Aromatic ring compound

Abstract

The present invention relates to an aromatic ring compound. Specifically, 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. The compound of the present invention has an excellent blood glucose lowering effect.

Description

An aromatic ring compound Technical Field

[0001] The present invention relates to the field of medicine, in particular to an aromatic ring compound. Background Art

[0002] Hyperglycemia is a common condition that can be caused by a variety of factors, including genetic factors such as a family history of diabetes, an unhealthy diet, and obesity. Long-term hyperglycemia can cause pathological changes in various tissues and organs throughout the body, leading to acute and chronic complications such as dehydration, electrolyte imbalances, nutritional deficiencies, decreased immunity, impaired renal function, neuropathy, fundus lesions, cardiovascular and cerebrovascular diseases, and diabetic foot. Therefore, timely and effective prevention and treatment of hyperglycemia is necessary. However, the current clinical practice still lacks an effective drug for lowering blood sugar, and the development of a drug that lowers blood sugar has been a hot topic of research.

[0003] Therefore, there is a need in the art to develop a drug that can effectively treat hyperglycemia. Summary of the Invention

[0004] The purpose of the present invention is to provide a compound that can effectively lower blood sugar.

[0005] In a first aspect, the present invention provides a compound of formula I, or an optical isomer thereof, or a racemate thereof, or a solvate thereof, or a pharmaceutically acceptable salt thereof, or a deuterated compound thereof;

[0006] in,

[0007] Ring A is a substituted or unsubstituted C6-C12 aromatic ring, a substituted or unsubstituted 3-12-membered heteroaromatic ring, a substituted or unsubstituted C6-C12 aromatic ring and a 3-10-membered heterocycloalkane ring, or a substituted or unsubstituted 3-12-membered heteroaromatic ring and a 3-10-membered heterocycloalkane ring;

[0008] R1 is

[0009] R2 is hydrogen, substituted or unsubstituted C6-C12 aryl, substituted or unsubstituted C6-C12 aryl-, substituted or unsubstituted C1-C8 alkyl-, substituted or unsubstituted 3-12 heteroaryl, substituted or unsubstituted 3-12 heteroaryl-, substituted or unsubstituted C1-C8 alkyl-, substituted or unsubstituted C1-C10 alkyl, substituted or unsubstituted C3-C10 cycloalkyl;

[0010] R3 and R4 are each independently hydrogen, substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C3-C8 cycloalkyl;

[0011] R5 is a substituted or unsubstituted C6-C14 aryl group, or a substituted or unsubstituted 3-12 membered heteroaryl group;

[0012] R6 is hydrogen, substituted or unsubstituted C1-C8 alkyl;

[0013] R7 and R8 are linked to form a substituted or unsubstituted C3-C12 cycloalkane ring, or a substituted or unsubstituted 3-12 membered heterocycloalkane ring;

[0014] R9 and R 10 are each independently hydrogen, substituted or unsubstituted C6-C12 aryl, substituted or unsubstituted C6-C12 aryl-substituted or unsubstituted C1-C8 alkyl-, substituted or unsubstituted C1-C10 alkyl; or R9 and R 10 Connected to form a substituted or unsubstituted 5-12 membered heterocycloalkyl group, or a substituted or unsubstituted 5-12 membered heteroaryl group;

[0015] n is 0, 1, 2, 3, 4 or 5;

[0016] Ring B is a substituted or unsubstituted C6-C12 aromatic ring, or a substituted or unsubstituted 3-12 membered heteroaromatic ring.

[0017] In another preferred embodiment, Ring A is a substituted or unsubstituted C6-C12 aromatic ring, a substituted or unsubstituted 3-10 membered heteroaromatic ring, a substituted or unsubstituted C6-C12 aromatic ring and a 3-10 membered heterocycloalkane ring, or a substituted or unsubstituted 3-10 membered heteroaromatic ring and a 3-10 membered heterocycloalkane ring.

[0018] In another preferred embodiment, Ring A is a substituted or unsubstituted C6-C12 aromatic ring, a substituted or unsubstituted 5-10 membered heteroaromatic ring, a substituted or unsubstituted C6-C12 aromatic ring and a 5-10 membered heterocycloalkane ring, or a substituted or unsubstituted 5-10 membered heteroaromatic ring and a 5-10 membered heterocycloalkane ring.

[0019] In another preferred embodiment, Ring A is a substituted or unsubstituted C6-C12 aromatic ring, a substituted or unsubstituted 5-10 membered heteroaromatic ring, a substituted or unsubstituted C6-C12 aromatic ring and a 5-8 membered heterocycloalkane ring, or a substituted or unsubstituted 5-8 membered heteroaromatic ring and a 5-8 membered heterocycloalkane ring.

[0020] In another preferred embodiment, ring A is a substituted or unsubstituted C6-C12 aromatic ring, a substituted or unsubstituted 5-12 membered heteroaromatic ring, a substituted or unsubstituted C6-C12 aromatic ring and a 3-10 membered heterocycloalkane ring, or a substituted or unsubstituted 5-12 membered heteroaromatic ring and a 3-10 membered heterocycloalkane ring.

[0021] In another preferred embodiment, Ring A is a substituted or unsubstituted C6-C12 aromatic ring, a substituted or unsubstituted C6-C12 aromatic ring and a 3-10 membered heterocycloalkane ring, a 3-membered heteroaromatic ring, a 4-membered heteroaromatic ring, a 5-membered heteroaromatic ring, a 6-membered heteroaromatic ring, a 7-membered heteroaromatic ring, an 8-membered heteroaromatic ring, a 9-membered heteroaromatic ring, a 10-membered heteroaromatic ring, an 11-membered heteroaromatic ring, a 12-membered heteroaromatic ring, a 6-membered heteroaromatic ring and a 5-membered heterocycloalkane ring, or a 6-membered heteroaromatic ring and a 6-membered heterocycloalkane ring.

[0022] In another preferred embodiment, ring A is a substituted or unsubstituted pyridine ring, a substituted or unsubstituted pyrrolopyridine ring, a substituted or unsubstituted pyrazolopyridine ring, a substituted or unsubstituted pyrimidine ring, a substituted or unsubstituted dihydropyrrolopyridine ring, a substituted or unsubstituted tetrahydropyridopyrimidine ring, a substituted or unsubstituted pyrrolopyrimidine ring, a substituted or unsubstituted dihydropyrrolopyrimidine ring, a substituted or unsubstituted pyrazolopyridine ring, or a substituted or unsubstituted imidazopyridine ring.

[0023] In another preferred embodiment, the substituted or unsubstituted pyrrolopyridine ring is a substituted or unsubstituted 1H-pyrrolo[2,3-c]pyridine ring, a substituted or unsubstituted 1H-5λ 4 -pyrrolo[3,2-c]pyridine ring, or a substituted or unsubstituted 3H-pyrrolo[2,3-c]pyridine ring.

[0024] In another preferred embodiment, the substituted or unsubstituted pyrazolopyridine ring is a substituted or unsubstituted 1H-pyrazolo[3,4-c]pyridine ring.

[0025] In another preferred embodiment, the substituted or unsubstituted dihydropyrrolopyridine ring is a substituted or unsubstituted 2,3-dihydro-1H-pyrrolo[3,2-c]pyridine ring.

[0026] In another preferred embodiment, the substituted or unsubstituted tetrahydropyridopyrimidine ring is a substituted or unsubstituted 5,6,7,8-tetrahydropyrido[2,3-d]pyrimidine ring.

[0027] In another preferred embodiment, the substituted or unsubstituted pyrrolopyrimidine ring is a substituted or unsubstituted 7H-pyrrolo[2,3-d]pyrimidine ring.

[0028] In another preferred embodiment, the substituted or unsubstituted dihydropyrrolopyrimidine ring is a substituted or unsubstituted 6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine ring.

[0029] In another preferred embodiment, the substituted or unsubstituted pyrazolopyridine ring is a substituted or unsubstituted 1H-pyrazolo[4,3-c]pyridine ring.

[0030] In another preferred embodiment, the substituted or unsubstituted imidazopyridine ring is a substituted or unsubstituted 1H-imidazo[4,5-c]pyridine ring, or a substituted or unsubstituted 3H-imidazo[4,5-c]pyridine ring.

[0031] In another preferred embodiment, R1 is connected to a pyridine ring, a pyrrole ring, a pyrazole ring, a pyrimidine ring, a dihydropyrrole ring, a tetrahydropyridine ring or an imidazole ring.

[0032] In another preferred embodiment, R1 is connected to a ring heteroatom or a ring carbon atom on the ring.

[0033] In another preferred embodiment, R1 is attached to a ring N atom on the ring.

[0034] In another preferred embodiment, R1 is connected to a ring N atom or a ring carbon atom on a pyridine ring, a pyrrole ring, a pyrazole ring, a pyrimidine ring, a dihydropyrrole ring, a tetrahydropyridine ring or an imidazole ring.

[0035] In another preferred embodiment, R2 is connected to a pyridine ring, a pyrrole ring, a pyrazole ring, a pyrimidine ring, a dihydropyrrole ring, a tetrahydropyridine ring or an imidazole ring.

[0036] In another preferred embodiment, R2 is connected to a ring heteroatom or a ring carbon atom on the ring.

[0037] In another preferred embodiment, R2 is attached to a ring nitrogen atom of the ring.

[0038] In another preferred embodiment, R2 is connected to a ring N atom or a ring carbon atom on a pyridine ring, a pyrrole ring, a pyrazole ring, a pyrimidine ring, a dihydropyrrole ring, a tetrahydropyridine ring or an imidazole ring.

[0039] In another preferred embodiment, ring A is ring, ring, ring, ring, ring, ring, ring, ring, ring, ring, ring, ring, ring, ring, ring, ring, ring, ring, ring, ring, ring, ring.

[0040] In another preferred embodiment, R3 and R4 are each independently hydrogen, substituted or unsubstituted C1-C6 alkyl, or substituted or unsubstituted C3-C6 cycloalkyl.

[0041] In another preferred embodiment, R3 and R4 are each independently hydrogen, substituted or unsubstituted C1-C4 alkyl, or substituted or unsubstituted C3-C6 cycloalkyl.

[0042] In another preferred embodiment, R3 and R4 are each independently hydrogen, substituted or unsubstituted C1-C2 alkyl, or substituted or unsubstituted C3-C6 cycloalkyl.

[0043] In another preferred embodiment, R3 and R4 are each independently hydrogen, methyl, ethyl, propyl or butyl.

[0044] In another preferred embodiment, n is 0, 1, 2 or 3.

[0045] In another preferred embodiment, n is 1.

[0046] In another preferred embodiment, R5 is a substituted or unsubstituted C6-C12 aryl group, or a substituted or unsubstituted 3-12 membered heteroaryl group.

[0047] In another preferred embodiment, R5 is a substituted or unsubstituted C6-C10 aryl group, or a substituted or unsubstituted 3-10 membered heteroaryl group.

[0048] In another preferred embodiment, R5 is a substituted or unsubstituted C6-C8 aryl group, or a substituted or unsubstituted 3-8 membered heteroaryl group.

[0049] In another preferred embodiment, R5 is a substituted or unsubstituted C6-C8 aryl group, or a substituted or unsubstituted 5-8 membered heteroaryl group.

[0050] In another preferred embodiment, R5 is substituted or unsubstituted C6 aryl, substituted or unsubstituted C7 aryl, substituted or unsubstituted C8 aryl, substituted or unsubstituted C6 heteroaryl, substituted or unsubstituted C7 heteroaromatic group, or substituted or unsubstituted C8 heteroaryl.

[0051] In another preferred embodiment, R5 is substituted or unsubstituted phenyl, or substituted or unsubstituted pyridyl.

[0052] In another preferred embodiment, R5 is

[0053] R 11 、R 12 、R 13 、R 14 and R 15Each is independently hydrogen, halogen, nitro, amino, C1-C8 alkyl, C1-C8 alkoxy, C1-C8 alkylthio, C1-C8 haloalkyl, C1-C8 haloalkoxy, or C1-C8 haloalkylthio.

[0054] In another preferred embodiment, R 11 、R 12 、R 13 、R 14 and R 15 Each is independently hydrogen, halogen, nitro, amino, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio, C1-C6 haloalkyl, C1-C6 haloalkoxy, or C1-C6 haloalkylthio.

[0055] In another preferred embodiment, R 11 、R 12 、R 13 、R 14 and R 15 Each is independently hydrogen, halogen, nitro, amino, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 haloalkyl, C1-C4 haloalkoxy, or C1-C4 haloalkylthio.

[0056] In another preferred embodiment, R 11 、R 12 、R 13 、R 14 and R 15 Each is independently hydrogen, halogen, nitro, amino, C1-C2 alkyl, C1-C2 alkoxy, C1-C2 alkylthio, C1-C2 haloalkyl, C1-C2 haloalkoxy, or C1-C2 haloalkylthio.

[0057] In another preferred embodiment, R 11 、R 12 、R 13 、R 14 and R 15 Each is independently hydrogen, methyl, halogen (such as fluorine, chlorine or bromine), nitro, methoxy, F3C-, or F3C-O-.

[0058] In another preferred embodiment, the halogen is fluorine, chlorine, bromine or iodine.

[0059] In another preferred embodiment, R5 is

[0060] In another preferred embodiment, R6 is hydrogen, or a substituted or unsubstituted C1-C6 alkyl group.

[0061] In another preferred embodiment, R6 is hydrogen, or a substituted or unsubstituted C1-C4 alkyl group.

[0062] In another preferred embodiment, R6 is hydrogen.

[0063] In another preferred embodiment, R7 and R8 are linked to form a substituted or unsubstituted C3-C10 cycloalkane ring, or a substituted or unsubstituted 3-10 membered heterocycloalkane ring.

[0064] In another preferred embodiment, R7 and R8 are linked to form a substituted or unsubstituted C3-C8 cycloalkane ring, or a substituted or unsubstituted 3-8 membered heterocycloalkane ring.

[0065] In another preferred embodiment, R7 and R8 are linked to form a substituted or unsubstituted C5-C8 cycloalkane ring, or a substituted or unsubstituted 5-8 membered heterocycloalkane ring.

[0066] In another preferred embodiment, R7 and R8 are linked to form a substituted or unsubstituted C5-C6 cycloalkane ring, or a substituted or unsubstituted 5-6 membered heterocycloalkane ring.

[0067] In another preferred embodiment, R7 and R8 are linked to form a substituted or unsubstituted C5 cycloalkane ring, a substituted or unsubstituted C6 cycloalkane ring, a substituted or unsubstituted 5-membered heterocycloalkane ring, or a substituted or unsubstituted 6-membered heterocycloalkane ring.

[0068] In another preferred embodiment, the cycloalkane ring has 1, 2 or 3 carbon-carbon double bonds (C=C).

[0069] In another preferred embodiment, R7 and R8 are linked to form a substituted or unsubstituted cyclopentene ring, or a substituted or unsubstituted cyclohexene ring.

[0070] In another preferred embodiment, R7 and R8 are linked to form a substituted or unsubstituted Cyclic, substituted or unsubstituted ring.

[0071] In another preferred embodiment, ring B is a substituted or unsubstituted C6-C10 aromatic ring, or a substituted or unsubstituted 3-10 membered heteroaromatic ring.

[0072] In another preferred embodiment, ring B is a substituted or unsubstituted C6-C8 aromatic ring, or a substituted or unsubstituted 5-8 membered heteroaromatic ring.

[0073] In another preferred embodiment, ring B is a substituted or unsubstituted C6 aromatic ring, a substituted or unsubstituted C7 aromatic ring, a substituted or unsubstituted C8 aromatic ring, a substituted or unsubstituted 6-membered heteroaromatic ring, a substituted or unsubstituted 7-membered heteroaromatic ring, or a substituted or unsubstituted 8-membered heteroaromatic ring.

[0074] In another preferred embodiment, ring B is a substituted or unsubstituted benzene ring.

[0075] In another preferred embodiment, ring B is a substituted or unsubstituted benzene ring, wherein the substitution is that 1, 2, 3 or 4 hydrogen atoms on the benzene ring are independently replaced by substituents selected from the group consisting of halogen (such as fluorine or chlorine), methyl, nitro, methoxy, F3C-, or F3C-O-.

[0076] In another preferred embodiment, ring B is

[0077] R 16 、R 17 、R 18 and R 19 Each is independently hydrogen, halogen, nitro, amino, C1-C8 alkyl, C1-C8 alkoxy, C1-C8 alkylthio, C1-C8 haloalkyl, C1-C8 haloalkoxy, or C1-C8 haloalkylthio.

[0078] In another preferred embodiment, R 16 、R 17 、R 18 and R 19 Each is independently hydrogen, halogen, nitro, amino, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio, C1-C6 haloalkyl, C1-C6 haloalkoxy, or C1-C6 haloalkylthio.

[0079] In another preferred embodiment, R 16 、R 17 、R 18 and R 19 Each is independently hydrogen, halogen, nitro, amino, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 haloalkyl, C1-C4 haloalkoxy, or C1-C4 haloalkylthio.

[0080] In another preferred embodiment, R 16 、R 17 、R 18 and R 19 Each is independently hydrogen, halogen, nitro, amino, C1-C2 alkyl, C1-C2 alkoxy, C1-C2 alkylthio, C1-C2 haloalkyl, C1-C2 haloalkoxy, or C1-C2 haloalkylthio.

[0081] In another preferred embodiment, R 16 、R 17 、R 18 and R 19 Each is independently hydrogen, halogen (such as fluorine or chlorine), methyl, nitro, methoxy, F3C-, or F3C-O-.

[0082] In another preferred embodiment, ring B is Among them, a or b refers to The linking site is connected to R8.

[0083] In another preferred embodiment, a or b refers to The linking site is connected to the C of the -C(O)- link.

[0084] In another preferred embodiment, ring B is

[0085] In another preferred embodiment, for

[0086] In another preferred embodiment, for

[0087] R6 and Ring B are each independently as defined above;

[0088] R 20 、R 21 、R 22 、R 22 、R 23 、R 24 and R 25 Each is independently hydrogen or C1-C8 alkyl.

[0089] In another preferred embodiment, for

[0090] In another preferred embodiment, R 20 、R 21 、R 22 、R 22 、R 23 、R 24 and R 25 Each is independently hydrogen or C1-C6 alkyl.

[0091] In another preferred embodiment, R 20 、R 21 、R 22 、R 22 、R 23 、R 24 and R 25 Each is independently hydrogen or C1-C4 alkyl.

[0092] In another preferred embodiment, R 20 、R 21 、R 22 、R 22 、R 23 、R 24 and R 25Each is independently hydrogen or C1-C2 alkyl.

[0093] In another preferred embodiment, R 20 、R 21 、R 22 、R 22 、R 23 、R 24 and R 25 are each independently hydrogen.

[0094] In another preferred embodiment, for

[0095] In another preferred embodiment, for

[0096] In another preferred embodiment, R2 is hydrogen, substituted or unsubstituted C6-C10 aryl, substituted or unsubstituted C6-C10 aryl-substituted or unsubstituted C1-C6 alkyl-, substituted or unsubstituted 3-10 heteroaryl, substituted or unsubstituted 3-10 heteroaryl-substituted or unsubstituted C1-C6 alkyl-, substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C3-C8 cycloalkyl.

[0097] In another preferred embodiment, R2 is hydrogen, substituted or unsubstituted C6-C8 aryl, substituted or unsubstituted C6-C8 aryl-substituted or unsubstituted C1-C4 alkyl-, substituted or unsubstituted 3-8 heteroaryl, substituted or unsubstituted 3-8 heteroaryl-substituted or unsubstituted C1-C4 alkyl-, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C3-C6 cycloalkyl.

[0098] In another preferred embodiment, R2 is hydrogen, substituted or unsubstituted C6-C8 aryl, substituted or unsubstituted C6-C8 aryl-, substituted or unsubstituted C1-C2 alkyl-, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C3-C6 cycloalkyl.

[0099] In another preferred embodiment, R2 is hydrogen, substituted or unsubstituted phenyl, substituted or unsubstituted phenyl-, substituted or unsubstituted methyl-, substituted or unsubstituted phenyl-, substituted or unsubstituted ethyl-, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C3-C6 cycloalkyl.

[0100] In another preferred embodiment, R2 is hydrogen, Ethyl, propyl, butyl, cyclopropyl;

[0101] R 26 、R 27 、R 28 、R 29 and R 30 Each is independently hydrogen, C1-C8 alkyl, halogen, C1-C8 haloalkoxy, or C1-C8 haloalkylthio.

[0102] In another preferred embodiment, R 26 、R 27 、R 28 、R 29 and R 30 Each is independently hydrogen, C1-C6 alkyl, halogen, C1-C6 haloalkoxy, or C1-C6 haloalkylthio.

[0103] In another preferred embodiment, R 26 、R 27 、R 28 、R 29 and R 30 Each is independently hydrogen, C1-C4 alkyl, halogen, C1-C4 haloalkoxy, or C1-C4 haloalkylthio.

[0104] In another preferred embodiment, R 26 、R 27 、R 28 、R 29 and R 30 Each is independently hydrogen, C1-C2 alkyl, halogen, C1-C2 haloalkoxy, or C1-C2 haloalkylthio.

[0105] In another preferred embodiment, R 26 、R 27 、R 28 、R 29 and R 30 Each is independently hydrogen, methyl, halogen (such as fluorine, chlorine), or F3C-O-.

[0106] In another preferred embodiment, Z1 is methylene or ethylene.

[0107] In another preferred embodiment, the structure of ethylene is

[0108] In another preferred embodiment, for

[0109] In another preferred embodiment, R9 and R 10are each independently hydrogen, substituted or unsubstituted C6-C10 aryl, substituted or unsubstituted C6-C10 aryl-substituted or unsubstituted C1-C6 alkyl-, substituted or unsubstituted C1-C8 alkyl; or R9 and R 10 The groups are connected to form a substituted or unsubstituted 5-10 membered heterocycloalkyl group or a substituted or unsubstituted 5-10 membered heteroaryl group.

[0110] In another preferred embodiment, R9 and R 10 are each independently hydrogen, substituted or unsubstituted C6-C8 aryl, substituted or unsubstituted C6-C8 aryl-substituted or unsubstituted C1-C4 alkyl-, substituted or unsubstituted C1-C6 alkyl; or R9 and R 10 The groups are connected to form a substituted or unsubstituted 5-10 membered heterocycloalkyl group or a substituted or unsubstituted 5-10 membered heteroaryl group.

[0111] In another preferred embodiment, R9 and R 10 are each independently hydrogen, substituted or unsubstituted phenyl, substituted or unsubstituted phenyl-, substituted or unsubstituted methyl-, substituted or unsubstituted phenyl-, substituted or unsubstituted ethyl-, substituted or unsubstituted phenyl-, substituted or unsubstituted propyl-, substituted or unsubstituted propyl; or R9 and R 10 The linkage forms a substituted or unsubstituted isoindole-1-one.

[0112] In another preferred embodiment, R9 and R 10 are independently hydrogen, phenyl-methyl-, phenyl-ethyl-, phenyl-propyl-, propyl; or R9 and R 10 Connection formation

[0113] In another preferred embodiment, R 10 For hydrogen.

[0114] In another preferred embodiment, the structure of phenyl-propyl- is

[0115] In another preferred embodiment, the structure of the propyl group is

[0116] In another preferred embodiment, the structure of butyl is

[0117] In another preferred embodiment, the structure of phenyl-ethyl- is

[0118] In another preferred embodiment, any of the "substituted" mentioned above means that one or more (preferably 1, 2, 3, 4, 5, 6, 7 or 8) hydrogen atoms on the ring or group are independently replaced by a substituent.

[0119] In another preferred embodiment, any of the "substituted" refers to that one or more (preferably 1, 2, 3, 4, 5, 6, 7 or 8) hydrogen atoms on the ring or group are independently replaced by a substituent selected from the group consisting of C1-C8 alkyl, C3-C8 cycloalkyl, C1-C8 haloalkyl, C3-C8 halocycloalkyl, C1-C8 alkoxy, C1-C8 alkylthio, C1-C8 haloalkoxy, C1-C8 haloalkylthio, C3-C8 cycloalkyloxy, C3-C8 cycloalkylthio, C3-C8 halocycloalkyloxy, C3-C8 halocycloalkylthio, halogen, nitro, hydroxyl, thiol, amino, carbonyl, C6-C12 aryl, 5-10 membered heteroaryl, and 5-10 membered heterocycloalkyl.

[0120] In another preferred embodiment, any of the "substituted" refers to that one or more (preferably 1, 2, 3, 4, 5, 6, 7 or 8) hydrogen atoms on the ring or group are independently replaced by a substituent selected from the group consisting of C1-C6 alkyl, C3-C8 cycloalkyl, C1-C6 haloalkyl, C3-C8 halocycloalkyl, C1-C6 alkoxy, C1-C6 alkylthio, C1-C6 haloalkoxy, C1-C6 haloalkylthio, C3-C8 cycloalkyloxy, C3-C8 cycloalkylthio, C3-C8 halocycloalkyloxy, C3-C8 halocycloalkylthio, halogen, nitro, hydroxyl, thiol, amino, carbonyl, C6-C12 aryl, 5-10 membered heteroaryl, and 5-10 membered heterocycloalkyl.

[0121] In another preferred embodiment, any of the "substituted" refers to that one or more (preferably 1, 2, 3, 4, 5, 6, 7 or 8) hydrogen atoms on the ring or group are independently replaced by a substituent selected from the group consisting of C1-C4 alkyl, C3-C8 cycloalkyl, C1-C4 haloalkyl, C3-C8 halocycloalkyl, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 haloalkoxy, C1-C4 haloalkylthio, C3-C8 cycloalkyloxy, C3-C8 cycloalkylthio, C3-C8 halocycloalkyloxy, C3-C8 halocycloalkylthio, halogen, nitro, hydroxyl, thiol, amino, carbonyl, C6-C12 aryl, 5-10 membered heteroaryl, and 5-10 membered heterocycloalkyl.

[0122] In another preferred embodiment, the heterocyclic ring of the heterocycloalkyl, heteroaryl, heterocycloalkane ring and heteroaryl ring has 1-4 (preferably 1, 2, 3 or 4) heteroatoms independently selected from N, O and S.

[0123] In another preferred embodiment, the heterocyclic ring of the heterocycloalkyl group has 1-4 (preferably 1, 2, 3 or 4) heteroatoms independently selected from N, O and S.

[0124] In another preferred embodiment, the heteroaryl group has 1-4 (preferably 1, 2, 3 or 4) heteroatoms independently selected from N, O and S on the heterocyclic ring.

[0125] In another preferred embodiment, the heterocyclic ring of the heterocycloalkane ring has 1-4 (preferably 1, 2, 3 or 4) heteroatoms independently selected from N, O and S.

[0126] In another preferred embodiment, the heteroaromatic ring has 1-4 (preferably 1, 2, 3 or 4) heteroatoms independently selected from N, O and S on the heterocyclic ring.

[0127] In another preferred embodiment, the heterocycloalkyl group has 0, 1 or 2 C=C ring double bonds.

[0128] In another preferred embodiment, the halogen is F, Cl, Br or I.

[0129] In another preferred embodiment, halo is fluoro, chloro, bromo, or iodo.

[0130] In another preferred embodiment, the cycloalkane ring has 1, 2 or 3 C=C ring double bonds.

[0131] In another preferred embodiment, the heterocycloalkane ring has 1, 2 or 3 C=C ring double bonds.

[0132] In another preferred embodiment, the halogenated group is monohalogenated, dihalogenated, trihalogenated or perhalogenated.

[0133] In another preferred embodiment, the structure of the compound of formula I is shown in the following formula I-1:

[0134] wherein R1 and R2 are each independently as defined above;

[0135] R 31 、R 32 、R 33 and R 34 Each is independently hydrogen or C1-C8 alkyl.

[0136] In another preferred embodiment, R 31 、R 32 、R 33 and R 34 Each is independently hydrogen or C1-C8 alkyl.

[0137] In another preferred embodiment, R 31 、R 32 、R 33 and R 34 Each is independently hydrogen or C1-C6 alkyl.

[0138] In another preferred embodiment, R 31 、R 32 、R 33 and R 34 Each is independently hydrogen or C1-C4 alkyl.

[0139] In another preferred embodiment, R 31 、R 32 、R 33 and R 34 Each is independently hydrogen or C1-C2 alkyl.

[0140] In another preferred embodiment, R 31 、R 32 、R 33 and R 34 are each independently hydrogen or methyl.

[0141] In another preferred embodiment, the structure of the compound of formula I is shown in the following formula I-2:

[0142] wherein R1 and R2 are each independently as defined above;

[0143] R 35 、R 36 、R 37 、R 38 and R 39 Each is independently hydrogen or C1-C8 alkyl.

[0144] In another preferred embodiment, R 35 、R 36 、R 37 、R 38 and R 39 Each is independently hydrogen or C1-C6 alkyl.

[0145] In another preferred embodiment, R 35 、R 36 、R 37 、R 38 and R 39 Each is independently hydrogen or C1-C4 alkyl.

[0146] In another preferred embodiment, R 35 、R 36 、R 37 、R 38 and R 39 Each is independently hydrogen or C1-C2 alkyl.

[0147] In another preferred embodiment, R 35 、R 36 、R 37 、R 38 and R39 are each independently hydrogen.

[0148] In another preferred embodiment, the structure of the compound of formula I is shown in the following formula I-3:

[0149] wherein R1 and R2 are each independently as defined above;

[0150] R 40 、R 41 、R 42 and R 43 Each is independently hydrogen or C1-C8 alkyl.

[0151] In another preferred embodiment, R 40 、R 41 、R 42 and R 43 Each is independently hydrogen or C1-C6 alkyl.

[0152] In another preferred embodiment, R 40 、R 41 、R 42 and R 43 Each is independently hydrogen or C1-C4 alkyl.

[0153] In another preferred embodiment, R 40 、R 41 、R 42 and R 43 Each is independently hydrogen or C1-C2 alkyl.

[0154] In another preferred embodiment, R 40 、R 41 、R 42 and R 43 are each independently hydrogen.

[0155] In another preferred embodiment, the structure of the compound of formula I is shown in the following formula I-4:

[0156] wherein R1 and R2 are each independently as defined above;

[0157] R 44 、R 45 、R 46 、R 47 and R 48 Each is independently hydrogen or C1-C8 alkyl.

[0158] In another preferred embodiment, R 44 、R 45 、R 46 、R 47 and R 48Each is independently hydrogen or C1-C6 alkyl.

[0159] In another preferred embodiment, R 44 、R 45 、R 46 、R 47 and R 48 Each is independently hydrogen or C1-C4 alkyl.

[0160] In another preferred embodiment, R 44 、R 45 、R 46 、R 47 and R 48 Each is independently hydrogen or C1-C2 alkyl.

[0161] In another preferred embodiment, R 44 、R 45 、R 46 、R 47 and R 48 are each independently hydrogen or methyl.

[0162] In another preferred embodiment, the structure of the compound of formula I is shown in the following formula I-5:

[0163] wherein R1 and R2 are each independently as defined above;

[0164] R 49 、R 50 、R 51 、R 52 and R 53 Each is independently hydrogen or C1-C8 alkyl.

[0165] In another preferred embodiment, R 49 、R 50 、R 51 、R 52 and R 53 Each is independently hydrogen or C1-C6 alkyl.

[0166] In another preferred embodiment, R 49 、R 50 、R 51 、R 52 and R 53 Each is independently hydrogen or C1-C4 alkyl.

[0167] In another preferred embodiment, R 49 、R 50 、R 51 、R 52 and R 53 Each is independently hydrogen or C1-C2 alkyl.

[0168] In another preferred embodiment, R 49 、R 50 、R 51 、R 52 and R 53 are each independently hydrogen.

[0169] In another preferred embodiment, the structure of the compound of formula I is shown in the following formula I-6:

[0170] wherein R1 and R2 are each independently as defined above;

[0171] R 54 、R 56 and R 56 Each is independently hydrogen or C1-C8 alkyl.

[0172] In another preferred embodiment, R 54 、R 56 and R 56 Each is independently hydrogen or C1-C8 alkyl.

[0173] In another preferred embodiment, R 54 、R 56 and R 56 Each is independently hydrogen or C1-C6 alkyl.

[0174] In another preferred embodiment, R 54 、R 56 and R 56 Each is independently hydrogen or C1-C4 alkyl.

[0175] In another preferred embodiment, R 54 、R 56 and R 56 Each is independently hydrogen or C1-C2 alkyl.

[0176] In another preferred embodiment, R 54 、R 56 and R 56 are each independently hydrogen or methyl.

[0177] In another preferred embodiment, the structure of the compound of formula I is shown in the following formula I-7:

[0178] wherein R1 and R2 are each independently as defined above;

[0179] R 57 、R 58 、R 59 、R 60 、R 61 and R 62Each is independently hydrogen or C1-C8 alkyl.

[0180] In another preferred embodiment, R 57 、R 58 、R 59 、R 60 、R 61 and R 62 Each is independently hydrogen or C1-C8 alkyl.

[0181] In another preferred embodiment, R 57 、R 58 、R 59 、R 60 、R 61 and R 62 Each is independently hydrogen or C1-C6 alkyl.

[0182] In another preferred embodiment, R 57 、R 58 、R 59 、R 60 、R 61 and R 62 Each is independently hydrogen or C1-C4 alkyl.

[0183] In another preferred embodiment, R 57 、R 58 、R 59 、R 60 、R 61 and R 62 Each is independently hydrogen or C1-C2 alkyl.

[0184] In another preferred embodiment, R 57 、R 58 、R 59 、R 60 、R 61 and R 62 are each independently hydrogen or methyl.

[0185] In another preferred embodiment, the structure of the compound of formula I is shown in the following formula I-8:

[0186] wherein R1 and R2 are each independently as defined above;

[0187] R 63 、R 64 、R 65 、R 66 and R 67 Each is independently hydrogen or C1-C8 alkyl.

[0188] In another preferred embodiment, R 63 、R 64、R 65 、R 66 and R 67 Each is independently hydrogen or C1-C8 alkyl.

[0189] In another preferred embodiment, R 63 、R 64 、R 65 、R 66 and R 67 Each is independently hydrogen or C1-C6 alkyl.

[0190] In another preferred embodiment, R 63 、R 64 、R 65 、R 66 and R 67 Each is independently hydrogen or C1-C4 alkyl.

[0191] In another preferred embodiment, R 63 、R 64 、R 65 、R 66 and R 67 Each is independently hydrogen or C1-C2 alkyl.

[0192] In another preferred embodiment, R 63 、R 64 、R 65 、R 66 and R 67 are each independently hydrogen or methyl.

[0193] In another preferred embodiment, the structure of the compound of formula I is shown in the following formula I-9:

[0194] wherein R1 and R2 are each independently as defined above;

[0195] R 68 、R 69 、R 70 and R 71 Each is independently hydrogen or C1-C8 alkyl.

[0196] In another preferred embodiment, R 68 、R 69 、R 70 and R 71 Each is independently hydrogen or C1-C8 alkyl.

[0197] In another preferred embodiment, R 68 、R 69 、R 70 and R 71 Each is independently hydrogen or C1-C6 alkyl.

[0198] In another preferred embodiment, R 68 、R 69 、R 70 and R 71 Each is independently hydrogen or C1-C4 alkyl.

[0199] In another preferred embodiment, R 68 、R 69 、R 70 and R 71 Each is independently hydrogen or C1-C2 alkyl.

[0200] In another preferred embodiment, R 68 、R 69 、R 70 and R 71 are each independently hydrogen.

[0201] In another preferred embodiment, the structure of the compound of formula I is shown in the following formula I-10:

[0202] wherein R1 and R2 are each independently as defined above;

[0203] R 72 、R 73 、R 74 、R 75 、R 76 、R 77 、R 78 and R 79 Each is independently hydrogen or C1-C8 alkyl.

[0204] In another preferred embodiment, R 72 、R 73 、R 74 、R 75 、R 76 、R 77 、R 78 and R 79 Each is independently hydrogen or C1-C8 alkyl.

[0205] In another preferred embodiment, R 72 、R 73 、R 74 、R 75 、R 76 、R 77 、R 78 and R 79 Each is independently hydrogen or C1-C6 alkyl.

[0206] In another preferred embodiment, R 72 、R 73 、R 74 、R75 、R 76 、R 77 、R 78 and R 79 Each is independently hydrogen or C1-C4 alkyl.

[0207] In another preferred embodiment, R 72 、R 73 、R 74 、R 75 、R 76 、R 77 、R 78 and R 79 Each is independently hydrogen or C1-C2 alkyl.

[0208] In another preferred embodiment, R 72 、R 73 、R 74 、R 75 、R 76 、R 77 、R 78 and R 79 are each independently hydrogen.

[0209] In another preferred embodiment, the structure of the compound of formula I is shown in the following formula I-11:

[0210] wherein R1 and R2 are each independently as defined above;

[0211] R 80 、R 81 、R 82 and R 83 Each is independently hydrogen or C1-C8 alkyl.

[0212] In another preferred embodiment, R 80 、R 81 、R 82 and R 83 Each is independently hydrogen or C1-C8 alkyl.

[0213] In another preferred embodiment, R 80 、R 81 、R 82 and R 83 Each is independently hydrogen or C1-C6 alkyl.

[0214] In another preferred embodiment, R 80 、R 81 、R 82 and R 83 Each is independently hydrogen or C1-C4 alkyl.

[0215] In another preferred embodiment, R80 、R 81 、R 82 and R 83 Each is independently hydrogen or C1-C2 alkyl.

[0216] In another preferred embodiment, R 80 、R 81 、R 82 and R 83 are each independently hydrogen or methyl.

[0217] In another preferred embodiment, the structure of the compound of formula I is shown in the following formula I-12:

[0218] wherein R1 and R2 are each independently as defined above;

[0219] R 84 、R 85 、R 86 and R 87 Each is independently hydrogen or C1-C8 alkyl.

[0220] In another preferred embodiment, R 84 、R 85 、R 86 and R 87 Each is independently hydrogen or C1-C8 alkyl.

[0221] In another preferred embodiment, R 84 、R 85 、R 86 and R 87 Each is independently hydrogen or C1-C6 alkyl.

[0222] In another preferred embodiment, R 84 、R 85 、R 86 and R 87 Each is independently hydrogen or C1-C4 alkyl.

[0223] In another preferred embodiment, R 84 、R 85 、R 86 and R 87 Each is independently hydrogen or C1-C2 alkyl.

[0224] In another preferred embodiment, R 84 、R 85 、R 86 and R 87 are each independently hydrogen or methyl.

[0225] In another preferred embodiment, the structure of the compound of formula I is shown in the following formula I-13:

[0226] wherein R1 and R2 are each independently as defined above;

[0227] R 88 、R 89 、R 90 、R 91 、R 92 and R 93 Each is independently hydrogen or C1-C8 alkyl.

[0228] In another preferred embodiment, R 88 、R 89 、R 90 、R 91 、R 92 and R 93 Each is independently hydrogen or C1-C8 alkyl.

[0229] In another preferred embodiment, R 88 、R 89 、R 90 、R 91 、R 92 and R 93 Each is independently hydrogen or C1-C6 alkyl.

[0230] In another preferred embodiment, R 88 、R 89 、R 90 、R 91 、R 92 and R 93 Each is independently hydrogen or C1-C4 alkyl.

[0231] In another preferred embodiment, R 88 、R 89 、R 90 、R 91 、R 92 and R 93 Each is independently hydrogen or C1-C2 alkyl.

[0232] In another preferred embodiment, R 88 、R 89 、R 90 、R 91 、R 92 and R 93 are each independently hydrogen.

[0233] In another preferred embodiment, the structure of the compound of formula I is shown in the following formula I-14:

[0234] wherein R1 and R2 are each independently as defined above;

[0235] R 94 、R 95 、R 96 and R 97 Each is independently hydrogen or C1-C8 alkyl.

[0236] In another preferred embodiment, R 94 、R 95 、R 96 and R 97 Each is independently hydrogen or C1-C8 alkyl.

[0237] In another preferred embodiment, R 94 、R 95 、R 96 and R 97 Each is independently hydrogen or C1-C6 alkyl.

[0238] In another preferred embodiment, R 94 、R 95 、R 96 and R 97 Each is independently hydrogen or C1-C4 alkyl.

[0239] In another preferred embodiment, R 94 、R 95 、R 96 and R 97 Each is independently hydrogen or C1-C2 alkyl.

[0240] In another preferred embodiment, R 94 、R 95 、R 96 and R 97 are each independently hydrogen or methyl.

[0241] In another preferred embodiment, the structure of the compound of formula I is shown in the following formula I-15:

[0242] wherein R1 and R2 are each independently as defined above;

[0243] R 98 、R 99 、R 100 and R 101 Each is independently hydrogen or C1-C8 alkyl.

[0244] In another preferred embodiment, R 98 、R 99 、R 100 and R 101 Each is independently hydrogen or C1-C6 alkyl.

[0245] In another preferred embodiment, R 98、R 99 、R 100 and R 101 Each is independently hydrogen or C1-C4 alkyl.

[0246] In another preferred embodiment, R 98 、R 99 、R 100 and R 101 Each is independently hydrogen or C1-C2 alkyl.

[0247] In another preferred embodiment, R 98 、R 99 、R 100 and R 101 are each independently hydrogen.

[0248] In another preferred embodiment, the structure of the compound of formula I is shown in the following formula I-16:

[0249] wherein R1 and R2 are each independently as defined above;

[0250] R 102 、R 103 、R 104 and R 105 Each is independently hydrogen or C1-C8 alkyl.

[0251] In another preferred embodiment, R 102 、R 103 、R 104 and R 105 Each is independently hydrogen or C1-C6 alkyl.

[0252] In another preferred embodiment, R 102 、R 103 、R 104 and R 105 Each is independently hydrogen or C1-C4 alkyl.

[0253] In another preferred embodiment, R 102 、R 103 、R 104 and R 105 Each is independently hydrogen or C1-C2 alkyl.

[0254] In another preferred embodiment, R 102 、R 103 、R 104 and R 105 are each independently hydrogen.

[0255] In another preferred embodiment, the structure of the compound of formula I is shown in the following formula I-17:

[0256] wherein R1 and R2 are each independently as defined above;

[0257] R 106 、R 107 、R 108 and R 109 Each is independently hydrogen or C1-C8 alkyl.

[0258] In another preferred embodiment, R 106 、R 107 、R 108 and R 109 Each is independently hydrogen or C1-C6 alkyl.

[0259] In another preferred embodiment, R 106 、R 107 、R 108 and R 109 Each is independently hydrogen or C1-C4 alkyl.

[0260] In another preferred embodiment, R 106 、R 107 、R 108 and R 109 Each is independently hydrogen or C1-C2 alkyl.

[0261] In another preferred embodiment, R 106 、R 107 、R 108 and R 109 are each independently hydrogen or methyl.

[0262] In another preferred embodiment, the structure of the compound of formula I is shown in the following formula I-18:

[0263] wherein R1 and R2 are each independently as defined above;

[0264] R 110 、R 111 、R 112 、R 113 and R 114 Each is independently hydrogen or C1-C8 alkyl.

[0265] In another preferred embodiment, R 110 、R 111 、R 112 、R 113 and R 114 Each is independently hydrogen or C1-C6 alkyl.

[0266] In another preferred embodiment, R 110 、R 111 、R 112 、R113 and R 114 Each is independently hydrogen or C1-C4 alkyl.

[0267] In another preferred embodiment, R 110 、R 111 、R 112 、R 113 and R 114 Each is independently hydrogen or C1-C2 alkyl.

[0268] In another preferred embodiment, R 110 、R 111 、R 112 、R 113 and R 114 are each independently hydrogen or methyl.

[0269] In another preferred embodiment, the structure of the compound of formula I is as follows:

[0270] wherein R1 and R2 are each independently as defined above.

[0271] In another preferred embodiment, the pharmaceutically acceptable salt of the compound of formula I includes a salt formed by the compound of formula I and an acid.

[0272] In another preferred embodiment, the pharmaceutically acceptable salts of the compound of formula I include salts formed by the compound of formula I and one or more of hydrochloric acid, mucic 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, phenylmethanesulfonic acid, benzenesulfonic acid, aspartic acid and glutamic acid.

[0273] In another preferred embodiment, the pharmaceutically acceptable salt of the compound of formula I includes F - 、Cl - Br - , I - HCOO - 、CH3COO - CF3COO - 、SO4 2- or NO3 - .

[0274] In another preferred embodiment, the compound of formula I is

[0275] The second aspect of the present invention provides a composition comprising (a) a compound of formula I as described in the first aspect of the present invention, or an optical isomer thereof, or a racemate thereof, or a solvate thereof, or a pharmaceutically acceptable salt thereof, or a deuterated compound thereof.

[0276] In another preferred embodiment, the composition comprises a pharmaceutical composition.

[0277] In another preferred embodiment, the composition further comprises (b) a pharmaceutically acceptable carrier.

[0278] In another preferred embodiment, the dosage form of the composition is a solid preparation, a liquid preparation or a semisolid preparation.

[0279] In another preferred embodiment, the composition is in the form of an oral preparation, an external preparation or an injection preparation.

[0280] In another preferred embodiment, the content of (a) the compound of formula I as described in the first aspect of the present invention, or its optical isomer, or its racemate, or its solvate, or its pharmaceutically acceptable salt, or its deuterated compound is 0.001-99.9 wt%, based on the weight of the composition.

[0281] In a third aspect, the present invention provides a use of a compound of formula I as described in the first aspect of the present invention, or an optical isomer thereof, or a racemate thereof, or a solvate thereof, or a pharmaceutically acceptable salt thereof, or a deuterated compound thereof, for preparing a composition or preparation, wherein the composition or preparation is used for one or more uses selected from the following groups: (1) lowering blood sugar; (2) preventing and / or treating hyperglycemia; and / or (3) preventing and / or treating diabetes.

[0282] In another preferred embodiment, the composition or preparation is administered to a human or non-human mammal.

[0283] In another preferred embodiment, the non-human mammal is a mouse, dog, cat, monkey, gorilla, baboon or rabbit.

[0284] In another preferred embodiment, the blood glucose includes human blood glucose.

[0285] In another preferred embodiment, the hyperglycemia includes hyperglycemia caused by insulin resistance.

[0286] In another preferred embodiment, the diabetes includes human diabetes.

[0287] In another preferred embodiment, the diabetes includes type 1 diabetes and / or type 2 diabetes.

[0288] In another preferred embodiment, the diabetes includes diabetes caused by insulin resistance.

[0289] In another preferred embodiment, lowering blood sugar includes lowering blood sugar by promoting glucose absorption.

[0290] In another preferred embodiment, the prevention and / or treatment of diabetes includes preventing and / or treating diabetes by promoting glucose absorption.

[0291] In another preferred embodiment, the composition or preparation is a pharmaceutical composition or pharmaceutical preparation.

[0292] In another preferred embodiment, the composition or preparation further comprises a pharmaceutically acceptable carrier.

[0293] In another preferred embodiment, the composition or preparation is in the form of a solid preparation, a liquid preparation or a semisolid preparation.

[0294] In another preferred embodiment, the composition or preparation is in the form of an oral preparation, an external preparation or an injection preparation.

[0295] In a fourth aspect, the present invention provides a method for (1) lowering blood sugar; (2) preventing and / or treating hyperglycemia; and / or (3) preventing and / or treating diabetes, the method comprising administering to a subject in need thereof a compound of formula I as described in the first aspect of the present invention, or an optical isomer thereof, or a racemate thereof, or a solvate thereof, or a pharmaceutically acceptable salt thereof, or a deuterated compound thereof, thereby (1) lowering blood sugar; (2) preventing and / or treating hyperglycemia; and / or (3) preventing and / or treating diabetes.

[0296] In another preferred embodiment, the subject includes a human or a non-human mammal.

[0297] In another preferred embodiment, the non-human mammal is a mouse, dog, cat, monkey, gorilla, baboon or rabbit.

[0298] In another preferred embodiment, the blood glucose includes human blood glucose.

[0299] In another preferred embodiment, the hyperglycemia includes hyperglycemia caused by insulin resistance.

[0300] In another preferred embodiment, the diabetes includes human diabetes.

[0301] In another preferred embodiment, the diabetes includes type 1 diabetes and / or type 2 diabetes.

[0302] In another preferred embodiment, the diabetes includes diabetes caused by insulin resistance.

[0303] In another preferred embodiment, lowering blood sugar includes lowering blood sugar by promoting glucose absorption.

[0304] In another preferred embodiment, the prevention and / or treatment of diabetes includes preventing and / or treating diabetes by promoting glucose absorption.

[0305] In another preferred embodiment, the administration is oral administration, external administration or injection administration.

[0306] Within the scope of the present invention, the above-mentioned technical features of the present invention and the technical features described in detail below can be combined with each other to form new or preferred technical solutions. Due to space limitations, they will not be listed here one by one. DETAILED DESCRIPTION

[0307] The present invention has developed a compound with excellent blood sugar lowering effect, which can be used to treat hyperglycemia and diabetes. Based on this, the inventors have completed the present invention.

[0308] the term

[0309] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

[0310] As used herein, the terms "include," "comprise," and "contain" are used interchangeably to encompass not only open definitions but also semi-closed and closed definitions. In other words, the terms encompass "consisting of," "consisting essentially of."

[0311] As used herein, the term "MS-ESI" refers to electrospray ionization mass spectrometry.

[0312] As used herein, the term “ 1 "H NMR" refers to proton nuclear magnetic resonance.

[0313] It will be appreciated that one of ordinary skill in the art can select substituents and substitution patterns on the compounds of the present invention to produce chemically stable compounds, which can be synthesized by techniques known in the art and as described below. If substituted with more than one substituent group, it will be appreciated that these multiple groups may be on the same carbon or on different carbons, as long as a stable structure results.

[0314] As used herein, the term "substituted" or "substituted" means that a hydrogen atom on a group is replaced by a non-hydrogen atom group, but the valence requirements need to be met and the substitution generates a chemically stable compound, that is, a compound that does not spontaneously undergo transformations such as cyclization, elimination, etc.

[0315] As used herein, Indicates the attachment site of a group.

[0316] As used herein, "deuterated" refers to a compound or group in which one or more hydrogen atoms are replaced by deuterium. Deuterated groups may be monosubstituted, disubstituted, polysubstituted, or fully substituted.

[0317] As used herein, the term "solvate" refers to a complex in which a compound is coordinated with solvent molecules to form a specific ratio.

[0318] As used herein, "R1", "R1" and "R 1 " have the same meaning and can be used interchangeably. Other similar definitions have the same meaning.

[0319] As used herein, the term "alkyl" refers to a straight-chain (i.e., unbranched) or branched saturated hydrocarbon group containing only carbon atoms and hydrogen atoms, or a combination of straight-chain and branched groups. When the number of carbon atoms in front of the alkyl group is specified (e.g., C1-C6 alkyl), it refers to the number of carbon atoms contained in the alkyl group (e.g., 1-6). For example, C1-C4 alkyl refers to an alkyl group containing 1-4 carbon atoms. Representative examples of alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, or similar groups.

[0320] As used herein, the term "alkylene" refers to a group formed by removing a hydrogen atom from an alkyl group. The alkyl group is as defined above. When the number of carbon atoms is specified before the alkylene group (such as C1-C6 alkylene), it refers to the number of carbon atoms contained in the alkylene group (such as 1-6). For example, C1-C4 alkylene refers to an alkylene group containing 1-4 carbon atoms. Representative examples of alkylene groups include, but are not limited to, methylene, ethylene, propylene, isopropylene, butylene, isobutylene, sec-butylene, tert-butylene, pentylene, hexylene, heptylene, octylene, or the like.

[0321] As used herein, the term "halogen" refers to F, Cl, Br, or I.

[0322] As used herein, the term "halo" refers to a group in which one or more (preferably 1, 2 or 3) hydrogen atoms are replaced by halogen.

[0323] As used herein, the term "haloalkyl" refers to an alkyl group in which one or more (preferably 1, 2, 3, or 4) hydrogen atoms are replaced by halogen, wherein the alkyl and halogen are as defined above. When the number of carbon atoms in the haloalkyl group is specified (e.g., C1-C8 haloalkyl), it refers to the number of carbon atoms in the haloalkyl group (e.g., 1-8). For example, C1-C6 haloalkyl refers to a haloalkyl group containing 1-6 carbon atoms. Representative examples of haloalkyl groups include, but are not limited to, -CF3, -CHF2, monofluoroisopropyl, difluorobutyl, or the like.

[0324] As used herein, the term "cycloalkane ring" refers to a cyclic hydrocarbon ring having a saturated or partially saturated single ring, a bicyclic ring, or a polycyclic ring (fused ring, bridged ring, or spiro ring). When a cycloalkane ring is preceded by a carbon atom number specification (e.g., C3-C12), this refers to the number of ring carbon atoms in the cycloalkane ring (e.g., 3-12). For example, the term "C3-C8 cycloalkane ring" refers to a saturated or partially saturated monocyclic or bicyclic hydrocarbon ring having 3-8 ring carbon atoms, including cyclopropyl, cyclobutyl, cyclopentyl, cycloheptyl, or similar rings. "Spirocycloalkane ring" refers to a bicyclic or polycyclic hydrocarbon ring in which the monocyclic rings share a single carbon atom (called a spiro atom). These rings may contain one or more double bonds, but none of the rings have a completely conjugated π electron system. "Fused cycloalkane ring" refers to an all-carbon bicyclic or polycyclic hydrocarbon ring in which each ring in the system shares a pair of adjacent carbon atoms with the other rings in the system, wherein one or more rings may contain one or more double bonds, but none of the rings have a completely conjugated π electron system. "Bridged cycloalkane ring" refers to an all-carbon polycyclic hydrocarbon ring in which any two rings share two carbon atoms that are not directly connected. These rings may contain one or more double bonds, but neither ring has a completely conjugated pi electron system.

[0325] As used herein, the term "cycloalkyl" refers to a cyclic hydrocarbon group having a saturated or partially saturated single ring, a bicyclic ring, or a polycyclic ring (fused, bridged, or spirocyclic). When a cycloalkyl group is preceded by a carbon atom number specification (e.g., C3-C12), this refers to the number of ring carbon atoms in the cycloalkyl group (e.g., 3-12). For example, the term "C3-C8 cycloalkyl" refers to a saturated or partially saturated monocyclic or bicyclic alkyl group having 3-8 ring carbon atoms, including cyclopropyl, cyclobutyl, cyclopentyl, cycloheptyl, or similar groups. "Spirocycloalkyl" refers to a bicyclic or polycyclic hydrocarbon group in which the rings share a single carbon atom (called a spiro atom) between the rings. These rings may contain one or more double bonds, but none of the rings have a completely conjugated π electron system. "Fused cycloalkyl" refers to an all-carbon bicyclic or polycyclic hydrocarbon group in which each ring in the system shares a pair of adjacent carbon atoms with the other rings in the system. One or more of the rings may contain one or more double bonds, but none of the rings have a completely conjugated π electron system. "Bridged cycloalkyl" refers to an all-carbon polycyclic hydrocarbon group in which any two rings share two carbon atoms that are not directly connected. These rings may contain one or more double bonds, but none of the rings has a completely conjugated π electron system. Representative examples of cycloalkyl groups include, but are not limited to:

[0326] As used herein, the term "halocycloalkyl" refers to a cycloalkyl group in which one or more (preferably 1, 2, 3 or 4) hydrogen atoms are replaced by halogen, wherein the cycloalkyl group and the halogen group are as defined above. When the number of carbon atoms in the halocycloalkyl group is specified (e.g., C3-C8 halocycloalkyl), the number of carbon atoms in the halocycloalkyl group (e.g., 3-8 ring carbon atoms) is specified. For example, C3-C8 halocycloalkyl refers to a halocycloalkyl group containing 3-8 ring carbon atoms. Representative examples of halocycloalkyl groups include, but are not limited to, monofluorocyclopropyl, monochlorocyclobutyl, monofluorocyclopentyl, difluorocycloheptyl, or the like.

[0327] As used herein, the term "alkoxy" refers to an RO- group, where R is an alkyl group, and alkyl is as defined above. Alkoxy is preceded by a carbon atom number, e.g., C1-C8 alkoxy refers to an alkoxy group in which the alkyl group has 1-8 carbon atoms. Representative examples of alkoxy groups include, but are not limited to, methoxy, ethoxy, n-propoxy, isopropoxy, tert-butoxy, and the like.

[0328] As used herein, the term "alkylthio" refers to an RS- group, where R is an alkyl group, and alkyl is as defined above. When the alkylthio group is preceded by a carbon atom number, for example, C1-C8 alkylthio means that the alkyl group in the alkylthio group has 1-8 carbon atoms. Representative examples of alkylthio groups include, but are not limited to, methylthio, ethylthio, n-propylthio, isopropylthio, tert-butylthio, or the like.

[0329] As used herein, the term "haloalkoxy" refers to a haloalkyl-O— group, where the haloalkyl group is as defined above, and is preceded by a carbon number limit. For example, a C1-C6 haloalkoxy group refers to a C1-C6 haloalkyl-O— group, i.e., a haloalkoxy group containing 1-6 carbon atoms. Representative examples of haloalkoxy groups include, but are not limited to, monofluoromethoxy, monofluoroethoxy, bisfluorobutoxy, and the like.

[0330] As used herein, the term "haloalkylthio" refers to a haloalkyl-S- group, where the haloalkyl group is as defined above, and is preceded by a carbon number limit. For example, a C1-C6 haloalkylthio group refers to a C1-C6 haloalkyl-S- group, i.e., a haloalkylthio group containing 1-6 carbon atoms. Representative examples of haloalkylthio groups include, but are not limited to, monofluoromethylthio, monofluoroethylthio, bisfluorobutylthio, and the like.

[0331] As used herein, the term "cycloalkoxy" refers to an RO- group, where R is a cycloalkyl group, and the cycloalkyl group is as defined above. When the cycloalkoxy group is preceded by a carbon atom number, for example, C3-C8 cycloalkoxy refers to a cycloalkoxy group in which the cycloalkyl group has 3-8 ring carbon atoms. Representative examples of cycloalkoxy groups include, but are not limited to, cyclopropyloxy, cyclobutyloxy, and the like.

[0332] As used herein, the term "cycloalkylthio" refers to an RS- group, where R is a cycloalkyl group, and the cycloalkyl group is as defined above. When the cycloalkylthio group is preceded by a carbon atom number, for example, C3-C8 cycloalkylthio refers to a cycloalkylthio group in which the cycloalkyl group has 3-8 ring carbon atoms. Representative examples of cycloalkylthio groups include, but are not limited to, cyclopropylthio, cyclobutylthio, and the like.

[0333] As used herein, the term "halocycloalkoxy" refers to a cycloalkoxy group in which one or more (preferably 1, 2, 3 or 4) hydrogen atoms are replaced by halogen, wherein the cycloalkoxy group and halogen are as defined above. When the number of carbon atoms in the halocycloalkoxy group is specified (e.g., C3-C8 halocycloalkoxy), the number of carbon atoms in the ring of the halocycloalkoxy group (e.g., 3-8) is specified. For example, C3-C8 halocycloalkoxy refers to a halocycloalkoxy group containing 3-8 ring carbon atoms. Representative examples of halocycloalkoxy groups include, but are not limited to, monofluorocyclopropyl-O-, monochlorocyclobutyl-O-, monofluorocyclopentyl-O-, difluorocycloheptyl-O-, or the like.

[0334] As used herein, the term "halocycloalkylthio" refers to a cycloalkylthio group in which one or more (preferably 1, 2, 3, or 4) hydrogen atoms are replaced by halogen, wherein the cycloalkylthio group and halogen are as defined above. When the number of carbon atoms in the halocycloalkylthio group is specified (e.g., C3-C8 halocycloalkylthio), it refers to the number of ring carbon atoms in the halocycloalkylthio group (e.g., 3-8). For example, C3-C8 halocycloalkylthio refers to a halocycloalkylthio group containing 3-8 ring carbon atoms. Representative examples of halocycloalkylthio include, but are not limited to, monofluorocyclopropyl-S-, monochlorocyclobutyl-S-, monofluorocyclopentyl-S-, difluorocycloheptyl-S-, or the like.

[0335] As used herein, the term "heterocycloalkane ring" refers to a fully saturated or partially unsaturated ring (including but not limited to a 3-7 membered monocyclic ring, a 7-11 membered bicyclic ring, or an 8-16 membered tricyclic ring system), wherein at least one ring heteroatom is present in a ring having at least one ring carbon atom. When the number of ring atoms is limited before the heterocycloalkane ring, it refers to the number of ring atoms of the heterocycloalkane ring, for example, a 3-16 membered heterocycloalkane ring refers to a heterocycloalkane ring having 3-16 ring atoms. Each heterocycle containing a ring heteroatom has one or more (such as 1, 2, 3 or 4) ring heteroatoms, each of which is independently selected from a nitrogen atom, an oxygen atom or a sulfur atom, wherein the nitrogen atom or the sulfur atom can be oxidized, and the nitrogen atom can also be quaternized. Typical monocyclic heterocycloalkane rings include but are not limited to azetidine rings, oxetane rings, tetrahydrofuran rings, piperidine rings, piperazine rings, etc. Polycyclic heterocycloalkane rings include spirocyclic, fused rings and bridged heterocycloalkane rings.

[0336] As used herein, the term "heterocycloalkyl" refers to a fully saturated or partially unsaturated cyclic (including but not limited to 3-7 membered monocyclic, 7-11 membered bicyclic, or 8-16 membered tricyclic) group, wherein at least one ring heteroatom is present in a ring having at least one ring carbon atom. When there is a number of atoms before the heterocycloalkyl group, it refers to the number of ring atoms of the heterocycloalkyl group, for example, a 3-16 membered heterocycloalkyl group refers to a heterocycloalkyl group having 3-16 ring atoms. Each heterocyclic ring containing a ring heteroatom has one or more (such as 1, 2, 3 or 4) ring heteroatoms, each of which is independently selected from a nitrogen atom, an oxygen atom or a sulfur atom, wherein the nitrogen atom or the sulfur atom can be oxidized, and the nitrogen atom can also be quaternized. Typical monocyclic heterocycloalkyl groups include but are not limited to azetidinyl, oxetanyl, tetrahydrofuranyl, piperidinyl, piperazinyl. Polycyclic heterocycloalkyl groups include spirocyclic, fused ring and bridged heterocycloalkyl groups.

[0337] As used herein, the term "aromatic ring" refers to an all-carbon monocyclic ring or fused polycyclic ring (i.e., a ring that shares adjacent pairs of carbon atoms) with a conjugated π electron system, and is an aromatic cyclic hydrocarbon compound. When the aromatic ring is preceded by a carbon atom number limit, such as a C6-C12 aromatic ring, it means that the aromatic ring has 6-12 ring carbon atoms, such as a benzene ring and a naphthalene ring.

[0338] As used herein, the term "aryl" refers to an all-carbon monocyclic or fused polycyclic (i.e., rings that share adjacent pairs of carbon atoms) group with a conjugated π electron system, and is an aromatic cyclic hydrocarbon compound group. When the aryl group is preceded by a carbon atom number limit, such as C6-C12 aryl, it means that the aryl group has 6-12 ring carbon atoms, such as phenyl and naphthyl.

[0339] As used herein, the term "heteroaromatic ring" refers to an aromatic heterocyclic ring system having one to multiple (preferably 1, 2, 3 or 4) heteroatoms, wherein at least one ring heteroatom is present in a ring having at least one ring carbon atom, which may be a single ring (monocyclic) or multiple rings (bicyclic, tricyclic or polycyclic) fused together or covalently linked, each heterocyclic ring containing a ring heteroatom has one or more (e.g., 1, 2, 3, 4) heteroatoms independently selected from the group consisting of oxygen, sulfur and nitrogen. When the number of members in a heteroaromatic ring is specified, it refers to the number of ring atoms in the heteroaromatic ring. For example, a 5-12 membered heteroaromatic ring refers to a heteroaromatic ring having 5-12 ring atoms. Representative examples include, but are not limited to, pyrrole rings, pyrazole rings, imidazole rings, thiazole rings, furan rings, pyridine rings, pyrimidine rings, and the like.

[0340] As used herein, the term "heteroaryl" refers to an aromatic heterocyclic ring group having one to multiple (preferably 1, 2, 3 or 4) heteroatoms, wherein at least one ring heteroatom is present in a ring having at least one ring carbon atom, which can be a monocyclic (monocyclic) or a polycyclic (bicyclic, tricyclic or polycyclic) group fused together or covalently linked, each heterocyclic ring containing a ring heteroatom having one or more (e.g., 1, 2, 3, 4) heteroatoms independently selected from the group consisting of oxygen, sulfur and nitrogen. When the number of atoms in the heteroaryl group is specified, it 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 5-12 ring atoms. Representative examples include, but are not limited to, pyrrolyl, pyrazolyl, imidazolyl, thiazolyl, furanyl, pyridinyl, pyrimidinyl, and the like.

[0341] As used herein, the term "carbonyl" refers to

[0342] As used herein, the term "amino" by itself or as part of another substituent refers to -NH2.

[0343] As used herein, the term "nitro" by itself or as part of another substituent refers to -NO2.

[0344] As used herein, the term "hydroxy," by itself or as part of another substituent, refers to -OH.

[0345] As used herein, the term "mercapto" by itself or as part of another substituent refers to -SH.

[0346] In this document, all substituents should be interpreted as being unsubstituted unless explicitly described herein as “substituted.” The term “substituted” means that one or more hydrogen atoms on a specified group are replaced with a specified substituent. The specific substituents are the substituents described above or the substituents appearing in the embodiments. Preferably, any "substituted" refers to that one or more (preferably 1, 2, 3, 4, 5, 6, 7 or 8) hydrogen atoms on the ring or group are independently replaced by substituents selected from the group consisting of C1-C8 alkyl, C3-C8 cycloalkyl, C1-C8 haloalkyl, C3-C8 halocycloalkyl, C1-C8 alkoxy, C1-C8 alkylthio, C1-C8 haloalkoxy, C1-C8 haloalkylthio, C3-C8 cycloalkyloxy, C3-C8 cycloalkylthio, C3-C8 halocycloalkyloxy, C3-C8 halocycloalkylthio, halogen, nitro, hydroxyl, thiol, amino, carbonyl, C6-C12 aryl, 5-10 membered heteroaryl, and 5-10 membered heterocycloalkyl. Unless otherwise specified, an optionally substituted group may be substituted at any substitutable position of the group, and the substituents at each position may be the same or different.

[0347] In the present invention, the term "prevention" refers to a method of preventing the onset of a disease and / or its attendant symptoms or protecting a subject from acquiring a disease.

[0348] In the present invention, the term "treatment" includes delaying and stopping the progression of the disease, or eliminating the disease, and does not require 100% inhibition, elimination and reversal. In some embodiments, the compounds of the present invention reduce, inhibit and / or reverse the relevant diseases (such as diabetes) and their complications by, for example, at least about 30%, at least about 50%, or at least about 80%, at least about 90%, or 100%, compared to the levels observed in the absence of the compounds of the present invention.

[0349] Compound

[0350] As used herein, "compounds of the present invention," "compounds described herein," "compounds of Formula I of the present invention," or "compounds of Formula I" are used interchangeably to refer to compounds of Formula I, or optical isomers, or racemates, or solvates, or pharmaceutically acceptable salts, or deuterated compounds thereof. It should be understood that the term also includes mixtures of the aforementioned components.

[0351] The structure of the compound of formula I of the present invention is as follows:

[0352] Specifically, the compound of formula I, or its optical isomer, or its racemate, or its solvate, or its pharmaceutically acceptable salt, or its deuterated compound according to the present invention is as described above in the first aspect of the present invention.

[0353] Typically, the compound of formula I described in the present invention is a specific compound prepared in the examples of the present invention (including its salt form or free form without salt radical).

[0354] The compound of formula I described in the present invention can be converted into its pharmaceutically acceptable salt by conventional methods. For example, the corresponding acid solution can be added to a solution of the above compound, and the solvent can be removed after the salt is completely formed to obtain the corresponding salt of the compound described in the present invention.

[0355] use

[0356] The present invention provides a use of the compound of the present invention for preparing a composition or preparation, wherein the composition or preparation is used for one or more uses selected from the following groups: (1) lowering blood sugar; (2) preventing and / or treating hyperglycemia; and / or (3) preventing and / or treating diabetes.

[0357] Specifically, the use is as described above in the third aspect of the present invention.

[0358] Composition or preparation

[0359] The composition or preparation of the present invention is preferably a pharmaceutical composition or preparation, and the composition or preparation of the present invention may include a pharmaceutically acceptable carrier.

[0360] As used herein, "pharmaceutically acceptable carrier" refers to one or more compatible solid, semisolid, liquid, or gel fillers suitable for human or animal use and of sufficient purity and low toxicity. "Compatibility" refers to the ability of the components of a pharmaceutical composition to function with the active ingredient of the drug, and for them to coexist with each other, without significantly reducing the efficacy of the drug.

[0361] It should be understood that in the present invention, the pharmaceutically acceptable carrier is not particularly limited and can be selected from materials commonly used in the art, or prepared by conventional methods, or purchased from the market. Some examples of pharmaceutically acceptable carriers include cellulose and its derivatives (such as methylcellulose, hydroxypropyl methylcellulose), gelatin, talc, solid lubricants, vegetable oils, polyols, emulsifiers, wetting agents, buffers, chelating agents, thickeners, pH regulators, transdermal enhancers, colorants, flavorings, stabilizers, antioxidants, preservatives, antibacterial agents, pyrogen-free water, etc.

[0362] In a preferred embodiment of the present invention, the composition or preparation is in the form of a solid preparation, a liquid preparation or a semisolid preparation.

[0363] In a preferred embodiment of the present invention, the composition or preparation is in the form of an oral preparation, an external preparation or an injection preparation.

[0364] Typically, the composition or preparation is in the form of a tablet, injection, infusion, ointment, gel, solution, microsphere or film.

[0365] The pharmaceutical formulation should be compatible with the route of administration. The agents of the present invention may also be used with other synergistic therapeutic agents (including before, during, or after administration). When using a pharmaceutical composition or formulation, a safe and effective amount of the drug is administered to the intended subject (e.g., a human or non-human mammal). Of course, the specific dosage should also take into account factors such as the route of administration and the patient's health status, all of which are within the skill of a skilled physician.

[0366] The main excellent technical effects of the present invention include:

[0367] The present invention develops a compound, which has an excellent blood sugar lowering effect and can be used for treating hyperglycemia and diabetes.

[0368] It should be understood that the following specific examples are based on the present technical solution and provide detailed implementation methods and specific operating processes, but the scope of protection of the present invention is not limited to these examples.

[0369] Example 1 Synthesis of Compound AB24801A

[0370] Step (1):

[0371] Compound 1 (100 mg) was dissolved in acetonitrile (5 mL), and compound 2 (116 mg) was added. The mixture was reacted at 80°C for 16 h. The reaction solution was spin-dried and the crude product was prepared by reverse phase (acetonitrile / water + 0.1% trifluoroacetic acid) to obtain compound AB24801A (37.6 mg).

[0372] MS-ESI: theoretical value [M] + :317.40; measured value:317.35.

[0373] 1H NMR (400MHz, DMSO-d6) δ9.23 (s, 1H), 8.14 (d, J = 8.0Hz, 1H), 8.02 (d, J = 8.0Hz, 1H), 7.78-7. 77(m,2H),7.43-7.34(m,7H),6.99(s,2H),5.88(s,2H),4.55(d,J=8.0Hz,2H),2.38(s,3H).

[0374] Example 2 Synthesis of Compound AB24802A

[0375] Step (1):

[0376] Compound 1 (144 mg) and compound 2 (200 mg) were dissolved in acetonitrile (10 mL), stirred at 80°C for 16 h, and a new spot was generated by spot plate detection. The mixture was then cooled to room temperature, and the reaction solution was spin-dried and sent for preparative purification (acetonitrile / water + 0.1% trifluoroacetic acid) to obtain compound AB24802A (50 mg).

[0377] MS-ESI theoretical value [M+1] + 317, measured value: 317.

[0378] 1 H NMR (399MHz, DMSO-d6) δ9.26(s,1H),8.18–7.91(m,3H),7.55(s,1H),7.37(s,7H),7.01(s,2H),5.81(s,2H),4.56(s,2H),2.43(s,3H).

[0379] Example 3 Synthesis of Compound AB24804A

[0380] Step (1):

[0381] Compound 1 (86.48 mg) and compound 2 (100 mg) were dissolved in acetonitrile (10 mL), stirred at 80°C for 16 h, and a new spot was generated by spot plate detection. The mixture was then cooled to room temperature, and the reaction solution was spin-dried and sent for preparative purification (acetonitrile / water + 0.1% trifluoroacetic acid) to obtain compound AB24804A (32 mg).

[0382] MS-ESI theoretical value [M+1] + 338, measured value: 338.

[0383] 1H NMR (400MHz, DMSO-d6) δ9.23 (s, 1H), 8.12 (s, 1H), 7.99 (d, J = 8.0Hz, 3H), 7.69 (d ,J=8.4Hz,2H),7.36(s,2H),7.30(s,4H),7.00(s,1H),5.88(s,2H),4.55(s,2H).

[0384] Example 4 Synthesis of Compound AB24806A

[0385] Step (1):

[0386] Compound 1 (500 mg) was dissolved in acetonitrile (20 mL), and compound 2 (1.3 g) was added. The mixture was then replaced with nitrogen three times, heated to 80°C and stirred overnight. New spots appeared on the plate detection. The organic solvent was directly removed by concentration under reduced pressure, and compound AB24806A (120 mg) was obtained by preparative purification (acetonitrile / water + 0.1% trifluoroacetic acid).

[0387] MS-ESI theoretical value [M+1] + 338, measured value: 338.

[0388] 1 H NMR (399MHz, DMSO-d6) δ9.25(s,1H),8.15(d,J=6.3Hz,1H),8.04(d,J=6.8Hz,1H),7.96(d,J=7.4Hz,1H),7. 63(s,2H),7.55(s,1H),7.37(d,J=6.3Hz,4H),7.30(s,1H),7.01(s,2H),5.80(s,2H),4.56(d,J=5.8Hz,2H).

[0389] Example 5 Synthesis of Compound AB24812A

[0390] Step (1):

[0391] Compound 1 (1.0 g) was dissolved in dichloromethane (30 ml), and aluminum chloride (2.3 g) and compound 2 (2.8 g) were added. The mixture was stirred in an ice-water bath for 1 h. A new spot appeared when detected by TLC. The mixture was diluted with ice water (50 mL), and then extracted with dichloromethane (30 mL x 3). The organic phases were combined, washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to remove the organic solvent to obtain compound 4 (1.5 g).

[0392] MS-ESI theoretical value [M+1] + 247, measured value: 247.

[0393] Step (2):

[0394] Compound 3 (200 mg) was dissolved in acetonitrile (10 mL), and compound 4 (539 mg) was added. The mixture was then replaced with nitrogen three times, and the temperature was raised to 80° C. and stirred overnight. A new spot appeared on TLC detection. The mixture was then cooled to room temperature, and the reaction solution was spin-dried and purified by thin-layer chromatography (dichloromethane:methanol=20:1) to obtain compound AB24812A (100 mg).

[0395] MS-ESI theoretical value [M+1] + 352, measured value: 352.

[0396] 1 H NMR (399MHz, DMSO-d6) δ9.37(s,1H),8.32(d,J=6.9Hz,1H),8.21(d,J=7.1Hz,1H),8.01(d,J=7.7Hz,2H),7.67(d,J= 7.8Hz, 2H), 7.32 (d, J = 25.3Hz, 5H), 6.99 (d, J = 9.9Hz, 2H), 6.41 (d, J = 7.0Hz, 1H), 4.55 (s, 2H), 1.70 (d, J = 7.1Hz, 3H).

[0397] Example 6 Synthesis of Compound AB24815

[0398] Step (1):

[0399] Compound 1-1 (100 mg) was dissolved in phosphorus oxychloride (10 mL), stirred at 110 ° C for 3 h, detected by LCMS, cooled, concentrated, and compound 1-2 (96 mg), dimethyl sulfoxide (20 mL) and triethylamine (122 mg) were added under ice bath, reacted at room temperature, concentrated and filtered to obtain compound AB24815 (50 mg).

[0400] MS-ESI theoretical value [M+1] + 366, measured value: 366.

[0401] 1H NMR (400MHz, DMSO-d6) δ9.69(s,1H),8.09(d,J=7.3Hz,1H),7.95(dd,J=20.0,7.0Hz,3H),7.66(d,J=7.6Hz ,2H),7.36(dd,J=13.4,6.5Hz,5H),7.26(t,J=6.5Hz,1H),6.04(d,J=7.0Hz,1H),5.95(s,2H),1.69(s,6H).

[0402] Example 7 Synthesis of Compound AB24816

[0403] Step (1):

[0404] Compound 1 (500 mg), N-bromosuccinimide (860 mg) and azobisisobutyronitrile (53 mg) were dissolved in dichloroethane (10 mL), stirred at 90° C. for 16 h, concentrated and filtered to obtain compound 2 (388 mg).

[0405] MS-ESI theoretical value [M+1] + 234, measured value: 234.

[0406] Step (2):

[0407] Compound 2 (388 mg) was dissolved in acetonitrile (20 mL), and compound 3 (312 mg) was added. The mixture was then replaced with nitrogen three times, heated to 80°C and stirred overnight. New spots appeared on the plate detection. The organic solvent was directly removed by concentration under reduced pressure, and compound AB24816 (120 mg) was obtained by preparative purification (acetonitrile / water + 0.1% trifluoroacetic acid).

[0408] MS-ESI theoretical value [M+1] + 339, measured value: 339.

[0409] 1 H NMR(399MHz,Chloroform-d)δ10.37(s,1H),8.65(s,1H),8.01(d,J=8.3Hz,1H),7.8 9(d,J=7.9Hz,1H),7.58(s,3H),7.33(s,5H),6.53(s,1H),5.73(s,2H),4.57(s,2H).

[0410] Example 8 Synthesis of Compound AB24836A

[0411] Step (1):

[0412] Compound 1 (2.57 g), compound 2 (7.2 g), bis(dibenzylideneacetone)palladium (915 mg), tri-tert-butylphosphine tetrafluoroborate (580.26 mg) and triethylenediamine (6.73 mg) were dissolved in N,N-dimethylacetamide (100 mL), and then replaced with nitrogen three times. After stirring at 120°C for 16 hours, a new spot was produced by spot plate detection. The mixture was then cooled to room temperature and extracted with water and ethyl acetate (100 mL x 3). The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the organic solvent. Compound 3 (1.2 g) was obtained by purification by column chromatography (ethyl acetate: petroleum ether = 66.6%).

[0413] MS-ESI theoretical value [M+1] + 195, measured value: 195.

[0414] Step (2):

[0415] Compound 3 (208 mg) and compound 4 (233.5 mg) were dissolved in acetonitrile (10 mL), stirred at 80°C for 3 h, and a new spot was generated by spot plate detection. The mixture was then cooled to room temperature. The reaction solution was directly filtered and the filter cake was washed with ethyl acetate to obtain compound AB24836A (150 mg).

[0416] MS-ESI theoretical value [M+1] + 347, measured value: 347.

[0417] 1 H NMR (399MHz, DMSO-d6) δ13.46(s,1H),9.27(s,1H),8.78(s,1H),8.47(d,J=6.8Hz,1H),8.36(d,J=6.9Hz,1H), 8.08 (d, J = 7.6 Hz, 2H), 7.77 (dd, J = 26.0, 7.6 Hz, 4H), 7.51 (t, J = 7.5 Hz, 2H), 7.38 (d, J = 6.7 Hz, 1H), 6.42 (s, 2H).

[0418] Example 9 Synthesis of Compound AB24855

[0419] Step (1):

[0420] Compound 3 (233 mg) and compound 4 (195 mg) were dissolved in acetonitrile (10 mL), stirred at 80 ° C for 3 h, and a new spot was generated by spot plate detection. Then, the mixture was cooled to room temperature, and the reaction solution was directly filtered. The filtrate was spin-dried, and the crude product was purified by preparative purification (acetonitrile / water + 0.1% trifluoroacetic acid) to obtain compound AB24855 (50 mg).

[0421] MS-ESI theoretical value [M] + 375.13, measured value: 375.15

[0422] 1 H NMR (400MHz, DMSO-d6) δ13.15(s,1H),9.15(s,1H),8.29–8.19(m,2H),8.08(d,J=6.2Hz,1H),7. 93(d,J=7.4Hz,2H),7.42(d,J=7.4Hz,2H),7.32(s,4H),6.32(s,2H),4.16(s,2H),2.39(s,3H).

[0423] Example 10 Synthesis of Compound AB24856

[0424] Step (1):

[0425] Compound 3 (242 mg) and compound 4 (195 mg) were dissolved in acetonitrile (10 mL), stirred at 80°C for 3 h, and a new spot was generated by spot plate detection. The mixture was then cooled to room temperature, and the reaction solution was directly filtered and the filter cake was washed with ethyl acetate to obtain compound AB24856 (50 mg).

[0426] MS-ESI theoretical value [M+1] + 355, measured value: 355.

[0427] 1 H NMR (399MHz, DMSO-d6) δ9.16 (s, 1H), 8.23 ​​(d, J = 5.8Hz, 1H), 8.11 (d, J = 3.5Hz, 1H), 8.04 (d, J = 6.5Hz, 1H), 7.95 (d, J = 5.7Hz, 2H), 7.44(d,J=7.3Hz,2H), 7.15(d,J=16.8Hz,4H), 6.35(s,2H), 4.17(d,J=3.7Hz,2H), 2.43(d,J=3.3Hz,3H), 2.29(t,J=2.9Hz,3H).

[0428] Example 11 Synthesis of Compound AB24857

[0429] Step (1):

[0430] Compound 3 (222 mg) and compound 4 (195 mg) were dissolved in acetonitrile (10 mL), stirred at 80°C for 3 h, and a new spot was generated by spot plate detection. The mixture was then cooled to room temperature, and the reaction solution was directly filtered and the filter cake was washed with ethyl acetate to obtain compound AB24857 (50 mg).

[0431] MS-ESI theoretical value [M+1] + 355, measured value: 355.

[0432] 1 H NMR (400MHz, DMSO-d6) δ9.15(s,1H),8.26–8.20(m,2H),8.09(d,J=5.9Hz,1H),7.94(d,J=7.3Hz,2H),7.44(d,J=7.2H z,2H),7.13(t,J=9.7Hz,3H),6.99(d,J=6.7Hz,1H),6.34(s,2H),4.13(s,2H),3.35(s,1H),2.41(s,3H),2.23(s,3H).

[0433] Example 12 Synthesis of Compound AB24858

[0434] Step (1):

[0435] Compound 3 (222 mg) and compound 4 (195 mg) were dissolved in acetonitrile (10 mL), stirred at 80°C for 3 h, and a new spot was generated by spot plate detection. The mixture was then cooled to room temperature. The reaction solution was directly filtered and the filter cake was washed with ethyl acetate to obtain compound AB24858 (50 mg).

[0436] MS-ESI theoretical value [M+1] + 355, measured value: 355.

[0437] 1 H NMR(400MHz, DMSO-d6)δ9.16(s,1H),8.23(d,J=7.9Hz,2H),8.12–8.05(m,1H),8.00–7.92(m,2H),7.44(d,J=7.8H z,2H),7.20(d,J=7.6Hz,2H),7.08(d,J=7.6Hz,2H),6.36(d,J=2.1Hz,2H),4.12(s,2H),2.41(s,3H),2.22(s,3H).

[0438] Example 13 Synthesis of Compound AB24860

[0439] Step (1):

[0440] Compound 3 (208 mg) and compound 4 (195 mg) were dissolved in acetonitrile (10 mL), stirred at 80°C for 3 h, and a new spot was generated by spot plate detection. The mixture was then cooled to room temperature. The reaction solution was directly filtered and the filter cake was washed with ethyl acetate to obtain compound AB24860 (50 mg).

[0441] MS-ESI theoretical value [M+1] + 341, measured value: 341.

[0442] 1 H NMR (399MHz, DMSO-d6) δ12.98(s,1H),9.16(s,1H),8.32–8.20(m,2H),8.11(d,J=7.0Hz,1H),7.86(d,J=9.2Hz,2H), 7.55(d,J=21.2Hz,2H),7.31(dt,J=14.3,7.1Hz,4H),7.19(t,J=7.2Hz,1H),6.37(s,2H),4.19(s,2H),2.42(s,3H).

[0443] Example 14 Synthesis of Compound AB24864

[0444] Step (1):

[0445] Compound 3 (208 mg) and compound 4 (244 mg) were dissolved in acetonitrile (10 mL), stirred at 80 ° C for 3 h, and a new spot was generated by spot plate detection. Then, the reaction solution was directly filtered and the filtrate was dried by spin drying. The crude product was purified by preparative purification (acetonitrile / water + 0.1% trifluoroacetic acid) to obtain compound AB24864 (50 mg).

[0446] MS-ESI theoretical value [M+1] + 371, measured value: 371.

[0447] 1H NMR (399MHz, DMSO) δ13.05(s,1H),9.14(s,1H),8.34–8.25(m,2H),8.19(d,J=3.3Hz,2H),8.02 (d, J=7.7Hz, 2H), 7.92 (d, J=7.7Hz, 1H), 7.30 (q, J=8.1, 7.6Hz, 4H), 7.19 (s, 1H), 6.22 (s, 2H).

[0448] Example 15 Synthesis of Compound AB24868

[0449] Step (1):

[0450] Compound 1 (1.2 g) was dissolved in tetrahydrofuran (10 mL), lithium diisopropylamide (2.82 ml) was added, and the mixture was stirred at 0°C for 3 h. A new spot was generated on the spot plate detector. The mixture was then heated to room temperature. The reaction solution was directly filtered and the filter cake was washed with ethyl acetate to obtain compound 2 (670 mg).

[0451] MS-ESI theoretical value [M+1] + 157, measured value: 157.

[0452] Step (2):

[0453] Compound 2 (670 mg) was dissolved in dichloromethane (10 mL), pyridinium chlorochromate (1.85 g) was added, and the mixture was stirred at 0°C for 1 h. A new spot was generated on the spot plate detector, and the mixture was then heated to room temperature. The reaction solution was directly filtered and the filter cake was washed with ethyl acetate to obtain compound 3 (200 mg).

[0454] MS-ESI theoretical value [M+1] + 155, measured value: 155.

[0455] Step (3):

[0456] Compound 3 (200 mg) was dissolved in N,N-dimethylaniline (10 mL), and triethylenediamine (72 mg), tris(dibenzylideneacetone)dipalladium (119 mg) and tri-tert-butylphosphine tetrafluoroborate (38 mg) were added. The mixture was stirred at 120°C for 16 h. A new spot was generated by spot plate detection. The mixture was then cooled to room temperature. The reaction solution was directly filtered and the filter cake was washed with ethyl acetate to obtain compound 4 (120 mg).

[0457] MS-ESI theoretical value [M+1] + 228, measured value: 228.

[0458] Step (4):

[0459] Compound 4 (228 mg) and compound 5 (213 mg) were dissolved in acetonitrile (10 mL), stirred at 80 ° C for 3 h, and a new spot was generated by spot plate detection. Then, the mixture was cooled to room temperature, and the reaction solution was directly filtered. The filtrate was spin-dried, and the crude product was purified by preparative purification (acetonitrile / water + 0.1% trifluoroacetic acid) to obtain compound AB24868 (50 mg).

[0460] MS-ESI theoretical value [M+1] + 361, measured value: 361.

[0461] 1 H NMR (400MHz, DMSO) δ13.59(s,1H),9.30(s,1H),8.63(s,1H),8.34(d,J=7.0Hz,1H),8.06(d,J=6.4Hz, 1H),7.97(d,J=7.7Hz,2H),7.65(dd,J=15.3,6.9Hz,2H),7.50–7.42(m,4H),6.40(s,2H),2.42(s,3H).

[0462] Example 16 Synthesis of Compound AB24869

[0463] Step (1):

[0464] Compound 1 (2 g) was dissolved in dichloromethane (50 mL), and Dess-Martin periodinane (6.4 g) was added at room temperature. The mixture was stirred at room temperature for 1 h. New spots were generated by spot plate detection. The filtrate was concentrated under reduced pressure to remove the organic solvent, and compound 2 (1.1 g) was obtained by column chromatography (ethyl acetate: petroleum ether = 0-10%).

[0465] MS-ESI theoretical value [M+1] + 155, measured value: 155.

[0466] Step (2):

[0467] Compound 2 (1.1 g) and compound 3 (304 mg) were dissolved in N,N-dimethylacetamide (8 mL), and triethylenediamine (796 mg), bis(dibenzylideneacetone)palladium (108 mg) and tri-tert-butylphosphine tetrafluoroborate (70 mg) were added. The mixture was stirred at 120°C for 16 h. A new spot was generated by spot plate detection. The mixture was extracted with water and ethyl acetate, and the organic phase was concentrated under reduced pressure to obtain a residue. The residue was purified by column chromatography (methanol: dichloromethane = 10%) to obtain compound 4 (400 mg).

[0468] MS-ESI theoretical value [M+1] + 228, measured value: 228.

[0469] Step (3):

[0470] Compound 4 (200 mg) and compound 5 (224 mg) were dissolved in acetonitrile (10 mL), stirred at room temperature for 2 h, and a new spot was generated by spot plate detection. The mixture was then cooled to room temperature, and the reaction solution was directly filtered. The filtrate was spin-dried, and the crude product was purified by preparative purification (acetonitrile / water + 0.1% trifluoroacetic acid) to obtain compound AB24869 (60 mg).

[0471] MS-ESI theoretical value [M+1] + 361, measured value: 361.

[0472] 1 H NMR (400MHz, DMSO) δ9.31(s,1H),8.85(s,1H),8.49(d,J=6.7Hz,1H),8.39(d,J=6.5Hz,1H),7.97 (d,J=7.5Hz,2H),7.91–7.78(m,2H),7.54(s,1H),7.46(d,J=8.2Hz,3H),6.41(s,2H),2.43(s,3H)

[0473] Example 17 Synthesis of Compound AB24870

[0474] Step (1):

[0475] Compound 1 (6 g) was dissolved in dichloromethane (15 mL), pyridinium chlorochromate (16.58 g) was added, and the mixture was stirred at room temperature for 3 h. A new spot was generated by spot plate detection to obtain compound 2 (1.3 g).

[0476] MS-ESI theoretical value [M+1] + 155, measured value: 155.

[0477] Step (2):

[0478] Compound 2 (1 g) was dissolved in N,N-dimethylacetamide (10 mL), and triethylenediamine (796 mg), bis(dibenzylideneacetone)palladium (594.75 mg) and tri-tert-butylphosphine tetrafluoroborate (146.9 mg) were added. The mixture was stirred at 120° C. for 16 h. A new spot was generated by spot plate detection. The mixture was extracted with water and ethyl acetate. The organic phase was concentrated under reduced pressure to obtain a residue. The residue was purified by column chromatography (methanol:dichloromethane = 10%) to obtain compound 3 (400 mg).

[0479] MS-ESI theoretical value [M+1] + 227, measured value: 227.

[0480] Step (3):

[0481] Compound 3 (200 mg) and compound 4 (224 mg) were dissolved in acetonitrile (10 mL), stirred at room temperature for 2 h, and a new spot was produced by spot plate detection. The mixture was then cooled to room temperature, and the reaction solution was directly filtered. The filtrate was spin-dried, and the crude product was purified by preparative purification (acetonitrile / water + 0.1% trifluoroacetic acid) to obtain compound AB24870 (60 mg).

[0482] MS-ESI theoretical value [M+1] + 361, measured value: 361.

[0483] 1 H NMR (400MHz, DMSO) δ13.54(s,1H),9.28(s,1H),8.80(s,1H),8.48–8.36(m,2H),7.97(d,J=7.8Hz, 2H),7.84(d,J=8.3Hz,2H),7.57(d,J=8.5Hz,1H),7.46(d,J=7.8Hz,2H),6.39(s,1H),2.42(s,3H)

[0484] Example 18 Synthesis of Compound AB24871

[0485] Step (1):

[0486] Compound 1 (500 mg) was dissolved in dichloromethane (50 mL), and Dess-Martin periodinane (1.87 g) was added at room temperature. The mixture was stirred at room temperature for 1 h. New spots were generated by spot plate detection. The filtrate was concentrated under reduced pressure to remove the organic solvent and the mixture was purified by column chromatography (ethyl acetate: petroleum ether = 0-10%) to obtain compound 2 (200 mg).

[0487] MS-ESI theoretical value [M+1] + 135, measured value: 135.

[0488] Step (2):

[0489] Compound 2 (500 mg) and compound 3 (473 mg) were dissolved in N,N-dimethylacetamide (10 mL), and triethylenediamine (796 mg), bis(dibenzylideneacetone)palladium (338 mg) and tri-tert-butylphosphine tetrafluoroborate (83.6 mg) were added. The mixture was stirred at 120°C for 16 h. A new spot was generated by spot plate detection. The mixture was extracted with water and ethyl acetate, and the organic phase was concentrated under reduced pressure to obtain a residue. The residue was purified by column chromatography (methanol: dichloromethane = 10%) to obtain compound 4 (200 mg).

[0490] MS-ESI theoretical value [M+1] + 209, measured value: 209.

[0491] Step (3):

[0492] Compound 4 (208 mg) and compound 5 (213 mg) were dissolved in acetonitrile (10 mL), stirred at room temperature for 2 h, and a new spot was generated by spot plate detection. The mixture was then cooled to room temperature. The reaction solution was directly filtered and the filter cake was washed with ethyl acetate to obtain compound AB24871 (60 mg).

[0493] MS-ESI theoretical value [M+1] + 341, measured value: 341.

[0494] 1 H NMR (400MHz, DMSO-d6) δ9.24(s,1H),8.71(s,1H),8.40(d,J=6.5Hz,1H),8.31(d,J=6.4Hz,1H),7.97(d,J=7.4Hz ,2H),7.69(d,J=7.4Hz,2H),7.45(d,J=7.5Hz,2H),7.32(d,J=7.3Hz,2H),6.38(s,2H),2.42(s,3H),2.35(s,3H).

[0495] Example 19 Synthesis of Compound AB24873

[0496] Step (1):

[0497] Compound 1 (2 g) was dissolved in dichloromethane (50 mL), and Dess-Martin periodinane (6.4 g) was added at room temperature. The mixture was stirred at room temperature for 1 h. New spots were generated by spot plate detection. The filtrate was concentrated under reduced pressure to remove the organic solvent, and compound 2 (1.1 g) was obtained by column chromatography (ethyl acetate: petroleum ether = 0-10%).

[0498] MS-ESI theoretical value [M+1] + 135, measured value: 135.

[0499] Step (2):

[0500] Compound 2 (1.1 g) and compound 3 (304 mg) were dissolved in N,N-dimethylacetamide (8 mL), and triethylenediamine (796 mg), bis(dibenzylideneacetone)palladium (108 mg) and tri-tert-butylphosphine tetrafluoroborate (70 mg) were added. The mixture was stirred at 120°C for 16 h. A new spot was generated by spot plate detection. The mixture was extracted with water and ethyl acetate, and the organic phase was concentrated under reduced pressure to obtain a residue. The residue was purified by column chromatography (methanol: dichloromethane = 10%) to obtain compound 4 (400 mg).

[0501] MS-ESI theoretical value [M+1] + 208, measured value: 208.

[0502] Step (3):

[0503] Compound 4 (227 mg) and compound 5 (213 mg) were dissolved in acetonitrile (10 mL), stirred at room temperature for 2 h, and a new spot was generated by spot plate detection. The mixture was then cooled to room temperature, and the reaction solution was directly filtered and the filter cake was washed with ethyl acetate to obtain compound AB24873 (60 mg).

[0504] MS-ESI theoretical value [M+1] + 341, measured value: 341.

[0505] 1 H NMR (400MHz, Methanol) δ9.20 (s, 1H), 8.44 (s, 1H), 8.20 (s, 1H), 7.89 (d, J = 6.5Hz, 3H), 7.38(d,J=7.2Hz,2H),7.32(s,2H),7.26(s,2H),6.32(s,2H),2.35(s,3H),2.21(s,3H).

[0506] Example 20 Synthesis of Compound AB24874

[0507] Step (1):

[0508] Compound 3 (100 mg) and compound 4 (132 g) were dissolved in acetonitrile (10 mL), stirred at room temperature for 4 h, and a new spot was generated by spot plate detection. The reaction solution was directly filtered and the filter cake was washed with acetonitrile to obtain compound AB24874 (20 mg).

[0509] MS-ESI theoretical value [M+1] + 327, measured value: 327.

[0510] 1 H NMR (399MHz, DMSO) δ13.49(s,1H),9.32(s,1H),8.79(s,1H),8.47(d,J=6.8Hz,1H),8.40(d,J=6.7Hz,1H),7.98(d,J=7.7Hz ,2H),7.82(d,J=7.4Hz,2H),7.53(t,J=7.4Hz,2H),7.47(d,J=7.7Hz,2H),7.38(t,J=7.3Hz,1H),6.45(s,2H),2.43(s,3H).

[0511] Example 21 Synthesis of Compound AB24875

[0512] Step (1):

[0513] Compound 3 (100 mg) and compound 4 (132 mg) were dissolved in acetonitrile (10 mL) and stirred at room temperature for 4 h. A new spot was generated by spot plate detection. The reaction solution was directly filtered and the filtrate was dried by spin drying. The crude product was purified by preparative purification (acetonitrile / water + 0.1% trifluoroacetic acid) to obtain compound AB24875 (50 mg).

[0514] MS-ESI theoretical value [M+1] + 327, measured value: 327.

[0515] 1 H NMR (400MHz, DMSO) δ13.47(s,1H),9.27(s,1H),8.77(s,1H),8.47(d,J=6.7Hz,1H),8.36(d,J=6.7Hz,1H),7.87(d,J=8.5Hz ,2H),7.81(d,J=7.5Hz,2H),7.59(d,J=7.3Hz,1H),7.52(t,J=6.9Hz,3H),7.38(t,J=6.9Hz,1H),6.41(s,2H),2.43(s,3H).

[0516] Example 22 Synthesis of Compound AB24876

[0517] Step (1):

[0518] Compound 3 (100 mg) and compound 4 (132 mg) were dissolved in acetonitrile (10 mL), stirred at room temperature for 16 h, and a new spot was generated by spot plate detection. The reaction solution was directly filtered and the filter cake was washed with acetonitrile to obtain compound AB24876 (120 mg).

[0519] MS-ESI theoretical value [M+1] + 327, measured value: 327.

[0520] 1 H NMR (399MHz, DMSO) δ13.47(s,1H),9.31(s,1H),8.79(s,1H),8.51–8.46(m,1H),8.40(d,J=6.8Hz,1H),8.10(d,J=7.9Hz,1 H),7.82(d,J=7.6Hz,2H),7.60(t,J=7.6Hz,1H),7.52(d,J=7.0Hz,3H),7.45–7.36(m,2H),6.37(s,2H),2.48–2.44(m,3H).

[0521] Example 23 Synthesis of Compound AB24879

[0522] Step (1):

[0523] Compound 1 (92 mg) and compound 2 (244 mg) were dissolved in acetonitrile (10 mL), stirred at room temperature for 16 h, and a new spot was generated by spot plate detection. The reaction solution was directly filtered and the filter cake was washed with acetonitrile to obtain compound AB24879 (120 mg).

[0524] MS-ESI theoretical value [M+1] + 358.11, measured value: 358.1.

[0525] 1H NMR (400MHz, DMSO-d6) δ13.43(s,1H),9.25(s,1H),8.80(s,1H),8.52(d,J=6.1Hz,1H),8.29(dd,J=17.3,7.4 Hz,2H),8.10–7.87(m,3H),7.80(d,J=7.3Hz,2H),7.52(t,J=7.2Hz,2H),7.39(d,J=6.8Hz,1H),6.29(s,2H).

[0526] Example 24 Synthesis of Compound AB24881

[0527] Step (1):

[0528] Compound 1 (300 mg) was dissolved in acetonitrile (10 mL), and compound 2 (1.38 g) and sodium acetate (669 mg) were added. The mixture was then replaced with nitrogen three times and stirred at room temperature for 16 h. A new spot appeared in the liquid chromatography-mass spectrometry. The mixture was then cooled to room temperature, and the reaction solution was dried and purified by thin layer chromatography (dichloromethane: methanol = 20:1) to obtain compound AB24881 (120 mg).

[0529] MS-ESI theoretical value [M+1] + 303, measured value: 303.

[0530] 1 H NMR (400MHz, DMSO-d6) δ9.30(s,1H),9.16(s,1H),8.88(s,1H),8.33(d,J=8.1Hz,1H),8.14(d,J=7.2Hz,1H),8.03(d ,J=7.2Hz,1H),7.66(d,J=7.7Hz,1H),7.34(d,J=25.1Hz,5H),7.02(s,2H),6.05–5.86(m,2H),4.57(d,J=5.7Hz,2H).

[0531] Example 25 Synthesis of Compound AB24889

[0532] Step 1):

[0533] Compound 1 (25 mg) and compound 2 (35 mg) were dissolved in acetonitrile (5 mL), stirred at room temperature for 3 h, and a new spot was produced by spot plate detection. The solid was precipitated by concentration under reduced pressure, filtered, and the filter cake was washed with acetonitrile and dried to obtain compound AB24889 (30 mg).

[0534] MS-ESI calculated value [M+1] + 342, measured value: 342.

[0535] 1 H NMR (400MHz, DMSO-d6) δ9.64(s,1H),8.27(s,2H),7.95(d,J=7.7Hz,2H),7.32(ddd,J=57.6,37.4,7.5Hz,8H),6.47(s,2H),4.47(s,2H),2.41(s,3H).

[0536] Example 26 Synthesis of Compound AB24896

[0537] Step (1):

[0538] Compound 1 (500 mg), compound 2 (962.96 mg), cuprous iodide (16.2 mg), potassium phosphate (1.79 g) and cyclohexanediamine (99 mg) were dissolved in N,N-dimethylacetamide (20 mL), stirred at 110 ° C for 12 h, and a new spot was generated by spot plate detection. The organic solvent was removed by concentration under reduced pressure, and compound 3 (580 mg) was obtained by purification by column chromatography (methanol: dichloromethane = 0-10%).

[0539] MS-ESI theoretical value [M+1] + 195, measured value: 195.

[0540] Step (2):

[0541] Compound 3 (290 mg) and compound 4 (549 mg) were dissolved in acetonitrile (10 mL), stirred at room temperature for 3 h, and a new spot was produced by spot plate detection. The organic solvent was removed by concentration under reduced pressure, and the product was purified by column chromatography (methanol: dichloromethane = 0-10%) to obtain compound AB24896 (200 mg).

[0542] MS-ESI theoretical value [M+1] + 327, measured value: 327.

[0543] 1H NMR(400MHz,DMSO-d6)δ9.37(s,1H),8.75(s,1H),8.58(s,1H),8.53–8.42(m,2H),8.33(s,1H),8.18(d ,J=7.0Hz,1H),7.95(s,1H),7.73(s,1H),7.67(t,J=7.7Hz,2H),7.58(s,1H),7.40(s,1H),6.52(s,2H).

[0544] Example 27 Synthesis of Compound AB24901

[0545] Step (1):

[0546] Compound 1 (500 mg) was dissolved in acetic acid (10 mL), and liquid bromine (384 mg) and 0.2 ml of aqueous hydrobromic acid solution were added. The mixture was stirred at room temperature for 3 h. A new spot was generated by spot plate detection. Ice water (30 ml) was added, and ethyl acetate (30 mL x 3) was added for extraction. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the organic solvent to obtain compound 2 (604 mg).

[0547] MS-ESI theoretical value [M+1] + 245, measured value: 245.

[0548] Step (2):

[0549] Compound 2 (604 mg) and compound 3 (460 mg) were dissolved in acetonitrile (10 mL), stirred at room temperature for 3 h, and a new spot was produced by spot plate detection. The organic solvent was removed by concentration under reduced pressure, and the product was purified by column chromatography (methanol: dichloromethane = 0-30%) to obtain compound AB24901 (67 mg).

[0550] MS-ESI theoretical value [M+1] + 349, measured value: 349.

[0551] 1H NMR (400MHz, DMSO-d6) δ9.34(s,1H),8.33(d,J=5.8Hz,1H),8.18(d,J=6.1Hz,1H),7.92(d,J=7.1Hz,1H),7.76(d,J=6.9Hz,1H), 7.59 (d, J = 7.1Hz, 1H), 7.33 (d, J = 22.2Hz, 5H), 6.99 (s, 2H), 5.66 (s, 1H), 4.59 (s, 2H), 3.83 (dd, J = 17.4, 8.4Hz, 1H), 3.39 (s, 1H).

[0552] Example 28 Synthesis of Compound AB24902

[0553] Step (1):

[0554] Compound 1 (664 mg) was dissolved in acetic acid (5 mL), and liquid bromine (254 mg) and 0.2 ml of aqueous hydrobromic acid solution were added. The mixture was stirred at room temperature for 3 h. A new spot was generated by spot plate detection. Ice water (30 ml) was added, and ethyl acetate (30 mL x 3) was added for extraction. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the organic solvent to obtain compound 2 (370 mg).

[0555] MS-ESI theoretical value [M+1] + 245, measured value: 245.

[0556] Step (2):

[0557] Compound 2 (133 mg) and compound 3 (100 mg) were dissolved in acetonitrile (10 mL), stirred at room temperature for 3 h, and a new spot was produced by spot plate detection. The organic solvent was removed by concentration under reduced pressure, and the product was purified by column chromatography (methanol: dichloromethane = 0-30%) to obtain compound AB24902 (20 mg).

[0558] MS-ESI theoretical value [M+1] + 349, measured value: 349.

[0559] 1H NMR (400MHz, DMSO-d6) δ9.33 (s, 1H), 8.31 (d, J = 4.4Hz, 1H), 8.17 (s, 1H), 7.71-7.02 (m, 2H), 7.69-7.66 (m, 1H) ,7.32(s,4H),7.31-7.30(m,1H),6.99(s,2H),5.65(s,1H),4.58(s,2H),3.83-3.79(m,1H),3.41-3.37(m,1H).

[0560] Example 29 Synthesis of Compound AB24903

[0561] Step (1):

[0562] Compound 1 (200 mg) was dissolved in acetic acid (10 mL), and liquid bromine (498 mg) and hydrobromic acid (0.2 ml) were added. The mixture was stirred at room temperature for 3 h. A new spot was detected by spot plate detection. The organic solvent was removed by concentration under reduced pressure, and the mixture was purified by column chromatography (ethyl acetate: petroleum ether = 0-20%) to give compound 2 (240 mg).

[0563] MS-ESI theoretical value [M] + 247, measured value: 247.

[0564] Step (2):

[0565] Compound 2 (240 mg) was dissolved in acetonitrile (10 mL), and compound 3 (128 mg) was added. The mixture was then replaced with nitrogen three times and stirred at room temperature overnight. New spots appeared on the plate detection. The organic solvent was removed by concentration under reduced pressure and purified by column chromatography (methanol: dichloromethane = 0-10%) to obtain compound AB24903 (100 mg).

[0566] MS-ESI theoretical value [M] + 349, measured value: 349.

[0567] 1 H NMR (400MHz, DMSO-d6) δ9.37(s,1H),8.33(d,J=6.4Hz,1H),8.17(s,1H),7.76(d,J=7.7Hz,1H),7.62(d,J=7.4Hz,1H),7.56 (d,J=7.8Hz,1H),7.36(s,5H),7.32(s,1H),5.64(s,1H),4.58(d,J=5.3Hz,2H),3.80(dd,J=17.2,7.7Hz,1H),3.42(s,1H).

[0568] Example 30 Synthesis of Compound AB24907

[0569] Step (1):

[0570] Compound 1 (292 mg) was dissolved in acetic acid (5 mL), and liquid bromine (254 mg) and 0.2 ml of aqueous hydrobromic acid solution were added. The mixture was stirred at room temperature for 3 h. A new spot was generated by spot plate detection. Ice water (30 ml) was added, and ethyl acetate (30 mL x 3) was added for extraction. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the organic solvent to obtain compound 2 (225 mg).

[0571] MS-ESI theoretical value [M+1] + 225, measured value: 225.

[0572] Step (2):

[0573] Compound 2 (225 mg) and compound 3 (184 mg) were dissolved in acetonitrile (10 mL), stirred at room temperature for 3 h, and a new spot was produced by spot plate detection. The organic solvent was removed by concentration under reduced pressure, and the product was purified by column chromatography (methanol: dichloromethane = 0-30%) to obtain compound AB24907 (36.3 mg).

[0574] MS-ESI theoretical value [M+1] + 329, measured value: 329.

[0575] 1 H NMR(400MHz,Chloroform-d)δ10.73(s,1H),8.19(s,1H),7.70(s,1H),7.62(d,J=7.8Hz,2H),7.52(d,J=7.4Hz,1H),7.39(d,J=7.6Hz, 1H), 7.29 (dd, J = 13.9, 7.1Hz, 5H), 6.45 (s, 1H), 5.75 (s, 1H), 4.53 (d, J = 4.7Hz, 2H), 4.02 (s, 1H), 3.07 (d, J = 16.9Hz, 1H), 2.35 (s, 3H).

[0576] Example 31 Synthesis of Compound AB24912

[0577] Step (1):

[0578] Compound 1 (360 mg) was dissolved in glacial acetic acid (10 mL), and liquid bromine (256 mg) and 0.2 ml of aqueous hydrobromic acid were added. The mixture was stirred at room temperature for 3 h. A new spot was produced by spot plate detection. The mixture was filtered and the filter cake was concentrated under reduced pressure to remove the organic solvent to obtain compound 2 (300 mg).

[0579] MS-ESI theoretical value [M] + 259, measured value: 259.

[0580] Step (2):

[0581] Compound 2 (300 mg) was dissolved in acetonitrile (10 mL), and compound 3 (184 mg) was added, followed by nitrogen replacement three times. The mixture was stirred at 80°C overnight, and a new spot was generated by spot plate detection. The mixture was purified by column chromatography (methanol: dichloromethane = 0-10%) to obtain compound AB24912 (100 mg).

[0582] MS-ESI theoretical value [M] + 363, measured value: 363.

[0583] 1 H NMR (400MHz, DMSO-d6) δ9.37(s,1H),8.22(d,J=7.3Hz,1H),8.10(d,J=7.1Hz,1H),7.59(t,J=7.8Hz,1H),7.47(d,J=7.9Hz,1H),7.43 –7.36(m,5H),7.31(s,1H),7.02(t,J=6.8Hz,2H),5.67(d,J=11.8Hz,1H),4.59(d,J=6.0Hz,2H),3.25(d,J=16.6Hz,2H),2.81(s,1H)

[0584] Example 32 Synthesis of Compound AB24914

[0585] Step (1):

[0586] Compound 1 (180 mg) was dissolved in acetic acid (7 mL), and liquid bromine (160 mg) and 0.2 ml of aqueous hydrobromic acid were added. The mixture was stirred at room temperature for 3 h. A new spot was generated by spot plate detection. Ice water (30 ml) was added, and ethyl acetate (30 mL x 3) was added for extraction. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the organic solvent to obtain compound 2 (260 mg).

[0587] MS-ESI theoretical value [M] +259, measured value: 259.

[0588] Step (2):

[0589] Compound 2 (260 mg) was dissolved in acetonitrile (10 mL), and compound 3 (184 mg) was added. The mixture was then replaced with nitrogen three times and stirred at room temperature overnight. New spots appeared on the spot plate test, and solids precipitated. The solids were filtered, and the filter cake was washed with acetonitrile and dried to obtain compound AB24914 (50 mg).

[0590] MS-ESI theoretical value [M] + 363, measured value: 363.

[0591] 1 H NMR (400MHz, DMSO-d6) δ9.68 (s, 1H), 8.26 (d, J = 7.4Hz, 1H), 8.16 (d, J = 7.3Hz, 1H) ,7.86(dd,J=22.4,7.8Hz,2H),7.47(t,J=8.1Hz,1H),7.38(d,J=4.7Hz,4H),7.30 (s,1H),7.11(d,J=7.3Hz,1H),7.00(d,J=7.4Hz,1H),5.82(d,J=13.5Hz,1H),4.5 7(d,J=6.0Hz,2H),3.28(s,1H),3.16(d,J=14.6Hz,1H),2.81(s,1H),2.55(s,1H).

[0592] Example 33 Synthesis of Compound AB24918

[0593] Step (1):

[0594] Compound 1 (320 mg) was dissolved in acetic acid (10 mL), and liquid bromine (256 mg) and 0.2 ml of aqueous hydrobromic acid were added. The mixture was stirred at room temperature for 3 h. A new spot was generated by spot plate detection. Ice water (30 ml) was added, and ethyl acetate (30 mL x 3) was added for extraction. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the organic solvent. The mixture was purified by column chromatography (ethyl acetate: petroleum ether = 0-20%) to give compound 2 (234 mg).

[0595] MS-ESI theoretical value [M]+239, measured value: 239.

[0596] Step (2):

[0597] Compound 2 (239 mg) was dissolved in acetonitrile (10 mL), and compound 3 (184 mg) was added. The mixture was then replaced with nitrogen three times and stirred at room temperature overnight. New spots appeared on the plate. The organic solvent was removed by concentration under reduced pressure and the mixture was purified by column chromatography (methanol: dichloromethane = 0-10%) to obtain compound AB24918 (47 mg).

[0598] MS-ESI theoretical value [M]+343, found value: 343.

[0599] 1 H NMR (400MHz, DMSO-d6) δ9.34(t,J=6.0Hz,0H),8.28(d,J=6.9Hz,1H),8.16(d,J=7.1Hz,1H ),7.79(d,J=7.7Hz,1H),7.57(d,J=7.3Hz,1H),7.41(d,J=5.9Hz,2H),7.35(q,J=6.7,5.9 Hz,1H),7.06–7.01(m,1H),5.67(dd,J=14.3,4.4Hz,1H),4.61(d,J=5.9Hz,1H),3.20(d,J =15.3Hz,1H),3.07(dd,J=15.5,10.3Hz,1H),2.86–2.70(m,1H),2.56(s,1H),2.35(s,2H).

[0600] Example 34 Synthesis of Compound AB24935

[0601] Step (1):

[0602] Compound 1 (1 g) was dissolved in N,N-dimethylacetamide (3 mL), and compound 2 (1.28 g), triethylenediamine (3.3 g), bis(dibenzylideneacetone)palladium (457 mg) and tri-tert-butylphosphine tetrafluoroborate (290 mg) were added. The mixture was stirred at 120°C for 16 h. A new spot was generated by spot plate detection. The mixture was extracted with water and ethyl acetate, and the organic phase was concentrated under reduced pressure to obtain a residue. The residue was purified by column chromatography (methanol: dichloromethane = 10%) to obtain compound 3 (40 mg).

[0603] MS-ESI theoretical value [M] + 175, measured value: 175.

[0604] Step (2):

[0605] Compound 3 (40 mg) was dissolved in acetonitrile (5 mL), and compound 4 (122 mg) was added. The mixture was then replaced with nitrogen three times and stirred at room temperature overnight. New spots appeared on the plate detection. The reaction solution was spin-dried and purified by column chromatography (methanol: dichloromethane = 0-10%) to obtain compound AB24935 (6.8 mg).

[0606] MS-ESI theoretical value [M] + 307, measured value: 307.

[0607] 1 H NMR (400MHz, DMSO-d6) δ13.16(s,1H),9.21(s,1H),8.41(d,J=6.8Hz,1H),8.27(dd,J=6.9,1.4Hz, 1H),8.18(s,1H),8.01–7.96(m,2H),7.48(d,J=8.0Hz,2H),6.41(s,2H),2.45(s,3H),1.47(s,9H).

[0608] Example 35 Synthesis of Compound AB24936

[0609] Step (1):

[0610] Compound 3 (200 mg) was dissolved in acetonitrile (5 mL), and compound 4 (322 mg) was added. The mixture was then replaced with nitrogen three times and stirred at room temperature overnight. A new spot appeared on the plate. The reaction solution was spin-dried and purified by column chromatography (methanol:dichloromethane = 0-10%) to obtain 100 mg of compound AB24936.

[0611] MS-ESI theoretical value [M] + 327, measured value: 327.

[0612] 1 H NMR (400MHz, DMSO-d6) δ13.22(s,1H),9.21(s,1H),8.43(d,J=6.8Hz,1H),8.26(d,J=6.9Hz,1H),8.20(s,1H) ,8.12(s,1H),8.04(d,J=7.8Hz,1H),7.88(d,J=8.2Hz,1H),7.71(t,J=7.9Hz,1H),6.45(s,2H),1.47(s,9H).

[0613] Example 36 Synthesis of Compound AB24937

[0614] Step (1):

[0615] Compound 1 (2 g) and compound 2 (2.5 g) were dissolved in N,N-dimethylacetamide (30 mL), and triethylenediamine (6.5 g), bis(dibenzylideneacetone)palladium (890 mg) and tri-tert-butylphosphine tetrafluoroborate (561 mg) were added. The mixture was stirred at 120° C. for 16 h under a sealed tube. A new spot was generated by spot plate detection. The mixture was extracted with water and ethyl acetate, and the organic phase was concentrated under reduced pressure to obtain a residue. The residue was purified by column chromatography (methanol: dichloromethane = 5%) to obtain compound 3 (800 mg).

[0616] MS-ESI theoretical value [M+1] + 161, measured value: 161.

[0617] Step (2):

[0618] Compound 3 (100 mg) was dissolved in acetonitrile (5 mL), and compound 4 (200 mg) was added. The mixture was then replaced with nitrogen three times and stirred at room temperature overnight. A new spot appeared on the plate. The reaction solution was spin-dried and purified by column chromatography (methanol:dichloromethane = 0-10%) to obtain compound AB24937 (70 mg).

[0619] MS-ESI theoretical value [M] + 293, measured value: 293.

[0620] 1 H NMR (400MHz, DMSO-d6) δ9.14 (s, 1H), 8.22 (d, J = 12.8Hz, 3H), 7.95 (d, J = 7.7Hz, 2H), 7.44(d,J=7.7Hz,2H),6.35(s,2H),3.14(s,1H),2.42(s,3H),1.33(d,J=6.7Hz,6H).

[0621] Example 37 Synthesis of Compound AB24946

[0622] Step (1):

[0623] Compound 3 (260 mg) was dissolved in acetonitrile (10 mL), and compound 4 (421 mg) was added. The mixture was then replaced with nitrogen three times and stirred at room temperature overnight. A new spot appeared on the plate and solid precipitated. Compound AB24946 (160 mg) was obtained by filtration.

[0624] MS-ESI theoretical value [M] + 361, measured value: 361.

[0625] 1 H NMR (400MHz, DMSO-d6) δ9.52(s,1H),8.56(s,1H),8.31(d,J=6.8Hz,1H),8.23(d,J=6.8Hz,1H),8.10(s,1H),8.02(d,J= 7.9Hz, 1H), 7.86 (d, J = 8.1Hz, 1H), 7.69 (t, J = 8.0Hz, 1H), 7.31 (d, J = 8.2Hz, 5H), 7.07 (s, 1H), 6.41 (s, 2H), 5.64 (s, 2H).

[0626] Example 38 Synthesis of Compound AB24951

[0627] Step (1):

[0628] Compound 1 (352 mg) was dissolved in acetic acid (7 mL), and liquid bromine (320 mg) and 0.2 ml of aqueous hydrobromic acid were added. The mixture was stirred at room temperature for 3 h. A new spot was generated by spot plate detection. Ice water (30 ml) was added, and ethyl acetate (30 mL x 3) was added for extraction. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the organic solvent to obtain compound 2 (230 mg).

[0629] MS-ESI theoretical value [M] + 255, measured value: 255.

[0630] Step (2):

[0631] Compound 2 (230 mg) was dissolved in acetonitrile (10 mL), and compound 3 (165 mg) was added. The mixture was then replaced with nitrogen three times and stirred at room temperature overnight. New spots appeared on the spot plate test, and solids precipitated. The solids were filtered, and the filter cake was washed with acetonitrile and dried to obtain compound AB24951 (65 mg).

[0632] MS-ESI theoretical value [M] + 359, measured value: 359.

[0633] 1H NMR (400MHz, DMSO-d6) δ9.75(t,J=6.1Hz,1H),8.25(dd,J=7.4,1.9Hz,1H),8.15(dd,J=7.5,1.9Hz,1H),7.5 8(t,J=8.0Hz,1H),7.44–7.37(m,2H),7.32(dq,J=6.0,2.6Hz,1H),7.14(dd,J=7.4,2.9Hz,1H),7.04(d,J=8 .4Hz,1H),7.02–6.94(m,1H),5.62(dd,J=13.9,4.4Hz,1H),4.60(d,J=6.1Hz,1H),3.78(s,2H),3.26(dd,J= 12.4, 4.6Hz, 1H), 3.18 (ddd, J=14.7, 4.1, 2.3Hz, 0H), 2.81–2.69 (m, 0H), 2.42 (ddd, J=10.0, 4.7, 2.4Hz, 1H).

[0634] Example 39 Synthesis of Compound AB24952

[0635] Step (1):

[0636] Compound 1 (200 mg) was dissolved in dichloromethane (10 mL), and compound 2 (470 mg) was added. The mixture was stirred at room temperature for 1 h. A new spot was generated on the spot plate detector. The reaction solution was spin-dried and subjected to thin layer chromatography to obtain compound 3 (280 mg).

[0637] MS-ESI theoretical value [M] + 255, measured value: 255.

[0638] Step (2):

[0639] Compound 3 (280 mg) was dissolved in acetonitrile (10 mL), and compound 4 (135 mg) was added. The mixture was then replaced with nitrogen three times and stirred at room temperature overnight. A new spot appeared on the plate. The reaction solution was spin-dried and purified by column chromatography (methanol: dichloromethane = 0-10%) to obtain compound AB24952 (60 mg).

[0640] MS-ESI theoretical value [M] + 359, measured value: 359.

[0641] 1H NMR (400MHz, DMSO-d6) δ9.49 (s, 1H), 8.25 (d, J = 7.3Hz, 1H), 8.15 (d, J = 7.2Hz, 1H), 7.41–7.22 (m, 8H), 7.02 (dd, J = 29. 2,7.2Hz,2H),5.68(d,J=13.8Hz,1H),4.57(d,J=5.7Hz,2H),3.76(s,3H),3.27–3.03(m,3H),2.74(d,J=13.3Hz,1H).

[0642] Example 40 Synthesis of Compound AB24958

[0643] Step (1):

[0644] Compound 1 (532 mg) was dissolved in dimethyl sulfoxide (20 mL), and cesium carbonate (3.28 g), cuprous iodide (152.4 mg) and 5 drops of N,N-dimethylethylenediamine were added. The reaction solution was stirred at room temperature for 10 min, and compound 2 (1.3 g) was added. The reaction solution was heated to 120 ° C. and stirred for 2 h. A new spot was generated on the spot plate detector. The product was extracted with water and ethyl acetate, and the organic phase was concentrated under reduced pressure to obtain a residue. The residue was purified by thin layer chromatography (methanol: dichloromethane = 0-10%) to obtain compound 3 (400 mg).

[0645] MS-ESI theoretical value [M] + 211, measured value: 211.

[0646] Step (2):

[0647] Compound 3 (105 mg) was dissolved in acetonitrile (5 mL), and compound 4 (130 mg) was added, followed by nitrogen replacement three times. The mixture was stirred at room temperature overnight. A new spot was generated by spot plate detection, and solid precipitated. The solid was filtered and washed with acetonitrile to obtain compound AB24958 (122 mg).

[0648] MS-ESI theoretical value [M] + 343, measured value: 343.

[0649] 1H NMR (400MHz, DMSO-d6) δ8.82(d,J=6.7Hz,2H),8.52(d,J=6.7Hz,2H),7.93(dd,J=13.7,7.7Hz,3H),7.81(t,J=7.6H z, 1H), 7.75 (d, J = 7.7Hz, 1H), 7.62 (t, J = 7.5Hz, 1H), 7.45 (d, J = 7.7Hz, 2H), 6.30 (s, 2H), 5.20 (s, 2H), 2.42 (s, 3H).

[0650] Example 41 Synthesis of Compound AB24962

[0651] Step (1):

[0652] Compound 1 (200 mg) was dissolved in acetonitrile (10 mL), and compound 2 (371 mg) was added. The mixture was then replaced with nitrogen three times and stirred at room temperature overnight. New spots appeared on the plate detection. The reaction solution was spin-dried and purified by column chromatography (methanol: dichloromethane = 0-10%) to obtain compound AB24962 (110 mg).

[0653] MS-ESI theoretical value [M] + 338, measured value: 338

[0654] 1 H NMR (400MHz, DMSO-d6) δ10.33(s,1H),8.76(s,1H),8.14(d,J=7.5Hz,1H),8.02(d,J=8.2Hz,2H),7.7 0(d,J=8.0Hz,2H),7.33(d,J=21.4Hz,5H),7.00(d,J=7.4Hz,1H),5.87(d,J=9.2Hz,2H),4.73(s,2H).

[0655] Example 42 Synthesis of Compound AB24965

[0656] Step (1):

[0657] Compound 1 (500 g) was dissolved in N,N-dimethylformamide (10 mL), potassium carbonate (1.4 g, 60% in mineral oil) and benzyl bromide (949 mg) were added, and the reaction was carried out at 80°C overnight. The reaction solution was diluted with water and the organic phase was extracted with ethyl acetate to separate the organic phase. The organic phase was dried over anhydrous sodium sulfate, filtered and dried by rotary evaporation. The crude product was prepared using normal phase (petroleum ether / ethyl acetate = 0%-10%) to give compound 2 (500 mg).

[0658] MS-ESI: theoretical value [M+H] + :186.10.

[0659] Step (2):

[0660] Compound 2 (100 mg) was dissolved in acetonitrile (5 mL), and compound 3 (126 mg) was added. The mixture was reacted at 80°C for 16 h. The reaction solution was spin-dried and the crude product was prepared by reverse phase (acetonitrile / water + 0.1% trifluoroacetic acid) to obtain compound AB24965 (24.2 mg).

[0661] MS-ESI: theoretical value [M] + :338.11; measured value:338.20.

[0662] 1 H NMR (400MHz, DMSO-d6) δ10.4(s,1H),8.7(s,1H),8.2-7.6(m,5H),7.77-7.73(m,5H),7.0(d,J=8.0Hz,1H),5.9(s,2H),4.7(s,2H).

[0663] Example 43 Synthesis of Compound AB24966

[0664] Step (1):

[0665] Compound 1 (300 mg) was dissolved in acetonitrile (15 mL), and compound 2 (558 mg) was added, followed by nitrogen replacement three times. The mixture was stirred at room temperature overnight, and a new spot was generated by spot plate detection. The organic solvent was removed by concentration under reduced pressure, and the mixture was purified by column chromatography (methanol: dichloromethane = 0-30%) to obtain compound AB24966 (40 mg).

[0666] MS-ESI theoretical value [M] + 334, measured value: 334.

[0667] 1 H NMR (400MHz, DMSO-d6) δ10.15(s,1H),8.76(s,1H),8.13(d,J=7.5Hz,1H),7.60(d,J=7.8Hz,1H),7.54(t,J=8.0Hz,1H), 7.48(s,1H),7.37(d,J=6.4Hz,6H),7.31(s,1H),6.95(d,J=7.3Hz,1H),5.87(s,2H),4.73(d,J=5.7Hz,2H),3.82(s,4H).

[0668] Example 44 Synthesis of Compound AB24969

[0669] Step 1):

[0670] Compound 1 (228 mg) was dissolved in N,N-dimethylformamide (20 mL), compound 2 (354.6 mg) was added, and then potassium carbonate (829 mg) was added. The reaction solution was heated to 80°C and stirred for 4 h. A new spot was generated on the spot plate detector. The product was extracted with water and ethyl acetate, and the organic phase was concentrated under reduced pressure to obtain a residue. The residue was purified by thin layer chromatography (methanol: dichloromethane = 0-10%) to obtain compound 3 (50 mg).

[0671] MS-ESI theoretical value [M] + 138, measured value: 138.

[0672] Step 2):

[0673] Compound 3 (50 mg) was dissolved in acetonitrile (5 mL), and then compound 4 (50 mg) was added. The mixture was then replaced with nitrogen three times and stirred at room temperature overnight. New spots appeared on the spot plate. The reaction solution was spin-dried and purified by preparative purification (acetonitrile / water + 0.1% trifluoroacetic acid) to obtain compound AB24969 (53.1 mg).

[0674] MS-ESI theoretical value [M-CF3COO - ] + 270, measured value: 270.

[0675] 1 H NMR (400MHz, DMSO-d6) δ9.79(s,1H),8.72(s,1H),8.07(d,J=6.9Hz,1H),7.90(d,J=7.1Hz,2H),7.42(d,J=7.1Hz ,2H),6.87(d,J=6.9Hz,1H),5.83(s,2H),3.31(s,2H),2.40(s,3H),1.58(d,J=6.8Hz,2H),0.91(d,J=6.8Hz,3H).

[0676] Example 45 Synthesis of Compound AB24976

[0677] Step (1):

[0678] Compound 1 (500 mg) was dissolved in acetic acid (7 mL), and liquid bromine (1.38 g) and 0.2 ml of aqueous hydrobromic acid were added. The mixture was stirred at room temperature for 3 h. A new spot was generated by spot plate detection. Ice water (30 ml) was added, and ethyl acetate (50 mL x 3) was added for extraction. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the organic solvent to obtain compound 2 (300 mg).

[0679] MS-ESI theoretical value [M] + 229, measured value: 229.

[0680] Step (2):

[0681] Compound 2 (270 mg) was dissolved in acetonitrile (5 mL), and compound 3 (239 mg) was added, followed by nitrogen replacement three times. The mixture was stirred at room temperature overnight. New spots appeared on the spot plate test, and solids precipitated. The solids were filtered, and the filter cake was washed with acetonitrile and dried to obtain compound AB24976 (132.1 mg).

[0682] MS-ESI theoretical value [M] + 333, measured value: 333.

[0683] 1 H NMR(400MHz, DMSO-d6)δ9.42(d,J=54.9Hz,1H),8.33(s,1H),8.18(s,1H),7.71(d,J=11.3Hz,2H),7.63–7.55 (m,1H),7.34(d,J=17.6Hz,5H),7.06–6.95(m,2H),5.69(s,1H),4.58(s,2H),3.87–3.76(m,1H),3.41(s,1H).

[0684] Example 46 Synthesis of Compound AB24979

[0685] Step (1):

[0686] Compound 1 (162 mg) was dissolved in acetic acid (7 mL), and liquid bromine (160 mg) and 0.2 ml of aqueous hydrobromic acid were added. The mixture was stirred at room temperature for 3 h. A new spot was generated by spot plate detection. Ice water (30 ml) was added, and ethyl acetate (30 mL x 3) was added for extraction. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the organic solvent to obtain compound 2 (180 mg).

[0687] MS-ESI theoretical value [M] +241, measured value: 241.

[0688] Step (2):

[0689] Compound 2 (180 mg) was dissolved in acetonitrile (10 mL), and compound 3 (150 mg) was added. The mixture was then replaced with nitrogen three times and stirred at room temperature overnight. New spots appeared on the spot plate test, and solids precipitated. The solids were filtered and the filter cake was washed three times with acetonitrile and dried to obtain compound AB24979 (26.7 mg).

[0690] MS-ESI theoretical value [M] + 345, measured value: 345.

[0691] 1 H NMR (400MHz, DMSO-d6) δ9.60(s,1H),8.29(d,J=6.8Hz,1H),8.15(d,J=6.7Hz,1H),7.73(t,J=7.5Hz,1H),7.36(s,4H),7.30(s,1H),7.14(d ,J=7.1Hz,1H),7.06(d,J=7.6Hz,2H),6.96(d,J=6.6Hz,1H),5.56(s,1H),4.56(d,J=4.5Hz,2H),3.86(s,3H),3.73(dd,J=16.7,8.4Hz,1H).

[0692] Example 47 Synthesis of Compound AB24980

[0693] Step (1):

[0694] Compound 1 (500 mg) was dissolved in acetic acid (5 mL), and liquid bromine (384 mg) and 0.2 ml of aqueous hydrobromic acid solution were added. The mixture was stirred at room temperature for 3 h. A new spot was generated by spot plate detection. Ice water (30 ml) was added, and ethyl acetate (30 mL x 3) was added for extraction. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the organic solvent to obtain compound 2 (311 mg).

[0695] MS-ESI theoretical value [M+1] + 241, measured value: 241.

[0696] Step (2):

[0697] Compound 2 (311 mg) and compound 3 (153 mg) were dissolved in acetonitrile (10 mL), stirred at room temperature for 3 h, and a new spot was produced by spot plate detection. The organic solvent was removed by concentration under reduced pressure, and the mixture was purified by column chromatography (methanol: dichloromethane = 0-30%) to obtain compound AB24980 (100 mg).

[0698] MS-ESI theoretical value [M+1] + 345, measured value: 345.

[0699] 1 H NMR(400MHz,DMSO-d6)δ9.42(s,1H),8.30(s,1H),8.15(s,1H),7.59(d,J=8.2Hz,1H),7 .34(d,J=17.8Hz,6H),7.22(s,1H),7.00(s,2H),5.64(s,1H),4.57(s,2H),3.81(s,3H).

[0700] Example 48 Synthesis of Compound AB24981

[0701] Step (1):

[0702] Compound 1 (486 mg) was dissolved in acetic acid (5 mL), and liquid bromine (381 mg) and 0.2 ml of aqueous hydrobromic acid were added. The mixture was stirred at room temperature for 3 h. A new spot was generated by spot plate detection. Ice water (30 ml) was added, and ethyl acetate (30 mL x 3) was added for extraction. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the organic solvent to obtain compound 2 (340 mg).

[0703] MS-ESI theoretical value [M+1] + 241, measured value: 241.

[0704] Step (2):

[0705] Compound 2 (340 mg) and compound 3 (100 mg) were dissolved in acetonitrile (10 mL), stirred at room temperature for 3 h, and a new spot was produced by spot plate detection. The organic solvent was removed by concentration under reduced pressure, and the product was purified by column chromatography (methanol: dichloromethane = 0-30%) to obtain compound AB24981 (140 mg).

[0706] MS-ESI theoretical value [M+1] + 345, measured value: 345.

[0707] 1H NMR(400MHz,DMSO-d6)δ9.72(s,1H),8.30(d,J=6.8Hz,1H),8.16(d,J=6.8Hz ,1H),7.69(d,J=8.3Hz,1H),7.36(s,4H),7.29(s,1H),7.21(s,1H),7.07(d, J=7.2Hz,2H),6.96(d,J=6.5Hz,1H),5.64(s,1H),4.56(d,J=4.3Hz,2H),3.8 8(s,3H),3.79(dd,J=17.0,8.2Hz,1H),3.38(s,0.5H),3.15–3.12(m,0.5H).

[0708] Example 49 Synthesis of Compound AB24990

[0709] Step (1):

[0710] Compound 1 (100 mg) was dissolved in acetonitrile (10 mL), and compound 2 (73 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-5%) to obtain compound AB24990 (87.9 mg).

[0711] MS-ESI: theoretical value [M] + : 411.13; measured value: 411.05.

[0712] 1 H NMR(400MHz,DMSO-d6)δ9.26(s,1H),8.46(s,1H),8.35(s,1H),8.20(s,1H),8.16(s ,1H),7.96(s,1H),7.80(s,2H),7.34(m,5H),7.19(s,1H),6.40(s,2H),5.67(s,2H).

[0713] Example 50 Synthesis of Compound AB24992

[0714] Step (1):

[0715] Compound 1 (500 mg) was dissolved in tetrahydrofuran (10 mL), and sodium hydroxide (253 mg, 60% in mineral oil) was added at 0°C. After reacting for 0.5 h, bromobenzene (664 mg) was added and the reaction was continued at room temperature for 1 h. The reaction solution was quenched with saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The organic phase was dried over anhydrous sodium sulfate, filtered and spin-dried. The crude product was prepared using normal phase (dichloromethane / methanol = 0%-10%) to give compound 2 (450 mg).

[0716] MS-ESI: Calculated value [M+H]: 195.09.

[0717] Step (2):

[0718] Compound 2 (100 mg) was dissolved in acetonitrile (5 mL), and compound 3 (165 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-20%) to obtain compound AB24992 (101.4 mg).

[0719] MS-ESI: theoretical value [M] + : 381.12; measured value: 381.05.

[0720] 1 H NMR (400MHz, DMSO-d6) δ9.38(s,1H),8.53(s,1H),8.25-8.18(m,4H),8.03(s,2H),7.73-7.59(m,5H),7.40(s,1H),6.49(s,2H).

[0721] Example 51 Synthesis of Compound AB24993

[0722] Step (1):

[0723] Compound 1 (120 mg) was dissolved in acetonitrile (10 mL), and compound 2 (262 mg) was added, followed by nitrogen replacement three times. The mixture was stirred at room temperature overnight, and a new spot was generated by spot plate detection. The organic solvent was removed by concentration under reduced pressure, and the mixture was purified by column chromatography (methanol: dichloromethane = 0-30%) to obtain compound AB24993 (176.9 mg).

[0724] MS-ESI theoretical value [M] + 397, measured value: 397.

[0725] 1H NMR (400MHz, DMSO-d6) δ9.42(s,1H),8.56(d,J=7.1Hz,1H),8.37(d,J=3.4Hz,1H),8.23(dd,J=10.5,8.0 Hz, 3H), 7.81–7.76 (m, 2H), 7.74–7.67 (m, 4H), 7.63 (d, J = 7.3Hz, 1H), 7.43 (d, J = 3.4Hz, 1H), 6.51 (s, 2H).

[0726] Example 52 Synthesis of Compound AB24998

[0727] Step (1):

[0728] Compound 1 (4.4 g) was dissolved in N,N-dimethylformamide (150 mL), and compound 2 (4.28 g), bistriphenylphosphine palladium dichloride (421 mg), N,N-diisopropylethylamine (8.25 g) and cuprous iodide (190 mg) were added, followed by nitrogen replacement three times, stirring at room temperature overnight, and a new spot appeared on the plate detection. The mixture was diluted with water (250 ml) and then extracted with ethyl acetate (100 mL x 3). The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to remove the organic solvent. The mixture was purified by column chromatography (ethyl acetate: petroleum ether = 0-50%) to give compound 3 (3.5 g).

[0729] MS-ESI theoretical value [M+1] + 195, measured value: 195.

[0730] Step (2):

[0731] Compound 3 (3.5 g) was dissolved in dioxane (100 mL), and 1 mol potassium tert-butoxide tetrahydrofuran solution (53.8 ml) was added. The mixture was then replaced with nitrogen three times, the temperature was raised to 110° C. and stirred for 16 h. A new spot appeared on the plate. The mixture was diluted with water (200 ml) and extracted with ethyl acetate (100 mL x 3). The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to remove the organic solvent. The mixture was purified by column chromatography (methanol:dichloromethane = 0-10%) to give compound 4 (2.2 g).

[0732] MS-ESI theoretical value [M+1] + 195, measured value: 195

[0733] Step (3):

[0734] Compound 4 (800 mg) was dissolved in glacial acetic acid (50 mL), and palladium carbon (100 mg) was added. The mixture was stirred at 80°C for 16 h under hydrogen conditions. New spots were generated by spot plate detection. The mixture was filtered through celite, and the filtrate was dried and purified by preparative purification (acetonitrile / water + 0.1% trifluoroacetic acid) to obtain compound 5 (100 mg).

[0735] MS-ESI theoretical value [M+1]+197, measured value: 197.

[0736] Step (4):

[0737] Compound 5 (50 mg) was dissolved in acetone (10 mL), and compound 6 (170 mg) and sodium acetate (102 mg) were added. The mixture was then replaced with nitrogen three times and stirred at 80° C. for 2 h. A new spot appeared on the plate. The organic solvent was removed by concentration under reduced pressure and purified by thin layer chromatography (dichloromethane: methanol = 20:1) to obtain compound AB24998 (20 mg).

[0738] MS-ESI theoretical value [M] + 383.39, measured value: 383.20.

[0739] 1 H NMR (400MHz, DMSO-d6) δ9.48(s,1H),8.19(d,J=7.1Hz,2H),8.09(s,1H),8.01(d,J=7.3Hz,2H),7.96(s,1H),7.39(s,2 H),7.34(d,J=6.5Hz,3H),6.85(d,J=6.3Hz,1H),5.96(s,2H),5.39(s,1H),3.78–3.65(m,1H),3.01(d,J=16.6Hz,1H).

[0740] Example 53 Synthesis of Compound AB25000

[0741] Step (1):

[0742] Compound 1 (80 mg) was dissolved in acetone (10 mL), and compound 2 (382 mg) and sodium acetate (176 mg) were added. The mixture was then replaced with nitrogen three times and stirred at 80°C for 2 h. New spots appeared on the spot plate detection. The organic solvent was removed by concentration under reduced pressure, and compound AB25000 (15 mg) was obtained by preparative purification (acetonitrile / water + 0.1% trifluoroacetic acid).

[0743] MS-ESI theoretical value [M+1] +409.15, measured value: 409.15.

[0744] 1 H NMR (400MHz, CD3OD) δ8.19(s,1H),8.08(s,1H),7.94(s,1H),7.75(d,J=34.6Hz,2H),7.38(s,5H),6.80(s,1H),5.55(d,J=13. 3Hz,1H),5.41(s,1H),3.75(d,J=11.2Hz,1H),3.54–3.34(m,2H),3.10(d,J=16.3Hz,1H),2.84(d,J=11.0Hz,1H),2.66(s,1H).

[0745] Example 54 Synthesis of Compound AB27108

[0746] Step (1):

[0747] Compound 1 (80 mg) and compound 2 (103 mg) were dissolved in acetonitrile (5 mL) and stirred at room temperature for 3 h. New spots were produced by spot plate detection, and solids were precipitated. The filter cake was washed with acetonitrile and dried to obtain compound AB27108 (20 mg).

[0748] MS-ESI theoretical value [M+1] + 381, measured value: 381.

[0749] 1 H NMR (400MHz, DMSO-d6) δ9.31(s,1H),8.83(s,1H),8.53(d,J=6.8Hz,1H),8.40(d,J=6.9Hz,1H),8.30(d,J=8.1H z, 2H), 8.08 (d, J = 8.3Hz, 2H), 7.85 (d, J = 7.2Hz, 2H), 7.56 (t, J = 7.7Hz, 2H), 7.42 (t, J = 7.4Hz, 1H), 6.51 (s, 2H).

[0750] Example 55 Synthesis of Compound AB27109

[0751] Step (1):

[0752] Compound 1 (80 mg) and compound 2 (103 mg) were dissolved in acetonitrile (5 mL), stirred at room temperature for 3 h, and a new spot was produced by spot plate detection. Solid precipitated, filtered, and the filter cake was washed with acetonitrile and dried to obtain compound AB27109 (20 mg).

[0753] MS-ESI theoretical value [M+1] + 397, measured value: 397.

[0754] 1 H NMR (400MHz, DMSO-d6) δ9.30(s,1H),8.81(s,1H),8.50(d,J=6.8Hz,1H),8.38(d,J=6.9Hz,1H),8.26–8.22( m,2H),7.86–7.82(m,2H),7.69(d,J=8.1Hz,2H),7.55(t,J=7.7Hz,2H),7.41(t,J=7.4Hz,1H),6.47(s,2H).

[0755] Example 56 Synthesis of Compound AB27113

[0756] Step (1):

[0757] Compound 1 (100 mg) was dissolved in acetonitrile (5 mL), and compound 2 (153 mg) was added. The mixture was reacted at 80°C for 16 h. The reaction solution was spin-dried and the crude product was purified using reverse phase preparation (acetonitrile / water + 0.1% trifluoroacetic acid) to obtain compound AB27113 (20.6 mg).

[0758] MS-ESI: theoretical value [M] + :388.13; measured value:388.25.

[0759] 1 H NMR (400MHz, DMSO-d6) δ10.61(s,1H),8.80(s,1H),8.16(s,3H),7.61(s,2H),7.30-7.28(m,5H),7.09(s,1H),5.96(s,2H),4.72(s,2H).

[0760] Example 57 Synthesis of Compound AB27115

[0761] Step (1):

[0762] Compound 1 (100 mg) and compound 2 (163 mg) were dissolved in acetonitrile (10 mL), stirred at room temperature for 3 h, and a new spot was produced by spot plate detection. The organic solvent was removed by concentration under reduced pressure, and the product was purified by column chromatography (methanol: dichloromethane = 0-30%) to obtain compound AB27115 (51.8 mg).

[0763] MS-ESI theoretical value [M+1] + 411, measured value: 411

[0764] 1 H NMR (400MHz, DMSO-d6) δ12.99(s,1H),9.09(s,1H),8.33(d,J=6.1Hz,1H),8.19(d,J=7.9Hz,2H),7.94( d,J=6.2Hz,1H),7.64(d,J=7.6Hz,2H),7.29(d,J=29.3Hz,5H),6.81(s,1H),6.36(s,2H),4.24(s,2H).

[0765] Example 58 Synthesis of Compound AB27156-1

[0766] Step 1):

[0767] Compound 1 (700 mg) was dissolved in acetonitrile (10 mL), and compound 2 (644 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction solution was spin-dried and the crude product was purified using normal phase preparation (dichloromethane / methanol = 0-5%) to obtain compound AB27156-1 (195.2 mg).

[0768] MS-ESI: theoretical value [M] + :413.15; measured value:413.10.

[0769] 1H NMR (400MHz, DMSO-d6) δ9.33-9.31(m,1H),8.26(d,J=8.0Hz,1H),8.15(d,J=4.0H z,1H),7.99(d,J=8.0Hz,1H),7.78(d,J=8.0Hz,1H),7.60-7.58(m,1H),7.35-7.33 (m,4H),7.32-7.29(m,1H),7.06-7.03(m,2H),5.80-5.75(m,1H),4.61(d,J=8.0Hz ,2H),3.32-3.17(m.1H),3.14-3.10(m,1H),2.80-2.76(m,1H),2.59-2.54(m,1H).

[0770] Example 59 Synthesis of Compound AB27119

[0771] Step (1):

[0772] Compound 1 (300 mg) was dissolved in N,N-dimethylacetamide (20 mL), and compound 2 (259 mg), triethylenediamine (585.8 mg), bis(dibenzylideneacetone)palladium (92.4 mg) and tri-tert-butylphosphine tetrafluoroborate (678 mg) were added. The mixture was stirred at 110°C for 16 h. A new spot was generated by spot plate detection. The mixture was extracted with water and ethyl acetate, and the organic phase was concentrated under reduced pressure to obtain a residue. The residue was purified by column chromatography (methanol: dichloromethane = 0-10%) to obtain compound 3 (100 mg).

[0773] MS-ESI theoretical value [M+1] + 223, measured value: 223.

[0774] Step (2):

[0775] Compound 3 (50 mg) was dissolved in acetonitrile (10 mL), and compound 4 (150 mg) was added. The mixture was then replaced with nitrogen three times. The temperature was raised to 110° C. and stirred for 2 h. A new spot appeared on the plate. The mixture was filtered and concentrated under reduced pressure to remove the organic solvent. The mixture was purified by thin layer chromatography (methanol: dichloromethane = 0-10%) to obtain compound AB27119 (11.5 mg).

[0776] MS-ESI theoretical value [M+1] + 425, measured value: 425.

[0777] 1H NMR (400MHz, DMSO-d6) δ9.14(s,1H),8.25(s,1H),8.18(d,J=8.8Hz,3H),8.08(d,J=6.5Hz,1H),7.64( d,J=8.0Hz,2H),7.20(d,J=7.4Hz,2H),7.09(d,J=7.3Hz,2H),6.38(s,2H),4.13(s,2H),2.23(s,3H).

[0778] Example 60 Synthesis of Compound AB27120

[0779] Step (1):

[0780] Compound 1 (4 g) was dissolved in dichloromethane (50 mL), and Dess-Martin reagent (15 g) was added in an ice bath. The mixture was stirred at room temperature for 2 h. A new spot was generated by spot plate detection. The mixture was filtered, and the organic phase was concentrated under reduced pressure to obtain a residue. The residue was purified by column chromatography (ethyl acetate: petroleum ether = 3%) to obtain compound 2 (2 g).

[0781] MS-ESI theoretical value [M+1] + 135, measured value: 135.

[0782] Step (2):

[0783] Compound 2 (2 g) was dissolved in N,N-dimethylacetamide (20 mL), and compound 3 (1.6 g), triethylenediamine (4.2 g), bis(dibenzylideneacetone)palladium (568 mg) and tri-tert-butylphosphine tetrafluoroborate (360 mg) were added. The mixture was stirred at 110° C. for 16 h. A new spot was generated by spot plate detection. The mixture was extracted with water and ethyl acetate, and the organic phase was concentrated under reduced pressure to obtain a residue. The residue was purified by column chromatography (methanol: dichloromethane = 3%) to obtain compound 4 (600 mg).

[0784] MS-ESI theoretical value [M+1] + 209, measured value: 209.

[0785] Step (3):

[0786] Compound 4 (200 mg) was dissolved in acetonitrile (5 mL), and compound 5 (308 mg) was added, followed by nitrogen replacement three times. The mixture was stirred at room temperature overnight. New spots appeared on the plate detection plate. The mixture was filtered and washed with acetonitrile to obtain compound AB27120 (80.8 mg).

[0787] MS-ESI theoretical value [M+1] +395, measured value: 395.

[0788] 1 H NMR (400MHz, DMSO-d6) δ13.47(s,1H),9.28(s,1H),8.78(s,1H),8.50(d,J=6.7Hz,1H),8.37(d,J=6.5Hz,1H),8.27(d,J=7. 8Hz,2H),8.05(d,J=7.9Hz,2H),7.65–7.57(m,2H),7.41(t,J=7.5Hz,1H),7.20(d,J=7.1Hz,1H),6.48(s,2H),2.41(s,3H).

[0789] Example 61 Synthesis of Compound AB27135

[0790] Step (1):

[0791] Compound 1 (60 mg) was dissolved in acetonitrile (10 mL), and then compound 2 (85 mg) was added. The mixture was then replaced with nitrogen three times and stirred at room temperature overnight. New spots appeared on the plate detection. The organic solvent was removed by concentration under reduced pressure and purified by thin layer chromatography (methanol: dichloromethane = 10%) to obtain compound AB27135 (20 mg).

[0792] MS-ESI theoretical value [M] + 424.16, measured value: 424.10.

[0793] 1 H NMR (400MHz, DMSO-d6) δ10.35(s,1H),8.80(s,1H),8.36(s,1H),8.14(s,1H),8.04(d,J=7.2Hz,1H),7.74(d,J=7.7Hz,1H),7.35(d ,J=23.9Hz,5H),5.94(d,J=11.7Hz,1H),4.92(s,1H),3.41(s,2H),2.80(s,2H),2.55(s,2H),2.10(s,1H),1.90(d,J=11.6Hz,1H).

[0794] Example 62 Synthesis of Compound AB27152

[0795] Step (1):

[0796] Compound 1 (700 mg) was dissolved in dichloromethane (80 mL), and compound 1-1 (1.5 g), triethylamine (1.2 g) and copper acetate (1.2 g) were added. The oxygen was replaced three times, and the mixture was stirred at room temperature overnight. A new spot appeared on the plate. The mixture was diluted with water (20 mL) and then extracted with dichloromethane (30 mL x 3). The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to remove the organic solvent. Compound 2 (170 mg) was obtained by purification by thin layer chromatography (methanol: dichloromethane = 10%).

[0797] MS-ESI theoretical value [M+1] + 159, measured value: 159.

[0798] Step (2):

[0799] Compound 2 (85 mg) was dissolved in acetonitrile (10 mL), and compound 3 (150 mg) was added, followed by nitrogen replacement three times. The mixture was stirred at 80°C overnight, and new spots appeared on the plate. The organic solvent was removed by concentration under reduced pressure, and compound AB27152 (40 mg) was obtained by preparative purification (acetonitrile / water + 0.1% trifluoroacetic acid).

[0800] MS-ESI theoretical value [M+1] + 371, measured value: 371.

[0801] 1 H NMR (400MHz, DMSO-d6) δ9.35(s,1H),8.58(d,J=6.3Hz,1H),8.26(d,J=6.5Hz,1H),8.15(s,1H),8.10–7.98(m,2H),7.77(d,J=7.4Hz ,1H),7.07(s,1H),6.21(d,J=13.6Hz,1H),3.75(s,1H),3.32(s,2H),3.06(s,1H),2.70(s,1H),1.18(d,J=7.3Hz,2H),1.12(s,2H).

[0802] Example 63 Synthesis of Compound AB27164

[0803] Step (1):

[0804] Compound 1 (50 mg) was dissolved in acetonitrile (5 mL), and compound 2 (66 mg) was added. The mixture was then replaced with nitrogen three times and stirred at room temperature overnight. New spots appeared on the plate. The organic solvent was removed by concentration under reduced pressure and the mixture was purified by column chromatography (methanol: dichloromethane = 0-30%) to obtain compound AB27164 (10.4 mg).

[0805] MS-ESI theoretical value [M] + 374, measured value: 374.

[0806] 1 H NMR (400MHz, DMSO-d6) δ9.41(s,1H),9.13(s,1H),8.11(d,J=7.0Hz,2H),7.88(s,1H),7.78(d,J=7.8Hz ,1H),7.56(d,J=7.4Hz,4H),7.48(s,2H),6.17(d,J=10.0Hz,1H),3.02(d,J=11.6Hz,2H),2.70(s,2H).

[0807] Example 64 Synthesis of Compound AB35542

[0808] Step (1):

[0809] Compound 1 (5 g) was dissolved in dichloromethane (100 mL), and N-bromosuccinimide (6.6 g) and p-toluenesulfonic acid (1.1 g) were added. The mixture was reacted at 40° C. for 16 h under nitrogen protection. The reaction was completed after monitoring by LCMS. The reaction solution was diluted with water and extracted with dichloromethane. The organic phase was dried over anhydrous sodium sulfate, filtered, and spin-dried. The crude product was purified by flash chromatography (petroleum ether / ethyl acetate = 50 / 1) to give compound 2 (6.6 g).

[0810] MS-ESI: Calculated [M+H]: 239.00.

[0811] Step (2):

[0812] Compound 2 (300 mg) was dissolved in acetonitrile (10 mL), and compound 3 (261 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction was completed as monitored by LCMS. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-5%) to obtain compound AB35542 (198.7 mg).

[0813] MS-ESI: theoretical value [M] + : 368.18, measured value: 368.35.

[0814] 1 H NMR(400MHz, DMSO-d6)δ9.67(s,1H),9.40(s,1H),8.32(d,J=4.0Hz,1H),7.76(s,1H),7.55(d,J=8.0Hz,1H),7.40-7.34(m,6H),7.22(d, J=4.0Hz,1H),6.26-6.21(m,1H),5.68(s,2H),3.39-3.35(m,1H),3.27-3.23(m,1H),3.04-2.96(m,1H),2.74-2.71(m,1H),2.37(s,3H).

[0815] Example 65 Synthesis of Compound AB35552

[0816] Step (1)

[0817] Compound 1 (3.38 g) was dissolved in dichloromethane (50 mL), and N-bromosuccinimide (3.4 g) and p-toluenesulfonic acid (543 mg) were added. The mixture was reacted at 40° C. for 16 h under nitrogen protection. The reaction was completed after monitoring by LCMS. The reaction solution was diluted with water and extracted with dichloromethane. The organic phase was dried over anhydrous sodium sulfate, filtered, and spin-dried. The crude product was subjected to flash chromatography (petroleum ether / ethyl acetate = 0-5%) to give compound 2 (3.6 g).

[0818] MS-ESI: Calculated [M+H]: 292.97.

[0819] Step (2):

[0820] Compound 2 (500 mg) was dissolved in acetonitrile (15 mL), and compound 3 (483 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction was completed after monitoring by LCMS. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-5%) to obtain compound 4 (350 mg).

[0821] MS-ESI: theoretical value [M] + :497.20.

[0822] Step (3):

[0823] Compound 4 (350 mg) was dissolved in dichloromethane (10 mL), and aqueous hydrobromic acid solution (1 mL, 48%) was added. The reaction was allowed to react at room temperature for 1 h. The reaction was completed as monitored by LCMS. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-5%) to obtain compound AB35552 (277 mg).

[0824] MS-ESI: theoretical value [M] + : 397.15; measured value: 397.10.

[0825] 1 H NMR(400MHz,DMSO-d6)δ9.35-9.33(m,1H),8.27-8.23(m,2H),8.16-8.10(m,2H),7.70-7.66(m,1H),7.41-7.33(m,5H) ,7.07-7.04(m,2H),5.83-5.78(m,1H),4.61(d,J=8.0Hz,2H),3.38-3.36(m,2H),2.91-2.82(m,1H),2.59-2.56(m,1H).

[0826] Example 66 Synthesis of Compound AB35553

[0827] Step (1):

[0828] Compound 1 (2 g) was dissolved in N,N-dimethylformamide (30 mL), sodium hydroxide (461 mg) was added at 0°C, the reaction was allowed to proceed at 0°C for 0.5 h, benzyl bromide (2 g) was added, the reaction was allowed to proceed at 0°C for 1 h, and the reaction was complete after LCMS monitoring. The reaction solution was quenched with saturated aqueous ammonium chloride solution, extracted with ethyl acetate, and the organic phase was dried over anhydrous sodium sulfate, filtered, and spin-dried. The crude product was subjected to flash chromatography (petroleum ether / ethyl acetate = 0-5%) to give compound 3 (1.4 g).

[0829] MS-ESI: Calculated [M+H]: 299.17.

[0830] Step (2):

[0831] Compound 3 (300 mg) was dissolved in acetonitrile (15 mL), and compound 4 (218 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction was completed after monitoring by LCMS. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-5%) to obtain compound 5 (300 mg).

[0832] MS-ESI: theoretical value [M] + :435.21.

[0833] Step (3):

[0834] Compound 5 (300 mg) was dissolved in dichloromethane (10 mL), and aqueous hydrobromic acid solution (1 ml) was added. The reaction was allowed to react at room temperature for 1 h. The reaction was completed as monitored by LCMS. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-5%) to obtain compound AB35553 (153.6 mg).

[0835] MS-ESI: theoretical value [M] + : 335.16; measured value: 355.10.

[0836] 1 H NMR (400MHz, DMSO-d6) δ9.21-9.12(m,1H),8.16-8.02(m,3H),7.52-7.44(m,2H),7.41-7.33( m, 5H), 7.04-6.90 (m, 2H), 6.02 (d, J = 4.0Hz, 2H), 4.58 (d, J = 4.0Hz, 2H), 2.36 (d, J = 8.0Hz, 3H).

[0837] Example 67 Synthesis of Compound AB35554

[0838] Step (1):

[0839] Compound 1 (250 mg) was dissolved in acetonitrile (15 mL), and compound 2 (230 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction was completed after monitoring by LCMS. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-5%) to obtain compound AB35554 (96.7 mg).

[0840] MS-ESI: theoretical value [M] + : 386.17; measured value: 386.20.

[0841] 1 H NMR(400MHz,DMSO-d6)δ9.73(s,1H),9.34(s,1H),8.04(s,1H),7.68-7.61(m,3H),7.37-7.35(m,5H), 6.26-6.22(m,1H),5.61(s,2H),3.34-3.30(m,2H),3.09-2.99(m,1H),2.75-2.70(m,1H),2.37(s,3H).

[0842] Example 68 Synthesis of Compound AB35557

[0843] Step (1):

[0844] Compound 1 (300 mg) was dissolved in acetonitrile (15 mL), and compound 2 (279 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction was completed after monitoring by LCMS. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-5%) to obtain compound AB35557 (115.8 mg).

[0845] MS-ESI: theoretical value [M] + : 381.20; measured value: 381.20.

[0846] 1 H NMR (400MHz, DMSO-d6) δ9.44(s,1H),8.56(d,J=8.0Hz,1H),8.32(d,J=4.0Hz,1H),7.91(s,1H),7.76(s,1H),7.54(d, J=8.0Hz,1H),7.42-7.37(m,5H),6.15-6.11(m,1H),5.62(s,2H),3.30-3.00(m,4H),2.66-2.64(m,1H),2.37(s,6H).

[0847] Example 69 Synthesis of Compound AB35558

[0848] Step (1):

[0849] Compound 1 (300 mg) was dissolved in acetonitrile (15 mL), and compound 2 (257 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction was completed after monitoring by LCMS. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-5%) to obtain compound AB35558 (145.1 mg).

[0850] MS-ESI: theoretical value [M] + : 401.14; measured value: 401.15.

[0851] 1H NMR (400MHz, DMSO-d6) δ9.43(s,1H),8.55(d,J=8.0Hz,1H),8.33(d,J=8.0Hz,1H),7.92-7.89(m,2H),7.81-7.78(m,1H),7.58(d,J=8 .0Hz,1H),7.40-7.32(m,5H),6.18-6.14(m,1H),5.62(s,2H),3.30-3.26(m,2H),3.12-3.02(m,1H),2.68-2.65(m,1H),2.37(s,3H).

[0852] Example 70 Synthesis of Compound AB35559

[0853] Step (1):

[0854] Compound 1 (500 mg) was dissolved in acetonitrile (20 mL), and compound 2 (357 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction was completed as monitored by LCMS. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-5%) to obtain compound AB35559 (202.9 mg).

[0855] MS-ESI: theoretical value [M] + : 422.15; measured value: 422.15.

[0856] 1 H NMR (400MHz, DMSO-d6) δ9.73(s,1H),9.45(s,1H),8.36(d,J=4.0Hz,1H),8.20(s,1H),8.13(d,J=8.0Hz,1H),7.83(d,J=8.0Hz,1H),7. 43-7.37(m,5H),7.27(d,J=4.0Hz,1H),6.43(d,J=12.0Hz,1H),5.71(s,2H),3.51-3.43(m,2H),3.13-3.04(m,1H),2.84-2.79(m,1H).

[0857] Example 71 Synthesis of Compound AB35560

[0858] Step (1):

[0859] Compound 1 (300 mg) was dissolved in acetonitrile (15 mL), and compound 2 (280 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction was completed after monitoring by LCMS. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-5%) to obtain compound AB35560 (32.3 mg).

[0860] MS-ESI: theoretical value [M] + : 382.19; measured value: 382.15.

[0861] 1 H NMR (400MHz, DMSO-d6) δ9.71(s,1H),9.33(s,1H),8.03(s,1H),7.77(s,1H),7.56(d,J=12.0Hz,1H),7.42-7.34 (m,6H),6.18-6.13(m,1H),5.60(s,2H),3.30-3.23(m,2H),3.05-2.95(m,1H),2.72-2.67(m,1H),2.37(s,6H).

[0862] Example 72 Synthesis of Compound AB35561

[0863] Step (1):

[0864] Compound 1 (500 mg) was dissolved in acetonitrile (25 mL), and compound 2 (457 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction was completed after monitoring by LCMS. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-5%) to obtain compound AB35561 (656.1 mg).

[0865] MS-ESI: theoretical value [M] + : 385.17; measured value: 385.10.

[0866] 1 H NMR(400MHz, DMSO-d6)δ9.46(s,1H),8.57(d,J=8.0Hz,1H),8.33(d,J=8.0Hz,1H),7.92(s,1H),7.66-7.60(m,3H),7.4 0-7.32(m,5H),6.23-6.19(m,1H),5.63(s,2H),3.34-3.26(m,2H),3.13-3.05(m,1H),2.68-2.66(m,1H),2.38(s,3H).

[0867] Example 73 Synthesis of Compound AB35562

[0868] Step (1):

[0869] Compound 1 (300 mg) was dissolved in acetonitrile (15 mL), and compound 2 (279 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction was completed after monitoring by LCMS. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-5%) to obtain compound 3 (300 mg).

[0870] MS-ESI: theoretical value [M] + :495.13.

[0871] Step (2):

[0872] Compound 3 (300 mg) was dissolved in dichloromethane (10 mL), and aqueous hydrobromic acid solution (1 mL) was added. The reaction was allowed to react at room temperature for 1 h. The reaction was completed as monitored by LCMS. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-5%) to obtain compound AB35562 (155.1 mg).

[0873] MS-ESI: theoretical value [M] + : 395.08; measured value: 395.05.

[0874] 1 H NMR(400MHz,DMSO-d6)δ9.21-9.12(m,1H),8.16-8.02(m,1H),7.99-7.86(m,4H),7.41-7.32(m ,5H),7.04-6.90(m,2H),6.02(d,J=4.0Hz,2H),4.58(d,J=4.0Hz,2H),2.36(d,J=12.0Hz,3H).

[0875] Example 74 Synthesis of Compound AB35566

[0876] Step (1):

[0877] Compound 1 (1 g) was dissolved in methanol (10 mL), and acetic acid (0.1 mL) and palladium carbon (300 mg) were added. The mixture was reacted under a hydrogen atmosphere for 16 h. After the reaction was completed, the solid was filtered and the filtrate was dried. The crude product was prepared using normal phase (dichloromethane / methanol = 0%-5%) to give compound 2 (170 mg).

[0878] MS-ESI: theoretical value [M+H] + :212.11.

[0879] Step (2):

[0880] Compound 2 (170 mg) was dissolved in acetonitrile (10 mL), and compound 3 (196 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction was completed after monitoring by LCMS. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-5%) to obtain compound AB35566 (91 mg).

[0881] MS-ESI: theoretical value [M] + : 374.17; measured value: 374.05.

[0882] 1 H NMR(400MHz,DMSO-d6)δ8.78(s,1H),8.08(s,1H),7.57-7.56(m,3H),7.44-7.37(m,5H),5.74-5.69(m,1H), 4.79(s,2H),3.91-3.87(m,2H),3.26-3.24(m,2H),3.20-3.16(m,2H),2.83-2.73(m,1H),2.55-2.53(m,1H).

[0883] Example 75 Synthesis of Compound AB35567

[0884] Step (1):

[0885] Compound 1 (300 mg) was dissolved in acetonitrile (10 mL), and compound 2 (228 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction was completed after monitoring by LCMS. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-5%) to obtain compound AB35567 (153 mg).

[0886] MS-ESI: theoretical value [M] + : 435.17; measured value: 435.30.

[0887] 1H NMR (400MHz, DMSO-d6) δ9.45(s,1H),8.57(d,J=8.0Hz,1H),8.34(d,J=8.0Hz,1H),8.17(s,1H),8.09(d,J=8.0Hz,1H)),7.92(s,1H),7.79( d,J=8.0Hz,1H)),7.40-7.33(m,5H),6.26-6.23(m,1H),5.63(s,2H), 3.50-3.42(m,2H),3.14-3.09(m,1H),2.72-2.70(m,1H),2.38(s,3H).

[0888] Example 76 Synthesis of Compound AB35568

[0889] Step (1):

[0890] Compound 1 (255 mg) was dissolved in acetonitrile (10 mL), and compound 2 (351 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction was completed after monitoring by LCMS. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-5%) to obtain compound 3 (300 mg).

[0891] MS-ESI: theoretical value [M] + :434.20.

[0892] Step (2):

[0893] Compound 3 (300 mg) was dissolved in dichloromethane (10 mL), and aqueous hydrobromic acid solution (1 mL, 48%) was added. The reaction was allowed to react at room temperature for 1 h. The reaction was completed as monitored by LCMS. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-5%) to obtain compound AB35568 (257.8 mg).

[0894] MS-ESI: theoretical value [M] + : 335.16; measured value: 335.10.

[0895] 1 H NMR (400MHz, DMSO-d6) δ9.23-9.14(m,1H),8.16-8.02(m,1H),7.91-7.84(m,2H),7.73-7.62(m,2H),7. 41-7.32(m,5H),7.05-6.90(m,2H),6.04(d,J=4.0Hz,2H),4.58(d,J=4.0Hz,2H),2.36(d,J=8.0Hz,3H).

[0896] Example 77 Synthesis of Compound AB35582

[0897] Step (1):

[0898] Compound 1 (500 mg) was dissolved in N,N-dimethylformamide (10 mL), sodium hydroxide (201 mg, 60% in mineral oil) was added at 0°C, and the reaction was continued for 0.5 h. Compound 2 (892 mg) was added and the reaction was continued at 0°C for 1 h. After the reaction was completed, saturated aqueous ammonium chloride solution was added to quench the reaction, and the reaction was carried out by extraction with ethyl acetate. The organic phase was dried over anhydrous sodium sulfate, filtered and dried by rotary evaporation. The crude product was prepared using normal phase (dichloromethane / methanol = 0%-5%) to give compound 3 (1 g).

[0899] MS-ESI: theoretical value [M+H] + :252.11.

[0900] Step (2):

[0901] Compound 3 (500 mg) was dissolved in acetonitrile (20 mL), and compound 4 (340 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction was completed as monitored by LCMS. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-10%) to obtain compound AB35582 (267.9 mg).

[0902] MS-ESI: theoretical value [M] + : 342.16; measured value: 342.70.

[0903] 1 H NMR (400MHz, DMSO-d6) δ9.74(d,J=4.0Hz,1H),9.56(d,J=4.0Hz,1H),8.11(d,J=4.0Hz,1H),8.03(d,J=8.0H z,2H),7.58-7.56(m,2H),7.46-7.44(m,5H),7.17(d,J=4.0Hz,1H),6.14(s,2H),5.84(s,2H),2.44(s,3H).

[0904] Example 78 Synthesis of Compound AB35583

[0905] Step (1):

[0906] Compound 1 (300 mg) was dissolved in acetonitrile (10 mL), and compound 2 (213 mg) was added. The mixture was reacted at 80° C. for 16 h. After the reaction, the reaction solution was concentrated, and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-5%) to obtain compound 3 (200 mg).

[0907] MS-ESI: Calculated value [M]: 431.23.

[0908] Step (2):

[0909] Compound 3 (200 mg) was dissolved in dichloromethane (10 mL), and aqueous hydrobromic acid solution (1 mL, 48%) was added. The reaction was allowed to react at room temperature for 1 h. The reaction was completed as monitored by LCMS. The reaction solution was spin-dried, and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-10%) to obtain compound AB35583 (103.7 mg).

[0910] MS-ESI: theoretical value [M] + : 331.18; measured value: 331.10.

[0911] 1 H NMR(400MHz,DMSO-d6)δ9.18-9.08(m,1H),8.15-8.01(m,1H),7.96-7.94(m,2H),7.46-7.34(m,7H ),7.04-6.88(m,2H),5.98(d,J=4.0Hz,2H),4.58-4.56(m,2H),2.43(s,3H),2.34(d,J=5.0Hz,3H).

[0912] Example 79 Synthesis of Compound AB35586

[0913] Step (1):

[0914] Compound 1 (2.3 g) was dissolved in methanol (20 mL), and 2 drops of acetic acid and palladium carbon (460 mg, 20% wt) were added. The reaction was carried out at room temperature for 16 h under a hydrogen atmosphere. After the reaction, the palladium carbon was filtered and the filtrate was concentrated. The crude product was prepared using normal phase (dichloromethane / methanol = 0%-5%) to give compound 2 (160 mg).

[0915] MS-ESI: Calculated value [M+H]: 212.11.

[0916] Step (2):

[0917] Compound 2 (160 mg) was dissolved in acetonitrile (10 mL), and compound 3 (181 m) was added. The mixture was reacted at 80° C. for 16 h. The reaction was completed after monitoring by LCMS. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-10%) to obtain compound AB35586 (42.9 mg).

[0918] MS-ESI: theoretical value [M] + : 370.19; measured value: 379.30.

[0919] 1 H NMR(400MHz,DMSO-d6)δ8.79(s,1H),8.08(s,1H),7.74(s,1H),7.52-7.50(m,1H),7.44-7.36(m,6H),5.70-5.6 6(m,1H),4.79(s,2H),3.91-3.86(m,2H),3.25-3.14(m,4H),2.80-2.70(m,1H),2.54-2.52(m,1H),2.36(s,3H).

[0920] Example 80 Synthesis of Compound AB35587

[0921] Step (1):

[0922] Compound 1 (100 mg) was dissolved in acetonitrile (5 mL), and compound 2 (139 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction was completed after monitoring by LCMS. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-10%) to obtain compound AB35587 (32.3 mg).

[0923] MS-ESI: theoretical value [M] + : 424.16; measured value: 424.50.

[0924] 1 H NMR(400MHz, DMSO-d6)δ8.77(s,1H),8.12-8.02(m,3H),7.72(d,J=8.0Hz,1H),7.40-7.33(m,5H),5.80-5.75(m, 1H),4.76(s,2H),3.88-3.83(m,2H),3.28-3.25(m,2H),3.17-3.13(m,2H),2.80-2.76(m,1H),2.55-2.53(m,1H).

[0925] Example 81 Synthesis of Compound AB35592

[0926] Step (1):

[0927] Compound 1 (300 mg) was dissolved in N,N-dimethylformamide (10 mL), sodium hydroxide (108 mg, 60% in mineral oil) was added at 0°C, and the reaction was continued for 0.5 h. Compound 2 (479 mg) was added and the reaction was continued at 0°C for 1 h. After the reaction was completed, saturated aqueous ammonium chloride solution was added to quench the reaction, and the reaction was carried out using ethyl acetate. The organic phase was dried over anhydrous sodium sulfate, filtered and dried by rotation. The crude product was prepared using normal phase (dichloromethane / methanol = 0%-5%) to give compound 3 (180 mg).

[0928] MS-ESI: theoretical value [M+H] + :266.12.

[0929] Step (2):

[0930] Compound 3 (90 mg) was dissolved in acetonitrile (20 mL), and benzyl bromide (58 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction was completed as monitored by LCMS. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-10%) to obtain compound AB35592 (102.3 mg).

[0931] MS-ESI: theoretical value [M] + : 356.18; measured value: 356.10.

[0932] 1 H NMR (400MHz, DMSO-d6) δ9.59 (s, 1H), 9.51 (s, 1H), 8.05 (d, J = 8.0Hz, 2H), 7.56-7.55 (m, 2 H),7.46-7.41(m,5H),6.95(s,1H),6.13(s,2H),5.81(s,2H),2.47(s,3H),2.44(s,3H).

[0933] Example 82 Synthesis of Compound AB35598

[0934] Step (1):

[0935] Compound 1 (500 mg) was dissolved in N,N-dimethylformamide (10 mL), sodium hydroxide (203 mg, 60% in mineral oil) was added at 0°C, and the reaction was continued for 0.5 h. Compound 2 (901 mg) was added and the reaction was continued at 0°C for 1 h. After the reaction was completed, saturated aqueous ammonium chloride solution was added to quench the reaction, and the reaction was carried out by extraction with ethyl acetate. The organic phase was dried over anhydrous sodium sulfate, filtered and dried by rotary evaporation. The crude product was prepared using normal phase (dichloromethane / methanol = 0%-5%) to give compound 3 (1 g).

[0936] MS-ESI: theoretical value [M+H] + :251.11.

[0937] Step (2):

[0938] Compound 3 (140 mg) was dissolved in acetonitrile (20 mL), and benzyl bromide (95.6 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction was completed as monitored by LCMS. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-10%) to obtain compound AB35598 (97.8 mg).

[0939] MS-ESI: theoretical value [M] + : 341.16; measured value: 341.10.

[0940] 1 H NMR (400MHz, DMSO-d6) δ9.59 (s, 1H), 8.69 (d, J = 8.0Hz, 1H), 8.05 (d, J = 8.0Hz, 1H), 7.97-7. 94(m,3H),7.50-7.40(m,7H),7.15(d,J=4.0Hz,1H),6.17(s,2H),5.82(s,2H),2.43(s,3H).

[0941] Example 83 Synthesis of Compound AB35600

[0942] Step (1):

[0943] Compound 1 (400 mg) was dissolved in acetonitrile (20 mL), potassium carbonate (1.4 g) and compound 2 (803 mg) were added, and the mixture was reacted at 80° C. for 16 h. After the reaction, the reaction solution was concentrated, and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-5%) to obtain compound 3 (260 mg).

[0944] MS-ESI: theoretical value [M+H] + :278.12.

[0945] Step (2):

[0946] Compound 3 (100 mg) was dissolved in acetonitrile (5 mL), and benzyl bromide (62 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction was completed as monitored by LCMS. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-10%) to obtain compound AB35600 (33.2 mg).

[0947] MS-ESI: theoretical value [M] + : 368.18; measured value: 368.20.

[0948] 1 H NMR (400MHz, DMSO-d6) δ9.74(s,1H),9.57(s,1H),8.23(d,J=4.0Hz,1H),7.72(s,1H),7.58-7.37(m,7H),7.19(d,J=4.0Hz,1 H),6.09-6.04(m,1H),5.84(s,2H),3.43-3.39(m,1H),3.16-3.12(m,1H),3.02-2.92(m,1H),2.47-2.43(m,1H),2.35(s,3H).

[0949] Example 84 Synthesis of Compound AB36401

[0950] Step (1):

[0951] Compound 1 (140 mg) was dissolved in acetonitrile (5 mL), and compound 2 (93 mg) was added. The mixture was reacted at 80°C for 16 h. The reaction was completed after monitoring by LCMS. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-10%) to obtain compound AB36401 (23.2 mg).

[0952] MS-ESI: theoretical value [M] + : 382.19; measured value: 382.35.

[0953] 1H NMR(400MHz,DMSO-d6)δ9.75(s,1H),9.55(d,J=4.0Hz,1H),8.19(d,J=4.0H z,1H),7.68(s,1H),7.55(d,J=8.0Hz,2H),7.48-7.34(m,5H),7.12(s,1H), 6.24-6.18(m,1H),6.04-5.99(m,1H),3.42-3.38(m,1H),3.14-3.07(m,1H) ,2.96-2.89(m,1H),2.44-2.40(m,1H),2.32(s,3H),2.06(d,J=8.0Hz,3H).

[0954] Example 85 Synthesis of Compound AB36402

[0955] Step (1):

[0956] Compound 1 (500 mg) was dissolved in acetonitrile (20 mL), potassium carbonate (1.7 g) and compound 2 (1 g) were added, and the reaction was carried out at 80° C. for 16 h. After the reaction was completed, the reaction solution was concentrated, and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-5%) to obtain compound 3 (440 mg).

[0957] MS-ESI: theoretical value [M+H] + :278.12.

[0958] Step (2):

[0959] Compound 3 (150 mg) was dissolved in acetonitrile (5 mL), and benzyl bromide (92 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction was completed as monitored by LCMS. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-10%) to obtain compound AB36402 (56.6 mg).

[0960] MS-ESI: theoretical value [M] + : 368.18; measured value: 368.35.

[0961] 1H NMR (400MHz, DMSO-d6) δ9.73 (s, 1H), 9.56 (s, 1H), 8.22 (d, J = 4.0Hz, 1H), 7.81 ( d,J=8.0Hz,1H),7.57(d,J=4.0Hz,2H),7.47-7.42(m,3H),7.30(s,1H),7.25(d, J=8.0Hz,1H),7.18(d,J=4.0Hz,1H),6.07-6.03(m,1H),5.83(s,2H),3.45-3.4 0(m,1H),3.16-3.10(m,1H),3.02-2.93(m,1H),2.47-2.45(m,1H),2.40(s,3H).

[0962] Example 86 Synthesis of Compound AB36406

[0963] Step (1):

[0964] Compound 1 (150 mg) was dissolved in acetonitrile (5 mL), and benzyl bromide (100 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction was completed after monitoring by LCMS. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-10%) to obtain compound AB36406 (47.6 mg).

[0965] MS-ESI: theoretical value [M] + : 382.19; measured value: 382.35.

[0966] 1 H NMR (400MHz, DMSO-d6) δ9.78(s,1H),9.59(d,J=4.0Hz,1H),8.23(d,J=4.0Hz,1H),7.81( d,J=8.0Hz,1H),7.59(d,J=8.0Hz,2H),7.48-7.42(m,3H),7.30(s,1H),7.25(d,J=8.0Hz, 1H),7.15(d,J=4.0Hz,1H),6.28-6.23(m,1H),6.07-6.02(m,1H),3.46-3.40(m,1H),3.1 5-3.11(m,1H),3.01-2.93(m,1H),2.48-2.43(m,1H),2.40(s,3H),2.10(d,J=8.0Hz,3H).

[0967] Example 87 Synthesis of Compound AB36408

[0968] Step (1):

[0969] Compound 1 (500 mg) was dissolved in acetonitrile (20 mL), potassium carbonate (1.7 g) and compound 2 (1.3 g) were added, and the mixture was reacted at 80° C. for 16 h. After the reaction, the reaction solution was concentrated, and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-5%) to obtain compound 3 (380 mg).

[0970] MS-ESI: theoretical value [M+H] + :348.09.

[0971] Step (2):

[0972] Compound 3 (190 mg) was dissolved in acetonitrile (5 mL), and benzyl bromide (94 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction was completed as monitored by LCMS. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-10%) to obtain compound AB36408 (69.9 mg).

[0973] MS-ESI: theoretical value [M] + : 438.14; measured value: 438.15.

[0974] 1 H NMR (400MHz, DMSO-d6) δ9.73 (s, 1H), 9.57 (s, 1H), 8.23 ​​(d, J = 4.0Hz, 1H), 7.76-7.65 (m, 3H), 7.57-7.56 (m, 2H), 7.46-7.42 (m, 3H), 7.19(d,J=4.0Hz,1H),6.20-6.16(m,1H),5.83(s,2H),3.50-3.42(m,1H),3.30-3.22(m,1H),3.06-2.95(m,1H),2.48-2.45(m,1H).

[0975] Example 88 Synthesis of Compound AB36409

[0976] Step (1):

[0977] Compound 1 (190 mg) was dissolved in acetonitrile (5 mL), and compound 2 (102 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction was completed after monitoring by LCMS. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-10%) to obtain compound AB36409 (7.7 mg).

[0978] MS-ESI: theoretical value [M] + : 452.16; measured value: 452.10.

[0979] 1 H NMR (400MHz, DMSO-d6) δ9.80 (s, 1H), 9.61 (d, J = 4.0Hz, 1H), 8.24 (d, J = 4.0Hz, 1H), 7.76-7.58 (m, 5H), 7.48-7.42 (m, 3H), 7.17-7. 16(m,1H),6.29-6.16(m,2H),3.49-3.42(m,1H),3.26-3.22(m,1H),3.05-2.95(m,1H),2.47-2.44(m,1H),2.10(d,J=8.0Hz,3H).

[0980] Example 89 Synthesis of Compound AB36414

[0981] Step (1):

[0982] Compound 1 (500 mg) was dissolved in acetonitrile (20 mL), potassium carbonate (1.7 g) and compound 2 (1.0 g) were added, and the mixture was reacted at 80° C. for 16 h. After the reaction, the reaction solution was concentrated, and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-5%) to obtain compound 3 (150 mg).

[0983] MS-ESI: theoretical value [M+H] + :282.10.

[0984] Step (2):

[0985] Compound 3 (150 mg) was dissolved in acetonitrile (5 mL), and compound 4 (91 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction was completed after monitoring by LCMS. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-10%) to obtain compound AB36414 (3.9 mg).

[0986] MS-ESI: theoretical value [M] + : 372.15; measured value: 372.25.

[0987] 1H NMR (400MHz, DMSO-d6) δ9.73(s,1H),9.56(s,1H),8.22(d,J=4.0Hz,1H),7.61-7.56(m,5H),7.48-7.42(m,3H),7.19(d,J= 4.0Hz,1H),6.16-6.11(m,1H),5.83(s,2H),3.419-3.43(m,1H),3.22-3.18(m,1H),3.04-2.93(m,1H),2.48-2.44(m,1H).

[0988] Example 90 Synthesis of Compound AB36417

[0989] Step (1):

[0990] Compound 1 (700 mg) was dissolved in acetonitrile (20 mL), potassium carbonate (2.4 g) and compound 2 (1.5 g) were added, and the mixture was reacted at 80° C. for 16 h. After the reaction, the reaction solution was concentrated, and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-5%) to obtain compound 3 (350 mg).

[0991] MS-ESI: theoretical value [M+H] + :298.07.

[0992] Step (2):

[0993] Compound 3 (150 mg) was dissolved in acetonitrile (5 mL), and compound 4 (92 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction was completed as monitored by LCMS. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-10%) to obtain compound AB36417 (32.3 mg).

[0994] MS-ESI: theoretical value [M] + : 402.14; measured value: 402.10.

[0995] 1H NMR (400MHz, DMSO-d6) δ9.78 (s, 1H), 9.59 (d, J = 4.0Hz, 1H), 8.22 (d, J = 4.0Hz ,1H),7.84(s,1H),7.77-7.74(m,1H),7.60-7.54(m,3H),7.48-7.40(m,3H),7 .16-7.15(m,1H),6.27-6.24(m,1H),6.16-6.11(m,1H),3.49-3.44(m,1H),3. 22-3.17(m,1H),3.03-2.91(m,1H),2.47-2.44(m,1H),2.10(d,J=8.0Hz,3H).

[0996] Example 91 Synthesis of Compound AB36421

[0997] Step (1):

[0998] Compound 1 (200 mg) was dissolved in acetonitrile (5 mL), and benzyl bromide (114 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction was completed as monitored by LCMS. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-10%) to obtain compound AB36421 (121.7 mg).

[0999] MS-ESI: theoretical value [M] + : 388.12; measured value: 388.25.

[1000] 1 H NMR(400MHz, DMSO-d6)δ9.73(s,1H),9.56(s,1H),8.22(d,J=4.0Hz,1H),7.85(d,J=4.0Hz,1H),7.77-7.74(m,1H),7.57-7.56(m,3H),7.46-7.42(m ,3H),7.19(d,J=4.0Hz,1H),6.17-6.12(d,J=4.0Hz,1H),5.83(s,2H),3. 45-3.38(m,1H),3.22-3.18(m,1H),3.03-2.93(m,1H),2.47-2.43(m,1H).

[1001] Example 92 Synthesis of Compound AB36429

[1002] Step (1):

[1003] Compound 1 (70 mg) was dissolved in acetonitrile (10 mL), and compound 2 (34 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction was completed after monitoring by LCMS. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-10%) to obtain compound AB36429 (13.4 mg).

[1004] MS-ESI: theoretical value [M] + : 294.16; measured value: 294.10.

[1005] 1 H NMR (400MHz, DMSO-d6) δ9.70(s,1H),9.38(s,1H),8.12(d,J=4.0Hz,1H),8.03(d,J=8.0Hz,2H),7.45(d,J=8.0Hz ,2H),7.18(d,J=4.0Hz,1H),6.15(s,2H),4.57-4.53(m,2H),2.44(s,3H),2.01-1.96(m,2H),0.95-0.91(m,3H).

[1006] Example 93 Synthesis of Compound AB36430

[1007] Step (1):

[1008] Compound 1 (100 mg) was dissolved in acetonitrile (10 mL), and cesium carbonate (547 mg) and compound 2 (115 mg) were added. The mixture was reacted at 80° C. under a nitrogen atmosphere for 16 h. After the reaction, the filtrate was concentrated, and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-5%) to give compound 3 (83 mg).

[1009] MS-ESI: Calculated value [M+H]: 176.11.

[1010] Step (2):

[1011] Compound 3 (83 mg) was dissolved in acetonitrile (10 mL), and compound 4 (140 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction was complete after monitoring by LCMS. The reaction solution was dried by rotary evaporation, and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-10%) to obtain compound AB36430 (17.9 mg).

[1012] MS-ESI: theoretical value [M] + : 354.14; measured value: 354.05.

[1013] 1H NMR (400MHz, DMSO-d6) δ9.64 (s, 1H), 9.36 (s, 1H), 8.27 (d, J = 4.0Hz, 1H), 7.89 (s, 1H),7.80(d,J=8.0Hz,1H),7.58(d,J=8.0Hz,1H),7.21(d,J=4.0Hz,1H),6.31-6. 27(m,1H),4.46-4.42(m,2H),3.42-3.39(m,1H),3.30-3.26(m,1H),3.08-2.97(m ,1H),2.75-2.73(m,1H),1.90-1.83(m,2H),1.30-1.23(m,2H),0.93-0.90(m,3H).

[1014] Example 94 Synthesis of Compound AB36431

[1015] Step (1):

[1016] Compound 1 (200 mg) was dissolved in N,N-dimethylformamide (10 mL) under nitrogen protection. Sodium hydroxide (101 mg, 60% in mineral oil) was added at 0°C. After reacting for 0.5 h, compound 2 (207 mg) was added and reacted for 1 h. After the reaction, the reaction solution was quenched by adding saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The organic phase was dried over anhydrous sodium sulfate, filtered and spin-dried. The crude product was prepared using normal phase (dichloromethane / methanol = 0%-5%) to give compound 3 (100 mg).

[1017] MS-ESI: Calculated value [M+H]: 162.10.

[1018] Step (2):

[1019] Compound 3 (100 mg) was dissolved in acetonitrile (10 mL), and compound 4 (161 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction was completed after monitoring by LCMS. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-10%) to obtain compound AB36431 (10.8 mg).

[1020] MS-ESI: theoretical value [M] + : 340.12; measured value: 340.05.

[1021] 1H NMR (400MHz, DMSO-d6) δ9.63 (s, 1H), 9.35 (s, 1H), 8.27 (d, J = 4.0Hz, 1H), 7. 89(s,1H),7.81-7.79(m,1H),7.58(d,J=8.0Hz,1H),7.21(d,J=4.0Hz,1H),6 .29-6.24(m,1H),4.46-4.42(m,2H),3.42-3.39(m,1H),3.31-3.27(m,1H), 3.08-2.96(m,1H),2.76-2.72(m,1H),1.93-1.88(m,2H),0.89-0.86(m,3H).

[1022] Example 95 Synthesis of Compound AB36454

[1023] Step (1):

[1024] Compound 1 (200 mg) was dissolved in acetonitrile (10 mL), and cesium carbonate (975 mg) and compound 2 (351 mg) were added. The mixture was reacted at 80° C. under a nitrogen atmosphere for 16 h. After the reaction, the filtrate was concentrated, and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-5%) to give compound 3 (200 mg).

[1025] MS-ESI: Calculated value [M+H]: 286.07.

[1026] Step (2):

[1027] Compound 3 (200 mg) was dissolved in acetonitrile (10 mL), and benzyl bromide (120 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction was completed as monitored by LCMS. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-10%) to obtain compound AB36454 (143.7 mg).

[1028] MS-ESI: theoretical value [M] + : 376.12; measured value: 376.20.

[1029] 1 H NMR (400MHz, DMSO-d6) δ9.58(s,1H),9.50(s,1H),8.16(d,J=8.0Hz,2H),7.74(d,J=8.0Hz,2H ),7.55-7.53(m,2H),7.47-7.41(m,3H),6.96(s,1H),6.17(s,2H),5.81(s,2H),2.48(s,3H).

[1030] Example 96 Synthesis of Compound AB36455

[1031] Step (1):

[1032] Compound 1 (200 mg) was dissolved in acetonitrile (10 mL), and cesium carbonate (975 mg) and compound 2 (319 mg) were added. The mixture was reacted at 80° C. under a nitrogen atmosphere for 16 h. After the reaction, the filtrate was concentrated, and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-5%) to give compound 3 (195 mg).

[1033] MS-ESI: Calculated value [M+H]: 266.12.

[1034] Step (2):

[1035] Compound 3 (195 mg) was dissolved in acetonitrile (10 mL), and benzyl bromide (120 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction was completed as monitored by LCMS. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-10%) to obtain compound AB36455 (52.6 mg).

[1036] MS-ESI: theoretical value [M] + : 356.18; measured value: 356.25.

[1037] 1 H NMR(400MHz,DMSO-d6)δ9.57(s,1H),9.48(s,1H),7.97-7.93(m,2H),7.61-7.51(m,4H ),7.46-7.41(m,3H),6.95(s,1H),6.14(s,2H),5.80(s,2H),2.47(s,3H),2.43(s,3H).

[1038] Example 97 Synthesis of Compound AB36456

[1039] Step (1):

[1040] Compound 1 (100 mg) was dissolved in acetonitrile (5 mL), and compound 2 (70 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction was completed after monitoring by LCMS. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-10%) to obtain compound AB36456 (83.7 mg).

[1041] MS-ESI: theoretical value [M] + :370.19; measured value:370.25

[1042] 1 H NMR (400MHz, DMSO-d6) δ9.55(s,1H),9.47(s,1H),8.05(d,J=8.0Hz,2H),7.46(d,J=8.0Hz,2H),7.37(s,1H),7.33( d,J=4.0Hz,2H),7.24-7.22(m,1H),6.95(s,1H),6.12(s,2H),5.75(s,2H),2.47(s,3H),2.44(s,3H),2.31(s,3H).

[1043] Example 98 Synthesis of Compound AB36457

[1044] Step (1):

[1045] Compound 1 (100 mg) was dissolved in acetonitrile (5 mL), and compound 2 (190 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction was completed as monitored by LCMS. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-10%) to obtain compound AB36457 (93.5 mg).

[1046] MS-ESI: theoretical value [M] + : 390.14; measured value: 390.25.

[1047] 1 H NMR (400MHz, DMSO-d6) δ9.45-9.52(m,2H),8.06(d,J=8.0Hz,2H),7.59(d,J=8.0Hz,2H ),7.51-7.44(m,5H),6.96(s,1H),6.14(s,2H),5.93(s,2H),2.48(s,3H),2.44(s,3H).

[1048] Example 99 Synthesis of Compound AB36464

[1049] Step 1):

[1050] Compound 1 (100 mg) was dissolved in acetonitrile (5 mL), and compound 2 (76 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction was completed after monitoring by LCMS. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-10%) to obtain compound AB36464 (23.7 mg).

[1051] MS-ESI: theoretical value [M] + : 374.17; measured value: 374.15.

[1052] 1 H NMR (400MHz, DMSO-d6) δ9.49 (s, 1H), 9.42 (s, 1H), 8.06 (d, J = 8.0Hz, 2H), 7.61-7.45 (m, 4 H),7.34-7.28(m,2H),6.95(s,1H),6.12(s,2H),5.89(s,2H),2.47(s,3H),2.44(s,3H).

[1053] Example 100 Synthesis of Compound AB36465

[1054] Step (1):

[1055] Compound 1 (100 mg) was dissolved in acetonitrile (5 mL), and compound 2 (83 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction was completed as monitored by LCMS. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-10%) to obtain compound AB36465 (77.2 mg).

[1056] MS-ESI: theoretical value [M] + : 392.16; measured value: 392.25.

[1057] 1 H NMR (400MHz, DMSO-d6) δ9.47(s,1H),9.39(s,1H),8.05(d,J=8.0Hz,2H),7.75-7.69(m,1H),7.46(d,J=8.0Hz ,2H),7.41-7.36(m,1H),7.24-7.19(m,1H),6.95(s,1H),6.12(s,2H),5.85(s,2H),2.47(s,3H),2.44(s,3H).

[1058] Example 101 Synthesis of Compound AB36466

[1059] Step (1):

[1060] Compound 1 (100 mg) was dissolved in acetonitrile (10 mL), and cesium carbonate (487 mg) and compound 2 (163 mg) were added. The mixture was reacted at 80° C. under a nitrogen atmosphere for 16 h. After the reaction, the filtrate was concentrated, and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-5%) to give compound 3 (130 mg).

[1061] MS-ESI: Calculated value [M+H]: 270.10.

[1062] Step (2):

[1063] Compound 3 (130 mg) was dissolved in acetonitrile (10 mL), and compound 4 (82 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction was completed as monitored by LCMS. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-10%) to obtain compound AB36466 (76.8 mg).

[1064] MS-ESI: theoretical value [M] + : 360.15; measured value: 360.10.

[1065] 1 H NMR(400MHz,DMSO-d6)δ9.60(s,1H),9.52(s,1H),8.01-7.96(m,2H),7.72-7.66(m,2H),7. 56(d,J=4.0Hz,2H),7.46-7.41(m,3H),6.96(s,1H),6.19(s,2H),5.82(s,2H),2.48(s,3H).

[1066] Example 102 Synthesis of Compound AB36468

[1067] Step (1):

[1068] Compound 1 (200 mg) was dissolved in acetonitrile (10 mL), and cesium carbonate (975 mg) and compound 2 (325 mg) were added. The mixture was reacted at 80° C. under a nitrogen atmosphere for 16 h. After the reaction, the filtrate was concentrated, and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-5%) to give compound 3 (210 mg).

[1069] MS-ESI: Calculated value [M+H]: 270.10.

[1070] Step (2):

[1071] Compound 3 (210 mg) was dissolved in acetonitrile (10 mL), and compound 4 (133 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction was completed after monitoring by LCMS. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-10%) to obtain compound AB36468 (255 mg).

[1072] MS-ESI: theoretical value [M] + : 360.15; measured value: 360.10.

[1073] 1 H NMR (400MHz, DMSO-d6) δ9.60(s,1H),9.52(s,1H),8.26-8.23(m,2H),7.50-7.41(m,8H),6.96(s,1H),6.17(s,2H),5.82(s,2H),2.50(s,3H).

[1074] Example 103 Synthesis of Compound AB36469

[1075] Step (1):

[1076] Compound 1 (200 mg) was dissolved in acetonitrile (10 mL), and cesium carbonate (975 mg) and compound 2 (350 mg) were added. The mixture was reacted at 80° C. under a nitrogen atmosphere for 16 h. After the reaction, the filtrate was concentrated, and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-5%) to give compound 3 (110 mg).

[1077] MS-ESI: Calculated value [M+H]: 286.07.

[1078] Step (2):

[1079] Compound 3 (110 mg) was dissolved in acetonitrile (10 mL), and compound 4 (66 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction was completed after monitoring by LCMS. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-10%) to obtain compound AB36469 (111.1 mg).

[1080] MS-ESI: theoretical value [M] + : 376.12; measured value: 376.10.

[1081] 1H NMR (400MHz, DMSO-d6) δ9.60(s,1H),9.52(s,1H),8.21(s,1H),8.09(d,J=8.0Hz,1H),7.86(d,J=8.0Hz,1H),7. 70-7.66(m,1H),7.56(d,J=4.0Hz,2H),7.46-7.41(m,3H),6.96(s,1H),6.21(s,2H),5.82(s,2H),2.48(s,3H).

[1082] Example 104 Synthesis of Compound AB36470

[1083] Step (1):

[1084] Compound 1 (200 mg) was dissolved in acetonitrile (10 mL), and cesium carbonate (975 mg) and compound 2 (343 mg) were added. The mixture was reacted at 80° C. under a nitrogen atmosphere for 16 h. After the reaction, the filtrate was concentrated, and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-5%) to give compound 3 (265 mg).

[1085] MS-ESI: Calculated value [M+H]: 282.12.

[1086] Step (2):

[1087] Compound 3 (265 mg) was dissolved in acetonitrile (10 mL), and compound 4 (161 mg) was added, and the reaction was carried out at 80°C for 16 h. The reaction was completed after monitoring by LCMS. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-10%) to obtain compound AB36470 (325 mg).

[1088] MS-ESI: theoretical value [M] + : 372.17; measured value: 372.15.

[1089] 1 H NMR (400MHz, DMSO-d6) δ9.59 (s, 1H), 9.51 (s, 1H), 7.76 (d, J = 8.0Hz, 1H), 7.62-7.55 (m, 4 H),7.46-7.35(m,4H),6.96(s,1H),6.17(s,2H),5.82(s,2H),3.86(s,3H),2.48(s,3H).

[1090] Example 105 Synthesis of Compound AB36475

[1091] Step (1):

[1092] Compound 1 (200 mg) was dissolved in acetonitrile (10 mL), and cesium carbonate (975 mg) and compound 2 (401 mg) were added. The mixture was reacted at 80° C. under a nitrogen atmosphere for 16 h. After the reaction, the filtrate was concentrated, and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-5%) to give compound 3 (86 mg).

[1093] MS-ESI: Calculated value [M+H]: 320.10.

[1094] Step (2):

[1095] Compound 3 (86 mg) was dissolved in acetonitrile (10 mL), and compound 4 (46 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction was completed after monitoring by LCMS. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-10%) to obtain compound AB36475 (75.1 mg).

[1096] MS-ESI: theoretical value [M] + : 410.15; measured value: 410.15.

[1097] 1 H NMR (400MHz, DMSO-d6) δ9.62(s,1H),9.54(s,1H),8.36(d,J=8.0Hz,2H),8.05(d,J=8.0Hz,2H ),7.58-7.55(m,2H),7.45-7.42(m,3H),6.98(s,1H),6.26(s,2H),5.83(s,2H),2.50(s,3H).

[1098] Example 106 Synthesis of Compound AB36478

[1099] Step (1):

[1100] Compound 1 (200 mg) was dissolved in acetonitrile (10 mL), and cesium carbonate (975 mg) and compound 2 (424 mg) were added. The mixture was reacted at 80° C. under a nitrogen atmosphere for 16 h. After the reaction, the filtrate was concentrated, and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-5%) to give compound 3 (130 mg).

[1101] MS-ESI: Calculated value [M+H]: 336.09.

[1102] Step (2):

[1103] Compound 3 (130 mg) was dissolved in acetonitrile (5 mL), and compound 4 (67 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction was completed as monitored by LCMS. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-10%) to obtain compound AB36478 (119.8 mg).

[1104] MS-ESI: theoretical value [M] + : 426.14; measured value: 426.15.

[1105] 1 H NMR (400MHz, CDCl3) δ9.91 (s, 1H), 9.41 (s, 1H), 8.17 (d, J = 4.0Hz, 1H), 7.83 (s, 1H), 7.66-7.62 (m, 3H),7.53(d,J=8.0Hz,1H),7.36-7.35(m,3H),6.76(s,1H),6.08(s,2H),5.99(s,2H),2.47(s,3H).

[1106] Example 107 Synthesis of Compound AB36479

[1107] Step 1):

[1108] Compound 1 (200 mg) was dissolved in acetonitrile (5 mL), and compound 2 (139 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction was completed after monitoring by LCMS. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-10%) to obtain compound AB36479 (161.6 mg).

[1109] MS-ESI: theoretical value [M] + : 370.19; measured value: 370.15.

[1110] 1 H NMR (400MHz, DMSO-d6) δ9.39(d,J=4.0Hz,2H),8.06(d,J=8.0Hz,2H),7.46(d,J=8.0Hz,2H),7.36-7.32(m,2H),7.28 -7.24(m,1H),7.13(d,J=8.0Hz,1H),6.95(s,1H),6.14(s,2H),5.85(s,2H),2.48(s,3H),2.44(s,3H),2.34(s,3H).

[1111] Example 108 Synthesis of Compound AB36482

[1112] Step (1):

[1113] Compound 1 (100 mg) was dissolved in acetonitrile (5 mL), and compound 2 (70 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction was completed as monitored by LCMS. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-10%) to obtain compound AB36482 (60.9 mg).

[1114] MS-ESI: theoretical value [M] + : 370.19; measured value: 370.20.

[1115] 1 H NMR (400MHz, DMSO-d6) δ9.63(s,1H),9.51(s,1H),8.05(d,J=8.0Hz,2H),7.56(d,J=8.0Hz,2H),7.47-7. 39(m,5H),6.93(s,1H),6.24-6.19(m,1H),6.12(s,2H),2.47(s,3H),2.44(s,3H),2.08(d,J=8.0Hz,3H).

[1116] Example 109 Synthesis of Compound AB36483

[1117] Step (1):

[1118] Compound 1 (200 mg) was dissolved in acetonitrile (5 mL), and compound 2 (70 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction was completed as monitored by LCMS. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-10%) to obtain compound AB36483 (104.6 mg).

[1119] MS-ESI: theoretical value [M] + : 392.16; measured value: 392.25.

[1120] 1H NMR (400MHz, DMSO-d6) δ9.42 (s, 1H), 9.37 (s, 1H), 8.04 (d, J = 8.0Hz, 2H), 7.61-7.58 (m, 1H), 7.46 (d ,J=8.0Hz,2H),7.24-7.23(m,2H),6.94(s,1H),6.12(s,2H),5.92(s,2H),2.47(s,3H),2.44(s,3H).

[1121] Example 110 Synthesis of Compound AB36487

[1122] Step (1):

[1123] Compound 1 (500 mg) was dissolved in tetrahydrofuran (10 mL), and compound 2 (1.2 g) was added. The mixture was reacted at 50° C. for 1 h under a nitrogen atmosphere. After the reaction, the solid was filtered and dried to obtain compound 3 (700 mg).

[1124] MS-ESI: Calculated value [M+H]: 230.98.

[1125] Step (2):

[1126] Compound 3 (200 mg) was dissolved in acetonitrile (10 mL), and cesium carbonate (559 mg) and compound 4 (115 mg) were added. The mixture was reacted at 80° C. under a nitrogen atmosphere for 16 h. After the reaction, the filtrate was concentrated, and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-5%) to give compound 5 (70 mg).

[1127] MS-ESI: Calculated value [M+H]: 284.12.

[1128] Step (3):

[1129] Compound 5 (70 mg) was dissolved in acetonitrile (5 mL), and benzyl bromide (43 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-10%) to obtain compound AB36487 (38.8 mg).

[1130] MS-ESI: theoretical value [M] + : 374.17; measured value: 374.10.

[1131] 1H NMR (400MHz, DMSO-d6) δ9.56 (s, 1H), 9.48 (s, 1H), 7.91 (d, J = 12.0Hz, 2H), 7.61-7.53 (m, 3H),7.47-7.41(m,3H),6.95(s,1H),6.14(s,2H),5.80(s,2H),2.47(s,3H),2.37(s,3H).

[1132] Example 111 Synthesis of Compound AB36490

[1133] Step (1):

[1134] Compound 1 (200 mg) was dissolved in acetonitrile (10 mL), and cesium carbonate (975 mg) and compound 2 (400 mg) were added. The mixture was reacted at 80° C. under a nitrogen atmosphere for 16 h. After the reaction, the filtrate was concentrated, and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-5%) to give compound 3 (164 mg).

[1135] MS-ESI: Calculated value [M+H]: 320.10.

[1136] Step (2):

[1137] Compound 3 (164 mg) was dissolved in acetonitrile (10 mL), and benzyl bromide (88 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-10%) to obtain compound AB36490 (126.5 mg).

[1138] MS-ESI: theoretical value [M] + :410.15; measured value:410.10.

[1139] 1 H NMR (400MHz, DMSO-d6) δ9.55 (s, 1H), 9.47 (s, 1H), 8.41-8.38 (m, 2H), 8.12 (d, J = 8.0Hz, 1H), 7.88-7.84 (m,1H),7.51(d,J=8.0Hz,2H),7.42-7.37(m,3H),6.92(s,1H),6.24(s,2H),5.77(s,2H),2.45(s,3H).

[1140] Example 112 Synthesis of Compound AB36491

[1141] Step (1):

[1142] Compound 1 (100 mg) was dissolved in acetonitrile (5 mL), p-methylbenzyl bromide (70 mg) was added, and the mixture was reacted at 80° C. for 16 h. The reaction solution was spin-dried, and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-10%) to obtain compound AB36491 (126.5 mg).

[1143] MS-ESI: theoretical value [M] + : 370.19; measured value: 370.20.

[1144] 1 H NMR (400MHz, DMSO-d6) δ9.54(s,1H),9.47(s,1H),8.04(d,J=8.0Hz,2H),7.45(d,J=8.0Hz,4H),7 .24(d,J=8.0Hz,2H),6.94(s,1H),6.12(s,2H),5.74(s,2H),2.45(d,J=8.0Hz,6H),2.30(s,3H).

[1145] Example 113 Synthesis of Compound AB36494

[1146] Step (1):

[1147] Compound 1 (5.86 mmol) was dissolved in tetrahydrofuran (20 mL), lithium aluminum hydride (11.72 mmol) was added at 0°C, and the reaction was carried out under a nitrogen atmosphere for 2 h. The reaction solution was quenched by adding saturated ammonium chloride solution, extracted with ethyl acetate, and the organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was spin-dried. The crude product was prepared using normal phase (petroleum ether / ethyl acetate = 1 / 1) to give compound 2 (800 mg).

[1148] MS-ESI: Calculated value [M+H]: 157.04.

[1149] Step (2):

[1150] Compound 2 (400 mg) was dissolved in dichloromethane (10 mL), phosphorus tribromide (830 mg) was added at 0°C, and the reaction was carried out under a nitrogen atmosphere for 1 h. The reaction solution was diluted with water and extracted with dichloromethane. The organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was spin-dried. The crude product was prepared using normal phase (petroleum ether / ethyl acetate = 3 / 1) to give compound 3 (350 mg).

[1151] MS-ESI: Calculated value [M+H]: 218.95.

[1152] Step (3):

[1153] Compound 4 (100 mg) was dissolved in acetonitrile (5 mL), and compound 3 (83 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-10%) to obtain compound AB36494 (52.6 mg).

[1154] MS-ESI: theoretical value [M] + : 405.16; measured value: 405.05.

[1155] 1 H NMR(400MHz,DMSO-d6)δ9.42(s,2H),8.06(d,J=8.0Hz,2H),7.46(d,J=8.0Hz,3H),7.32-7 .29(m,2H),6.96(s,1H),6.14(s,2H),5.87(s,2H),2.48(s,3H),2.44(s,3H),2.30(s,3H).

[1156] Example 114 Synthesis of Compound AB36495

[1157] Step (1):

[1158] Compound 1 (100 mg) was dissolved in acetonitrile (5 mL), and compound 2 (76 mg) was added. The mixture was reacted at 80°C for 16 h. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-10%) to obtain compound AB36495 (87 mg).

[1159] MS-ESI: theoretical value [M] + :390.14; measured value:390.15.

[1160] 1 H NMR (400MHz, DMSO-d6) δ9.54(s,1H),9.46(s,1H),8.05(d,J=8.0Hz,2H),7.57(d,J=8.0H z,2H),7.53-7.45(m,4H),6.95(s,1H),6.12(s,2H),5.79(s,2H),2.46(d,J=12.0Hz,6H).

[1161] Example 115 Synthesis of Compound AB36499

[1162] Step (1):

[1163] Compound 1 (100 mg) was dissolved in acetonitrile (5 mL), and compound 2 (77 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-10%) to obtain compound AB36499 (89.8 mg).

[1164] MS-ESI: theoretical value [M] + :390.14; measured value:390.15.

[1165] 1 H NMR (400MHz, DMSO-d6) δ9.56 (s, 1H), 9.47 (s, 1H), 8.05 (d, J = 8.0Hz, 2H), 7.72 (s, 1H) ),7.53-7.44(m,5H),6.95(s,1H),6.12(s,2H),5.79(s,2H),2.46(d,J=12.0Hz,6H).

[1166] Example 116 Synthesis of Compound AB36500

[1167] Step (1):

[1168] Compound 1 (400 mg) was dissolved in acetonitrile (10 mL), and compound 2 (694 mg) and potassium carbonate (828 mg) were added. The mixture was reacted at 80° C. for 16 h. The reaction solution was spin-dried, and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-10%) to obtain compound 3 (120 mg).

[1169] MS-ESI: theoretical value [M+H] + :284.12.

[1170] Step (2):

[1171] Compound 3 (120 mg) was dissolved in acetonitrile (5 mL), and compound 4 (72 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-10%) to obtain compound AB36500 (81.5 mg).

[1172] MS-ESI: theoretical value [M] + :374.17; measured value:374.05.

[1173] 1H NMR(400MHz,DMSO-d6)δ9.57(s,1H),9.49(s,1H),7.89-7.85(m,1H),7.55-7.53(m,2H),7.43-7.34(m,3H),7. 36(d,J=16.0Hz,1H),7.26(d,J=8.0Hz,1H),6.94(s,1H),5.91(s,2H),5.80(s,2H),2.49(s,3H),2.44(s,3H).

[1174] Example 117 Synthesis of Compound AB36502

[1175] Step (1):

[1176] Compound 1 (3.96 mmol) was dissolved in tetrahydrofuran (20 mL) under nitrogen protection. n-Butyl lithium (5.94 mmol) was added at -78 ° C. and the reaction was carried out at -78 ° C for 0.5 h. Compound 2 (261 mg) was added at -78 ° C. and the reaction was carried out at room temperature for 1 h. The reaction solution was quenched with saturated aqueous ammonium chloride solution, and the organic phase was separated by extraction with ethyl acetate. The organic phase was dried over anhydrous sodium sulfate, filtered and dried to obtain compound 3 (630 mg).

[1177] MS-ESI: theoretical value [M+H] + :171.05.

[1178] Step (2):

[1179] Compound 3 (300 mg) was dissolved in dichloromethane (10 mL), and Dess-Martin periodinane (1.5 g) was added at 0°C. The reaction was allowed to proceed at room temperature for 2 h. The solid was filtered and washed with dichloromethane. The filtrate was dried by rotary evaporation, and the crude product was purified by flash chromatography (petroleum ether / ethyl acetate = 0%-10%) to give compound 4 (150 mg).

[1180] MS-ESI: theoretical value [M+H] + :169.04.

[1181] Step (3):

[1182] Compound 4 (150 mg) was dissolved in tetrahydrofuran (10 mL), and compound 5 (401 mg) was added. The mixture was reacted at 50° C. for 16 h. The solid was filtered and washed with tetrahydrofuran. The filtrate was dried by rotary evaporation. The crude product was purified by flash chromatography (petroleum ether / ethyl acetate = 0%-10%) to give compound 6 (200 mg).

[1183] MS-ESI: theoretical value [M+H]+ :246.94.

[1184] Step (4):

[1185] Compound 6 (200 mg) was dissolved in acetonitrile (10 mL), and compound 7 (107 mg) and cesium carbonate (526 mg) were added. The mixture was reacted at 80° C. for 16 h. The reaction solution was spin-dried and the crude product was purified by flash chromatography (dichloromethane / methanol = 0%-10%) to give compound 8 (260 mg).

[1186] MS-ESI: theoretical value [M+H] + :300.09.

[1187] Step (5):

[1188] Compound 8 (260 mg) was dissolved in acetonitrile (5 mL), and benzyl bromide (149 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction solution was spin-dried and the crude product was purified by flash chromatography (dichloromethane / methanol = 0%-10%) to obtain compound AB36502 (227.4 mg).

[1189] MS-ESI: theoretical value [M] + :390.14; measured value:390.05.

[1190] 1 H NMR (400MHz, DMSO-d6) δ9.58(s,1H),9.50(s,1H),8.19(s,1H),8.01-7.99(m,1H),7.64(d,J=8.0Hz,1H),7. 56-7.54(m,2H),47.47-7.42(m,3H),6.96(d,J=4.0Hz,1H),6.17(s,2H),5.81(s,2H),2.47(d,J=4.0Hz,6H).

[1191] Example 118 Synthesis of Compound AB36506

[1192] Step (1):

[1193] Compound 1 (300 mg) was dissolved in acetonitrile (10 mL), and compound 2 (537 mg) and cesium carbonate (1.6 g) were added. The mixture was reacted at 80° C. for 16 h. The reaction solution was spin-dried and the crude product was purified by flash chromatography (dichloromethane / methanol = 0%-10%) to give compound 3 (100 mg).

[1194] MS-ESI: theoretical value [M+H]+ :252.11.

[1195] Step (2):

[1196] Compound 3 (100 mg) was dissolved in acetonitrile (5 mL), and compound 4 (68 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction solution was spin-dried and the crude product was purified by flash chromatography (dichloromethane / methanol = 0%-10%) to obtain compound AB36506 (100.1 mg).

[1197] MS-ESI: theoretical value [M] + :342.16; measured value:342.05.

[1198] 1 H NMR (400MHz, DMSO-d6) δ9.98(s,1H),8.95(s,1H),8.83(d,J=8.0Hz,1H),8.36(d,J=8.0Hz,1H),8. 00(d,J=8.0Hz,2H),7.56-7.54(m,2H),7.47-7.42(m,5H),6.44(s,2H),5.89(s,2H),2.43(s,3H).

[1199] Example 119 Synthesis of Compound AB36515

[1200] Step (1):

[1201] Compound 1 (80 mg) was dissolved in N,N-dimethylformamide (5 mL), and compound 2 (63 mg) and N,N-diisopropylethylamine (104 mg) were added. The mixture was reacted at 80°C for 16 h. The reaction solution was spin-dried and the crude product was prepared using reverse phase (acetonitrile / water + 0.1% formic acid) to obtain compound AB36515 (47.9 mg).

[1202] MS-ESI: theoretical value [M] + :362.11; measured value:362.00.

[1203] 1 H NMR(400MHz,DMSO-d6)δ10.03(s,1H),9.04-8.87(m,2H),8.45-8.40(m,2H),8.15-8.03(m,2H),7.88 -7.85(m,1H),7.71-7.67(m,1H),7.58(d,J=8.0Hz,1H),7.50-7.39(m,4H),6.31(s,2H),5.89(s,2H).

[1204] Example 120 Synthesis of Compound AB36548

[1205] Step (1):

[1206] Compound 1 (300 mg) was dissolved in dichloromethane (10 mL), and N-bromosuccinimide (279 mg) and p-toluenesulfonic acid (27 mg) were added. The mixture was reacted at 40° C. under a nitrogen atmosphere for 2 h. The reaction solution was diluted with water and extracted with dichloromethane. The organic phase was dried over anhydrous sodium sulfate, filtered and dried by rotary evaporation. The crude product was prepared using normal phase (petroleum ether / ethyl acetate = 50 / 1) to give compound 2 (420 mg).

[1207] MS-ESI: Calculated value [M+H]: 270.97.

[1208] Step (2):

[1209] Compound 2 (200 mg) was dissolved in acetonitrile (5 mL), and compound 3 (155 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-50%) to obtain compound AB36548 (11.4 mg).

[1210] MS-ESI: theoretical value [M] + : 399.15; measured value: 399.10.

[1211] 1 H NMR (400MHz, DMSO-d6) δ9.67(d,J=4.0Hz,1H),9.40(d,J=4.0Hz,1H),8.61(d,J=4.0Hz,1H),8.54-8.52(m,1H),8.32(d,J=4.0Hz,1H),7.83(d,J =8.0Hz,1H),7.40-7.35(m,5H),7.25(d,J=4.0Hz,1H),6.37-6.32(m,1H ),5.68(s,2H),3.50-3.47(m,2H),3.12-3.02(m,1H),2.83-2.76(m,1H).

[1212] Example 121 Synthesis of Compound AB36549

[1213] Step (1):

[1214] Compound 1 (500 mg) was dissolved in N,N-dimethylformamide (10 mL), and sodium hydroxide (225 mg, 60% in mineral oil) was added at 0°C. After reacting for 0.5 h, compound 2 (641 mg) was added and reacted at room temperature for 1 h. The reaction solution was quenched with saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The organic phase was dried over anhydrous sodium sulfate, filtered and spin-dried. The crude product was prepared using normal phase (dichloromethane / methanol = 0%-10%) to give compound 3 (810 mg).

[1215] MS-ESI: Calculated value [M+H]: 224.11.

[1216] Step (2):

[1217] Compound 3 (150 mg) was dissolved in acetonitrile (5 mL), and compound 4 (160 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-20%) to obtain compound AB36549 (5 mg).

[1218] MS-ESI: theoretical value [M] + : 382.19; measured value: 382.20.

[1219] 1 H NMR (400MHz, DMSO-d6) δ9.63(s,1H),8.17(d,J=4.0Hz,1H),7.77(s,1H),7.54(d,J=8.0Hz,1H),7.41-7.35(m,6H),7.06(d,J=4.0 Hz,1H),6.24-6.22(m,1H),5.66-5.56(m,2H),3.24-3.19(m,2H),3.01(s,3H),2.95-2.91(m,1H),2.74-2.70(m,1H),2.37(s,3H).

[1220] Example 122 Synthesis of Compound AB36550

[1221] Step (1):

[1222] Compound 1 (100 mg) was dissolved in acetonitrile (5 mL), and compound 2 (124 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-20%) to obtain compound AB36550 (142 mg).

[1223] MS-ESI: theoretical value [M] +: 426.14; measured value: 426.15.

[1224] 1 H NMR (400MHz, DMSO-d6) δ9.44 (s, 1H), 8.19-8.16 (m, 2H), 8.04 (s, 1H), 7.85 (d, J = 4.0Hz ,2H),7.39-7.34(m,5H),7.17(d,J=4.0Hz,1H),6.51(s,2H),5.62(s,2H),2.87(s,3H).

[1225] Example 123 Synthesis of Compound AB36551

[1226] Step (1):

[1227] Compound 1 (500 mg) was dissolved in tetrahydrofuran (10 mL), and sodium hydroxide (253 mg, 60% in mineral oil) was added at 0°C. After reacting for 0.5 h, compound 2 (461 mg) was added and reacted at room temperature for 1 h. The reaction solution was quenched with saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The organic phase was dried over anhydrous sodium sulfate, filtered and spin-dried. The crude product was prepared using normal phase (dichloromethane / methanol = 0%-10%) to give compound 2 (450 mg).

[1228] MS-ESI: Calculated value [M+H]: 147.09.

[1229] Step (2):

[1230] Compound 2 (100 mg) was dissolved in acetonitrile (5 mL), and compound 3 (165 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-20%) to obtain compound AB36551 (103.8 mg).

[1231] MS-ESI: theoretical value [M] + : 309.14; measured value: 309.75.

[1232] 1H NMR (400MHz, DMSO-d6) δ9.35(s,1H),8.55(d,J=8.0Hz,1H),8.29(d,J=8.0Hz,1H),8.08(d,J=4.0Hz,1H),7.63-7.56(m,3H),7.12( d,J=4.0Hz,1H),6.17-6.12(m,1H),4.46-4.40(m,2H),3.27-3.23(m,2H),3.04-3.02(m,1H),2.66-2.64(m,1H),1.43-1.39(m,3H).

[1233] Example 124 Synthesis of Compound AB36552

[1234] Step (1):

[1235] Compound 1 (100 mg) was dissolved in N,N-dimethylformamide (10 mL), NaH (36 mg) was added at 0°C, the reaction was continued for 0.5 h, and then compound 2 (132 mg) was added and the reaction was continued at room temperature for 0.5 h. The reaction solution was quenched with saturated aqueous ammonium chloride solution and extracted with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and filtered. The filtrate was dried by rotary evaporation, and the crude product was prepared using normal phase (dichloromethane / methanol = 0-20%) to give compound 3 (140 mg).

[1236] MS-ESI: theoretical value [M+H] + :223.29.

[1237] Step (2):

[1238] Compound 3 (140 mg) was dissolved in acetonitrile (5 mL), and compound 4 (163 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0-20%) to obtain compound AB36552 (11.5 mg).

[1239] MS-ESI: theoretical value [M] + :401.14, measured value:401.10.

[1240] 1H NMR (400MHz, DMSO-d6) δ9.40 (s, 1H), 8.29 (s, 1H), 8.08 (d, J = 3.4Hz, 1H), 7.88 (d,J=2.3Hz,1H),7.78(dd,J=8.3,2.4Hz,1H),7.57(d,J=8.3Hz,1H),7.41–7. 30(m,5H),7.02(d,J=3.2Hz,1H),6.22-6.17(m,1H),5.62(s,2H),3.50–3.43( m,1H),3.28–3.21(m,1H),3.03–2.95(m,1H),2.81(s,3H),2.72–2.66(m,1H).

[1241] Example 125 Synthesis of Compound AB36553

[1242] Step (1):

[1243] Compound 1 (100 mg) was dissolved in acetonitrile (5 mL), and compound 2 (58 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0-20%) to obtain compound AB36553 (54.1 mg).

[1244] MS-ESI: theoretical value [M] + : 396.13; measured value: 396.00.

[1245] 1 H NMR (400MHz, DMSO-d6) δ = 9.75 (s, 1H), 9.58 (s, 1H), 8.32 (d, J = 8.0Hz, 2H), 8.07 (d, J = 4.0Hz, 1H), 8.03 ( d,J=8.0Hz,2H),7.55–7.50(m,2H),7.46-7.42(m,3H),7.19(d,J=4.0Hz,1H),6.25(s,2H),5.85(s,2H).

[1246] Example 126 Synthesis of Compound AB36554

[1247] Step (1):

[1248] Compound 1 (100 mg) was dissolved in N,N-dimethylformamide (10 mL), NaH (40 mg) was added at 0°C, the reaction was continued for 0.5 h, and then compound 2 (180 mg) was added and the reaction was continued at room temperature for 0.5 h. The reaction solution was quenched with saturated aqueous ammonium chloride solution and extracted with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and filtered. The filtrate was dried by rotary evaporation, and the crude product was prepared using normal phase (dichloromethane / methanol = 0-20%) to give compound 3 (50 mg).

[1249] MS-ESI: theoretical value [M+1] + :256.

[1250] Step (2):

[1251] Compound 3 (50 mg) was dissolved in acetonitrile (5 mL), and compound 4 (41 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0-20%) to obtain compound AB36554 (29.2 mg).

[1252] MS-ESI: theoretical value [M] + :346.14, measured value:345.95.

[1253] 1 H NMR(400MHz,DMSO-d6)δ9.69(s,1H),9.52(s,1H),8.19-8.16(s,2H),8.06(d, J=4Hz,1H),7.46-7.40(m,7H),7.14(d,J=4Hz,1H),6.13(s,2H),5.80(s,2H).

[1254] Example 127 Synthesis of Compound AB36555

[1255] Step (1):

[1256] Compound 1 (1 g) was dissolved in N,N-dimethylformamide (10 mL), NaH (360.5 mg) was added at 0°C, the reaction was continued for 0.5 h, and then compound 2 (1.3 g) was added and the reaction was continued at room temperature for 0.5 h. The reaction solution was quenched with saturated aqueous ammonium chloride solution and extracted with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and filtered. The filtrate was dried by rotary evaporation, and the crude product was prepared using normal phase (dichloromethane / methanol = 0-20%) to give compound 3 (600 mg).

[1257] MS-ESI: theoretical value [M] + :224.

[1258] Step (2):

[1259] Compound 3 (100 mg) was dissolved in acetonitrile (5 mL), and compound 4 (157 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0-20%) to obtain compound AB36555 (50.5 mg).

[1260] MS-ESI: theoretical value [M] + :436.16, measured value:436.10.

[1261] 1 H NMR(400MHz, DMSO-d6)δ9.72(s,1H),9.34(s,1H),8.18-8.03(m,3H),7.80(d,J=8.0Hz,1H),7.37–7.32( m,5H),6.31-6.27(m,1H),5.60(s,2H),3.44(s,2H),3.06-3.00(m,1H),2.77-2.75(m,1H),2.377(s,3H).

[1262] Example 128 Synthesis of Compound AB36559

[1263] Step (1):

[1264] Compound 1 (50 mg) was dissolved in acetonitrile (3 mL), and compound 2 (57 mg) was added. The mixture was reacted at 80°C for 16 h. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0-20%) to obtain compound AB36559 (64.2 mg).

[1265] MS-ESI: theoretical value [M] + :360.15, measured value:360.05.

[1266] 1 H NMR(400MHz,DMSO-d6)δ9.45(s,1H),8.19(d,J=4.0Hz,1H),7.95-7.90(m,2H),7.74–7.67 (m,2H),7.38–7.34(m,5H),7.17(d,J=4.0Hz,1H),6.49(s,2H),5.62(s,2H),2.83(s,3H).

[1267] Example 129 Synthesis of Compound AB36560

[1268] Step (1):

[1269] Compound 1 (50 mg) was dissolved in acetonitrile (3 mL), and compound 2 (57 mg) was added. The mixture was reacted at 80°C for 16 h. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0-20%) to obtain compound AB36560 (59.7 mg).

[1270] MS-ESI: theoretical value [M] + :356.18, measured value:356.10.

[1271] 1 H NMR (400MHz, DMSO-d6) δ = 9.46 (s, 1H), 8.19 (d, J = 4.0Hz, 1H), 7.94-7.91 (m, 2H), 7.563-7.55 (m, 2 H),7.36-7.32(m,5H),7.16(d,J=4.0Hz,1H),6.48(s,2H),5.62(s,2H),2.85(s,3H),2.45(s,3H).

[1272] Example 130 Synthesis of Compound AB36561

[1273] Step (1):

[1274] Compound 1 (400 mg) was dissolved in N,N-dimethylformamide (10 mL), NaH (145 mg) was added at 0°C, the reaction was continued for 30 min, and then compound 2 (517 mg) was added and the reaction was continued at room temperature for 0.5 h. The reaction solution was diluted with water and extracted with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and filtered. The filtrate was dried by rotary evaporation, and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-20%) to give compound 3 (600 mg).

[1275] MS-ESI: theoretical value [M+1] + :223.

[1276] Step (2):

[1277] Compound 3 (100 mg) was dissolved in acetonitrile (5 mL), and compound 4 (115 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0-20%) to obtain compound AB36561 (114.5 mg).

[1278] MS-ESI: theoretical value [M+H] +:355.18, measured value:355.50.

[1279] 1 H NMR(400MHz,DMSO-d6)δ9.26(s,1H),8.31(s,1H),8.09(s,1H),7.93-7.90(m,2H),7.62-7.56(m,2 H),7.41–7.30(m,5H),7.12(d,J=4.0Hz,1H),6.45(s,2H),5.63(s,2H),2.63(s,3H),2.45(s,3H).

[1280] Example 131 Synthesis of Compound AB36562

[1281] Step (1):

[1282] Compound 1 (100 mg) was dissolved in acetonitrile (5 mL), and compound 2 (126 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0-20%) to obtain compound AB36562 (107.6 mg).

[1283] MS-ESI: theoretical value [M] + :375.13, measured value:375.15.

[1284] 1 H NMR (400MHz, DMSO-d6) δ9.28(s,1H),8.35(s,1H),8.16(s,1H),8.11(s,1H),7.0.6(d,J=8.0Hz,1H),7.88(d,J= 8.0Hz,1H),7.73-7.69(m,1H),7.37-7.33(m,5H),7.13(d,J=4.0Hz,1H),6.52(s,2H),5.64(s,2H),2.65(s,3H).

[1285] Example 132 Synthesis of Compound AB36563

[1286] Step (1):

[1287] Compound 1 (100 mg) was dissolved in N,N-dimethylformamide (5 mL), NaH (36 mg) was added at 0°C, the reaction was continued for 0.5 h, and then compound 2 (163 mg) was added and the reaction was continued at room temperature for 0.5 h. The reaction solution was quenched with saturated ammonium chloride solution and extracted with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and filtered. The filtrate was dried by rotary evaporation, and the crude product was prepared using normal phase (dichloromethane / methanol = 0-20%) to give compound 3 (120 mg).

[1288] MS-ESI: theoretical value [M+1] + :270.

[1289] Step (2):

[1290] Compound 3 (120 mg) was dissolved in acetonitrile (5 mL), and compound 4 (83 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0-20%) to obtain compound AB36563 (98.3 mg).

[1291] MS-ESI: theoretical value [M] + :374.17, measured value:374.00.

[1292] 1 H NMR(400MHz,DMSO-d6)δ9.63(s,1H),9.52(s,1H),8.26–8.23(m,2H),7.55-7.41(m ,7H),6.93(s,1H),6.23-6.16(m,3H),2.48(d,J=8.4Hz,3H),2.08(d,J=6.8Hz,3H).

[1293] Example 133 Synthesis of Compound AB36565

[1294] Step (1):

[1295] Compound 1 (200 mg) was dissolved in dichloromethane (10 mL), and di-tert-butyl dicarbonate (360 mg), triethylamine (181 mg) and 4-dimethylaminopyridine (181 mg) were added. The reaction was allowed to react for 0.5 h. The reaction solution was diluted with water and extracted with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and filtered. The filtrate was spin-dried and the crude product was prepared using normal phase (petroleum ether / ethyl acetate = 0-20%) to give compound 2 (210 mg).

[1296] MS-ESI: theoretical value [M+1] + :210.

[1297] Step (2):

[1298] Compound 2 (210 mg) was dissolved in N,N-dimethylformamide (5 mL), and NaH (48 mg) was added at 0°C for 0.5 h. Compound 3 (172 mg) was then added and reacted at room temperature for 0.5 h. The reaction solution was quenched with saturated ammonium chloride solution and extracted with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and filtered. The filtrate was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0-20%) to give compound 4 (250 mg).

[1299] MS-ESI: theoretical value [M+1] + :300.

[1300] Step (3):

[1301] Compound 4 (250 mg) was dissolved in ethyl acetate (5 mL), and hydrochloric acid / ethyl acetate (5 mL, 4 M) was added. The mixture was reacted at room temperature for 2 h. The reaction solution was dried by rotary evaporation to obtain compound 5 (190 mg).

[1302] MS-ESI: theoretical value [M+1] + :200.

[1303] Step (4):

[1304] Compound 5 (100 mg) was dissolved in acetonitrile (5 mL), and compound 6 (128 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0-20%) to obtain compound AB36565 (30 mg).

[1305] MS-ESI: theoretical value [M] + :332.18, measured value:332.00.

[1306] 1 H NMR(400MHz, DMSO-d6)δ8.43(s,1H),8.07(d,J=7.2Hz,1H),7.87-7.85(m,2H),7.61–7.42(m,2H ),7.39-7.31(m,5H),7.00(d,J=4.5Hz,1H),5.99(s,2H),4.73(s,2H),2.48(s,3H),2.43(s,3H).

[1307] Example 134 Synthesis of Compound AB36567

[1308] Step (1):

[1309] Compound 1 (100 mg) was dissolved in acetonitrile (3 mL), and compound 2 (144 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0-20%) to obtain compound AB36567 (107.7 mg).

[1310] MS-ESI: theoretical value [M] + :410.15, measured value:409.95.

[1311] 1 H NMR (400MHz, DMSO-d6) δ9.46 (s, 1H), 8.40 (d, J = 9.2Hz, 2H), 8.20 (s, 2H), 7.96-7.92 (m ,1H),7.38–7.34(m,5H),7.17(d,J=4.0Hz,1H),6.59(s,2H),5.63(s,2H),2.88(s,3H).

[1312] Example 135 Synthesis of Compound AB36569

[1313] Step (1):

[1314] Compound 1 (500 mg) was dissolved in dichloromethane (10 mL), and triethylamine (603 mg), 4-dimethylaminopyridine (56 mg) and (Boc)2O (1.0 g) were added. The reaction was carried out at room temperature for 0.5 h. The reaction solution was diluted with water and extracted with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and filtered. The filtrate was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-20%) to give compound 2 (790 mg).

[1315] MS-ESI: theoretical value [M+1] + :210.12, measured value:210.00.

[1316] Step (2):

[1317] Compound 2 (390 mg) was dissolved in N,N-dimethylformamide (5 mL), and NaH (90 mg) was added at 0°C for 0.5 h, followed by addition of benzyl bromide (319 mg) and reaction at room temperature for 0.5 h. The reaction solution was quenched with saturated ammonium chloride solution and extracted with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and filtered. The filtrate was spin-dried, and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-20%) to give compound 3 (330 mg).

[1318] MS-ESI: theoretical value [M+1] + :300.17, measured value:300.00.

[1319] Step (3):

[1320] Compound 3 (160 mg) was dissolved in acetonitrile (3 mL), and compound 4 (114 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction solution was filtered, and the solid was washed with ether to obtain compound AB36569 (72.1 mg).

[1321] MS-ESI: theoretical value [M] + :332.43, measured value:332.00.

[1322] 1 H NMR(400MHz,DMSO-d6)δ9.73(s,1H),8.77(s,1H),8.22(s,1H),7.83(d,J=8.8Hz,2H),7.60–7.50(m,2H ),7.39-7.34(m,4H),7.30–7.27(m,1H),5.93(s,2H),4.81(d,J=6.0Hz,2H),2.42(s,3H),2.21(s,3H).

[1323] Example 136 Synthesis of Compound AB36570

[1324] Step (1):

[1325] Compound 1 (500 mg) was dissolved in N,N-dimethylformamide (10 mL), NaH (252 mg) was added at 0°C, the reaction was continued for 0.5 h, and then compound 2 (1.1 g) was added and the reaction was continued at room temperature for 0.5 h. The reaction solution was quenched with saturated ammonium chloride solution and extracted with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and filtered. The filtrate was dried by rotary evaporation, and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-20%) to give compound 3 (260 mg).

[1326] MS-ESI: theoretical value [M+1] + :298.07, measured value:297.90.

[1327] Step (2):

[1328] Compound 3 (260 mg) was dissolved in acetonitrile (5 mL), and compound 4 (162 mg) was added. The mixture was reacted at 80°C for 16 h. The reaction solution was spin-dried and the crude product was prepared by reverse phase (acetonitrile / water + 0.1% formic acid) to give compound AB36570 (18.8 mg).

[1329] MS-ESI: theoretical value [M] + :402.14, measured value:402.00.

[1330] 1 H NMR(400MHz,DMSO-d6)δ10.01(s,1H),9.02(s,1H),8.94(d,J=9.6Hz,1H),8 .34(d,J=6.8Hz,1H),7.83(s,1H),7.78–7.75(m,1H),7.63–7.48(m,3H),7.4 7–7.4(m,3H),6.30-6.25(m,1H),6.21-6.17(m,1H),3.41-3.36(m,1H),3.2 7-3.24(m,1H),3.10-2.94(m,1H),2.59-2.53(m,1H),2.13(d,J=7.2Hz,3H).

[1331] Example 137 Synthesis of Compound AB36571

[1332] Step (1):

[1333] Compound 1 (500 mg) was dissolved in acetonitrile (10 mL), and compound 2 (775 mg) and potassium carbonate (1.7 g) were added. The mixture was reacted at 80° C. for 16 h. The reaction solution was diluted with water and extracted with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and filtered. The filtrate was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-20%) to give compound 3 (240 m).

[1334] MS-ESI: theoretical value [M+1] + :224.11, measured value:223.95.

[1335] Step (2):

[1336] Compound 3 (240 mg) was dissolved in acetonitrile (5 mL), and compound 4 (279 mg) was added. The mixture was reacted at 80°C for 16 h. The reaction solution was spin-dried and the crude product was prepared by reverse phase (acetonitrile / water + 0.1% formic acid) to obtain compound AB36571 (26.5 mg).

[1337] MS-ESI: theoretical value [M] + :402.14, measured value:401.95.

[1338] 1 H NMR (400MHz, DMSO-d6) δ9.65(s,1H),9.37(s,1H),8.49(d,J=4.0Hz,1H),7.88–7.80(m,2H),7.58(d,J=8.4Hz,1H) ,7.43–7.25(m,6H),6.31–6.27(m,2H),3.30-3.28(m,2H),3.03-2.98(m,1H),2.74(s,1H),2.01(d,J=7.2Hz,3H).

[1339] Example 138 Synthesis of Compound AB36572

[1340] Step (1):

[1341] Compound 1 (2 g) was dissolved in dichloromethane (10 mL), and Boc2O (4.6 g), triethylamine (2.7 g) and 4-dimethylaminopyridine (258 mg) were added. The reaction was allowed to react for 0.5 h. The reaction solution was diluted with water and extracted with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and filtered. The filtrate was spin-dried and the crude product was prepared using normal phase (petroleum ether / ethyl acetate = 0%-20%) to give compound 2 (2 g).

[1342] MS-ESI: theoretical value [M+1] + :210.12.

[1343] Step (2):

[1344] Compound 2 (500 mg) was dissolved in N,N-dimethylformamide (10 mL), NaH (229 mg) was added at 0°C, the reaction was continued for 0.5 h, and then compound 3 (884 mg) was added and the reaction was continued at room temperature for 0.5 h. The reaction solution was quenched with saturated ammonium chloride solution and extracted with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and filtered. The filtrate was dried by rotary evaporation, and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-20%) to give compound 4 (600 mg).

[1345] MS-ESI: theoretical value [M+1] + :314.18.

[1346] Step (3):

[1347] Compound 4 (600 mg) was dissolved in ethyl acetate (5 mL), and hydrochloric acid / ethyl acetate (5 mL) was added. The mixture was reacted at room temperature for 2 h. The reaction solution was dried by rotary evaporation to obtain compound 5 (420 mg).

[1348] MS-ESI: theoretical value [M+1] + :214.13.

[1349] Step (4):

[1350] Compound 5 (200 mg) was dissolved in acetonitrile (10 mL), and compound 6 (239 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0-20%) to obtain compound AB36572 (8.2 mg).

[1351] MS-ESI: theoretical value [M+H] + :346.19, measured value:346.25.

[1352] 1 H NMR(400MHz, DMSO-d6)δ8.50(s,1H),8.02(d,J=7.6Hz,1H),7.86-7.83(m,2H),7.58(s,1H),7.53-7.50(m,1H),7.45-7.40(m,2H),7 .38-7.36(m,2H),7.30-7.28(m,1H),7.05(s,1H),5.95(s,2H),5.43-5.41(m,1H),2.46(s,3H),2.42(s,3H),1.55(d,J=6.8Hz,3H).

[1353] Example 139 Synthesis of Compound AB36575

[1354] Step (1):

[1355] Compound 1 (500 mg) was dissolved in dichloromethane (10 mL), and compound 2 (1.1 g), triethylamine (692 mL) and 4-dimethylaminopyridine (115 mg) were added. The reaction was allowed to react at room temperature for 1 h. The reaction solution was diluted with water and extracted with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and filtered. The filtrate was spin-dried and the crude product was prepared using normal phase (petroleum ether / ethyl acetate = 0%-20%) to give compound 3 (390 mg).

[1356] MS-ESI: theoretical value [M+1] + :196.10.

[1357] Step (2):

[1358] Compound 3 (390 mg) was dissolved in N,N-dimethylformamide (10 mL), NaH (96 mg) was added at 0°C, the reaction was continued for 0.5 h, and then compound 4 (341 mg) was added and the reaction was continued at room temperature for 0.5 h. The reaction solution was quenched with saturated ammonium chloride solution and extracted with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and filtered. The filtrate was dried by rotary evaporation, and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-20%) to give compound 5 (250 mg).

[1359] MS-ESI: theoretical value [M+1] + :286.15.

[1360] Step (3):

[1361] Compound 5 (250 mg) was dissolved in acetonitrile (5 mL), and compound 6 (224 mg) was added. The mixture was reacted at 80°C for 16 h. The reaction solution was spin-dried and the crude product was prepared by reverse phase (acetonitrile / water + 0.1% formic acid) to obtain compound AB36575 (203.4 mg).

[1362] MS-ESI: theoretical value [M] + :318.16, measured value:318.00.

[1363] 1 H NMR (400MHz, DMSO-d6) δ10.17-10.14(m,1H),8.80(s,1H),8.16(d,J=7.6Hz,1H),7.85-7.82(m,2H),7.60 -7.55(m,2H),7.37–7.31(m,5H),6.99(d,J=7.2Hz,1H),5.90(s,2H),4.76(d,J=5.6Hz,2H),2.43(s,3H).

[1364] Example 140 Synthesis of Compound AB36576

[1365] Step (1):

[1366] Compound 1 (1 g) was dissolved in dichloromethane (10 mL), and compound 2 (2 g), triethylamine (988 mg) and 4-dimethylaminopyridine (92 mg) were added. The reaction mixture was allowed to react for 1 h. The reaction solution was diluted with water and extracted with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and filtered. The filtrate was spin-dried and the crude product was prepared using normal phase (petroleum ether / ethyl acetate = 0%-20%) to give compound 3 (1.6 g).

[1367] MS-ESI: theoretical value [M+1] + :234.12.

[1368] Step (2):

[1369] Compound 3 (200 mg) was dissolved in acetonitrile (10 mL), and compound 4 (147 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction solution was spin-dried, and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-20%) to give compound 5 (120 mg).

[1370] MS-ESI: theoretical value [M] + :224.12.

[1371] Step (3):

[1372] Compound 5 (120 mg) was dissolved in N,N-dimethylformamide (5 mL), and compound 6 (167.5 mg) and N,N-diisopropylethylamine (138 mg) were added. The mixture was reacted at 80°C for 16 h. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-20%) to obtain compound AB36576 (8.8 mg).

[1373] MS-ESI: theoretical value [M+H] + :402.41, measured value:402.10.

[1374] 1 H NMR (400MHz, DMSO-d6) δ9.57 (s, 1H), 9.40 (s, 1H), 7.86 (s, 1H), 7.76 (d, J = 8.8Hz, 1H), 7.55-7.53 (m, 3H), 7.44 -7.42(m,3H),6.94(s,1H),5.77(s,2H),3.20-3.16(m,2H),3.15-3.10(m,2H),2.58(s,3H),2.01-1.99(m,1H).

[1375] Example 141 Synthesis of Compound AB36577

[1376] Step (1):

[1377] Compound 1 (300 mg) was dissolved in dichloromethane (10 mL), and Boc2O (591 mg)\triethylamine (297 mg) and 4-dimethylaminopyridine (28 mg) were added. The reaction was allowed to react for 1 h. The reaction solution was diluted with water and extracted with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and filtered. The filtrate was spin-dried and the crude product was prepared using normal phase (petroleum ether / ethyl acetate = 0%-20%) to give compound 2 (360 mg).

[1378] MS-ESI: theoretical value [M+1] + :234.12.

[1379] Step (2):

[1380] Compound 2 (200 mg) was dissolved in acetonitrile (10 mL), and compound 3 (159 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction solution was dried by rotary evaporation. The crude product was prepared using normal phase (dichloromethane / methanol = 0%-20%) to obtain compound 4 (200 mg).

[1381] MS-ESI: theoretical value [M] + :238.13.

[1382] Step (3):

[1383] Compound 4 (200 mg) was dissolved in N,N-dimethylformamide (10 mL), and compound 5 (263 mg) and N,N-diisopropylethylamine (218 mg) were added. The mixture was reacted at 80°C for 16 h. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0%-20%) to obtain compound AB36577 (24.3 m).

[1384] MS-ESI: theoretical value [M] + :416.15, measured value:416.00.

[1385] 1 H NMR (400MHz, DMSO-d6) δ9.86 (s, 1H), 9.54 (d, J = 3.2Hz, 1H), 7.98 (s, 1H), 7.83 (s, 1H), 7.76-7.74 (m, 1H), 7.61-7.56 (m, 3H), 7.48-7.41 (m, 3H),6.22(d,J=4.8Hz,1H),6.08-6.05(m,1H),3.43-3.40(m,2H),3.19-3.17(m,1H),2.94-2.90(m,1H),2.42(s,3H),2.13(d,J=6.8Hz,3H).

[1386] Example 142 Synthesis of Compound AB36578

[1387] Step (1):

[1388] Compound 1 (300 mg) was dissolved in acetonitrile (10 mL), and compound 2 (238 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction solution was evaporated to dryness, and the crude product was prepared using normal phase (dichloromethane / methanol = 0-20%) to obtain compound 3 (200 mg).

[1389] MS-ESI: theoretical value [M] + :238.13.

[1390] Step (2):

[1391] Compound 3 (200 mg) was dissolved in N,N-dimethylformamide (10 mL), and compound 4 (263 mg) and N,N-diisopropylethylamine (217 mg) were added. The mixture was reacted at 80°C for 16 h. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0-20%) to obtain compound AB36578 (61.5 mg).

[1392] MS-ESI: theoretical value [M] + :416.15, measured value:416.15.

[1393] 1 H NMR(400MHz,DMSO-d6)δ9.64(s,1H),9.43(s,1H),7.85(s,1H),7.77-7.74(m,1H),7.56(d,J=8.0Hz,3H), 7.43-7.36(m,3H),6.93(s,1H),6.18-5.89(m,2H),3.20-3.05(m,4H),2.58(s,3H),2.06(d,J=4.8Hz,3H).

[1394] Example 143 Synthesis of Compound AB36579

[1395] Step (1):

[1396] Compound 1 (200 mg) was dissolved in acetonitrile (10 mL), and compound 2 (160 mg) was added. The mixture was reacted at 80° C. for 16 h. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0-20%) to obtain compound 3 (50 mg).

[1397] MS-ESI: theoretical value [M] + :238.13.

[1398] Step (2):

[1399] Compound 3 (50 mg) was dissolved in N,N-dimethylformamide (10 mL), and compound 4 (66 mg) and N,N-diisopropylethylamine (54 mg, 0.42 mmol, 2.0 eq) were added. The mixture was reacted at 80°C for 16 h. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0-20%) to obtain compound AB36579 (8.8 mg).

[1400] MS-ESI: theoretical value [M] + :416.15, measured value:416.10.

[1401] 1 H NMR(400MHz,DMSO-d6)δ9.62(d,J=8.4,Hz 1H),8.12(s,1H),7.85(s,1H),7.75(d,J=8.4Hz,1H),7.56(d,J=8.4Hz,1H),7.47-7.43(m,5H),7.06(s,1H),6.37 (d,J=4.0Hz,1H),6.11-6.18(m,1H),3.47-3.40(m,1H),3.22-3.18(m,1H),3.04-2.97(m,5H),2.04-2.01(m,3H).

[1402] Example 144 Synthesis of Compound AB36580

[1403] Step (1):

[1404] Compound 1 (230 mg) was dissolved in acetonitrile (10 mL), and compound 2 (183 mg) was added. The mixture was reacted at 80°C for 16 h. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0-20%) to obtain compound 3 (250 mg).

[1405] MS-ESI: theoretical value [M] + :224.12.

[1406] Step (2):

[1407] Compound 3 (150 mg) was dissolved in N,N-dimethylformamide (10 mL), and compound 4 (210 mg) and N,N-diisopropylethylamine (173.2 mg) were added. The mixture was reacted at 80°C for 16 h. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0-20%) to obtain compound AB36580 (5.6 mg).

[1408] MS-ESI: theoretical value [M] + :402.14, measured value:402.10.

[1409] 1 H NMR (400MHz, DMSO-d6) δ9.69 (s, 1H), 8.12 (d, J = 3.6Hz, 1H), 7.81 (s, 1H), 7. 71(d,J=8.4Hz,1H),7.52(d,J=8.4Hz,1H),7.43-7.40(m,3H),7.32(d,J=6.4 Hz,2H),7.13(d,J=3.6Hz,1H),6.09-6.05(m,1H),5.86(s,2H),3.35-3.31(m ,1H),3.18-3.15(m,1H),2.80-2.77(m,1H),2.79(s,3H),1.97-1.94(m,1H).

[1410] Example 145 Synthesis of Compound AB36581

[1411] Step (1):

[1412] Compound 1 (230 mg) was dissolved in N,N-dimethylformamide (5 mL), and compound 2 (322 mg) and N,N-diisopropylethylamine (267 mg) were added. The mixture was reacted at 80°C for 16 h. The reaction solution was spin-dried and the crude product was prepared using normal phase (dichloromethane / methanol = 0-20%) to obtain compound AB36581 (27.1 mg).

[1413] MS-ESI: theoretical value [M+H] + :402.14, measured value:402.15.

[1414] 1H NMR(400MHz,DMSO-d6)δ9.81(s,1H),8.82(s,1H),8.19(s,1H),7.86(s,1H),7.78–7.76(m,1H),7.58–7.54(m,3H),7.44-7.3 9(m,3H),6.11(s,1H),5.87(s,2H),3.49-3.42(m,1H),3.22-3.18(m,1H),2.93-2.90(m,1H),2.72(s,3H),2.57-2.55(m,1H).

[1415] Example 146

[1416] This example investigates the effects of different compounds prepared in Examples 1-145 on glucose absorption by adipocytes.

[1417] Maintenance medium: DMEM medium containing 10% FBS (fetal bovine serum) (+P / S).

[1418] Differentiation medium I: DMEM medium containing 10 μg / mL insulin, 0.5 mM IBMX (3-isobutyl-1-methylxanthine) and 1 μM dexamethasone.

[1419] Differentiation medium II: DMEM medium containing 10 μg / ml insulin.

[1420] Cell culture: Cells were cultured at 37°C and 5% CO2.

[1421] Experimental methods

[1422] 1. Inoculate low-passage, healthy 3T3-L1 cells (preadipocytes) into a culture flask and culture in maintenance medium until confluence reaches 100%;

[1423] 2. Remove the maintenance medium and add DMEM medium containing 10% newborn calf serum to continue culturing for 48 hours;

[1424] 3. Remove the culture medium and add differentiation medium I to initiate differentiation and culture for 48 hours;

[1425] 4. Remove the culture medium, add differentiation medium II, and continue culturing for 48 hours;

[1426] 5. Remove the culture medium, add maintenance medium, and culture to obtain 3T3-L1 differentiated adipocytes;

[1427] 6. 3T3-L1 differentiated adipocytes were cultured at a rate of 1×10 5The cells were seeded into a 96-well cell culture plate at a density of 100 cells / well, and DMEM medium (+P / S) containing 10% FBS (fetal bovine serum) was added and cultured for 24 hours.

[1428] 7. The culture medium was removed, and the cells were rinsed twice with PBS 7.4 buffer. The cells were divided into experimental and blank control groups. 100 μl of DMEM medium (without fetal bovine serum) containing different concentrations of the compounds prepared in the examples was added to the wells of the experimental groups, while DMEM medium (without fetal bovine serum) was added to the wells of the blank control group and cultured overnight.

[1429] 8. Remove the culture medium, rinse the cells twice with PBS 7.4 buffer, replace with sugar-free DMEM medium, and culture;

[1430] 9. Remove the culture medium, rinse the cells twice with PBS 7.4 buffer, add 50 μL / well of 2DG (2-deoxyglucose, 1 mM) in PBS 7.4 buffer, and incubate at room temperature for 10 min.

[1431] 10. Add 25 μL / well of stop buffer and shake for 1 minute.

[1432] 11. Add 25 μL / well of neutralization buffer and shake for 1 minute.

[1433] 12. Add 100 μL / well of 2DG6P (2-deoxyglucose-6-phosphate) detection reagent, shake for 1 minute, and then incubate at room temperature for 1 hour. The detection reagent includes:

[1434] 13. Fluorescence signals were measured using an Envision instrument, and the enhancement factor of glucose uptake by 3T3-L1 differentiated adipocytes was calculated for the different compounds prepared in this example compared to the blank control group. The enhancement factor was calculated as follows: enhancement factor = average signal value of the experimental group / average signal value of the blank control group.

[1435] Compared with the blank control group, the enhancement factors of glucose absorption by 3T3-L1 differentiated adipocytes by the different compounds prepared in this example are shown in Table 1.

[1436] Table 1 Compared with the blank control group, the enhancement factor of glucose absorption by 3T3-L1 differentiated adipocytes by different compounds prepared in Examples 1-145 of the present invention

[1437] As can be seen from Table 1, the different compounds prepared in Examples 1-145 of the present invention can effectively enhance the absorption of glucose by adipocytes, thereby having an excellent blood sugar lowering effect.

[1438] The above is an implementation scheme of the present invention designed for a case. It should be pointed out that for ordinary technicians in this technical field, several improvements can be made without departing from the principles of the present invention, and these improvements should also be regarded as the scope of protection of the present invention.

Claims

1. 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; in, Ring A is a substituted or unsubstituted C6-C12 aromatic ring, a substituted or unsubstituted 3-12-membered heteroaromatic ring, a substituted or unsubstituted C6-C12 aromatic ring and a 3-10-membered heterocycloalkane ring, or a substituted or unsubstituted 3-12-membered heteroaromatic ring and a 3-10-membered heterocycloalkane ring; R1 is R2 is hydrogen, substituted or unsubstituted C6-C12 aryl, substituted or unsubstituted C6-C12 aryl-, substituted or unsubstituted C1-C8 alkyl-, substituted or unsubstituted 3-12 heteroaryl, substituted or unsubstituted 3-12 heteroaryl-, substituted or unsubstituted C1-C8 alkyl-, substituted or unsubstituted C1-C10 alkyl, substituted or unsubstituted C3-C10 cycloalkyl; R3 and R4 are each independently hydrogen, substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C3-C8 cycloalkyl; R5 is a substituted or unsubstituted C6-C14 aryl group, or a substituted or unsubstituted 3-12 membered heteroaryl group; R6 is hydrogen, substituted or unsubstituted C1-C8 alkyl; R7 and R8 are linked to form a substituted or unsubstituted C3-C12 cycloalkane ring, or a substituted or unsubstituted 3-12 membered heterocycloalkane ring; R9 and R 10 are each independently hydrogen, substituted or unsubstituted C6-C12 aryl, substituted or unsubstituted C6-C12 aryl-substituted or unsubstituted C1-C8 alkyl-, substituted or unsubstituted C1-C10 alkyl; or R9 and R 10 Connected to form a substituted or unsubstituted 5-12 membered heterocycloalkyl group, or a substituted or unsubstituted 5-12 membered heteroaryl group; n is 0, 1, 2, 3, 4 or 5; Ring B is a substituted or unsubstituted C6-C12 aromatic ring, or a substituted or unsubstituted 3-12 membered heteroaromatic ring; Any of the "substituted" mentioned above means that one or more (preferably 1, 2, 3, 4, 5, 6, 7 or 8) hydrogen atoms on a ring or group are independently substituted by a substituent selected from the group consisting of C1-C8 alkyl, C3-C8 cycloalkyl, C1-C8 haloalkyl, C3-C8 halocycloalkyl, C1-C8 alkoxy, C1-C8 alkylthio, C1-C8 haloalkoxy, C1-C8 haloalkylthio, C3-C8 cycloalkyloxy, C3-C8 cycloalkylthio, C3-C8 halocycloalkyloxy, C3-C8 halocycloalkylthio, halogen, nitro, hydroxyl, thiol, amino, carbonyl, C6-C12 aryl, 5-10 membered heteroaryl, and 5-10 membered heterocycloalkyl; The heterocyclic ring of the heterocycloalkyl, heteroaryl, heterocycloalkane ring and heteroaryl ring has 1-4 (preferably 1, 2, 3 or 4) heteroatoms independently selected from N, O and S.

2. The compound of formula I according to claim 1, or its optical isomer or racemate, or solvate, or pharmaceutically acceptable salt, or deuterated compound thereof, wherein: The compound is selected from the following group:

3. A composition, characterized in that The composition comprises (a) the compound of formula I according to claim 1, or its optical isomer, or its racemate, or its solvate, or its pharmaceutically acceptable salt, or its deuterated compound.

4. The composition according to claim 3, wherein The compositions include pharmaceutical compositions.

5. The composition according to claim 3, wherein The composition further comprises (b) a pharmaceutically acceptable carrier.

6. Use of the compound of formula I according to claim 1, or its optical isomer, or its racemate, or its solvate, or its pharmaceutically acceptable salt, or its deuterated compound, for preparing a composition or preparation for one or more uses selected from the group consisting of: (1) lowering blood sugar; (2) preventing and / or treating hyperglycemia; and / or (3) preventing and / or treating diabetes.

7. The use according to claim 6, characterized in that The diabetes mellitus includes type 1 diabetes mellitus and / or type 2 diabetes mellitus.

8. The use according to claim 6, characterized in that The hyperglycemia includes hyperglycemia caused by insulin resistance; and / or The diabetes mellitus includes diabetes mellitus caused by insulin resistance.

9. The use according to claim 6, characterized in that The composition or preparation is a pharmaceutical composition or pharmaceutical preparation.

10. A method for (1) lowering blood sugar; (2) preventing and / or treating hyperglycemia; and / or (3) preventing and / or treating diabetes, characterized in that: The method comprises administering to a subject in need thereof a compound of formula I as described in claim 1, or an optical isomer thereof, or a racemate thereof, or a solvate thereof, or a pharmaceutically acceptable salt thereof, or a deuterated compound thereof, thereby (1) lowering blood sugar; (2) preventing and / or treating hyperglycemia; and / or (3) preventing and / or treating diabetes.

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