Nitrogen-containing heterocyclic compound

Abstract

The present invention relates to a nitrogen-containing heterocyclic compound and its use, which has a significantly superior therapeutic effect on tumors having low expression, no expression, low activity or inactivity of the mitochondrial membrane permeability transition pore and / or low expression, no expression, low activity or inactivity of peptidylprolyl isomerase F. In particular, the present invention provides a compound of formula I, or an optical isomer or racemate thereof, or a solvate thereof, or a pharma- ceutically acceptable salt thereof, or a deuterated compound thereof. JPEG2025509622000598.jpg75147

Description

[Technical Field]

[0001] The present invention relates to the technical field of medicine, and in particular to nitrogen-containing heterocyclic compounds. [Background technology]

[0002] Tumors, as a common disease that seriously endangers human health, have been associated with a steadily increasing trend in the mortality rate from malignant tumors. Due to the heterogeneity of tumors, simply using the same treatment or drug for each tumor based on its origin and pathological characteristics can easily lead to problems caused by inappropriate treatment, delaying patients' critical treatment time and opportunity. Therefore, there is a great need to adopt precision therapy for various tumor conditions. With the development of biological technology, tumors exhibit a continuous genotype distribution at the molecular level, including genes and proteins. Changes in the expression and activity of tumor-related genes and proteins have been increasingly discovered, and these changes play an important role in the development of malignant tumors. The discovery and application of biomarkers provides precise guidance for the application of relevant drugs, enabling precision tumor therapy, thereby achieving targeted dosing, significantly improving therapeutic efficacy, and reducing drug dosage and toxic side effects.

[0003] Therefore, there is an urgent need in the art to develop drugs that can precisely treat tumors. Summary of the Invention [Problem to be solved by the invention]

[0004] The present invention aims to provide a compound that has significantly superior therapeutic effects on tumors with low expression, no expression, low activity, or inactivity of the mitochondrial permeability transition pore and / or tumors with low expression, no expression, low activity, or inactivity of peptidylprolyl isomerase F. [Means for solving the problem]

[0005] A first aspect of the present invention provides a compound of formula I, or an optical isomer or racemate thereof, or a solvate thereof, or a pharmaceutically acceptable salt thereof, or a deuterated compound thereof. [ka] I wherein R1 and R2 each independently represent a hydrogen atom, a deuterium atom, a halogen atom, a substituted or unsubstituted C1-C16 alkyl group, a substituted or unsubstituted C3-C16 cycloalkyl group, a substituted or unsubstituted 3-12 membered heterocycloalkyl group, a substituted or unsubstituted C1-C16 halogenated alkyl group, a substituted or unsubstituted C3-C16 halogenated cycloalkyl group, a substituted or unsubstituted C6-C16 aryl group, or a substituted or unsubstituted 5-12 membered heteroaryl group; R3, R4, and R5 each independently represent a hydrogen atom, a halogen atom, or R 17 -O-, R 17 -S- or (R 18 R 19 )N-; or R3 and R4, or R4 and R5, join to form a substituted or unsubstituted 3- to 12-membered heterocycloalkyl ring; R6, R8, R 11 , R 12 , R 13 , R 14 and R 15 each independently represents a hydrogen atom, a substituted or unsubstituted C1-C8 alkyl group, or a halogen atom; R7 represents a hydrogen atom, a substituted or unsubstituted C1-C12 alkyl group, a substituted or unsubstituted C1-C12 halogenated alkyl group, a substituted or unsubstituted C6-C16 aryl group-substituted or unsubstituted C1-C12 alkyl group-, or a substituted or unsubstituted 5-16 membered heteroaryl group-substituted or unsubstituted C1-C12 alkyl group-; R9 and R 10 are joined to form a substituted or unsubstituted 3- to 12-membered heterocycloalkyl ring; R 17 represents a hydrogen atom, a substituted or unsubstituted C1-C16 alkyl group, [ka] , Substituted or unsubstituted C3-C16 cycloalkyl group, substituted or unsubstituted 3-12 membered heterocycloalkyl group, substituted or unsubstituted C3-C16 cycloalkyl group-substituted or unsubstituted C2-C10 acyl group-, substituted or unsubstituted C3-C16 cycloalkyl group-C(O)-, substituted or unsubstituted C1-C16 halogenated alkyl group, substituted or unsubstituted C3-C16 halogenated cycloalkyl group, substituted or unsubstituted 3-12 membered heterocycloalkyl group-substituted or unsubstituted C1-C12 alkyl group-, substituted or unsubstituted C6-C16 aryl group-substituted or unsubstituted C1-C12 alkyl group-, substituted or unsubstituted C6-C16 aryl group-substituted or unsubstituted C6-C16 aryl group-substituted or unsubstituted C1-C12 alkyl group-, substituted or unsubstituted 5- 16-membered heteroaryl group-substituted or unsubstituted C1-C12 alkyl group-, substituted or unsubstituted C6-C16 aryl group-O-substituted or unsubstituted C1-C12 alkyl group-, substituted or unsubstituted C6-C16 aryl group-S-substituted or unsubstituted C1-C12 alkyl group-, substituted or unsubstituted 5-16-membered heteroaryl group-O-substituted or unsubstituted C1-C12 alkyl group-, substituted or unsubstituted 5-16-membered heteroaryl group-S-substituted or unsubstituted C1-C12 alkyl group-, substituted or unsubstituted C2-C8 alkenyl group-substituted or unsubstituted C1-C8 alkyl group-substituted or unsubstituted C2-C8 alkenyl group-substituted or unsubstituted C1-C8 alkyl group-, substituted or unsubstituted C2-C8 alkenyl group-substituted or unsubstituted C1-C8 alkyl group-, or (R 20 R 21 ) N-substituted or unsubstituted C1-C12 alkyl group; R 18 and R 19 each independently represents a hydrogen atom, a substituted or unsubstituted C1-C12 alkyl group, a substituted or unsubstituted C3-C12 cycloalkyl group, or a substituted or unsubstituted C6-C16 aryl group-substituted or unsubstituted C1-C12 alkyl group; or R 18 and R 19 are joined to form a substituted or unsubstituted 3- to 12-membered heterocycloalkyl ring; R20 and R 21 each independently represents a hydrogen atom, a substituted or unsubstituted C1-C12 alkyl group, a substituted or unsubstituted C3-C12 cycloalkyl group, or a substituted or unsubstituted C2-C10 ester group; or R 20 and R 21 are joined to form a substituted or unsubstituted 3- to 12-membered heterocycloalkyl group.

[0006] In another preferred example, the heterocycloalkyl group, the heteroaryl group, and the heterocycloalkyl ring each independently have 1 to 4 (preferably 1, 2, 3, or 4) heteroatoms selected from N, O, and S on the heterocycle.

[0007] In another preferred example, the heterocycloalkyl group has 1 to 4 (preferably 1, 2, 3, or 4) heteroatoms independently selected from N, O, and S on the heterocycle.

[0008] In another preferred example, the heteroaryl group has 1 to 4 (preferably 1, 2, 3 or 4) heteroatoms independently selected from N, O and S on the heterocyclic ring.

[0009] In another preferred example, the heterocycloalkyl ring has 1 to 4 (preferably 1, 2, 3 or 4) heteroatoms independently selected from N, O and S on the heterocyclic ring.

[0010] In another preferred embodiment, the heterocycloalkyl group has 0, 1, or 2 C=C cyclic double bonds.

[0011] In another preferred embodiment, the heterocycloalkyl ring has 0, 1, or 2 C=C cyclic double bonds.

[0012] In another preferred example, the optional "substitution" means that one or more (preferably 1, 2, 3, 4, 5, 6, 7, or 8) hydrogen atoms on the ring or atomic group are each independently replaced with a C1-C10 alkyl group, a C2-C6 alkenyl group, a C3-C12 cycloalkyl group, a C1-C10 halogenated alkyl group, a C3-C8 halogenated cycloalkyl group, a C3-C8 cycloalkoxyl group, a C3-C8 cycloalkylthiol group, a C3-C8 halogenated cycloalkoxyl group, a C3-C8 halogenated cycloalkylthiol group, a halogenated a nitro group, -CN, a carbonyl group (=O), a hydroxyl group, a mercapto group, an amino group, a C1-C4 carboxyl group, a C2-C8 ester group, a C2-C4 acylamino group, a C2-C6 acyl group, a C1-C10 alkoxyl group, a C1-C10 alkylthiol group, a C1-C10 halogenated alkoxyl group, a C1-C10 halogenated alkylthiol group, a C6-C12 aryl group, a C6-C12 aryl group-O-, a 5- to 10-membered heteroaryl group, a 5- to 10-membered heteroaryl group-O-, a 5- to 10-membered heterocycloalkyl group, and (R 20 R 21 )N-.

[0013] In another preferred example, the optional "substitution" means that one or more (preferably 1, 2, 3, 4, 5, 6, 7, or 8) hydrogen atoms on the ring or atomic group are each independently replaced with a C1-C8 alkyl group, a C2-C6 alkenyl group, a C3-C12 cycloalkyl group, a C1-C8 halogenated alkyl group, a C3-C8 halogenated cycloalkyl group, a C3-C8 cycloalkoxyl group, a C3-C8 cycloalkylthiol group, a C3-C8 halogenated cycloalkoxyl group, a C3-C8 halogenated cycloalkylthiol group, a halo a hydrogen atom, a nitro group, -CN, a carbonyl group (=O), a hydroxyl group, a mercapto group, an amino group, a C1-C4 carboxyl group, a C2-C8 ester group, a C2-C4 acylamino group, a C2-C4 acyl group, a C1-C8 alkoxyl group, a C1-C8 alkylthiol group, a C1-C8 halogenated alkoxyl group, a C1-C8 halogenated alkylthiol group, a C6-C12 aryl group, a C6-C12 aryl group-O-, a 5-10 membered heteroaryl group, a 5-10 membered heteroaryl group-O-, a 5-10 membered heterocycloalkyl group, and (R 20 R 21 )N-.

[0014] In another preferred example, the optional "substitution" means that one or more (preferably 1, 2, 3, 4, 5, 6, 7, or 8) hydrogen atoms on the ring or atomic group are each independently replaced with a C1-C6 alkyl group, a C2-C4 alkenyl group, a C3-C10 cycloalkyl group, a C1-C6 halogenated alkyl group, a C3-C8 halogenated cycloalkyl group, a C3-C8 cycloalkoxyl group, a C3-C8 cycloalkylthiol group, a C3-C8 halogenated cycloalkoxyl group, a C3-C8 halogenated cycloalkylthiol group, a halo a hydrogen atom, a nitro group, -CN, a carbonyl group (=O), a hydroxyl group, a mercapto group, an amino group, a C1-C4 carboxyl group, a C2-C6 ester group, a C2-C4 acylamino group, a C2-C4 acyl group, a C1-C6 alkoxyl group, a C1-C6 alkylthiol group, a C1-C6 halogenated alkoxyl group, a C1-C6 halogenated alkylthiol group, a C6-C12 aryl group, a C6-C12 aryl group-O-, a 5-10 membered heteroaryl group, a 5-10 membered heteroaryl group-O-, a 5-10 membered heterocycloalkyl group, and (R 20 R 21 )N-.

[0015] In another preferred example, the optional "substitution" means that one or more (preferably 1, 2, 3, 4, 5, 6, 7, or 8) hydrogen atoms on the ring or atomic group are each independently replaced with a C1-C4 alkyl group, a C2-C4 alkenyl group, a C3-C10 cycloalkyl group, a C1-C4 halogenated alkyl group, a C3-C8 halogenated cycloalkyl group, a C3-C8 cycloalkoxyl group, a C3-C8 cycloalkylthiol group, a C3-C8 halogenated cycloalkoxyl group, a C3-C8 halogenated cycloalkylthiol group, a halo a hydrogen atom, a nitro group, -CN, a carbonyl group (=O), a hydroxyl group, a mercapto group, an amino group, a C1-C4 carboxyl group, a C2-C4 ester group, a C2-C4 acylamino group, a C2-C4 acyl group, a C1-C4 alkoxyl group, a C1-C4 alkylthiol group, a C1-C4 halogenated alkoxyl group, a C1-C4 halogenated alkylthiol group, a C6-C12 aryl group, a C6-C12 aryl group-O-, a 5-10 membered heteroaryl group, a 5-10 membered heteroaryl group-O-, a 5-10 membered heterocycloalkyl group, and (R 20 R 21 )N-.

[0016] In another preferred example, the optional "substitution" refers to one or more (preferably 1, 2, 3, 4, 5, 6, 7, or 8) hydrogen atoms on the ring or atomic group being each independently replaced by a substituent.

[0017] In another preferred example, R1 and R2 each independently represent a hydrogen atom, a deuterium atom, a halogen atom, a substituted or unsubstituted C1-C12 alkyl group, a substituted or unsubstituted C3-C12 cycloalkyl group, a substituted or unsubstituted 3- to 12-membered heterocycloalkyl group, a substituted or unsubstituted C1-C12 halogenated alkyl group, a substituted or unsubstituted C3-C12 halogenated cycloalkyl group, a substituted or unsubstituted C6-C12 aryl group, or a substituted or unsubstituted 5- to 10-membered heteroaryl group.

[0018] In another preferred example, R1 and R2 each independently represent a hydrogen atom, a deuterium atom, a halogen atom, a substituted or unsubstituted C1-C10 alkyl group, a substituted or unsubstituted C3-C10 cycloalkyl group, a substituted or unsubstituted 3- to 10-membered heterocycloalkyl group, a substituted or unsubstituted C1-C10 halogenated alkyl group, a substituted or unsubstituted C3-C10 halogenated cycloalkyl group, a substituted or unsubstituted C6-C10 aryl group, or a substituted or unsubstituted 5- to 10-membered heteroaryl group.

[0019] In another preferred example, R1 and R2 each independently represent a hydrogen atom, a deuterium atom, a halogen atom, a substituted or unsubstituted C1-C10 alkyl group, a substituted or unsubstituted C3-C8 cycloalkyl group, a substituted or unsubstituted 3-10 membered heterocycloalkyl group, a substituted or unsubstituted C1-C6 halogenated alkyl group, a substituted or unsubstituted C3-C10 halogenated cycloalkyl group, a substituted or unsubstituted C6-C10 aryl group, or a substituted or unsubstituted 5-8 membered heteroaryl group.

[0020] In another preferred example, R1 and R2 each independently represent a hydrogen atom, a deuterium atom, a halogen atom, a substituted or unsubstituted C1-C10 alkyl group, a substituted or unsubstituted C3-C8 cycloalkyl group, a substituted or unsubstituted 3-10 membered heterocycloalkyl group, a substituted or unsubstituted C1-C4 halogenated alkyl group, a substituted or unsubstituted C3-C10 halogenated cycloalkyl group, a substituted or unsubstituted C6-C10 aryl group, or a substituted or unsubstituted 5-8 membered heteroaryl group.

[0021] In another preferred example, R1 and R2 each independently represent a hydrogen atom, a deuterium atom, a halogen atom, a substituted or unsubstituted C1-C8 alkyl group, a substituted or unsubstituted C3-C8 cycloalkyl group, a substituted or unsubstituted 3- to 8-membered heterocycloalkyl group, a substituted or unsubstituted C1-C8 halogenated alkyl group, a substituted or unsubstituted C3-C8 halogenated cycloalkyl group, a substituted or unsubstituted C6-C8 aryl group, or a substituted or unsubstituted 5- to 8-membered heteroaryl group.

[0022] In another preferred example, R1 and R2 each independently represent a hydrogen atom, a deuterium atom, a halogen atom, a substituted or unsubstituted C1-C6 alkyl group, a substituted or unsubstituted C3-C8 cycloalkyl group, a substituted or unsubstituted 3- to 8-membered heterocycloalkyl group, a substituted or unsubstituted C1-C6 halogenated alkyl group, a substituted or unsubstituted C3-C8 halogenated cycloalkyl group, a substituted or unsubstituted C6-C8 aryl group, or a substituted or unsubstituted 5- to 8-membered heteroaryl group.

[0023] In another preferred example, R1 and R2 each independently represent a hydrogen atom, a deuterium atom, a halogen atom, a substituted or unsubstituted C1-C6 alkyl group, a substituted or unsubstituted C3-C8 cycloalkyl group, a substituted or unsubstituted 3- to 8-membered heterocycloalkyl group, a substituted or unsubstituted C1-C4 halogenated alkyl group, a substituted or unsubstituted C3-C8 halogenated cycloalkyl group, a substituted or unsubstituted C6-C8 aryl group, or a substituted or unsubstituted 5- to 8-membered heteroaryl group.

[0024] In another preferred example, R1 and R2 each independently represent a hydrogen atom, a deuterium atom, a halogen atom, a substituted or unsubstituted C1-C6 alkyl group, a substituted or unsubstituted C3-C8 cycloalkyl group, a substituted or unsubstituted 3- to 8-membered heterocycloalkyl group, a substituted or unsubstituted C1-C2 halogenated alkyl group, a substituted or unsubstituted C3-C8 halogenated cycloalkyl group, a substituted or unsubstituted C6-C8 aryl group, or a substituted or unsubstituted 5- to 8-membered heteroaryl group.

[0025] In another preferred example, R1 and R2 are each independently a hydrogen atom, a deuterium atom, a halogen atom, a substituted or unsubstituted methyl group, a substituted or unsubstituted ethyl group, a substituted or unsubstituted propyl group, a substituted or unsubstituted butyl group, a substituted or unsubstituted amyl group, a substituted or unsubstituted hexyl group, a substituted or unsubstituted heptyl group, a substituted or unsubstituted octyl group, a substituted or unsubstituted cyclopropyl group, a substituted or unsubstituted cyclobutyl group, a substituted or unsubstituted cycloamyl group, a substituted or unsubstituted cyclohex ... and represents a substituted or unsubstituted cycloheptyl group, a substituted or unsubstituted cyclooctyl group, a substituted or unsubstituted halomethyl group, a substituted or unsubstituted haloethyl group, a substituted or unsubstituted halopropyl group, a substituted or unsubstituted halobutyl group, a substituted or unsubstituted haloamyl group, a substituted or unsubstituted halohexyl group, a substituted or unsubstituted phenyl group, a substituted or unsubstituted acetyl-methyl group, a substituted or unsubstituted pyridinyl group, a substituted or unsubstituted pyrrolyl group, or a substituted or unsubstituted cyclohexanone group.

[0026] In another preferred example, R1 and R2 each independently represent a hydrogen atom, a deuterium atom, a halogen atom, a methyl group, an ethyl group, a propyl group, a butyl group, an amyl group, a hexyl group, a heptyl group, an octyl group, a cyclopropyl group, a cyclobutyl group, a cycloamyl group, a cyclohexyl group, a cycloheptyl group, a cyclooctyl group, a halogenated methyl group, a halogenated ethyl group, a halogenated propyl group, a halogenated butyl group, a halogenated amyl group, a halogenated hexyl group, a phenyl group, an acetyl group-methyl group, a pyridinyl group, a pyrrolyl group, or a cyclohexanone group.

[0027] In another preferred embodiment, the pyridinyl group is [ka] is.

[0028] In another preferred example, the acetyl group-methyl group- [ka] is.

[0029] In another preferred embodiment, the pyrrolyl group is [ka] is.

[0030] In another preferred embodiment, the cyclohexanone group is [ka] is.

[0031] In another preferred example, R1 and R2 represent a hydrogen atom or a deuterium atom.

[0032] In another preferred example, at least one of R1 and R2 does not represent a hydrogen atom or a deuterium atom.

[0033] In another preferred example, R1 represents a hydrogen atom or a deuterium atom, and R2 does not represent a hydrogen atom or a deuterium atom.

[0034] In another preferred example, R1 does not represent a hydrogen atom or a deuterium atom, and R2 represents a hydrogen atom or a deuterium atom.

[0035] In another preferred example, neither R1 nor R2 represents a hydrogen atom or a deuterium atom.

[0036] In another preferred example, R1 does not represent a hydrogen atom or a deuterium atom.

[0037] In another preferred example, R2 does not represent a hydrogen atom or a deuterium atom.

[0038] In another preferred embodiment, R1 and R2 represent the same or different atomic groups.

[0039] In another preferred example, the halogen atom is a fluorine atom, a chlorine atom, a bromine atom, or an iodine atom.

[0040] In another preferred example, the halogenation refers to 1-position halogenation, 2-position halogenation, 3-position halogenation or total halogenation.

[0041] In another preferred example, the halogenation refers to fluorination, chlorination, bromination or iodination.

[0042] In another preferred embodiment, the halogenated methyl group is trichloromethyl.

[0043] In another preferred example, the deuteration refers to 1-position deuteration, 2-position deuteration, 3-position deuteration, or total deuteration.

[0044] In another preferred example, R1 and R2 each independently represent a hydrogen atom, a deuterium atom, a trichloromethyl group, a methyl group, a cyclobutyl group, a cycloamyl group, a butyl group, a hexyl group, or a phenyl group.

[0045] In another preferred example, the propyl group is an n-propyl group.

[0046] In another preferred example, the propyl group is [ka] is.

[0047] In another preferred example, the butyl group is an n-butyl group.

[0048] In another preferred example, the butyl group is [ka] is.

[0049] In another preferred embodiment, the amyl group is an n-amyl group.

[0050] In another preferred embodiment, the amyl group is [ka] is.

[0051] In another preferred example, the hexyl group is an n-hexyl group.

[0052] In another preferred embodiment, the hexyl group is [ka] is.

[0053] In another preferred embodiment, the cyclobutyl group is [ka]

[0054] In another preferred example, the cyclohexyl group is [ka] is.

[0055] In another preferred example, R3, R4, and R5 are each independently a hydrogen atom, a halogen atom, or 17 -O-, R 17 -S- or (R 18 R 19 )N—; or R3 and R4, or R4 and R5, are joined to form a substituted or unsubstituted 3- to 10-membered heterocycloalkyl ring.

[0056] In another preferred example, R3, R4, and R5 are each independently a hydrogen atom, a halogen atom, or 17 -O-, R 17 -S- or (R 18 R 19 )N-; or R3 and R4, or R4 and R5, are joined to form a substituted or unsubstituted 3-8 membered heterocycloalkyl ring.

[0057] In another preferred example, R3, R4, and R5 are each independently a hydrogen atom, a halogen atom, or 17 -O-, R 17 -S- or (R 18 R19 )N-; or R3 and R4, or R4 and R5, joined to form a substituted or unsubstituted 3-membered heterocycloalkyl ring, a substituted or unsubstituted 4-membered heterocycloalkyl ring, a substituted or unsubstituted 5-membered heterocycloalkyl ring, a substituted or unsubstituted 6-membered heterocycloalkyl ring, a substituted or unsubstituted 7-membered heterocycloalkyl ring, a substituted or unsubstituted 8-membered heterocycloalkyl ring, a substituted or unsubstituted 9-membered heterocycloalkyl ring, or a substituted or unsubstituted 10-membered heterocycloalkyl ring.

[0058] In another preferred example, R3, R4, and R5 are each independently a hydrogen atom, a halogen atom (e.g., Cl, Br), R 17 -O-, R 17 -S- or (R 18 R 19 )N-; or R3 and R4, or R4 and R5, are joined to form a substituted or unsubstituted 5-membered heterocycloalkyl ring.

[0059] In another preferred example, R3, R4, and R5 are each independently a hydrogen atom, a halogen atom (e.g., Cl, Br), R 17 -O-, R 17 -S- or (R 18 R 19 )N—; or R3 and R4, or R4 and R5, combine to form a substituted or unsubstituted dioxopentene ring.

[0060] In another preferred example, R3, R4, and R5 are each independently a hydrogen atom, a halogen atom (e.g., Cl, Br), R 17 -O-, R 17 -S- or (R 18 R 19 )N-; or R3 and R4, or R4 and R5, are joined together [ka] Forming; W1 and W2 each independently represent O or S; R 41represents a hydrogen atom or a substituted or unsubstituted C1-C8 alkyl group.

[0061] In another preferred example, W1 represents O or S.

[0062] In another preferred embodiment, W2 represents O or S.

[0063] In another preferred example, R3 represents a hydrogen atom.

[0064] In another preferred example, R5 represents a hydrogen atom.

[0065] In another preferred embodiment, R3 and R4 are bonded to each other. [ka] Form.

[0066] In another preferred embodiment, R4 and R5 are bonded to each other. [ka] Form.

[0067] In another preferred example, R6, R8, R 11 , R 12 , R 13 , R 14 and R 15 each independently represents a hydrogen atom, a substituted or unsubstituted C1-C8 alkyl group, or a halogen atom (for example, Br).

[0068] In another preferred example, R6, R8, R 11 , R 12 , R 13 , R 14 and R 15 each independently represents a hydrogen atom, a substituted or unsubstituted C1-C6 alkyl group, or a halogen atom (for example, Br).

[0069] In another preferred example, R6, R8, R 11 , R 12 , R 13, R 14 and R 15 each independently represents a hydrogen atom, a substituted or unsubstituted C1-C4 alkyl group, or a halogen atom (for example, Br).

[0070] In another preferred example, R6, R8, R 11 , R 12 , R 13 , R 14 and R 15 each independently represents a hydrogen atom or a halogen atom (for example, Br).

[0071] In another preferred example, R7 represents a hydrogen atom, a substituted or unsubstituted C1-C10 alkyl group, a substituted or unsubstituted C1-C10 halogenated alkyl group, a substituted or unsubstituted C6-C16 aryl group-substituted or unsubstituted C1-C12 alkyl group-, or a substituted or unsubstituted 5-16 membered heteroaryl group-substituted or unsubstituted C1-C12 alkyl group-.

[0072] In another preferred example, R7 represents a hydrogen atom, a substituted or unsubstituted C1-C8 alkyl group, a substituted or unsubstituted C1-C8 halogenated alkyl group, a substituted or unsubstituted C6-C16 aryl group-substituted or unsubstituted C1-C12 alkyl group-, or a substituted or unsubstituted 5-16 membered heteroaryl group-substituted or unsubstituted C1-C12 alkyl group-.

[0073] In another preferred example, R7 represents a hydrogen atom, a substituted or unsubstituted C1-C10 alkyl group, a substituted or unsubstituted C1-C10 halogenated alkyl group, a substituted or unsubstituted C6-C12 aryl group-substituted or unsubstituted C1-C10 alkyl group-, or a substituted or unsubstituted 5-12 membered heteroaryl group-substituted or unsubstituted C1-C10 alkyl group-.

[0074] In another preferred example, R7 represents a hydrogen atom, a substituted or unsubstituted C1-C10 alkyl group, a substituted or unsubstituted C1-C10 halogenated alkyl group, a substituted or unsubstituted C6-C10 aryl group-substituted or unsubstituted C1-C8 alkyl group-, or a substituted or unsubstituted 5-10 membered heteroaryl group-substituted or unsubstituted C1-C10 alkyl group-.

[0075] In another preferred example, R7 represents a hydrogen atom, a substituted or unsubstituted C1-C8 alkyl group, a substituted or unsubstituted C1-C8 halogenated alkyl group, a substituted or unsubstituted C6-C12 aryl group-substituted or unsubstituted C1-C10 alkyl group-, or a substituted or unsubstituted 5-12 membered heteroaryl group-substituted or unsubstituted C1-C12 alkyl group-.

[0076] In another preferred example, R7 represents a hydrogen atom, a substituted or unsubstituted C1-C8 alkyl group, a substituted or unsubstituted C1-C8 halogenated alkyl group, a substituted or unsubstituted C6-C12 aryl group-substituted or unsubstituted C1-C10 alkyl group-, or a substituted or unsubstituted 5-12 membered heteroaryl group-substituted or unsubstituted C1-C10 alkyl group-.

[0077] In another preferred example, R7 represents a hydrogen atom, a substituted or unsubstituted C1-C8 alkyl group, a substituted or unsubstituted C1-C8 halogenated alkyl group, a substituted or unsubstituted C6-C12 aryl group-substituted or unsubstituted C1-C8 alkyl group-, or a substituted or unsubstituted 5-12 membered heteroaryl group-substituted or unsubstituted C1-C8 alkyl group-.

[0078] In another preferred example, R7 represents a hydrogen atom, a substituted or unsubstituted C1-C6 alkyl group, a substituted or unsubstituted C1-C8 halogenated alkyl group, a substituted or unsubstituted C6-C12 aryl group-substituted or unsubstituted C1-C6 alkyl group-, or a substituted or unsubstituted 5-10 membered heteroaryl group-substituted or unsubstituted C1-C6 alkyl group-.

[0079] In another preferred example, R7 represents a hydrogen atom, a substituted or unsubstituted C1-C6 alkyl group, a substituted or unsubstituted C1-C8 halogenated alkyl group, a substituted or unsubstituted C6-C8 aryl group-substituted or unsubstituted C1-C5 alkyl group-, or a substituted or unsubstituted 5-8 membered heteroaryl group-substituted or unsubstituted C1-C5 alkyl group-.

[0080] In another preferred example, R7 is a hydrogen atom, a substituted or unsubstituted C1-C8 alkyl group, a substituted or unsubstituted C1-C8 halogenated alkyl group, a substituted or unsubstituted 5-8 membered heteroaryl group-substituted or unsubstituted C1-C4 alkyl group-, [ka] , or JPEG2025509622000018.jpg1516; Z1 and Z2 each independently represent a substituted or unsubstituted C1-C8 alkylidene group; R 22 , R 23 , R 24 , R 25 , R 26 , R 27 , R 28 , R 29 and R 30 each independently represent a hydrogen atom, a C1-C8 alkyl group, a C3-C12 cycloalkyl group, a C1-C8 halogenated alkyl group, a C3-C8 halogenated cycloalkyl group, a C3-C8 cycloalkoxyl group, a C3-C8 cycloalkylthiol group, a C3-C8 halogenated cycloalkoxyl group, a C3-C8 halogenated cycloalkylthiol group, a halogen atom, a nitro group, -CN, a hydroxyl group, a mercapto group, an amino group, a C1-C4 carboxyl group, a C2-C6 ester group, a C2-C4 acylamino group, a C1-C8 alkoxyl group, a C1-C8 alkylthiol group, a C1-C8 halogenated alkoxyl group, a C1-C8 halogenated alkylthiol group, a C6-C12 aryl group, a C6-C12 aryl group-O-, a 5- to 10-membered heteroaryl group, a 5- to 10-membered heteroaryl group-O-, or a 5- to 10-membered heterocycloalkyl group.

[0081] In another preferred example, R7 is a hydrogen atom, a substituted or unsubstituted C1-C6 alkyl group, a substituted or unsubstituted C1-C8 halogenated alkyl group, a pyridinyl group, a methyl group, [ka] , or Represents JPEG2025509622000020.jpg1516.

[0082] In another preferred example, R7 is a hydrogen atom, a substituted or unsubstituted methyl group, a substituted or unsubstituted ethyl group, a substituted or unsubstituted propyl group, a substituted or unsubstituted butyl group, a substituted or unsubstituted amyl group, a substituted or unsubstituted hexyl group, a substituted or unsubstituted heptyl group, a substituted or unsubstituted octyl group, a halogenated hexyl group, a pyridinyl group-methyl group-, [ka] , or Represents JPEG2025509622000022.jpg1516.

[0083] In another preferred example, R7 is a hydrogen atom, a methyl group, an ethyl group, a propyl group, a butyl group, an amyl group, a hexyl group, a heptyl group, an octyl group, a halogenated hexyl group, a pyridinyl group, a methyl group, [ka] , or Represents JPEG2025509622000024.jpg1516.

[0084] In another preferred embodiment, the amyl group is an n-amyl group.

[0085] In another preferred embodiment, the amyl group is [ka] is.

[0086] In another preferred example, the octyl group is [ka] is.

[0087] In another preferred example, the halogenated hexyl group is a 1-position halogenated hexyl group.

[0088] In another preferred example, the halogenated hexyl group is [ka] or JPEG2025509622000028.jpg423.

[0089] Another preferred example is R9 and R 10 are joined to form a substituted or unsubstituted 3- to 10-membered heterocycloalkyl ring.

[0090] Another preferred example is R9 and R 10 are joined to form a substituted or unsubstituted 3-8 membered heterocycloalkyl ring.

[0091] Another preferred example is R9 and R 10 are joined to form a substituted or unsubstituted 5-8 membered heterocycloalkyl ring.

[0092] Another preferred example is R9 and R 10 are joined to form a substituted or unsubstituted 5-7 membered heterocycloalkyl ring.

[0093] Another preferred example is R9 and R 10are joined to form a substituted or unsubstituted 3-membered heterocycloalkyl ring, a substituted or unsubstituted 4-membered heterocycloalkyl ring, a substituted or unsubstituted 5-membered heterocycloalkyl ring, a substituted or unsubstituted 6-membered heterocycloalkyl ring, a substituted or unsubstituted 7-membered heterocycloalkyl ring, a substituted or unsubstituted 8-membered heterocycloalkyl ring, a substituted or unsubstituted 9-membered heterocycloalkyl ring, a substituted or unsubstituted 10-membered heterocycloalkyl ring, a substituted or unsubstituted 11-membered heterocycloalkyl ring, or a substituted or unsubstituted 12-membered heterocycloalkyl ring.

[0094] Another preferred example is R9 and R 10 is bonded to a substituted or unsubstituted [ka] or substituted or unsubstituted form JPEG2025509622000030.jpg1112; W3, W4, W5 and W6 each independently represent O or S; R 31 , R 32 , R 33 , R 34 and R 35 each independently represent a hydrogen atom, a C1-C8 alkyl group, a C3-C12 cycloalkyl group, a C1-C8 halogenated alkyl group, a C3-C8 halogenated cycloalkyl group, a C3-C8 cycloalkoxyl group, a C3-C8 cycloalkylthiol group, a C3-C8 halogenated cycloalkoxyl group, a C3-C8 halogenated cycloalkylthiol group, a halogen atom, a nitro group, -CN, a hydroxyl group, a mercapto group, an amino group, a C1-C4 carboxyl group, a C2-C4 ester group, a C2-C4 acylamino group, a C1-C8 alkoxyl group, a C1-C8 alkylthiol group, a C1-C8 halogenated alkoxyl group, a C1-C8 halogenated alkylthiol group, a C6-C12 aryl group, a C6-C12 aryl group-O-, a 5- to 10-membered heteroaryl group, a 5- to 10-membered heteroaryl group-O-, or a 5- to 10-membered heterocycloalkyl group.

[0095] Another preferred example is R9 and R10 is combined [ka] or Form JPEG2025509622000032.jpg1112.

[0096] In another preferred embodiment, W3 represents O or S.

[0097] In another preferred embodiment, W4 represents O or S.

[0098] In another preferred embodiment, W5 represents O or S.

[0099] In another preferred embodiment, W6 represents O or S.

[0100] Another preferred example has the following chemical structure: propyl group-phenyl group-methyl group. JPEG2025509622000033.jpg135 Propyl group-phenyl group-methyl group

[0101] Another good example is R 17 represents a hydrogen atom, a substituted or unsubstituted C1-C12 alkyl group, [ka] , Substituted or unsubstituted C3-C14 cycloalkyl group, substituted or unsubstituted 3-10 membered heterocycloalkyl group, substituted or unsubstituted C3-C14 cycloalkyl group-substituted or unsubstituted C2-C8 acyl group-, substituted or unsubstituted C3-C14 cycloalkyl group-C(O)-, substituted or unsubstituted C1-C12 halogenated alkyl group, substituted or unsubstituted C3-C12 halogenated cycloalkyl group, substituted or unsubstituted 3-10 membered heterocycloalkyl group-substituted or unsubstituted C1-C10 alkyl group-, substituted or unsubstituted C6-C12 aryl group-substituted or unsubstituted C1-C10 alkyl group-, substituted or unsubstituted C6-C12 aryl group-substituted or unsubstituted C6-C12 aryl group-substituted or unsubstituted C1-C10 alkyl group-, substituted or unsubstituted 5-1 2-membered heteroaryl group-substituted or unsubstituted C1-C10 alkyl group-, substituted or unsubstituted C6-C12 aryl group-O-substituted or unsubstituted C1-C10 alkyl group-, substituted or unsubstituted C6-C12 aryl group-S-substituted or unsubstituted C1-C10 alkyl group-, substituted or unsubstituted 5-12-membered heteroaryl group-O-substituted or unsubstituted C1-C10 alkyl group-, substituted or unsubstituted 5-12-membered heteroaryl group-S-substituted or unsubstituted C1-C10 alkyl group-, substituted or unsubstituted C2-C6 alkenyl group-substituted or unsubstituted C1-C6 alkyl group-substituted or unsubstituted C2-C6 alkenyl group-substituted or unsubstituted C1-C6 alkyl group-, substituted or unsubstituted C2-C6 alkenyl group-substituted or unsubstituted C1-C6 alkyl group-, or (R 20 R 21 )N-represents a substituted or unsubstituted C1-C10 alkyl group.

[0102] Another good example is R 17 represents a hydrogen atom, a substituted or unsubstituted C1-C10 alkyl group, [ka] , Substituted or unsubstituted C3-C12 cycloalkyl group, substituted or unsubstituted 3-10 membered heterocycloalkyl group, substituted or unsubstituted C3-C12 cycloalkyl group-substituted or unsubstituted C2-C6 acyl group-, substituted or unsubstituted C3-C12 cycloalkyl group-C(O)-, substituted or unsubstituted C1-C10 halogenated alkyl group, substituted or unsubstituted C3-C10 halogenated cycloalkyl group, substituted or unsubstituted 3-10 membered heterocycloalkyl group-substituted or unsubstituted C1-C8 alkyl group-, substituted or unsubstituted C6-C12 aryl group-substituted or unsubstituted C1-C8 alkyl group-, substituted or unsubstituted C6-C12 aryl group-substituted or unsubstituted C6-C12 aryl group-substituted or unsubstituted C1-C8 alkyl group-, substituted or unsubstituted 5- a 12-membered heteroaryl group-substituted or unsubstituted C1-C8 alkyl group-, a substituted or unsubstituted C6-C12 aryl group-O-substituted or unsubstituted C1-C8 alkyl group-, a substituted or unsubstituted C6-C12 aryl group-S-substituted or unsubstituted C1-C8 alkyl group-, a substituted or unsubstituted 5-12-membered heteroaryl group-O-substituted or unsubstituted C1-C8 alkyl group-, a substituted or unsubstituted 5-12-membered heteroaryl group-S-substituted or unsubstituted C1-C8 alkyl group-, a substituted or unsubstituted C2-C4 alkenyl group-substituted or unsubstituted C1-C4 alkyl group-substituted or unsubstituted C2-C4 alkenyl group-substituted or unsubstituted C1-C4 alkyl group-, a substituted or unsubstituted C2-C4 alkenyl group-substituted or unsubstituted C1-C4 alkyl group-, or (R 20 R 21 )N-represents a substituted or unsubstituted C1-C10 alkyl group.

[0103] Another good example is R 17 represents a hydrogen atom, a substituted or unsubstituted C1-C8 alkyl group, [ka] , Substituted or unsubstituted C3-C10 cycloalkyl group, substituted or unsubstituted 3-10 membered heterocycloalkyl group, substituted or unsubstituted C3-C12 cycloalkyl group-substituted or unsubstituted C2-C4 acyl group-, substituted or unsubstituted C3-C12 cycloalkyl group-C(O)-, substituted or unsubstituted C1-C8 halogenated alkyl group, substituted or unsubstituted C3-C8 halogenated cycloalkyl group, substituted or unsubstituted 3-10 membered heterocycloalkyl group-substituted or unsubstituted C1-C6 alkyl group-, substituted or unsubstituted C6-C12 aryl group-substituted or unsubstituted C1-C6 alkyl group-, substituted or unsubstituted C6-C12 aryl group-substituted or unsubstituted C6-C12 aryl group-substituted or unsubstituted C1-C6 alkyl group-, substituted or unsubstituted 5-1 2-membered heteroaryl group-substituted or unsubstituted C1-C6 alkyl group-, substituted or unsubstituted C6-C12 aryl group-O-substituted or unsubstituted C1-C6 alkyl group-, substituted or unsubstituted C6-C12 aryl group-S-substituted or unsubstituted C1-C6 alkyl group-, substituted or unsubstituted 5-12-membered heteroaryl group-O-substituted or unsubstituted C1-C6 alkyl group-, substituted or unsubstituted 5-12-membered heteroaryl group-S-substituted or unsubstituted C1-C6 alkyl group-, substituted or unsubstituted C2-C4 alkenyl group-substituted or unsubstituted C1-C4 alkyl group-substituted or unsubstituted C2-C4 alkenyl group-substituted or unsubstituted C1-C4 alkyl group-, substituted or unsubstituted C2-C4 alkenyl group-substituted or unsubstituted C1-C4 alkyl group-, or (R 20 R 21 ) N-represents a substituted or unsubstituted C1-C8 alkyl group.

[0104] Another good example is R 17 represents a hydrogen atom, a substituted or unsubstituted C1-C8 alkyl group, [ka] , Substituted or unsubstituted C3-C10 cycloalkyl group, substituted or unsubstituted 3-10 membered heterocycloalkyl group, substituted or unsubstituted C3-C12 cycloalkyl group-substituted or unsubstituted C2-C4 acyl group-, substituted or unsubstituted C3-C12 cycloalkyl group-C(O)-, substituted or unsubstituted C1-C8 halogenated alkyl group, substituted or unsubstituted C3-C8 halogenated cycloalkyl group, substituted or unsubstituted 3-10 membered heterocycloalkyl group-substituted or unsubstituted C1-C6 alkyl group-, substituted or unsubstituted C6-C10 aryl group-substituted or unsubstituted C1-C4 alkyl group-, substituted or unsubstituted C6-C10 aryl group-substituted or unsubstituted C6-C10 aryl group-substituted or unsubstituted C1-C4 alkyl group-, substituted or unsubstituted 5-1 a 0-membered heteroaryl group-substituted or unsubstituted C1-C4 alkyl group-, a substituted or unsubstituted C6-C10 aryl group-O-substituted or unsubstituted C1-C4 alkyl group-, a substituted or unsubstituted C6-C10 aryl group-S-substituted or unsubstituted C1-C4 alkyl group-, a substituted or unsubstituted 5-10-membered heteroaryl group-O-substituted or unsubstituted C1-C4 alkyl group-, a substituted or unsubstituted 5-12-membered heteroaryl group-S-substituted or unsubstituted C1-C4 alkyl group-, a substituted or unsubstituted C2-C4 alkenyl group-substituted or unsubstituted C1-C4 alkyl group-substituted or unsubstituted C2-C4 alkenyl group-substituted or unsubstituted C1-C4 alkyl group-, a substituted or unsubstituted C2-C4 alkenyl group-substituted or unsubstituted C1-C4 alkyl group-, or (R 20 R 21 ) N-represents a substituted or unsubstituted C1-C8 alkyl group.

[0105] Another good example is R 17 represents a hydrogen atom, a substituted or unsubstituted C1-C6 alkyl group, [ka] , Substituted or unsubstituted C3-C10 cycloalkyl group, substituted or unsubstituted 3-10 membered heterocycloalkyl group, substituted or unsubstituted C5-C12 cycloalkyl group-substituted or unsubstituted C2-C4 acyl group-, substituted or unsubstituted C5-C12 cycloalkyl group-C(O)-, substituted or unsubstituted C1-C8 halogenated alkyl group, substituted or unsubstituted C3-C8 halogenated cycloalkyl group, substituted or unsubstituted 3-10 membered heterocycloalkyl group-substituted or unsubstituted C1-C6 alkyl group-, substituted or unsubstituted C6-C10 aryl group-substituted or unsubstituted C1-C4 alkyl group-, substituted or unsubstituted C6-C10 aryl group-substituted or unsubstituted C6-C10 aryl group-substituted or unsubstituted C1-C4 alkyl group-, substituted or unsubstituted 5-1 a 0-membered heteroaryl group-substituted or unsubstituted C1-C4 alkyl group, a substituted or unsubstituted C6-C10 aryl group-O-substituted or unsubstituted C1-C4 alkyl group, a substituted or unsubstituted C6-C10 aryl group-S-substituted or unsubstituted C1-C4 alkyl group, a substituted or unsubstituted 5-10-membered heteroaryl group-O-substituted or unsubstituted C1-C4 alkyl group, a substituted or unsubstituted 5-10-membered heteroaryl group-S-substituted or unsubstituted C1-C4 alkyl group, a substituted or unsubstituted C2-C4 alkenyl group-substituted or unsubstituted C1-C4 alkyl group-substituted or unsubstituted C2-C4 alkenyl group-substituted or unsubstituted C1-C4 alkyl group, a substituted or unsubstituted C2-C4 alkenyl group-substituted or unsubstituted C1-C4 alkyl group, or (R 20 R 21 ) N-represents a substituted or unsubstituted C1-C8 alkyl group.

[0106] Another good example is R 17 represents a hydrogen atom, a substituted or unsubstituted C1-C6 alkyl group, [ka] , Substituted or unsubstituted C3-C10 cycloalkyl group, substituted or unsubstituted 3-10 membered heterocycloalkyl group, substituted or unsubstituted C6-C12 cycloalkyl group-substituted or unsubstituted C2 acyl group-, substituted or unsubstituted C6-C12 cycloalkyl group-C(O)-, substituted or unsubstituted C1-C6 halogenated alkyl group, substituted or unsubstituted C3-C8 halogenated cycloalkyl group, substituted or unsubstituted 3-10 membered heterocycloalkyl group-substituted or unsubstituted C1-C4 alkyl group-, substituted or unsubstituted C6-C8 aryl group-substituted or unsubstituted C1-C4 alkyl group-, substituted or unsubstituted C6-C8 aryl group-substituted or unsubstituted C6-C8 aryl group-substituted or unsubstituted C1-C2 alkyl group-, substituted or unsubstituted 5-8 substituted or unsubstituted C1-C2 alkyl group-, substituted or unsubstituted C6-C8 aryl group-O-substituted or unsubstituted C1-C2 alkyl group-, substituted or unsubstituted C6-C8 aryl group-S-substituted or unsubstituted C1-C2 alkyl group-, substituted or unsubstituted 5-8 membered heteroaryl group-O-substituted or unsubstituted C1-C2 alkyl group-, substituted or unsubstituted 5-8 membered heteroaryl group-S-substituted or unsubstituted C1-C2 alkyl group-, substituted or unsubstituted C2-C4 alkenyl group-substituted or unsubstituted C1-C4 alkyl group-substituted or unsubstituted C2-C4 alkenyl group-substituted or unsubstituted C1-C2 alkyl group-, substituted or unsubstituted C2-C4 alkenyl group-substituted or unsubstituted C1-C2 alkyl group-, or (R 20 R 21 ) N-represents a substituted or unsubstituted C1-C8 alkyl group.

[0107] Another good example is R 17 represents a hydrogen atom, a substituted or unsubstituted C1-C6 alkyl group, [ka] , Substituted or unsubstituted C6-C12 cycloalkyl group-substituted or unsubstituted C2-C4 acyl group-, substituted or unsubstituted C6-C12 cycloalkyl group-C(O)-, substituted or unsubstituted 3-10 membered heterocycloalkyl group, substituted or unsubstituted C1-C6 halogenated alkyl group, substituted or unsubstituted 5-7 membered heterocycloalkyl group-substituted or unsubstituted C1-C4 alkyl group-, substituted or unsubstituted C6-C10 aryl group-substituted or unsubstituted C1-C4 alkyl group-, substituted or unsubstituted C6-C10 aryl group-substituted or unsubstituted C6-C10 aryl group-substituted or unsubstituted C1-C4 alkyl group-, substituted or unsubstituted 5-10 membered heteroaryl group-substituted or unsubstituted C1-C4 acyl alkyl group-, a substituted or unsubstituted C6-C10 aryl group-O-substituted or unsubstituted C1-C4 alkyl group-, a substituted or unsubstituted C6-C10 aryl group-S-substituted or unsubstituted C1-C4 alkyl group-, a substituted or unsubstituted 5-10 membered heteroaryl group-O-substituted or unsubstituted C1-C4 alkyl group-, a substituted or unsubstituted 5-10 membered heteroaryl group-S-substituted or unsubstituted C1-C4 alkyl group-, a substituted or unsubstituted C2-C4 alkenyl group-substituted or unsubstituted C1-C2 alkyl group-substituted or unsubstituted C2-C4 alkenyl group-substituted or unsubstituted C1-C2 alkyl group-, a substituted or unsubstituted C2-C4 alkenyl group-substituted or unsubstituted C1-C2 alkyl group-, or (R 20 R 21 ) N-represents a substituted or unsubstituted C1-C8 alkyl group.

[0108] Another good example is R 17 represents a hydrogen atom, a substituted or unsubstituted C1-C6 alkyl group, [ka] , Substituted or unsubstituted C8-C10 cycloalkyl group-substituted or unsubstituted C2 acyl group-, substituted or unsubstituted C8-C10 cycloalkyl group-C(O)-, substituted or unsubstituted 5-7 membered heterocycloalkyl group, substituted or unsubstituted C1-C6 halogenated alkyl group, substituted or unsubstituted 5-7 membered heterocycloalkyl group-substituted or unsubstituted C1-C2 alkyl group-, substituted or unsubstituted C6-C8 aryl group-substituted or unsubstituted C1-C4 alkyl group-, substituted or unsubstituted C6-C8 aryl group-substituted or unsubstituted C6-C8 aryl group-substituted or unsubstituted C1-C2 alkyl group-, substituted or unsubstituted 5-8 membered heteroaryl group-substituted or unsubstituted C1-C4 alkyl a substituted or unsubstituted C6-C8 aryl group-O-substituted or unsubstituted C1-C2 alkyl group-, a substituted or unsubstituted C6-C8 aryl group-S-substituted or unsubstituted C1-C2 alkyl group-, a substituted or unsubstituted 5-8 membered heteroaryl group-O-substituted or unsubstituted C1-C2 alkyl group-, a substituted or unsubstituted 5-8 membered heteroaryl group-S-substituted or unsubstituted C1-C2 alkyl group-, a substituted or unsubstituted C2-C4 alkenyl group-substituted or unsubstituted C1-C2 alkyl group-substituted or unsubstituted C2-C4 alkenyl group-substituted or unsubstituted C1-C2 alkyl group-, a substituted or unsubstituted C2-C4 alkenyl group-substituted or unsubstituted C1-C2 alkyl group-, or (R 20 R 21 ) N-represents a substituted or unsubstituted C1-C8 alkyl group.

[0109] Another good example is R 17 represents a hydrogen atom, a substituted or unsubstituted C1-C4 alkyl group, [ka] , Substituted or unsubstituted C3-C10 cycloalkyl group, substituted or unsubstituted 3-10 membered heterocycloalkyl group, substituted or unsubstituted C6-C12 cycloalkyl group-substituted or unsubstituted C2 acyl group-, substituted or unsubstituted C6-C12 cycloalkyl group-C(O)-, substituted or unsubstituted C1-C6 halogenated alkyl group, substituted or unsubstituted C3-C8 halogenated cycloalkyl group, substituted or unsubstituted 3-10 membered heterocycloalkyl group-substituted or unsubstituted C1-C4 alkyl group-, substituted or unsubstituted C6-C8 aryl group-substituted or unsubstituted C1-C2 alkyl group-, substituted or unsubstituted C6-C8 aryl group-substituted or unsubstituted C6-C8 aryl group-substituted or unsubstituted C1-C2 alkyl group-, substituted or unsubstituted 5-8 substituted or unsubstituted C1-C2 alkyl group-, substituted or unsubstituted C6-C8 aryl group-O-substituted or unsubstituted C1-C2 alkyl group-, substituted or unsubstituted C6-C8 aryl group-S-substituted or unsubstituted C1-C2 alkyl group-, substituted or unsubstituted 5-8 membered heteroaryl group-O-substituted or unsubstituted C1-C2 alkyl group-, substituted or unsubstituted 5-8 membered heteroaryl group-S-substituted or unsubstituted C1-C2 alkyl group-, substituted or unsubstituted C2-C4 alkenyl group-substituted or unsubstituted C1-C4 alkyl group-substituted or unsubstituted C2-C4 alkenyl group-substituted or unsubstituted C1-C2 alkyl group-, substituted or unsubstituted C2-C4 alkenyl group-substituted or unsubstituted C1-C2 alkyl group-, or (R 20 R 21 ) N-represents a substituted or unsubstituted C1-C8 alkyl group.

[0110] Another good example is R 17 represents a hydrogen atom, a substituted or unsubstituted C1-C4 alkyl group, [ka] , Substituted or unsubstituted C6-C12 cycloalkyl group-substituted or unsubstituted C2-C4 acyl group-, substituted or unsubstituted C6-C12 cycloalkyl group-C(O)-, substituted or unsubstituted 3-10 membered heterocycloalkyl group, substituted or unsubstituted C1-C6 halogenated alkyl group, substituted or unsubstituted 5-7 membered heterocycloalkyl group-substituted or unsubstituted C1-C4 alkyl group-, substituted or unsubstituted C6-C10 aryl group-substituted or unsubstituted C1-C4 alkyl group-, substituted or unsubstituted C6-C10 aryl group-substituted or unsubstituted C6-C10 aryl group-substituted or unsubstituted C1-C4 alkyl group-, substituted or unsubstituted 5-10 membered heteroaryl group-substituted or unsubstituted C1-C4 acyl alkyl group-, a substituted or unsubstituted C6-C10 aryl group-O-substituted or unsubstituted C1-C4 alkyl group-, a substituted or unsubstituted C6-C10 aryl group-S-substituted or unsubstituted C1-C4 alkyl group-, a substituted or unsubstituted 5-10 membered heteroaryl group-O-substituted or unsubstituted C1-C4 alkyl group-, a substituted or unsubstituted 5-10 membered heteroaryl group-S-substituted or unsubstituted C1-C4 alkyl group-, a substituted or unsubstituted C2-C4 alkenyl group-substituted or unsubstituted C1-C2 alkyl group-substituted or unsubstituted C2-C4 alkenyl group-substituted or unsubstituted C1-C2 alkyl group-, a substituted or unsubstituted C2-C4 alkenyl group-substituted or unsubstituted C1-C2 alkyl group-, or (R 20 R 21 ) N-represents a substituted or unsubstituted C1-C8 alkyl group.

[0111] Another good example is R 17 represents a hydrogen atom, a substituted or unsubstituted C1-C2 alkyl group, [ka] , Substituted or unsubstituted C8-C10 cycloalkyl group-substituted or unsubstituted C2 acyl group-, substituted or unsubstituted C8-C10 cycloalkyl group-C(O)-, substituted or unsubstituted 5-7 membered heterocycloalkyl group, substituted or unsubstituted C3-C6 halogenated alkyl group, substituted or unsubstituted 5-7 membered heterocycloalkyl group-substituted or unsubstituted C1-C2 alkyl group-, substituted or unsubstituted C6-C8 aryl group-substituted or unsubstituted C1-C2 alkyl group-, substituted or unsubstituted C6-C8 aryl group-substituted or unsubstituted C6-C8 aryl group-substituted or unsubstituted C1-C2 alkyl group-, substituted or unsubstituted 5-8 membered heteroaryl group-substituted or unsubstituted C1-C4 alkyl a substituted or unsubstituted C6-C8 aryl group-O-substituted or unsubstituted C1-C2 alkyl group-, a substituted or unsubstituted C6-C8 aryl group-S-substituted or unsubstituted C1-C2 alkyl group-, a substituted or unsubstituted 5-8 membered heteroaryl group-O-substituted or unsubstituted C1-C2 alkyl group-, a substituted or unsubstituted 5-8 membered heteroaryl group-S-substituted or unsubstituted C1-C2 alkyl group-, a substituted or unsubstituted C2-C4 alkenyl group-substituted or unsubstituted C1-C2 alkyl group-substituted or unsubstituted C2-C4 alkenyl group-substituted or unsubstituted C1-C2 alkyl group-, a substituted or unsubstituted C2-C4 alkenyl group-substituted or unsubstituted C1-C2 alkyl group-, or (R 20 R 21 ) N-represents a substituted or unsubstituted C1-C8 alkyl group.

[0112] Another good example is R 17 represents a hydrogen atom, a substituted or unsubstituted methyl group, [ka] , a substituted or unsubstituted ethyl group, a substituted or unsubstituted propyl group, a substituted or unsubstituted amyl group, a substituted or unsubstituted hexyl group, a substituted or unsubstituted phenyl group-O-substituted or unsubstituted butyl group, a halogenated ethyl group, a halogenated propyl group, a halogenated butyl group, a halogenated hexyl group, a substituted or unsubstituted phenyl group-substituted or unsubstituted ethyl group, a substituted or unsubstituted phenyl group-substituted or unsubstituted propyl group, a substituted or unsubstituted phenyl group-substituted or unsubstituted butyl group, a substituted or unsubstituted cyclodecyl group-substituted or unsubstituted acetyl group, a substituted or unsubstituted butenyl group-substituted or unsubstituted ethyl group-substituted or unsubstituted propenyl group-substituted or unsubstituted methyl group, (R 20 R 21 ) N-substituted or unsubstituted hexyl group-, (R 20 R 21 ) N-substituted or unsubstituted butyl group -, (R 20 R 21 ) N-substituted or unsubstituted ethyl group, substituted or unsubstituted piperidinyl group-substituted or unsubstituted ethyl group, substituted or unsubstituted butyl group-substituted or unsubstituted piperazine ring, substituted or unsubstituted methyl group-substituted or unsubstituted piperidinyl group, substituted or unsubstituted phenyl group-substituted or unsubstituted phenyl group-substituted or unsubstituted methyl group, substituted or unsubstituted vinyl group-substituted or unsubstituted methyl group, substituted or unsubstituted piperidinyl group-substituted or unsubstituted propyl group, substituted or unsubstituted piperidinyl group-substituted or unsubstituted ethyl group, or dimethylamino group-ethyl group.

[0113] Another good example is R 17 is a hydrogen atom, a methyl group, [ka] , Ethyl, propyl, amyl, hexyl, phenyl-O-butyl, halogenated ethyl, halogenated propyl, halogenated butyl, halogenated hexyl, phenyl-ethyl, phenyl-propyl, phenyl-butyl, cyclodecyl-acetyl, butenyl-ethyl-propenyl-methyl, (R 20 R21 ) N-hexyl group -, (R 20 R 21 ) N-butyl group -, (R 20 R 21 ) N-ethyl, piperidinyl-ethyl, butyl-piperazinyl, methyl-piperidinyl, phenyl-phenyl-methyl, vinyl-methyl, piperidinyl-propyl, piperidinyl-ethyl, or dimethylamino-ethyl.

[0114] In another preferred example, the butyl group is an n-butyl group.

[0115] In another preferred example, the butyl group is [ka] is.

[0116] In another preferred embodiment, the hexyl group is [ka] or JPEG2025509622000049.jpg610.

[0117] In another preferred embodiment, the amyl group is an n-amyl group.

[0118] In another preferred embodiment, the amyl group is [ka] is.

[0119] In another preferred embodiment, the cycloamyl group is [ka] is.

[0120] In another preferred example, the chemical structure of the phenyl group-propyl group is as follows: [ka] Phenyl group-Propyl group-

[0121] In another preferred example, the chemical structure of the phenyl group-butyl group is as follows: [ka] Phenyl group-Butyl group-

[0122] In another preferred example, the chemical structure of the phenyl group-O-butyl group- is as follows: [ka] Phenyl group-O-butyl group-

[0123] In another preferred example, the halogenated ethyl group is a 1-position fluorinated ethyl group, a 1-position chlorinated ethyl group, or a 1-position brominated ethyl group.

[0124] In another preferred example, the chemical structure of the halogenated ethyl group is as follows: [ka] , JPEG2025509622000056.jpg514

[0125] In another preferred example, the propyl group is an n-propyl group.

[0126] In another preferred example, the propyl group is [ka] is.

[0127] In another preferred example, the halogenated propyl group is a halogenated n-propyl group.

[0128] In another preferred example, the halogenated propyl group is a 1-position fluorinated propyl group, a 1-position chlorinated propyl group, or a 1-position brominated propyl group.

[0129] In another preferred example, the chemical structure of the halogenated propyl group is as follows: [ka] , JPEG2025509622000059.jpg414, JPEG2025509622000060.jpg414

[0130] In another preferred example, the butyl group is an n-butyl group.

[0131] In another preferred embodiment, the halogenated butyl group is a halogenated n-butyl group.

[0132] In another preferred example, the halogenated butyl group is a 1-position fluorinated butyl group, a 1-position chlorinated butyl group, or a 1-position brominated butyl group.

[0133] In another preferred example, the chemical structure of the halogenated butyl group is as follows: [ka]

[0134] In another preferred example, the hexyl group is an n-hexyl group.

[0135] In another preferred embodiment, the halogenated hexyl group is a halogenated n-hexyl group.

[0136] In another preferred example, the halogenated hexyl group is a 1-position chlorinated hexyl group or a 1-position brominated hexyl group.

[0137] In another preferred example, the chemical structure of the halogenated hexyl group is as follows: [ka] , JPEG2025509622000063.jpg317

[0138] In another preferred example, the chemical structure of the cyclodecyl group-acetyl group is as follows: [ka] Cyclodecyl group-acetyl group-

[0139] In another preferred example, the chemical structure of the butenyl group-ethyl group-propenyl group-methyl group is as follows: [ka] Butenyl group - Ethyl group - Propenyl group - Methyl group

[0140] In another preferred example, the chemical structure of the piperidinyl group-ethyl group is as follows: [ka] Piperidinyl group-ethyl group-

[0141] In another preferred example, the chemical structure of the phenyl group-phenyl group-methyl group is as follows: [ka] Phenyl group-Phenyl group-Methyl group-

[0142] In another preferred embodiment, the chemical structure of the vinyl group-methyl group is [ka] is.

[0143] In another preferred example, the chemical structure of the piperidinyl group-propyl group- is as follows: [ka] Piperidinyl group-Propyl group-

[0144] In another preferred example, the chemical structure of the piperidinyl group-ethyl group is as follows: [ka] Piperidinyl group-ethyl group-

[0145] In another preferred example, the chemical structure of the dimethylamino group-ethyl group is as follows: [ka] Dimethylamino group-ethyl group-

[0146] Another good example is R 18 and R 19 each independently represents a hydrogen atom, a substituted or unsubstituted C1-C8 alkyl group, a substituted or unsubstituted C3-C10 cycloalkyl group, or a substituted or unsubstituted C6-C12 aryl group-substituted or unsubstituted C1-C10 alkyl group; or R 18 and R 19 are joined to form a substituted or unsubstituted 3- to 12-membered heterocycloalkyl ring.

[0147] Another good example is R 18 and R 19 each independently represents a hydrogen atom, a substituted or unsubstituted C1-C8 alkyl group, a substituted or unsubstituted C3-C10 cycloalkyl group, or a substituted or unsubstituted C6-C12 aryl group-substituted or unsubstituted C1-C8 alkyl group; or R 18 and R 19 are joined to form a substituted or unsubstituted 3- to 12-membered heterocycloalkyl ring.

[0148] Another good example is R 18 and R 19 each independently represents a hydrogen atom, a substituted or unsubstituted C1-C6 alkyl group, a substituted or unsubstituted C3-C10 cycloalkyl group, or a substituted or unsubstituted C6-C12 aryl group-substituted or unsubstituted C1-C6 alkyl group; or R 18 and R 19 are joined to form a substituted or unsubstituted 3- to 10-membered heterocycloalkyl ring.

[0149] Another good example is R 18 and R 19 each independently represents a hydrogen atom, a substituted or unsubstituted C1-C4 alkyl group, a substituted or unsubstituted C3-C10 cycloalkyl group, or a substituted or unsubstituted C6-C12 aryl group-substituted or unsubstituted C1-C4 alkyl group; or R 18 and R 19 are joined to form a substituted or unsubstituted 3-8 membered heterocycloalkyl ring.

[0150] Another good example is R 18 and R 19 each independently represents a hydrogen atom, a substituted or unsubstituted C1-C4 alkyl group, a substituted or unsubstituted C3-C10 cycloalkyl group, or a substituted or unsubstituted C6-C10 aryl group-substituted or unsubstituted C1-C4 alkyl group; or R 18 and R 19 are joined to form a substituted or unsubstituted 3-8 membered heterocycloalkyl ring.

[0151] Another good example is R 18 and R 19 each independently represents a hydrogen atom, a substituted or unsubstituted C1-C4 alkyl group, a substituted or unsubstituted C3-C10 cycloalkyl group, or a substituted or unsubstituted C6-C8 aryl group-substituted or unsubstituted C1-C4 alkyl group; or R 18 and R 19 are joined to form a substituted or unsubstituted 5-8 membered heterocycloalkyl ring.

[0152] Another good example is R 18 and R 19 each independently represents a hydrogen atom, a substituted or unsubstituted C1-C4 alkyl group, a substituted or unsubstituted C3-C10 cycloalkyl group, or a substituted or unsubstituted C6-C8 aryl group-substituted or unsubstituted C1-C4 alkyl group; or R 18 and R 19 are joined to form a substituted or unsubstituted 5-membered heterocycloalkyl ring, a substituted or unsubstituted 6-membered heterocycloalkyl ring, a substituted or unsubstituted 7-membered heterocycloalkyl ring, or a substituted or unsubstituted 8-membered heterocycloalkyl ring.

[0153] Another good example is R 18 and R 19 each independently represents a hydrogen atom or a substituted or unsubstituted phenyl group, or a substituted or unsubstituted ethyl group; or R 18 and R 19 are bonded to form a substituted or unsubstituted piperazine ring, a substituted or unsubstituted piperidine ring, or a substituted or unsubstituted nitrogen-containing heterocyclic heptane ring.

[0154] Another good example is R 18 and R 19 each independently represents a hydrogen atom, a substituted or unsubstituted C1-C4 alkyl group, a substituted or unsubstituted C3-C10 cycloalkyl group, or a substituted or unsubstituted C6-C8 aryl group-substituted or unsubstituted C1-C4 alkyl group; or R 18 and R 19 are bonded to form a substituted or unsubstituted piperazine ring, a substituted or unsubstituted piperidine ring, or a substituted or unsubstituted nitrogen-containing heterocyclic heptane ring.

[0155] Another good example is R 18 and R 19 each independently represents a hydrogen atom or a substituted or unsubstituted phenyl group, or a substituted or unsubstituted ethyl group; or R 18 and R 19are bonded to form a substituted or unsubstituted methyl group-substituted or unsubstituted piperazine ring, a substituted or unsubstituted butyl group-substituted or unsubstituted piperazine ring, a substituted or unsubstituted methyl group-substituted or unsubstituted piperidine ring, a trifluoromethyl group-piperidine ring, a halogenated piperidine ring, or a substituted or unsubstituted nitrogen-containing heterocyclic heptane ring.

[0156] Another good example is R 18 and R 19 each independently represents a hydrogen atom or a phenyl group or an ethyl group; or R 18 and R 19 are bonded to form a methyl group-piperazine ring, a butyl group-piperazine ring, a trifluoromethyl group-piperazine ring, a trifluoromethoxy group-piperazine ring, a halogenated piperazine ring, a methyl group-piperidine ring, a trifluoromethyl group-piperidine ring, a trifluoromethoxy group-piperidine ring, a halogenated piperidine ring, a nitrogen-containing heterocyclic heptane ring, or (R 20 R 21 ) Forms an N-piperidine ring.

[0157] In another preferred example, R3 is a hydrogen atom, a hydroxyl group, a mercapto group, an amino group, a methyl group -O-, [ka] , Ethyl group-O-, propyl group-O-, amyl group-O-, hexyl group-O-, phenyl group-O-butyl group-O-, halogenated ethyl group-O-, halogenated propyl group-O-, halogenated butyl group-O-, halogenated hexyl group-O-, phenyl group-ethyl group-O-, phenyl group-propyl group-O-, phenyl group-butyl group-O-, cyclodecyl group-acetyl group-O-, butenyl group-ethyl group-propenyl group-methyl group-O-, (R 20 R 21 ) N-hexyl group -O-, (R 20 R 21 ) N-butyl group -O-, (R 20 R 21)N-ethyl group-O-, piperidinyl group-ethyl group-O-, butyl group-piperazinyl group-O-, methyl group-piperidinyl group-O-, phenyl group-phenyl group-methyl group-O-, vinyl group-methyl group-O-, piperidinyl group-propyl group-O-, piperidinyl group-ethyl group-O-, dimethylamino group-ethyl group-O-, phenyl group-ethyl group-NH-, butyl group-piperazinyl group, methyl group-piperazinyl group, trifluoromethyl group-piperazinyl group, trifluoromethoxy group-piperazinyl group, halogenated piperazinyl group, methyl group-piperidinyl group, trifluoromethyl group-piperidinyl group, trifluoromethoxy group-piperidinyl group, halogenated piperidinyl group, nitrogen-containing heterocyclic heptane group or (R 20 R 21 ) represents an N-piperidine group -.

[0158] In another preferred example, the chemical structure of the phenyl group-ethyl group is as follows: [ka] Phenyl group-Ethyl group-

[0159] In another preferred example, the chemical structural formula of the methyl group-piperazine ring is as follows: [ka] Methyl group-piperazine ring

[0160] In another preferred example, the chemical structure of the methyl group-piperazinyl group is as follows: [ka] Methyl group-piperazinyl group-

[0161] In another preferred example, the chemical structure of the butyl group-piperazine ring is as follows: [ka] Butyl group-piperazine ring

[0162] In another preferred example, the chemical structure of the butyl group-piperazinyl group is as follows: [ka] Butyl group-piperazinyl group-

[0163] In another preferred example, the chemical structural formula of the trifluoromethyl group-piperazine ring is as follows: [ka] Trifluoromethyl group-piperazine ring

[0164] In another preferred example, the chemical structural formula of the trifluoromethyl group-piperazinyl group is as follows: [ka] Trifluoromethyl group-piperazinyl group-

[0165] In another preferred example, the chemical structural formula of the trifluoromethoxy group-piperazine ring is as follows: [ka] Trifluoromethoxy group-piperazine ring

[0166] In another preferred example, the chemical structural formula of the trifluoromethoxy group-piperazinyl group is as follows: [ka] Trifluoromethoxy group-piperazinyl group-

[0167] In another preferred embodiment, the halogenated piperazine ring is a chlorinated piperazine ring.

[0168] In another preferred example, the halogenated piperazine ring has the following chemical structural formula: [ka] Halogenated piperazine ring

[0169] In another preferred embodiment, the halogenated piperazinyl group is a chlorinated piperazinyl group.

[0170] In another preferred embodiment, the halogenated piperazinyl group has the following chemical structure: [ka] Halogenated piperazinyl group

[0171] In another preferred example, the chemical structure of the methyl group-piperidinyl group is as follows: [ka] Methyl group-Piperidinyl group-

[0172] In another preferred example, the chemical structural formula of the methyl group-piperidine ring is as follows: [ka] Methyl group-piperidine ring

[0173] In another preferred example, the chemical structural formula of the trifluoromethyl group-piperidinyl group is as follows: [ka] Trifluoromethyl group-piperidinyl group-

[0174] In another preferred example, the chemical structural formula of the trifluoromethyl group-piperidine ring is as follows: [ka] Trifluoromethyl group-piperidine ring

[0175] In another preferred example, the chemical structural formula of the trifluoromethoxy group-piperidinyl group is as follows: [ka] Trifluoromethoxy group-piperidinyl group-

[0176] In another preferred example, the chemical structural formula of the trifluoromethoxy group-piperidine ring is as follows: [ka] Trifluoromethoxy group-piperidine ring

[0177] In another preferred embodiment, the halogenated piperidine ring is a chlorinated piperidine ring.

[0178] In another preferred example, the halogenated piperidine ring has the following chemical structural formula: [ka] Halogenated piperidine ring

[0179] In another preferred embodiment, the halogenated piperidinyl group is a chlorinated halogenated piperidinyl group.

[0180] In another preferred embodiment, the halogenated piperidinyl group has the following chemical structure: [ka] Halogenated piperidinyl group

[0181] In another preferred example, the nitrogen-containing heterocyclic heptane ring has the following chemical structural formula: [ka] Nitrogen-containing heterocyclic heptane ring

[0182] In another preferred example, the nitrogen-containing heterocyclic heptane group has the following chemical structural formula: [ka] Nitrogen-containing heterocyclic heptane group

[0183] In another preferred embodiment, the (R 20 R 21 The chemical structure of the N-piperidine group is as follows: [ka] (R 20 R 21 ) N-piperidine group -

[0184] In another preferred embodiment, the (R 20 R 21 The chemical structure of the N-piperidine ring is as follows: [ka] (R 20 R 21 ) N-piperidine ring

[0185] Another good example is R 18 and R 19 each independently represent a hydrogen atom, a substituted or unsubstituted C1-C4 alkyl group, a substituted or unsubstituted C3-C10 cycloalkyl group, or a substituted or unsubstituted C6-C8 aryl group-substituted or unsubstituted C1-C4 alkyl group; Or R 18 and R 19 is combined [ka] or form JPEG2025509622000097.jpg1922; where R 42 , R 43 , R 44 , R 45 , R 46 , R 47 , R 48 , R 49 , R 50 and R 51 each independently represents a hydrogen atom, a C1-C10 alkyl group, a C1-C10 halogenated alkyl group, a C1-C10 halogenated alkoxyl group, a C1-C10 halogenated alkylthiol group, or a halogen atom; R 52 , R 53 , R 54 , R 55 , R 56 , R 57 , R 58 , R 59 and R 60 each independently represents a hydrogen atom, a C1-C10 alkyl group, a C1-C10 halogenated alkyl group, a C1-C10 halogenated alkoxyl group, a C1-C10 halogenated alkylthiol group, or a halogen atom.

[0186] Another preferred example is (R 20 R 21 )N- is [ka] or JPEG2025509622000099.jpg1720; R 42 , R 43 , R 44 , R 45 , R 46 , R 47 , R 48 , R 49 , R50 and R 51 each independently represents a hydrogen atom, a C1-C10 alkyl group, a C1-C10 halogenated alkyl group, a C1-C10 halogenated alkoxyl group, a C1-C10 halogenated alkylthiol group, or a halogen atom; R 52 , R 53 , R 54 , R 55 , R 56 , R 57 , R 58 , R 59 and R 60 each independently represents a hydrogen atom, a C1-C10 alkyl group, a C1-C10 halogenated alkyl group, a C1-C10 halogenated alkoxyl group, a C1-C10 halogenated alkylthiol group, or a halogen atom.

[0187] Another good example is R 20 and R 21 each independently represents a hydrogen atom, a substituted or unsubstituted C1-C10 alkyl group, a substituted or unsubstituted C3-C10 cycloalkyl group, or a substituted or unsubstituted C2-C8 ester group; or R 20 and R 21 are joined to form a substituted or unsubstituted 3- to 10-membered heterocycloalkyl group.

[0188] Another good example is R 20 and R 21 each independently represents a hydrogen atom, a substituted or unsubstituted C1-C8 alkyl group, a substituted or unsubstituted C3-C8 cycloalkyl group, or a substituted or unsubstituted C2-C8 ester group; or R 20 and R 21 are joined to form a substituted or unsubstituted 3-8 membered heterocycloalkyl group.

[0189] Another good example is R 20 and R 21 each independently represents a hydrogen atom, a substituted or unsubstituted C1-C6 alkyl group, a substituted or unsubstituted C3-C8 cycloalkyl group, or a substituted or unsubstituted C3-C7 ester group; or R 20 and R21 are joined to form a substituted or unsubstituted 5-8 membered heterocycloalkyl group.

[0190] Another good example is R 20 and R 21 each independently represents a hydrogen atom or a substituted or unsubstituted amyl ester; or R 20 and R 21 are linked to form a substituted or unsubstituted piperidine ring.

[0191] Another good example is R 20 and R 21 each independently represents a hydrogen atom or an amyl ester; or R 20 and R 21 are linked to form a piperidine ring.

[0192] In another preferred embodiment, the amyl ester has the following chemical structure: [ka] is.

[0193] In another preferred embodiment, the (R 20 R 21 )N-hexyl group - The chemical structure is [ka] is.

[0194] In another preferred embodiment, the (R 20 R 21 )N-butyl group - the chemical structure is [ka] is.

[0195] In another preferred embodiment, the (R 20 R 21 )N-ethyl group - the chemical structure is [ka] is.

[0196] Another good example is R 22 , R 23 , R 24 , R 25 , R 26 , R 27 , R 28 , R 29 and R 30 each independently represent a hydrogen atom, a C1-C6 alkyl group, a C3-C8 cycloalkyl group, a C1-C6 halogenated alkyl group, a C3-C8 halogenated cycloalkyl group, a C3-C8 cycloalkoxyl group, a C3-C8 cycloalkylthiol group, a C3-C8 halogenated cycloalkoxyl group, a C3-C8 halogenated cycloalkylthiol group, a halogen atom, a nitro group, -CN, a hydroxyl group, a mercapto group, an amino group, a C1-C4 carboxyl group, a C2-C6 ester group, a C2-C4 acylamino group, a C1-C6 alkoxyl group, a C1-C6 alkylthiol group, a C1-C6 halogenated alkoxyl group, a C1-C6 halogenated alkylthiol group, a C6-C12 aryl group, a C6-C12 aryl group-O-, a 5- to 10-membered heteroaryl group, a 5- to 10-membered heteroaryl group-O-, or a 5- to 10-membered heterocycloalkyl group.

[0197] Another good example is R 22 , R 23 , R 24 , R 25 , R 26 , R 27 , R 28 , R 29 and R 30 each independently represents a hydrogen atom, a C1-C6 alkyl group, a C1-C6 alkoxyl group, or a C1-C6 alkylthiol group.

[0198] Another good example is R 22 , R 23 , R 24 , R 25 , R 26 , R 27 , R 28 , R 29 and R 30each independently represents a hydrogen atom, a C1-C4 alkyl group, a C1-C4 alkoxyl group, or a C1-C4 alkylthiol group.

[0199] Another good example is R 22 , R 23 , R 24 , R 25 , R 26 , R 27 , R 28 , R 29 and R 30 each independently represents a hydrogen atom, a C1-C3 alkyl group, a C1-C2 alkoxyl group, or a C1-C2 alkylthiol group.

[0200] Another good example is R 22 , R 23 , R 24 , R 25 , R 26 , R 27 , R 28 , R 29 and R 30 each independently represents a hydrogen atom, a trifluoromethoxy group, or a propyl group.

[0201] In another preferred example, the propyl group is an isopropyl group.

[0202] In another preferred example, Z1 and Z2 each independently represent a substituted or unsubstituted C1-C6 alkylidene group.

[0203] In another preferred example, Z1 and Z2 each independently represent a substituted or unsubstituted C1-C4 alkylidene group.

[0204] In another preferred example, Z1 and Z2 each independently represent a substituted or unsubstituted methylidene group, a substituted or unsubstituted ethylidene group, a substituted or unsubstituted propylidene group, a substituted or unsubstituted butylidene group, a substituted or unsubstituted amylidene group, or a substituted or unsubstituted hexamethylidene group.

[0205] In another preferred example, Z1 and Z2 each independently represent a methylidene group, an ethylidene group, a propylidene group, a butylidene group, an amytylidene group, or a hexamethylidene group.

[0206] In another preferred embodiment, the ethylidene group is [ka] is.

[0207] In another preferred example, the propyl group is [ka] is.

[0208] In another preferred example, the propylidene group is an n-propylene group.

[0209] In another preferred embodiment, the chemical structure of the propylidene group is [ka] is.

[0210] In another preferred embodiment, the chemical structure of the butylidene group is [ka] is.

[0211] Another good example is R 31 , R 32 , R 33 , R 34 and R 35 each independently represents a hydrogen atom or a C1-C6 alkyl group.

[0212] Another good example is R 31 , R 32 , R 33 , R 34 and R 35 each independently represents a hydrogen atom or a C1-C4 alkyl group.

[0213] Another good example is R 41 represents a hydrogen atom or a substituted or unsubstituted C1-C6 alkyl group.

[0214] Another good example is R 41 represents a hydrogen atom or a substituted or unsubstituted C1-C4 alkyl group.

[0215] Another good example is R 42 , R 43 , R 44 , R 45 , R 46 , R 47 , R 48 , R 49 , R 50 and R 51 each independently represents a hydrogen atom, a C1-C8 alkyl group, a C1-C8 halogenated alkyl group, a C1-C8 halogenated alkoxyl group, a C1-C8 halogenated alkylthiol group, or a halogen atom.

[0216] Another good example is R 42 , R 43 , R 44 , R 45 , R 46 , R 47 , R 48 , R 49 , R 50 and R 51 each independently represents a hydrogen atom, a C1-C6 alkyl group, a C1-C6 halogenated alkyl group, a C1-C6 halogenated alkoxyl group, a C1-C6 halogenated alkylthiol group, or a halogen atom.

[0217] Another good example is R 42 , R 43 , R 44 , R 45 , R 46 , R 47 , R 48 , R 49 , R 50 and R 51each independently represents a hydrogen atom, a C1-C4 alkyl group, a C1-C4 halogenated alkyl group, a C1-C4 halogenated alkoxyl group, a C1-C4 halogenated alkylthiol group, or a halogen atom.

[0218] Another good example is R 42 , R 43 , R 44 , R 45 , R 46 , R 47 , R 48 , R 49 , R 50 and R 51 each independently represents a hydrogen atom, a methyl group, a butyl group, a trifluoromethoxy group, a trifluoromethoxy group, or a halogen atom (for example, Cl).

[0219] Another good example is R 52 , R 53 , R 54 , R 55 , R 56 , R 57 , R 58 , R 59 and R 60 each independently represents a hydrogen atom, a C1-C8 alkyl group, a C1-C8 halogenated alkyl group, a C1-C8 halogenated alkoxyl group, a C1-C8 halogenated alkylthiol group, or a halogen atom.

[0220] Another good example is R 52 , R 53 , R 54 , R 55 , R 56 , R 57 , R 58 , R 59 and R 60 each independently represents a hydrogen atom, a C1-6 alkyl group, a C1-C6 halogenated alkyl group, a C1-C6 halogenated alkoxyl group, a C1-C6 halogenated alkylthiol group, or a halogen atom.

[0221] Another good example is R 52 , R 53 , R 54, R 55 , R 56 , R 57 , R 58 , R 59 and R 60 each independently represents a hydrogen atom, a C1-4 alkyl group, a C1-C4 halogenated alkyl group, a C1-C4 halogenated alkoxyl group, a C1-C4 halogenated alkylthiol group, or a halogen atom.

[0222] Another good example is R 52 , R 53 , R 54 , R 55 , R 56 , R 57 , R 58 , R 59 and R 60 each independently represents a hydrogen atom, a methyl group, a butyl group, a trifluoromethoxy group, a trifluoromethoxy group, or a halogen atom (for example, Cl).

[0223] In another preferred example, the halogen atom is a fluorine atom, a chlorine atom, a bromine atom, or an iodine atom.

[0224] In another preferred example, the halogenation refers to fluorination, chlorination, bromination and / or iodination.

[0225] In another preferred example, the halogenation refers to 1-position halogenation, 2-position halogenation, or 3-position halogenation.

[0226] In another preferred embodiment, the aryl group refers to a phenyl group.

[0227] In another preferred embodiment, the compound of formula I is optically inactive or optically active.

[0228] In another preferred embodiment, the compound of formula I has no chiral carbon atoms or has a chiral carbon atom.

[0229] In another preferred embodiment, the compound of formula I has one chiral carbon atom.

[0230] In another preferred embodiment, the structure of the compound of formula I is a racemate, an R-configuration, or an S-configuration.

[0231] In another preferred embodiment, the chemical structure of the compound of formula I is as follows: [ka] I-1 where R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 , R 11 , R 12 , R 13 , R 14 sum R 15 are each independently as defined above.

[0232] In another preferred example, "*" represents the structure of the compound.

[0233] In another preferred example, "*" indicates that the compound is in the racemic, R- or S-configuration.

[0234] In another preferred example, "*" represents a chiral carbon atom.

[0235] In another preferred embodiment, the structure of the chiral carbon atom is a racemate, an R-structure, or an S-structure.

[0236] In another preferred embodiment, the structure of the chiral carbon atom is an R-structure and / or an S-structure.

[0237] In another preferred example, the R-type structure and the S-type structure of the chiral carbon atom refer to a racemic structure.

[0238] In another preferred embodiment, the chemical structure of the compound of formula I is as follows: [ka] I-2 where R1, R2, R3, R4, R5, R6, R7, R8, R 11 , R 12 , R 13 , R 14 , R 15 , R 31 , W3 and W4 are each independently as defined above.

[0239] In another preferred embodiment, the chemical structure of the compound of formula I is as shown in formula I-3. [ka] I-3 where R1, R2, R3, R4, R5, R6, R7, R8, R 11 , R 12 , R 13 , R 14 , R 15 , R 31 , W3, W4 and * are each independently as defined above.

[0240] In another preferred embodiment, the chemical structure of the compound of formula I is as follows: [ka] I-4 where R1, R2, R3, R4, R5, R6, R7, R8, R 11 , R 12 , R 13 , R 14 , R 15 , R 32 , R 33 , R 34 , R 35 , W5 and W6 are each independently as defined above.

[0241] In another preferred embodiment, the chemical structure of the compound of formula I is as shown in formula I-5. [ka] I-5 where R1, R2, R3, R4, R5, R6, R7, R8, R 11 , R 12 , R 13 , R 14 , R 15 , R 32 , R 33 , R 34 , R 35 , W5, W6 and * are each independently as defined above.

[0242] In another preferred embodiment, the chemical structure of the compound of formula I is as shown in formula I-6. [ka] I-6 where R1, R2, R5, R6, R7, R8, R 11 , R 12 , R 13 , R 14 , R 15 , R 31 , R 41 , W1, W2, W3 and W4 are each independently as defined above.

[0243] In another preferred embodiment, the chemical structure of the compound of formula I is as follows: Formula I-7. [ka] I-7 where R1, R2, R5, R6, R7, R8, R 11 , R 12 , R 13 , R 14 , R 15 , R 31 , R 41 , W1, W2, W3, W4 sum * are each independently as defined above.

[0244] In another preferred embodiment, the chemical structure of the compound of formula I is as follows: Formula I-8. [ka] I-8 where R1, R2, R3, R6, R7, R8, R 11 , R 12 , R 13 , R 14 , R 15 , R 31 , R 41 , W1, W2, W3 and W4 are each independently as defined above.

[0245] In another preferred embodiment, the chemical structure of the compound of formula I is as follows: Formula I-9. [ka] I-9 where R1, R2, R3, R6, R7, R8, R 11 , R 12 , R 13 , R 14 , R 15 , R 31 , R 41 , W1, W2, W3, W4 and * are each independently as defined above.

[0246] In another preferred embodiment, the chemical structure of the compound of formula I is as follows: Formula I-11. [ka] I-11 where R1, R2, R4, R5, R6, R7, R8, R 11 , R 12 , R 13 , R 14 , R 15 , R 31 , R 42 , R 43 , R 44 , R 45 , R 46 , R 47 , R 48 , R 49 , R 50 , R 51, W3 and W4 are each independently as defined above.

[0247] In another preferred embodiment, the chemical structure of the compound of formula I is as follows: Formula I-12. [ka] I-12 where R1, R2, R4, R5, R6, R7, R8, R 11 , R 12 , R 13 , R 14 , R 15 , R 31 , R 42 , R 43 , R 44 , R 45 , R 46 , R 47 , R 48 , R 49 , R 50 , R 51 , W3, W4 and * are each independently as defined above.

[0248] In another preferred embodiment, the chemical structure of the compound of formula I is as follows: Formula I-13. [ka] I-13 where R1, R2, R4, R5, R6, R7, R8, R 11 , R 12 , R 13 , R 14 , R 15 , R 31 , R 52 , R 53 , R 54 , R 55 , R 56 , R 57 , R 58 , R 59 , R 60 , W3 and W4 are each independently as defined above.

[0249] In another preferred embodiment, the chemical structure of the compound of formula I is as follows: [ka] I-14 where R1, R2, R4, R5, R6, R7, R8, R 11 , R 12 , R 13 , R 14 , R 15 , R 31 , R 52 , R 53 , R 54 , R 55 , R 56 , R 57 , R 58 , R 59 , R 60 , W3, W4 and * are each independently as defined above.

[0250] In another preferred embodiment, the chemical structure of the compound of formula I is as follows: Formula I-15. [ka] I-15 where R1, R2, R4, R5, R6, R7, R8, R 11 , R 12 , R 13 , R 14 , R 15 , R 32 , R 33 , R 34 , R 35 , R 42 , R 43 , R 44 , R 45 , R 46 , R 47 , R 48 , R 49 , R 50 , R 51 , W5 and W6 are each independently as defined above.

[0251] In another preferred embodiment, the chemical structure of the compound of formula I is as follows: [ka] I-16 where R1, R2, R4, R5, R6, R7, R8, R 11 , R 12 , R 13 , R 14 , R 15 , R 32 , R 33 , R 34 , R 35 , R 42 , R 43 , R 44 , R 45 , R 46 , R 47 , R 48 , R 49 , R 50 , R 51 , W5, W6 and * are each independently as defined above.

[0252] In another preferred embodiment, the chemical structure of the compound of formula I is as follows: Formula I-17. [ka] I-17 where R1, R2, R4, R5, R6, R7, R8, R 11 , R 12 , R 13 , R 14 , R 15 , R 32 , R 33 , R 34 , R 35 , R 52 , R 53 , R 54 , R 55 , R 56 , R 57 , R 58 , R 59 , R 60 , W5 and W6 are each independently as defined above.

[0253] In another preferred embodiment, the chemical structure of the compound of formula I is as follows: [ka] I-18 where R1, R2, R4, R5, R6, R7, R8, R 11 , R 12 , R 13 , R 14 , R 15 , R 32 , R 33 , R 34 , R 35 , R 52 , R 53 , R 54 , R 55 , R 56 , R 57 , R 58 , R 59 , R 60 , W5, W6 and * are each independently as defined above.

[0254] In another preferred embodiment, the chemical structure of the compound of formula I is as follows: [ka] I-19 where R1, R2, R5, R6, R7, R8, R 11 , R 12 , R 13 , R 14 , R 15 , R 32 , R 33 , R 34 , R 35 , R 41 , W1, W2, W5 and W6 are each independently as defined above.

[0255] In another preferred embodiment, the chemical structure of the compound of formula I is as follows: Formula I-20. [ka] I-20 where R1, R2, R5, R6, R7, R8, R 11 , R 12 , R 13 , R 14 , R 15 , R 32 , R 33 , R 34 , R 35 , R 41 , W1, W2, W5, W6 and * are each independently as defined above.

[0256] In another preferred embodiment, the chemical structure of the compound of formula I is as follows: Formula I-21. [ka] I-21 where R1, R2, R3, R6, R7, R8, R 11 , R 12 , R 13 , R 14 , R 15 , R 32 , R 33 , R 34 , R 35 , R 41 , W1, W2, W5 and W6 are each independently as defined above.

[0257] In another preferred embodiment, the chemical structure of the compound of formula I is as follows: I-22. [ka] I-22 where R1, R2, R3, R6, R7, R8, R 11 , R 12 , R 13 , R 14 , R 15 , R 32 , R 33 , R 34 , R 35 , R 41 , W1, W2, W5, W6 and * are each independently as defined above.

[0258] In another preferred embodiment, pharmaceutically acceptable salts of the compounds of formula I include salts formed from compounds of formula I and acids.

[0259] In another preferred example, the acid comprises one or more of hydrochloric acid, galactaric acid, D-glucuronic acid, hydrobromic acid, hydrofluoric acid, hydroiodic acid, sulfuric acid, nitric acid, phosphoric acid, formic acid, acetic acid, trifluoroacetic acid, propionic acid, oxalic acid, malonic acid, succinic acid, fumaric acid, maleic acid, lactic acid, malic acid, tartaric acid, citric acid, picric acid, methanesulfonic acid, benzenemethanesulfonic acid, benzenesulfonic acid, aspartic acid, and glutamic acid.

[0260] In another preferred example, the pharmaceutically acceptable salts of the compounds of formula I include salts formed by the compounds of formula I with one or more of hydrochloric acid, galactaric acid, D-glucuronic acid, hydrobromic acid, hydrofluoric acid, hydroiodic acid, sulfuric acid, nitric acid, phosphoric acid, formic acid, acetic acid, trifluoroacetic acid, propionic acid, oxalic acid, malonic acid, succinic acid, fumaric acid, maleic acid, lactic acid, malic acid, tartaric acid, citric acid, picric acid, methanesulfonic acid, benzenemethanesulfonic acid, benzenesulfonic acid, aspartic acid, and glutamic acid.

[0261] In another preferred example, the pharmaceutically acceptable salts of the compounds of formula I include salts formed by the compounds of formula I with hydrochloric acid, galactaric acid, D-glucuronic acid, hydrobromic acid, hydrofluoric acid, hydroiodic acid, sulfuric acid, nitric acid, phosphoric acid, formic acid, acetic acid, trifluoroacetic acid, propionic acid, oxalic acid, malonic acid, succinic acid, fumaric acid, maleic acid, lactic acid, malic acid, tartaric acid, citric acid, picric acid, methanesulfonic acid, benzenemethanesulfonic acid, benzenesulfonic acid, aspartic acid, or glutamic acid.

[0262] In another preferred embodiment, the base of the pharmaceutically acceptable salt of the compound of formula I is a pharmaceutically acceptable salt of the compound of formula I, wherein the acid is one H + This includes bases formed by loss of

[0263] In another preferred example, the base of the pharmaceutically acceptable salt of the compound of formula I comprises a base formed by the loss of one H from hydrochloric acid, galactaric acid, D-glucuronic acid, hydrobromic acid, hydrofluoric acid, hydroiodic acid, sulfuric acid, nitric acid, phosphoric acid, formic acid, acetic acid, trifluoroacetic acid, propionic acid, oxalic acid, malonic acid, succinic acid, fumaric acid, maleic acid, lactic acid, malic acid, tartaric acid, citric acid, picric acid, methanesulfonic acid, benzenemethanesulfonic acid, benzenesulfonic acid, aspartic acid, or glutamic acid.

[0264] In another preferred embodiment, the base of the pharmaceutically acceptable salt of the compound of formula I is F - , Cl - , Br - , I - , H.C.O.O. - , CH3COO - , SO4 2- or NO3 - Includes:

[0265] In another preferred embodiment, the chemical structure of the compound of formula I, or an optical isomer or racemate thereof, or a solvate thereof, or a pharmaceutically acceptable salt thereof, or a deuterated compound thereof, is as follows: [ka] JPEG2025509622000130.jpg233163JPEG2025509622000131.jpg231161JPEG2025509622000132.jpg241167JPEG202 5509622000133.jpg232164JPEG2025509622000134.jpg220163JPEG2025509622000135.jpg231163JPEG2025509622 000136.jpg231165JPEG2025509622000137.jpg234162JPEG2025509622000138.jpg220163JPEG2025509622000139. jpg230163JPEG2025509622000140.jpg232159JPEG2025509622000141.jpg229162JPEG2025509622000142.jpg22916 4JPEG2025509622000143.jpg235161JPEG2025509622000144.jpg234162JPEG2025509622000145.jpg229162JPEG20 25509622000146.jpg229162JPEG2025509622000147.jpg239165JPEG2025509622000148.jpg237163JPEG2025509622 000149.jpg232161JPEG2025509622000150.jpg229157JPEG2025509622000151.jpg225162JPEG2025509622000152. jpg230160JPEG2025509622000153.jpg231158JPEG2025509622000154.jpg238160JPEG2025509622000155.jpg85161

[0266] A second aspect of the present invention provides a composition comprising (a) the compound of formula I according to the first aspect of the present invention, or an optical isomer or racemate thereof, or a solvate thereof, or a pharmaceutically acceptable salt thereof, or a deuterated compound thereof, and (b) a pharmaceutically acceptable carrier.

[0267] In another preferred example, the content of (a) the compound of formula I according to the first aspect of the present invention, or an optical isomer or racemate thereof, or a solvate thereof, or a pharmaceutically acceptable salt thereof, or a deuterated compound thereof, relative to the total weight of the composition is 0.001-99.9 wt%.

[0268] In another preferred embodiment, the composition is a pharmaceutical composition.

[0269] In another preferred embodiment, the composition further comprises a pharmaceutically acceptable carrier.

[0270] In another preferred embodiment, the composition is in the form of a solid, liquid, or semi-solid.

[0271] In another preferred embodiment, the composition is an oral agent, an external agent, or an injectable preparation.

[0272] In another preferred embodiment, the composition is in the form of a tablet, an injection, an infusion, an ointment, a gel, a solution, a pill, or a film.

[0273] A third aspect of the present invention provides the use of the compound of formula I according to the first aspect of the present invention, or an optical isomer or racemate thereof, or a solvate thereof, or a pharmaceutically acceptable salt thereof, or a deuterated compound thereof, for the manufacture of a composition or formulation for use in the prevention and / or treatment of tumors.

[0274] In another preferred embodiment, the tumor is of human origin.

[0275] In another preferred embodiment, the tumor is a human tumor.

[0276] In another preferred embodiment, the tumor comprises a tumor in which the mitochondrial permeability transition pore is underexpressed, not expressed, underactivated, or inactivated.

[0277] In another preferred embodiment, the tumor comprises a tumor in which peptidyl prolyl isomerase F is underexpressed, not expressed, underactivated or inactivated.

[0278] In another preferred example, peptidylprolyl isomerase F has the protein number UniProtKB / Swiss-Prot: P30405 and the gene number NCBI Entrez Gene: 10105.

[0279] In another preferred embodiment, the tumor in which the mitochondrial permeability transition pore is underexpressed or underactivated refers to a tumor in which the expression level or activity of the mitochondrial permeability transition pore in tumor cells is lower than the expression level or activity of the mitochondrial permeability transition pore in similar cells or normal cells (e.g., cancerous bladder tissue cells).

[0280] In another preferred embodiment, the tumor in which the mitochondrial permeability transition pore is underexpressed or underactivated refers to a tumor in which the ratio (H1 / H0) between the expression level or activity H1 of the mitochondrial permeability transition pore in a certain cell (e.g., a tumor cell) and the expression level or activity H0 of the mitochondrial permeability transition pore in a similar cell or a normal cell (e.g., a cancerous bladder tissue cell) is <1.0, preferably ≦0.8, and more preferably ≦0.7, ≦0.6, ≦0.5, ≦0.4, ≦0.3, ≦0.2, ≦0.1, ≦0.05, ≦0.01, ≦0.005, ≦0.001, ≦0.0001, ≦0.00001, ≦0.000001, or ≦0.0000001.

[0281] In another preferred embodiment, the certain cells include tumor cells.

[0282] In another preferred embodiment, the allogeneic cells comprise cells of the same type.

[0283] In another preferred embodiment, the allogeneic cells comprise allogeneic tumor cells.

[0284] In another preferred embodiment, the allogeneic cells comprise tumor cells of the same type.

[0285] In another preferred embodiment, the allogeneic cells refer to cells (allogeneic tumor cells) in which the mitochondrial permeability transition pore is normally expressed, highly expressed, normally activated, or highly activated.

[0286] In another preferred embodiment, the allogeneic cells refer to cells of the same type, but in which the mitochondrial permeability transition pore is normally expressed, highly expressed, normally activated, or highly activated (allogeneic tumor cells).

[0287] In another preferred embodiment, the normal cells refer to normal tissue cells (e.g., tumor cell-derived cells, tumor-adjacent cells, or cancerous bladder tissue cells) in which the mitochondrial permeability transition pore is normally expressed or normally activated.

[0288] In another preferred embodiment, H0 represents the expression level or activity of the mitochondrial permeability transition pore of a cell in which the mitochondrial permeability transition pore is normally expressed, highly expressed, normally activated, or highly activated.

[0289] In another preferred embodiment, the cells in which the mitochondrial permeability transition pore is normally expressed, highly expressed, normally activated, or highly activated include cells that are insensitive to the compound of formula I, or an optical isomer or racemate thereof, or a solvate thereof, or a pharmaceutically acceptable salt thereof, or a deuterated compound thereof.

[0290] In another preferred embodiment, the tumor in which peptidylprolyl isomerase F is underexpressed or underactivated refers to a tumor in which the expression level or activity of peptidylprolyl isomerase F in tumor cells is lower than the expression level or activity of peptidylprolyl isomerase F in related cells or normal cells (e.g., cancerous bladder tissue cells).

[0291] In another preferred embodiment, the tumor in which peptidyl prolyl isomerase F is underexpressed or underactivated refers to a tumor in which the ratio (C1 / C0) between the expression level or activity C1 of peptidyl prolyl isomerase F in a certain cell (e.g., a tumor cell) and the expression level or activity C0 of peptidyl prolyl isomerase F in a similar cell or a normal cell (e.g., a cancerous bladder tissue cell) is <1.0, preferably ≦0.8, and more preferably ≦0.7, ≦0.6, ≦0.5, ≦0.4, ≦0.3, ≦0.2, ≦0.1, ≦0.05, ≦0.01, ≦0.005, ≦0.001, ≦0.0001, ≦0.00001, ≦0.000001, or ≦0.0000001.

[0292] In another preferred embodiment, the certain cells include tumor cells.

[0293] In another preferred embodiment, the allogeneic cells comprise cells of the same type.

[0294] In another preferred embodiment, the allogeneic cells comprise allogeneic tumor cells.

[0295] In another preferred embodiment, the allogeneic cells comprise tumor cells of the same type.

[0296] In another preferred embodiment, the allogeneic cells refer to cells in which peptidylprolyl isomerase F is normally expressed, highly expressed, normally activated, or highly activated (allogeneic tumor cells).

[0297] In another preferred embodiment, the allogeneic cells refer to cells of the same type, but in which peptidylprolyl isomerase F is normally expressed, highly expressed, normally activated or highly activated (allogeneic tumor cells).

[0298] In another preferred embodiment, the normal cells refer to normal tissue cells in which peptidylprolyl isomerase F is normally expressed or activated (e.g., cells derived from tumor cells, tumor-adjacent cells, or cancerous bladder tissue cells).

[0299] In another preferred embodiment, C0 represents the expression level or activity of peptidyl prolyl isomerase F in cells in which peptidyl prolyl isomerase F is normally expressed, highly expressed, normally activated, or highly activated.

[0300] In another preferred embodiment, the cells in which peptidylprolyl isomerase F is normally expressed, highly expressed, normally activated, or highly activated include cells that are insensitive to the compound of formula I, or an optical isomer or racemate thereof, or a solvate thereof, or a pharmaceutically acceptable salt thereof, or a deuterated compound thereof.

[0301] In another preferred embodiment, the tumor in which the mitochondrial permeability transition pore is under-expressed, not expressed, hypoactive, or inactivated can be treated by administering an inhibitor of the mitochondrial permeability transition pore.

[0302] In another preferred embodiment, the tumor in which peptidyl prolyl isomerase F is under-expressed, not expressed, hypoactive or inactivated can be treated by administering a peptidyl prolyl isomerase F inhibitor.

[0303] In another preferred embodiment, the inhibitor comprises an inhibitor having specificity.

[0304] In another preferred embodiment, the inhibitor of the mitochondrial permeability transition pore includes an inhibitor capable of causing the mitochondrial permeability transition pore in tumors to be underexpressed, not expressed, underactivated, or inactivated.

[0305] In another preferred embodiment, the inhibitor of peptidyl prolyl isomerase F includes an inhibitor capable of under-expressing, not expressing, under-activating or inactivating peptidyl prolyl isomerase F in tumors.

[0306] In another preferred embodiment, the inhibitor of the mitochondrial permeability transition pore is selected from Cyclosporin A, a CyP-D protein inhibitor, a peroxide scavenger, or a combination thereof.

[0307] In another preferred embodiment, said inhibitor of peptidyl prolyl isomerase F comprises shRNA.

[0308] In another preferred example, the nucleotide sequence of the shRNA is GTTCTTCATCTGCACCATAAA.

[0309] In another preferred embodiment, the tumor comprises a brain tumor.

[0310] In another preferred embodiment, the brain tumor comprises a glioblastoma.

[0311] In another preferred embodiment, the brain tumor comprises a cranial fossa malignant glioblastoma.

[0312] In another preferred embodiment, the brain tumor comprises a medulloblastoma.

[0313] In another preferred embodiment, the tumor cells of the brain tumor include Daoy cells.

[0314] In another preferred embodiment, the level includes the protein level and / or the mRNA level.

[0315] In another preferred embodiment, the expression comprises protein expression and / or mRNA expression.

[0316] In another preferred embodiment, the composition or formulation is a drug composition or drug formulation.

[0317] In another preferred embodiment, the composition or formulation further comprises a pharmaceutically acceptable carrier.

[0318] In another preferred embodiment, the composition or preparation is in the form of a solid, liquid or semi-solid.

[0319] In another preferred embodiment, the type of the composition or preparation is an oral preparation, an external preparation, or an injectable preparation.

[0320] In another preferred embodiment, the injectable formulation is an intravenous formulation.

[0321] In another preferred embodiment, the composition or preparation is in the form of a tablet, an injection, an infusion, an ointment, a gel, a solution, a pill, or a film.

[0322] A fourth aspect of the present invention provides a marker for determining whether the compound of formula I according to the first aspect of the present invention, or an optical isomer or racemate thereof, or a solvate thereof, or a pharmaceutically acceptable salt thereof, or a deuterated compound thereof, is suitable for the prevention and / or treatment of tumor in a tumor patient, wherein the marker has a mitochondrial permeability transition pore and / or peptidylprolyl isomerase F.

[0323] In another preferred embodiment, the marker comprises the expression level or activity of the mitochondrial permeability transition pore and / or the expression level or activity of peptidylprolyl isomerase F.

[0324] In another preferred embodiment, the mitochondrial permeability transition pore and / or peptidyl prolyl isomerase F comprises the mitochondrial permeability transition pore and / or peptidyl prolyl isomerase F of a tumor cell.

[0325] In another preferred example, when the mitochondrial permeability transition pore is underexpressed, not expressed, underactivated or inactivated in tumor cells of a tumor patient, and / or peptidylprolyl isomerase F is underexpressed, not expressed, underactivated or inactivated, the compound of formula I according to the first aspect of the present invention, or an optical isomer or racemate thereof, or a solvate thereof, or a pharmaceutically acceptable salt thereof, or a deuterated compound thereof becomes suitable for the prevention and / or treatment of tumors in the tumor patient.

[0326] In another preferred example, when the mitochondrial permeability transition pore and / or peptidylprolyl isomerase F are overexpressed or overactivated in tumor cells of a tumor patient, the compound of formula I according to the first aspect of the present invention, or an optical isomer or racemate thereof, or a solvate thereof, or a pharmaceutically acceptable salt thereof, or a deuterated compound thereof becomes unsuitable for the prevention and / or treatment of tumors in the tumor patient.

[0327] In another preferred example, the statement that the compound of formula I according to the first aspect of the present invention, or an optical isomer or racemate thereof, or a solvate thereof, or a pharmaceutically acceptable salt thereof, or a deuterated compound thereof is suitable for the prevention and / or treatment of tumors in tumor patients means that tumor cells in the tumor patient are sensitive to the compound of formula I according to the first aspect of the present invention, or an optical isomer or racemate thereof, or a solvate thereof, or a pharmaceutically acceptable salt thereof, or a deuterated compound thereof.

[0328] In another preferred example, the content that the compound of formula I according to the first aspect of the present invention, or an optical isomer or racemate thereof, or a solvate thereof, or a pharmaceutically acceptable salt thereof, or a deuterated compound thereof is not suitable for the prevention and / or treatment of tumor in a tumor patient means that tumor cells of the tumor patient are insensitive to the compound of formula I according to the first aspect of the present invention, or an optical isomer or racemate thereof, or a solvate thereof, or a pharmaceutically acceptable salt thereof, or a deuterated compound thereof.

[0329] In another preferred embodiment, the tumor in which the mitochondrial permeability transition pore is underexpressed, absent, underactivated or inactivated is a tumor according to the third aspect of the present invention.

[0330] In another preferred embodiment, the tumor in which peptidylprolyl isomerase F is underexpressed, not expressed, underactivated or inactivated is a tumor according to the third aspect of the present invention.

[0331] In another preferred embodiment, the tumor exhibiting high expression or activation of the mitochondrial permeability transition pore refers to a tumor in which the ratio (H1 / H0) between the expression level or activity H1 of the mitochondrial permeability transition pore in a certain cell (e.g., a tumor cell) and the expression level or activity H0 of the mitochondrial permeability transition pore in a similar cell or a normal cell (e.g., a cancerous bladder tissue cell) is >1.0, preferably ≧1.2 or ≧1.5, and more preferably ≧2, ≧3, ≧5, ≧8, ≧10, ≧15, ≧20, ≧30, or ≧50, for example, 2-50.

[0332] In another preferred embodiment, the tumor with high expression or activation of peptidyl prolyl isomerase F refers to a tumor in which the ratio (C1 / C0) between the expression level or activity C1 of peptidyl prolyl isomerase F in a certain cell (e.g., a tumor cell) and the expression level or activity C0 of peptidyl prolyl isomerase F in a similar cell or a normal cell (e.g., a cancerous bladder tissue cell) is >1.0, preferably ≧1.2 or ≧1.5, and more preferably ≧2, ≧3, ≧5, ≧8, ≧10, ≧15, ≧20, ≧30, or ≧50, for example, 2-50.

[0333] A fifth aspect of the present invention provides a detection reagent kit, comprising: (i) A detection reagent is provided for detecting the expression level or activity of the mitochondrial permeability transition pore and / or the expression level or activity of peptidylprolyl isomerase F.

[0334] In another preferred embodiment, the detection sample of the detection reagent kit contains tumor cells.

[0335] In another preferred embodiment, the level comprises a protein level and / or an mRNA level.

[0336] In another preferred embodiment, said expression comprises mRNA and / or protein expression.

[0337] A sixth aspect of the present invention provides use of the detection reagent kit according to the fifth aspect of the present invention for the manufacture of a concomitant diagnostic kit for use in determining whether the compound of formula I according to the first aspect of the present invention, or an optical isomer or racemate thereof, or a solvate thereof, or a pharmaceutically acceptable salt thereof, or a deuterated compound thereof, is suitable for the prevention and / or treatment of tumors in tumor patients.

[0338] In another preferred embodiment, the companion detection reagent kit further comprises an instruction manual or label.

[0339] In another preferred embodiment, the instructions or label include:

[0340] The present invention provides that, when the mitochondrial permeability transition pore is underexpressed, not expressed, underactivated or inactivated in tumor cells of a tumor patient, and / or peptidylprolyl isomerase F is underexpressed, not expressed, underactivated or inactivated, the compound of formula I according to the first aspect of the present invention, or an optical isomer or racemate thereof, or a solvate thereof, or a pharmaceutically acceptable salt thereof, or a deuterated compound thereof becomes suitable for the prevention and / or treatment of tumors in the tumor patient.

[0341] In another preferred embodiment, the instructions or label include: The present invention discloses that when the mitochondrial permeability transition pore and / or peptidylprolyl isomerase F are overexpressed or overactivated in tumor cells of a tumor patient, the compound of formula I according to the first aspect of the present invention, or an optical isomer or racemate thereof, or a solvate thereof, or a pharmaceutically acceptable salt thereof, or a deuterated compound thereof becomes unsuitable for the prevention and / or treatment of tumors in the tumor patient.

[0342] In another preferred embodiment, the content that the compound of formula I according to the first aspect of the present invention, or an optical isomer or racemate thereof, or a solvate thereof, or a pharmaceutically acceptable salt thereof, or a deuterated compound thereof is suitable for the prevention and / or treatment of tumors in tumor patients has the meaning according to the fourth aspect of the present invention.

[0343] In another preferred embodiment, the content that the compound of formula I according to the first aspect of the present invention, or an optical isomer or racemate thereof, or a solvate thereof, or a pharmaceutically acceptable salt thereof, or a deuterated compound thereof is not suitable for the prevention and / or treatment of tumors in tumor patients has the meaning according to the fourth aspect of the present invention.

[0344] A seventh aspect of the present invention provides a medical kit.

[0345] The medical kit comprises: (i) a detection reagent used to detect the expression level or activity of the mitochondrial permeability transition pore and / or the expression level or activity of peptidylprolyl isomerase F; (ii) the compound of formula I according to the first aspect of the present invention, or an optical isomer or racemate thereof, or a solvate thereof, or a pharmaceutically acceptable salt thereof, or a deuterated compound thereof.

[0346] In another preferred example, the expression level or activity of the mitochondrial permeability transition pore and / or the expression level or activity of peptidylprolyl isomerase F means the expression level or activity of the mitochondrial permeability transition pore and / or the expression level or activity of peptidylprolyl isomerase F in tumor cells.

[0347] In another preferred embodiment, the sample for detection comprises a tumor.

[0348] In another preferred embodiment, the medical kit further comprises an instruction manual or label.

[0349] In another preferred embodiment, the instructions or label include: The present invention provides that, when the mitochondrial permeability transition pore is underexpressed, not expressed, underactivated or inactivated in tumor cells of a tumor patient, and / or peptidylprolyl isomerase F is underexpressed, not expressed, underactivated or inactivated, the compound of formula I according to the first aspect of the present invention, or an optical isomer or racemate thereof, or a solvate thereof, or a pharmaceutically acceptable salt thereof, or a deuterated compound thereof becomes suitable for the prevention and / or treatment of tumors in the tumor patient.

[0350] In another preferred embodiment, the instructions or label include: The present invention discloses that when the mitochondrial permeability transition pore and / or peptidylprolyl isomerase F are overexpressed or overactivated in tumor cells of a tumor patient, the compound of formula I according to the first aspect of the present invention, or an optical isomer or racemate thereof, or a solvate thereof, or a pharmaceutically acceptable salt thereof, or a deuterated compound thereof becomes unsuitable for the prevention and / or treatment of tumors in the tumor patient.

[0351] An eighth aspect of the present invention provides a method for preventing and / or treating tumors by administering to a subject the compound of formula I according to the first aspect of the present invention, or an optical isomer or racemate thereof, or a solvate thereof, or a pharmaceutically acceptable salt thereof, or a deuterated compound thereof, to achieve tumor prevention and / or treatment.

[0352] In another preferred embodiment, the tumor is a tumor according to the third aspect of the invention.

[0353] In another preferred embodiment, the subject to be treated is a human or non-human mammal (eg, rodents, rabbits, monkeys, livestock, dogs, cats).

[0354] In another preferred embodiment, the method comprises: The method includes first causing the tumor to be treated to have underexpression, no expression, underactivation or inactivation of the mitochondrial permeability transition pore and / or to have underexpression, no expression, underactivation or inactivation of peptidylprolyl isomerase F, and then administering the compound of formula I according to the first aspect of the present invention, or an optical isomer or racemate thereof, or a solvate thereof, or a pharmaceutically acceptable salt thereof, or a deuterated compound thereof, to carry out prophylaxis and / or treatment.

[0355] In another preferred embodiment, the method comprises: First, an inhibitor of the mitochondrial permeability transition pore and / or an inhibitor of peptidylprolyl isomerase F is administered to tumor cells so that the tumor to be treated becomes under-expressed, not-expressed, under-activated or inactivated in the mitochondrial permeability transition pore and / or becomes under-expressed, not-expressed, under-activated or inactivated in the tumor, and then the compound of formula I according to the first aspect of the present invention, or an optical isomer or racemate thereof, or a solvate thereof, or a pharmaceutically acceptable salt thereof, or a deuterated compound thereof is administered to carry out prevention and / or treatment.

[0356] In another preferred embodiment, the inhibitor of the mitochondrial permeability transition pore and / or the inhibitor of peptidylprolyl isomerase F is as described in the third aspect of the present invention.

[0357] A ninth aspect of the present invention provides an apparatus or system.

[0358] The device or system comprises: (i) a detection module used to detect the expression level or activity of the mitochondrial permeability transition pore and / or the expression level or activity of peptidylprolyl isomerase F; (ii) an output module.

[0359] The output module includes: information that when the mitochondrial permeability transition pore is underexpressed, not expressed, underactivated or inactivated in tumor cells of a tumor patient, and / or when peptidylprolyl isomerase F is underexpressed, not expressed, underactivated or inactivated, the compound of formula I according to the first aspect of the present invention, or an optical isomer or racemate thereof, or a solvate thereof, or a pharmaceutically acceptable salt thereof, or a deuterated compound thereof becomes suitable for the prevention and / or treatment of tumors in said tumor patient; and / or When the mitochondrial permeability transition pore and / or peptidylprolyl isomerase F are overexpressed or overactivated in tumor cells of a tumor patient, the compound of formula I according to the first aspect of the present invention, or an optical isomer or racemate thereof, or a solvate thereof, or a pharmaceutically acceptable salt thereof, or a deuterated compound thereof, is output as information that the compound becomes unsuitable for tumor prevention and / or treatment in the tumor patient.

[0360] In another preferred embodiment, the sample for detection comprises a tumor.

[0361] In another preferred embodiment, the device comprises a gene detector or a protein detector.

[0362] In another preferred embodiment, the device or system further comprises a sample supply module.

[0363] In another preferred embodiment, the sample supply module is used to supply a tumor cell extract.

[0364] In another preferred embodiment, the device or system further comprises a data processing module.

[0365] In another preferred embodiment, the data processing module processes the expression level or activity of the mitochondrial permeability transition pore and / or the expression level or activity of peptidylprolyl isomerase F to obtain their numerical ranges.

[0366] A tenth aspect of the present invention provides the use of an inhibitor of the mitochondrial permeability transition pore and / or an inhibitor of peptidylprolyl isomerase F to manufacture a composition or formulation used to enhance the antitumor effect of an antitumor drug.

[0367] In another preferred embodiment, the inhibitor of the mitochondrial permeability transition pore includes an inhibitor capable of causing the mitochondrial permeability transition pore in tumors to be underexpressed, not expressed, underactivated, or inactivated.

[0368] In another preferred embodiment, the inhibitor of peptidyl prolyl isomerase F includes an inhibitor capable of under-expressing, not expressing, under-activating or inactivating peptidyl prolyl isomerase F in tumors.

[0369] In another preferred embodiment, the inhibitor comprises an inhibitor having specificity.

[0370] In another preferred embodiment, the antitumor medicament comprises the compound of formula I according to the first aspect of the present invention, or an optical isomer or racemate thereof, or a solvate thereof, or a pharmaceutically acceptable salt thereof, or a deuterated compound thereof.

[0371] In another preferred embodiment, the tumor is a tumor according to the third aspect of the invention.

[0372] In another preferred embodiment, the inhibitor of the mitochondrial permeability transition pore is selected from Cyclosporin A, a CyP-D protein inhibitor, a peroxide scavenger, or a combination thereof.

[0373] In another preferred embodiment, said inhibitor of peptidyl prolyl isomerase F comprises shRNA.

[0374] In another preferred example, the nucleotide sequence of the shRNA is GTTCTTCATCTGCACCATAAA.

[0375] In another preferred embodiment, the composition or formulation is a drug composition or drug formulation.

[0376] In another preferred embodiment, the composition or formulation further comprises a pharmaceutically acceptable carrier.

[0377] In another preferred embodiment, the composition or preparation is in the form of a solid, liquid or semi-solid.

[0378] In another preferred embodiment, the type of the composition or preparation is an oral preparation, an external preparation, or an injectable preparation.

[0379] In another preferred embodiment, the injectable formulation is an intravenous formulation.

[0380] In another preferred embodiment, the composition or preparation is in the form of a tablet, an injection, an infusion, an ointment, a gel, a solution, a pill, or a film.

[0381] An eleventh aspect of the present invention provides a combination of active ingredients comprising: (1) a first active ingredient comprising an antitumor drug; and (2) A second active ingredient comprising an inhibitor of the mitochondrial permeability transition pore and / or an inhibitor of peptidylprolyl isomerase F.

[0382] In another preferred embodiment, the antitumor medicament comprises the compound of formula I according to the first aspect of the present invention, or an optical isomer or racemate thereof, or a solvate thereof, or a pharmaceutically acceptable salt thereof, or a deuterated compound thereof.

[0383] In another preferred embodiment, the term "inhibitor of the mitochondrial permeability transition pore and / or inhibitor of peptidylprolyl isomerase F" has the meaning described in the tenth aspect of the present invention.

[0384] In another preferred embodiment, the molar ratio between the first active ingredient and the second active ingredient is 0.01-600:1, preferably 0.05-500:1, and more preferably 0.1-400:1, 0.2-200:1, 0.5-100:1, 0.5-80:1 or 1-50:1.

[0385] In another preferred embodiment, the combination of active ingredients comprises at least one independent active ingredient.

[0386] In another preferred embodiment, the combination of active ingredients includes a first active ingredient and a second active ingredient that are independent of each other.

[0387] A twelfth aspect of the present invention provides a composition comprising the following components: (1) a first active ingredient comprising an antitumor drug; and (2) A second active ingredient comprising an inhibitor of the mitochondrial permeability transition pore and / or an inhibitor of peptidylprolyl isomerase F.

[0388] In another preferred embodiment, the antitumor medicament comprises the compound of formula I according to the first aspect of the present invention, or an optical isomer or racemate thereof, or a solvate thereof, or a pharmaceutically acceptable salt thereof, or a deuterated compound thereof.

[0389] In another preferred embodiment, the term "inhibitor of the mitochondrial permeability transition pore and / or inhibitor of peptidylprolyl isomerase F" has the meaning described in the tenth aspect of the present invention.

[0390] In another preferred embodiment, the composition is a pharmaceutical composition.

[0391] In another preferred embodiment, the pharmaceutical composition further comprises a pharmaceutically acceptable carrier.

[0392] In another preferred embodiment, the composition or preparation is in the form of a solid, liquid or semi-solid.

[0393] In another preferred embodiment, the type of the composition or preparation is an oral preparation, an external preparation, or an injectable preparation.

[0394] In another preferred embodiment, the composition or preparation is in the form of a tablet, an injection, an infusion, an ointment, a gel, a solution, a pill, or a film.

[0395] In another preferred embodiment, the content of the first active ingredient relative to the total weight of active ingredients in the composition is 0.01-99.99 wt%, preferably 0.1-99.9 wt%, and more preferably 1-99 wt%, 10-99 wt% or 20-99 wt%.

[0396] In another preferred embodiment, the content of the second active ingredient relative to the total weight of the active ingredients of the composition is 0.01-99.99 wt%, preferably 0.1-99.9 wt%, and more preferably 1-99 wt%, 10-99 wt% or 20-99 wt%.

[0397] A thirteenth aspect of the present invention provides a medical kit comprising the following formulation: (A) a first formulation having a first active ingredient comprising an anti-tumor drug; and (B) A second formulation having a second active ingredient comprising an inhibitor of the mitochondrial permeability transition pore and / or an inhibitor of peptidylprolyl isomerase F.

[0398] In another preferred embodiment, the antitumor medicament comprises the compound of formula I according to the first aspect of the present invention, or an optical isomer or racemate thereof, or a solvate thereof, or a pharmaceutically acceptable salt thereof, or a deuterated compound thereof.

[0399] In another preferred embodiment, the term "inhibitor of the mitochondrial permeability transition pore and / or inhibitor of peptidylprolyl isomerase F" has the meaning described in the tenth aspect of the present invention.

[0400] In another preferred embodiment, the medical kit further comprises an instruction manual.

[0401] In another preferred embodiment, the first formulation and the second formulation are independent of each other.

[0402] In another preferred embodiment, the first and second formulations are combined.

[0403] In another preferred embodiment, the instructions state that the first formulation and the second formulation are used in combination to enhance the antitumor activity of the antitumor drug.

[0404] In another preferred embodiment, the method of combination is to first administer the second formulation having the second active ingredient, followed by administering the first formulation having the first active ingredient.

[0405] A fourteenth aspect of the present invention provides a method for inhibiting tumor cells, said method comprising contacting tumor cells with the compound of formula I according to the first aspect of the invention, or an optical isomer or racemate thereof, or a solvate thereof, or a pharmaceutically acceptable salt thereof, or a deuterated compound thereof, to inhibit said tumor cells.

[0406] In another preferred embodiment, the method is performed ex vivo or is an ex vivo method.

[0407] In another preferred embodiment, the method is an in vitro, non-therapeutic, non-diagnostic method.

[0408] In another preferred embodiment, the contacting is performed in an in vitro culture.

[0409] In another preferred embodiment, the tumor is a tumor according to the third aspect of the invention.

[0410] In another preferred embodiment, the method comprises: The method comprises first causing tumor cells to have under-expression, no-expression, under-activation or inactivation of the mitochondrial permeability transition pore and / or under-expression, no-expression, under-activation or inactivation of peptidylprolyl isomerase F, and then contacting the tumor cells with the compound of formula I according to the first aspect of the present invention, or an optical isomer or racemate thereof, or a solvate thereof, or a pharmaceutically acceptable salt thereof, or a deuterated compound thereof, thereby inhibiting the tumor cells.

[0411] In another preferred embodiment, the method comprises: First, an inhibitor of the mitochondrial permeability transition pore and / or an inhibitor of peptidyl prolyl isomerase F is administered to tumor cells so that the tumor cells become under-expressed, not expressed, under-activated or inactivated in the mitochondrial permeability transition pore and / or become under-expressed, not expressed, under-activated or inactivated in the peptidyl prolyl isomerase F, and then the tumor cells are contacted with the compound of formula I according to the first aspect of the present invention, or an optical isomer or racemate thereof, or a solvate thereof, or a pharmaceutically acceptable salt thereof, or a deuterated compound thereof, thereby inhibiting the tumor cells.

[0412] In another preferred embodiment, the term "inhibitor of the mitochondrial permeability transition pore and / or inhibitor of peptidylprolyl isomerase F" has the meaning described in the tenth aspect of the present invention.

[0413] A fifteenth aspect of the present invention provides the use of the medical kit according to the seventh aspect of the present invention for the manufacture of a pharmaceutical kit for use in the prevention and / or treatment of tumors.

[0414] In another preferred embodiment, the pharmaceutical kit further comprises an instruction manual or label.

[0415] In another preferred embodiment, the instructions or label include: The present invention provides that, when the mitochondrial permeability transition pore is underexpressed, not expressed, underactivated or inactivated in tumor cells of a tumor patient, and / or peptidylprolyl isomerase F is underexpressed, not expressed, underactivated or inactivated, the compound of formula I according to the first aspect of the present invention, or an optical isomer or racemate thereof, or a solvate thereof, or a pharmaceutically acceptable salt thereof, or a deuterated compound thereof becomes suitable for the prevention and / or treatment of tumors in the tumor patient.

[0416] In another preferred embodiment, the instructions or label include: The present invention discloses that when the mitochondrial permeability transition pore and / or peptidylprolyl isomerase F are overexpressed or overactivated in tumor cells of a tumor patient, the compound of formula I according to the first aspect of the present invention, or an optical isomer or racemate thereof, or a solvate thereof, or a pharmaceutically acceptable salt thereof, or a deuterated compound thereof becomes unsuitable for the prevention and / or treatment of tumors in the tumor patient.

[0417] Within the scope of the present invention, each of the above technical features of the present invention may be combined with the following specific technical features to form new or preferred technical solutions, which will not be repeated here due to the limited size of the full text. [Brief explanation of the drawings]

[0418] [Figure 1] Figure 1 shows the expression levels of PPIF protein detected by Western blotting. Here, Con shRNA represents the control group for the expression level of PPIF protein in Daoy cells transfected with an empty viral vector that does not contain shRNA for specific induced degradation of PPIF mRNA; PPIF shRNA represents the experimental group for the expression level of PPIF protein in Daoy cells transfected with a viral vector containing shRNA for specific induced degradation of PPIF mRNA. [Figure 2] Figure 2 shows the relative cell vitality of Daoy cells with mPTP inactivation and Daoy cells with mPTP activation, where Con shRNA represents the control group relative to the vitality of Daoy cells transfected with an empty viral vector without shRNA for specificity-induced degradation of PPIF mRNA; PPIF shRNA represents the experimental group relative to the vitality of Daoy cells transfected with a viral vector containing shRNA for specificity-induced degradation of PPIF mRNA. DETAILED DESCRIPTION OF THE INVENTION

[0419] As a result of long-term and in-depth research, the present inventors have unexpectedly discovered for the first time a compound that has significantly superior therapeutic effects on tumors with low expression, no expression, low activity, or inactivity of the mitochondrial permeability transition pore and / or low expression, no expression, low activity, or inactivity of peptidylprolyl isomerase F. The expression level or activity of the mitochondrial permeability transition pore and / or the expression level or activity of peptidylprolyl isomerase F can serve as a marker for determining whether the compound of the present invention is suitable for tumor prevention and / or treatment in tumor patients. The present inventors have achieved the present invention based on this finding.

[0420] term Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art.

[0421] As used herein, the terms "including," "comprising," and "having" may be used interchangeably and have closed definitions as well as semi-closed and open definitions. In other words, the terms have the meaning "consisting of" or "consisting essentially of."

[0422] As used herein, the terms "anti-cancer drug" and "anti-tumor drug" may be used interchangeably.

[0423] As used herein, the terms "cancer" and "tumor" may be used interchangeably.

[0424] As used herein, the term "a certain cell" refers to a certain cell (e.g., a single tumor cell) or a group of cells including multiple similar cells (e.g., a certain tumor tissue).

[0425] As used herein, "the compound of the present invention is suitable for tumor patients" means that the tumor of the tumor patient is sensitive to the compound of the present invention.

[0426] As used herein, "the compounds of the present invention are not suitable for tumor patients" means that the tumors of the tumor patients are insensitive to the compounds of the present invention.

[0427] As used herein, "IC50" and "IC 50 The terms "50% inhibiting concentration" and "50% inhibitory concentration" may be used interchangeably and refer to the concentration of an inhibitor at which 50% of the inhibitory effect is achieved.

[0428] As used herein, the term "P / S" refers to the addition of penicillin and streptomycin to the relevant medium.

[0429] As used herein, "expression level or activity of the mitochondrial permeability transition pore and / or expression level or activity of peptidylprolyl isomerase F" refers to one or more of the expression level or activity of the mitochondrial permeability transition pore and the expression level or activity of peptidylprolyl isomerase F.

[0430] As used herein, "under-expression, under-expression, low activity, or inactivity of the mitochondrial permeability transition pore and / or under-expression, under-expression, low activity, or inactivity of peptidylprolyl isomerase F" refers to one or more of under-expression, under-expression, low activity, or inactivity of the mitochondrial permeability transition pore and under-expression, under-expression, low activity, or inactivity of peptidylprolyl isomerase F.

[0431] As used herein, "high expression or activation of the mitochondrial permeability transition pore and / or high expression or activation of peptidylprolyl isomerase F" refers to one or more of high expression or activation of the mitochondrial permeability transition pore and high expression or activation of peptidylprolyl isomerase F.

[0432] As used herein, the term "mitochondria permeability transition pore" is abbreviated as mPTP (mitochondria permeability transition pore).

[0433] As used herein, the term "peptidyl-prolyl isomerase F" is abbreviated as PPIF (Peptidyl-prolyl cis-trans isomerase F).

[0434] As used herein, the term "MS-ESI" refers to Electro Spray Ionization-Mass Spectroscopy.

[0435] As used herein, " 1 The term "H NMR" refers to nuclear magnetic resonance hydrogen spectroscopy.

[0436] It should be understood that one skilled in the art can prepare chemically stable compounds by selecting the substituents and substitution patterns on the compounds of the present invention, and can synthesize such compounds using techniques known in the art and the methods described below. When substituted with one or more substituents, it should be understood that these substituents can be located on the same carbon or on different carbons, as long as a stable structure is produced.

[0437] As used herein, the terms "substituted" or "substituted" refer to the replacement of hydrogen atoms on a group of atoms with non-hydrogen atom groups, as needed to satisfy their valences, and which produce chemically stable compounds, i.e., compounds that do not spontaneously undergo transformations such as cyclization or elimination.

[0438] As used herein, "deuteration" refers to the replacement of one or more hydrogen atoms in a compound or group of atoms by a deuterium atom. The deuteration can be 1-deuteration, 2-deuteration, 3-deuteration, or total deuteration.

[0439] As used herein, the term "solvate" refers to a complex formed by coordination of a compound with solvent molecules in a specific ratio.

[0440] As used herein, "R", "R1" and "R 1 " have the same meaning and may be used interchangeably, and have the same meaning as other similar definitions.

[0441] As used herein, [ka]

[0442] As used herein, the term "alkyl group" refers to a straight-chain (i.e., unbranched) or branched saturated hydrocarbon group containing only carbon and hydrogen atoms, or a group of atoms that combines straight and branched chains. When the alkyl group is specified by the number of carbon atoms (e.g., a C1-C6 alkyl group), the alkyl group has the specified number of carbon atoms (e.g., 1 to 6). For example, a C1-C4 alkyl group refers to an alkyl group containing 1 to 4 carbon atoms. Representative examples of these alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, s-butyl, t-butyl, or similar groups.

[0443] As used herein, the term "alkylidene group" refers to an atomic group formed by removing one hydrogen atom from an alkyl group. The alkyl group is as defined above. When the alkylidene group is specified by the number of carbon atoms (e.g., a C1-C6 alkylidene group), the alkylidene group has the specified number of carbon atoms (e.g., 1 to 6). For example, a C1-C4 alkylidene group refers to an alkylidene group containing 1 to 4 carbon atoms. Representative examples of these alkylidene groups include, but are not limited to, a methylidene group, an ethylidene group, a propylidene group, an isopropylidene group, a butylidene group, an isobutylidene group, an s-butylidene group, a t-butylidene group, or similar atomic groups.

[0444] As used herein, the term "alkenyl group" refers to a hydrocarbyl group formed by removing one hydrogen atom connected to a double bond from a straight- or branched-chain molecule having one or more double bonds. When the alkenyl group is specified by the number of carbon atoms (e.g., a C2-C6 alkenyl group), the alkenyl group has the specified number of carbon atoms (e.g., 1 to 6). For example, a C2-C4 alkenyl group refers to an alkenyl group containing 2 to 4 carbon atoms. Representative examples of these alkenyl groups include, but are not limited to, vinyl (CH2=CH-), butenyl (C(CH3)2=CH-), or similar atomic groups.

[0445] As used herein, the term "halogen atom" refers to a fluorine atom, chlorine atom, bromine atom, or iodine atom.

[0446] As used herein, the term "halogenated" refers to substitution with a halogen atom.

[0447] As used herein, the term "halogenated alkyl group" refers to an atomic group formed by replacing one or more (preferably one, two, three, or four) hydrogen atoms of an alkyl group with halogen atoms. The alkyl group and halogen atoms are as defined above. When the halogenated alkyl group is specified by the number of carbon atoms (e.g., a C1-C8 halogenated alkyl group), the halogenated alkyl group has the specified number of carbon atoms (e.g., 1 to 8). For example, a C1-C6 halogenated alkyl group refers to a halogenated alkyl group containing 1 to 6 carbon atoms. Representative examples of these halogenated alkyl groups include, but are not limited to, -CF3, -CHF2, a monofluoroisopropyl group, a difluorobutyl group, or similar atomic groups.

[0448] As used herein, the term "cycloalkyl group" refers to a saturated or partially saturated monocyclic, bicyclic, or polycyclic (fused, bridged, or spiro) ring group. A carbon number specification (e.g., C3-C12) before the cycloalkyl group indicates that the cycloalkyl group has the specified number of ring carbon atoms (e.g., 3 to 12). For example, the term "C3-C8 cycloalkyl group" refers to a saturated or partially saturated monocycloalkyl or dicycloalkyl group having 3 to 8 ring carbon atoms, including cyclopropyl, cyclobutyl, cycloamyl, cycloheptyl, or similar groups. A "spirocycloalkyl group" refers to a bicyclic or polycyclic group that shares a carbon atom (called a spiro atom) between monocyclic rings; such groups may contain one or more double bonds, but neither ring has a completely conjugated π-electron system. A "fused cycloalkyl group" refers to a bicyclic or polycyclic group of atoms in which each ring in the system shares an entire pair of adjacent carbon atoms with another ring in the system, where one or more rings may contain one or more double bonds, but neither ring has a completely conjugated π-electron system. A "bridged cycloalkyl group" refers to a polycyclic group of atoms in which any two rings share two carbon atoms that are not directly connected, where such a group may contain one or more double bonds, but neither ring has a completely conjugated π-electron system. Representative examples of these cycloalkyl groups are as follows: [ka]

[0449] As used herein, the term "halogenated cycloalkyl group" refers to an atomic group formed by replacing one or more (preferably one, two, three, or four) hydrogen atoms in a cycloalkyl group with halogen atoms. The cycloalkyl group and halogen atoms are as defined above. When the cycloalkyl group is specified by the number of carbon atoms (e.g., a C3-C8 halogenated cycloalkyl group), the cycloalkyl group has the specified number of ring carbon atoms (e.g., 3 to 8). For example, a C3-C8 halogenated cycloalkyl group refers to a halogenated cycloalkyl group containing 3 to 8 ring carbon atoms. Representative examples of these halogenated cycloalkyl groups include, but are not limited to, a monofluorinated cyclopropyl group, a monochlorinated cyclobutyl group, a monofluorinated cycloamyl group, a difluorinated cycloheptyl group, or similar atomic groups.

[0450] As used herein, the term "alkoxyl group" refers to the R-O-atom group, where R is an alkyl group. Alkyl groups are as defined above. When the alkoxyl group is specified by the number of carbon atoms before it (e.g., a C1-C8 alkoxyl group), the alkyl group in the alkoxyl group has the specified number of carbon atoms (e.g., 1 to 8). Representative examples of these alkoxyl groups include, but are not limited to, methoxy, ethoxy, N-propoxy, isopropoxy, t-butoxy, or similar groups.

[0451] As used herein, the term "alkylthiol group" refers to an R-S atomic group, where R is an alkyl group. The alkyl group is as defined above. An alkylthiol group specified by the number of carbon atoms before the alkylthiol group (e.g., a C1-C8 alkoxyl group) refers to an alkylthiol group in which the alkyl group has the specified number of carbon atoms (e.g., 1 to 8). Representative examples of these alkylthiol groups include, but are not limited to, a methylthio group, an ethylthio group, an N-propylthio group, an isopropylthio group, a t-butylthio group, or similar atomic groups.

[0452] As used herein, the term "halogenated alkoxyl group" refers to a halogenated alkyl group -O-, where the halogenated alkyl group is as defined above. For example, a C1-C6 halogenated alkoxyl group refers to a halogenated alkoxyl group having 1 to 6 carbon atoms. Representative examples of these halogenated alkoxyl groups include, but are not limited to, a monofluorinated methoxy group, a monofluorinated ethoxy group, a difluorinated butoxy group, or similar atomic groups.

[0453] As used herein, the term "halogenated alkylthiol group" refers to a halogenated alkyl group -S-. The halogenated alkyl group is as defined above. For example, a C1-C6 halogenated alkylthiol group refers to a halogenated alkylthiol group having 1 to 6 carbon atoms. Representative examples of these halogenated alkylthiol groups include, but are not limited to, a monofluoromethylthio group, a monofluoroethylthio group, a difluorobutylthiol group, or similar atomic groups.

[0454] As used herein, the term "cycloalkoxyl group" refers to the R-O- group, where R is a cycloalkyl group. Cycloalkyl groups are as defined above. When the cycloalkoxyl group is specified by the number of carbon atoms before the cycloalkoxyl group (e.g., a C3-C8 cycloalkoxyl group), the cycloalkyl group in the cycloalkoxyl group has the specified number of carbon atoms (e.g., 3 to 8). Representative examples of these cycloalkoxyl groups include, but are not limited to, cyclopropoxy, cyclobutoxy, and similar groups.

[0455] As used herein, the term "cycloalkylthiol group" refers to an RS-atom group, where R is a cycloalkyl group. Cycloalkyl groups are as defined above. A cycloalkylthiol group specified by the number of carbon atoms before the cycloalkylthiol group (e.g., a C3-C8 cycloalkoxyl group) refers to a cycloalkylthiol group having the specified number of carbon atoms (e.g., 3 to 8). Representative examples of these cycloalkylthiol groups include, but are not limited to, a cyclopropylthiol group, a cyclobutylthiol group, or similar groups.

[0456] As used herein, the term "halogenated cycloalkoxyl group" refers to an atomic group formed by replacing one or more (preferably one, two, three, or four) hydrogen atoms of a cycloalkoxyl group with halogen atoms. The cycloalkoxyl group and halogen atoms are as defined above. When the halogenated cycloalkoxyl group is specified by the number of carbon atoms before the halogenated cycloalkoxyl group (e.g., a C3-C8 halogenated cycloalkoxyl group), the halogenated cycloalkoxyl group has the specified number of ring carbon atoms (e.g., 3 to 8). For example, a C3-C8 halogenated cycloalkoxyl group refers to a halogenated cycloalkoxyl group containing 3 to 8 ring carbon atoms. Representative examples of these halogenated cycloalkoxyl groups include, but are not limited to, a monofluorinated cyclopropyl group -O-, a monochlorinated cyclobutyl group -O-, a monofluorinated cycloamyl group -O-, a difluorinated cycloheptyl group -O-, or similar atomic groups.

[0457] As used herein, the term "halogenated cycloalkylthiol group" refers to an atomic group formed by replacing one or more (preferably one, two, three, or four) hydrogen atoms of a cycloalkylthiol group with halogen atoms. The cycloalkylthiol group and halogen atoms are as defined above. A halogenated cycloalkylthiol group specified by the number of carbon atoms before the halogenated cycloalkylthiol group (e.g., a C3-C8 halogenated cycloalkoxyl group) refers to a halogenated cycloalkylthiol group having the specified number of ring carbon atoms (e.g., 3 to 8). For example, a C3-C8 halogenated cycloalkylthiol group refers to a halogenated cycloalkylthiol group containing 3 to 8 ring carbon atoms. Representative examples of these halogenated cycloalkylthiol groups include, but are not limited to, a monofluorinated cyclopropyl group -S-, a monochlorinated cyclobutyl group -S-, a monofluorinated cycloamyl group -S-, a difluorinated cycloheptyl group -S-, or similar atomic groups.

[0458] As used herein, the term "heterocycloalkyl ring" refers to a fully saturated or partially unsaturated ring (including, but not limited to, a 3- to 7-membered monocyclic ring, a 7- to 11-membered bicyclic ring, or an 8- to 16-membered tricyclic ring) in which at least one heteroatom is present in a ring having at least one carbon atom. The number of members preceding a heterocycle refers to the number of ring atoms in the heterocycloalkyl ring. For example, a 3- to 16-membered heterocycle refers to a heterocycle having 3 to 16 ring atoms. Each heterocycle having a heteroatom may have one or more (e.g., 1, 2, 3, or 4) heteroatoms, each independently selected from nitrogen, oxygen, or sulfur atoms, where the nitrogen or sulfur atoms may be oxidized and the nitrogen atom may also be quaternized. Representative examples of these monocyclic heterocycloalkyl rings include, but are not limited to, an azetidinyl ring, an oxetane ring, a tetrahydrofuranyl ring, a piperidine ring, and a piperazine ring. Multicyclic heterocycloalkyl rings include spiro, fused, and bridged piperazine rings, where the associated spiro, fused, and bridged heterocycles are optionally connected to other rings by a single bond or are further fused to other cycloalkyl and heterocycles through any two or more atoms on the ring.

[0459] As used herein, the term "heterocycloalkyl group" refers to a fully saturated or partially unsaturated cyclic group (including, but not limited to, a 3- to 7-membered monocyclic group, a 7- to 11-membered bicyclic group, an 8- to 16-membered tricyclic group, etc.) in which at least one heteroatom is present in a ring having at least one carbon atom. The number of members in the heterocycloalkyl group refers to the number of ring atoms in the heterocycloalkyl group. For example, a 3- to 16-membered heterocycloalkyl group refers to a heterocycloalkyl group having 3 to 16 ring atoms. Each heterocyclic ring may have one or more (e.g., 1, 2, 3, or 4) heteroatoms, each independently selected from nitrogen, oxygen, or sulfur atoms, where the nitrogen or sulfur atoms may be oxidized and the nitrogen atom may also be quaternized. Representative examples of these monocyclic heterocycloalkyl groups include, but are not limited to, azetidinyl, oxetane, tetrahydrofuranyl, piperidine, piperazine, etc. Polycyclic heterocycloalkyl groups include spirocyclic, fused-ring, and bridged-ring heterocyclic groups. Related spirocyclic, fused-ring, and bridged-ring heterocycloalkyl groups are optionally connected to other atomic groups through a single bond or are further fused to other cycloalkyl and heterocyclic rings through any two or more atoms on the ring.

[0460] As used herein, the term "aryl group" refers to an all-carbon atom monocyclic or fused polycyclic (rings sharing adjacent pairs of carbon atoms) atomic group having a conjugated π-electron system, and is an atomic group of an aromatic cyclic hydrocarbon compound. An aryl group specified by the number of carbon atoms before the aryl group (e.g., a C6-C12 aryl group) refers to an aryl group having the specified number of ring carbon atoms (e.g., 6 to 12). Representative examples of these aryl groups include a phenyl group and a naphthoyl group.

[0461] As used herein, the term "heteroaryl group" refers to an aromatic heterocyclic group having one or more (preferably, one, two, three, or four) heteroatoms. The group may be a single ring (monocyclic) or multiple fused or covalently linked rings (bicyclic, tricyclic, or polycyclic), and each heteroatom-containing heterocycle may have one or more (e.g., one, two, three, or four) heteroatoms independently selected from oxygen, sulfur, and nitrogen atoms. The number of members used in defining a heteroaryl group refers to the number of ring atoms in the heteroaryl group. For example, a 5-12-membered heteroaryl group refers to a heteroaryl group having 5 to 12 ring atoms. Representative examples of these heteroaryl groups include, but are not limited to, pyrrolyl, pyrazole, imidazole, thiazole, furan, pyridine, and pyrimidine groups.

[0462] As used herein, the term "carboxyl group" refers to a group of atoms of -COOH or -alkyl-COOH, where alkyl is as defined above. For example, a "C2-C4 carboxyl group" refers to a group of atoms of -C1-C3 alkyl-COOH. Representative examples of these carboxyl groups include, but are not limited to, -COOH, -CH2COOH, or similar groups.

[0463] As used herein, the term "ester group" refers to a group of atoms of the formula -RC(O)-O- or -C(O)-OR, where alkyl (R) is as defined above. For example, a "C2-C4 ester group" refers to a group of atoms of the formula -C1-C3 alkyl group -C(O)-O- or a group of atoms of the formula -C(O)-O-C1-C3 alkyl group. Representative examples of these ester groups include, but are not limited to, CH3C(O)O-, CH5C(O)O-, (CH3)2CHC(O)O-, -C(O)OCH3, -C(O)OC2H5, or similar groups.

[0464] As used herein, the term "acylamino group" refers to the group RC(O)-N- or the group -C(O)-NR, where the alkyl group (R) is as defined above. For example, a "C2-C4 acylamino group" refers to the group -C1-C3 alkyl group -C(O)-N- or the group -C(O)-N-C1-C3 alkyl group. Representative examples of these acylamino groups include, but are not limited to, CH3C(O)-N-, CH5C(O)-N-, (CH3)2CHC(O)-N-, -C(O)-N-CH3, -C(O)-N-C2H5, or similar groups.

[0465] As used herein, the term "acyl group" means [ka] Refers to... Here, R represents an alkyl group, and the alkyl group is as defined above. When the acyl group is specified by the number of carbon atoms (e.g., a C2-C6 acyl group), the acyl group has the specified number of ring carbon atoms (e.g., 2 to 6). For example, a C2-C4 acyl group refers to an atomic group having the structure C1-C3 alkyl group -C(O)-. Representative examples of these acyl groups include, but are not limited to, CH3C(O)-, C2H5C(O)-, or similar atomic groups.

[0466] As used herein, "-C(O)-" and [ka] teeth, May be used interchangeably.

[0467] As used herein, an "amino group" refers to -NH2, either alone or as part of another substituent.

[0468] As used herein, a "nitro group" alone or as part of another substituent refers to --NO2.

[0469] As used herein, a "cyano group" alone or as part of another substituent refers to -CN.

[0470] As used herein, a "hydroxyl group" refers to -OH, either alone or as part of another substituent.

[0471] As used herein, a "mercapto group" refers to -SH, either alone or as part of another substituent.

[0472] As used herein, "(R 20 R 21 )N-" [ka] teeth, May be used interchangeably.

[0473] As used herein, "R3 and R4, or R4 and R5, joined to form a substituted or unsubstituted 3- to 12-membered heterocycloalkyl ring" refers to R3 and R4 joining to form a substituted or unsubstituted 3- to 12-membered heterocycloalkyl ring, or R4 and R5 joining to form a substituted or unsubstituted 3- to 12-membered heterocycloalkyl ring, and many more.

[0474] In this specification, all substituents are meant to be unsubstituted unless expressly stated as "substituted." The term "substituted" refers to a substituent replacing one or more hydrogen atoms on an atomic group. The substituents are those described above or those appearing in each Example. Preferably, the "substituted" refers to one or more (preferably 1, 2, 3, 4, 5, 6, 7, or 8) hydrogen atoms on a ring or atomic group being replaced with a C1-C10 alkyl group, a C2-C6 alkenyl group, a C3-C12 cycloalkyl group, a C1-C10 halogenated alkyl group, a C3-C8 halogenated cycloalkyl group, a C3-C8 cycloalkoxyl group, a C3-C8 cycloalkylthiol group, a C3-C8 halogenated cycloalkoxyl group, a C3-C8 halogenated cycloalkylthiol group, a halogen atom, a nitro group, or a methyl group. , -CN, carbonyl group (=O), hydroxyl group, mercapto group, amino group, C1-C4 carboxyl group, C2-C8 ester group, C2-C4 acylamino group, C2-C6 acyl group, C1-C10 alkoxyl group, C1-C10 alkylthiol group, C1-C10 halogenated alkoxyl group, C1-C10 halogenated alkylthiol group, C6-C12 aryl group, C6-C12 aryl group-O-, 5-10 membered heteroaryl group, 5-10 membered heteroaryl group-O-, 5-10 membered heterocycloalkyl group, and (R 20 R 21 )N-.

[0475] In the present invention, "prevention" refers to a method of preventing the onset of a disease and / or its associated symptoms or protecting a subject from contracting the disease. As used herein, "prevention" also refers to delaying the onset of a disease and / or its associated symptoms, as well as reducing a subject's risk of contracting the disease.

[0476] "Treatment" according to the present invention means slowing or terminating the progression of a disease or eliminating the disease, but does not require 100% inhibition, elimination, or reversal. In some embodiments, the compound of the present invention reduces, inhibits, and / or reverses the associated disease (e.g., tumor) and its complications by at least about 10%, 30%, 50%, 80%, or 100%, etc., compared to levels observed in the absence of the compound.

[0477] compound As used herein, "a compound of the present invention," "the compound of the present invention," "a compound of Formula I of the present invention," or "a compound of Formula I," may be used interchangeably, and refer to a compound having the chemical structure of Formula I, or an optical isomer or racemate thereof, or a solvate thereof, or a pharmaceutically acceptable salt thereof, or a deuterated compound thereof. This term should be understood to include mixtures of the above components. [ka] I

[0478] In particular, the compound of formula I, or an optical isomer or racemate thereof, or a solvate thereof, or a pharmaceutically acceptable salt thereof, or a deuterated compound thereof, is described in the first aspect of the present invention.

[0479] In the present invention, the compound of formula I can be a racemate, an R-structure or an S-structure. The racemate, R-structure or S-structure of the compound of the present invention and the method for determining the same are well known to those skilled in the art. For example, the racemate, R-structure or S-structure is as follows: [ka]

[0480] Other compounds may be in racemic, R- or S-configuration, among many others.

[0481] Typically, the compounds of formula I of the present invention are the specific compounds prepared in the examples of the present invention (including their salt forms or the free form after removing the salt).

[0482] The compounds of formula I of the present invention may be prepared by organic synthesis methods known in the art.

[0483] In the present invention, the term "pharmaceutically acceptable salt" refers to a salt formed by a compound of the present invention with an acid or base and suitable for use as a drug. Pharmaceutically acceptable salts include inorganic salts and organic salts. One type of preferred salt is a salt formed by a compound of the present invention with an acid, and acids suitable for forming such salts include, but are not limited to, inorganic acids such as hydrochloric acid, hydrobromic acid, hydrofluoric acid, sulfuric acid, nitric acid, and phosphoric acid; organic acids such as formic acid, acetic acid, trifluoroacetic acid, trifluoroformic acid, propionic acid, oxalic acid, malonic acid, succinic acid, fumaric acid, maleic acid, lactic acid, malic acid, tartaric acid, citric acid, picric acid, methanesulfonic acid, benzenemethanesulfonic acid, and benzenesulfonic acid; and acidic amino acids such as aspartic acid and glutamic acid. One type of preferred salt is a metal salt formed by a compound of the present invention and a base, and bases suitable for forming such salts include, but are not limited to, inorganic bases such as sodium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate, and sodium phosphate, and organic bases such as ammonia, triethylamine, and diethylamine.

[0484] The present invention may convert the compounds of formula I into their pharmaceutically acceptable salts in a conventional manner, for example, by adding a solution of a corresponding acid to a solution of the compound, and removing the solvent after complete salification, the corresponding salt of the compound of the present invention can be obtained.

[0485] Preferably, said compounds of formula I of the present invention are those prepared in the Examples of the present invention.

[0486] Mitochondrial permeability transition pore In the present invention, the English name of the term "mitochondria permeability transition pore" is mitochondria permeability transition pore, abbreviated as mPTP.

[0487] The significantly superior therapeutic effect of the compounds of the present invention on tumors with low expression, no expression, low activity or inactivity of the mitochondrial permeability transition pore means that tumors with low expression, no expression, low activity or inactivity of the mitochondrial permeability transition pore are sensitive to the compounds of the present invention.

[0488] Preferably, the tumor in which the mitochondrial permeability transition pore is under-expressed, unexpressed, under-active or inactive is as described in the third aspect of the present invention.

[0489] In the present invention, the expression level or activity of the mitochondrial permeability transition pore is measured using a conventional method, for example, by measuring the activity of mPTP or measuring the expression level of mPTP at the protein level or mRNA level.

[0490] Peptidylprolyl isomerase F In the present invention, the English name of the term "peptidyl-prolyl isomerase F" is Peptidyl-prolyl cis-trans isomerase F, abbreviated as PPIF.

[0491] The significantly superior therapeutic effect of the compounds of the present invention on tumors with low expression, no expression, low activity or inactivity of peptidyl prolyl isomerase F means that tumors with low expression, no expression, low activity or inactivity of peptidyl prolyl isomerase F are sensitive to the compounds of the present invention.

[0492] Preferably, the tumor with low expression, no expression, low activity or inactivity of peptidylprolyl isomerase F is as described in the third aspect of the present invention.

[0493] In the present invention, the expression level or activity of peptidylprolyl isomerase F is measured by a conventional method, for example, by measuring the activity of PPIF or measuring the expression level of PPIF at the protein level or mRNA level.

[0494] tumor According to the present study, the compounds of the present invention are used for the prevention and / or treatment of tumors.

[0495] In the present invention, the terms "tumor," "carcinosis," "cancer," and "mass" may be used interchangeably.

[0496] In a preferred embodiment of the present invention, the "tumor" described in the present invention includes a tumor in which the mitochondrial permeability transition pore is underexpressed, absent, underactive, or inactive. As a representative example, the tumor in which the mitochondrial permeability transition pore is underexpressed, absent, underactive, or inactive is as described in the third aspect of the present invention.

[0497] In a preferred embodiment of the present invention, the "tumor" according to the present invention includes a tumor with low expression, no expression, low activity, or inactivity of peptidyl prolyl isomerase F. As a representative example, a tumor with low expression, no expression, low activity, or inactivity of peptidyl prolyl isomerase F according to the present invention is as described in the third aspect of the present invention.

[0498] Typically, the tumor according to the invention is as described in the third aspect of the invention.

[0499] In the present invention, representative tumor types corresponding to various tumor cell lines are shown in Table 1 below. [Table 1]

[0500] Antitumor drugs In the present invention, the antitumor drug can be the compound of formula I of the present invention, or an optical isomer or racemate thereof, or a solvate thereof, or a pharmaceutically acceptable salt thereof, or a deuterated compound thereof.

[0501] use The present invention provides the use of the compounds of the present invention in the prevention and / or treatment of tumors.

[0502] In particular, the compounds of the present invention have significantly superior therapeutic effects on tumors with low expression, no expression, low activity, or inactivity of the mitochondrial permeability transition pore and / or low expression, no expression, low activity, or inactivity of peptidylprolyl isomerase F. That is, tumors with low expression, no expression, low activity, or inactivity of the mitochondrial permeability transition pore and / or low expression, no expression, low activity, or inactivity of peptidylprolyl isomerase F are sensitive to the compounds of the present invention. The expression level or activity of the mitochondrial permeability transition pore and / or the expression level or activity of peptidylprolyl isomerase F can serve as markers for determining whether the compounds of the present invention are suitable for the refinement of tumor cells. Such markers can effectively identify tumor patients sensitive to the compounds of the present invention and improve their therapeutic efficacy, and may also avoid administering the compounds of the present invention to tumor patients who are not sensitive to them, thereby realizing the refinement of tumor treatment.

[0503] The present invention provides a method for preventing and / or treating tumors, which comprises administering the compound of the present invention to a subject.

[0504] The compounds of the present invention have significantly excellent therapeutic effects against tumors with low expression, no expression, low activity, or inactivity of the mitochondrial permeability transition pore and / or low expression, no expression, low activity, or inactivity of peptidylprolyl isomerase F. In the process of preventing and / or treating tumors, first, an inhibitor of the mitochondrial permeability transition pore and / or an inhibitor of peptidylprolyl isomerase F is administered to the tumor cells to cause low expression, no expression, low activity, or inactivity of the mitochondrial permeability transition pore and / or low expression, no expression, low activity, or inactivity of peptidylprolyl isomerase F in the tumor to be treated, and then the compound of the present invention is administered to prevent and / or treat the tumor. Therefore, a compound has been developed that can significantly enhance antitumor effects when used in combination with an inhibitor of the mitochondrial permeability transition pore and / or an inhibitor of peptidylprolyl isomerase F. The compounds of the present invention can be used in combination with inhibitors of the mitochondrial permeability transition pore and / or inhibitors of peptidylprolyl isomerase F, thereby significantly enhancing the therapeutic effect of the compounds of the present invention on tumors.

[0505] In another preferred embodiment, the subject to be treated is a human or non-human mammal (eg, rodents, rabbits, monkeys, livestock, dogs, cats).

[0506] In the present invention, the method for under-expressing, not expressing, low-active or inactivating the mitochondrial permeability transition pore and / or under-expressing, not expressing, low-active or inactivating peptidylprolyl isomerase F in tumors is not particularly limited, and for example, the expression or activity of the mitochondrial permeability transition pore and / or peptidylprolyl isomerase F can be specifically suppressed in tumors through means such as gene insertion, gene knockout or gene suppression (e.g., introduction of shRNA).

[0507] In another preferred embodiment, said inhibitor of peptidyl prolyl isomerase F comprises shRNA.

[0508] In another preferred example, the nucleotide sequence of the shRNA is GTTCTTCATCTGCACCATAAA.

[0509] marker The present invention provides a marker for determining whether a compound of the present invention is suitable for tumor prevention and / or treatment in a tumor patient, the marker comprising the expression level or activity level of a mitochondrial permeability transition pore and / or the expression level or activity level of peptidylprolyl isomerase F.

[0510] In one embodiment, the expression level or activity of the mitochondrial permeability transition pore and / or the expression level or activity of peptidylprolyl isomerase F serves as a marker for determining whether a compound of the present invention is suitable for tumor prevention and / or treatment in a tumor patient. when the mitochondrial permeability transition pore is underexpressed, not expressed, underactivated or inactivated in tumor cells of a tumor patient, and / or when peptidylprolyl isomerase F is underexpressed, not expressed, underactivated or inactivated, the compound of formula I according to the first aspect of the present invention, or an optical isomer or racemate thereof, or a solvate thereof, or a pharmaceutically acceptable salt thereof, or a deuterated compound thereof, becomes suitable for the prevention and / or treatment of tumors in said tumor patient; and / or This includes, but is not limited to, situations in which overexpression or overactivation of the mitochondrial permeability transition pore and / or overexpression or overactivation of peptidylprolyl isomerase F in tumor cells of a tumor patient renders the compound of formula I according to the first aspect of the present invention, or an optical isomer or racemate thereof, or a solvate thereof, or a pharmaceutically acceptable salt thereof, or a deuterated compound thereof, unsuitable for tumor prevention and / or treatment in the tumor patient.

[0511] Preferably, the statement that the compound of formula I according to the first aspect of the present invention, or an optical isomer or racemate thereof, or a solvate thereof, or a pharmaceutically acceptable salt thereof, or a deuterated compound thereof, is suitable for the prevention and / or treatment of tumors in tumor patients means that tumor cells in the tumor patients are sensitive to the compound of formula I according to the first aspect of the present invention, or an optical isomer or racemate thereof, or a solvate thereof, or a pharmaceutically acceptable salt thereof, or a deuterated compound thereof.

[0512] Preferably, the content that the compound of formula I according to the first aspect of the present invention, or an optical isomer or racemate thereof, or a solvate thereof, or a pharmaceutically acceptable salt thereof, or a deuterated compound thereof is not suitable for the prevention and / or treatment of tumors in tumor patients means that tumor cells of the tumor patients are insensitive to the compound of formula I according to the first aspect of the present invention, or an optical isomer or racemate thereof, or a solvate thereof, or a pharmaceutically acceptable salt thereof, or a deuterated compound thereof.

[0513] Specifically, the tumors having low expression, no expression, low activity or inactivity of the mitochondrial permeability transition pore and / or the tumors having low expression, no expression, low activity or inactivity of peptidylprolyl isomerase F are as described in the third aspect of the present invention.

[0514] Specifically, the tumors having high expression or activation of the mitochondrial permeability transition pore and / or high expression or activation of peptidylprolyl isomerase F are as described in the fourth aspect of the present invention.

[0515] The present invention further provides the use of the marker (or its expression level) or detection reagent to prepare a detection reagent kit, which is used to determine whether the compound of the present invention is suitable for tumor prevention and / or treatment in tumor patients.

[0516] Compositions or formulations, combinations of active ingredients and medical kits, and methods of administration Preferably, the composition or formulation according to the present invention is a drug composition or drug formulation, and the composition or formulation according to the present invention may comprise a pharmaceutically acceptable carrier.

[0517] As used herein, "pharmaceutically acceptable carrier" refers to one or more compatible solid, semi-solid, liquid, and gel fillers that must be suitable for human or animal use and have sufficient purity and low toxicity. "Compatibility" refers to the ability of each component in a drug composition or formulation to be mixed with the active ingredient of a drug and to prevent significant loss of efficacy when mixed together.

[0518] In the present invention, the pharmaceutically acceptable carrier is not particularly limited and may be selected from materials commonly used in the art, prepared by conventional methods, or purchased from the market. Some representative examples of pharmaceutically acceptable carriers include cellulose and its derivatives (e.g., methylcellulose, ethylcellulose, hydroxypropylmethylcellulose, sodium carboxymethylcellulose, etc.), gelatin, talc, solid lubricants (e.g., stearic acid and magnesium stearate), calcium sulfate, vegetable oils (e.g., soybean oil, sesame oil, peanut oil, olive oil, etc.), polyhydric alcohols (e.g., propylene glycol, glycerin, mannitol, sorbitol, etc.), emulsifiers (e.g., Tween), wetting agents (e.g., sodium lauryl sulfate), buffers, chelating agents, thickeners, pH adjusters, penetration enhancers, colorants, flavorings, stabilizers, antioxidants, preservatives, bacteriostats, heat-free raw water, etc.

[0519] In a preferred embodiment of the present invention, the composition or formulation is in the form of a solid, liquid or semi-solid.

[0520] In a preferred embodiment of the present invention, the composition or preparation is an oral preparation, an external preparation, or an injectable preparation.

[0521] Representative examples of the type of the composition or preparation include tablets, injections, infusions, ointments, gels, solutions, pills, and coatings.

[0522] The drug formulation should be consistent with the dosage regimen. The agents of the present invention may also be used in conjunction with other synergistic therapeutic agents (before, during, or after use). When using a drug composition or formulation, a safe and effective amount of the drug is administered to the subject (e.g., a human or non-human mammal). The safe and effective amount is usually at least about 10 μg / kg of body weight, usually less than about 8 mg / kg of body weight, and preferably about 10 μg / kg of body weight / about 1 mg / kg of body weight. Of course, the specific dosage must take into account factors such as the route of administration and the patient's health condition, and these factors are within the scope of a skilled physician's consideration.

[0523] The present invention mainly has the following excellent technical effects. The present invention has developed a compound that has significantly superior therapeutic effects against tumors with low expression, no expression, low activity, or inactivity of the mitochondrial permeability transition pore and / or tumors with low expression, no expression, low activity, or inactivity of peptidylprolyl isomerase F. Tumors with low expression, no expression, low activity, or inactivity of the mitochondrial permeability transition pore and / or tumors with low expression, no expression, low activity, or inactivity of peptidylprolyl isomerase F are highly sensitive to the compound of the present invention, i.e., the compound of the present invention has significantly superior therapeutic effects against tumors with low expression, no expression, low activity, or inactivity of the mitochondrial permeability transition pore and / or tumors with low expression, no expression, low activity, or inactivity of peptidylprolyl isomerase F. Therefore, the compounds of the present invention can be used to treat tumors with low, absent, low activity, or inactive mitochondrial permeability transition pore expression and / or low, absent, low activity, or inactive peptidylprolyl isomerase F, thereby improving the therapeutic efficacy and potentially avoiding the administration of the compounds of the present invention to tumor patients who are not sensitive to them. Therefore, the compounds of the present invention, which have significantly superior therapeutic efficacy against tumors with low, absent, low activity, or inactive mitochondrial permeability transition pore expression and / or low, absent, low activity, or inactive peptidylprolyl isomerase F expression, have advantages such as better preventive and therapeutic effects against tumors, lower drug dosages, and fewer side effects. This not only improves the preventive and therapeutic efficacy of the compounds of the present invention against tumors, but also reduces side effects and improves patient compliance. Furthermore, the expression or activity of the mitochondrial permeability transition pore and peptidylprolyl isomerase F is a mature, stable, and reliable detection method, making them suitable for the development of biomarkers.

[0524] We will now further describe the present invention in conjunction with specific examples, which provide detailed embodiments and specific operating procedures based on the present technical solutions, but it should be understood that the protection scope of the present invention is not limited to these examples. [Example]

[0525] The English name for the term "mitochondria permeability transition pore" is mitochondria permeability transition pore, abbreviated as mPTP.

[0526] The English name for the term "peptidyl-prolyl isomerase F" is Peptidyl-prolyl cis-trans isomerase F, abbreviated as PPIF.

[0527] Example 1 Synthesis of compound AB31866 The chemical structure of the compound AB31866 is as follows: [ka] Compound AB31866

[0528] The compound AB31866 was synthesized as follows. [ka]

[0529] Compound 1 (100 mg, 0.29 mmol, 1 eq) and compound 2 (122 mg, 0.58 mmol, 2.0 eq) were dissolved in acetonitrile (4 mL) and sodium iodide (87 mg, 0.58 mmol, 2.0 eq) was added. The reaction was performed in a microwave oven at 80 °C for 30 minutes. After the reaction was confirmed to be complete by LCMS, the reaction mixture was diluted with water, and the organic phase was extracted twice with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by reverse-phase column chromatography (acetonitrile / water + 0.01% formic acid) to give compound AB31866.

[0530] Compound AB31866: MS-ESI: Theoretical value [M+H] + :512.16, Measured value [M+H] + :512.10. 1H NMR(400 MHz, CDCl3) δ 7.24(s, 1H), 7.09(d, J = 8.0 Hz, 2H), 7.01-6.93(m, 4H), 6.77(s, 1H), 6.08(d, J = 12.0 Hz, 2H), 5.66(d, J = 20.0 Hz, 1H), 5.06(d, J = 20.0 Hz, 1H), 4.90-4.86(m, 1H), 4.48-4.44(m, 1H), 4.07-3.98(m, 1H), 3.94(s, 3H), 3.89(m, 3H), 3.49-3.43(m, 1H), 3.28-3.23(m, 1H), 309-3.02(m, 1H).

[0531] Example 2 Synthesis of compound AB31870 The chemical structure of the compound AB31870 is as follows: [ka] Compound AB31870

[0532] The compound AB31870 was synthesized as follows. [ka]

[0533] Compound 1 (100 mg, 0.29 mmol, 1 eq) and compound 2 (97 mg, 0.58 mmol, 2.0 eq) were dissolved in acetonitrile (4 mL) and sodium iodide (87 mg, 0.58 mmol, 2.0 eq) was added. The reaction was performed in a microwave oven at 80 °C for 30 minutes. After the reaction was confirmed to be complete by LCMS, the reaction mixture was diluted with water, and the organic phase was extracted twice with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by reverse-phase column chromatography (acetonitrile / water + 0.01% formic acid) to obtain compound AB31870.

[0534] Compound AB31870: MS-ESI: Theoretical value [M+H] + : 470.23, Measured value [M+H] + :470.20. 1 H NMR(400 MHz, CDCl3) δ 7.52(s, 1H), 7.08(d, J = 8.0 Hz, 1H), 6.98(d, J = 8.0 Hz, 3H), 6.86(s, 1H), 6.55(d, J = 8.0 Hz, 2H), 6.13(s, 2H), 5.04-4.92(m, 2H), 4.17-4.13(m, 2H), 3.89(s, 3H), 3.85(m, 3H), 3.36-3.17(m, 4H), 2.86-2.79(m, 1H), 1.17(d, J = 8.0 Hz, 6H).

[0535] Example 3 Synthesis of compound AB31873 The chemical structure of compound AB31873 is as follows: [ka] Compound AB31873

[0536] The compound AB31873 was synthesized as follows. Step (1): [ka]

[0537] Compound 1 (1.0 g, 2.69 mmol, 1 eq) was dissolved in acetic acid (10 mL), bromine (2.1 g, 13.45 mmol, 5 eq) was added dropwise, and the temperature was raised to 120 °C for 4 h. After the reaction was confirmed to be complete by LCMS, the reaction mixture was diluted with water, and the organic phase was extracted twice with dichloromethane, backwashed once with brine, dried over anhydrous sodium sulfate, filtered, and centrifuged to obtain compound 2 via flash chromatography (100-200 mesh silica gel, DCM / MeOH=30 / 1). MS-ESI: Theoretical value [M+H] + : 415.04, measured value [M+H] + :413.95. Step (2): [ka]

[0538] Compound 2 (200 mg, 0.40 mmol, 1 eq) was dissolved in anhydrous tetrahydrofuran (10 mL), and butylmagnesium bromide (0.4 mL, 1.2 mmol, 5 eq, 3M) was added dropwise under nitrogen gas protection at 0 ° C. The reaction was carried out for 0.5 hours, and the complete reaction was confirmed by LCMS. The reaction was quenched with saturated aqueous ammonium chloride solution, and the organic phase was extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and then centrifuged to obtain compound AB31873 from the crude product via thin layer chromatography (DCM / MeOH = 30 / 1).

[0539] Compound AB31873: MS-ESI: Theoretical value [M+H] + : 472.11, Measured value [M+H] + :472.10. 1 H NMR(400 MHz, CDCl3) δ 7.23(s, 1H), 6.97(s, 1H), 6.60(s, 1H), 6.02(s, 1H), 5.95(d, J= 4.0 Hz, 2H), 4.70-4.67(m, 1H), 3.86(s, 3H), 3.83(s, 3H), 3.48-3.45(m, 1H), 3.33-3.30(m, 1H), 2.88-2.80(m, 2H), 1.71-1.64(m, 2H),1.25-1.17(m, 4H), 0.82-078(m, 3H).

[0540] Example 4 Synthesis of compound AB31880 The chemical structure of compound AB31880 is as follows: [ka] Compound AB31880

[0541] The compound AB31880 was synthesized as follows. Step (1): [ka]

[0542] Compound 1 (300 mg, 0.70 mmol, 1 eq) was dissolved in anhydrous tetrahydrofuran (10 mL), and under the protection of nitrogen gas, hexylmagnesium bromide (3.5 mL, 3.50 mmol, 5 eq, 1M / L) was added dropwise at 0 ° C. The mixture was warmed to room temperature and the reaction was carried out for 0.5 hours. TLC check was performed, and the complete reaction was confirmed by LCMS check. The mixture was quenched with saturated aqueous ammonium chloride solution, and the organic phase was extracted twice with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and centrifuged to obtain compound AB31880 from the crude product via thin layer chromatography (DCM / MeOH=50 / 1).

[0543] Compound AB31880: MS-ESI: Theoretical value [M+H] + : 436.24, Measured value [M+H] + :436.20. 1 H NMR(400 MHz, CDCl3) δ 7.19(s, 1H), 6.75-6.68(m, 2H), 6.62(s, 1H), 5.81(s, 1H), 4.70-4.67(m, 1H), 4.26(s, 4H), 3.87(s, 3H), 3.84(s, 3H), 3.46-3.45(m, 1H), 3.31-3.29(m, 1H), 2.87-2.78(m, 2H), 1.75-1.50(m, 4H), 1.38-1.26(m, 6H), 0.82-0.79(m, 3H).

[0544] Example 5 Synthesis of compound AB31881 The chemical structure of compound AB31881 is as follows: [ka] Compound AB31881

[0545] The compound AB31881 was synthesized as follows. Step (1): [ka]

[0546] Compound 0 (10.0 g, 26.89 mmol, 1 eq) was placed in a 500 ml eggplant bottle and heated to 190°C under vacuum. The reaction was carried out for 8 hours, and the complete reaction was confirmed by LCMS to give compound 1. MS-ESI: Theoretical value [M] + :322.11, measured value [M+H] + :322.30. Step (2): [ka]

[0547] Compound 1 (500 mg, 1.40 mmol, 1 eq) and compound 2 (642 mg, 2.80 mmol, 2.0 eq) were dissolved in acetonitrile (10 mL) and reacted overnight at 80 °C under nitrogen gas protection. After confirming the completeness of the reaction by LCMS, the reaction mixture was diluted with water, the organic phase was extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by flash chromatography (100-200 mesh silica gel, DCM / MeOH = 50 / 1) to obtain compound 3. MS-ESI: Theoretical value [M] + : 470.20, Measured value [M+H] + :470.10. Step (3): [ka]

[0548] Compound 3 (200 mg, 0.36 mmol, 1 eq) was dissolved in anhydrous tetrahydrofuran (10 mL), and methyl magnesium bromide (0.6 mL, 1.8 mmol, 5 eq, 3M) was added dropwise under nitrogen gas protection at 0 ° C. The reaction was carried out for 0.5 hours, and the complete reaction was confirmed by LCMS. The reaction was quenched with saturated aqueous ammonium chloride solution, and the organic phase was extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and then centrifuged to obtain compound AB31881 from the crude product via thin layer chromatography (DCM / MeOH = 30 / 1).

[0549] Compound AB31881: MS-ESI: Theoretical value [M+H] + : 486.22, Measured value [M+H] + :486.20. 1 H NMR(400 MHz, CDCl3) δ 7.31-7.27(m, 2H), 7.16(s, 1H), 6.96-6.92(m, 3H), 6.73(s, 2H), 6.59(s, 1H), 5.94(s, 2H), 5.86(s, 1H), 4.87-4.82(m, 1H), 4.20-4.14(m, 1H), 4.10-4.07(m, 3H), 3.82(s, 3H), 3.42-3.36(m, 1H), 3.21-3.18(m, 1H), 2.95-2.88(m, 1H), 2.78-2.74(m, 1H), 2.06-1.98(m, 4H), 1.18(d, J= 8.0 Hz, 3H).

[0550] Example 6 Synthesis of compound AB31887 The chemical structure of the compound AB31887 is as follows: [ka] Compound AB31887

[0551] The compound AB31887 was synthesized as follows. Step (1): [ka]

[0552] Compound 0 (10.0 g, 26.89 mmol, 1 eq) was placed in a 500 ml eggplant bottle and heated to 190°C under vacuum. The reaction was carried out for 8 hours, and the complete reaction was confirmed by LCMS to give compound 1. MS-ESI: Theoretical value [M] + :322.11, measured value [M+H] + :322.30. Step (2): [ka]

[0553] Compound 1 (500 mg, 1.40 mmol, 1 eq) and compound 2 (565 mg, 2.80 mmol, 2.0 eq) were dissolved in acetonitrile (10 mL) and reacted overnight at 80 °C under nitrogen gas protection. After confirming the completeness of the reaction by LCMS, the reaction mixture was diluted with water, the organic phase was extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by flash chromatography (100-200 mesh silica gel, DCM / MeOH=50 / 1) to obtain compound 3. MS-ESI: Theoretical value [M] + : 444.06, Measured value [M+H] + :444.00. Step (3): [ka]

[0554] Compound 3 (160 mg, 0.30 mmol, 1 eq) was dissolved in anhydrous tetrahydrofuran (10 mL), and methyl magnesium bromide (0.5 mL, 1.5 mmol, 5 eq, 3M) was added dropwise under nitrogen gas protection at 0 °C. The reaction was carried out for 0.5 hours, and the complete reaction was confirmed by LCMS. The reaction was quenched with saturated aqueous ammonium chloride solution, and the organic phase was extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and centrifuged to obtain compound AB31887 from the crude product via thin layer chromatography (DCM / MeOH = 30 / 1).

[0555] Compound AB31887: MS-ESI: Theoretical value [M+H] + :458.09, measured value [M+H] + :458.05. 1 H NMR(400 MHz, CDCl3) δ 7.15(s, 1H), 6.74(s, 2H), 6.59(s, 1H), 5.94(s, 2H), 5.85(s, 1H), 4.90-4.85(m, 1H), 4.20-4.11(m, 2H), 3.83(s, 3H), 3.71-3.69(m, 2H), 3.42-3.25(m, 2H), 2.98-2.77(m, 2H), 2.43-2.23(m, 2H), 1.18(d, J= 4.0 Hz, 3H).

[0556] Example 7 Synthesis of compound AB31888 The chemical structure of the compound AB31888 is as follows: [ka] Compound AB31888

[0557] The compound AB31888 was synthesized as follows. Step (1): [ka]

[0558] Compound 1 (300 mg, 0.84 mmol, 1 eq) and compound 2 (592 mg, 4.20 mmol, 5.0 eq) were dissolved in N,N-dimethylformamide (10 mL) and reacted overnight at 80 °C under nitrogen gas protection. After confirming the completeness of the reaction by LCMS, the reaction product was diluted with water, the organic phase was extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by flash chromatography (100-200 mesh silica gel, DCM / MeOH = 50 / 1) to obtain compound 3. MS-ESI: Theoretical value [M] + : 443.18, Measured value [M+H] + :443.05. Step (2): [ka]

[0559] Compound 3 (100 mg, 0.21 mmol, 1 eq) was dissolved in anhydrous tetrahydrofuran (10 mL), and methyl magnesium bromide (0.4 mL, 1.05 mmol, 5 eq, 3M) was added dropwise under nitrogen gas protection at 0 ° C. The reaction was carried out for 0.5 hours, and the complete reaction was confirmed by LCMS. The reaction was quenched with saturated aqueous ammonium chloride solution, and the organic phase was extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and centrifuged to obtain compound AB31888 from the crude product via thin layer chromatography (DCM / MeOH = 30 / 1).

[0560] Compound AB31888: MS-ESI: Theoretical value [M+H] + : 456.19, Measured value [M+H] + :456.15. 1H NMR(400 MHz, DMSO-d6) δ 7.25(s, 1H), 6.81(d, J= 4.0 Hz, 2H), 6.77(s, 1H), 6.66(d, J= 4.0 Hz, 1H), 6.00(d, J= 4.0 Hz, 2H), 5.93(s, 1H), 4.77-4.73(m, 1H), 3.97-3.94(m, 2H), 3.75(s, 3H), 3.68-3.64(m, 2H), 3.27-3.21(m, 2H), 2.84-2.74(m, 2H), 1.78-1.70(m, 4H), 1.49-1.45(m, 4H), 1.05(d, J = 8.0 Hz, 3H).

[0561] Example 8 Synthesis of compound AB31895 The chemical structure of the compound AB31895 is as follows: [ka] Compound AB31895

[0562] The compound AB31895 was synthesized as follows. Step (1): [ka]

[0563] In a 50 mL sealed tube, compound 1 (1.0 g, 2.69 mmol, 1 eq) was dissolved in alcohol (20 mL) and phenethylamine (326 mg, 26.9 mmol, 10 eq) was added. The temperature was raised to 100 °C and the reaction was carried out for 48 h. After the reaction was confirmed to be complete by LCMS, the reaction mixture was diluted with water, and the organic phase was extracted twice with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by flash chromatography (DCM / MeOH = 30 / 1) to obtain compound 3. MS-ESI: Theoretical value [M] + : 425.19, Measured value [M+H] +:425.15. Step (2): [ka]

[0564] Compound 3 (190 mg, 0.41 mmol, 1 eq) was dissolved in anhydrous tetrahydrofuran (10 mL), and methyl magnesium bromide (0.7 mL, 2.05 mmol, 5 eq, 3M) was added dropwise under nitrogen gas protection at 0°C. The reaction was carried out for 0.5 hours, and the complete reaction was confirmed by LCMS. The reaction was quenched with saturated aqueous ammonium chloride solution, and the organic phase was extracted twice with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and centrifuged to obtain compound AB31895 from the crude product via thin layer chromatography (DCM / MeOH = 50 / 1).

[0565] Compound AB31895: MS-ESI: Theoretical value [M+H] + : 441.21, Measured value [M+H] + :441.20. 1 H NMR(400 MHz, DMSO-d6) δ 7.28-7.18(m, 6H), 6.72(s, 1H), 6.68(d, J= 8.0 Hz, 1H), 6.48(d, J= 8.0 Hz, 1H), 5.96(d, J= 4.0 Hz, 2H), 5.87(s, 1H), 4.54-4.50(m, 1H), 3.68(s, 3H), 3.18-3.04(m, 5H), 2.76-2.73(m, 4H), 0.91(d, J= 4.0 Hz, 3H).

[0566] Example 9 Synthesis of compound AB31896 The chemical structure of compound AB31896 is as follows: [ka] Compound AB31896

[0567] The compound AB31896 was synthesized as follows. Step (1): [ka]

[0568] Compound 1 (500 mg, 2.57 mmol, 1 eq) was dissolved in dichloromethane (10 mL) and cooled to 0 °C. Oxalyl chloride (1.6 g, 12.85 mmol, 5 eq) and two drops of N,N-dimethylformamide were added, and the reaction was carried out at room temperature for 2 hours. After the reaction was complete as determined by LCMS, the solvent was evaporated under reduced pressure to give compound 2. MS-ESI: Theoretical value [M+H] + :213.10, measured value [M+H] + : Not measured. Step (2): [ka]

[0569] Compound 3 (100 mg, 0.29 mmol, 1 eq) was dissolved in dichloromethane (10 mL), triethylamine (88 mg, 0.87 mmol, 3 eq) was added, and the mixture was cooled to 0°C. Compound 2 (420 mg, 1.97 mmol, 6.8 eq) was added, and the reaction was carried out at 0°C for 0.5 hours. The complete reaction was confirmed by LCMS check, and the reaction product was diluted with water. The organic phase was extracted twice with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and then centrifuged. The crude product was purified by reverse phase column chromatography (acetonitrile / water + 0.01% formic acid) to obtain compound AB31896.

[0570] Compound AB31896: MS-ESI: Theoretical value [M+H] + :514.25, measured value [M+H] + :514.25. 1H NMR(400 MHz, DMSO-d6) δ 7.27(s, 1H), 6.91-6.83(m, 2H), 6.77(s, 1H), 6.01(s, 1H), 5.99(s, 2H), 4.61-4.55(m, 1H), 3.71(s, 3H), 3.28-3.14(m, 2H), 2.79-2.74(m, 2H), 2.34(s, 2H), 1.72-1.63(m, 15H), 1.02(d, J= 8.0 Hz, 3H).

[0571] Example 10 Synthesis of compound AB31897 The chemical structure of the compound AB31897 is as follows: [ka] Compound AB31897

[0572] The compound AB31897 was synthesized as follows. Step (1): [ka]

[0573] Compound 0 (10.0 g, 26.89 mmol, 1 eq) was placed in a 500 ml eggplant bottle and heated to 190°C under vacuum. The reaction was carried out for 8 hours, and the complete reaction was confirmed by LCMS to give compound 1. Step (2): [ka]

[0574] Compound 1 (2 g, 5.59 mmol, 1 eq) was dissolved in anhydrous tetrahydrofuran (10 mL), and methylmagnesium bromide (11.2 mL, 33.54 mmol, 6 eq, 3 M) was added dropwise under nitrogen gas protection at 0 °C. The mixture was warmed to room temperature and the reaction was carried out for 0.5 hours. The complete reaction was confirmed by LCMS. The mixture was quenched with saturated aqueous ammonium chloride solution, and the organic phase was extracted twice with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and centrifuged to obtain compound 2 from the crude product via thin layer chromatography (DCM / MeOH = 100 / 1 to 50 / 1). Step (3): [ka]

[0575] Compound 2 (300 mg, 0.89 mmol, 1 eq) was dissolved in acetonitrile (10 mL), compound 3 (868 mg, 3.56 mmol, 4 eq) and potassium carbonate (491 mg, 3.56 mmol, 4 eq) were added, and the mixture was heated to 80 °C overnight. After confirming the completeness of the reaction by LCMS, the reaction mixture was diluted with water, and the organic phase was extracted twice with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by flash chromatography (DCM / MeOH = 50 / 1) to give compound AB31897.

[0576] Compound AB31897: MS-ESI: Theoretical value [M+H] + :501.13, measured value [M+H] + :501.10. 1H NMR(400 MHz, DMSO-d6) δ 7.22(s, 1H), 6.79-6.74(m, 2H), 6.64(d, J= 12.0 Hz, 1H), 5.97(d, J= 4.0 Hz, 2H), 5.89(s, 1H), 4.74-4.69(m, 1H), 3.94-3.91(m, 2H), 3.72(s, 3H), 3.55-3.51(m, 2H), 3.25-3.15(m, 2H), 2.79-2.68(m, 2H), 1.85-1.79(m, 2H), 1.72-1.65(m, 2H), 1.44(s, 4H), 1.03(d, J= 4.0 Hz, 3H).

[0577] Example 11 Synthesis of compound AB31898 The chemical structure of the compound AB31898 is as follows: [ka] Compound AB31898

[0578] The compound AB31898 was synthesized as follows. [ka]

[0579] Compound 1 (200 mg, 0.52 mmol, 1 eq) was dissolved in anhydrous tetrahydrofuran (10 mL), and methyl magnesium bromide (2.7 mL, 2.7 mmol, 5 eq, 1M) was added dropwise under nitrogen gas protection at 0°C. The reaction was carried out for 0.5 hours, and the complete reaction was confirmed by LCMS. The reaction was quenched with saturated aqueous ammonium chloride solution, and the organic phase was extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and centrifuged to obtain compound AB31898 from the crude product via thin layer chromatography (DCM / MeOH=30 / 1).

[0580] Compound AB31898: MS-ESI: Theoretical value [M+H]+ :366.17, Measured value [M+H] + :366.10. 1 H NMR(400 MHz, DMSO-d6) δ 7.11(s, 1H), 6.81(d, J= 8.0 Hz, 1H), 6.68(s, 1H), 6.67(s, 1H), 5.87(s, 1H), 4.77-4.73(m, 1H), 4.23(s, 4H), 3.77(d, J= 8.0 Hz, 6H), 3.28-3.20(m, 2H), 2.79-2.66(m, 2H), 1.05(d, J= 8.0 Hz, 3H).

[0581] Example 12 Synthesis of compound AB35402 The chemical structure of compound AB35402 is as follows: [ka] Compound AB35402

[0582] The compound AB35402 was synthesized as follows. Step (1): [ka]

[0583] Compound 0 (10.0 g, 26.89 mmol, 1 eq) was placed in a 500 ml eggplant bottle and heated to 190°C under vacuum. The reaction was carried out for 8 hours, and the complete reaction was confirmed by LCMS to give compound 1. MS-ESI: Theoretical value [M] + :322.11, measured value [M+H] + :322.30. Step (2): [ka]

[0584] Compound 1 (500 mg, 1.40 mmol, 1 eq) was dissolved in acetonitrile (10 mL), compound 2 (912 mg, 4.20 mmol, 3 eq) and potassium carbonate (773 mg, 5.6 mmol, 4 eq) were added, and the reaction was allowed to proceed overnight at room temperature. After confirming the completeness of the reaction by LCMS, the reaction mixture was diluted with water, and the organic phase was extracted twice with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by flash chromatography (DCM / MeOH = 30 / 1) to obtain compound 3. MS-ESI: Theoretical value [M] + : 458.23, Measured value [M+H] + :458.30. Step (3): [ka]

[0585] Compound 3 (200 mg, 0.37 mmol, 1 eq) was dissolved in anhydrous tetrahydrofuran (10 mL), and methyl magnesium bromide (0.6 mL, 1.85 mmol, 5 eq, 3M) was added dropwise under nitrogen gas protection at 0 °C. The mixture was warmed to room temperature and the reaction was carried out for 0.5 hours. The complete reaction was confirmed by LCMS. The mixture was quenched with saturated aqueous ammonium chloride solution, and the organic phase was extracted twice with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and centrifuged to obtain compound AB35402 from the crude product via thin layer chromatography (DCM / MeOH=50 / 1).

[0586] Compound AB35402: MS-ESI: Theoretical value [M+H] + : 474.26, Measured value [M+H] + :474.35. 1H NMR(400 MHz, DMSO-d6) δ 7.24(s, 1H), 6.821(d, J= 8.0 Hz, 1H), 6. 77(s, 1H), 6.67(d, J= 12.0 Hz, 1H), 6.03(s, 2H), 5.92(s, 1H), 5.51-5.48(m, 1H), 5.10-5.05(m, 1H), 4.76-4.73(m, 1H), 4.54-4.46(m, 2H), 3.76(s, 3H), 3.29-3.15(m, 2H), 2.78-2.66(m, 2H), 2.09-1.99(m, 4H), 1.63(s, 6H), 1.55(s, 3H), 1.03(d, J= 4.0 Hz, 3H).

[0587] Example 13 Synthesis of compound AB35405 The chemical structure of the compound AB35405 is as follows: [ka] Compound AB35405

[0588] The compound AB35405 was synthesized as follows. [ka]

[0589] Compound 1 (200 mg, 0.37 mmol, 1 eq) was dissolved in chloroform (5 mL), and aqueous ammonia (2 mL) was added. The reaction was allowed to proceed overnight at room temperature. After confirming the completeness of the reaction by LCMS, the reaction product was diluted with water, and the organic phase was extracted with dichloromethane, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by flash chromatography (PE / EA = 200:1) to obtain compound AB35405.

[0590] Compound AB35405: MS-ESI: Theoretical value [M+H] + :576.14, Measured value [M+H]+ :576.15. 1 H NMR(400 MHz, CDCl3) δ 7.17(s, 1H), 6.98-6.86(m, 2H), 6.62(s, 1H), 6.10(s, 1H), 5.95(d, J= 4.0 Hz, 2H), 5.67(s, 1H), 5.57-5.53(m, 1H), 5.10-5.06(m, 1H), 4.72-4.56(m, 2H), 3.89-3.83(m, 4H), 3.69-3.64(m, 1H), 3.37-3.32(m, 1H), 2.74-2.70(m, 1H), 2.11-2.03(m, 4H), 1.66(d, J = 8.0 Hz, 6H), 1.58(s, 3H).

[0591] Example 14 Synthesis of compound AB35407 The chemical structure of the compound AB35407 is as follows: [ka] Compound AB35407

[0592] The compound AB35407 was synthesized as follows. Step (1): [ka]

[0593] Compound 0 (10.0 g, 26.89 mmol, 1 eq) was placed in a 500 ml eggplant bottle and heated to 190°C under vacuum. The reaction was carried out for 8 hours, and the complete reaction was confirmed by LCMS to give compound 1.

[0594] MS-ESI: Theoretical value [M] + :322.11, measured value [M+H] + :322.30. Step (2): [ka]

[0595] Compound 1 (600 mg, 1.67 mmol, 1 eq) was dissolved in N,N-dimethylformamide (10 mL), and compound 2 (1.9 g, 6.71 mmol, 4 eq) and potassium carbonate (926 mg, 6.71 mmol, 4 eq) were added. The reaction was carried out overnight at 60 °C under nitrogen gas protection. After confirming the completeness of the reaction by LCMS, the reaction product was diluted with water, and the organic phase was extracted twice with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by flash chromatography (DCM / MeOH = 50 / 1) to obtain compound 3. MS-ESI: Theoretical value [M] + :521.26, measured value [M+H] + :521.30. Step (3): [ka]

[0596] Compound 3 (200 mg, 0.33 mmol, 1 eq) was dissolved in chloroform (5 mL), and aqueous ammonia (2 mL) was added. The reaction was carried out at 40 °C for 48 h. After confirming the completeness of the reaction by LCMS, the reaction product was diluted with water, and the organic phase was extracted with dichloromethane, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by flash chromatography (PE / EA = 200:1) to obtain compound AB35407.

[0597] Compound AB35407: MS-ESI: Theoretical value [M+H] + :639.18, Measured value [M+H] + :639.15. 1H NMR(400 MHz, CDCl3) δ 7.16(s, 1H), 6.97-6.85(m, 2H), 6.62(s, 1H), 6.08(s, 1H), 5.95(d, J= 4.0 Hz, 2H), 5.62(s, 1H), 4.52(s, 1H), 4.28-4.23(m, 1H), 3.89-3.82(m, 5H), 3.69-3.67(m, 1H), 3.36-3.31(m, 1H), 3.16-3.09(m, 2H), 2.76-2.72(m, 1H), 1.83-1.69(m, 4H), 1.58-1.51(m, 4H), 1.44(s, 9H).

[0598] Example 15 Synthesis of compound AB35411 The chemical structure of compound AB35411 is as follows: [ka]

[0599] The compound AB35411 was synthesized as follows. Step (1): [ka]

[0600] Compound 1 (2.0 g, 5.93 mmol, 1 eq) was dissolved in alcohol / acetic acid (10 mL / 8 mL), and phenylpropyl aldehyde (7.9 g, 59.3 mmol, 10 eq) was added. o The reaction was carried out in C for 4 hours, and then an appropriate amount of hydrochloric acid was added to the reaction mixture and concentrated. A small amount of dichloromethane and an appropriate amount of ethyl acetate were added to the crude product, and the mixture was left for 0.5 hours. The solid matter was then filtered off. The filtrate was left overnight to precipitate a solid matter. The solid matter was filtered off and collected to give compound 3 (1.4 g). Step (2): [ka]

[0601] Compound 3 (200 mg, 0.41 mmol, 1 eq) was dissolved in anhydrous tetrahydrofuran (10 mL), and methylmagnesium bromide (0.7 mL, 2.05 mmol, 5 eq, 3M) was added under nitrogen gas protection at 0 °C. The reaction was carried out at room temperature for 0.5 hours. The reaction solution was quenched with saturated aqueous ammonium chloride solution, and the organic phase was extracted twice with ethyl acetate, washed with brine, dried over anhydrous sodium sulfate, filtered, and centrifuged to obtain compound AB35411 from the crude product via thin layer chromatography (DCM / MeOH=20 / 1).

[0602] Compound AB35411: MS-ESI: Theoretical value [M+H] + :470.23, Measured value [M+H] + :470.30. 1 H NMR(400 MHz, CDCl3) δ 7.34-7.28(m, 2H), 7.24-7.16(m, 3H), 6.97(s, 1H), 6.90-6.76(m, 2H), 6.65(s, 1H), 5.97-5.96(m, 2H), 4.77-4.73(m, 1H), 3.89(s, 3H), 3.86(s, 3H), 3.24-3.22(m, 2H), 2.84-2.65(m, 6H), 2.14-2.08(m, 1H), 1.90-1.81(m, 1H), 1.07(d, J= 4.0 Hz, 3H).

[0603] Example 16 Synthesis of compound AB35413 The chemical structure of compound AB35413 is as follows: [ka]

[0604] The compound AB35413 was synthesized as follows. [ka]

[0605] Compound 1 (100 mg, 0.28 mmol, 1 eq) was dissolved in anhydrous tetrahydrofuran (10 mL), and methylmagnesium bromide (0.5 mL, 1.4 mmol, 5 eq, 3M) was added under nitrogen gas protection at 0 °C. The reaction was carried out at room temperature for 0.5 hours. The reaction solution was quenched with saturated aqueous ammonium chloride solution, and the organic phase was extracted twice with ethyl acetate, washed with brine, dried over anhydrous sodium sulfate, filtered, and centrifuged to obtain compound AB35413 from the crude product via thin layer chromatography (DCM / MeOH=30 / 1).

[0606] Compound AB35413: MS-ESI: Theoretical value [M+H] + :336.12, Measured value [M+H] + :336.10. 1 H NMR(400 MHz, DMSO-d6) δ 7.25(s, 1H), 6.78(s, 1H), 6.79(d, J= 8.0 Hz, 1H), 6.46(d, J= 8.0 Hz, 1H), 6.04(s, 1H), 6.00(d, J= 4.0 Hz, 2H), 5.94(s, 1H), 5.89(s, 1H), 4.71-4.66(m, 1H), 3.28-3.20(m, 2H), 2.83-2.70(m, 2H), 1.11(d, J= 8.0 Hz, 3H).

[0607] Example 17 Synthesis of compound AB35415 The chemical structure of the compound AB35415 is as follows: [ka]

[0608] The compound AB35415 was synthesized as follows. [ka]

[0609] Compound 1 (200 mg, 0.59 mmol, 1 eq) was dissolved in N,N-dimethylformamide (10 mL), and compound 2 (661 mg, 2.36 mmol, 4 eq) and potassium carbonate (326 mg, 2.36 mmol, 4 eq) were added. The reaction was carried out at 60 °C overnight. The reaction mixture was diluted with water, and the organic phase was extracted twice with ethyl acetate, washed with brine, dried over anhydrous sodium sulfate, filtered, and then centrifuged. The crude product was purified by reverse phase column chromatography (acetonitrile / water + 0.01% formic acid) to obtain compound AB35415.

[0610] Compound AB35415: MS-ESI: Theoretical value [M+H] + :537.29, Measured value [M+H] + :537.35. 1 H NMR(400 MHz, CDCl3) δ 7.15(s, 1H), 6.72(s, 2H), 6.59(s, 1H), 5.94(s, 2H), 5.85(s, 1H), 4.85-4.80(m, 1H), 4.53(s, 1H), 4.05-4.09(m, 2H), 3.82(s, 3H), 3.44-3.39(m, 1H), 3.24-3.14(m, 3H), 2.98-2.77(m, 2H), 1.82-1.79(m, 2H), 1.55-1.50(m, 4H), 1.44(s, 11H), 1.17(d, J= 8.0 Hz, 3H).

[0611] Example 18 Synthesis of compound AB35416 The chemical structure of compound AB35416 is as follows: [ka]

[0612] The compound AB35416 was synthesized as follows. [ka]

[0613] Compound 1 (200 mg, 0.33 mmol, 1 eq) was dissolved in chloroform (5 mL), and aqueous ammonia (2 mL) was added. The reaction was carried out at 40°C for 48 hours. The reaction mixture was diluted with water, and the organic phase was extracted with dichloromethane, washed with brine, dried over anhydrous sodium sulfate, filtered, and then centrifuged to obtain compound AB35416 from the crude product via thin layer chromatography (PE / EA = 10 / 1).

[0614] Compound AB35416: MS-ESI: Theoretical value [M+H] + :583.11, Measured value [M+H] + :583.10. 1 H NMR(400 MHz, CDCl3) δ 7.16(s, 1H), 6.97-6.89(m, 2H), 6.62(s, 1H), 6.09(s, 1H), 5.96(s, 2H), 5.64(s, 1H), 4.34(s, 1H), 4.24(s, 1H), 3.96-3.87(m, 5H), 3.71(s, 1H), 3.56-3.49(m, 2H), 3.35-3.30(m, 1H), 2.76-2.73(m, 1H), 1.47(s, 9H).

[0615] Example 19 Synthesis of compound AB35417 The chemical structure of the compound AB35417 is as follows: [ka]

[0616] The compound AB35417 was synthesized as follows. [ka]

[0617] Compound 1 (200 mg, 0.41 mmol, 1 eq) was dissolved in chloroform (5 mL), and aqueous ammonia (2 mL) was added. The reaction was carried out at room temperature for 24 hours. The reaction mixture was diluted with water, and the organic phase was extracted with dichloromethane, washed with brine, dried over anhydrous sodium sulfate, filtered, and then centrifuged to obtain compound AB35417 from the crude product via thin layer chromatography (PE / EA=10 / 1).

[0618] Compound AB35417: MS-ESI: Theoretical value [M+H] + :572.11, Measured value [M+H] + :572.1. 1 H NMR(400 MHz, CDCl3) δ 7.32-7.30(m, 2H), 7.24-7.20(m, 3H), 6.99-6.90(m, 2H), 6.85(s, 1H), 6.68(s, 1H), 5.99(s, 2H), 5.58(s, 1H), 4.09-4.03(m, 1H), 3.93(s, 3H), 3.90(s, 3H), 3.46-3.44(m, 1H), 2.75-2.56(m, 6H), 2.12-2.04(m, 1H), 1.88-1.77(m, 1H).

[0619] Example 20 Synthesis of compound AB35418 The chemical structure of compound AB35418 is as follows: [ka]

[0620] The compound AB35418 was synthesized as follows. [ka]

[0621] Compound 1 (200 mg, 0.45 mmol, 1 eq) was dissolved in chloroform (5 mL), and aqueous ammonia (2 mL) was added. The reaction was allowed to proceed at room temperature overnight. The reaction mixture was diluted with water, and the organic phase was extracted with dichloromethane, washed with brine, dried over anhydrous sodium sulfate, filtered, and then centrifuged to obtain compound AB35418 from the crude product via thin layer chromatography (PE / EA=10 / 1).

[0622] Compound AB35418: MS-ESI: Theoretical value [M+H] + :524.11, Measured value [M+H] + :524.15. 1 H NMR(400 MHz, DMSO-d6) δ 7.13-7.04(m, 2H), 6.91(s, 1H), 6.68(s, 1H), 5.99(s, 2H), 5.60(s, 1H), 4.11-4.05(m, 1H), 3.94(s, 3H), 3.91(s, 3H), 3.47-3.45(m, 1H), 2.73-2.53(m, 4H), 1.82-1.74(m, 1H), 1.46-1.38(m, 5H), 0.95-0.92(m, 3H).

[0623] Example 21 Synthesis of compound AB35420 The chemical structure of the compound AB35420 is as follows: [ka]

[0624] The compound AB35420 was synthesized as follows. Step (1): [ka]

[0625] Compound 1 (5.0 g, 13.97 mmol, 1 eq) and compound 2 (21.0 g, 111.76 mmol, 8 eq) were dissolved in N,N-dimethylformamide (50 mL) and reacted at 60 °C overnight. The reaction mixture was diluted with water, and the organic phase was extracted twice with dichloromethane, washed with brine, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by flash chromatography (DCM / MeOH = 50 / 1 to 20 / 1) to obtain compound 3. Step (2): [ka]

[0626] Compound 3 (250 mg, 0.49 mmol, 1 eq) and compound 4 (167 mg, 1.96 mmol, 4 eq) were dissolved in N,N-dimethylformamide (10 mL), potassium carbonate (270 mg, 1.96 mmol, 4 eq) was added, and the reaction was stirred at 60 °C overnight. The reaction mixture was diluted with water, and the organic phase was extracted with dichloromethane, washed with brine, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by flash chromatography (DCM / MeOH = 10 / 1) to give compound 5. Step (3): [ka]

[0627] Compound 5 (100 mg, 0.19 mmol, 1 eq) was dissolved in chloroform (5 mL), and aqueous ammonia (2 mL) was added. The reaction was carried out at room temperature for 48 hours. The reaction mixture was diluted with water, and the organic phase was extracted with dichloromethane, washed with brine, dried over anhydrous sodium sulfate, filtered, and then centrifuged. The crude product was purified by thin-layer chromatography (PE / EA=10 / 1) to obtain compound AB35420.

[0628] Compound AB35420: MS-ESI: Theoretical value [M+H] +:551.12, Measured value [M+H] + :551.10. 1 H NMR(400 MHz, CDCl3) δ 7.14(s, 1H), 6.95-6.84(m, 2H), 6.60(s, 1H), 6.06(s, 1H), 5.93(s, 2H), 5.84(s, 1H), 4.41-4.36(m, 1H), 3.93-3.88(m, 1H), 3.84(s, 3H), 3.75-3.27(m, 1H), 3.33-3.27(m, 1H), 2.86-2.56(m, 6H), 1.66-1.47(m, 10).

[0629] Example 22 Synthesis of compound AB35421 The chemical structure of compound AB35421 is as follows: [ka]

[0630] The compound AB35421 was synthesized as follows. [ka]

[0631] Compound 1 (100 mg, 0.28 mmol, 1 eq) was dissolved in chloroform (5 mL), and aqueous ammonia (2 mL) was added. The reaction was carried out at room temperature for 48 hours. The reaction mixture was diluted with water, and the organic phase was extracted with dichloromethane, washed with brine, dried over anhydrous sodium sulfate, filtered, and then centrifuged to obtain compound AB35421 from the crude product via thin layer chromatography (PE / EA= 10 / 1).

[0632] Compound AB35421: MS-ESI: Theoretical value [M+H] + :438.00, Actual value [M+H] + :437.95. 1H NMR(400 MHz, CDCl3) δ 7.16(s, 1H), 6.86(d, J= 8.0 Hz, 1H), 6.87(d, J= 8.0 Hz, 1H), 6.61(s, 1H), 6.14(s, 1H), 6.03(s, 1H), 5.96-5.94(m, 2H), 5.91(s, 1H), 5.41(s, 1H), 3.86-3.80(m, 1H), 3.72-3.68(m, 1H), 3.39-3.32(m, 1H), 2.75-2.68(m, 1H).

[0633] Example 23 Synthesis of compound AB35422 The chemical structure of compound AB35422 is as follows: [ka]

[0634] The compound AB35422 was synthesized as follows. [ka]

[0635] Compound 1 (110 mg, 0.25 mmol, 1 eq) was dissolved in anhydrous tetrahydrofuran (10 mL), and methyl magnesium bromide (0.4 mL, 1.25 mmol, 5 eq, 3M) was added dropwise under nitrogen gas protection at 0 ° C. The reaction was carried out for 0.5 hours, and the complete reaction was confirmed by LCMS. The reaction was quenched with saturated aqueous ammonium chloride solution, and the organic phase was extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and centrifuged to obtain compound AB35422 from the crude product via thin layer chromatography (DCM / MeOH=20 / 1).

[0636] Compound AB35422: MS-ESI: Theoretical value [M+H] + : 422.23, Measured value [M+H] + :422.20. 1H NMR(400 MHz, DMSO-d6) δ 6.88-6.83(m, 4H), 6.00(d, J= 8.0 Hz, 2H), 4.65-4.61(m, 1H), 3.76(d, J= 8.0 Hz, 6H), 3.16-3.08(m, 3H), 2.74-2.70(m, 3H), 1.71-1.63(m, 1H), 1.42-1.32(m, 5H), 0.94(d, J= 4.0 Hz, 3H), 0.89-0.86(m, 3H).

[0637] Example 24 Synthesis of compound AB35423 The chemical structure of compound AB35423 is as follows: [ka]

[0638] The compound AB35423 was synthesized as follows. Step (1): [ka]

[0639] Compound 1 (300 mg, 0.84 mmol, 1 eq) was dissolved in N,N-dimethylformamide (10 mL), potassium carbonate (464 mg, 3.36 mmol, 4 eq) and compound 2 (847 mg, 3.36 mmol, 4 eq) were added, and the mixture was incubated at 60 °C overnight. The reaction mixture was diluted with water, and the organic phase was extracted twice with dichloromethane, washed with brine, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by flash chromatography (DCM / MeOH = 50 / 1 to 20 / 1) to give compound 3. Step (2): [ka]

[0640] Compound 3 (200 mg, 0.35 mmol, 1 eq) was dissolved in chloroform (5 mL), and aqueous ammonia (2 mL) was added. o C, the reaction is carried out for 48 hours, the reaction solution is diluted with water, the organic phase is extracted with dichloromethane, washed with brine, dried over anhydrous sodium sulfate, filtered, and then centrifuged to obtain compound AB35423 from the crude product via thin layer chromatography (PE / EA=10 / 1).

[0641] Compound AB35423: MS-ESI: Theoretical value [M+H] + :611.14, Measured value [M+H] + :611.05. 1 H NMR(400 MHz, CDCl3) δ 7.16(s, 1H), 6.97-6.86(m, 2H), 6.62(s, 1H), 6.09(s, 1H), 5.95-5.94(m, 2H), 5.60(s, 1H), 4.64(s, 1H), 4.27-4.23(m, 1H), 3.90-3.86(m, 5H), 3.73-3.67(m, 1H), 3.35-3.22(m, 3H), 2.77-2.71(m, 1H), 1.84-1.72(m, 4H), 1.44(s, 9H).

[0642] Example 25 Synthesis of compound AB35424 The chemical structure of compound AB35424 is as follows: [ka]

[0643] The compound AB35424 was synthesized as follows. Step (1): [ka]

[0644] Compound 1 (300 mg, 0.84 mmol, 1 eq) was dissolved in N,N-dimethylformamide (10 mL), potassium carbonate (464 mg, 3.36 mmol, 4 eq) and compound 2 (753 mg, 3.36 mmol, 4 eq) were added, and the reaction was stirred at 60 °C overnight. The reaction mixture was diluted with water, and the organic phase was extracted twice with dichloromethane, washed with brine, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by flash chromatography (DCM / MeOH = 50 / 1 to 20 / 1) to give compound 3. Step (2): [ka]

[0645] Compound 3 (50 mg, 0.09 mmol, 1 eq) was dissolved in anhydrous tetrahydrofuran (10 mL), and methyl magnesium bromide (0.15 mL, 0.45 mmol, 5 eq, 3M) was added dropwise under nitrogen gas protection at 0 °C. The reaction was carried out for 0.5 hours, quenched with saturated aqueous ammonium chloride, and the organic phase was extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and centrifuged. Compound AB35424 was obtained from the crude product via reverse phase column chromatography (acetonitrile / water + 0.01% formic acid).

[0646] Compound AB35424: MS-ESI: Theoretical value [M+H] + :481.23, Measured value [M+H] + :481.20. 1H NMR(400 MHz, DMSO-d6) δ 7.25(s, 1H), 7.04-7.02(m, 1H), 6.82-6.66(m, 3H), 6.00(d, J= 4.0 Hz, 2H), 5.92(s, 1H), 4.86-4.81(m, 1H), 3.96-3.91(m, 2H), 3.75(s, 3H), 3.28-3.26(m, 4H), 2.84-2.74(m, 2H), 1.39(s, 9H), 1.03(d, J= 8.0 Hz, 3H).

[0647] Example 26 Synthesis of compound AB35426 The chemical structure of compound AB35426 is as follows: [ka] Compound AB35426

[0648] The compound AB35426 was synthesized as follows. [ka]

[0649] Compound 1 (200 mg, 0.56 mmol, 1 eq) was dissolved in anhydrous tetrahydrofuran (10 mL), and hexylmagnesium bromide (3.4 mL, 3.36 mmol, 6 eq, 1M) was added under nitrogen gas protection at 0 °C. The reaction was carried out at room temperature for 0.5 hours. The reaction solution was quenched with saturated aqueous ammonium chloride solution, and the organic phase was extracted twice with ethyl acetate, washed with brine, dried over anhydrous sodium sulfate, filtered, and centrifuged to obtain compound AB35426 from the crude product via thin layer chromatography (DCM / MeOH=30 / 1).

[0650] Compound AB35426: MS-ESI: Theoretical value [M+H] + :405.19, Measured value [M+H] + :406.25. 1 H NMR(400 MHz, CDCl3) δ 7.13(s, 1H), 6.66(d, J= 4.0 Hz, 1H), 6.59(s, 1H), 6.51(d, J= 8.0 Hz, 1H), 5.95-5.94(m, 3H), 5.83(d, J= 8.0 Hz, 2H), 4.58-4.56(m, 1H), 3.46-3.41(m, 1H), 3.26-3.23(m, 1H), 2.89-2.77(m, 2H), 1.85-1.76(m, 1H), 1.64-1.57(m, 1H), 1.28-1.19(m, 8H), 0.84-0.81(m, 3H).

[0651] Example 27 Synthesis of compound AB35427 The chemical structure of the compound AB35427 is as follows: [ka]

[0652] The compound AB35427 was synthesized as follows. Step (1): [ka]

[0653] Compound 1 (500 mg, 1.41 mmol, 1 eq) was dissolved in methanol (10 mL), potassium carbonate (583 mg, 4.22 mmol, 3.0 eq) was added, and the mixture was stirred for 0 o In step C, sodium borohydride (53 mg, 1.41 mmol, 1.0 eq) was dissolved in 5% aqueous sodium hydroxide, and the above solution was added dropwise. The reaction was allowed to proceed for 2 hours. After the reaction was complete, the reaction solution was filtered and the solid was washed with ethanol 2-3 times. The solid was filtered and collected to obtain compound 2 (800 mg, yield: 99.9%) as a yellow solid. Step (2): [ka]

[0654] Compound 2 (400 mg, 1.26 mmol, 1 eq) was dissolved in alcohol / acetic acid (12 mL / 2 mL), and phenylpropylaldehyde (1.69 g, 12.58 mmol, 10 eq) was added. o The reaction was carried out in C for 4 hours, and then an appropriate amount of hydrochloric acid was added to the reaction mixture and concentrated. A small amount of dichloromethane and an appropriate amount of ethyl acetate were added to the crude product, and the mixture was left for 0.5 hours. The solid was then filtered off. The filtrate was left overnight to precipitate a solid. The solid was filtered and collected to obtain compound 4 (160 mg, yield: 29.9%) as a yellow solid. Step (3): [ka]

[0655] Compound 4 (90 mg, 0.21 mmol, 1 eq) was dissolved in anhydrous tetrahydrofuran (10 mL), and methylmagnesium bromide (1 mL, 1.03 mmol, 5 eq, 3 M) was added under nitrogen gas protection at 0 °C. The reaction was carried out at room temperature for 0.5 hours. The reaction solution was quenched with saturated aqueous ammonium chloride solution, and the organic phase was extracted twice with ethyl acetate, washed with brine, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by reverse phase column chromatography (acetonitrile / water + 0.01% formic acid) to obtain compound AB35427.

[0656] Compound AB35427: MS-ESI: Theoretical value [M+H] + : 453.20, Measured value [M+H] + :454.20. 1H NMR(400 MHz, DMSO-d6) δ 7.23-7.21(m, 2H), 7.17-7.15(m, 3H), 6.81(s, 2H), 6.69(d, J= 8.0 Hz, 1H), 6.53(d, J= 8.0 Hz, 1H), 6.00-5.99(m, 3H), 5.90(s, 1H), 4.55-4.51(m, 1H), 3.16-3.04(m, 2H), 2.73-2.46(m, 6H), 1.95-1.69(m, 2H), 20.99(d, J= 4.0 Hz, 3H).

[0657] Example 28 Synthesis of compound AB35428 The chemical structure of compound AB35428 is as follows: [ka]

[0658] The compound AB35428 was synthesized as follows. [ka]

[0659] Compound 1 (100 mg, 0.21 mmol, 1 eq) was dissolved in chloroform (4 mL), and aqueous ammonia (2 mL) was added. The reaction was carried out at room temperature for 48 hours. The reaction mixture was diluted with water, and the organic phase was extracted with dichloromethane, dried over anhydrous sodium sulfate, filtered, and then centrifuged. Compound AB35428 was obtained from the crude product via thin-layer chromatography (DCM / MeOH=30 / 1).

[0660] Compound AB35428: MS-ESI: Theoretical value [M+H] + :556.08, measured value [M+H] + :556.00. 1H NMR(400 MHz, DMSO-d6) δ 7.28-7.24(m, 2H), 7.21-7.14(m, 3H), 6.96(d, J= 12.0 Hz, 1H), 6.85(s, 1H), 6.73-6.71(m, 2H), 6.07(s, 1H), 6.02(d, J= 4.0 Hz, 2H), 5.97(s, 1H), 5.44(s, 1H), 3.80-3.75(m, 1H), 3.63-3.61(m, 1H), 2.70-2.53(m, 6H), 1.88-1.74(m, 2H).

[0661] Example 29 Synthesis of compound AB35429 The chemical structure of compound AB35429 is as follows: [ka]

[0662] The compound AB35428 was synthesized as follows. Step (1): [ka]

[0663] Compound 1 (400 mg, 0.81 mmol, 1.0 eq) was dissolved in methanol (30 mL), and aqueous ammonia (7 mL) was added. Ammonium chloride (44 mg, 0.81 mmol, 1.0 eq) was further added, and the mixture was stirred for 70 minutes. o The temperature was raised to 25°C and the reaction was allowed to proceed for 16 hours. After checking by TLC and confirming the complete reaction by LCMS, the reaction mixture was diluted with water, and the organic phase was extracted twice with dichloromethane, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by flash chromatography (DCM / MeOH = 100 / 1 to 50 / 1) to obtain compound 2 (190 mg, yield: 42.2%) as a yellow solid. Step (2): [ka]

[0664] Compound 2 (80 mg, 0.19 mmol, 1.0 eq) was dissolved in tetrahydrofuran (5 mL), and methylmagnesium bromide (0.4 mL, 1.14 mmol, 6.0 eq, 3M) was added dropwise under nitrogen gas protection at 0 °C. The mixture was warmed to room temperature and the reaction was carried out for 0.5 hours. TLC check was performed, and the complete reaction was confirmed by LCMS check. The mixture was quenched with saturated aqueous ammonium chloride solution, and the organic phase was extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by reverse phase column chromatography (acetonitrile / water + 0.01% formic acid) to obtain compound AB35429 (10 mg, yield: 12.5%) as a yellow solid.

[0665] Compound AB35429: MS-ESI: Theoretical value [M+H] + : 409.21, Measured value [M+H+H2O] + :428.10. 1H NMR (400 MHz, DMSO-d6) δ 7.23(s, 1H), 6.80-6.64(m, 3H), 5.98(d, J= 4.0 Hz, 2H), 5.90(s, 1H), 4.75-4.70(m, 1H), 3.96-3.87(m, 2H), 3.74-3.71(m, 5H), 3.26-3.20(m, 2H), 2.81-2.72(m, 2H), 1.95-1.79(m, 4H), 1.03(d, J= 8.0 Hz, 3H).

[0666] Example 30 Synthesis of compound AB35430 The chemical structure of compound AB35430 is as follows: [ka]

[0667] The compound AB35430 was synthesized as follows. [ka]

[0668] Compound 1 (150 mg, 0.28 mmol, 1.0 eq) was dissolved in tetrahydrofuran (10 mL), and cycloamylmagnesium bromide (1.4 mL, 1.4 mmol, 5 eq, 1M) was added at 0°C. The reaction was carried out at room temperature for 0.5 hours, and TLC was performed. The complete reaction was confirmed by LCMS. The mixture was quenched with saturated aqueous ammonium chloride solution, and the organic phase was extracted twice with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and centrifuged to obtain compound AB35430 from the crude product via thin layer chromatography (DCM / MeOH=30 / 1).

[0669] Compound AB35430: MS-ESI: Theoretical value [M+H] + :512.14, Measured value [M+H] + :512.10. 1H NMR(400 MHz, CDCl3) δ 7.13(s, 1H), 6.74(s, 2H), 6.58(s, 1H), 5.93(s, 2H), 5.83(s, 1H), 4.65(d, J= 4.0 Hz, 1H), 4.26-4.21(m, 1H), 4.03-3.97(m, 1H), 3.82(s, 3H), 3.80-3.67(m, 2H), 3.60-3.44(m, 2H), 2.89-2.76(m, 2H), 2.46-2.16(m, 3H), 1.76-1.70(m, 1H), 1.48-1.30(m, 7H).

[0670] Example 31 Synthesis of compound AB35434 The chemical structure of compound AB35434 is as follows: [ka]

[0671] The compound AB35434 was synthesized as follows. Step (1): [ka]

[0672] Compound 1 (500 mg, 1.4 mmol, 1.0 eq) was dissolved in DMF (10 mL), compound 2 (949 mg, 8.4 mmol, 6 eq) was added, and the reaction was carried out at 75 °C for 16 h under nitrogen gas protection. After TLC and LCMS analysis, the organic phase was centrifuged and purified by flash chromatography (100-200 mesh silica gel, DCM / MeOH = 20 / 1) to obtain the crude yellow solid compound 3 (300 mg, yield: 49.3%). Step (2): [ka]

[0673] Compound 3 (200 mg, 0.46 mmol, 1.0 eq) was dissolved in tetrahydrofuran (10 mL), and cycloamylmagnesium bromide (2.8 mL, 2.76 mmol, 6.0 eq, 1M) was added at 0 °C under the protection of nitrogen gas. o The reaction was carried out at C for 0.5 hours, followed by TLC check, and the complete reaction was confirmed by LCMS check. The reaction was quenched with saturated aqueous ammonium chloride solution, and the organic phase was extracted twice with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and then centrifuged. The crude product was purified by reverse phase column chromatography (acetonitrile / water + 0.01% formic acid) to obtain compound AB35434.

[0674] Compound AB35434: MS-ESI: Theoretical value [M+H] + : 468.19, Measured value [M+H] + :468.45. 1H NMR(400 MHz, CDCl3) δ 7.13(s, 1H), 6.74(s, 2H), 6.57(s, 1H), 5.92(s, 2H), 5.82(s, 1H), 4.61(d, J= 8.0 Hz, 1H), 4.23-4.21(m, 1H), 4.00-3.84(m, 2H), 3.79(s, 4H), 3.58-3.43(m, 2H), 2.88-2.81(m, 2H), 2.36-2.28(m, 2H), 2.16-2.06(m, 1H), 1.74-1.37(m, 8H).

[0675] Example 32 Synthesis of compound AB35436 The chemical structure of compound AB35436 is as follows: [ka]

[0676] The compound AB35436 was synthesized as follows. Step (1): [ka]

[0677] Compound 1 (2.0 g, 5.93 mmol, 1 eq) was dissolved in alcohol / acetic acid (10 mL / 8 mL), and phenylpropyl aldehyde (7.9 g, 59.3 mmol, 10 eq) was added. o The reaction was carried out in C for 4 hours, and then an appropriate amount of hydrochloric acid was added to the reaction mixture and concentrated. A small amount of dichloromethane and an appropriate amount of ethyl acetate were added to the crude product, and the mixture was left for 0.5 hours before filtering off the solid. The filtrate was left overnight to precipitate the solid. The solid was filtered and collected to obtain compound 3 (1.4 g, yield: 48.2%) as a yellow solid. Step (2): [ka]

[0678] Compound 3 (200 mg, 0.41 mmol, 1 eq) was dissolved in anhydrous tetrahydrofuran (10 mL), and cycloamylmagnesium bromide (0.7 mL, 2.05 mmol, 5 eq, 3M) was added under nitrogen gas protection at 0 °C. The reaction was carried out at room temperature for 0.5 hours. The reaction solution was quenched with saturated aqueous ammonium chloride solution, and the organic phase was extracted twice with ethyl acetate, washed with brine, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by reverse phase column chromatography (acetonitrile / water + 0.01% formic acid) to obtain compound AB35436.

[0679] Compound AB35436: MS-ESI: Theoretical value [M+H] + :524.28, Measured value [M+H] + :524.30. 1 H NMR(400 MHz, CDCl3) δ 7.26-7.16(m, 5H), 6.83-6.74(m, 4H), 6.01(d, J= 4.0 Hz, 2H), 4.40(d, J= 8.0 Hz, 1H), 3.76(s, 3H), 3.72(s, 3H), 2.69-2.65(m, 2H), 2.12-2.05(m, 1H), 1.98-1.85(m, 2H), 1.76-1.68(m, 1H), 1.47-1.43(m, 4H), 1.34-1.16(m, 9H).

[0680] Example 33 Synthesis of compound AB35438 The chemical structure of compound AB35438 is as follows: [ka]

[0681] The compound AB35438 was synthesized as follows. Step (1): [ka]

[0682] Compound 1 (2 g, 5.59 mmol, 1 eq) was dissolved in anhydrous tetrahydrofuran (20 mL) and cycloamylmagnesium bromide (28 mL, 27.95 mmol, 5 eq, 1M) was added at 0 °C under nitrogen gas protection. The reaction was allowed to proceed at room temperature for 0.5 h. The reaction mixture was quenched with saturated aqueous ammonium chloride solution, and the organic phase was extracted twice with ethyl acetate, washed with brine, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by flash chromatography (DCM / MeOH = 100 / 1 to 50 / 1) to obtain compound 3 (1.2 g, 54.5% yield) as a yellow solid. Step (2): [ka]

[0683] Compound 3 (200 mg, 0.51 mmol, 1 eq) was dissolved in dimethylformamide (10 mL), potassium carbonate (211 mg, 1.53 mmol, 3 eq) and compound 4 (222 mg, 1.02 mmol, 2 eq) were added, and the reaction was carried out at room temperature for 12 hours. The reaction mixture was diluted with water, and the organic phase was extracted twice with dichloromethane, washed with brine, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by reverse phase column chromatography (acetonitrile / water + 0.01% formic acid) to obtain compound AB35438.

[0684] Compound AB35438: MS-ESI: Theoretical value [M+H] + :528.31, Measured value [M+H] + :528.45. 1H NMR(400 MHz, DMSO-d6) δ 6.81(s, 2H), 6.77(d, J= 8.0 Hz, 1H), 6.55(d, J= 8.0 Hz, 1H), 5.98(d, J= 12.0 Hz, 2H), 5.09-5.00(m, 2H), 4.58(d, J= 8.0 Hz, 1H), 3.75(s, 3H), 3.30-3.10(s, 5H), 2.70-2.51(m, 2H), 2.10-1.98(m, 5H), 1.66(s, 3H), 1.53(s, 3H), 1.50(s, 3H), 1.41-1.37(m, 4H), 1.30-1.21(m, 4H).

[0685] Example 34 Synthesis of compound AB35440 The chemical structure of compound AB35440 is as follows: [ka]

[0686] The compound AB35440 was synthesized as follows. Step (1): [ka]

[0687] Compound 1 (500 mg, 1.40 mmol, 1 eq) was dissolved in N,N-dimethylformamide (50 mL), compound 2 (862 mg, 5.6 mmol, 4 eq) was added, and the reaction was heated at 60 °C for 16 hours. TLC confirmed the complete reaction, and LCMS confirmed the complete reaction. The reaction mixture was diluted with water, and the organic phase was extracted twice with dichloromethane, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by flash chromatography (DCM / MeOH = 50 / 1 to 20 / 1) to obtain compound 3 (100 mg, yield: 15%) as a yellow solid. Step (2): [ka]

[0688] Compound 3 (100 mg, 0.21 mmol, 1 eq) was dissolved in anhydrous tetrahydrofuran (5 mL), and cycloamylmagnesium bromide (0.4 mL, 1.05 mmol, 5 eq, 3M) was added under nitrogen gas protection at 0 °C. The reaction was carried out at room temperature for 0.5 hours, and the reaction solution was quenched with saturated aqueous ammonium chloride solution. The organic phase was extracted twice with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and then centrifuged. The crude product was purified by reverse phase column chromatography (acetonitrile / water + 0.01% formic acid) to obtain compound AB35440.

[0689] Compound AB35440: MS-ESI: Theoretical value [M+H]+: 510.24, Measured value [M+H] + :510.25. 1 H NMR(400 MHz, DMSO-d6) δ 7.21(s, 1H), 6.79(d, J= 8.0 Hz, 1H), 6.74(s, 1H), 6.64(d, J= 8.0 Hz, 1H), 5.97(s, 2H), 5.89(s, 1H), 4.50(d, J= 8.0 Hz, 1H), 4.03-4.00(m, 1H), 3.77-3.72(m, 4H), 3.65-3.61(m, 2H), 3.42-3.36(m, 2H), 2.90-2.84(m, 1H), 2.66-2.64(m, 1H), 2.20-2.13(m, 1H), 1.73-1.57(m, 6H), 1.47-1.41(m, 6H), 1.28-1.15(m, 4H).

[0690] Example 35 Synthesis of compound AB35441 The chemical structure of compound AB35441 is as follows: [ka]

[0691] The compound AB35441 was synthesized as follows. [ka]

[0692] Compound 1 (100 mg, 0.23 mmol, 1 eq) was dissolved in aqueous ammonia (3 mL) and chloroform (6 mL) and stirred at room temperature for 48 hours. The reaction mixture was diluted with water, and the organic phase was extracted with dichloromethane, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by thin-layer chromatography (DCM / MeOH = 50 / 1) to obtain compound AB35441.

[0693] Compound AB35441: MS-ESI: Theoretical value [M+H] + :516.02, measured value [M+H] + :516.25. 1 H NMR(400 MHz, DMSO-d6) δ 7.31(s, 1H), 7.09(d, J= 12.0 Hz, 1H), 6.89(d, J= 4.0 Hz, 1H), 6.77(s, 1H), 6.32(s, 1H), 5.99(d, J= 4.0 Hz, 2H), 5.63(s, 1H), 4.23-4.19(m, 1H), 3.90-3.88(m, 3H), 3.79-3.74(m, 4H), 3.65-3.60(m, 1H), 3.27-3.21(m, 1H), 2.73-2.67(m, 1H), 2.21-2.20(m, 1H), 2.09-2.02(m, 1H).

[0694] Example 36 Synthesis of compound AB35444 The chemical structure of compound AB35444 is as follows: [ka]

[0695] The compound AB35444 was synthesized as follows. Step (1): [ka]

[0696] Compound 1 (3 g, 8.89 mmol, 1 eq) was dissolved in alcohol / acetic acid (30 mL / 5 mL), and phenylpropylaldehyde (10.7 g, 88.9 mmol, 10 eq) was added. o The reaction was carried out in C for 4 hours, and then an appropriate amount of hydrochloric acid was added to the reaction mixture and concentrated. A small amount of dichloromethane and an appropriate amount of ethyl acetate were added to the crude product, and the mixture was left for 0.5 hours before filtering off the solid. The filtrate was left overnight to precipitate a solid. The solid was filtered and collected to obtain compound 3 (1.8 g, yield: 42.8%) as a yellow solid. Step (2): [ka]

[0697] Compound 3 (300 mg, 0.63 mmol, 1 eq) was dissolved in aqueous ammonia (4 mL), chloroform (8 mL) was added, and the reaction was carried out at room temperature under nitrogen gas protection for 48 hours. The reaction mixture was diluted with water, and the organic phase was extracted with dichloromethane, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by flash chromatography (DCM / MeOH = 100 / 1 to 50 / 1) to obtain compound AB35444.

[0698] Compound AB35444: MS-ESI: Theoretical value [M+H] + :558.10, Measured value [M+H] + :558.05. 1H NMR(400 MHz, DMSO-d6) δ 7.30(d, J= 4.0 Hz, 4H), 7.21-7.18(m, 3H), 6.97(s, 1H), 6.87(s, 1H), 6.03(s, 1H), 6.00(s, 1H), 5.58(s, 1H), 3.85-3.79(m, 7H), 3.62-3.59(m, 1H), 2.90-2.70(m, 5H), 2.58-2.51(m, 1H).

[0699] Example 37 Synthesis of compound AB35445 The chemical structure of the compound AB35445 is as follows: [ka]

[0700] The compound AB35445 was synthesized as follows. Step (1): [ka]

[0701] Compound 1 (5.0 g, 13.97 mmol, 1.0 eq) was dissolved in dichloromethane (300 mL) and trifluoromethanesulfonic anhydride (4.3 g, 15.37 mmol, 1.1 eq) was added dropwise at 0 °C. The reaction was allowed to proceed at room temperature for 1 h. TLC confirmed the complete reaction, and LCMS confirmed the reaction was complete. The reaction mixture was quenched with water, and the organic phase was extracted twice with dichloromethane, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by flash chromatography (DCM / MeOH = 100 / 1 to 50 / 1) to give compound 2 (3.4 g, yield: 40.5%) as a yellow solid. Step (2): [ka]

[0702] Compound 2 (300 mg, 0.49 mmol, 1.0 eq) was dissolved in dioxane (10 mL), and compound 3 (330 mg, 2.32 mmol, 4.6 eq), triethylamine (201 mg, 1.99 mmol, 4.0 eq), palladium acetate (22 mg, 0.099 mmol, 0.2 eq), and 1,1'-binaphthyl-2,2'-diphenylphosphine (62 mg, 0.099 mmol, 0.2 eq) were added. The mixture was heated at 100°C under nitrogen gas protection. o The reaction was carried out at C for 16 hours. After TLC and LCMS analysis showed the reaction was complete, the reaction mixture was diluted with water, and the organic phase was extracted twice with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by flash chromatography (DCM / MeOH=50 / 1) to obtain compound 4 (150 mg, yield: 51.4%) as a yellow solid. Step (3): [ka]

[0703] Compound 4 (150 mg, 0.25 mmol, 1.0 eq) was dissolved in chloroform (8 mL) and aqueous ammonia (4 mL) and incubated overnight at 40 °C. TLC analysis confirmed the complete reaction. LCMS analysis confirmed the complete reaction. The reaction mixture was diluted with water, and the organic phase was extracted twice with dichloromethane, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by flash chromatography (DCM / MeOH = 100 / 1 to 50 / 1) to obtain compound AB35445.

[0704] Compound AB35445: MS-ESI: Theoretical value [M+H] + :564.15, measured value [M+H] + :564.40. 1H NMR(400 MHz, DMSO-d6) δ 7.27(s, 1H), 7.03-6.98(m, 2H), 6.77(s, 1H), 6.25(s, 1H), 5.98(d, J= 8.0 Hz, 2H), 5.93(s, 1H), 3.76(s, 3H), 3.72-3.59(m, 3H), 3.17-3.03(m, 2H), 2.81-2.68(m, 4H), 2.59-2.48(m, 1H), 2.29-2.25(m, 2H), 2.18-2.03(m, 2H), 1.42-1.39(m, 2H), 1.29-1.26(m, 2H), 0.89-0.85(m, 3H).

[0705] Example 38 Synthesis of compound AB35448 The chemical structure of compound AB35448 is as follows: [ka]

[0706] The compound AB35448 was synthesized as follows. [ka]

[0707] Compound 1 (300 mg, 0.63 mmol, 1 eq) was dissolved in anhydrous tetrahydrofuran (10 mL), and cycloamylmagnesium bromide (3.2 mL, 3.15 mmol, 5 eq, 1M) was added under nitrogen gas protection at 0 °C. The reaction was carried out at room temperature for 0.5 hours, and the reaction solution was quenched with saturated aqueous ammonium chloride solution. The organic phase was extracted twice with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by reverse phase column chromatography (acetonitrile / water + 0.01% formic acid) to obtain compound AB35448.

[0708] Compound AB35448: MS-ESI: Theoretical value [M+H] + :510.26, Measured value [M+H]+ :510.20. 1 H NMR(400 MHz, DMSO-d6) δ 7.30-7.25(m, 4H), 7.20-7.16(m, 1H), 7.05-6.93(m, 2H), 6.81(d, J= 4.0 Hz, 2H), 6.00(s, 2H), 4.43(d, J= 8.0 Hz, 1H), 3.79(s, 3H), 3.75(s, 3H), 3.35-3.32(m, 2H), 2.91-2.65(m, 5H), 2.51-2.48(m, 1H), 2.21-2.13(m, 1H), 1.50-1.24(m, 9H).

[0709] Example 39 Synthesis of compound AB35453 The chemical structure of compound AB35453 is as follows: [ka]

[0710] The compound AB35453 was synthesized as follows. Step (1): [ka]

[0711] Compound 1 (700 mg, 1.16 mmol, 1.0 eq) was dissolved in dioxane (20 mL), and compound 2 (460 mg, 4.64 mmol, 4.0 eq), triethylamine (469 mg, 4.64 mmol, 4.0 eq), palladium acetate (52 mg, 0.232 mmol, 0.2 eq), and 1,1'-binaphthyl-2,2'-diphenylphosphine (144 mg, 0.232 mmol, 0.2 eq) were added. The mixture was heated at 100°C under nitrogen gas protection. oThe reaction was carried out at C for 16 hours. After TLC and LCMS analysis showed the reaction was complete, the reaction mixture was diluted with water, the organic phase was extracted twice with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by flash chromatography (DCM / MeOH=50 / 1) to give compound 3 (280 mg). Step (2): [ka]

[0712] Compound 3 (150 mg, 0.27 mmol, 1.0 eq) was dissolved in chloroform (8 mL) and aqueous ammonia (4 mL) and incubated overnight at 40 °C. TLC analysis confirmed the complete reaction. LCMS analysis confirmed the complete reaction. The reaction mixture was diluted with water, and the organic phase was extracted twice with dichloromethane, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by flash chromatography (DCM / MeOH = 100 / 1 to 50 / 1) to obtain compound AB35453.

[0713] Compound AB35453: MS-ESI: Theoretical value [M+H] + :521.11, measured value [M+H] + :521.15. 1 H NMR(400 MHz, CDCl3) δ 7.15(s, 1H), 6.98-6.90(m, 2H), 6.61(s, 1H), 6.07(s, 1H), 6.03(s, 1H), 5.95(d, J= 4.0 Hz, 2H), 3.91-3.86(m, 1H), 3.81(s, 3H), 3.68-3.64(m, 1H), 3.55-3.49(m, 1H), 3.31-3.26(m, 1H), 3.06-2.99(m, 2H), 2.78-2.72(m, 2H), 1.68-1.61(m, 1H), 1.49-1.45(m, 1H), 1.36-1.26(m, 3H), 0.99(d, J= 4.0 Hz, 3H).

[0714] Example 40 Synthesis of compound AB35454 The chemical structure of compound AB35454 is as follows: [ka] AB35454

[0715] The compound AB35454 was synthesized as follows. [ka]

[0716] Compound 1 (200 mg, 0.36 mmol, 1.0 eq) was dissolved in tetrahydrofuran (10 mL), and cycloamylmagnesium bromide (2.2 mL, 2.16 mmol, 6 eq, 1M) was added dropwise under nitrogen gas protection at 0 °C. The mixture was warmed to room temperature and the reaction was carried out for 0.5 hours. TLC check was performed, and the complete reaction was confirmed by LCMS check. The reaction mixture was quenched with saturated aqueous ammonium chloride solution, and the organic phase was extracted twice with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and then centrifuged to obtain compound AB35454 from the crude product via reverse phase column chromatography (acetonitrile / water + 0.01% formic acid). [ka] Compound AB35454: MS-ESI: Theoretical value [M+H] + :540.27, Measured value [M+H] + :540.40. 1H NMR(400 MHz, DMSO-d6): δ 7.27-7.23(m, 2H), 7.20(s, 1H), 6.92-6.89(m, 3H), 6.79(d, J= 8.0 Hz, 1H), 6.72(s, 1H), 6.65(d, J= 8.0 Hz, 1H), 5.96(s, 2H), 5.88(s, 1H), 4.51(d, J= 8.0 Hz, 1H), 4.11-4.02(m, 3H), 3.81-3.79(m, 1H), 3.71(s, 3H), 3.35-3.28(m, 2H), 2.89-2.79(m, 1H), 2.61-2.56(m, 1H), 2.18-2.12(m, 1H), 1.91-1.82(m, 4H), 1.54-1.15(m, 8H).

[0717] Example 41 Synthesis of compound AB35455 The chemical structure of the compound AB35455 is as follows: [ka] AB35455

[0718] The compound AB35455 was synthesized as follows. Step (1): [ka]

[0719] Compound 1 (500 mg, 1.40 mmol, 1.0 eq) was dissolved in DMF (30 mL), compound 2 (784 mg, 2.8 mmol, 2 eq) and potassium carbonate (386 mg, 2.8 mmol, 2 eq) were added, and the reaction was carried out at 60 °C for 16 h under nitrogen gas protection. After TLC and LCMS analysis showed a complete reaction, the reaction mixture was diluted with water, and the organic phase was extracted twice with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by flash chromatography (DCM / MeOH = 50 / 1) to give compound 3 (580 mg, 68.9% yield) as a yellow solid. Step (2): [ka]

[0720] Compound 3 (580 mg, 0.96 mmol, 1.0 eq) was dissolved in tetrahydrofuran (20 mL), and cycloamylmagnesium bromide (6 mL, 5.8 mmol, 6 eq, 1M) was added dropwise under nitrogen gas protection at 0 °C. The mixture was warmed to room temperature and the reaction was carried out for 0.5 hours. The complete reaction was confirmed by LCMS. The reaction mixture was quenched with saturated aqueous ammonium chloride solution, and the organic phase was extracted twice with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and centrifuged to obtain compound AB35455 from the crude product via reverse phase column chromatography (acetonitrile / water + 0.1% formic acid).

[0721] Compound AB35455: MS-ESI: Theoretical value [M+H] + :591.34, Measured value [M+H] + :591.45. 1H NMR(400 MHz, DMSO-d6) δ 7.20(s, 1H), 6.79-6.63(m, 4H), 5.97(s, 2H), 5.88(s, 1H), 4.50(d, J= 8.0 Hz, 1H), 4.04-4.00(m, 1H), 3.71(s, 4H), 3.35-3.33(m, 2H), 2.90-2.85(m, 3H), 2.66-2.61(m, 1H), 2.19-2.12(m, 1H), 1.65-1.57(m, 3H), 1.38-1.15(m, 22H).

[0722] Example 42 Synthesis of compound AB35456 The chemical structure of compound AB35456 is as follows: [ka]

[0723] The compound AB35456 was synthesized as follows. [ka]

[0724] Compound 1 (100 mg, 0.23 mmol, 1.0 eq) was dissolved in tetrahydrofuran (10 mL), and methyl magnesium bromide (0.4 mL, 1.15 mmol, 5.0 eq, 3M) was added under nitrogen gas protection at 0 °C. The reaction was carried out at room temperature for 0.5 hours, and TLC was performed. The complete reaction was confirmed by LCMS. The reaction solution was quenched with saturated aqueous ammonium chloride solution, and the organic phase was extracted twice with dichloromethane, dried over anhydrous sodium sulfate, filtered, and then centrifuged. The crude product was purified by reverse phase column chromatography (acetonitrile / water + 0.1% formic acid) to obtain compound AB35456.

[0725] Compound AB35456: MS-ESI: Theoretical value [M+H] + : 413.14, Measured value [M+H] + :413.90. 1 H NMR(400 MHz, DMSO-d6) δ 7.23(s, 1H), 6.80(d, J= 8.0 Hz, 1H), 6.75(s, 1H), 6.65(d, J= 8.0 Hz, 1H), 5.98(d, J= 4.0 Hz, 2H), 5.91(s, 1H), 4.78-4.73(m, 1H), 4.06-4.03(m, 2H), 3.86-3.83(m, 2H), 3.73(s, 3H), 3.32-3.18(m, 2H), 2.81-2.72(m, 2H), 2.17-2.11(m, 2H), 1.04(d, J= 4.0 Hz, 3H).

[0726] Example 43 Synthesis of compound AB35457 The chemical structure of the compound AB35457 is as follows: [ka]

[0727] The compound AB35457 was synthesized as follows. Step (1): [ka]

[0728] In a sealed tube, compound 1 (500 mg, 1.34 mmol, 1.0 eq) was dissolved in alcohol (5 mL), compound 2 (815 mg, 6.72 mmol, 5 eq) was added, and the reaction was carried out at 110 °C for 16 h under nitrogen gas protection. TLC check was performed, and the reaction was confirmed to be complete by LCMS check. The reaction mixture was centrifuged and purified by flash chromatography (DCM / MeOH = 20 / 1) to obtain the crude compound 3 (150 mg, yield: 24.3%). Step (2): [ka]

[0729] Compound 3 (150 mg, 0.32 mmol, 1.0 eq) was dissolved in tetrahydrofuran (10 mL), cycloamylmagnesium bromide (3 mL) was added at 0°C, and the reaction was carried out at room temperature for 0.5 hours. TLC check was performed, and the complete reaction was confirmed by LCMS check. The reaction solution was quenched with saturated aqueous ammonium chloride solution, and the organic phase was extracted twice with dichloromethane, dried over anhydrous sodium sulfate, filtered, and then centrifuged. The crude product was purified by reverse phase column chromatography (acetonitrile / water + 0.1% formic acid) to obtain compound AB35457.

[0730] Compound AB35457: MS-ESI: Theoretical value [M+H] + : 495.26, Measured value [M+H] + :495.40. 1 H NMR(400 MHz, DMSO-d6) δ 7.29-7.19(m, 6H), 6.72-6.67(m, 2H), 6.49(d, J= 8.0 Hz, 1H), 5.96(s, 2H), 5.84(s, 1H), 4.23(d, J= 8.0 Hz, 1H), 3.71-3.68(m, 4H), 3.34-3.24(m, 4H), 2.87-2.77(m, 3H), 2.62-2.59(m, 1H), 2.12-2.06(m, 1H), 1.44-1.33(m, 4H), 1.15-0.96(m, 4H).

[0731] Example 44 Synthesis of compound AB35458 The chemical structure of compound AB35458 is as follows: [ka]

[0732] The compound AB35458 was synthesized as follows. Step (1): [ka]

[0733] Compound 1 (500 mg, 1.4 mmol, 1.0 eq) was dissolved in DMF (10 mL), compound 2 (1.7 g, 7 mmol, 5 eq) was added, and the reaction was carried out at 75 °C for 16 h under nitrogen gas protection. After TLC and LCMS analysis, the reaction mixture was centrifuged and purified by flash chromatography (DCM / MeOH = 30 / 1) to obtain the crude compound 3 (500 mg, 63.2% yield). Step (2): [ka]

[0734] Compound 3 (150 mg, 0.26 mmol, 1.0 eq) was dissolved in anhydrous tetrahydrofuran (10 mL), and cycloamylmagnesium bromide (1.3 mL, 1.3 mmol, 5.0 eq, 1M) was added at 0 °C. The reaction was carried out at room temperature for 0.5 hours, and TLC was performed. The complete reaction was confirmed by LCMS. The mixture was quenched with saturated aqueous ammonium chloride solution, and the organic phase was extracted twice with dichloromethane, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by reverse-phase column chromatography (acetonitrile / water + 0.1% formic acid) to obtain compound AB35458.

[0735] Compound AB35458: MS-ESI: Theoretical value [M+H] + :554.19, Measured value [M+H] + :554.15. 1H NMR(400 MHz, DMSO-d6) δ 7.23(s, 1H), 6.81(d, J= 8.0 Hz, 1H), 6.76(s, 1H), 6.66(d, J= 8.0 Hz, 1H), 5.99(s, 2H), 5.91(s, 1H), 4.52(d, J= 8.0 Hz, 1H), 4.08-4.02(m, 1H), 3.78-3.74(m, 4H), 23.55-3.53(m, 2H), 3.42-3.35(m, 2H), 2.92-2.86(m, 1H), 2.69-2.63(m, 1H), 2.22-2.15(m, 1H), 1.85-1.82(m, 2H), 1.70-1.66(m, 2H), 1.60-1.48(m, 8H), 1.31-1.17(m, 4H).

[0736] Example 45 Synthesis of compound AB35459 The chemical structure of the compound AB35459 is as follows: [ka]

[0737] The compound AB35459 was synthesized as follows. Step (1): [ka]

[0738] Compound 1 (1 g, 5.15 mmol, 1 eq) was dissolved in dichloromethane (10 mL), and compound 2 (2.0 g, 15.45 mmol, 3 eq) and a small amount of dimethylformamide (two drops) were added at 0 °C. The mixture was allowed to cool to room temperature for 2 hours, and the reaction was checked by TLC. LCMS confirmed the complete reaction. The organic phase was centrifuged to obtain compound 3 (1.0 g, yield: 90.9%). Step (2): [ka]

[0739] Compound 4 (434 mg, 1.11 mmol, 1 eq) was dissolved in dichloromethane, triethylamine (560 mg, 5.55 mmol, 5 eq) was added, and compound 3 (708 mg, 3.33 mmol, 3 eq) was added at 0 ° C. The mixture was returned to room temperature and the reaction was carried out for 16 hours. TLC check was performed, and the complete reaction was confirmed by LCMS check. The reaction product was diluted with water, and the organic phase was extracted twice with dichloromethane, dried over anhydrous sodium sulfate, filtered, and then centrifuged. The crude product was purified by reverse phase column chromatography (acetonitrile / water + 0.1% formic acid) to obtain compound AB35459.

[0740] Compound AB35459: MS-ESI: Theoretical value [M+H] + :568.30, Measured value [M+H] + :568.30. 1 H NMR(400 MHz, DMSO-d6) δ 7.22(s, 1H), 6.89-6.80(m, 2H), 6.74(s, 1H),5.97(s, 2H), 5.94(s, 1H), 4.33(d, J= 4.0 Hz, 1H), 3.68(s, 3H), 3.30-3.26(m, 2H), 2.88-2.80(m, 1H), 2.68-2.60(m, 1H), 2.30(s, 2H), 2.19-2.11(m, 1H), 1.70-1.60(m, 16H), 1.45-1.35(m, 3H), 1.27-1.20(m, 4H).

[0741] Example 46 Synthesis of compound AB35465 The chemical structure of the compound AB35465 is as follows: [ka]

[0742] The compound AB35465 was synthesized as follows. Step (1): [ka]

[0743] Compound 1 (1.0 g, 1.66 mmol, 1.0 eq) was dissolved in dioxane (30 mL), and compound 2 (1.3 g, 6.64 mmol, 4.0 eq), triethylamine (671 mg, 6.64 mmol, 4.0 eq), palladium acetate (74 mg, 0.332 mmol, 0.2 eq), and 1,1'-binaphthyl-2,2'-diphenylphosphine (207 mg, 0.332 mmol, 0.2 eq) were added. The mixture was heated at 100°C under nitrogen gas protection. o The reaction was carried out at C for 16 hours. After TLC and LCMS analysis showed the reaction was complete, the reaction mixture was diluted with water, and the organic phase was extracted twice with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by flash chromatography (DCM / MeOH = 50 / 1) to obtain compound 3 (1.0 g, yield: 92.6%). Step (2): [ka]

[0744] Compound 3 (300 mg, 0.46 mmol, 1.0 eq) was dissolved in chloroform (8 mL) and aqueous ammonia (4 mL) and incubated overnight at 30 °C. TLC analysis confirmed the complete reaction. LCMS analysis confirmed the complete reaction. The reaction mixture was diluted with water, and the organic phase was extracted twice with dichloromethane, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by flash chromatography (DCM / MeOH = 100 / 1 to 50 / 1) to obtain compound AB35465.

[0745] Compound AB35465: MS-ESI: Theoretical value [M+H] + :622.16, Measured value [M+H] + :622.30. 1H NMR(400 MHz, CDCl3) δ 7.12(s, 1H), 6.97-6.87(m, 2H), 6.60(s, 1H), 6.04(s, 1H), 5.96- 5.93(m, 3H), 4.48(s, 1H), 3.88-3.84(s, 1H), 3.79(s, 3H), 3.62-3.53(m, 3H), 3.24-3.20(m, 1H), 3.14-3.02(m, 2H), 2.76-2.71(m, 2H), 2.02-1.82(m, 2H), 1.52-1.44(m, 11H).

[0746] Example 47 Synthesis of compound AB35466 The chemical structure of compound AB35466 is as follows: [ka]

[0747] The compound AB35466 was synthesized as follows. Step (1): [ka]

[0748] Compound 1 (500 mg, 1.40 mmol, 1 eq) was dissolved in N,N-dimethylformamide (10 mL), compound 2 (1.1 g, 5.6 mmol, 4 eq) was added, and the reaction was heated at 60 °C for 16 hours. TLC confirmed the complete reaction, and LCMS confirmed the complete reaction. The reaction mixture was diluted with water, and the organic phase was extracted twice with dichloromethane, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by flash chromatography (DCM / MeOH = 50 / 1 to 20 / 1) to obtain compound 3 (420 mg, yield: 57.4%) as a yellow solid. Step (2): [ka]

[0749] Compound 3 (200 mg, 0.38 mmol, 1.0 eq) was dissolved in chloroform (8 mL) and aqueous ammonia (4 mL) and incubated overnight at 30 °C. TLC analysis confirmed the complete reaction. LCMS analysis confirmed the complete reaction. The reaction mixture was diluted with water, and the organic phase was extracted twice with dichloromethane, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by flash chromatography (DCM / MeOH = 100 / 1 to 50 / 1) to obtain compound AB35466.

[0750] Compound AB35466: MS-ESI: Theoretical value [M+H] + :559.95, Measured value [M+H] + :559.95. 1 H NMR(400 MHz, DMSO-d6) δ 7.31(s, 1H), 7.08(d, J= 8.0 Hz, 1H), 6.89(d, J= 8.0 Hz, 1H), 6.77(s, 1H), 6.32(s, 1H), 5.99(d, J= 4.0 Hz, 2H), 5.65(s, 1H), 4.22-4.20(m, 1H), 3.88-3.85(m, 1H), 3.79-3.74(m, 6H), 3.67-3.60(m, 1H), 3.28-3.20(m, 1H), 2.73-2.66(m, 1H), 2.33-2.26(m, 1H), 2.15-2.08(m, 1H).

[0751] Example 48 Synthesis of compound AB35433 The chemical structure of compound AB35433 is as follows: [ka]

[0752] The compound AB35433 was synthesized as follows. Step (1): [ka]

[0753] Compound 1 (6.2 g, 28.29 mmol, 1.2 eq) and compound 2 (5.4 g, 23.58 mmol, 1.0 eq) were dissolved in tetrahydrofuran (100 mL), and cuprous iodide (135 mg, 0.71 mmol, 0.03 eq), bistriphenylphosphine palladium dichloride (492 mg, 0.70 mmol, 0.03 eq), and triethylamine (7.2 g, 70.74 mmol, 3 eq) were added. The mixture was heated under nitrogen gas for 60 minutes. o The reaction was heated to 25°C for 16 hours. After TLC and LCMS analysis, the reaction mixture was diluted with water, and the organic phase was extracted twice with dichloromethane, backwashed once with brine, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by flash chromatography (100-200 mesh silica gel, PE / EA=3 / 1) to obtain compound 3 (6.5 g, 75.6% yield) as a yellow solid. Step (2): [ka]

[0754] Compound 3 (2.0 g, 5.46 mmol, 1.0 eq) was dissolved in potassium t-butoxide (50 mL), ammonium acetate (2.1 g, 27.32 mmol, 5.0 eq) and silver nitrate (1.85 g, 10.93 mmol, 0.2 eq) were added, and the reaction was allowed to proceed at room temperature for 16 h. After TLC and LCMS analysis showed a complete reaction, the reaction mixture was diluted with water, and the organic phase was extracted twice with dichloromethane, backwashed once with brine, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by flash chromatography (100-200 mesh silica gel, PE / EA = 3 / 1) to obtain compound 4 (1.5 g, 75.3% yield) as a yellow solid. Step (3): [ka]

[0755] Compound 4 (1.5 g, 4.11 mmol, 1.0 eq) was dissolved in tetrahydrofuran (20 mL), and lithium triethylborohydride (16.4 mL, 16.44 mmol, 4 eq) was added dropwise at -78 °C. The mixture was allowed to return to room temperature and the reaction was carried out for 3 hours. TLC check was performed, and the complete reaction was confirmed by LCMS check. Saturated aqueous sodium chloride solution was added, and the organic phase was extracted twice with ethyl acetate, backwashed once with brine, dried over anhydrous sodium sulfate, filtered, and then centrifuged to obtain compound 5 (630 mg, yield: 47.1%) as a yellow solid. Step (4): [ka]

[0756] Compound 5 (100 mg, 0.29 mmol, 1.0 eq) was dissolved in THF (5 mL), and methanesulfonyl chloride (68 mg, 0.58 mmol, 2.0 eq) and triethylamine (117 mg, 1.16 mmol, 4.0 eq) were added at 0°C. The reaction was carried out at room temperature for 2 hours, and TLC was performed. The complete reaction was confirmed by LCMS. The reaction solution was filtered and purified by reverse phase column chromatography (acetonitrile / water + 0.01% formic acid) to obtain compound AB35433 as a solid.

[0757] Compound AB35433: MS-ESI: Theoretical value [M+H] + :320.09, measured value [M+H] + :320.06. 1 H NMR(400 MHz, DMSO-d6) δ 9.48(s, 1H), 8.72(s, 1H), 7.73(s, 1H), 7.69(s, 1H), 7.50(s, 1H), 7.08(s, 1H), 6.40(s, 2H), 6.15(s, 2H), 4.74-4.41(m, 2H), 3.18-3.14(m, 2H).

[0758] Example 49 Synthesis of compound AB35467 The chemical structure of the compound AB35467 is as follows: [ka] AB35467

[0759] The compound AB35467 was synthesized as follows. [ka]

[0760] Compound 1 (200 mg, 0.56 mmol, 1.0 eq) was dissolved in anhydrous tetrahydrofuran (10 mL), and cycloamylmagnesium bromide (3.4 mL, 3.36 mmol, 6 eq, 1M) was added at 0°C. The reaction was carried out at room temperature for 0.5 hours, and TLC was performed. The complete reaction was confirmed by LCMS. The reaction was quenched with saturated aqueous ammonium chloride, and the organic phase was extracted twice with dichloromethane, dried over anhydrous sodium sulfate, filtered, and then centrifuged. The crude product was purified by reverse phase column chromatography (acetonitrile / water + 0.1% formic acid) to obtain compound AB35467.

[0761] Compound AB35467: MS-ESI: Theoretical value [M+H] + :390.17, Measured value [M+H] + :390.15. 1 H NMR(400 MHz, DMSO-d6) δ 7.17(s, 1H), 6.75(s, 1H), 6.58(s, 1H), 6.52(s, 1H), 5.97(s, 2H), 5.88(s, 2H), 5.79(s, 1H), 4.15(d, J= 8.0 Hz, 1H), 3.42-3.37(m, 1H), 2.87-2.82(m, 1H), 2.65-2.60(m, 1H), 2.21-2.15(m, 1H), 1.60-1.56(m, 1H), 1.45-1.10(m, 8H).

[0762] Example 50 Synthesis of compound AB35468 The chemical structure of the compound AB35468 is as follows: [ka] AB35468

[0763] The compound AB35468 was synthesized as follows. [ka]

[0764] Compound 1 (200 mg, 0.39 mmol, 1 eq) was dissolved in tetrahydrofuran (10 mL), and methyl magnesium bromide (0.6 mL, 1.95 mmol, 5 eq, 3M) was added under nitrogen gas protection at 0 ° C. The reaction was carried out at room temperature for 0.5 hours, and TLC was performed. The complete reaction was confirmed by LCMS. The reaction solution was quenched with saturated aqueous ammonium chloride, and the organic phase was extracted twice with dichloromethane, dried over anhydrous sodium sulfate, filtered, and then centrifuged. The crude product was purified by reverse phase column chromatography (acetonitrile / water + 0.1% formic acid, 30%-40% acetonitrile, reverse phase column Green ODS, 21.2 * 250 mm, 10 um, 120A) to obtain compound AB35468.

[0765] Compound AB35468: MS-ESI: Theoretical value [M+H] + : 484.24, Measured value [M+H] + :484.25. 1H NMR(400 MHz, DMSO-d6): δ 7.27-7.23(m, 2H), 7.18-7.12(m, 3H), 6.85-6.82(m, 4H), 6.01(d, J= 4.0Hz, 2H), 4.65-4.60(m, 1H), 3.76(s, 3H), 3.74(s, 3H), 3.18-3.08(m, 2H), 2.74-2.59(m, 6H), 1.72-1.63(m, 3H), 1.45-1.40(m, 1H), 0.93(d, J= 4.0Hz, 3H).

[0766] Example 51 Synthesis of compound AB35469 The chemical structure of the compound AB35469 is as follows: [ka]

[0767] The compound AB35469 was synthesized as follows. Step (1): [ka]

[0768] Compound 1 (10 g, 66.57 mmol, 1 eq) was dissolved in dichloromethane (200 mL), and Dyss-Martin oxidant (3.4 g, 79.88 mmol, 1.2 eq) was added in batches at 0 °C. The reaction was carried out at room temperature for 2 h. The reaction was confirmed to be complete by TLC. The reaction mixture was filtered, and the filtrate was concentrated and purified by flash chromatography (PE / EA = 100 / 1) to obtain the crude product as a yellow solid, compound 2 (7.8 g, yield: 79.6%). Step (2): [ka]

[0769] Compound 3 (2 g, 5.9 mmol, 1 eq) was dissolved in alcohol / acetic acid (30 mL / 5 mL), and compound 2 (7.8 g, 52.6 mmol, 9 eq) was added. o The reaction was carried out in C for 4 hours, and then an appropriate amount of hydrochloric acid was added to the reaction mixture and concentrated. A small amount of dichloromethane and an appropriate amount of ethyl acetate were added to the crude product, and the mixture was left for 0.5 hours before filtering off the solid. The filtrate was left overnight to precipitate a solid. The solid was filtered and collected to obtain compound 4 (1.2 g, yield: 40.4%) as a yellow solid. Step (3): [ka]

[0770] Compound 4 (200 mg, 0.39 mmol, 1 eq) was dissolved in chloroform (8 mL), and aqueous ammonia (4 mL) was added. The mixture was stirred for 30 minutes under the protection of nitrogen gas. o The reaction was carried out in C for 48 hours, the reaction mixture was diluted with water, the organic phase was extracted with dichloromethane, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by flash chromatography (DCM / MeOH = 100 / 1 to 50 / 1) to obtain compound AB35469.

[0771] Compound AB35469: MS-ESI: Theoretical value [M+H] + :586.13, Measured value [M+H] + :586.10. 1 H NMR(400 MHz, CDCl3) δ 7.30-7.26(m, 2H), 7.21-7.17(m, 3H), 7.07-7.00(m, 2H), 6.86(s, 1H), 6.67(s, 1H), 5.97(s, 2H), 5.58(s, 1H), 4.09-4.02(m, 1H), 3.93(s, 3H), 3.89(s, 3H), 3.46-3.42(m, 1H), 2.80-2.53(m, 6H), 1.83-1.75(m, 3H), 1.54-1.47(m, 1H).

[0772] Example 52 Synthesis of compound AB35475 The chemical structure of the compound AB35475 is as follows: [ka]

[0773] The compound AB35475 was synthesized as follows. Step (1): [ka]

[0774] Compound 1 (1.0 g, 2.79 mmol, 1 eq) was dissolved in N,N-dimethylformamide (20 mL), compound 2 (1.7 g, 11.16 mmol, 4 eq) was added, and the reaction was heated at 75 °C for 16 hours. TLC confirmed the complete reaction, and LCMS confirmed the complete reaction. The reaction mixture was diluted with water, and the organic phase was extracted twice with dichloromethane, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by flash chromatography (DCM / MeOH = 50 / 1 to 20 / 1) to give compound 3 (400 mg, yield: 25.6%). Step (2): [ka]

[0775] Compound 3 (200 mg, 0.42 mmol, 1.0 eq) was dissolved in chloroform (8 mL) and aqueous ammonia (4 mL). The reaction was allowed to proceed overnight at room temperature. TLC analysis was performed. LCMS analysis confirmed the complete reaction. The reaction mixture was diluted with water, and the organic phase was extracted twice with dichloromethane, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by flash chromatography (DCM / MeOH = 100 / 1 to 50 / 1) to obtain compound AB35475.

[0776] Compound AB35475: MS-ESI: Theoretical value [M+H] + :558.07, measured value [M+H] + :558.05. 1 H NMR(400 MHz, DMSO-d6) δ 7.29(s, 1H), 7.05(d, J= 8.0 Hz, 1H), 6.85(d, J= 8.0 Hz, 1H), 6.77(s, 1H), 6.29(s, 1H), 5.98(d, J= 4.0 Hz, 2H), 5.55(s, 1H), 4.12-4.08(m, 1H), 3.81-3.78(m, 1H), 3.77(s, 3H), 3.74-3.71(m, 1H), 3.63-3.60(m, 3H), 3.25-3.19(m, 1H), 2.72-2.66(m, 1H), 1.73-1.64(m, 4H), 1.47-1.41(m, 4H).

[0777] Example 53 Synthesis of compound AB35476 The chemical structure of compound AB35476 is as follows: [ka]

[0778] The compound AB35476 was synthesized as follows. Step (1): [ka]

[0779] Compound 1 (2.0 g, 5.59 mmol, 1 eq) was dissolved in acetonitrile (40 mL), compound 2 (5.1 g, 22.36 mmol, 4 eq) was added, and the reaction was heated at 80 °C for 16 hours. TLC analysis confirmed the complete reaction. LCMS analysis confirmed the complete reaction. The reaction mixture was diluted with water, and the organic phase was extracted twice with dichloromethane, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by flash chromatography (DCM / MeOH = 50 / 1 to 20 / 1) to obtain compound 3 (1.48 g, 48.2% yield) as a yellow solid. Step (2): [ka]

[0780] Compound 3 (1.3 g, 2.36 mmol, 1.0 eq) was dissolved in chloroform (40 mL) and aqueous ammonia (20 mL), and the resulting mixture was stirred for 30 minutes. o The reaction was carried out overnight at C, followed by TLC analysis and LCMS analysis to confirm the complete reaction. The reaction mixture was diluted with water, and the organic phase was extracted twice with dichloromethane, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by flash chromatography (DCM / MeOH = 100 / 1 to 50 / 1) to obtain compound AB35476.

[0781] Compound AB35476: MS-ESI: Theoretical value [M+H] + :588.11, Measured value [M+H] + :588.11. 1H NMR(400 MHz, DMSO-d6) δ 7.30(s, 1H), 7.27-7.23(m, 2H), 7.07(d, J= 12.0 Hz, 1H), 6.91-6.85(m, 4H), 6.76(s, 1H), 6.29(s, 1H), 5.98(d, J= 8.0 Hz, 2H), 5.58(s, 1H), 4.21-4.16(m, 1H), 4.04-4.01(m, 2H), 3.91-3.86(m, 1H), 3.77(s, 3H), 3.69-3.65(m, 1H), 3.59-3.53(m, 1H), 3.22-3.14(m, 1H), 2.66-2.62(m, 1H), 1.90-1.82(m, 2H), 1.21-1.10(m, 1H), 0.83-0.71(m, 1H).

[0782] Example 54 Synthesis of compound AB35478 The chemical structure of the compound AB35478 is as follows: [ka]

[0783] The compound AB35478 was synthesized as follows. Step (1): [ka]

[0784] Compound 1 (1.5 g, 4.19 mmol, 1 eq) was dissolved in N,N-dimethylformamide (30 mL), compound 2 (3.1 g, 16.76 mmol, 4 eq) was added, and the reaction was heated at 70 °C for 16 hours. TLC confirmed the complete reaction, and LCMS confirmed the complete reaction. The reaction mixture was diluted with water, and the organic phase was extracted twice with dichloromethane, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by flash chromatography (DCM / MeOH = 50 / 1 to 20 / 1) to obtain compound 3 (560 mg, yield: 26.2%). Step (2): [ka]

[0785] Compound 3 (160 mg, 0.31 mmol, 1.0 eq) was dissolved in chloroform (8 mL) and aqueous ammonia (4 mL), and the resulting mixture was stirred for 30 minutes. o The reaction was carried out overnight at C, followed by TLC analysis and LCMS analysis to confirm the complete reaction. The reaction mixture was diluted with water, and the organic phase was extracted twice with dichloromethane, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by flash chromatography (DCM / MeOH = 100 / 1 to 50 / 1) to obtain compound AB35478.

[0786] Compound AB35478: MS-ESI: Theoretical value [M+H] + :550.05, Actual value [M+H] + :500.25. 1 H NMR(400 MHz, CDCl3) δ 7.15(s, 1H), 6.97-6.87(m, 2H), 6.60(s, 1H), 6.09(s, 1H), 5.94(d, J= 4.0 Hz, 2H), 5.61(s, 1H), 4.98-4.80(m, 1H), 4.78-4.62(m, 1H), 4.37-4.33(m, 1H), 3.96-3.82(m, 5H), 3.71-3.64(m, 1H), 3.35-3.28(m, 1H), 2.74-2.68(m, 1H), 2.24-2.10(m, 2H).

[0787] Example 55 Compound SJ0002 was synthesized by conventional methods and has the following chemical structure: [ka] Compound SJ0002

[0788] Example 56 Compound SJ0003 was synthesized by conventional methods and has the following chemical structure: [ka] Compound SJ0003

[0789] Example 57 Compound SJ0005 was synthesized by conventional methods and has the following chemical structure: [ka] Compound SJ0005

[0790] Example 58 Compound SJ0006 was synthesized by conventional methods and has the following chemical structure: [ka] Compound SJ0006

[0791] Example 59 Compound SJ0007 was synthesized by conventional methods and has the following chemical structure: [ka] Compound SJ0007

[0792] Example 60 Compound SJ0008 was synthesized by conventional methods and has the following chemical structure: [ka] Compound SJ0008

[0793] Example 61 Compound SJ0010 was synthesized by conventional methods and has the following chemical structure: [ka] Compound SJ0010

[0794] Example 62 Compound SJ0011 was synthesized by conventional methods and has the following chemical structure: [ka] Compound SJ0011

[0795] Example 63 Compound SJ0013 was synthesized by conventional methods and has the following chemical structure: [ka] Compound SJ0013

[0796] Example 64 Compound SJ0014 was synthesized by conventional methods and has the following chemical structure: [ka] Compound SJ0014

[0797] Example 65 Compound SJ0015 was synthesized by conventional methods and has the following chemical structure: [ka] Compound SJ0015

[0798] Example 66 Compound SJ0017 was synthesized by conventional methods and has the following chemical structure: [ka] Compound SJ0017

[0799] Example 67 Compound SJ0018 was synthesized by conventional methods and has the following chemical structure: [ka] Compound SJ0018

[0800] Example 68 Compound SJ0019 was synthesized by conventional methods and has the following chemical structure: [ka] Compound SJ0019

[0801] Example 69 Compound SJ0020 was synthesized by conventional methods and has the following chemical structure: [ka] Compound SJ0020

[0802] Example 70 Compound SJ0021 was synthesized by conventional methods and has the following chemical structure: [ka] Compound SJ0021

[0803] Example 71 Compound SJ0022 was synthesized by conventional methods and has the following chemical structure: [ka] Compound SJ0022

[0804] Example 72 Compound SJ0023 was synthesized by conventional methods and has the following chemical structure: [ka] Compound SJ0023

[0805] Example 73 Compound SJ0025 was synthesized by conventional methods and has the following chemical structure: [ka] Compound SJ0025

[0806] Example 74 Compound SJ0026 was synthesized by conventional methods and has the following chemical structure: [ka] Compound SJ0026

[0807] Example 75 Compound SJ0027 was synthesized by conventional methods and has the following chemical structure: [ka] Compound SJ0027

[0808] Example 76 Compound SJ0029 was synthesized by conventional methods and has the following chemical structure: [ka] Compound SJ0029

[0809] Example 77 Compound SJ0030 was synthesized by conventional methods and has the following chemical structure: [ka] Compound SJ0030

[0810] Example 78 Compound SJ0031 was synthesized by conventional methods and has the following chemical structure: [ka] Compound SJ0031

[0811] Example 79 Compound SJ0032 was synthesized by conventional methods and has the following chemical structure: [ka] Compound SJ0032

[0812] Example 80 Compound SJ0033 was synthesized by conventional methods and has the following chemical structure: [ka] Compound SJ0033

[0813] Example 81 Compound SJ0034 was synthesized by conventional methods and has the following chemical structure: [ka] Compound SJ0034

[0814] Example 82 Compound SJ0035 was synthesized by conventional methods and has the following chemical structure: [ka] Compound SJ0035

[0815] Example 83 Synthesis of compound AB35484 The chemical structure of compound AB35484 is as follows: [ka] AB35484

[0816] The compound AB35484 was synthesized as follows. Step (1): [ka]

[0817] Compound 1 (7.1 g, 16.5 mmol, 1 eq) was dissolved in methanol (50 mL) and o At C, potassium carbonate (6.8 g, 49.5 mmol, 3 eq) and sodium borohydride (499 mg, 13.2 mmol, 0.8 eq) were added, and the mixture was stirred at 0 o The reaction was carried out at C for 1 hour, and the complete reaction was confirmed by LCMS check. The reaction was quenched with saturated aqueous ammonium chloride, and the solid was filtered and washed with a small amount of water and methanol to give compound 2. Step (2): [ka]

[0818] Compound 2 (1.0 g, 2.84 mmol, 1 eq) was dissolved in alcohol / acetic acid (10 mL / 8 mL), and phenylpropylaldehyde (3.8 g, 28.4 mmol, 10 eq) was added. The mixture was heated under nitrogen gas for 90 minutes. o C. The reaction is carried out for 4 hours, and when the reaction is complete, an appropriate amount of hydrochloric acid is added to the reaction solution to convert it into the hydrochloride salt. The product is concentrated and centrifuged, and a small amount of dichloromethane and an appropriate amount of ethyl acetate are added. The mixture is left to stand for 0.5 hours, and solid impurities are filtered off. The filtrate is left to stand overnight and then filtered to obtain compound 4. Step (3): [ka]

[0819] Compound 4 (200 mg, 0.39 mmol, 1 eq) was dissolved in aqueous ammonia (5 mL) and chloroform (10 mL) and stirred overnight at room temperature. After confirming the completeness of the reaction by LCMS, the reaction mixture was diluted with water, the organic phase was extracted with dichloromethane, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by flash chromatography (DCM / MeOH = 100 / 1 to 50 / 1) to obtain compound AB35484.

[0820] Compound AB35484: MS-ESI: Theoretical value [M+H] + :586.13, Measured value [M+H] + :586.10. 1 H NMR(400 MHz, DMSO-d6) δ 7.29-7.25(m, 2H), 7.21-7.17(m, 3H), 7.06(d, J= 8.0 Hz, 1H), 6.88(d, J= 8.0 Hz, 1H), 6.75(s, 2H), 5.53(s, 1H), 4.28-4.21(m, 4H), 3.84-3.79(m, 7H), 3.56-3.54(m, 1H), 2.68-2.51(m, 6H), 1.90-1.70(m, 2H).

[0821] Example 84 Synthesis of compound AB35485 The chemical structure of the compound AB35485 is as follows: [ka] AB35485

[0822] The compound AB35485 was synthesized as follows. [ka]

[0823] Compound 1 (200 mg, 0.39 mmol, 1 eq) was dissolved in tetrahydrofuran (10 mL), and methylmagnesium bromide (0.7 mL, 1.95 mmol, 5 eq, 3M) was added under nitrogen gas protection at 0°C. The reaction was carried out at room temperature for 0.5 hours. The reaction mixture was quenched with saturated aqueous ammonium chloride solution, and the organic phase was extracted twice with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by reverse phase column chromatography (acetonitrile / water + 0.1% formic acid) to obtain compound AB35485. [ka] Compound AB35485: MS-ESI: Theoretical value [M+H] + : 398.17, Measured value [M+H] + :398.15. 1H NMR(400 MHz, DMSO-d6) δ 7.21(s, 1H), 6.79(d, J= 8.0 Hz, 1H), 6.74(s, 1H), 6.65(d, J= 8.0 Hz, 1H),5.97(d, J= 4.0 Hz, 2H), 5.90(s, 1H), 4.73-4.68(m, 2H), 4.59-4.56(m, 1H), 4.03-4.00(m, 2H), 3.72(s, 3H), 3.24-3.16(m, 2H), 2.76-2.71(m, 2H), 2.11-2.01(m, 2H), 1.02(d, J= 8.0 Hz, 3H).

[0824] Example 85 Synthesis of compound AB35486 The chemical structure of compound AB35486 is as follows: [ka] AB35486

[0825] The compound AB35486 was synthesized as follows. Step (1): [ka]

[0826] Compound 1 (3.0 g, 5.38 mmol, 1 eq) was dissolved in alcohol (50 mL) and phenethylamine (652 mg, 53.8 mmol, 10 eq) was added. The reaction was carried out at 110 °C under nitrogen gas protection for 48 h. After the reaction was completed, the reaction mixture was concentrated and purified by flash chromatography (DCM / MeOH = 50 / 1) to obtain compound 3. Step (2): [ka]

[0827] Compound 3 (1.5 g, 3.25 mmol, 1 eq) was dissolved in chloroform (20 mL), and aqueous ammonia (10 mL) was added. The reaction was carried out overnight at room temperature under nitrogen gas protection. The complete reaction was confirmed by LCMS. The reaction mixture was diluted with water, and the organic phase was extracted with dichloromethane, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by flash chromatography (DCM / MeOH = 100 / 1 to 50 / 1) to obtain compound AB35486.

[0828] Compound AB35486: MS-ESI: Theoretical value [M+H] + :543.09, measured value [M+H] + :543.10. 1 H NMR(400 MHz, DMSO-d6) δ 7.30-7.25(m, 3H), 7.21-7.17(m, 3H), 6.92(d, J= 8.0 Hz, 1H), 6.74(s, 1H), 6.67(d, J= 12.0 Hz, 1H), 6.24(s, 1H), 5.97(d, J= 8.0 Hz, 2H), 5.68(s, 1H), 4.38-4.35(m, 1H), 3.74(s, 3H), 3.70-3.44(m, 2H), 3.28-3.24(m, 2H), 2.77-2.65(m, 4H).

[0829] Example 86 Synthesis of compound AB35487 The chemical structure of the compound AB35487 is as follows: [ka] AB35487

[0830] The compound AB35487 was synthesized as follows. Step (1): [ka]

[0831] Compound 1 (2.0 g, 5.59 mmol, 1 eq) was dissolved in N,N-dimethylformamide (30 mL), compound 2 (4.6 g, 27.95 mmol, 5 eq) was added, and the reaction was allowed to proceed at 60 °C overnight. The reaction mixture was diluted with water, and the organic phase was extracted twice with dichloromethane, washed with brine, dried over anhydrous sodium sulfate, filtered, and centrifuged to obtain compound 3 via flash chromatography (DCM / MeOH = 50 / 1 to 30 / 1). Step (2): [ka]

[0832] Compound 3 (200 mg, 0.41 mmol, 1 eq) was dissolved in chloroform (10 mL), and aqueous ammonia (5 mL) was added. The reaction mixture was stirred at room temperature overnight. The reaction mixture was diluted with water, and the organic phase was extracted with dichloromethane, washed with brine, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by flash chromatography (DCM / MeOH=100 / 1) to give compound AB35487.

[0833] Compound AB35487: MS-ESI: Theoretical value [M+H] + :524.10, measured value [M+H] + :524.10. 1H NMR(400 MHz, DMSO-d6) δ 7.33(s, 1H), 7.09(d, J= 8.0 Hz, 1H), 6.89(d, J= 8.0 Hz, 1H), 6.80(s, 1H), 6.32(s, 1H), 6.01(d, J= 8.0 Hz, 2H), 5.59(s, 1H), 4.18-4.13(m, 1H), 3.80(s, 3H), 3.73-3.62(m, 2H), 3.26-3.24(m, 1H), 2.76-2.70(m, 1H), 2.01-1.97(m, 1H), 1.75-1.70(m, 2H), 1.50-1.48(m, 2H), 1.35-1.32(m, 4H), 0.91-0.87(m, 3H).

[0834] Example 87 Synthesis of compound AB35488 The chemical structure of the compound AB35488 is as follows: [ka] AB35488

[0835] The compound AB35488 was synthesized as follows. Step (1): [ka]

[0836] Compound 1 (2.0 g, 5.93 mmol, 1 eq) was dissolved in alcohol / acetic acid (10 mL / 8 mL), and acetaldehyde (12 mL, 59.3 mmol, 10 eq, 5 M in THF) was added. The mixture was then heated under nitrogen gas for 90 minutes. o C. The reaction is carried out for 4 hours, and when the reaction is complete, an appropriate amount of hydrochloric acid is added to the reaction solution to convert it into the hydrochloride salt. The product is concentrated and centrifuged, and a small amount of dichloromethane and an appropriate amount of ethyl acetate are added. The mixture is left to stand for 0.5 hours, after which solid impurities are filtered off. The filtrate is left to stand overnight and then filtered to obtain compound 3. Step (2): [ka]

[0837] Compound 3 (200 mg, 0.50 mmol, 1 eq) was dissolved in chloroform (10 mL) and aqueous ammonia (5 mL). The reaction was carried out overnight at room temperature under nitrogen gas protection. The complete reaction was confirmed by LCMS. The reaction mixture was diluted with water, and the organic phase was extracted with dichloromethane, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by flash chromatography (DCM / MeOH=100 / 1) to obtain compound AB35488.

[0838] Compound AB35488: MS-ESI: Theoretical value [M+H] + :482.06, Measured value [M+H] + :482.05. 1 H NMR(400 MHz, DMSO-d6) δ 7.15-7.08(m, 2H), 6.88(s, 1H), 6.82(s, 1H), 6.02(s, 2H), 5.55(s, 1H), 3.87-3.80(s, 7H), 3.58-3.56(m, 1H), 2.70-2.58(m, 4H), 1.15-1.11(m, 3H).

[0839] Example 88 Synthesis of compound AB35489 The chemical structure of the compound AB35489 is as follows: [ka] AB35489

[0840] The compound AB35489 was synthesized as follows. Step (1): [ka]

[0841] Compound 1 (2.0 g, 5.93 mmol, 1 eq) was dissolved in alcohol / acetic acid (20 mL / 10 mL), caproaldehyde (5.9 g, 59.3 mmol, 10 eq) was added, and the mixture was heated under nitrogen gas for 90 minutes. o C. The reaction is carried out for 4 hours, and when the reaction is complete, an appropriate amount of hydrochloric acid is added to the reaction solution to convert it into the hydrochloride salt. The product is concentrated and centrifuged, and a small amount of dichloromethane and an appropriate amount of ethyl acetate are added. The mixture is left to stand for 0.5 hours, after which solid impurities are filtered off. The filtrate is left to stand overnight and then filtered to obtain compound 3. Step (2): [ka]

[0842] Compound 3 (200 mg, 0.44 mmol, 1 eq) was dissolved in anhydrous tetrahydrofuran (10 mL), and cycloamylmagnesium bromide (2.2 mL, 0.50 mmol, 5 eq, 1M) was added under nitrogen gas protection at 0 °C. The reaction was carried out at room temperature for 0.5 h. The complete reaction was confirmed by LCMS. The reaction mixture was quenched with saturated aqueous ammonium chloride solution, and the organic phase was extracted twice with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and centrifuged to obtain compound AB35489 via flash chromatography (DCM / MeOH=100 / 1).

[0843] Compound AB35489: MS-ESI: Theoretical value [M+H] + : 490.29, Measured value [M+H] + :490.30. 1H NMR(400 MHz, DMSO-d6) δ 6.88(s, 2H), 6.84(d, J= 4.0 Hz, 2H), 6.01(d, J= 4.0 Hz, 2H), 4.41(d, J= 8.0 Hz, 1H), 3.76(s, 3H), 3.73(s, 3H), 2.66-2.60(m, 2H), 2.12-2.05(m, 1H), 1.63-1.61(m, 1H), 1.38-1.21(m, 19H), 0.87-0.83(m, 3H).

[0844] Example 89 Synthesis of compound AB35490 The chemical structure of compound AB35490 is as follows: [ka] AB35490

[0845] The compound AB35490 was synthesized as follows. [ka]

[0846] Compound 1 (150 mg, 0.34 mmol, 1 eq) was dissolved in anhydrous tetrahydrofuran (10 mL), and cyclobutylmagnesium bromide (0.6 mL, 1.7 mmol, 5 eq, 3M) was added under nitrogen gas protection at 0 °C. The reaction was carried out at room temperature for 0.5 hours, and the reaction solution was quenched with saturated aqueous ammonium chloride solution. The organic phase was extracted twice with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and then centrifuged. The crude product was purified by reverse phase column chromatography (acetonitrile / water + 0.1% formic acid) to obtain compound AB35490.

[0847] Compound AB35490: MS-ESI: Theoretical value [M+H] + : 454.17, Measured value [M+H] + :454.25. 1H NMR(400 MHz, DMSO-d6) δ 7.21(s, 1H), 6.80-6.65(m, 3H), 5.97(s, 2H), 5.88(s, 1H), 4.53(d, J= 8.0 Hz, 1H), 4.13-4.11(m, 1H), 3,89-3.86(m, 3H), 3.73(s, 3H), 3.32-3.31(m, 2H), 2.80-2.75(m, 2H), 2.65-2.62(m, 1H), 2.20-2.07(m, 2H), 1.83-1.75(m, 3H), 1.57-1.55(m, 2H), 1.38-1.32(m, 1H).

[0848] Example 90 Synthesis of compound AB35491 The chemical structure of compound AB35491 is as follows: [ka] AB35491

[0849] The compound AB35491 was synthesized as follows. [ka]

[0850] Compound 1 (150 mg, 0.34 mmol, 1 eq) was dissolved in anhydrous tetrahydrofuran (10 mL), and cyclohexylmagnesium bromide (1.7 mL, 1.7 mmol, 5 eq, 1M) was added under nitrogen gas protection at 0 °C. The reaction was carried out at room temperature for 0.5 hours, and the reaction solution was quenched with saturated aqueous ammonium chloride solution. The organic phase was extracted twice with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and then centrifuged. The crude product was purified by reverse phase column chromatography (acetonitrile / water + 0.1% formic acid) to obtain compound AB35491.

[0851] Compound AB35491: MS-ESI: Theoretical value [M+H] +: 482.21, Measured value [M+H] + :482.20. 1 H NMR(400 MHz, DMSO-d6) δ 7.20(s, 1H), 6.81-6.63(m, 3H), 5.96(s, 2H), 5.83(s, 1H), 4.45(d, J= 4.0 Hz, 1H), 4.09-4.07(m, 1H), 3.90-3.86(m, 3H), 3.72(s, 3H), 3.38-3.35(m, 2H), 2.89-2.87(m, 1H), 2.63-2.61(m, 1H), 2.14-2.02(m, 2H), 1.64-1.46(m, 6H), 1.04-0.95(m, 5H).

[0852] Example 91 Synthesis of compound AB35492 The chemical structure of compound AB35492 is as follows: [ka] AB35492

[0853] The compound AB35492 was synthesized as follows. Step (1): [ka]

[0854] Compound 1 (2.0 g, 5.93 mmol, 1 eq) was dissolved in alcohol / acetic acid (20 mL / 10 mL), caproaldehyde (3.4 g, 59.3 mmol, 10 eq) was added, and the mixture was heated under nitrogen gas for 90 minutes. o C. The reaction is carried out for 4 hours, and when the reaction is complete, an appropriate amount of hydrochloric acid is added to the reaction solution to convert it into the hydrochloride salt. The product is concentrated and centrifuged, and a small amount of dichloromethane and an appropriate amount of ethyl acetate are added. The mixture is left to stand for 0.5 hours, after which solid impurities are filtered off. The filtrate is left to stand overnight and then filtered to obtain compound 3. Step (2): [ka]

[0855] Compound 3 (200 mg, 0.48 mmol, 1 eq) was dissolved in chloroform (10 mL), and aqueous ammonia (5 mL) was added. The reaction was carried out at room temperature under nitrogen gas protection overnight. The reaction mixture was diluted with water, and the organic phase was extracted with dichloromethane, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by flash chromatography (DCM / MeOH = 100 / 1) to obtain compound AB35492.

[0856] Compound AB35492: MS-ESI: Theoretical value [M+H] + : 496.07, Measured value [M+H] + :496.50. 1 H NMR(400 MHz, DMSO-d6) δ 7.14-7.06(m, 2H), 6.87(s, 1H), 6.77(s, 1H), 6.02(d, J= 8.0 Hz, 2H), 5.54(s, 1H), 3.86-3.79(m, 7H), 3.59-3.56(m, 1H), 2.73-2.70(m, 1H), 2.56-2.49(m, 3H), 1.66-1.59(m, 1H), 1.42-1.38(m, 1H), 0.97-0.94(m, 3H).

[0857] Example 92 Synthesis of compound AB35494 The chemical structure of compound AB35494 is as follows: [ka] AB35494

[0858] The compound AB35494 was synthesized as follows. Step (1): [ka]

[0859] Compound 1 (500 mg, 1.40 mmol, 1 eq) was dissolved in N,N-dimethylformamide (10 mL), butyl bromide (959 mg, 7.0 mmol, 5 eq) was added, and the reaction was carried out under nitrogen gas protection at 75 °C for 16 h. After the reaction was completed, the reaction mixture was concentrated and the crude product was purified by flash chromatography (DCM / MeOH = 50 / 1) to obtain compound 3. Step (2): [ka]

[0860] Compound 3 (200 mg, 0.44 mmol, 1 eq) was dissolved in chloroform (10 mL), and aqueous ammonia (5 mL) was added. The mixture was allowed to react overnight at room temperature under nitrogen gas protection. After the reaction was completed, the reaction mixture was diluted with water, and the organic phase was extracted with dichloromethane, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by flash chromatography (DCM / MeOH=100 / 1) to obtain compound AB35494.

[0861] Compound AB35494: MS-ESI: Theoretical value [M+H] + : 496.07, Measured value [M+H] + :496.30. 1 H NMR(400 MHz, DMSO-d6) δ 7.30(s, 1H), 7.06(d, J= 8.0 Hz, 1H), 6.86(d, J= 8.0 Hz, 1H), 6.77(s, 1H), 6.30(s, 1H), 5.99(d, J= 4.0 Hz, 2H), 5.56(s, 1H), 4.15-4.10(m, 1H), 3.77-3.73(m, 4H), 3.61-3.59(m, 2H), 3.26-3.19(m, 1H), 2.72-2.66(m, 1H), 1.64-1.55(m, 2H), 1.50-1.45(m, 2H), 0.94-0.91(m, 3H).

[0862] Example 93 Synthesis of compound AB35496 The chemical structure of compound AB35496 is as follows: [ka] AB35496

[0863] The compound AB35496 was synthesized as follows. Step (1): [ka]

[0864] Compound 1 (1.0 g, 2.79 mmol, 1 eq) was dissolved in N,N-dimethylformamide (20 mL), compound 2 (1.8 g, 13.95 mmol, 5 eq) was added, and the reaction was carried out at 60 °C for 16 h under nitrogen gas protection. After the reaction was completed, the reaction mixture was concentrated and the crude product was purified by flash chromatography (DCM / MeOH = 50 / 1) to obtain compound 3. Step (2): [ka]

[0865] Compound 3 (200 mg, 0.45 mmol, 1 eq) was dissolved in chloroform (10 mL), and aqueous ammonia (5 mL) was added. The mixture was allowed to react overnight at room temperature under nitrogen gas protection. After the reaction was completed, the reaction mixture was diluted with water, and the organic phase was extracted with dichloromethane, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by flash chromatography (DCM / MeOH=100 / 1) to obtain compound AB35496.

[0866] Compound AB35496: MS-ESI: Theoretical value [M+H] + :530.03, measured value [M+H] +:530.25. 1 H NMR(400 MHz, DMSO-d6) δ 7.30(s, 1H), 7.07(d, J= 8.0 Hz, 1H), 6.87(d, J= 8.0 Hz, 1H), 6.77(s, 1H), 6.29(s, 1H), 5.99(d, J= 4.0 Hz, 2H), 5.56(s, 1H), 4.16-4.11(m, 1H), 3.80-3.78(m, 1H), 3.72(s, 3H), 3.61-3.59(m, 3H), 3.56-3.54(m, 1H), 3.26-3.19(m, 1H), 2.72-2.67(m, 1H), 1.95-1.90(m, 2H), 1.82-1.78(m, 2H).

[0867] Example 94 Synthesis of compound AB35497 The chemical structure of the compound AB35497 is as follows: [ka] AB35497

[0868] The compound AB35497 was synthesized as follows. Step (1): [ka]

[0869] Compound 1 (2.0 g, 5.93 mmol, 1 eq) was dissolved in alcohol / acetic acid (20 mL / 10 mL), and octylaldehyde (7.6 g, 59.3 mmol, 10 eq) was added. The mixture was heated under nitrogen gas for 90 minutes. o C. The reaction is carried out for 4 hours, and when the reaction is complete, an appropriate amount of hydrochloric acid is added to the reaction solution to convert it into the hydrochloride salt. The product is concentrated and centrifuged, and a small amount of dichloromethane and an appropriate amount of ethyl acetate are added. The mixture is left to stand for 0.5 hours, after which solid impurities are filtered off. The filtrate is left to stand overnight and then filtered to obtain compound 3. Step (2): [ka]

[0870] Compound 3 (200 mg, 0.48 mmol, 1 eq) was dissolved in chloroform (10 mL), and aqueous ammonia (5 mL) was added. The mixture was allowed to react overnight at room temperature under nitrogen gas protection. After the reaction was completed, the reaction mixture was diluted with water, and the organic phase was extracted with dichloromethane, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by flash chromatography (DCM / MeOH=100 / 1) to obtain compound AB35497. [ka] Compound AB35497: MS-ESI: Theoretical value [M+H] + :566.16, Measured value [M+H] + :566.15. 1 H NMR(400 MHz, DMSO-d6) δ 7.15-7.04(m, 2H), 6.88(s, 1H), 6.79(s, 1H), 6.02(d, J= 4.0 Hz, 2H), 5.55(s, 1H), 3.87-3.80(m, 7H), 3.57-3.54(m, 1H), 2.70-2.65(m, 1H), 2.57-2.51(m, 3H), 1.66-1.58(m, 1H), 1.37-1.24(m, 11H), 0.85-0.82(m, 3H).

[0871] Example 95 Synthesis of compound AB35498 The chemical structure of the compound AB35498 is as follows: [ka] AB35498

[0872] The compound AB35498 was synthesized as follows. [ka]

[0873] Compound 1 (240 mg, 0.50 mmol, 1 eq) was dissolved in tetrahydrofuran (10 mL), and methyl magnesium bromide (0.8 mL, 2.5 mmol, 5 eq, 3M) was added under nitrogen gas protection at 0°C. The reaction was carried out at room temperature for 0.5 hours. The reaction mixture was quenched with saturated aqueous ammonium chloride solution, and the organic phase was extracted twice with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and centrifuged to obtain compound AB35498 from the crude product via thin layer chromatography (DCM / MeOH=30 / 1).

[0874] Compound AB35498: MS-ESI: Theoretical value [M+H] + : 456.21, Measured value [M+H] + :456.40. 1 H NMR(400 MHz, DMSO-d6) δ 7.29-7.24(m, 4H), 7.19-7.16(m, 1H), 7.05-6.94(m, 2H), 6.89(s, 1H), 6.81(s, 1H), 5.99(s, 2H), 4.69-4.65(m, 1H), 3.78(d, J= 8.0 Hz, 6H), 3.25-3.10(m, 2H), 2.90-2.60(m, 6H), 0.98(d, J= 4.0 Hz, 3H).

[0875] Example 96 Synthesis of compound AB35499 The chemical structure of the compound AB35499 is as follows: [ka] AB35499

[0876] The compound AB35499 was synthesized as follows. Step (1): [ka]

[0877] Compound 1 (2.0 g, 5.59 mmol, 1 eq) was dissolved in N,N-dimethylformamide (50 mL), ethyl bromide (53.0 g, 27.95 mmol, 10 eq) was added, and the reaction was carried out under nitrogen gas protection at 60 °C for 16 h. After the reaction was completed, the reaction mixture was concentrated and the crude product was purified by flash chromatography (DCM / MeOH = 50 / 1) to obtain compound 3. Step (2): [ka]

[0878] Compound 3 (200 mg, 0.46 mmol, 1 eq) was dissolved in chloroform (10 mL), and aqueous ammonia (5 mL) was added. The reaction was carried out at room temperature under nitrogen gas protection overnight. After the reaction was completed, the reaction solution was diluted with water, and the organic phase was extracted with dichloromethane, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by flash chromatography (DCM / MeOH=100 / 1) to obtain compound AB35499.

[0879] Compound AB35499: MS-ESI: Theoretical value [M+H] + :468.04, measured value [M+H] + :468.05. 1 H NMR(400 MHz, DMSO-d6) δ 7.30(s, 1H), 7.06(d, J= 8.0 Hz, 1H), 6.86(d, J= 8.0 Hz, 1H), 6.77(s, 1H), 6.29(s, 1H), 5.98(d, J= 8.0 Hz, 2H), 5.60(s, 1H), 4.09-3.96(m, 2H), 3.78-3.75(m, 4H), 3.60-3.58(m, 1H), 3.22-3.19(m, 1H), 2.67-2.65(m, 1H), 1.28-1.24(m, 3H).

[0880] Example 97 Synthesis of compound AB35500 The chemical structure of the compound AB35500 is as follows: [ka] AB35500

[0881] The compound AB35500 was synthesized as follows. Step (1): [ka]

[0882] Compound 1 (30 g, 219.59 mmol, 1 eq) was dissolved in dichloromethane (300 mL), and Dyss-Martin oxidant (111.7 g, 263.51 mmol, 1.2 eq) was added in batches at 0 °C. The reaction was carried out at room temperature for 2 h. After the reaction was completed, the solid was filtered off, and the filtrate was concentrated and purified by flash chromatography (PE / EA = 100 / 1) to give compound 2. Step (2): [ka]

[0883] Compound 3 (2 g, 5.93 mmol, 1 eq) was dissolved in alcohol / acetic acid (30 mL / 5 mL), and compound 2 (8.0 g, 59.3 mmol, 10 eq) was added. o C. The reaction is carried out for 4 hours, and when the reaction is complete, an appropriate amount of hydrochloric acid is added to form the hydrochloride salt. The mixture is concentrated and centrifuged, and a small amount of dichloromethane and an appropriate amount of ethyl acetate are added. The mixture is left for 0.5 hours, and the solid is filtered off. The filtrate is left overnight, and the solid is filtered off and dried to obtain compound 4. Step (3): [ka]

[0884] Compound 4 (300 mg, 0.61 mmol, 1 eq) was dissolved in anhydrous tetrahydrofuran (10 mL) and cycloamylmagnesium bromide (3 mL, 3.05 mmol, 5 eq, 1M) was added under nitrogen gas protection at 0 °C. The reaction was allowed to proceed at room temperature for 0.5 h. The reaction mixture was quenched with saturated aqueous ammonium chloride solution, and the organic phase was extracted twice with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and centrifuged. The crude product was purified by flash chromatography (DCM / MeOH = 100 / 1 to 50 / 1) to obtain compound AB35500.

[0885] Compound AB35500: MS-ESI: Theoretical value [M+H] + :524.25, measured value [M+H] + :524.25. 1 H NMR(400 MHz, DMSO-d6) δ 6.88(s, 2H),6.84(d, J= 4.0 Hz, 2H), 6.01(s, 2H), 4.41(d, J= 8.0 Hz, 1H), 3.76(s, 3H), 3.73(s, 3H), 3.62-3.59(m, 2H), 3.34(s, 1H), 2.66-2.53(m, 4H), 2.12-2.05(m, 1H), 1.71-1.58(m, 3H), 1.40-1.19(m, 14H).

[0886] Example 98 Synthesis of compound AB35501 The chemical structure of compound AB35501 is as follows: [ka] AB35501

[0887] The compound AB35501 was synthesized as follows. Step (1): [ka]

[0888] Compound 1 (25 g, 138.07 mmol, 1 eq) was dissolved in dichloromethane (300 mL), and Dyss-Martin oxidant (70.2 g, 165.68 mmol, 1.2 eq) was added in batches at 0 °C. The reaction was carried out at room temperature for 2 h. After the reaction was completed, the solid was filtered off, and the filtrate was concentrated and purified by flash chromatography (PE / EA = 100 / 1) to give compound 2. Step (2): [ka]

[0889] Compound 3 (2 g, 5.93 mmol, 1 eq) was dissolved in alcohol / acetic acid (30 mL / 5 mL), and compound 2 (10.6 g, 59.3 mmol, 10 eq) was added. o C. The reaction is carried out for 4 hours, and when the reaction is complete, an appropriate amount of hydrochloric acid is added to form the hydrochloride salt. The mixture is concentrated and centrifuged, and a small amount of dichloromethane and an appropriate amount of ethyl acetate are added. The mixture is left for 0.5 hours, and the solid is filtered off. The filtrate is left overnight, and the solid is filtered off and dried to obtain compound 4. Step (3): [ka]

[0890] Compo...

Claims

1. A compound of formula I, or an optical isomer or racemate thereof, or a solvate thereof, or a pharma- ceutically acceptable salt thereof, or a deuterated compound thereof. 【Chemistry 1】 (R １ and R ２ each independently represents a hydrogen atom, a deuterium atom, a halogen atom, a substituted or unsubstituted C1-C16 alkyl group, a substituted or unsubstituted C3-C16 cycloalkyl group, a substituted or unsubstituted 3-12 membered heterocycloalkyl group, a substituted or unsubstituted C1-C16 halogenated alkyl group, a substituted or unsubstituted C3-C16 halogenated cycloalkyl group, a substituted or unsubstituted C6-C16 aryl group, or a substituted or unsubstituted 5-12 membered heteroaryl group; R ３ , R ４ and R ５ are each independently a hydrogen atom, a halogen atom, R １７ -O-, R １７ -S- or (R １８ R １９ )N-; or R ３ and R ４ , or R ４ and R ５ are joined to form a substituted or unsubstituted 3- to 12-membered heterocycloalkyl ring; R ６ , R ８ , R １１ , R １２ , R １３ , R １４ and R １５ each independently represents a hydrogen atom, a substituted or unsubstituted C1-C8 alkyl group, or a halogen atom; R ７ represents a hydrogen atom, a substituted or unsubstituted C1-C12 alkyl group, a substituted or unsubstituted C1-C12 halogenated alkyl group, a substituted or unsubstituted C6-C16 aryl group-substituted or unsubstituted C1-C12 alkyl group-, or a substituted or unsubstituted 5-16 membered heteroaryl group-substituted or unsubstituted C1-C12 alkyl group-; R ９ and R １０ are joined to form a substituted or unsubstituted 3- to 12-membered heterocycloalkyl ring; R １７ represents a hydrogen atom or a substituted or unsubstituted C1-C16 alkyl group; 【Chemistry 2】 Substituted or unsubstituted C3-C16 cycloalkyl group, substituted or unsubstituted 3-12 membered heterocycloalkyl group, substituted or unsubstituted C3-C16 cycloalkyl group-substituted or unsubstituted C2-C10 acyl group-, substituted or unsubstituted C3-C16 cycloalkyl group-C(O)-, substituted or unsubstituted C1-C16 halogenated alkyl group, substituted or unsubstituted C3-C16 halogenated cycloalkyl group, substituted or unsubstituted 3-12 membered heterocycloalkyl group-substituted or unsubstituted C1-C12 alkyl group-, substituted or unsubstituted C6-C16 aryl group-substituted or unsubstituted C1-C12 alkyl group-, substituted or unsubstituted C6-C16 aryl group-substituted or unsubstituted C6-C16 aryl group-substituted or unsubstituted C1-C12 alkyl group-, substituted or unsubstituted 5- 16-membered heteroaryl group-substituted or unsubstituted C1-C12 alkyl group-, substituted or unsubstituted C6-C16 aryl group-O-substituted or unsubstituted C1-C12 alkyl group-, substituted or unsubstituted C6-C16 aryl group-S-substituted or unsubstituted C1-C12 alkyl group-, substituted or unsubstituted 5-16-membered heteroaryl group-O-substituted or unsubstituted C1-C12 alkyl group-, substituted or unsubstituted 5-16-membered heteroaryl group-S-substituted or unsubstituted C1-C12 alkyl group-, substituted or unsubstituted C2-C8 alkenyl group-substituted or unsubstituted C1-C8 alkyl group-substituted or unsubstituted C2-C8 alkenyl group-substituted or unsubstituted C1-C8 alkyl group-, substituted or unsubstituted C2-C8 alkenyl group-substituted or unsubstituted C1-C8 alkyl group-, or (R ２０ R ２１ ) N-substituted or unsubstituted C1-C12 alkyl group-; R １８ and R １９ each independently represents a hydrogen atom, a substituted or unsubstituted C1-C12 alkyl group, a substituted or unsubstituted C3-C12 cycloalkyl group, or a substituted or unsubstituted C6-C16 aryl group-substituted or unsubstituted C1-C12 alkyl group-; or R １８ and R １９ are joined to form a substituted or unsubstituted 3- to 12-membered heterocycloalkyl ring; R ２０ and R ２１ each independently represents a hydrogen atom, a substituted or unsubstituted C1-C12 alkyl group, a substituted or unsubstituted C3-C12 cycloalkyl group, or a substituted or unsubstituted C2-C10 ester group; or R ２０ and R ２１ are linked to form a substituted or unsubstituted 3- to 12-membered heterocycloalkyl group; said heterocycloalkyl group, said heteroaryl group and said heterocycloalkyl ring each independently have from 1 to 4 (preferably 1, 2, 3 or 4) heteroatoms selected from N, O and S on the heterocycle; The optional "substitution" mentioned above means that one or more (preferably 1, 2, 3, 4, 5, 6, 7, or 8) hydrogen atoms on the ring or atomic group are each independently replaced by a C1-C10 alkyl group, a C2-C6 alkenyl group, a C3-C12 cycloalkyl group, a C1-C10 halogenated alkyl group, a C3-C8 halogenated cycloalkyl group, a C3-C8 cycloalkoxyl group, a C3-C8 cycloalkylthiol group, a C3-C8 halogenated cycloalkoxyl group, a C3-C8 halogenated cycloalkylthiol group, a halo a halogen atom, a nitro group, -CN, a hydroxyl group, a mercapto group, an amino group, a C1-C4 carboxyl group, a C2-C8 ester group, a C2-C4 acylamino group, a C2-C6 acyl group, a C1-C10 alkoxyl group, a C1-C10 alkylthiol group, a C1-C10 halogenated alkoxyl group, a C1-C10 halogenated alkylthiol group, a C6-C12 aryl group, a C6-C12 aryl group-O-, a 5-10 membered heteroaryl group, a 5-10 membered heteroaryl group-O-, a 5-10 membered heterocycloalkyl group, and (R ２０ R ２１ )N-)

2. 2. The compound of formula I according to claim 1, characterized in that the compound has the following chemical structure: 【Chemistry 3】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】

3. (a) a compound of formula I according to claim 1, or an optical isomer or racemate thereof, or a solvate thereof, or a pharma- ceutically acceptable salt thereof, or a deuterated compound thereof; and (b) a pharma- ceutically acceptable carrier. A composition comprising:

4. Use of a compound of formula I according to claim 1, or an optical isomer or racemate thereof, or a solvate thereof, or a pharma- ceutically acceptable salt thereof, or a deuterated compound thereof, for the preparation of a composition or preparation for use in the prevention and / or treatment of tumors; The tumor is Tumors in which the mitochondrial permeability transition pore is underexpressed, absent, underactivated, or inactivated; and / or tumors in which peptidyl prolyl isomerase F is underexpressed, not expressed, underactivated, or inactivated; 23. The method of claim 22,

5. The tumor in which the mitochondrial permeability transition pore is underexpressed or underactivated refers to a tumor in which the ratio (H1 / H0) between the expression level or activity H1 of the mitochondrial permeability transition pore in a certain cell (e.g., a tumor cell) and the expression level or activity H0 of the mitochondrial permeability transition pore in a similar cell or a normal cell (e.g., a cancerous bladder tissue cell) is <1.0, preferably ≦0.8, and more preferably ≦0.7, ≦0.6, ≦0.5, ≦0.4, ≦0.3, ≦0.2, ≦0.1, ≦0.05, ≦0.01, ≦0.005, ≦0.001, ≦0.0001, ≦0.00001, ≦0.000001 or ≦0.0000001; and / or The tumor in which peptidyl prolyl isomerase F is underexpressed or underactivated refers to a tumor in which the ratio (C1 / C0) between the expression level or activity C1 of peptidyl prolyl isomerase F in a certain cell (e.g., a tumor cell) and the expression level or activity C0 of peptidyl prolyl isomerase F in a similar cell or a normal cell (e.g., a cancerous bladder tissue cell) is <1.0, preferably ≦0.8, and more preferably ≦0.7, ≦0.6, ≦0.5, ≦0.4, ≦0.3, ≦0.2, ≦0.1, ≦0.05, ≦0.01, ≦0.005, ≦0.001, ≦0.0001, ≦0.00001, ≦0.000001, or ≦0.0000001.

5. The use according to claim 4.

6. The allogeneic cells are Tumor cells in which the mitochondrial permeability transition pore is normally expressed, highly expressed, normally activated, or highly activated; and / or tumor cells in which peptidyl prolyl isomerase F is normally expressed, highly expressed, normally activated, or highly activated, 6. Use according to claim 5.

7. The use according to claim 4, characterized in that the tumor comprises a brain tumor.

8. is used to determine whether a compound of formula I according to claim 1, or an optical isomer or racemate thereof, or a solvate thereof, or a pharma- ceutically acceptable salt thereof, or a deuterated compound thereof, is suitable for tumor prevention and / or treatment in a tumor patient, A marker having a mitochondrial permeability transition pore and / or peptidylprolyl isomerase F.

9. 2. The compound of formula I according to claim 1, or an optical isomer or racemate thereof, or a solvate thereof, or a pharma- ceutically acceptable salt thereof, or a deuterated compound thereof, for use in the manufacture of a companion diagnostic kit for determining whether a tumor patient is suitable for the prevention and / or treatment of a tumor, (i) Use of a detection reagent kit comprising a detection reagent used for detecting the expression level or activity of a mitochondrial membrane permeability transition pore and / or the expression level or activity of peptidyl prolyl isomerase F, The accompanying diagnostic kit when the mitochondrial permeability transition pore is underexpressed, not expressed, underactivated or inactivated in the tumor cells of a tumor patient, and / or when peptidylprolyl isomerase F is underexpressed, not expressed, underactivated or inactivated, said compound of formula I according to the first aspect of the invention, or an optical isomer or racemate thereof, or a solvate thereof, or a pharma- ceutically acceptable salt thereof, or a deuterated compound thereof, becomes suitable for the prevention and / or treatment of tumors in said tumor patient, and / or and further comprising an instruction manual or label stating that when the mitochondrial permeability transition pore and / or peptidyl prolyl isomerase F are overexpressed or overactivated in tumor cells of a tumor patient, the compound of formula I according to the first aspect of the present invention, or an optical isomer or racemate thereof, or a solvate thereof, or a pharma- ceutically acceptable salt thereof, or a deuterated compound thereof becomes unsuitable for tumor prevention and / or treatment in said tumor patient. Use of a detection reagent kit comprising:

10. (i) a detection agent for detecting the expression level or activity of the mitochondrial membrane permeability transition pore and / or the expression level or activity of peptidyl prolyl isomerase F; (ii) a compound of formula I according to claim 1, or an optical isomer or racemate thereof, or a solvate thereof, or a pharma- ceutically acceptable salt thereof, or a deuterated compound thereof; A medical kit comprising:

11. The use of an inhibitor of the mitochondrial permeability transition pore and / or an inhibitor of peptidylprolyl isomerase F for producing a composition or formulation used to enhance the antitumor effect of an antitumor drug.

12. The antitumor drug comprises a compound of formula I according to claim 1, or an optical isomer or racemate thereof, or a solvate thereof, or a pharma- ceutically acceptable salt thereof, or a deuterated compound thereof; 12. The use according to claim 11 .

13. (1) a first active ingredient comprising an antitumor drug; (2) a second active ingredient containing an inhibitor of the mitochondrial membrane permeability transition pore and / or an inhibitor of peptidyl prolyl isomerase F; A composition comprising:

14. The antitumor drug comprises a compound of formula I according to claim 1, or an optical isomer or racemate thereof, or a solvate thereof, or a pharma- ceutically acceptable salt thereof, or a deuterated compound thereof; The composition of claim 13.

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