6, 5, 7, 6-tetracyclic derivative as well as preparation method and application thereof

Abstract

The invention relates to a 6, 5, 7, 6-tetracyclic derivative with a structural characteristic shown in a formula (I) as well as a preparation method and application of the 6, 5, 7, 6-tetracyclic derivative, including application of pharmaceutically acceptable salt of the 6, 5, 7, 6-tetracyclic derivative in treatment of tuberculosis. The compound is novel in structure, has good in-vitro and in-vivo anti-tubercle bacillus activity, and is a novel anti-tubercle bacillus compound with a good application prospect in the field of medicines. # imgabs0 #

Description

6,5,7,6-tetracyclic derivatives, preparation methods and applications thereof Technical Field

[0001] The present invention belongs to the technical field of medicinal chemistry, and particularly relates to a 6,5,7,6-tetracyclic derivative, a preparation method and an application thereof. Background Art

[0002] It is currently estimated that there are 2 billion people infected with tuberculosis worldwide, 20 million current cases of tuberculosis, 8-9 million new cases each year, more than half of which are infectious pulmonary tuberculosis, and 3 million people die from tuberculosis each year.

[0003] Mycobacterium tuberculosis can infect the patient's lungs and cause pulmonary tuberculosis. It can also infect extrapulmonary organs such as the intestines, peritoneum, kidneys, parasites, ureters, pleura, bones, joints, brain, reproductive system, etc. Extrapulmonary tuberculosis is more common in people with weakened immunity. Pulmonary tuberculosis includes primary pulmonary tuberculosis, hematogenously disseminated pulmonary tuberculosis and secondary pulmonary tuberculosis. Primary pulmonary tuberculosis, also known as primary tuberculosis, is more common in children. Classic lesions include tuberculous inflammation of the primary lung lesion, draining lymphatic vessels and hilar or mediastinal lymph nodes. The combination of the three is called the primary syndrome. Tuberculosis patients often experience low-grade fever, night sweats, fatigue, and weight loss. High fever may occur when the lesions progress rapidly. Other symptoms vary depending on the site of infection: Pulmonary tuberculosis patients often have cough, sputum, hemoptysis, chest pain, and shortness of breath. Allergic reactions and anergic tuberculosis may also occur. Intestinal tuberculosis is most commonly acquired through the oral route, when patients with open pulmonary or laryngeal tuberculosis swallow sputum containing Mycobacterium tuberculosis. It often develops in the ileocecal region, causing abdominal pain, diarrhea, constipation, and abdominal masses. It can also be complicated by intestinal obstruction, fistulas, abscesses, and acute intestinal perforation. Tuberculous peritonitis is often accompanied by abdominal pain, ascites, a tender abdominal wall or abdominal mass, and diarrhea.

[0004] Currently, the first-line treatment for tuberculosis includes isoniazid, rifampicin, streptomycin, pyrazinamide, and ethambutol. However, drug resistance and severe side effects are now common in these drugs.

[0005] CN109942523A discloses the use of a class of benzofuranocoumarin compounds for the treatment of Mycobacterium tuberculosis. Although these compounds have good in vitro inhibitory activity against Mycobacterium tuberculosis, the inventors of the present invention have found that they have poor solubility, and are expected to have poor absorption and conversion effects in the body. In addition, they have been shown to have strong toxicity in repeated in vivo dosing toxicity tests.

[0006] Therefore, there is an urgent need in this field to find a new anti-tuberculosis drug to overcome the limitations of existing drugs.

[0007] Summary of the Invention

[0008] In a first aspect, the present invention provides a class of 6,5,7,6-tetracyclic derivatives having anti-tuberculosis effects and pharmaceutically acceptable salts, stereoisomers, tautomers, N-oxides, hydrates, solvates, prodrugs, and isotopic variants thereof, which have the structure shown in Formula I below. The compounds provided by the present invention have good tuberculosis inhibitory activity and low in vivo toxicity and can be used as anti-tuberculosis drugs.

[0009] A second aspect of the present invention provides a simple and efficient method for synthesizing the compounds described in any embodiment herein.

[0010] In a third aspect, the present invention provides the use of the compound described in any embodiment herein and its pharmaceutically acceptable salts, stereoisomers, tautomers, N-oxides, hydrates, solvates, prodrugs and isotopic variants in the preparation of antibacterial, anticancer, anti-rheumatic, antioxidant, anti-inflammatory, antiviral, hepatoprotective or hepatoprotective drugs or drugs for treating and / or preventing cardiovascular diseases, or in the preparation of drugs for treating infectious diseases, in particular diseases caused by sensitive or resistant Mycobacterium tuberculosis.

[0011] The fourth aspect of the present invention provides a pharmaceutical composition comprising: (i) an effective amount of the compound of the present invention and its pharmaceutically acceptable salts, stereoisomers, tautomers, N-oxides, hydrates, solvates, prodrugs and isotopic variants as an active ingredient, and (ii) a pharmaceutically acceptable carrier or excipient.

[0012] In a fifth aspect, the present invention provides a method for antibacterial, anticancer, antirheumatic, antioxidant, anti-inflammatory, antiviral, hepatoprotective or treatment and / or prevention of cardiovascular disease, which comprises administering to a subject in need thereof an effective amount of a compound according to any embodiment of the present invention or a pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide, hydrate, solvate, prodrug or isotopic variant thereof.

[0013] In a sixth aspect, the present invention provides a method for treating infectious diseases, particularly diseases caused by sensitive or resistant Mycobacterium tuberculosis, comprising administering to a subject in need thereof an effective amount of a compound according to any embodiment of the present invention or a pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide, hydrate, solvate, prodrug or isotopic variant thereof. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] Figure 1: Anti-TB activity of compounds TY176 and TY177 in mice DETAILED DESCRIPTION

[0015] I. Terminology

[0016] It should be understood that the features of the various embodiments described herein can be arbitrarily combined to form the technical solutions of this invention; the definition of each group herein is applicable to any embodiment described herein, for example, the definition of the substituent of the alkyl group herein is applicable to any embodiment described herein, unless the embodiment has clearly defined the substituent of the alkyl group.

[0017] The heteroatoms described herein include oxygen (O), sulfur (S) and nitrogen (N).

[0018] As used herein, "alkyl" refers to a straight or branched chain saturated hydrocarbon group having 1 to 10 carbon atoms, preferably 1 to 8 or 1 to 6 carbon atoms. In certain embodiments, the alkyl group is a C1-C4 alkyl group. In some embodiments, the alkyl group is a C1-C3 alkyl group. Exemplary alkyl groups include methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, hexyl, and octyl.

[0019] As used herein, "alkenyl" refers to a straight or branched unsaturated hydrocarbon group containing 2 to 10 carbon atoms, containing at least one carbon-carbon double bond. In some embodiments, the alkenyl group is a C2-C8 alkenyl group. Exemplary alkenyl groups include ethenyl, 1-propenyl, 2-propenyl, 2-methyl-1-propenyl, 1-butenyl, and 2-butenyl.

[0020] As used herein, "alkynyl" refers to a straight or branched unsaturated hydrocarbon group containing 2 to 10 carbon atoms, which contains at least one carbon-carbon triple bond. In some embodiments, the alkynyl group is a C2-C6 alkynyl group. Exemplary alkynyl groups include ethynyl, 1-propynyl, 1-methyl-2-propynyl, 2-propynyl, 1-butynyl, and 2-butynyl.

[0021] The "alkoxy" used herein refers to a C1-C 10 Alkyl, preferably C1-C6 alkyl or C1-C4 alkyl or oxy substituted by C1-C3 alkyl, such as methoxy, ethoxy, etc.

[0022] As used herein, "aryl" is a monocyclic, bicyclic, or tricyclic aromatic group containing 6 to 14 carbon atoms. In some embodiments, aryl is C6-C 10 Aryl. Exemplary aryl groups include phenyl, naphthyl, phenanthrenyl, anthracenyl, indenyl, azulenyl, biphenyl, biphenylene, and fluorenyl.

[0023] As used herein, "carbocyclyl" includes saturated and partially saturated carbocyclyl groups. The number of ring carbon atoms in a carbocyclyl group is 3-15. Saturated carbocyclyl groups include cycloalkyl groups, which are typically C3-C8 cycloalkyl groups, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl. Partially saturated carbocyclyl groups include cycloalkenyl groups, such as C3-C8 cycloalkenyl groups, for example cyclopentenyl, cycloheptenyl and cyclooctenyl. Herein, carbocyclyl groups also include bridged ring groups and spirocyclyl groups. Preferably, herein, the number of ring carbon atoms in a bridged ring group and spirocyclyl groups can be 4-12.

[0024] Herein, halogen includes fluorine, chlorine, bromine and iodine.

[0025] As used herein, an acylamino group is any C1-C 10 Acyl, which can be represented by R-NH-, where R is C1-C 10 Acyl. Exemplary acylamino groups include acetylamino, propionylamino, butyrylamino, valerylamino, and hexanoylamino.

[0026] Herein, acyl groups may be represented by RC(O)-, wherein R is H or an alkyl group as described herein. Exemplary acyl groups are C1-C 10 Acyl groups, such as acetyl.

[0027] Herein, an ester group can be represented as RC(O)-O- or ROC(O)-, wherein R is an alkyl group as described herein, or R is a portion of an amino acid molecule other than a carboxyl group (i.e., an ester group is a monovalent group obtained by removing the hydrogen from the carboxyl group of an amino acid molecule).

[0028] Herein, polyethylene glycol refers to -O(CH2CH2O) n H, wherein n is an integer of 1-300, such as 1-200, 1-150, 5-300 or 5-150.

[0029] Herein, the glycosidic group refers to a monovalent group obtained by removing H from the hydroxyl group of a glycoside.

[0030] Herein, a phosphate group refers to a group having the following structure:

[0031] Among them, R c and R d Each is independently H, alkyl (such as C1-C6 alkyl) or metal cation (such as Na + ).

[0032] As used herein, "heterocyclyl" refers to a saturated or partially saturated 3-7 membered monocyclic group, a 7-10 membered bicyclic group, a spirocyclic group, or a bridged cyclic group, which consists of carbon atoms and 1-4 heteroatoms selected from O, N, and S. The number of ring atoms in the spirocyclic group (also referred to herein as a "spiroheterocyclyl") or bridged cyclic group (also referred to herein as a "bridged heterocyclyl") may generally be 4 to 12. Exemplary heterocyclyls include tetrahydrofuranyl, pyranyl, piperidinyl, piperazinyl, 1,4-diazepanyl, azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, imidazolinyl, indolinyl, isoindolinyl, quinuclidinyl, morpholinyl, isochromanyl, chromanyl, pyrazolidinyl, pyrazolinyl, tetrahydroisoquinolinyl, tetronoyl, and tetramoyl.

[0033] As used herein, "heteroaryl" refers to a group containing 5-14, preferably 5-10, ring atoms, and having 6, 10 or 14 π electrons shared in the ring system. The ring atoms contained in the heteroaryl group are carbon atoms and 1-3 heteroatoms selected from oxygen, nitrogen and sulfur. Exemplary heteroaryl groups include thienyl, benzo[d]isothiazol-3-yl, benzo[b]thienyl, naphtho[2,3-b]thienyl, thianthrenyl, furanyl, pyranyl, isobenzofuranyl, chromenyl, xanthrenyl, thienoxanyl, pyrrolyl, imidazolyl, pyrazolyl, pyridyl (including but not limited to 2-pyridyl, 3-pyridyl and 4-pyridyl), pyrazinyl, pyrimidinyl, pyridazinyl, indolizinyl, isoindolyl, 3H-indolyl, indolyl, indazolyl, purinyl, 4H-quinolizinyl, isoquinolyl, quinolyl, phthalazinyl, naphthyridinyl, quinazolinyl, cinnolinyl, pteridinyl, carbazolyl, β-carbolinyl, phenanthridinyl, acridinyl, perylene, pyrimidinyl, pyridaz ... Phenyl, phenanthroline, phenazinyl, isothiazolyl, phenothiazinyl, isoxazolyl, furazanyl, phenoxazinyl, tetrahydropyridopyrimidinyl, tetrahydropenta[c]pyrazol-3-yl, benzisoxazolyl such as 1,2-benzisoxazol-3-yl, benzimidazolyl, 2-hydroxyindolyl, thiadiazide, 2-oxobenzimidazolyl, imidazopyridazinyl, imidazopyridinyl, triazolopyridazinyl, tetrahydropyridopyrimidinyl, pyrazolopyrimidinyl, pyrrolopyrimidinyl, pyrrolopyridinyl, pyrrolopyrazinyl, triazolopyrazinyl, thienoquinolyl, furanoquinolyl, thiazoquinolyl, pyrazoloquinolyl, pyrroloquinolyl, imidazoquinolyl, oxazoloquinolyl, and the like.

[0034] As used herein, unless otherwise indicated, when substituted, the alkyl, carbocyclyl, alkoxy, alkenyl, alkynyl, heterocyclyl, aryl, or heteroaryl groups described in any embodiment herein may be substituted with one or more (e.g., 1, 2, 3, or 4) substituents selected from the group consisting of halogen, hydroxy, thiol, carboxyl, amino, nitro, cyano, C1-C6 acylamino, C1-C6 acyloxy, C1-C6 alkoxy, aryloxy, alkylthio, C1-C6 alkyl, C1-C6 alkyl, 10 Acyl, C6-C 14 Aryl, C3-C8 cycloalkyl, C2-C6 alkenyl, C3-C8 cycloalkenyl, C2-C6 alkynyl, heterocyclic or heteroaryl, etc. Among these substituents, amino, C1-C6 acylamino, C1-C6 acyloxy, C1-C6 alkoxy, aryloxy, alkylthio, C1-C6 alkyl, C1-C 10 Acyl, C6-C 14 Aryl, C3-C8 cycloalkyl, C2-C6 alkenyl, C3-C8 cycloalkenyl, C2-C6 alkynyl, heterocyclyl or heteroaryl itself may also be optionally substituted, for example each may be optionally substituted with 1, 2, 3 or 4 groups selected from halogen, hydroxy, mercapto, carboxyl, amino, nitro, cyano, C1-C6 acylamino, C1-C6 acyloxy, C1-C6 alkoxy, aryloxy, alkylthio, C1-C6 alkyl, C1-C6 acyl, C6-C6 alkyl, 14 The substituents may be substituted by aryl, C3-C8 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, heterocyclyl or heteroaryl. Herein, the substituents may also include =N-C1-C4 alkoxy.

[0035] It should be understood that in each embodiment herein, when the substituent is a carbocyclyl, heterocyclyl, aryl or heteroaryl group, the number of the carbocyclyl, heterocyclyl, aryl or heteroaryl substituents is generally one or two.

[0036] In the present invention, the term "comprising" means that the pharmaceutical composition may also contain any other components, and these components may be present in any amount, as long as the components present in this amount are acceptable to the human body and have no unacceptable effect on the activity of the active ingredients in the pharmaceutical composition of the present invention.

[0037] II. 6,5,7,6-Tetracyclic Derivatives

[0038] The 6,5,7,6-tetracyclic derivatives of the present invention have a structure as shown in Formula I:

[0039] in,

[0040] X is selected from: -O-, -NH-, -S- and -CH2-;

[0041] Y is selected from: -O, -NH- and -S;

[0042] Z1 is selected from: -O-, -NH-, -S- and -CH2-;

[0043] Z2 is selected from: -N- and -C-;

[0044] Z3 is selected from: -N- and -C-;

[0045] Z4 is selected from: -N- and -C-;

[0046] Z5 is selected from: -N- and -C-;

[0047] Z6 is selected from: -N- and -C-;

[0048] Z7 is selected from: -N- and -C-;

[0049] R3 is selected from: halogen, optionally substituted C1-C 10 Alkyl, optionally substituted C1-C 10 Alkoxy, -NR'R", nitro, hydroxy, carboxyl, mercapto, cyano, ester, acylamino, optionally substituted C3-C8 carbocyclic group, optionally substituted C6-C 14 Aryl, optionally substituted C5-C 10 Heteroaryl, optionally substituted C4-C 10 Heterocyclic group, phosphate group, polyethylene glycol group, polyethylene glycol-C1-C4 alkyl-C(O)-O- and glycoside group;

[0050] R4 is selected from the group consisting of: H, halogen, aldehyde, hydroxy, thiol, -NR'R", cyano, nitro, optionally substituted C1-C 10 Alkyl, optionally substituted C2-C 10 Alkenyl, optionally substituted C2-C 10 Alkynyl, optionally substituted C3-C8 carbocyclyl, optionally substituted C6-C 14 Aryl, optionally substituted C5-C 10 Heteroaryl and optionally substituted C4-C 10 heterocyclic group;

[0051] R5 is selected from the group consisting of: H, hydroxy, thiol, halogen, optionally substituted C1-C 10 Alkoxy, optionally substituted C1-C 10 Alkyl, C1-C 10 ester, -NR'R", nitro, amido and polyethylene glycol groups;

[0052] R6 is selected from the group consisting of: H, halogen, optionally substituted C1-C 10 Alkyl, optionally substituted C1-C 10Alkoxy, -NR'R", nitro, hydroxy, carboxyl, mercapto, cyano, ester, acylamino, optionally substituted C3-C8 carbocyclic group, optionally substituted C6-C 14 Aryl, optionally substituted C5-C 10 Heteroaryl and optionally substituted C4-C 10 heterocyclic group;

[0053] R7 is selected from the group consisting of: H, hydroxy, thiol, cyano, carboxyl, nitro, -NR'R", optionally substituted C1-C 10 Alkyl, optionally substituted C2-C 10 Alkenyl, optionally substituted C2-C 10 Alkynyl, C1-C 10 Ester group, acylamino group, halogen, optionally substituted C3-C8 carbocyclic group, optionally substituted C1-C 10 Alkoxy, optionally substituted C6-C 14 Aryl, optionally substituted C5-C 10 Heteroaryl and optionally substituted C4-C 10 heterocyclic group;

[0054] R8 is selected from: H, optionally substituted C1-C 10 Alkyl, optionally substituted C2-C 10 Alkenyl, optionally substituted C6-C 14 aryl;

[0055] R' and R" are each independently selected from: H, optionally substituted C1-C 10 alkyl, optionally substituted C2-C8 alkenyl, and optionally substituted C1-C 10 alkoxy; and

[0056] n is 0, 1, 2 or 3.

[0057] In Formula I and various structural formulas of the present invention, unless otherwise specified, when an alkyl, alkenyl, alkynyl, or alkoxy group is substituted, the number of substituents thereof may be 1 to 5, and exemplary substituents include, but are not limited to, cyano, hydroxyl, nitro, halogen, carboxyl, -NR a R b , =N-C1-C4 alkoxy, optionally substituted carbocyclic group, optionally substituted aryl group, optionally substituted heterocyclic group and optionally substituted heteroaryl group and the like; wherein, R a and R b Preferably each independently is H, optionally substituted C1-C 10 Alkyl, optionally substituted C2-C 10 Alkenyl, optionally substituted C2-C 10 Alkynyl, optionally substituted C1-C 10alkyl, optionally substituted carbocyclyl, optionally substituted heteroaryl, optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted carbocyclyl C1-C6 alkyl, optionally substituted heteroaryl C1-C6 alkyl, optionally substituted aryl C1-C6 alkyl and optionally substituted heterocyclyl C1-C6 alkyl, etc. Or R a and R b Together with the nitrogen to which they are attached, they form an optionally substituted 4- to 10-membered heterocyclyl or benzoheterocyclyl, such as a 5-, 6- or 7-membered heterocyclyl. a and R b When each is substituted or the 4-10 membered heterocyclic group or benzoheterocyclic group formed thereby is substituted, exemplary substituents thereof may be 1, 2, 3 or 4 selected from halogen, hydroxy, optionally substituted C1-C4 alkyl, carboxyl, cyano, nitro, -NR'R", optionally substituted C1-C4 alkoxy and optionally substituted C1-C4 acyl, C1-C6 alkoxycarbonyl, C2-C8 alkenyloxycarbonyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted carbocyclic group and optionally substituted heterocyclic group, etc.

[0058] In the formula I and various structural formulas of the present invention, unless otherwise specified, the optionally substituted carbocyclic group, optionally substituted aryl group, optionally substituted heterocyclic group and optionally substituted heteroaryl group themselves or as substituents of other groups, when substituted, their exemplary substituents may be independently 1-5 selected from halogen, hydroxyl, carboxyl, halogenated C1-C6 alkyl, hydroxyl substituted C1-C6 alkyl, optionally substituted C6-C6 alkyl, 14 Aryl-C1-C6 alkyl, optionally substituted C5-C 10 Heteroaryl-C1-C6 alkyl, optionally substituted C3-C8 carbocyclyl-C1-C6 alkyl, optionally substituted C4-C 10 Heterocyclyl-C1-C6 alkyl, -NR'R", cyano, optionally substituted C1-C6 acyl, C1-C4 alkoxy, halogen-substituted C1-C4 alkoxy and hydroxy-substituted C1-C4 alkoxy, optionally substituted C3-C8 carbocyclyl, optionally substituted C6-C 14 aryl, optionally substituted 4-10 membered heterocyclic group, optionally substituted 5-10 membered heteroaryl, C1-C6 alkoxycarbonyl and C2-C8 alkenyloxycarbonyl, wherein R' and R" are each independently selected from: H, C1-C 10 Alkyl, C2-C8 alkenyl and C1-C 10 Alkoxy.

[0059] In some embodiments of Formula I, when Z1 is -NH- and X is -CH2-, -NH-, or -O-, R4 is not H.

[0060] In some embodiments of Formula I, at least one of R4, R5, R6, and R7 is a non-hydrogen substituent.

[0061] In Formula I, X is preferably -O- or -NH-. In some embodiments, X is -O-.

[0062] In Formula I, Y is preferably -O- or -S-. In some embodiments, Y is -O-.

[0063] In Formula I, Z1 is preferably -O-, -NH- or -CH2-. In some embodiments, Z1 is -O-.

[0064] In formula I, Z2, Z3, Z4, Z5, Z6 and Z7 are preferably all -C-.

[0065] In Formula I, R8 is preferably H or C1-C4 alkyl. In some embodiments, R8 is H.

[0066] In formula I, R3 is preferably selected from: halogen, C1-C 10 In some embodiments, R3 is selected from halogen, C1-C4 alkyl and hydroxyl. In some embodiments, R3 is hydroxyl.

[0067] In Formula I, preferably, n is 0, 1 or 2, more preferably 0 or 1.

[0068] In formula I, R4 is preferably selected from: H, -NR'R", optionally substituted C1-C 10 Alkyl, optionally substituted C2-C 10 Alkenyl, optionally substituted C2-C 10 Alkynyl, optionally substituted C3-C8 carbocyclyl, optionally substituted C6-C 14 Aryl, optionally substituted C5-C 10 Heteroaryl and optionally substituted C4-C 10 wherein R' and R" are each independently selected from H, C1-C6 alkyl, C2-C8 alkenyl, and C1-C6 alkoxy. In some embodiments, the optionally substituted C1-C 10 The alkyl group is an optionally substituted C1-C4 alkyl group.

[0069] Preferably, the optionally substituted C1-C 10 Alkyl, optionally substituted C2-C 10 Alkenyl and optionally substituted C2-C 10Each alkynyl group may be optionally substituted with 1 to 5 substituents selected from the group consisting of carboxyl, cyano, C6-C4 alkyl, halo-C1-C4 alkyl, -NR'R", and hydroxy. 14 Aryl, C5-C4 alkyl, C1-C4 alkyl, halogenated C1-C4 alkyl, -NR'R" and hydroxyl, optionally substituted with 1-5 substituents 10 Heteroaryl, C4-C4 alkyl, C1-C4 alkyl haloalkyl, -NR'R" and hydroxyl, optionally substituted with 1-5 substituents 10 Heterocyclyl, hydroxy, C3-C8 cycloalkyl, C2-C8 alkenyl, halogen and -NR a R b ; wherein R' and R" are each independently selected from H, C1-C6 alkyl, C2-C8 alkenyl and C1-C6 alkoxy; wherein R a and R b Each independently selected from: H, C1-C1 optionally substituted with 1-5 substituents selected from halogen and hydroxy 10 C2-C8 alkyl, C2-C8 alkenyl optionally substituted by 1-5 substituents selected from halogen and hydroxy, 3-14 membered carbocyclic group optionally substituted by 1-5 substituents selected from halogen and C1-C4 alkyl (the 3-14 membered carbocyclic group may be C3-C8 cycloalkyl and C4-C 14 bridged ring), a 3-14 membered carbocyclic group optionally substituted by 1-5 substituents selected from halogen and C1-C4 alkyl (the 3-14 membered carbocyclic group may be a C3-C8 cycloalkyl and C4-C 14 C1-C6 alkyl substituted with a bridged ring) or a C1-C6 alkyl group substituted with a 4-10 membered heterocyclic group optionally substituted with 1-5 substituents selected from halogen, hydroxyl and C1-C4 alkyl, or a C1-C6 alkyl group substituted with 1-5 substituents selected from halogen, hydroxyl, C1-C4 alkoxy and C1-C4 alkyl. 14 Aryl, and C6-C4 substituted by 1-5 groups selected from halogen, hydroxyl and C1-C4 alkyl 14 Aryl-C1-C6 alkyl, or R a and R bTogether with the nitrogen atom to which they are attached, they form a heterocyclic group (including a saturated or partially saturated 4-7 membered monocyclic heteroaryl, a saturated or partially saturated 7-10 membered bicyclic group, a 4-12 membered spiroheterocyclic group or a 4-12 membered bridged heterocyclic group) or a benzoheterocyclic group, which is optionally substituted by 1-5 substituents selected from the following: optionally substituted by 1-5 substituents selected from halogen, hydroxy, =N-C1-C4 alkoxy, C1-C4 alkoxy and -NR'R". substituted C1-C8 alkyl, C2-C8 alkenyl optionally substituted by 1-5 substituents selected from halogen, hydroxy and -NR'R", C1-C6 alkoxy optionally substituted by 1-5 substituents selected from halogen and hydroxy, cyano, carboxyl, halogen, -NR'R", hydroxy, optionally substituted by 1-5 substituents selected from C1-C4 acyl, halogen, -NR'R", C1-C4 alkoxy, C1-C4 alkyl, cyano, hydroxy, C1-C4 alkoxycarbonyl, C6-C 14 C6-C4 substituted aryl and halogenated C1-C4 alkyl 14 Aryl, C1-C 10 Acyl, C1-C6 alkoxycarbonyl, C2-C8 alkenyloxycarbonyl, -NR'R" substituted C1-C6 acyl, C6-C6 alkyl optionally substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy 14 C1-C4 acyl substituted by aryl, C3-C8 cycloalkyl substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, C6-C8 cycloalkyl substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, 14C1-C6 alkyl substituted by aryl, C3-C8 cycloalkyl substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, C3-C8 cycloalkyl substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, 4-7 membered heterocyclyl optionally substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, C1-C6 alkyl optionally substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-substituted C1-C4 alkyl and hydroxy, 5-10 membered heteroaryl optionally substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-substituted C1-C4 alkyl and hydroxy, and C1-C6 alkyl optionally substituted with 5-10 membered heteroaryl substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-substituted C1-C4 alkyl and hydroxy, wherein R' and R" are each independently selected from H, C1-C6 alkyl, C2-C8 alkenyl and C1-C6 alkoxy. In some embodiments, R a and R b The heterocyclic or benzoheterocyclic radical formed together with the nitrogen atom to which they are attached is optionally substituted by 1-5 substituents selected from the group consisting of C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkyl, cyano, carboxyl, halogen, -NR'R", hydroxyl, C1-C4 acyl, halogen, -NR'R", C1-C4 alkoxy, C1-C4 alkyl, cyano, hydroxyl, C1-C4 alkoxycarbonyl, C6-C 14 C6-C4 substituted aryl and halogenated C1-C4 alkyl 14 Aryl, C1-C 10 Acyl, C1-C6 alkoxycarbonyl, C2-C8 alkenyloxycarbonyl, -NR'R" substituted C1-C6 acyl, C6-C6 alkyl optionally substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy 14 C1-C4 acyl substituted by aryl, C3-C8 cycloalkyl substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, C6-C8 cycloalkyl substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, 14C1-C6 alkyl substituted by aryl, C3-C8 cycloalkyl substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, C3-C8 cycloalkyl substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, 4-7 membered heterocyclyl optionally substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, C1-C6 alkyl optionally substituted with 4-7 membered heterocyclyl substituted with a substituent selected from halogen, C1-C4 alkyl, halo-substituted C1-C4 alkyl and hydroxy, a 5-10 membered heteroaryl optionally substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-substituted C1-C4 alkyl and hydroxy, and a 5-10 membered heteroaryl optionally substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-substituted C1-C4 alkyl and hydroxy, wherein R' and R" are each independently selected from H, C1-C6 alkyl, C2-C8 alkenyl and C1-C6 alkoxy.

[0070] Preferably, the optionally substituted C3-C8 carbocyclic group, the optionally substituted C6-C 14 Aryl, optionally substituted C5-C 10 Heteroaryl and optionally substituted C4-C 10 Each heterocyclic group may be optionally substituted with 1-5 substituents selected from halogen, hydroxy, carboxyl, cyano, -NR'R", C1-C6 acyl, C1-C4 alkyl, halo-substituted C1-C4 alkyl, C1-C4 alkoxy, halo-substituted C1-C4 alkoxy, hydroxy-substituted C1-C4 alkyl, hydroxy-substituted C1-C4 alkoxy and C2-C8 alkenyl; wherein R' and R" are each independently selected from H, C1-C6 alkyl, C2-C8 alkenyl and C1-C6 alkoxy.

[0071] In some embodiments, in Formula I, R4 is hydroxy, C3-C8 cycloalkyl, C2-C8 alkenyl, halogen or -NR a R b Substituted C1-C 10 Alkyl, preferably -NR a R b Substituted C1-C4 alkyl, wherein R a and R b Each independently selected from: H, C1-C1 optionally substituted with 1-5 substituents selected from halogen and hydroxy 10C2-C8 alkyl, C2-C8 alkenyl optionally substituted by 1-5 substituents selected from halogen and hydroxy, 3-14 membered carbocyclic group optionally substituted by 1-5 substituents selected from halogen and C1-C4 alkyl (the 3-14 membered carbocyclic group may be C3-C8 cycloalkyl and C4-C 14 bridged ring), a 3-14 membered carbocyclic group optionally substituted by 1-5 substituents selected from halogen and C1-C4 alkyl (the 3-14 membered carbocyclic group may be a C3-C8 cycloalkyl and C4-C 14 C1-C6 alkyl substituted with a bridged ring) or a C1-C6 alkyl group substituted with a 4-10 membered heterocyclic group optionally substituted with 1-5 substituents selected from halogen, hydroxyl and C1-C4 alkyl, or a C1-C6 alkyl group substituted with 1-5 substituents selected from halogen, hydroxyl and C1-C4 alkyl 14 Aryl, and C6-C4 substituted by 1-5 groups selected from halogen, hydroxyl and C1-C4 alkyl 14 Aryl-C1-C6 alkyl; or R a and R b Together with the nitrogen atom to which they are attached, they form a heterocyclic group (including a saturated or partially saturated 4-7 membered monocyclic heteroaryl, a saturated or partially saturated 7-10 membered bicyclic group, a 4-12 membered spiroheterocyclic group or a 4-12 membered bridged heterocyclic group) or a benzoheterocyclic group, which is optionally substituted by 1-5 substituents selected from the following: optionally substituted by 1-5 substituents selected from halogen, hydroxy, =N-C1-C4 alkoxy, C1-C4 alkoxy and -NR'R" substituted C1-C8 alkyl, C2-C8 alkenyl optionally substituted by 1-5 substituents selected from halogen, hydroxy and -NR'R", C1-C6 alkoxy optionally substituted by 1-5 substituents selected from halogen and hydroxy, cyano, carboxyl, halogen, -NR'R", hydroxy, optionally substituted by 1-5 substituents selected from C1-C4 acyl, halogen, NR'R", C1-C4 alkoxy, C1-C4 alkyl, cyano, hydroxy, C1-C4 alkoxycarbonyl, C6-C 14 C6-C4 substituted aryl and halogenated C1-C4 alkyl 14 Aryl, C1-C 10 Acyl, C1-C6 alkoxycarbonyl, C2-C8 alkenyloxycarbonyl, NR'R" substituted C1-C6 acyl, C6-C6 alkyl optionally substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy 14 Aryl-substituted C1-C4 acyl, C6-C4 acyl optionally substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy 14C1-C6 alkyl substituted by aryl, C3-C8 cycloalkyl substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, C3-C8 cycloalkyl substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, 4-7 membered heterocyclyl optionally substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, C1-C6 alkyl optionally substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-substituted C1-C4 alkyl and hydroxy, 5-10 membered heteroaryl optionally substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-substituted C1-C4 alkyl and hydroxy, and C1-C6 alkyl optionally substituted with 5-10 membered heteroaryl substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-substituted C1-C4 alkyl and hydroxy; wherein R' and R" are each independently selected from H, C1-C6 alkyl, C2-C8 alkenyl and C1-C6 alkoxy. In some embodiments, R a and R b The heterocyclic or benzoheterocyclic group formed together with the nitrogen atom to which they are attached is optionally substituted by 1-5 substituents selected from the group consisting of C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkoxy, C6-C6 acyl, C1-C4 acyl, C1-C4 acyl, C1-C4 acyl, C1-C4 acyl, C1-C4 acyl, C1-C4 acyl, C1-C4 acyl, C1-C4 acyl, C1-C4 acyl, C1-C4 acyl, C1-C4 acyl, C1-C4 acyl, C1-C4 acyl, C1-C4 acyl, C1-C4 alkoxy ... 14 C6-C4 substituted aryl and halogenated C1-C4 alkyl 14 Aryl, C1-C 10 Acyl, C1-C6 alkoxycarbonyl, C2-C8 alkenyloxycarbonyl, NR'R" substituted C1-C6 acyl, C6-C6 alkyl optionally substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy 14 Aryl-substituted C1-C4 acyl, C6-C4 acyl optionally substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy 14C1-C6 alkyl substituted by aryl, C3-C8 cycloalkyl substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, C3-C8 cycloalkyl substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, 4-7 membered heterocyclyl optionally substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, C1-C6 alkyl optionally substituted with 4-7 membered heterocyclyl substituted with a substituent selected from halogen, C1-C4 alkyl, halo-substituted C1-C4 alkyl and hydroxy, a 5-10 membered heteroaryl optionally substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-substituted C1-C4 alkyl and hydroxy, and a 5-10 membered heteroaryl optionally substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-substituted C1-C4 alkyl and hydroxy; wherein R' and R" are each independently selected from H, C1-C6 alkyl, C2-C8 alkenyl and C1-C6 alkoxy.

[0072] Preferably, in R4 of Formula I, the C6-C 14 Aryl as a substituent itself or as a part of other substituents, including but not limited to phenyl or naphthyl; preferably, the heteroaryl mentioned as a substituent itself or as a part of other substituents is a nitrogen-containing 5- or 6-membered heteroaryl, including but not limited to pyrrolyl, pyrazolyl, imidazolyl, pyridyl, pyrimidinyl and pyrazinyl; preferably, the carbocyclic group mentioned as a substituent itself or as a part of other substituents is C3-C8 cycloalkyl or C4-C 14 Bridged ring group; Preferably, the heterocyclic group mentioned as a substituent itself or as part of other substituents is a 4-7 membered monocyclic saturated or partially saturated heterocyclic group containing nitrogen and optionally containing oxygen, including but not limited to azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl,

[0073] Or it is a nitrogen-containing 7-10 membered saturated or partially saturated heterocyclic group, such as:

[0074] Or it is a 4-12 membered bridged heterocyclic group or spiro heterocyclic group containing nitrogen and optionally oxygen, such as:

[0075] In some embodiments, R4 is optionally substituted C4-C 10 Heterocyclyl or optionally substituted C4-C 10 Heterocyclic substituted C1-C 10 Preferably, the C4-C 10The heterocyclic group is a nitrogen-containing heterocyclic group, more preferably a C4-C8 nitrogen-containing heterocyclic group; preferably, the heterocyclic group is a saturated heterocyclic group, preferably selected from azetidinyl, pyrrolidinyl, piperidinyl and piperazinyl, more preferably piperidinyl. Preferably, the heterocyclic group is covalently linked to the rest of the compound via its ring nitrogen atom. Preferably, the heterocyclic group is optionally substituted with 1, 2 or 3 substituents selected from the group consisting of C1-C8 alkyl, optionally substituted with 1-5 substituents selected from the group consisting of halogen, hydroxy, =N-C1-C4 alkoxy, C1-C4 alkoxy and -NR'R", C2-C8 alkenyl, optionally substituted with 1-5 substituents selected from the group consisting of halogen, hydroxy and -NR'R", C1-C6 alkoxy, optionally substituted with 1-5 substituents selected from the group consisting of halogen and hydroxy, cyano, carboxyl, halogen, -NR'R", hydroxy, optionally substituted with 1-5 substituents selected from the group consisting of C1-C4 acyl, halogen, NR'R", C1-C4 alkoxy, C1-C4 alkyl, cyano, hydroxy, C1-C4 alkoxycarbonyl, C6-C 14 C6-C4 substituted aryl and halogenated C1-C4 alkyl 14 Aryl, C1-C 10 Acyl, C1-C6 alkoxycarbonyl, C2-C8 alkenyloxycarbonyl, NR'R" substituted C1-C6 acyl, C6-C6 alkyl optionally substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy 14 Aryl-substituted C1-C4 acyl, C6-C4 acyl optionally substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy 14C1-C6 alkyl optionally substituted by aryl, C1-C6 alkyl optionally substituted by 1-5 substituents selected from the group consisting of halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, C3-C8 cycloalkyl optionally substituted by 1-5 substituents selected from the group consisting of halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, 4-7 membered heterocyclyl optionally substituted by 1-5 substituents selected from the group consisting of halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, C1-C6 alkyl optionally substituted by 4-7 membered heterocyclyl optionally substituted by 1-5 substituents selected from the group consisting of halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, 5-10 membered heteroaryl optionally substituted by 1-5 substituents selected from the group consisting of halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, and C1-C6 alkyl substituted with 5-10 membered heteroaryl optionally substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy; wherein R' and R" are each independently selected from H, C1-C6 alkyl, C2-C8 alkenyl and C1-C6 alkoxy. In some embodiments, the heterocyclyl is optionally substituted with 1, 2 or 3 substituents selected from the following: C1-C6 alkyl optionally substituted with 1-5 substituents selected from halogen and hydroxy, C1-C6 alkoxy optionally substituted with 1-5 substituents selected from halogen and hydroxy, cyano, carboxyl, halogen, -NR'R", hydroxy, optionally substituted with 1-5 substituents selected from C1-C4 acyl, halogen, NR'R", C1-C4 alkoxy, C1-C4 alkyl, cyano, hydroxy, C1-C4 alkoxycarbonyl, C6-C 14 C6-C4 substituted aryl and halogenated C1-C4 alkyl 14 Aryl, C1-C 10 Acyl, C1-C6 alkoxycarbonyl, C2-C8 alkenyloxycarbonyl, NR'R" substituted C1-C6 acyl, C6-C6 alkyl optionally substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy 14 Aryl-substituted C1-C4 acyl, C6-C4 acyl optionally substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy 14C1-C6 alkyl substituted by aryl, C3-C8 cycloalkyl substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, C3-C8 cycloalkyl substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, 4-7 membered heterocyclyl optionally substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, C1-C6 alkyl optionally substituted with 4-7 membered heterocyclyl substituted with a substituent selected from halogen, C1-C4 alkyl, halo-substituted C1-C4 alkyl and hydroxy, a 5-10 membered heteroaryl optionally substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-substituted C1-C4 alkyl and hydroxy, and a 5-10 membered heteroaryl optionally substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-substituted C1-C4 alkyl and hydroxy; wherein R' and R" are each independently selected from H, C1-C6 alkyl, C2-C8 alkenyl and C1-C6 alkoxy.

[0076] In some embodiments, R4 is:

[0077] wherein R9 is selected from the group consisting of: H, hydroxy, C1-C6 alkyl, C2-C8 alkenyl, C1-C6 alkoxy, C2-C8 alkenyloxy, C3-C8 cycloalkenyl, -NR'R", and optionally substituted by 1-5 groups selected from the group consisting of C1-C6 acyl, halogen, NR'R", C1-C4 alkoxy, C1-C4 alkyl, cyano, hydroxy, C1-C4 alkoxycarbonyl, C6-C 14 C6-C4 substituted aryl and halogenated C1-C4 alkyl 14 Aryl; wherein R' and R" are each independently selected from H, C1-C6 alkyl, C2-C8 alkenyl and C1-C6 alkoxy. In some embodiments, R9 is selected from: H, hydroxyl, C1-C6 alkyl, C2-C8 alkenyl, C1-C6 alkoxy, C2-C8 alkenyloxy, -NR'R" and C6-C 14 Aryl; wherein R' and R" are each independently selected from H, C1-C6 alkyl, C2-C8 alkenyl and C1-C6 alkoxy.

[0078] In Formula I, preferably, R5 is selected from the group consisting of: H, hydroxy, halogen, C1-C4 alkoxy, and C1-C4 alkyl. In some embodiments, R5 is selected from the group consisting of: hydroxy, C1-C4 alkoxy, and C1-C4 alkyl. Preferably, in Formula I, R5 is hydroxy.

[0079] In formula I, preferably, when R6 is substituted C1-C 10 Alkyl and C1-C 10When R6 is substituted C3-C8 carbocyclyl, C6-C8 alkenyl and C1-C6 alkoxy, each of the substituents thereof may be 1-5 selected from halogen, hydroxyl, carboxyl, -NR'R", optionally substituted C3-C8 cycloalkyl and optionally substituted 4-10 membered heteroaryl, wherein R' and R" are each independently selected from H, C1-C6 alkyl, C2-C8 alkenyl and C1-C6 alkoxy, wherein the C3-C8 cycloalkyl and 4-10 membered heteroaryl are optionally substituted by 1-3 substituents selected from halogen, C1-C4 alkyl, halo C1-C4 alkyl, C1-C4 alkoxy and halo C1-C4 alkoxy; preferably, the 4-10 membered heterocyclyl is a saturated nitrogen-containing heterocyclyl, preferably a 4-7 membered saturated nitrogen-containing monocyclic heterocyclyl, including but not limited to azetidinyl, pyrrolidinyl and piperidinyl. When R6 is substituted C3-C8 carbocyclyl, C6-C 14 Aryl, C5-C 10 Heteroaryl and C4-C 10 In the case of a heterocyclic group, each of its substituents may be 1-5 selected from halogen, hydroxy, C1-C4 alkyl, halo-substituted C1-C4 alkyl, hydroxy-substituted C1-C4 alkyl, C1-C4 alkoxy, halo-substituted C1-C4 alkoxy, hydroxy-substituted C1-C4 alkoxy and -NR'R", wherein R' and R" are each independently selected from H, C1-C6 alkyl, C2-C8 alkenyl and C1-C6 alkoxy. Preferably, in Formula I, R6 is selected from: H and C1-C4 alkyl, wherein the C1-C4 alkyl is optionally substituted with a 4-7 membered monocyclic saturated heterocyclic group or a C3-C8 cycloalkyl, and the 4-7 membered monocyclic saturated heterocyclic group and the C3-C8 cycloalkyl are each optionally substituted with 1-3 substituents selected from halogen, C1-C4 alkyl, halo-substituted C1-C4 alkyl, C1-C4 alkoxy and halo-substituted C1-C4 alkoxy.

[0080] In formula I, preferably, when R7 is substituted C1-C 10 Alkyl, C2-C 10 Alkenyl, C1-C 10 Alkoxy and C2-C 10 When R7 is substituted C3-C8 carbocyclyl, C6-C8 alkenyl and C1-C6 alkoxy, the C3-C8 cycloalkyl and 4-10 membered heteroaryl groups are optionally substituted with 1-3 substituents selected from halogen, C1-C4 alkyl, halo C1-C4 alkyl, C1-C4 alkoxy and halo C1-C4 alkoxy; preferably, the 4-10 membered heterocyclyl is a saturated nitrogen-containing heterocyclyl, preferably a 4-7 membered saturated nitrogen-containing monocyclic heterocyclyl, including but not limited to azetidinyl, pyrrolidinyl and piperidinyl. When R7 is substituted C3-C8 carbocyclyl, C6-C8 alkenyl and C1-C6 alkoxy, the C3-C8 cycloalkyl and 4-10 membered heteroaryl groups are optionally substituted with 1-3 substituents selected from halogen, C1-C4 alkyl, halo C1-C4 alkyl, C1-C4 alkoxy and halo C1-C4 alkoxy; preferably, the 4-10 membered heterocyclyl is a saturated nitrogen-containing heterocyclyl, preferably a 4-7 membered saturated nitrogen-containing monocyclic heterocyclyl, including but not limited to azetidinyl, pyrrolidinyl and piperidinyl. 14Aryl, C5-C 10 Heteroaryl and C4-C 10 When the heterocyclic group is a C1-C4 alkyl group, each of the substituents thereof may be 1-5 selected from halogen, hydroxy, C1-C4 alkyl, halogenated C1-C4 alkyl, C1-C4 alkyl substituted with hydroxy, C1-C4 alkoxy, halogenated C1-C4 alkoxy, C1-C4 alkoxy substituted with hydroxy and -NR'R", wherein R' and R" are each independently selected from H, C1-C6 alkyl, C2-C8 alkenyl and C1-C6 alkoxy. Preferably, in Formula I, R7 is selected from: H, C1-C6 alkyl optionally substituted with 1-5 selected from halogen and hydroxy, C2-C6 alkenyl optionally substituted with 1-5 selected from halogen and hydroxy, C3-C8 saturated or partially saturated carbocyclic group, halogen, hydroxy, C6-C6 alkyl optionally substituted with 1-3 substituents selected from C1-C4 alkyl, halogenated C1-C4 alkyl, halogen, C2-C4 alkenyl and hydroxy. 14 C1-C6 alkoxy substituted by aryl, 5-10 membered heteroaryl optionally substituted by 1-3 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, and C6-C4 alkyl optionally substituted by 1-3 substituents selected from C1-C4 alkyl, halo-C1-C4 alkyl, halogen, C2-C4 alkenyl and hydroxy 14 In some embodiments, R7 is selected from: H, C1-C6 alkyl optionally substituted by 1-5 groups selected from halogen and hydroxy, C2-C6 alkenyl optionally substituted by 1-5 groups selected from halogen and hydroxy, C3-C8 saturated or partially saturated carbocyclyl, halogen, hydroxy, C6-C 14 Aryl-substituted C1-C4 alkoxy, 5-10 membered heteroaryl, and C6-C4 alkyl optionally substituted with 1-3 substituents selected from C1-C4 alkyl, halo-substituted C1-C4 alkyl, halogen, C2-C4 alkenyl and hydroxyl. 14 Preferably, the C6-C 14 The aryl group is phenyl or naphthyl. Preferably, the 5-10 membered heteroaryl group is a nitrogen-containing heteroaryl group, including but not limited to pyridyl, pyrimidinyl, pyrazinyl, pyrrolyl and imidazolyl.

[0081] In some embodiments, the compound of Formula I has the structure shown in Formula II below:

[0082] wherein Z1, X, Y, R3, R5, R6, R7 and n are as described in any embodiment of Formula I herein; R1 is selected from hydroxy, C3-C8 cycloalkyl, C2-C8 alkenyl, halogen or -NR a R b ; Among them, R a and R b As described in any embodiment of Formula I herein.

[0083] In some embodiments, the compound of Formula I has the structure shown in Formula III below:

[0084] Where, Z1, X, Y, R3, R5, R6, R7, R a 、R b and n is as described herein in any embodiment of Formula I;

[0085] In some embodiments, the compound of Formula I has the structure shown below in Formula IV:

[0086] wherein Z1, X, Y, R3, R5, R6, R7 and n are as described in any embodiment of Formula I herein; m is 0, 1, 2 or 3, preferably 0, 1 or 2; R2 is selected from: C1-C8 alkyl optionally substituted with 1-5 substituents selected from halogen, hydroxy, =N-C1-C4 alkoxy, C1-C4 alkoxy and -NR'R", C2-C8 alkenyl optionally substituted with 1-5 substituents selected from halogen, hydroxy and -NR'R", C1-C6 alkoxy optionally substituted with 1-5 substituents selected from halogen and hydroxy, cyano, carboxyl, halogen, -NR'R", hydroxy, C1-C4 acyl, halogen, NR'R", C1-C4 alkoxy, C1-C4 alkyl, cyano, hydroxy, C1-C4 alkoxycarbonyl, C6-C 14 C6-C4 substituted aryl and halogenated C1-C4 alkyl 14 Aryl, C1-C 10 Acyl, C1-C6 alkoxycarbonyl, C2-C8 alkenyloxycarbonyl, NR'R" substituted C1-C6 acyl, C6-C6 alkyl optionally substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy 14 Aryl-substituted C1-C4 acyl, C6-C4 acyl optionally substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy 14Aryl-substituted C1-C6 alkyl, C3-C8 cycloalkyl-substituted C1-C6 alkyl optionally substituted by 1-5 substituents selected from the group consisting of halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, C3-C8 cycloalkyl optionally substituted by 1-5 substituents selected from the group consisting of halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, 4-7 membered heterocyclyl optionally substituted by 1-5 substituents selected from the group consisting of halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, C1-C6 alkyl optionally substituted by 4-7 membered heterocyclyl substituted by 1-5 substituents selected from the group consisting of halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, optionally substituted by 1-5 substituents selected from the group consisting of halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy wherein R' and R" are each independently selected from H, C1-C6 alkyl, C2-C8 alkenyl, and C1-C6 alkoxy. In some embodiments, R2 is selected from: C1-C6 alkyl optionally substituted with 1-5 substituents selected from halogen and hydroxy, C1-C6 alkoxy optionally substituted with 1-5 substituents selected from halogen and hydroxy, cyano, carboxyl, halogen, -NR'R", hydroxy, optionally substituted with 1-5 substituents selected from C1-C4 acyl, halogen, NR'R", C1-C4 alkoxy, C1-C4 alkyl, cyano, hydroxy, C1-C4 alkoxycarbonyl, C6-C 14 C6-C4 substituted aryl and halogenated C1-C4 alkyl 14 Aryl, C1-C 10 Acyl, C1-C6 alkoxycarbonyl, C2-C8 alkenyloxycarbonyl, NR'R" substituted C1-C6 acyl, C6-C6 alkyl optionally substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy 14 Aryl-substituted C1-C4 acyl, C6-C4 acyl optionally substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy 14C1-C6 alkyl substituted by aryl, C3-C8 cycloalkyl substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, C3-C8 cycloalkyl substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, 4-7 membered heterocyclyl optionally substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, C1-C6 alkyl optionally substituted with 4-7 membered heterocyclyl substituted with a substituent selected from halogen, C1-C4 alkyl, halo-substituted C1-C4 alkyl and hydroxy, a 5-10 membered heteroaryl optionally substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-substituted C1-C4 alkyl and hydroxy, and a 5-10 membered heteroaryl optionally substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-substituted C1-C4 alkyl and hydroxy; wherein R' and R" are each independently selected from H, C1-C6 alkyl, C2-C8 alkenyl and C1-C6 alkoxy.

[0087] In some embodiments of Formula IV, m is 1, R2 is R9-C(O)-, R9-CH(OH)-, R9-CH(NH2)-, or R9-CH(SH)-, wherein R9 is as described in any of the above embodiments. Preferably, R9 is located in the para position relative to N.

[0088] In some embodiments of Formula I, X is O; Y is O; Z1 is O; Z2, Z3, Z4, Z5, Z6 and Z7 are preferably all -C-; R3 is OH; R4 is -NR a R b Substituted C1-C4 alkyl, wherein R a and R b Each independently selected from: H, C1-C6 alkyl, halogenated C1-C6 alkyl, C2-C8 alkenyl and C3-C8 cycloalkyl, or R a and R b Together with the nitrogen to which they are attached, they form a heterocyclic group, which is optionally substituted by 1-2 substituents selected from the group consisting of C1-C6 alkyl, C2-C6 alkenyl, hydroxy-substituted C1-C6 alkyl, C1-C6 10 Acyl, C1-C6 alkoxycarbonyl, 5-7 membered nitrogen-containing heteroaryl, C6-C6 optionally substituted by 1-2 halogens 14 Aryl-substituted C1-C4 acyl, optionally substituted by 1-2 groups selected from halogen, hydroxyl, C6-C 14 C6-C4 alkyl substituted with aryl, C1-C4 alkyl and C1-C4 alkoxy 14 Aryl or C6-C 14 Aryl C1-C4 alkyl. In some embodiments, Ra and R b The heterocyclic group formed together with the nitrogen to which they are attached is optionally substituted by 1-2 substituents selected from the group consisting of C1-C6 alkyl, hydroxy-substituted C1-C6 alkyl, C1-C 10 Acyl, C1-C6 alkoxycarbonyl, 5-7 membered nitrogen-containing heteroaryl, C6-C6 optionally substituted by 1-2 halogens 14 Aryl-substituted C1-C4 acyl, optionally substituted by 1-2 groups selected from halogen, hydroxyl, C6-C 14 C6-C4 alkyl substituted with aryl, C1-C4 alkyl and C1-C4 alkoxy 14 Aryl or C6-C 14 Aryl C1-C4 alkyl.

[0089] In some embodiments, the compound of Formula I is a compound TY001-TY066 having the structure shown in Formula V below:

[0090] In some embodiments, the compound of formula I is a compound TY067-TY163, TY179-TY185 having the structure shown in formula VI below:

[0091] In some embodiments, the compound of Formula I is a compound TY164-TY175 having the structure shown in Formula VII below:

[0092] In some embodiments of Formula I, the compounds of Formula I are TY176, TY177, and TY178, which are the hydrochloride salts of compounds TY086, TY125, and TY001, respectively, and have the following structures:

[0093] In some embodiments of Formula I, the compound of Formula I is:

[0094] The present invention also includes pharmaceutically acceptable salts of the compounds of Formula I. "Pharmaceutically acceptable salts" include pharmaceutically acceptable acid addition salts and pharmaceutically acceptable base addition salts. "Pharmaceutically acceptable acid addition salts" refer to salts formed with inorganic or organic acids that retain the biological effectiveness of the free base without the other side effects. Inorganic acid salts include, but are not limited to, hydrochloride, hydrobromide, sulfate, nitrate, phosphate, and the like; organic acid salts include, but are not limited to, formate, acetate, 2,2-dichloroacetate, trifluoroacetate, propionate, caproate, octanoate, decanoate, undecylenate, glycolate, gluconate, lactate, sebacate, adipate, glutarate, malonate, oxalate, maleate, succinate, fumarate, tartrate, citrate, palmitate, stearate, oleate, cinnamate, laurate, malate, glutamate, pyroglutamate, aspartate, benzoate, methanesulfonate, benzenesulfonate, p-toluenesulfonate, alginate, ascorbate, salicylate, 4-aminosalicylate, naphthalene disulfonate, and the like. "Pharmaceutically acceptable base addition salt" refers to a salt formed with an inorganic or organic base that retains the biological effectiveness of the free acid without other side effects. Salts derived from inorganic bases include, but are not limited to, sodium salts, potassium salts, lithium salts, ammonium salts, calcium salts, magnesium salts, iron salts, zinc salts, copper salts, manganese salts, aluminum salts, and the like. Preferred inorganic salts are ammonium salts, sodium salts, potassium salts, calcium salts, and magnesium salts. Salts derived from organic bases include, but are not limited to, salts of primary, secondary, and tertiary amines, substituted amines, including natural substituted amines, cyclic amines, and basic ion exchange resins, such as ammonia, isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, ethanolamine, diethanolamine, triethanolamine, dimethylethanolamine, 2-dimethylaminoethanol, 2-diethylaminoethanol, dicyclohexylamine, lysine, arginine, histidine, caffeine, procaine, choline, betaine, ethylenediamine, glucosamine, methylglucamine, theobromine, purine, piperazine, piperidine, N-ethylpiperidine, polyamine resins, and the like. Preferred organic bases include isopropylamine, diethylamine, ethanolamine, trimethylamine, dicyclohexylamine, choline and caffeine. In some embodiments, the pharmaceutically acceptable salt of the compound of formula I of the present invention is its hydrochloride.

[0095] The present invention also includes stereoisomers, tautomers, N-oxides, hydrates, solvates, prodrugs and isotopic variants of the compound of Formula I. In the present invention, "solvate" refers to an association formed by one or more solvent molecules and the compound of the present invention. Solvents that form solvates include but are not limited to isopropanol, ethanol, methanol, dimethyl sulfoxide, ethyl acetate and acetic acid.

[0096] Prodrugs of the compounds of formula I of the present invention include: simple esters of compounds containing carboxylic acids; esters of compounds containing hydroxy groups (for example, esters obtained by condensation with C1-C4 carboxylic acids, C3-C6 diacids or their anhydrides such as succinic anhydride and fumaric anhydride according to methods known in the art); imines of compounds containing amino groups; carbamates of compounds containing amino groups; acetals or ketals of compounds containing alcohols; carbonates, etc.

[0097] III. Pharmaceutical Compositions

[0098] The present invention provides a pharmaceutical composition comprising:

[0099] (i) an effective amount of a compound of Formula I or a pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide, hydrate, solvate, prodrug or isotopic variant thereof as an active ingredient; and

[0100] (ii) a pharmaceutically acceptable carrier or excipient.

[0101] In some embodiments, the pharmaceutical composition of the present invention further comprises: (iii) a second active ingredient. Herein, the second active ingredient is related to the use of the pharmaceutical composition comprising the active ingredient described in (i) above, and can be various microbial inhibitors (e.g., anti-tuberculosis drugs), anticancer drugs, anti-rheumatic drugs, antioxidant drugs, anti-inflammatory drugs, antiviral drugs, hepatoprotective drugs, and drugs for treating cardiovascular diseases known in the art.

[0102] As used herein, "pharmaceutically acceptable" refers to a substance (such as a carrier or diluent) that does not significantly affect the biological activity or properties of the compounds of the invention and is relatively non-toxic. In this application, "pharmaceutically acceptable carriers or excipients" include, but are not limited to, any adjuvant, carrier, excipient, glidant, sweetener, diluent, preservative, dye / colorant, flavoring agent, surfactant, wetting agent, dispersant, suspending agent, stabilizer, isotonic agent, solvent or emulsifier approved by the relevant government regulatory authorities as acceptable for use by humans or livestock.

[0103] The pharmaceutical composition of the present invention may contain 0.01-99%, 0.05-80%, 0.10-70%, or 0.10-50% of the active ingredient described in item (i) based on the total weight of the composition.

[0104] The pharmaceutical compositions of the present invention can be administered topically (e.g., through the skin) in the form of creams, solutions, suspensions, aerosols, and dry powder formulations; or systemically, for example, orally in the form of tablets, capsules, syrups, powders, or granules; or gastrointestinal administration in the form of solutions or suspensions; or subcutaneously (injection); or intravenously (injection); or rectal administration in the form of suppositories; or transdermally. The compositions of the present invention can be obtained by conventional methods using conventional pharmaceutical excipients well known in the art.

[0105] IV. Use and Methods

[0106] The compound represented by Formula I of the present invention or its pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide, hydrate, solvate, prodrug or isotopic variant, or a pharmaceutical composition containing the compound represented by Formula I or its pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide, hydrate, solvate, prodrug or isotopic variant can be used as a microbial inhibitor for treating and / or preventing diseases caused by the microorganism, as well as for anti-cancer, anti-rheumatic, antioxidant, anti-inflammatory, antiviral, hepatoprotective and hepatoprotective effects and for treating and / or preventing cardiovascular diseases.

[0107] Therefore, in some embodiments, provided herein is a compound of formula I as described in any embodiment herein, or a pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide, hydrate, solvate, prodrug or isotopic variant thereof for the preparation of antibacterial, anticancer, antirheumatic, antioxidant, anti-inflammatory, antiviral, hepatoprotective or hepatoprotective drugs for the treatment and / or prevention of cardiovascular disease, or for the preparation of drugs for the treatment of infectious diseases, especially diseases caused by sensitive or drug-resistant Mycobacterium tuberculosis. In some embodiments, provided herein is a compound of formula I as described in any embodiment herein for antibacterial, anticancer, antirheumatic, antioxidant, anti-inflammatory, antiviral, hepatoprotective or hepatoprotective drugs for the treatment and / or prevention of cardiovascular disease, especially for the treatment of infectious diseases (especially diseases caused by sensitive or drug-resistant Mycobacterium tuberculosis), or a pharmaceutical composition thereof.

[0108] In some embodiments, provided herein are methods for antibacterial, anticancer, antirheumatic, antioxidant, anti-inflammatory, antiviral, hepatoprotective, or treatment and / or prevention of cardiovascular disease, particularly methods for treating infectious diseases (especially diseases caused by sensitive or resistant Mycobacterium tuberculosis), comprising administering to a subject in need thereof an effective amount of a compound of Formula I as described in any embodiment herein, or a pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide, hydrate, solvate, prodrug, or isotopic variant thereof, or a pharmaceutical composition thereof.

[0109] Herein, the subject may be a mammal, especially a human.

[0110] Herein, the microorganisms or bacteria may include: Mycobacterium tuberculosis, drug-resistant Mycobacterium tuberculosis, Mycobacterium smegmatis, Klebsiella pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, Mycobacterium leprae, Mycobacterium bovis, Mycobacterium marinum, Corynebacterium diphtheriae, Bordetella pertussis, Haemophilus influenzae, and Streptococcus pneumoniae. In some embodiments, the drug-resistant Mycobacterium tuberculosis is rifampicin-resistant, isoniazid-resistant, or rifampicin- and isoniazid-resistant.

[0111] As used herein, "preventing" includes reducing the likelihood of a disease or condition occurring or becoming worse in a patient.

[0112] As used herein, "treating" includes the following meanings: inhibiting a disease or condition, that is, curbing its development; alleviating a disease or condition, that is, causing the condition of the disease or condition to subside; and alleviating the symptoms caused by the disease or condition.

[0113] As used herein, an "effective amount" refers to an amount of at least one agent or compound sufficient to alleviate to some extent one or more symptoms of the disease or condition being treated. The result can be a reduction and / or alleviation of symptoms or causes, or any other desired change in a biological system. For example, an "effective amount" for therapeutic purposes is the amount of a composition comprising a compound disclosed herein required to provide a clinically significant symptom alleviation effect. Techniques such as dose escalation studies can be used to determine the effective amount appropriate for any individual case.

[0114] Preferably, the compound of formula I described in any embodiment herein or its pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide, hydrate, solvate or prodrug or its pharmaceutical composition is used to treat or prevent pulmonary tuberculosis or other tuberculosis diseases.

[0115] In the uses and methods herein, the compound of formula I described in any embodiment herein, or its pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide, hydrate, solvate, prodrug or isotopic variant, or pharmaceutical composition thereof, can be administered using techniques known in the art. These methods include, but are not limited to, oral route, duodenal route, parenteral injection (including intravenous, subcutaneous, intraperitoneal, intramuscular, intraarterial injection or infusion), topical administration, and rectal administration.

[0116] In general, the compounds of this invention are administered so as to obtain a daily dose of, for example, 0.01 mg to 1000 mg of active ingredient / kg body weight, which may be administered in divided doses if desired. However, the daily dose must vary depending on the subject being treated, the specific route of administration, and the severity of the disease being treated. Therefore, the optimal dose can be determined by the physician treating any particular patient.

[0117] V. Preparation Methods of Compounds

[0118] The present invention also provides a method for preparing the compound of the present invention. Illustratively, the present invention provides a method for preparing the compound represented by the following formula Ia:

[0119] wherein Z4-Z7 and n are as described in any embodiment herein, one of R4 and R6 is H, and the other is -CH2-NR a R b , R3 is hydroxyl, halogen, C1-C 10 Alkyl or C1-C 10 Alkoxy, R7 is H, halogen, C1-C8 alkyl or C3-C7 cycloalkyl,

[0120] Among them, R a and R b As described in any embodiment herein, the method comprises:

[0121] (1) In an organic solvent, the compound represented by the following formula 1 is reacted with Cu 2+ reacting with the substituted benzoquinone of formula 2 under catalysis to prepare a compound of formula 3; and

[0122] (2) reacting the compound of formula 3, formaldehyde solution, and a primary amine, a secondary amine, or a salt thereof in an alcohol to prepare a compound represented by formula Ia; wherein, when the reactant is a primary amine or a salt of a secondary amine, a base is added to the reaction system.

[0123] In some embodiments, the method further comprises making R3 C1-C 10 The alkoxy compound of formula 3 is subjected to a dealkylation reaction in the presence of boron tribromide to prepare the compound of formula Ia wherein R3 is a hydroxyl group. The dealkylation reaction can be carried out in ultra-dry dichloromethane.

[0124] In the above step (1), the organic solvent can be a benzene solvent, such as toluene or xylene. For example, copper trifluoromethanesulfonate can be used to provide the Cu required for catalysis. 2+ions. The reaction can be carried out at a temperature of 100-130°C and can last for 1-15 hours, depending on the reaction conditions. In the reaction system, the equivalent ratio of the compound of Formula 1 to the compound of Formula 2 can be 1.0-1.3:1.0. The amount of catalyst can be added appropriately depending on the amount of the reactants, for example, 0.05-0.15 equivalents of catalyst can be used for every 1 equivalent of the compound of Formula 2. After the reaction is completed, the reaction can be quenched with saturated ammonium chloride aqueous solution, extracted with ethyl acetate, and purified by silica gel column chromatography.

[0125] In the above step (2), the alcohol can be ethanol or isopropanol. The concentration of the formaldehyde solution can be 35 to 40 wt%. The reaction can be carried out at 70 to 90 ° C, and the reaction time can be 1 to 15 hours. In the reaction system, the equivalent ratio of the compound of formula 3 to the formaldehyde solution and the primary amine or secondary amine or its salt can be 1.0: 1.5 to 4.0: 1.5 to 4.0. The base can be an organic base or an inorganic base, such as triethylamine or sodium bicarbonate. After the reaction is completed, it can be concentrated under reduced pressure and purified by column chromatography to obtain the compound of formula Ia. The compound of formula 1 can be prepared by conventional methods. For example, an exemplary preparation method includes:

[0126] Step a: Compound 1-1 is dissolved in an alcohol solvent (e.g., methanol), and a reducing agent, such as sodium cyanoborohydride or sodium borohydride, is added under ice bath, and the mixture is reacted at room temperature for 0.5 to 1 hour. After the reaction is completed, the methanol (e.g., methanol) is evaporated under reduced pressure, and the pH is adjusted to a weakly acidic state (e.g., 5.8 to 6.5). The solid is precipitated and filtered to obtain compound 1-2.

[0127] Step b: Compound 1-2 and sodium hydride are dissolved in an ultra-dry solvent (such as tetrahydrofuran), iodomethane is added dropwise at low temperature, and then reacted at room temperature. After the reaction is completed, the reaction is quenched, the pH is adjusted to a weak acidity (such as 5.8 to 6.5) with an inorganic acid, and compound 1-3 is extracted and purified.

[0128] Step c: Compound 1-3, a palladium catalyst such as palladium acetate, 1,3-bis(diphenylphosphino)propane, potassium carbonate, and sodium carbonate are added to a reaction flask. Under inert gas protection, water and 2-vinylethanol are added and reacted at 70-90° C. After the reaction is completed, an intermediate transition product is generated. The mixture is extracted with an organic solvent, separated, and concentrated hydrochloric acid is added to the organic layer. The reaction is continued at room temperature. After the intermediate product reacts completely, the pH is adjusted to approximately neutral, extracted with an organic solvent, and purified to obtain compound 1-4.

[0129] Step d: Sodium hydride and diethyl carbonate were dissolved in xylene, stirred at room temperature, and then a xylene solution containing compound 1-4 was added. The reaction was carried out at 90-120°C. After the reaction was completed, the reaction solution was poured into ice water, the pH value was adjusted to neutral to slightly acidic, and organic solvent extraction was performed and purified to obtain compound 1.

[0130] In some embodiments, the above step (2) can be used to introduce -CH2-NR at the R6 position corresponding to the compound of formula Ia. a R b group.

[0131] In some embodiments, the compound of Formula 3 introduces a non-hydrogen substituent at the R4 or R6 position, especially an optionally substituted alkyl substituent as described in any embodiment herein, by the following method:

[0132] (i) dissolving the compound of formula 3 and potassium carbonate or sodium carbonate in ultra-dry N,N-dimethylformamide or ultra-dry tetrahydrofuran, adding iodomethane dropwise, and reacting at room temperature to prepare a compound with a protected hydroxyl group;

[0133] (ii) adding titanium tetrachloride dropwise to a chloroform solution containing the compound prepared in step (i) and dichloromethyl methyl ether at low temperature and under inert gas protection, and reacting at room temperature to obtain a compound wherein R4 or R6 is -CHO;

[0134] (iii) For a compound wherein R4 is -CHO, the compound can be first dissolved in ultra-dry dichloromethane, and boron tribromide is added dropwise at -20°C, and the reaction is carried out at room temperature to prepare a hydroxyl-deprotected compound. The deprotected compound is then dissolved in ultra-dry tetrahydrofuran, and alkylmagnesium bromide is added below 4°C, and the reaction is carried out at room temperature to obtain a compound wherein R4 is -CH(OH)-R, wherein R is a substituent on the alkyl group as defined in any embodiment herein. The compound can be dissolved in ultra-dry dichloromethane, and triethylsilane and trifluoroacetic acid are added at -78°C, and the reaction is carried out at room temperature to deprotect the hydroxyl group. Alternatively, the -CH(OH)-R group may be introduced at the R4 position by the above method, and then the hydroxyl group may be removed, and then deprotected; for a compound wherein R6 is -CHO, the -CH(OH)-R group may be introduced at the R6 position by the same method, and then the hydroxyl group may be removed, and then deprotected; or the compound, cyclic amine or substituted amino group and its salt may be dissolved in methanol, reacted at room temperature for a period of time under the catalysis of an acid (such as acetic acid), and then sodium cyanoborohydride may be added, and the reaction may be continued at room temperature to prepare a compound wherein R6 is -CH2-NR a R b A compound wherein R a and R b Deprotection is then performed as described in any of the embodiments herein.

[0135] In some embodiments, the method of the present invention comprises dissolving the compound of formula 3 and sodium hydroxide or potassium hydroxide in a mixed solvent of alcohol (such as methanol) and water, reacting at 50-70° C. for a period of time, and after the reaction, concentrating under reduced pressure to remove the alcohol solvent, adjusting the pH to acidic, and precipitating a solid, which is then filtered to obtain a compound of the following formula:

[0136] Then, the compound and pyridinium chlorochromate were dissolved in ultra-dry dichloromethane and reacted at room temperature. After the reaction was completed, the mixture was concentrated under reduced pressure and purified to obtain the following compound:

[0137] Then, under anhydrous and oxygen-free conditions, the compound, urea, and formic acid were dissolved in ethylene glycol and reacted at 140-160° C. After the reaction was completed, the reaction was quenched, and a solid precipitated. The solid was filtered and purified to obtain the following compound:

[0138] Thereafter, a substituted alkyl group can be introduced at the R4 or R6 position using the methods described above.

[0139] In some embodiments, the compound of Formula 1 and the compound of Formula 2 are dissolved in ultra-dry dichloromethane, protected by inert gas, and reacted at 50-60° C. for 10-18 hours to obtain the compound of the following formula:

[0140] Then, the compound and p-toluenesulfonic acid monohydrate are dissolved in toluene and reacted at 90-110° C. to obtain the compound of formula 3. The compound of formula Ia can be prepared using the compound of formula 3 according to the above method.

[0141] In some embodiments, in the aforementioned step (2), a halobenzoquinone in which R7 is a halogen is reacted to prepare a compound of formula 3 in which R7 is a halogen. A protective agent is then used to protect the hydroxyl group in the compound of formula 3 in which R7 is a halogen. A suitable protective agent may be, for example, tert-butyldimethylsilyl chloride. The reaction may be carried out in the presence of imidazole and N,N-dimethylformamide. In the case where, for example, R3 is not a hydroxyl group, for example, when R3 is an alkoxy group, the compound of formula 3 in which R7 is a halogen group may be first treated with boron tribromide, and then the hydroxyl group in the compound may be protected. Subsequently, a reaction can be carried out in a 1,4-dioxane solution in the presence of bis(pinacolato)diboron, potassium acetate, and a palladium catalyst such as tetrakistriphenylphosphine palladium to obtain an intermediate transition state. A hydrogen peroxide solution is then added to the reaction solution to replace the halogen group at position 11 (i.e., the R7 group) with a hydroxyl group. The hydroxyl group is then replaced with RO- (R can be a C1-C4 alkyl group) in the presence of triphenylphosphine, ROH, and diisopropyl azodicarboxylate. Deprotection is then performed (e.g., using tetramethylammonium fluoride in a tetrahydrofuran solution) to obtain a hydroxyl-deprotected compound. A substituted alkyl group can then be introduced at the R4 or R6 position using the method described above. The prepared compound of Formula Ia in which R7 is the optionally substituted alkoxy group can also be demethylated, for example, by demethylating the compound in the presence of boron tribromide and ultra-dry dichloromethane to obtain a compound of Formula Ia in which R7 is the hydroxyl group.

[0142] For R7, optionally substituted C2-C 10 Alkenyl, optionally substituted C3-C8 carbocyclic group, optionally substituted C6-C 14 Aryl, optionally substituted C5-C 10 Heteroaryl or optionally substituted C4-C 10 When the heterocyclic group is present, the compound of formula 3 wherein R7 is a halogen can be prepared first, and then, under the protection of an inert gas, the compound is reacted with R7-B(OH)2 or R7-BF3 - In the presence of potassium carbonate and a palladium catalyst such as tetrakistriphenylphosphine palladium, the halogen group at position 11 of the compound (i.e., R7 group) is replaced with R7 in 1,4-dioxane solvent. A substituted alkyl group can then be introduced at the R4 or R6 position using the method described above. For example, if R3 is a hydroxyl group, demethylation can be performed with boron tribromide before or after step (2) to obtain compound Ia in which R3 is a hydroxyl group.

[0143] In each of the above reactions, the amounts of reactants and the specific reaction conditions (such as temperature, etc.) of each reaction can be appropriately selected according to the chemical reaction formula and reaction conditions well known in the art.

[0144] The present invention will be further described below in conjunction with specific examples. It should be understood that these examples are intended to illustrate the present invention only and are not intended to limit the scope of the invention. The experimental methods in the following examples, for which specific conditions are not specified, are generally based on conventional conditions or the conditions recommended by the manufacturer. Unless otherwise stated, percentages and parts are calculated by weight.

[0145] Example 1:

[0146] Preparation of 3,9-dihydroxy-8-(piperidin-1-ylmethyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY001)

[0147] 1.1 Dissolve 2-bromo-5-hydroxybenzaldehyde (1.0 eq) in methanol, add sodium borohydride (0.5 eq) under ice-cooling, and react at room temperature for 0.5 h. After the reaction is complete as monitored by TLC, concentrate under reduced pressure to remove methanol, dilute with water, and adjust the pH to about 6 with 1 M hydrochloric acid to precipitate a solid. Filter the solid, wash with water, and dry to obtain 2-bromo-5-hydroxybenzyl alcohol.

[0148] 1.2 Under an ice bath, add 2-bromo-5-hydroxybenzyl alcohol (1.0 eq) and sodium hydride (2.5 eq) to a reaction flask, add ultra-dry tetrahydrofuran, and dropwise add iodomethane (2.5 eq). The reaction is allowed to react overnight at room temperature. After TLC monitoring, the reaction is quenched with ice water, the pH is adjusted to approximately 6 with 1M hydrochloric acid, and the product is extracted with ethyl acetate. The mixture is dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain 1-bromo-4-methoxy-2-(methoxymethyl)benzene.

[0149] 1.3 1-Bromo-4-methoxy-2-(methoxymethyl)benzene (1.0 eq), palladium acetate (0.025 eq), 1,3-bis(diphenylphosphino)propane (0.05 eq), and potassium carbonate (2.0 eq) were added to a reaction flask under nitrogen protection. Water and 2-vinylethanol (2.5 eq) were added and the reaction was allowed to proceed at 80°C overnight. The reaction was complete as monitored by TLC to generate an intermediate transition product. The product was extracted with ethyl acetate. Concentrated hydrochloric acid was added to the ethyl acetate phase and the reaction was continued at room temperature for approximately 1 h. After the reaction of the intermediate transition product was complete as monitored by TLC, a saturated aqueous sodium bicarbonate solution was added to quench the reaction and the pH was adjusted to approximately 7. The product was extracted with ethyl acetate and purified by silica gel column chromatography to obtain 2-(methoxymethyl)-4-methoxyacetophenone.

[0150] 1.4 Under nitrogen at room temperature, dissolve sodium hydride (3.2 eq) and diethyl carbonate (2.5 eq) in xylene and stir at room temperature for 30 minutes. Dissolve 2-(methoxymethyl)-4-methoxyacetophenone (1.0 eq) in xylene and add dropwise to the reaction system. Continue the reaction at 110°C for 30 minutes. After TLC (PE:EA = 4:1) confirms the reaction is complete, pour the reaction solution into ice water, adjust the pH to neutral to slightly acidic with hydrochloric acid, extract with ethyl acetate, and purify by silica gel column chromatography to obtain ethyl 3-[4-methoxy-2-(methoxymethyl)phenyl]-3-oxopropanoate.

[0151] 1.5 Dissolve ethyl 3-[4-methoxy-2-(methoxymethyl)phenyl]-3-oxopropanoate (1.05 eq), copper trifluoromethanesulfonate (0.1 eq), and benzoquinone (1.0 eq) in xylene and react at 110°C overnight. After completion of the reaction as monitored by TLC, concentrate under reduced pressure and purify by silica gel column chromatography to obtain 9-hydroxy-3-methoxybenzo[5,6]oxazepam[4,3-b]benzofuran-7(5H)-one.

[0152] 1.6 Method 1: 9-Hydroxy-3-methoxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (1 eq), piperidine (4.0 eq), and 37% formaldehyde solution (4.0 eq) were dissolved in ethanol and reacted at 80°C overnight. After completion of the reaction monitored by TLC, the mixture was concentrated under reduced pressure at 45°C and purified by C18 column chromatography to obtain 3-methoxy-9-hydroxy-8-(piperidin-1-ylmethyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one and 3-methoxy-9-hydroxy-10-(piperidin-1-ylmethyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one. Method 2: 9-hydroxy-3-methoxybenzo[5,6]oxadenosine[4,3-b]benzofuran-7(5H)-one (1.0 eq), piperidine hydrochloride (4.0 eq), 37% formaldehyde solution (4.0 eq), and triethylamine (4.0 eq) were dissolved in ethanol and reacted at 80°C overnight. After the reaction was completed as monitored by TLC, the mixture was concentrated under reduced pressure at 45°C and purified by C18 column chromatography to obtain 3-methoxy-9-hydroxy-8-(piperidin-1-ylmethyl)benzo[5,6]oxadenosine[4,3-b]benzofuran-7(5H)-one and 3-methoxy-9-hydroxy-10-(piperidin-1-ylmethyl)benzo[5,6]oxadenosine[4,3-b]benzofuran-7(5H)-one;

[0153] 1.7 3-Methoxy-9-hydroxy-8-(piperidin-1-ylmethyl)benzo[5,6]oxadenosine[4,3-b]benzofuran-7(5H)-one (1.0 eq) was dissolved in ultra-dry dichloromethane. Boron tribromide (4.0 eq, 1 M in DCM) was added dropwise at -20°C. The mixture was allowed to react overnight at room temperature. After completion of the reaction as monitored by TLC, the reaction was quenched with methanol and the mixture was directly concentrated under reduced pressure. The mixture was purified by C18 column chromatography and then treated with saturated aqueous sodium bicarbonate to obtain 3,9-dihydroxy-8-(piperidin-1-ylmethyl)benzo[5,6]oxadenosine[4,3-b]benzofuran-7(5H)-one (Compound TY001) as a golden solid. 1 H NMR (600MHz, DMSO-d6) δ10.59 (s, 2H), 7.84 (d, J=8.5Hz, 1H), 7.45 (d, J=8.7Hz, 1H), 7.10 (d, J=2.4Hz, 1H), 7.05 (dd, J=8.5, 2 .4Hz, 1H), 6.85 (d, J=8.8Hz, 1H), 5.17 (s, 2H), 3.96 (s, 2H), 3.51-3.22 (m, 2H), 2.46-2.32 (m, 2H), 1.51 (s, 4H), 1.42 (s, 2H). 13C NMR (151MHz, DMSO-d6) δ165.38, 160.12, 157.96, 154.09, 147.02, 136.97, 127.81, 127.21, 118.38, 116.47 , 115.32, 113.96, 108.60, 107.78, 68.07, 59.23, 52.23, 51.08, 39.44, 21.95, 20.62.HRMS (ESI) m / z: Calcd for C 22 H 21 NO5(M+H) + 380.14979; Found 380.14883.

[0154] Example 2:

[0155] Preparation of 3,9-dihydroxy-8-((methylamino)methyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY002)

[0156] The preparation method is similar to that of Example 1, except that methylamine is used instead of piperidine to obtain a yellow-brown solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.44 (s, 1H), 8.55 (dd, J=12.0, 6.5Hz, 2H), 7.88 (d, J=8.5Hz, 1H), 7.68 (dd, J=8.9, 1.7Hz, 1H), 7.1 4-7.09 (m, 2H), 7.07 (dd, J=8.5, 2.5Hz, 1H), 5.25 (s, 2H), 4.50 (t, J=5.8Hz, 2H), 2.63 (t, J=5.5Hz, 3H). HRMS (ESI) m / z: Calcd for C 18 H 16 NO5(M+H) + 326.10285; Found 326.10196.

[0157] Example 3:

[0158] Preparation of 8-((ethylamino)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY003)

[0159] The preparation method is similar to that of Example 1, except that ethylamine is used instead of piperidine to obtain a brown solid final product. 1H NMR (600MHz, DMSO-d6) δ10.63 (s, 1H), 10.45-10.22 (m, 1H), 8.44 (s, 1H), 7.88 (d, J = 8.5Hz, 1H), 7.69 (d, J = 8.9Hz, 1H), 7.13-7.09 (m, 2H), 7.07 (dd, J=8.5, 2.4Hz, 1H), 5.25 (s, 2H), 4.51 (t, J=5.7Hz, 2H), 3.06-3.03 (m, 2H), 1.25 (t, J=7.2Hz, 3H). HRMS (ESI) m / z: Calcd for C 19 H 18 NO5(M+H) + 340.11850; Found 340.11768.

[0160] Example 4:

[0161] Preparation of 3,9-dihydroxy-8-((propylamino)methyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY004)

[0162] The preparation method is similar to that of Example 1, except that n-propylamine is used instead of piperidine to obtain a brown solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.65 (s, 1H), 10.40 (s, 1H), 8.48 (s, 1H), 7.88 (d, J = 8.5Hz, 1H), 7.69 (d, J = 8.9Hz, 1H), 7.22-6.89 (m, 3H), 5.25 (s, 2H), 4.52 (s, 2H), 2.95 (dq, J=10.8, 5.9Hz, 2H), 1.68 (hept, J=8.6, 8.0Hz, 2H), 0.92 (t, J=7.4Hz, 3H). HRMS (ESI) m / z: Calcd for C 20 H 20 NO5(M+H) + 354.13415; Found 354.13281.

[0163] Embodiment 5:

[0164] Preparation of 8-((butylamino)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY005)

[0165] The preparation method is similar to that of Example 1, except that n-butylamine is used instead of piperidine to obtain a brown solid product. 1H NMR (600MHz, DMSO-d6) δ10.63 (s, 1H), 10.37 (s, 1H), 8.44 (s, 1H), 7.88 (d, J=8.5Hz, 1H), 7.69 (d, J=8.9Hz, 1H), 7.24-6.99 (m, 3H), 5.25 (s, 2H), 4.59-4.45 (m, 2H), 2.99 (dq, J=11.6, 6.0Hz, 2H), 1.65 (p, J=7.5Hz, 2H), 1.35 (h, J=7.4Hz, 2H), 0.90 (t, J=7.4Hz, 3H). HRMS (ESI) m / z: Calcd for C 21 H 22 NO5(M+H) + 368.14980; Found 368.14893.

[0166] Example 6:

[0167] Preparation of 3,9-dihydroxy-8-((pentylamino)methyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY006)

[0168] The preparation method is similar to that of Example 1, except that n-pentylamine is used instead of piperidine to obtain a colorless oily product. 1 H NMR (600MHz, DMSO-d6) δ10.67 (s, 1H), 10.43 (s, 1H), 8.47 (s, 1H), 7.88 (d, J =8.5Hz, 1H), 7.69 (d, J = 8.8Hz, 1H), 7.14-7.10 (m, 2H), 7.08 (dd, J = 8.5, 2.4 Hz, 1H), 5.25 (s, 2H), 4.52 (s, 2H), 2.98 (dt, J=11.6, 5.9Hz, 2H), 1.68 (t, J= 7.9Hz, 2H), 1.31 (h, J=3.8Hz, 4H), 0.97-0.82 (m, 3H). HRMS (ESI) m / z: Calcd for C 22 H 24 NO5(M+H) + 382.16545; Found 382.16409.

[0169] Embodiment seven:

[0170] Preparation of 8-((hept-6-en-1-amino)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY007)

[0171] The preparation method is as described in Example 1, except that the steps after 9-hydroxy-3-methoxybenzo[5,6]oxazepine[4,3-b]benzofuran-7(5H)-one are as follows:

[0172] 7.1 9-Hydroxy-3-methoxybenzo[5,6]oxazolidinone[4,3-b]benzofuran-7(5H)-one (1.0 eq) was dissolved in ultra-dry dichloromethane. 1M BBr3 (4.0 eq, 1M in DCM) was added dropwise at -20°C. The reaction was allowed to react overnight at room temperature. After completion of the reaction as monitored by TLC, the reaction was quenched with methanol and concentrated under reduced pressure to obtain a crude product, which was washed with methanol to obtain 3,9-dihydroxybenzo[5,6]oxazolidinone[4,3-b]benzofuran-7(5H)-one.

[0173] 7.2 3,9-Dihydroxybenzo[5,6]oxazepine[4,3-b]benzofuran-7(5H)-one (1.0 eq), 37% formaldehyde solution (3.0 eq), and 1-ene-7heptylamine (3.0 eq) were dissolved in ethanol and reacted at 80°C overnight. After completion of the reaction as monitored by TLC, the mixture was concentrated under reduced pressure and purified by C18 column chromatography. The product was then treated with saturated aqueous sodium bicarbonate to obtain the final product as a light yellow solid. 1 H NMR (600MHz, DMSO-d6) δ7.95 (d, J=8.4Hz, 1H), 7.59 (d, J=8.8Hz, 1H), 7.08-7.02 (m, 3H), 5.83 (ddt, J=17.0, 10.2, 6.8Hz, 1H), 5.24 (s, 2H), 5.06-4.93(m, 2H), 4.57(s, 2H), 3.17-3.08(m, 2H), 2.13-2.09(m, 2H), 1.82-1.73(m, 2H), 1.52-1.43(m, 4H). HRMS(ESI) m / z: Calcd for C24H26NO5(M+H) + 408.18110; Found 408.17975.

[0174] Embodiment 8:

[0175] Preparation of 8-(((6-bromoheptyl)amino)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY008)

[0176] The preparation method is similar to that of Example 1, except that 1-ene-7-heptylamine is used instead of piperidine to obtain a light yellow solid final product. 1H NMR (600MHz, Methanol-d4) δ7.96 (d, J=8.4Hz, 1H), 7.61 (d, J=8.9Hz, 1H), 7.11-7.05 (m, 4H), 5.25 (s, 2H), 4.59 (s, 2H), 4.19 (h, J=6. 6Hz, 1H), 3.18 (t, J=8.0Hz, 3H), 1.86-1.77 (m, 5H), 1.70 (d, J=6.6Hz, 3H), 1.67-1.57 (m, 1H), 1.57-1.41 (m, 2H). HRMS (ESI) m / z: Calcd for C 24 H 27 BrNO5(M+H) + 488.10726; Found 488.10651.

[0177] Embodiment 9:

[0178] Preparation of 3,9-dihydroxy-8-(((2-hydroxyethyl)amino)methyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY009)

[0179] The preparation method is similar to that of Example 7, except that ethanolamine is used instead of 1-ene-7-heptylamine to obtain a yellow solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.64 (s, 1H), 10.41 (s, 1H), 7.88 (d, J=8.5Hz, 1H), 7.69 (d, J=8.8Hz, 1H), 7.12 (d, J=2.5Hz, 1H), 7.10 (d, J=8.9Hz, 1H), 7.07 (d d, J=8.5, 2.5Hz, 1H), 5.25 (s, 2H), 5.18 (d, J=14.1Hz, 1H), 4.58 (s, 2H), 3.6 8 (t, J=5.5Hz, 2H), 3.07 (t, J=5.8Hz, 2H), 2.54 (s, 1H). HRMS (ESI) m / z: Calcd for C 19 H 17 NO6(M+H) + 356.1124; Found 356.1138.

[0180] Embodiment 10:

[0181] Preparation of 3,9-dihydroxy-8-(((2-hydroxypropyl)amino)methyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY010)

[0182] The preparation method is similar to that of Example 7, except that 1-amino-2-propanol is used instead of 1-ene-7-heptylamine to obtain a yellow-brown solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.67 (s, 1H), 10.49 (s, 1H), 8.66 (s, 1H), 7.89 (d, J=8.5Hz, 1H), 7.73 (d, J=8.9Hz , 1H), 7.15-7.07(m, 3H), 5.29(s, 2H), 4.57(s, 2H), 3.96-3.94(m, 2H), 3.03-3.00(m, 1H), 1.10(d, J=6.3Hz 3H).HRMS(ESI)m / z:Calcd for C 20 H 19 NO6(M+H) + 370.1288; Found 370.1279.

[0183] Example 11:

[0184] Preparation of 3,9-dihydroxy-8-((isobutylamino)methyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY011)

[0185] The preparation method is similar to that of Example 1, except that isobutylamine is used instead of piperidine to obtain a yellow-brown solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.67 (s, 1H), 10.44 (s, 1H), 7.88 (d, J = 8.5Hz, 1H), 7.69 (d, J = 8.9Hz, 1H), 7.12 (d, J = 2.4Hz, 1H), 7. 10 (d, J=8.9Hz, 1H), 7.07 (dd, J=8.5, 2.4Hz, 1H), 5.25 (s, 2H), 4.52 (s, 2H), 2.84 (s, 2H), 1.23 (s, 1H), 0.96 (d, J=6.7Hz, 6H). 13 C NMR (151MHz, DMSO-d6) δ165.58, 161.15, 158.75, 154.75, 148.02, 138.02, 128.84, 127.71, 119.44, 117 .51, 116.44, 114.82, 113.99, 110.25, 109.46, 68.55, 54.77, 43.26, 25.60, 20.52.HRMS (ESI) m / z: Calcd for C 21 H 21 NO5(M+H) +368.14979; Found 368.14865.

[0186] Example 12:

[0187] Preparation of 8-((tert-butylamino)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY012)

[0188] The preparation method is similar to that of Example 1, except that tert-butylamine is used instead of piperidine to obtain a yellow-brown solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.66 (s, 1H), 10.42 (s, 1H), 7.89 (d, J = 8.5Hz, 1H), 7.70 (d, J = 8.8Hz, 1 H), 7.12 (d, J=9.1Hz, 2H), 7.08 (dd, J=8.5, 2.4Hz, 1H), 5.26 (s, 2H), 4.63 (s, 2H), 1.41 (s, 9H). 13 C NMR (176MHz, DMSO-d6) δ165.05, 160.40, 157.56, 153.57, 146.85, 136.86, 127.76, 126.25, 118.29, 116.38, 115.29, 113.64, 112.71, 109.48, 108.28, 68.52, 57.01, 36.34, 24.78.HRMS (ESI) m / z: Calcd for C 21 H 21 NO5(M+H) + 368.14979; Found 368.14886.

[0189] Example 13:

[0190] Preparation of 8-(((adamantan-1-yl)amino)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY013)

[0191] The preparation method is similar to that of Example 1, except that adamantaneamine is used instead of piperidine to obtain a yellow solid final product. 1H NMR (600MHz, DMSO-d6) δ10.69 (s, 1H), 10.40 (s, 1H), 7.88 (d, J=8.5Hz, 1H), 7.71 (t, J=8.1Hz, 1 H), 7.14-7.10 (m, 2H), 7.08 (dd, J=8.5, 2.4Hz, 1H), 5.26 (d, J=5.8Hz, 2H), 4.74-4.55 (m, 2H), 4. 10-4.00 (m, 1H), 3.37 (dt, J=45.6, 9.7Hz, 2H), 2.69 (d, J=3.7Hz, 1H), 2.17 (d, J=11.3Hz, 1H), 1. 84-1.70(m, 2H), 1.70-1.55(m, 2H), 1.43-1.33(m, 1H), 0.87-0.77(m, 1H).HRMS(ESI)m / z: Calcd for C 27 H 28 NO5(M+H) + 446.19675; Found 446.19522.

[0192] Example 14:

[0193] Preparation of 8-((cyclopropylamino)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (TY014)

[0194] The preparation method is similar to that of Example 1, except that cyclopropylamine is used instead of piperidine to obtain a pink solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.65 (s, 1H), 10.40 (s, 1H), 7.88 (d, J = 8.5Hz, 1H), 7.69 (d, J = 8.9Hz, 1H), 7.1 3-7.09 (m, 2H), 7.07 (dd, J=8.5, 2.5Hz, 1H), 5.24 (s, 2H), 4.68 (s, 2H), 2.76 (s, 1H), 0.94-0.66 (m, 4H). 13 C NMR (151MHz, DMSO-d6) δ165.84, 161.06, 158.66, 154.71, 147.92, 137.99, 128.79, 127.47, 119.40, 117 .42, 116.36, 114.71, 113.91, 110.24, 109.36, 69.02, 49.06, 43.60, 30.64, 3.90.HRMS (ESI) m / z: Calcd for C 20 H 17 NO5(M+H)+ 352.11849; Found 352.11728.

[0195] Embodiment 15:

[0196] Preparation of 8-((cyclobutylamino)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY-015)

[0197] The preparation method is similar to that of Example 1, except that cyclobutylamine is used instead of piperidine to obtain a light yellow solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.66 (s, 1H), 10.41 (s, 1H), 7.88 (d, J=8.5Hz, 1H), 7.69 (d, J=8.8Hz, 1H), 7.14-7.09 (m, 2H ), 7.08 (dd, J=8.5, 2.4Hz, 1H), 5.25 (s, 2H), 4.46 (s, 2H), 3.78-3.75 (m,, 1H), 2.32-2.07 (m, 4H), 1.86-1.65 (m, 2H). 13 C NMR (151MHz, DMSO-d6) δ165.82, 161.07, 158.66, 154.67, 147.96, 137.98, 128.80, 127.44, 119.40, 117.43, 116.36, 114.71, 113.86, 110.30, 109.33, 69.03, 51.69, 26.61, 14.95.HRMS (ESI) m / z: Calcd for C 21 H 19 NO5(M+H) + 366.13414; Found 366.13284.

[0198] Example 16:

[0199] Preparation of 8-(((3,3-difluorocyclobutyl)amino)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY-016)

[0200] The preparation method is similar to that of Example 7, except that 3,3-difluorocyclobutylamine is used instead of 1-ene-7-heptylamine to obtain a light yellow solid final product. 1H NMR (600MHz, DMSO-d6) δ10.67 (s, 1H), 10.50 (s, 1H), 7.89 (d, J=8.5Hz, 1H), 7.71 (d, J=8.9Hz, 1H), 7.14-7.10 (m, 2H) , 7.08 (dd, J=8.5, 2.5Hz, 1H), 5.26 (s, 2H), 4.51 (s, 2H), 3.88-3.76 (m, 1H), 2.99-2.95 (m, 4H). HRMS (ESI) m / z: Calcd for C 21 H 17 F2NO5(M+H) + 402.11530; Found 402.11459.

[0201] Embodiment 17:

[0202] Preparation of 8-((cyclopentylamino)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY017)

[0203] The preparation method is similar to that of Example 1, except that cyclopentylamine is used instead of piperidine to obtain a pink solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.65 (s, 1H), 10.41 (s, 1H), 7.88 (d, J = 8.5Hz, 1H), 7.69 (d, J = 8.8Hz, 1H), 7.14-7.10 (m, 2H), 7.08 (dd . 13 C NMR (151MHz, DMSO-d6) δ164.63, 159.95, 158.07, 153.59, 147.38, 137.87, 128.73, 126.90, 118.83, 116 .86, 115.79, 114.16, 112.73, 110.02, 109.19, 68.46, 58.86, 41.42, 28.05, 23.64.HRMS (ESI) m / z: Calcd for C 22 H 21 NO5(M+H) + 380.14979; Found 380.14880.

[0204] Embodiment 18:

[0205] Preparation of 8-((cyclohexylamino)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY018)

[0206] The preparation method is similar to that of Example 1, except that cyclohexylamine is used instead of piperidine to obtain a yellow solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.65 (s, 1H), 10.39 (s, 1H), 7.88 (d, J=8.5Hz, 1H), 7.69 (d, J =8.9Hz, 1H), 7.13 (d, J = 2.4Hz, 1H), 7.11 (d, J = 8.9Hz, 1H), 7.08 (dd, J = 8.5, 2.4Hz, 1H ), 5.25 (s, 2H), 4.56 (s, 2H), 2.12 (d, J = 16.2Hz, 2H), 2.06 (d, J = 11.1Hz, 1H), 1.80 (d, J=13.1Hz, 2H), 1.63 (d, J=12.9Hz, 2H), 1.28 (d, J=13.1Hz, 2H), 1.13 (d, J=9.2Hz, 2H). 13 C NMR (176MHz, DMSO-d6) δ166.06, 161.07, 158.63, 154.59, 147.95, 137.96, 128.78, 127.54, 119.39, 117.44, 116.3 7, 114.72, 113.81, 110.64, 109.38, 69.04, 58.74, 57.75, 29.11, 28.70, 25.22, 24.59, 24.50.HRMS (ESI) m / z: Calcd for C 23 H 23 NO5(M+H) + 394.16544; Found 394.16492.

[0207] Embodiment 19:

[0208] Preparation of 8-(((cyclopropylmethyl)amino)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY019)

[0209] The preparation method is similar to that of Example 1, except that cyclopropylmethylamine is used instead of piperidine to obtain a brick-red solid final product. 1H NMR (600MHz, DMSO-d6) δ10.65 (s, 1H), 10.40 (s, 1H), 7.88 (d, J = 8.5Hz, 1H), 7.69 (d, J = 8.8Hz, 1H), 7.12 (d, J = 2.4Hz, 1H), 7.10 (d, J = 8.9Hz, 1H), 7.08(dd, J=8.5, 2.5Hz, 1H), 5.25(s, 2H), 4.55(s, 2H), 2.91(s, 2H), 1.1 3(td, J=7.7, 4.7Hz, 1H), 0.59 (dd, J=8.0, 1.9Hz, 2H), 0.46-0.33 (m, 2H). 13 C NMR (151MHz, DMSO-d6)) δ165.46, 160.49, 158.03, 154.01, 147.38, 137.39, 128.18, 127.01, 118.81, 11 6.85, 115.80, 114.16, 113.25, 109.97, 108.84, 68.44, 51.70, 41.80, 6.94, 3.89.HRMS (ESI) m / z: Calcd for C 21 H 19 NO5(M+H) + 366.13414; Found 366.13333.

[0210] Embodiment 20:

[0211] Preparation of 8-(((cyclobutylmethyl)amino)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY020)

[0212] The preparation method is similar to that of Example 1, except that cyclobutylmethylamine is used instead of piperidine to obtain a yellow-green solid final product. 1 H NMR (600MHz, DMSO-d6) δ7.85 (d, J=8.4Hz, 1H), 7.48 (d, J=8.8Hz, 1H), 7.10 (s, 1H), 7.05 (dd, J=8.5, 2.4Hz, 1H), 6.85 (d, J=8.8Hz, 1H), 5. 19 (s, 2H), 4.26 (s, 2H), 2.67 (d, J=7.2Hz, 2H), 2.60 (q, J=7.2Hz, 1H), 2.01 (d, J=8.7Hz, 2H), 1.68 (q, J=9.0Hz, 2H), 0.99 (t, J=7.2Hz, 2H). 13C NMR (176MHz, DMSO-d6) δ165.11, 160.76, 157.18, 156.13, 147.76, 137.96, 128.48, 126.13, 119.61, 117.36 , 116.30, 115.58, 111.25, 108.67, 68.77, 54.11, 46.14, 34.49, 21.69, 18.46, 11.33.HRMS (ESI) m / z: Calcd for C 22 H 21 NO5(M+H) + 380.14979; Found 380.14908.

[0213] Embodiment 21:

[0214] Preparation of 8-(((cyclopentylmethyl)amino)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY021)

[0215] The preparation method is similar to that of Example 1, except that (aminomethyl)cyclopentane is used instead of piperidine to obtain a light yellow solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.66 (s, 1H), 10.44 (s, 1H), 7.88 (d, J=8.5Hz, 1H), 7.69 (d, J =8.8Hz, 1H), 7.15-7.09(m, 2H), 7.08(dd, J=8.5, 2.4Hz, 1H), 5.25(s, 2H), 4.54(s, 2H ), 2.97 (d, J=6.6Hz, 2H), 2.23 (p, J=7.7Hz, 1H), 1.80 (dq, J=12.0, 6.8Hz, 2H), 1.60 (t , J=7.8Hz, 2H), 1.55-1.45 (m, 2H), 1.23 (dq, J=15.3, 7.7Hz, 2H).HRMS (ESI) m / z: Calcd for C 23 H 23 NO5(M+H) + 394.16544; Found 394.16467.

[0216] Embodiment 22:

[0217] Preparation of 8-(((cyclohexylmethyl)amino)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY022)

[0218] The preparation method is similar to that of Example 1, except that cyclohexylmethylamine is used instead of piperidine to obtain a light yellow solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.64 (s, 1H), 10.40 (s, 1H), 7.88 (d, J = 8.5Hz, 1H), 7.69 (d, J = 8.7Hz, 1H), 7 .13 (d, J=2.5Hz, 1H), 7.10 (d, J=10.0Hz, 1H), 7.08 (dd, J=8.5, 2.5Hz, 1H), 5.25 (s, 2H), 4.50 (s, 2H), 2.85 (q, J=6.3Hz, 2H), 1.79 (d, J=12.9Hz, 2H), 1.74 (ddt, J=11.0, 7.3, 3.6Hz, 1H), 1.68 (d, J=13.1Hz , 2H), 1.61 (d, J=12.3Hz, 1H), 1.24-1.09 (m, 4H), 0.95 (qd, J=12.2, 3.5Hz, 2H). HRMS (ESI) m / z: Calcd for C 24 H 25 NO5(M+H) + 408.18109; Found 408.17950.

[0219] Embodiment 23:

[0220] Preparation of 3,9-dihydroxy-8-((((1-methylpiperidin-4-yl)methyl)amino)methyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY023)

[0221] The preparation method is similar to that of Example 7, except that (1-methyl-4-piperidinyl)methylamine is used instead of 1-ene-7-heptylamine to obtain a yellow solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.66 (s, 1H), 9.44 (s, 1H), 7.89 (d, J=8.5Hz, 1H), 7.70 (d, J=8.9Hz, 1H), 7.15-7.07 (m, 3H), 5.26 (s, 2H), 4. 51 (s, 2H), 3.45 (d, J = 12.1Hz, 2H), 3.17 (s, 1H), 2.94 (d, J = 34.2Hz, 4H), 2.75 (s, 4H), 2.02 (d, J = 13.8Hz, 3H), .HRMS (ESI) m / z: Calcd for C 24 H 26 N2O5(M+H) + 423.1918; Found 423.1904.

[0222] Embodiment 24:

[0223] Preparation of 3,9-dihydroxy-8-(((4-hydroxyphenethyl)amino)methyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY024)

[0224] The preparation method is similar to that of Example 7, except that 4-hydroxyphenylethylamine is used instead of 1-ene-7-heptylamine to obtain a light yellow solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.60 (s, 1H), 10.34 (s, 1H), 9.31 (s, 1H), 7.88 (d, J =8.5Hz, 1H), 7.69 (d, J = 8.9Hz, 1H), 7.12 (d, J = 2.5Hz, 1H), 7.09 (d, J = 9.1Hz, 1H), 7.08-7.06(m, 1H), 7.05-7.02(m, 2H), 6.72-6.69(m, 2H), 5.24(s, 2H), 4 .55 (s, 2H), 3.16 (s, 2H), 2.88 (dd, J=9.8, 7.0Hz, 2H), .HRMS (ESI) m / z: Calcd for C 25 H 21 NO6(M+H) + 432.1435; Found 432.1448.

[0225] Embodiment 25:

[0226] Preparation of 8-((dimethylamino)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY025)

[0227] The preparation method is similar to that of Example 1, except that dimethylamine is used instead of piperidine to obtain a white solid final product. 1 H NMR (600MHz, Methanol-d4) δ7.94 (d, J=8.4Hz, 1H), 7.65 (d, J=8.9Hz, 1H), 7.10-7.04 (m, 3H), 5.23 (s, 2H), 4.71 (s, 2H), 2.97 (s, 6H). 13C NMR (151MHz, Methanol-d4) δ167.30, 161.16, 159.87, 154.77, 148.56, 137.36, 128.41, 127.53, 11 9.55, 116.76, 115.38, 114.19, 114.15, 108.47, 108.28, 69.16, 53.05, 42.34.HRMS (ESI) m / z: Calcd for C 19 H 17 NO5(M+H) + 340.11849; Found 340.11679.

[0228] Example 26:

[0229] Preparation of 8-((diethylamino)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY026)

[0230] The preparation method is similar to that of Example 1, except that diethylamine is used instead of piperidine to obtain a white solid final product. 1 H NMR (600MHz, Methanol-d4) δ7.91 (d, J=8.4Hz, 1H), 7.61 (d, J=8.9Hz, 1H), 7.05-7.04 (m, 1H), 7.04-7.0 2 (m, 1H), 7.02 (d, J = 2.4Hz, 1H), 5.20 (s, 2H), 4.70 (s, 2H), 3.27 (p, J = 1.7Hz, 4H), 1.34 (t, J = 7.3Hz, 6H). 13 C NMR (151MHz, Methanol-d4) δ167.45, 161.19, 159.88, 154.94, 148.63, 137.38, 128.44, 127.57, 11 9.50, 116.79, 115.37, 114.12, 114.08, 108.48, 108.33, 69.21, 49.01, 7.79.HRMS (ESI) m / z: Calcd for C 21 H 21 NO5(M+H) + 368.14979; Found 368.14789.

[0231] Embodiment 27:

[0232] Preparation of 8-((ethyl(propyl)amino)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY027)

[0233] The preparation method is similar to that of Example 1, except that N-ethyl-n-propylamine is used instead of piperidine to obtain a light yellow solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.69 (s, 1H), 10.60 (s, 1H), 7.89 (d, J=8.5Hz, 1H), 7.74 (d, J=8.9Hz, 1H), 7.16-7.11 (m, 2H), 7.08 (dd, J=8. 5, 2.5Hz, 1H), 5.27 (s, 2H), 4.72 (s, 2H), 3.19 (s, 2H), 3.06 (s, 2H), 1.82-1.59 (m, 2H), 1.28 (t, J=7.2Hz, 3H), 0.91 (t, J=7.3Hz, 3H). 13 C NMR (151MHz, DMSO-d6) δ166.26, 161.17, 159.02, 155.20, 148.07, 137.99, 128.88, 127.85, 119.31, 117 .48, 116.34, 114.91, 114.56, 109.34, 109.11, 69.11, 48.54, 16.82, 11.35, 8.98.HRMS (ESI) m / z: Calcd for C 22 H 23 NO5(M+H) + 382.16544; Found 382.16467.

[0234] Embodiment 28:

[0235] Preparation of 8-((dipropylamino)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY028)

[0236] The preparation method is similar to that of Example 1, except that di-n-propylamine is used instead of piperidine to obtain a light yellow solid final product. 1H NMR (600MHz, DMSO-d6) δ10.68 (s, 1H), 10.60 (s, 1H), 7.89 (d, J = 8.5Hz, 1H), 7.74 (d, J = 8.9Hz, 1H), 7.13 (dd, J = 5.7, 3.2Hz , 2H), 7.08 (dd, J=8.5, 2.4Hz, 1H), 5.26 (s, 2H), 4.72 (s, 2H), 3.07 (s, 4H), 1.72 (d, J=63.7Hz, 4H), 0.90 (t, J=7.3Hz, 6H). 13 C NMR (151MHz, DMSO-d6) δ166.37, 161.18, 159.05, 155.22, 148.07, 137.98, 128.89, 127.87, 119.31, 117 .49, 116.35, 114.91, 114.61, 109.31, 109.08, 69.13, 49.51, 49.06, 16.87, 11.32.HRMS (ESI) m / z: Calcd for C 23 H 25 NO5(M+H) + 396.18109; Found 396.18072.

[0237] Embodiment 29:

[0238] Preparation of 8-((dibutylamino)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY029)

[0239] The preparation method is similar to that of Example 1, except that di-n-butylamine is used instead of piperidine to obtain a white solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.67 (s, 1H), 10.60 (s, 1H), 7.89 (d, J=8.5Hz, 1H), 7.74 (d, J=8.9Hz, 1H), 7.15-7.11 (m, 2H), 7.08 (dd, J=8.5, 2.4Hz, 1H), 5.26 (s, 2H), 4.73 (s, 2H), 3.16-2.98 (m, 4H), 1.73 (tt, J=12.2, 6.3Hz, 2H), 1.62 (td, J=12.6, 12.0, 5.9Hz, 2H), 1.31 (h, J=7.5Hz, 4H), 0.90 (t, J=7.4Hz, 6H). 13C NMR (151MHz, DMSO-d6) δ165.79, 160.61, 158.49, 154.64, 147.49, 137.39, 128.31, 127.28, 118.73, 116.92 , 115.77, 114.30, 114.03, 108.70, 108.48, 68.53, 48.92, 39.95, 24.70, 19.35, 13.41.HRMS (ESI) m / z: Calcd for C 25 H 29 NO5(M+H) + 424.21239; Found 424.21124.

[0240] Embodiment 30:

[0241] Preparation of 3,9-dihydroxy-8-{[(2-hydroxyethyl)(methyl)amino]methyl}-5,7-dihydrobenzo[e]benzo[2,3]furo[4,5-c]oxepan-7-one (Compound TY030)

[0242] The preparation method is similar to that of Example 7, except that N-methylethanolamine is used instead of 1-ene-7-heptylamine to obtain a brown solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.71-10.60 (m, 1H), 10.53 (s, 1H), 7.89 (d, J=8.5Hz, 1H) , 7.74 (d, J=8.9Hz, 1H), 7.13 (dd, J=5.7, 3.2Hz, 2H), 7.08 (dd, J=8.5, 2.5Hz, 1H), 5.27(s, 3H), 4.85-4.63(m, 3H), 3.27(s, 2H), 2.86(s, 3H).HRMS(ESI)m / z: Calcd for C 20 H 19 NO6(M+H) + 370.1281; Found 370.1288.

[0243] Embodiment 31:

[0244] Preparation of 3,9-dihydroxy-8-(((3-hydroxypropyl)(methyl)amino)methyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY031)

[0245] The preparation method is similar to that of Example 7, except that N-methyl-3-hydroxypropylamine is used instead of 1-ene-7-heptylamine to obtain a brown solid final product. 1H NMR (600MHz, DMSO-d6) δ10.63 (s, 1H), 10.50 (s, 1H), 8.80 (s, 1H), 7.89 (d, J=8.5Hz, 1H), 7.74 (d, J=8.9Hz, 1H), 7.18-7.07 (m, 3H), 5.26 (s, 2H), 4.75 (s, 1H), 4.65 (dd, J=12.9, 6.7Hz, 1H), 3.53-3.47 (m, 2H), 3.28 (d, J=25.6Hz, 2H), 2.78 (d, J=4.5Hz, 3H), 1.88 (d, J=8.5Hz, 2H). HRMS (ESI) m / z: Calcd for C 21 H 21 NO6(M+H) + 384.1450; Found 384.1433.

[0246] Embodiment 32:

[0247] Preparation of 3,9-dihydroxy-8-(((2-hydroxyethyl)(propyl)amino)methyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY032)

[0248] The preparation method is similar to that of Example 7, except that 2-(propylamino)ethanol is used instead of 1-ene-7-heptylamine to obtain a gray solid final product. 1 H NMR (600MHz, Methanol-d4) δ7.93 (d, J=8.4Hz, 1H), 7.52 (d, J=8.8Hz, 1H), 7.06 (dd, J=8.5, 2.4Hz, 1H), 7.03 (d, J=2.4Hz, 1H), 6.97 (d, J=8.8Hz, 1H), 5. 20 (s, 2H), 4.54 (s, 2H), 3.74 (t, J = 5.7Hz, 2H), 3.10 (t, J = 5.7Hz, 2H), 3.05- 2.91 (m, 2H), 1.84-1.70 (m, 2H), 0.98 (t, J = 7.4Hz, 3H). RMS (ESI) m / z: Calcd for C 22 H 23 NO6(M+H) + 398.16036; Found 398.15811.

[0249] Embodiment 33:

[0250] Preparation of 8-{[butyl(2-hydroxyethyl)amino]methyl}-3,9-dihydroxy-5,7-dihydrobenzo[e]benzo[2,3]furo[4,5-c]oxepan-7-one (Compound TY033)

[0251] The preparation method is similar to that of Example 7, except that 2-(butylamino)ethanol is used instead of 1-ene-7-heptylamine to obtain a light yellow solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.67 (d, J=8.0Hz, 2H), 7.89 (d, J=8.5Hz, 1H), 7.74 ( d, J=8.9Hz, 1H), 7.14-7.11 (m, 2H), 7.08 (d, J=8.5Hz, 1H), 5.27 (s, 2H), 4.81- 4.71 (m, 2H), 3.74 (t, J=8.3Hz, 1H), 3.66-3.53 (m, 2H), 3.17 (s, 2H), 1.81-1. 69 (m, 2H), 1.34 (d, J = 7.6Hz, 2H), 0.92 (t, J = 7.3Hz, 4H). HRMS (ESI) m / z: Calcd for C 23 H 25 NO6(M+H) + 412.1751; Found 412.1758.

[0252] Embodiment 34:

[0253] Preparation of 8-((Benzyl(methyl)amino)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY034)

[0254] The preparation method is similar to that of Example 7, except that N-methylbenzylamine is used instead of 1-ene-7-heptylamine to obtain a yellow-white solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.67 (s, 1H), 10.49 (s, 1H), 7.89 (d, J=8.5Hz, 1H), 7.73 (d, J=8.9Hz, 1H), 7.59 (dd, J=6.7, 2.9Hz, 2H), 7.47 (dd, J=4.9, 2.0Hz, 3H), 7.15-7.07 ( m, 3H), 5.29 (s, 2H), 4.92-4.82 (m, 1H), 4.63 (dd, J=12.7, 8.4Hz, 1H), 4.55 (d, J=13. 0Hz, 1H), 4.43 (dd, J=12.6, 7.3Hz, 1H), 2.58 (d, J=4.8Hz, 3H). HRMS (ESI) m / z: Calcd for C25 H 21 NO5(M+H) + 416.1498; Found 416.1482.

[0255] Embodiment 35:

[0256] Preparation of 8-(azetidin-1-ylmethyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY035)

[0257] The preparation method is similar to that of Example 1, except that azetidine is used instead of piperidine to obtain a light yellow solid final product. 1 H NMR (600MHz, DMSO-d6) δ 10.66 (s, 1H), 10.44 (s, 1H), 7.88 (d, J = 8.5Hz, 1H), 7.68 (d, J = 8.9Hz, 1H), 7.12 (d, J = 2.4Hz, 1H), 7.09 (d . 13 C NMR (151MHz, DMSO-d6) δ166.11, 161.11, 158.77, 154.68, 147.95, 138.00, 128.78, 127.71, 119.34, 117 .43, 116.39, 114.89, 114.11, 109.56, 109.28, 69.02, 50.59, 49.06, 44.60, 16.51.HRMS (ESI) m / z: Calcd for C 20 H 17 NO5(M+H) + 352.11849; Found 352.11801.

[0258] Embodiment 36:

[0259] Preparation of 3,9-dihydroxy-8-((3-methylazetidin-1-yl)methyl)benzo[5,6]oxazepizo[4,3-b]benzofuran-7(5H)-one (Compound TY036)

[0260] The preparation method is similar to that of Example 1, except that 3-methylazetidine is used instead of piperidine to obtain a pink solid final product. 1H NMR (600MHz, DMSO-d6) δ10.68 (s, 1H), 9.65-9.37 (m, 1H), 7.88 (d, J=8.5Hz, 1H), 7.69 (dd, J=8.9, 3.2Hz, 1H), 7.14-7.09 (m, 2H), 7.08 (dd, J=8.5, 2.5Hz, 1H), 5.25 (s, 2H), 4 .78-4.60 (m, 2H), 4.32 (td, J=9.6, 4.9Hz, 1H), 4.15 (tdd, J=8.5, 6.2, 2.1Hz, 1H), 3.95 (q, J=9.0Hz, 1H), 3.91-3.76 (m, 1H), 2.99-2.78 (m, 1H), 1.20 (dd, J=23.0, 6.9Hz, 3H). 13 C NMR (151MHz, DMSO) δ165.64, 160.65, 158.28, 154.25, 147.47, 137.53, 128.30, 127.23, 118.86, 116.97, 1 15.93, 114.40, 113.60, 109.17, 108.81, 68.54, 54.92, 50.57, 24.53, 23.56, 17.60.HRMS (ESI) m / z: Calcd for C 21 H 20 NO5(M+H) + 366.13415; Found 366.13318.

[0261] Embodiment 37:

[0262] Preparation of 3,9-dihydroxy-8-((3-methoxyazetidin-1-yl)methyl)benzo[5,6]oxazepizo[4,3-b]benzofuran-7(5H)-one (Compound TY037)

[0263] The preparation method is similar to that of Example 7, except that 3-methoxycyclobutylamine hydrochloride is used instead of 1-ene-7-heptylamine to obtain an off-white solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.66 (s, 1H), 10.51 (s, 1H), 7.88 (dd, J=8.5, 2.9Hz, 1H), 7.69 (t, J=9.0Hz, 1H), 7.15-7 .05(m,3H),5.25(s,2H),4.75(s,2H),4.47-4.36(m,2H),4.23-4.08(m,3H),3.17(s,3H).HRMS(ESI)m / z:Calcd for C 21 H 19NO6(M+H) + 382.1290; Found 382.1282.

[0264] Embodiment 38:

[0265] Preparation of 1-((3,9-dihydroxy-7-oxo-5,7-dihydrobenzo[5,6]oxo-4,3-b]benzofuran-8-yl)methyl)azetidine-3-carbonitrile (Compound TY038)

[0266] The preparation method is as described in Example 7, except that the steps after 3,9-dihydroxybenzo[5,6]oxazolidinone[4,3-b]benzofuran-7(5H)-one are as follows:

[0267] 38.1 3,9-Dihydroxybenzo[5,6]oxazepine[4,3-b]benzofuran-7(5H)-one (1.0 eq), 37% formaldehyde solution (4.0 eq), 3-acetonitrile cyclobutylamine hydrochloride (4.0 eq), and triethylamine (4.0 eq) were dissolved in ethanol and reacted at 80°C overnight. After completion of the reaction as monitored by TLC, the mixture was concentrated under reduced pressure and purified by C18 column chromatography, followed by treatment with saturated aqueous sodium bicarbonate to obtain the final product as a pale yellow solid. 1 H NMR (600MHz, DMSO-d6) δ10.68 (s, 1H), 10.55 (s, 1H), 7.88 (d, J=8.5Hz, 1H), 7.69 (d, J=8.9Hz, 1H), 7.13 (d, J=2. 4Hz, 1H), 7.11-7.06 (m, 2H), 5.25 (s, 2H), 4.75 (s, 2H), 4.61 (d, J=29.5Hz, 2H), 4.36 (s, 2H), 4.17-3.99 (m, 1H). 13 C NMR (151MHz, DMSO-d6) δ166.28, 161.16, 158.58, 158.62, 158.41, 154.76, 147.92, 137.97, 128.77, 127. 84, 119.28, 117.46, 116.45, 114.86, 114.32, 109.26, 69.05, 51.11, 49.06, 40.52. HRMS (ESI) m / z: Calcd for C 21 H 16 N2O5(M+H) + 377.11374; Found 377.11264.

[0268] Embodiment 39:

[0269] Preparation of 1-((3,9-dihydroxy-7-oxo-5,7-dihydrobenzo[5,6]oxo-4,3-b]benzofuran-8-yl)methyl)azetidine-3-carboxylic acid (Compound TY039)

[0270] The preparation method is similar to that of Example 7, except that 3-azetidinecarboxylic acid is used instead of 1-ene-7-heptylamine to obtain a brown solid final product. 1 H NMR (600MHz, DMSO-d6) δ7.85 (d, J=8.5Hz, 1H), 7.47 (d, J=8.8Hz, 1H), 7.11 (d, J=2.4Hz, 1H), 7.05 (dd, J=8 .5, 2.4Hz, 1H), 6.88 (d, J=8.8Hz, 1H), 5.19 (s, 2H), 4.12 (s, 2H), 3.62-3.08 (m, 5H). HRMS (ESI) m / z: Calcd for C 21 H 17 NO7(M+H) + 396.10832; Found 396.10945.

[0271] Embodiment 40:

[0272] Preparation of 8-((3-chloroazetidin-1-yl)methyl)-3,9-dihydroxybenzo[5,6]oxazepizo[4,3-b]benzofuran-7(5H)-one (Compound TY040)

[0273] The preparation method is similar to that of Example 1, except that 3-chloroazetidine hydrochloride is used instead of piperidine hydrochloride to obtain a yellow solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.64 (s, 1H), 10.54 (s, 1H), 7.84 (d, J=8.5Hz, 1H), 7.71-7.63 (m, 1H), 7.09 (d, J=2.4Hz, 1H), 7.06 (dd, J=9.1, 1.7Hz, 1H), 7 .03(dd, J=8.5, 2.4Hz, 1H), 5.21(s, 2H), 4.78(2, 2H), 4.73(s, 1H), 4.64( s, 1H), 4.46 (s, 1H), 4.27 (s, 1H), 4.11-3.93 (m, 1H). HRMS (ESI) m / z: Calcd for C 20 H 16 ClNO5(M+H) + 386.07952; Found 386.07861.

[0274] Embodiment 41:

[0275] Preparation of 8-((3-(dimethylamino)azetidin-1-yl)methyl)-3,9-dihydroxybenzo[5,6]oxazepizo[4,3-b]benzofuran-7(5H)-one (Compound TY041)

[0276] The preparation method is similar to that of Example 1, except that N,N-dimethylazetidine-3-amine hydrochloride is used instead of piperidine hydrochloride to obtain a pink solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.67 (s, 1H), 10.55 (s, 1H), 7.88 (d, J = 8.5Hz, 1H), 7.71 (d, J = 8.8Hz, 1H), 7.14-7.10 (m, 2H), 7.08 ( dd, J=8.5, 2.4Hz, 1H), 5.27 (s, 2H), 4.78 (s, 2H), 4.62 (s, 2H), 4.46 (s, 2H), 4.20 (s, 1H), 2.78 (s, 6H). HRMS (ESI) m / z: Calcd for C 22 H 22 N2O5(M+H) + 395.16069; Found 395.15945.

[0277] Embodiment 42:

[0278] Preparation of 3,9-dihydroxy-8-(pyrrolidin-1-ylmethyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY042)

[0279] The preparation method is similar to that of Example 1, except that tetrahydropyrrole is used instead of piperidine to obtain a yellow-white solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.65 (s, 1H), 10.47 (s, 1H), 7.88 (d, J=8.5Hz, 1H), 7.71 (d, J=8.9Hz, 1H), 7.13-7.10 (m, 2H), 7.07 ( dd, J=8.5, 2.4Hz, 1H), 5.25 (s, 2H), 4.71 (d, J=5.6Hz, 2H), 3.49 (s, 2H), 3.34-3.28 (m, 2H), 2.14-2.00 (m, 2H), 1.90 (m, 2H). 13C NMR (151MHz, DMSO-d6) δ166.20, 161.12, 158.91, 154.71, 14801, 137.99, 128.83, 127 .78, 119.38, 117.45, 116.34, 115.02, 114.33, 109.90, 109.41.HRMS (ESI) m / z: Calcd for C 21 H 19 NO5(M+H) + 366.13414; Found 366.13348.

[0280] Embodiment 43:

[0281] Preparation of 8-((2,5-dihydro-1H-pyrrol-1-yl)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY043)

[0282] The preparation method is similar to that of Example 1, except that 3-pyrroline hydrochloride is used instead of piperidine hydrochloride to obtain an off-white solid final product. 1 H NMR (700MHz, DMSO-d6) δ10.58 (s, 2H), 7.88 (d, J = 8.5Hz, 1H), 7.73 (d, J = 8.9Hz, 1H), 7.16-7.11 (m , 2H), 7.08 (dd, J=8.5, 2.4Hz, 1H), 5.97 (s, 2H), 5.26 (s, 2H), 4.84 (s, 2H), 4.22 (d, J=5.5Hz, 4H). 13 C NMR (176MHz, DMSO-d6) δ166.23, 161.13, 158.96, 154.65, 148.05, 137.99, 128.86, 127.77, 125.48, 1 19.38, 117.44, 116.33, 115.09, 114.53, 109.60, 109.45, 69.10, 60.22, 50.95.HRMS (ESI) m / z: Calcd for C 21 H 17 NO5(M+H) + 364.11849; Found 364.11786.

[0283] Embodiment 44:

[0284] Preparation of 3,9-dihydroxy-8-((3-methoxypyrrolidin-1-yl)methyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY044)

[0285] The preparation method is similar to that of Example 38, except that 3-methoxypyrrolidine is used instead of 3-acetonitrilecyclobutylamine hydrochloride to obtain a yellow solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.65 (s, 1H), 10.52 (s, 1H), 7.88 (dd, J=8.5, 1.7Hz, 1H), 7.72 (t, J=8.3Hz, 1H), 7.15-7.05 (m, 2H), 7.08 (dd, J=8.5, 2.5Hz, 1H), 5 .26(s, 2H), 4.76(d, J=5.6Hz, 2H), 4.19-4.10(m, 1H), 3.30(s, 3H), 3.22(s, 2 H), 3.17 (s, 1H), 2.18-2.13 (m, 1H), 2.21-1.92 (m, 2H). HRMS (ESI) m / z: Calcd for C 22 H 21 NO6(M+H) + 396.1450; Found 396.1437.

[0286] Embodiment 45:

[0287] Preparation of 3,9-dihydroxy-8-((2-methylpyrrolidin-1-yl)methyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY045)

[0288] The preparation method is similar to that of Example 7, except that 2-methylpyrrolidine is used instead of 1-ene-7-heptylamine to obtain a red solid final product. 1 H NMR (600MHz, Methanol-d4) δ7.95 (d, J=8.5Hz, 1H), 7.64 (d, J=8.9Hz, 1H), 7.11-7.05 (m, 3 H), 5.28-5.19 (m, 2H), 4.75 (d, J=12.8Hz, 2H), 3.84 (h, J=7.0Hz, 1H), 3.62-3.50 (m, 1H), 3. 46 (ddd, J=11.7, 7.9, 6.2Hz, 1H), 2.42 (dtd, J=13.1, 8.1, 4.9Hz, 1H), 2.23-2.13 (m, 1H), 2. 09-1.97 (m, 1H), 1.80 (dq, J=13.1, 8.3Hz, 1H), 1.45 (d, J=6.6Hz, 3H). HRMS (ESI) m / z: Calcd for C 22 H 22 NO5(M+H) +380.14980; Found 380.15012.

[0289] Embodiment 46:

[0290] Preparation of 3,9-dihydroxy-8-((3-hydroxypyrrolidin-1-yl)methyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY046)

[0291] The preparation method is similar to that of Example 7, except that 3-pyrrolidinol is used instead of 1-ene-7-heptylamine to obtain a light yellow solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.66 (s, 1H), 10.50 (d, J=4.3Hz, 1H), 9.36 (dt, J=142.9, 6.1Hz, 1H), 7.88 (d, J=8.5Hz, 1H), 7.72 (d, J=8.9H z, 1H), 7.23-7.00 (m, 3H), 5.30-5.17 (m, 2H), 4.77 (dd, J=33.9, 5.9Hz, 2H), 4.57-4.32 (m, 1H), 3.70-3.54 (m, 2H), 3.36-3.21 (m, 2H), 2.09-1.73(m,2H).HRMS(ESI)m / z:Calcd for C 21 H 19 NO6(M+H) + 382.1290; Found 382.1277.

[0292] Embodiment 47:

[0293] Preparation of (R)-3,9-dihydroxy-8-((3-hydroxypyrrolidin-1-yl)methyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY047)

[0294] The preparation method is similar to that of Example 7, except that 3R-pyrrolidinol is used instead of 1-ene-7-heptylamine to obtain a light brown solid final product. 1H NMR (600MHz, DMSO-d6) δ10.66 (s, 1H), 10.50 (s, 1H), 9.36 (d, J = 141.7Hz, 1H), 7.88 (d, J = 8.5Hz, 1H), 7.72 (d, J = 8.9Hz, 1H), 7.19-6.98 (m, 3H), 5.26 (d, J = 4.3Hz, 2H), 4.82-4.66 (m, 2H), 4.46 (d, J = 52.9Hz, 1H), 3.73-3.39 (m, 4H), 2.11-1.75 (m, 2H). HRMS (ESI) m / z: Calcd for C 21 H 19 NO6(M+H) + 382.1290; Found 382.1277.

[0295] Embodiment 48:

[0296] Preparation of 8-((3,3-difluoropyrrolidin-1-yl)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY048)

[0297] The preparation method is similar to that of Example 7, except that 3,3-difluoropyrrolidine is used instead of 1-ene-7-heptylamine to obtain a brown solid final product. 1 H NMR (600MHz, Methanol-d4) δ7.96 (d, J=8.4Hz, 1H), 7.66 (d, J=8.9Hz, 1H), 7.18-6.99 (m34H), 5. 25 (s, 2H), 4.90 (s, 2H), 4.11 (t, J = 11.8Hz, 2H), 3.91 (s, 2H), 2.72 (s, 2H). HRMS (ESI) m / z: Calcd for C 21 H 18 F2NO5(M+H) + 402.11531; Found 402.11441.

[0298] Embodiment 49:

[0299] Preparation of 8-((3,6-dihydropyridin-1(2H)-yl)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY049)

[0300] The preparation method is similar to that of Example 1, except that 1,2,3,6-tetrahydropyridine hydrochloride is used instead of piperidine hydrochloride to obtain a brown solid final product. 1H NMR (600MHz, DMSO-d6) δ10.50 (s, 1H), 9.13 (s, 1H), 7.88 (d, J = 8.5Hz, 1H), 7.73 (d, J = 8.9Hz, 1H), 7.15-7.10 (m, 2H), 7.07 (dd, J = 8.5, 2.4Hz, 1H), 5.92 (d, J=10.4Hz, 1H), 5.73 (d, J=10.4Hz, 1H), 5.25 (s, 2H), 4.76 (d, J=38.0Hz, 2H), 3.78 (d, J=20.8Hz, 4H), 2.41 (s, 2H). 13 C NMR (151MHz, DMSO-d6) δ166.36, 161.19, 158.99, 155.21, 148.11, 138.02, 128.91, 128.24, 125.51, 120.93, 119.46, 117.52, 116.38, 115.02, 114.65, 109.70, 108.73, 69.16, 50.95, 50.17, 22.38. HRMS (ESI) m / z: Calcd for C 22 H 19 NO5(M+H) + 378.13414; Found 378.13324.

[0301] Embodiment 50:

[0302] Preparation of 3,9-dihydroxy-8-(morpholinomethyl)[5,6]oxazepam[4,3-b]benzofuran-7(5H)-one (Compound TY050)

[0303] The preparation method is similar to that of Example 1, except that morpholine is used instead of piperidine to obtain a pink solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.69 (s, 1H), 10.50 (s, 1H), 7.88 (d, J = 8.5Hz, 1H), 7.73 (d, J = 8.4Hz, 1H), 7.13 (d, J = 2.5Hz, 1H ), 7.11 (d, J=8.9Hz, 1H), 7.08 (dd, J=8.5, 2.4Hz, 1H), 5.26 (s, 2H), 4.70 (s, 2H), 3.98 (s, 2H), 3.70 (s, 2H), 3.48 (s, 4H). 13C NMR (151MHz, DMSO-d6) δ166.31, 161.21, 159.18, 155.80, 148.58, 138.81, 129.75, 127.96, 121.34, 117.54, 116.43, 115.58, 114.49, 109.74, 108.37, 69.11, 63.88, 52.40, 49.13.HRMS (ESI) m / z: Calcd for C 21 H 19 NO6(M+H) + 382.12906; Found 382.12787.

[0304] Embodiment 51:

[0305] Preparation of 3,9-dihydroxy-8-(piperazin-1-ylmethyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY051)

[0306] The preparation method is similar to that of Example 1, except that piperazine is used instead of piperidine to obtain a light brick red solid final product. 1 H NMR (600MHz, DMSO-d6) δ9.09 (s, 2H), 7.88 (d, J = 8.5Hz, 1H), 7.71 (d, J = 8.9Hz, 1H) ,7.16-7.06(m,3H),5.25(s,2H),4.66(s,2H),3.37(s,8H).HRMS(ESI)m / z:Calcd for C 21 H 20 N2O5(M+H) + 381.14504; Found 381.14407.

[0307] Embodiment 52:

[0308] Preparation of 3,9-dihydroxy-8-((4-methylpiperazin-1-yl)methyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY052)

[0309] The preparation method is similar to that of Example 1, except that 4-methylpiperazine is used instead of piperidine to obtain a yellow solid final product.

[0310] 1H NMR (600MHz, DMSO-d6) δ10.60 (s, 1H), 9.77 (s, 1H), 7.88 (d, J = 8.5Hz, 1H), 7.69 (s, 1H), 7.13 (d, J = 2.4Hz, 1 H), 7.08 (dd, J=8.5, 2.4Hz, 2H), 5.25 (s, 2H), 4.56 (s, 2H), 3.61 (s, 8H), 2.86 (s, 3H). HRMS (ESI) m / z: Calcd for C 22 H 22 N2O5(M+H) + 395.16069; Found 395.15970.

[0311] Embodiment 53:

[0312] Preparation of 3,9-dihydroxy-8-((4-(3-propionylphenyl)-3,6-dihydropyridin-1(2H)-yl)methyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY053)

[0313] The preparation method is similar to that of Example 38, except that 4-(3-propionylphenyl)-1,2,3,6-tetrahydropyridine hydrochloride is used instead of 3-acetonitrile cyclobutylamine hydrochloride to obtain a yellow solid final product. 1 H NMR (400MHz, DMSO-d6) δ10.82 (s, 1H), 10.46 (s, 1H), 7.97 (t, J=1.8Hz, 1H), 7. 85(d, J=8.3Hz, 2H), 7.74-7.63(m, 1H), 7.50-7.47(m, 2H), 7.12-7.00(m, 2H), 6 .91(d, J=8.8Hz, 1H), 6.28(t, J=4.0Hz, 1H), 5.08(s, 2H), 4.10(s, 2H), 3.14(s , 2H), 3.08 (q, J=7.2Hz, 2H), 2.71 (t, J=5.6Hz, 2H), 2.54 (s, 2H), 1.08 (t, J=7.1 Hz, 3H).HRMS(ESI)m / z: Calcd for C 31 H 27 NO6(M+H) + 510.19166; Found 510.18945.

[0314] Embodiment 54:

[0315] Preparation of 8-((4-(3-fluorophenyl)-3,6-dihydropyridin-1(2H)-yl)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY054)

[0316] The preparation method is similar to Example 38, except that 4-(3-fluorophenyl)-1,2,3,6-tetrahydropyridine hydrochloride is used instead of 3-acetonitrile cyclobutylamine hydrochloride to obtain a yellow solid final product. 1 H NMR (400MHz, DMSO-d6) δ10.75 (s, 1H), 10.49 (s, 1H), 7.84 (d, J=8.4Hz, 1H), 7 .47(d, J=8.8Hz, 1H), 7.37(td, J=7.9, 6.3Hz, 1H), 7.32-7.21(m, 2H), 7.09-7 .02(m, 3H), 6.90(d, J=8.8Hz, 1H), 6.25(t, J=6.0Hz, 1H), 5.07(s, 2H), 4.07( s, 2H), 3.11 (s, 2H), 2.66 (t, J=6.0Hz, 2H), 2.48 (s, 2H). HRMS (ESI) m / z: Calcd for C 28 H 22 FNO5(M+H) + 472.15602; Found 472.15329.

[0317] Embodiment 55:

[0318] Preparation of 8-(1-nitrohexylmethyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY055)

[0319] The preparation method is similar to that of Example 1, except that cycloheximide is used instead of piperidine to obtain a gray-black oily final product. 1 H NMR (600MHz, DMSO-d6) δ10.67 (s, 1H), 10.53 (s, 1H), 7.88 (d, J = 8.5Hz, 1H), 7.73 (d, J = 8.9Hz, 1H), 7.12 (dd, J = 6.8, 2.2Hz, 2H), 7.08 (dd, J =8.5, 2.4Hz, 1H), 5.26 (s, 2H), 4.75 (s, 2H), 3.38 (s, 2H), 3.28 (q, J = 14.1, 10.8Hz, 2H), 1.99-1.86 (m, 2H), 1.85-1.70 (m, 2H), 1.62 (s, 4H). 13C NMR (151MHz, DMSO-d6) δ166.44, 161.16, 159.06, 155.12, 148.06, 137.97, 128.88, 127.90, 119.35, 117.47, 116.3 3, 114.99, 114.19, 109.43, 109.16, 69.15, 51.76, 49.07, 46.17, 44.61, 26.86, 22.82, 8.75. HRMS (ESI) m / z: Calcd for C 23 H 23 NO5(M+H) + 394.16544; Found 394.16473.

[0320] Embodiment 56:

[0321] Preparation of 8-((hexahydrocyclopenta[c]pyrrol-2(1H)-yl)methyl)-3,9-dihydroxybenzo[5,6]oxazepine[4,3-b]benzofuran-7(5H)-one (Compound TY056)

[0322] The preparation method is similar to Example 38, except that 3-azabicyclo[3.3.0]octane hydrochloride is used instead of 3-acetonitrilecyclobutylamine hydrochloride to obtain the final product as a yellow-white solid. 1 H NMR (600MHz, DMSO-d6) δ10.63 (d, J=11.1Hz, 1H), 10.41 (d, J=66.0Hz, 1H), 7.93-7.83 (m, 1H), 7.70 (d, J=8.9Hz, 1H), 7.17- 7.00 (m, 3H), 5.29 (s, 2H), 4.74 (d, J=5.0Hz, 2H), 3.65 (s, 2H), 2.91-2.67 (m, 4H), 1.83-1.53 ​​(m, 6H). HRMS (ESI) m / z: Calcd for C24H23NO5(M+H) + 406.1658; Found 406.1642.

[0323] Embodiment 57:

[0324] Preparation of 8-(azetidin-1-ylmethyl)-3,9-dihydroxy-11-methylbenzo[5,6]oxazepizo[4,3-b]benzofuran-7(5H)-one (Compound TY057)

[0325] The preparation method is similar to that of Example 1, except that azetidine is used instead of piperidine, and 2-methyl-1,4-benzoquinone is used instead of benzoquinone to obtain a yellow-white solid final product. 1H NMR (600MHz, DMSO-d6) δ10.56 (s, 1H), 9.59 (s, 1H), 7.85 (d, J=8.5Hz, 1H), 7.09-7.05 (m, 2H), 6.91 (s, 1H), 5. 23 (s, 2H), 4.63 (s, 2H), 4.14 (s, 2H), 4.04-3.79 (m, 2H), 2.34 (s, 3H), 2.31-2.16 (m, 2H). HRMS (ESI) m / z: Calcd for C 21 H 19 NO5(M+H) + 366.13414; Found 366.13272.

[0326] Embodiment 58:

[0327] Preparation of 8-(azetidin-1-ylmethyl)-11-ethyl-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (TY058)

[0328] The preparation method is similar to that of Example 1, except that azetidine is used instead of piperidine, and 2-ethyl-1,4-benzoquinone is used instead of benzoquinone to obtain a light yellow solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.67 (s, 1H), 10.35 (s, 1H), 7.91 (d, J = 8.5Hz, 1H), 7.12 (d, J = 2.4Hz, 1H), 7.09 (dd, J = 8.5, 2.4Hz, 1H), 6.94 (s, 1H), 5.24 (s, 2H), 4.64 (s, 2H), 4.30-4.24 (m, 2H), 4.10-4.04 (m, 2H), 2.90 (q, J=7.6Hz, 2H), 2.45-2.24 (m, 2H), 1.30 (t, J=7.6Hz, 3H). HRMS (ESI) m / z: Calcd for C22H21NO5(M+H) + 380.14979; Found 380.14859.

[0329] Embodiment 59:

[0330] Preparation of 8-(azetidin-1-ylmethyl)-3,9-dihydroxy-11-isopropylbenzo[5,6]oxazepizo[4,3-b]benzofuran-7(5H)-one (Compound TY059)

[0331] The preparation method is similar to that of Example 1, except that azetidine is used instead of piperidine, and 2-isopropyl-1,4-benzoquinone is used instead of benzoquinone to obtain a yellow solid final product.1 H NMR (600MHz, DMSO-d6) δ7.90 (d, J=8.4Hz, 1H), 7.17-7.06 (m, 2H), 6.98 (s, 1H), 5.27 (s, 2H), 4.64 (s, 2H), 4.12 (s, 3H), 3.42 (h, J=7.0Hz, 1H), 2.33 (p, J=8.1Hz, 2H), 1.35 (d, J=6.9Hz, 6H), 1.30-1.17 (m, 1H)..HRMS (ESI) m / z: Calcd for C 23 H 22 NO5(MH) - 392.14980; Found 392.15042.

[0332] Embodiment 60:

[0333] Preparation of 8-(azetidin-1-ylmethyl)-11-(tert-butyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY060)

[0334] The preparation method is similar to that of Example 1, except that azacyclotidine is used instead of piperidine, and 2-tert-butyl-1,4-benzoquinone is used instead of p-benzoquinone to obtain a light yellow solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.64 (s, 1H), 10.29 (s, 1H), 7.87 (d, J=9.1Hz, 1H), 7.13 (d, J=7.1Hz, 2H), 7.02 (s, 1H), 5.26 (s, 2H), 4.63 (s, 2H), 4.29 (p, J=9.1Hz, 2H), 4.09 (d, J=4.5Hz, 2H), 2.44-2.26 (m, 2H), 1.49 (s, 9H). 13 C NMR (176MHz, DMSO-d6) δ166.16, 161.09, 157.84, 154.49, 146.10, 137.95, 137.07, 128.56, 128.09, 119.41 , 117.64, 116.03, 112.08, 109.03, 107.33, 69.01, 55.53, 50.22, 34.62, 29.89, 16.49.HRMS (ESI) m / z: Calcd for C 24 H 25 NO5(M+H) + 408.18109; Found 408.18042.

[0335] Embodiment 61:

[0336] Preparation of 8-(azetidin-1-ylmethyl)-11-cyclopropyl-3,9-dihydroxybenzo[5,6]oxazepizo[4,3-b]benzofuran-7(5H)-one (Compound TY061)

[0337] The preparation method is similar to that of Example 1, except that azetidine is used instead of piperidine, and 2-cyclopropane-1,4-benzoquinone is used instead of benzoquinone to obtain a light yellow solid final product. 1 H NMR (600MHz, DMSO-d6) δ7.92 (d, J=8.5Hz, 1H), 7.12 (d, J=2.5Hz, 1H), 7.09 (dd, J=8.5, 2.5Hz, 1H), 6.64 (s, 1H), 5.2 5(s, 2H), 4.59(s, 2H), 4.09(s, 4H), 2.42-2.24(m, 3H), 1.15-1.09(m, 2H), 0.92-0.87(m, 2H).HRMS(ESI)m / z: Calcd for C 23 H 21 NO5(M+H) + 392.14979; Found 392.14816.

[0338] Embodiment 62:

[0339] Preparation of 8-(azetidin-1-ylmethyl)-11-cyclohexyl-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY062)

[0340] The preparation method is similar to that of Example 1, except that azetidine is used instead of piperidine, and 2-cyclohexyl-1,4-benzoquinone is used instead of benzoquinone to obtain a gray solid final product. 1H NMR (600MHz, DMSO-d6) δ10.64 (s, 1H), 10.30 (s, 1H), 7.90 (d, J=8.3Hz, 1H), 7.13-7.09 (m, 2H), 6.9 4(s, 1H), 5.24(s, 2H), 4.63(s, 2H), 4.37-4.19(m, 2H), 4.15-4.01(m, 2H), 3.07(tt, J=11.9, 3.4Hz , 1H), 2.44-2.35 (m, 1H), 2.33 (dt, J=10.2, 4.9Hz, 1H), 1.97-1.89 (m, 2H), 1.85 (dt, J=13.1, 3.3Hz , 2H), 1.77 (dt, J=13.0, 3.3Hz, 1H), 1.56 (qd, J=12.5, 3.2Hz, 2H), 1.52-1.42 (m, 2H), 1.32 (m, 1H). 13 C NMR (151MHz, DMSO-d6) δ165.09, 160.00, 157.12, 153.74, 144.85, 136.82, 132.80, 127.70, 126.39, 118.39, 116.45, 115. 29, 111.25, 108.27, 106.06, 68.92, 54.17, 49.56, 47.99, 39.42, 37.54, 31.71, 25.58, 25.04, 15.42.HRMS (ESI) m / z: Calcd for C 26 H 27 NO5(M+H) + 434.19674; Found 434.19577.

[0341] Embodiment 63:

[0342] Preparation of 11-bromo-3,9-dihydroxy-8-(azetidin-1-ylmethyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY063)

[0343] The preparation method is as follows: Example 1, except that the steps after ethyl 3-[4-methoxy-2-(methoxymethyl)phenyl]-3-oxopropionate are:

[0344] Under nitrogen, ethyl 3-[4-methoxy-2-(methoxymethyl)phenyl]-3-oxopropanoate (1.0 eq), 2-bromo-1,4-p-benzoquinone (1.0 eq), and trifluoromethanesulfonate (0.1 eq) were dissolved in ultra-dry dichloromethane and reacted overnight at 55°C. After completion of the reaction as monitored by TLC, saturated aqueous ammonium chloride was added to quench the reaction. The mixture was extracted with ethyl acetate, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified on a silica gel column to obtain ethyl 7-bromo-5-hydroxy-2-[4-methoxy-2-(methoxymethyl)phenyl]-1-benzofuran-3-carboxylate.

[0345] Ethyl 7-bromo-5-hydroxy-2-[4-methoxy-2-(methoxymethyl)phenyl]-1-benzofuran-3-carboxylate (1.0 eq) and p-toluenesulfonic acid monohydrate (0.8 eq) were added to a reaction flask. The mixture was degassed under vacuum and toluene was added under continuous nitrogen protection. The reaction was allowed to proceed overnight at 100°C. After TLC monitoring of the reaction completion, the solid was filtered, washed, and dried to obtain 11-bromo-9-hydroxy-3-methoxybenzo[5,6]oxazepam[4,3-b]benzofuran-7(5H)-one.

[0346] Under nitrogen protection and at -20°C, BBr3 (4.0eq, 1M in DCM) was added dropwise to ultra-dry dichloromethane containing 9-hydroxy-3-methoxybenzo[5,6]oxazo[4,3-b]benzofuran-7(5H)-one (1.0eq) and allowed to react overnight at room temperature. After TLC monitoring, the reaction was completed, quenched with methanol, and concentrated under reduced pressure to obtain a crude intermediate product. The crude intermediate product was dissolved in ethanol, N,N-diisopropylethylamine was added to adjust the pH to a weak base, and then formaldehyde (4.0eq) and azetidine (3.0eq) were added and reacted at 80°C for about 4h. After TLC monitoring, the reaction was completed, concentrated under reduced pressure, and purified by C18 column chromatography to obtain a yellow solid final product. 1 H NMR (600MHz, Methanol-d4) δ7.99 (d, J=8.5Hz, 1H), 7.26 (s, 1H), 7.16-7.07 (m, 2H), 5.26 (s, 2H) , 4.73 (s, 2H), 4.46 (q, J=9.7Hz, 2H), 4.31-4.16 (m, 2H), 2.66-2.45 (m, 2H). HRMS (ESI) m / z: Calcd for C 20 H 16 BrNO5(M+H) + 430.0283; Found 430.0288.

[0347] Example 64:

[0348] Preparation of 1-(tert-butyl)-3,9-dihydroxy-8-(pyrrolidin-1-ylmethyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY064)

[0349] The preparation method is similar to that of Example 1, except that tetrahydropyrrole is used instead of piperidine, and 2-tert-butyl-1,4-benzoquinone is used instead of benzoquinone to obtain a light yellow solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.67 (s, 1H), 10.36 (s, 1H), 7.96-7.82 (m, 1H), 7.16-7.10 (m, 2H), 7.05 (s, 1H), 5.27 (s, 2H), 4.65 (d, J= 5.6Hz, 2H), 3.48 (s, 2H), 3.31-3.26 (m, 2H), 2.06 (dtt, J=11.5, 7.4, 4.4Hz, 2H), 1.90 (tdt, J=10.4, 7.3, 4.3Hz, 2H), 1.49 (s, 9H). 13 C NMR (151MHz, DMSO-d6) δ166.31, 161.17, 158.00, 154.59, 146.21, 138.03, 137.28, 128.67, 128.24, 119.52, 11 7.72, 116.41, 112.27, 109.24, 107.70, 69.10, 54.32, 50.08, 40.57, 34.71, 29.95, 23.05. HRMS (ESI) m / z: Calcd for C25H27NO5(M+H) + 422.19674; Found 422.19550.

[0350] Embodiment 65:

[0351] Preparation of 11-bromo-3,9-dihydroxy-8-(pyrrolidin-1-ylmethyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY065)

[0352] The preparation method is similar to Example 63, except that pyrrolidine is used instead of azetidine to obtain a yellow solid final product. 1H NMR (600MHz, DMSO-d6) δ10.80 (s, 1H), 10.70 (s, 1H), 7.88 (d, J=8.5Hz, 1H), 7.31 (s, 1H), 7.15-7.09 (m, 2H), 5.28 (s, 2H), 4.69 (d, J=5.5Hz, 2H), 2.07 (s, 3H), 1.90 (d, J= 6.7Hz, 3H), 1.29-1.21(m, 3H).HRMS(ESI)m / z: Calcd for C 21 H 18 BrNO5(M+H) + 444.0436; Found 444.0448.

[0353] Embodiment 66:

[0354] Preparation of 3,9-dihydroxy-11-isopropyl-8-(pyrrolidin-1-ylmethyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY066)

[0355] The preparation method is similar to that of Example 1, except that pyrrolidine is used instead of piperidine, and 2-isopropyl-1,4-benzoquinone is used instead of benzoquinone to obtain a yellow solid final product. 1 H NMR (600MHz, Methanol-d4) δ7.94 (d, J=8.5Hz, 1H), 7.09 (dd, J=8.5, 2.4Hz, 1H), 7.06 (d, J=2.4Hz, 1H), 6.97 (d, J=0.6Hz, 1H), 5.23 (s, 2H), 4.72 (s, 2H), 3. 61(d, J=11.5Hz, 2H), 3.55-3.48(m, 1H), 3.48-3.38(m, 2H), 3.35(s, 2H), 2.28 -2.16 (m, 2H), 2.12-1.96 (m, 2H), 1.42 (d, J = 7.0Hz, 6H). HRMS (ESI) m / z: Calcd for C 24 H 26 NO5(M+H) + 408.18110; Found 408.18005.

[0356] Embodiment 67:

[0357] Preparation of 9-hydroxy-8-(piperidin-1-ylmethyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY067)

[0358] The preparation method is similar to that of Example 1, except that 2-bromobenzaldehyde is used instead of 2-bromo-5-hydroxybenzaldehyde to obtain a yellow oily final product. 1 H NMR (600MHz, DMSO-d6) δ10.60 (s, 1H), 8.05 (dd, J=7.5, 1.5Hz, 1H), 7.79 (ddd, J=14.1, 8.1, 1.4Hz, 2H), 7.75-7.65 (m, 2H), 7.22-7. 14 (m, 1H), 5.37 (s, 2H), 4.66 (s, 2H), 3.43-3.33 (m, 2H), 3.13 (s, 2H), 1.85 (d, J=14.0Hz, 2H), 1.74-1.60 (m, 3H), 1.53-1.37 (m, 1H). 13 C NMR (151MHz, DMSO-d6) δ165.38, 157.15, 154.72, 147.87, 135.14, 131.40, 130.04, 129.09, 127.92, 127.36, 126.14, 115.27, 114.24, 111.56, 108.38, 68.50, 51.39, 22.33, 21.01.HRMS (ESI) m / z: Calcd for C 22 H 21 NO4(M+H) + 364.15488; Found 364.15256.

[0359] Embodiment 68:

[0360] Preparation of 3-fluoro-9-hydroxy-8-(piperidin-1-ylmethyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY068)

[0361] The preparation method is similar to that of Example 1, except that 2-bromo-5-fluorobenzaldehyde is used instead of 2-bromo-5-hydroxybenzaldehyde to obtain a yellow solid final product. 1 H NMR (600MHz, Methanol-d4) δ8.09 (dd, J=8.7, 5.3Hz, 1H), 7.60 (d, J=8.9Hz, 1H), 7.47 (dd, J=8.6, 2.6Hz, 1H), 7.42 (td, J=8.6, 2 .6Hz, 1H), 7.06 (d, J=8.9Hz, 1H), 5.28 (s, 2H), 4.55 (s, 2H), 3.25-3.15 (m, 4H), 1.82-1.78 (m, J=5.8Hz, 4H), 1.68-1.60 (m, 2H). 13C NMR (151MHz, Methanol-d4) δ166.45, 164.99, 163.32, 157.40, 155.37, 148.75, 137.86, 137.8 0, 128.86, 128.80, 126.96, 124.99, 124.97, 117.00, 116.85, 115.91, 115.75, 115.21, 113.51, 110.71, 109.18, 68.27, 68.26, 53.12, 23.46, 22.00, 21.80.HRMS(ESI)m / z: Calcd for C 22 H 20 FNO4(M+H) + 382.14546; Found 382.14456.

[0362] Embodiment 69:

[0363] Preparation of 9-hydroxy-3-methyl-8-(piperidin-1-ylmethyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY069)

[0364] The preparation method is similar to that of Example 1, except that 2-bromo-5-methylbenzaldehyde is used instead of 2-bromo-5-hydroxybenzaldehyde to obtain a yellow solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.50 (s, 1H), 7.93 (d, J = 7.9Hz, 1H), 7.77 (d, J = 8.9Hz, 1H), 7.58 (s, 1H), 7.53 (d, J = 8.0Hz, 1H), 7.15 (d, J = 8.9Hz, 1H), 5.31 (s , 2H), 4.64 (s, 2H), 3.12-3.08 (m, 2H), 3.02-3.00 (m, 2H), 2.45 (s, 3H), 1.8 5-1.83 (m, 2H), 1.75-1.59 (m, 4H), 1.57-1.39 (m, 2H). HRMS (ESI) m / z: Calcd for C23H23NO4(M+H) + 378.17053; Found 378.16940.

[0365] Embodiment 70:

[0366] Preparation of 4,9-dihydroxy-8-(piperidin-1-ylmethyl)benzo[5,6]oxazepa[4,3-b]benzofuran-7(5H)-one (Compound TY070)

[0367] The preparation method is similar to that of Example 1, except that 2-bromo-6-hydroxybenzaldehyde is used instead of 2-bromo-5-hydroxybenzaldehyde to obtain a gray solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.77 (s, 1H), 10.29 (s, 1H), 7.59 (d, J = 8.9Hz, 1H), 7.40 (t, J = 7.9Hz, 1H), 7.16 (d, J = 8.7Hz, 1H), 7.07 (d, J=9.1Hz, 1H), 6.93 (d, J=8.7Hz, 1H), 4.52 (s, 2H), 4.00 (s, 2H), 1.85 (d, J=13.8Hz, 3H), 1.67 (s, 8H). HRMS (ESI) m / z: Calcd for C 22 H 21 NO5(M+H) + 380.14979; Found 380.14902.

[0368] Embodiment 71:

[0369] Preparation of 3,9-dihydroxy-8-(piperidin-1-ylmethyl)-5,6-dihydro-7H-benzo[c]benzofuro[2,3-e]azepin-7-one (Compound TY071)

[0370] The preparation method is similar to Example 1, except that the steps after the synthesis of 9-hydroxy-3-methoxybenzo[5,6]oxazepine[4,3-b]benzofuran-7(5H)-one are as follows:

[0371] 9-Hydroxy-3-methoxybenzo[5,6]oxazepine[4,3-b]benzofuran-7(5H)-one (1.0 eq) and sodium hydroxide (4.0 eq) were added to methanol and reacted at 60°C overnight. After the reaction was completed as monitored by TLC, the mixture was concentrated under reduced pressure to remove methanol. The pH was adjusted to acidic with hydrochloric acid to precipitate a solid, which was filtered to obtain 5-hydroxy-2-[2-(hydroxymethyl)-4-methoxyphenyl]-1-benzofuran-3-carboxylic acid.

[0372] 5-Hydroxy-2-[2-(hydroxymethyl)-4-methoxyphenyl]-1-benzofuran-3-carboxylic acid (1.0 eq) and pyridinium chlorochromate (1.2 eq) were added to ultra-dry dichloromethane and reacted overnight at room temperature. The reaction was monitored to be complete by TLC. The product was directly concentrated under reduced pressure and purified by C18 column chromatography to obtain 2-(2-formyl-4-methoxyphenyl)-5-hydroxy-1-benzofuran-3-carboxylic acid.

[0373] 2-(2-Formyl-4-methoxyphenyl)-5-hydroxy-1-benzofuran-3-carboxylic acid (1.0 eq) and urea (8.0 eq) were added to a reaction flask, and the mixture was dehydrated and degased while maintaining nitrogen protection. Ethylene glycol and formic acid (6.0 eq) were added, and the mixture was reacted at 150° C. for 3 h. The reaction was monitored to be complete by TLC. Water was added to quench the reaction, and the solid was filtered to obtain a solid. The solid was purified by silica gel column chromatography to obtain 9-hydroxy-3-methoxy-5,6-dihydro-7H-benzo[c]benzofuran[2,3-e]azepin-7-one;

[0374] 9-Hydroxy-3-methoxy-5,6-dihydro-7H-benzo[c]benzofuran[2,3-e]azepin-7-one (1.0 eq), 37% formaldehyde solution (3.0 eq), and piperidine (3.0 eq) were dissolved in ethanol and reacted at 80°C overnight. After the reaction was completed under TLC monitoring (DCM:MeOH=1:1), the mixture was concentrated under reduced pressure to remove ethanol and purified by C18 column chromatography to obtain 9-hydroxy-3-methoxy-8-(piperidin-1-ylmethyl)-5,6-dihydro-7H-benzo[c]benzofuran[2,3-e]azepin-7-one.

[0375] To a solution of 9-hydroxy-3-methoxy-8-(piperidin-1-ylmethyl)-5,6-dihydro-7H-benzo[c]benzofuran[2,3-e]azepin-7-one (1.0 eq) in ultra-dry dichloromethane was added dropwise boron tribromide (4.0 eq, 1 M in DCM) under nitrogen atmosphere at -20°C. After the addition was complete, the mixture was allowed to react overnight at room temperature. The reaction was monitored for completion by TLC. The reaction was quenched by ethanol and the mixture was concentrated under reduced pressure. The final product was purified by C18 column chromatography to obtain a yellow solid. 1 H NMR (600MHz, DMSO-d6) δ10.35 (s, 1H), 10.23 (s, 1H), 7.79 (d, J=8.5Hz, 1H), 7 .67 (d, J=8.8Hz, 1H), 7.06 (d, J=8.9Hz, 1H), 6.97 (dd, J=8.5, 2.4Hz, 1H), 6.9 2 (d, J=2.4Hz, 1H), 4.49 (s, 2H), 4.15 (d, J=6.0Hz, 2H), 3.20-3.06 (m, 2H), 3. 02-3.00(m,2H),1.66-1.62(m,4H),1.57-1.53(m,2H).HRMS(ESI)m / z: Calcd for C 22 H 22 N2O4(M+H) + 379.16578; Found 379.16394.

[0376] Embodiment 72:

[0377] Preparation of 3,9-dihydroxy-8-((4-hydroxypiperidin-1-yl)methyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY072)

[0378] The preparation method is similar to that of Example 1, except that 4-hydroxypiperidine is used instead of piperidine to obtain a yellow-brown solid final product. 1 H NMR (600MHz, Methanol-d4) δ7.95 (d, J=8.4Hz, 1H), 7.64 (dd, J=8.9, 1.2Hz, 1H), 7.08 (t, J=2.3Hz, 1H), 7.07-7.04 (m, 2H), 5.24 (s, 2H), 4.69 (s, 2H), 3.6 3(d, J=9.6Hz, 1H), 3.50(d, J=9.4Hz, 1H), 3.44(s, 1H), 3.34(s, 2H), 2.18(d , J=14.1Hz, 1H), 2.06-1.91 (m, 2H), 1.80-1.66 (m, 1H).HRMS (ESI) m / z: Calcd for C22H21NO6(M+H) + 396.14471; Found 396.14447.

[0379] Embodiment 73:

[0380] Preparation of 3,9-dihydroxy-8-((4-methylpiperidin-1-yl)methyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY073)

[0381] The preparation method is similar to that of Example 1, except that 4-methylpiperidine is used instead of piperidine to obtain a white solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.61 (s, 1H), 10.34 (s, 1H), 7.88 (d, J = 8.5Hz, 1H), 7.73 (dd, J = 8.9, 4.0Hz, 1H), 7.11 (d, J = 11.3Hz, 2H), 7.08 ( dd, J=8.5, 2.4Hz, 1H), 5.27 (s, 2H), 4.63 (d, J=5.2Hz, 2H), 3.16 (s, 3H), 1.79 (d, J=10.0Hz, 4H), 1.39 (d, J=13.1Hz, 2H), 0.89 (d, J=6.5 Hz, 3H). 13C NMR (151MHz, DMSO-d6) δ166.49, 161.16, 159.01, 155.11, 148.08, 137.54, 128.88, 128.34, 119.47, 117.53, 11 6.39, 115.02, 114.56, 109.79, 108.45, 69.17, 52.55, 49.13, 44.67, 31.52, 28.39, 21.63.HRMS (ESI) m / z: Calcd for C 23 H 23 NO5(M+H) + 394.16544; Found 394.16510.

[0382] Embodiment 74:

[0383] Preparation of 1-((3,9-dihydroxy-7-oxo-5,7-dihydrobenzo[5,6]oxo-4,3-b]benzofuran-8-yl)methyl)piperidine-4-carboxylic acid (Compound TY074)

[0384] The preparation method is similar to that of Example 7, except that 4-piperidinic acid is used instead of 1-ene-7-heptylamine to obtain a light grey solid final product. 1 H NMR (600MHz, DMSO-d6) δ7.84 (d, J=8.5Hz, 1H), 7.44 (d, J=8.8Hz, 1H), 7.11 (d, J=2.4Hz, 1H), 7.05 (dd, J=8.5, 2.4Hz, 1H), 6.87 (d, J=8. 8Hz, 1H), 5.15 (s, 2H), 3.88 (s, 2H), 2.84-2.73 (s, 1H), 2.11 (s, 2H), 2.11 (s, 2H), 1.82-1.77 (m, 2H), 1.53 (s, 2H). HRMS (ESI) m / z: Calcd for C 23 H 21 NO7(M+H) + 424.13962; Found 424.13602.

[0385] Embodiment 75:

[0386] Preparation of 8-((4,4-difluoropiperidin-1-yl)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY075)

[0387] The preparation method is similar to that of Example 7, except that 4,4-difluoropiperidine is used instead of 1-ene-7-heptylamine to obtain a milky white solid final product. 1H NMR (600MHz, DMSO-d6) δ10.67 (s, 1H), 10.53 (s, 1H), 7.88 (d, J=8.5Hz, 1H), 7.74 (d, J=8.9Hz, 1H), 7.14-7.10 (m, 2H) , 7.08 (dd, J=8.5, 2.4Hz, 1H), 5.26 (s, 2H), 4.74 (s, 2H), 3.53-3.42 (m, 4H), 2.42-2.35 (m, 4H). HRMS (ESI) m / z: Calcd for C 22 H 19 F2NO5(M+H) + 416.13095; Found 416.13031.

[0388] Embodiment 76:

[0389] Preparation of 1-((3,9-dihydroxy-7-oxo-5,7-dihydrobenzo[5,6]oxazepin[4,3-b]benzofuran-8-yl)methyl)piperidine-4-carbonitrile (Compound TY076)

[0390] The preparation method is similar to that of Example 7, except that 4-cyanopiperidine is used instead of 1-ene-7-heptylamine to obtain a brown solid final product. 1 H NMR (600MHz, DMSO-d6) δ7.88 (d, J=8.5Hz, 1H), 7.73 (d, J=8.9Hz, 1H), 7.14-7.10 (m, 2H), 7.08 (dd, J=8.5, 2.4Hz, 1H), 5.26 (s, 2H), 4.78-4.5 9 (m, 2H), 3.10 (qd, J=7.3, 4.6Hz, 2H), 2.37-2.15 (m, 2H), 2.12-2.03 (m, 1H), 2.02-1.92 (m, 2H), 1.18 (t, J=7.3Hz, 2H). HRMS (ESI) m / z: Calcd for C 23 H 21 N2O5(M+H) + 405.14505; Found 405.14371.

[0391] Embodiment 77:

[0392] Preparation of 8-((3,5-dimethylpiperidin-1-yl)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY077)

[0393] The preparation method is similar to that of Example 7, except that 3,5-dimethoxypiperidine is used instead of 1-ene-7-heptylamine to obtain a brown solid final product. 1 H NMR (600MHz, DMSO-d6) δ7.84 (dd, J=8.5, 5.9Hz, 1H), 7.45 (t, J=9.0Hz, 1H), 7.09 (d, J=2.5Hz, 1H), 7.04 (dd, J=8.5, 2.4Hz, 1H), 6.85 (dd, J=8.8, 5.8H z, 1H), 5.15 (d, J=7.9Hz, 2H), 3.94 (s, 2H), 3.17 (s, 1H), 2.75 (s, 2H), 1.71 -1.53(m, 4H), 0.95-0.73(m, 7H), 0.59-0.48(m, 1H).HRMS(ESI)m / z: Calcd for C 24 H 25 NO5(M+H) + 408.1803; Found 408.1808.

[0394] Embodiment 78:

[0395] Preparation of 3,9-dihydroxy-8-((4-methoxypiperidin-1-yl)methyl)benzo[5,6]oxazepa[4,3-b]benzofuran-7(5H)-one (Compound TY078)

[0396] The preparation method is similar to that of Example 7, except that 4-methoxypiperidine is used instead of 1-ene-7-heptylamine to obtain a brown solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.51 (d, J=14.0Hz, 1H), 8.73 (s, 1H), 7.88 (d, J=8.5Hz, 1H), 7.73 ( d, J=8.8Hz, 1H), 7.14-7.10 (m, 2H), 7.08 (dd, J=8.5, 2.4Hz, 1H), 5.25 (s, 2H), 4.66 (d, J=4.7 Hz, 2H), 3.44 (tq, J=7.3, 3.6Hz, 2H), 3.25 (s, 3H), 2.96 (tdd, J=9.3, 6.6, 3.1Hz, 1H), 2.22- 2.13 (m, 1H), 2.00 (d, J=16.4Hz, 1H), 1.95-1.81 (m, 2H), 1.63 (dtd, J=15.6, 7.9, 4.0Hz, 2H). 13C NMR (151MHz, DMSO) δ165.9, 165.9, 160.7, 158.5, 147.5, 137.5, 128.3, 127.7, 118.9, 117.0, 115.9 , 114.5, 114.0, 109.1, 108.4, 71.8, 68.6, 55.3, 55.2, 48.6, 40.5, 27.0, 26.2.HRMS (ESI) m / z: Calcd for C 23 H 24 NO6(M+H) + 410.16036; Found 410.58842.

[0397] Embodiment 79:

[0398] Preparation of 8-((4-fluoropiperidin-1-yl)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY079)

[0399] The preparation method is similar to that of Example 7, except that 4-fluoropiperidine is used instead of 1-ene-7-heptylamine to obtain a brown solid final product. 1 H NMR (600MHz, DMSO-d6) δ7.88 (d, J=8.5Hz, 1H), 7.74 (d, J=8.9Hz, 1H), 7.15-7.10 (m, 2H), 7.08 (dd, J=8.5, 2.5Hz, 1H), 5.26 (s , 2H), 5.03-4.84 (m, 1H), 4.69 (d, J=7.0Hz, 2H), 3.32 (d, J=73.7Hz, 2H), 2.31 (s, 1H), 2.20-1.81 (m, 2H). HRMS (ESI) m / z: Calcd for C 22 H 21 FNO5(M+H) + 398.14038; Found 398.13931.

[0400] Embodiment 80:

[0401] Preparation of 8-((4,4-dimethylpiperidin-1-yl)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY080)

[0402] The preparation method is similar to that of Example 1, except that 4,4-dimethylpiperidine is used instead of piperidine to obtain a light brown solid final product. 1H NMR (600MHz, DMSO-d6) δ10.66 (s, 1H), 8.46 (s, 1H), 7.88 (d, J = 8.5Hz, 1H), 7.72 (d, J = 8.9Hz, 1H), 7.14-7.10 (m, 2H), 7.08 (dd, J=8.5, 2.5Hz, 1H), 5.25 (s, 2H), 4.67 (s, 2H), 3.27 (d, J=20.2Hz, 4H), 1.59 (dd, J=40.3, 12.5Hz, 4H), 1.06 (s, 3H), 0.94 (s, 3H). 13 C NMR (151MHz, DMSO) δ165.87, 160.54, 158.31, 154.50, 147.44, 137.39, 128.21, 127.69, 118.81, 11 6.89, 115.74, 114.40, 113.87, 109.08, 108.38, 68.48, 54.80, 50.58, 48.28, 34.32, 30.16, 27.31.

[0403] Embodiment 81:

[0404] 3,9-Dihydroxy-8-((4-(trifluoromethyl)piperidin-1-yl)methyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Preparation of Compound TY081)

[0405] The preparation method is similar to that of Example 1, except that 4-trifluoromethylpiperidine is used instead of piperidine to obtain a yellow solid final product. 1H NMR (600MHz, DMSO-d6) δ9.58 (d, J=9.4Hz, 1H), 9.00 (s, 1H), 7.88 (d, J=8.5Hz, 1 H), 7.75 (dd, J=9.0, 5.2Hz, 1H), 7.18-7.11 (m, 2H), 7.08 (dd, J=8.5, 2.4Hz, 1H) , 5.31 (s, 2H), 4.68 (d, J = 5.1Hz, 2H), 3.04-2.90 (m, 2H), 2.30 (d, J = 12.9Hz, 2H) , 2.20-2.03(m, 2H), 1.83(td, J=34.0, 30.9, 10.3Hz, 5H), 1.49-1.38(m, 1H).13C NMR (151MHz, DMSO) δ165.9, 160.6, 158.5, 154.5, 147.5, 137.6, 128.4, 127.9, 118.9, 117.0, 115.9 , 114.5, 114.2, 109.4, 108.0, 68.7, 59.4, 51.9, 49.3, 48.6, 23.4, 22.6, 21.3.HRMS (ESI) m / z: Calcd for C 23 H 21 F3NO5(M+H) + 448.13718; Found 448.13611.

[0406] Embodiment 82:

[0407] Preparation of 3,9-dihydroxy-8-((4-(hydroxymethyl)piperidin-1-yl)methyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY082)

[0408] The preparation method is similar to that of Example 1, except that 4-piperidinemethanol is used instead of piperidine to obtain a brown solid final product. 1 H NMR (600MHz, Methanol-d4) δ7.92 (d, J=8.5Hz, 1H), 7.51 (d, J=8.8Hz, 1H), 7.07-7.00 (m, 2H), 6.96 (d, J=8.8Hz, 1H), 5.20 (s, 2H), 4.42 (s, 2H), 3.44 (d, J=6.3Hz, 2H), 3.35 (s, 2H), 2.77 (d, J=10.8Hz, 2H), 1.90 (d, J=11.9Hz, 2H), 1.70 (s, 1H), 1.43 (q, J=14.6, 12.7Hz, 2H). 13C NMR (151MHz, MeOD) δ166.90, 161.38, 159.10, 155.32, 148.38, 137.30, 128.13, 126.72, 119.34, 116. 83, 115.41, 114.54, 112.13, 108.35, 69.07, 65.68, 52.96, 36.99, 27.20, 8.16.HRMS (ESI) m / z: Calcd for C 23 H 23 NO6(M+H) + 410.16036; Found 410.16013.

[0409] Embodiment 83:

[0410] Preparation of 8-((2-azabicyclo[2.2.1]hept-2-yl)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY083)

[0411] The preparation method is similar to that of Example 1, except that 2-aza-bicyclo[2,2,1]heptane is used instead of piperidine to obtain a yellow-brown solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.69 (s, 1H), 8.57 (s, 1H), 7.88 (d, J=8.5Hz, 1H), 7.71 (t, J=8.1H z, 1H), 7.14-7.10 (m, 2H), 7.08 (dd, J=8.5, 2.4Hz, 1H), 5.26 (d, J=5.8Hz, 2H), 4.74-4.55 (m , 2H), 4.10-4.00 (m, 1H), 3.37 (dt, J=45.6, 9.7Hz, 2H), 2.69 (d, J=3.7Hz, 1H), 2.17 (d, J=11 .3Hz, 1H), 1.84-1.70(m, 2H), 1.70-1.55(m, 2H), 1.43-1.33(m, 1H), .HRMS(ESI)m / z: Calcd for C 23 H 22 NO5(M+H) + 392.14980; Found 392.14868.

[0412] Embodiment 84:

[0413] Preparation of 3,9-dihydroxy-8-(2-aza-5-oxabicyclo[2.2.1]hept-2-ylmethyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY084)

[0414] The preparation method is similar to that of Example 38, except that (1R, 4R)-2-oxa-5-azabicyclo[2.2.1]heptane hydrochloride is used instead of 3-acetonitrilecyclobutylamine hydrochloride to obtain a yellow solid final product. 1 H NMR (600MHz, DMSO-d6) δ7.84 (t, J=8.7Hz, 1H), 7.48-7.45 (m, 1H), 7.10-7.07 (m, 1H ), 7.05 (dd, J=8.5, 2.5Hz, 1H), 6.86 (d, J=8.8Hz, 1H), 5.21-5.11 (m, 2H), 4.39 (d, J =6.7Hz, 2H), 3.94(s, 1H), 3.91-3.81(m, 2H), 3.56(dd, J=7.8, 2.0Hz, 2H), 3.51(s, 1H), 1.84 (dd, J=9.9, 2.2Hz, 1H), 1.66 (dd, J=9.9, 2.5Hz, 1H). HRMS (ESI) m / z: Calcd for C 22 H 19 NO6(M+H) + 394.1290; Found 394.1279.

[0415] Embodiment 85:

[0416] Preparation of 8-((4-acetylpiperidin-1-yl)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY085)

[0417] The preparation method is similar to that of Example 1, except that 1-piperidin-4-ethanone hydrochloride is used instead of piperidine hydrochloride to obtain a yellow solid final product. 1 H NMR (600MHz, Methanol-d4) δ7.96 (d, J=8.4Hz, 1H), 7.66 (d, J=8.9Hz, 1H), 7.13-7.04 (m, 3H), 5.25 (s, 2H), 4.71 (s, 2H), 3.74-3 .62 (m, 2H), 3.31-3.21 (m, 2H), 2.82 (tt, J=12.2, 3.6Hz, 1H), 2.23 (s, 1H), 2.20 (s, 3H), 1.84-1.73 (m, 2H). HRMS (ESI) m / z: Calcd for C 24 H 24 NO6(M+H) + 422.16036; Found 422.15875.

[0418] Embodiment 86:

[0419] Preparation of 8-((4-butyrylpiperidin-1-yl)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY086)

[0420] The preparation method is similar to that of Example 38, except that 1-piperidin-4-ethanone hydrochloride is used instead of 3-acetonitrile cyclobutylamine hydrochloride to obtain a light yellow solid final product. 1 H NMR (600MHz, DMSO-d6) δ7.84 (d, J=8.5Hz, 1H), 7.44 (d, J=8.8Hz, 1H), 7.11 (d, J=2.4Hz, 1H), 7.05 (dd, J=8.5, 2.4Hz , 1H), 6.87 (d, J=8.8Hz, 1H), 5.14 (s, 2H), 3.92 (s, 2H), 2.78 (s, 2H), 2.44 (t, J=7.1Hz, 2H), 2.41-2.35 (m, 1H), 2.08 (t, J=11.4Hz, 2H), 1.84-1.67 (m, 2H), 1.46 (q, J=7.3Hz, 2H), 1.43 (s, 2H), 0.82 (t, J=7.4Hz, 3H). HRMS (ESI) m / z: Calcd for C 26 H 26 NO6(MH) - 448.17601; Found 448.17657.

[0421] Embodiment 87:

[0422] Preparation of 3,9-dihydroxy-8-((4-pentanoylpiperidin-1-yl)methyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY087)

[0423] The preparation method is similar to that of Example 1, except that 1-piperidin-4-pentanone hydrochloride is used instead of piperidine hydrochloride to obtain a yellow solid final product. 1H NMR (600MHz, DMSO-d6) δ10.66 (s, 1H), 10.46 (d, J = 15.6Hz, 1H), 7.88 (d, J = 8.5Hz, 1H), 7.73 (d, J = 8.9Hz, 1H), 7.14-7.09 (m, 2H), 7.08 (dd, J=8.5, 2.4Hz, 1H), 5.26 (s, 2H), 4.65 (d, J=4.9Hz, 2H), 3.51-3.41 (m, 2 H), 3.24-3.13 (m, 2H), 2.72 (tt, J=12.3, 3.8Hz, 1H), 2.47-2.56 (m, 1H), 2.15-1.91 (m, 3H), 1.68 (td, J=1 4.1, 13.1, 6.6Hz, 2H), 1.38-1.50 (m, 2H), 1.19-1.30 (m, 2H), 0.84 (t, J=7.4Hz, 3H). HRMS (ESI) m / z: Calcd for C 27 H 30 NO6(M+H) + 464.20731; Found 464.20578.

[0424] Embodiment 88:

[0425] Preparation of 8-((4-hexanoylpiperidin-1-yl)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY088)

[0426] The preparation method is similar to that of Example 1, except that 1-piperidine-4-hexanone hydrochloride is used instead of piperidine hydrochloride to obtain a yellow solid final product. 1 H NMR (600MHz, Methanol-d4) δ7.96 (d, J=8.5Hz, 1H), 7.66 (d, J=8.9Hz, 1H), 7.06-7 .11(m,3H),5.25(s,2H),4.71(s,2H),3.75-3.63(m,2H),3.35-3.22(m,2H),2.87- 2.75 (m, 1H), 2.56 (t, J=7.3Hz, 2H), 2.17 (d, J=14.6Hz, 2H), 1.89-1.74 (m, 2H), 1.5 6 (p, J=7.4Hz, 2H), 1.43-1.21 (m, 4H), 0.91 (t, J=7.2Hz, 3H). HRMS (ESI) m / z: Calcd for C 28 H 32 NO6(M+H) +478.22296; Found 478.22128.

[0427] Embodiment 89:

[0428] Preparation of methyl 1-((3,9-dihydroxy-7-oxo-5,7-dihydrobenzo[5,6]oxo-4,3-b]benzofuran-8-yl)methyl)-4-methylpiperidine-4-carboxylate (Compound TY089)

[0429] The preparation method is similar to Example 38, except that 4-methylpiperidine-4-carboxylic acid methyl ester hydrochloride is used instead of 3-acetonitrile cyclobutylamine hydrochloride to obtain a yellow solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.65 (s, 1H), 10.42 (d, J=18.9Hz, 1H), 7.88 (d, J=8.5Hz, 1H), 7.73 (d, J=8.9Hz, 1H), 7.15-7.06 (m, 3H), 5.26 (s, 2H), 4.7 4-4.59 (m, 2H), 3.73 (s, 3H), 3.38-3.31 (m, 2H), 3.12-3.09 (m, 2H), 2.23 (d, J=14.5Hz, 2H), 1.84-1.67 (m, 2H), 1.15 (s, 3H). HRMS (ESI) m / z: Calcd for C 25 H 25 NO7(M+H) + 452.1704; Found 452.1708.

[0430] Embodiment 90:

[0431] Preparation of methyl 1-((3,9-dihydroxy-7-oxo-5,7-dihydrobenzo[5,6]oxo-4,3-b]benzofuran-8-yl)methyl)piperidine-4-carboxylate (Compound TY090)

[0432] The preparation method is similar to that of Example 7, except that methyl 4-piperidincarboxylate is used instead of 1-ene-7-heptylamine to obtain a yellow solid final product. 1H NMR (600MHz, DMSO-d6) δ10.63 (s, 1H), 10.41 (s, 1H), 7.91-7.86 (m, 1H), 7.73 (d, J=8.9Hz, 1H), 7.14-7.07 (m, 3H), 5.26 (s, 2H), 4.6 4 (d, J=5.0Hz, 2H), 3.61 (s, 3H), 3.25-3.17 (m, 2H), 2.71-2.67 (m, 1H), 2.10-1.80 (m, 4H), 1.83-1.80 (m, 2H). HRMS (ESI) m / z: Calcd for C 24 H 23 NO7(M+H) + 438.1542; Found 438.1548.

[0433] Embodiment 91:

[0434] Preparation of ethyl 1-((3,9-dihydroxy-7-oxo-5,7-dihydrobenzo[5,6]oxo-4,3-b]benzofuran-8-yl)methyl)piperidine-4-carboxylate (Compound TY091)

[0435] The preparation method is similar to that of Example 7, except that ethyl 4-piperidincarboxylate is used instead of 1-ene-7-heptylamine to obtain a white solid final product. 1 H NMR (600MHz, DMSO-d6) δ7.83 (d, J=8.5Hz, 1H), 7.44 (d, J=8.8Hz, 1H), 7.11 (d, J=2.4 Hz, 1H), 7.04 (dd, J=8.5, 2.4Hz, 1H), 6.87 (d, J=8.8Hz, 1H), 5.14 (s, 2H), 4.06 (q, J= 7.1Hz, 2H), 3.91 (s, 2H), 2.84-2.60 (m, 2H), 2.36-2.32 (m, 1H), 2.09 (d, J=12.0Hz, 2 H), 1.79 (d, J=12.9Hz, 2H), 1.53 (s, 2H), 1.17 (t, J=7.1Hz, 3H). HRMS (ESI) m / z: Calcd for C 25 H 25 NO7(M+H) + 452.1699; Found 452.1708.

[0436] Embodiment 92:

[0437] Preparation of 1-((3,9-dihydroxy-7-oxo-5,7-dihydrobenzo[5,6]oxazepin[4,3-b]benzofuran-8-yl)methyl)piperidine-4-carboxylic acid propyl ester (Compound TY092)

[0438] The preparation method is similar to that of Example 7, except that 4-piperidinylcarboxylic acid propyl ester is used instead of 1-ene-7-heptylamine to obtain a yellow solid final product. 1 H NMR (600MHz, Methanol-d4) δ7.89 (t, J=7.9Hz, 1H), 7.40 (dd, J=16.9, 8.8Hz, 1H), 7.08 -6.96 (m, 2H), 6.92-6.85 (m, 1H), 5.15 (d, J=9.8Hz, 2H), 4.19 (s, 2H), 4.03 (t, J=6.6Hz , 2H), 2.46 (d, J=11.8Hz, 3H), 1.99-1.94 (m, 2H), 1.77 (d, J=12.2Hz, 1H), 1.64 (dtd, J= 14.0, 7.4, 6.6Hz, 2H), 1.32-1.25 (m, 3H), 0.93 (t, J=7.4Hz, 3H). HRMS (ESI) m / z: Calcd for C 26 H 28 NO7(M+H) + 466.18658; Found 466.18683.

[0439] Embodiment 93:

[0440] Preparation of hept-6-en-1-yl-1-((3,9-dihydroxy-7-oxo-5,7-dihydrobenzo[5,6]oxazepin[4,3-b]benzofuran-8-yl)methyl)piperidine-4-carboxylate (Compound TY093)

[0441] The preparation method is similar to that of Example 7, except that 4-piperidinyl heptyl ester is used instead of 1-en-7-heptylamine to obtain a yellow solid final product. 1H NMR (600MHz, Methanol-d4) δ7.89 (d, J=8.5Hz, 1H), 7.40 (d, J=8.8Hz, 1H), 7.11-6.95 (m, 2H), 6.89 (d, J=8.8Hz, 1H), 5.80 (m, 1H), 5.14 (m, 2H), 4.98 (m, 1H), 4.92 (m, 1H), 4. 08(td, J=6.6, 2.6Hz, 2H), 3.02(d, J=11.7Hz, 2H), 2.52-2.35(m, 3H), 2.14-1.91(m, 5H ), 1.78 (t, J=12.8Hz, 2H), 1.75-1.57 (m, 3H), 1.46-1.33 (m, 4H). HRMS (ESI) m / z: Calcd for C 30 H 34 NO7(M+H) + 520.23353; Found 520.23273.

[0442] Embodiment 94:

[0443] Preparation of 1-((3,9-dihydroxy-7-oxo-5,7-dihydrobenzo[5,6]oxo-4,3-b]benzofuran-8-yl)methyl)piperidine-4-carboxamide (Compound TY094)

[0444] The preparation method is similar to that of Example 7, except that 4-piperidinecarboxamide is used instead of 1-ene-7-heptylamine to obtain a white solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.66 (s, 1H), 10.43 (s, 1H), 7.88 (d, J=8.5Hz, 1H), 7.73 (dd, J=9.0, 3.8Hz, 1H), 7.15-7.06 (m, 3H), 5.26 (s, 2H), 4 .65 (d, J=4.9Hz, 2H), 3.48-3.44 (m, 2H), 3.15 (s, 2H), 2.40-2.36 (m, 1H), 1.93 (d, J=14.4Hz, 2H), 1.79-1.76 (m, 2H).HRMS (ESI) m / z: Calcd for C 23 H 23 N2O6(M+H) + 423.1543; Found 423.1558.

[0445] Embodiment 95:

[0446] Preparation of 1-((3,9-dihydroxy-7-oxo-5,7-dihydrobenzo[5,6]oxazepine[4,3-b]benzofuran-8-yl)methyl)-N-ethylpiperidine-4-carboxamide (Compound TY095)

[0447] The preparation method is similar to Example 38, except that N-ethylpiperidine-4-carboxamide hydrochloride is used instead of 3-acetonitrile cyclobutylamine hydrochloride to obtain a brown solid final product. 1 H NMR (600MHz, Methanol-d4) δ7.89 (d, J=8.4Hz, 1H), 7.59 (dd, J=8.9, 2.9Hz, 1 H), 7.05-6.99 (m, 3H), 5.19 (s, 2H), 4.65 (s, 2H), 3.63 (d, J=12.6Hz, 2H), 3.25 -3.17 (m, 2H), 3.14 (q, J=7.2Hz, 2H), 2.49 (tt, J=12.1, 3.8Hz, 1H), 2.01 (d, J =14.5Hz, 2H), 1.96-1.85 (m, 2H), 1.06 (t, J = 7.3Hz, 3H). HRMS (ESI) m / z: Calcd for C 25 H 27 N2O6(M+H) + 451.18691; Found 451.18570.

[0448] Embodiment 96:

[0449] Preparation of 1-((3,9-dihydroxy-7-oxo-5,7-dihydrobenzo[5,6]oxazo[4,3-b]benzofuran-8-yl)methyl)-N-(hept-6-en-1-yl)piperidine-4-carboxamide (Compound TY096)

[0450] The preparation method is similar to Example 38, except that N-octylpiperidine-4-carboxamide hydrochloride is used instead of 3-acetonitrile cyclobutylamine hydrochloride to obtain a light yellow solid final product. 1H NMR (600MHz, DMSO-d6) δ10.66 (s, 1H), 10.45 (s, 1H), 7.88 (d, J=8.5Hz, 1H), 7.72 (d, J=8.9Hz, 1H), 7.14-7.09 (m, 2H), 7.08 (dd, J=8.5, 2.4Hz, 1H), 5.80-5.73 (m, 1 H), 5.25 (s, 2H), 5.03-4.89 (m, 2H), 4.64 (d, J = 5.1Hz, 2H), 3.45 (d, J = 11.8Hz, 2H) , 3.17 (s, 1H), 3.01 (q, J=6.6Hz, 2H), 2.45-2.32 (m, 1H), 2.14-1.94 (m, 2H), 1.93- 1.76(m, 4H), 1.44-1.28(m, 4H), 1.28-1.18(m, 2H).HRMS(ESI)m / z: Calcd for C 30 H 35 N2O6(M+H) + 519.24951; Found 519.24823.

[0451] Embodiment 97:

[0452] Preparation of 8-((4-benzoylpiperidin-1-yl)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY097)

[0453] The preparation method is similar to that of Example 38, except that phenyl(4-piperidinyl)methanone hydrochloride is used instead of 3-acetonitrilecyclobutylamine hydrochloride to obtain a light yellow solid final product. 1 H NMR (400MHz, DMSO-d6) δ10.69 (s, 1H), 10.51 (s, 1H), 8.08-7.98 (m, 2H), 7.88 (dd, J=8.5, 2.4Hz, 1H), 7.74 (d, J=8.9Hz, 1H), 7.67 (t, J=7.3Hz, 1H), 7.57 (q, J=7.3Hz, 2H), 7.13 (dd, J=5.7, 3.2Hz, 2H), 7.11-7.03 (m, 1H), 5.28 (s, 2H), 4.71 (d, J=4.7Hz, 2H), 3.80 (td, J=10.0, 8.4, 5.8Hz, 1H), 3 .60-3.43(m, 2H), 3.44-3.23(m, 3H), 2.10-1.97(m, 2H), 1.95-1.80(m, 1H).HRMS(ESI)m / z: Calcd for C 29 H 26NO6(M+H) + 484.17601; Found 484.17377.

[0454] Embodiment 98:

[0455] Preparation of 8-((4-benzylpiperidin-1-yl)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY098)

[0456] The preparation method is similar to that of Example 7, except that 4-benzylpiperidine is used instead of 1-ene-7-heptylamine to obtain a yellow solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.65 (s, 1H), 10.38 (s, 1H), 7.88 (d, J=8.5Hz, 1H) , 7.72(d, J=8.8Hz, 1H), 7.31-7.27(m, 3H), 7.18-7.15(m, 2H), 7.14-7.06(m , 3H), 5.25 (d, J=6.3Hz, 2H), 4.60 (d, J=4.9Hz, 2H), 3.12-3.08 (m, 2H), 2.5 4-2.51 (m, 2H), 1.87-1.66 (m, 5H), 1.48-1.39 (m, 2H). HRMS (ESI) m / z: Calcd for C 29 H 27 NO5(M+H) + 470.1962; Found 470.1968.

[0457] Embodiment 99:

[0458] Preparation of 8-((4-(cyclohexylmethyl)piperazin-1-yl)methyl)-3,9-dihydroxybenzo[5,6]oxybenzo[4,3-b]benzofuran-7(5H)-one (Compound TY-099)

[0459] The preparation method is similar to that of Example 1, except that 1-(cyclohexylmethyl)piperazine is used instead of piperidine to obtain a yellow-white solid product. 1H NMR (600MHz, DMSO-d6) δ7.84 (d, J=8.5Hz, 1H), 7.64 (s, 1H), 7.09 (d, J=2.4Hz, 1H), 7.04 (dd, J=8.5, 2.4Hz, 2H), 5.21 (s, 2H), 4.32 (s, 7H), 2.8 3 (s, 4H), 1.75-1.60 (m, 6H), 1.58 (d, J=11.8Hz, 1H), 1.19 (q, J=12.6Hz, 2H), 1.10 (q, J=12.3Hz, 1H), 0.96-0.83 (m, 2H). HRMS (ESI) m / z: Calcd for C 28 H 32 N2O5(M+H) + 477.23894; Found 477.23758.

[0460] Embodiment 100:

[0461] Preparation of 8-([1,4′-bipiperidinyl]-1′-ylmethyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY100)

[0462] The preparation method is similar to that of Example 1, except that 4-piperidinylpiperidine is used instead of piperidine to obtain a yellow solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.62 (s, 1H), 10.41 (s, 1H), 7.89 (d, J = 8.2Hz, 1H), 7.74 (d, J = 8.8Hz, 1H), 7.15-7.11 (m, 2H), 7.08 (dd, J = 8.4, 2 .5Hz, 1H), 5.28 (s, 2H), 4.67 (s, 2H), 4.30-3.81 (m, 5H), 2.78-2.65 (m, 1H), 2.16-1.92 (m, 2H), 1.90-1.74 (m, 2H), 1.23 (d, J=4.3Hz, 2H). 13 CNMR (151MHz, DMSO) δ166.3, 161.1, 159.0, 155.0, 148.0, 138.0, 128.8, 119.4, 117.5, 116.3, 115.0, 109.7, 69.1, 52.7, 29.5, 22.3.HRMS (ESI) m / z: Calcd for C27H31N2O5(M+H) + 463.22330; Found 463.22177.

[0463] Embodiment 101:

[0464] Preparation of 3,9-dihydroxy-8-(8-aza-1,4-dioxaspiro[4.5]dec-8-ylmethyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY101)

[0465] The preparation method is similar to that of Example 7, except that 4-piperidone ethylene glycol acetal is used instead of 1-ene-7-heptylamine to obtain a yellow-white solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.44 (s, 1H), 7.83 (d, J = 8.5Hz, 1H), 7.44 (d, J = 8.8Hz, 1H), 7.13-7.01 (m, 2H), 6.88 (d, J = 8.8Hz, 1H), 5.15 (s, 2H), 4.09 (s, 5H), 3.92 (s, 2H), 2.48-2.37 (m, 2H), 1.60 (t, J=5.6Hz, 4H). HRMS (ESI) m / z: Calcd for C 24 H 23 NO7(M+H) + 438.1544; Found 438.1548.

[0466] Embodiment 102:

[0467] Preparation of 8-((4-cyclopentylpiperazin-1-yl)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY102)

[0468] The preparation method is similar to that of Example 1, except that 1-cyclopentylpiperazine is used instead of piperidine to obtain a white solid final product. 1 H NMR (600MHz, Methanol-d4) δ7.96 (d, J=8.4Hz, 1H), 7.67 (d, J=8.9Hz, 1H), 7.16-7.02 (m, 3H), 5.26 (s, 2H), 4.85 (s, 2 H), 3.71 (d, J=108.4Hz, 8H), 2.17 (q, J=8.5, 5.3Hz, 2H), 1.94-1.76 (m, 4H), 1.76-1.62 (m, 2H). HRMS (ESI) m / z: Calcd for C 26 H 28 N2O5(M+H) + 449.20764; Found 449.20633.

[0469] Embodiment 103:

[0470] Preparation of 3,9-dihydroxy-8-((4-(pyrrolidin-1-yl)piperidin-1-yl)methyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY103)

[0471] The preparation method refers to Example 1, except that 4-pyrrolidin-1-yl-piperidine replaces piperidine to obtain a white solid final product 1 H NMR (600MHz, DMSO-d6) δ10.53 (s, 1H), 10.22 (s, 1H), 7.89 (d, J=8.5Hz, 1H), 7.75 (d, J=8.9Hz, 1H), 7.14-7.12 (m, 2H), 7.08 (dd, J=8.5, 2.4Hz, 1H), 5.26 (s, 2H), 4.65 (d, J=4.5Hz, 2H), 3.55 (s, 4H), 3.44-3 .32(m,1H),3.23(s,2H),3.09-3.05(m,2H),2.31-2.29(m,2H),2.00-1.98(m,2H),1.91-1.83(m,4H).HRMS(ESI)m / z:Calcd for C 26 H 28 N2O5(M+H) + 449.20764; Found 449.20590.

[0472] Embodiment 104:

[0473] Preparation of 8-(decahydroisoquinolin-2-ylmethyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY104)

[0474] The preparation method is similar to that of Example 7, except that perhydroquinoline is used instead of 1-ene-7-heptylamine to obtain a yellow solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.40 (s, 1H), 7.88 (dd, J=8.5, 1.8Hz, 1H), 7.73 (dd, J=8.9, 1.4Hz, 1H), 7.14-7.06 (m, 3H), 5.26 (d, J=6.2 Hz, 2H), 4.73-4.56 (m, 2H), 3.26-3.10 (m, 4H), 1.96 (d, J=13.8Hz, 2H), 1.55-1.32 (m, 8H), 1.02-0.85 (m, 2H). HRMS (ESI) m / z: Calcd for C 24 H 23 NO5(M+H) +434.1968; Found 434.1956.

[0475] Embodiment 105:

[0476] Preparation of 3,9-dihydroxy-8-(1,2,3,4-tetrahydroisoquinolin-2-ylmethyl)-5,7-dihydrobenzo[e]benzo[2,3]furo[4,5-c]oxepan-7-one (Compound TY105)

[0477] The preparation method is similar to that of Example 7, except that 1,2,3,4-tetrahydroxyquinoline is used instead of 1-ene-7-heptylamine to obtain a yellow-white solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.63 (s, 1H), 10.48 (s, 1H), 7.88 (d, J=8.5Hz, 1H), 7.75 (d, J=8.9Hz, 1H), 7.33-7.18 (m, 4H), 7.15-7.01 (m, 3H), 5.24 (s, 2H), 4.86 (d, J=29.2Hz, 2H), 4.65-4.36 (m, 2H), 3.73-3.55 (m, 2H), 3.16 (t, J=6.0Hz, 2H). HRMS (ESI) m / z: Calcd for C 26 H 21 NO5(M+H) + 428.1498; Found 428.1484.

[0478] Embodiment 106:

[0479] Preparation of 3,9-dihydroxy-8-((4-(pyridin-3-yl)piperidin-1-yl)methyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY106)

[0480] The preparation method is similar to Example 1, except that 3-(piperidin-4-yl)pyridine hydrochloride is used instead of piperidine hydrochloride to obtain a light yellow solid final product. 1H NMR (400MHz, DMSO-d6) δ10.57 (s, 1H), 8.71-8.63 (m, 2H), 8.10 (d, J=8.1Hz, 1H ), 7.89 (d, J=8.5Hz, 1H), 7.80-7.70 (m, 2H), 7.18-7.11 (m, 2H), 7.08 (dd, J=8.5 , 2.4Hz, 1H), 5.27 (s, 2H), 4.72 (d, J=4.7Hz, 2H), 3.57 (d, J=11.8Hz, 2H), 3.37 (t, J=11.3Hz, 2H), 3.14-3.03 (m, 1H), 2.14-1.89 (m, 4H). HRMS (ESI) m / z: Calcd for C 27 H 25 N2O5(M+H) + 457.17635; Found 457.17371.

[0481] Embodiment 107:

[0482] Preparation of 3,9-dihydroxy-8-((4-(pyridin-4-yl)piperidin-1-yl)methyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY107)

[0483] The preparation method is similar to that of Example 7, except that 4-(piperidin-4-yl)pyridine is used instead of 1-ene-7-heptylamine to obtain a light yellow solid final product. 1 H NMR (600MHz, Methanol-d4) δ8.76 (d, J=6.5Hz, 2H), 8.05-7.96 (m, 2H), 7.92 (d, J=8.4Hz, 1H), 7.62 (d, J=8.9Hz, 1H), 7.07-7.02 (m, 3H), 5.23 (s, 2H ), 4.74 (s, 2H), 3.77 (d, J = 12.5Hz, 2H), 3.45 (t, J = 12.4Hz, 2H), 3.39-3.33 (m, 1H), 2.25 (d, J = 14.2Hz, 2H), 2.14-2.02 (m, 2H). HRMS (ESI) m / z: Calcd for C 27 H 25 N2O5(M+H) + 457.17635; Found 457.17468.

[0484] Embodiment 108:

[0485] Preparation of 3,9-dihydroxy-8-((4-phenylpiperidin-1-yl)methyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY108)

[0486] The preparation method is similar to that of Example 1, except that 4-phenylpiperidine is used instead of piperidine to obtain a light yellow solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.66 (s, 1H), 10.46 (s, 1H), 7.89 (d, J = 8.5Hz, 1H), 7.75 (d, J = 8.9Hz, 1H), 7.41-7.29 (m, 2H), 7.23-7.20 (m 3H), 7.15-7.11 (m, 2H), 7.08 (dd, J=8.5, 2.4Hz, 1H), 5.27 (s, 2H), 4.71 (d, J=5.0Hz, 2H), 3.60-3.28 (m, 5H), 2.13-1.84 (m, 4H). 13 C NMR (151MHz, DMSO-d6) δ165.90, 160.67, 158.55, 154.63, 147.57, 144.27, 137.53, 128.59, 128.36, 127.80, 126.57, 126.55 , 118.92, 117.01, 115.87, 114.53, 114.08, 109.16, 108.29, 68.60, 52.22, 48.59, 40.06, 38.55, 30.15.HRMS (ESI) m / z: Calcd for C 28 H 25 NO5(M+H) + 456.18109; Found 456.17996.

[0487] Embodiment 109:

[0488] Preparation of 8-((4-(4-aminophenyl)piperidin-1-yl)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY109)

[0489] The preparation method is similar to that of Example 7, except that 4-(4-aminophenyl)piperidine is used instead of 1-ene-7-heptylamine to obtain a yellow solid final product. 1H NMR (600MHz, DMSO-d6) δ10.67 (s, 1H), 10.49 (s, 1H), 7.89 (d, J=8.5Hz, 1H), 7 .74 (d, J=8.9Hz, 1H), 7.21 (d, J=8.2Hz, 2H), 7.13 (dd, J=5.7, 3.2Hz, 2H), 7.1 0-7.07 (m, 3H), 5.27 (s, 2H), 4.70 (d, J = 4.7Hz, 2H), 3.54 (d, J = 12.0Hz, 2H), 3 .39-3.24(m, 2H), 2.90-2.82(m, 1H), 2.02-1.79(m, 6H).HRMS(ESI)m / z: Calcd for C 28 H 26 N2O5(M+H) + 471.19199; Found 471.19000.

[0490] Embodiment 110:

[0491] Preparation of 3,9-dihydroxy-8-((4-(4-methoxyphenyl)piperidin-1-yl)methyl)benzo[5,6]oxazepa[4,3-b]benzofuran-7(5H)-one (Compound TY110)

[0492] The preparation method is similar to that of Example 7, except that 4-(4-methoxyphenyl)piperidine is used instead of 1-ene-7-heptylamine to obtain a light yellow solid final product. 1 H NMR (600MHz, Methanol-d4) δ7.90 (d, J=8.5Hz, 1H), 7.61-7.58 (m, 1H), 7.12 -7.08(m, 2H), 7.05-7.00(m, 3H), 6.81-6.78(m, 2H), 5.18(d, J=14.7Hz, 2H), 4.68(s, 2H), 3.69(s, 3H), 3.59(d, J=2.6Hz, 2H), 3.35-3.29(m, 2H), 2.88-2 .82 (m, 1H), 2.03 (d, J = 14.4Hz, 2H), 1.95-1.88 (m, 2H). HRMS (ESI) m / z: Calcd for C 29 H 26 NO6(MH)-484.17601; Found 484.21082.

[0493] Embodiment 111:

[0494] Preparation of 3,9-dihydroxy-8-((4-(p-methylphenyl)piperidin-1-yl)methyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY111)

[0495] The preparation method is similar to that of Example 1, except that 4-(4-methylphenyl)piperidine is used instead of piperidine to obtain a beige solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.67 (s, 1H), 10.47 (s, 1H), 7.89 (d, J=8.5Hz, 1H), 7.74 (d, J=8.9Hz, 1H), 7.16-7.06 (m, 7H), 5.27 (s, 2H), 4 .69 (d, J=5.0Hz, 2H), 3.53-3.51 (m, 2H), 3.33-3.26 (m, 2H), 2.88-2.77 (m, 1H), 2.25 (s, 3H), 2.05-1.82 (m, 4H). HRMS (ESI) m / z: Calcd for C 29 H 27 NO5(M+H) + 170.19674; Found 470.19519.

[0496] Embodiment 112:

[0497] Preparation of 8-((4-(4-fluorophenyl)piperidin-1-yl)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY112)

[0498] The preparation method is similar to that of Example 1, except that 4-(4-fluorophenyl)piperidine is used instead of piperidine to obtain a beige solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.67 (s, 1H), 10.50 (s, 1H), 7.85 (d, J=8.6Hz, 1H), 7 .71(d, J=8.9Hz, 1H), 7.21(dd, J=8.7, 5.6Hz, 2H), 7.13-7.08(m, 4H), 7.05(dd , J=8.5, 2.4Hz, 1H), 5.23 (s, 2H), 4.67 (d, J=5.0Hz, 2H), 3.57-3.43 (m, 2H), 3 .30-3.25(m, 2H), 2.87-2.82(m, 1H), 1.97-1.73(m, 4H).HRMS(ESI)m / z: Calcd for C 28 H 24 FNO5(M+H) +474.17167; Found 474.17072.

[0499] Embodiment 113:

[0500] Preparation of 8-((4-(4-bromophenyl)piperidin-1-yl)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY113)

[0501] The preparation method is similar to that of Example 1, except that 4-(3-bromophenyl)piperidine is used instead of piperidine to obtain a yellow solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.67 (s, 1H), 10.48 (s, 1H), 7.89 (d, J = 8.5Hz, 1H), 7.75 (d, J = 8.9Hz, 1H), 7.54-7.49 (m, 2H), 7.22-7.16 (m, 2H ), 7.15-7.11 (m, 2H), 7.08 (dd, J=8.5, 2.4Hz, 1H), 5.27 (s, 2H), 4.69 (d, J=5.0Hz, 2H), 3.51-3.44 (m, 4H), 2.90-2.85 (m, 1H), 2.03-1.79 (m, 4H).HRMS(ESI)m / z:Calcd for C 28 H 24 BrNO5(M+H) + 534.09161; Found 534.09161.

[0502] Embodiment 114:

[0503] Preparation of 8-((4-(4-chlorophenyl)piperidin-1-yl)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY114)

[0504] The preparation method is similar to that of Example 1, except that 4-(4-chlorophenyl)piperidine hydrochloride is used instead of piperidine hydrochloride to obtain a yellow solid final product. 1H NMR (600MHz, DMSO-d6) δ7.85 (d, J=8.5Hz, 1H), 7.46 (d, J=8.8Hz, 1H), 7.41-7.3 1 (m, 2H), 7.27 (d, J = 8.5Hz, 2H), 7.12 (d, J = 2.4Hz, 1H), 7.05 (dd, J = 8.5, 2.4Hz, 1H), 6.89 (d, J=8.8Hz, 1H), 5.21 (s, 2H), 4.017 (s, 2H), 2.90 (s, 2H), 2.66-2.53 (m, 1H), 2.19 (s, 2H), 1.75 (d, J = 12.7Hz, 2H), 1.59 (s, 2H). HRMS (ESI) m / z: Calcd for C 28 H 24 ClNO5(M+H) + 490.14212; Found 490.14203.

[0505] Embodiment 115:

[0506] Preparation of 4-(1-((3,9-dihydroxy-7-oxo-5,7-dihydrobenzo[5,6]oxazepin[4,3-b]benzofuran-8-yl)methyl)piperidin-4-yl)benzonitrile (Compound TY115)

[0507] The preparation method is similar to that of Example 1, except that 4-(3-cyanophenyl)piperidine is used instead of piperidine to obtain a beige solid final product. 1 H NMR (600MHz, DMSO-d6) δ7.85 (d, J=8.5Hz, 1H), 7.76 (d, J=8.3Hz, 2H), 7.47-7.44 (m, 3H), 7.12 (d, J=2.4Hz, 1H), 7.05 (dd, J=8.5, 2.4Hz, 1H), 6.89 (d , J=8.8Hz, 1H), 5.21 (s, 2H), 3.97 (s, 2H), 2.89 (s, 2H), 2.69-2.64 (m, 1H) , 2.18-2.16(m, 2H), 1.82-1.70(m, 2H), 1.61(s, 2H).HRMS(ESI)m / z: Calcd for C 29 H 24 N2O5(M+H) + 481.17634; Found 481.17441.

[0508] Embodiment 116:

[0509] Preparation of 3,9-dihydroxy-8-((4-(4-hydroxyphenyl)piperidin-1-yl)methyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY116)

[0510] The preparation method is similar to that of Example 1, except that 4-(4-methoxyphenyl)piperidine is used instead of piperidine to obtain a light yellow solid final product. 1 H NMR (600MHz, Methanol-d4) δ7.94 (d, J=8.4Hz, 1H), 7.63 (d, J=8.9Hz, 1H), 7.12-6.98 (m, 5H), 6.73-6.64 (m, 2H), 5.23 ( s, 2H), 4.70 (s, 2H), 3.69 (d, J=12.2Hz, 2H), 3.34 (s, 2H), 2.83-2.81 (m, 1H), 2.05 (d, J=14.5Hz, 2H), 1.96-1.86 (m, 1H).

[0511] Embodiment 117:

[0512] Preparation of ethyl 4-(1-((3,9-dihydroxy-7-oxo-5,7-dihydrobenzo[5,6]oxazepin[4,3-b]benzofuran-8-yl)methyl)piperidin-4-yl)benzoate (Compound TY117)

[0513] The preparation method is similar to that of Example 7, except that 4-(ethyl 4-benzoate)piperidine is used instead of 1-ene-7-heptylamine to obtain a light yellow solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.95 (s, 1H), 10.48 (s, 1H), 7.90 (d, J = 8.1Hz, 2H), 7.85 (d, J = 8.4Hz, 1H), 7.46 (d, J=8.8Hz, 1H), 7.40 (d, J=8.1Hz, 2H), 7.13 (d, J=2.4Hz, 1H), 7.06 (dd, J=8.5, 2.5Hz, 1H), 6. 90 (d, J=8.8Hz, 1H), 5.22 (s, 2H), 4.30 (q, J=7.1Hz, 2H), 3.99 (s, 2H), 2.91 (s, 2H), 2.68-2.64 (m, 1 H), 2.27-2.11 (m, 2H), 1.84-1.71 (m, 2H), 1.64 (s, 2H), 1.31 (t, J=7.1Hz, 3H). HRMS (ESI) m / z: Calcd for C31H 29 NO7(M+H) + 528.20222; Found 528.20105.

[0514] Embodiment 118:

[0515] Preparation of 8-((4-([1,1′-biphenyl]-4-yl)piperidin-1-yl)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY118)

[0516] The preparation method is similar to that of Example 1, except that 4-biphenyl-4-ylpiperidine is used instead of piperidine to obtain a yellow solid final product. 1 H NMR (600MHz, DMSO-d6) δ7.85 (dd, J=8.5, 1.4Hz, 1H), 7.66-7.62 (m, 2H), 7.61-7.56 (m, 2 H), 7.51-7.41 (m, 3H), 7.34 (ddt, J=7.4, 4.0, 1.9Hz, 3H), 7.13 (t, J=1.9Hz, 1H), 7.06 (d t, J=8.5, 1.9Hz, 1H), 6.89 (dd, J=8.8, 1.4Hz, 1H), 5.23 (s, 2H), 3.99 (s, 2H), 2.91 (s, 2H) ), 2.61-2.57(m, 1H), 2.19-2.16(m, 2H), 1.79(s, 2H), 1.65(s, 2H).HRMS(ESI)m / z: Calcd for C 34 H 29 NO5(M+H) + 532.21239; Found 532.21100.

[0517] Embodiment 119:

[0518] Preparation of 3,9-dihydroxy-8-((4-(3-hydroxyphenyl)piperidin-1-yl)methyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY119)

[0519] The preparation method is similar to that of Example 1, except that 4-(3-hydroxyphenyl)piperidine is used instead of piperidine to obtain a yellow solid final product. 1H NMR (600MHz, DMSO-d6) δ10.68 (s, 1H), 10.48 (s, 1H), 9.37 (s, 1H), 7.89 (d, J = 8.5Hz, 1H), 7.74 (d, J = 8.9Hz, 1H), 7.18-7.04 (m, 4H), 6.67-6.53 (m , 3H), 5.27 (s, 2H), 4.69 (d, J=5.0Hz, 2H), 3.52 (d, J=11.6Hz, 2H), 3.32-3.28 (m, 2H), 2.79-2.74 (m, 1H), 1.97-1.86 (m, 4H). HRMS (ESI) m / z: Calcd for C 28 H 25 NO6(M+H) + 472.17601; Found 472.17441.

[0520] Embodiment 120:

[0521] Preparation of 3,9-dihydroxy-8-((4-(3-(trifluoromethyl)phenyl)piperidin-1-yl)methyl)benzo[5,6]oxazepa[4,3-b]benzofuran-7(5H)-one (Compound TY120)

[0522] The preparation method is similar to that of Example 7, except that 4-(3-trifluoromethylphenyl)piperidine is used instead of 1-ene-7-heptylamine to obtain a yellow solid final product. 1 H NMR (600MHz, Methanol-d4) δ7.96 (d, J=8.4Hz, 1H), 7.65 (d, J=8.9Hz, 1H), 7.60-7.50 (m, 4H), 7.08 (ddd, J=12.5, 6.5, 2.8Hz , 3H), 5.25(s, 2H), 4.76(s, 2H), 3.86-3.68(m, 2H), 3.48-3.38(m, 2H), 3.10-3.08(m, 1H), 2.28-1.92(m, 4H).HRMS(ESI)m / z: Calcd for C 29 H 25 F3NO5(M+H) + 524.16848; Found 524.16705.

[0523] Embodiment 121:

[0524] Preparation of 3,9-dihydroxy-8-((4-(m-tolyl)piperidin-1-yl)methyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY121)

[0525] The preparation method is similar to Example 38, except that 4-(3-methylphenyl)piperidine hydrochloride is used instead of 3-acetonitrilecyclobutylamine hydrochloride to obtain a brown solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.64 (s, 1H), 10.47 (s, 1H), 7.89 (d, J=8.5Hz, 1H), 7.75 (d, J=8.9H z, 1H), 7.19 (t, J=7.6Hz, 1H), 7.13 (dd, J=6.5, 2.1Hz, 2H), 7.08 (dd, J=8.5, 2.4Hz, 1H), 7.04 -6.98 (m, 3H), 5.26 (d, J=7.1Hz, 2H), 4.70 (d, J=5.0Hz, 2H), 3.53 (d, J=11.6Hz, 2H), 3.39-3. 26 (m, 2H), 2.83 (q, J=6.6, 5.6Hz, 1H), 2.27 (s, 3H), 2.02-1.88 (m, 4H). HRMS (ESI) m / z: Calcd for C 29 H 27 NO5(M+H) + 470.1955; Found 470.5448.

[0526] Embodiment 122:

[0527] Preparation of 8-((4-(3-ethylphenyl)piperidin-1-yl)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY122)

[0528] The preparation method is similar to Example 38, except that 4-(3-ethylphenyl)-piperidine hydrochloride is used instead of 3-acetonitrile cyclobutylamine hydrochloride to obtain a yellow solid final product. 1H NMR (400MHz, DMSO-d6) δ10.79 (s, 1H), 10.54 (s, 1H), 7.85 (d, J=8.5Hz, 1H), 7.46 (d, J=8.8Hz , 1H), 7.20 (t, J=7.5Hz, 1H), 7.13 (d, J=2.4Hz, 1H), 7.07-7.01 (m, 4H), 6.88 (d, J=8.8Hz, 1H), 5.21(s, 2H), 3.97(s, 2H), 2.90(s, 2H), 2.58(q, J=7.6Hz, 2H), 2.51-2.50(m, 1H), 2.16(t, J= 6.0Hz, 2H), 1.75 (d, J=12.4Hz, 2H), 1.62 (s, 2H), 1.17 (t, J=7.7Hz, 3H). HRMS (ESI) m / z: Calcd for C 30 H 29 NO5(M+H) + 484.21239; Found 484.21002.

[0529] Embodiment 123:

[0530] Preparation of 3,9-dihydroxy-8-((4-(3-methoxyphenyl)piperidin-1-yl)methyl)benzo[5,6]oxazepa[4,3-b]benzofuran-7(5H)-one (Compound TY123)

[0531] The preparation method is similar to Example 38, except that 4-(3-methoxyphenyl)piperidine hydrochloride is used instead of 3-acetonitrilecyclobutylamine hydrochloride to obtain a light yellow solid final product. 1 H NMR (600MHz, DMSO-d6) δ7.85 (d, J=8.5Hz, 1H), 7.45 (d, J=8.8Hz, 1H), 7.20 (t, J=7.9Hz, 1H), 7.12 ( d, J=2.4Hz, 1H), 7.05 (dd, J=8.5, 2.4Hz, 1H), 6.88 (d, J=8.8Hz, 1H), 6.81 (d, J=7.6Hz, 1H), 6.78 (t, J=2.1Hz, 1H), 6.75 (dd, J=8.1, 2.6Hz, 1H), 5.20 (s, 2H), 3.98 (s, 2H), 3.73 (s, 3H), 2.89 (s, 2H), 2. 54-2.51 (m, 1H), 2.17 (t, J = 10.2Hz, 2H), 1.75 (d, J = 12.4Hz, 2H), 1.61 (s, 2H). HRMS (ESI) m / z: Calcd for C 29 H 27 NO6 (M+H)+ 486.19166; Found 486.19016.

[0532] Embodiment 124:

[0533] Preparation of 8-((4-(3-fluorophenyl)piperidin-1-yl)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY124)

[0534] The preparation method is similar to Example 38, except that 4-(3-fluorophenyl)piperidine hydrochloride is used instead of 3-acetonitrilecyclobutylamine hydrochloride to obtain a yellow solid final product. 1 H NMR (400MHz, DMSO-d6) δ7.85 (d, J=8.5Hz, 1H), 7.46 (d, J=8.8Hz, 1H), 7.34 (q, J=7.3Hz, 1H), 7.15-6.97 (m, 5H), 6.89 (d, J=8.8Hz, 1H), 5.20 (s, 2H), 3.98 (s, 2H), 2.96 (s, 2H), 2.67-2.54 (m, 1H), 2.18 (t, J=7.4Hz, 2H), 1.77 (t, J=7.4Hz, 2H), 1.64-1.57 (m, 2H). HRMS (ESI) m / z: Calcd for C 28 H 24 FNO5(M+H) + 474.17167; Found 474.16992.

[0535] Embodiment 125:

[0536] Preparation of 8-((4-(3-chlorophenyl)piperidin-1-yl)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY125)

[0537] The preparation method is similar to that of Example 1, except that 4-(3-chlorophenyl)piperidine hydrochloride is used instead of piperidine hydrochloride to obtain a light yellow solid final product. 1H NMR (600MHz, DMSO-d6) δ7.85 (d, J=8.5Hz, 1H), 7.46 (d, J=8.8Hz, 1H), 7.37-7.29 ( m, 2H), 7.28-7.19 (m, 2H), 7.12 (d, J=2.4Hz, 1H), 7.06 (dd, J=8.5, 2.4Hz, 1H), 6.89 (d, J=8.8Hz, 1H), 5.21 (s, 2H), 4.00 (s, 2H), 2.92-2.88 (m, 2H), 2.59-2.56 (m, 1H), 2.17 (t, J=11.6Hz, 2H), 1.78 (d, J=12.6Hz, 2H), 1.62 (s, 2H). HRMS (ESI) m / z: Calcd for C 28 H 24 ClNO5(M+H) + 490.14212; Found 490.14218.

[0538] Example 126:

[0539] Preparation of 8-((4-(3-bromophenyl)piperidin-1-yl)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY126)

[0540] The preparation method is similar to that of Example 1, except that 4-(3-bromophenyl)piperidine is used instead of piperidine to obtain a beige solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.68 (s, 2H), 10.51 (s, 1H), 7.90 (d, J=8.5Hz, 1H), 7.75 (d, J=8.9H z, 1H), 7.42 (dd, J=7.6, 1.2Hz, 2H), 7.29 (t, J=7.7Hz, 1H), 7.23 (dt, J=7.9, 1.4Hz, 1H), 7.1 4-7.13 (m, 2H), 7.09 (dd, J=8.5, 2.4Hz, 1H), 5.27 (s, 2H), 4.71 (d, J=5.0Hz, 2H), 3.54 (d, J= 12.0Hz, 2H), 3.40-3.24(m, 2H), 2.93-2.87(m, 1H), 2.04-1.88(m, 4H).HRMS(ESI)m / z: Calcd for C 28 H 24 BrNO5(M+H) + 534.09161; Found 536.08826.

[0541] Embodiment 127:

[0542] Preparation of 8-((4-(3-propionylphenyl)piperidin-1-yl)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY127)

[0543] The preparation method is similar to that of Example 1, except that 4-(3-propionylphenyl)piperidine is used instead of piperidine to obtain a light yellow solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.66 (s, 1H), 10.48 (s, 1H), 7.90 (d, J=8.5Hz, 1H), 7.87-7.83 (m, 1H), 7.80 (d, J=2.0Hz, 1H), 7.75 (d, J=8.9Hz, 1H), 7.48 (dd, J=4.9, 1.3Hz, 2H), 7.14 (dd, J=5.7, 3.2H z, 2H), 7.11-7.06 (m, 1H), 5.28 (s, 2H), 4.71 (d, J=5.0Hz, 2H), 3.43-3.26 (m, 4H), 3.03 (q, J=7.1 Hz, 2H), 2.99-2.91 (m, 1H), 2.00 (t, J=12.3Hz, 4H), 1.07 (t, J=7.2Hz, 3H). HRMS (ESI) m / z: Calcd for C31H 29 NO6(M+H) + 512.20731; Found 512.20679.

[0544] Embodiment 128:

[0545] Preparation of 3,9-dihydroxy-8-((4-([1,1'-diphenyl]-3-yl)piperidin-1-yl]methyl)-5,7-dihydrobenzo[e]benzo[2,3]furo[4,5-c]oxepan-7-one (Compound TY128)

[0546] The preparation method is similar to that of Example 7, except that 4-(3-phenylphenyl)piperidine is used instead of 1-ene-7-heptylamine to obtain a yellow solid final product. 1H NMR (600MHz, DMSO-d6) δ7.83 (d, J=8.5Hz, 1H), 7.43 (d, J=8.8Hz, 1H), 7.29-7.16 (m, 9H), 7.09 (d, J=2.5Hz, 1H), 7.04 (dd, J=8.5, 2.5Hz, 1H), 6.86 ( d, J=8.8Hz, 1H), 5.21-5.14(m, 2H), 3.98(s, 2H), 2.96-2.93(m, 2H), 2.59 -1.57(m,1H),2.13-2.07(m,2H),1.84-1.47(m,4H).HRMS(ESI)m / z: Calcd for C 28 H 25 NO5(M+H) + 456.1800; Found 456.1808.

[0547] Embodiment 129:

[0548] Preparation of 3,9-dihydroxy-8-((4-(2-methoxyphenyl)piperidin-1-yl)methyl)benzo[5,6]oxazepa[4,3-b]benzofuran-7(5H)-one (Compound TY129)

[0549] The preparation method is similar to Example 38, except that 4-(2-methoxy)phenylpiperidine hydrochloride is used instead of 3-acetonitrilecyclobutylamine hydrochloride to obtain a yellow solid final product. 1 H NMR (600MHz, DMSO-d6) δ7.85 (d, J=8.5Hz, 1H), 7.45 (d, J=8.8Hz, 1H), 7.21-7.15 (m, 2H), 7.13 (d, J=2.5Hz, 1H), 7.05 (dd, J=8.5, 2.4Hz, 1H), 6 .96-6.86 (m, 3H), 5.21 (s, 2H), 3.98 (s, 2H), 3.77 (s, 3H), 3.00-2.83 (m, 3H), 2.18 (t, J=11.7Hz, 2H), 1.75-1.50 (m, 4H). HRMS (ESI) m / z: Calcd for C 29 H 27 NO6(M+H) + 486.1900; Found 486.5438.

[0550] Embodiment 130:

[0551] Preparation of 3,9-dihydroxy-8-((4-(2-hydroxyphenyl)piperidin-1-yl)methyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY130)

[0552] The preparation method is similar to that of Example 1, except that 4-(2-methoxy)phenylpiperidine is used instead of piperidine to obtain a brown solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.58 (s, 1H), 10.39 (s, 1H), 9.48 (s, 1H), 7.89 (d, J=8.5Hz, 1H), 7.74 (d, J=8.9Hz, 1H), 7.15-7.10 (m, 2H), 7.08 (dd, J=8.5, 2.5Hz, 1H), 7.01 (t, J=7.8Hz, 2H), 6.82-6.78 (m, 1H), 6.74 (td, J=7.5, 1.2Hz, 1H), 5.27 (s, 2H), 4.69 (d, J=5.1Hz, 2H), 3.53 (d, J=12.0Hz, 2H), 3.34 (s, 2H), 3.20-3.05 (m, 1H), 1.95-1.92 (m, 4H). HRMS (ESI) m / z: Calcd for C 28 H 25 NO6(M+H) + 472.1746; Found 472.1758.

[0553] Embodiment 131:

[0554] Preparation of 8-((4-(2-fluorophenyl)piperidin-1-yl)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY131)

[0555] The preparation method is similar to that of Example 1, except that 4-(2-fluorophenyl)piperidine is used instead of piperidine to obtain a brown solid final product. 1H NMR (600MHz, DMSO-d6) δ7.85 (d, J=8.5Hz, 1H), 7.45 (d, J=8.8Hz, 1H), 7.34 (td, J=7.7, 1.8Hz, 1H), 7.25 (tdd, J=7.5, 5.3, 1.8Hz, 1H), 7.19-7.10 (m, 3H) , 7.05 (dd, J=8.5, 2.5Hz, 1H), 6.89 (d, J=8.8Hz, 1H), 5.21 (s, 2H), 3.97 (s, 2 H), 3.05-2.66 (m, 3H), 2.18-2.16 (m, 2H), 1.72 (s, 4H). HRMS (ESI) m / z: Calcd for C 28 H 24 FNO5(M+H) + 474.17167; Found 474.16986.

[0556] Embodiment 132:

[0557] Preparation of 8-((4-(3,5-dichlorophenyl)piperidin-1-yl)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY132)

[0558] The preparation method is similar to Example 38, except that 4-(3,5-dichlorophenyl)-piperidine hydrochloride is used instead of 3-acetonitrile cyclobutylamine hydrochloride to obtain a yellow solid final product. 1 H NMR (400MHz, Chloroform-d) δ7.92 (d, J=8.5Hz, 1H), 7.38 (d, J=8.8Hz, 1H), 7.20 (t, J=1.9Hz, 1H), 7.13-7.05 (m, 3H), 7.01 (d, J=2.4Hz, 1H), 6. 97 (d, J=8.8Hz, 1H), 5.11 (s, 2H), 4.26 (s, 2H), 3.23 (d, J=11.6Hz, 2H), 2.65-2.52 (m, 1H), 2.46 (s, 2H), 1.96-1.74 (m, 4H). HRMS (ESI) m / z: Calcd for C 28 H 23 NO5Cl2(M+H) + 524.10315; Found 524.10089.

[0559] Embodiment 133:

[0560] Preparation of 3,9-dihydroxy-11-isopropyl-8-((4-methylpiperidin-1-yl)methyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY133)

[0561] The preparation method is similar to that of Example 1, except that 4-methylpiperidine is used instead of piperidine, and 2-isopropyl-1,4-benzoquinone is used instead of benzoquinone to obtain a light yellow oily final product. 1 H NMR (600MHz, DMSO-d6) δ7.91 (d, J=8.4Hz, 1H), 7.13 (d, J=2.4Hz, 1H), 7.10 (dd, J=8.4, 2.4Hz, 1H), 6.99 (d, J=3.3Hz, 1H), 5.26 (s, 2H), 4.58 (d, J=5.1Hz, 2H), 3.51-3.37 (m, 3H), 3.15-3.03 (m, 2H), 1.79 (d, J=14.0Hz, 2H), 1.36 (d, J=6.9Hz, 6H), 0.89 (d, J=6.5Hz, 3H). HRMS (ESI) m / z: Calcd for C 26 H 30 NO5(M+H) + 436.21240; Found 436.21173.

[0562] Embodiment 134:

[0563] Preparation of 11-bromo-3,9-dihydroxy-8-[(4-methylpiperidin-1-yl)methyl]-5,7-dihydrobenzo[e]benzo[2,3]furo[4,5-c]oxepan-7-one (Compound TY134)

[0564] The preparation method is similar to Example 63, except that 4-methylpiperidine is used instead of azetidine to obtain a yellow solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.83 (s, 1H), 10.73 (s, 1H), 7.88 (d, J=8.5Hz, 1H), 7.31 (s, 1H), 7.15-7.08 (m, 2H), 5.28 (s, 2H), 4.60 (d, J=4.0Hz, 2H), 3.17 (s, 3H), 2.82 (d, J=4.4Hz, 1H), 1.88-1.75 (m, 4H), 1.64 (p, J=5.8Hz, 4H). HRMS (ESI) m / z: Calcd for C 23 H 22 BrNO5(M+H) +472.0750; Found 472.0758.

[0565] Embodiment 135:

[0566] Preparation of 3,9-dihydroxy-11-methyl-8-(piperidin-1-ylmethyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY135)

[0567] The preparation method is similar to that of Example 1, except that 2-methyl-1,4-benzoquinone is used instead of p-benzoquinone to obtain a light yellow solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.69 (s, 1H), 10.35 (s, 1H), 7.92 (d, J = 8.5Hz, 1H), 7.12 (d, J = 2.4Hz, 1H), 7.09 (dd, J = 8.5, 2.4Hz, 1H), 6.94 (s, 1H), 5.7 6(s, 3H), 5.25(s, 2H), 4.60(s, 2H), 3.37(d, J=13.5Hz, 2H), 3.09(s, 2H) , 1.83 (d, J=12.7Hz, 2H), 1.67 (d, J=14.5Hz, 3H), 1.44 (d, J=15.9Hz, 1H). 13 C NMR (151MHz, DMSO-d6) δ166.53, 161.15, 158.65, 155.04, 147.13, 137.94, 128.91, 127.64, 124.64, 119.59, 11 7.52, 116.33, 115.71, 109.86, 106.30, 69.12, 55.45, 52.02, 44.64, 22.94, 21.69, 15.24.HRMS (ESI) m / z: Calcd for C 23 H 23 NO5(M+H) + 394.16544; Found 394.16467.

[0568] Embodiment 136:

[0569] Preparation of 11-ethyl-3,9-dihydroxy-8-(piperidin-1-ylmethyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY136)

[0570] The preparation method is similar to that of Example 1, except that 2-ethyl-1,4-benzoquinone is used instead of p-benzoquinone to obtain a yellow solid final product. 1H NMR (600MHz, DMSO-d6) δ7.90 (d, J=8.5Hz, 1H), 7.11 (d, J=2.4Hz, 1H), 7.08 (dd, J=8.5, 2.4Hz, 1H), 6.88 (s, 1H) , 5.23 (s, 2H), 4.38 (s, 2H), 3.01 (s, 2H), 2.90 (q, J=7.6Hz, 3H), 1.59 (d, J=99.1Hz, 8H), 1.31 (t, J=7.6Hz, 3H). 13 C NMR (151MHz, DMSO-d6) δ160.86, 158.34, 158.14, 155.14, 146.52, 137.91, 128.64, 119.66, 118.83, 11 7.44, 116.84, 116.29, 114.25, 109.85, 68.91, 53.19, 49.07, 22.62, 14.35, 0.58. HRMS (ESI) m / z: Calcd for C 24 H 25 NO5(M+H) + 408.18109; Found 408.18021.

[0571] Embodiment 137:

[0572] Preparation of 3,9-dihydroxy-11-isopropyl-8-(piperidin-1-ylmethyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY137)

[0573] The preparation method is similar to that of Example 1, except that 2-isopropyl-1,4-benzoquinone is used instead of p-benzoquinone to obtain an off-white solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.65 (s, 1H), 10.32 (s, 1H), 7.91 (d, J = 8.4Hz, 1H), 7.21-7.07 (m, 2H), 6.99 (s, 1H), 5.26 (s, 2H), 4.60 (d, J = 4.8Hz, 2H), 3.50-3.29 (m, 3H), 3.15-3.03 (m, 2H), 1.84 (d, J=13.9Hz, 2H), 1.77-1.60 (m, 3H), 1.36 (d, J=6.9Hz, 6H), 0.87-0.78 (m, 1H). HRMS (ESI) m / z: Calcd for C 25 H 28 NO5(M+H) + 422.19675; Found 422.19553.

[0574] Embodiment 138:

[0575] Preparation of 11-cyclopropyl-3,9-dihydroxy-8-(piperidin-1-ylmethyl)benzo[5,6]oxazepa[4,3-b]benzofuran-7(5H)-one (Compound TY138)

[0576] The preparation method is similar to that of Example 1, except that 2-cyclopropyl-1,4-benzoquinone is used instead of p-benzoquinone to obtain a yellow solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.64 (s, 1H), 10.24 (s, 1H), 7.92 (d, J = 8.5Hz, 1H), 7.13 (d, J = 2.4Hz, 1H), 7.10 (dd, J = 8.5, 2.4Hz, 2H) , 5.26 (s, 2H), 4.58 (s, 2H), 3.09 (s, 2H), 2.41-2.34 (m, 1H), 1.91-1.60 (m, 8H), 1.15 (dd, J=8.4, 2.2Hz, 2H), 0.93-0.86 (m, 2H). 13 C NMR (151MHz, DMSO-d6) δ165.86, 160.50, 158.03, 154.68, 146.35, 137.33, 130.38, 128.26, 127.13, 119.21, 11 8.93, 116.90, 115.29, 109.57, 109.10, 105.09, 68.49, 51.39, 22.33, 21.04, 9.65, 8.54. HRMS (ESI) m / z: Calcd for C 25 H 25 NO5(M+H) + 420.18109; Found 420.18015.

[0577] Embodiment 139:

[0578] Preparation of 11-(tert-butyl)-3,9-dihydroxy-8-(piperidin-1-ylmethyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY139)

[0579] The preparation method is similar to that of Example 1, except that 2-tert-butyl-1,4-benzoquinone is used instead of benzoquinone to obtain a milky white solid final product. 1H NMR (600MHz, DMSO-d6) δ10.64 (s, 1H), 10.28 (s, 1H), 7.87 (d, J=9.1Hz, 1H), 7.15-7.10 (m, 3H), 7.04 (s, 1H), 5.26 (s, 2H), 4.57 (d, J=5.1Hz, 2H), 3.41-3.34 (m, 2H), 3.14-3.04 (m, 3H), 1.83 (d, J=13.8Hz, 2H), 1.68-1.43 (m, 4H), 1.49 (s, 9H). HRMS (ESI) m / z: Calcd for C 26 H 29 NO5(M+H) + 436.21239; Found 436.21198.

[0580] Embodiment 140:

[0581] Preparation of 3,9,11-trihydroxy-8-(piperidin-1-ylmethyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY140)

[0582] The preparation method is as follows: Example 63, except that the steps after 11-bromo-9-hydroxy-3-methoxybenzo[5,6]oxazolidinone[4,3-b]benzofuran-7(5H)-one are as follows:

[0583] Under nitrogen protection and at -20°C, boron tribromide (4.0 eq, 1 M in DCM) was added dropwise to ultra-dry dichloromethane containing 11-bromo-9-hydroxy-3-methoxybenzo[5,6]oxazo[4,3-b]benzofuran-7(5H)-one (1.0 eq), and then reacted at room temperature overnight. After completion of the reaction monitored by TLC, the reaction was quenched with methanol, concentrated under reduced pressure, washed with methanol, and filtered to obtain 11-bromo-3,9-dihydroxybenzo[5,6]oxazo[4,3-b]benzofuran-7(5H)-one as a solid;

[0584] 11-Bromo-3,9-dihydroxybenzo[5,6]oxazo[4,3-b]benzofuran-7(5H)-one (1.0 eq), imidazole (4.0 eq), and tert-butyldimethylsilyl chloride (4.0 eq) were added to N,N-dimethylformamide and reacted at room temperature for about 3 h. After TLC detection, the reaction was quenched with glacial sodium bicarbonate aqueous solution, extracted with ethyl acetate, and purified by silica gel column chromatography to obtain 11-bromo-3,9-bis((tert-butyldimethylsilyl)oxy)benzo[5,6]oxazo[4,3-b]benzofuran-7(5H)-one;

[0585] Under nitrogen protection, to a solution of 11-bromo-3,9-bis((tert-butyldimethylsilyl)oxy)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (1.0 eq) in 1,4-dioxane was added bis(pinacolato)diboron (1.5 eq), potassium acetate (3.0 eq), and tetrakistriphenylphosphine palladium (10% wt), and the mixture was reacted at 90°C overnight. TLC monitored the formation of an intermediate transition product, and then 30% H2O2 (4.0 eq) was added to the reaction solution. The reaction was allowed to react at room temperature for 4-6 hours. After the intermediate transition product was complete as monitored by TLC, the reaction was quenched with water, extracted with ethyl acetate, and purified by silica gel column chromatography to obtain 3,9-bis((tert-butyldimethylsilyl)oxy)-11-hydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one.

[0586] 3,9-bis((tert-butyldimethylsilyl)oxy)-11-hydroxybenzo[5,6]oxazo[4,3-b]benzofuran-7(5H)-one (1.0 eq) and triphenylphosphine (5.0 eq) were dissolved in tetrahydrofuran, methanol (10 eq) was added, and then diisopropyl azodicarboxylate (5.0 eq) was slowly added dropwise under ice bath. After the addition was completed, the reaction was monitored by TLC, and water was added to quench the reaction. The product was extracted with ethyl acetate and purified by silica gel column chromatography to obtain 3,9-bis((tert-butyldimethylsilyl)oxy)-11-methoxybenzo[5,6]oxazo[4,3-b]benzofuran-7(5H)-one.

[0587] Tetramethylammonium fluoride (4.0 eq) was added dropwise to a tetrahydrofuran solution containing 3,9-bis((tert-butyldimethylsilyl)oxy)-11-methoxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (1.0 eq), and the mixture was reacted at 60°C for 1 h. After completion of the reaction, the reaction solution was directly concentrated under reduced pressure and purified by silica gel column chromatography to obtain 3,9-dihydroxy-11-methoxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one.

[0588] 3,9-Dihydroxy-11-methoxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (1.0 eq), 37% formaldehyde (4.0 eq), and piperidine (2.0 eq) were added to ethanol and stirred at room temperature for 12 h. After completion of the reaction, the reaction solution was directly concentrated under reduced pressure and purified by silica gel column chromatography to obtain 3,9-dihydroxy-11-methoxy-8-(piperidin-1-ylmethyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY141);

[0589] TY141 (1.0 eq) was dissolved in ultra-dry dichloromethane, and BBr3 (1 M in DCM) was added dropwise at -20°C. The mixture was stirred at room temperature for 12 h. After completion of the reaction monitored by TLC, the reaction solution was directly concentrated under reduced pressure and purified by C18 column chromatography to obtain the final product as a brown solid. 1 H NMR (600MHz, Methanol-d4) δ7.98 (d, J=8.5Hz, 1H), 7.13-7.03 (m, 2H), 6.58 (s, 1H), 5.23 (s, 2H), 4.55 (s, 2H), 3.54 (d, J=12.8Hz, 2H), 3.12 (s, 2H), 1.97 (d, J=12.8Hz, 2H), 1.85-1.52 (m, 4H). HRMS (ESI) m / z: Calcd for C 22 H 21 NO6(M+H) + 396.14;Found 396.14.

[0590] Embodiment 141:

[0591] Preparation of 3,9-dihydroxy-11-methoxy-8-(piperidin-1-ylmethyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY141)

[0592] The preparation method was prepared by referring to Example 140 to obtain a yellow solid final product. 1 H NMR (600MHz, Methanol-d4) δ7.84 (d, J=8.5Hz, 1H), 6.99-6.89 (m, 2H), 6.50 (s, 1H), 5.13 (s, 2H), 4.21 (s, 2H), 3.95 (s, 3H), 2.87 (s, 3H), 1.78-1.54 (m, 7H). HRMS (ESI) m / z: Calcd for C 23 H 23 NO6(M+H) + 410.16; Found 410.4467.

[0593] Embodiment 142:

[0594] Preparation of 11-chloro-3,9-dihydroxy-8-(piperidin-1-ylmethyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY142)

[0595] The preparation method is similar to Example 63, except that 2-chloro-1,4-benzoquinone is used instead of 2-bromo-1,4-benzoquinone, and piperidine is used instead of azocyclobutane to obtain a yellow solid final product.1 H NMR (600MHz, DMSO-d6) δ10.81 (s, 1H), 10.71 (s, 1H), 7.90 (d, J = 8.5Hz, 1H), 7.19 (s, 1H), 7.14 (d, J = 2.4Hz, 1H), 7.11 (dd, J = 8.5, 2.4Hz, 1 H), 5.29 (s, 2H), 4.62 (d, J=5.0Hz, 2H), 3.37 (s, 3H), 3.03-3.00 (m, 1H), 1.84 (d, J=14.3Hz, 2H), 1.70-1.63 (m, 4H). HRMS (ESI) m / z: Calcd for C 22 H 20 ClNO5(M+H) + 414.1095; Found 414.1108.

[0596] Embodiment 143:

[0597] Preparation of 11-bromo-3,9-dihydroxy-8-(piperidin-1-ylmethyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY143)

[0598] The preparation method is similar to Example 63, except that piperidine is used instead of azocyclobutane to obtain a yellow solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.80 (s, 1H), 10.72 (s, 1H), 7.88 (d, J=8.5Hz, 1H), 7.31 (s, 1H), 7.23-7.09 (m, 2H), 5.28 (s, 2H), 4.61 (d, J=4.7Hz, 2H), 3.37 (s, 2H), 3.11 (s, 2H), 1.84 (d, J=12.0Hz, 2H), 1.70-1.60 (m, 3H), 1.44 (d, J=13.2Hz, 1H). HRMS (ESI) m / z: Calcd for C 22 H 20 NO5(M+H) + 458.0594; Found 458.5087.

[0599] Embodiment 144:

[0600] Preparation of 11-cyclohexyl-3,9-dihydroxy-8-(piperidin-1-ylmethyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY144)

[0601] The preparation method is similar to that of Example 1, except that 2-cyclohexyl-1,4-benzoquinone is used instead of benzoquinone to obtain a brown solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.65 (s, 1H), 10.30 (s, 1H), 7.97-7.81 (m, 1H), 7.11 (d, J=8.1Hz, 2H), 6.96 (s, 1H), 5.25 (s, 2H), 4.58 (d, J=4.6Hz, 2H), 3.45-3.40 (m, 2H), 3.08-3.05 (m, 2H), 1.99-1.24 (m, 17H). 13 C NMR (151MHz, DMSO-d6) δ166.42, 161.09, 158.36, 155.21, 146.01, 137.87, 134.22, 128.80, 127.94, 119.51, 117.57, 1 16.28, 112.39, 109.68, 106.33, 69.04, 49.06, 40.52, 38.64, 32.77, 26.65, 26.12, 22.96, 21.62.HRMS (ESI) m / z: Calcd for C 28 H 31 NO5(M+H) + 462.22804; Found 462.22632.

[0602] Embodiment 145:

[0603] Preparation of 11-(cyclohex-1-enyl)-8-(hexahydropyridin-1-ylmethyl)-3,9-dihydroxy-5,7-dihydrobenzo[e]benzo[2,3]furo[4,5-c]oxepan-7-one (Compound TY145)

[0604] The preparation method is as follows: Example 63, except that the steps after 11-bromo-9-hydroxy-3-methoxybenzo[5,6]oxazolidinone[4,3-b]benzofuran-7(5H)-one are as follows:

[0605] Under nitrogen, to a solution of 11-bromo-9-hydroxy-3-methoxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (1.0 eq) in 1,4-dioxane were added 1-cyclohexeneboronic acid (5.0 eq), potassium carbonate (5.0 eq), tetrakistriphenylphosphine palladium (10% wt), and 2 drops of pure water. The mixture was allowed to react overnight at 90°C. After completion of the reaction, monitored by TLC, the mixture was concentrated under reduced pressure and purified by silica gel column chromatography to obtain 11-(cyclohex-1-en-1-yl)-9-hydroxy-3-methoxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one.

[0606] 11-(Cyclohex-1-en-1-yl)-9-hydroxy-3-methoxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (1.0 eq) was dissolved in ultra-dry dichloromethane. Boron tribromide (4.0 eq, 1 M in DCM) was added dropwise at -20°C and allowed to react overnight at room temperature. After completion of the reaction, monitored by TLC, the reaction was quenched with methanol, the solvent was concentrated under reduced pressure, and the product was purified by silica gel column chromatography to obtain 1-(cyclohex-1-en-1-yl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one.

[0607] 1-(Cyclohex-1-en-1-yl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (1.0 eq) was dissolved in ethanol, and the pH was adjusted to a weak base with N,N-diisopropylethylamine. Formaldehyde (4.0 eq) and piperidine (3.0 eq) were then added to the reaction tube. The atmosphere was purged with nitrogen three times and the reaction was continued at 80°C for 8 h. After completion of the reaction, the mixture was concentrated under reduced pressure and purified by C18 column chromatography to obtain the final product as an off-white solid. 1 H NMR (600MHz, Methanol-d4) δ7.87 (d, J=8.5Hz, 1H), 7.07 (dd, J=8.5, 2.4Hz, 1H), 7.04 (d, J=2.4Hz, 1H), 6.96 (s, 1H), 6.49 (s, 1H), 5.22 (s, 2H), 4.61 (s, 2 H), 3.54 (d, J=12.6Hz, 2H), 3.18-3.09 (m, 2H), 2.56 (s, 2H), 2.32 (dt, J=3.9, 2.5Hz, 2H), 1.95 (d, J=14.6Hz, 2H), 1.89-1.69 (m, 8H). HRMS (ESI) m / z: Calcd for C 28 H 29 NO5(M+H) + 460.2105: Found 460.5507.

[0608] Embodiment 146:

[0609] Preparation of 3,9-dihydroxy-11-(4-methylcyclohexyl)-8-(piperidin-1-ylmethyl)benzo[5,6]oxazepa[4,3-b]benzofuran-7(5H)-one (Compound TY146)

[0610] The preparation method is similar to that of Example 1, except that 2-(4-methylcyclohexyl)cyclohexa-2,5-diene-1,4-dione is used instead of benzoquinone to obtain a yellow solid final product. 1H NMR (600MHz, DMSO-d6) δ10.65 (s, 1H), 10.31 (s, 1H), 7.89 (dd, J=14.9, 8.3Hz, 1H), 7.21-7.06 (m, 2H), 7.00 (d, J=39.9Hz, 1H), 5 .25 (s, 2H), 4.59 (s, H), 3.52-3.32 (m, 2H), 3.18-2.99 (m, 3H), 2.20-1.41 (m, 16H), 1.08 (d, J=7.1Hz, 3H).HRMS (ESI) m / z: Calcd for C 29 H 33 NO5(M+H) + 476.24369; Found 476.24191.

[0611] Embodiment 147:

[0612] Preparation of 11-(cyclopent-1-enyl)-8-(hexahydropyridin-1-ylmethyl)-3,9-dihydroxy-5,7-dihydrobenzo[e]benzo[2,3]furo[4,5-c]oxepan-7-one (Compound TY147)

[0613] The preparation method is similar to Example 145, except that 1-cyclopenteneboronic acid is used instead of 1-cyclohexeneboronic acid to obtain a yellow solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.61 (d, J=11.5Hz, 1H), 10.35 (s, 1H), 7.93 (d, J=8.3Hz, 1H), 7.14-7.11 (m, 2H), 7.04 (s, 1H), 6.89 (p, J=2.3Hz, 1H), 5.27 ( s, 2H), 4.65-4.56 (m, 2H), 2.82 (tt, J=6.8, 2.2Hz, 2H), 2.69-2.63 (m, 2H) , 2.05-1.99(m, 2H), 1.78-1.59(m, 8H), 1.23(s, 2H).HRMS(ESI)m / z: Calcd for C 27 H 27 NO5(M+H) + 446.1949; Found 446.1968.

[0614] Embodiment 148:

[0615] Preparation of 11-cycloheptyl-3,9-dihydroxy-8-(piperidin-1-ylmethyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY148)

[0616] The preparation method is similar to that of Example 1, except that 2-cycloheptyl-1,4-benzoquinone is used instead of benzoquinone to obtain a yellow solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.66 (s, 1H), 10.30 (s, 1H), 8.14-7.76 (m, 1H), 7.12-7.11 (m, 2H), 6.96 (s, 1H), 5.25 (s, 2H), 4. 57(s, 2H), 3.39-3.35(m, 2H), 3.25-3.20(m, 1H), 3.09(s, 2H), 1.95-1.90(m, 2H), 1.89-1.76(m, 6H), 1.75-1.52(m, 10H). 13 C NMR (151MHz, DMSO-d6) δ165.50, 161.16, 158.44, 155.23, 145.67, 137.95, 135.96, 128.82, 128.05, 119.60, 117.65, 1 16.35, 112.45, 109.78, 106.20, 69.10, 52.13, 40.78, 40.57, 35.00, 28.08, 27.16, 23.01, 21.69.HRMS (ESI) m / z: Calcd for C 29 H 33 NO5(M+H) + 476.24369; Found 476.24225.

[0617] Embodiment 149:

[0618] Preparation of 8-(hexahydropyridin-1-ylmethyl)-3,9-dihydroxy-11-(pyridin-4-yl)-5,7-dihydrobenzo[e]benzo[2,3]furo[4,5-c]oxepan-7-one compound TY149

[0619] The preparation method is similar to Example 145, except that 4-pyridineboronic acid is used instead of 1-cyclohexeneboronic acid to obtain a yellow-brown solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.59 (s, 1H), 8.80-8.77 (m, 2H), 7.94-7.88 (m, 3H), 7.30 (s, 1H), 7.13 (d, J=2.4Hz, 1H), 7.10 (dd, J=8.5, 2.4Hz, 1H), 5.28 (s, 2H), 4.47 (s, 2H), 3.66-3.58 (m, 2H), 3.17 (s, 2H), 1.70 (s, 6H). HRMS (ESI) m / z: Calcd for C27 H 24 N2O5(M+H) + 457.1755; Found 457.1768.

[0620] Embodiment 150:

[0621] Preparation of 3,9-dihydroxy-8-(piperidin-1-ylmethyl)-11-(pyrimidin-5-yl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY150)

[0622] The preparation method is similar to Example 145, except that 5-pyrimidineboronic acid is used instead of 1-cyclohexeneboronic acid to obtain a yellow solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.79 (s, 1H), 10.69 (s, 1H), 9.33 (s, 2H), 8.62 (s, 1H) , 7.89 (dd, J=12.8, 8.5Hz, 1H), 7.34 (s, 1H), 7.15-7.13 (m, 1H), 7.10 (dd, J=8.5 , 2.5Hz, 1H), 5.29 (s, 2H), 4.71 (d, J=5.1Hz, 2H), 3.46-3.39 (m, 3H), 1.87 (d, J =14.1Hz, 2H), 1.73-1.65 (m, 4H), 1.47 (d, J = 12.7Hz, 1H). HRMS (ESI) m / z: Calcd for C 26 H 23 N3O5(M+H) + 458.1700; Found 458.4947.

[0623] Embodiment 151:

[0624] Preparation of 3,9-dihydroxy-11-phenyl-8-(piperidin-1-ylmethyl)benzo[5,6]oxazepa[4,3-b]benzofuran-7(5H)-one (Compound TY151)

[0625] The preparation method is similar to that of Example 145, except that phenylboronic acid is used instead of 1-cyclohexeneboronic acid to obtain a yellow solid product. 1H NMR (600MHz, DMSO-d6) δ10.65 (s, 1H), 10.55 (s, 1H), 7.85 (dd, J=8.4, 1.0Hz, 3H), 7.61 (t, J=7.8Hz, 2H), 7.52 (s, 1H), 7.24 (s, 1H), 7.16-7.06 (m, 2H ), 5.28 (s, 2H), 4.68 (d, J = 5.1Hz, 2H), 3.49-3.38 (m, 2H), 3.17 (s, 2H), 1.8 5 (s, 2H), 1.68 (d, J = 11.9Hz, 3H), 1.53-1.42 (m, 1H). HRMS (ESI) m / z: Calcd for C 28 H 25 NO5(M+H) + 456.1809; Found 456.1808.

[0626] Embodiment 152:

[0627] Preparation of 3,9-dihydroxy-11-(4-isopropylphenyl)-8-(piperidin-1-ylmethyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY152)

[0628] The preparation method is similar to Example 145, except that 4-isopropylphenylboronic acid is used instead of 1-cyclohexeneboronic acid to obtain a yellow-white solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.67 (s, 1H), 10.55 (s, 1H), 7.86 (d, J=8.5Hz, 1H), 7.80-7.77 (m, 2H), 7.50 -7.47 (m, 2H), 7.23 (s, 1H), 7.13 (d, J=2.4Hz, 1H), 7.10 (dd, J=8.5, 2.4Hz, 1H), 5.28 (s, 2H), 4.66 (d , J=4.6Hz, 2H), 3.16 (d, J=6.6Hz, 2H), 2.99-2.97 (m, 1H), 1.86 (d, J=13.8Hz, 2H), 1.68 (dd, J=17.8, 10.7Hz, 3H), 1.46 (d, J=12.1Hz, 1H), 1.28 (d, J=6.9Hz, 6H), 1.25-1.18 (m, 2H). HRMS (ESI) m / z: Calcd for C 31 H 31 NO5(M+H) + 498.2271; Found 498.2278.

[0629] Embodiment 153:

[0630] Preparation of 3,9-dihydroxy-11-(4-trifluoromethylphenyl)-8-(piperidin-1-ylmethyl)benzo[5,6]oxazepa[4,3-b]benzofuran-7(5H)-one (Compound TY153)

[0631] The preparation method is similar to Example 145, except that 4-trifluoromethylboric acid is used instead of 1-cyclohexeneboric acid to obtain a yellow solid final product. 1 H NMR (600MHz, Methano1-d4) δ 8.11-8.06 (m, 2H), 7.95-7.90 (m, 3H), 7.28-7.25 (m, 1H), 7.10 (d, J=7.9Hz, 2H), 5.30 (s, 2H), 4. 76 (d, J=13.3Hz, 2H), 3.66-3.59 (m, 2H), 3.30-3.22 (m, 2H), 2.03 (d, J=14.8Hz, 2H), 1.91-1.75 (m, 4H). HRMS (ESI) m / z: Calcd for C 29 H 24 F3NO5(M+H) + 524.1664; Found 524.5157.

[0632] Embodiment 154:

[0633] Preparation of 3,9-dihydroxy-11-(4-fluorophenyl)-8-(piperidin-1-ylmethyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY154)

[0634] The preparation method is similar to Example 145, except that 4-fluorophenylboric acid is used instead of 1-cyclohexeneboric acid to obtain a bright yellow solid final product. 1 H NMR (600MHz, DMSO-d6) δ7.93 (dd, J=8.7, 5.6Hz, 2H), 7.84 (d, J=8.5Hz, 1H), 7.39 (t, J=8.8Hz, 2H), 7.11 (d, J=2.5Hz, 1H), 7.06 ( dd, J=8.5, 2.4Hz, 1H), 7.02 (s, 1H), 5.19 (s, 2H), 4.0 (s, 2H), 2.46 (s, 4H), 1.53-1.51 (m, 4H), 1.40 (m, 2H). HRMS (ESI) m / z: Calcd for C 28 H 24 FNO5(M+H) + 474.1700; Found 474.5087.

[0635] Embodiment 155:

[0636] Preparation of 3,9-dihydroxy-11-(4-vinylphenyl)-8-(piperidin-1-ylmethyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY155)

[0637] The preparation method is similar to Example 145, except that potassium ethylene trifluoroborate is used instead of 1-cyclohexeneboric acid to obtain a white solid final product. 1 H NMR (600MHz, Methanol-d4) δ7.93 (d, J=8.5Hz, 1H), 7.07-7.02 (m, 2H), 7.02-6.95 (m, 2H), 6.19 (dd, J=17.8, 1.2Hz, 1H), 5 .56 (dd, J=11.2, 1.2Hz, 1H), 5.19 (s, 2H), 4.25 (s, 2H), 2.81 (s, 4H), 1.72-1.68 (m, 4H), 1.59 (s, 2H). HRMS (ESI) m / z: Calcd for C 24 H 23 NO5(M+H) + 406.1650; Found 406.4587.

[0638] Embodiment 156:

[0639] Preparation of 3,9-dihydroxy-11-(3,5-difluorophenyl)-8-(piperidin-1-ylmethyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY156)

[0640] The preparation method is similar to Example 145, except that 3,5-difluorophenylboric acid is used instead of 1-cyclohexeneboric acid to obtain a yellow-white solid final product. 1 H NMR (600MHz, Methanol-d4) δ7.90 (d, J=8.5Hz, 1H), 7.54-7.49 (m, 2H), 7.22 (s, 1H), 7.15-7.08 (m, 3H), 5.29 (s, 2H), 4.72 (s, 2H) , 3.61 (d, J=12.5Hz, 2H), 3.28-3.19 (m, 2H), 2.02 (d, J=14.6Hz, 2H), 1.82-1.79 (mz, 4H), 1.67-1.56 (m, 2H). HRMS (ESI) m / z: Calcd for C 28 H 23 F2NO5(M+H)+ 492.1613; Found 492.1618.

[0641] Embodiment 157:

[0642] Preparation of 3,9-dihydroxy-11-(4-hydroxyphenyl)-8-(piperidin-1-ylmethyl)benzo[5,6]oxazepa[4,3-b]benzofuran-7(5H)-one (Compound TY157)

[0643] The preparation method is similar to Example 145, except that 4-hydroxyphenylboronic acid is used instead of 1-cyclohexeneboronic acid to obtain a yellow-green solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.48 (s, 1H), 9.80 (s, 1H), 7.86 (d, J=8.5Hz, 1H), 7.69 (d, J=8.6Hz, 2H), 7.22-7.04 (m, 3H), 6.97 (d, J= 8.6Hz, 2H), 5.26 (s, 2H), 4.46 (s, 2H), 3.70-3.53 (m, 2H), 3.14 (d, J=7.5Hz, 2H), 1.70 (s, 4H), 1.52 (s, 2H). HRMS (ESI) m / z: Calcd for C 28 H 25 NO6(M+H) + 472.1753; Found 472.1758.

[0644] Embodiment 158:

[0645] Preparation of 3,9-dihydroxy-11-(naphthyl-2-yl)-8-(piperidin-1-ylmethyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY158)

[0646] The preparation method is similar to Example 145, except that 2-naphthaleneboronic acid is used instead of 1-cyclohexeneboronic acid to obtain a yellow solid final product. 1H NMR (600MHz, DMSO-d6) δ10.54 (s, 1H), 8.43 (d, J=1.8Hz, 1H), 8.13-8.08 (m , 2H), 8.04-7.99 (m, 2H), 7.88 (d, J=8.5Hz, 1H), 7.62-7.58 (m, 2H), 7.28-7. 21 (m, 1H), 7.12 (d, J=2.5Hz, 1H), 7.08 (dd, J=8.5, 2.5Hz, 1H), 5.24 (s, 2H) , 4.41(s, 2H), 2.65(s, 2H), 1.60(s, 4H), 1.47(s, 2H).HRMS(ESI)m / z: Calcd for C 32 H 27 NO5(M+H) + 506.1948; Found 506.5787.

[0647] Embodiment 159:

[0648] Preparation of 3,9-dihydroxy-11-benzyloxy-8-(piperidin-1-ylmethyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY159)

[0649] The preparation method is similar to Example 141, except that benzyl alcohol is used instead of methanol to obtain a white solid final product. 1 H NMR (600MHz, DMSO-d6) δ7.82 (d, J=8.5Hz, 1H), 7.54-7.50 (m, 2H), 7.43 (dd, J=8.4, 6.8Hz, 2H), 7.39-7.35 (m, 1H), 7.09 (d, J=2.4Hz, 1H), 7.03 ( dd, J=8.5, 2.5Hz, 1H), 6.61 (s, 1H), 5.28 (s, 2H), 5.16 (s, 2H), 3.87 (s, 2H), 3.33 (s, 2H), 2.40 (s, 2H), 1.55-1.37 (m, 6H), .HRMS (ESI) m / z: Calcd for C 29 H 27 NO6(M+H) + 486.1918; Found 486.5438.

[0650] Embodiment 160:

[0651] Preparation of 11-(1-bromo-5-hydroxypentane)-3,9-dihydroxy-8-(piperidin-1-ylmethyl)benzo[5,6]oxazepine[4,3-b]benzofuran-7(5H)-one (Compound TY160)

[0652] The preparation method is similar to that of Example 1, except that 2-(4'-tetrahydropyran)-1,4-benzoquinone is used instead of benzoquinone to obtain a light grey solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.65 (s, 1H), 10.32 (s, 1H), 7.90 (d, J=8.4Hz, 1H), 7.13-7.10 (m, 2H), 6.97 (s, 1H), 5.26 (s, 2H), 4.60 (s, 2H), 3 .61-3.31 (m, 4H), 3.29-3.21 (m, 2H), 3.14-3.05 (m, 2H), 2.41-2.23 (m, 1H), 2.08-1.57 (m, 9H), 1.48-1.43 (m, 1H). HRMS (ESI) m / z: Calcd for C 27 H 30 BrNO6(M+H) + 544.13347; Found 544.13326.

[0653] Embodiment 161:

[0654] 3,9-dihydroxy-8-((4-(1-hydroxybutyl)piperidin-1-yl)methyl)benzo[5,6]oxepin Preparation of [4,3-b]benzofuran-7(5H)-one (Compound TY161)

[0655] The preparation method is as follows: Example 86, except that the steps after compound TY086 are:

[0656] Compound TY086 (1.0 eq) was dissolved in methanol, sodium cyanoborohydride (3.0 eq) was added, and concentrated hydrochloric acid was added dropwise under ice bath until the reaction solution was free of bubbles. After completion of the reaction monitored by TLC, the reaction solution was concentrated under reduced pressure and purified by C18 column chromatography to obtain the final product as a white solid. 1H NMR (600 MHz, DMSO-d6) δ 10.67 (s, 1H), 10.41 (s, 1H), 7.88 (d, J = 8.5 Hz, 1H), 7.72 (d, J = 8.9 Hz, 1H), 7.15-7.09 (m, 2H), 7.08 (dd, J = 8.5, 2.4 Hz, 1H), 5.26 (s, 2H), 4.62 (t, J = 4.1 Hz, 2H), 3.43 (d , J=15.1Hz, 2H), 3.20-3.18 (m, 1H), 3.11 (s, 2H), 1.95-1.79 (m, 2H), 1.71 (d, J=13.3Hz, 1H), 1. 65-1.45(m, 2H), 1.43-1.37(m, 1H), 1.31-1.22(m, 3H), 0.92-0.81(m, 4H).HRMS(ESI)m / z: Calcd for C 26 H 29 NO6(M+H)+452.20645; Found 452.20731.

[0657] Embodiment 162:

[0658] 8-((4-(cyclopropanecarbonyl)piperidin-1-yl)methyl)-3,9-dihydroxybenzo[5,6]oxepin Preparation of [4,3-b]benzofuran-7(5H)-one (Compound TY162)

[0659] The preparation method was similar to that of Example 38, except that 4-(cyclopropylcarbonyl)piperidine hydrochloride was used instead of 3-acetonitrilecyclobutylamine hydrochloride to obtain the final product as a pale yellow solid. 1H NMR (600 MHz, DMSO-d6) δ 10.70 (s, 1H), 10.52 (d, J = 3.8 Hz, 1H), 7.89 (d, J = 8.6 Hz, 1H), 7.74 (d, J = 9.0 Hz, 1H), 7.15-7.11 (m, 2H), 7.08 (dd, J = 8.6, 2.5 Hz, 1H), 5.26 (s, 2H), 4.66 (m, 2H). (s, 2H), 3.50 (d, J=12.3Hz, 3H), 3.23 (d, J=13.6Hz, 2H), 2.96-2.81 (m, 1H), 2.32-1.89 (m, 3H), 1.71-1.63 (m, 2H), 0.91-0.87 (m, 2H), 0.82-0.79 (m, 1H). HRMS (ESI) m / z: Calcd for C 26 H 25 NO6(M+H)+448.17601; Found 448.17267.

[0660] Embodiment 163:

[0661] 8-((4-(3-chlorobenzoyl)piperidin-1-yl)methyl)-3,9-dihydroxybenzo[5,6]oxepin Preparation of [4,3-b]benzofuran-7(5H)-one (Compound TY163)

[0662] The preparation method was similar to that of Example 38, except that 4-(3-chlorobenzoyl)piperidine hydrochloride was used instead of 3-acetonitrilecyclobutylamine hydrochloride to obtain a yellow solid final product. 1H NMR (600 MHz, DMSO-d6) δ 7.98 (s, 1H), 7.95 (d, J = 7.8 Hz, 1H), 7.84 (d, J = 8.4 Hz, 1H), 7.71 (dd, J = 7.9, 2.2 Hz, 1H), 7.57 (t, J = 7.9 Hz, 1H), 7.46 (s, 1H), 7.13 (d, J=2.4Hz, 1H), 7.05 (dd, J=8.5, 2.4Hz, 1H), 6.89 (d, J=8.9Hz, 1H), 5.17 (s, 2H), 4.01 (s, 2H), 3.50 (s, 2H), 2.86 (s, 1H), 2.26 (s, 2H), 1.78 (s, 2H), 1.55 (s, 2H). HRMS (ESI) m / z: Calcd for C 29 H 24NO6Cl(M+H)+518.13704; Found 518.13550.

[0663] Example 164:

[0664] Preparation of 8-(cyclohexyl(hydroxy)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY164)

[0665] The preparation method is as described in Example 1, except that the steps after 9-hydroxy-3-methoxybenzo[5,6]oxazepine[4,3-b]benzofuran-7(5H)-one are as follows:

[0666] 9-Hydroxy-3-methoxybenzo[5,6]oxazepam[4,3-b]benzofuran-7(5H)-one (1.0 eq) and potassium carbonate (1.3 eq) were added to ultra-dry N,N-dimethylformamide, and iodomethane (1.3 eq) was added dropwise. The mixture was allowed to react at room temperature for approximately 1.5 h. After TLC monitoring, the reaction was quenched with water. A solid precipitated and was filtered to obtain 3,9-dimethoxybenzo[5,6]oxazepam[4,3-b]benzofuran-7(5H)-one.

[0667] Under ice-cooling, dichloromethyl methyl ether (5 eq) was added to a chloroform solution containing 3,9-dimethoxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (1.0 eq), followed by dropwise addition of titanium tetrachloride (2.5 eq), and the mixture was allowed to react at room temperature for approximately 40 minutes. TLC monitored the reaction completion, and the reaction was quenched with water. The pH was adjusted to neutral with saturated sodium bicarbonate aqueous solution, and the mixture was extracted with ethyl acetate. Purification by silica gel column chromatography afforded 3,9-dimethoxy-7-oxo-5,7-dihydrobenzo[5,6]oxazepin[4,3-b]benzofuran-8-carboxaldehyde and 3,9-dimethoxy-7-oxo-5,7-dihydrobenzo[5,6]oxazepin[4,3-b]benzofuran-10-carboxaldehyde.

[0668] 3,9-dimethoxy-7-oxo-5,7-dihydrobenzo[5,6]oxalope[4,3-b]benzofuran-8-carbaldehyde (1.0 eq) was dissolved in ultra-dry dichloromethane, and boron tribromide (4.0 eq, 1 M in DCM) was added dropwise at -20°C. The mixture was reacted at room temperature for about 3 h. TLC (PE:EA=1:1) confirmed the completion of the reaction. Methanol was added to quench the reaction, and the mixture was concentrated under reduced pressure. The mixture was purified by silica gel column chromatography to obtain 3,9-dihydroxy-7-oxo-5,7-dihydrobenzo[5,6]oxalope[4,3-b]benzofuran-8-carbaldehyde.

[0669] Under ice bath, cyclohexylmagnesium bromide solution (1.5 eq) was added dropwise to a solution of 3,9-dihydroxy-7-oxo-5,7-dihydrobenzo[5,6]oxazepine[4,3-b]benzofuran-8-carbaldehyde (1.0 eq) in ultra-dry tetrahydrofuran, and then reacted at room temperature for about 1 h. After TLC monitoring, the reaction was complete, and water was added to quench the reaction. The pH was adjusted to approximately neutral with dilute hydrochloric acid, extracted with ethyl acetate, and purified by silica gel column chromatography to obtain the final product as a white solid. 1 H NMR (600MHz, DMSO-d6) δ7.86 (d, J=8.5Hz, 1H), 7.48 (d, J=8.8Hz, 1H), 7.09 (d, J=2.4Hz, 1H), 7.06 (dd, J=8.5, 2.3Hz, 1H), 6.86 (d, J =8.8Hz, 1H), 5.72 (s, 1H), 5.41-4.95 (m, 2H), 1.81-1.50 (m, 5H), 1.37 (d, J = 8.9Hz, 1H), 1.09 (t, J = 8.3Hz, 5H). HRMS (ESI) m / z: Calcd for C 23 H 22 O6(M+Na) + 417.13140; Found 417.13110.

[0670] Embodiment 165:

[0671] Preparation of 3,9-dihydroxy-8-(1-hydroxyhept-6-en-1-yl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY165)

[0672] The preparation method is similar to that of Example 164, except that hexacarbon-5-enylmagnesium bromide is used instead of cyclohexylmagnesium bromide to obtain a yellow solid final product. 1 H NMR (600MHz, Methanol-d4) δ7.88 (d, J=8.4Hz, 1H), 7.35 (d, J=8.8Hz, 1H), 7.04-6.97 (m, 2H), 6.88 (d, J=8.8Hz, 1H), 5.78 (dt , J=16.9, 9.0Hz, 1H), 5.10 (q, J=12.5Hz, 2H), 4.94 (d, J=17.1Hz, 1H), 2.01 (s, 2H), 1.80 (d, J=75.3Hz, 2H), 1.62-1.26 (m, 6H). 13C NMR (151MHz, Methanol-d4) δ160.57, 158.16, 148.61, 140.08, 136.89, 128.12, 123.85, 119.92, 116.68, 115.92, 115.15, 114.23, 109.43, 107.68, 68.87, 60.66, 55.41, 35.85, 33.56, 32.31, 29.70, 28.09.HRMS (ESI) m / z: Calcd for C 23 H 22 O6(MH) - 393.13381; Found 393.13419.

[0673] Embodiment 166:

[0674] Preparation of 8-(6-bromoheptyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY166)

[0675] The preparation method is as follows: Example 164, except that the steps after 3,9-dimethoxy-7-oxo-5,7-dihydrobenzo[5,6]oxazo[4,3-b]benzofuran-8-carbaldehyde are as follows:

[0676] Under ice bath, to a solution of ultra-dry tetrahydrofuran containing 3,9-dimethoxy-7-oxo-5,7-dihydrobenzo[5,6]oxazepin[4,3-b]benzofuran-8-carbaldehyde (1.0 eq) was dropwise added a hexacarbonyl-5-enylmagnesium bromide solution (1.5 eq), followed by reaction at room temperature for about 1 h. The reaction was complete as monitored by TLC, and water was added to quench the reaction. The pH was adjusted to approximately neutral with dilute hydrochloric acid, and the reaction was extracted with ethyl acetate. The mixture was concentrated under reduced pressure to obtain a crude product of 3,9-dimethoxy-8-(1-hydroxyhept-6-en-1-yl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one;

[0677] The crude product of the corresponding compound of 3,9-dimethoxy-8-(1-hydroxyhept-6-en-1-yl)benzo[5,6]oxazela[4,3-b]benzofuran-7(5H)-one was dissolved in ultra-dry DCM. Triethylsilane (2.0 eq) and trifluoroacetic acid (6.0 eq) were added at -78°C, and the mixture was allowed to react at room temperature for approximately 40 minutes. After TLC monitoring, the reaction was quenched with water, extracted with ethyl acetate, and purified by silica gel column chromatography to obtain 8-(hept-6-en-1-yl)-3,9-dimethoxybenzo[5,6]oxazela[4,3-b]benzofuran-7(5H)-one.

[0678] 8-(Hept-6-en-1-yl)-3,9-dimethoxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (1.0 eq) was dissolved in ultra-dry dichloromethane. Boron tribromide (3.0 eq, 1 M in DCM) was added dropwise at -20°C and allowed to react overnight at room temperature. TLC (PE:EA = 1:1) confirmed the completion of the reaction. The reaction was quenched with methanol, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the final product as a yellow solid. 1 H NMR (600MHz, DMSO-d6) δ8.32 (d, J=8.4Hz, 1H), 7.77 (d, J=8.7Hz, 1H), 7.58 (d, J=2 .4Hz, 1H), 7.54 (dd, J=8.5, 2.4Hz, 1H), 7.46 (d, J=8.7Hz, 1H), 5.63 (s, 2H), 3.48 (s , 1H), 2.95 (p, J=1.9Hz, 3H), 2.29-2.18 (m, 2H), 2.13 (d, J=6.6Hz, 2H), 2.05 (p, J= 7.7Hz, 2H), 1.93 (dt, J=36.4, 7.0Hz, 2H), 1.83-1.67 (m, 2H). HRMS (ESI) m / z: Calcd for C 23 H 22 BrO5(M+H) + 458.07288; Found 459.07993.

[0679] Embodiment 167:

[0680] Preparation of 8-(hept-6-en-1-yl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY167)

[0681] The preparation method is as follows: Example 165, except that the steps after compound TY165 are as follows:

[0682] Compound TY165 (1.0 eq) was dissolved in extra-dry DCM. Triethylsilane (2.0 eq) and trifluoroacetic acid (6.0 eq) were added at -78°C, and the mixture was allowed to react at room temperature for approximately 40 min. After completion of the reaction as monitored by TLC, the reaction was quenched with water, extracted with ethyl acetate, and purified by silica gel column chromatography to obtain the final product as a yellow solid. 1H NMR (600MHz, Methanol-d4) δ7.86 (d, J=8.4Hz, 1H), 7.23 (dd, J=8.7, 4.1Hz, 1H), 7.03-6.99 (m, 2H), 6.88 (dd, J=8.7, 1.8Hz, 1H) , 5.10 (s, 2H), 2.02 (q, J=6.8Hz, 2H), 1.78 (s, 1H), 1.58 (q, J=7.5Hz, 4H), 1.43-1.36 (m, 4H), 1.25 (s, 2H). HRMS (ESI) m / z: Calcd for C 23 H 22 O5(M+H) + 379.15455; Found 379.15430.

[0683] Example 168:

[0684] Preparation of 8-(cyclohexylmethyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY168)

[0685] The preparation method is similar to that of Example 166, except that cyclohexylmagnesium bromide is used instead of hexacarbon-5-enylmagnesium bromide to obtain a light pink solid final product. 1 H NMR (600MHz, DMSO-d6) δ7.83 (d, J=8.4Hz, 1H), 7.35 (d, J=8.7Hz, 1H), 7.09 (d, J=2.5Hz, 1H), 7.05 (dd, J=8.5, 2.4Hz, 1H), 6.96 (d, J=8 .7Hz, 1H), 5.12(s, 2H), 3.00(s, 2H), 1.64-1.57(m, 3H), 1.56-1.49(m, 2H), 1.49-1.39(m, 1H), 1.14-1.01(m, 3H), 1.00-0.89(m, 2H). 13 CNMR (151MHz, DMSO-d6) δ164.39, 160.52, 157.46, 152.83, 148.32, 138.04, 128.48, 126.64, 121.28, 119.96 , 117.42, 116.28, 114.63, 109.80, 109.21, 68.67, 38.86, 33.14, 32.56, 26.68, 26.43.HRMS (ESI) m / z: Calcd for C 23 H 22 O5(M+H) + 379.15455; Found 379.15311.

[0686] Example 169:

[0687] Preparation of 10-(azetidin-1-ylmethyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY169)

[0688] The preparation method is as described in Example 164, except that the steps after 3,9-dimethoxy-7-oxo-5,7-dihydrobenzo[5,6]oxazo[4,3-b]benzofuran-10-carbaldehyde are as follows:

[0689] 3,9-dimethoxy-7-oxo-5,7-dihydrobenzo[5,6]oxazo[4,3-b]benzofuran-10-carbaldehyde (1.0 eq), azetidine (1.2 eq), and acetic acid (1 drop) were added to methanol and reacted at room temperature for 10 min. TLC detection showed the formation of an intermediate transition product, sodium cyanoborohydride (2.0 eq) was added, and the reaction was allowed to proceed overnight at room temperature. After TLC detection, the reaction was quenched with saturated aqueous sodium bicarbonate solution, extracted with ethyl acetate, and purified by C18 column chromatography to obtain 10-(azetidin-1-ylmethyl)-3,9-dimethoxybenzo[5,6]oxazo[4,3-b]benzofuran-7(5H)-one;

[0690] To a solution of 10-(azetidin-1-ylmethyl)-3,9-dimethoxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (1.0 eq) in ultra-dry dichloromethane was added dropwise boron tribromide (4.0 eq, 1 M in DCM) under nitrogen at -20°C. The mixture was then allowed to react overnight at room temperature. After completion of the reaction, TLC (DCM:MeOH = 10:1) was performed and the final product was purified by C18 column chromatography to obtain a pale yellow solid. 1 H NMR (600MHz, Methanol-d4) δ7.92 (d, J=8.5Hz, 1H), 7.66 (s, 1H), 7.53 (s, 1H), 7.07 (dd, J=8.4, 2.5Hz, 1H), 7.05 (d, J= 2.4Hz, 1H), 5.18(s, 2H), 4.49(s, 2H), 4.31-4.19(m, 2H), 4.17-4.07(m, 2H), 2.64-2.38(m, 2H).HRMS(ESI)m / z: Calcd for C 20 H 17 NO5(M+H) + 352.11849; Found 352.11722.

[0691] Embodiment 170:

[0692] Preparation of 10-(azetidin-1-ylmethyl)-3,9-dihydroxy-11-isopropylbenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY170)

[0693] The preparation method is similar to that of Example 1, except that azetidine is used instead of piperidine, and 2-isopropyl-1,4-benzoquinone is used instead of benzoquinone to obtain a yellow solid final product. 1 H NMR (600MHz, Methanol-d4) δ7.92 (d, J=8.5Hz, 1H), 7.44 (s, 1H), 7.05 (dd, J=8.5, 2.5Hz, 1H), 7.03 (d, J=2.4Hz, 1H), 5.19 (s, 2H), 4.40 (s, 2H), 3.73 (t, J=7.5Hz, 4H), 3.44 (hept, J=6.9Hz, 1H), 2.31 (p, J=7.5Hz, 2H), 1.30 (d, J=6.9Hz, 6H). HRMS (ESI) m / z: Calcd for C 23 H 22 NO5(MH)-392.14980; Found 392.15042.

[0694] Embodiment 171:

[0695] Preparation of 10-(azetidin-1-ylmethyl)-11-cyclohexyl-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY171)

[0696] The preparation method is similar to that of Example 1, except that azetidine replaces piperidine, and 2-cyclohexyl-1,4-benzoquinone replaces benzoquinone to obtain a gray solid final product. 1H NMR (600MHz, DMSO-d6) δ10.63 (s, 1H), 9.52 (s, 1H), 7.85 (d, J = 8.5Hz, 1H), 7.63 (s, 1H), 7.12 ( d, J=2.5Hz, 1H), 7.08 (dd, J=8.5, 2.5Hz, 1H), 5.23 (s, 2H), 4.75 (s, 2H), 4.39-4.24 (m, 2H), 4.0 9 (dq, J=10.0, 4.9, 4.4Hz, 2H), 3.13-3.00 (m, 1H), 2.40 (dt, J=11.3, 9.2Hz, 1H), 2.32 (dq, J=11 .2, 4.8Hz, 1H), 1.91-1.69 (m, 5H), 1.46-1.40 (m, 3H), 1.33-1.19 (m, 2H). HRMS (ESI) m / z: Calcd for C 26 H 27 NO5(M+H) + 434.19674; Found 434.19577.

[0697] Embodiment 172:

[0698] Preparation of 9-hydroxy-3-methyl-10-(piperidin-1-ylmethyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY172)

[0699] The preparation method is similar to that of Example 1, except that 2-bromo-5-methylbenzaldehyde is used instead of 2-bromo-5-hydroxybenzaldehyde to obtain a yellow solid final product. 1 H NMR (600MHz, DMSO-d6) δ7.90 (d, J=7.9Hz, 1H), 7.55 (s, 1H), 7.52-7.46 (m, 2H), 6.90 (d, J=8.8Hz , 1H), 5.22(s, 2H), 3.98(s, 2H), 2.44(s, 3H), 2.42-2.32(m, 4H), 1.51-1.47(m, 4H), 1.42(s, 2H). 13 C NMR (151MHz, DMSO-d6) δ164.21, 156.01, 154.98, 148.39, 141.53, 135.85, 131.01, 130.25, 126.25, 126.12, 125.98, 115.80, 115.65, 11 1.83, 110.95, 68.65, 55.96, 53.47, 26.15, 24.27, 21.53.HRMS(ESI)m / z: Calcd for C 23 H23 NO4(M+H) + 378.17053; Found 378.16940.

[0700] Embodiment 173:

[0701] Preparation of 3,9-dihydroxy-11-methyl-10-(piperidin-1-ylmethyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY173)

[0702] The preparation method is similar to that of Example 1, except that 2-methyl-1,4-benzoquinone is used instead of p-benzoquinone to obtain a light yellow solid final product. 1 H NMR (600MHz, DMSO-d6) δ7.83 (d, J=8.5Hz, 1H), 7.39 (s, 0H), 7.09 (d, J=2.5Hz, 1H), 7.04 (dd, J=8.5, 2.4Hz, 1H) , 5.17 (s, 2H), 4.02 (s, 0H), 2.52 (s, 0H), 2.25 (s, 2H), 1.56 (p, J = 5.6Hz, 4H), 1.45 (s, 2H). HRMS (ESI) m / z: Calcd for C 23 H 23 NO5(M+H) + 394.16544; Found 394.16437.

[0703] Embodiment 174:

[0704] Preparation of 11-ethyl-3,9-dihydroxy-10-(piperidin-1-ylmethyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY174)

[0705] The preparation method is similar to that of Example 1, except that 2-ethyl-1,4-benzoquinone is used instead of p-benzoquinone to obtain a yellow solid final product. 1 H NMR (600MHz, DMSO-d6) δ7.83 (d, J=8.5Hz, 1H), 7.38 (s, 1H), 7.09 (d, J=2.5Hz, 1H), 7.05 (dd, J=8.5, 2.4Hz, 1H), 5.17 (s, 2 H), 4.08 (s, 2H), 2.67 (q, J=7.5Hz, 2H), 2.54 (s, 2H), 1.51 (d, J=64.7Hz, 8H), 1.19 (t, J=7.5Hz, 3H). HRMS (ESI) m / z: Calcd for C 24 H 25 NO5(M+H)+ 408.18109; Found 408.18021.

[0706] Embodiment 175:

[0707] Preparation of 10-(cyclohexylmethyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY175)

[0708] The preparation method is as described in Example 166, except that cyclohexylmagnesium bromide is used instead of hexacarbon-5-enylmagnesium bromide, and 3,9-dimethoxy-7-oxo-5,7-dihydrobenzo[5,6]oxazo[4,3-b]benzofuran-10-carbaldehyde is used instead of 3,9-dimethoxy-7-oxo-5,7-dihydrobenzo[5,6]oxazo[4,3-b]benzofuran-8-carbaldehyde to give a white solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.46 (s, 1H), 9.43 (s, 1H), 7.82 (d, J = 8.5Hz, 1H), 7.35 (s, 1H), 7.34 (s, 1H), 7.08 (d, J = 2.4Hz, 1H) , 7.04 (dd, J=8.5, 2.4Hz, 1H), 5.17 (s, 2H), 2.53 (d, J=6.7Hz, 2H), 1.84-1.44 (m, 6H), 1.25-1.02 (m, 3H), 0.99-0.93 (m, 2H). 13 CNMR (151MHz, DMSO-d6) δ164.98, 160.54, 157.39, 153.35, 147.86, 137.15, 128.18, 127.36, 125.99, 120.32 , 117.29, 116.80, 112.96, 108.31, 106.11, 68.95, 38.52, 38.12, 33.26, 26.69, 26.31.HRMS (ESI) m / z: Calcd for C 23 H 22 O5 (M+H) + 379.15455; Found 379.15308.

[0709] Embodiment 176:

[0710] Preparation of 8-((4-butyrylpiperidin-1-yl)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one hydrochloride (Compound TY176)

[0711] Compound TY086 (1.0 eq) was dissolved in ethyl acetate, and a solution of hydrochloric acid in ethyl acetate (2.0 eq) was added dropwise. The mixture was stirred at room temperature overnight, and concentrated to dryness to obtain compound TY176 as a white solid final product. 1 H NMR (400MHz, DMSO-d6) δ10.63 (s, 1H), 10.43 (s, 1H), 9.44 (s, 1H), 7.87 (d, J=8.5Hz, 1H), 7.71 (d, J=8 .9Hz, 1H), 7.19 (d, J=8.9Hz, 1H), 7.13 (d, J=2.5Hz, 1H), 7.09 (dd, J=8.5, 2.4Hz, 1H), 5.33 (s, 2H), 4. 72 (s, 2H), 3.44 (d, J = 12.0Hz, 2H), 3.21-3.11 (m, 2H), 2.76-2.62 (m, 1H), 2.47 (t, J = 7.1Hz, 2H), 2.07 -1.97 (m, 2H), 1.85-1.79 (m, 2H), 1.47 (q, J = 7.3Hz, 2H), 0.83 (t, J = 7.4Hz, 3H). HRMS (ESI) m / z: Calcd for C 26 H 28 NO6Cl(M+H) + 486.16834; Found (M-HCl+H) + 450.19083.

[0712] Embodiment 177:

[0713] Preparation of 8-((4-(3-chlorophenyl)piperidin-1-yl)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one hydrochloride (Compound TY177)

[0714] Compound TY125 (1.0 eq) was dissolved in ethyl acetate, and a solution of hydrochloric acid in ethyl acetate (2.0 eq) was added dropwise. The mixture was stirred at room temperature overnight, concentrated to dryness, and compound TY177 was obtained as a white solid final product. 1H NMR (600MHz, DMSO-d6) δ10.62 (s, 1H), 10.43 (s, 1H), 9.52 (s, 1H), 7.89 (d, J=8.4Hz, 1H) , 7.73 (d, J=8.9Hz, 1H), 7.36 (t, J=8.1Hz, 1H), 7.33-7.26 (m, 2H), 7.16 (d, J=7.7Hz, 1H), 7.12-7.07 (m, 2H), 7.04 (dd, J=8.5, 2.4Hz, 1H), 5.36 (s, 2H), 4.78 (s, 2H), 3.50 (d, J=12. 1Hz, 2H), 3.29-3.23(m, 2H), 2.94-2.88(m, 1H), 2.24-1.79(m, 4H).HRMS(ESI)m / z: Calcd for C 28 H 25 NO5Cl2(M+H) + 526.11880;Found(M-HCl+H) + 490.13934.

[0715] Embodiment 178:

[0716] Preparation of 3,9-dihydroxy-8-(piperidin-1-ylmethyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one hydrochloride (Compound TY178)

[0717] Compound TY001 (1.0 eq) was dissolved in ethyl acetate, and a solution of hydrogen chloride in ethyl acetate (2.0 eq) was added dropwise. The mixture was stirred at room temperature overnight and concentrated to obtain compound TY178 as a white solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.63 (s, 1H), 10.41 (s, 1H), 9.37 (s, 1H), 7.86 (d, J=8.5H z, 1H), 7.70 (d, J=8.9Hz, 1H), 7.16 (d, J=8.9Hz, 1H), 7.12 (d, J=2.4Hz, 1H), 7.08 (d d, J=8.4, 2.4Hz, 1H), 5.33 (s, 2H), 4.71 (s, 2H), 3.36-3.28 (m, 2H), 3.11-3.03 (m, 2 H), 1.82-1.77(m, 4H), 1.69-1.59(m, 1H), 1.55-1.34(m, 1H).HRMS(ESI)m / z: Calcd for C 22 H 22 NO5Cl(M+H) + 416.13647; Found (M-HCl+H)+ 379.70.

[0718] Embodiment 179:

[0719] Preparation of 3,9-dihydroxy-8-((4-(1-(methoxyimino)butyl)piperidin-1-yl)methyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY179)

[0720] The preparation method is similar to Example 86, except that the steps after TY086 are as follows:

[0721] TY086 (1.0 eq), sodium acetate (10 eq), and 1-(piperidin-4-yl)-1-butanone O-methyloxime hydrochloride (10 eq) were added to a reaction flask, and ethanol and pure water were added. The reaction was carried out at 100° C. After TLC monitoring, the reaction was directly concentrated and purified by column chromatography and recrystallized to obtain an off-white solid final product. 1 H NMR (400MHz, DMSO-d6) δ10.56 (s, 2H), 7.85 (d, J = 8.5Hz, 1H), 7.45 (d, J = 8.8Hz, 1H), 7.12 (d, J=2.4Hz, 1H), 7.05 (dd, J=8.5, 2.4Hz, 1H), 6.87 (d, J=8.8Hz, 1H), 5.17(s, 2H), 3.95(s, 2H), 3.72(s, 3H), 2.83(s, 2H), 2.29-1.97(m, 5H), 1.70(d , J=12.6Hz, 2H), 1.46-1.41 (m, 4H), 0.88 (t, J=7.4Hz, 3H). HRMS (ESI) m / z: Calcd for C 27 H 30 N2O6(M+H) + 479.21821; Found 479.36012.

[0722] Embodiment 180:

[0723] Preparation of 3,9-dihydroxy-8-((4-(pent-1-en-2-yl)piperidin-1-yl)methyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY180)

[0724] The preparation method is as described in Example 7, except that the steps after 3,9-dihydroxybenzo[5,6]oxazolidinone[4,3-b]benzofuran-7(5H)-one are as follows:

[0725] 3,9-Dihydroxybenzo[5,6]oxazepine[4,3-b]benzofuran-7(5H)-one (1.0 eq), 37% formaldehyde solution (2.0 eq), triethylamine (2.2 eq), and 4-(pent-1-en-2-yl)piperidine hydrochloride (1.5 eq) were added to anhydrous ethanol and reacted at 80°C overnight. After the reaction was completed as monitored by TLC, the mixture was concentrated under reduced pressure and purified by column chromatography to obtain a milky white solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.67 (s, 1H), 10.44 (s, 1H), 7.87 (d, J = 8.5Hz, 1H), 7.71 (d, J = 8.9Hz, 1H ), 7.18 (d, J = 8.9Hz, 1H), 7.13 (d, J = 2.4Hz, 1H), 7.09 (dd, J = 8.5, 2.4Hz, 1H), 5.35 (s, 2H), 4, 74 ( s, 2H), 4, 73 (s, 2H), 3.42 (d, J=11.9Hz, 2H), 3.26-2.95 (m, 2H), 2.19-2.18 (m, 1H), 1.98 (t, J=7. 6Hz, 2H), 1.88-1.72 (m, 4H), 1.41 (q, J=7.5Hz, 2H), 0.87 (t, J=7.3Hz, 3H). HRMS (ESI) m / z: Calcd for C 27 H 29 NO5(M+H) + 448.01239; Found 448.05010.

[0726] Embodiment 181:

[0727] Preparation of 8-((4-butylpiperidin-1-yl)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY181)

[0728] The preparation method is as follows: Example 1, except that the steps after ethyl 3-[4-methoxy-2-(methoxymethyl)phenyl]-3-oxopropionate are:

[0729] 3-[4-methoxy-2-(methoxymethyl)phenyl]-3-oxopropionic acid ethyl ester (1.0 eq) and benzoquinone (1.2 eq) were dissolved in xylene under nitrogen protection, copper trifluoromethanesulfonate (0.1 eq) was added, and the mixture was reacted at 80-90° C. for 1-2 h. The reaction was stopped when TLC monitoring showed that the reaction of the raw materials was complete and only a small amount of 9-hydroxy-3-methoxybenzo[5,6]oxazepine[4,3-b]benzofuran-7(5H)-one was produced. The mixture was directly purified by column chromatography to obtain 5-hydroxy-2-(4-methoxy-2-(methoxymethyl)phenyl)benzofuran-3-carboxylic acid ethyl ester.

[0730] 5-Hydroxy-2-(4-methoxy-2-(methoxymethyl)phenyl)benzofuran-3-carboxylic acid ethyl ester (1.0 eq), 4-butylpiperidine hydrochloride (1.5 eq), 37% formaldehyde aqueous solution (2.0 eq), and triethylamine (2.2 eq) were added to ethanol and reacted at 80° C. overnight. The reaction was monitored to be complete by TLC, and the product was purified by column chromatography to obtain 4-(4-butylpiperidin-1-ylmethyl)-5-hydroxy-2-(4-methoxy-2-(methoxymethyl)phenyl)benzofuran-3-carboxylic acid ethyl ester;

[0731] Under anhydrous and oxygen-free conditions, ethyl 4-(4-butylpiperidin-1-ylmethyl)-5-hydroxy-2-(4-methoxy-2-(methoxymethyl)phenyl)benzofuran-3-carboxylate (1.0 eq) was dissolved in ultra-dry DCM, and a dichloromethane solution of boron tribromide (2.0 M in DCM, 4.0 eq) was added dropwise at low temperature (0°C). The reaction was allowed to react at room temperature. The reaction was completed as monitored by TLC to generate an intermediate transition state product. Methanol was added to quench the reaction at low temperature (0°C) and the reaction was concentrated. 1,4-dioxane and purified water were then added and the reaction was allowed to proceed at 100°C. The intermediate transition state product was completely converted into the target molecule as monitored by TLC. The reaction was stopped and a saturated sodium bicarbonate solution was added to adjust the pH to a weak alkaline state. The reaction was extracted with DCM, the organic phase was concentrated, and the final product was purified by column chromatography to obtain a milky white solid. 1 H NMR (400MHz, DMSO-d6) δ10.66 (s, 1H), 10.42 (s, 1H), 7.87 (d, J=8.5Hz, 1H), 7.70 (d, J= 8.9Hz, 1H), 7.18 (d, J=8.9Hz, 1H), 7.13 (d, J=2.4Hz, 1H), 7.09 (dd, J=8.5, 2.4Hz, 1H), 5.34 (s, 2H), 4.70 (s, 2H), 3.38 (d, J = 11.8Hz, 2H), 3.13-3.08 (m, 2H), 1.80 (d, J = 10.4H z, 2H), 1.51-1.47 (m, 3H), 1.34-1.11 (m, 6H), 0.94-0.78 (m, 3H). HRMS (ESI) m / z: Calcd for C 26 H 29 NO5(M+H) + 436.01230; Found 435.95907.

[0732] Embodiment 182:

[0733] Preparation of 3,9-dihydroxy-8-((4-(2-propyl-1,3-dioxolan-2-yl)piperidin-1-yl)methyl)benzo[5,6]oxazepa[4,3-b]benzofuran-7(5H)-one (Compound TY182)

[0734] The preparation method is as described in Example 86, except for the step after TY086: TY086 (1.0 eq) and p-toluenesulfonic acid (0.4 eq) were added to a reaction flask, ethylene glycol was added as the reaction solvent, and the reaction was carried out at 100° C. overnight. After TLC monitoring showed no obvious progress in the reaction, the reaction was stopped, the pH was adjusted to weak alkaline with saturated sodium bicarbonate solution, the product was extracted with dichloromethane, the organic phase was concentrated, and the product was purified by column chromatography to obtain a yellow-green solid final product. 1 H NMR (400MHz, DMSO-d6) δ10.70 (s, 1H), 10.46 (s, 1H), 7.87 (d, J = 8.5Hz, 1H), 7.70 (d, J = 8.9Hz, 1 H), 7.19 (d, J=8.9Hz, 1H), 7.13 (d, J=2.4Hz, 1H), 7.10 (dd, J=8.5, 2.4Hz, 1H), 5.32 (s, 2H), 4.68 (s, 2H), 3.96-3.71 (m, 4H), 3.42 (d, J=11.4Hz, 2H), 3.11-3.09 (m, 2H), 1.97-1.84 (m, 1H), 1.85- 1.63 (m, 4H), 1.55-1.43 (m, 2H), 1.38-1.21 (m, 2H), 0.85 (t, J=7.3Hz, 3H). HRMS (ESI) m / z: Calcd for C 28 H 31 NO7(M+H) + 494.21787; Found 494.16610.

[0735] Embodiment 183:

[0736] Preparation of 3,9-dihydroxy-8-((4-(1-methoxybutyl)piperidin-1-yl)methyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY183)

[0737] The preparation method is similar to Example 180 (TY180), except that 4-(1-methoxybutyl)piperidine hydrochloride is used instead of 4-(pent-1-en-2-yl)piperidine hydrochloride to obtain a light yellow solid final product. 1H NMR (600MHz, DMSO-d6) δ10.67 (s, 1H), 10.43 (s, 1H), 7.87 (d, J=8.5Hz, 1H), 7.71 (d, J=8 .9Hz, 1H), 7.18 (d, J=8.9Hz, 1H), 7.13 (d, J=2.5Hz, 1H), 7.09 (dd, J=8.5, 2.4Hz, 1H), 5.3 3(s, 2H), 4.69(s, 2H), 3.46-3.37(m, 2H), 3.24(s, 3H), 3.16-3.06(m, 2H), 2.94-2.92(m , 1H), 1.89-1.55 (m, 5H), 1.41-1.20 (m, 4H), 0.88 (t, J=5.5Hz, 3H). HRMS (ESI) m / z: Calcd for C 27 H 31 NO6(M+H) + 466.22296; Found 466.2222.

[0738] Embodiment 184:

[0739] Preparation of 3,9-dihydroxy-8-((4-(4-hydroxyheptane-4-yl)piperidin-1-yl)methyl)benzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY184)

[0740] The preparation method is similar to Example 180 (TY180), except that 4-(4-piperidinyl)-4-heptanol hydrochloride is used instead of 4-(pent-1-en-2-yl)piperidine hydrochloride to obtain a yellow solid final product. 1 H NMR (600MHz, DMSO-d6) δ10.65 (s, 1H), 10.40 (s, 1H), 7.88 (d, J=8.5Hz, 1H), 7.71 (d, J=8.8Hz, 1H), 7.16 (d, J=8.8Hz, 1H), 7.13 (d, J=2.4Hz, 1H), 7.09 (dd, J=8.5, 2.4Hz, 1H), 5.30 (s, 2H), 4.65 (s, 2H), 3.96 (s, 1H), 3.43 (s, 2H), 3.08 (s, 2H), 1. 81-1.48(m, 5H), 1.41-1.21(m, 8H), 0.85(t, J=6.7Hz, 6H).HRMS(ESI)m / z: Calcd for C 29 H 35 NO6(M+H) + 494.25426; Found 494.74406.

[0741] Embodiment 185:

[0742] Preparation of 8-((4-(1-aminobutyl)piperidin-1-yl)methyl)-3,9-dihydroxybenzo[5,6]oxazepin[4,3-b]benzofuran-7(5H)-one (Compound TY185)

[0743] The preparation method is similar to Example 180 (TY180), except that 1-(4-piperidinyl)-1-butylamine hydrochloride is used instead of 4-(pent-1-en-2-yl)piperidine hydrochloride to obtain a yellow solid final product. 1 H NMR (400MHz, DMSO-d6) δ10.66 (s, 1H), 10.45 (s, 1H), 10.05 (s, 1H), 9.69 (s, 1H), 7.87 (d, J=8. 5Hz, 1H), 7.72 (d, J=8.9Hz, 1H), 7.18 (d, J=9.0Hz, 1H), 7.12 (d, J=2.4Hz, 1H), 7.09 (dd, J=8.5, 2.4Hz, 1H), 5.34 (d, J=13.4Hz, 2H), 4.74 (s, 2H), 3.44-3.41 (m, 2H), 3.14-3.13 (m, 2H), 2.97-2 .95 (m, 1H), 2.11-1.66 (m, 5H), 1.48-1.45 (m, 4H), 0.87 (t, J=6.8Hz, 3H).HRMS (ESI) m / z: Calcd for C 26 H 30 N2O5 (M+H) + 451.22330; Found 451.15966.

[0744] Embodiment 186:

[0745] This example detects the minimum inhibitory concentration (MIC) of the compound of the present invention against the standard strain of Mycobacterium tuberculosis H37Rv.

[0746] 1.1 Experimental Materials

[0747] The compound of the present invention; Mycobacterium tuberculosis H37Rv (cultured in Middlebrook 7H9 culture medium), provided by Shanghai Pulmonary Hospital.

[0748] 1.2 Preparation of test compounds

[0749] The test compound was completely dissolved in dimethyl sulfoxide (DMSO) to prepare a 1 mg / mL stock solution, which was then sterilized by filtration. As needed, the stock solution was serially diluted with Middlebrook 7H9 medium to obtain solutions of the test compound at varying concentrations. 100 μL was added to each well of a 96-well culture plate.

[0750] 1.3 Experimental methods

[0751] Mycobacterium tuberculosis H37Rv (standard strain) in the logarithmic growth phase was diluted with Middlebrook 7H9 culture medium to a turbidity OD600 of 1.0 (approximately 5×10 6 CFU / mL), 200 μL of which was diluted to 10 mL with Middlebrook 7H9 culture medium to obtain a bacterial solution containing H37Rv. 100 μL of this bacterial solution was then added to the culture plate containing the test compound to create the experimental groups. The final concentrations of the test compounds were 64, 32, 16, 8, 4, 2, 1, 0.5, 0.25, 0.125, 0.0625, 0.03125, 0.0156, 0.0078, and 0.0039 μg / mL, respectively.

[0752] The drug-free control groups were set up with 100% inoculation (100 μL diluted H37Rv bacterial solution + 100 μL Middlebrook 7H9 culture medium), 10% inoculation (10 μL diluted H37Rv bacterial solution + 190 μL Middlebrook 7H9 culture medium) or no inoculation group (200 μL Middlebrook 7H9 culture medium).

[0753] After 15 days of culture, the size of the bacterial plaque observed by naked eyes was no larger than 10% of the inoculum size of the drug-free control group, which was taken as the minimum inhibitory concentration (MIC) of the compound to inhibit 90% of the growth of Mycobacterium tuberculosis H37Rv. 90 The activity results are shown in Table 1.

[0754] Table 1: MIC of the compounds of the present invention against Mycobacterium tuberculosis H37Rv 90 Value data

[0755] As shown in Table 1, the compounds of the present invention exhibited good resistance to Mycobacterium tuberculosis.

[0756] Embodiment 187:

[0757] The method of Example 186 was used, except that Mycobacterium tuberculosis H37Rv was replaced with clinical strains of Mycobacterium tuberculosis (including sensitive strains S1, S2, and S3; single rifampicin-resistant strains R1 and R2; single isoniazid-resistant H1; rifampicin- and isoniazid-resistant strains M1 and M2; derived from clinical strains of Shanghai Pulmonary Hospital). The rest of the detection methods used were the same.

[0758] The experimental results are shown in Table 2. The compounds of the present invention have good activity against clinical tuberculosis strains and drug-resistant tuberculosis strains. Their activity against drug-resistant strains is significantly better than that of rifampicin and isoniazid, the first-line tuberculosis treatment drugs that produce drug resistance, indicating that the compounds of the present invention have activity against drug-resistant tuberculosis strains.

[0759] Table 2: MICs of compounds against clinical tuberculosis strains 90 Value (μg / mL)

[0760] Embodiment 188:

[0761] This example tests the anti-tuberculosis activity of the compound of the present invention in mice.

[0762] 1.1 Experimental Materials and Reagents

[0763] The compound of the present invention; 5-6 week old female BALB / c mice, sourced from Zhejiang Weitong Lihua Experimental Animal Co., Ltd.; Mycobacterium tuberculosis H37Rv, provided by Shanghai Pulmonary Hospital; 10% Tween 80-normal saline;

[0764] The test compound was prepared into a 10 mg / mL uniform suspension in 10% Tween 80-physiological saline.

[0765] 1.2 Experimental methods

[0766] Experimental mice (approximately 10 2 ~10 3 CFU / lung). Two days after infection, mice were killed and lungs were harvested for bacterial load determination (plate count method). The remaining groups then began group treatment. Six mice were administered to each group, with the compound administered once daily for five days per week for a total of four weeks. Three days after the end of administration, mice were killed, lungs harvested, and bacterial load determined (plate count method). The dosing regimen and dosage are shown in Table 3.

[0767] Table 3: Specific administration methods and dosages

[0768] 1.3 Experimental Results

[0769] The results are shown in FIG1 , showing that compound TY176 and compound TY177 have very significant anti-tuberculosis activity in mice.

[0770] Embodiment 189:

[0771] This example tests the solubility of the compounds.

[0772] Experimental materials: Compounds of the present invention

[0773] Experimental Method: Dispense each compound listed in Table 4 into a centrifuge tube and add purified water to create a supersaturated solution. Shake the tubes in a 37°C incubator for 48 hours. After sampling, centrifuge at 5000 rpm for 5 minutes at 37°C. The supernatant is diluted and analyzed by HPLC or HPLC-MS.

[0774] Structural comparison of the parent core compound TY001 in this series and the parent core compound C48 disclosed in CN109942523A:

[0775] The results are shown in Table 4.

[0776] Table 4: Solubility of compounds in water

[0777] As shown in Table 4, TY001 has a solubility approximately threefold higher than C48 (the compound disclosed in CN109942523A), demonstrating that the solubility of the new core compound of the present invention is superior to that disclosed in CN109942523A. The solubility of the compound is further enhanced after salt formation. This increased solubility facilitates the selection of a diverse range of pharmaceutical formulations and effectively improves the compound's in vivo bioavailability.

[0778] Embodiment 190:

[0779] This example tests repeated-dose toxicity in animals.

[0780] Experimental materials: 6-week-old Balb / c mice, half male and half female, 10% Tween 80-water, the compound of the present invention, and compound C48;

[0781] Experimental Method: The test compound was prepared into a 10 mg / mL suspension in 10% Tween-80. Mice were randomly divided into groups of 12 per sex. After one week of acclimatization, dosing began, with each mouse receiving 100 mg / kg via gavage. Dosing was once daily, five days per week, for four consecutive weeks. The mice were observed daily for physical signs (hair, skin, eyes, mucous membranes, respiration, autonomic nervous system, and body), behavioral activity, fecal characteristics, local reactions to administration, and mortality, and these characteristics were recorded to determine the effects of repeated dose toxicity. The results are shown in Table 5.

[0782] Table 5: Observation results of 4-week continuous administration

[0783] The experimental results showed that after 4 weeks of oral administration at a dose of 100 mg / kg, C48 (the compound disclosed in CN109942523A) exhibited extremely strong in vivo toxicity, with 7 mice dying, while the compounds TY001, TY176, and TY177 of the present invention showed no obvious abnormalities at the same dosage.

Claims

1. A compound represented by the following formula I, or a pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide, hydrate, solvate, prodrug, and isotopic variant thereof: Where, X is selected from: -O-, -NH-, -S- and -CH2-; Y is selected from: -O, -NH- and -S; Z1 is selected from: -O-, -NH-, -S- and -CH2-; Z2 is selected from: -N- and -C-; Z3 is selected from: -N- and -C-; Z4 is selected from: -N- and -C-; Z5 is selected from: -N- and -C-; Z6 is selected from: -N- and -C-; Z7 is selected from: -N- and -C-; R3 is selected from: halogen, optionally substituted C1-C 10 Alkyl, optionally substituted C1-C 10 Alkoxy, -NR'R", nitro, hydroxy, carboxyl, mercapto, cyano, ester, acylamino, optionally substituted C3-C8 carbocyclic group, optionally substituted C6-C 14 Aryl, optionally substituted C5-C 10 Heteroaryl, optionally substituted C4-C 10 Heterocyclic group, phosphate group, polyethylene glycol group, polyethylene glycol-C1-C4 alkyl-C(O)-O- and glycoside group; R4 is selected from the group consisting of: H, halogen, aldehyde, hydroxy, thiol, -NR'R", cyano, nitro, optionally substituted C1-C 10 Alkyl, optionally substituted C2-C 10 Alkenyl, optionally substituted C2-C 10 Alkynyl, optionally substituted C3-C8 carbocyclyl, optionally substituted C6-C 14 Aryl, optionally substituted C5-C 10 Heteroaryl and optionally substituted C4-C 10 heterocyclic group; R5 is selected from the group consisting of: H, hydroxy, thiol, halogen, optionally substituted C1-C 10 Alkoxy, optionally substituted C1-C 10 Alkyl, C1-C 10 ester, -NR'R", nitro, amido and polyethylene glycol groups; R6 is selected from the group consisting of: H, halogen, optionally substituted C1-C 10 Alkyl, optionally substituted C1-C 10 Alkoxy, -NR'R", nitro, hydroxy, carboxyl, mercapto, cyano, ester, acylamino, optionally substituted C3-C8 carbocyclic group, optionally substituted C6-C 14 Aryl, optionally substituted C5-C 10 Heteroaryl and optionally substituted C4-C 10 heterocyclic group; R7 is selected from the group consisting of: H, hydroxy, thiol, cyano, carboxyl, nitro, -NR'R", optionally substituted C1-C 10 Alkyl, any Select C2-C 10 Alkenyl, optionally substituted C2-C 10 Alkynyl, C1-C 10 Ester group, acylamino group, halogen, optionally substituted C3-C8 carbocyclic group, optionally substituted C1-C 10 Alkoxy, optionally substituted C6-C 14 Aryl, optionally substituted C5-C 10 Heteroaryl and optionally substituted C4-C 10 heterocyclic group; R8 is selected from: H, optionally substituted C1-C 10 Alkyl, optionally substituted C2-C 10 Alkenyl and optionally substituted C6-C 14 aryl; R' and R" are each independently selected from: H, optionally substituted C1-C 10 alkyl, optionally substituted C2-C8 alkenyl, and optionally substituted C1-C 10 alkoxy; and n is 0, 1, 2, 3 or 4.

2. The compound of claim 1, or a pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide, hydrate, solvate, prodrug, or isotopic variant thereof, wherein: The compound has one or more of the following characteristics: When Z1 is -NH- and X is -CH2-, -NH- or -O-, R4 is not H; At least one of R4, R5, R6 and R7 is a non-hydrogen substituent; X is -O- or -NH-, preferably -O-; Y is -O- or -S-, preferably -O-; Z1 is -O-, -NH- or -CH2-, preferably -O-; Z2, Z3, Z4, Z5, Z6 and Z7 are all -C-; and R8 is H or C1-C4 alkyl, preferably H.

3. The compound of claim 1, or a pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide, hydrate, solvate, prodrug, or isotopic variant thereof, wherein: R3 is selected from: halogen, C1-C 10 Alkyl, hydroxyl, phosphate, polyethylene glycol, polyethylene glycol-C1-C4 alkyl-C(O)-O- and glycoside; preferably, R3 is selected from halogen, C1-C4 alkyl and hydroxyl; more preferably, R3 is hydroxyl; Preferably, n is 0, 1 or 2, more preferably 0 or 1.

4. The compound of claim 1, or a pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide, hydrate, solvate, prodrug, or isotopic variant thereof, wherein: R4 is selected from: H, -NR'R", optionally substituted C1-C 10 Alkyl, optionally substituted C2-C 10 Alkenyl, optionally substituted C2-C 10 Alkynyl, optionally substituted C3-C8 carbocyclyl, optionally substituted C6-C 14 Aryl, optionally substituted C5-C 10 Heteroaryl and optionally substituted C4-C 10 Heterocyclyl; wherein R' and R" are each independently selected from H, C1-C6 alkyl, C2-C8 alkenyl and C1-C6 alkoxy; The optionally substituted C1-C 10 Alkyl, optionally substituted C2-C 10 Alkenyl and optionally substituted C2-C 10 Each alkynyl group is optionally substituted with 1-5 substituents selected from the group consisting of carboxyl, cyano, C6-C4 alkyl, halo-C1-C4 alkyl, -NR'R", and hydroxy. 14 Aryl, C5-C4 alkyl, C1-C4 alkyl, halogenated C1-C4 alkyl, -NR'R" and hydroxyl, optionally substituted with 1-5 substituents 10 Heteroaryl, C4-C4 alkyl, C1-C4 alkyl haloalkyl, -NR'R" and hydroxyl, optionally substituted with 1-5 substituents 10 Heterocyclic group, hydroxyl alkyl, C3-C8 cycloalkyl, C2-C8 alkenyl, halogen and -NR a R b ; wherein R' and R" are each independently selected from H, C1-C6 alkyl, C2-C8 alkenyl and C1-C6 alkoxy; wherein R a and R b Each independently selected from: H, C1-C1 optionally substituted with 1-5 substituents selected from halogen and hydroxy 10 C2-C8 alkyl optionally substituted by 1-5 substituents selected from halogen and hydroxy, C2-C8 alkenyl optionally substituted by 1-5 substituents selected from halogen and C1-C4 alkyl, C1-C6 alkyl optionally substituted by 3-14 membered carbocyclyl selected by 1-5 substituents selected from halogen and C1-C4 alkyl, C1-C6 alkyl optionally substituted by 1-5 substituents selected from halogen, hydroxy and C1-C4 alkyl, C6-C8 alkyl optionally substituted by 1-5 substituents selected from halogen, hydroxy, C1-C4 alkoxy and C1-C4 alkyl 14 Aryl, and C6-C4 substituted by 1-5 groups selected from halogen, hydroxyl and C1-C4 alkyl 14 Aryl-C1-C6 alkyl, or R a and R b Together with the nitrogen atom to which they are attached, they form a heterocyclic or benzoheterocyclic group, which is optionally substituted by 1-5 substituents selected from the group consisting of C1-C8 alkyl, optionally substituted by 1-5 substituents selected from the group consisting of halogen, hydroxy, =N-C1-C4 alkoxy, C1-C4 alkoxy and -NR'R", C2-C8 alkenyl, optionally substituted by 1-5 substituents selected from the group consisting of halogen, hydroxy and -NR'R", C1-C6 alkoxy, cyano, carboxyl, halogen, -NR'R", hydroxy, optionally substituted by 1-5 substituents selected from the group consisting of C1-C4 acyl, halogen, -NR'R", C1-C4 alkoxy, C1-C4 alkyl, cyano, hydroxy, C1-C4 alkoxycarbonyl, C6-C 14 C6-C4 substituted aryl and halogenated C1-C4 alkyl 14 Aryl, C1-C 10 Acyl, C1-C6 alkoxycarbonyl, C2-C8 alkenyloxycarbonyl, -NR'R" substituted C1-C6 acyl, C6-C6 alkyl optionally substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy 14 C1-C4 acyl substituted by aryl, C3-C8 cycloalkyl substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, C6-C8 cycloalkyl substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, 14 C1-C6 alkyl substituted by aryl, C3-C8 cycloalkyl substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, C3-C8 cycloalkyl substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, 4-7 membered heterocyclyl optionally substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, C1-C6 alkyl optionally substituted with 4-7 membered heterocyclyl substituted with a substituent selected from halogen, C1-C4 alkyl, halo-substituted C1-C4 alkyl and hydroxy, 5-10 membered heteroaryl optionally substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-substituted C1-C4 alkyl and hydroxy, and C1-C6 alkyl optionally substituted with 5-10 membered heteroaryl substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-substituted C1-C4 alkyl and hydroxy, wherein R' and R" are each independently selected from H, C1-C6 alkyl, C2-C8 alkenyl and C1-C6 alkoxy; The optionally substituted C3-C8 carbocyclic group, the optionally substituted C6-C 14 Aryl, optionally substituted C5-C 10 Heteroaryl and optionally substituted C4-C 10 Each heterocyclic group is optionally substituted with 1-5 substituents selected from halogen, hydroxy, carboxyl, cyano, -NR'R", C1-C6 acyl, C1-C4 alkyl, halo-C1-C4 alkyl, C1-C4 alkoxy, halo-C1-C4 alkoxy, hydroxy-substituted C1-C4 alkyl, hydroxy-substituted C1-C4 alkoxy and C2-C8 alkenyl; wherein R' and R" are each independently selected from H, C1-C6 alkyl, C2-C8 alkenyl and C1-C6 alkoxy.

5. The compound of claim 1, or a pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide, hydrate, solvate, prodrug, or isotopic variant thereof, wherein: R4 is selected from the group consisting of: H, -NR'R", optionally substituted C1-C 10 Alkyl, optionally substituted C2-C 10 Alkenyl, optionally substituted C2-C 10 Alkynyl, optionally substituted C3-C8 carbocyclyl, optionally substituted C6-C 14 Aryl, optionally substituted C5-C 10 Heteroaryl and optionally substituted C4-C 10 Heterocyclyl; wherein R' and R" are each independently selected from H, C1-C6 alkyl, C2-C8 alkenyl and C1-C6 alkoxy; The optionally substituted C1-C 10 Alkyl, optionally substituted C2-C 10 Alkenyl and optionally substituted C2-C 10 Each alkynyl group is optionally substituted with 1-5 substituents selected from the group consisting of carboxyl, cyano, C6-C4 alkyl, halo-C1-C4 alkyl, -NR'R", and hydroxy. 14 Aryl, C5-C4 alkyl, C1-C4 alkyl, halogenated C1-C4 alkyl, -NR'R" and hydroxyl, optionally substituted with 1-5 substituents 10 Heteroaryl, C4-C4 alkyl, C1-C4 alkyl haloalkyl, -NR'R" and hydroxyl, optionally substituted with 1-5 substituents 10 Heterocyclyl, hydroxy, C3-C8 cycloalkyl, C2-C8 alkenyl, halogen and -NR a R b ; wherein R' and R" are each independently selected from H, C1-C6 alkyl, C2-C8 alkenyl and C1-C6 alkoxy; wherein R a and R b Each independently selected from: H, C1-C1 optionally substituted with 1-5 substituents selected from halogen and hydroxy 10 C2-C8 alkyl optionally substituted by 1-5 substituents selected from halogen and hydroxy, C2-C8 alkenyl optionally substituted by 1-5 substituents selected from halogen and C1-C4 alkyl, C1-C6 alkyl optionally substituted by 3-14 membered carbocyclyl selected by 1-5 substituents selected from halogen and C1-C4 alkyl, C1-C6 alkyl optionally substituted by 1-5 substituents selected from halogen, hydroxy and C1-C4 alkyl, C6-C8 alkyl optionally substituted by 1-5 substituents selected from halogen, hydroxy, C1-C4 alkoxy and C1-C4 alkyl 14 Aryl, and C6-C14 aryl-C1-C6 alkyl optionally substituted by 1-5 groups selected from halogen, hydroxyl and C1-C4 alkyl, or R a and R b Together with the nitrogen atom to which they are attached, they form a heterocyclic or benzoheterocyclic group, which is optionally substituted by 1-5 substituents selected from the group consisting of C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkoxy, C6-C6 acyl, halogen, -NR'R", C1-C4 alkoxy, C1-C4 alkyl, cyano, hydroxy, C1-C4 alkoxycarbonyl, C6-C 14 C6-C4 substituted aryl and halogenated C1-C4 alkyl 14 Aryl, C1-C 10 Acyl, C1-C6 alkoxycarbonyl, C2-C8 alkenyloxycarbonyl, -NR'R" substituted C1-C6 acyl, C6-C6 alkyl optionally substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy 14 C1-C4 acyl substituted by aryl, C3-C8 cycloalkyl substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, C6-C8 cycloalkyl substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, 14 C1-C6 alkyl substituted by aryl, C3-C8 cycloalkyl substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, C3-C8 cycloalkyl substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, 4-7 membered heterocyclyl optionally substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, C1-C6 alkyl optionally substituted with 4-7 membered heterocyclyl substituted with a substituent selected from halogen, C1-C4 alkyl, halo-substituted C1-C4 alkyl and hydroxy, 5-10 membered heteroaryl optionally substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-substituted C1-C4 alkyl and hydroxy, and C1-C6 alkyl optionally substituted with 5-10 membered heteroaryl substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-substituted C1-C4 alkyl and hydroxy, wherein R' and R" are each independently selected from H, C1-C6 alkyl, C2-C8 alkenyl and C1-C6 alkoxy; The optionally substituted C3-C8 carbocyclic group, the optionally substituted C6-C 14 Aryl, optionally substituted C5-C 10 Heteroaryl and optionally substituted C4-C 10 Each heterocyclic group is optionally substituted with 1-5 substituents selected from halogen, hydroxy, carboxyl, cyano, -NR'R", C1-C6 acyl, C1-C4 alkyl, halo-C1-C4 alkyl, C1-C4 alkoxy, halo-C1-C4 alkoxy, hydroxy-substituted C1-C4 alkyl, hydroxy-substituted C1-C4 alkoxy and C2-C8 alkenyl; wherein R' and R" are each independently selected from H, C1-C6 alkyl, C2-C8 alkenyl and C1-C6 alkoxy.

6. The compound of claim 1, or a pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide, hydrate, solvate, prodrug, or isotopic variant thereof, wherein: R4 is hydroxy, C3-C8 cycloalkyl, C2-C8 alkenyl, halogen or -NR a R b Substituted C1-C 10 Alkyl, preferably -NR a R b Substituted C1-C4 alkyl; wherein R a and R b Each independently selected from: H, C1-C1 optionally substituted with 1-5 substituents selected from halogen and hydroxy 10 C2-C8 alkyl optionally substituted by 1-5 substituents selected from halogen and hydroxy, C2-C8 alkenyl optionally substituted by 1-5 substituents selected from halogen and C1-C4 alkyl, C1-C6 alkyl optionally substituted by 3-14 membered carbocyclyl selected by 1-5 substituents selected from halogen and C1-C4 alkyl, C1-C6 alkyl optionally substituted by 1-5 substituents selected from halogen, hydroxy and C1-C4 alkyl, C6-C8 alkyl optionally substituted by 1-5 substituents selected from halogen, hydroxy and C1-C4 alkyl, 14 Aryl, and C6-C4 substituted by 1-5 groups selected from halogen, hydroxyl and C1-C4 alkyl 14 Aryl-C1-C6 alkyl; or R a and R b Together with the nitrogen atom to which they are attached, they form a heterocyclic or benzoheterocyclic group, which is optionally substituted by 1-5 substituents selected from the group consisting of C1-C8 alkyl, optionally substituted by 1-5 substituents selected from the group consisting of halogen, hydroxy, =N-C1-C4 alkoxy, C1-C4 alkoxy and -NR'R", C2-C8 alkenyl, optionally substituted by 1-5 substituents selected from the group consisting of halogen, hydroxy and -NR'R", C1-C6 alkoxy, optionally substituted by 1-5 substituents selected from the group consisting of halogen and hydroxy, cyano, carboxyl, halogen, -NR'R", hydroxy, optionally substituted by 1-5 substituents selected from the group consisting of C1-C4 acyl, halogen, NR'R", C1-C4 alkoxy, C1-C4 alkyl, cyano, hydroxy, C1-C4 alkoxycarbonyl, C6-C 14 C6-C4 substituted aryl and halogenated C1-C4 alkyl 14 Aryl, C1-C 10 Acyl, C1-C6 alkoxycarbonyl, C2-C8 alkenyloxycarbonyl, NR'R" substituted C1-C6 acyl, C6-C6 alkyl optionally substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy 14 Aryl-substituted C1-C4 acyl, C6-C4 acyl optionally substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy 14 C1-C6 alkyl substituted by aryl, C3-C8 cycloalkyl substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, C3-C8 cycloalkyl substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, 4-7 membered heterocyclyl optionally substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, C1-C6 alkyl optionally substituted with 4-7 membered heterocyclyl substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-substituted C1-C4 alkyl and hydroxy, 5-10 membered heteroaryl optionally substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-substituted C1-C4 alkyl and hydroxy, and C1-C6 alkyl optionally substituted with 5-10 membered heteroaryl substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-substituted C1-C4 alkyl and hydroxy; wherein R' and R" are each independently selected from H, C1-C6 alkyl, C2-C8 alkenyl and C1-C6 alkoxy; Preferably, R4 is an optionally substituted C4-C 10 Heterocyclic or optionally substituted C4-C 10 Heterocyclic substituted C1-C 10 alkyl Preferably, the heterocyclic group is optionally substituted by 1, 2 or 3 substituents selected from the following: C1-C8 alkyl optionally substituted by 1-5 substituents selected from halogen, hydroxy, =N-C1-C4 alkoxy, C1-C4 alkoxy and -NR'R", C2-C8 alkenyl optionally substituted by 1-5 substituents selected from halogen, hydroxy and -NR'R", C1-C6 alkoxy optionally substituted by 1-5 substituents selected from halogen and hydroxy, cyano, carboxyl, halogen, -NR'R", hydroxy, optionally substituted by 1-5 substituents selected from C1-C4 acyl, halogen, NR'R", C1-C4 alkoxy, C1-C4 alkyl, cyano, hydroxy, C1-C4 alkoxycarbonyl, C6-C 14 C6-C4 substituted aryl and halogenated C1-C4 alkyl 14 Aryl, C1-C 10 Acyl, C1-C6 alkoxycarbonyl, C2-C8 alkenyloxycarbonyl, NR'R" substituted C1-C6 acyl, C6-C6 alkyl optionally substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy 14 Aryl-substituted C1-C4 acyl, C6-C4 acyl optionally substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy 14 C1-C6 alkyl substituted by aryl, C3-C8 cycloalkyl substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, C3-C8 cycloalkyl substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, 4-7 membered heterocyclyl optionally substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, C1-C6 alkyl optionally substituted with 4-7 membered heterocyclyl substituted with a substituent selected from halogen, C1-C4 alkyl, halo-substituted C1-C4 alkyl and hydroxy, a 5-10 membered heteroaryl optionally substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-substituted C1-C4 alkyl and hydroxy, and a 5-10 membered heteroaryl optionally substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-substituted C1-C4 alkyl and hydroxy; wherein R' and R" are each independently selected from H, C1-C6 alkyl, C2-C8 alkenyl and C1-C6 alkoxy.

7. The compound of claim 1, or a pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide, hydrate, solvate, prodrug, or isotopic variant thereof, wherein: R4 is hydroxy, C3-C8 cycloalkyl, C2-C8 alkenyl, halogen or -NR a R b Substituted C1-C 10 Alkyl, preferably -NR a R b Substituted C1-C4 alkyl; wherein R a and R b Each independently selected from: H, C1-C1 optionally substituted with 1-5 substituents selected from halogen and hydroxy 10 C2-C8 alkyl optionally substituted by 1-5 substituents selected from halogen and hydroxy, C2-C8 alkenyl optionally substituted by 1-5 substituents selected from halogen and C1-C4 alkyl, C1-C6 alkyl optionally substituted by 3-14 membered carbocyclyl selected by 1-5 substituents selected from halogen and C1-C4 alkyl, C1-C6 alkyl optionally substituted by 1-5 substituents selected from halogen, hydroxy and C1-C4 alkyl, C6-C8 alkyl optionally substituted by 1-5 substituents selected from halogen, hydroxy and C1-C4 alkyl, 14 Aryl, and C6-C4 substituted by 1-5 groups selected from halogen, hydroxyl and C1-C4 alkyl 14 Aryl-C1-C6 alkyl; or R a and R b Together with the nitrogen atom to which they are attached, they form a heterocyclic or benzoheterocyclic group, which is optionally substituted by 1-5 substituents selected from the group consisting of C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkoxy, C6-C6 acyl, halogen, NR'R", C1-C4 alkoxy, C1-C4 alkyl, cyano, hydroxy, C1-C4 alkoxycarbonyl, C6-C 14 C6-C4 substituted aryl and halogenated C1-C4 alkyl 14 Aryl, C1-C 10 Acyl, C1-C6 alkoxycarbonyl, C2-C8 alkenyloxycarbonyl, NR'R" substituted C1-C6 acyl, C6-C6 alkyl optionally substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy 14 Aryl-substituted C1-C4 acyl, C6-C4 acyl optionally substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy 14 C1-C6 alkyl substituted by aryl, C3-C8 cycloalkyl substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, C3-C8 cycloalkyl substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, 4-7 membered heterocyclyl optionally substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, C1-C6 alkyl optionally substituted with 4-7 membered heterocyclyl substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-substituted C1-C4 alkyl and hydroxy, 5-10 membered heteroaryl optionally substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-substituted C1-C4 alkyl and hydroxy, and C1-C6 alkyl optionally substituted with 5-10 membered heteroaryl substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-substituted C1-C4 alkyl and hydroxy; wherein R' and R" are each independently selected from H, C1-C6 alkyl, C2-C8 alkenyl and C1-C6 alkoxy; Preferably, R4 is an optionally substituted C4-C 10 Heterocyclic or optionally substituted C4-C 10 Heterocyclic substituted C1-C 10 alkyl; preferably, the heterocyclic group is optionally substituted by 1, 2 or 3 substituents selected from the following: C1-C6 alkyl optionally substituted by 1-5 substituents selected from halogen and hydroxy, C1-C6 alkoxy optionally substituted by 1-5 substituents selected from halogen and hydroxy, cyano, carboxyl, halogen, -NR'R", hydroxy, optionally substituted by 1-5 substituents selected from C1-C4 acyl, halogen, NR'R", C1-C4 alkoxy, C1-C4 alkyl, cyano, hydroxy, C1-C4 alkoxycarbonyl, C6-C 14 C6-C4 substituted aryl and halogenated C1-C4 alkyl 14 Aryl, C1-C 10 Acyl, C1-C6 alkoxycarbonyl, C2-C8 alkenyloxycarbonyl, NR'R" substituted C1-C6 acyl, C6-C6 alkyl optionally substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy 14 Aryl-substituted C1-C4 acyl, C6-C4 acyl optionally substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy 14 C1-C6 alkyl substituted by aryl, C3-C8 cycloalkyl substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, C3-C8 cycloalkyl substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, 4-7 membered heterocyclyl optionally substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, C1-C6 alkyl optionally substituted with 4-7 membered heterocyclyl substituted with a substituent selected from halogen, C1-C4 alkyl, halo-substituted C1-C4 alkyl and hydroxy, a 5-10 membered heteroaryl optionally substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-substituted C1-C4 alkyl and hydroxy, and a 5-10 membered heteroaryl optionally substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-substituted C1-C4 alkyl and hydroxy; wherein R' and R" are each independently selected from H, C1-C6 alkyl, C2-C8 alkenyl and C1-C6 alkoxy.

8. The compound of claim 1, or a pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide, hydrate, solvate, prodrug, or isotopic variant thereof, wherein: R4 is: wherein R9 is selected from the group consisting of: H, hydroxy, C1-C6 alkyl, C2-C8 alkenyl, C1-C6 alkoxy, C2-C8 alkenyloxy, C3-C8 cycloalkenyl, -NR'R", and optionally substituted by 1-5 groups selected from the group consisting of C1-C4 acyl, halogen, NR'R", C1-C4 alkoxy, C1-C4 alkyl, cyano, hydroxy, C1-C4 alkoxycarbonyl, C6-C 14 C6-C4 substituted aryl and halogenated C1-C4 alkyl 14 Aryl; wherein R' and R" are each independently selected from H, C1-C6 alkyl, C2-C8 alkenyl and C1-C6 alkoxy; preferably, R9 is selected from: H, hydroxy, C1-C6 alkyl, C2-C8 alkenyl, C1-C6 alkoxy, C2-C8 alkenyloxy, -NR'R" and C6-C 14 Aryl; wherein R' and R" are each independently selected from H, C1-C6 alkyl, C2-C8 alkenyl and C1-C6 alkoxy.

9. The compound of claim 1, or a pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide, hydrate, solvate, prodrug, or isotopic variant thereof, wherein: R5 is selected from the group consisting of: H, hydroxy, halogen, C1-C4 alkoxy and C1-C4 alkyl; preferably, R5 is selected from the group consisting of: hydroxy, C1-C4 alkoxy and C1-C4 alkyl; more preferably, R5 is hydroxy.

10. The compound of claim 1, or a pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide, hydrate, solvate, prodrug, or isotopic variant thereof, wherein: R6 is selected from: H and C1-C4 alkyl, wherein the C1-C4 alkyl is optionally substituted by a 4-7 membered monocyclic saturated heterocyclic group or a C3-C8 cycloalkyl, and the 4-7 membered monocyclic saturated heterocyclic group and the C3-C8 cycloalkyl are each optionally substituted by 1-3 substituents selected from halogen, C1-C4 alkyl, halo-substituted C1-C4 alkyl, C1-C4 alkoxy and halo-substituted C1-C4 alkoxy.

11. The compound of claim 1, or a pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide, hydrate, solvate, prodrug, or isotopic variant thereof, wherein: R7 is selected from the group consisting of: H, C1-C6 alkyl optionally substituted by 1-5 substituents selected from halogen and hydroxy, C2-C6 alkenyl optionally substituted by 1-5 substituents selected from halogen and hydroxy, C3-C8 saturated or partially saturated carbocyclyl, halogen, hydroxy, C6-C8 optionally substituted by 1-3 substituents selected from C1-C4 alkyl, halo-C1-C4 alkyl, halogen, C2-C4 alkenyl and hydroxy. 14 C1-C6 alkoxy substituted by aryl, 5-10 membered heteroaryl optionally substituted by 1-3 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, and C6-C4 alkyl optionally substituted by 1-3 substituents selected from C1-C4 alkyl, halo-C1-C4 alkyl, halogen, C2-C4 alkenyl and hydroxy 14 aryl; Preferably, R7 is selected from: H, C1-C6 alkyl optionally substituted with 1-5 halogen and hydroxyl groups, Selected from halogen and hydroxy substituted C2-C6 alkenyl, C3-C8 saturated or partially saturated carbocyclic group, halogen, hydroxy, C6-C 14 Aryl-substituted C1-C4 alkoxy, 5-10 membered heteroaryl, and C6-C4 alkyl optionally substituted with 1-3 substituents selected from C1-C4 alkyl, halo-substituted C1-C4 alkyl, halogen, C2-C4 alkenyl and hydroxyl. 14 Aryl.

12. The compound of claim 1, or a pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide, hydrate, solvate, prodrug, or isotopic variant thereof, wherein: The compound of formula I has the structure shown in the following formula II: wherein Z1, X, Y, R3, R5, R6, R7 and n are as described in any one of claims 1 to 11; R1 is selected from hydroxy, C3-C8 cycloalkyl, C2-C8 alkenyl, halogen or -NR a R b ; Among them, R a and R b As claimed in any one of claims 4 to 7; or The compound of formula I has the structure shown in the following formula III: In the formula, Z1, X, Y, R3, R5, R6, R7 and n are as described in any one of claims 1 to 11, and R a and R b As claimed in any one of claims 4 to 7; or The compound of formula I has the structure shown in the following formula IV: wherein Z1, X, Y, R3, R5, R6, R7 and n are as described in any one of claims 1 to 11; m is 0, 1, 2, 3, 4 or 5, preferably 0, 1 or 2; R2 is selected from: C1-C8 alkyl optionally substituted with 1-5 substituents selected from halogen, hydroxy, =N-C1-C4 alkoxy, C1-C4 alkoxy and -NR'R", C2-C8 alkenyl optionally substituted with 1-5 substituents selected from halogen, hydroxy and -NR'R", C1-C6 alkoxy optionally substituted with 1-5 substituents selected from halogen and hydroxy, cyano, carboxyl, halogen, -NR'R", hydroxy, C1-C4 acyl, halogen, NR'R", C1-C4 alkoxy, C1-C4 alkyl, cyano, hydroxy, C1-C4 alkoxycarbonyl, C6-C 14 C6-C4 substituted aryl and halogenated C1-C4 alkyl 14 Aryl, C1-C 10 Acyl, C1-C6 alkoxycarbonyl, C2-C8 alkenyloxycarbonyl, NR'R" substituted C1-C6 acyl, C6-C6 alkyl optionally substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy 14 Aryl-substituted C1-C4 acyl, C6-C4 acyl optionally substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy 14 C1-C6 alkyl optionally substituted by aryl, C3-C8 cycloalkyl optionally substituted by 1-5 substituents selected from the group consisting of halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, C3-C8 cycloalkyl optionally substituted by 1-5 substituents selected from the group consisting of halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, 4-7 membered heterocyclyl optionally substituted by 1-5 substituents selected from the group consisting of halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, C1-C6 alkyl optionally substituted by 1-5 substituents selected from the group consisting of halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, -5 5-10 membered heteroaryl substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, and C1-C6 alkyl substituted with 5-10 membered heteroaryl optionally substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy; wherein R' and R" are each independently selected from H, C1-C6 alkyl, C2-C8 alkenyl and C1-C6 alkoxy; preferably, in formula IV, m is 1, R2 is R9-C(O)-, R9-CH(OH)-, R9-CH(NH2)- or R9-CH(SH)-, wherein R9 is as defined in claim 8, preferably, R9 is located in the para position relative to N.

13. The compound of claim 12, wherein R2 is selected from the group consisting of: C1-C6 alkyl optionally substituted with 1-5 substituents selected from halogen and hydroxy, C1-C6 alkoxy optionally substituted with 1-5 substituents selected from halogen and hydroxy, cyano, carboxyl, halogen, -NR'R", hydroxy, C1-C4 acyl, halogen, NR'R", C1-C4 alkoxy, C1-C4 alkyl, cyano, hydroxy, C1-C4 alkoxycarbonyl, C6-C 14 C6-C4 substituted aryl and halogenated C1-C4 alkyl 14 Aryl, C1-C 10 Acyl, C1-C6 alkoxycarbonyl, C2-C8 alkenyloxycarbonyl, NR'R" substituted C1-C6 acyl, C6-C6 alkyl optionally substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy 14 Aryl-substituted C1-C4 acyl, C6-C4 acyl optionally substituted by 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy 14 C1-C6 alkyl substituted with aryl, C1-C6 alkyl substituted with C3-C8 cycloalkyl optionally substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, C3-C8 cycloalkyl optionally substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, 4-7 membered heterocyclyl optionally substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, C1-C6 alkyl optionally substituted with 4-7 membered heterocyclyl substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, 5-10 membered heteroaryl optionally substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy, and C1-C6 alkyl optionally substituted with 5-10 membered heteroaryl substituted with 1-5 substituents selected from halogen, C1-C4 alkyl, halo-C1-C4 alkyl and hydroxy; wherein, R' and R" are each independently selected from H, C1-C6 alkyl, C2-C8 alkenyl and C1-C6 alkoxy.

14. The compound of claim 1, or a pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide, hydrate, solvate, prodrug, or isotopic variant thereof, wherein: X is O; Y is O; Z1 is O; Z2, Z3, Z4, Z5, Z6 and Z7 are all -C-; R3 is OH; R4 is -NR a R b Substituted C1-C4 alkyl, wherein R a and R b Each independently selected from: H, C1-C6 alkyl, halogenated C1-C6 alkyl, C2-C8 alkenyl and C3-C8 cycloalkyl, or R a and R b Together with the nitrogen to which they are attached, they form a heterocyclic group, which is optionally substituted by 1-2 substituents selected from the group consisting of C1-C6 alkyl, C2-C6 alkenyl, hydroxy-substituted C1-C6 alkyl, C1-C6 10 Acyl, C1-C6 alkoxycarbonyl, 5-7 membered nitrogen-containing heteroaryl, C6-C6 optionally substituted with 1-2 halogens 14 Aryl-substituted C1-C4 acyl, optionally substituted by 1-2 groups selected from halogen, hydroxyl, C6-C 14 C6-C4 alkyl substituted with aryl, C1-C4 alkyl and C1-C4 alkoxy 14 Aryl or C6-C 14 Aryl C1-C4 alkyl.

15. The compound of claim 1, or a pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide, hydrate, solvate, prodrug, or isotopic variant thereof, wherein: X is O; Y is O; Z1 is O; Z2, Z3, Z4, Z5, Z6 and Z7 are all -C-; R3 is OH; R4 is -NR a R b Substituted C1-C4 alkyl, wherein R a and R b Each independently selected from: H, C1-C6 alkyl, halogenated C1-C6 alkyl, C2-C8 alkenyl and C3-C8 cycloalkyl, or R a and R b Together with the nitrogen to which they are attached, they form a heterocyclic group, which is optionally substituted by 1-2 substituents selected from the group consisting of C1-C6 alkyl, hydroxy-substituted C1-C6 alkyl, C1-C 10 Acyl, C1-C6 alkoxycarbonyl, 5-7 membered nitrogen-containing heteroaryl, C6-C6 optionally substituted with 1-2 halogens 14 Aryl-substituted C1-C4 acyl, optionally substituted by 1-2 groups selected from halogen, hydroxyl, C6-C 14 C6-C4 alkyl substituted with aryl, C1-C4 alkyl and C1-C4 alkoxy 14 Aryl or C6-C 14 Aryl C1-C4 alkyl.

16. The compound of claim 1, or a pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide, hydrate, solvate, prodrug, or isotopic variant thereof, wherein: The compound of formula I is a compound having the following structure:

17. The compound of claim 1, or a pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide, hydrate, solvate, prodrug, or isotopic variant thereof, wherein: The compound of formula I is a compound having the following structure:

18. The compound of any one of claims 1 to 17, or a pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide, hydrate, solvate, prodrug, and isotopic variant thereof, characterized in that: The pharmaceutically acceptable salt is hydrochloride or hydrobromide.

19. A pharmaceutical composition comprising: (i) an effective amount of a compound according to any one of claims 1 to 18 or a pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide, hydrate, solvate, prodrug or isotopic variant thereof as an active ingredient; and (ii) a pharmaceutically acceptable carrier or excipient; The pharmaceutical composition optionally further contains: (iii) a second active ingredient; preferably, the second active ingredient is selected from: microbial inhibitors, anticancer drugs, antirheumatic drugs, antioxidant drugs, anti-inflammatory drugs, antiviral drugs, liver-protecting drugs and drugs for treating cardiovascular diseases.

20. Use of a compound according to any one of claims 1 to 18, or a pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide, hydrate, solvate, prodrug or isotopic variant thereof, in the preparation of antibacterial, anticancer, antirheumatic, antioxidant, anti-inflammatory, antiviral, hepatoprotective or hepatoprotective medicament for the treatment and / or prevention of cardiovascular disease, or in the preparation of a medicament for the treatment of infectious diseases, in particular diseases caused by sensitive or resistant Mycobacterium tuberculosis.

21. The use according to claim 20, characterized in that The bacteria are selected from the group consisting of Mycobacterium tuberculosis, drug-resistant Mycobacterium tuberculosis, Klebsiella pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, Mycobacterium leprae, Mycobacterium bovis, Mycobacterium marinum, Corynebacterium diphtheriae, Bordetella pertussis, Haemophilus influenzae and Streptococcus pneumoniae.

22. A method for preparing the compound represented by the following formula Ia: In the formula, Z4-Z7 and n are as described in any one of claims 1-15, and one of R4 and R6 is H and the other is -CH2-NR a R b , R3 is hydroxyl, halogen, C1-C 10 Alkyl or C1-C 10 Alkoxy, R7 is H, halogen, C1-C4 alkyl or C3-C7 cycloalkyl, wherein, R a and R b The method according to any one of claims 4 to 7, wherein the method comprises: (1) In an organic solvent, the compound represented by the following formula 1 is reacted with Cu 2+ reacting with the substituted benzoquinone of formula 2 under catalysis to prepare a compound of formula 3; and (2) reacting the compound of formula 3, formaldehyde solution, and a primary amine, a secondary amine, or a salt thereof in an alcohol to prepare a compound represented by formula Ia; wherein, when the reactant is a primary amine or a salt of a secondary amine, a base is added to the reaction system; Optionally, when R3 in the compound of formula 3 is C1-C 10 When R3 is an alkoxy group, the method further comprises the step of subjecting the compound of formula 3 to a dealkylation reaction in the presence of boron tribromide, thereby preparing a compound of formula Ia wherein R3 is a hydroxyl group.

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