The reaction mixture was purified by preparative HPLC (H2O / ACN) to obtain a racemic mixture of the white solid 63C (71.9 mg, yield: 74%). LCMS [M+H] + =671.3.

[1140] Step 4: BH3 / DMS (0.13 mL, 0.33 mmol) and TFA (12.50 mg, 0.11 mmol) were added to a THF (2.5 mL) solution of the racemic mixture of compound 63C (72 mg, 0.11 mmol) and reacted at 20 °C for 12 hours. The reaction mixture was purified by preparative HPLC (H2O / ACN) to obtain a racemic mixture of the yellow oil-form substance 63D (28.4 mg, yield: 40%). LC-MS: [M+H] + =657.2.

[1141] Step 5: 6N HCl (1 mL) was added to a THF (1 mL) solution of a racemic mixture of compound 63D (28.3 mg, 0.04 mmol) and reacted at 15°C for 12 hours. The reaction mixture was purified by preparative HPLC (H2O / ACN) to obtain a racemic mixture of white solid 63 (5.8 mg, yield: 24%), which was further separated by a chiral column to obtain compound 63.

[1142] LCMS [M+H] + =557.2.

[1143] 1 ¹H NMR (400 MHz, DMSO- d 6) δ 8.31 (s, 1H), 8.24 (s, 1H), 7.54 (s, 1H), 7.14 (d, J = 8.8 Hz, 2H), 6.95 (s, 2H), 6.68 (t, J = 7.8 Hz, 1H), 6.62 (d, J = 9.2 Hz, 2H), 6.25 (s, 1H), 6.19-6.17 (m, 1H), 6.07 (d, J = 7.6 Hz, 1H), 5.05 (s, 1H), 4.80 (brs, 1H), 4.45 (d, J= 4.4 Hz, 1H), 3.82 (s, 1H), 3.62 (s, 3H), 3.48-3.44 (m,...

Claims

Claim 1 A compound represented by Formula II or a racemic mixture thereof, enantiomer, diastereomer, pharmaceutically acceptable salt, isotope-labeled compound, or a mixture of the aforementioned forms, Here, X 1 is N and C(R 1 Selected from ), and R 1 is selected from hydrogen, halogen, cyano, -OH, -(C1-C6) alkyl and -O-(C1-C6) alkyl; X 2 is N and C(R 2 Selected from ), and R 2 is selected from hydrogen, halogen, cyano, -OH, -(C1-C6) alkyl and -O-(C1-C6) alkyl; R 3 -(C3-C6) cycloalkyl, -(3-8) heterocyclyl, -(C6-C 10 ) selected from aryl and -(5-12 member) heteroaryl, and the -(C3-C6) cycloalkyl, -(3-8 member) heterocyclyl, -(C6-C 10 ) aryls and -(5-12-membered) heteroaryls have one or more R 31 It is optionally substituted by;R 31 Each is independently 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 won) heterocyclyl, -O-(C3-C6) cycloalkyl, -O-(4-10 won) 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 moieties) 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) Selected from -(C1-C6) alkyl]-NH2, -P(=O)[(C1-C6) alkyl]-NH(C1-C6) alkyl and -P(=O)[(C1-C6) alkyl]-N[(C1-C6) alkyl]2, and the above -(C1-C6) alkyl, -(C2-C6) alkenyl, -(C2-C6) alkynyl, -(C3-C6) cycloalkyl, -(4-10 member) heterocyclyl, -(C6-C 10 ) Aryl and -(5-12) heteroaryls are 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 ) optionally substituted by one or more groups selected from aryl and -(5-12-membered) heteroaryl, -(C1-C6) alkylene-O(C1-C6) alkyl, and oxo; R 4 is 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 won) heterocyclyl, -O-(4-10 won) heterocyclyl, -(C6-C 10 ) Aryl, -O-(C6-C 10 ) selected from aryl, -(5-12-membered) heteroaryl and -O-(5-12-membered) heteroaryl; X is 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 ], selected from S(=O) and S(=O)2;R a and R b are each independently hydrogen, halogen, cyano, -OR c , -SR c , -N(R c )R c , selected from -(C1-C6) alkyl and -(C1-C6) haloalkyl; R c is hydrogen, -(C1-C6) alkyl, -(C1-C6) haloalkyl, -O-(C1-C6) alkyl, -O-(C1-C6) haloalkyl, -(C3-C6) cycloalkyl, -O-(C3-C6) cycloalkyl, -(4-10 won) heterocyclyl, -O-(4-10 won) heterocyclyl, -(C6-C 10 ) Aryl, -O-(C6-C 10 ) selected from aryl, -(5-12-membered) heteroaryl and -O-(5-12-membered) heteroaryl; ring B is -(C6-C 10 Selected from aryls and -(5-12-membered) heteroaryls;R 5 and R 6 Each is independently 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 member) heterocyclyl, -O-(C3-C6) cycloalkyl, -O-(4-10 member) 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 groups selected from hydrogen, halogen, oxo, -OH, -O-(C1-C4) alkyl, -NH2, -NH(C1-C4) alkyl, and N[(C1-C4) alkyl]2, and or, R 5 and R 6 It forms a 5-membered heterocyclyl with the carbon atom connected to it; ring C is -(C6-C 10 Selected from aryls and -(5-12-membered) heteroaryls;R 7 Each is independently 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 member) heterocyclyl, -O-(C3-C6) cycloalkyl, -O-(4-10 member) 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 and -NHC(=O)-(C1-C6) alkyl, 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 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 and;R 8a , R 8b , R 9a and R 9b Each is independently 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, -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 ) selected from aryl, -(5-12 member) heteroaryl, -(C3-C6) cycloalkyl and -(4-10 member) heterocyclyl, where R is each independently 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 member) heterocyclyl, -O-(C3-C6) cycloalkyl, -O-(4-10 member) 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]-(C3-C6) cycloalkyl, -[(C1-C6) alkylene]-(4-10 atom) heterocyclyl, -(C6-C 10 ) aryl, -[(C1-C6) alkylene]-(C6-C 10 ) selected from aryl and -(5-12 group) heteroaryl, and the above -(C1-C6) alkylene-, -(C1-C6) alkyl, -(C2-C6) alkenyl, -(C2-C6) alkynyl, -(C3-C6) cycloalkyl, -(4-10 group) heterocyclyl, -(C6-C 10 ) The aryl, -(5-12 group) heteroaryl is 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 ... combines to form an oxo, -(C2-C6) alkenyl, -(C3-C6) cycloalkyl, or -(4-10 member) heterocyclyl, or, R 9a and R 9b ... combines to form an oxo, -(C2-C6) alkenyl, -(C3-C6) cycloalkyl, or -(4-10 member) heterocyclyl, or, R 8a and R 9a together with the carbon atoms connected thereto, it forms (C3-C6) cycloalkyl, (4-10) heterocyclyl, or (5-10) heteroaryl, and the aforementioned groups are hydrogen, halogen, -OH, -O-(C1-C4) alkyl, -NH2, -NH(C1-C4) alkyl, -N[(C1-C4) alkyl]2, -(C3-C6) cycloalkyl, -(4-8) heterocyclyl, -(5-6) heteroaryl and -(C6-C 10 ) Optionally substituted by one or more groups selected from aryls, or, R 8b and R 9b together with the carbon atoms connected thereto, it forms (C3-C6) cycloalkyl, (4-10) heterocyclyl, or (5-10) heteroaryl, and the aforementioned groups are hydrogen, halogen, -OH, -O-(C1-C4) alkyl, -NH2, -NH(C1-C4) alkyl, -N[(C1-C4) alkyl]2, -(C3-C6) cycloalkyl, -(4-8) heterocyclyl, -(5-6) heteroaryl and -(C6-C 10 ) Optionally substituted by one or more groups selected from aryls; R 10 Silver is selected from hydrogen, cyano, -OH and -NH2, or R 10 and R 9a A compound represented by Formula II, or a racemic mixture, enantiomer, diastereomer, pharmaceutically acceptable salt, isotope-labeled compound, or mixture of the above forms, wherein the (5-6) heterocyclyl 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. Claim 2 In claim 1, the compound is selected from compounds represented by formula I, and Here, X 1 is N and C(R 1 Selected from ), and R 1 is selected from hydrogen, halogen, cyano, -OH, -(C1-C6) alkyl and -O-(C1-C6) alkyl; X 2 is N and C(R 2 Selected from ), and R 2 is selected from hydrogen, halogen, cyano, -OH, -(C1-C6) alkyl and -O-(C1-C6) alkyl; R 3 -(C3-C6) cycloalkyl, -(3-8) heterocyclyl, -(C6-C 10 ) selected from aryl and -(5-12 member) heteroaryl, and the -(C3-C6) cycloalkyl, -(3-8 member) heterocyclyl, -(C6-C 10 ) aryls and -(5-12-membered) heteroaryls have one or more R 31 It is optionally substituted by;R 31 Each is independently 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 won) heterocyclyl, -O-(C3-C6) cycloalkyl, -O-(4-10 won) 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 moieties) 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) Selected from -(C1-C6) alkyl]-NH2, -P(=O)[(C1-C6) alkyl]-NH(C1-C6) alkyl and -P(=O)[(C1-C6) alkyl]-N[(C1-C6) alkyl]2, and the above -(C1-C6) alkyl, -(C2-C6) alkenyl, -(C2-C6) alkynyl, -(C3-C6) cycloalkyl, -(4-10 member) heterocyclyl, -(C6-C 10 ) Aryl and -(5-12) heteroaryls are 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 ) optionally substituted by one or more groups selected from aryl and -(5-12-membered) heteroaryl, -(C1-C6) alkylene-O(C1-C6) alkyl, and oxo; R 4 is 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 won) heterocyclyl, -O-(4-10 won) heterocyclyl, -(C6-C 10 ) Aryl, -O-(C6-C 10 ) selected from aryl, -(5-12-membered) heteroaryl and -O-(5-12-membered) heteroaryl; X is 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 ], selected from S(=O) and S(=O)2;R a and R b are each independently hydrogen, halogen, cyano, -OR c , -SR c , -N(R c )R c , selected from -(C1-C6) alkyl and -(C1-C6) haloalkyl; R c is hydrogen, -(C1-C6) alkyl, -(C1-C6) haloalkyl, -O-(C1-C6) alkyl, -O-(C1-C6) haloalkyl, -(C3-C6) cycloalkyl, -O-(C3-C6) cycloalkyl, -(4-10 won) heterocyclyl, -O-(4-10 won) heterocyclyl, -(C6-C 10 ) Aryl, -O-(C6-C 10 ) selected from aryl, -(5-12-membered) heteroaryl and -O-(5-12-membered) heteroaryl; ring B is -(C6-C 10 Selected from aryls and -(5-12-membered) heteroaryls;R 5 and R 6 Each is independently 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 member) heterocyclyl, -O-(C3-C6) cycloalkyl, -O-(4-10 member) 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 groups selected from hydrogen, halogen, oxo, -OH, -O-(C1-C4) alkyl, -NH2, -NH(C1-C4) alkyl, and N[(C1-C4) alkyl]2, and or, R 5 and R 6 It forms a 5-membered heterocyclyl with the carbon atom connected to it; ring C is -(C6-C 10 Selected from aryls and -(5-12-membered) heteroaryls;R 7 Each is independently 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 member) heterocyclyl, -O-(C3-C6) cycloalkyl, -O-(4-10 member) 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 and -NHC(=O)-(C1-C6) alkyl, 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 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 and;R 8a , R 8b , R 9a and R 9b Each is independently 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 ) selected from aryl, -(5-12 member) heteroaryl, -(C3-C6) cycloalkyl and -(4-10 member) heterocyclyl, where R is each independently 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 member) heterocyclyl, -O-(C3-C6) cycloalkyl, -O-(4-10 member) 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]-(C3-C6) cycloalkyl, -[(C1-C6) alkylene]-(4-10 atom) heterocyclyl, -(C6-C 10 ) aryl, -[(C1-C6) alkylene]-(C6-C 10 ) selected from aryl and -(5-12 group) heteroaryl, and the above -(C1-C6) alkylene-, -(C1-C6) alkyl, -(C2-C6) alkenyl, -(C2-C6) alkynyl, -(C3-C6) cycloalkyl, -(4-10 group) heterocyclyl, -(C6-C 10 ) The aryl, -(5-12 group) heteroaryl is 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 ... combines to form an oxo, -(C2-C6) alkenyl, -(C3-C6) cycloalkyl, or -(4-10 member) heterocyclyl, or, R 9a and R 9b ... combines to form an oxo, -(C2-C6) alkenyl, -(C3-C6) cycloalkyl, or -(4-10 member) heterocyclyl, or, R 8a and R 9a together with the carbon atoms connected thereto, it forms (C3-C6) cycloalkyl, (4-10) heterocyclyl, or (5-10) heteroaryl, and the aforementioned groups are hydrogen, halogen, -OH, -O-(C1-C4) alkyl, -NH2, -NH(C1-C4) alkyl, -N[(C1-C4) alkyl]2, -(C3-C6) cycloalkyl, -(4-8) heterocyclyl, -(5-6) heteroaryl and -(C6-C 10 ) Optionally substituted by one or more groups selected from aryls, or, R 8b and R 9b together with the carbon atoms connected thereto, it forms (C3-C6) cycloalkyl, (4-10) heterocyclyl, or (5-10) heteroaryl, and the aforementioned groups are hydrogen, halogen, -OH, -O-(C1-C4) alkyl, -NH2, -NH(C1-C4) alkyl, -N[(C1-C4) alkyl]2, -(C3-C6) cycloalkyl, -(4-8) heterocyclyl, -(5-6) heteroaryl and -(C6-C 10 ) Optionally substituted by one or more groups selected from aryls; R 10 Silver is selected from hydrogen, cyano, -OH and -NH2, or R 10 and R 9a A compound or a racemic mixture, enantiomer, diastereomer, pharmaceutically acceptable salt, isotope-labeled compound, or a mixture of the above forms a (5-6 member) heterocyclyl together with an atom connected thereto, wherein the (5-6 member) heterocyclyl 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. Claim 3 In paragraph 1 or 2, where, R 1 It is selected from hydrogen, halogen, cyano, -OH, -(C1-C4) alkyl and -O-(C1-C4) alkyl; preferably, R 1 Silver is selected from hydrogen, fluorine, chlorine, cyano, -OH, methyl, ethyl, propyl, -O-methyl, -O-ethyl, and -O-propyl; preferably, R 1 It is selected from hydrogen and -O-methyl; preferably, R 1 is -O-methyl, and X 1 A compound selected from N and C(OCH3), or a racemic mixture thereof, enantiomer, diastereomer, pharmaceutically acceptable salt, isotope-labeled compound, or a mixture of the aforementioned forms. Claim 4 In any one of paragraphs 1 to 3, where, R 2 is selected from hydrogen, halogen, cyano, -OH, -(C1-C4) alkyl and -O-(C1-C4) alkyl; preferably, R 2 is selected from hydrogen, fluorine, chlorine, cyano, -OH, methyl, ethyl, propyl, -O-methyl, -O-ethyl, and -O-propyl; preferably, R 2 is hydrogen, and X 2 is a compound selected from N and CH, or a racemic mixture thereof, enantiomer, diastereomer, pharmaceutically acceptable salt, isotope-labeled compound, or a mixture of the aforementioned forms. Claim 5 In any one of paragraphs 1 to 4, where, R 31 Silver, iodine, 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, -(C3-C6) cycloalkyl, -(4-8-membered) heterocyclyl, -O-(C3-C6) cycloalkyl, -O-(4-8-membered) heterocyclyl, Selected from -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 It is selected 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, preferably, R 31 Silver is selected from hydrogen, fluorine, chlorine, cyano, -OH, -SH, -NH2, methyl, halomethyl, -O-methyl, -CH2OH, -CH2NH2, and -CH2CH2N(CH3)2, and preferably, R 31 Silver is selected from hydrogen, fluorine, chlorine, cyano, -OH, -SH, and -NH2;R 3 -(C3-C6) cycloalkyl, -(3-6 member) heterocyclyl, -(C6-C 10 ) selected from aryl and -(5-12 member) heteroaryl, and the -(C3-C6) cycloalkyl, -(3-6 member) heterocyclyl, -(C6-C 10 ) aryls and -(5-12-membered) heteroaryls have one or more R 31 It is optionally substituted by, and R 31 The definition of is as set forth in the claims herein, and preferably, R 3 -(C6-C 10 ) selected from aryls and -(5-12-membered) heteroaryls, and the -(C6-C 10 ) aryls and -(5-12-membered) heteroaryls have one or more R 31 It is optionally substituted by, and R 31 The definition of is as set forth in the claims herein, and preferably, R 3 is selected from phenyl and -(5-10) heteroaryls, and said phenyl and -(5-10) heteroaryls are one or more R 31 It is optionally substituted by, and R 31 The definition of is as set forth in the claims herein, and preferably, R 3 is selected from -(5-6 member) heteroaryls, and said -(5-6 member) heteroaryls have 1, 2, 3, or 4 R groups. 31 It is optionally substituted by, and R 31 The definition of is as set forth in the claims herein, and preferably, R 3 is selected from oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, isothiazolyl, imidazolyl, triazolyl, tetrazolyl, pyridyl, pyrazinyl, pyridazinyl, pyrimidinyl, pyridazinoimidazolyl, pyrazinoimidazolyl, and pyrimidinonyl, wherein the oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, isothiazolyl, imidazolyl, triazolyl, tetrazolyl, pyridyl, pyrazinyl, pyridazinyl, pyrimidinyl, pyridazinoimidazolyl, pyrazinoimidazolyl, and pyrimidinonyl have 1, 2, or 3 R 31 It is optionally substituted by, and R 31 The definition of is as set forth in the claims herein, and preferably, R 3 silver , , , , , , , , , , , , , , , , , , , , , and Selected from, and the above , , , , , , , , , , , , , , , , , , , , , and is 1, 2, or 3 R 31 It is optionally substituted by, and R 31 The definition of is as set forth in the claims herein, and preferably, R 3 silver , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , and Selected from, more preferably, R 3 is selected from oxazolyl, pyrazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyridazinoimidazolyl, and pyrazinoimidazolyl, wherein the oxazolyl, pyrazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyridazinoimidazolyl, and pyrazinoimidazolyl have 1, 2, or 3 R 31 It is optionally substituted by, and R 31 The definition of is as set forth in the present claim; more preferably, R 3 silver , , , , , , , , , , , , , , , , , , , , , , , , , and Selected from; more preferably, R 3 is selected from oxazolyl, pyrazolyl, pyrimidinyl, and pyrazinyl, wherein the oxazolyl, pyrazolyl, pyrimidinyl, and pyrazinyl have 1, 2, or 3 R 31 Optionally substituted by (as defined in the claims), e.g., fluorine, cyano, amino, methyl, trifluoromethyl, -methylene-OH and -O-methyl; more preferably, R 3 silver , , , and Selected from, and the above , , , and is 1, 2, or 3 R 31 Optionally substituted by (as defined in the claims), e.g., fluorine, cyano, amino, methyl, trifluoromethyl, -methylene-OH and -O-methyl; more preferably, R 3 silver , , , , , , , , , , , and Selected from; or, R 3 It is selected from -(C3-C6) cycloalkyl and -(3-6 member) heterocyclyl, and said -(C3-C6) cycloalkyl and -(3-6 member) heterocyclyl is one or more R 31 It is optionally substituted by, and R 31 The definition of is as set forth in the present claim; preferably, R 3 ...is selected from cyclopropyl, oxetanil, azetidinil, tetrahydrofuranil, pyrrolidinil, tetrahydropyranil, piperidinil, piperazinil, piperazinonil, morpholinil, and morpholinonil, and the aforementioned group is one or more R 31 It is optionally substituted by, and R 31 The definition of is as set forth in the present claim; preferably, R 3 silver , , and A compound or a racemic mixture thereof selected from, enantiomers, diastereomers, pharmaceutically acceptable salts, isotope-labeled compounds, or mixtures of the aforementioned forms. Claim 6 In any one of paragraphs 1 to 5, where, R 4 is 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 member) heterocyclyl, -O-(4-8 member) heterocyclyl, -(C6-C 10 ) Aryl, -O-(C6-C 10 Selected from ) aryl, -(5-10 group) heteroaryl and -O-(5-10 group) heteroaryl; preferably, R 4 is selected from hydrogen, fluorine, chlorine, cyano, -OH, -NH2, methyl, halomethyl, -O-methyl, -NH-methyl, and cyclopropyl; preferably, R 4 is selected from hydrogen, fluorine, chlorine, cyano, -OH, and -NH2; preferably, R 4 is hydrogen, a compound or a racemic mixture thereof, enantiomer, diastereomer, pharmaceutically acceptable salt, isotope-labeled compound, or a mixture of the aforementioned forms. Claim 7 In any one of claims 1 to 6, 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, and preferably, X is selected from O, S and NH; more preferably, X is a compound or a racemic mixture thereof, enantiomer, diastereomer, pharmaceutically acceptable salt, isotope-labeled compound, or a mixture of the aforementioned forms. Claim 8 In any one of paragraphs 1 through 7, where, ring B is -(C6-C 10 ) selected from aryl and 5-10-membered heteroaryl, preferably, ring B is selected from phenyl, naphthyl, oxazolyl, thiazolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, pyridyl, pyrimidinyl, benzofuranyl, benzothienyl, indolyl, quinolinyl, and isoquinolinyl, preferably, ring B is phenyl, and preferably, structural unit Is Igo;R 5 and R 6 Each is independently 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, wherein the -(C1-C4) alkyl, -(C2-C4) alkenyl, -(C2-C4) alkynyl, -(C3-C6) cycloalkyl, and -(4-8-membered) heterocyclyl are 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, Optionally substituted by groups 1, 2, 3, 4, or 5 selected from -N(ethyl)2 and -N(ethyl)-propyl, preferably, 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; preferably, 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, and 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 Silver is selected from hydrogen, fluorine, chlorine, bromine, cyano, -OH, -NH2, -O-methyl, and cyclopropyl; or, R 5 and R 6 silver together with the atoms connected to it A compound or a racemic mixture thereof, enantiomer, diastereomer, pharmaceutically acceptable salt, isotope-labeled compound, or mixture of the aforementioned forms, wherein * indicates the position of the connected atoms. Claim 9 In any one of paragraphs 1 through 8, where, ring C is -(C6-C 10 ) selected from aryl and -(5-10-membered) heteroaryl, preferably, ring C is selected from phenyl, naphthyl, oxazolyl, thiazolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, pyridyl, pyrimidinyl, benzofuranyl, benzothienyl, indolyl, quinolinyl, and isoquinolinyl, preferably, ring C is phenyl, and preferably, structural unit Is or Igo;R 7 Each is independently 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, wherein the -(C1-C4) alkyl, -(C2-C4) alkenyl, -(C2-C4) alkynyl, -(C3-C6) cycloalkyl, and -(4-8-membered) heterocyclyl are 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, Optionally substituted by groups 1, 2, 3, 4, or 5 selected from -N(ethyl)2 and -N(ethyl)-propyl, preferably, 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, and preferably, 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, and preferably, R 7 Each is independently selected from hydrogen, -OH, and -NH2, and more preferably, R 7 Each is independently selected from hydrogen and -NH2; preferably, m is 1, 2 or 3, a compound or a racemic mixture thereof, enantiomer, diastereomer, pharmaceutically acceptable salt, isotope-labeled compound, or a mixture of the aforementioned forms. Claim 10 In any one of claims 1 to 9, wherein R is each independently 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 member) heterocyclyl, -(C6-C 10 ) aryl, -[(C1-C4) alkylene]-(C6-C 10 ) selected from aryl and -(5-10 member) heteroaryl, and the above -(C1-C4) alkylene-, -(C1-C4) alkyl, -(C2-C4) alkenyl, -(C2-C4) alkynyl, -(C3-C6) cycloalkyl, -(4-8 member) heterocyclyl, -(C6-C 10 ) Aryl and -(5-10 member) heteroaryls 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, R is each independently 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 member) The group is selected from heterocyclil, -C(=O)-H, -C(=O)-(C1-C4) alkyl, -C(=O)-(C3-C6) cycloalkyl, -[(C1-C4) alkylene]-(C3-C6) cycloalkyl, and -[(C1-C4) alkylene]-(4-8-membered) heterocyclil, wherein the -(C1-C4) alkylene-, -(C1-C4) alkyl, -(C3-C6) cycloalkyl, and -(4-8-membered) heterocyclil are 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, -N(ethyl)-propyl, methyl, and It is optionally substituted by groups 1, 2, 3, 4, or 5 selected from ethyl, and preferably, R is each independently hydrogen, -OH, -NH2, methyl, ethyl, propyl, halomethyl, haloethyl, halopropyl, -methylene-O-methyl, -methylene-O-ethyl, -ethylene-O-methyl, -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, tetrahydrofuranil, tetrahydropyranil, azetidinyl, Pyrrolidinyl, piperidinyl,Selected from piperazinyl, morpholinyl, -methylene-cyclobutyl, -methylene-oxetanyl, and -methylene-azetidinyl, wherein the methyl, ethyl, propyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, tetrahydrofuranil, tetrahydropyranil, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, and morpholinyl are optionally substituted by one, two, or three groups selected from -OH, -OCH3, -NH2, NHCH3, N(CH3)2, and -CH3, and preferably, R is each independently 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; more preferably, R is each 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 members) Selected from heterocyclil, -methylene-(C3-C6)cycloalkyl and -methylene-(4-8-membered) heterocyclil, wherein the -(C1-C4)alkyl, -(C3-C6)cycloalkyl and -(4-8-membered) heterocyclil are each selectively 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, and more preferably, R is each independently hydrogen, -OH, methyl, ethyl, propyl, -O-methyl, -O-ethyl, -O-propyl, -methylene-O-ethyl, -C(=O)-methyl,-S(=O)2-methyl, cyclobutyl, oxetanil, azetidinyl, pyrrolidinyl, piperazinyl, -methylene-cyclobutyl, -methylene-oxetanil and -methylene-azetidinyl are selected from, and each of the aforementioned groups is 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 is independently 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, -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 Selected from aryl, -(5-10 group) heteroaryl, -(C3-C6) cycloalkyl, and -(4-8 group) heterocyclyl, and the definition of R is as described in the present claim, preferably, R 8a , R 8b , R 9a and R 9b Each 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 The definition of R is as set forth in the present claim; preferably, 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 the definition of R is as set forth in the claims herein, preferably, 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 the definition of R is as set forth in the claims herein, 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 said -(C1-C4) alkyl and -(4-8-membered) heterocyclyl are each 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 and, preferably, R 8b is hydrogen, , , , , , , , , , , , , , , , , , , , , , , , , , and Selected from, preferably, R 8b is hydrogen, , , , , , , , , , , , , , , , , , , , , , , , , , and Selected from, 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, and the definition of R is as set forth in the claims herein, for example, R is each independently selected from hydrogen, -OH, methyl, ethyl, -O-methyl, -C(=O)-methyl, -S(=O)2-methyl, azetidinyl, pyrrolidinyl, and piperazinyl, and each of the aforementioned groups is each independently optionally substituted by one, two, or three groups selected from -OH and -NH2, more preferably, R 8b is hydrogen, , , , , , , , , , , , , , , , and Selected from, more preferably, R 8b is hydrogen, , , , , , and Selected from; preferably, 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 the definition of R is as set forth 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, and the definition of R is as set forth in the claims herein, 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, and the -(C1-C4) alkyl, -(C3-C6) cycloalkyl, and -(4-8-membered) heterocyclyl are each hydrogen, Optionally substituted by 1, 2, 3, 4, or 5 groups selected from halogen, -OH, -NH2, -NH(C1-C4) alkyl, -N[(C1-C4) alkyl]2, -O-(C1-C4) alkyl, and -(C1-C4) alkyl; preferably, 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, and the definition of R is as set forth in the claims herein, for example, R is each independently selected from hydrogen, -OH, methyl, ethyl, -methylene-O-ethyl, -S(=O)2-methyl, cyclobutyl, azetidinyl, -methylene-cyclobutyl, and -methylene-azetidinyl, and each of the aforementioned groups is each independently optionally substituted by one, two, or three groups selected from -OH, OCH3, NHCH3, N(CH3)2, and CH3; preferably, R 9a is 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(CH3)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, Selected from -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 is hydrogen, , , , , , , , , , , , , , , , , , , , , , , , , , and Selected from, preferably, R 9a is hydrogen, , , , , , , , , , , , , , and Selected from, preferably, R 9a Is and; preferably, R 9b is hydrogen and Selected from; or, R 8a and R 8b ... combines to form an oxo, -(C2-C4) alkenyl, -(C3-C6) cycloalkyl, or -(4-8-membered) heterocyclyl, or, R 9a and R 9b It combines to form an oxo, -(C2-C4) alkenyl, -(C3-C6) cycloalkyl, or -(4-8-membered) heterocyclyl, and preferably, R 8a and R 8b It combines to form oxo, vinyl, propene, cyclopropyl, cyclobutyl, cyclopentyl, oxetanil, tetrahydrofuranil, tetrahydropyranil, azetidinil, pyrrolidinyl, piperidinyl, or piperazinyl, and preferably, R 9a and R 9b ... combines to form oxo, vinyl, propene, cyclopropyl, cyclobutyl, cyclopentyl, oxetanil, tetrahydrofuranil, tetrahydropyranil, azetidinil, pyrrolidinyl, piperidinyl, or piperazinyl; or, R 8a and R 9a together with the carbon atoms connected thereto, it forms (C3-C6) cycloalkyl, (4-8) heterocyclyl, or (5-9) heteroaryl, and the aforementioned groups are hydrogen, halogen, -OH, -O-(C1-C4) alkyl, -NH2, -NH(C1-C4) alkyl, -N[(C1-C4) alkyl]2, -(C3-C6) cycloalkyl and -(C6-C 10 ) Optionally substituted by 1, 2, 3, 4, 5, 6, or 7 groups selected from aryls, or, R 8b and R 9b together with the carbon atoms connected thereto, it forms (C3-C6) cycloalkyl, (4-8) heterocyclyl, or (5-9) heteroaryl, and the aforementioned groups are hydrogen, halogen, -OH, -O-(C1-C4) alkyl, -NH2, -NH(C1-C4) alkyl, -N[(C1-C4) alkyl]2, -(C3-C6) cycloalkyl and -(C6-C 10 ) Optionally substituted by 1, 2, 3, 4, 5, 6, or 7 groups selected from aryls, preferably, R 8a and R 9a is formed with the carbon atoms connected thereto as (4-8 members) heterocyclyl or (5-9 members) heteroaryl, and the aforementioned group is 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, and preferably, R 8b and R 9b is formed with the carbon atoms connected thereto as (4-8 members) heterocyclyl or (5-9 members) heteroaryl, and the aforementioned group is 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, and preferably, R 8a and R 9a is formed together with the carbon atom connected thereto as oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, pyridinonyl, pyrimidinonyl, oxazolyl, thiazolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, pyridyl, pyrimidinyl, benzothienyl or indolyl, and the aforementioned group is optionally substituted by one, two, or three 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, and preferably, R 8b and R 9b is formed together with the carbon atom connected thereto as oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, pyridinonyl, pyrimidinonyl, oxazolyl, thiazolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, pyridyl, pyrimidinyl, benzothienyl or indolyl, and the aforementioned group is optionally substituted by one, two, or three 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, and preferably, R 8a and R 9a is absent, and R 8b and R 9b together with the atoms connected to it A compound or a racemic mixture thereof, enantiomer, diastereomer, pharmaceutically acceptable salt, isotope-labeled compound, or mixture of the aforementioned forms, wherein * indicates the position of the connected atoms. Claim 11 In any one of paragraphs 1 through 10, where, R 10 is selected from -OH, or R 10 and R 9a ... forms a pentatonic nitrogen-containing heterocyclyl together with an atom connected thereto, wherein the pentatonic nitrogen-containing heterocyclyl is selectively 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, and preferably, R 10 is selected from -OH, or R 10 and R 9a is formed with an atom connected thereto to form imidazolinyl, said imidazolinyl is optionally substituted by one, two, or three groups selected from halogen, -OH, methyl, -NH2, -NH-methyl, and -N(methyl)2, and preferably, R 10 is -OH, or, R 10 and R 9a together with the atoms connected to it It forms, where * indicates the position of the connected atom; preferably, R 10 It is -OH, and preferably Phosphorus, a compound or a racemic mixture thereof, enantiomer, diastereomer, pharmaceutically acceptable salt, isotope-labeled compound, or a mixture of the aforementioned forms. Claim 12 In any one of claims 1 to 11, the compound is selected from the compounds represented by Formula I-1, and Here, 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 The definitions of and m are as described in any one of claims 1 to 11, n is 0, 1, 2, 3, 4 or 5, and the structural fragment The definition of is R 3 As defined in, and R 3 The definition is as described in any one of claims 1 to 11, and preferably, ring A is selected from 5-10-membered heteroaryls, preferably 5-9-membered heteroaryls, preferably 5-6-membered heteroaryls, preferably oxazolyl, thiazolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, pyridyl, and pyrimidinyl, preferably , , , , , , , , , , and and, preferably, oxazolyl and pyrimidinyl, for example , , and And; preferably, the compound is selected from the compound represented by Formula I-1-A, and Here, 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 through 11, and the definitions of ring A and n are as described in the present claims, and structural unit is preferably or and preferably And; preferably, the compound is selected from the compound represented by Formula I-1-B, and Here, 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 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; preferably, said compound is selected from compounds represented by the formula I-1-AB-1D, and Here, R 31 , R 1 , R 4 , R 5 , R 6 , R 7 , R 8b , R 9a , R 9b The definitions of and m are as set forth in any one of claims 1 through 11, and the definitions of ring A and n are as set forth in the present claims; R 8b1 is selected from R and N(R)R, and the definition of R is a compound or a racemic mixture thereof, enantiomer, diastereomer, pharmaceutically acceptable salt, isotope-labeled compound, or a mixture of the aforementioned forms as described in claim 1, 2 or 10. Claim 13 In any one of claims 1 to 12, the compound is Compounds or racemic mixtures thereof selected from, enantiomers, diastereomers, pharmaceutically acceptable salts, isotope-labeled compounds. Claim 14 A pharmaceutical composition comprising at least one compound according to any one of claims 1 to 13 or a racemic mixture thereof, enantiomers, diastereomers, pharmaceutically acceptable salts, isotope-labeled compounds, or mixtures of the aforementioned forms, and one or more pharmaceutically acceptable carriers and / or excipients. Claim 15 A use of a compound according to any one of claims 1 to 13 or a racemic mixture thereof, enantiomer, diastereomer, pharmaceutically acceptable salt, isotope-labeled compound, or mixture of the aforementioned forms, or a pharmaceutical composition according to claim 14, for the treatment and / or prevention of a disease or disease or for the reduction of the severity of said disease or disease, wherein said disease or disease is a tumor or cancer; preferably, said tumor or cancer is selected from gastric cancer, colorectal cancer, breast cancer, ovarian cancer and liver cancer.

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